Institution
University of Southern Denmark
Education•Odense, Syddanmark, Denmark•
About: University of Southern Denmark is a education organization based out in Odense, Syddanmark, Denmark. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 11928 authors who have published 37918 publications receiving 1258559 citations. The organization is also known as: SDU.
Papers published on a yearly basis
Papers
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TL;DR: In this article, heat shock protein 70 (Hsp70) is shown to stabilize lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential co-factor for acid sphingomyelin metabolism.
Abstract: Heat shock protein 70 (Hsp70) is an evolutionarily highly conserved molecular chaperone that promotes the survival of stressed cells by inhibiting lysosomal membrane permeabilization, a hallmark of stress-induced cell death. Clues to its molecular mechanism of action may lay in the recently reported stress- and cancer-associated translocation of a small portion of Hsp70 to the lysosomal compartment. Here we show that Hsp70 stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential co-factor for lysosomal sphingomyelin metabolism. In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70 (Trp90Phe), as well as the pharmacological and genetic inhibition of ASM, effectively revert the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease (NPD) A and B-severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1) encoding for ASM-is also associated with a marked decrease in lysosomal stability, and this phenotype can be effectively corrected by treatment with recombinant Hsp70. Taken together, these data open exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway.
422 citations
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TL;DR: A simple and rapid strategy, SIMAC (sequential elution from IMAC), for sequential separation of monophosphorylation peptides and multiply phosphorylated peptides from highly complex biological samples is reported.
420 citations
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TL;DR: The current status of the Standard Model calculation of the anomalous magnetic moment of the muon has been reviewed in this paper, where the authors present a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach.
Abstract: We review the present status of the Standard Model calculation of the anomalous magnetic moment of the muon. This is performed in a perturbative expansion in the fine-structure constant $\alpha$ and is broken down into pure QED, electroweak, and hadronic contributions. The pure QED contribution is by far the largest and has been evaluated up to and including $\mathcal{O}(\alpha^5)$ with negligible numerical uncertainty. The electroweak contribution is suppressed by $(m_\mu/M_W)^2$ and only shows up at the level of the seventh significant digit. It has been evaluated up to two loops and is known to better than one percent. Hadronic contributions are the most difficult to calculate and are responsible for almost all of the theoretical uncertainty. The leading hadronic contribution appears at $\mathcal{O}(\alpha^2)$ and is due to hadronic vacuum polarization, whereas at $\mathcal{O}(\alpha^3)$ the hadronic light-by-light scattering contribution appears. Given the low characteristic scale of this observable, these contributions have to be calculated with nonperturbative methods, in particular, dispersion relations and the lattice approach to QCD. The largest part of this review is dedicated to a detailed account of recent efforts to improve the calculation of these two contributions with either a data-driven, dispersive approach, or a first-principle, lattice-QCD approach. The final result reads $a_\mu^\text{SM}=116\,591\,810(43)\times 10^{-11}$ and is smaller than the Brookhaven measurement by 3.7$\sigma$. The experimental uncertainty will soon be reduced by up to a factor four by the new experiment currently running at Fermilab, and also by the future J-PARC experiment. This and the prospects to further reduce the theoretical uncertainty in the near future-which are also discussed here-make this quantity one of the most promising places to look for evidence of new physics.
420 citations
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TL;DR: Findings show SIRT3 regulates ketone body production during fasting and provide molecular insight into how protein acetylation can regulate enzymatic activity.
420 citations
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TL;DR: The aim is to investigate how ELECTRE and ELECTRE-based methods have been considered in various areas, including area of applications, modifications to the methods, comparisons with other methods, and general studies of the ELECTRE methods.
419 citations
Authors
Showing all 12150 results
Name | H-index | Papers | Citations |
---|---|---|---|
Paul M. Ridker | 233 | 1242 | 245097 |
George Davey Smith | 224 | 2540 | 248373 |
Matthias Mann | 221 | 887 | 230213 |
Eric Boerwinkle | 183 | 1321 | 170971 |
Gang Chen | 167 | 3372 | 149819 |
Jun Wang | 166 | 1093 | 141621 |
Harvey F. Lodish | 165 | 782 | 101124 |
Jens J. Holst | 160 | 1536 | 107858 |
Rajesh Kumar | 149 | 4439 | 140830 |
J. Fraser Stoddart | 147 | 1239 | 96083 |
Debbie A Lawlor | 147 | 1114 | 101123 |
Børge G. Nordestgaard | 147 | 1047 | 95530 |
Oluf Pedersen | 135 | 939 | 106974 |
Rasmus Nielsen | 135 | 556 | 84898 |
Torben Jørgensen | 135 | 883 | 86822 |