Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.

BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection

Research on temperature field and microstructure distribution of cross wedge rolling based on square billet

With the deepening and popularization of the cross wedge rolling process, the requirements for the cross wedge rolling blanks have become wider and wider. Relying only on the traditional round blanks will restrict the promotion of the cross wedge rolling process to a certain extent. The emergence of the square billet is a breakthrough in the selection of raw materials, but related research is relatively scarce. Therefore, this paper conducts a finite element simulation for the rolling process of the square billet. Four characteristic points are taken on the longitudinal section of the billet to track the temperature change. Research on the law of field changes. At the same time, the change of the grain size and dynamic recrystallization percentage of the rolled piece during the rolling process is studied. Simulation and experiment are combined to obtain the change rule of the average grain size of the characteristic points of the longitudinal section of the billet with time

Research on temperature field and microstructure distribution of cross wedge rolling based on square billet

With the deepening and popularization of the cross wedge rolling process, the requirements for the cross wedge rolling blanks have become wider and wider. Relying only on the traditional round blanks will restrict the promotion of the cross wedge rolling process to a certain extent. The emergence of the square billet is a breakthrough in the selection of raw materials, but related research is relatively scarce. Therefore, this paper conducts a finite element simulation for the rolling process of the square billet. Four characteristic points are taken on the longitudinal section of the billet to track the temperature change. Research on the law of field changes. At the same time, the change of the grain size and dynamic recrystallization percentage of the rolled piece during the rolling process is studied. Simulation and experiment are combined to obtain the change rule of the average grain size of the characteristic points of the longitudinal section of the billet with time

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

Performance-based analysis of large steel truss roof structure in fire

Due to the fast developments of large-space multi-functional architectures, large-span steel structures have been widely used in recent years. Therefore, the fire-resistance design of this kind of structures has attracted more attentions. Since traditional ISO834 standard fire curve is not suitable for large space structures, performance-based fire resistance design method is required. This paper presents the comprehensive case studies on the fire performance of a large space exhibition centre in Shanxi province, China under real fire scenarios including heating and cooling phases. The non-uniform fire temperature fields of the large space exhibition centre for the designed fire scenarios have been generated by using Fire Dynamic Simulator (FDS). A finite element (FE) model has been developed using FE software ANSYS for modelling the structural behaviour of the exhibition centre under different fire scenarios. Based on the results generated in this research some recommendations for the fire resistance design of large space steel truss structures have been proposed

A unique distant submillimeter galaxy with an X-ray-obscured radio-luminous active galactic nucleus

We present a multiwavelength study of an atypical submillimeter galaxy in the GOODS-North field, with the aim to understand its physical properties of stellar and dust emission, as well as the central AGN activity. Although it is shown that the source is likely an extremely dusty galaxy at high redshift, its exact position of submillimeter emission is unknown. With the new NOEMA interferometric imaging, we confirm that the source is a unique dusty galaxy. It has no obvious counterpart in the optical and even NIR images observed with HST at lambda~<1.4um. Photometric-redshift analyses from both stellar and dust SED suggest it to likely be at z~>4, though a lower redshift at z~>3.1 cannot be fully ruled out (at 90% confidence interval). Explaining its unusual optical-to-NIR properties requires an old stellar population (~0.67 Gyr), coexisting with a very dusty ongoing starburst component. The latter is contributing to the FIR emission, with its rest-frame UV and optical light being largely obscured along our line of sight. If the observed fluxes at the rest-frame optical/NIR wavelengths were mainly contributed by old stars, a total stellar mass of ~3.5x10^11Msun would be obtained. An X-ray spectral analysis suggests that this galaxy harbors a heavily obscured AGN with N_H=3.3x10^23 cm^-2 and an intrinsic 2-10 keV luminosity of L_X~2.6x10^44 erg/s, which places this object among distant type 2 quasars. The radio emission of the source is extremely bright, which is an order of magnitude higher than the star-formation-powered emission, making it one of the most distant radio-luminous dusty galaxies. The combined characteristics of the galaxy suggest that the source appears to have been caught in a rare but critical transition stage in the evolution of submillimeter galaxies, where we are witnessing the birth of a young AGN and possibly the earliest stage of its jet formation and feedback.Comment: 13 pages in printer format, 10 figures, 1 table, accepted for publication in the A&

Exact solution for infinitely strongly interacting Fermi gases in tight waveguides

We present an exact analytical solution of the fundamental systems of quasi-one-dimensional spin-1/2 fermions with infinite repulsion for arbitrary confining potential. The eigenfunctions are constructed by the combination of Gireardeau's hard-core contacting boundary condition and group theoretical method which guarantees the obtained states to be simultaneously the eigenstates of $S$ and $S_z$ and fulfill the antisymmetry under odd permutation. We show that the total ground-state density profile behaves like the polarized noninteracting fermions, whereas the spin-dependent densities display different properties for different spin configurations. We also discuss the splitting of the ground states for large but finite repulsion.Comment: 4 pages, 3 figures, version accepted for publication in Phys. Rev. Let

Feasibility analysis of short process flexible precision forming of aluminum alloy automobile hollow shaft

Aiming at the large weight of automobile steel solid shaft, this paper innovates aluminum alloy hollow shaft. The rolling process of automobile hollow shaft was simulated by using the short process flexible precision forming process and the Finite Element Method (FEM). The variation of the shape and inner hole of the rolled piece, the roundness of the outer surface and the wall thickness during the rolling process were analyzed. The numerical results verify the feasibility of rolling aluminum alloy automobile hollow shaft by this process, and provide a theoretical basis for forming aluminum alloy automobile hollow shaft in China