Lysyl-tRNA synthetase (KRS) can be released from cancer cells to cause inflammation, but the mechanism of KRS secretion is unknown. Kim et al. demonstrate that KRS is cleaved by caspase-8, which exposes a binding motif for syntenin and facilitates the secretion of KRS in exosomes.

Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 (LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine-binding. The phosphorylated LARS1 showed decreased leucine-binding, which may inhibit protein synthesis and help save energy. Leucine, not used to anabolic process, may be available to catabolic pathway for energy generation. The LARS1-mediated changes in leucine utilization might help support cell survival deprived of glucose. Thus, dependent on the availability of glucose, LARS1 may help regulate whether leucine is used for protein synthesis or energy production.

In recent years, drones have been widely used in many areas such as farming, movie making, surveillance and delivery. So, there is a need to protect these drones against security attacks including hijacking, spying and theft of stored data through the utilization of security mechanisms. Cryptographic keys are needed to operate these security mechanisms, and they must be generated by using random number generators which create unpredictable and non-regenerable random numbers. However, existing random number generators used in drones are not tailored for drones specifically as they use random sources generated on a desktop, not a drone. Recently, random number generators utilizing sensors in mobile phones and IoT (Internet of Things) devices have been studied, but are not appropriate for drones. In this paper, considering that drone sensors must be applied to flight and stationary modes, we proposed a drone specific random number generator called DroneRNG and implemented it. Then, we showed that our DroneRNG passed all of the NIST randomization tests and possesses better statistical properties and unpredictability than random number generators that are currently used in drones.

BackgroundThe generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands of Toll-like receptors (TLRs) have been suggested to activate adaptive immune responses by modulating the function of antigen-presenting cells (APCs). Despite their therapeutic potential, the development of TLR ligands for immunotherapy is often hampered due to rapid systemic toxicity. Regarding the safety concerns of currently available TLR ligands, finding a new TLR agonist with potent efficacy and safety is needed.MethodsA unique structural domain (UNE-C1) was identified as a novel TLR2/6 in the catalytic region of human cysteinyl-tRNA synthetase 1 (CARS1) using comprehensive approaches, including RNA sequencing, the human embryonic kidney (HEK)-TLR Blue system, pull-down, and ELISA. The potency of its immunoadjuvant properties was analyzed by assessing antigen-specific antibody and CTL responses. In addition, the efficacy of tumor growth inhibition and the presence of the tumor-infiltrating leukocytes were evaluated using E.G7-OVA and TC-1 mouse models. The combined effect of UNE-C1 with an immune checkpoint inhibitor, anti-CTLA-4 antibody, was also evaluated in vivo. The safety of UNE-C1 immunization was determined by monitoring splenomegaly and cytokine production in the blood.ResultsHere, we report that CARS1 can be secreted from cancer cells to activate immune responses via specific interactions with TLR2/6 of APCs. A unique domain (UNE-C1) inserted into the catalytic region of CARS1 was determined to activate dendritic cells, leading to the stimulation of robust humoral and cellular immune responses in vivo. UNE-C1 also showed synergistic efficacy with cancer antigens and checkpoint inhibitors against different cancer models in vivo. Further, the safety assessment of UNE-C1 showed lower systemic cytokine levels than other known TLR agonists.ConclusionsWe identified the endogenous TLR2/6 activating domain from human cysteinyl-tRNA synthetase CARS1. This novel TLR2/6 ligand showed potent immune-stimulating activity with little toxicity. Thus, the UNE-C1 domain can be developed as an effective immunoadjuvant with checkpoint inhibitors or cancer antigens to boost antitumor immunity.