Frequencies of insecticide resistance mutations detected by the amplicon sequencing in Plutella xylostella (Lepidoptera: Plutellidae) and Spodoptera exigua (Lepidoptera: Noctuidae) from China.

The globally prevalent pests, Diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae) and Beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), pose significant threats to cruciferous vegetables. They have rapidly developed resistance to a wide range of insecticides, leading to significant yield losses and increased control expenses. In this study, we have established an efficient approach utilizing amplicon sequencing to detect the frequency of 15 target resistance mutant sites in 6 molecular targets, acetylcholinesterase 1 (ACE1), chitin synthase 1 (CHS1), the γ-aminobutyric acid receptor (GABAR), glutamate-gated chloride channel (GluCl), voltage-gated sodium channels (NaV), and ryanodine receptor (RyR) in P. xylostella and the frequency of 11 mutations in 5 molecular targets (except GluCl) in S. exigua in China. Our findings indicate that P. xylostella exhibits remarkably high frequency (over 88.67%) in pyrethroid resistance-related mutations T929I and L1014F of NaV. In S. exigua, the frequencies of L659F mutation were ranging from 41.92% to 74.89%. In addition, the organophosphorus resistance-related mutations A298S and G324A of ACE1 were detected at frequencies ranging from 34.29% to 75.66%, and these 2 mutations occurred simultaneously (from 29.22% to 65.79%) in P. xylostella. An interannual variation in mutation frequency from 2019 to 2021 was found for P. xylostella in HNCS. The frequency of A298S and G324A mutations steadily increased while the frequency of G4946E and I4790M mutations continuously decreased. These results unveil a worrisome scenario of multiple resistance sites in these 2 pests in China and provide valuable insights for the practical application of pesticides in the field.

EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50.

Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As relatively long-lived mammals based on body size, bats display unique telomeric patterns, including the up-regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion. Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro-cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans. In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.

Streptomyces longhuiensis sp. nov, a novel species isolated from soil of Lilium brownii in Hunan Province, PR China.

An actinobacterium strain, designated BH-MK-02T, was isolated from the soil of Lilium brownii. The taxonomic position was determined using a polyphasic approach. Strain BH-MK-02T grew well on International Streptomyces Project series media and formed well-developed, branched substrate hyphae and aerial mycelium that differentiated into straight spore chains with a wrinkled surface. The diagnostic diamino acid was ll-diaminopimelic acid. The major menaquinones were MK-9(H4), MK-9(H6) and MK-9(H8). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannosides, phosphatidylglycerol and unidentified lipid spots. The predominant fatty acids were anteiso-C15 : 0, iso-C16 : 0, C16 : 0 and C16 : 1 ω7c/C16 : 1 ω6c. The phenotypic characteristics of strain BH-MK-02T indicated that it belonged to the genus Streptomyces. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain BH-MK-02T was most closely related to Streptomyces aureus CGMCC 4.1833T (99.7 %). However, the average nucleotide identity and digital DNA-DNA hybridization values between the whole-genome sequences of strain BH-MK-02T and S. aureus CGMCC 4.1833T were 78.1 and 23.2 %, respectively, below the 96.7 and 70 % cut-off points respectively recommended for delineating Streptomyces species. Furthermore, the novel isolate could be distinguished from S. aureus CGMCC 4.1833T by morphological, physiological and biochemical characteristics. Based on all these data, strain BH-MK-02T (=MCCC 1K06237T=JCM 34789T) clearly represents a novel species within the genus Streptomyces, for which the name Streptomyces longhuiensis sp. nov. is proposed.

Nocardiopsis changdeensis sp. nov., an endophytic actinomycete isolated from the roots of Eucommia ulmoides Oliv.

Strain Mg02T was isolated from roots of Eucommia ulmoides Oliv. collected from Changde City, Hunan Province, China. Strain Mg02T, which exhibited distinct chemotaxonomic characteristics of the genus Nocardiopsis: cell-wall chemotype III/C, i.e., meso-diaminopimelic acid as diagnostic amino acid in whole-cell hydrolysates and menaquinone MK-10 with variable degrees of saturation in the side chain as the predominant isoprenoid quinone, was investigated by a polyphasic approach to determine their taxonomic position. Sequence analysis of the 16S rRNA gene indicated that strain Mg02T is affiliated to the genus Nocardiopsis, having highest sequence similarity to Nocardiopsis flavescens CGMCC 4.5723T (99.1%) and <98.7% to other species of the genus Nocardiopsis with validly published names. Phylogenetic analysis of 16S rRNA gene indicated strain Mg02T formed a separate evolutionary clade, suggesting that it could be a novel Nocardiopsis species. Phylogenomic analysis showed that strain Mg02T was closely related to N. flavescens CGMCC 4.5723T and distinct from the latter according to the clustering patterns. The Average Nucleotide Identity and digital DNA-DNA hybridization values between strain Mg02T and N. flavescens CGMCC 4.5723T were far below the species-level thresholds. Based on phenotypic, phylogenetic and chemotaxonomic characteristics, we think that strain Mg02T should represent a novel Nocardiopsis species, for which the name Nocardiopsis changdeensis sp. nov. is proposed. The type strain is Mg02T (=MCCC 1K06174T = JCM 34709T).

Genetic regulatory and biological implications of the 10q24.32 schizophrenia risk locus.

Genome-wide association studies have identified 10q24.32 as a robust schizophrenia risk locus. Here we identify a regulatory variant (rs10786700) that disrupts binding of transcription factors at 10q24.32. We independently confirmed the association between rs10786700 and schizophrenia in a large Chinese cohort (n = 11 547) and uncovered the biological mechanism underlying this association. We found that rs10786700 resides in a super-enhancer element that exhibits dynamic activity change during the development process and that the risk allele (C) of rs10786700 conferred significant lower enhancer activity through enhancing binding affinity to repressor element-1 silencing transcription factor (REST). CRISPR-Cas9-mediated genome editing identified SUFU as a potential target gene by which rs10786700 might exert its risk effect on schizophrenia, as deletion of rs10786700 downregulated SUFU expression. We further investigated the role of Sufu in neurodevelopment and found that Sufu knockdown inhibited proliferation of neural stem cells and neurogenesis, affected molecular pathways (including neurodevelopment-related pathways, PI3K-Akt and ECM-receptor interaction signalling pathways) associated with schizophrenia and altered the density of dendritic spines. These results reveal that the functional risk single nucleotide polymorphism rs10786700 at 10q24.32 interacts with REST synergistically to regulate expression of SUFU, a novel schizophrenia risk gene which is involved in schizophrenia pathogenesis by affecting neurodevelopment and spine morphogenesis.

RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma.

BACKGROUND: Severe hypoxia is a prominent character of pancreatic ductal adenocarcinoma (PDAC) microenvironment. In the process of gemcitabine based chemotherapy, PDAC cells are insulted from replication stresses co-induced by hypoxia and gemcitabine. However, PDAC cells get outstanding abilities to resist to such harsh conditions and keep proliferating, causing a major obstacle for current therapy. RETSAT (Retinol Saturase) is defined as a hypoxia convergent gene recently, with high expression in PDAC hypoxic sectors. This study aimed to explore the roles of RETSAT in replication stress resistance and hypoxia adaptation in PDAC cells, and decipher the underlying mechanism. METHODS: The expression of RETSAT was examined in TCGA (The Cancer Genome Atlas), human pancreatic cancer microarray, clinical specimens and cell lines. Functions of RETSAT were studied by means of DNA fiber assay and comet assay in monolayer cultured PDAC cell lines, three dimensional spheroids, patient derived organoids and cell derived xenograft mouse models. Mechanism was investigated by using iPOND (isolate proteins on nascent DNA) combined with mass spectrometry, immunoprecipitation and immunoblotting. RESULTS: First, we found the converse relationship of RETSAT expression and PDAC chemotherapy. That is, PDAC patients with high RETSAT expression correlated with poor survival, while ones holding low RETSAT expression were benefitted more in Gemcitabine based chemotherapy. Second, we identified RETSAT as a novel replication fork associated protein. HIF-1α signaling promotes RETSAT expression under hypoxia. Functionally, RETSAT promoted fork restarting under replication stress and maintained genomic stability. Third, we uncovered the interaction of RETSAT and R-loop unwinding helicase DDX39B. RETSAT detained DDX39B on forks to resolve R-loops, through which avoided fork damage and CHK1 initiated apoptosis. Targeting DDX39B using chemical CCT018159 sensitized PDAC cells and organoids to gemcitabine induced apoptosis, highlighting the synergetic application of CCT018159 and gemcitabine in PDAC chemotherapy. CONCLUSIONS: This study identified RETSAT as a novel replication fork protein, which functions through interacting with DDX39B mediated R-loop clearance to promote fork restarting, leading to cellular resistance to replication stresses co-induced by tumor environmental hypoxia and gemcitabine in pancreatic ductal adenocarcinoma.

A new species, Cylindroeme yunnanensis sp. nov. from China (Coleoptera, Cerambycidae, Cerambycinae).

A new species, Cylindroeme yunnanensis sp. nov., is described and illustrated from Yunnan Province of China. Cylindroeme vietnamica Vives, 2019 is recorded from China for the first time. A key to the species of Cylindroeme is provided.

Streptomyces akebiae sp. nov., a novel actinomycete isolated from rhizosphere soil of Akebia trifoliate.

A novel actinomycete strain, designated as MG28T, was isolated from rhizosphere soil of Akebia trifoliate. The taxonomic position of the strain was investigated by using a polyphasic approach. BLAST search of the full-length 16S rRNA gene sequence of strain MG28T indicated it represented a member of the genus Streptomyces, and displayed 99.03%, 98.90%, 98.90%, 98.89%, 98.83% and less than 98.70% sequence similarities with S. phaeolivaceus GY16T, S. deccanensis KCTC 19241T, S. europaeiscabiei KACC 20186T, S. fructofermentans CGMCC 4.1593T, S. scabiei NRRL B-16523T and other species of the genus Streptomyces with validly published names, respectively. Phylogenomic analysis indicated that strain MG28T was closely related to Streptomyces deccanensis KCTC 19241T. However, the average nucleotide identity values and the digital DNA-DNA hybridization values between them indicated that strain MG28T represented a distinct species. Furthermore, strain MG28T was also distinctly differentiated from strain KCTC 19241T by morphological, physiological and biochemical characteristics. Therefore, strain MG28T (= MCCC 1K06895T = JCM 34922T) represents a novel species of the genus Streptomyces, for which the name Streptomyces akebiae sp. nov. is proposed.

New Insights Into the Threshold Values of Multi-Locus Sequence Analysis, Average Nucleotide Identity and Digital DNA-DNA Hybridization in Delineating Streptomyces Species.

Multi-locus sequence analysis (MLSA) has been proved to be a useful method for Streptomyces identification and MLSA distance of 0.007 is considered as the boundary value. However, we found that MLSA distance of 0.007 might be insufficient to act as a threshold according to the correlations among average nucleotide identity based on MuMmer ultra-rapid aligning tool (ANIm), digital DNA-DNA hybridization (dDDH) and MLSA from the 80 pairs of Streptomyces species; in addition, a 70% dDDH value did not correspond to a 95∼96% ANIm value but approximately to 96.7% in the genus Streptomyces. Based on our analysis, it was proposed that when the MLSA distance value between a novel Streptomyces and a reference strain was < 0.008, the novel strain could be considered as a heterotypic synonym of the reference strain; when the MLSA distance value was ≥ 0.014, the novel strain could be regarded as a new Streptomyces species; when the MLSA distance value was between 0.008 and 0.014 (not included), the dDDH or ANIm value between a new strain and a reference strain must be calculated in order to determine the taxonomic status of a novel strain. In this context, a 70% dDDH or 96.7% ANIm value could act as the threshold value in delineating Streptomyces species, but if the dDDH or ANIm value was less than but close to 70 or 96.7% cut-off point, the taxonomic status of a novel strain could only be determined by a combination of phenotypic characteristics, chemotaxonomic characteristics and phylogenomic analysis.

Streptomyces liliifuscus sp. nov and an anti-ginger plague agent Streptomyces liliiviolaceus sp. nov, two novel species isolated from soil of Lilium lancifolium.

Two novel strains of actinobacteria, ZYC-3T and BH-SS-21T, were isolated from Hunan Province, PR China. The fermentation broth of BH-SS-21T inhibited the rapid spread of ginger blast, unlike that of ZYC-3T. The taxonomic characteristics of ZYC-3T and BH-SS-21T were defined using a polyphasic approach. The analysis of the full-length 16S rRNA gene sequence revealed that ZYC-3T and BH-SS-21T represented members of the genus Streptomyces. ZYC-3T had less than 98.7% sequence similarities to all species of the genus Streptomyces, while BH-SS-21T exhibited 99.97, 98.95, 98.83, 98.82, 98.75 and less than 98.7% sequence similarities to 'Streptomyces dioscori' A217, Streptomyces ederensis JCM 4958T, Streptomyces glomeroaurantiacus NBRC 15418T, Streptomyces aurantiacus NBRC 13017T, Streptomyces umbrinus JCM 4521T and other species with validly published names in the genus Streptomyces. However, the digital DNA-DNA relatedness and average nucleotide identity values between ZYC-3T, BH-SS-21T, and their closely related strains were significantly lower than the recommended threshold values. Also, phenotypic, chemotaxonomic and genetic features distinguished ZYC-3T and BH-SS-21T from their reference strains. On the basis of their genotypic and phenotypic characteristics, strains ZYC-3T and BH-SS-21T were classified as representing novel species of the genus Streptomyces under the names Streptomyces liliifuscus sp. nov. ZYC-3T (=CICC 25040T=JCM 34560T=MCCC 1K04978T) and Streptomyces liliiviolaceus sp. nov. BH-SS-21T (=MCCC 1K06236T=JCM 34767T), respectively.

Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression.

Genome-wide association studies have identified 3p21.1 as a robust risk locus for schizophrenia. However, the underlying molecular mechanisms remain elusive. Here a functional regulatory variant (rs2535629) is identified that disrupts CTCF binding at 3p21.1. It is confirmed that rs2535629 is also significantly associated with schizophrenia in Chinese population and the regulatory effect of rs2535629 is validated. Expression quantitative trait loci analysis indicates that rs2535629 is associated with the expression of three distal genes (GLT8D1, SFMBT1, and NEK4) in the human brain, and CRISPR-Cas9-mediated genome editing confirmed the regulatory effect of rs2535629 on GLT8D1, SFMBT1, and NEK4. Interestingly, differential expression analysis of GLT8D1, SFMBT1, and NEK4 suggested that rs2535629 may confer schizophrenia risk by regulating SFMBT1 expression. It is further demonstrated that Sfmbt1 regulates neurodevelopment and dendritic spine density, two key pathological characteristics of schizophrenia. Transcriptome analysis also support the potential role of Sfmbt1 in schizophrenia pathogenesis. The study identifies rs2535629 as a plausibly causal regulatory variant at the 3p21.1 risk locus and demonstrates the regulatory mechanism and biological effect of this functional variant, indicating that this functional variant confers schizophrenia risk by altering CTCF binding and regulating expression of SFMBT1, a distal gene which plays important roles in neurodevelopment and synaptic morphogenesis.

Functional variant rs2270363 on 16p13.3 confers schizophrenia risk by regulating NMRAL1.

Recent genome-wide association studies have reported multiple schizophrenia risk loci, yet the functional variants and their roles in schizophrenia remain to be characterized. Here we identify a functional single nucleotide polymorphism (rs2270363: G>A) at the schizophrenia risk locus 16p13.3. rs2270363 lies in the E-box element of the promoter of NMRAL1 and disrupts binding of the basic helix-loop-helix leucine zipper family proteins, including USF1, MAX and MXI1. We validated the regulatory effects of rs2270363 using reporter gene assays and electrophoretic mobility shift assay. Besides, expression quantitative trait loci analysis showed that the risk allele (A) of rs2270363 was significantly associated with elevated NMRAL1 expression in the human brain. Transcription factors knockdown and CRISPR-Cas9-mediated editing further confirmed the regulatory effects of the genomic region containing rs2270363 on NMRAL1. Intriguingly, NMRAL1 was significantly downregulated in the brain of schizophrenia patients compared with healthy subjects, and knockdown of Nmral1 expression affected proliferation and differentiation of mouse neural stem cells, as well as genes and pathways associated with brain development and synaptic transmission. Of note, Nmral1 knockdown resulted in significant decrease of dendritic spine density, revealing the potential pathophysiological mechanisms of NMRAL1 in schizophrenia. Finally, we independently confirmed the association between rs2270363 and schizophrenia in the Chinese population and found that the risk allele of rs2270363 was the same in European and Chinese populations. These lines of evidence suggest that rs2270363 may confer schizophrenia risk by regulating NMRAL1, a gene whose expression dysregulation might be involved in the pathogenesis of schizophrenia by affecting neurodevelopment and synaptic plasticity.

Photodynamic therapy for synovial hyperplasia in patients with refractory rheumatoid arthritis: a study protocol for a randomized, double-blind, blank-controlled prospective trial.

BACKGROUND: Persistent synovial hyperplasia with inflammation in rheumatoid arthritis is one of the main pathogeneses of refractory rheumatoid arthritis (RRA). Photodynamic therapy (PDT) causes less trauma than steroid injections or arthroscopic synovectomy while providing stronger targeting and more durable curative effects. The aim of this trial was to evaluate the short-, medium-, and long-term clinical efficacy of PDT when applied as a treatment for RRA synovial hyperplasia and synovitis. METHODS AND ANALYSIS: This protocol is for a single-center, randomized, double-blind, blank-controlled prospective trial. A sample of 126 RRA patients will be randomly divided into 3 groups: the control group, the "PDT once" group, and the "PDT twice" group, with 42 participants per group. The trial will be conducted by the Rheumatology and Immunology Department of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University. The Ultrasound Compound Score of Synovitis (UCSS) has been selected as the primary outcome measure. The secondary outcome measures include knee joint clinical assessments, ratio of relapse, duration of remission, Disease Activity Score in 28 joints (DAS28), inflammation indexes, serum concentrations of specific antibodies, and changes in articular structures as detected by X-ray scans in the 48th week. The improvement ratios of the UCSS at the 8th, 24th, and 48th weeks (compared with baseline) reflect short-, medium-, and long-term time frames, respectively. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Ethics Committee of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, China (Approval No. granted by the ethics committee: NFZXYEC-2017-005) and then entered in the Chinese Clinical Trials Registry under registration number ChiCTR1800014918 (approval date: February 21, 2018). All procedures are in accordance with Chinese laws and regulations and with the Declaration of Helsinki by the World Medical Association (WMA). Any modifications of this protocol during execution will need additional approval from the Ethics Committee of our hospital. TRIAL REGISTRATION NUMBER: ChiCTR1800014918 .

Proposal of Streptomyces aureorectus (ex Taig et al. 1969) Taig and Solovieva 1986 as a later heterotypic synonym of Streptomyces calvus Backus et al. 1957 (Approved Lists 1980) on the basis of a polyphasic taxonomic approach.

As two separate genomic species, Streptomyces calvus and Streptomyces aureorectus were approved in 1980 and 1986, respectively. However, recently, it has been found that the average nucleotide identity and digital DNA-DNA hybridization values between S. calvus JCM 4326T and S. aureorectus DSM 41692T were 99.19 and 92.70 %, respectively, much higher than 95-96 and 70  % cut-off points proposed and the generally accepted species boundaries. These data indicated that they should be classified as the same genomic species. Furthermore, this result was also supported by a comprehensive comparison of phenotypic, chemotaxonomic and physio-biochemical characteristics between the two type strains. All these data indicated that S. calvus and S. aureorectus had the same taxonomic position. In accordance with the principle of priority, it is proposed that S. aureorectus is a later heterotypic synonyms of S. calvus.

Streptomyces genisteinicus sp. nov., a novel genistein-producing actinomycete isolated from a Chinese medicinal plant and proposal of Streptomyces michiganensis Corbaz et al. 1957 as a later heterotypic synonym of Streptomyces xanthochromogenes Arishima et al. 1956.

A novel genistein-producing actinobacterial strain, designated strain CRPJ-33T, was isolated from the healthy leaves of a medicinal plant Xanthium sibiricum collected from Hunan Province, PR China. 16S rRNA gene sequence analysis indicated strain CRPJ-33T belonged to the genus Streptomyces and had 99.7, 99.0, 98.9, 98.9, 98.8 and 98.7% sequence similarities to Streptomyces zhihengii YIM T102T, Streptomyces eurocidicus NRRL B-1676T, Streptomyces xanthochromogenes NRRL B-5410T, Streptomyces michiganensis NBRC 12797T, Streptomyces mauvecolor LMG 20100T and Streptomyces lavendofoliae NBRC 12882T, respectively. Phylogenetic analysis of 16S rRNA gene sequences showed that strain CRPJ-33T was most closely related to S. zhihengii YIM T102T. However, digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between them were much less than the recommended threshold values. Furthermore, differential comparisons of the phenotypic characteristics were enough to distinguish strain CRPJ-33T from S. zhihengii YIM T102T. Meanwhile, the ANI and dDDH values or MLSA distances between strain CRPJ-33T and other type strains, which exhibited ≥98.7 % 16S rRNA gene sequence similarities to strain CRPJ-33T, were far away from the recommended threshold values. Based on these results, it is thought that strain CRPJ-33T should represent a novel species of the genus Streptomyces, for which the name Streptomyces genisteinicus sp. nov. is proposed. The type strain is CRPJ-33T (=MCCC 1K04965T=JCM 34526T). In addition, the phenotypic, chemotaxonomic and genotypic characteristics, as well as phylogenetic information revealed that the type strains of S. xanthochromogenes and S. michiganensis should belong to same genomic species. Consequently, it is proposed that S. michiganensis is a heterotypic synonym of S. xanthochromogenes for which an emended description is given.

A missense variant in NDUFA6 confers schizophrenia risk by affecting YY1 binding and NAGA expression.

Genome-wide association studies (GWASs) have revealed that genetic variants at the 22q13.2 risk locus were robustly associated with schizophrenia. However, the causal variants at this risk locus and their roles in schizophrenia remain elusive. Here we identify the risk missense variant rs1801311 (located in the 1st exon of NDUFA6 gene) as likely causal for schizophrenia at 22q13.2 by disrupting binding of YY1, TAF1, and POLR2A. We systematically elucidated the regulatory mechanisms of rs1801311 and validated the regulatory effect of this missense variant. Intriguingly, rs1801311 physically interacted with NAGA (encodes the alpha-N-acetylgalactosaminidase, which is mainly involved in regulating metabolisms of glycoproteins and glycolipids in lysosome) and showed the most significant association with NAGA expression in the human brain, with the risk allele (G) associated with higher NAGA expression. Consistent with eQTL analysis, expression analysis showed that NAGA was significantly upregulated in brains of schizophrenia cases compared with controls, further supporting that rs1801311 may confer schizophrenia risk by regulating NAGA expression. Of note, we found that NAGA regulates important neurodevelopmental processes, including proliferation and differentiation of neural stem cells. Transcriptome analysis corroborated that NAGA regulates pathways associated with neuronal differentiation. Finally, we independently confirmed the association between rs1801311 and schizophrenia in a large Chinese cohort. Our study elucidates the regulatory mechanisms of the missense schizophrenia risk variant rs1801311 and provides mechanistic links between risk variant and schizophrenia etiology. In addition, this study also revealed the novel role of coding variants in gene regulation and schizophrenia risk, i.e., genetic variant in coding region of a specific gene may confer disease risk through regulating distal genes (act as regulatory variant for distal genes).

Proposal of Bacillus ciccensis Liu et al. as a Later Heterotypic Synonym of Cytobacillus solani (Liu et al.) Patel and Gupta Using Comparative Genomic Analysis.

Bacillus ciccensis and Cytobacillus solani were reported to belong to separate genomic species based on a polyphasic taxonomic approach. However, we found that type strains of B. ciccensis and C. solani should belong to the same genomic species based on the clustering patterns resulting from genome phylogenetic analysis. The average nucleotide identity and digital DNA-DNA hybridization values between the genomes of two type strains were 99.6% and 96.9%, respectively, much higher than 95 ~ 96% and 70% cut-off point proposed and generally accepted species boundary. This result was also supported by a comprehensive comparison of phenotypic characteristics between the two type strains. These results suggested that B. ciccensis and C. solani had the same taxonomic position. Consequently, we propose that B. ciccensis is a later heterotypic synonym of C. solani.

Steptomyces fagopyri sp. nov., a novel actinomycete isolated from rhizospheric soil of Fagopyrum dibotrys.

A novel actinomycete, designated strain QMT-28T, was isolated from rhizosphere soil of Fagopyrum dibotrys collected from Shuangfeng, Hunan Province, PR China. Strain QMT-28T grew well on International Streptomyces Project series media and formed well-developed, branched substrate hyphae and aerial mycelium that differentiated into loose spiral spore chains consisting of cylindrical spores with smooth surfaces. The diagnostic diamino acid was ll-diaminopimelic acid and the whole-cell sugars were galactose and glucose. The predominant fatty acids were C18 : 1 cis9, summed feature 6 (C18 : 2 cis 9,12/C18 : 0 a) and C16 : 0. The polar lipids included diphosphatidylglycerol, hydroxy phospatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides, phospholipids of unknown structure containing glucosamine and several unidentified phospholipids. The major menaquinones were MK-9, MK-9(H2), MK-9(H4), MK-9(H6) and MK-9(H8). The genome size of strain QMT-28T was about 8.7 Mbp with a G+C content of 71.2 mol%. Phylogenetic analysis showed that the novel strain was closely related to Streptomyces olivochromogenes DSM 40451T (99.5 % similarity), Streptomyces mirabilis NBRC 13450T (98.9 %), Streptomyces kanamyceticus NBRC 13414T (98.9 %), Streptomyces kaempferi I37T (98.9 %) and Streptomyces arcticus ZLN234T (98.8 %). However, the average nucleotide identity values, the digital DNA-DNA hybridization values and the multilocus sequence analysis evolutionary distances between this strain and closely related strains showed that it belonged to a distinct species. In addition, these results were also supported by differences in the phenotypic characteristics between QMT-28T and five closely related type strains. Consequently, strain QMT-28T should represent a novel species of the genus Streptomyces, with the suggested name Streptomyces fagopyri sp. nov. The type strain is QMT-28T (=CICC 24808T=JCM 33796T).