Material Supplementary 4.DC1http://www.jimmunol.org/content/suppl/2010/06/16/jimmunol.090387

No abstract

Stringent control of inflammasome signaling pathway is important for maintaining immunological balance, yet the molecular mechanisms responsible for its tight regulation are still poorly understood. In this study, we found that the signaling pathway dependent on mitochondrial antiviral signaling protein (MAVS) was required for the optimal activation of apoptosis-associated specklike protein (ASC)–dependent inflammasome. In particular, TNFR-associated factor 3 was found to be a direct E3 ligase for ASC. Ubiquitination of ASC at Lys174 was critical for speck formation and inflammasome activation. Deficiency in MAVS or TNFR-associated factor 3 impaired ASC ubiquitination and cytosolic aggregates formation, resulting in reduced inflammasome response upon RNA virus infection. This study has identified a previously unrecognized role of MAVS in the regulation of inflammasome signaling and provided molecular insight into the mechanisms by which ubiquitination of ASC controls inflammasome activity through the formation of ASC specks.

Innate immunity to viruses involves receptors such as Retinoic Acid Induced Gene-1 (RIG-I), which senses viral RNA and triggers a signaling pathway involving the outer mitochondrial membrane protein mitochondrial antiviral signaling (MAVS). Recent work has identified that NLRX1, a member of another class of innate immune receptors, sequesters MAVS away from RIG-I and thereby prevents mitochondrial antiviral immunity. In this study, we demonstrate that the proteasome PSMA7 (α4) subunit associates with MAVS in vivo and in vitro. Expression of PSMA7 results in a potent inhibition of RIG-1 and MAVS-mediated IFN-β promoter activity; conversely, depletion of PSMA7 with small interference RNA enhances virus-induced type I IFN production, with consequent reduction of virus replication. Furthermore, a striking reduction in the abundance of endogenous MAVS with overexpressed PSMA7 was found and virus infection leads to transient increase in the endogenous PSMA7 protein level. Cumulatively, these results suggest that PSMA7 is a negative regulator of the MAVS-mediated innate immunity that probably serves to attenuate the establishment of an antiviral state during viral infection, highlighting the biological significance of PSMA7-MAVS association as an important cellular regulatory control.

Hash coding has been widely used in the approximate nearest neighbor search for large-scale image retrieval. Recently, many deep hashing methods have been proposed and shown largely improved performance over traditional featurelearning methods. Most of these methods examine the pairwise similarity on the semantic-level labels, where the pairwise similarity is generally defined in a hard-assignment way. That is, the pairwise similarity is '1' if they share no less than one class label and '0' if they do not share any. However, such similarity definition cannot reflect the similarity ranking for pairwise images that hold multiple labels. In this paper, an improved deep hashing method is proposed to enhance the ability of multi-label image retrieval. We introduce a pairwise quantified similarity calculated on the normalized semantic labels. Based on this, we divide the pairwise similarity into two situations -'hard similarity' and 'soft similarity', where cross-entropy loss and mean square error loss are adapted respectively for more robust feature learning and hash coding. Experiments on four popular datasets demonstrate that, the proposed method outperforms the competing methods and achieves the state-of-the-art performance in multi-label image retrieval.Index Terms-image retrieval, convolutional neural network, semantic label, pairwise similarity, deep hashing.

No abstract

Retinoic acid-inducible gene I (RIG-I) is an intracellular RNA virus sensor that induces type I interferon-mediated host-protective innate immunity against viral infection. Although cylindromatosis (CYLD) has been shown to negatively regulate innate antiviral response by removing K-63-linked polyubiquitin from RIG-I, the regulation of its expression and the underlying regulatory mechanisms are still incompletely understood. Here we show that RIG-I activity is regulated by inhibition of CYLD expression mediated by the microRNA miR-526a. We found that viral infection specifically upregulates miR-526a expression in macrophages via interferon regulatory factor (IRF)-dependent mechanisms. In turn, miR-526a positively regulates virus-triggered type I interferon (IFN-I) production, thus suppressing viral replication, the underlying mechanism of which is the enhancement of RIG-I K63-linked ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virusinduced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein, while ectopic miR526a expression inhibits the replication of EV71 virus. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and suggest a novel mechanism for the evasion of the innate immune response controlled by EV71. IMPORTANCERNA virus infection upregulates the expression of miR-526a in macrophages through IRF-dependent pathways. In turn, miR526a positively regulates virus-triggered type I IFN production and inhibits viral replication, the underlying mechanism of which is the enhancement of RIG-I K-63 ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein; cells with overexpressed miR-526a were highly resistant to EV71 infection. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and propose a novel mechanism for the evasion of the innate immune response controlled by EV71.

We study the local indistinguishability of mutually orthogonal product basis quantum states in the high-dimensional quantum system. In the quantum system of C d ⊗ C d , where d is odd, Zhang et al have constructed d 2 orthogonal product basis quantum states which are locally indistinguishable in [Phys. Rev. A. 90, 022313(2014)]. We find a subset contains with 6d − 9 orthogonal product states which are still locally indistinguishable. Then we generalize our method to arbitrary bipartite quantum system C m ⊗ C n . We present a small set with only 3(m + n) − 9 orthogonal product states and prove these states are LOCC indistinguishable. Even though these 3(m + n) − 9 product states are LOCC indistinguishable, they can be distinguished by separable measurements. This shows that separable operations are strictly stronger than the local operations and classical communication.