By exploiting novel transport phenomena such as ion selectivity at the nanoscale, it has been shown that nanochannel systems can exhibit electrically controllable conductance, suggesting their potential use in neuromorphic devices. However, several critical features of biological synapses, particularly their conductance modulation, which is both memorable and gradual, have rarely been reported in these types of systems due to the fast flow property of typical inorganic electrolytes. In this work, we demonstrate that electrically manipulating the nanochannel conductance can result in nonvolatile conductance tuning capable of mimicking the analog behavior of synapses by introducing a room-temperature ionic liquid (IL) and a KCl solution into the two ends of a nanochannel system. The gradual conductance-tuning mechanism is identified through fluorescence measurements as the voltage-induced movement of the interface between the immiscible IL and KCl solution, while the successful memorization of the conductance tuning is ascribed to the large viscosity of the IL. We applied a nanochannel-based synapse to a handwritten digit-recognition task, reaching an accuracy of 94%. These promising results provide important guidance for the future design of nanochannel-based neuromorphic devices and the manipulation of nanochannel transport for computing.

Epithelial tissues covering the external and internal surface of a body are constantly under physical, chemical or biological assaults. To protect the epithelial tissues and maintain their homeostasis, multiple layers of immune defense mechanisms are required. Besides the epithelial tissue-resident immune cells that provide the first line of defense, circulating immune cells are also recruited into the local tissues in response to challenges. Chemokines and chemokine receptors regulate tissue-specific migration, maintenance and functions of immune cells. Among them, chemokine receptor CCR10 and its ligands chemokines CCL27 and CCL28 are uniquely involved in the epithelial immunity. CCL27 is expressed predominantly in the skin by keratinocytes while CCL28 is expressed by epithelial cells of various mucosal tissues. CCR10 is expressed by various subsets of innate-like T cells that are programmed to localize to the skin during their developmental processes in the thymus. Circulating T cells might be imprinted by skin-associated antigen-presenting cells to express CCR10 for their recruitment to the skin during the local immune response. On the other hand, IgA antibody-producing B cells generated in mucosa-associated lymphoid tissues express CCR10 for their migration and maintenance at mucosal sites. Increasing evidence also found that CCR10/ligands are involved in regulation of other immune cells in epithelial immunity and are frequently exploited by epithelium-localizing or -originated cancer cells for their survival, proliferation and evasion from immune surveillance. Herein, we will review current knowledge on roles of CCR10/ligands in regulation of epithelial immunity and diseases and speculate on related important questions worth further investigation.

In higher eukaryotes, one of the two arginyl-tRNA synthetases (ArgRSs) has evolved to have an extended N-terminal domain that plays a crucial role in protein synthesis and cell growth and in integration into the multisynthetase complex (MSC). Here, we report a crystal structure of the MSC subcomplex comprising ArgRS, glutaminyl-tRNA synthetase (GlnRS), and the auxiliary factor aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1)/p43. In this complex, the N-terminal domain of ArgRS forms a long coiled-coil structure with the N-terminal helix of AIMP1 and anchors the C-terminal core of GlnRS, thereby playing a central role in assembly of the three components. Mutation of AIMP1 destabilized the N-terminal helix of ArgRS and abrogated its catalytic activity. Mutation of the N-terminal helix of ArgRS liberated GlnRS, which is known to control cell death. This ternary complex was further anchored to AIMP2/p38 through interaction with AIMP1. These findings demonstrate the importance of interactions between the N-terminal domains of ArgRS and AIMP1 for the catalytic and noncatalytic activities of ArgRS and for the assembly of the higher-order MSC protein complex.arginyl-tRNA synthetase | multisynthetase complex | crystal structure | AIMP1 | glutaminyl-tRNA synthetase

Metastasis is one of the main causes of death in patients with colorectal cancer (CRC). Brg-1 is a central component of the SWItch/Sucrose NonFermentable chromatin-remodeling complex, which features a bromodomain and helicase/ATPase activity. The gene encoding Brg-1 is frequently mutated or silenced in human cancers. Several reports have proposed Brg-1 as a tumor suppressor; however, little is known about its role in oncogenesis and metastasis. Here we demonstrated that decreased Brg-1 regulates a novel miR-550a-5p/RNF43/Wnt/β-catenin signaling pathway, to promote CRC metastasis in vitro and in vivo. In particular, we used high-throughput RNA-sequencing analysis to show that Brg-1 negatively regulates miR-550a-5p in CRC cells. We further found that Brg-1 inhibits the transcriptional activity of miR-550a-5p promoter, and that decreased Brg-1 expression increased miR-550a-5p expression. We also identified ring finger 43 (RNF43), an inhibitor of Wnt/β-catenin signaling, as a target of miR-550a-5p. Knockdown of Brg-1 by small interfering RNA led to decreased RNF43 expression, increased Wnt signaling and increased CRC cell migration and invasion. This novel pathway defines a new function for Brg-1 and provides potential targets for the treatment of Brg-1 mutant and loss-of-function tumors.