Noncanonical contribution of microglial transcription factor NR4A1 to post-stroke recovery through TNF mRNA destabilization.

Microglia-mediated neuroinflammation is involved in various neurological diseases, including ischemic stroke, but the endogenous mechanisms preventing unstrained inflammation is still unclear. The anti-inflammatory role of transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) in macrophages and microglia has previously been identified. However, the endogenous mechanisms that how NR4A1 restricts unstrained inflammation remain elusive. Here, we observed that NR4A1 is up-regulated in the cytoplasm of activated microglia and localizes to processing bodies (P-bodies). In addition, we found that cytoplasmic NR4A1 functions as an RNA-binding protein (RBP) that directly binds and destabilizes Tnf mRNA in an N6-methyladenosine (m6A)-dependent manner. Remarkably, conditional microglial deletion of Nr4a1 elevates Tnf expression and worsens outcomes in a mouse model of ischemic stroke, in which case NR4A1 expression is significantly induced in the cytoplasm of microglia. Thus, our study illustrates a novel mechanism that NR4A1 posttranscriptionally regulates Tnf expression in microglia and determines stroke outcomes.

c-Abl-induced Olig2 phosphorylation regulates the proliferation of oligodendrocyte precursor cells.

Oligodendrocytes (OLs), the myelinating cells in the central nervous system (CNS), are differentiated from OL progenitor cells (OPCs). The proliferation of existing OPCs is indispensable for myelination during CNS development and remyelination in response to demyelination stimulation. The transcription factor Olig2 is required for the specification of OLs and is expressed in the OL lineage. However, the post-translational modification of Olig2 in the proliferation of OPCs is poorly understood. Herein, we identified that c-Abl directly phosphorylates Olig2 mainly at the Tyr137 site, and that Olig2 phosphorylation is essential for OPC proliferation. The expression levels of c-Abl gradually decreased with brain development; moreover, c-Abl was highly expressed in OPCs. OL-specific c-Abl knockout at the developmental stage led to an insufficient proliferation of OPCs, a decreased expression of myelin-related genes, and myelination retardation. Accordingly, a c-Abl-specific kinase inhibitor suppressed OPC proliferation in vitro. Furthermore, we observed that OL-specific c-Abl knockout reduced OPC proliferation and remyelination in a cuprizone model of demyelination. In addition, we found that nilotinib, a clinically used c-Abl inhibitor, decreased the expression of myelin basic protein (Mbp) and motor coordination in mice, indicating a neurological side effect of a long-term administration of the c-Abl inhibitor. Thus, we identified the important role of c-Abl in OLs during developmental myelination and remyelination in a disease model.

Arthrobacter wenxiniae sp. nov., a novel plant growth-promoting rhizobacteria species harbouring a carotenoids biosynthetic gene cluster.

A bacterial strain, designated AETb3-4T was isolated from the rhizosphere of lily. Comparison of 16S rRNA gene sequences showed that the sequence from strain AETb3-4T exhibits high sequence similarity with those of Arthrobacter silviterrae KIS14-16T (97.9%), Arthrobacter livingstonensis LI2T (97.2%) and Arthrobacter stackebrandtii CCM 2783T (97.0%). Whole genome average nucleotide identity (ANI) and the digital DNA-DNA hybridization (dDDH) values between strain AETb3-4T and the reference strains A. silviterrae DSM 27180T, A. livingstonensis L12T and A. stackebrandtii DSM 16005T were below 83.6% and 27.7%, respectively, values which are considerably below the proposed thresholds for the species delineation, consistent with the proposal that strain AETb3-4T represents a novel species. The genome size of strain AETb3-4T is 4.33 Mb and the genomic DNA G + C content is 67.3%. The main polar lipids were identified as phosphatidylglycerol, diphosphatidylglycero, phosphatidylinositol and an unidentified glycolipid. The major fatty acids (> 10%) were identified as anteiso-C15: 0 and anteiso-C17: 0. The predominant menaquinone was found to be menaquinone 9 (MK-9) (H2) (82.2%). Phenotypic tests allowed the strain to be differentiated from its close phylogenetic neighbors. Based on the results obtained, it is proposed that the strain AETb3-4T (= CFCC 16390T = LMG 31708T) represents a novel species in the genus Arthrobacter, for which the names Arthrobacter wenxiniae sp. nov. is proposed. In addition, the novel strain AETb3-4T has multiple plant growth-promoting characters including ACC-deaminase activity and production of IAA. Furthermore, the genome contains secondary metabolite biosynthesis gene clusters, including a carotenoid biosynthetic gene cluster, suggesting potential capacities for secondary metabolite synthesis. These data suggest that strain AETb3-4T may have potential applications both in medicine and sustainable agriculture.

Hypoxia inducible factor-3α promotes osteosarcoma progression by activating KDM3A-mediated demethylation of SOX9.

Hypoxia/oxygen-sensing signally is closely associated with many tumor progressions, including osteosarcoma (OS). Previous research principally focused on the function of hypoxia-inducible factor (HIF)-1α and HIF-2α as the major hypoxia-associated transcription factors in OS, however, the role of HIF-3α has not been investigated. Our study found that HIF-3α was upregulated in OS tissues and cell lines. HIF-3α overexpression facilitated cell proliferation and invasion, and inhibited apoptosis, whereas HIF-3α knockdown showed the opposite results. Chromatin immunoprecipitation analysis revealed that lysine demethylase 3A (KDM3A) expression was transcriptionally activated by HIF-3α under hypoxia, and KDM3A occupied the SRY-box transcription factor 9 (SOX9) gene promoter region through H3 lysine 9 dimethylation (H3K9me2). Additionally, rescue results revealed that KDM3A or SOX9 overexpression reversed the effects of HIF-3α silence on cell functions. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway inhibitor cucurbitacin I suppressed the promotive effects of HIF-3α overexpression on cell proliferation, invasion and TAK2/STAT3 pathway. Finally, OS cell line MG-63 transfected with HIF-3α short hairpin RNA (HIF-3α shRNA) were subcutaneously injected into nude mice, and the results found that HIF-3α knockdown significantly inhibited the xenograft tumor growth of OS in vivo. In conclusion, this study reveals that HIF-3α promotes OS progression in vitro and in vivo by activating KDM3A-mediated SOX9 promoter demethylation, which may provide a potential therapeutic mechanism for OS.

Caulobacter endophyticus sp. nov., an endophytic bacterium harboring three lasso peptide biosynthetic gene clusters and producing indoleacetic acid isolated from maize root.

A novel Gram-stain-negative, aerobic and rod-shaped bacterium with a single polar flagellum or a stalk at the end of the cell, was isolated from maize roots in the Fangshan District of Beijing, People's Republic of China. The new strain designated 774T produced indole acetic acid (IAA). The 16S rRNA gene sequence analysis indicated that strain 774T belongs to the genus Caulobacter and is closely related to Caulobacter flavus RHGG3T, Caulobacter zeae 410Tand Caulobacter radices 695T, all with sequence similarities of 99.9%. The genome size of strain774T was 5.4 Mb, comprising 5042 predicted genes with a DNA G+C content of 68.7%.Three striking lasso peptide biosynthetic gene clusters and two IAA synthesis genes belonging to the TPM pathway were also found in the genome of strain 774T. The average nucleotide identity values and digital DNA-DNA hybridization values of the strain774T with its closely phylogenetic neighbours were less than 91.5% and 45.0%, respectively, indicating a new Caulobacter species. The major fatty acids of strain774T were identified as C16: 0 (27.7%), summed feature 3 (C16: 1ω6c and/or C16: 1ω7c) (12.6%) and summed feature 8 (C18: 1ω7c and/or C18: 1ω6c) (42.9%).The major polar lipids consisted of phosphatidyl-glycerol and glycolipids. The predominant ubiquinone was identified as Quinone 10. Based on the polyphasic characterization, strain 774T represents a novel species of the genus Caulobacter, for which the name Caulobacter endophyticus sp. nov. is proposed with 774T (= CGMCC 1.16558T = DSM 106777T) as the type strain.

Isolation and screening of stress-resistant endophytic fungus strains from wild and cultivated soybeans in cold region of China.

In this study, we firstly reported the large-scale screening and isolation of endophytic fungi from nine wild and six cultivated soybeans in the cold regions of China. We totally isolated 302 endophytic fungal strains, of which 215 strains are isolated from the wild soybeans and 87 are identified from cultivated soybeans. Among these endophytic fungal strains, in the roots, stems, and leaves, 24.17% were isolated from roots, 28.8% were isolated from stems, and 47.01% were isolated from leaves, respectively. Most endophytic fungal strains isolated from the wild soybean roots were the species of Fusarium genus, and the fungal strains in the stems were the species of ascomycetes and Fusarium fungi, whereas most strains in the leaves were Alternaria fungi. To analyze the taxonomy of the obtained samples, we sequenced and compared their rDNA internal transcribed spacer (ITS) sequences. The data showed that 6 strains are putatively novel strains exhibiting ≤ 97% homology with the known strains. We next measured the secondary metabolites produced by the different strains and we found 11 strains exhibited high-performance synthesis of triterpenoids, phenols, and polysaccharides. Furthermore, we characterized their tolerance to abiotic stresses. The results indicated that 4 strains exhibited high tolerance to cadmium, and some strains exhibited resistance to acid, and alkali. The results of the study could facilitate the further exploration of the diversity of plant endophytic fungi and the potential applications of the fungi to practical agriculture and medicine industries. KEY POINTS: • 302 endophytic fungal strains isolated from wild soybean and cultivated soybean • 11 strains had high contents of triterpenoids, phenols, and polysaccharides • 4 strains exhibited high Cd tolerance, and a few strains with strong tolerance to acid and alkali solution.

Paenibacillus apii sp. nov., a novel nifH gene-harbouring species isolated from the rhizospheres of vegetable plants grown in different regions of northern China.

Two nifH gene-harbouring bacterial strains were isolated from rhizospheres of different vegetable plants grown in different regions of northern PR China. The two strains possessed almost identical 16S rRNA gene sequences. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two strains were 99.21 and 93.6% respectively, suggesting they belong to one species. Based on 16S rRNA gene phylogeny, the two strains were clustered together with Paenibacillus rhizophilus 7197T, Paenibacillus sabinae T27T and Paenibacillus forsythiae T98T, but on a separate branch. Novelty of the species was confirmed by ANI and dDDH comparisons between the type strain 7124T and its closest relatives, since the obtained values were considerably below the proposed thresholds for the species delineation. The genome size of strain 7124T was 5.40 Mb, comprising 5050 predicted genes with a DNA G+C content of 52.3 mol%. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and three unidentified lipids. The major cellular fatty acids were anteiso-C15  :  0 (52.9%) and C16  :  0 (23.4 %). Menaquinone-7 was reported as the major respiratory quinone. The diamino acid in the cell-wall peptidoglycan was found to be meso-diaminopimelic acid. Based on phylogenetic, genomic, chemotaxonomic and phenotypic data, the two isolates are considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus apii sp. nov. is proposed, with 7124T (=DSM 103172T=CGMCC 1.15689T) as type strain.

Variovorax beijingensis sp. nov., a novel plant-associated bacterial species with plant growth-promoting potential isolated from different geographic regions of Beijing, China.

Two plant-associated bacterial strains were isolated from Beijing, China. The two strains possessed almost identical 16S rRNA gene sequences. However, REP-PCR fingerprint patterns discriminated that they were not from one clonal origin. The average nucleotide identity (ANI) value and the digital DNA-DNA hybridization (dDDH) value between the two strains were 99.4% and 94.7%, respectively, suggesting that they belonged to the same species. The 16S rRNA gene phylogeny analysis indicated that the two strains belonged to the genus Variovorax and were closely related to V. paradoxus NBRC 15149T and V. boronicumulans BAM-48T. Their phylogenetic relationship were confirmed in both phylogenetic trees constructed with house-keeping gene sequences and concatenated core genes of the genome. The ANI and dDDH comparisons among 502T and the most related type strains showed values below the accepted threshold for species discrimination. The genome sizes of strains 502T and T529 were 6.76 and 6.69 Mbp, respectively. The strain 502T had 6,227 predicted genes with DNA G+C content of 67.4 %. The respiratory quinone was ubiquinone-8 and the major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphospatidylglycerol. The major fatty acids of strain 502T were C10: 03-OH (26.2%), C16:0 (12.9%), C17:0 cyclo (14.5%) and summed feature 3 (21.4%). Furthermore, both strains showed the potential of plant growth promotion. Based on these results, the two isolates could be considered to represent a novel species of the genus Variovorax, for which the name Variovorax beijingensis sp. nov., is proposed, with 502T (= DSM 106862T = CGMCC 1.16560T) as the type strain.

Rhizobium rhizophilum sp. nov., an indole acetic acid-producing bacterium isolated from rape (Brassica napus L.) rhizosphere soil.

A novel Gram-stain-negative, aerobic, rod-shaped and indole acetic acid-producing strain, designated 7209-2T, was isolated from rhizosphere of rape (Brassica napus L.) grown in the Yakeshi City, Inner Mongolia, PR China. The 16S rRNA gene sequence analysis indicated that strain 7209-2T belongs to the genus Rhizobium and is closely related to Rhizobium rosettiformans W3T, Rhizobium ipomoeae shin9-1T and Rhizobium wuzhouense W44T with sequence similarities of 98.2, 98.1 and 97.9 %, respectively. Phylogenetic analysis based on concatenated housekeeping recA and atpD gene sequences showed that strain 7209-2T formed a group together with R. wuzhouense W44T and R. rosettiformans W3T, with sequences similarities of 92.6 and 91.1 %, respectively. The genome size of strain 7209-2T was 5.25 Mb, comprising 5027 predicted genes with a DNA G+C content of 61.2 mol%. The average nucleotide identity and digital DNA-DNA hybridization comparisons among 7209-2T and reference strains for the most closely related species showed values below the accepted threshold for species discrimination. The major fatty acids of strain 7209-2T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 2 (C12 : 0 aldehyde and/or unknown 10.953) . The major polar lipids were found to consist of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and an unidentified aminophospholipid. The predominant ubiquinone was identified as quinone 10. Based on all the above results, strain 7209-2T represents a novel species of the genus Rhizobium, for which the name Rhizobium rhizophilum sp. nov. is proposed with 7209-2T (=CGMCC 1.15691T=DSM 103161T) as the type strain.

Mesorhizobium rhizophilum sp. nov., a 1-aminocyclopropane-1-carboxylate deaminase producing bacterium isolated from rhizosphere of maize in Northeast China.

A novel 1-aminocyclopropane-1-carboxylate deaminase producing bacterium, Gram- stain-negative, aerobic, motile, rod-shaped strain designated YM1C-6-2T was isolated from rhizosphere of maize grown in Northeast China. The 16S rRNA gene sequence analysis indicated that strain YM1C-6-2T belongs to the genus Mesorhizobium and is closely related to Mesorhizobium alhagi CCNWXJ12-2T and M. camelthorni CCNWXJ40-4T with sequence similarities of 98.4% and 97.9%, respectively. Multilocus sequence analysis of other housekeeping genes revealed that the new isolates YM1C-6-2T forms a phylogenetically group with some species in the genus Mesorhizobium. The genome size of strain YM1C-6-2T was 5.51 Mb, comprising 5378 predicted genes with a DNA G+C content of 64.5%. The average nucleotide identity and digital DNA-DNA hybridization comparisons between YM1C-6-2T and the most related type strains showed values below the accepted threshold for species discrimination. The major fatty acids of strain YM1C-6-2T were C19:0 cyclo ω8c (47.5%), summed feature 8 (C18:1ω7c and/or C18:1ω6c) (19.5%) and C16:0 (15.1%), which differed from the closely related reference strains in their relative abundance. The major polar lipids consist of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and an unidentified aminophospholipid. The predominant ubiquinone was identified as Quinone 10. Phenotypic and biochemical analysis results indicated that strain YM1C-6-2T can be distinguished from closely related type strains. Based on the above results, strain YM1C-6-2T represents a novel species of the genus Mesorhizobium, for which the name Mesorhizobium rhizophilum sp. nov. is proposed with YM1C-6-2T (= CGMCC 1.15487T = DSM 101712T) as the type strain.

MiR-125a-5p inhibits the proliferation and invasion of breast cancer cells and induces apoptosis by targeting GAB2.

Objective: To investigate whether miR-125a-5p can inhibit the proliferation and invasion of breast cancer cells and induce apoptosis by targeting GAB2. Methods: qRT-PCR was used to detect the expression of miR-125a-5p in normal mammary epithelial cells and breast cancer cell lines; The miR-125a-5p overexpression plasmid was transiently transfected into MDA-MB-157 cells, and the proliferation, invasion and apoptosis of breast cancer cells were detected by CCK8 kit, Transwell chamber and flow cytometry, respectively; Gene silencing was used to knock down GAB2 gene in MDA-MB-157 cells, and the changes of proliferation, invasion, apoptosis and apoptosis-related proteins in breast cancer cells were detected by CCK8 kit, Transwell chamber, flow cytometry and western blot, respectively; The direct interaction between miR-125a-5p and GAB2 was detected by dual-luciferase reporter assay. The miR-125a-5p overexpression plasmid was transiently transfected into MDA-MB-157 cells, and the expression levels of GAB2 and apoptosis-related proteins were detected by western blot. Results: The expression of miR-125a-5p in breast cancer cell lines, MDA-MB-157 cells, MDA-MB-361 cells and MDA-MB-415 cells, was significantly lower than that in normal breast epithelial cells, MCF-10A cells; The proliferation and invasion ability of MDA-MB-157 cells transfected with miR-125a-5p were significantly inhibited, and the apoptosis rate was significantly increased; Since GAB2 knocked down, the proliferation and invasion ability of MDA-MB-157 cells were significantly inhibited, while the apoptosis rate was significantly increased, the Bax protein expression was significantly down-regulated, and the Bcl-2 protein expression was significantly up-regulated; The dual-luciferase reporter assay demonstrated that miR-125a-5p can specifically target GAB2. Transfected with miR-125a-5p, the GAB2 protein expression and Bax protein expression were significantly down-regulated, but the Bcl-2 protein expression was significantly up-regulated. Conclusion: miR-125a-5p inhibits the proliferation and invasion of breast cancer cells and induces their apoptosis by negatively regulating GAB2.

Paenibacillus rhizophilus sp. nov., a nitrogen-fixing bacterium isolated from the rhizosphere of wheat (Triticum aestivum L.).

A novel Gram-stain-variable, endospore-forming, motile, rod-shaped, facultative aerobic bacterium, designated 7197T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) collected from Yakeshi County, Inner Mongolia, PR China. This isolate was found to have the highest 16S rRNA gene sequence similarity to Paenibacillussabinae T27T (98.0 %), followed by Paenibacillussophorae S27T (97.9 %) and Paenibacillusforsythiae T98T (97.7 %). To ascertain the genomic relatedness of this strain to its phylogenetic neighbours, its genome sequence was determined. The average nucleotide identity values of genome sequences between the novel isolate and the type strains of related species P. sabinae T27T, P. sophorae S27T and P. forsythiae T98T were 87.9 %, 85.8 and 83.9 %, respectively. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids and one unidentified aminolipid. The major cellular fatty acids were anteiso-C15 : 0 (56.3 %), C16 : 0 (15.7 %) and iso-C15 : 0 (14.1 %).The genome size of strain 7197T was 5.21 Mb, comprising 4879 predicted genes with a DNA G+C content of 51.9 mol%. Menaquinone-7 was reported as the major respiratory quinone. The diamino acid in the cell-wall peptidoglycan was found to be meso-diaminopimelic acid. Based on phylogenetic, genomic, chemotaxonomic and phenotypic characteristics, strain 7197T was classified as a novel species within the genus Paenibacillus, for which the name Paenibacillus rhizophilus sp. nov. is proposed. The type strain of Paenibacillus rhizophilus is 7197T (=DSM 103168T=CGMCC 1.15699T).

Pantoea endophytica sp. nov., novel endophytic bacteria isolated from maize planting in different geographic regions of northern China.

Four endophytic bacterial strains were isolated from root, stem and leaf of maize planted in different regions of northern China. The four strains possessed almost identical 16S rRNA gene sequences. However, REP-PCR fingerprint patterns discriminated that they were not from one clonal origin. Furthermore, the average nucleotide identity (ANI) values among them were higher than 95%, suggesting they all belong to one species. Based on 16S rRNA gene phylogeny, the four strains were clustered together with Pantoea rodasii LMG 26273T and Pantoea rwandensis LMG 26275T, but on a separate branch. Multilocus sequence analysis (MLSA) indicated that the four strains form a novel Pantoea species. Authenticity of the novel species was confirmed by ANI comparisons between strain 596T and its closest relatives, since obtained values were considerably below the proposed thresholds for the species delineation. The genome size of 596T was 5.1Mbp, comprising 4896 predicted genes with DNA G+C content of 57.8mol%. The respiratory quinone was ubiquinone-8 (Q-8) and the polar lipid profile consisted of phosphatidylethanolamin, diphosphatidylglycerol, phosphatidylglycerol, unidentified aminophospholipid and unidentified phospholipid. The major fatty acids of strain 596T were C16:0, summed feature 2 (C12:0 aldehyde), summed feature 3 (C16:1ω7c and/or C16:1ω6c) and summed feature 8 (C18:1ω7c and/or C18:1ω6c). Based on phylogenetic, genomic, phenotypic and chemotaxonomic data, the four isolates are considered to represent a novel species of the genus Pantoea, for which the name Pantoea endophytica sp. nov., is proposed, with 596T (=DSM 100,785T=CGMCC 1.15280T) as type strain.

Assessment of Plant Growth Promoting and Abiotic Stress Tolerance Properties of Wheat Endophytic Fungi.

The aims of the present work were to isolate and characterize fungal endophytic communities associated with healthy wheat (Triticum aestivum L.) plants, collected from the North China. Segregated endophytes were screened for their PGP traits, abiotic stresses (heavy metals, salinity, drought, and temperature), and antibiotic sensitivity. A total of 16 endophytic fungi were isolated using the culture-dependent approach from different tissue parts of wheat plants. Based upon their internal transcribed spacer (ITS) rDNA gene sequencing, 15 out of 16 isolates were selected for further analysis. In the contemporary investigation, a number of the tested endophytes exhibited fairly good 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) (0.03±0.011 to 1.43±0.01 µmol α-KB mg-1 protein hr-1), indole acetic acid (IAA) (1.125±0.04 to36.12±0.004µgml-1), and phosphate solubilizing index (PSI) (2.08±0.03to5.16±0.36) activities. More than 30% isolates gave positive result for siderophore and ammonia tests, whereas all exhibited catalase activity but only 2 (582PDA1 and 582PDA11) produced hydrogen cyanide. Trichoderma strains showed salt, heavy metals, and drought tolerance at high levels and also exhibited resistance to all the tested antibiotics. Strain 582PDA4 was found to be the most temperature (55°C) tolerant isolate. The findings of this study indicated that the microbial endophytes isolated from wheat plants possessing a crucial function to improve plant growth could be utilized as biofertilizers or bioagents to establish a sustainable crop production system.

A novel m6A reader Prrc2a controls oligodendroglial specification and myelination.

While N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6A modification in mammalian glial development remains unknown. Here, we identify a novel m6A reader, Prrc2a (Proline rich coiled-coil 2 A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model. Further analyses reveal that Prrc2a is involved in oligodendrocyte progenitor cells (OPCs) proliferation and oligodendrocyte fate determination. Accordingly, oligodendroglial-lineage specific deletion of Prrc2a causes a similar phenotype of Nestin-Cre-mediated deletion. Combining transcriptome-wide RNA-seq, m6A-RIP-seq and Prrc2a RIP-seq analysis, we find that Olig2 is a critical downstream target gene of Prrc2a in oligodendrocyte development. Furthermore, Prrc2a stabilizes Olig2 mRNA through binding to a consensus GGACU motif in the Olig2 CDS (coding sequence) in an m6A-dependent manner. Interestingly, we also find that the m6A demethylase, Fto, erases the m6A modification of Olig2 mRNA and promotes its degradation. Together, our results indicate that Prrc2a plays an important role in oligodendrocyte specification through functioning as a novel m6A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases.

Caulobacter zeae sp. nov. and Caulobacter radicis sp. nov., novel endophytic bacteria isolated from maize root (Zea mays L.).

Four bacterial strains designated 410T, 441, 695T and 736 were isolated from maize root in Beijing, P. R. China. Based on 16S rRNA gene phylogeny, the four strains formed two clusters in the genus Caulobacter. Since strain 441 was a clonal variety of strain 410T, only three strains were selected for further taxonomic studies. The whole genome average nucleotide identity (ANI) value between strains 410T and 695T was 94.65%, and both strains shared less than 92.10% ANI values with their close phylogenetic neighbors Caulobacter vibrioides DSM 9893T, Caulobacter segnis ATCC 21756T and Caulobacter flavus CGMCC 1.15093T. Strains 410T and 695T contained Q-10 as the sole ubiquinone and their major fatty acids were C16:0, 11-methyl C18:1ω 0, 11-methyl C18: 1ω7c, summed feature 3 (C16:1ω7c and/or C16:1ω 1ω7c and/or C16: 1ω6c) and summed feature 8 (C18:1ω7c and/or C18:1ω 1ω7c and/or C18: 1ω6c). Their major polar lipids consisted of glycolipids and phosphatidylglycerol, and phenotypic tests differentiated them from their closest phylogenetic neighbors. Based on the results obtained, it is proposed that the three strains represent two novel species, for which the names Caulobacter zeae sp. nov. (type strain 410T=CGMCC 1.15991=DSM 104304) and Caulobacter radicis sp. nov. (type strain 695T=CGMCC 1.16556=DSM 106792) are proposed.

Rhizobium wenxiniae sp. nov., an endophytic bacterium isolated from maize root.

A novel Gram-stain-negative, aerobic, rod-shaped strain designated 166T was isolated from surface-sterilized root tissue of maize planted in the Fangshan District of Beijing, PR China. The 16S rRNA gene sequence analysis indicated that strain 166T belongs to the genus Rhizobium and is closely related to Rhizobium cellulosilyticum ALA10B2T and Rhizobium yantingense H66T with sequence similarities of 98.8 and 98.3 %, respectively. According to atpD and recA sequence analysis, the highest sequence similarity between strain 166T and R. cellulosilyticum ALA10B2T is 93.8 and 84.7 %, respectively. However, the new isolate exhibited relatively low levels of DNA-DNA relatedness with respect to R. cellulosilyticum DSM 18291T (20.8±2.3 %) and Rhizobium yantingense CCTCC AB 2014007T (47.2±1.4 %). The DNA G+C content of strain 166T was 59.8 mol%. The main polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, an unidentified aminophospholipid and an unidentified aminolipid. The major fatty acids of strain 166T were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The results of the physiological and biochemical tests and minor differences in the fatty acid profiles allowed a clear phenotypic differentiation of strain 166T from the type strains of closely related species, R. cellulosilyticum DSM 18291T and R. yantingense CCTCC AB 2014007T. Strain 166T represents a novel species within the genus Rhizobium, for which the name Rhizobium wenxiniae sp. nov. is proposed, with the type strain 166T (=CGMCC 1.15279T=DSM 100734T).

DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue.

DJ-1 protein is involved in multiple physiological processes, including Parkinson's disease. However, the role of DJ-1 in the metabolism is largely unknown. Here we found that DJ-1 maintained energy balance and glucose homeostasisvia regulating brown adipose tissue (BAT) activity. DJ-1-deficient mice reduced body mass, increased energy expenditure and improved insulin sensitivity. DJ-1 deletion also resisted high-fat-diet (HFD) induced obesity and insulin resistance. Accordingly, DJ-1 transgene triggered autonomous obesity and glucose intolerance. Further BAT transplantation experiments clarified DJ-1 regulates energy and glucose homeostasis by modulating BAT function. Mechanistically, we found that DJ-1 promoted PTEN proteasomal degradation via an E3 ligase, mind bomb-2 (Mib2), which led to Akt activation and inhibited FoxO1-dependent Ucp1 (Uncoupling protein-1) expression in BAT. Consistently, ablation of Akt1 mitigated the obesity and BAT dysfunction induced by DJ-1 transgene. These findings define a new biological role of DJ-1 protein in regulating BAT function, with an implication of the therapeutic target in the treatment of metabolic disorders.

Microbacterium zeae sp. nov., an endophytic bacterium isolated from maize stem.

A novel Gram-stain positive, aerobic, non-motile, non-spore-forming and rod-shaped strain designated 1204T was isolated from surface-sterilised stem tissue of maize planted in Fangshan District of Beijing, People's Republic of China. A polyphasic taxonomic study was performed on the new isolate. On the basis of 16S rRNA gene sequence similarity studies, this isolate belongs to the genus Microbacterium. High levels of 16S rRNA gene sequence similarity were found between strain 1204T and Microbacterium enclense NIO-1002T (98.8%) and Microbacterium proteolyticum RZ36T (98.4%) respectively. However, the DNA-DNA hybridization values between strain 1204T and its closely related species M. proteolyticum DSM 27100T and M. enclense DSM 25125T were 53.9 ± 1.6 and 20.9 ± 1.5% respectively. The DNA G+C content of strain 1204T was determined to be 68.0 mol%. The major fatty acids were found to consist of anteiso-C15:0 (37.6%), iso-C16:0 (28.6%) and anteiso-C17:0 (16.6%). The predominant menaquinone was MK-11 and the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified glycolipid and an unidentified lipid. The results of physiological and biochemical tests and minor differences in the fatty acid profiles allowed a clear phenotypic differentiation of strain 1204T from the closely related species in the genus Microbacterium. Thus, it was concluded that strain 1204T represents a novel species within the genus Microbacterium, for which the name Microbacterium zeae sp. nov. is proposed, with the type strain 1204T (= CGMCC 1.15289 = DSM 100750).