SUMO Modification Stabilizes Enterovirus 71 Polymerase 3D To Facilitate Viral Replication.

Accumulating evidence suggests that viruses hijack cellular proteins to circumvent the host immune system. Ubiquitination and SUMOylation are extensively studied posttranslational modifications (PTMs) that play critical roles in diverse biological processes. Cross talk between ubiquitination and SUMOylation of both host and viral proteins has been reported to result in distinct functional consequences. Enterovirus 71 (EV71), an RNA virus belonging to the family Picornaviridae, is a common cause of hand, foot, and mouth disease. Little is known concerning how host PTM systems interact with enteroviruses. Here, we demonstrate that the 3D protein, an RNA-dependent RNA polymerase (RdRp) of EV71, is modified by small ubiquitin-like modifier 1 (SUMO-1) both during infection and in vitro Residues K159 and L150/D151/L152 were responsible for 3D SUMOylation as determined by bioinformatics prediction combined with site-directed mutagenesis. Also, primer-dependent polymerase assays indicated that mutation of SUMOylation sites impaired 3D polymerase activity and virus replication. Moreover, 3D is ubiquitinated in a SUMO-dependent manner, and SUMOylation is crucial for 3D stability, which may be due to the interplay between the two PTMs. Importantly, increasing the level of SUMO-1 in EV71-infected cells augmented the SUMOylation and ubiquitination levels of 3D, leading to enhanced replication of EV71. These results together suggested that SUMO and ubiquitin cooperatively regulated EV71 infection, either by SUMO-ubiquitin hybrid chains or by ubiquitin conjugating to the exposed lysine residue through SUMOylation. Our study provides new insight into how a virus utilizes cellular pathways to facilitate its replication. IMPORTANCE: Infection with enterovirus 71 (EV71) often causes neurological diseases in children, and EV71 is responsible for the majority of fatalities. Based on a better understanding of interplay between virus and host cell, antiviral drugs against enteroviruses may be developed. As a dynamic cellular process of posttranslational modification, SUMOylation regulates global cellular protein localization, interaction, stability, and enzymatic activity. However, little is known concerning how SUMOylation directly influences virus replication by targeting viral polymerase. Here, we found that EV71 polymerase 3D was SUMOylated during EV71 infection and in vitro Moreover, the SUMOylation sites were determined, and in vitro polymerase assays indicated that mutations at SUMOylation sites could impair polymerase synthesis. Importantly, 3D is ubiquitinated in a SUMOylation-dependent manner that enhances the stability of the viral polymerase. Our findings indicate that the two modifications likely cooperatively enhance virus replication. Our study may offer a new therapeutic strategy against virus replication

Distribution of Spectral Lags in Gamma Ray Bursts

Using the data acquired in the Time To Spill (TTS) mode for long gamma-ray bursts (GRBs) collected by the Burst and Transient Source Experiment on board the Compton Gamma Ray Observatory (BATSE/CGRO), we have carefully measured spectral lags in time between the low (25-55 keV) and high (110-320 keV) energy bands of individual pulses contained in 64 multi-peak GRBs. We find that the temporal lead by higher-energy gamma-ray photons (i.e., positive lags) is the norm in this selected sample set of long GRBs. While relatively few in number, some pulses of several long GRBs do show negative lags. This distribution of spectral lags in long GRBs is in contrast to that in short GRBs. This apparent difference poses challenges and constraints on the physical mechanism(s) of producing long and short GRBs. The relation between the pulse peak count rates and the spectral lags is also examined. Observationally, there seems to be no clear evidence for systematic spectral lag-luminosity connection for pulses within a given long GRB.Comment: 20 pages, 4 figure

Simulation and forming mechanism analysis of multi-pass spinning process of deep cylinder parts

In this paper, the forming mechanism of 3103 aluminum alloy forming deep cylinder part under ten passes spinning is studied. The forming process of each step is simulated by finite element method. The distribution characteristics of equivalent stress field and strain field in forming were analyzed in detail. The influence of feed ratio on spinning force is obtained. By measuring the thickness and circularity of the final forming deep cylinder part, the final forming effect of multi-pass spinning is obtained

Global axisymmetric stability analysis for a composite system of two gravitationally coupled scale-free discs

In a composite system of gravitationally coupled stellar and gaseous discs, we perform linear stability analysis for axisymmetric coplanar perturbations using the two-fluid formalism. The background stellar and gaseous discs are taken to be scale-free with all physical variables varying as powers of cylindrical radius $r$ with compatible exponents. The unstable modes set in as neutral modes or stationary perturbation configurations with angular frequency $\omega=0$.Comment: 7 pages using AAS styl

Simulation and forming mechanism analysis of multi-pass spinning process of deep cylinder parts

In this paper, the forming mechanism of 3103 aluminum alloy forming deep cylinder part under ten passes spinning is studied. The forming process of each step is simulated by finite element method. The distribution characteristics of equivalent stress field and strain field in forming were analyzed in detail. The influence of feed ratio on spinning force is obtained. By measuring the thickness and circularity of the final forming deep cylinder part, the final forming effect of multi-pass spinning is obtained

Movement analysis of lower limb during backward walking with unstable intervention

Backward walking (BW), an emerging rehabilitative and training modality, was integrated with unstable sole construction with various hardness levels to analyze the kinematic and kinetic characteristics of the lower extremities. Eighteen participants volunteered to participate in the test. They performed walking tests under three conditions: 1) BW with normal shoes (NBW); 2) BW with unstable shoes with soft unstable elements (UBW-S); 3) BW with unstable shoes with hard unstable elements (UBW-H). The results show increased hip and ankle flexion and increased knee flexion-extension extent in the stance phase during BW with unstable shoes. The motor control mechanism of unstable BW enhanced the rehabilitation of lower limb deficiency. The attached unstable elements (UBW-S and UBW-H) induced local perturbation to stimulate proprioceptive ability and the neuromuscular system, changing the plantar loading distribution in a certain region. Future study should concentrate on the possible rehabilitative effect of unstable BW on neurological disorders and motor system deficiency

The Euler Number of Bloch States Manifold and the Quantum Phases in Gapped Fermionic Systems

We propose a topological Euler number to characterize nontrivial topological phases of gapped fermionic systems, which originates from the Gauss-Bonnet theorem on the Riemannian structure of Bloch states established by the real part of the quantum geometric tensor in momentum space. Meanwhile, the imaginary part of the geometric tensor corresponds to the Berry curvature which leads to the Chern number characterization. We discuss the topological numbers induced by the geometric tensor analytically in a general two-band model. As an example, we show that the zero-temperature phase diagram of a transverse field XY spin chain can be distinguished by the Euler characteristic number of the Bloch states manifold in a (1+1)-dimensional Bloch momentum space

Effect of process parameters on forming quality of Mg alloy(MZ21)-Al alloy(7075) composite pipe

This paper mainly studies the effect of process parameters on the deformation mechanism of MZ21 magnesium alloy and 7075 aluminum alloy bimetal composite pipe in spinning process.The two parameters of spinning, the rotary wheel feed ratio and the double tube wall thinning rate were selected to study, and the influence rule of each process parameter on the forming quality of composite tube was simulated by Simufact software. Under different thinning rates of the total wall thickness, the coordinated deformation and the rebound law of the wall thickness of the composite pipe are obtained. The results provide a certain reference for the preparation of magnesium aluminum composite pipe and the selection of reasonable spinning parameters

In-shoe plantar prressure measurement and analysis system based on fabric pressure sensing array

Author name used in this publication: David Dagan Feng2009-2010 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe