The RNA-binding protein PKR serves as a crucial antiviral innate immune factor that globally suppresses translation by sensing viral double-stranded RNA (dsRNA) and by phosphorylating the translation ...initiation factor eIF2α. Recent findings have unveiled that single-stranded RNAs (ssRNAs), including in vitro transcribed (IVT) mRNA, can also bind to and activate PKR. However, the precise mechanism underlying PKR activation by ssRNAs, remains incompletely understood. Here, we developed a NanoLuc Binary Technology (NanoBiT)-based in vitro PKR dimerization assay to assess the impact of ssRNAs on PKR dimerization. Our findings demonstrate that, akin to double-stranded polyinosinic:polycytidylic acid (polyIC), an encephalomyocarditis virus (EMCV) RNA, as well as NanoLuc luciferase (Nluc) mRNA, can induce PKR dimerization. Conversely, homopolymeric RNA lacking secondary structure fails to promote PKR dimerization, underscoring the significance of secondary structure in this process. Furthermore, adenovirus VA RNA 1, another ssRNA, impedes PKR dimerization by competing with Nluc mRNA. Additionally, we observed structured ssRNAs capable of forming G-quadruplexes induce PKR dimerization. Collectively, our results indicate that ssRNAs have the ability to either induce or inhibit PKR dimerization, thus representing potential targets for the development of antiviral and anti-inflammatory agents.
•A class of ssRNAs with secondary structure induces PKR dimerization.•ssRNAs lacking secondary structure minimally affect dimerization.•ssRNA of adenovirus VA RNA 1 impedes PKR dimerization.•m1Ψ modification prevents ssRNA from inducing PKR dimerization.
The regulation of mRNA deadenylation constitutes a pivotal mechanism of the post-transcriptional control of gene expression. Here we show that the antiproliferative protein Tob, a component of the ...Caf1-Ccr4 deadenylase complex, is involved in regulating the expression of the proto-oncogene c-myc. The c-myc mRNA contains cis elements (CPEs) in its 3'-untranslated region (3'-UTR), which are recognized by the cytoplasmic polyadenylation element-binding protein (CPEB). CPEB recruits Caf1 deadenylase through interaction with Tob to form a ternary complex, CPEB-Tob-Caf1, and negatively regulates the expression of c-myc by accelerating the deadenylation and decay of its mRNA. In quiescent cells, c-myc mRNA is destabilized by the trans-acting complex (CPEB-Tob-Caf1), while in cells stimulated by the serum, both Tob and Caf1 are released from CPEB, and c-Myc expression is induced early after stimulation by the stabilization of its mRNA as an 'immediate-early gene'. Collectively, these results indicate that Tob is a key factor in the regulation of c-myc gene expression, which is essential for cell growth. Thus, Tob appears to function in the control of cell growth at least, in part, by regulating the expression of c-myc.
MicroRNA (miRNA, miR)-18a is a member of the miR-17-92 cluster, an important locus that is markedly overexpressed in several cancers and associated with cancer development and progression. However, ...the mechanism of action of the miR-17-92 cluster and its individual miRNAs are largely unknown.
In this study, we investigated the expression of the miR-17-92 cluster by in situ hybridisation (ISH) assay and copy-number analysis in gastric tissue microarray (TMA) specimens. We determined that miR-18a was present at higher levels than the other five miRNAs in the cluster. In addition, we identified Protein Inhibitor of Activated Signal Transducer and Activator of Transcription 3 (PIAS3) as a direct target of miR-18a in gastric cancer. miR-18a level was positively correlated with levels of Survivin, Bcl-xL, and c-Myc, which are downstream transcriptional targets of Signal Transducer and Activator of Transcription 3 (STAT3). STAT3-induced transcription can be negatively regulated by PIAS3; consistent with this, PIAS3 level was negatively correlated with levels of Survivin, Bcl-xL, and c-Myc.
Our findings indicate that miR-18a acts as an oncogene and plays a role in gastric adenocarcinogenesis, at least in part by negatively regulating PIAS3 and thereby modulating expression of STAT3 target genes.
Currently, progress is made globally to construct the ITER, to test the feasibility of fusion at a large scale. Currently cable in conduit (CIC) conductors are used for large scale magnet designs. ...Here the individual strand positions are a concern, due to the possibilities of non-uniform current distribution and the consequences that arise with it. Thus, knowing the position of individual strands is necessary. Many studies have been conducted in simulating the strand position. At the same time, it is necessary to physically map the positions of the strands, for confirmation and refinement of simulations. Our lab conducted measurements using thermal imaging by slicing a CIC conductor in sections, heating up a strand on one side and detecting the change in temperature on the other side by the thermal camera. The strand that heats up fastest should be the same one that was heated up on the other side, allowing a one-to-one matching. The results were promising, but struggled in identifying closely packed sections, due to response speed of the camera. To improve the response speed, it was suggested to use thermistor chips, capable of detecting changes in temperature in the form of voltage with little lag. This should allow the identification of the path that a single strand takes. In this paper, an array of thermistors was tested to see the feasibility of the method, and results will be shown.
In order for robots to exist together with humans, safety for the humans has to be strictly ensured. On the other hand, safety might decrease working efficiency of robots. Namely, this is a trade-off ...problem between human safety and robot efficiency in a field of human-robot interaction. For this problem, we propose a novel motion planning technique of multiple mobile robots. Two artificial potentials are presented for generating repulsive force. The first potential is provided for humans. The von Mises distribution is used to consider the behavioral property of humans. The second potential is provided for the robots. The Kernel density estimation is used to consider the global robot congestion. Through simulation experiments, the effectiveness of the behavior and congestion potentials of the motion planning technique for human safety and robot efficiency is discussed. Moreover, a sensing system for humans in a real environment is developed. From experimental results, the significance of the behavior potential based on the actual humans is discussed. For the coexistence of humans and robots, it is important to evaluate a mutual influence between them. For this purpose, a virtual space is built using projection mapping. Finally, the effectiveness of the motion planning technique for the human-robot interaction is discussed from the point of view of not only robots but also humans.
Goldstone modes emerge associated with spontaneous breakdown of the continuous symmetry in the two-channel Kondo lattice, which describes strongly correlated f-electron systems with a non-Kramers ...doublet at each site. This paper derives the spectra of these collective modes by the equation of motion method together with the random phase approximation. The diagonal composite order breaks the SU(2) channel symmetry, and the symmetry-restoring collective mode couples with magnetic field. On the other hand, the off-diagonal or superconducting composite order breaks the gauge symmetry of conduction electrons, and the collective mode couples with charge excitations near the zone boundary. At half-filling of the conduction bands, the spectra of these two modes become identical by a shift of the momentum, owing to the SO(5) symmetry of the system. The velocity of each Goldstone mode involves not only the Fermi velocity of conduction electrons but amplitude of the mean field as a multiplying factor. Detection of the Goldstone mode should provide a way to identify the composite order parameter.
This paper focuses on patrolling missions for monitoring visitors in an environment. A single mobile robot is used. For the robot, it is required to monitor as many visitors as possible utilizing the ...mobility and monitoring capabilities. A challenge in the patrolling missions is that the robot does not have information about the visitors beforehand. For the unknown visitors, the robot is required to identify the trends. For this purpose, a Bayesian learning approach is applied to this robot. The identified visitor trends allow the robot to employ patrolling strategies. This is the adaptability of the patrolling robot to the unknown visitors. In this paper, we present an optimal patrolling strategy based on a value iteration method. The robot is enabled to have an optimal policy that suggests three patrolling decisions, such as the target monitoring area, monitoring time, and patrolling path in an integrated way. Furthermore, the optimal patrolling strategy is improved from the viewpoint of exploration and exploitation of information about the unknown visitors in the environment. Through simulation experiments, we discuss the effectiveness of the patrolling strategy.
Background
Recently reported normal values for esophageal motility obtained by high‐resolution manometry (HRM) using a system with a Unisensor catheter were significantly different from those ...obtained by the ManoScan®, which could result in a wrong diagnosis. To clarify whether these differences were due to system or subject differences, we compared the manometric parameter values between ManoScan and a new system with a Unisensor catheter (Starlet) in the same subjects.
Methods
A total of 103 volunteers without any symptoms related to esophageal motility disorders were recruited. Esophageal HRM was performed using both the ManoScan and the Starlet in all subjects. Data from the ManoScan were analyzed using ManoView, and data from the Starlet were analyzed by a program with e‐sleeve function. Integrated relaxation pressure, distal contractile integral, contractile front velocity (CFV), intrabolus pressure, and distal latency were calculated by both analyzing programs, and the values of these parameters were compared between the two systems by a signed rank test.
Key Results
Data from a total of 97 participants were analyzed. The values of all parameters, except CFV, measured by the Starlet were significantly higher than those obtained by the ManoScan (p < 0.01).
Conclusions & Inferences
Both systems can measure esophageal motility appropriately; nevertheless, we confirmed that the two systems showed different values of the parameters defined by the Chicago criteria. These differences should be recognized to evaluate esophageal motility precisely.
Both the ManoScan and the instrument with a Unisensor catheter (Starlet) can evaluate esophageal motility precisely, but as the results differ significantly between the two, care should be taken in using the values obtained. A: ManoScan, B: Starlet.
Summary
Autoantibodies, including anti‐ribosomal P proteins (anti‐P), are thought to be produced by an antigen‐driven immune response in systemic lupus erythematosus (SLE). To test this hypothesis, ...we reconstituted the ribosomal antigenic complex in vitro using human P0, phosphorylated P1 and P2 and a 28S rRNA fragment covering the P0 binding site, and immunized Murphy Roths large (MRL)/lrp lupus mice with this complex without any added adjuvant to generate anti‐P antibodies. Using hybridoma technology, we subsequently obtained 34 clones, each producing an anti‐P monoclonal antibody (mAb) that recognized the conserved C‐terminal tail sequence common to all three P proteins. We also obtained two P0‐specific monoclonal antibodies, but no antibody specific to P1, P2 or rRNA fragment. Two types of mAbs were found among these anti‐P antibodies: one type (e.g. 9D5) reacted more strongly with the phosphorylated P1 and P2 than that with their non‐phosphorylated forms, whereas the other type (e.g. 4H11) reacted equally with both phosphorylated and non‐phosphorylated forms of P1/P2. Both 9D5 and 4H11 inhibited the ribosome/eukaryotic elongation factor‐2 (eEF‐2)‐coupled guanosine triphosphate (GTP)ase activity. However, preincubation with a synthetic peptide corresponding to the C‐terminal sequence common to all three P proteins, but not the peptide that lacked the last three C‐terminal amino acids, mostly prevented the mAb‐induced inhibition of GTPase activity. Thus, at least two types of anti‐P were produced preferentially following the immunization of MRL mice with the reconstituted antigenic complex. Presence of multiple copies of the C‐termini, particularly that of the last three C‐terminal amino acid residues, in the antigenic complex appears to contribute to the immunogenic stimulus.
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