Institution
University of Bern
Education•Bern, Switzerland•
About: University of Bern is a education organization based out in Bern, Switzerland. It is known for research contribution in the topics: Population & Medicine. The organization has 35422 authors who have published 79413 publications receiving 3125088 citations. The organization is also known as: Bern University & UNIBE.
Topics: Population, Medicine, Context (language use), Cancer, Immune system
Papers published on a yearly basis
Papers
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TL;DR: The 53 BP1 effector complex shieldin is involved in non-homologous end-joining and immunoglobulin class switching, and acts to protect DNA ends to facilitate the repair of DNA by 53BP1, it is shown that binding of single-stranded DNA by SHLD2 is critical for shieldin function.
Abstract: 53BP1 is a chromatin-binding protein that regulates the repair of DNA double-strand breaks by suppressing the nucleolytic resection of DNA termini1,2. This function of 53BP1 requires interactions with PTIP3 and RIF14–9, the latter of which recruits REV7 (also known as MAD2L2) to break sites10,11. How 53BP1-pathway proteins shield DNA ends is currently unknown, but there are two models that provide the best potential explanation of their action. In one model the 53BP1 complex strengthens the nucleosomal barrier to end-resection nucleases12,13, and in the other 53BP1 recruits effector proteins with end-protection activity. Here we identify a 53BP1 effector complex, shieldin, that includes C20orf196 (also known as SHLD1), FAM35A (SHLD2), CTC-534A2.2 (SHLD3) and REV7. Shieldin localizes to double-strand-break sites in a 53BP1- and RIF1-dependent manner, and its SHLD2 subunit binds to single-stranded DNA via OB-fold domains that are analogous to those of RPA1 and POT1. Loss of shieldin impairs non-homologous end-joining, leads to defective immunoglobulin class switching and causes hyper-resection. Mutations in genes that encode shieldin subunits also cause resistance to poly(ADP-ribose) polymerase inhibition in BRCA1-deficient cells and tumours, owing to restoration of homologous recombination. Finally, we show that binding of single-stranded DNA by SHLD2 is critical for shieldin function, consistent with a model in which shieldin protects DNA ends to mediate 53BP1-dependent DNA repair.
406 citations
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TL;DR: The findings indicate that the type of opponent influences playing experiences: participants who played against a human-controlled opponent reported more experiences of presence, flow, and enjoyment, whereby the strongest effect refers to the experience of presence.
406 citations
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TL;DR: In the early Holocene, the Egesen stadial moraines can be divided into three or in some cases even more phases (sub-stadials) as mentioned in this paper.
406 citations
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Spanish National Research Council1, University of Alicante2, Pablo de Olavide University3, Swansea University4, Henan University of Technology5, Chinese Academy of Sciences6, National University of Luján7, International Trademark Association8, National Scientific and Technical Research Council9, University of Bern10, Université du Québec à Trois-Rivières11, Free University of Berlin12, Santa Fe Institute13
TL;DR: Investigation of how 20 structural and functional ecosystem attributes respond to aridity in global drylands found evidence for a series of abrupt ecological events occurring sequentially in three phases, culminating with a shift to low-cover ecosystems that are nutrient- and species-poor at high aridity values.
Abstract: Aridity, which is increasing worldwide because of climate change, affects the structure and functioning of dryland ecosystems. Whether aridification leads to gradual (versus abrupt) and systemic (versus specific) ecosystem changes is largely unknown. We investigated how 20 structural and functional ecosystem attributes respond to aridity in global drylands. Aridification led to systemic and abrupt changes in multiple ecosystem attributes. These changes occurred sequentially in three phases characterized by abrupt decays in plant productivity, soil fertility, and plant cover and richness at aridity values of 0.54, 0.7, and 0.8, respectively. More than 20% of the terrestrial surface will cross one or several of these thresholds by 2100, which calls for immediate actions to minimize the negative impacts of aridification on essential ecosystem services for the more than 2 billion people living in drylands.
405 citations
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TL;DR: It is shown, in several model tumours in mice, that systemic glucose–insulin feedback caused by targeted inhibition of this pathway is sufficient to activate PI3K signalling, even in the presence ofPI3K inhibitors.
Abstract: Mutations in PIK3CA, which encodes the p110α subunit of the insulin-activated phosphatidylinositol-3 kinase (PI3K), and loss of function mutations in PTEN, which encodes a phosphatase that degrades the phosphoinositide lipids generated by PI3K, are among the most frequent events in human cancers1,2. However, pharmacological inhibition of PI3K has resulted in variable clinical responses, raising the possibility of an inherent mechanism of resistance to treatment. As p110α mediates virtually all cellular responses to insulin, targeted inhibition of this enzyme disrupts glucose metabolism in multiple tissues. For example, blocking insulin signalling promotes glycogen breakdown in the liver and prevents glucose uptake in the skeletal muscle and adipose tissue, resulting in transient hyperglycaemia within a few hours of PI3K inhibition. The effect is usually transient because compensatory insulin release from the pancreas (insulin feedback) restores normal glucose homeostasis3. However, the hyperglycaemia may be exacerbated or prolonged in patients with any degree of insulin resistance and, in these cases, necessitates discontinuation of therapy3-6. We hypothesized that insulin feedback induced by PI3K inhibitors may reactivate the PI3K-mTOR signalling axis in tumours, thereby compromising treatment effectiveness7,8. Here we show, in several model tumours in mice, that systemic glucose-insulin feedback caused by targeted inhibition of this pathway is sufficient to activate PI3K signalling, even in the presence of PI3K inhibitors. This insulin feedback can be prevented using dietary or pharmaceutical approaches, which greatly enhance the efficacy/toxicity ratios of PI3K inhibitors. These findings have direct clinical implications for the multiple p110α inhibitors that are in clinical trials and provide a way to increase treatment efficacy for patients with many types of tumour.
405 citations
Authors
Showing all 35931 results
Name | H-index | Papers | Citations |
---|---|---|---|
Yi Chen | 217 | 4342 | 293080 |
Nahum Sonenberg | 167 | 647 | 104053 |
Marc Weber | 167 | 2716 | 153502 |
Joseph Jankovic | 153 | 1146 | 93840 |
Matthias Egger | 152 | 901 | 184176 |
Markus W. Büchler | 148 | 1545 | 93574 |
Robert J. Glynn | 146 | 748 | 88387 |
Mark A. Rubin | 145 | 699 | 95640 |
Antonio Ereditato | 144 | 1448 | 97008 |
Hans Peter Beck | 143 | 1134 | 91858 |
Kim Nasmyth | 142 | 294 | 59231 |
Tomas Ganz | 141 | 480 | 73316 |
Stephan Windecker | 140 | 1227 | 151063 |
Claude Amsler | 138 | 1454 | 135063 |
Thomas F. Lüscher | 134 | 1560 | 79034 |