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Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells

2012, Sanges, C., Scheuermann, C., Zahedi, R.P., Sickmann, A., Lamberti, A., Migliaccio, N., Baljuls, A., Marra, M., Zappavigna, S., Reinders, J., Rapp, U., Abbruzzese, A., Caraglia, M., Arcari, P.

We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes.

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Nanowire-supported plasmonic waveguide for remote excitation of surface-enhanced Raman scattering

2014, Huang, Y., Fang, Y., Zhang, Z., Zhu, L., Sun, M.

Due to its amazing ability to manipulate light at the nanoscale, plasmonics has become one of the most interesting topics in the field of light-matter interaction. As a promising application of plasmonics, surface-enhanced Raman scattering (SERS) has been widely used in scientific investigations and material analysis. The large enhanced Raman signals are mainly caused by the extremely enhanced electromagnetic field that results from localized surface plasmon polaritons. Recently, a novel SERS technology called remote SERS has been reported, combining both localized surface plasmon polaritons and propagating surface plasmon polaritons (PSPPs, or called plasmonic waveguide), which may be found in prominent applications in special circumstances compared to traditional local SERS. In this article, we review the mechanism of remote SERS and its development since it was first reported in 2009. Various remote metal systems based on plasmonic waveguides, such as nanoparticle-nanowire systems, single nanowire systems, crossed nanowire systems and nanowire dimer systems, are introduced, and recent novel applications, such as sensors, plasmon-driven surface-catalyzed reactions and Raman optical activity, are also presented. Furthermore, studies of remote SERS in dielectric and organic systems based on dielectric waveguides remind us that this useful technology has additional, tremendous application prospects that have not been realized in metal systems.

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Tuning the interplay between nematicity and spin fluctuations in Na1-x Li x FeAs superconductors

2018, Baek, S.-H., Bhoi, D., Nam, W., Lee, B., Efremov, D.V., Büchner, B., Kim, K.H.

Strong interplay of spin and charge/orbital degrees of freedom is the fundamental characteristic of the iron-based superconductors (FeSCs), which leads to the emergence of a nematic state as a rule in the vicinity of the antiferromagnetic state. Despite intense debate for many years, however, whether nematicity is driven by spin or orbital fluctuations remains unsettled. Here, by use of transport, magnetization, and 75As nuclear magnetic resonance (NMR) measurements, we show a striking transformation of the relationship between nematicity and spin fluctuations (SFs) in Na1-x Li x FeAs; For x ≤ 0.02, the nematic transition promotes SFs. In contrast, for x ≥ 0.03, the system undergoes a non-magnetic phase transition at a temperature T 0 into a distinct nematic state that suppresses SFs. Such a drastic change of the spin fluctuation spectrum associated with nematicity by small doping is highly unusual, and provides insights into the origin and nature of nematicity in FeSCs.

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Synthesis of quasi-free-standing bilayer graphene nanoribbons on SiC surfaces

2015, Oliveira, Myriano H., Jr., Lopes, Joao Marcelo J., Schumann, Timo, Galves, Lauren A., Ramsteiner, Manfred, Berlin, Katja, Trampert, Achim, Riechert, Henning

Scaling graphene down to nanoribbons is a promising route for the implementation of this material into devices. Quantum confinement of charge carriers in such nanostructures, combined with the electric field-induced break of symmetry in AB-stacked bilayer graphene, leads to a band gap wider than that obtained solely by this symmetry breaking. Consequently, the possibility of fabricating AB-stacked bilayer graphene nanoribbons with high precision is very attractive for the purposes of applied and basic science. Here we show a method, which includes a straightforward air annealing, for the preparation of quasi-free-standing AB-bilayer nanoribbons with different widths on SiC(0001). Furthermore, the experiments reveal that the degree of disorder at the edges increases with the width, indicating that the narrower nanoribbons are more ordered in their edge termination. In general, the reported approach is a viable route towards the large-scale fabrication of bilayer graphene nanostructures with tailored dimensions and properties for specific applications.

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Oxaliplatin-DNA adduct formation in white blood cells of cancer patients

2008, Pieck, A.C., Drescher, A., Wiesmann, K.G., Messerschmidt, J., Weber, G., Strumberg, D., Hilger, R.A., Scheulen, M.E., Jaehde, U.

In this study, we investigated the kinetics of oxaliplatin-DNA adduct formation in white blood cells of cancer patients in relation to efficacy as well as oxaliplatin-associated neurotoxicity. Thirty-seven patients with various solid tumours received 130 mg m−2 oxaliplatin as a 2-h infusion. Oxaliplatin-DNA adduct levels were measured in the first cycle using adsorptive stripping voltammetry. Platinum concentrations were measured in ultrafiltrate and plasma using a validated flameless atomic absorption spectrometry method. DNA adduct levels showed a characteristic time course, but were not correlated to platinum pharmacokinetics and varied considerably among individuals. In patients showing tumour response, adduct levels after 24 and 48 h were significantly higher than in nonresponders. Oxaliplatin-induced neurotoxicity was more pronounced but was not significantly different in patients with high adduct levels. The potential of oxaliplatin-DNA adduct measurements as pharmacodynamic end point should be further investigated in future trials.

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Size control in mammalian cells involves modulation of both growth rate and cell cycle duration

2018, Cadar, Clotilde, Monnier, Sylvain, Grilli, Jacopo, Sáez, Pablo J., Srivastava, Nishit, Attia, Rafaele, Terriac, Emmanuel, Baum, Buzz, Cosentino-Lagomarsino, Marco, Piel, Matthieu

Despite decades of research, how mammalian cell size is controlled remains unclear because of the difficulty of directly measuring growth at the single-cell level. Here we report direct measurements of single-cell volumes over entire cell cycles on various mammalian cell lines and primary human cells. We find that, in a majority of cell types, the volume added across the cell cycle shows little or no correlation to cell birth size, a homeostatic behavior called “adder”. This behavior involves modulation of G1 or S-G2 duration and modulation of growth rate. The precise combination of these mechanisms depends on the cell type and the growth condition. We have developed a mathematical framework to compare size homeostasis in datasets ranging from bacteria to mammalian cells. This reveals that a near-adder behavior is the most common type of size control and highlights the importance of growth rate modulation to size control in mammalian cells.

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Abrupt transitions in time series with uncertainties

2018, Goswami, B., Boers, N., Rheinwalt, A., Marwan, N., Heitzig, J., Breitenbach, S.F.M., Kurths, J.

Identifying abrupt transitions is a key question in various disciplines. Existing transition detection methods, however, do not rigorously account for time series uncertainties, often neglecting them altogether or assuming them to be independent and qualitatively similar. Here, we introduce a novel approach suited to handle uncertainties by representing the time series as a time-ordered sequence of probability density functions. We show how to detect abrupt transitions in such a sequence using the community structure of networks representing probabilities of recurrence. Using our approach, we detect transitions in global stock indices related to well-known periods of politico-economic volatility. We further uncover transitions in the El Niño-Southern Oscillation which coincide with periods of phase locking with the Pacific Decadal Oscillation. Finally, we provide for the first time an 'uncertainty-aware' framework which validates the hypothesis that ice-rafting events in the North Atlantic during the Holocene were synchronous with a weakened Asian summer monsoon.

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High-fidelity multimode fibre-based endoscopy for deep brain in vivo imaging

2018, Turtaev, Sergey, Leite, Ivo T., Altwegg-Boussac, Tristan, Pakan, Janelle M. P., Rochefort, Nathalie L., Čižmár, Tomáš

Progress in neuroscience relies on new techniques for investigating the complex dynamics of neuronal networks. An ongoing challenge is to achieve minimally invasive and high-resolution observations of neuronal activity in vivo inside deep brain areas. Recently introduced methods for holographic control of light propagation in complex media enable the use of a hair-thin multimode optical fibre as an ultranarrow imaging tool. Compared to endoscopes based on graded-index lenses or fibre bundles, this new approach offers a footprint reduction exceeding an order of magnitude, combined with a significant enhancement in resolution. We designed a compact and high-speed system for fluorescent imaging at the tip of a fibre, achieving a resolution of 1.18 ± 0.04 µm across a 50-µm field of view, yielding 7-kilopixel images at a rate of 3.5 frames/s. Furthermore, we demonstrate in vivo observations of cell bodies and processes of inhibitory neurons within deep layers of the visual cortex and hippocampus of anaesthetised mice. This study paves the way for modern microscopy to be applied deep inside tissues of living animal models while exerting a minimal impact on their structural and functional properties.

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Salt concentration and charging velocity determine ion charge storage mechanism in nanoporous supercapacitors

2018, Prehal, C., Koczwara, C., Amenitsch, H., Presser, V., Paris, O.

A fundamental understanding of ion charge storage in nanoporous electrodes is essential to improve the performance of supercapacitors or devices for capacitive desalination. Here, we employ in situ X-ray transmission measurements on activated carbon supercapacitors to study ion concentration changes during electrochemical operation. Whereas counter-ion adsorption was found to dominate at small electrolyte salt concentrations and slow cycling speed, ion replacement prevails for high molar concentrations and/or fast cycling. Chronoamperometry measurements reveal two distinct time regimes of ion concentration changes. In the first regime the supercapacitor is charged, and counter- and co-ion concentration changes align with ion replacement and partially co-ion expulsion. In the second regime, the electrode charge remains constant, but the total ion concentration increases. We conclude that the initial fast charge neutralization in nanoporous supercapacitor electrodes leads to a non-equilibrium ion configuration. The subsequent, charge-neutral equilibration slowly increases the total ion concentration towards counter-ion adsorption.

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When optimization for governing human-environment tipping elements is neither sustainable nor safe

2018, Barfuss, W., Donges, J.F., Lade, S.J., Kurths, J.

Optimizing economic welfare in environmental governance has been criticized for delivering short-term gains at the expense of long-term environmental degradation. Different from economic optimization, the concepts of sustainability and the more recent safe operating space have been used to derive policies in environmental governance. However, a formal comparison between these three policy paradigms is still missing, leaving policy makers uncertain which paradigm to apply. Here, we develop a better understanding of their interrelationships, using a stylized model of human-environment tipping elements. We find that no paradigm guarantees fulfilling requirements imposed by another paradigm and derive simple heuristics for the conditions under which these trade-offs occur. We show that the absence of such a master paradigm is of special relevance for governing real-world tipping systems such as climate, fisheries, and farming, which may reside in a parameter regime where economic optimization is neither sustainable nor safe.