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
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TL;DR: The results of this study identify cathepsin D as the first endosomal ceramide target that colocalizes with and may mediate downstream signaling effects of A‐SMase.
Abstract: Ceramide has been recognized as a common intracellular second messenger for various cytokines, growth factors and other stimuli, such as CD95, chemotherapeutic drugs and stress factors. To understand the role of ceramide during apoptosis and other cellular responses, it is critically important to characterize direct targets of ceramide action. In this paper, we show that ceramide specifically binds to and activates the endosomal acidic aspartate protease cathepsin D. Direct interaction of ceramide with cathepsin D results in autocatalytic proteolysis of the 52 kDa pre-pro cathepsin D to form the enzymatically active 48/32 kDa isoforms of cathepsin D. Acid sphingomyelinase (A-SMase)-deficient cells show decreased cathepsin D activity, which could be reconstituted by transfection with A-SMase cDNA. The results of our study identify cathepsin D as the first endosomal ceramide target that colocalizes with and may mediate downstream signaling effects of A-SMase.
355 citations
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University of Maryland, College Park1, University of California, Santa Barbara2, Oregon State University3, University of California, San Diego4, University of British Columbia5, University of Cologne6, University of California, Irvine7, Arizona State University8, Northeastern University9, University of Florida10
TL;DR: It was showed that producer community biomass increased with fertilization across all systems, although increases were greatest in freshwater habitats, and herbivore removal generally increased producer biomass in both freshwater and marine systems, but effects were inconsistent on land.
Abstract: Nutrient availability and herbivory control the biomass of primary producer communities to varying degrees across ecosystems. Ecological theory, individual experiments in many different systems, and system-specific quantitative reviews have suggested that (i) bottom‐up control is pervasive but top‐down control is more influential in aquatic habitats relative to terrestrial systems and (ii) bottom‐up and top‐down forces are interdependent, with statistical interactions that synergize or dampen relative influences on producer biomass. We used simple dynamic models to review ecological mechanisms that generate independent vs. interactive responses of community-level biomass. We calibrated these mechanistic predictions with the metrics of factorial meta-analysis and tested their prevalence across freshwater, marine and terrestrial ecosystems with a comprehensive meta-analysis of 191 factorial manipulations of herbivores and nutrients. Our analysis showed that producer community biomass increased with fertilization across all systems, although increases were greatest in freshwater habitats. Herbivore removal generally increased producer biomass in both freshwater and marine systems, but effects were inconsistent on land. With the exception of marine temperate rocky reef systems that showed positive synergism of nutrient enrichment and herbivore removal, experimental studies showed limited support for statistical interactions between nutrient and herbivory treatments on producer biomass. Top‐down control of herbivores, compensatory behaviour of multiple herbivore guilds, spatial and temporal heterogeneity of interactions, and herbivore-mediated nutrient recycling may lower the probability of consistent interactive effects on producer biomass. Continuing studies should expand the temporal and spatial scales of experiments, particularly in understudied terrestrial systems; broaden factorial designs to manipulate independently multiple producer resources (e.g. nitrogen, phosphorus, light), multiple herbivore taxa or guilds (e.g. vertebrates and invertebrates) and multiple trophic levels; and ‐ in addition to measuring producer biomass ‐ assess the responses of species diversity, community composition and nutrient status.
355 citations
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TL;DR: Endothelium-restricted inhibition of NF-kappaB activation resulted in strongly reduced atherosclerotic plaque formation in ApoE(-/-) mice fed with a cholesterol-rich diet and inhibited proinflammatory gene expression at the arterial wall and promotes the pathogenesis of atherosclerosis.
355 citations
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TL;DR: In this paper, the relationship between specific mutations in BRCA1 and cancer risk has been investigated and limited information about the relationship has been available about specific mutations for specific mutations.
Abstract: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.
355 citations
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TL;DR: Surprisingly, data indicate that HdmX acts as a stimulator, rather than as an inhibitor, of the E3 activity of Hdm2 and that, at least under certain conditions, HDMX is actively involved in the degradation of both p53 and HDM2.
Abstract: The RING finger proteins HdmX and Hdm2 share significant structural and functional similarity. Hdm2 is a member of the RING finger family of ubiquitin-protein ligases E3 and targets the tumor suppressor protein p53 for degradation. Although HdmX also binds to p53, HdmX does not induce p53 degradation. Moreover, HdmX has been reported to interfere with p53 degradation in overexpression experiments. To obtain insight into the mechanism by which HdmX interferes with p53 degradation, we studied the effect of HdmX on the E3 activity of Hdm2 in vitro. Surprisingly, this revealed that HdmX stimulates Hdm2-mediated ubiquitination of p53 and that HdmX facilitates ubiquitination of Hdm2 and vice versa. In addition, down-regulation of HdmX expression within cells results in the accumulation of both p53 and Hdm2. Because HdmX alone does not have appreciable E3 activity, these data indicate that HdmX acts as a stimulator, rather than as an inhibitor, of the E3 activity of Hdm2 and that, at least under certain conditions, HdmX is actively involved in the degradation of both p53 and Hdm2.
355 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 |