Institution
University of Zurich
Education•Zurich, Switzerland•
About: University of Zurich is a education organization based out in Zurich, Switzerland. It is known for research contribution in the topics: Population & Transplantation. The organization has 50842 authors who have published 124042 publications receiving 5304521 citations. The organization is also known as: UZH & Uni Zurich.
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TL;DR: It is shown that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the Hypoxia-inducible gene REDD1/RTP801 to be inhibited, and that down-regulation of mTOR activity by hyp oxia requires de novo mRNA synthesis and correlates with increased expression of the hypoxIA-Inducible REDD 1 gene.
Abstract: Mammalian target of rapamycin (mTOR) is a central regulator of protein synthesis whose activity is modulated by a variety of signals. Energy depletion and hypoxia result in mTOR inhibition. While energy depletion inhibits mTOR through a process involving the activation of AMP-activated protein kinase (AMPK) by LKB1 and subsequent phosphorylation of TSC2, the mechanism of mTOR inhibition by hypoxia is not known. Here we show that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the hypoxia-inducible gene REDD1/RTP801. Disruption of the TSC1/TSC2 complex through loss of TSC1 or TSC2 blocks the effects of hypoxia on mTOR, as measured by changes in the mTOR targets S6K and 4E-BP1, and results in abnormal accumulation of Hypoxia-inducible factor (HIF). In contrast to energy depletion, mTOR inhibition by hypoxia does not require AMPK or LKB1. Down-regulation of mTOR activity by hypoxia requires de novo mRNA synthesis and correlates with increased expression of the hypoxia-inducible REDD1 gene. Disruption of REDD1 abrogates the hypoxia-induced inhibition of mTOR, and REDD1 overexpression is sufficient to down-regulate S6K phosphorylation in a TSC1/TSC2-dependent manner. Inhibition of mTOR function by hypoxia is likely to be important for tumor suppression as TSC2-deficient cells maintain abnormally high levels of cell proliferation under hypoxia.
1,299 citations
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TL;DR: It is suggested that while large-scale trends show considerable geographical and temporal variability, amphibian populations are in fact declining—and that this decline has been happening for several decades.
Abstract: Although there is growing concern that amphibian populations are declining globally, much of the supporting evidence is either anecdotal or derived from short-term studies at small geographical scales. This raises questions not only about the difficulty of detecting temporal trends in populations which are notoriously variable, but also about the validity of inferring global trends from local or regional studies. Here we use data from 936 populations to assess large-scale temporal and spatial variations in amphibian population trends. On a global scale, our results indicate relatively rapid declines from the late 1950s/early 1960s to the late 1960s, followed by a reduced rate of decline to the present. Amphibian population trends during the 1960s were negative in western Europe (including the United Kingdom) and North America, but only the latter populations showed declines from the 1970s to the late 1990s. These results suggest that while large-scale trends show considerable geographical and temporal variability, amphibian populations are in fact declining--and that this decline has been happening for several decades.
1,297 citations
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TL;DR: The coupled immunohistochemical and immunocytochemical methods with high-resolution laser ablation to CyTOF mass cytometry enables the simultaneous imaging of 32 proteins and protein modifications at subcellular resolution and complements existing imaging approaches.
Abstract: Mass cytometry enables high-dimensional, single-cell analysis of cell type and state. In mass cytometry, rare earth metals are used as reporters on antibodies. Analysis of metal abundances using the mass cytometer allows determination of marker expression in individual cells. Mass cytometry has previously been applied only to cell suspensions. To gain spatial information, we have coupled immunohistochemical and immunocytochemical methods with high-resolution laser ablation to CyTOF mass cytometry. This approach enables the simultaneous imaging of 32 proteins and protein modifications at subcellular resolution; with the availability of additional isotopes, measurement of over 100 markers will be possible. We applied imaging mass cytometry to human breast cancer samples, allowing delineation of cell subpopulations and cell-cell interactions and highlighting tumor heterogeneity. Imaging mass cytometry complements existing imaging approaches. It will enable basic studies of tissue heterogeneity and function and support the transition of medicine toward individualized molecularly targeted diagnosis and therapies.
1,288 citations
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TL;DR: It is proposed that this tissue-specific enhancer contributes to the activation of somatically rearranged immunoglobulin variable region genes and possibly to abnormal expression of other genes (e.g. c-myc) that become translocated to its domain of influence.
1,285 citations
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TL;DR: It is reported here that mice homozygous for a disrupted Tnfr l allele (Tnfr1 0) are resistant to the lethal effect of low doses of lipopolysaccharide after sensitization with D-galactosamine, but remain sensitive to high doses oflipopoly Saccharide.
Abstract: Tumour necrosis factor (TNF), jointly referring to TNF alpha and TNF beta, is a central mediator of immune and inflammatory responses; its activities are mediated by two distinct receptors, TNFR1 (p55) and TNFR2 (p75) (reviewed in refs 1-3). The cytoplasmic domains of the TNFRs are unrelated, suggesting that they link to different intracellular signalling pathways. Although most TNF responses have been assigned to one or the other of the TNF receptors (mostly TNFR1), there is no generally accepted model for the physiological role of the two receptor types. To investigate the role of TNFR1 in beneficial and detrimental activities of TNF, we generated TNFR1-deficient mice by gene targeting. We report here that mice homozygous for a disrupted Tnfr1 allele (Tnfr1(0)) are resistant to the lethal effect of low doses of lipopolysaccharide after sensitization with D-galactosamine, but remain sensitive to high doses of lipopolysaccharide. The increased susceptibility of Tnfr1(0)/Tnfr1(0) mutant mice to infection with the facultative intracellular bacterium Listeria monocytogenes indicates an essential role of TNF in nonspecific immunity.
1,283 citations
Authors
Showing all 51384 results
Name | H-index | Papers | Citations |
---|---|---|---|
Richard A. Flavell | 231 | 1328 | 205119 |
Peer Bork | 206 | 697 | 245427 |
Thomas C. Südhof | 191 | 653 | 118007 |
Stuart H. Orkin | 186 | 715 | 112182 |
Ruedi Aebersold | 182 | 879 | 141881 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
Stanley B. Prusiner | 168 | 745 | 97528 |
Yang Yang | 164 | 2704 | 144071 |
Tomas Hökfelt | 158 | 1033 | 95979 |
Dan R. Littman | 157 | 426 | 107164 |
Hans Lassmann | 155 | 724 | 79933 |
Matthias Egger | 152 | 901 | 184176 |
Lorenzo Bianchini | 152 | 1516 | 106970 |
Robert M. Strieter | 151 | 612 | 73040 |
Ashok Kumar | 151 | 5654 | 164086 |