Lacticaseibacillus pabuli sp. nov., isolated from fermented cattle feed.

Strain BSF-3MT is a Gram-stain-positive, non-flagellated, facultative anaerobic and rod-shaped bacterium that was isolated from fermented feed collected at a cattle farm in the Daejeon region of the Republic of Korea. It was studied using polyphasic taxonomic methods. Using 16S rRNA gene sequences and the resulting phylogenetic tree, the strain was primarily identified as a member of the genus Lacticaseibacillus. Strain BSF-3MT contained a chromosome of 2.5 Mbp and a plasmid of 33.4 kbp. The G+C content of genomic DNA was 51.3 mol%. Strain BSF-3MT had the highest ortho-average nucleotide identity value of 73.7 % with Lacticaseibacillus songhuajiangensis 7-19T, its closest relative in the phylogenetic tree based on the 16S rRNA gene sequences and the phylogenomic tree based on up-to-date bacterial core genes. Based on the results of a polyphasic taxonomic study, strain BSF-3MT represents a novel species in the genus Lacticaseibacillus, for which the name Lacticaseibacillus pabuli sp. nov. is proposed. The type strain is BSF-3MT (=KACC 23028T=NBRC 116014T).

The Defined TLR3 Agonist, Nexavant, Exhibits Anti-Cancer Efficacy and Potentiates Anti-PD-1 Antibody Therapy by Enhancing Immune Cell Infiltration.

Nexavant was reported as an alternative to the TLR3 agonist of Poly(I:C) and its derivatives. The physicochemical properties, signaling pathways, anti-cancer effects, and mechanisms of Nexavant were investigated. The distinctive characteristics of Nexavant compared to that of Poly(I:C) were demonstrated by precise quantification, enhanced thermostability, and increased resistance to RNase A. Unlike Poly(I:C), which activates TLR3, RIG-I, and MDA5, Nexavant stimulates signaling through TLR3 and RIG-I but not through MDA5. Compared to Poly(I:C), an intratumoral Nexavant treatment led to a unique immune response, immune cell infiltration, and suppression of tumor growth in various animal cancer models. Nexavant therapy outperformed anti-PD-1 antibody treatment in all the tested models and showed a synergistic effect in combinational therapy, especially in well-defined cold tumor models. The effect was similar to that of nivolumab in a humanized mouse model. Intranasal instillation of Nexavant led to the recruitment of immune cells (NK, CD4+ T, and CD8+ T) to the lungs, suppressing lung metastasis and improving animal survival. Our study highlighted Nexavant's defined nature for clinical use and unique signaling pathways and its potential as a standalone anti-cancer agent or in combination with anti-PD-1 antibodies.

Five novel Hymenobacter species isolated from air: Hymenobacter cellulosilyticus sp. nov., Hymenobacter cellulosivorans sp. nov., Hymenobacter aerilatus sp. nov., Hymenobacter sublimis sp. nov. and Hymenobacter volaticus sp. nov.

Five Hymenobacter strains isolated from air samples collected from the Suwon and Jeju regions of the Republic of Korea were studied using polyphasic taxonomic methods. Using 16S rRNA gene sequences and the resulting phylogenetic tree, the strains were primarily identified as members of the genus Hymenobacter. Digital DNA-DNA hybridization values and average nucleotide identities values for species delineation (70 and 95-96 %, respectively) between the five strains and their nearest type strains indicated that each strain represented a novel species. All strains were aerobic, Gram-stain-negative, mesophilic, rod-shaped and catalase- and oxidase-positive, with red to pink coloured colonies. The genome sizes of the five strains varied from 4.8 to 7.1 Mb and their G+C contents were between 54.1 and 59.4 mol%. Based on their phenotypic, chemotaxonomic and genotypic characteristics, we propose to classify these isolates into five novel species within the genus Hymenobacter for which we propose the names, Hymenobacter cellulosilyticus sp. nov., Hymenobacter cellulosivorans sp. nov., Hymenobacter aerilatus sp. nov., Hymenobacter sublimis sp. nov. and Hymenobacter volaticus sp. nov., with strains 5116 S-3T (=KACC 21925T=JCM 35216T), 5116 S-27T (=KACC 21926T=JCM 35217T), 5413 J-13T (=KACC 21928T=JCM 35219T), 5516 S-25T (=KACC 21931T=JCM 35222T) and 5420 S-77T (=KACC 21932T=JCM 35223T) as the type strains, respectively.

A phase Ia/Ib study of novel anti-ErbB3 monoclonal antibody, barecetamab (ISU104) in refractory solid cancers and monotherapy or in combination with cetuximab in recurrent or metastatic head and neck cancer.

We evaluated the safety, tolerability, pharmacokinetics and antitumor activity of barecetamab monotherapy and combination cetuximab therapy in patients with advanced solid cancers, especially head and neck cancer (HNC). Part 1 was a 3 + 3 dose-escalation study in which 15 patients received barecetamab at 1, 3, 5, 10 and 20 mg/kg intravenously (IV) on days 1 and 28 and weekly in patients with advanced solid cancer. Part 2 was a dose-expansion study including two patient groups with advanced HNC, including six patients receiving barecetamab at 20 mg/kg IV every 3 weeks and 12 patients receiving barecetamab and cetuximab (400 mg/m2 on day 1 followed by 250 mg/m2 every week). No dose-limiting toxicities (DLTs) were observed. Maximum serum target engagement was reached with trough levels of doses ≥3 mg/kg IV weekly. Common adverse drug reactions were diarrhea, stomatitis, dermatitis acneiform and decreased appetite. One durable complete response of more than 17 months was observed, and the overall response and disease control rates were 36.4% (4/11) and 81.1% (9/11), respectively, in the combination therapy group. In conclusion, DLT was not observed in barecetamab at 1 to 20 mg/kg. The recommended phase II dose was determined to be 20 mg/kg triweekly. Barecetamab and in cetuximab combination was well tolerated and demonstrated meaningful antitumor effects.

Transcriptomic Analysis of Heat Stress Response in Brassica rapa L. ssp. pekinensis with Improved Thermotolerance through Exogenous Glycine Betaine.

Chinese cabbage (Brassica rapa L. ssp. pekinensis) is sensitive to high temperature, which will cause the B. rapa to remain in a semi-dormancy state. Foliar spray of GB prior to heat stress was proven to enhance B. rapa thermotolerance. In order to understand the molecular mechanisms of GB-primed resistance or adaptation towards heat stress, we investigated the transcriptomes of GB-primed and non-primed heat-sensitive B. rapa 'Beijing No. 3' variety by RNA-Seq analysis. A total of 582 differentially expressed genes (DEGs) were identified from GB-primed plants exposed to heat stress relative to non-primed plants under heat stress and were assigned to 350 gene ontology (GO) pathways and 69 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. The analysis of the KEGG enrichment pathways revealed that the most abundantly up-regulated pathways were protein processing in endoplasmic reticulum (14 genes), followed by plant hormone signal transduction (12 genes), ribosome (8 genes), MAPK signaling pathway (8 genes), homologous recombination (7 genes), nucleotide excision repair metabolism (5 genes), glutathione metabolism (4 genes), and ascorbate and aldarate metabolism (4 genes). The most abundantly down-regulated pathways were plant-pathogen interaction (14 genes), followed by phenylpropanoid biosynthesis (7 genes); arginine and proline metabolism (6 genes); cutin, suberine, and wax biosynthesis (4 genes); and tryptophan metabolism (4 genes). Several calcium sensing/transducing proteins, as well as transcription factors associated with abscisic acid (ABA), salicylic acid (SA), auxin, and cytokinin hormones were either up- or down-regulated in GB-primed B. rapa plants under heat stress. In particular, expression of the genes for antioxidant defense, heat shock response, and DNA damage repair systems were highly increased by GB priming. On the other hand, many of the genes involved in the calcium sensors and cell surface receptors involved in plant innate immunity and the biosynthesis of secondary metabolites were down-regulated in the absence of pathogen elicitors in GB-primed B. rapa seedlings. Overall GB priming activated ABA and SA signaling pathways but deactivated auxin and cytokinin signaling pathways while suppressing the innate immunity in B. rapa seedlings exposed to heat stress. The present study provides a preliminary understanding of the thermotolerance mechanisms in GB-primed plants and is of great importance in developing thermotolerant B. rapa cultivars by using the identified DEGs through genetic modification.

Spirosoma oryzicola sp. nov., isolated from dried rice husk.

Strain RHs26T is an aerobic, Gram-stain-negative, non-flagellated and rod- or filamentous-shaped (1.0-1.1×2.3-50 µm) bacterium that was isolated from dried rice husk. It was positive for oxidase and catalase, hydrolysed starch and Tween 80, and weakly hydrolysed CM-cellulose. The strain grew at temperatures between 10 and 37 °C (optimum, 28 °C), in 0-1 % NaCl (optimum, 0 %) and at pH 6.0-9.0 (optimum, pH 7.0-8.0). The predominant membrane fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 1 ω5c, iso-C15 : 0 and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, an unidentified aminolipid, two unidentified aminophospholipids and two unidentified lipids. The predominant quinone was menaquinone MK-7. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain RHs26T belongs to the genus Spirosoma, presenting the highest sequence similarity to Spirosoma agri S7-3-3T (95.8 %). The genomic DNA G+C content of strain RHs26T was 49.5 %. Strain RHs26T showed the highest orthologous average nucleotide identity (OrthoANI) and digital DNA-DNA hybridization (dDDH) values of 76.4 % and 20.0 % with S. agri KCTC 52727T while sharing OrthoANI and dDDH values of 74.6 % and 19.2 % with Spirosoma terrae KCTC 52035T, the closest relative in the phylogenomic tree. Based on the results of a polyphasic taxonomic study, strain RHs26T represents a novel species in the genus Spirosoma, for which the name Spirosoma oryzicola sp. nov. is proposed. The type strain is RHs26T (=JCM 35224T=KACC 17318T).

Glutamic Acid and Poly-γ-glutamic Acid Enhanced the Heat Resistance of Chinese Cabbage (Brassica rapa L. ssp. pekinensis) by Improving Carotenoid Biosynthesis, Photosynthesis, and ROS Signaling.

Heat stress is one of the most common agrometeorological risks in crop production in the middle and lower reaches of the Yangtze River in China. This study aimed to investigate whether glutamic acid (Glu) or poly-γ-glutamic acid (γ-PGA) biostimulants can improve the thermotolerance of a cool-season Chinese cabbage (Brassica rapa L. ssp. pekinensis) crop. Priming with Glu (2.0 mM) or γ-PGA (20 mg·L-1) was conducted at the third leaf stage by applying as daily foliar sprays for 5 days before 5 days of heat stress (45 °C in 16-h light/35 °C in 8-h dark). Coupled with morpho-physiological and biochemical analyses, transcriptomes of Glu or γ-PGA-primed Chinese cabbage under heat stress were examined by RNA-seq analysis. The results showed that the thermotolerance conferred by Glu and γ-PGA priming was associated with the increased parameters of vegetative growth, gas exchange, and chlorophyll fluorescence. Compared with the control, the dry weights of plants treated with Glu and γ-PGA increased by 51.52% and 39.39%, respectively. Glu and γ-PGA application also significantly increased the contents of total chlorophyll by 42.21% and 23.12%, and carotenoid by 32.00% and 24.00%, respectively. In addition, Glu- and γ-PGA-primed plants markedly inhibited the levels of malondialdehyde, electrolyte leakage, and super-oxide anion radical, which was accompanied by enhanced activity levels of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POD). Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) categories within the differentially expressed genes (DEGs) functional clusters of RNA-seq data indicated that the expression levels of the genes for DNA replication, DNA repair system, linoleic acid metabolism, cysteine and methionine metabolism, glutathione metabolism, purine and pyrimidine metabolism, carotenoid biosynthesis, and plant-pathogen interaction were commonly up-regulated by both Glu and γ-PGA priming. Glu treatment enhanced the expression levels of the genes involved in aliphatic glucosinolate and 2-oxocarboxylic acid, while γ-PGA treatment activated carotenoid cleavage reaction to synthesize abscisic acid. Taken together, both Glu and γ-PGA have great potential for the preadaptation of Chinese cabbage seedlings to heat stress, with Glu being more effective than γ-PGA.

Cohnella herbarum sp. nov., isolated from wild grass fermentation broth.

A novel strictly aerobic, Gram-stain-positive, rod-shaped, motile, endospore-forming, white-coloured bacterium, designated strain MFER-1T, was isolated from a fermented liquor of wild grasses sampled in the Republic of Korea. The respiratory quinone of strain MFER-1T was menaquinone-7 and its major cellular fatty acids were anteiso-C15 : 0 (55.3 %), iso-C16 : 0 (17.5 %) and C16 : 0 (12.1 %). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids and an unidentified phospholipid. The 16S rRNA gene sequence of strain MFER-1T showed similarity of 98.1 % to 'Cohnella cholangitidis' 1 605-214T and below 98.0 % sequence similarity to the other Cohnella species. The phylogenomic tree indicated that strain MFER-1T formed a reliable cluster with several Cohnella species. The estimated genome size of strain MFER-1T was 8.52 Mb. Genomic DNA G+C content was 50.7mol%. The orthologous average nucleotide identity, digital DNA-DNA hybridization and amino acid identity values of strain MFER-1T with the most closely related species 'Cohnella cholangitidis' 1 605-214T were 78.7, 23.0 and 79.6 %, respectively. Based on the phenotypic, chemotaxonomic and phylogenetic results, strain MFER-1T should represent a novel species of the genus Cohnella, for which the name Cohnella herbarum sp. nov. is proposed, with strain MFER-1T (=KACC 21 257T=NBRC 114 628T) as the type strain.

Role of melatonin in promoting plant growth by regulating carbon assimilation and ATP accumulation.

Melatonin (MT) is a phytohormone important in mediating diverse plant growth processes. In this study, we performed transcriptomic, qRT-PCR, physiological and biochemical analyses of Brassica rapa seedlings in order to understand how MT promotes plant growth. The results showed that exogenous MT increased the rate of cyclic electron flow around photosystem (PS) I, fluorescence quantum yield, and electron transport efficiency between PSII and PSI to promote the vegetative growth of B. rapa seedlings without affecting oxidative stress level, as compared to control. However, MT treatment significantly reduced photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs) by 2.25-, 1.23- and 3.50-fold at 0.05 level, respectively. This occurred in parallel with the down-regulation of the genes for carbon fixation in photosynthetic organisms in a KEGG pathway enrichment. More accelerated plant growth despite the reduced photosynthesis rate and the enhanced electron transport rate suggested that NADPH and adenosine triphosphate (ATP) were preferentially diverted into other anabolic reactions than the Calvin cycle upon MT application. MT treatment increased ATP level and facilitated carbon assimilation into primary metabolism that led to a significant enhancement of soluble protein, sucrose, and fructose, but a significant decrease in glucose content. MT-induced carbon assimilation into primary metabolism was driven by up-regulation of the genes for glutathione metabolism, Krebs cycle, ribosome, and DNA replication in a KEGG pathway enrichment, as well as down-regulation of the genes for secondary metabolites. Our results provide an insight into MT-mediated metabolic adjustments triggered by coordinate changes in a wide range of gene expression profiles to help improve the plant functionality.

Spirosoma rhododendri sp. nov., isolated from a flower of royal azalea (Rhododendron schlippenbachii).

A Gram-negative, non-motile, strictly aerobic and rod- or filamentous-shaped strain, CJU-R4T, was isolated from a flower of royal azalea (Rhododendron schlippenbachii) collected in the Republic of Korea. Strain CJU-R4T was catalase-positive and oxidase-negative, and grew at 15-33 °C (optimum, 28-20 °C), at pH 5.0-8.0 (optimum, pH 7.0-8.0), and in the presence of 0-1 % NaCl (w/v; optimum, 0 %). Strain CJU-R4T had the highest 16S rRNA gene sequence similarity to Spirosoma oryzae RHs22T (96.6 %), revealing less than 93 % sequence similarity to other type strains. Phylogenetic and phylogenomic analysis also revealed strain CJU-R4T formed a robust cluster with S. oryzae RHs22T. The major fatty acids were summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c; 33.0 %), C16 : 1 ω5c (22.1 %), iso-C15 : 0 (12.6 %) and C16 : 0 (10.7 %). The polar lipids were composed of phosphatidylethanolamine, three unidentified aminophospholipids, one unidentified phospholipid and four unidentified lipids. Menaquinone-7 was detected as the sole respiratory quinone. The genomic DNA G+C content was 55.2 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain CJU-R4T and Spirosoma oryzae DSM 28354T were 81.5 and 23.9 %, respectively. Based on the results of the phenotypic and genotypic analyses, strain CJU-R4T is considered to represent a novel species of the genus Spirosoma, for which the name Spirosoma rhododendri sp. nov. is proposed. The type strain is CJU-R4T (=KACC 21264T=NBRC 114513T).

Blue mold rot caused by Penicillium expansum on Polygonatum odoratum var. pluriflorum.

Polygonatum odoratum var. pluriflorum, called "Dunggulle", is cultivated in East Asia to obtain rhizomes. In Korea and China, these rhizomes are used in traditional teas, health beverages, and herbal medicines (Zhao and Li, 2015). In 2019, Dunggulle was cultivated in 47 hectares, with an annual output of 120M/T in Korea. In November 2020, Dunggulle rhizomes with symptoms of blue mold rot were observed at a Dunggulle farm storage (36°06'01''N, 127°29'20''E) in Geuman, Korea, where the temperature ranged from 9 to 13°C, with an average humidity of 70%. The disease incidence was 2 to 3% out of 200 rhizomes across all markets surveyed. The disease begins with a greenish blue mold covering the rhizome surface (30 to 60%), followed by rhizome rot with a dark brown color as the disease progresses. Leading edges of the rotten rhizome pieces were sterilized with 1% NaOCl and 70% ethanol and placed on MEA (Malt Extract Agar) with penicillin G and streptomycin (both 50 µg/mL). After 7 days of incubation at 25°C, greenish-blue colonies appeared, from which a monospore was isolated. A representative isolated strain was deposited in the Korean Agricultural Culture Collection (KACC, Wanju, Korea) with Acc. No. KACC 49832. The strain grew slowly on MEA at 25°C (8 to 18 mm diam. after 7 days), producing greenish blue conidia. The conidiophores were hyaline and mostly terverticillate; the branches were appressed against the main axis; the stipes were smooth-walled; and the metulae were cylindrical, 10 to 13 × 2.7 to 3.2 µm, with 6 to 10 flask-shaped phialides, measured 9 to 12 × 2.7 to 3.1 µm. The conidia were globose or subglobose and 2.8 to 4.1 µm diam. These morphological characteristics fit well with the description of Penicillium expansum (Frisvad & Samson, 2004). Genomic DNA was extracted from the mycelia of the KACC 49832 MEA plate. ITS rDNA, beta-tubulin (BenA), and calmodulin (CaM) gene regions were sequenced for identification (Houbraken et al., 2020), and the rsulting sequences were deposited in GenBank (Acc. Nos. MZ189258, MZ226688, and MZ226689, respectively). Comparison with the GenBank sequences revealed that the Korean isolate was highly similar to P. expansum (ITS rDNA 99.8%, BenA 98.6%, and CaM 97.8%). Phylogenetic results based on the maximum-likelihood analysis revealed that KACC 49832 was grouped with P. expansum. To demonstrate pathogenicity, 10 µL of conidial suspension (1.3 × 105 conidia/mL) was dropped on the surface of three Dunggulle rhizomes scratched with a syringe needle. For the control, sterile water was applied on three control rhizomes. All rhizomes were surface-sterilized as referred above before being sprayed and dried. All inoculated and control rhizomes were kept in incubator at 25°C and 90-95% relative humidity. After a week, the inoculated points showed symptoms similar to those of the initial infection, whereas controls remained symptomless. The re-isolated fungus matched KACC 49832 based on morphological and sequence analyses, thereby fulfilling Koch's postulates. The experiment was performed three times. To our knowledge, this is the first report of P. expansum as a Dunggulle rhizome pathogen in Korea. As this pathogen is known to produce patulin, a carcinogenic fungal metabolite, further studies on the mycotoxicity of the infected rhizomes are required. This report might help manage the storage conditions of Dunggulle rhizomes to prevent the blue mold rot.

Anti-inflammatory spiroditerpenoids from Penicillium bialowiezense.

Inflammation is a vital process that maintains tissue homeostasis. However, it is widely known that uncontrolled inflammation can contribute to the development of various diseases. This study aimed to discover anti-inflammatory metabolites from Penicillium bialowiezense. Seven spiroditerpenoids, including two new compounds, breviones P and Q (1 and 2), were isolated and characterized by various spectroscopic and spectrometric methods. All isolated compounds were initially tested for their inhibitory effects against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages. Of these, brevione A (3) exhibited this activity with a half-maximal inhibitory concentration value of 9.5 µM. Further mechanistic studies demonstrated that 3 could suppress the expression of pro-inflammatory cytokines and mediators, such as NO, prostaglandin E2, interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, and IL-12 by inhibiting the activation of nuclear factor-kappa B and c-Jun N-terminal kinase.

Melatonin elevated Sclerotinia sclerotiorum resistance via modulation of ATP and glucosinolate biosynthesis in Brassica rapa ssp. pekinensis.

Sclerotinia stem rot is a common disease found in Brassica rapa that is caused by the necrotic plant pathogen Sclerotinia sclerotiorum. Melatonin (MT) has known biological activity and effectively relieved this type of Sclerotinia stem rot in B. rapa. To better understand the mechanisms behind MT-induced S. sclerotiorum resistance in B. rapa, we performed both proteomic and metabolomic analysis. Our results showed that during S. sclerotiorum infection, thiamine synthesis was activated and defended against it. In infected leaves, ribosomal synthesis-related proteins responded positively to MT treatment. Integrated proteomic and metabolomic analysis showed that amino acid metabolism was activated by MT treatment. After MT treatment, adenosine-triphosphate (ATP) content and the activity of antioxidant enzymes were both increased in B. rapa infected leaves. Cysteine synthase, sulfur transfer-related proteins, and glucosinolate (GS) were all increased after MT treatment in infected B. rapa leaves. Taken together, these results indicated that B. rapa leaves promoted thiamine formation to defend against S. sclerotiorum infection. Moreover, MT helped further induce antioxidant activation in B. rapa in an ATP-dependent manner and stimulating GS biosynthesis to well inhibit the S. sclerotiorum infection. SIGNIFICANCE: Melatonin (MT) has biological activity and effectively relieved the Sclerotinia stem rot of Brassica rapa caused by the necrotic plant pathogen Sclerotinia sclerotiorum. In order to reveal the molecular mechanisms of MT-induced S. sclerotiorum resistance in B. rapa, comprehensive proteomic and metabolomic analyses were conducted. The integration analysis of omic-data illustrated that the modulation of ATP and glucosinolate biosynthesis induced by MT administration helped to defend the infection of S. sclerotiorum in B. rapa. Our results will provide insights into MT-induced anti-fungal mechanism and therapeutic strategies to mitigate Sclerotinia stem rot of B. rapa, thereby increasing plant yield and decreasing economic losses.

A Novel Therapeutic Anti-ErbB3, ISU104 Exhibits Potent Antitumorigenic Activity by Inhibiting Ligand Binding and ErbB3 Heterodimerization.

ErbB3, a member of the ErbB receptor family, is a potent mediator in the development and progression of cancer, and its activation plays pivotal roles in acquired resistance against anti-EGFR therapies and other standard-of-care therapies. Upon ligand (NRG1) binding, ErbB3 forms heterodimers with other ErbB proteins (i.e., EGFR and ErbB2), which allows activation of downstream PI3K/Akt signaling. In this study, we developed a fully human anti-ErbB3 antibody, named ISU104, as an anticancer agent. ISU104 binds potently and specifically to the domain 3 of ErbB3. The complex structure of ErbB3-domain 3::ISU104-Fab revealed that ISU104 binds to the NRG1 binding region of domain 3. The elucidated structure suggested that the binding of ISU104 to ErbB3 would hinder not only ligand binding but also the structural changes required for heterodimerization. Biochemical studies confirmed these predictions. ISU104 inhibited ligand binding, ligand-dependent heterodimerization and phosphorylation, and induced the internalization of ErbB3. As a result, downstream Akt phosphorylation and cell proliferation were inhibited. The anticancer efficacy of ISU104 was demonstrated in xenograft models of various cancers. In summary, a highly potent ErbB3 targeting antibody, ISU104, is suitable for clinical development.

Anti-inflammatory Metabolites from Chaetomium nigricolor.

Twelve metabolites were obtained from the culture media of Chaetomium nigricolor, including a new furan derivative, methyl succinyl Sumiki's acid (1), and two new atropisomers of the previously reported bis-naphtho-γ-pyrones, (aS)-asperpyrone A and (aS)-fonsecinone A (2 and 3). The structures were elucidated by spectroscopic, chemical, and chiroptical techniques. Compounds 2 and 3 inhibited nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compound 2 was found to inhibit nuclear factor-kappa B and c-Jun N-terminal kinase activation, in turn suppressing pro-inflammatory mediators and cytokines including nitric oxide, prostaglandin E2, interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, and IL-12.

Comparative genomics of Lactobacillus species as bee symbionts and description of Lactobacillus bombintestini sp. nov., isolated from the gut of Bombus ignitus.

The Lactobacillus genus is widely used for fermentation of plant materials and dairy products. These species are typically found in highly specialized environments, with the bee gut serving as one of the niche locations in which Lactobacillus is detected. Lactobacillus species isolated from the bee gut and bee-related habitats were phylogenetically classified into three distinct groups, Lactobacillus kunkeei, Firm-4, and Firm-5. The L. kunkeei group was clearly differentiated from other members of the Lactobacillus buchneri group isolated from non-bee habitats. In comparison with non-bee members of the L. buchneri group, three bee-symbiotic Lactobacillus groups had a small-sized genome with low G + C content and showed a sharp reduction in the number of genes involved in energy production, carbohydrate transport and metabolism, and amino acid transport and metabolism. In addition, all three groups lacked the mutY gene, which encodes A/G-specific adenine glycosylase. The phylogenetic dendrogram based on the presence or absence of 1,199 functional genes indicated that these bee-symbiotic groups experienced convergent evolution. The occurrence of convergent evolution is thought to stem from the three bee-symbiotic groups sharing a similar habitat, i.e., the bee gut. The causative factor underlying genomic reduction was postulated to be mutY, which was absent in all three groups. Here, a novel strain, BHWM-4T, isolated from the gut of Bombus ignites was studied using polyphasic taxonomy and classified as a new member of the L. kunkeei group. The strain was Gram-positive, facultative anaerobic, and rod-shaped. The 16S ribosomal RNA gene sequence and genome analysis revealed that strain BHWM-4T was clustered into the L. kunkeei group, forming a compact cluster with L. kunkeei and Lactobacillus apinorum. Biochemical, chemotaxonomic, and genotypic data of strain BHWM-4T supports the proposal of a novel species, Lactobacillus bombintestini sp. nov., whose type strain is BHWM-4T (= KACC 19317 = NBRC 113067T).

Xylanimonas allomyrinae sp. nov. isolated from the gut of larva of Allomyrina dichotoma, reclassification of Xylanibacterium ulmi as Xylanimonas ulmi comb. nov. and Xylanimicrobium pachnodae as Xylanimonas pachnodae comb. nov., and emendation of the genus Xylanimonas.

A bacterium that was Gram-staining-positive, facultatively anaerobic, non-motile, rod- or filamentous-shaped, designated as strain 2JSPR-7T, was isolated from a gut of larvae of Allomyrina dichotoma which were raised at the National Institute of Agricultural Sciences, Wanju-gun, Republic of Korea. 2JSPR-7T had the highest 16S rRNA gene sequence similarity to Xylanibacterium ulmi XIL08T (98.1 %), Xylanimicrobium pachnodae NBRC 107786T (97.8 %) and Xylanimonas cellulosilytica DSM 15894T (97.5 %). Optimum growth conditions were at 28-30 °C, pH 7-8 and 0 % salt concentration. The cellular fatty acids mainly consisted of anteiso-C15 : 0, C14 : 0 and C16 : 0. The polar lipids were diphosphatidylglycerol, four unidentified phospholipids and two unidentified glycophospholipids. The major menaquinones were MK-8(H4) and MK-9(H4). The peptidoglycan structure was suggested to be the type A3α (A11.14) l-Lys-l-Ser with the presence of d-Ala, l-Ala, d-Glu, l-Ser and l-Lys. Whole cell sugars were rhamnose, ribose and glucose. The DNA G+C content was 72.7 mol%. We encountered difficulty in selecting a suitable genus to accommodate strain 2JSPR-7T from any of the genera Xylanimonas, Xylanimicrobium and Xylanibacterium based on the polyphasic approach including phylogenetic and phenotypic characterization. Therefore, it is proposed to combine the genera Xylanimicrobium and Xylanibacterium with the genus Xylanimonas considering the priority of publication and to classify strain 2JSPR-7T in the genus as Xylanimonas allomyrinae sp. nov. The type strain of the novel species is 2JSPR-7T (=KACC 19330T=NBRC 113052T). In addition, the description of the genus Xylanimonas is emended, and Xylanibacterium ulmi and Xylanimicrobium pachnodae are reclassified as Xylanimonas ulmi comb. nov. and Xylanimonas pachnodae comb. nov., respectively.

Lactococcus allomyrinae sp. nov., isolated from gut of larvae of Allomyrina dichotoma.

Strain 1JSPR-7T, a facultatively anaerobic bacterium isolated from the gut of larvae of Allomyrina dichotoma raised in Wanju-gun, Republic of Korea, was characterized using a polyphasic approach. Comparative analysis of 16S rRNA gene and rpoB gene sequences showed that strain 1JSPR-7T fell within the genus Lactococcus, forming a compact cluster with the type strain of four subspecies of Lactococcus lactis and Lactococcus taiwanensis. The 16S rRNA gene sequence of strain 1JSPR-7T revealed the highest homology with L. lactissubsp. lactis JCM 5805T (97.3 %) and L. lactissubsp. hordniae NBRC 100931T (97.1 %), and the rpoB gene sequence showed the highest similarity to L. lactissubsp. cremoris DSM 20069T (91.4 %) and L. lactissubsp. tructae L105T (91.4 %). The average nucleotide identity and digital DNA-DNA hybridization values indicated that strain 1JSPR-7T was a novel species of the genus Lacococcus. The major fatty acids (>10 % of the total fatty acids) were summed feature 7 (unknown 18.846, C19 : 1ω6c and/or C19 : 0cyclo ω10c), C16 : 0 and C14 : 0, and the predominant menaquinone was MK-8 with MK-7 as a minor one. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and three unidentified glycolipids with diphosphatidylglycerol as the major one. The cell-wall peptidoglycan was of the A4α type with an interpeptide bridge comprising l-Lys-d-Asp. The DNA G+C content based on the whole genome sequences was 37.4 mol%. Based on the data obtained, strain 1JSPR-7T represents a novel species of the genus Lactococcus, for which the name Lactococcusallomyrinae sp. nov. is proposed. The type strain is 1JSPR-7T (=KACC 19319T=NBRC 113068T).

Controlling aflatoxin contamination and propagation of Aspergillus flavus by a soy-fermenting Aspergillus oryzae strain.

Aflatoxins (AFs) are a group of carcinogenic and immunosuppressive mycotoxins that threaten global food safety. Globally, over 4.5 billion people are exposed to unmonitored levels of AFs. Aspergillus flavus is the major source of AF contamination in agricultural crops. One approach to reduce levels of AFs in agricultural commodities is to apply a non-aflatoxigenic competitor, e.g., Afla-Guard, to crop fields. In this study, we demonstrate that the food fermenting Aspergillus oryzae M2040 strain, isolated from Korean Meju (a brick of dry-fermented soybeans), can inhibit aflatoxin B1 (AFB1) production and proliferation of toxigenic A. flavus in lab culture conditions and peanuts. In peanuts, 1% inoculation level of A. oryzae M2040 could effectively displace the toxigenic A. flavus and inhibit AFB1 production. Moreover, cell-free culture filtrate of A. oryzae M2040 effectively inhibited AFB1 production and A. flavus growth, suggesting A. oryzae M2040 secretes inhibitory compounds. Whole genome-based comparative analyses indicate that the A. oryzae M2040 and Afla-Guard genomes are 37.9 and 36.4 Mbp, respectively, with each genome containing ~100 lineage specific genes. Our study establishes the idea of using A. oryzae and/or its cell-free culture fermentate as a potent biocontrol agent to control A. flavus propagation and AF contamination.

Ottowia oryzae sp. nov., isolated from Andong sikhye, a Korean traditional rice beverage.

A Gram-stain-negative, non-spore-forming, non-motile, short-rod-shaped bacterial strain, designated KADR8-3T, isolated from Andong sikhye in Andong-si, Gyeongsangbuk-do, Republic of Korea, was characterized using a polyphasic approach. On the basis of morphological, genetic and chemotaxonomic characteristics, it was determined to belong to the genus Ottowia. The phylogenetic similarity based on the 16S rRNA gene sequences indicated the strain formed a clade with Ottowia beijingensis GCS-AN-3T, Ottowia thiooxydans DSM 14619T, Ottowia pentelensis RB3-7T and 'Ottowia shaoguanensis' J5-66T, showing the highest similarity to O. beijingensis GCS-AN-3T (96.3 %). The major fatty acids were C16 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c). The predominant respiratory quinone was Q-8. The polar lipids present were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, two unidentified aminolipids and two unidentified lipids. The genomic DNA G+C content was 66.80 mol%. These results supported that strain KADR8-3T was clearly distinguishable from its closely related species and represents a novel species of the genus Ottowia, for which the name Ottowia oryzae is proposed. The type strain is KADR8-3T (=KACC 19325T=NBRC 113109T).