Integrative Genomic Analysis Reveals Four Protein Biomarkers for Platelet Traits.

RATIONALE: Mean platelet volume (MPV) and platelet count (PLT) are platelet measures that have been linked to cardiovascular disease (CVD) and mortality risk. Identifying protein biomarkers for these measures may yield insights into CVD mechanisms. OBJECTIVE: We aimed to identify causal protein biomarkers for MPV and PLT among 71 CVD-related plasma proteins measured in FHS (Framingham Heart Study) participants. METHODS AND RESULTS: We conducted integrative analyses of genetic variants associated with PLT/MPV with protein quantitative trait locus variants associated with plasma proteins followed by Mendelian randomization to infer causal relations of proteins for PLT/MPV. We also tested protein-PLT/MPV association in FHS participants. Using induced pluripotent stem cell-derived megakaryocyte clones that produce functional platelets, we conducted RNA-sequencing and analyzed expression differences between low- and high-platelet producing clones. We then performed small interfering RNA gene knockdown experiments targeting genes encoding proteins with putatively causal platelet effects in megakaryocyte clones to examine effects on platelet production. In protein-trait association analyses, ten proteins were associated with MPV and 31 with PLT. Mendelian randomization identified 4 putatively causal proteins for MPV and 4 for PLT. GP-5 (Glycoprotein V), GRN (granulin), and MCAM (melanoma cell adhesion molecule) were associated with PLT, while MPO (myeloperoxidase) showed significant association with MPV in both analyses. RNA-sequencing analysis results were directionally concordant with observed and Mendelian randomization-inferred associations for GP-5, GRN, and MCAM. In siRNA gene knockdown experiments, silencing GP-5, GRN, and MPO decreased PLTs. Genome-wide association study results suggest several of these may be linked to CVD risk. CONCLUSIONS: We identified 4 proteins that are causally linked to PLTs. These proteins may also have roles in the pathogenesis of CVD via a platelet/blood coagulation-based mechanism.

Melaminivora jejuensis sp. nov., isolated from Swinery waste.

A sulfur-oxidizing bacterium, designated strain KBB12T, was isolated from swinery waste collected in Jeju, Republic of Korea. The cells were Gram-stain-negative, flagellated and rod-shaped. Growth occurred at 15-45 °C (optimum, 30-37 °C), at pH 6-9 (optimum, pH 7.0) and in the presence of 0-1 % (w/v) NaCl. The major cellular fatty acids were summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c, C16 : 0 and C18 : 1ω7c. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phospholipid and an unidentified lipid. The major isoprenoid quinone was ubiquinone-8 (Q-8) and the DNA G+C content of the genomic DNA was 69.6 mol%. Phylogenetic analyses, based on 16S rRNA gene sequences, showed that the novel isolate belongs to the genus Melaminivora and was most closely related to Melaminivora alkalimesophila CY1T (97.2 % similarity). The DNA-DNA relatedness values between strain KBB12T and M. alkalimesophila DSM26005T was 43.4±2.7 %. On the basis of phylogenetic and phenotypic evidence, it is proposed that strain KBB12T represents a novel species of the genus Melaminivora, for which the name Melaminivora jejuensis sp. nov. is proposed. The type strain is KBB12T (=KCTC 32230T=JCM 18740T).

Pore Parameters-Dependent Adsorption Behavior of Volatile Organic Compounds on Graphene-Based Material.

Mesoporous graphenes (MPGs) with interpenetrating porous networks are successfully obtained by the pyrolysis of composite gel consisting of graphite oxide (GO) and the amphiphilic triblock copolymer (Pluronic P123) under Ar atmosphere, wherein P123 is used as a soft-template. The as-prepared composite gel is obtained following self-assembly and freeze-drying. The obtained MPGs have high BET specific surface area (531-746 m2 g-1 and ink-bottle like pores with three dimensional interconnected network. Furthermore, the specific surface area and porous parameters such as pore volume, pore size, and pore size distribution of MPGs can be rationally controlled by regulating the initial mass ratio of P123 to GO. With the increase of P123 ratio, the average mesopore size is decreased from ∼16.4 nm to ∼9.5 nm, which is similar to the diameter size of P123 micelles. Also, the adsorption capacities of MPG-20 for 52 indoor air standard components (100 µg mL-1, Supelco) are compared with two different materials, namely commercial porous polymers (2,6-diphenyleneoxide) and reduced graphene oxide (RGO). The result shows that MPG-20 has significantly better adsorption capacity than RGO but also similar or slightly better than commercial porous polymer. The mesoporous structure and surface chemistry of MPGs were the most important factors for the enhancement of the adsorption efficiency for volatile organic compounds.

Shewanella algicola sp. nov., a marine bacterium isolated from brown algae.

A Gram-stain-negative, aerobic, rod-shaped bacterium motile by means of a single polar flagella, strain ST-6T, was isolated from a brown alga (Sargassum thunbergii) collected in Jeju, Republic of Korea. Strain ST-6T was psychrotolerant, growing at 4-30 °C (optimum 20 °C). Phylogenetic analysis based on 16S rRNA and gyrB gene sequences revealed that strain ST-6T belonged to a distinct lineage in the genus Shewanella. Strain ST-6T was related most closely to Shewanella basaltis J83T, S. gaetbuli TF-27T, S. arctica IT12T, S. vesiculosa M7T and S. aestuarii SC18T, showing 96-97 % and 85-70 % 16S rRNA and gyrB gene sequences similarities, respectively. DNA-DNA relatedness values between strain ST-6T and the type strains of two species of the genus Shewanella were <22.6 %. The major cellular fatty acids (>5 %) were summed feature 3 (comprising C16:1ω7c and/ or iso-C15:0 2-OH), C16:0, iso-C13:0 and C17:1ω8c. The DNA G+C content of strain ST-6Twas 42.4 mol%, and the predominant isoprenoid quinones were menaquinone MK-7 and ubiquinones Q-7 and Q-8. On the basis of its phenotypic properties and phylogenetic distinctiveness, strain ST-6T is considered to represent a novel species of the genus Shewanella, for which the name Shewanella algicola sp. nov. is proposed. The type strain is ST-6T (= KCTC 23253T = JCM 31091T).

Two Distinctive Hierarchical Products through the Hydrothermal Process for ß-Co(OH)2 Reacting with NaH2PO2 and Their Morphological Effect on Electrochemical Hydrogen Storage.

This paper reports a study of the reaction behavior of ß-Co(OH)2 with NaH2PO2 under hydrothermal conditions, depending on the concentration of NaOH (0-9.0 M). Uniform sized ß-Co(OH)2 microplatelets, as the precursor, were prepared by the method of homogeneous precipitation using hydrolysis reaction with hexamethylenetetramine as the base. After the hydrothermal reaction, two distinctive products were obtained: cobalt phosphite [Co11(HPO3)8(OH)6] and hcp Co metal. The XRD analysis reveals that the Co11(HPO3)8(OH)6 appeared in the absence of NaOH. Then, Co11(HPO3)8(OH)6 and the hcp Co metal simultaneously appeared under 1.125 M NaOH. At 2.25-4.5 M NaOH, ß-Co(OH)2 and hcp Co metal appeared concurrently, and only pure hcp Co metal appeared under 9.0 M NaOH. The FE-SEM observations indicated that the obtained particles were dendritic-like Co11(HPO3)8(OH)6 and flower-like Co metal. We found that the solubility of ß-Co(OH)2 and the role of the NaH2PO2 were strongly influenced by the concentration of NaOH during this reaction. To investigate the morphological effect of the two obtained products on the electrochemical hydrogen storage performance, materials with the same crystal structures yet with different morphologies were used for comparison. The evaluations of electrochemical performance proved that the two products showed better reversibility, and higher storage capacity and rate dischargeability than the comparative materials. Their relatively good performances can be attributed to their morphology, which resulted in increased surface area, reduced diffusion pathway, and the accommodation of volume change during cycling.

Enhanced Cellular Uptake of Silica-Coated Magnetite Nanoparticles Compared with PEG-Coated Ones in Stem Cells.

Monodispersed magnetite (Fe3O4) nanoparticles (NPs) were prepared through the thermal decomposition method. The obtained NPs were surface modified with silica (SiO2) and polyethylene glycol (PEG), to enhance their stability in aqueous environment and their cellular uptake efficiency for biomedical applications. The NPs were characterized by X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FT-IR) spectroscopy, and dynamic light scattering (DLS). The cytotoxicity of these NPs on bone marrow mesenchymal stem cells (BM-MSCs) was measured by MTT assay (cell viability test) at various concentrations (2, 5, 12.5, 25, and 50 µg/mL). The cells remained more than 90% viable at concentrations as high as 50 µg/mL. To compare the cellular uptake efficiency, these NPs were treated in BM-MSCs and the Fe concentration within the cells was measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. The uptake process displayed a time- and dose-dependency. The uptake amount of SiO2-coated Fe3O4 (Fe3O4@SiO2) NPs was about 10 times higher than that of the PEG-coated ones (Fe3O4@PEG).

Selective interactions of Co2+-Ca2+-concanavalin A with high mannose N-glycans.

Concanavalin A (ConA) has an intrinsic binding affinity to carbohydrates. Here, we obtained Co2+-Ca2+-ConA (2.83 Å, PDB: 8I7Q) via X-ray crystallography by substituting native ConA (Mn2+-Ca2+); it has binding selectivity for high-mannose N-glycan similar to native ConA. Our findings may thus inform antiviral reagent design.

Sphingobacterium cladoniae sp. nov., isolated from lichen, Cladonia sp., and emended description of Sphingobacterium siyangense.

A strictly aerobic, Gram-stain-negative bacterium, designated strain No.6(T), was isolated from a lichen (Cladonia sp.) collected in Geogeum Island, Korea, and its taxonomic status was established by a polyphasic study. Cells of strain No.6(T) were non-motile, catalase- and oxidase-positive, non-spore-forming rods. Growth was observed at 15-35 °C (optimum, 25-30 °C), at pH 5.0-10.0 (optimum, pH 6.0-8.0) and with 0-3 % NaCl (optimum, 0-2 %). The predominant cellular fatty acids were summed feature 3 (comprising iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c, 41.5 %), iso-C(15 : 0) (26.7 %) and C(16 : 0) (9.6 %), and menaquinone MK-7 was the only respiratory quinone. The G+C content of the genomic DNA of strain No.6(T) was 36.8 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain No.6(T) fell within the evolutionary group encompassed by the genus Sphingobacterium. Levels of 16S rRNA gene sequence similarity between the novel strain and the type strains of recognized Sphingobacterium species ranged from 92.1 to 99.1 %, the highest values being with Sphingobacterium siyangense SY1(T) (99.1 %) and Sphingobacterium multivorum IAM 14316(T) (98.5 %). DNA-DNA relatedness between strain No.6(T) and these two type strains were 32.0 and 5.7 %, respectively. The polar lipids found in strain No.6(T) were phosphatidylethanolamine, two unidentified phospholipids, three unidentified aminophospholipids, one glycolipid and four unidentified lipids. One unidentified sphingolipid was also found. On the basis of phenotypic and genotypic data, strain No.6(T) represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium cladoniae sp. nov. is proposed. The type strain is No.6(T) ( = KCTC 22613(T) = JCM 16113(T)). An emended description of Sphingobacterium siyangense is also proposed.

Erythrobacter jejuensis sp. nov., isolated from seawater.

A Gram-staining-negative, yellow-pigmented, non-motile, strictly aerobic, rod-shaped bacterium, designated strain CNU001(T), was isolated from seawater collected on the coast of Jeju Island, South Korea, and subjected to a polyphasic taxonomic study. The temperature, pH and NaCl ranges for growth were 10-30 °C, pH 6.0-10.0 and 2.0-5.0 %, respectively. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain CNU001(T) belonged to the genus Erythrobacter in the family Erythrobacteraceae, with Erythrobacter longus DSM 6997(T) (96.6 % sequence similarity), Erythrobacter gaetbuli SW-161(T) (96.3 %), Erythrobacter vulgaris 022 2-10(T) (96.2 %), Erythrobacter nanhaisediminis T30(T) (96.1 %) and other members of the genus Erythrobacter (<96.0 %) identified as the novel strain's closest relatives. The major cellular fatty acids were C18 : 1ω7c and C17 : 1ω6c. The polar lipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, one sphingoglycolipid, one unidentified aminolipid and six other unidentified lipids. The major respiratory quinone was ubiquinone-10 (UQ-10) and the genomic DNA G+C content of the novel strain was 58.9 mol%. On the basis of phenotypic, phylogenetic and genotypic data, strain CNU001(T) represents a novel species within the genus Erythrobacter, for which the name Erythrobacter jejuensis sp. nov. is proposed. The type strain is CNU001(T) ( = KCTC 23090(T)  = JCM 16677(T)).

Psychroserpens damuponensis sp. nov., isolated from seawater.

A novel bacterium, designated strain F051-1(T), isolated from a seawater sample collected from the coast at Damupo beach in Pohang, Korea, was investigated in a polyphasic taxonomic study. Cells were yellow-pigmented, strictly aerobic, Gram-staining-negative and rod-shaped. The temperature, pH and NaCl ranges for growth were 4-30 °C, pH 6.0-9.0 and 1.0-6.0 % (w/v), respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F051-1(T) belongs to the genus Psychroserpens in the family Flavobacteriaceae. Its closest relatives were Psychroserpens burtonensis ACAM 188(T) (96.8 % 16S rRNA gene sequence similarity) and Psychroserpens mesophilus KOPRI 13649(T) (95.7 %). The major cellular fatty acids were iso-C(15 : 0), iso-C(15 : 1) G and anteiso-C(15 : 0). The polar lipid profile consisted of a mixture of phosphatidylethanolamine, two unidentified aminolipids, one unidentified phospholipid and eight unidentified lipids. The major respiratory quinone was menaquinone-6 and the genomic DNA G+C content of the strain was 33.5 mol%. On the basis of phenotypic, phylogenetic and genotypic data, strain F051-1(T) represents a novel species within the genus Psychroserpens, for which the name Psychroserpens damuponensis sp. nov. is proposed. The type strain is F051-1(T) ( = KCTC 23539(T)  = JCM 17632(T)).

Sagittula marina sp. nov., isolated from seawater and emended description of the genus Sagittula.

A novel bacterium, designated strain F028-2(T), was isolated from seawater at Damupo beach in Pohang, Korea, and investigated in a taxonomic study using a polyphasic approach. This novel strain was strictly aerobic, non-motile, Gram-stain-negative and rod-shaped, and occasionally formed aggregates. The temperature, pH and NaCl ranges for growth were 4-30 °C, pH 6.5-9.0 and 1-7% (w/v), respectively. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain F028-2(T) formed a lineage within the family Rhodobacteraceae of the class Alphaproteobacteria, and was closely related to members of the genera Sagittula and Antarctobacter with 96.3-96.4% sequence similarities. The polar lipid profile of strain F028-2(T) comprised diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids, one unidentified phospholipid and six unidentified lipids. The predominant cellular fatty acids were C18:1ω7c and C12:1 3-OH. The genomic DNA G+C content of strain F028-2(T) was 61.6 mol% and the major respiratory quinone was Q-10. Based on phenotypic, phylogenetic and genotypic data, strain F028-2(T) is considered to represent a novel species in the genus Sagittula, for which the name Sagittula marina sp. nov. is proposed. The type strain is F028-2(T) (=KCTC 23543(T)=JCM 17627(T)). An emended description of the genus Sagittula is also proposed.

Winogradskyella damuponensis sp. nov., isolated from seawater.

A novel bacterium, designated F081-2(T), isolated from seawater from Damupo beach in Pohang, Korea, was investigated using a polyphasic taxonomic approach. Cells were yellow-pigmented, strictly aerobic, motile by gliding, Gram-negative-staining and rod-shaped. The temperature, pH and NaCl ranges for growth were 4-35 °C, pH 5.5-9.5 and 1.0-5.0 %, respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain F081-2(T) belonged to a distinct lineage in the genus Winogradskyella of the family Flavobacteriaceae, sharing 93.7-98.1 % similarity with recognized members of the genus. Low levels of DNA-DNA relatedness values were found between strain F081-2(T) and Winogradskyella eximia KCTC 12219(T) (61.1 %), Winogradskyella thalassocola KCTC 12221(T) (47.0 %), Winogradskyella echinorum KCTC 22026(T) (39.3 %), Winogradskyella rapida CCUG 56098(T) (34.3 %) and Winogradskyella arenosi JCM 17633(T) (33.4 %). The major cellular fatty acids were iso-C(15 : 0) (25.3 %), iso-C(15 : 1) G (14.6 %), iso-C(17 : 0) 3-OH (9.3 %), anteiso-C(15 : 0) (7.8 %) and iso-C(15 : 0) 3-OH (7.6 %). The polar lipid profile was composed of phosphatidylethanolamine, one unidentified aminolipid, one unidentified phospholipid, one unidentified aminophospholipid and six unidentified lipids. The major respiratory quinone was menaquinone-6 and the DNA G+C content of the strain was 32.3 mol%. On the basis of phenotypic, phylogenetic and genotypic data, strain F081-2(T) represents a novel species within the genus Winogradskyella, for which the name Winogradskyella damuponensis sp. nov. is proposed. The type strain is F081-2(T) (=KCTC 23552(T) = JCM 17633(T)).

Effects of magnetic nanoparticle-incorporated human bone marrow-derived mesenchymal stem cells exposed to pulsed electromagnetic fields on injured rat spinal cord.

Transplanting mesenchymal stem cells into injured lesions is currently under study as a therapeutic approach for spinal cord injury. In this study, the effects of a pulsed electromagnetic field (PEMF) on injured rat spinal cord were investigated in magnetic nanoparticle (MNP)-incorporated human bone marrow-derived mesenchymal stem cells (hBM-MSCs). A histological analysis revealed significant differences in MNP-incorporated cell distribution near the injured site under the PEMF in comparison with that in the control group. We confirmed that MNP-incorporated cells were widely distributed in the lesions under PEMF. The results suggest that MNP-incorporated hBM-MSCs were guided by the PEMF near the injured site, and that PEMF exposure for 8 H per day over 4 weeks promoted behavioral recovery in spinal cord injured rats. The results show that rats with MNP-incorporated hBM-MSCs under a PEMF were more effective on the Basso, Beattie, and Bresnahan behavioral test and suggest that the PEMF enhanced the action of transplanted cells for recovery of the injured lesion.

1,3-Bis(6-methyl-pyridin-2-yl)-1H-imidazol-3-ium hexa-fluoro-phosphate.

In the title salt, C17H19N4 (+)·PF6 (-), the two pyridine rings of the cation are inclined to one another by 15.89 (8)°, and inclined to the imidazole ring by 65.05 (10) and 64.07 (10)°. In the crystal, the cations and anions are linked via a series of C-H⋯N and C-H⋯F hydrogen bonds, forming two-dimensional networks lying parallel to (001).

Tuberculous Lymphadenitis in a Patient Treated with Dupilumab: A Case Report.

Tuberculous lymphadenitis is among the most frequent presentations of extrapulmonary tuberculosis; the most common presentation is isolated chronic non-tender lymphadenopathy in young adults without systemic symptoms. Dupilumab is a fully human monoclonal antibody directed against interleukin-4 receptor-α that blocks the synergistic effects of interleukin-4 and interleukin-13 on allergic inflammation. Its well-known adverse events are allergic conjunctivitis, injection site reaction, and dupilumab facial redness. A 32-year-old female with severe atopic dermatitis was treated with dupilumab for 2 months at our clinic. She complained of multiple enlarged palpable lymph nodes on the right side of the neck and inguinal area for 2 months. Laboratory tests showed an increased total eosinophil count and immunoglobulin E level, as well as positive interferon-γ release assays. Radiological examination showed multiple low echoic and heterogeneous well-enhancing lymph nodes in level II, III, IV, and V of the neck. Histological examination revealed caseous necrosis and tuberculoid granuloma. The lymph node enlargements were completely relieved after antituberculosis treatment. The mechanism for the development of tuberculous lymphadenitis in a patient receiving dupilumab is not fully understood yet. In some previous studies, treatment with dupilumab suppressed the expression of genes related not only to T helper 2 and eosinophil response but also to proinflammatory responses. It could not inhibit the intracellular growth of Mycobacterium tuberculosis in macrophages, predisposing them to the development of tuberculous infection. To the best of our knowledge, this is the first report on the development of tuberculosis lymphadenitis in a patient treated with dupilumab.