Summary Phagocytosis and autophagy are two important and related arms of the host's first-line defense against microbial invasion. Rubicon is a RUN domain containing cysteine-rich protein that functions as part of a Beclin-1-Vps34-containing autophagy complex. We report that Rubicon is also an essential, positive regulator of the NADPH oxidase complex. Upon microbial infection or Toll-like-receptor 2 (TLR2) activation, Rubicon interacts with the p22phox subunit of the NADPH oxidase complex, facilitating its phagosomal trafficking to induce a burst of reactive oxygen species (ROS) and inflammatory cytokines. Consequently, ectopic expression or depletion of Rubicon profoundly affected ROS, inflammatory cytokine production, and subsequent antimicrobial activity. Rubicon's actions in autophagy and in the NADPH oxidase complex are functionally and genetically separable, indicating that Rubicon functions in two ancient innate immune machineries, autophagy and phagocytosis, depending on the environmental stimulus. Rubicon may thus be pivotal to generating an optimal intracellular immune response against microbial infection.
What are the apparent research and methodological trends in PAR’s content over the past decade? From the perspective of the journal’s 70‐year history, with its aim to “mesh” practitioner and academic knowledge creation, topical coverage since 2000 reflects striking continuity, emphasizing many of the “bread and butter” administrative issues such as planning, human resources, budgeting, and public management. A marked increase in coverage is apparent in the application of more sophisticated quantitative statistical methodology, as well as in the number of female authors, while the number of practitioner authors declined sharply. Throughout the first turbulent decade of the twenty‐first century, three intellectual themes stood out: evaluations of New Public Management, connections between practitioners and academicians, and responsiveness to immediate social, economic, and political challenges. Given the constant demand for usable knowledge, scholars seem to have marginalized attention to the historical context and epistemological foundations of the study. The central challenge in the years ahead will be to effectively use research methods in response to the big questions of government and society that defy measurement. Since many [empiricists], especially the younger, do not know very much about epistemology, they tend to be quite dogmatic about the one set of canons that dominate them. —C. Wright Mills, 1959
This paper presents novel Ultrareliable and lowlatency communication (URLLC) techniques for URLLC services, such as Tactile Internet services. Among typical use-cases of URLLC services are tele-operation, immersive virtual reality, cooperative automated driving, and so on. In such URLLC services, new kinds of traffic such as haptic information including kinesthetic information and tactile information need to be delivered in addition to high-quality video and audio traffic in traditional multimedia services. Further, such a variety of traffic has various characteristics in terms of packet sizes and data rates with a variety of requirements of latency and reliability. Furthermore, some traffic may occur in a sporadic manner but require reliable delivery of packets of medium to large sizes within a low latency, which is not supported by current state-of-the-art wireless communication systems and is very challenging for future wireless communication systems. Thus, to meet such a variety of tight traffic requirements in a wireless communication system, novel technologies from the physical layer to the network layer need to be devised. In this paper, some novel physical layer technologies such as waveform multiplexing, multiple access scheme, channel code design, synchronization, and full-duplex transmission for spectrally-efficient URLLC are introduced. In addition, a novel performance evaluation approach, which combines a ray-tracing tool and system-level simulation, is suggested for evaluating the performance of the proposed schemes. Simulation results show the feasibility of the proposed schemes providing realistic URLLC services in realistic geographical environments, which encourages further efforts to substantiate the proposed work 1 .
The use of bicistronic vectors, which contain two target genes under one promoter, has been the most common practice for the heterologous production of binary protein complexes. The major problem of this method is the much lower expression of the second gene compared with that of the first gene next to the promoter. We tested a simple idea of whether inclusion of an additional promoter in front of the second gene may remove the problem. Compared with bicistronic vectors, corresponding two-promoter vectors yielded four to nine times larger amounts of the complexes between BCL-2 family proteins, BCL-X L :BAD, BCL-X L :BIM-S, and CED-9:EGL-1 in bacterial cells as a result of significantly increased expression of the second genes in a manner independent of the order of the target genes. With the two-promoter system, we produced two other complexes in large quantity suitable for extensive crystallization trial. The method does not accompany any technical disadvantages, and represents a significant improvement from the conventional method, which should enjoy wide application for the coexpression of binary or higher order protein complexes by extension.
RIG-I is a cytosolic receptor for non-self RNA that mediates immune responses against viral infections through IFNα/β production. In an attempt to identify novel tools that modulate IFNα/β production, we used SELEX technology to screen RNA aptamers that specifically target RIG-I protein. Most of the selected RIG-I aptamers contained polyU motifs in the second half regions that played critical roles in the activation of RIG-I-mediated IFNβ production. Unlike other known ligands, RIG-I aptamer bound and activated RIG-I in a 5′-triphosphate-independent manner. The helicase and RD domain of RIG-I were used for aptamer binding, but intact RIG-I protein was required to exert aptamer-mediated signaling activation. Furthermore, replication of NDV, VSV and influenza virus in infected host cells was efficiently blocked by pre- or post-treatment with RIG-I aptamer. Based on these data, we propose that RIG-I aptamer has strong potential to be an antiviral agent that specifically boosts the RIG-I-dependent signaling cascade.
Transport protein particle (TRAPP) comprises a family of two highly related multiprotein complexes, with seven common subunits, that serve to target different classes of transport vesicles to their appropriate compartments. Defining the architecture of the complexes will advance our understanding of the functional differences between these highly related molecular machines. Genetic analyses in yeast suggested a specific interaction between the TRAPP subunits Bet3p and Trs33p. A mammalian bet3-trs33 complex was crystallized, and the structure was solved to 2.2 Å resolution. Intriguingly, the overall fold of the bet3 and trs33 monomers was similar, although the proteins had little overall sequence identity. In vitro experiments using yeast TRAPP subunits indicated that Bet3p binding to Trs33p facilitates the interaction between Bet3p and another TRAPP subunit, Bet5p. Mutational analysis suggests that yeast Trs33p facilitates other Bet3p protein-protein interactions. Furthermore, we show that Trs33p can increase the Golgi-localized pool of a mutated Bet3 protein normally found in the cytosol. We propose that one of the roles of Trs33p is to facilitate the incorporation of the Bet3p subunit into assembling TRAPP complexes.
Using simple microwave irradiation under the presence of sodium amide as a nitrogen source, preparation of nitrogen-doped graphene nanosheets has been successfully demonstrated. It is notable that exfoliation and nitrogen doping of graphite to nitrogen-doped graphene simultaneously occurred during the microwave irradiation within a minute, and nitrogen content of the doped graphene could reach up to 8.1%. It was also found that the binding configuration of nitrogen atom on graphitic layer consisted of various nitrogen-containing moieties such as pyridine-N, pyrrolic-N, and quaternary-N, and their composition was changed as a function of irradiation power. Although formation of undoped reduced graphene oxide by microwave irradiation resulted in slight increase of electrical conductivity because of the reductive recovery of oxidized graphite to graphene, nitrogen doping involved during irradiation induced much more notable increase of electrical conductivity more than 300 S cm(-1). Furthermore, nitrogen-doped graphene showed highly enhanced capacitive performance than that of undoped reduced graphene oxide, the specific capacitance of 200 F/g (current density of 0.5 A/g), which ascribes the pseudocapacitive effect from the incorporation of nitrogen atom on graphitic layer.
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