The recent advent of DNA sequencing technologies facilitates the use of genome sequencing data that provide means for more informative and precise classification and identification of members of the ...Bacteria and Archaea. Because the current species definition is based on the comparison of genome sequences between type and other strains in a given species, building a genome database with correct taxonomic information is of paramount need to enhance our efforts in exploring prokaryotic diversity and discovering novel species as well as for routine identifications. Here we introduce an integrated database, called EzBioCloud, that holds the taxonomic hierarchy of the Bacteria and Archaea, which is represented by quality-controlled 16S rRNA gene and genome sequences. Whole-genome assemblies in the NCBI Assembly Database were screened for low quality and subjected to a composite identification bioinformatics pipeline that employs gene-based searches followed by the calculation of average nucleotide identity. As a result, the database is made of 61 700 species/phylotypes, including 13 132 with validly published names, and 62 362 whole-genome assemblies that were identified taxonomically at the genus, species and subspecies levels. Genomic properties, such as genome size and DNA G+C content, and the occurrence in human microbiome data were calculated for each genus or higher taxa. This united database of taxonomy, 16S rRNA gene and genome sequences, with accompanying bioinformatics tools, should accelerate genome-based classification and identification of members of the Bacteria and Archaea. The database and related search tools are available at www.ezbiocloud.net/.
Genome-based phylogeny plays a central role in the future taxonomy and phylogenetics of
Bacteria
and
Archaea
by replacing 16S rRNA gene phylogeny. The concatenated core gene alignments are frequently ...used for such a purpose. The bacterial core genes are defined as single-copy, homologous genes that are present in most of the known bacterial species. There have been several studies describing such a gene set, but the number of species considered was rather small. Here we present the up-to-date bacterial core gene set, named UBCG, and software suites to accommodate necessary steps to generate and evaluate phylogenetic trees. The method was successfully used to infer phylogenomic relationship of
Escherichia
and related taxa and can be used for the set of genomes at any taxonomic ranks of
Bacteria
. The UBCG pipeline and file viewer are freely available at
https://www.ezbiocloud.net/tools/ubcg
and
https://www.ezbiocloud.net/tools/ubcg_viewer
, respectively.
Background and Aims
Mitochondrial double‐stranded RNA (mtdsRNA) and its innate immune responses have been reported previously; however, mtdsRNA generation and its effects on alcohol‐associated liver ...disease (ALD) remain unclear. Here, we report that hepatic mtdsRNA stimulates toll‐like receptor 3 (TLR3) in Kupffer cells through the exosome (Exo) to enhance interleukin (IL)‐17A (IL‐17A) production in ALD.
Approach and Results
Following binge ethanol (EtOH) drinking, IL‐17A production primarily increased in γδ T cells of wild‐type (WT) mice, whereas the production of IL‐17A was mainly facilitated by CD4+ T cells in acute‐on‐chronic EtOH consumption. These were not observed in TLR3 knockout (KO) or Kupffer cell–depleted WT mice. The expression of polynucleotide phosphorylase, an mtdsRNA‐restricting enzyme, was significantly decreased in EtOH‐exposed livers and hepatocytes of WT mice. Immunostaining revealed that mtdsRNA colocalized with the mitochondria in EtOH‐treated hepatocytes from WT mice and healthy humans. Bioanalyzer analysis revealed that small‐sized RNAs were enriched in EtOH‐treated Exos (EtOH‐Exos) rather than EtOH‐treated microvesicles in hepatocytes of WT mice and humans. Quantitative real‐time PCR and RNA sequencing analyses indicated that mRNA expression of mitochondrial genes encoded by heavy and light strands was robustly increased in EtOH‐Exos from mice and humans. After direct treatment with EtOH‐Exos, IL‐1β expression was significantly increased in WT Kupffer cells but not in TLR3 KO Kupffer cells, augmenting IL‐17A production of γδ T cells in mice and humans.
Conclusions
EtOH‐mediated generation of mtdsRNA contributes to TLR3 activation in Kupffer cells through exosomal delivery. Consequently, increased IL‐1β expression in Kupffer cells triggers IL‐17A production in γδ T cells at the early stage that may accelerate IL‐17A expression in CD4+ T cells in the later stage of ALD. Therefore, mtdsRNA and TLR3 may function as therapeutic targets in ALD.
Mitochondrial dysfunction is associated with aging‐mediated inflammatory responses, leading to metabolic deterioration, development of insulin resistance, and type 2 diabetes. Growth differentiation ...factor 15 (GDF15) is an important mitokine generated in response to mitochondrial stress and dysfunction; however, the implications of GDF15 to the aging process are poorly understood in mammals. In this study, we identified a link between mitochondrial stress‐induced GDF15 production and protection from tissue inflammation on aging in humans and mice. We observed an increase in serum levels and hepatic expression of GDF15 as well as pro‐inflammatory cytokines in elderly subjects. Circulating levels of cell‐free mitochondrial DNA were significantly higher in elderly subjects with elevated serum levels of GDF15. In the BXD mouse reference population, mice with metabolic impairments and shorter survival were found to exhibit higher hepatic Gdf15 expression. Mendelian randomization links reduced GDF15 expression in human blood to increased body weight and inflammation. GDF15 deficiency promotes tissue inflammation by increasing the activation of resident immune cells in metabolic organs, such as in the liver and adipose tissues of 20‐month‐old mice. Aging also results in more severe liver injury and hepatic fat deposition in Gdf15‐deficient mice. Although GDF15 is not required for Th17 cell differentiation and IL‐17 production in Th17 cells, GDF15 contributes to regulatory T‐cell‐mediated suppression of conventional T‐cell activation and inflammatory cytokines. Taken together, these data reveal that GDF15 is indispensable for attenuating aging‐mediated local and systemic inflammation, thereby maintaining glucose homeostasis and insulin sensitivity in humans and mice.
Aging‐induced GDF15 production is observed in humans and mice, which is positively correlated with systemic inflammation and mitochondrial stress. GDF15 deficiency promotes glucose intolerance as well as hepatic and adipose inflammation in old mice. GDF15 contributes to regulatory T cells‐mediated suppression of conventional T cell activation, but senescent T cells were resistant to regulatory T cells‐mediated suppression compared to conventional T cells.
Background and Aims
The important roles of glutamate and metabotropic glutamate receptor 5 (mGluR5) in HSCs have recently been reported in various liver diseases; however, the mechanism linking the ...glutamine/glutamate metabolism and mGluR5 in liver fibrosis remains unclear. Here, we report that mGluR5 activation in natural killer (NK) cells attenuates liver fibrosis through increased cytotoxicity and interferon‐γ (IFN‐γ) production in both mice and humans.
Approach and Results
Following 2‐week injection of carbon tetrachloride (CCl4) or 5‐week methionine‐deficient and choline‐deficient diet, liver fibrosis was more aggravated in mGluR5 knockout mice with significantly decreased frequency of NK cells compared with wild‐type mice. Consistently, NK cell–specific mGluR5 knockout mice had aggravated CCl4‐induced liver fibrosis with decreased production of IFN‐γ. Conversely, in vitro activation of mGluR5 in NK cells significantly increased the expression of anti‐fibrosis‐related genes including Ifng, Prf1 (perforin), and Klrk1 (killer cell lectin like receptor K1) and the production of IFN‐γ through the mitogen‐activated extracellular signal‐regulated kinase/extracellular signal‐related kinase pathway, contributing to the increased cytotoxicity against activated HSCs. However, we found that the uptake of glutamate was increased in activated HSCs, resulting in shortage of extracellular glutamate and reduced stimulation of mGluR5 in NK cells. Consequently, this could enable HSCs to evade NK cell cytotoxicity in advanced liver fibrosis. In vivo, pharmacologic activation of mGluR5 accelerated CCl4‐induced liver fibrosis regression by restoring NK cell cytotoxicity. In humans, mGluR5 activation enhanced the cytotoxicity of NK cells isolated from healthy donors, but not from patients with cirrhosis with significantly reduced mGluR5 expression in NK cells.
Conclusions
mGluR5 plays important roles in attenuating liver fibrosis by augmenting NK cell cytotoxicity, which could be used as a potential therapeutic target for liver fibrosis.
Carbon-based fillers for thermal interface materials (TIMs) are attractive due to their advantages such as high thermal conductivity, low thermal expansion, mechanical strength, flexibility, and low ...weight. In this work, we report a 330% enhancement of the through-plane thermal conductivity (kth) of a graphite-polymer composite TIM film by vertically aligning the graphite fillers with a 10 T superconducting magnet. The filler alignment is based on the large anisotropy in the magnetic susceptibility of graphite platelets. As the filler content increases from 10 to 60 wt%, the anisotropy of thermal conductivity (kth/kin) increases from 1.2 up to 2.3 for a perpendicular magnetic field alignment, whereas it remains the same for a parallel magnetic field alignment. The increased anisotropy is associated with better filler alignment at high filler loadings. This work provides a simple and effective solution to improve the physical properties of composite films by controlling their microstructure.
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This letter studies the optimization of rate-splitting multiple access (RSMA) transmission technique for a cloud radio access network (C-RAN) downlink system. Main idea of RSMA is to split the ...message for each user equipment (UE) to private and common messages and perform superposition coding at transmitters so as to enable flexible decoding at receivers. It is challenging to implement ideal RSMA scheme particularly when there are many UEs, since the number of common signals exponentially increases with the number of UEs. An efficient RSMA scheme is hence proposed that uses a linearly increasing number of common signals whose decoding UEs are selected using hierarchical clustering. Via numerical results, we show the performance gains of the proposed RSMA scheme over conventional space-division multiple access (SDMA) and non-orthogonal multiple access (NOMA) schemes as well as over a conventional RSMA scheme that uses a single common signal.
Fog radio access networks (F-RANs), which consist of a cloud and multiple edge nodes (ENs) connected via fronthaul links, have been regarded as promising network architectures. The F-RAN entails a ...joint optimization of cloud and edge computing as well as fronthaul interactions, which is challenging for traditional optimization techniques. This paper proposes a Cloud-Enabled Cooperation-Inspired Learning (CECIL) framework, a structural deep learning mechanism for handling a generic F-RAN optimization problem. The proposed solution mimics cloud-aided cooperative optimization policies by including centralized computing at the cloud, distributed decision at the ENs, and their uplink-downlink fronthaul interactions. A group of deep neural networks (DNNs) are employed for characterizing computations of the cloud and ENs. The forwardpass of the DNNs is carefully designed such that the impacts of the practical fronthaul links, such as channel noise and signling overheads, can be included in a training step. As a result, operations of the cloud and ENs can be jointly trained in an end-to-end manner, whereas their real-time inferences are carried out in a decentralized manner by means of the fronthaul coordination. To facilitate fronthaul cooperation among multiple ENs, the optimal fronthaul multiple access schemes are designed. Training algorithms robust to practical fronthaul impairments are also presented. Numerical results validate the effectiveness of the proposed approaches.
This letter investigates a learning solution for robust beamforming optimization in downlink multi-user systems. A base station (BS) identifies efficient multi-antenna transmission strategies only ...with imperfect channel state information (CSI) and its stochastic features. To this end, we propose a robust training algorithm where a deep neural network (DNN), which only accepts estimates and statistical knowledge of the perfect CSI, is optimized to fit to real-world propagation environment. Consequently, the trained DNN can provide efficient robust beamforming solutions based only on imperfect observations of the actual CSI. Numerical results validate the advantages of the proposed learning approach compared to conventional schemes.
In-wheel motors bring a fundamental change in electric vehicle technology by removing conventional mechanical components and freeing up space inside the vehicle body. This approach ultimately helps ...to realize all-wheel independent control for improved vehicle dynamics and increased vehicle design freedom. However, when space allowed for an in-wheel motor is taken into consideration, high torque density, high efficiency, and wide-speed-range capability are typically required. This paper specifically investigates a 20-pole-24-slot surface permanent magnet synchronous motor with consequent pole rotor for in-wheel direct drive since this topology is well suited for high-pole motors and thus high-torque direct-drive applications. Extensive finite-element analysis is carried out to characterize the proposed motor, and the practical feasibility of the proposed motor is discussed. Finally, the validity of the analysis was experimentally verified.
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