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The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) plays a critical role in antiviral immunity and autoimmunity. The activity and stability of cGAS are fine-tuned by post-translational modifications. Here, we show that ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1) catalyzes the mono-ISGylation and induces the oligomerization of cGAS, thereby promoting antiviral immunity and autoimmunity. Knockdown or knockout of ARIH1 significantly inhibits herpes simplex virus 1 (HSV-1)- or cytoplasmic DNA-induced expression of type I interferons (IFNs) and proinflammatory cytokines. Consistently, tamoxifen-treated ER-Cre;Arih1fl/fl mice and Lyz2-Cre; Arih1fl/fl mice are hypersensitive to HSV-1 infection compared with the controls. In addition, deletion of ARIH1 in myeloid cells alleviates the autoimmune phenotypes and completely rescues the autoimmune lethality caused by TREX1 deficiency. Mechanistically, HSV-1- or cytosolic DNA-induced oligomerization and activation of cGAS are potentiated by ISGylation at its K187 residue, which is catalyzed by ARIH1. Our findings thus reveal an important role of ARIH1 in innate antiviral and autoimmune responses and provide insight into the post-translational regulation of cGAS.

MAVS and MITA are essential adaptor proteins mediating innate antiviral immune responses against RNA and DNA viruses, respectively. Here we show that RNF115 plays dual roles in response to RNA or DNA virus infections by catalyzing distinct types of ubiquitination of MAVS and MITA at different phases of viral infection. RNF115 constitutively interacts with and induces K48-linked ubiquitination and proteasomal degradation of homeostatic MAVS in uninfected cells, whereas associates with and catalyzes K63-linked ubiquitination of MITA after HSV-1 infection. Consistently, the protein levels of MAVS are substantially increased in Rnf115−/− organs or cells without viral infection, and HSV-1-induced aggregation of MITA is impaired in Rnf115−/− cells compared to the wild-type counterparts. Consequently, the Rnf115−/− mice exhibit hypo- and hyper-sensitivity to EMCV and HSV-1 infection, respectively. These findings highlight dual regulation of cellular antiviral responses by RNF115-mediated ubiquitination of MAVS and MITA and contribute to our understanding of innate immune signaling., MAVS and MITA are adapter proteins that play distinct roles in the context of the host response to RNA and DNA viruses, respectively. Here the authors implicate RNF115 in dual temporal and spatial mechanisms of interacting and catalyzing distinct ubiquitination of MAVS and MITA to modulate RNA and DNA antiviral immune responses.

The subcellular localization and intracellular trafficking of Toll-like receptors (TLRs) critically regulate TLRs-mediated antimicrobial immunity and autoimmunity. Here, it is demonstrated that the E3 ubiquitin ligase RNF115 inhibits the post-endoplasmic reticulum (ER) trafficking of TLRs and TLRs-mediated immune responses by catalyzing ubiquitination of the small GTPases RAB1A and RAB13. It is shown that the 14-3-3 chaperones bind to AKT1-phosphorylated RNF115 and facilitate RNF115 localizing on the ER and the Golgi apparatus. RNF115 interacts with RAB1A and RAB13 and catalyzes K11-linked ubiquitination on the Lys49 and Lys61 residues of RAB1A and on the Lys46 and Lys58 residues of RAB13, respectively. Such a modification impairs the recruitment of guanosine diphosphate (GDP) dissociation inhibitor 1 (GDI1) to RAB1A and RAB13, a prerequisite for the reactivation of RAB proteins. Consistently, knockdown of RAB1A and RAB13 in Rnf115

Order reconstruction in an inverse twisted nematic (ITN) liquid crystal cell with an applied electric field is investigated based on Landau–de Gennes theory and the two-dimensional finite-difference iterative method. Twice eigenvalue exchange in three-axis layer configuration, thrice eigenvalue exchange in four-axis layer configuration, and negative order parameter uniaxial twisted state exist in this cell, which can be described by the order parameter tensor Q in equilibrium state. The twice eigenvalue exchange also has two degenerate configurations with reduced electric field E from 0.8 to 2.8 in 10ξ cell (ξ is the biaxial correlation length). Moreover, two critical cell gaps d c ⁎ ⁎ = 7 ξ and d c ⁎ = 12 ξ are included in the study of the ITN cell. When d ≤ d c ⁎ ⁎ , only the eigenvalue change state exists. When d ≥ d c ⁎ , only a positive order parameter uniaxial twisted state exists near the threshold electric field. When d c ⁎ ⁎ d d c ⁎ , a negative order parameter uniaxial twisted state exists near the threshold electric field. Comparison of the eigenvalue exchange solutions of different cell gaps of 5ξ, 10ξ, and 20ξ shows that smaller cell gap can inhibit the complexity of the eigenvalue exchange solution and reduce the number of axis layers. This research provides a theoretical basis for the change of multi-axis layer defect and promotes the concept of eigenvalue exchange.

Liquid-crystal display technology is ubiquitous, but these materials can also be used to make electrically tunable components for optics and photonics. The authors demonstrate voltage control of the wavelength of flexoelectric domains in a transmissive diffraction grating, which enables dynamic light steering. They prove that the mechanism of pattern onset differs from that of switching between flexodomain states, and they explain the surprising finding that the response to increasing voltage is much slower than that to decreasing voltage.

STING (also known as MITA) is critical for host defence against viruses and the activity of STING is regulated by ubiquitination. However, the deubiquitination of STING is not fully understood. Here, we show that ubiquitin-specific protease 13 (USP13) is a STING-interacting protein that catalyses deubiquitination of STING. Knockdown or knockout of USP13 potentiates activation of IRF3 and NF-κB and expression of downstream genes after HSV-1 infection or transfection of DNA ligands. USP13 deficiency results in impaired replication of HSV-1. Consistently, USP13 deficient mice are more resistant than wild-type littermates to lethal HSV-1 infection. Mechanistically, USP13 deconjugates polyubiquitin chains from STING and prevents the recruitment of TBK1 to the signalling complex, thereby negatively regulating cellular antiviral responses. Our study thus uncovers a function of USP13 in innate antiviral immunity and provides insight into the regulation of innate immunity., The cGAS-STING pathway is a DNA sensing mechanism that enables response to viral infection by inducing type 1 interferon expression. Here the authors show a mechanism by which the deubiquitinating enzyme USP13 prevents STING from enabling response to virus.

A nematic liquid crystal slab composed of N molecular layers is investigated using a simple cubic lattice model, based upon the molecular pair potential which is spatially anisotropic and dependent on elastic constants of liquid crystals. A perfect nematic order is assumed in the theoretical treatment, which means the orientation of the molecular long axis coincides with the director of liquid crystal and the total free energy equals to the total interaction energy. We present a modified Gruhn–Hess model, which is relative to the splay-bend elastic constant K 13 . Furthermore, we have studied the free nematic interfacial behavior (intrinsic anchoring) by this model in the assumption of the perfect nematic order. We find that the preferred orientation at the free interface and the intrinsic anchoring strength change with the value of modification, and that the director profile can be determined by the competition of the intrinsic anchoring with external forces present in the system. Also we simulate the intrinsic anchoring at different temperatures using Monte Carlo method and the simulation results show that the intrinsic anchoring favors planar alignment and the free interface is more disordered than the bulk.

An overview of the mathematical structure of the three-dimensional (3D) Ising model is given, from the viewpoints of topologic, algebraic and geometric aspects. By analyzing the relations among transfer matrices of the 3D Ising model, Reidemeister moves in the knot theory, Yang-Baxter and tetrahedron equations, the following facts are illustrated for the 3D Ising model: 1) The complexified quaternion basis constructed for the 3D Ising model represents naturally the rotation in a (3 + 1) - dimensional space-time, as a relativistic quantum statistical mechanics model, which is consistent with the 4-fold integrand of the partition function by taking the time average. 2) A unitary transformation with a matrix being a spin representation in 2^(nlo)-space corresponds to a rotation in 2nlo-space, which serves to smooth all the crossings in the transfer matrices and contributes as the non-trivial topologic part of the partition function of the 3D Ising model. 3) A tetrahedron relation would ensure the commutativity of the transfer matrices and the integrability of the 3D Ising model, and its existence is guaranteed also by the Jordan algebra and the Jordan-von Neumann-Wigner procedures. 4) The unitary transformation for smoothing the crossings in the transfer matrices changes the wave functions by complex phases {\Phi}x, {\Phi}y, and {\Phi}z. The relation with quantum field and gauge theories, physical significance of weight factors are discussed in details. The conjectured exact solution is compared with numerical results, and singularities at/near infinite temperature are inspected. The analyticity in {\beta} = 1/(kB T) of both the hard-core and Ising models has been proved for {\beta} > 0, not for {\beta} = 0. Thus the high-temperature series cannot serve as a standard for judging a putative exact solution of the 3D Ising model., Comment: 53 pages; 0 figures

High‐field magnetization behavior of (Nd,Pr)2Co14B compounds at T=4.2 K has been studied through applying high fields up to 35 T. Taking the misalignment of grains in the samples into account, the anisotropy constants K1, K2, and K3 were determined by means of fitting the hard magnetization curves. Within the framework of the theory developed by Asti and Bolzoni, FOMP phenomena are predicted to occur in the whole system (0

Studies of bulk MgCu2-type rare-earth iron compounds with Laves phase are reviewed. The relationship between magnetostriction and structural distortion and the consequent crystallographic method for measuring magnetostriction are introduced at first. Then we review recent progress in understanding bulk magnetostrictive Laves phase materials, especially the magnetostriction and the minimization of the anisotropy of the light rare-earth Pr- and Sm-based compounds. Finally, a summary and outlook for this kind of compounds are presented.