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.
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/.
Average nucleotide identity (ANI) is a category of computational analysis that can be used to define species boundaries of Archaea and Bacteria. Calculating ANI usually involves the fragmentation of ...genome sequences, followed by nucleotide sequence search, alignment, and identity calculation. The original algorithm to calculate ANI used the BLAST program as its search engine. An improved ANI algorithm, called OrthoANI, was developed to accommodate the concept of orthology. Here, we compared four algorithms to compute ANI, namely ANIb (ANI algorithm using BLAST), ANIm (ANI using MUMmer), OrthoANIb (OrthoANI using BLAST) and OrthoANIu (OrthoANI using USEARCH) using >100,000 pairs of genomes with various genome sizes. By comparing values to the ANIb that is considered a standard, OrthoANIb and OrthoANIu exhibited good correlation in the whole range of ANI values. ANIm showed poor correlation for ANI of <90%. ANIm and OrthoANIu runs faster than ANIb by an order of magnitude. When genomes that are larger than 7 Mbp were analysed, the run-times of ANIm and OrthoANIu were shorter than that of ANIb by 53- and 22-fold, respectively. In conclusion, ANI calculation can be greatly sped up by the OrthoANIu method without losing accuracy. A web-service that can be used to calculate OrthoANIu between a pair of genome sequences is available at
http://www.ezbiocloud.net/tools/ani
. For large-scale calculation and integration in bioinformatics pipelines, a standalone JAVA program is available for download at
http://www.ezbiocloud.net/tools/orthoaniu
.
Activated T and B cells participate in the development and progression of Sjögren's syndrome (SS). Metformin, a first-line anti-diabetic drug, exerts anti-inflammatory and immunomodulatory effects by ...activating AMPK. We investigated the therapeutic effect of metformin in non-obese diabetic (NOD)/ShiLtJ mice, an animal model of SS.
Metformin or vehicle was administered orally to the mice for 9 weeks. The salivary flow rate was measured at 11, 13, 15, 17, and 20 weeks. Histological analysis of the salivary glands from vehicle- and metformin-treated mice was conducted. CD4
T and B cell differentiation in the peripheral blood and/or spleen was determined by flow cytometry. Serum total IgG, IgG1, and IgG2a levels were determined by enzyme-linked immunosorbent assay.
Metformin reduced salivary gland inflammation and restored the salivary flow rate. Moreover, metformin reduced the interleukin (IL)-6, tumor necrosis factor-α, IL-17 mRNA, and protein levels in the salivary glands. Metformin reduced the Th17 and Th1 cell populations and increased the regulatory T cell population in the peripheral blood and spleen and modulated the balance between Tfh and follicular regulatory T cells. In addition, metformin reduced B cell differentiation into germinal center B cells, decreased the serum immunoglobulin G level, and maintained the balance between IL-10- and IL-17-producing B cells.
Metformin suppresses effector T cells, induces regulatory T cells, and regulates B cell differentiation in an animal model of SS. In addition, metformin ameliorates salivary gland inflammation and hypofunction, suggesting that it has potential for the treatment of SS.
Recent studies highlighted the biosynthetic potential of nocardiae to produce diverse novel natural products comparable to that of Streptomyces, thereby making them an attractive source of new drug ...leads. Many of the 119 Nocardia validly named species were isolated from natural habitats but little is known about the diversity and the potential of the endophytic nocardiae of root nodule of actinorhizal plants.
The taxonomic status of an actinobacterium strain, designated ncl2
, was established in a genome-based polyphasic study. The strain was Gram-stain-positive, produced substrate and aerial hyphae that fragmented into coccoid and rod-like elements and showed chemotaxonomic properties that were also typical of the genus Nocardia. It formed a distinct branch in the Nocardia 16S rRNA gene tree and was most closely related to the type strains of Nocardia nova (98.6%), Nocardia jiangxiensis (98.4%), Nocardia miyuensis (97.8%) and Nocardia vaccinii (97.7%). A comparison of the draft genome sequence generated for the isolate with the whole genome sequences of its closest phylogenetic neighbours showed that it was most closely related to the N. jiangxiensis, N. miyuensis and N. vaccinii strains, a result underpinned by average nucleotide identity and digital DNA-DNA hybridization data. Corresponding taxogenomic data, including those from a pan-genome sequence analysis showed that strain ncl2
was most closely related to N. vaccinii DSM 43285
. A combination of genomic, genotypic and phenotypic data distinguished these strains from one another. Consequently, it is proposed that strain ncl2
(= DSM 110931
= CECT 30122
) represents a new species within the genus Nocardia, namely Nocardia alni sp. nov. The genomes of the N. alni and N. vaccinii strains contained 36 and 29 natural product-biosynthetic gene clusters, respectively, many of which were predicted to encode for a broad range of novel specialised products, notably antibiotics. Genome mining of the N. alni strain and the type strains of its closest phylogenetic neighbours revealed the presence of genes associated with direct and indirect mechanisms that promote plant growth. The core genomes of these strains mainly consisted of genes involved in amino acid transport and metabolism, energy production and conversion and transcription.
Our genome-based taxonomic study showed that isolate ncl2
formed a new centre of evolutionary variation within the genus Nocardia. This novel endophytic strain contained natural product biosynthetic gene clusters predicted to synthesize novel specialised products, notably antibiotics and genes associated with the expression of plant growth promoting compounds.
Thanks to the recent advancement of DNA sequencing technology, the cost and time of prokaryotic genome sequencing have been dramatically decreased. It has repeatedly been reported that genome ...sequencing using high-throughput next-generation sequencing is prone to contaminations due to its high depth of sequencing coverage. Although a few bioinformatics tools are available to detect potential contaminations, these have inherited limitations as they only use protein-coding genes. Here we introduce a new algorithm, called ContEst16S, to detect potential contaminations using 16S rRNA genes from genome assemblies. We screened 69 745 prokaryotic genomes from the NCBI Assembly Database using ContEst16S and found that 594 were contaminated by bacteria, human and plants. Of the predicted contaminated genomes, 8 % were not predicted by the existing protein-coding gene-based tool, implying that both methods can be complementary in the detection of contaminations. A web-based service of the algorithm is available at www.ezbiocloud.net/tools/contest16s.
Airborne microorganisms have significant effects on human health, and children are more vulnerable to pathogens and allergens than adults. However, little is known about the microbial communities in ...the air of childcare facilities. Here, we analyzed the bacterial and fungal communities in 50 air samples collected from five daycare centers and five elementary schools located in Seoul, Korea using culture-independent high-throughput pyrosequencing. The microbial communities contained a wide variety of taxa not previously identified in child daycare centers and schools. Moreover, the dominant species differed from those reported in previous studies using culture-dependent methods. The well-known fungi detected in previous culture-based studies (Alternaria, Aspergillus, Penicillium, and Cladosporium) represented less than 12% of the total sequence reads. The composition of the fungal and bacterial communities in the indoor air differed greatly with regard to the source of the microorganisms. The bacterial community in the indoor air appeared to contain diverse bacteria associated with both humans and the outside environment. In contrast, the fungal community was largely derived from the surrounding outdoor environment and not from human activity. The profile of the microorganisms in bioaerosols identified in this study provides the fundamental knowledge needed to develop public health policies regarding the monitoring and management of indoor air quality.
Cesium azide (CsN3) is employed as a novel n‐dopant because of its air stability and low deposition temperature. CsN3 is easily co‐deposited with the electron transporting materials in an organic ...molecular beam deposition chamber so that it works well as an n‐dopant in the electron transport layer because its evaporation temperature is similar to that of common organic materials. The driving voltage of the p‐i‐n device with the CsN3‐doped n‐type layer and a MoO3‐doped p‐type layer is greatly reduced, and this device exhibits a very high power efficiency (57 lm W−1). Additionally, an n‐doping mechanism study reveals that CsN3 was decomposed into Cs and N2 during the evaporation. The charge injection mechanism was investigated using transient electroluminescence and capacitance–voltage measurements. A very highly efficient tandem organic light‐emitting diodes (OLED; 84 cd A−1) is also created using an n–p junction that is composed of the CsN3‐doped n‐type organic layer/MoO3 p‐type inorganic layer as the interconnecting unit. This work demonstrates that an air‐stable and low‐temperature‐evaporable inorganic n‐dopant can very effectively enhance the device performance in p‐i‐n and tandem OLEDs, as well as simplify the material handling for the vacuum deposition process.
A low‐temperature, evaporable cesium azide (CsN3) is employed as an n‐dopant in an electron transport layer. The driving voltage of the p‐i‐n device using the CsN3‐doped n‐type layer and a MoO3‐doped p‐type layer is greatly reduced, and it shows very high power efficiency.
The usefulness of 3-dimensional (3D)-printed disease models has been recognized in various medical fields. This study aims to introduce a production platform for patient-specific 3D-printed brain ...tumor model in clinical practice and evaluate its effectiveness. A full-cycle platform was created for the clinical application of a 3D-printed brain tumor model (3D-printed model) production system. Essential elements included automated segmentation software, cloud-based interactive communication tools, customized brain models with exquisite expression of brain anatomy in transparent material, adjunctive devices for surgical simulation, and swift process cycles to meet practical needs. A simulated clinical usefulness validation was conducted in which neurosurgeons assessed the usefulness of the 3D-printed models in 10 cases. We successfully produced clinically applicable patient-specific models within 4 days using the established platform. The simulated clinical usefulness validation results revealed the significant superiority of the 3D-printed models in surgical planning regarding surgical posture (p = 0.0147) and craniotomy design (p = 0.0072) compared to conventional magnetic resonance images. The benefit was more noticeable for neurosurgeons with less experience. We established a 3D-printed brain tumor model production system that is ready to use in daily clinical practice for neurosurgery.
In implantable bioelectronics, which aim for semipermanent use of devices, biosafe energy sources and packaging materials to protect devices are essential elements. However, research so far has been ...conducted in a direction where they cannot coexist. Here, the development of capacitance‐matched triboelectric implants driven is reported by ultrasound under 500 mW cm−2 safe intensity and realize a battery‐free, miniatured, and wireless neurostimulator with full titanium (Ti) packaging. The triboelectric implant with high dielectric composite, which has ultralow output impedance, can efficiently deliver sufficient power to generate the stimulation pulse without an energy‐storing battery, despite ultrasound attenuation due to the Ti, and has the highest energy transmission efficiency among those reported so far. In vivo study using a rat model demonstrated that the proposed device system is an effective solution for relieving urinary symptoms. These achievements provide a significant step toward permanently implantable devices for controlling human organs and treating various diseases.
The ultrasound‐driven triboelectric nanogenerator using a high‐dielectric composite not only improves the output of the device, but also improves the connectivity between the energy harvester and the circuit, enabling the semipermanent use and miniaturization of implantable medical devices. These triboelectric implants provide a significant step toward permanently implantable devices for controlling human organs and treating various diseases.