4,483 research outputs found

    p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates

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    Glutamine synthetase (GS) plays an essential role in metabolism by catalyzing the synthesis of glutamine from glutamate and ammonia. Our recent study showed that CRBN, a direct protein target for the teratogenic and antitumor activities of immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide, recognizes an acetyl degron of GS, resulting in ubiquitylation and degradation of GS in response to glutamine. Here, we report that valosin-containing protein (VCP)/p97 promotes the degradation of ubiquitylated GS, resulting in its accumulation in cells with compromised p97 function. Notably, p97 is also required for the degradation of all four known CRBN neo-substrates [Ikaros family zinc finger proteins 1 (IKZF1) and 3 (IKZF3), casein kinase 1α (CK1α), and the translation termination factor GSPT1] whose ubiquitylation is induced by immunomodulatory drugs. Together, these data point to an unexpectedly intimate relationship between the E3 ubiquitin ligase CRL4^(CRBN) and p97 pathways

    Molecular dynamics study of the fragmentation of silicon doped fullerenes

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    Tight binding molecular dynamics simulations, with a non orthogonal basis set, are performed to study the fragmentation of carbon fullerenes doped with up to six silicon atoms. Both substitutional and adsorbed cases are considered. The fragmentation process is simulated starting from the equilibrium configuration in each case and imposing a high initial temperature to the atoms. Kinetic energy quickly converts into potential energy, so that the system oscillates for some picoseconds and eventually breaks up. The most probable first event for substituted fullerenes is the ejection of a C2 molecule, another very frequent event being that one Si atom goes to an adsorbed position. Adsorbed Si clusters tend to desorb as a whole when they have four or more atoms, while the smaller ones tend to dissociate and sometimes interchange positions with the C atoms. These results are compared with experimental information from mass abundance spectroscopy and the products of photofragmentation.Comment: Seven two-column pages, six postscript figures. To be published in Physical Review

    Nonlinear and conventional biosignal analyses applied to tilt table test for evaluating autonomic nervous system and autoregulation

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    Copyright © Tseng et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.Tilt table test (TTT) is a standard examination for patients with suspected autonomic nervous system (ANS) dysfunction or uncertain causes of syncope. Currently, the analytical method based on blood pressure (BP) or heart rate (HR) changes during the TTT is linear but normal physiological modulations of BP and HR are thought to be predominately nonlinear. Therefore, this study consists of two parts: the first part is analyzing the HR during TTT which is compared to three methods to distinguish normal controls and subjects with ANS dysfunction. The first method is power spectrum density (PSD), while the second method is detrended fluctuation analysis (DFA), and the third method is multiscale entropy (MSE) to calculate the complexity of system. The second part of the study is to analyze BP and cerebral blood flow velocity (CBFV) changes during TTT. Two measures were used to compare the results, namely correlation coefficient analysis (nMxa) and MSE. The first part of this study has concluded that the ratio of the low frequency power to total power of PSD, and MSE methods are better than DFA to distinguish the difference between normal controls and patients groups. While in the second part, the nMxa of the three stages moving average window is better than the nMxa with all three stages together. Furthermore the analysis of BP data using MSE is better than CBFV data.The Stroke Center and Department of Neurology, National Taiwan University, National Science Council in Taiwan, and the Center for Dynamical Biomarkers and Translational Medicine, National Central University, which is sponsored by National Science Council and Min-Sheng General Hospital Taoyuan

    SnTox3 Acts in Effector Triggered Susceptibility to Induce Disease on Wheat Carrying the Snn3 Gene

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    The necrotrophic fungus Stagonospora nodorum produces multiple proteinaceous host-selective toxins (HSTs) which act in effector triggered susceptibility. Here, we report the molecular cloning and functional characterization of the SnTox3-encoding gene, designated SnTox3, as well as the initial characterization of the SnTox3 protein. SnTox3 is a 693 bp intron-free gene with little obvious homology to other known genes. The predicted immature SnTox3 protein is 25.8 kDa in size. A 20 amino acid signal sequence as well as a possible pro sequence are predicted. Six cysteine residues are predicted to form disulfide bonds and are shown to be important for SnTox3 activity. Using heterologous expression in Pichia pastoris and transformation into an avirulent S. nodorum isolate, we show that SnTox3 encodes the SnTox3 protein and that SnTox3 interacts with the wheat susceptibility gene Snn3. In addition, the avirulent S. nodorum isolate transformed with SnTox3 was virulent on host lines expressing the Snn3 gene. SnTox3-disrupted mutants were deficient in the production of SnTox3 and avirulent on the Snn3 differential wheat line BG220. An analysis of genetic diversity revealed that SnTox3 is present in 60.1% of a worldwide collection of 923 isolates and occurs as eleven nucleotide haplotypes resulting in four amino acid haplotypes. The cloning of SnTox3 provides a fundamental tool for the investigation of the S. nodorum-wheat interaction, as well as vital information for the general characterization of necrotroph-plant interactions.This work was supported by USDA-ARS CRIS projects 5442-22000-043-00D and 5442-22000-030-00D

    Integral equation method for the electromagnetic wave propagation in stratified anisotropic dielectric-magnetic materials

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    We investigate the propagation of electromagnetic waves in stratified anisotropic dielectric-magnetic materials using the integral equation method (IEM). Based on the superposition principle, we use Hertz vector formulations of radiated fields to study the interaction of wave with matter. We derive in a new way the dispersion relation, Snell's law and reflection/transmission coefficients by self-consistent analyses. Moreover, we find two new forms of the generalized extinction theorem. Applying the IEM, we investigate the wave propagation through a slab and disclose the underlying physics which are further verified by numerical simulations. The results lead to a unified framework of the IEM for the propagation of wave incident either from a medium or vacuum in stratified dielectric-magnetic materials.Comment: 14pages, 3figure

    Leveraging Optical Communication Fiber and AI for Distributed Water Pipe Leak Detection

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    Detecting leaks in water networks is a costly challenge. This article introduces a practical solution: the integration of optical network with water networks for efficient leak detection. Our approach uses a fiber-optic cable to measure vibrations, enabling accurate leak identification and localization by an intelligent algorithm. We also propose a method to access leak severity for prioritized repairs. Our solution detects even small leaks with flow rates as low as 0.027 L/s. It offers a cost-effective way to improve leak detection, enhance water management, and increase operational efficiency.Comment: Accepte

    Single- and multi-walled carbon nanotubes viewed as elastic tubes with Young's moduli dependent on layer number

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    The complete energy expression of a deformed single-walled carbon nanotube (SWNT) is derived in the continuum limit from the local density approximation model proposed by Lenosky {\it et al.} \lbrack Nature (London) {\bf 355}, 333 (1992)\rbrack and shows to be content with the classic shell theory by which the Young's modulus, the Poisson ratio and the effective wall thickness of SWNTs are obtained as Y=4.70Y=4.70TPa, Îœ=0.34\nu=0.34, h=0.75A˚h=0.75{\rm \AA}, respectively. The elasticity of a multi-walled carbon nanotube (MWNT) is investigated as the combination of the above SWNTs of layer distance d=3.4A˚d=3.4 {\rm \AA} and the Young's modulus of the MWNT is found to be an apparent function of the number of layers, NN, varying from 4.70TPa to 1.04TPa for N=1 to ∞\infty.Comment: 4 pages, 1 figur

    Impurity effect on weak anti-localization in the topological insulator Bi2Te3

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    We study weak anti-localization (WAL) effect in topological insulator Bi2Te3 thin films at low temperatures. Two-dimensional WAL effect associated with surface carriers is revealed in the tilted magnetic field dependence of magneto-conductance. Our data demonstrates that the observed WAL is robust against deposition of non-magnetic Au impurities on the surface of the thin films. But it is quenched by deposition of magnetic Fe impurities which destroy the pi Berry's phase of the topological surface states. The magneto-conductance data of a 5 nm Bi2Te3 film suggests that a crossover from symplectic to unitary classes is observed with the deposition of Fe impurities.Comment: 4 pages, 3 figures. Corresponding author email address: [email protected]
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