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.
Papers published on a yearly basis
Papers
More filters
••
TL;DR: It is demonstrated the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence and it is demonstrated that NR delays senescences of neural SCs and melanocyteSCs and increases mouse life span.
Abstract: Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals.
833 citations
••
TL;DR: The discovery of six hominid specimens from Chad, central Africa, 2,500 km from the East African Rift Valley, suggest that the earliest members of the hominids clade were more widely distributed than has been thought, and that the divergence between the human and chimpanzee lineages was earlier than indicated by most molecular studies.
Abstract: The search for the earliest fossil evidence of the human lineage has been concentrated in East Africa. Here we report the discovery of six hominid specimens from Chad, central Africa, 2,500 km from the East African Rift Valley. The fossils include a nearly complete cranium and fragmentary lower jaws. The associated fauna suggest the fossils are between 6 and 7 million years old. The fossils display a unique mosaic of primitive and derived characters, and constitute a new genus and species of hominid. The distance from the Rift Valley, and the great antiquity of the fossils, suggest that the earliest members of the hominid clade were more widely distributed than has been thought, and that the divergence between the human and chimpanzee lineages was earlier than indicated by most molecular studies. From their initial description in 1925 1 until 1995, hominids from the Pliocene (5.3‐1.6 million years, Myr) and late Upper Miocene (,7.5‐5.3 Myr) were known only from southern and eastern Africa. This distribution led some authors to postulate an East African origin for the hominid clade (where the term ‘hominid’ refers to any member of that group more closely related to extant humans than to
831 citations
••
TL;DR: It is shown that lipopolysaccharide from Gram-negative bacteria activates interleukin-5 (IL-5)- or interferon-γ–primed eosinophils to release mitochondrial DNA in a reactive oxygen species–dependent manner, but independent of eosInophil death, suggesting a previously undescribed mechanism of eOSinophil-mediated innate immune responses that might be crucial for maintaining the intestinal barrier function after inflammation-associated epithelial cell damage
Abstract: Although eosinophils are considered useful in defense mechanisms against parasites, their exact function in innate immunity remains unclear. The aim of this study is to better understand the role of eosinophils within the gastrointestinal immune system. We show here that lipopolysaccharide from Gram-negative bacteria activates interleukin-5 (IL-5)- or interferon-gamma-primed eosinophils to release mitochondrial DNA in a reactive oxygen species-dependent manner, but independent of eosinophil death. Notably, the process of DNA release occurs rapidly in a catapult-like manner--in less than one second. In the extracellular space, the mitochondrial DNA and the granule proteins form extracellular structures able to bind and kill bacteria both in vitro and under inflammatory conditions in vivo. Moreover, after cecal ligation and puncture, Il5-transgenic but not wild-type mice show intestinal eosinophil infiltration and extracellular DNA deposition in association with protection against microbial sepsis. These data suggest a previously undescribed mechanism of eosinophil-mediated innate immune responses that might be crucial for maintaining the intestinal barrier function after inflammation-associated epithelial cell damage, preventing the host from uncontrolled invasion of bacteria.
829 citations
••
University of Cologne1, University of Zurich2, Cornell University3, University of Bonn4, Max Planck Society5, Peter MacCallum Cancer Centre6, St. Vincent's Health System7, Joseph Fourier University8, Oslo University Hospital9, Schiller International University10, University of Groningen11, VU University Medical Center12, Vanderbilt University13
TL;DR: F focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
Abstract: Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
828 citations
••
TL;DR: Whereas most clinical trials with anti-inflammatory, anti-coagulant, or antioxidant strategies failed, the implementation of pre- and in-hospital trauma protocols and the principle of damage control procedures have reduced post-traumatic complications, the development of immunomonitoring will help in the selection of patients at risk of post- traumatic complications and the choice of the most appropriate treatment protocols for severely injured patients.
Abstract: Immediate and early trauma deaths are determined by primary brain injuries, or significant blood loss (haemorrhagic shock), while late mortality is caused by secondary brain injuries and host defence failure. First hits (hypoxia, hypotension, organ and soft tissue injuries, fractures), as well as second hits (e.g. ischaemia/reperfusion injuries, compartment syndromes, operative interventions, infections), induce a host defence response. This is characterized by local and systemic release of pro-inflammatory cytokines, arachidonic acid metabolites, proteins of the contact phase and coagulation systems, complement factors and acute phase proteins, as well as hormonal mediators: it is defined as systemic inflammatory response syndrome (SIRS), according to clinical parameters. However, in parallel, anti-inflammatory mediators are produced (compensatory anti-inflammatory response syndrome (CARS). An imbalance of these dual immune responses seems to be responsible for organ dysfunction and increased susceptibility to infections. Endothelial cell damage, accumulation of leukocytes, disseminated intravascular coagulation (DIC) and microcirculatory disturbances lead finally to apoptosis and necrosis of parenchymal cells, with the development of multiple organ dysfunction syndrome (MODS), or multiple organ failure (MOF). Whereas most clinical trials with anti-inflammatory, anti-coagulant, or antioxidant strategies failed, the implementation of pre- and in-hospital trauma protocols and the principle of damage control procedures have reduced post-traumatic complications. However, the development of immunomonitoring will help in the selection of patients at risk of post-traumatic complications and, thereby, the choice of the most appropriate treatment protocols for severely injured patients.
828 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 |