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 & Medicine. The organization has 50842 authors who have published 124042 publications receiving 5304521 citations. The organization is also known as: UZH & Uni Zurich.
Topics: Population, Medicine, Context (language use), Gene, Transplantation
Papers published on a yearly basis
Papers
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TL;DR: Libraries of native folded proteins can now be screened and made to evolve in a cell-free system without any transformation or constraints imposed by the host cell.
Abstract: We report here a system with which a correctly folded complete protein and its encoding mRNA both remain attached to the ribosome and can be enriched for the ligand-binding properties of the native protein. We have selected a single-chain fragment (scFv) of an antibody 108-fold by five cycles of transcription, translation, antigen-affinity selection, and PCR. The selected scFv fragments all mutated in vitro by acquiring up to four unrelated amino acid exchanges over the five generations, but they remained fully compatible with antigen binding. Libraries of native folded proteins can now be screened and made to evolve in a cell-free system without any transformation or constraints imposed by the host cell.
1,329 citations
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TL;DR: In this review recent achievements and new perspectives on protein adsorption processes are comprehensively discussed and the main focus is put on commonly postulated mechanistic aspects and their translation into mathematical concepts and model descriptions.
1,328 citations
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TL;DR: Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.
Abstract: Oncogenic mutations in the serine/threonine kinase B-RAF (also known as BRAF) are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAF(V600E) mutation predicts a dependency on the mitogen-activated protein kinase (MAPK) signalling cascade in melanoma-an observation that has been validated by the success of RAF and MEK inhibitors in clinical trials. However, clinical responses to targeted anticancer therapeutics are frequently confounded by de novo or acquired resistance. Identification of resistance mechanisms in a manner that elucidates alternative 'druggable' targets may inform effective long-term treatment strategies. Here we expressed ∼600 kinase and kinase-related open reading frames (ORFs) in parallel to interrogate resistance to a selective RAF kinase inhibitor. We identified MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines. COT activates ERK primarily through MEK-dependent mechanisms that do not require RAF signalling. Moreover, COT expression is associated with de novo resistance in B-RAF(V600E) cultured cell lines and acquired resistance in melanoma cells and tissue obtained from relapsing patients following treatment with MEK or RAF inhibitors. We further identify combinatorial MAPK pathway inhibition or targeting of COT kinase activity as possible therapeutic strategies for reducing MAPK pathway activation in this setting. Together, these results provide new insights into resistance mechanisms involving the MAPK pathway and articulate an integrative approach through which high-throughput functional screens may inform the development of novel therapeutic strategies.
1,326 citations
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Karlstad University1, Dresden University of Technology2, Karolinska University Hospital3, Mental Health Services4, Phillips University5, University of Florence6, Karolinska Institutet7, John Radcliffe Hospital8, King's College London9, London School of Economics and Political Science10, Lund University11, Harvard University12, University of Basel13, Norwegian University of Science and Technology14, University of Zurich15, Umeå University16, University of Cambridge17, University of Lausanne18, University of Sassari19, European Monitoring Centre for Drugs and Drug Addiction20, Aalborg University21, Cliniques Universitaires Saint-Luc22, Maastricht University Medical Centre23, Radboud University Nijmegen24, Stockholm School of Economics25
TL;DR: The present report presents much improved cost estimates for the total cost of disorders of the brain in Europe in 2010, covering 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items.
1,325 citations
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TL;DR: The capacity for CNS axons to regenerate and elongate within differentiated CNS tissue after the neutralization of myelin-associated neurite growth inhibitors is demonstrated.
Abstract: After lesions in the differentiated central nervous system (CNS) of higher vertebrates, interrupted fibre tracts do not regrow and elongate by more than an initial sprout of approximately 1 mm. Transplantations of pieces of peripheral nerves into various parts of the CNS demonstrate the widespread capability of CNS neurons to regenerate lesioned axons over long distances in a peripheral nerve environment. CNS white matter, cultured oligodendrocytes (the myelin-producing cells of the CNS), and CNS myelin itself, are strong inhibitors of neuron growth in culture, a property associated with defined myelin membrane proteins of relative molecular mass (Mr) 35,000 (NI-35) and 250,000 (NI-250). We have now intracerebrally applied the monoclonal antibody IN-1, which neutralizes the inhibitory effect of both these proteins, to young rats by implanting antibody-producing tumours. In 2-6-week-old rats we made complete transections of the cortico-spinal tract, a major fibre tract of the spinal cord, the axons of which originate in the motor and sensory neocortex. Previous studies have shown a complete absence of cortico-spinal tract regeneration after the first postnatal week in rats, and in adult hamsters and cats. In IN-1-treated rats, massive sprouting occurred at the lesion site, and fine axons and fascicles could be observed up to 7-11 mm caudal to the lesion within 2-3 weeks. In control rats, a similar sprouting reaction occurred, but the maximal distance of elongation rarely exceeded 1 mm. These results demonstrate the capacity for CNS axons to regenerate and elongate within differentiated CNS tissue after the neutralization of myelin-associated neurite growth inhibitors.
1,320 citations
Authors
Showing all 51384 results
Name | H-index | Papers | Citations |
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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 |