Neaumycin, a new 30-membered macrolide featuring an internal diester bridge, a molecular architecture that is unprecedented among known macrolide natural products, was isolated from a soil actinomycete strain Streptomyces sp. neau-x211. The structure of neaumycin was elucidated on the basis of comprehensive mass and NMR spectroscopic interpretation, including the relative stereochemistry of four independent coupling systems.

SUMMARY

Cancer cell-of-origin is difficult to identify by analyzing cells within terminal-stage tumors, whose identity could be concealed by the acquired plasticity. Thus an ideal approach to identify the cell-of-origin is to analyze proliferative abnormalities in distinct lineages prior to malignancy. Here we use Mosaic Analysis with Double Markers (MADM) in mice to model gliomagenesis by initiating concurrent p53/Nf1 mutations sporadically in neural stem cells (NSCs). Surprisingly, MADM-based lineage tracing revealed significant aberrant growth prior to malignancy only in oligodendrocyte precursor cells (OPCs), but not in any other NSC-derived lineages or NSCs themselves. Upon tumor formation, phenotypic and transcriptome analyses of tumor cells revealed salient OPC features. Finally, introducing the same p53/Nf1 mutations directly into OPCs consistently led to gliomagenesis. Our findings suggest OPCs as the cell-of-origin in this model even when initial mutations occur in NSCs, and highlight the importance of analyzing pre-malignant stages to identify the cancer cell-of-origin.

Background

Haemophilus parasuis (H. parasuis) is the etiological agent of Glässer's disease in pigs. Currently, the molecular basis of this infection is largely unknown. The innate immune response is the first line of defense against the infectious disease. Systematical analysis on host innate immune response to the infection is important for understanding the pathogenesis of the infectious microorganisms.

Results

A total of 428 differentially expressed (DE) genes were identified in the porcine alveolar macrophages (PAMs) 6 days after H. parasuis infection. These genes were principally related to inflammatory response, immune response, microtubule polymerization, regulation of transcript and signal transduction. Through the pathway analysis, the significant pathways mainly concerned with cell adhesion molecules, cytokine-cytokine receptor interaction, complement and coagulation cascades, toll-like receptor signaling pathway, MAPK signaling pathway, suggesting that the host took different strategies to activate immune and inflammatory response upon H. parasuis infection. The global interactions network and two subnetworks of the proteins encoded by DE genes were analyzed by using STRING. Further immunostimulation analysis indicated that mRNA levels of S100 calcium-binding protein A4 (S100A4) and S100 calcium-binding protein A6 (S100A6) in porcine PK-15 cells increased within 48 h and were sustained after administration of lipopolysaccharide (LPS) and Poly (I:C) respectively. The s100a4 and s100a6 genes were found to be up-regulated significantly in lungs, spleen and lymph nodes in H. parasuis infected pigs. We firstly cloned and sequenced the porcine coronin1a gene. Phylogenetic analysis showed that poCORONIN 1A belonged to the group containing the Bos taurus sequence. Structural analysis indicated that the poCORONIN 1A contained putative domains of Trp-Asp (WD) repeats signature, Trp-Asp (WD) repeats profile and Trp-Asp (WD) repeats circular profile at the N-terminus.

Conclusions

Our present study is the first one focusing on the response of porcine alveolar macrophages to H. parasuis. Our data demonstrate a series of genes are activated upon H. parasuis infection. The observed gene expression profile could help screening the potential host agents for reducing the prevalence of H. parasuis and further understanding the molecular pathogenesis associated with H. parasuis infection in pigs.

A novel Shigella strain (Shigella flexneri G3) showing high cellulolytic activity under mesophilic, anaerobic conditions was isolated and characterized. The bacterium is Gram negative, short rod shaped, and nonmotile and displays effective production of glucose, cellobiose, and other oligosaccharides from cellulose (Avicel PH-101) under optimal conditions (40°C and pH 6.5). Approximately 75% of the cellulose was hydrolyzed in modified ATCC 1191 medium containing 0.3% cellulose, and the oligosaccharide production yield and specific production rate reached 375 mg g Avicel−1 and 6.25 mg g Avicel−1 h−1, respectively, after a 60-hour incubation. To our knowledge, this represents the highest oligosaccharide yield and specific rate from cellulose for mesophilic bacterial monocultures reported so far. The results demonstrate that S. flexneri G3 is capable of rapid conversion of cellulose to oligosaccharides, with potential biofuel applications under mesophilic conditions.

Anisodamine, an antagonist of muscarinic receptor, has been used therapeutically to improve blood flow in circulatory disorders such as septic shock in China since 1965. The main mechanism of anisodamine for anti-shock proposed in Pharmacology for Chinese medical students is to improve blood flow in the microcirculation. Here, we suggest a new mechanism for its anti-shock effect. That is, anisodamine, by blocking muscarinic receptor, results in rerouting of acetylcholine to α7 nicotinic acetylcholine receptor (α7nAChR) bringing about increased acetylcholine-mediated activation of α7nAChR and the cholinergic anti-inflammatory pathway.

Streptomyces bingchenggensis is a soil-dwelling bacterium producing the commercially important anthelmintic macrolide milbemycins. Besides milbemycins, the insecticidal polyether antibiotic nanchangmycin and some other antibiotics have also been isolated from this strain. Here we report the complete genome sequence of S. bingchenggensis. The availability of the genome sequence of S. bingchenggensis should enable us to understand the biosynthesis of these structurally intricate antibiotics better and facilitate rational improvement of this strain to increase their titers.

Communication between the SR (sarcoplasmic reticulum, SR) and mitochondria is important for cell survival and apoptosis. The SR supplies Ca2+ directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). Although it has been demonstrated that CaR (calcium sensing receptor) activation is involved in intracellular calcium overload during hypoxia/reoxygenation (H/Re), the role of CaR activation in the cardiomyocyte apoptotic pathway remains unclear. We postulated that CaR activation plays a role in the regulation of SR-mitochondrial inter-organelle Ca2+ signaling, causing apoptosis during H/Re. To investigate the above hypothesis, cultured cardiomyocytes were subjected to H/Re. We examined the distribution of IP3Rs in cardiomyocytes via immunofluorescence and Western blotting and found that type 3 IP3Rs were located in the SR. [Ca2+]i, [Ca2+]m and [Ca2+]SR were determined using Fluo-4, x-rhod-1 and Fluo 5N, respectively, and the mitochondrial membrane potential was detected with JC-1 during reoxygenation using laser confocal microscopy. We found that activation of CaR reduced [Ca2+]SR, increased [Ca2+]i and [Ca2+]m and decreased the mitochondrial membrane potential during reoxygenation. We found that the activation of CaR caused the cleavage of BAP31, thus generating the pro-apoptotic p20 fragment, which induced the release of cytochrome c from mitochondria and the translocation of bak/bax to mitochondria. Taken together, these results reveal that CaR activation causes Ca2+ release from the SR into the mitochondria through IP3Rs and induces cardiomyocyte apoptosis during hypoxia/reoxygenation.

AIM: To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction.

METHODS: Male Wistar rats were randomly distributed into two groups: control group and lipopolysaccharide (LPS) group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold (M)-cells, dendritic cells (DCs), CD4+ T cells, CD8+ T cells, regulatory T (Tr) cells and IgA+ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin (IL)-4, interferon (IFN)-γ and forkhead box P3 (Foxp3) in mucosal homogenates were measured by ELISA. The secretory IgA (sIgA) content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.

RESULTS: This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8+ T cells, and IgA+ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4+ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-γ increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.

CONCLUSION: Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunodeficiency.

In the title complex, {[Co(C10H8N2)(H2O)4](C11H10O5)}n, the unique CoII ion lies on an inversion center and is coordinated by two N atoms from two 4,4′-bipyridine ligands and four O atoms from four water mol­ecules in a slightly distorted octa­hedral coordination geometry. The 4,4′-bipyridine ligands bridge CoII ions into a one-dimensional chain structure. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds link cations and anions into a three-dimensional network. The dianions are completely disordered about an inversion center.

The title complex, [Dy(C8H6NO4)(C2O4)(H2O)]n, is a dysprosium coordination polymer with mixed anions and was obtained under hydrothermal conditions. In the structure, the oxalate and 5-amino­isophthalate ligands link the dysprosium ions, building up a two-dimensional metal–organic framework parallel to the (10) plane. These sheets are further connected through O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds, forming a three-dimensional supra­molecular structure.

Clogging of anode flow channels by CO2 bubbles is a vital problem for further performance improvements of the micro direct methanol fuel cell (μDMFC). In this paper, a new type anode structure using the concept of the non-equipotent serpentine flow field (NESFF) to solve this problem was designed, fabricated and tested. Experiments comparing the μDMFC with and without this type of anode flow field were implemented using a home-made test loop. Results show that the mean-value, amplitude and frequency of the inlet-to-outlet pressure drops in the NESFF is far lower than that in the traditional flow fields at high μDMFC output current. Furthermore, the sequential images of the CO2 bubbles as well as the μDMFC performance with different anode flow field pattern were also investigated, and the conclusions are in accordance with those derived from the pressure drop experiments. Results of this study indicate that the non-equipotent design of the μDMFC anode flow field can effectively mitigate the CO2 clogging in the flow channels, and hence lead to a significant promotion of the μDMFC performance.

In the title compound, C11H13N2O+·C2H3O2 −·H2O, the dihedral angle between the benzene ring and the imidazole ring is 7.83 (6)°. In the crystal structure, N—H⋯O and O—H⋯O hydrogen bonds form a two-dimensional network. All the methyl H atoms are disorderd over two sites with equal occupancies.

In the title compound, C16H9BrO5·2C3H7NO, the chromene ring system is essentially planar. The two dimethyl­formamide solvent mol­ecules are linked by inter­molecular O—H⋯O hydrogen bonds to the 6-bromo-3-hydr­oxy-4-oxo-2-phenyl-4H-chromene-8-carboxylic acid molecules.

In the organic molecule of the title compound, C16H10O8·H2O, the dihedral angle between the two benzene rings is 42.30 (11)°. Extensive O—H⋯O hydrogen bonding helps to stabilize the crystal structure.

The europiumIII ion in the title compound, [Eu2(C8H6NO2)6(C12H8N2)2]·5H2O, is coordinated by seven carboxyl­ate O atoms and two N atoms from one phenanthroline mol­ecule. The carboxyl­ate groups of 3-(3-pyrid­yl)acrylate link pairs of europium(III) ions, forming centrosymmetric dinuclear units, which further assemble into a sheet parallel to the (001) plane through hydrogen-bonding inter­actions involving the uncoordinated water mol­ecules. One water molecule is disordered.

In the title mol­ecule, C16H10O4, all the non-H atoms are coplanar. The crystal structure is stabilized by weak inter­molecular C—H⋯O contacts and π–π stacking inter­actions (the inter­planar distance is 3.43 Å).

The title compound, C7H4Br2O3, has an intra­molecular O—H⋯O=C hydrogen bond and aggregates to form hydrogen-bonded dimers via O—H⋯O inter­actions. The formation of zigzag one-dimensional mol­ecular tapes via C—H⋯Br inter­actions and π–π stacking inter­actions (inter­planar separation = 3.42 Å) completes the crystal structure.

Si/Si0.66Ge0.34coupled quantum well (CQW) structures with different barrier thickness of 40, 4 and 2 nm were grown on Si substrates using an ultra high vacuum chemical vapor deposition (UHV-CVD) system. The samples were characterized using high resolution x-ray diffraction (HRXRD), cross-sectional transmission electron microscopy (XTEM) and photoluminescence (PL) spectroscopy. Blue shift in PL peak energy due to interwell coupling was observed in the CQWs following increase in the Si barrier thickness. The Si/SiGe heterostructure growth process and theoretical band structure model was validated by comparing the energy of the no-phonon peak calculated by the 6 + 2-bandk·pmethod with experimental PL data. Close agreement between theoretical calculations and experimental data was obtained.