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Sample records for acid coordinates nod

  1. Consumption of acidic water alters the gut microbiome and decreases the risk of diabetes in NOD mice.

    Science.gov (United States)

    Wolf, Kyle J; Daft, Joseph G; Tanner, Scott M; Hartmann, Riley; Khafipour, Ehsan; Lorenz, Robin G

    2014-04-01

    Infant formula and breastfeeding are environmental factors that influence the incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To determine if altering the intestinal microbiome is one mechanism through which an acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt mice on neutral (N) or acidified H2O and monitored the impact on microbial composition and diabetes incidence. NOD-N mice showed an increased development of diabetes, while exhibiting a decrease in Firmicutes and an increase in Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of age. NOD-N mice had a decrease in the levels of Foxp3 expression in CD4(+)Foxp3(+) cells, as well as decreased CD4(+)IL17(+) cells, and a lower ratio of IL17/IFNγ CD4+ T-cells. Our data clearly indicates that a change in the acidity of liquids consumed dramatically alters the intestinal microbiome, the presence of protective Th17 and Treg cells, and the incidence of diabetes. This data suggests that early dietary manipulation of intestinal microbiota may be a novel mechanism to delay T1D onset in genetically pre-disposed individuals.

  2. Nodding Syndrome

    Centers for Disease Control (CDC) Podcasts

    2013-12-19

    Dr. Scott Dowell, a CDC director, discusses the rare illness, nodding syndrome, in children in Africa.  Created: 12/19/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/27/2014.

  3. Structural models of zebrafish (Danio rerio NOD1 and NOD2 NACHT domains suggest differential ATP binding orientations: insights from computational modeling, docking and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Jitendra Maharana

    Full Text Available Nucleotide-binding oligomerization domain-containing protein 1 (NOD1 and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, γ-phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds and Aspartic acid (Walker B formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2 interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with γ-phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.

  4. Cloning, expression, purification, crystallization and preliminary X-ray analysis of NodS N-methyltransferase from Bradyrhizobium japonicum WM9

    International Nuclear Information System (INIS)

    Cakici, Ozgur; Sikorski, Michal; Stepkowski, Tomasz; Bujacz, Grzegorz; Jaskolski, Mariusz

    2008-01-01

    The NodS N-methyltransferase, an enzyme participating in the biosynthesis of the bacterial nodulation (Nod) factor necessary to establish symbiotic nitrogen fixation with a legume plant host, has been crystallized in the apo form as well as in complex with SAH. SAH is a byproduct of SAM degradation during the SAM-dependent methylation reaction. The Nod factor (NF) is a rhizobial signal molecule that is involved in recognition of a legume host and the formation of root and stem nodules. Some unique enzymes are involved in the biosynthesis of NF, which is a variously but specifically substituted lipochitooligosaccharide. One of these enzymes is NodS, an N-methyltransferase that methylates end-deacetylated chitooligosaccharide substrates. In the methylation reaction, NodS uses S-adenosyl-l-methionine (SAM) as a methyl donor. To date, no structural information is available about NodS from any rhizobium. X-ray crystallographic studies of the NodS protein from Bradyrhizobium japonicum WM9, which infects the legumes lupin and serradella, have been undertaken. The nodS gene was cloned and the recombinant protein was expressed in Escherichia coli cells using natural amino acids and as an SeMet derivative. NodS without ligands was crystallized in the presence of PEG 3350 and MgCl 2 . The protein was also crystallized in complex with S-adenosyl-l-homocysteine (SAH) in the presence of PEG 8000 and MgCl 2 . SAH is produced from SAM as a byproduct of the methylation reaction. The crystals of apo NodS are tetragonal and diffracted X-rays to 2.42 Å resolution. The NodS–SAH complex crystallizes in an orthorhombic space group and the crystals diffracted X-rays to 1.85 Å resolution

  5. Coordination compounds of cobalt and cadmium with isobutyric acid amide

    International Nuclear Information System (INIS)

    Tsivadze, A.Yu.; Ivanova, I.S.; Solovkina, O.A.

    1983-01-01

    Coordination compounds of cobalt and cadmium with isobutyric acid amide (IBAA) of Co(NCS) 2 x(IBAA) 2 (H 2 O) 2 , CoCl 2 (IBAA) 4 , CoI 2 (IBAA) 8 (H 2 O) 2 , CdI 2 (IBAA) 2 composition have been synthesized and characterized. Their infrared absorption spectra (200-400 cm -1 ), electron reflection spectra (200-750 nm) were studied. It is shown that in all compounds there are IBAA molecUles coordinated through an oxygen atom. Thiocyanogroups are coordinated throUgh nitrogen atoms

  6. Antigen Loading (e.g., Glutamic Acid Decarboxylase 65 of Tolerogenic DCs (tolDCs Reduces Their Capacity to Prevent Diabetes in the Non-Obese Diabetes (NOD-Severe Combined Immunodeficiency Model of Adoptive Cotransfer of Diabetes As Well As in NOD Mice

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    David P. Funda

    2018-02-01

    Full Text Available Tolerogenic DCs (tolDCs are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D. T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e., proinsulin, insulin, glutamic acid decarboxylase 65 (GAD65, that have been used in animal as well as human intervention trials in attempts to achieve a more efficient, specific immunotherapy. In this study, we have tested tolerogenic DCs for their effectiveness to prevent adoptive transfer of diabetes by diabetogenic splenocytes into non-obese diabetes (NOD-severe combined immunodeficiency (NOD-SCID recipients. While i.p. application of tolDCs prepared from bone marrow of prediabetic NOD mice by vitamin D2 and dexamethasone significantly reduced diabetes transfer into the NOD-SCID females, this effect was completely abolished when tolDCs were loaded with the mouse recombinant GAD65, but also with a control protein—ovalbumin (OVA. The effect was not dependent on the presence of serum in the tolDC culture. Similar results were observed in NOD mice. Removal of possible bystander antigen-presenting cells within the diabetogenic splenocytes by negative magnetic sorting of T cells did not alter this surprising effect. Tolerogenic DCs loaded with an immunodominant mouse GAD65 peptide also displayed diminished diabetes-preventive effect. Tolerogenic DCs were characterized by surface maturation markers (CD40, CD80, CD86, MHC II and the lipopolysaccharide stability test. Data from alloreactive T cell proliferation and cytokine induction assays (IFN-γ did not reveal the differences observed in the diabetes incidence. Migration of tolDCs, tolDCs-GAD65 and tolDCs-OVA to spleen, mesenteric- and pancreatic lymph nodes displayed similar, mucosal pattern with highest accumulation in pancreatic lymph nodes present up to 9 days after the i.p. application. These data document that mechanisms by which tol

  7. Coordination compounds of cobalt and cadmium with isobutyric acid amide

    Energy Technology Data Exchange (ETDEWEB)

    Tsivadze, A.Yu.; Ivanova, I.S.; Solovkina, O.A. (AN SSSR, Moscow. Inst. Obshchej i Neorganicheskoj Khimii)

    1983-06-01

    Coordination compounds of cobalt and cadmium with isobutyric acid amide (IBAA) of Co(NCS)/sub 2/x(IBAA)/sub 2/(H/sub 2/O)/sub 2/, CoCl/sub 2/(IBAA)/sub 4/, CoI/sub 2/(IBAA)/sub 8/(H/sub 2/O)/sub 2/, CdI/sub 2/(IBAA)/sub 2/ composition have been synthesized and characterized. Their infrared absorption spectra (200-400 cm/sup -1/), electron reflection spectra (200-750 nm) were studied. It is shown that in all compounds there are IBAA molecUles coordinated through an oxygen atom. Thiocyanogroups are coordinated through nitrogen atoms.

  8. Coordination features and use of aspartic acid in chelatometry

    International Nuclear Information System (INIS)

    Sergeev, G.M.; Korenman, I.M.

    1978-01-01

    Considered are coordination peculiarities and application of aspartic and as selective reagent for Be(2) and Mo(6) in chelatometry. pH range of the complexes with aspartic acid for Be(2), pH 4-9, for Mo(6), pH 3-9 are determined. Stability constants of the complexes are found. These values can serve as the basis for selective determination of Be(2) and Mo(6) with asparic acid, which are not always successful with EDTA and DTPA

  9. Homology modeling and in silico prediction of Ulcerative colitis associated polymorphisms of NOD1.

    Science.gov (United States)

    Majumdar, Ishani; Nagpal, Isha; Paul, Jaishree

    2017-10-01

    Cytosolic pattern recognition receptors play key roles in innate immune response. Nucleotide binding and oligomerisation domain containing protein 1 (NOD1) belonging to the Nod-like receptor C (NLRC) sub-family of Nod-like receptors (NLRs) is important for detection and clearance of intra-cellular Gram negative bacteria. NOD1 is involved in activation of pro-inflammatory pathways. Limited structural data is available for NOD1. Using different templates for each domain of NOD1, we determined the full-length homology model of NOD1. ADP binding amino acids within the nucleotide binding domain (NBD) of NOD1 were also predicted. Key residues in inter-domain interaction were identified by sequence comparison with Oryctolagus cuniculus NOD2, a related protein. Interactions between NBD and winged helix domain (WHD) were found to be conserved in NOD1. Functional and structural effect of single nucleotide polymorphisms within the NOD1 NBD domain associated with susceptibility risk to Ulcerative colitis (UC), an inflammatory disorder of the colon was evaluated by in silico studies. Mutations W219R and L349P were predicted to be damaging and disease associated by prediction programs SIFT, PolyPhen2, PANTHER, SNP&GO, PhD SNP and SNAP2. We further validated the effect of W219R and L349P mutation on NOD1 function in vitro. Elevated mRNA expression of pro-inflammatory cytokines IL8 and IL-1β was seen as compared to the wild type NOD1 in intestinal epithelial cell line HT29 when stimulated with NOD1 ligand. Thus, these mutations may indeed have a bearing on pathogenesis of inflammation during UC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Acid rain compliance: Coordination of state and federal regulation

    International Nuclear Information System (INIS)

    Nordhaus, R.R.

    1992-01-01

    The Clean Air Act (CAA) Amendments of 1990 impose new controls on emissions by electric utilities of the two major precursors of acid rain: sulfur dioxide (SO2) and oxides of nitrogen (NOx). Utilities, and the utility holding company systems and power pools of which they are members, will be subject to extensive and costly compliance obligations under the new statute. Most of these utilities, utility systems, and power pools are regulated by more than one utility regulatory authority. Some utilities are regulated by several states, some by a single state and by the Federal Energy Regulatory Commission (FERC), and some by multiple states, by the FERC, and by the Securities and Exchange Commission (SEC). Utility regulators will need to coordinate their policies for ratemaking and for reviewing acid rain compliance strategies if least cost solutions are to be implemented without imposing on ratepayers and utility shareholders the costs and risks of inconsistent regulatory determinations. This article outlines the scope of the coordination problem and addresses possible approaches that utility regulators may take to deal with this problem

  11. DMPD: Nod1 and Nod2 in innate immunity and human inflammatory disorders. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18031249 Nod1 and Nod2 in innate immunity and human inflammatory disorders. Le Bour...w Nod1 and Nod2 in innate immunity and human inflammatory disorders. PubmedID 18031249 Title Nod1 and Nod2 in innate immunity and hum...an inflammatory disorders. Authors Le Bourhis L, Benko S

  12. The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

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    Mami Shimizu

    Full Text Available Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C. In addition, injection of high-dose poly(I: C to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

  13. Achieving Consensus Through Professionalized Head Nods

    DEFF Research Database (Denmark)

    Oshima, Sae

    2014-01-01

    of nodding in a particular professional-client setting, namely, hair salon interactions. My interest specifically lies in the frequent occurrence of synchronized head nods during the “service-assessment sequence,” where both service provider and customer inspect and determine whether the completed work...... is adequate. I pursue mechanisms of synchronized head nods by revealing exactly how participants collaborate in producing a nod, and how their verbal actions may at times be designed accordingly. In doing so, the study provides insight into what consensus may look like at service encounters in Japan......While the interactional functions of head nodding in everyday Japanese conversation have been frequently studied, a discourse on head nodding as a professional communicative practice has yet to be explored. With the method of multimodal conversation analysis, the current study examines the role...

  14. Coordinations between gene modules control the operation of plant amino acid metabolic networks

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    Galili Gad

    2009-01-01

    Full Text Available Abstract Background Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results. Results Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes. Conclusion Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.

  15. Altered metabolic signature in pre-diabetic NOD mice.

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    Rasmus Madsen

    Full Text Available Altered metabolism proceeding seroconversion in children progressing to Type 1 diabetes has previously been demonstrated. We tested the hypothesis that non-obese diabetic (NOD mice show a similarly altered metabolic profile compared to C57BL/6 mice. Blood samples from NOD and C57BL/6 female mice was collected at 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13 and 15 weeks and the metabolite content was analyzed using GC-MS. Based on the data of 89 identified metabolites OPLS-DA analysis was employed to determine the most discriminative metabolites. In silico analysis of potential involved metabolic enzymes was performed using the dbSNP data base. Already at 0 weeks NOD mice displayed a unique metabolic signature compared to C57BL/6. A shift in the metabolism was observed for both strains the first weeks of life, a pattern that stabilized after 5 weeks of age. Multivariate analysis revealed the most discriminative metabolites, which included inosine and glutamic acid. In silico analysis of the genes in the involved metabolic pathways revealed several SNPs in either regulatory or coding regions, some in previously defined insulin dependent diabetes (Idd regions. Our result shows that NOD mice display an altered metabolic profile that is partly resembling the previously observation made in children progressing to Type 1 diabetes. The level of glutamic acid was one of the most discriminative metabolites in addition to several metabolites in the TCA cycle and nucleic acid components. The in silico analysis indicated that the genes responsible for this reside within previously defined Idd regions.

  16. NOD2 and inflammation: current insights

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    Negroni A

    2018-02-01

    Full Text Available Anna Negroni,1 Maria Pierdomenico,2 Salvatore Cucchiara,2 Laura Stronati3 1Division of Health Protection Technologies, Territorial and Production Systems Sustainability Department, ENEA, Rome, Italy; 2Department of Pediatrics and Infantile Neuropsychiatry, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy; 3Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy Abstract: The nucleotide-binding oligomerization domain (NOD protein, NOD2, belonging to the intracellular NOD-like receptor family, detects conserved motifs in bacterial peptidoglycan and promotes their clearance through activation of a proinflammatory transcriptional program and other innate immune pathways, including autophagy and endoplasmic reticulum stress. An inactive form due to mutations or a constitutive high expression of NOD2 is associated with several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the maintenance of immune homeostasis. In this review, we discuss recent developments about the pathway and mechanisms of regulation of NOD2 and illustrate the principal functions of the gene, with particular emphasis on its central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation. Furthermore, we survey recent studies illustrating the role of NOD2 in several inflammatory diseases, in particular, inflammatory bowel disease, of which it is the main susceptibility gene. Keywords: innate immunity, intestinal homeostasis, ER stress, autophagy, inflammatory bowel disease, extraintestinal disease

  17. Supramolecular Coordination Assemblies Constructed From Multifunctional Azole-Containing Carboxylic Acids

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    Yuheng Deng

    2010-05-01

    Full Text Available This paper provides a brief review of recent progress in the field of metal coordination polymers assembled from azole-containing carboxylic acids and gives a diagrammatic summary of the diversity of topological structures in the resulting infinite metal-organic coordination networks (MOCNs. Azole-containing carboxylic acids are a favorable kind of multifunctional ligand to construct various metal complexes with isolated complexes and one, two and three dimensional structures, whose isolated complexes are not the focus of this review. An insight into the topology patterns of the infinite coordination polymers is provided. Analyzed topologies are compared with documented topologies and catalogued by the nature of nodes and connectivity pattern. New topologies which are not available from current topology databases are described and demonstrated graphically.

  18. Neuropsychiatric perspectives on nodding syndrome in northern ...

    African Journals Online (AJOL)

    Objective: To explore a possible relationship of exposure to prolonged ... its characteristic symptoms of psychomotor retardation, anxiety, anhedonia and ... Key words: Nodding Syndrome, Post-traumatic Stress disorder, Epilepsy, Depression ...

  19. Identification of different coordination geometries by XAFS in copper(II) complexes with trimesic acid

    Science.gov (United States)

    Gaur, A.; Klysubun, W.; Soni, Balram; Shrivastava, B. D.; Prasad, J.; Srivastava, K.

    2016-10-01

    X-ray absorption spectroscopy (XAS) is very useful in revealing the information about geometric and electronic structure of a transition-metal absorber and thus commonly used for determination of metal-ligand coordination. But XAFS analysis becomes difficult if differently coordinated metal centers are present in a system. In the present investigation, existence of distinct coordination geometries around metal centres have been studied by XAFS in a series of trimesic acid Cu(II) complexes. The complexes studied are: Cu3(tma)2(im)6 8H2O (1), Cu3(tma)2(mim)6 17H2O (2), Cu3(tma)2(tmen)3 8.5H2O (3), Cu3(tma) (pmd)3 6H2O (ClO4)3 (4) and Cu3(tma)2 3H2O (5). These complexes have not only Cu metal centres with different coordination but in complexes 1-3, there are multiple coordination geometries present around Cu centres. Using XANES spectra, different coordination geometries present in these complexes have been identified. The variation observed in the pre-edge features and edge features have been correlated with the distortion of the specific coordination environment around Cu centres in the complexes. XANES spectra have been calculated for the distinct metal centres present in the complexes by employing ab-initio calculations. These individual spectra have been used to resolve the spectral contribution of the Cu centres to the particular XANES features exhibited by the experimental spectra of the multinuclear complexes. Also, the variation in the 4p density of states have been calculated for the different Cu centres and then correlated with the features originated from corresponding coordination of Cu. Thus, these spectral features have been successfully utilized to detect the presence of the discrete metal centres in a system. The inferences about the coordination geometry have been supported by EXAFS analysis which has been used to determine the structural parameters for these complexes.

  20. Crystal structures of thiosemicarbazide diacetic acid and coordination compounds on its basis

    International Nuclear Information System (INIS)

    Burshtejn, I.F.; Petukhov, L.I.; Gehrbehlehu, N.V.; Volodina, G.F.; Bologa, O.A.

    1985-01-01

    Results of X-ray structure investigation of thiosemicarbazide diacetic acid (H 2 tscda) and its complex derivatives of the composition Mtscda (M=Cd, Co, Cu) have been reviewed. Structure characteristics of Cdtscdax4H 2 O are as follows: a=14.513, b=8.648, c=9.871 A, γ=98.46 deg, sp.gr. P2 1 /a, z=4. Cadmium complex structure represents a centrosymmetrical dimer with bridge oxygen atom of carboxylic group. Cd-Cd distance is 3.815 A. Cd atom has coordination number 7. Coordination Cd-polyhedron in the structure has configuration of trigonal one-cap prism

  1. Synthesis, Characterization, and Antimicrobial Activities of Coordination Compounds of Aspartic Acid

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    T. O. Aiyelabola

    2016-01-01

    Full Text Available Coordination compounds of aspartic acid were synthesized in basic and acidic media, with metal ligand M : L stoichiometric ratio 1 : 2. The complexes were characterized using infrared, electronic and magnetic susceptibility measurements, and mass spectrometry. Antimicrobial activity of the compounds was determined against three Gram-positive and three Gram-negative bacteria and one fungus. The results obtained indicated that the availability of donor atoms used for coordination was a function of the pH of the solution in which the reaction was carried out. This resulted in varying geometrical structures for the complexes. The compounds exhibited a broad spectrum of activity and in some cases better activity than the standard.

  2. Investigation of the complex reaction coordinate of acid catalyzed amide hydrolysis from molecular dynamics simulations

    International Nuclear Information System (INIS)

    Zahn, Dirk

    2004-01-01

    The rate-determining step of acid catalyzed peptide hydrolysis is the nucleophilic attack of a water molecule to the carbon atom of the amide group. Therein the addition of the hydroxyl group to the amide carbon atom involves the association of a water molecule transferring one of its protons to an adjacent water molecule. The protonation of the amide nitrogen atom follows as a separate reaction step. Since the nucleophilic attack involves the breaking and formation of several bonds, the underlying reaction coordinate is rather complex. We investigate this reaction step from path sampling Car-Parrinello molecular dynamics simulations. This approach does not require the predefinition of reaction coordinates and is thus particularly suited for investigating reaction mechanisms. From our simulations the most relevant components of the reaction coordinate are elaborated. Though the C···O distance of the oxygen atom of the water molecule performing the nucleophilic attack and the corresponding amide carbon atom is a descriptor of the reaction progress, a complete picture of the reaction coordinate must include all three molecules taking part in the reaction. Moreover, the proton transfer is found to depend on favorable solvent configurations. Thus, also the arrangement of non-reacting, i.e. solvent water molecules needs to be considered in the reaction coordinate

  3. Ruthenium (3) coordination compounds with ethylenediamine-N,N,N',N'-tetramethylphosphonic acid

    International Nuclear Information System (INIS)

    Ezerskaya, N.A.; Buj Kuang Ki; Shubochkin, L.K.

    1987-01-01

    In the process of interaction of K 2 Ru(H 2 O)Cl 5 with ethylenediamine-N,N,N',N'-tetramethylphosphonic acid (H 8 EDTP) Ru 3 mono-, bi- and trinuclear complexonates are synthesized. On the basis of IR and X-ray electron spectroscopy and potentiometry suppositions are made on the way of ligand (EDTP, Cl - , H 2 O) coordination. Ru 3 complexonates are characterized using spectrophotometry, polarography, conductometry. Thermal decomposition of the complexonates is studied

  4. Brønsted acid sites based on penta-coordinated aluminum species

    Science.gov (United States)

    Wang, Zichun; Jiang, Yijiao; Lafon, Olivier; Trébosc, Julien; Duk Kim, Kyung; Stampfl, Catherine; Baiker, Alfons; Amoureux, Jean-Paul; Huang, Jun

    2016-12-01

    Zeolites and amorphous silica-alumina (ASA), which both provide Brønsted acid sites (BASs), are the most extensively used solid acid catalysts in the chemical industry. It is widely believed that BASs consist only of tetra-coordinated aluminum sites (AlIV) with bridging OH groups in zeolites or nearby silanols on ASA surfaces. Here we report the direct observation in ASA of a new type of BAS based on penta-coordinated aluminum species (AlV) by 27Al-{1H} dipolar-mediated correlation two-dimensional NMR experiments at high magnetic field under magic-angle spinning. Both BAS-AlIV and -AlV show a similar acidity to protonate probe molecular ammonia. The quantitative evaluation of 1H and 27Al sites demonstrates that BAS-AlV co-exists with BAS-AlIV rather than replaces it, which opens new avenues for strongly enhancing the acidity of these popular solid acids.

  5. Hydrothermal synthesis and crystal structure of a new lanthanum(III coordination polymer with fumaric acid

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    Hayet Anana

    2015-05-01

    Full Text Available The title compound, poly[diaquatris(μ4-but-2-enedioato(μ2-but-2-enedioic aciddilanthanum(III], [La2(C4H2O43(C4H4O4(H2O2]n, was synthesized by the reaction of lanthanum chloride pentahydrate with fumaric acid under hydrothermal conditions. The asymmetric unit comprises an LaIII cation, one and a half fumarate dianions (L2−, one a half-molecule of fumaric acid (H2L and one coordinated water molecule. Each LaIII cation has the same nine-coordinate environment and is surrounded by eight O atoms from seven distinct fumarate moieties, including one protonated fumarate unit and one water molecule in a distorted tricapped trigonal–prismatic environment. The LaO8(H2O polyhedra centres are edge-shared through three carboxylate bridges of the fumarate ligand, forming chains in three dimensions to construct the MOF. The crystal structure is stabilized by O—H...O hydrogen-bond interactions between the coordinated water molecule and the carboxylate O atoms, and also between oxygen atoms of fumaric acid

  6. Concurrent synthesis and release of nod-gene-inducing flavonoids from alfalfa roots

    International Nuclear Information System (INIS)

    Maxwell, C.A.; Phillips, D.A.

    1990-01-01

    Flavonoid signals from alfalfa (Medicago sativa L.) induce transcription of nodulation (nod) genes in Rhizobium meliloti. Alfalfa roots release three major nod-gene inducers: 4',7-dihydroxyflavanone, 4',7-dihydroxyflavone, and 4,4'-dihydroxy-2'-methoxychalcone. The objective of the present study was to define temporal relationships between synthesis and exudation for those flavonoids. Requirements for concurrent flavonoid biosynthesis were assessed by treating roots of intact alfalfa seedlings with [U- 14 C]-L-phenylalanine in the presence or absence of the phenylalanine ammonia-lyase inhibitor L-2-aminoxy-3-phenylpropionic acid (AOPP). In the absence of AOPP, each of the three flavonoids in exudates contained 14 C. In the presence of AOPP, 14 C labeling and release of all the exuded nod-gene inducers were reduced significantly. AOPP inhibited labeling and release of the strongest nod-gene inducer, methoxychalcone, by more than 90%. The release process responsible for exudation of nod-gene inducers appears to be specific rather than a general phenomenon such as a sloughing off of cells during root growth

  7. Metals in proteins: correlation between the metal-ion type, coordination number and the amino-acid residues involved in the coordination.

    Science.gov (United States)

    Dokmanić, Ivan; Sikić, Mile; Tomić, Sanja

    2008-03-01

    Metal ions are constituents of many metalloproteins, in which they have either catalytic (metalloenzymes) or structural functions. In this work, the characteristics of various metals were studied (Cu, Zn, Mg, Mn, Fe, Co, Ni, Cd and Ca in proteins with known crystal structure) as well as the specificity of their environments. The analysis was performed on two data sets: the set of protein structures in the Protein Data Bank (PDB) determined with resolution metal ion and its electron donors and the latter was used to assess the preferred coordination numbers and common combinations of amino-acid residues in the neighbourhood of each metal. Although the metal ions considered predominantly had a valence of two, their preferred coordination number and the type of amino-acid residues that participate in the coordination differed significantly from one metal ion to the next. This study concentrates on finding the specificities of a metal-ion environment, namely the distribution of coordination numbers and the amino-acid residue types that frequently take part in coordination. Furthermore, the correlation between the coordination number and the occurrence of certain amino-acid residues (quartets and triplets) in a metal-ion coordination sphere was analysed. The results obtained are of particular value for the identification and modelling of metal-binding sites in protein structures derived by homology modelling. Knowledge of the geometry and characteristics of the metal-binding sites in metalloproteins of known function can help to more closely determine the biological activity of proteins of unknown function and to aid in design of proteins with specific affinity for certain metals.

  8. Syntheses, Characterization, Resolution, and Biological Studies of Coordination Compounds of Aspartic Acid and Glycine

    Science.gov (United States)

    Akinkunmi, Ezekiel; Ojo, Isaac; Adebajo, Clement; Isabirye, David

    2017-01-01

    Enantiomerically enriched coordination compounds of aspartic acid and racemic mixtures of coordination compounds of glycine metal-ligand ratio 1 : 3 were synthesized and characterized using infrared and UV-Vis spectrophotometric techniques and magnetic susceptibility measurements. Five of the complexes were resolved using (+)-cis-dichlorobis(ethylenediamine)cobalt(III) chloride, (+)-bis(glycinato)(1,10-phenanthroline)cobalt(III) chloride, and (+)-tris(1,10-phenanthroline)nickel(II) chloride as resolving agents. The antimicrobial and cytotoxic activities of these complexes were then determined. The results obtained indicated that aspartic acid and glycine coordinated in a bidentate fashion. The enantiomeric purity of the compounds was in the range of 22.10–32.10%, with (+)-cis-dichlorobis(ethylenediamine)cobalt(III) complex as the more efficient resolving agent. The resolved complexes exhibited better activity in some cases compared to the parent complexes for both biological activities. It was therefore inferred that although the increase in the lipophilicity of the complexes may assist in the permeability of the complexes through the cell membrane of the pathogens, the enantiomeric purity of the complexes is also of importance in their activity as antimicrobial and cytotoxic agents. PMID:28293149

  9. Two multi-dimensional frameworks constructed from zinc coordination polymers with pyridine carboxylic acids

    International Nuclear Information System (INIS)

    Guo Yuanyuan; Ma Pengtao; Wang Jingping; Niu Jingyang

    2011-01-01

    Two novel zinc coordination polymers [Zn 2 (H 2 O)L(MoO 4 )] n (1) and [Zn 4 (PO 4 ) 2 L'(H 2 O)] n (2) (H 2 L=2,2'-bipyridine-6.6'-dicarboxylic acid, H 2 L'=2,2'-bipyridine-4,4'-dicarboxylic acid) have been hydrothermally synthesized and characterized by elemental analyses, IR spectra, UV spectra, single-crystal X-ray diffraction and thermogravimetric analyses. Structural analyses indicate that 1 represents a 2-D sheet structure built by dimeric [Zn 2 L(H 2 O)] 2+ units and MoO 4 2- groups whereas 2 displays an interesting 3-D framework constructed by tetranuclear zinc clusters, L' 2- ligands and PO 4 3- groups. Examination of UV spectra suggests that both 1 and 2 can stably exist in the pH range of 2.45-5.45 and 3.01-8.55 in aqueous solution, respectively. The room-temperature solid-state photoluminescence of 1 and 2 are derived from the intra-ligands π-π* transitions of H 2 L and H 2 L' ligands and the ligand-to-metal-charge-transfer transitions. - Graphical Abstract: Two new transition metal coordination polymers, namely, [Zn 2 (H 2 O)L 1 (MoO 4 )] n (1), [Zn 4 (PO 4 ) 2 L 2 (H 2 O)] n (2) (H 2 L 1 =2,2'-bipyridine-6,6'-dicarboxylic acid, H 2 L 2 =2,2'-bipyridine-4,4'-dicarboxylic acid) have been hydrothermally synthesized. 1 represents a 2-D sheet structure while 2 represents 3-D network. Highlights: →Two new transition metal coordination polymers have been hydrothermally synthesized. → The two compounds have been characterized by elemental analyses, IR, UV spectra, single-crystal X-ray diffraction, thermogravimetric analyses and photoluminescence. → Compound 1 represents a 2-D sheet structure while 2 represents 3-D network.

  10. Nodding syndrome: origins and natural history of a longstanding ...

    African Journals Online (AJOL)

    Nodding syndrome: origins and natural history of a longstanding epileptic disorder in sub-Saharan Africa. ... Conclusion: Historical accounts of head nodding (amesinzia kichwa, Swahili) among the Wapogoro tribe fit the August 2012 World Health Organization (WHO) case definition of probable Nodding Syndrome.

  11. The inflammatory bowel disease (IBD susceptibility genes NOD1 and NOD2 have conserved anti-bacterial roles in zebrafish

    Directory of Open Access Journals (Sweden)

    Stefan H. Oehlers

    2011-11-01

    Inflammatory bowel disease (IBD, in the form of Crohn’s disease (CD or ulcerative colitis (UC, is a debilitating chronic immune disorder of the intestine. A complex etiology resulting from dysfunctional interactions between the intestinal immune system and its microflora, influenced by host genetic susceptibility, makes disease modeling challenging. Mutations in NOD2 have the highest disease-specific risk association for CD, and a related gene, NOD1, is associated with UC. NOD1 and NOD2 encode intracellular bacterial sensor proteins acting as innate immune triggers, and represent promising therapeutic targets. The zebrafish has the potential to aid in modeling genetic and environmental aspects of IBD pathogenesis. Here, we report the characterization of the Nod signaling components in the zebrafish larval intestine. The nod1 and nod2 genes are expressed in intestinal epithelial cells and neutrophils together with the Nod signaling pathway genes ripk2, a20, aamp, cd147, centaurin b1, erbin and grim-19. Using a zebrafish embryo Salmonella infection model, morpholino-mediated depletion of Nod1 or Nod2 reduced the ability of embryos to control systemic infection. Depletion of Nod1 or Nod2 decreased expression of dual oxidase in the intestinal epithelium and impaired the ability of larvae to reduce intracellular bacterial burden. This work highlights the potential use of zebrafish larvae in the study of components of IBD pathogenesis.

  12. Ruthenium (3) coordination compounds with ethylenediamine-N,N,N',N'-tetramethylphosphonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Ezerskaya, N A; Ki, Buj Kuang; Shubochkin, L K

    1987-12-01

    In the process of interaction of K/sub 2/Ru(H/sub 2/O)Cl/sub 5/ with ethylenediamine-N,N,N',N'-tetramethylphosphonic acid (H/sub 8/EDTP) Ru/sup 3/ mono-, bi- and trinuclear complexonates are synthesized. On the basis of IR and X-ray electron spectroscopy and potentiometry suppositions are made on the way of ligand (EDTP, Cl/sup -/, H/sub 2/O) coordination. Ru/sup 3/ complexonates are characterized using spectrophotometry, polarography, conductometry. Thermal decomposition of the complexonates is studied.

  13. Reply to Noddings, Darwall, Wren, and Fullinwider

    Science.gov (United States)

    Slote, Michael

    2010-01-01

    I respond to Noddings with further clarification of the notion of empathy and also argue that previous care ethics has put too much of an exclusive emphasis on relationships. I respond to Darwall by pointing out some implausible implications of his own and Kantian views about respect and by showing how a sentimentalist approach can avoid those…

  14. Analysis of Pathogenesis of Autoimmune Insulitis in NOD Mice: Adoptive Transfer Experiments of Insulitis in ILI and NOD Nude Mice

    OpenAIRE

    Nakamura, Moritaka; Nishimura, Masahiko; Koide, Yukio; Takato, O.Yoshida

    2003-01-01

    In an effort to study the pathophysiological events in the development of insulitis in NOD mice, we have developed ILI- and NOD-nu/nu mice. ILI mice are a nondiabetic inbred strain but are derived from the same Jcl:ICR mouse as NOD mice and share the same H-2 allotype with NOD mice. Splenocytes and CD4+ cells from diabetic NOD mice appeared to transfer insulitis to ILI-nu/nu mice, suggesting that ILI mice already express autoantigen(s) responsible for insulitis. But reciprocal thymic grafts f...

  15. Copper coordination polymers constructed from thiazole-5-carboxylic acid: Synthesis, crystal structures, and structural transformation

    Energy Technology Data Exchange (ETDEWEB)

    Meundaeng, Natthaya; Rujiwatra, Apinpus [Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Prior, Timothy J., E-mail: t.prior@hull.ac.uk [Chemistry, University of Hull, Kingston upon Hull HU6 7RX (United Kingdom)

    2017-01-15

    We have successfully prepared crystals of thiazole-5-carboxylic acid (5-Htza) (L) and three new thiazole-5-carboxylate-based Cu{sup 2+} coordination polymers with different dimensionality, namely, 1D [Cu{sub 2}(5-tza){sub 2}(1,10-phenanthroline){sub 2}(NO{sub 3}){sub 2}] (1), 2D [Cu(5-tza){sub 2}(MeOH){sub 2}] (2), and 3D [Cu(5-tza){sub 2}]·H{sub 2}O (3). These have been characterized by single crystal X-ray diffraction and thermogravimetry. Interestingly, the 2D network structure of 2 can directly transform into the 3D framework of 3 upon removal of methanol molecules at room temperature. 2 can also undergo structural transformation to produce the same 2D network present in the known [Cu(5-tza){sub 2}]·1.5H{sub 2}O upon heat treatment for 2 h. This 2D network can adsorb water and convert to 3 upon exposure to air. - Highlights: • Rare examples of coordination polymers of thiazole-5-carboxylic acid were prepared. • Non-covalent interactions play a key role on the assembly of the complexes in solid state. • Structural transformation of a 2D framework to a 3D upon removal of methanol is observed.

  16. Coordination Polymers and Metal Organic Frameworks Derived from 1,2,4-Triazole Amino Acid Linkers

    Directory of Open Access Journals (Sweden)

    Yann Garcia

    2011-10-01

    Full Text Available The perceptible appearance of biomolecules as prospective building blocks in the architecture of coordination polymers (CPs and metal-organic frameworks (MOFs are redolent of their inclusion in the synthon/tecton library of reticular chemistry. In this frame, for the first time a synthetic strategy has been established for amine derivatization in amino acids into 1,2,4-triazoles. A set of novel 1,2,4-triazole derivatized amino acids were introduced as superlative precursors in the design of 1D coordination polymers, 2D chiral helicates and 3D metal-organic frameworks. Applications associated with these compounds are diverse and include gas adsorption-porosity partitioning, soft sacrificial matrix for morphology and phase selective cadmium oxide synthesis, FeII spin crossover materials, zinc-b-lactamases inhibitors, logistics for generation of chiral/non-centrosymmetric networks; and thus led to a foundation of a new family of functional CPs and MOFs that are reviewed in this invited contribution.

  17. Formation of Gd coordination polymer with 1D chains mediated by Bronsted acidic ionic liquids

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Qianqian; Han, Ying [Key Laboratory of Polar Materials and Devices, Ministry of Education, East China Normal University, Shanghai (China); Lin, Hechun, E-mail: hclin@ee.ecnu.edu.cn [Key Laboratory of Polar Materials and Devices, Ministry of Education, East China Normal University, Shanghai (China); Zhang, Yuanyuan; Duan, Chungang [Key Laboratory of Polar Materials and Devices, Ministry of Education, East China Normal University, Shanghai (China); Peng, Hui, E-mail: hpeng@ee.ecnu.edu.cn [Key Laboratory of Polar Materials and Devices, Ministry of Education, East China Normal University, Shanghai (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, Shanxi 030006 (China)

    2017-03-15

    One dimensional coordination polymer Gd[(SO{sub 4})(NO{sub 3})(C{sub 2}H{sub 6}SO){sub 2}] (1) is prepared through the mediation of Bronsted acid ionic liquid, which crystallized in the monoclinic space of C2/c. In this polymer, adjacent Gd atoms are linked by two SO{sub 4}{sup 2-} ions to generate a 1-D chain, and all oxygen atoms in SO{sub 4}{sup 2-} groups are connected to three nearest Gd atoms in µ{sup 3}:η{sup 1}:η{sup 1}:η{sup 2} fashion. Gd, S and N from SO{sub 4}{sup 2-} and NO{sub 3}{sup -} are precisely coplanar. The planar is coordinated by a pair of DMSO molecules, which is parallel and linked by hydrogen bonding to form a three-dimensional supramolecular network. Magnetic susceptibility measurement of 1 reveals weak antiferromagnetic interactions between the Gd (III) ions. It exhibits relatively large magneto-caloric effect with –ΔS{sub m}=28.8 J Kg{sup −1} K{sup −1} for ΔH=7 T. - Graphical abstract: Coordination polymer Gd[(SO{sub 4})(NO{sub 3})(C{sub 2}H{sub 6}SO){sub 2}] was obtained mediated by Bronsted acid Ionic Liquid, which presents a 1-D chains collected by SO{sub 4}{sup 2-} groups. Magnetic susceptibility of the polymer reveals weak antiferromagnetic interactions between the Gd(III) ions with the relatively large magneto-caloric effect of –ΔS{sub m}=28.8 J Kg{sup −1} K{sup −1} for ΔH= 7T.

  18. Methylene-bis[(aminomethyl)phosphinic acids]: synthesis, acid-base and coordination properties.

    Science.gov (United States)

    David, Tomáš; Procházková, Soňa; Havlíčková, Jana; Kotek, Jan; Kubíček, Vojtěch; Hermann, Petr; Lukeš, Ivan

    2013-02-21

    Three symmetrical methylene-bis[(aminomethyl)phosphinic acids] bearing different substituents on the central carbon atom, (NH(2)CH(2))PO(2)H-C(R(1))(R(2))-PO(2)H(CH(2)NH(2)) where R(1) = OH, R(2) = Me (H(2)L(1)), R(1) = OH, R(2) = Ph (H(2)L(2)) and R(1),R(2) = H (H(2)L(3)), were synthesized. Acid-base and complexing properties of the ligands were studied in solution as well as in the solid state. The ligands show unusually high basicity of the nitrogen atoms (log K(1) = 9.5-10, log K(2) = 8.5-9) if compared with simple (aminomethyl)phosphinic acids and, consequently, high stability constants of the complexes with studied divalent metal ions. The study showed the important role of the hydroxo group attached to the central carbon atom of the geminal bis(phosphinate) moiety. Deprotonation of the hydroxo group yields the alcoholate anion which tends to play the role of a bridging ligand and induces formation of polynuclear complexes. Solid-state structures of complexes [H(2)N=C(NH(2))(2)][Cu(2)(H(-1)L(2))(2)]CO(3)·10H(2)O and Li(2)[Co(4)(H(-1)L(1))(3)(OH)]·17.5H(2)O were determined by X-ray diffraction. The complexes show unexpected geometries forming dinuclear and cubane-like structures, respectively. The dinuclear copper(II) complex contains a bridging μ(2)-alcoholate group with the (-)O-P(=O)-CH(2)-NH(2) fragments of each ligand molecule chelated to the different central ion. In the cubane cobalt(II) complex, one μ(3)-hydroxide and three μ(3)-alcoholate anions are located in the cube vertices and both phosphinate groups of one ligand molecule are chelating the same cobalt(II) ion while each of its amino groups are bound to different neighbouring metal ions. All such three metal ions are bridged by the alcoholate group of a given ligand.

  19. Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression

    DEFF Research Database (Denmark)

    Wang, Qian; Bailey, Charles G; Ng, Cynthia

    2011-01-01

    was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cells. These cells maintained levels of amino acid influx through androgen receptor-mediated regulation of LAT3 expression and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses remained intact in primary......L-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function...... prostate cancer, as indicated by high levels of LAT3 in primary disease, and by increased levels of LAT1 after hormone ablation and in metastatic lesions. Taken together, our results show how prostate cancer cells respond to demands for increased essential amino acids by coordinately activating amino acid...

  20. The Role of NOD Mice in Type 1 Diabetes Research: Lessons from the Past and Recommendations for the Future

    Directory of Open Access Journals (Sweden)

    Yi-Guang Chen

    2018-02-01

    Full Text Available For more than 35 years, the NOD mouse has been the primary animal model for studying autoimmune diabetes. During this time, striking similarities to the human disease have been uncovered. In both species, unusual polymorphisms in a major histocompatibility complex (MHC class II molecule confer the most disease risk, disease is caused by perturbations by the same genes or different genes in the same biological pathways and that diabetes onset is preceded by the presence of circulating autoreactive T cells and autoantibodies that recognize many of the same islet antigens. However, the relevance of the NOD model is frequently challenged due to past failures translating therapies from NOD mice to humans and because the appearance of insulitis in mice and some patients is different. Nevertheless, the NOD mouse remains a pillar of autoimmune diabetes research for its usefulness as a preclinical model and because it provides access to invasive procedures as well as tissues that are rarely procured from patients or controls. The current article is focused on approaches to improve the NOD mouse by addressing reasons why immune therapies have failed to translate from mice to humans. We also propose new strategies for mixing and editing the NOD genome to improve the model in ways that will better advance our understanding of human diabetes. As proof of concept, we report that diabetes is completely suppressed in a knock-in NOD strain with a serine to aspartic acid substitution at position 57 in the MHC class II Aβ. This supports that similar non-aspartic acid substitutions at residue 57 of variants of the human class II HLA-DQβ homolog confer diabetes risk.

  1. Coordination-Assisted Bioorthogonal Chemistry: Orthogonal Tetrazine Ligation with Vinylboronic Acid and a Strained Alkene.

    Science.gov (United States)

    Eising, Selma; Xin, Bo-Tao; Kleinpenning, Fleur; Heming, Juriaan; Florea, Bogdan; Overkleeft, Herman; Bonger, Kimberly Michelle

    2018-05-28

    Bioorthogonal chemistry can be used for the selective modification of biomolecules without interfering with any other functionality present. Recent developments in the field provided orthogonal bioorthogonal reactions for modification of multiple biomolecules simultaneously. During our research, we have observed exceptional high reaction rates in the bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction between non-strained vinylboronic acids (VBAs) and dipyridyl-s-tetrazines relative to that of tetrazines bearing a methyl or phenyl substituent. As VBAs are mild Lewis acids, we hypothesize that coordination of the pyridyl nitrogen to the boronic acid promotes the tetrazine ligation. Here, we explore the molecular basis and scope of the VBA-tetrazine ligation in more detail and benefit from its unique reactivity in the simultaneous orthogonal tetrazine labelling of two proteins modified with VBA and norbornene, a widely used strained alkene. We further show that the two orthogonal iEDDA reactions can be carried out in living cells by labelling of the proteasome using a non-selective probe equipped with a VBA and a subunit-selective one bearing a norbornene. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Studies on the structural, optical and dielectric properties of samarium coordinated with salicylic acid single crystal

    Science.gov (United States)

    Singh, Harjinder; Slathia, Goldy; Gupta, Rashmi; Bamzai, K. K.

    2018-04-01

    Samarium coordinated with salicylic acid was successfully grown as a single crystal by low temperature solution technique using mixed solvent of methanol and water in equal ratio. Structural characterization was carried out by single crystal X-ray diffraction analysis and it crystallizes in centrosymmetric space group P121/c1. FTIR and UV-Vis-NIR spectroscopy confirmed the compound formation and help to determine the mode of binding of the ligand to the rare earth-metal ion. Dielectric constant and dielectric loss have been measured over the frequency range 100 Hz - 30MHz. The decrease in dielectric constant with increases in frequency is due to the transition from interfacial polarization to dipolar polarization. The small value of dielectric constant at higher frequency ensures that the crystal is good candidate for NLO devices. Dielectric loss represents the resistive nature of the material.

  3. Two new coordination polymers based on tartaric acid ligand: Syntheses, crystal structure and thermal stability

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fei-Yan; Lan, You-Zhao, E-mail: sky37@zjnu.cn; Han, Min-Min; Feng, Yun-Long, E-mail: lyzhao@zjnu.cn [Zhejiang Normal University, Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, Institute of Physical Chemistry (China)

    2016-09-15

    Two new coordination polymers [Cd{sub 3}(D-Tar){sub 3}]{sub n} (1) and [Pb(meso-Tar)]{sub n} (2) (H{sub 2}Tar = tartaric acid) have been synthesized by hydrothermal reaction and characterized by single crystal X-ray diffraction analysis and IR spectra. 1 crystallizes in the C222{sub 1} chiral space group and shows a 3D (4,4)-connected net with the (4.6.8{sup 4}){sub 4}(4.6{sup 2}.8{sup 2}.10)(4.6{sup 2}.8{sup 3})(4.6{sup 3}.8{sup 2})(4.6{sup 3}.8{sup 2}){sub 4}(4.8{sup 5}){sub 2} topology. 2 possesses a 3D (4,4)-connected net with the (4{sup 3}.6{sup 2}.8) topology. In addition, the thermogravimetric analyses (TGA) results for polymers are discussed.

  4. Acid-base and coordination properties of Meso-substituted porphyrins in nonaqueous solutions

    Science.gov (United States)

    Pukhovskaya, S. G.; Nam, Dao Tkhe; Fien, Chan Ding; Domanina, E. N.; Ivanova, Yu. B.; Semeikin, A. S.

    2017-09-01

    Acid-base and coordination properties of alkyl and aryl meso-substituted porphyrins are studied spectrophotometrically in nonaqueous solutions. It is found that the nature of the substituent greatly affects the basicity of ligands for porphyrins characterized by a flat structure of macrocycle. The electronic effects of substituents have a much weaker influence on the kinetics of complexing. These effects could be due to the opposite orientation of some factors: an increase in the basicity and stability of the N-H bonds of porphyrin reaction centers. Dissociation constants p K b of the cationic forms of meso-substituted derivatives of porphyrin are measured. The values of p K b are in good agreement with classic concepts of the nature of substituents, particularly those indirectly included in the macrocycle through phenyl buffer rings.

  5. Nod2 mediates susceptibility to Yersinia pseudotuberculosis in mice.

    Directory of Open Access Journals (Sweden)

    Ulrich Meinzer

    Full Text Available Nucleotide oligomerisation domain 2 (NOD2 is a component of the innate immunity known to be involved in the homeostasis of Peyer patches (PPs in mice. However, little is known about its role during gut infection in vivo. Yersinia pseudotuberculosis is an enteropathogen causing gastroenteritis, adenolymphitis and septicaemia which is able to invade its host through PPs. We investigated the role of Nod2 during Y. pseudotuberculosis infection. Death was delayed in Nod2 deleted and Crohn's disease associated Nod2 mutated mice orogastrically inoculated with Y. pseudotuberculosis. In PPs, the local immune response was characterized by a higher KC level and a more intense infiltration by neutrophils and macrophages. The apoptotic and bacterial cell counts were decreased. Finally, Nod2 deleted mice had a lower systemic bacterial dissemination and less damage of the haematopoeitic organs. This resistance phenotype was lost in case of intraperitoneal infection. We concluded that Nod2 contributes to the susceptibility to Y. pseudotuberculosis in mice.

  6. Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

    OpenAIRE

    Alkan , Manal; Machavoine , François; Rignault , Rachel; Dam , Julie; Dy , Michel; Thieblemont , Nathalie

    2015-01-01

    International audience; Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC −/− m...

  7. TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.

    Science.gov (United States)

    Marchesan, Julie; Jiao, Yizu; Schaff, Riley A; Hao, Jie; Morelli, Thiago; Kinney, Janet S; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J; Inohara, Naohiro; Giannobile, William V

    2016-06-01

    Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Nodding syndrome in Tanzania may not be associated with ...

    African Journals Online (AJOL)

    2014-06-02

    Jun 2, 2014 ... Department of Psychiatry, University of British Columbia, Vancouver, Canada. 5. ... primary generalized seizures and community controls were not significantly different. However ..... Nodding Syndrome meeting, researchers.

  9. Bradyrhizobium elkanii nod regulon: insights through genomic analysis

    Directory of Open Access Journals (Sweden)

    Luciane M. P. Passaglia

    2017-07-01

    Full Text Available Abstract A successful symbiotic relationship between soybean [Glycine max (L. Merr.] and Bradyrhizobium species requires expression of the bacterial structural nod genes that encode for the synthesis of lipochitooligosaccharide nodulation signal molecules, known as Nod factors (NFs. Bradyrhizobium diazoefficiens USDA 110 possesses a wide nodulation gene repertoire that allows NF assembly and modification, with transcription of the nodYABCSUIJnolMNOnodZ operon depending upon specific activators, i.e., products of regulatory nod genes that are responsive to signaling molecules such as flavonoid compounds exuded by host plant roots. Central to this regulatory circuit of nod gene expression are NodD proteins, members of the LysR-type regulator family. In this study, publicly available Bradyrhizobium elkanii sequenced genomes were compared with the closely related B. diazoefficiens USDA 110 reference genome to determine the similarities between those genomes, especially with regards to the nod operon and nod regulon. Bioinformatics analyses revealed a correlation between functional mechanisms and key elements that play an essential role in the regulation of nod gene expression. These analyses also revealed new genomic features that had not been clearly explored before, some of which were unique for some B. elkanii genomes.

  10. Synthesis and structural evaluation of five coordination complexes of benzenepentacarboxylic acid with aza-donor ligands

    Science.gov (United States)

    Shimpi, Manishkumar R.; Biswas, Sharmita Nandy; Sarkar, Sohini; Pedireddi, V. R.

    2016-06-01

    Synthesis and structural features of five new coordination assemblies, [Co(bpyH)(H2O)5](BPCH)·(bpyH2)0.5·(H2O) (1a), [{Cu(H2O)3}·{Cu0.5(bpy)0.5(H2O)0.5}2(μ-BPCH)] (1b), [{Cd0.5(BPCH)}2·{Cd0.5(bpy)(H2O)2}2]·6(H2O) (1c), [Cu(BPCH2)(bpyeaH)]·2(H2O) (1d) and [Cd2 (bpyea)0.5(oxalate)0.5(μ-BPC) (H2O)]·(bpyeaH2)·2(H2O) (1e), have been reported. All the assemblies were prepared by co-crystallization of benzenepentacarboxylic acid (BPCH5) either with 4,4‧-bipyridine (bpy) or 1,2-bis(4-pyridyl)ethane (bpyea) in the presence of a transition metal ion (either Co(II), Cu(II) or Cd(II)) as the case may be. All the five compounds were synthesized by hydrothermal method and structures were determined by single crystal X-ray diffraction. All the obtained compounds, 1a-1e, exhibit distinct 3-D polymeric architectures either in the form of stacked layers or host-guest networks in which water molecules play a pivotal role providing additional stabilization by coordinate bonds as well as hydrogen bonds. Other non-covalent interactions such as C-H … π and π … π stacking also participate in the formation of exotic 3-D structures of these complexes.

  11. Stereotypes on Nodding syndrome: responses of health workers in ...

    African Journals Online (AJOL)

    Objective: To identify stereotypes and negative attitudes held by primary care health workers about nodding syndrome. Method: Of one hundred health workers invited by the Uganda Ministry of Health for training on nodding syndrome from the three most affected districts of Pader, Lamwo and Kitgum forty were interviewed ...

  12. First research coordination meeting for the coordinated research programme on the use of isotope techniques in investigating acidic fluids in geothermal exploitation. Report

    International Nuclear Information System (INIS)

    Gerardo-Abaya, J.

    1998-02-01

    Geothermal exploration and development for electrical and non-electrical applications is taking place in more than 36 countries worldwide. Although the technology has fully emerged, there are still hindrances to the full exploitation of the available heat. Most of the high temperature geothermal areas are situated in volcanic environments that produce acidic fluids which are corrosive for wells, as well as pipelines. Incidental drilling in those areas, for lack of better data, cause high economic losses ar a cost of about US D 2 million per well. In addition, a potential natural resource for electricity remains untapped. In realization of the problems associated with with geothermal exploitation and the potential role that isotope techniques could provide for a greater understanding of the complex behavior of geothermal systems, particularly those affected by acidic fluids, the Coordinated Research Programme (CRP) on the Use of Isotope Techniques in Problems Associated with Geothermal Exploitation is implemented in 1997-2000. An understanding of the phenomena will assist the scientific community involved in geothermal development. The information generated from the scientific investigations will be an input to management of the resource as well as to decision-making for monitoring and development of geothermal areas. The First Research Coordination Meeting for this CRP was held on 21-23 October 1997 in the IAEA Headquarters, Vienna, Austria. The results of the current investigations relating to acid fluids in the various geothermal systems were presented by the participants. The report provides the hydrological concept on which research on acid fluids is based. The report includes also the summaries of the researches under the CRP as well as the agreed actions for follow-up work

  13. Human umbilical cord blood mesenchymal stem cells reduce colitis in mice by activating NOD2 signaling to COX2.

    Science.gov (United States)

    Kim, Hyung-Sik; Shin, Tae-Hoon; Lee, Byung-Chul; Yu, Kyung-Rok; Seo, Yoojin; Lee, Seunghee; Seo, Min-Soo; Hong, In-Sun; Choi, Soon Won; Seo, Kwang-Won; Núñez, Gabriel; Park, Jong-Hwan; Kang, Kyung-Sun

    2013-12-01

    Decreased levels or function of nucleotide-binding oligomerization domain 2 (NOD2) are associated with Crohn's disease. NOD2 regulates intestinal inflammation, and also is expressed by human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), to regulate their differentiation. We investigated whether NOD2 is required for the anti-inflammatory activities of MSCs in mice with colitis. Colitis was induced in mice by administration of dextran sulfate sodium or trinitrobenzene sulfonic acid. Mice then were given intraperitoneal injections of NOD2-activated hUCB-MSCs; colon tissues and mesenteric lymph nodes were collected for histologic analyses. A bromodeoxyuridine assay was used to determine the ability of hUCB-MSCs to inhibit proliferation of human mononuclear cells in culture. Administration of hUCB-MSCs reduced the severity of colitis in mice. The anti-inflammatory effects of hUCB-MSCs were greatly increased by activation of NOD2 by its ligand, muramyl dipeptide (MDP). Administration of NOD2-activated hUCB-MSCs increased anti-inflammatory responses in colons of mice, such as production of interleukin (IL)-10 and infiltration by T regulatory cells, and reduced production of inflammatory cytokines. Proliferation of mononuclear cells was inhibited significantly by co-culture with hUCB-MSCs that had been stimulated with MDP. MDP induced prolonged production of prostaglandin (PG)E2 in hUCB-MSCs via the NOD2-RIP2 pathway, which suppressed proliferation of mononuclear cells derived from hUCB. PGE2 produced by hUCB-MSCs in response to MDP increased production of IL-10 and T regulatory cells. In mice, production of PGE2 by MSCs and subsequent production of IL-10 were required to reduce the severity of colitis. Activation of NOD2 is required for the ability of hUCB-MSCs to reduce the severity of colitis in mice. NOD2 signaling increases the ability of these cells to suppress mononuclear cell proliferation by inducing production of PGE2. Copyright © 2013 AGA

  14. SYNTHESIS, CHARACTERIZATION AND ANTITUMOR ACTIVITY OF A Ca (II COORDINATION POLYMER BASED ON 3-AMINO-2-PYRAZINECARBOXYLIC ACID

    Directory of Open Access Journals (Sweden)

    XI-SHI TAI

    2015-10-01

    Full Text Available A new Ca(II coordination polymer has been obtained by reaction of Ca(ClO42·H2O with 3-amino-2-pyrazinecarboxylic acid in CH3CH2OH/H2O. It was characterized by IR, 1HNMR, thermal analysis and X-ray single crystal diffraction analysis. X-ray analysis reveals that each Ca(II center is seven-coordination with a N2O5 distorted pentagonal bipyramidal coordination environment. The Ca(II ions are linked through the O atoms of 3-amino-2-pyrazinecarboxylic acid ligands to form 1D chain structure. And then a 3D network structure is constructed by hydrogen bonds and π-π stacking. The antitumor activity of 3-amino-2-pyrazinecarboxylic acid ligand and its Ca(II coordination polymer against human intestinal adenocarcinoma HCT-8 cells, lung adenocarcinoma HCT-116 cells and human lung adenocarcinoma A549 cells line have been investigated.

  15. Diverse CdII coordination complexes derived from bromide isophthalic acid binding with auxiliary N-donor ligands

    International Nuclear Information System (INIS)

    Tang, Meng; Dong, Bao-Xia; Wu, Yi-Chen; Yang, Fang; Liu, Wen-Long; Teng, Yun-Lei

    2016-01-01

    The coordination characteristics of 4-bromoisophthalic acid (4-Br-H 2 ip) have been investigated in a series of Cd II -based frameworks. Hydrothermal reactions of Cd II salts and 4-Br-H 2 ip together with flexible or semiflexible N-donor auxiliary ligands resulted in the formation of four three-dimensional coordination complexes with diverse structures: (Cd(bix) 0.5 (bix) 0.5 (4-Br-ip)]·H 2 O) n (1), [Cd(bbi) 0.5 (bbi) 0.5 (4-Br-ip)] n (2), ([Cd(btx) 0.5 (4-Br-ip)(H 2 O)]·0.5CH 3 OH·H 2 O) n (3) and ([Cd(bbt) 0.5 (4-Br-ip)(H 2 O)]·3·5H 2 O) n (4). These compounds were characterized by elemental analyses, IR spectra, single-crystal and powder X-ray diffraction. They displayed diverse structures depending on the configuration of the 4-connected metal node, the coordination mode of the 4-Br-H 2 ip, the coordination ability and conformationally flexibility of the N-donor auxiliary. Compound 1 exhibits 3-fold interpenetrated 6 6 topology and compound 2 has a 4 12 topology. Compounds 3–4 have similar 3D pillar-layered structures based on 3,4-connected binodal net with the Schläfli symbol of (4·3 8 ). The thermal stabilities and photoluminescence properties of them were discussed in detail. - Graphical abstract: Four 3D Cd II coordination complexes on the basis of 4-bromoisophthalic acid (4-Br-H 2 ip) and two types of flexible (bbi, bbt) and semiflexible (bix, btx) N-donor ligands are prepared. They displayed diverse topology structures of 6 6 (1), 4 12 (2) and 4·3 8 (3−4), depending on the configuration of the 4-connected metal node, the coordination mode of the 4-Br-H 2 ip, the coordination ability and conformationally flexibility of the N-donor auxiliary ligand. - Highlights: • Four 3D Cd II coordination complexes based on 4-Br-H 2 ip and flexible/semiflexible N-donor ligands have been synthesized. • They displayed diverse topology structures of 6 6 for 1, 4 12 for 2 and 4·3 8 for 3–4. • The structural diversity depends on the configuration of 4-Br

  16. N-(sulfoethyl) iminodiacetic acid-based lanthanide coordination polymers: Synthesis, magnetism and quantum Monte Carlo studies

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang Guilin, E-mail: glzhuang@zjut.edu.cn [Institute of Industrial Catalysis, College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310032 (China); Chen Wulin [Institute of Industrial Catalysis, College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310032 (China); Zheng Jun [Center of Modern Experimental Technology, Anhui University, Hefei 230039 (China); Yu Huiyou [Institute of Industrial Catalysis, College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310032 (China); Wang Jianguo, E-mail: jgw@zjut.edu.cn [Institute of Industrial Catalysis, College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310032 (China)

    2012-08-15

    A series of lanthanide coordination polymers have been obtained through the hydrothermal reaction of N-(sulfoethyl) iminodiacetic acid (H{sub 3}SIDA) and Ln(NO{sub 3}){sub 3} (Ln=La, 1; Pr, 2; Nd, 3; Gd, 4). Crystal structure analysis exhibits that lanthanide ions affect the coordination number, bond length and dimension of compounds 1-4, which reveal that their structure diversity can be attributed to the effect of lanthanide contraction. Furthermore, the combination of magnetic measure with quantum Monte Carlo(QMC) studies exhibits that the coupling parameters between two adjacent Gd{sup 3+} ions for anti-anti and syn-anti carboxylate bridges are -1.0 Multiplication-Sign 10{sup -3} and -5.0 Multiplication-Sign 10{sup -3} cm{sup -1}, respectively, which reveals weak antiferromagnetic interaction in 4. - Graphical abstract: Four lanthanide coordination polymers with N-(sulfoethyl) iminodiacetic acid were obtained under hydrothermal condition and reveal the weak antiferromagnetic coupling between two Gd{sup 3+} ions by Quantum Monte Carlo studies. Highlights: Black-Right-Pointing-Pointer Four lanthanide coordination polymers of H{sub 3}SIDA ligand were obtained. Black-Right-Pointing-Pointer Lanthanide ions play an important role in their structural diversity. Black-Right-Pointing-Pointer Magnetic measure exhibits that compound 4 features antiferromagnetic property. Black-Right-Pointing-Pointer Quantum Monte Carlo studies reveal the coupling parameters of two Gd{sup 3+} ions.

  17. Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease

    Directory of Open Access Journals (Sweden)

    Ingrid Stroo

    2012-10-01

    It is indispensable to thoroughly characterize each animal model in order to distinguish between primary and secondary effects of genetic changes. The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO mice under physiological and inflammatory conditions. Nod1 and Nod2 are members of the Nucleotide-binding domain and Leucine-rich repeat containing Receptor (NLR family. Several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2. These associations suggest that Nod1 and Nod2 play important roles in regulating the immune system. Three-month-old wildtype (Wt and Nod1/2 DKO mice were sacrificed, body and organ weight were determined, and blood was drawn. Except for lower liver weight in Nod1/2 DKO mice, no differences were found in body/organ weight between both strains. Leukocyte count and composition was comparable. No significant changes in analyzed plasma biochemical markers were found. Additionally, intestinal and vascular permeability was determined. Nod1/2 DKO mice show increased susceptibility for intestinal permeability while vascular permeability was not affected. Next we induced septic shock and organ damage by administering LPS+PGN intraperitoneally to Wt and Nod1/2 DKO mice and sacrificed animals after 2 and 24 hours. The systemic inflammatory and metabolic response was comparable between both strains. However, renal response was different as indicated by partly preserved kidney function and tubular epithelial cell damage in Nod1/2 DKO at 24 hours. Remarkably, renal inflammatory mediators Tnfα, KC and Il-10 were significantly increased in Nod1/2 DKO compared with Wt mice at 2 hours. Systematic analysis of Nod1/2 DKO mice revealed a possible role of Nod1/2 in the development of renal disease during systemic inflammation.

  18. Stereotypes on Nodding syndrome: responses of health workers in ...

    African Journals Online (AJOL)

    EB

    Background: Nodding Syndrome is a debilitating disorder of yet unknown etiology that has affected children .... Stigma of Mental Illness (ISMI) tool which was ..... Mental illness stigma: concepts, consequences, and initiatives to reduce stigma.

  19. A one-step colorimetric acid-base titration sensor using a complementary color changing coordination system.

    Science.gov (United States)

    Cho, Hui Hun; Kim, Si Hyun; Heo, Jun Hyuk; Moon, Young Eel; Choi, Young Hun; Lim, Dong Cheol; Han, Kwon-Hoon; Lee, Jung Heon

    2016-06-21

    We report the development of a colorimetric sensor that allows for the quantitative measurement of the acid content via acid-base titration in a single-step. In order to create the sensor, we used a cobalt coordination system (Co-complex sensor) that changes from greenish blue colored Co(H2O)4(OH)2 to pink colored Co(H2O)6(2+) after neutralization. Greenish blue and pink are two complementary colors with a strong contrast. As a certain amount of acid is introduced to the Co-complex sensor, a portion of greenish blue colored Co(H2O)4(OH)2 changes to pink colored Co(H2O)6(2+), producing a different color. As the ratio of greenish blue and pink in the Co-complex sensor is determined by the amount of neutralization reaction occurring between Co(H2O)4(OH)2 and an acid, the sensor produced a spectrum of green, yellow green, brown, orange, and pink colors depending on the acid content. In contrast, the color change appeared only beyond the end point for normal acid-base titration. When we mixed this Co-complex sensor with different concentrations of citric acid, tartaric acid, and malic acid, three representative organic acids in fruits, we observed distinct color changes for each sample. This color change could also be observed in real fruit juice. When we treated the Co-complex sensor with real tangerine juice, it generated diverse colors depending on the concentration of citric acid in each sample. These results provide a new angle on simple but quantitative measurements of analytes for on-site usage in various applications, such as in food, farms, and the drug industry.

  20. Syntheses and structures of three heterometallic coordination polymers derived from 4-pyridin-3-yl-benzoic acid

    International Nuclear Information System (INIS)

    Fang, Wei-Hui; Yang, Guo-Yu

    2014-01-01

    Three lanthanide–transition-metal coordination polymers, namely, [Er 2 L 6 (H 2 O)][Cu 2 I 2 ] (1), [ErL 3 ][CuI] (2), and [Dy 2 L 6 (BPDC) 0.5 (H 2 O) 4 ][Cu 3 I 2 ] (3) (HL=4-pyridin-3-yl-benzoic acid, H 2 BPDC=4,4′-biphenyldicarboxylic acid) have been made by reacting Ln 2 O 3 and CuI with HL at different temperatures under hydrothermal conditions. All the complexes are characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and single-crystal X-ray diffraction, respectively. 1–3 all construct from dimeric (Ln 2 ) and (Cu 2 ) units and exhibit two types of the structural features: 1 is a two-dimensional layer, 2–3 are three-dimensional frameworks. Interestingly, the in situ formation of the BPDC ligand is found in the structure of 3. The distinct architectures of these complexes indicated that the reaction temperature plays an important role in the formation of higher dimensional coordination polymers. - Graphical abstract: By hydrothermal reaction of lanthanide oxide, copper halide, and 4-pyridin-3-yl-benzoic ligand at different temperatures, a series of 1-D to 3-D 3d–4f coordination polymers, namely [ErL 3 (H 2 O) 2 ][CuI], [Er 2 L 6 (H 2 O)][Cu 2 I 2 ], [ErL 3 ][CuI], and [Dy 2 L 6 (BPDC) 0.5 (H 2 O) 4 ][Cu 3 I 2 ], have been made, respectively. - Highlights: • Three novel heterometallic coordination polymers derived from 4-pyridin-3-yl-benzoic acid have been hydrothermally synthesized. • Mixed dinuclear motifs of (Ln 2 ) and (Cu 2 ) serve as secondary building units to generate 2-D layer and 3-D frameworks. • It is proved that higher temperature is apt to permit construction of high dimensional architectures

  1. Caring to Care: Applying Noddings' Philosophy to Medical Education.

    Science.gov (United States)

    Balmer, Dorene F; Hirsh, David A; Monie, Daphne; Weil, Henry; Richards, Boyd F

    2016-12-01

    The authors argue that Nel Noddings' philosophy, "an ethic of caring," may illuminate how students learn to be caring physicians from their experience of being in a caring, reciprocal relationship with teaching faculty. In her philosophy, Noddings acknowledges two important contextual continuities: duration and space, which the authors speculate exist within longitudinal integrated clerkships. In this Perspective, the authors highlight core features of Noddings' philosophy and explore its applicability to medical education. They apply Noddings' philosophy to a subset of data from a previously published longitudinal case study to explore its "goodness of fit" with the experience of eight students in the 2012 cohort of the Columbia-Bassett longitudinal integrated clerkship. In line with Noddings' philosophy, the authors' supplementary analysis suggests that students (1) recognized caring when they talked about "being known" by teaching faculty who "cared for" and "trusted" them; (2) responded to caring by demonstrating enthusiasm, action, and responsibility toward patients; and (3) acknowledged that duration and space facilitated caring relations with teaching faculty. The authors discuss how Noddings' philosophy provides a useful conceptual framework to apply to medical education design and to future research on caring-oriented clinical training, such as longitudinal integrated clerkships.

  2. Circulatory and Renal Consequences of Pregnancy in Diabetic NOD Mice

    Science.gov (United States)

    Burke, S.D.; Barrette, V.F.; David, S.; Khankin, E. V.; Adams, M.A.; Croy, B.A.

    2011-01-01

    Objectives Women with diabetes have elevated gestational risks for severe hemodynamic complications, including preeclampsia in mid- to late pregnancy. This study employed continuous, chronic radiotelemetry to compare the hemodynamic patterns in non-obese diabetic (NOD) mice who were overtly diabetic or normoglycemic throughout gestation. We hypothesized that overtly diabetic, pregnant NOD mice would develop gestational hypertension and provide understanding of mechanisms in progression of this pathology. Study Design Telemeter-implanted, age-matched NOD females with and without diabetes were assessed for six hemodynamic parameters (mean, systolic, diastolic, pulse pressures, heart rate and activity) prior to mating, over pregnancy and over a 72 hr post-partum interval. Urinalysis, serum biochemistry and renal histopathology were also conducted. Results Pregnant, normoglycemic NOD mice had a hemodynamic profile similar to other inbred strains, despite insulitis. This pattern was characterized by an interval of pre-implantation stability, post implantation decline in arterial pressure to mid gestation, and then a rebound to pre-pregnancy baseline during later gestation. Overtly diabetic NOD mice had a blood pressure profile that was normal until mid-gestation then become mildly hypotensive (−7mmHg, Ppost-partum (−10% pre-pregnancy pressure and HR, P<0.05). Conclusions Pregnancy accelerates circulatory and renal pathologies in overtly diabetic NOD mice and is characterized by depressed arterial pressure from mid-gestation and birth of growth 45 restricted offspring. PMID:22014504

  3. Role of NOD2/CARD15 in coronary heart disease

    Directory of Open Access Journals (Sweden)

    Förster Matti

    2007-11-01

    Full Text Available Abstract Background: Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD patients. Phylogenetic signatures in the atheroma lesions that are similar to those of bacterial biofilms on human barrier organs, including the respiratory or gastrointestinal tract, raise the question of a defective barrier function in CHD. NOD2 plays a major role in defense against bacterial invasion. Genetic variation in the CARD15 gene, which encodes NOD2, was previously shown to result in a barrier defect that causes chronic inflammatory disorders (e.g. Crohn disease. In the present study, we investigated the possible involvement of NOD2/CARD15 in the pathology of CHD by i analyzing the local expression of NOD2 in atherectomy versus healthy tissue (n = 5 each using histochemical immunofluorescence and ii by testing the three major functional CARD15 variants (R702W, G908R and 1007fs for association with early-onset CHD in 900 German patients and 632 healthy controls. Results: In atherectomy tissue of CHD patients, NOD2 was detected in inflammatory cells at the luminal sides of the lesions. However, the allele and genotype frequencies of the three major CARD15 polymorphisms did not differ between CHD patients and controls. Conclusion: The NOD2 up-regulation in atheroma lesions indicates an involvement of this protein in the pathology of CHD. Although NOD2 could be important in local immune response mechanisms, none of the analyzed CARD15 variants seem to play a significant role in the etiology of CHD.

  4. Vibrational treatment of the formic acid double minimum case in valence coordinates

    Science.gov (United States)

    Richter, Falk; Carbonnière, P.

    2018-02-01

    One single full dimensional valence coordinate HCOOH ground state potential energy surface accurate for both cis and trans conformers for all levels up to 6000 cm-1 relative to trans zero point energy has been generated at CCSD(T)-F12a/aug-cc-pVTZ level. The fundamentals and a set of eigenfunctions complete up to about 3120 and 2660 cm-1 for trans- and cis-HCOOH, respectively, have been calculated and assigned using the improved relaxation method of the Heidelberg multi-configuration time-dependent Hartree package and an exact expression for the kinetic energy in valence coordinates generated by the TANA program. The calculated trans fundamental transition frequencies agree with experiment to within 5 cm-1. A few reassignments are suggested. Our results discard any cis trans delocalization effects for vibrational eigenfunctions up to 3640 cm-1 relative to trans zero point energy.

  5. Functional Roles of NOD1 in Odontoblasts on Dental Pulp Innate Immunity

    Directory of Open Access Journals (Sweden)

    Yuki Hosokawa

    2016-01-01

    Full Text Available Caries-related pathogens are first recognized by odontoblasts and induce inflammatory events that develop to pulpitis. Generally, initial sensing of microbial pathogens is mediated by pattern recognition receptors, such as Toll-like receptor and nucleotide-binding oligomerization domain (NOD; however, little is known about NODs in odontoblasts. In this study, the levels of NODs expressed in rat odontoblastic cell line, KN-3, were assessed by flow cytometry and the levels of chemokines in NOD-specific ligand-stimulated KN-3 cells were analyzed by real-time PCR and ELISA. The signal transduction pathway activated with NOD-specific ligand was assessed by blocking assay with specific inhibitors and reporter assay. In KN-3 cells, the expression level of NOD1 was stronger than that of NOD2 and the production of chemokines, such as CINC-1, CINC-2, CCL20, and MCP-1, was upregulated by stimulation with NOD1-specific ligand, but not with NOD2-specific ligand. CINC-2 and CCL20 production by stimulation with NOD1-specific ligand was reduced by p38 MAPK and AP-1 signaling inhibitors. Furthermore, the reporter assay demonstrated AP-1 activation in NOD1-specific ligand-stimulated KN-3 cells. These findings indicated that NOD1 expressed in odontoblasts functions to upregulate the chemokines expression via p38-AP-1 signaling pathway and suggested that NOD1 may play important roles in the initiation and progression of pulpitis.

  6. Functional Roles of NOD1 in Odontoblasts on Dental Pulp Innate Immunity.

    Science.gov (United States)

    Hosokawa, Yuki; Hirao, Kouji; Yumoto, Hiromichi; Washio, Ayako; Nakanishi, Tadashi; Takegawa, Daisuke; Kitamura, Chiaki; Matsuo, Takashi

    2016-01-01

    Caries-related pathogens are first recognized by odontoblasts and induce inflammatory events that develop to pulpitis. Generally, initial sensing of microbial pathogens is mediated by pattern recognition receptors, such as Toll-like receptor and nucleotide-binding oligomerization domain (NOD); however, little is known about NODs in odontoblasts. In this study, the levels of NODs expressed in rat odontoblastic cell line, KN-3, were assessed by flow cytometry and the levels of chemokines in NOD-specific ligand-stimulated KN-3 cells were analyzed by real-time PCR and ELISA. The signal transduction pathway activated with NOD-specific ligand was assessed by blocking assay with specific inhibitors and reporter assay. In KN-3 cells, the expression level of NOD1 was stronger than that of NOD2 and the production of chemokines, such as CINC-1, CINC-2, CCL20, and MCP-1, was upregulated by stimulation with NOD1-specific ligand, but not with NOD2-specific ligand. CINC-2 and CCL20 production by stimulation with NOD1-specific ligand was reduced by p38 MAPK and AP-1 signaling inhibitors. Furthermore, the reporter assay demonstrated AP-1 activation in NOD1-specific ligand-stimulated KN-3 cells. These findings indicated that NOD1 expressed in odontoblasts functions to upregulate the chemokines expression via p38-AP-1 signaling pathway and suggested that NOD1 may play important roles in the initiation and progression of pulpitis.

  7. Comparative genomic analysis of buffalo (Bubalus bubalis NOD1 and NOD2 receptors and their functional role in in-vitro cellular immune response.

    Directory of Open Access Journals (Sweden)

    Biswajit Brahma

    Full Text Available Nucleotide binding and oligomerization domain (NOD-like receptors (NLRs are innate immune receptors that recognize bacterial cell wall components and initiate host immune response. Structure and function of NLRs have been well studied in human and mice, but little information exists on genetic composition and role of these receptors in innate immune system of water buffalo--a species known for its exceptional disease resistance. Here, a comparative study on the functional domains of NOD1 and NOD2 was performed across different species. The NOD mediated in-vitro cellular responses were studied in buffalo peripheral blood mononuclear cells, resident macrophages, mammary epithelial, and fibroblast cells. Buffalo NOD1 (buNOD1 and buNOD2 showed conserved domain architectures as found in other mammals. The domains of buNOD1 and buNOD2 showed analogy in secondary and tertiary conformations. Constitutive expressions of NODs were ubiquitous in different tissues. Following treatment with NOD agonists, peripheral lymphocytes showed an IFN-γ response along-with production of pro-inflammatory cytokines. Alveolar macrophages and mammary epithelial cells showed NOD mediated in-vitro immune response through NF-κB dependent pathway. Fibroblasts showed pro-inflammatory cytokine response following agonist treatment. Our study demonstrates that both immune and non-immune cells could generate NOD-mediated responses to pathogens though the type and magnitude of response depend on the cell types. The structural basis of ligand recognition by buffalo NODs and knowledge of immune response by different cell types could be useful for development of non-infective innate immune modulators and next generation anti-inflammatory compounds.

  8. Compatibility of nitrilotriacetic acid and 3-acetyl-4-hydroxy-6-methyl-2-pyrone in the coordination sphere of lanthanon ions

    International Nuclear Information System (INIS)

    Kadian, R.K.; Garg, B.S.; Singh, R.P.

    1982-01-01

    A study of the competetion of 3-acetyl-4-hydroxy-6-methyl-2-pyrone (dehydracetic acid, DHA) and nitrilotriacetic acid (NTA) in the coordination sphere of lanthanon ions has been carried out by calculating reproportionation constant which relates the stability of the mixed ligand complex to those of the parent complexes formed by the same ligands. It has been found that NTA and DHA are incompatible ligands and mixed ligand complexes formed are less stable than either of the parent complexes. The fact is also supported by the observed change in free energy occuring during mixed ligand complex formation. All these studies have been carried out at 30.0 +- 0.5 0 and μ-0.01 (NaClO 4 ) in 50 percent v/v aqueous dioxane medium. (author)

  9. Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

    Directory of Open Access Journals (Sweden)

    Manal Alkan

    2015-01-01

    Full Text Available Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD mouse model. To this end, we used mice (inactivated knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC−/− mice decreased the incidence of diabetes in relation to their wild-type counterpart. Whereas the proportion of regulatory T and myeloid-derived suppressive cells was similar in both strains, histamine deficiency was associated with increased levels of immature macrophages, as compared with wild-type NOD mice. Concerning the cytokine pattern, we found a decrease in circulating IL-12 and IFN-γ in HDC−/− mice, while IL-6 or leptin remained unchanged, suggesting that histamine primarily modulates the inflammatory environment. Paradoxically, exogenous histamine given to NOD HDC−/− mice provided also protection against T1D. Our study supports the notion that histamine is involved in the pathogenesis of diabetes, thus providing additional evidence for its role in the regulation of the immune response.

  10. Nodding syndrome (NS) and Onchocerca Volvulus (OV) in Northern Uganda.

    Science.gov (United States)

    Lagoro, David Kitara; Arony, Denis Anywar

    2017-01-01

    Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus ( OV ). These findings suggest a neuro-inflammatory cause of NS and they are important findings in the search for the cause of Nodding Syndrome. These observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus . Many clinical and epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease, Onchocerciasis , some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with ( OV infection (using positive skin snips), we observe that ( OV is generally endemic in many parts of Sub Saharan Africa and Latin America and that to date, no NS cases have been recorded in those regions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda.

  11. Symbiotic Activity of Pea (Pisum sativum) after Application of Nod Factors under Field Conditions

    OpenAIRE

    Siczek, Anna; Lipiec, Jerzy; Wielbo, Jerzy; Kidaj, Dominika; Szarlip, Paweł

    2014-01-01

    Growth and symbiotic activity of legumes are mediated by Nod factors (LCO, lipo-chitooligosaccharides). To assess the effects of application of Nod factors on symbiotic activity and yield of pea, a two-year field experiment was conducted on a Haplic Luvisol developed from loess. Nod factors were isolated from Rhizobium leguminosarum bv. viciae strain GR09. Pea seeds were treated with the Nod factors (10−11 M) or water (control) before planting. Symbiotic activity was evaluated by measurement...

  12. Cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model.

    Science.gov (United States)

    Arita, Minetaro; Ami, Yasushi; Wakita, Takaji; Shimizu, Hiroyuki

    2008-02-01

    Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

  13. DMPD: NOD-like receptors (NLRs): bona fide intracellular microbial sensors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18585455 NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Shaw...tml) (.csml) Show NOD-like receptors (NLRs): bona fide intracellular microbial sensors. PubmedID 18585455 Ti...tle NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Authors

  14. Molecular cloning and functional characterization of duck nucleotide-binding oligomerization domain 1 (NOD1).

    Science.gov (United States)

    Li, Huilin; Jin, Hui; Li, Yaqian; Liu, Dejian; Foda, Mohamed Frahat; Jiang, Yunbo; Luo, Rui

    2017-09-01

    Nucleotide-binding oligomerization domain 1 (NOD1) is an imperative cytoplasmic pattern recognition receptor (PRR) and considered as a key member of the NOD-like receptor (NLR) family which plays a critical role in innate immunity through sensing microbial components derived from bacterial peptidoglycan. In the current study, the full-length of duck NOD1 (duNOD1) cDNA from duck embryo fibroblasts (DEFs) was cloned. Multiple sequence alignment and phylogenetic analysis demonstrated that duNOD1 exhibited a strong evolutionary relationship with chicken and rock pigeon NOD1. Tissue-specific expression analysis showed that duNOD1 was widely distributed in various organs, with the highest expression observed in the liver. Furthermore, duNOD1 overexpression induced NF-κB activation in DEFs and the CARD domain is crucial for duNOD1-mediated NF-κB activation. In addition, silencing the duNOD1 decreased the activity of NF-κB in DEFs stimulated by iE-DAP. Overexpression of duNOD1 significantly increased the expression of TNF-α, IL-6, and RANTES in DEFs. These findings highlight the crucial role of duNOD1 as an intracellular sensor in duck innate immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. DMPD: Role of Nods in bacterial infection. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17379560 Role of Nods in bacterial infection. Bourhis LL, Werts C. Microbes Infect.... 2007 Apr;9(5):629-36. Epub 2007 Jan 27. (.png) (.svg) (.html) (.csml) Show Role of Nods in bacterial infect...ion. PubmedID 17379560 Title Role of Nods in bacterial infection. Authors Bourhis LL, Werts C. Publication M

  16. Control of amino acid transport coordinates metabolic reprogramming in T-cell malignancy.

    Science.gov (United States)

    Grzes, K M; Swamy, M; Hukelmann, J L; Emslie, E; Sinclair, L V; Cantrell, D A

    2017-12-01

    This study explores the regulation and importance of System L amino acid transport in a murine model of T-cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1α (HIF1α) and c-Myc; drivers of glucose metabolism in T cells. A key finding is that PTEN deletion and phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P 3 ) accumulation is insufficient to initiate leucine uptake, mTORC1 activity, HIF1α or c-Myc expression in T cells and hence cannot drive T-ALL metabolic reprogramming. Instead, a key regulator for leucine transport in T-ALL is identified as NOTCH. Mass spectrometry based proteomics identifies SLC7A5 as the predominant amino acid transporter in primary PTEN -/- T-ALL cells. Importantly, expression of SLC7A5 is critical for the malignant transformation induced by PTEN deletion. These data reveal the importance of regulated amino acid transport for T-cell malignancies, highlighting how a single amino acid transporter can have a key role.

  17. TLR4, NOD1 and NOD2 Mediate Immune Recognition of Putative Newly-Identified Periodontal Pathogens

    Science.gov (United States)

    Schaff, Riley A.; Hao, Jie; Morelli, Thiago; Kinney, Janet S.; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J.; Inohara, Naohiro; Giannobile, William V.

    2015-01-01

    SUMMARY Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. While the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, 6 being classical pathogens and 4 putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone marrow–derived macrophages (BMDM) from wild-type (WT) and toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. C. concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney (HEK) cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2-stimulatory activity. These studies allowed us to provide important evidence on newly-identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). PMID:26177212

  18. Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the tricarboxylic acid (TCA) cycle.

    Science.gov (United States)

    Gameiro, Paulo A; Laviolette, Laura A; Kelleher, Joanne K; Iliopoulos, Othon; Stephanopoulos, Gregory

    2013-05-03

    Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of α-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)(+) cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P)H/NAD(P)(+) ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle.

  19. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Science.gov (United States)

    Ryan, Veronica H; Primiani, Christopher T; Rao, Jagadeesh S; Ahn, Kwangmi; Rapoport, Stanley I; Blanchard, Helene

    2014-01-01

    The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  20. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Directory of Open Access Journals (Sweden)

    Veronica H Ryan

    Full Text Available The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades.AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging.The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism.Expression patterns were split into Development (0 to 20 years and Aging (21 to 78 years intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2, cyclooxygenases (COX-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA and PTGS2 (COX-2 genes at 1q25, highly inter-correlated genes were at distant chromosomal loci.Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  1. Synthesis, Crystal Structure, and Luminescence Properties of a New Calcium(II Coordination Polymer Based on L-Malic Acid

    Directory of Open Access Journals (Sweden)

    Duraisamy Senthil Raja

    2013-01-01

    Full Text Available A new calcium coordination polymer [Ca(HL-MA]n (H3L-MA = L-malic acid has been solvothermally synthesized. The structure of the newly synthesized complex has been determined by single-crystal X-ray diffraction analysis and further characterized by elemental analysis, reflectance UV-Vis & IR spectra, powder X-ray diffraction (PXRD, and thermogravimetric analysis (TGA. The single crystal structure analysis showed that the complex forms three-dimensional framework. The new Ca(II complex has displayed very high thermal stability which was inferred from TGA and PXRD results. As far as the optical property of the new complex is concerned, the complex emitted its own characteristic sensitized luminescence.

  2. Synthesis, crystal structure and optical property of three coordination polymer constructed from m-phenylenediacrylate acid

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, YiFan; Wang, TingTing; Zeng, HePing, E-mail: hpzeng@scut.edu.cn

    2015-01-15

    Three new complexes of the wholly deprotonated flexible ligand m-phenylenediacrylate acid (H{sub 2}mpda), namely, [Zn (mpda) (H{sub 2}O)] [1], [Pr{sub 2}(mpda){sub 2}(H{sub 2}O){sub 2}(CHOO){sub 2}] [2], and [Mn{sub 2}(mpda){sub 2} (H{sub 2}O){sub 4}] [3], were synthesized by the solvothermal reaction. The complexes were characterized by IR spectroscopy, thermogravimetric analysis, and X-ray single-crystal diffraction. A mixed sample [Nd(mpda)(H{sub 2}O)(CHOO)·Pr(mpda)(H{sub 2}O)(CHOO)] [2{sup ]} was also synthesized and studied. Compounds [1] and [2] exhibit a selective sensing function with respect to acetone, and they are a potential luminescent sensory material for the selective detection of Zn{sup 2+} and Ni{sup 2+} ions, respectively. Furthermore, the fluorescent changes of compound [1] upon the addition of cations (Fe{sup 3+} and Zn{sup 2+}, Bi{sup 2+} and Zn{sup 2+}) are utilized to construct two logic gates at the molecular level. - Graphical abstract: Three new complexes of flexible ligand m-phenylenedicarboxylic acid were synthesized by solvothermal reaction. Three metal−organic frameworks exhibiting 1D, 2D, 3D structures, respectively. - Highlights: • Three new complexes of m-phenylenedicarboxylic acid were synthesized. • Three metal−organic frameworks exhibiting 1D, 2D, 3D structures, respectively. • [1] and [2] exhibits a very high quenching effect with acetone. • [1] and [2] are a potential luminescent sensory material for Zn{sup 2+}, Ni{sup 2+} ions. • Two logic gates have been constructed using compound [1].

  3. Nodding syndrome in Mundri county, South Sudan: Environmental ...

    African Journals Online (AJOL)

    Background: Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda. Objective: To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 ...

  4. Coupling of Nod1D and HOTCHANNEL: static case

    International Nuclear Information System (INIS)

    Gomez T, A.M.; Ovando C, R.

    2003-01-01

    In this work the joining of the programs Nod1D and HOTCHANNEL, developed in the National Polytechnic Institute (IPN) and in the Electrical Research Institute (IIE) respectively is described. The first one allows to study the neutronic of a nuclear reactor and the second one allows to carry out the analysis of hot channel of a Boiling Water Reactor (BWR). Nod1 D is a program that it solves by nodal methods type finite element those diffusion equations in multigroup, and it is the static part of Nod Kin that it solves the diffusion equation in their time dependent part. For another side HOTCHANNEL is based on a mathematical model constituted by four conservation equations (two of mass conservation, one of motion quantity and one of energy), which are solved applying one discretization in implicit finite differences. Both programs have been verified in independent form using diverse test problems. In this work the modifications that were necessary to carry out to both for obtaining a coupled program that it provides the axial distribution of the neutron flux, the power, the burnup and the void fraction, among others parameters as much as neutronic as thermal hydraulics are described. Those are also mentioned limitations, advantages and disadvantages of the final product to which has been designated Nod1 D-HotChn. Diverse results for the Cycle 1 of the Laguna Verde Unit 1 reactor of the Nucleo electric central comparing them with those obtained directly with the CoreMasterPresto code are provided. (Author)

  5. Caring and Agency: Noddings on Happiness in Education

    Science.gov (United States)

    Alexander, Hanan

    2013-01-01

    In this short essay I express my own deep sympathy with Nel Noddings's ethic of care and applaud her stubborn resistance in "Happiness and Education" to what John Dewey would have called false dualisms, such as those between intelligence and emotion, theory and practice, or vocation and academic studies.However, I question whether…

  6. Noddings's caring ethics theory applied in a paediatric setting.

    Science.gov (United States)

    Lundqvist, Anita; Nilstun, Tore

    2009-04-01

    Since the 1990s, numerous studies on the relationship between parents and their children have been reported on in the literature and implemented as a philosophy of care in most paediatric units. The purpose of this article is to understand the process of nurses' care for children in a paediatric setting by using Noddings's caring ethics theory. Noddings's theory is in part described from a theoretical perspective outlining the basic idea of the theory followed by a critique of her work. Important conceptions in her theory are natural caring (reception, relation, engrossment, motivational displacement, reciprocity) and ethical caring (physical self, ethical self, and ethical ideal). As a nurse one holds a duty of care to patients and, in exercising this duty, the nurse must be able to develop a relationship with the patient including giving the patient total authenticity in a 'feeling with' the patient. Noddings's theory is analysed and described in three examples from the paediatrics. In the first example, the nurse cared for the patient in natural caring while in the second situation, the nurse strived for the ethical caring of the patient. In the third example, the nurse rejected the impulse to care and deliberately turned her back to ethics and abandoned her ethical caring. According to the Noddings's theory, caring for the patient enables the nurse to obtain ethical insights from the specific type of nursing care which forms an important contribution to an overall increase of an ethical consciousness in the nurse.

  7. Investigation into the Nodding syndrome in Witto Payam, Western ...

    African Journals Online (AJOL)

    2011-02-01

    Feb 1, 2011 ... b MBBS, Resident Field Epidemiology and Laboratory Training. Program Kenya ... Training Program Kenya, Ministry of Health d BSc, MSc ... 52% of their parents said that “nodding is induced by ... of eyes, salivation, loss of sphincter control, confusion .... the Jambo area (or in Witto Payam) around 1992.

  8. Human LT-alpha-mediated resistance to autoimmune diabetes is induced in NOD, but not NOD-scid, mice and abrogated by IL-12.

    Science.gov (United States)

    Miyaguchi, S; Satoh, J; Takahashi, K; Sakata, Y; Nakazawa, T; Miyazaki, J; Toyota, T

    2001-01-01

    Systemic administration of human lymphotoxin-alpha (hLT-alpha) made NOD mice resistant not only to spontaneous autoimmune type 1 diabetes mellitus but also to cyclophosphamide (CY)-induced diabetes and diabetes transfer by diabetic NOD spleen cells (triple resistance). In this study we analyzed the mechanisms of hLT-alpha-induced resistance, focusing on (1) hLT-alpha-induced resistance in the pancreatic beta cell, (2) CY-resistant suppressor cells, (3) suppression of induction or function of effector cells for beta cell destruction, or (4) others. To examine the first possibility in vitro, a NOD-derived beta cell line (MIN6N) was pretreated with hLT-alpha and then mixed with diabetic NOD spleen cells and MIN6N cell viability was measured. Treatment with hLT-alpha did not protect MIN6N cells but rather enhanced cytotoxicity. Next NOD-scid mice were pretreated with hLT-alpha and then transferred with diabetic NOD spleen. All the recipients developed diabetes. These results excluded the first possibility. The second possibility was also excluded by a cotransfer experiment, in which diabetic NOD spleen cells were cotransferred to NOD-scid mice with nontreated or hLT-alpha-treated nondiabetic NOD spleens. There was no significant difference in diabetes incidence between the two groups. To observe the third possibility, spleen cells of hLT-alpha-treated triple-resistant NOD mice were transferred to NOD-scid mice. Diabetes developed in the recipients, although the onset of diabetes was slightly delayed. Finally, hLT-alpha-treated triple-resistant NOD mice developed diabetes 1 week after daily IL-12 treatment. In summary, hLT-alpha administration made NOD mice resistant to effector cells for beta cell destruction. This resistance was induced in NOD, but not in NOD-scid, mice, indicating that lymphocytes were obligatory for the resistance. However, it was not mediated by transferable suppressor cells. Because effector cells were present in hLT-alpha-treated NOD spleen and

  9. Coupling of Nod1D and HOTCHANNEL: static case; Acoplamiento de Nod1D y HOTCHANNEL: caso estatico

    Energy Technology Data Exchange (ETDEWEB)

    Gomez T, A.M. [IPN-ESFM, 07738 Mexico D.F. (Mexico); Ovando C, R. [IIE-Gcia. de Energia Nuclear, Cuernavaca, Morelos (Mexico)]. e-mail: rovando@iie.org.mx

    2003-07-01

    In this work the joining of the programs Nod1D and HOTCHANNEL, developed in the National Polytechnic Institute (IPN) and in the Electrical Research Institute (IIE) respectively is described. The first one allows to study the neutronic of a nuclear reactor and the second one allows to carry out the analysis of hot channel of a Boiling Water Reactor (BWR). Nod1 D is a program that it solves by nodal methods type finite element those diffusion equations in multigroup, and it is the static part of Nod Kin that it solves the diffusion equation in their time dependent part. For another side HOTCHANNEL is based on a mathematical model constituted by four conservation equations (two of mass conservation, one of motion quantity and one of energy), which are solved applying one discretization in implicit finite differences. Both programs have been verified in independent form using diverse test problems. In this work the modifications that were necessary to carry out to both for obtaining a coupled program that it provides the axial distribution of the neutron flux, the power, the burnup and the void fraction, among others parameters as much as neutronic as thermal hydraulics are described. Those are also mentioned limitations, advantages and disadvantages of the final product to which has been designated Nod1 D-HotChn. Diverse results for the Cycle 1 of the Laguna Verde Unit 1 reactor of the Nucleo electric central comparing them with those obtained directly with the CoreMasterPresto code are provided. (Author)

  10. Candidatus Frankia Datiscae Dg1, the Actinobacterial Microsymbiont of Datisca glomerata, Expresses the Canonical nod Genes nodABC in Symbiosis with Its Host Plant

    Science.gov (United States)

    Persson, Tomas; Battenberg, Kai; Demina, Irina V.; Vigil-Stenman, Theoden; Vanden Heuvel, Brian; Pujic, Petar; Facciotti, Marc T.; Wilbanks, Elizabeth G.; O'Brien, Anna; Fournier, Pascale; Cruz Hernandez, Maria Antonia; Mendoza Herrera, Alberto; Médigue, Claudine; Normand, Philippe; Pawlowski, Katharina; Berry, Alison M.

    2015-01-01

    Frankia strains are nitrogen-fixing soil actinobacteria that can form root symbioses with actinorhizal plants. Phylogenetically, symbiotic frankiae can be divided into three clusters, and this division also corresponds to host specificity groups. The strains of cluster II which form symbioses with actinorhizal Rosales and Cucurbitales, thus displaying a broad host range, show suprisingly low genetic diversity and to date can not be cultured. The genome of the first representative of this cluster, Candidatus Frankia datiscae Dg1 (Dg1), a microsymbiont of Datisca glomerata, was recently sequenced. A phylogenetic analysis of 50 different housekeeping genes of Dg1 and three published Frankia genomes showed that cluster II is basal among the symbiotic Frankia clusters. Detailed analysis showed that nodules of D. glomerata, independent of the origin of the inoculum, contain several closely related cluster II Frankia operational taxonomic units. Actinorhizal plants and legumes both belong to the nitrogen-fixing plant clade, and bacterial signaling in both groups involves the common symbiotic pathway also used by arbuscular mycorrhizal fungi. However, so far, no molecules resembling rhizobial Nod factors could be isolated from Frankia cultures. Alone among Frankia genomes available to date, the genome of Dg1 contains the canonical nod genes nodA, nodB and nodC known from rhizobia, and these genes are arranged in two operons which are expressed in D. glomerata nodules. Furthermore, Frankia Dg1 nodC was able to partially complement a Rhizobium leguminosarum A34 nodC::Tn5 mutant. Phylogenetic analysis showed that Dg1 Nod proteins are positioned at the root of both α- and β-rhizobial NodABC proteins. NodA-like acyl transferases were found across the phylum Actinobacteria, but among Proteobacteria only in nodulators. Taken together, our evidence indicates an Actinobacterial origin of rhizobial Nod factors. PMID:26020781

  11. Nod2 is required for antigen-specific humoral responses against antigens orally delivered using a recombinant Lactobacillus vaccine platform.

    Directory of Open Access Journals (Sweden)

    Sara A Bumgardner

    Full Text Available Safe and efficacious orally-delivered mucosal vaccine platforms are desperately needed to combat the plethora of mucosally transmitted pathogens. Lactobacillus spp. have emerged as attractive candidates to meet this need and are known to activate the host innate immune response in a species- and strain-specific manner. For selected bacterial isolates and mutants, we investigated the role of key innate immune pathways required for induction of innate and subsequent adaptive immune responses. Co-culture of murine macrophages with L. gasseri (strain NCK1785, L. acidophilus (strain NCFM, or NCFM-derived mutants-NCK2025 and NCK2031-elicited an M2b-like phenotype associated with TH2 skewing and immune regulatory function. For NCFM, this M2b phenotype was dependent on expression of lipoteichoic acid and S layer proteins. Through the use of macrophage genetic knockouts, we identified Toll-like receptor 2 (TLR2, the cytosolic nucleotide-binding oligomerization domain containing 2 (NOD2 receptor, and the inflammasome-associated caspase-1 as contributors to macrophage activation, with NOD2 cooperating with caspase-1 to induce inflammasome derived interleukin (IL-1β in a pyroptosis-independent fashion. Finally, utilizing an NCFM-based mucosal vaccine platform with surface expression of human immunodeficiency virus type 1 (HIV-1 Gag or membrane proximal external region (MPER, we demonstrated that NOD2 signaling is required for antigen-specific mucosal and systemic humoral responses. We show that lactobacilli differentially utilize innate immune pathways and highlight NOD2 as a key mediator of macrophage function and antigen-specific humoral responses to a Lactobacillus acidophilus mucosal vaccine platform.

  12. Dynamics of ethylene production in response to compatible Nod factor

    DEFF Research Database (Denmark)

    Reid, Dugald; Liu, Huijun; Kelly, Simon

    2018-01-01

    Establishment of symbiotic nitrogen-fixation in legumes is regulated by the plant hormone ethylene, but it has remained unclear whether and how its biosynthesis is regulated by the symbiotic pathway. We established a sensitive ethylene detection system for Lotus japonicus and found that ethylene...... production increased as early as six hours after inoculation with Mesorhizobium loti. This ethylene response was dependent on Nod factor production by compatible rhizobia. Analyses of nodulation mutants showed that perception of Nod factor was required for ethylene emission, while downstream transcription...... factors including CYCLOPS, NIN and ERN1 were not required for this response. Activation of the nodulation signalling pathway in spontaneously nodulating mutants was also sufficient to elevate ethylene production. Ethylene signalling is controlled by EIN2, which is duplicated in L. japonicus. We obtained...

  13. Preparation of epoxy/zirconia hybrid materials via in situ polymerization using zirconium alkoxide coordinated with acid anhydride

    International Nuclear Information System (INIS)

    Ochi, Mitsukazu; Nii, Daisuke; Harada, Miyuki

    2011-01-01

    Highlights: → Novel epoxy/zirconia hybrid materials were synthesized via in situ polymerization using zirconium alkoxide coordinated with acid anhydride. → The half-ester compound of acid anhydride desorbed from zirconium played as curing agent of epoxy resin. → The zirconia was uniformly dispersed in the epoxy matrix on the nanometer or sub-nanometer scale by synchronizing the epoxy curing and sol-gel reactions. → The refractive indices of the hybrid materials significantly improved with an increase in the zirconia content. - Abstract: Novel epoxy/zirconia hybrid materials were synthesized using a bisphenol A epoxy resin (diglycidyl ether of bisphenol A; DGEBA), zirconium(IV)-n-propoxide (ZTNP), and hexahydrophthalic anhydride (HHPA) via in situ polymerization. HHPA played two roles in this system: it acted as a modifier to control the hydrolysis and condensation reactions of zirconium alkoxide and also as a curing agent - the half-ester compound of HHPA desorbed from zirconium reacted with the epoxy resin to form the epoxy network. As a result, both the sol-gel reaction and epoxy curing occurred simultaneously in a homogeneous solution, and organic-inorganic hybrid materials were readily obtained. Further, the zirconia produced by the in situ polymerization was uniformly dispersed in the epoxy matrix on the nanometer or sub-nanometer scale; thus, hybrid materials that exhibited excellent optical transparency were obtained. Furthermore, the heat resistance of the hybrid materials could be improved by hybridization with zirconia. And, the refractive indices of the hybrid materials significantly improved with an increase in the zirconia content.

  14. Cu(II) coordination polymers constructed by tetrafluoroterephthalic acid and varied imidazole-containing ligands: Syntheses, structures and properties

    Science.gov (United States)

    Liu, Kang; Sun, Yayong; Deng, Liming; Cao, Fan; Han, Jishu; Wang, Lei

    2018-02-01

    Six new copper(II) coordination polymers combining 2,3,5,6-tetrafluoroterephthalatic acid (H2tfBDC) and diverse imidazole-containing ligands, {[Cu(tfBDC)(1,2-bix)2]·2(H2O)}n (1), {Cu(tfBDC)(Im)2}n (2), {[Cu(1,4-bmimb)2(H2O)]·(tfBDC)·2(H2O)}n (3), {Cu(1,4-bimb)2(H2O)2·(tfBDC)}n (4), {[Cu(1,3-bix)2(H2O)2]·(tfBDC)·6(H2O)}n (5) and {[Cu(1,4-bix)2(H2O)2]·(tfBDC)·(1,4-bix)·4(H2O)}n (6) (1,2-bix = 1,2-bis(imidazole-1-ylmethyl)-benzene, Im = imidazole, 1,4-bmimb = 1,4-bis((2-methyl-1H-imidazol-1-yl)methyl)benzene, 1,4-bimb = 1,4-bis(imidazol-1-yl)-butane, 1,3-bix = 1,3-bis(imidazole-1-ylmethyl)-benzene, 1,4-bix = 1,4-bis(imidazole-1-ylmethyl)-benzene), have been obtained and structurally verified by single-crystal X-ray diffraction analyses and further characterized by powder X-ray diffraction (PXRD), elemental analyses and infrared spectroscopy (IR). Single crystal X-ray diffraction analysis revealed that 1 is 2D 4-connected sql topology (point symbol: {44·62}) based on a single metal ion node. Compound 2 is characterized as an infinite 1D chain structure, which is further extended into a 2D layer through N-H···O hydrogen bonds and then a 3D supramolecular architecture via π···π stacking interactions. Note that 2 was prepared through an in situ ligand reaction in which N,N'-carbonyldiimidazole (cdi) broke up into imidazole ligand. Compound 3 possesses a 3D 4-fold interpenetrated architecture with 4-connected dia topology (Schläfli symbol: {66}) in which tfBDC2- is stabilized in the channel by hydrogen bonds. Compounds 4-6 are all linear 1D coordination polymers. In 4, the free tfBDC2- ligand acts as a μ4-bridge to link four coordinated water molecules from the chain to construct a 2D structure via hydrogen bonds. While in 5 and 6, the uncoordinated tfBDC2- ligands and multimeric water clusters is responsible for the conversion of these 1D coordination polymers into 3D supramolecular assemblies through O-H⋯O hydrogen bonding interactions. Moreover

  15. Three coordination polymers constructed from 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid: Synthesis, crystal structure and properties

    Science.gov (United States)

    Zhai, Dandan; Sun, Wujuan; Fan, Fei; Liao, Xuzhao; Chen, Sanping; Yang, Xuwu

    2017-04-01

    Three new coordination polymers, namely, {[Co2(TPA)(μ3-O)3]·0.5DMA}n (1), {[Co(H2TPA)(bibp)(H2O)3]·H2O}n (2) and {[Cd3(TPA)2(phen)4]·4H2O}n (3), (H3TPA = 5-(4-(tetrazol-5-yl)phenyl)isophthalic acid, bibp = 4,4'-bis(imidazolyl)biphenyl, phen = 1,10-phenanthroline and DMA = N,N-dimethylacetamide), have been synthesized under solvothermal conditions and structurally characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction analysis. Polymer 1 exhibits a three-dimensional (3D) structure constructed from 5-connected secondary building units (SBUs) [Co3(μ3-O)] and 3-connected H3TPA ligands. Polymer 2 has a 1D zigzag polymer chain connected by H3TPA and bibp ligands. Polymer 3 features an unusual 3D framework with a (3,4,2)-connected {4; 6;8}{4; 62;83} topology. Moreover, the thermal stabilities of 1-3 and photoluminescence properties of 3 have been investigated. Magnetic susceptibility measurements indicate that polymers 1-2 display antiferromagnetic exchange properties.

  16. Towards Acid-Tolerated Ethanol Dehydration: Chitosan-Based Mixed Matrix Membranes Containing Cyano-Bridged Coordination Polymer Nanoparticles.

    Science.gov (United States)

    Wu, C-W; Kang, Chao-Hsiang; Lin, Yi-Feng; Tung, Kuo-Lun; Deng, Yu-Heng; Ahamad, Tansir; Alshehri, Saad M; Suzuki, Norihiro; Yamauchi, Yusuke

    2016-04-01

    Prussian blue (PB) nanoparticles, one of many cyano-bridged coordination polymers, are successfully incorporated into chitosan (CS) polymer to prepare PB/CS mixed matrix membranes (MMMs). The PB nanoparticles are uniformly distributed in the MMMs without the collapse of the original PB structure. As-prepared PB/CS MMMs are used for ethanol dehydration at 25 °C in the pervaporation process. The effect of loading PB in CS matrix on pervaporation performance is carefully investigated. The PB/CS membrane with 30 wt% PB loading shows the best performance with a permeate flux of 614 g. m-2 . h-1 and a separation factor of 1472. The pervaporation using our PB/CS membranes exhibits outstanding performance in comparison with the previously reported CS-based membranes and MMMs. Furthermore, the addition of PB allows PB/CS MMMs to be tolerant of acidic environment. The present work demonstrates good pervaporation performance of PB/CS MMMs for the separation of an ethanol/water (90:10 in wt%) solution. Our new system provides an opportunity for dehydration of bioethanol in the future.

  17. The Nucleotide Synthesis Enzyme CAD Inhibits NOD2 Antibacterial Function in Human Intestinal Epithelial Cells

    Science.gov (United States)

    Richmond, Amy L.; Kabi, Amrita; Homer, Craig R.; García, Noemí Marina; Nickerson, Kourtney P.; NesvizhskiI, Alexey I.; Sreekumar, Arun; Chinnaiyan, Arul M.; Nuñez, Gabriel; McDonald, Christine

    2013-01-01

    BACKGROUND & AIMS Polymorphisms that reduce the function of nucleotide-binding oligomerization domain (NOD)2, a bacterial sensor, have been associated with Crohn’s disease (CD). No proteins that regulate NOD2 activity have been identified as selective pharmacologic targets. We sought to discover regulators of NOD2 that might be pharmacologic targets for CD therapies. METHODS Carbamoyl phosphate synthetase/ aspartate transcarbamylase/dihydroorotase (CAD) is an enzyme required for de novo pyrimidine nucleotide synthesis; it was identified as a NOD2-interacting protein by immunoprecipitation-coupled mass spectrometry. CAD expression was assessed in colon tissues from individuals with and without inflammatory bowel disease by immunohistochemistry. The interaction between CAD and NOD2 was assessed in human HCT116 intestinal epithelial cells by immunoprecipitation, immunoblot, reporter gene, and gentamicin protection assays. We also analyzed human cell lines that express variants of NOD2 and the effects of RNA interference, overexpression and CAD inhibitors. RESULTS CAD was identified as a NOD2-interacting protein expressed at increased levels in the intestinal epithelium of patients with CD compared with controls. Overexpression of CAD inhibited NOD2-dependent activation of nuclear factor κB and p38 mitogen-activated protein kinase, as well as intracellular killing of Salmonella. Reduction of CAD expression or administration of CAD inhibitors increased NOD2-dependent signaling and antibacterial functions of NOD2 variants that are and are not associated with CD. CONCLUSIONS The nucleotide synthesis enzyme CAD is a negative regulator of NOD2. The antibacterial function of NOD2 variants that have been associated with CD increased in response to pharmacologic inhibition of CAD. CAD is a potential therapeutic target for CD. PMID:22387394

  18. Synthesis, structural characterization and antitumor activity of a Ca(II) coordination polymer based on 4-formyl-1,3-benzenedisulfonate-2-furoic acid hydrazide ligands

    Energy Technology Data Exchange (ETDEWEB)

    Tai, Xi-Shi, E-mail: taixs@wfu.edu.cn [Weifang University, College of Chemistry and Chemical Engineering (China); Wang, Xin [Qinghai Normal University, Department of Chemistry (China)

    2017-03-15

    A new Ca(II) coordination polymer, ([CaL(H{sub 2}O){sub 4}] · (H{sub 2}O){sub 4}){sub n} (L = 4-formyl-1,3-benzenedisulfonate-2-furoic acid hydrazide) has been prepared by one-pot synthesis method. And it was characterized by elemental analysis, IR and thermal analysis. The result of X-ray single-crystal diffraction analysis shows that the Ca(II) complex molecules form one-dimensional chain structure by the bridging oxygen atoms. The anti-tumor activity of L ligand and the Ca(II) coordination polymer has also been studied.

  19. Solvent induced synthesis, structure and properties of coordination polymers based on 5-hydroxyisophthalic acid as linker and 1,10-phenanthroline as auxiliary ligand

    International Nuclear Information System (INIS)

    Kariem, Mukaddus; Yawer, Mohd; Sheikh, Haq Nawaz

    2015-01-01

    Three new coordination polymers [Mn(hip)(phen) (H_2O)]_n (1), [Co(hip)(phen) (H_2O)]_n (2), and [Cd(hip) (phen) (H_2O)]_n (3) (H_2hip=5-hydroxyisophthalic acid; phen=1,10-phenanthroline) have been synthesized by solvo-hydrothermal method using diethyl formamide-water (DEF-H_2O) as solvent system. Single-crystal X-ray diffraction analysis reveals that all three coordination polymers 1, 2 and 3 crystallize in monoclinic space group P2/n. Metal ions are inter-connected by hydroxyisophthalate anions forming zig-zag 1D chain. 1D chains are further inter-connected by hydrogen bonding and π–π stacking interactions leading to 3D supramolecular architecture. Hydrogen-bonding and π–π stacking provide thermal stability to polymers. Compounds 1 and 2 are paramagnetic at room temperature and variable temperature magnetic moment measurements revealed weak ferromagnetic interactions between metal ions at low temperature. Compound 3 exhibits excellent photoluminescence with large Stokes shift. - Graphical abstract: 1D helical chains of coordination polymers were synthesized by solvo-hydrothermal reaction of 5-hydroxyisopthalic acid and 1,10-phenanthroline with MnCl_2·4H_2O / CoCl_2·6H_2O / Cd(NO_3)_2·6H_2O. - Highlights: • Solvent induced synthesis of three coordination polymers with 1D zig-zag structure. • Crystal structures of coordination polymers are reported and discussed. • 1,10-Phenanthroline influences magnetic and luminescent properties of polymers. • Coordination polymer of Cd is luminescent exhibiting large Stokes shift.

  20. Solvent induced synthesis, structure and properties of coordination polymers based on 5-hydroxyisophthalic acid as linker and 1,10-phenanthroline as auxiliary ligand

    Energy Technology Data Exchange (ETDEWEB)

    Kariem, Mukaddus; Yawer, Mohd; Sheikh, Haq Nawaz, E-mail: hnsheikh@rediffmail.com

    2015-11-15

    Three new coordination polymers [Mn(hip)(phen) (H{sub 2}O)]{sub n} (1), [Co(hip)(phen) (H{sub 2}O)]{sub n} (2), and [Cd(hip) (phen) (H{sub 2}O)]{sub n} (3) (H{sub 2}hip=5-hydroxyisophthalic acid; phen=1,10-phenanthroline) have been synthesized by solvo-hydrothermal method using diethyl formamide-water (DEF-H{sub 2}O) as solvent system. Single-crystal X-ray diffraction analysis reveals that all three coordination polymers 1, 2 and 3 crystallize in monoclinic space group P2/n. Metal ions are inter-connected by hydroxyisophthalate anions forming zig-zag 1D chain. 1D chains are further inter-connected by hydrogen bonding and π–π stacking interactions leading to 3D supramolecular architecture. Hydrogen-bonding and π–π stacking provide thermal stability to polymers. Compounds 1 and 2 are paramagnetic at room temperature and variable temperature magnetic moment measurements revealed weak ferromagnetic interactions between metal ions at low temperature. Compound 3 exhibits excellent photoluminescence with large Stokes shift. - Graphical abstract: 1D helical chains of coordination polymers were synthesized by solvo-hydrothermal reaction of 5-hydroxyisopthalic acid and 1,10-phenanthroline with MnCl{sub 2}·4H{sub 2}O / CoCl{sub 2}·6H{sub 2}O / Cd(NO{sub 3}){sub 2}·6H{sub 2}O. - Highlights: • Solvent induced synthesis of three coordination polymers with 1D zig-zag structure. • Crystal structures of coordination polymers are reported and discussed. • 1,10-Phenanthroline influences magnetic and luminescent properties of polymers. • Coordination polymer of Cd is luminescent exhibiting large Stokes shift.

  1. The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation of Dectin-1 Expression

    Directory of Open Access Journals (Sweden)

    Mark S. Gresnigt

    2017-12-01

    Full Text Available One of the major life-threatening infections for which severely immunocompromised patients are at risk is invasive aspergillosis (IA. Despite the current treatment options, the increasing antifungal resistance and poor outcome highlight the need for novel therapeutic strategies to improve outcome of patients with IA. In the current study, we investigated whether and how the intracellular pattern recognition receptor NOD1 is involved in host defense against Aspergillus fumigatus. When exploring the role of NOD1 in an experimental mouse model, we found that Nod1−/− mice were protected against IA and demonstrated reduced fungal outgrowth in the lungs. We found that macrophages derived from bone marrow of Nod1−/− mice were more efficiently inducing reactive oxygen species and cytokines in response to Aspergillus. Most strikingly, these cells were highly potent in killing A. fumigatus compared with wild-type cells. In line, human macrophages in which NOD1 was silenced demonstrated augmented Aspergillus killing and NOD1 stimulation decreased fungal killing. The differentially altered killing capacity of NOD1 silencing versus NOD1 activation was associated with alterations in dectin-1 expression, with activation of NOD1 reducing dectin-1 expression. Furthermore, we were able to demonstrate that Nod1−/− mice have elevated dectin-1 expression in the lung and bone marrow, and silencing of NOD1 gene expression in human macrophages increases dectin-1 expression. The enhanced dectin-1 expression may be the mechanism of enhanced fungal killing of Nod1−/− cells and human cells in which NOD1 was silenced, since blockade of dectin-1 reversed the augmented killing in these cells. Collectively, our data demonstrate that NOD1 receptor plays an inhibitory role in the host defense against Aspergillus. This provides a rationale to develop novel immunotherapeutic strategies for treatment of aspergillosis that target the NOD1 receptor, to enhance the

  2. Syntheses, structures, and photoluminescence of lanthanide coordination polymers based on 4-oxo-1,4-dihydro-2,6-pyridinedicarboxylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Jing; Li, Lei; Peng, Jing-Wei; Qiao, Wei-Wei; Sun, Mei-Mei [College of Chemistry, Tianjin Normal University, Tianjin (China); Gu, Wen [College of Chemistry, Nankai University, Tianjin (China)

    2018-03-15

    Investigating the coordination chemistry of H{sub 2}CDA (4-oxo-1,4-dihydro-2,6-pyridinedicarboxylic acid) with rare earth salts Ln(NO{sub 3}){sub 3} under hydrothermal conditions, structure transformation phenomenon was observed. The ligand, H{sub 2}CDA charged to its position isomer, enol type structure, H{sub 3}CAM (4-hydroxypyridine-2,6-dicarboxylic acid). Six new lanthanide(III) coordination polymers with the formulas [Ln(CAM)(H{sub 2}O){sub 3}]{sub n} [Ln = La (1), Pr, (2)] and {[Ln(CAM)(H_2O)_3].H_2O}{sub n} [Ln = Nd, (3), Sm, (4), Eu, (5), Y, (6)] were synthesized and characterized. The X-ray structure analyses show two kinds of coordination structures. The complexes 1 and 2 and 3-6 are isostructural. Complexes 1 and 2 crystallize in the monoclinic C{sub 2}/c space group, whereas 3-6 crystallize in the monoclinic system with space group P2{sub 1}/n. In the two kinds of structures, H{sub 3}CAM displays two different coordination modes. The Sm{sup III} and Eu{sup III} complexes exhibit the corresponding characteristic luminescence in the visible region at an excitation of 376 nm. (copyright 2018 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. Reaction titration: a convenient method for titering reactive hydride agents (Red-Al, LiAlH4, DIBALH, L-Selectride, NaH, and KH) by No-D NMR spectroscopy.

    Science.gov (United States)

    Hoye, Thomas R; Aspaas, Andrew W; Eklov, Brian M; Ryba, Troy D

    2005-05-26

    The concentration of reactive metal hydride (Met-H) reducing agents can be determined (in < or = 20 min) using No-D NMR spectroscopy. The method involves (i) reacting Met-H with an excess of p-methoxybenzaldehyde, (ii) quenching with excess acetic acid, (iii) recording the No-D NMR spectrum of this homogeneous mixture, and (iv) deducing the concentration of Met-H from the % conversion (as measured by integration). By a conceptually related method, the titer of the basic alkali metal hydrides KH and NaH can also be determined.

  4. Nodding syndrome: origins and natural history of a longstanding epileptic disorder in sub-Saharan Africa.

    Science.gov (United States)

    Spencer, P S; Palmer, V S; Jilek-Aall, L

    2013-06-01

    Repetitive involuntary head nodding was first reported in the 1960s in the Wapogoro tribe of Tanzania. We describe the natural history of head nodding in the Wapogoro tribe, with special reference to the earliest reported dates of onset. We analyzed clinical data from 150 historical patients seen between 1960 and 1971. Head nodding with or without grand mal convulsions was present in 33/150 (∼20%) cases, was mostly familial and equally distributed by gender. Age at onset of head nodding ranged from 2-22 years (mean: ∼10 years) in the period 1934-1962. Head nodding preceded onset of grand mal convulsions by up to 12 months, and motor and psychomotor deficits indicative of brain damage developed with time. Fourteen of the 33 cases died at 13-39 years of age (mean: ∼20 years) while nineteen aged 16-28 years (mean: ∼16 years) were still alive. Historical accounts of head nodding (amesinzia kichwa, Swahili) among the Wapogoro tribe fit the August 2012 World Health Organization (WHO) case definition of probable Nodding Syndrome. Reported to have existed in this population for at least 80 years, Nodding Syndrome is a progressive seizure disorder that leads to generalized convulsions (kifafa), brain damage and death.

  5. Expression and function of NOD-like receptors by human term gestation-associated tissues.

    Science.gov (United States)

    Bryant, Aled H; Bevan, Ryan J; Spencer-Harty, Samantha; Scott, Louis M; Jones, Ruth H; Thornton, Catherine A

    2017-10-01

    Nucleotide-binding oligomerization domain (NOD)-like receptors or NOD-like receptors (NLRs) have been implicated in several disease pathologies associated with inflammation. Since local and systemic inflammation is a hallmark of both term and preterm labour, a role for NLRs at the materno-fetal interface has been postulated. Gene expression and immunolocalisation of NLR family members in human placenta, choriodecidua, and amnion were examined. Tissue explants were used to examine the response to activators of NOD1 (Tri-DAP), NOD2 (MDP) and NLRP3 (nigericin). Cell/tissue-free supernatants were examined for the production of interleukin (IL)-1β, IL-6, IL-8 and IL-10 using specific ELISAs. Expression of transcripts for NOD1, NOD2, NLRP3, NLRC4, NLRX1, NLRP1 and NAIP and protein expression of NOD1, NOD2 and NLRP3 were a broad feature of all term gestation-associated tissues. Production of cytokines was increased significantly in response to all ligands in placenta and choriodecidua, except for MDP-induced IL-10. Similarly, there was a significant in the amnion except for MDP induced IL-1β and IL-10 response to either agonist. IL-1β production was dependent on caspase-1 regardless of agonist used or tissue examined. Term human gestation-associated tissues express functional NLRs which likely play a role in both sterile and pathogen-driven inflammatory responses at the materno-fetal interface. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Postnatal hematopoiesis and gut microbiota in NOD mice deviate from C57BL/6 mice

    DEFF Research Database (Denmark)

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss

    2016-01-01

    , a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface...

  7. Backchannel Head Nods in Danish First Meeting Encounters with a Humanoid Robot

    DEFF Research Database (Denmark)

    Krogsager, Anders; Segato, Nicolaj; Rehm, Matthias

    2014-01-01

    Head nods have been shown to play an important role for communication management in human communication, e.g. as a non-verbal feedback signal from the listener. Based on a study with virtual agents, which showed that the use of head nods helps eliciting more verbal input from the user, we...

  8. Salmonella enterica serovar Typhimurium ΔmsbB triggers exacerbated inflammation in Nod2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Claes

    Full Text Available The intracellular pathogen Salmonella enterica serovar Typhimurium causes intestinal inflammation characterized by edema, neutrophil influx and increased pro-inflammatory cytokine expression. A major bacterial factor inducing pro-inflammatory host responses is lipopolysaccharide (LPS. S. Typhimurium ΔmsbB possesses a modified lipid A, has reduced virulence in mice, and is being considered as a potential anti-cancer vaccine strain. The lack of a late myristoyl transferase, encoded by MsbB leads to attenuated TLR4 stimulation. However, whether other host receptor pathways are also altered remains unclear. Nod1 and Nod2 are cytosolic pattern recognition receptors recognizing bacterial peptidoglycan. They play important roles in the host's immune response to enteric pathogens and in immune homeostasis. Here, we investigated how deletion of msbB affects Salmonella's interaction with Nod1 and Nod2. S. Typhimurium Δ msbB-induced inflammation was significantly exacerbated in Nod2-/- mice compared to C57Bl/6 mice. In addition, S. Typhimurium ΔmsbB maintained robust intestinal colonization in Nod2-/- mice from day 2 to day 7 p.i., whereas colonization levels significantly decreased in C57Bl/6 mice during this time. Similarly, infection of Nod1-/- and Nod1/Nod2 double-knockout mice revealed that both Nod1 and Nod2 play a protective role in S. Typhimurium ΔmsbB-induced colitis. To elucidate why S. Typhimurium ΔmsbB, but not wild-type S. Typhimurium, induced an exacerbated inflammatory response in Nod2-/- mice, we used HEK293 cells which were transiently transfected with pathogen recognition receptors. Stimulation of TLR2-transfected cells with S. Typhimurium ΔmsbB resulted in increased IL-8 production compared to wild-type S. Typhimurium. Our results indicate that S. Typhimurium ΔmsbB triggers exacerbated colitis in the absence of Nod1 and/or Nod2, which is likely due to increased TLR2 stimulation. How bacteria with "genetically detoxified" LPS

  9. Negative regulation of NOD1 mediated angiogenesis by PPARγ-regulated miR-125a

    International Nuclear Information System (INIS)

    Kang, Hyesoo; Park, Youngsook; Lee, Aram; Seo, Hyemin; Kim, Min Jung; Choi, Jihea; Jo, Ha-neul; Jeong, Ha-neul; Cho, Jin Gu; Chang, Woochul; Lee, Myeong-Sok; Jeon, Raok; Kim, Jongmin

    2017-01-01

    Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3′ untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis. - Highlights: • Expression of NOD1 is regulated by

  10. Nakalanga Syndrome: Clinical Characteristics, Potential Causes, and Its Relationship with Recently Described Nodding Syndrome.

    Directory of Open Access Journals (Sweden)

    Kathrin Föger

    2017-02-01

    Full Text Available Nakalanga syndrome is a condition that was described in Uganda and various other African countries decades ago. Its features include growth retardation, physical deformities, endocrine dysfunction, mental impairment, and epilepsy, amongst others. Its cause remains obscure. Nodding syndrome is a neurological disorder with some features in common with Nakalanga syndrome, which has been described mainly in Uganda, South Sudan, and Tanzania. It has been considered an encephalopathy affecting children who, besides head nodding attacks, can also present with stunted growth, delayed puberty, and mental impairment, amongst other symptoms. Despite active research over the last years on the pathogenesis of Nodding syndrome, to date, no convincing single cause of Nodding syndrome has been reported. In this review, by means of a thorough literature search, we compare features of both disorders. We conclude that Nakalanga and Nodding syndromes are closely related and may represent the same condition. Our findings may provide new directions in research on the cause underlying this neurological disorder.

  11. Symbiotic Activity of Pea (Pisum sativum after Application of Nod Factors under Field Conditions

    Directory of Open Access Journals (Sweden)

    Anna Siczek

    2014-04-01

    Full Text Available Growth and symbiotic activity of legumes are mediated by Nod factors (LCO, lipo-chitooligosaccharides. To assess the effects of application of Nod factors on symbiotic activity and yield of pea, a two-year field experiment was conducted on a Haplic Luvisol developed from loess. Nod factors were isolated from Rhizobium leguminosarum bv. viciae strain GR09. Pea seeds were treated with the Nod factors (10−11 M or water (control before planting. Symbiotic activity was evaluated by measurements of nitrogenase activity (acetylene reduction assay, nodule number and mass, and top growth by shoot mass, leaf area, and seed and protein yield. Nod factors generally improved pea yield and nitrogenase activity in the relatively dry growing season 2012, but not in the wet growing season in 2013 due to different weather conditions.

  12. DMPD: The role of Toll-like receptors and Nod proteins in bacterial infection. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15476921 The role of Toll-like receptors and Nod proteins in bacterial infection. P...of Toll-like receptors and Nod proteins in bacterial infection. PubmedID 15476921 Title The role of Toll-like receptors and Nod prote...ins in bacterial infection. Authors Philpott DJ, Girardi

  13. Brucella abortus 2308ΔNodVΔNodW double-mutant is highly attenuated and confers protection against wild-type challenge in BALB/c mice.

    Science.gov (United States)

    Li, Zhiqiang; Wang, Shuli; Zhang, Jinliang; Yang, Guangli; Yuan, Baodong; Huang, Jie; Han, Jincheng; Xi, Li; Xiao, Yanren; Chen, Chuangfu; Zhang, Hui

    2017-05-01

    Brucellosis is an important zoonotic disease of worldwide distribution, which causes animal and human disease. However, the current Brucella abortus (B. abortus) vaccines (S19 and RB51) have several drawbacks, including residual virulence for animals and humans. Moreover, S19 cannot allow serological differentiation between infected and vaccinated animals. We constructed double deletion (ΔNodVΔNodW) mutant from virulent B. abortus 2308 (S2308) by deleting the genes encoding two-component regulatory system (TCS) in chromosome II in S2308.2308ΔNodVΔNodW was significantly reduced survival in murine macrophages (RAW 264.7) and BALB/c mice. Moreover, the inoculated mice showed no splenomegaly. The mutant induced high protective immunity in BALB/c mice against challenge with S2308, and elicited an anti-Brucella-specific immunoglobulin G (IgG) response and induced the secretion of gamma interferon (IFN-γ) and interleukin-4 (IL-4). Moreover, NODV and NODW antigens would allow the serological differentiation between infected and vaccinated animals. These results suggest that 2308ΔNodVΔNodW mutant is a potential live attenuated vaccine candidate and can be used effectively against bovine brucellosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/γ chainnull Mice

    Directory of Open Access Journals (Sweden)

    Shanbao Cai

    2011-01-01

    Full Text Available Humanized bone-marrow xenograft models that can monitor the long-term impact of gene-therapy strategies will help facilitate evaluation of clinical utility. The ability of the murine bone-marrow microenvironment in NOD/SCID versus NOD/SCID/γ chainnull mice to support long-term engraftment of MGMTP140K-transduced human-hematopoietic cells following alkylator-mediated in vivo selection was investigated. Mice were transplanted with MGMTP140K-transduced CD34+ cells and transduced cells selected in vivo. At 4 months after transplantation, levels of human-cell engraftment, and MGMTP140K-transduced cells in the bone marrow of NOD/SCID versus NSG mice varied slightly in vehicle- and drug-treated mice. In secondary transplants, although equal numbers of MGMTP140K-transduced human cells were transplanted, engraftment was significantly higher in NOD/SCID/γ chainnull mice compared to NOD/SCID mice at 2 months after transplantation. These data indicate that reconstitution of NOD/SCID/γ chainnull mice with human-hematopoietic cells represents a more promising model in which to test for genotoxicity and efficacy of strategies that focus on manipulation of long-term repopulating cells of human origin.

  15. Synthesis, Structural Characterization and Catalytic Activity of A Cu(II Coordination Polymer Constructed from 1,4-Phenylenediacetic Acid and 2,2’-Bipyridine

    Directory of Open Access Journals (Sweden)

    Wang Li-Hua

    2017-04-01

    Full Text Available In order to study the catalytic activity of Cu(II coordination polymer material, a novel 1D chained Cu(II coordination polymer material, [CuL(bipy(H2O5]n (A1 (H2L = 1,4-phenylenediacetic acid, bipy = 2,2’-bipyridine, has been prepared by the reaction of 1,4-phenylenediacetic acid, 2,2’-bipyridine, Cu(CH3COO2·H2O and NaOH. The composition of A1 was determined by elemental analysis, IR spectra and single crystal X-ray diffraction. The results of characterization show that each Cu(II atom adopts six-coordination and forms a distorted octahedral configuration. The catalytic activity and reusability of A1 catalyst for A3 coupling reaction of benzaldehyde, piperidine, and phenylacetylene have been investigated. And the results show that the Cu(II complex catalyst has good catalytic activity with a maximum yield of 54.3% and stability. Copyright © 2017 BCREC GROUP. All rights reserved Received: 21st October 2016; Revised: 17th November 2016; Accepted: 22nd November 2016 How to Cite: Li-Hua, W., Lei, L., Xin, W. (2017. Synthesis, Structural Characterization and Catalytic Activity of A Cu(II Coordination Polymer Constructed from 1,4-Phenylenediacetic Acid and 2,2’-Bipyridine. Bulletin of Chemical Reaction Engineering & Catalysis, 12 (1: 113-118 (doi:10.9767/bcrec.12.1.735.113-118 Permalink/DOI: http://dx.doi.org/10.9767/bcrec.12.1.735.113-118

  16. Comparative genetics: synergizing human and NOD mouse studies for identifying genetic causation of type 1 diabetes.

    Science.gov (United States)

    Driver, John P; Chen, Yi-Guang; Mathews, Clayton E

    2012-01-01

    Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.

  17. Syntheses, structures and properties of two new coordination polymers based on D-camphoric acid and 2-phenyl-4,6-diamino-1,3,5-triazine

    Energy Technology Data Exchange (ETDEWEB)

    Lun, Huijie; Yang, Jinghe; Jin, Linyu; Cui, Sasa; Bai, Yanlong [Henan Key Laboratory of Polyoxometalate, Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004 (China); Zhang, Xudong [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Li, Yamin, E-mail: liyamin@henu.edu.cn [Henan Key Laboratory of Polyoxometalate, Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004 (China)

    2015-05-15

    By hydrothermal method, two new coordination polymers [Co(ca)(phdat)]{sub n} (1), [Ni(ca)(phdat).0.125H{sub 2}O]{sub n} (2) (H{sub 2}ca=D-camphoric acid, phdat=2-phenyl-4,6-diamino-1,3,5-triazine) have been achieved and structurally characterized by IR, elemental analyses, X-ray single-crystal diffraction and TGA. The X-ray single-crystal diffraction reveals that compounds 1 and 2 are isostructural, both of which exhibit two-dimensional layered network built up from paddle-wheel Co{sub 2}(CO{sub 2}){sub 4}/Ni{sub 2}(CO{sub 2}){sub 4} SBUs by ca{sup 2−} ligand. In the existence of π…π stacking interactions between triazine rings and phenyl rings, the 3D networks are constructed with the hanging phdat filled between the neighboring layers. Furthermore, compounds 1–2 exhibit antiferromagnetic behavior and compound 2 displays a good activity for methanol oxidation. - Graphical abstract: Two new coordination compounds 1–2 have been synthesized and characterized by single-crystal X-ray diffractions, IR spectra, elemental analyses, thermogravimetric analyses, magnetic and electrochemical measurement. - Highlights: • This paper reports two new coordination polymers based on D-camphoric acid. • Both the compounds feather two-dimensional layered networks built up from paddle-wheel SBUs. • The magnetism and electrochemical property are investigated.

  18. Co-ordinate changes in enzymes of fatty acid synthesis, activation and esterification in rabbit mammary gland druing pregnancy and lactation.

    Science.gov (United States)

    Short, V J; Brindley, D N; Dils, R

    1977-01-01

    1. The activities of fatty acid synthetase, acyl-CoA synthetase, glycerol phosphate acyltransferase and phosphatidate phosphatase were measured in the mammary glands of rabbits from day 16 of pregnancy to day 15 of post partum. 2. There were significant correlations between the increases in activities of these enzymes during this period. This was the case whether the activities were expressed per mg of homogenate protein, per g wet wt. of tissue or per total wet weight of the whole glands. The only exception was the lack of correlation between the activities of fatty acid synthetase and of phosphatidate phosphatase per g wet wt. of tissue. 3. These co-ordinate increases are discussed in relation to the changes which occur in fatty acid metabolism in the mammary gland during pregnancy and lactation. PMID:192226

  19. Low pH, Aluminum, and Phosphorus Coordinately Regulate Malate Exudation through GmALMT1 to Improve Soybean Adaptation to Acid Soils1[W][OA

    Science.gov (United States)

    Liang, Cuiyue; Piñeros, Miguel A.; Tian, Jiang; Yao, Zhufang; Sun, Lili; Liu, Jiping; Shaff, Jon; Coluccio, Alison; Kochian, Leon V.; Liao, Hong

    2013-01-01

    Low pH, aluminum (Al) toxicity, and low phosphorus (P) often coexist and are heterogeneously distributed in acid soils. To date, the underlying mechanisms of crop adaptation to these multiple factors on acid soils remain poorly understood. In this study, we found that P addition to acid soils could stimulate Al tolerance, especially for the P-efficient genotype HN89. Subsequent hydroponic studies demonstrated that solution pH, Al, and P levels coordinately altered soybean (Glycine max) root growth and malate exudation. Interestingly, HN89 released more malate under conditions mimicking acid soils (low pH, +P, and +Al), suggesting that root malate exudation might be critical for soybean adaptation to both Al toxicity and P deficiency on acid soils. GmALMT1, a soybean malate transporter gene, was cloned from the Al-treated root tips of HN89. Like root malate exudation, GmALMT1 expression was also pH dependent, being suppressed by low pH but enhanced by Al plus P addition in roots of HN89. Quantitative real-time PCR, transient expression of a GmALMT1-yellow fluorescent protein chimera in Arabidopsis protoplasts, and electrophysiological analysis of Xenopus laevis oocytes expressing GmALMT1 demonstrated that GmALMT1 encodes a root cell plasma membrane transporter that mediates malate efflux in an extracellular pH-dependent and Al-independent manner. Overexpression of GmALMT1 in transgenic Arabidopsis, as well as overexpression and knockdown of GmALMT1 in transgenic soybean hairy roots, indicated that GmALMT1-mediated root malate efflux does underlie soybean Al tolerance. Taken together, our results suggest that malate exudation is an important component of soybean adaptation to acid soils and is coordinately regulated by three factors, pH, Al, and P, through the regulation of GmALMT1 expression and GmALMT1 function. PMID:23341359

  20. Low pH, aluminum, and phosphorus coordinately regulate malate exudation through GmALMT1 to improve soybean adaptation to acid soils.

    Science.gov (United States)

    Liang, Cuiyue; Piñeros, Miguel A; Tian, Jiang; Yao, Zhufang; Sun, Lili; Liu, Jiping; Shaff, Jon; Coluccio, Alison; Kochian, Leon V; Liao, Hong

    2013-03-01

    Low pH, aluminum (Al) toxicity, and low phosphorus (P) often coexist and are heterogeneously distributed in acid soils. To date, the underlying mechanisms of crop adaptation to these multiple factors on acid soils remain poorly understood. In this study, we found that P addition to acid soils could stimulate Al tolerance, especially for the P-efficient genotype HN89. Subsequent hydroponic studies demonstrated that solution pH, Al, and P levels coordinately altered soybean (Glycine max) root growth and malate exudation. Interestingly, HN89 released more malate under conditions mimicking acid soils (low pH, +P, and +Al), suggesting that root malate exudation might be critical for soybean adaptation to both Al toxicity and P deficiency on acid soils. GmALMT1, a soybean malate transporter gene, was cloned from the Al-treated root tips of HN89. Like root malate exudation, GmALMT1 expression was also pH dependent, being suppressed by low pH but enhanced by Al plus P addition in roots of HN89. Quantitative real-time PCR, transient expression of a GmALMT1-yellow fluorescent protein chimera in Arabidopsis protoplasts, and electrophysiological analysis of Xenopus laevis oocytes expressing GmALMT1 demonstrated that GmALMT1 encodes a root cell plasma membrane transporter that mediates malate efflux in an extracellular pH-dependent and Al-independent manner. Overexpression of GmALMT1 in transgenic Arabidopsis, as well as overexpression and knockdown of GmALMT1 in transgenic soybean hairy roots, indicated that GmALMT1-mediated root malate efflux does underlie soybean Al tolerance. Taken together, our results suggest that malate exudation is an important component of soybean adaptation to acid soils and is coordinately regulated by three factors, pH, Al, and P, through the regulation of GmALMT1 expression and GmALMT1 function.

  1. Crystal structures of a manganese(I and a rhenium(I complex of a bipyridine ligand with a non-coordinating benzoic acid moiety

    Directory of Open Access Journals (Sweden)

    Sheri Lense

    2018-05-01

    Full Text Available The structures of two facially coordinated Group VII metal complexes are reported, namely: fac-bromido[2-(2,2′-bipyridin-6-ylbenzoic acid-κ2N,N′]tricarbonylmanganese(I tetrahydrofuran monosolvate, [MnBr(C17H12N2O2(CO3]·C4H8O, I, and fac-[2-(2,2′-bipyridin-6-ylbenzoic acid-κ2N,N′]tricarbonylchloridorhenium(I tetrahydrofuran monosolvate, [ReCl(C17H12N2O2(CO3]·C4H8O, II. In both complexes, the metal ion is coordinated by three carbonyl ligands, a halide ion, and a 2-(2,2′-bipyridin-6-ylbenzoic acid ligand, in a distorted octahedral geometry. In manganese complex I, the tetrahydrofuran (THF solvent molecule could not be refined due to disorder. The benzoic acid fragment is also disordered over two positions, such that the carboxylic acid group is either positioned near to the bromide ligand or to the axial carbonyl ligand. In the crystal of I, the complex molecules are linked by a pair of C—H...Br hydrogen bonds, forming inversion dimers that stack up the a-axis direction. In the rhenium complex II, there is hydrogen bonding between the benzoic acid moiety and a disordered co-crystallized THF molecule. In the crystal, the molecules are linked by C—H...Cl hydrogen bonds, forming layers parallel to (100 separated by layers of THF solvent molecules.

  2. ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, J.; Sindelar, C; Mulko, N; Collins, K; Kong, S; Hawley, R; Kull, F

    2009-01-01

    Segregation of nonexchange chromosomes during Drosophila melanogaster meiosis requires the proper function of NOD, a nonmotile kinesin-10. We have determined the X-ray crystal structure of the NOD catalytic domain in the ADP- and AMPPNP-bound states. These structures reveal an alternate conformation of the microtubule binding region as well as a nucleotide-sensitive relay of hydrogen bonds at the active site. Additionally, a cryo-electron microscopy reconstruction of the nucleotide-free microtubule-NOD complex shows an atypical binding orientation. Thermodynamic studies show that NOD binds tightly to microtubules in the nucleotide-free state, yet other nucleotide states, including AMPPNP, are weakened. Our pre-steady-state kinetic analysis demonstrates that NOD interaction with microtubules occurs slowly with weak activation of ADP product release. Upon rapid substrate binding, NOD detaches from the microtubule prior to the rate-limiting step of ATP hydrolysis, which is also atypical for a kinesin. We propose a model for NOD's microtubule plus-end tracking that drives chromosome movement.

  3. Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells.

    Directory of Open Access Journals (Sweden)

    Guomin Jiang

    Full Text Available On entering the tissues, infiltrating autoreactive T cells must be reactivated locally to gain pathogenic activity. We have previously reported that, when activated by Toll-like receptor 3 (TLR3 and TLR4 ligands, retinal astrocytes (RACs are able to function as antigen-presenting cells to re-activate uveitogenic T cells and allow responder T cells to induce uveitis in mice. In the present study, we found that, although the triggering of TLR2 or nucleotide-binding oligomerization domain receptor 2 (NOD2 alone did not activate RACs, their combined triggering induced RACs with the phenotypes required to efficiently re-activate interphotoreceptor retinoid-binding protein (IRBP-specific T cells. The synergistic effect of TLR2 and NOD2 ligands on RAC activation might be explained by the observations that bacterial lipoprotein (BLP, a TLR2 ligand was able to upregulate NOD2 expression and the combination of BLP and muramyldipeptide (MDP, a NOD2 ligand enhanced the expression of RICK (Rip2, the signaling molecule of NOD2. Moreover, the synergistic effect of MDP and BLP on RACs was lost when the RACs were derived from NOD2 knockout mice or were pre-treated with Rip2 antagonist. Thus, our data suggest that exogenous or endogenous molecules acting on both TLR2 and NOD2 on RACs might have an enhancing effect on susceptibility to autoimmune uveitis.

  4. CXCL-8 Regulates Head and Neck Carcinoma Progression through NOD Signalling Pathway

    Directory of Open Access Journals (Sweden)

    Chan Leong-Perng

    2017-01-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth among the most common cancers in the world. Interlukin-8 (CXCL-8, a major role in inflammatory response and tumor microenvironment, correlates with tumor progression, metastasis and invasion. We explored CXCL-8 promotes tumor progression in different differentiation HNSCC cells. This project would apply to development on biomarker and target in HNSCC as well as provide a basis of early diagnosis and treatment for clinical. CXCL-8, NOD1 (nucleotide-binding oligomerization domain-containing protein 1 and receptor-interacting protein kinase (RIPK2 levels were detected statistically higher in patient tissue with HNSCC than in non-cancerous matched tissue (NCMT in the microarray and qRT-PCR study, whereas NOD2 was weakly expressed. Similar results were obtained for CXCL-8, NOD1, NOD2 and RIP2 from RT-PCR and western blotting. High CXCL-8, NOD1 and RIP2 expressions were found on HNSCC patient tissue than that of NCMT, whereas NOD2 was weakly expressed. The analytical results indicate that CXCL-8 is required in NOD 1-mediated signalling pathways in HNSCC.

  5. Islet-specific T cell clones transfer diabetes to nonobese diabetic (NOD) F1 mice.

    Science.gov (United States)

    Peterson, J D; Pike, B; McDuffie, M; Haskins, K

    1994-09-15

    To investigate diabetes resistance to T cell-mediated disease transfer, we administered islet-specific T cell clones to the F1 progeny of nonobese diabetic (NOD) mice that were crossed with various nondiabetes-prone inbred mouse strains. We investigated four diabetogenic CD4+ T cell clones and all induced insulitis and full development of diabetes in (SWR x NOD)F1, (SJL x NOD)F1, and (C57BL/6 x NOD)F1 mice. In contrast, (BALB/c x NOD)F1 and (CBA x NOD)F1 mice were susceptible to disease transfer by some T cell clones but not others, and (C57/L x NOD)F1 mice seemed to be resistant to both insulitis and disease transfer by all of the clones tested. Disease induced by the T cell clones in susceptible F1 strains was age dependent and could only be observed in recipients younger than 13 days old. Full or partial disease resistance did not correlate with the presence or absence of I-E, different levels of Ag expression in islet cells, or differences in APC function. The results from this study suggest that there may be multiple factors contributing to susceptibility of F1 mice to T cell clone-mediated induction of diabetes, including non-MHC-related genetic background, the immunologic maturity of the recipient, and individual characteristics of the T cell clones.

  6. Outer Membrane Vesicles From Probiotic and Commensal Escherichia coli Activate NOD1-Mediated Immune Responses in Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    María-Alexandra Cañas

    2018-03-01

    Full Text Available Gut microbiota plays a critical role in maintaining human intestinal homeostasis and host health. Bacterial extracellular vesicles are key players in bacteria–host communication, as they allow delivery of effector molecules into the host cells. Outer membrane vesicles (OMVs released by Gram-negative bacteria carry many ligands of pattern recognition receptors that are key components of innate immunity. NOD1 and NOD2 cytosolic receptors specifically recognize peptidoglycans present within the bacterial cell wall. These intracellular immune receptors are essential in host defense against bacterial infections and in the regulation of inflammatory responses. Recent contributions show that NODs are also fundamental to maintain intestinal homeostasis and microbiota balance. Peptidoglycan from non-invasive pathogens is delivered to cytosolic NODs through OMVs, which are internalized via endocytosis. Whether this pathway could be used by microbiota to activate NOD receptors remains unexplored. Here, we report that OMVs isolated from the probiotic Escherichia coli Nissle 1917 and the commensal ECOR12 activate NOD1 signaling pathways in intestinal epithelial cells. NOD1 silencing and RIP2 inhibition significantly abolished OMV-mediated activation of NF-κB and subsequent IL-6 and IL-8 expression. Confocal fluorescence microscopy analysis confirmed that endocytosed OMVs colocalize with NOD1, trigger the formation of NOD1 aggregates, and promote NOD1 association with early endosomes. This study shows for the first time the activation of NOD1-signaling pathways by extracellular vesicles released by gut microbiota.

  7. Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD 2 in Host Defense during Pneumococcal Pneumonia.

    Directory of Open Access Journals (Sweden)

    Tijmen J Hommes

    Full Text Available Streptococcus (S. pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/- and wild-type (Wt alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39, an isogenic capsule locus deletion mutant (D39Δcps or serotype 3 S. pneumoniae (6303 via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.

  8. Fast-growing Acer rubrum differs from slow-growing Quercus alba in leaf, xylem and hydraulic trait coordination responses to simulated acid rain.

    Science.gov (United States)

    Medeiros, Juliana S; Tomeo, Nicholas J; Hewins, Charlotte R; Rosenthal, David M

    2016-08-01

    We investigated the effects of historic soil chemistry changes associated with acid rain, i.e., reduced soil pH and a shift from nitrogen (N)- to phosphorus (P)-limitation, on the coordination of leaf water demand and xylem hydraulic supply traits in two co-occurring temperate tree species differing in growth rate. Using a full-factorial design (N × P × pH), we measured leaf nutrient content, water relations, leaf-level and canopy-level gas exchange, total biomass and allocation, as well as stem xylem anatomy and hydraulic function for greenhouse-grown saplings of fast-growing Acer rubrum (L.) and slow-growing Quercus alba (L.). We used principle component analysis to characterize trait coordination. We found that N-limitation, but not P-limitation, had a significant impact on plant water relations and hydraulic coordination of both species. Fast-growing A. rubrum made hydraulic adjustments in response to N-limitation, but trait coordination was variable within treatments and did not fully compensate for changing allocation across N-availability. For slow-growing Q. alba, N-limitation engendered more strict coordination of leaf and xylem traits, resulting in similar leaf water content and hydraulic function across all treatments. Finally, low pH reduced the propensity of both species to adjust leaf water relations and xylem anatomical traits in response to nutrient manipulations. Our data suggest that a shift from N- to P-limitation has had a negative impact on the water relations and hydraulic function of A. rubrum to a greater extent than for Q. alba We suggest that current expansion of A. rubrum populations could be tempered by acidic N-deposition, which may restrict it to more mesic microsites. The disruption of hydraulic acclimation and coordination at low pH is emphasized as an interesting area of future study. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Daintain/AIF-1 (Allograft Inflammatory Factor-1) accelerates type 1 diabetes in NOD mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yan-Ying, E-mail: biozyy@163.com [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Huang, Xin-Yuan [College of Life Science and Technology, Hubei Engineering University, Xiaogan 432000 (China); Chen, Zheng-Wang [Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Daintain/AIF-1 is over-expressed in the blood of NOD mice suffering from insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 stimulates white blood cell proliferation in NOD mice. Black-Right-Pointing-Pointer Daintain/AIF-1 increases blood glucose levels and triggers type 1 diabetes. Black-Right-Pointing-Pointer Daintain/AIF-1 accelerates insulitis, while its antibody prevents insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 enhances the levels of nitric oxide in the pancreases of NOD mice. -- Abstract: A large body of experimental evidence suggests that cytokines trigger pancreatic {beta}-cell death in type 1 diabetes mellitus. Daintain/AIF-1 (Allograft Inflammatory Factor-1), a specific marker for activated macrophages, is accumulated in the pancreatic islets of pre-diabetic BB rats. In the present study, we demonstrate that daintain/AIF-1 is released into blood and the levels of daintain/AIF-1 in the blood of type 1 diabetes-prone non-obese diabetic (NOD) mice suffering from insulitis are significantly higher than that in healthy NOD mice. When injected intravenously into NOD mice, daintain/AIF-1 stimulates white blood cell proliferation, increases the concentrations of blood glucose, impairs insulin expression, up-regulates nitric oxide (NO) production in pancreases and accelerates diabetes in NOD mice, while the antibody against daintain/AIF-1 delays or prevents insulitis in NOD mice. These results imply daintain/AIF-1 triggers type 1 diabetes probably via arousing immune cells activation and induction of NO production in pancreas of NOD mice.

  10. Divergence in function and expression of the NOD26-like intrinsic proteins in plants

    Directory of Open Access Journals (Sweden)

    Feng Ying

    2009-07-01

    Full Text Available Abstract Background NOD26-like intrinsic proteins (NIPs that belong to the aquaporin superfamily are plant-specific and exhibit a similar three-dimensional structure. Experimental evidences however revealed that functional divergence should have extensively occurred among NIP genes. It is therefore intriguing to further investigate the evolutionary mechanisms being responsible for the functional diversification of the NIP genes. To better understand this process, a comprehensive analysis including the phylogenetic, positive selection, functional divergence, and transcriptional analysis was carried out. Results The origination of NIPs could be dated back to the primitive land plants, and their diversification would be no younger than the emergence time of the moss P. patens. The rapid proliferation of NIPs in plants may be primarily attributed to the segmental chromosome duplication produced by polyploidy and tandem duplications. The maximum likelihood analysis revealed that NIPs should have experienced strong selective pressure for adaptive evolution after gene duplication and/or speciation, prompting the formation of distinct NIP groups. Functional divergence analysis at the amino acid level has provided strong statistical evidence for shifted evolutionary rate and/or radical change of the physiochemical properties of amino acids after gene duplication, and DIVERGE2 has identified the critical amino acid sites that are thought to be responsible for the divergence for further investigation. The expression of plant NIPs displays a distinct tissue-, cell-type-, and developmental specific pattern, and their responses to various stress treatments are quite different also. The differences in organization of cis-acting regulatory elements in the promoter regions may partially explain their distinction in expression. Conclusion A number of analyses both at the DNA and amino acid sequence levels have provided strong evidences that plant NIPs have

  11. Kinetics and mechanism of the conversion of a coordinated thiol to a coordinated disulfide by the one-equivalent oxidants neptunium(VI) and cobalt(III) in aqueous perchloric acid

    International Nuclear Information System (INIS)

    Woods, M.; Karbwang, J.; Sullivan, J.C.; Deutsch, E.

    1976-01-01

    Reaction of excess (2-mercaptoethylamine-N,S)bis(ethylenediamine)cobalt(III), I, with the 1-equiv oxidant Np(VI) (or Co 3+ (aq)) in aqueous perchloric acid media is shown to lead to (2-aminoethyl-N 2-ammonioethyl disulfide-S 1 ) bis(ethylenediamine)cobalt(III), II, according to the stoichiometry 5H + + 2I + Np(VI) → II + Co 2+ (aq) + Np(V) + 2enH 2 2+ . This reaction follows the rate law -d[I]/dt = k'' [I] [oxidant]. For Np(VI) as oxidant k'' is independent of [H + ]; at 25 0 C, μ = 1.00 M (LiClO 4 ), k'' = k 0 = 2842 +- 15 M -1 s -1 , ΔH 0 * = 7.57 +- 0.08 kcal/mol, and ΔS 0 * = -17.4 +- 0.3 eu. For Co 3+ (aq) as oxidant, k'' = k 0 + k/sub -1/[H + ] -1 where the inverse acid path is taken to reflect oxidation by CoOH 2+ (aq); at 25 0 C, μ = 1.00 M (LiClO 4 ), k 0 = 933 +- 32 M -1 s -1 , k/sub -1/ = 1152 +- 22 s -1 , ΔH 0 * = 12.5 +- 0.7 kcal/mol, ΔH*/sub -1/ = 18.0 +- 0.4 kcal/mol, ΔS 0 *= -3.1 +- 2.4 eu, and ΔS*/sub -1/ = 15.8 +- 1.2 eu. It is proposed that the conversion of I to II proceeds by initial 1-equiv oxidation of the coordinated thiol, reaction of the resultant coordinated thiol radical (RS.) with additional I to form a relatively stable radical ion dimer (RSSR. - ), and then internal electron transfer within the dimer to yield Co 2+ (aq) and II which contains a coordinated disulfide. The possible generality of this mechanism and its relevance to biological metal-thiol-disulfide interactions are noted

  12. Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice.

    Science.gov (United States)

    Zhang, Zifeng; Wang, Xin; Zheng, Guihong; Shan, Qun; Lu, Jun; Fan, Shaohua; Sun, Chunhui; Wu, Dongmei; Zhang, Cheng; Su, Weitong; Sui, Junwen; Zheng, Yuanlin

    2016-12-25

    Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA) was used to inhibit endoplasmic reticulum stress (ER stress). Our results showed that troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, troxerutin notably suppressed nuclear factor-κB (NF-κB) p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, troxerutin dramatically decreased Nucleotide oligomerization domain (NOD) expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2), by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect.

  13. Plant-based vaccines for oral delivery of type 1 diabetes-related autoantigens: Evaluating oral tolerance mechanisms and disease prevention in NOD mice.

    Science.gov (United States)

    Posgai, Amanda L; Wasserfall, Clive H; Kwon, Kwang-Chul; Daniell, Henry; Schatz, Desmond A; Atkinson, Mark A

    2017-02-13

    Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3 + and LAP + regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy. Recently, dogma was challenged in a report demonstrating oral insulin does not prevent T1D in NOD mice, possibly due to antigen digestion prior to mucosal immune exposure. We used transplastomic plants expressing proinsulin and GAD to protect the autoantigens from degradation in an oral vaccine and tested the optimal combination, dose, and treatment duration for the prevention of T1D in NOD mice. Our data suggest oral autoantigen therapy alone does not effectively influence disease incidence or result in antigen-specific tolerance assessed by IL-10 measurement and Treg frequency. A more aggressive approach involving tolerogenic cytokine administration and/or lymphocyte depletion prior to oral antigen-specific immunotherapy will likely be required to impart durable therapeutic efficacy.

  14. Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice

    Directory of Open Access Journals (Sweden)

    Zifeng Zhang

    2016-12-01

    Full Text Available Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA was used to inhibit endoplasmic reticulum stress (ER stress. Our results showed that troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, troxerutin notably suppressed nuclear factor-κB (NF-κB p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, troxerutin dramatically decreased Nucleotide oligomerization domain (NOD expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2, by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect.

  15. Co-ordinated research programme on application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report on the second research co-ordination meeting

    International Nuclear Information System (INIS)

    1996-01-01

    The use of isotopes has revolutionized the field of human nutrition research, but has been of greatest benefit to industrialized countries. The International Atomic Energy Agency is sponsoring programmes using isotopic and related technologies in human nutrition research to address issues that are of priority to developing countries. Scientists participating in the Coordinated Research Programme (CRP) on ''Amino Acid and Protein Metabolism in Malnourished Populations of Developing Countries'' are conducting research on the interaction between infection and amino acid metabolism, particularly the potential diversion of substrates from anabolic pathways to fight infection in marginally nourished children during periods of infections. This topic is of great importance to the nutritional status of children in developing countries, who frequently or chronically have infections and who, as a consequence, may have alterations in nutrient requirements. The CRP has developed and implemented a standardized protocol for measuring leucine oxidation during infection in 8 different countries. The CRP is expected to contribute important new knowledge about interactions between protein utilization, the stresses of unhygienic environments, and infections in marginally nourished people. This information is expected to be applicable to efforts to increase efficient utilization of limited food resources in developing countries. Another highlight of the CRP is that it represents an international team of nutrition scientists who together are building nutritional biology research capabilities in developing countries. Refs, figs, tabs

  16. Co-ordinated research programme on application of stable isotope tracer methods to studies of amino acid, protein, and energy metabolism in malnourished populations of developing countries. Report on the second research co-ordination meeting

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The use of isotopes has revolutionized the field of human nutrition research, but has been of greatest benefit to industrialized countries. The International Atomic Energy Agency is sponsoring programmes using isotopic and related technologies in human nutrition research to address issues that are of priority to developing countries. Scientists participating in the Coordinated Research Programme (CRP) on ``Amino Acid and Protein Metabolism in Malnourished Populations of Developing Countries`` are conducting research on the interaction between infection and amino acid metabolism, particularly the potential diversion of substrates from anabolic pathways to fight infection in marginally nourished children during periods of infections. This topic is of great importance to the nutritional status of children in developing countries, who frequently or chronically have infections and who, as a consequence, may have alterations in nutrient requirements. The CRP has developed and implemented a standardized protocol for measuring leucine oxidation during infection in 8 different countries. The CRP is expected to contribute important new knowledge about interactions between protein utilization, the stresses of unhygienic environments, and infections in marginally nourished people. This information is expected to be applicable to efforts to increase efficient utilization of limited food resources in developing countries. Another highlight of the CRP is that it represents an international team of nutrition scientists who together are building nutritional biology research capabilities in developing countries. Refs, figs, tabs.

  17. Serum uric acid is associated with new-onset diabetes in hypertensive patients with left ventricular hypertrophy: The LIFE Study

    DEFF Research Database (Denmark)

    Wiik, Benedicte P; Larstorp, Anne C K; Høieggen, Aud

    2010-01-01

    It is unclear whether serum uric acid (SUA) is associated with development of new-onset diabetes (NOD) in patients with hypertension and left ventricular hypertrophy (LVH). The aim of the present investigation was to test the hypothesis that SUA predicts development of NOD in these patients....

  18. Tung tree (Vernicia fordii, Hemsl.) genome and transcriptome sequencing reveals coordinate upregulation of fatty acid beta-oxidation and triacylglycerol biosynthesis pathways during eleostearic acid accumulation in seeds

    Science.gov (United States)

    The tung tree (Vernicia fordii) is one of only a few plant species that produces high oil-yielding seeds rich in a-eleostearic acid (a-ESA, 18:3'9cis,11trans,13trans), a conjugated trienoic fatty acid with valuable industrial and medical properties. Previous attempts have been made to engineer tung...

  19. A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production

    DEFF Research Database (Denmark)

    Nachbur, Ueli; Stafford, Che A; Bankovacki, Aleksandra

    2015-01-01

    Intracellular nucleotide binding and oligomerization domain (NOD) receptors recognize antigens including bacterial peptidoglycans and initiate immune responses by triggering the production of pro-inflammatory cytokines through activating NF-κB and MAP kinases. Receptor interacting protein kinase ...

  20. Nucleotide-binding oligomerization domain 2 (NOD2) activation induces apoptosis of human oral squamous cell carcinoma cells.

    Science.gov (United States)

    Yoon, Hyo-Eun; Ahn, Mee-Young; Kwon, Seong-Min; Kim, Dong-Jae; Lee, Jun; Yoon, Jung-Hoon

    2016-04-01

    Microbial Pattern-recognition receptors (PRRs), such as nucleotide-binding oligomerization domains (NODs), are essential for mammalian innate immune response. This study was designed to determine the effect of NOD1 and NOD2 agonist on innate immune responses and antitumor activity in oral squamous cell carcinoma (OSCC) cells. NODs expression was examined by RT-PCR, and IL-8 production by NODs agonist was examined by ELISA. Western blot analysis was performed to determine the MAPK activation in response to their agonist. Cell proliferation was determined by MTT assay. Flow cytometry and Western blot analysis were performed to determine the MDP-induced cell death. The levels of NODs were apparently expressed in OSCC cells. NODs agonist, Tri-DAP and MDP, led to the production of IL-8 and MAPK activation. NOD2 agonist, MDP, inhibited the proliferation of YD-10B cells in a dose-dependent manner. Also, the ratio of Annexin V-positive cells and cleaved PARP was increased by MDP treatment in YD-10B cells, suggesting that MDP-induced cell death in YD-10B cells may be owing to apoptosis. Our results indicate that NODs are functionally expressed in OSCC cells and can trigger innate immune responses. In addition, NOD2 agonist inhibited cell proliferation and induced apoptosis. These findings provide the potential value of MDP as novel candidates for antitumor agents of OSCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: implications for diabetic nephropathy.

    Science.gov (United States)

    Lupia, E; Elliot, S J; Lenz, O; Zheng, F; Hattori, M; Striker, G E; Striker, L J

    1999-08-01

    Nonobese diabetic (NOD) mice develop glomerulosclerosis shortly after the onset of diabetes. We showed that mesangial cells (MCs) from diabetic mice exhibited a stable phenotypic switch, consisting of both increased IGF-1 synthesis and proliferation (Elliot SJ, Striker LJ, Hattori M, Yang CW, He CJ, Peten EP, Striker GE: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. Endocrinology 133:1783-1788, 1993). Because the extracellular matrix (ECM) accumulation in diabetic glomerulosclerosis may be partly due to decreased degradation, we examined the effect of excess IGF-1 on collagen turnover and the activity of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in diabetic and nondiabetic NOD-MC. Total collagen degradation was reduced by 58 +/- 18% in diabetic NOD-MCs, which correlated with a constitutive decrease in MMP-2 activity and mRNA levels, and nearly undetectable MMP-9 activity and mRNA. TIMP levels were slightly decreased in diabetic NOD-MC. The addition of recombinant IGF-1 to nondiabetic NOD-MC resulted in a decrease in MMP-2 and TIMP activity. Furthermore, treatment of diabetic NOD-MC with a neutralizing antibody against IGF-1 increased the latent form, and restored the active form, of MMP-2. In conclusion, the excessive production of IGF-1 contributes to the altered ECM turnover in diabetic NOD-MC, largely through a reduction of MMP-2 activity. These data suggest that IGF-1 could be a major contributor to the development of diabetic glomerulosclerosis.

  2. Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae.

    Science.gov (United States)

    Schenk, Mirjam; Mahapatra, Sebabrata; Le, Phuonganh; Kim, Hee Jin; Choi, Aaron W; Brennan, Patrick J; Belisle, John T; Modlin, Robert L

    2016-09-01

    The innate immune system recognizes microbial pathogens via pattern recognition receptors. One such receptor, NOD2, via recognition of muramyl dipeptide (MDP), triggers a distinct network of innate immune responses, including the production of interleukin-32 (IL-32), which leads to the differentiation of monocytes into dendritic cells (DC). NOD2 has been implicated in the pathogenesis of human leprosy, yet it is not clear whether Mycobacterium leprae, which has a distinct MDP structure, can activate this pathway. We investigated the effect of MDP structure on the innate immune response, finding that infection of monocytes with M. leprae induces IL-32 and DC differentiation in a NOD2-dependent manner. The presence of the proximal l-Ala instead of Gly in the common configuration of the peptide side chain of M. leprae did not affect recognition by NOD2 or cytokine production. Furthermore, amidation of the d-Glu residue did not alter NOD2 activation. These data provide experimental evidence that NOD2 recognizes naturally occurring structural variants of MDP. Copyright © 2016 Schenk et al.

  3. Flaxseed Oil Attenuates Intestinal Damage and Inflammation by Regulating Necroptosis and TLR4/NOD Signaling Pathways Following Lipopolysaccharide Challenge in a Piglet Model.

    Science.gov (United States)

    Zhu, Huiling; Wang, Haibo; Wang, Shuhui; Tu, Zhixiao; Zhang, Lin; Wang, Xiuying; Hou, Yongqing; Wang, Chunwei; Chen, Jie; Liu, Yulan

    2018-05-01

    Flaxseed oil is a rich source of α-linolenic acid (ALA), which is the precursor of the long-chain n-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This study investigates the protective effect of flaxseed oil against intestinal injury induced by lipopolysaccharide (LPS). Twenty-four weaned pigs were used in a 2 × 2 factorial experiment with dietary treatment (5% corn oil vs 5% flaxseed oil) and LPS challenge (saline vs LPS). On day 21 of the experiment, pigs were administrated with LPS or saline. At 2 h and 4 h post-administration, blood samples were collected. After the blood harvest at 4 h, all piglets were slaughtered and intestinal samples were collected. Flaxseed oil supplementation led to the enrichment of ALA, EPA, and total n-3 PUFAs in intestine. Flaxseed oil improved intestinal morphology, jejunal lactase activity, and claudin-1 protein expression. Flaxseed oil downregulated the mRNA expression of intestinal necroptotic signals. Flaxseed oil also downregulated the mRNA expression of intestinal toll-like receptors 4 (TLR4) and its downstream signals myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), and nucleotide-binding oligomerization domain proteins 1, 2 (NOD1, NOD2) and its adapter molecule, receptor-interacting protein kinase 2 (RIPK2). These results suggest that dietary addition of flaxseed oil enhances intestinal integrity and barrier function, which is involved in modulating necroptosis and TLR4/NOD signaling pathways. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses.

    Directory of Open Access Journals (Sweden)

    Timothy Gatheral

    Full Text Available Understanding the mechanisms by which pathogens induce vascular inflammation and dysfunction may reveal novel therapeutic targets in sepsis and related conditions. The intracellular receptor NOD1 recognises peptidoglycan which features in the cell wall of gram negative and some gram positive bacteria. NOD1 engagement generates an inflammatory response via activation of NFκB and MAPK pathways. We have previously shown that stimulation of NOD1 directly activates blood vessels and causes experimental shock in vivo. In this study we have used an ex vivo vessel-organ culture model to characterise the relative contribution of the endothelium in the response of blood vessels to NOD1 agonists. In addition we present the novel finding that NOD1 directly activates human blood vessels. Using human cultured cells we confirm that endothelial cells respond more avidly to NOD1 agonists than vascular smooth muscle cells. Accordingly we have sought to pharmacologically differentiate NOD1 and TLR4 mediated signalling pathways in human endothelial cells, focussing on TAK1, NFκB and p38 MAPK. In addition we profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1 ligand induced inflammatory signalling in the vasculature. This paper is the first to demonstrate activation of whole human artery by NOD1 stimulation and the relative importance of the endothelium in the sensing of NOD1 ligands by vessels. This data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock.

  5. Critical role of IFN-gamma in CFA-mediated protection of NOD mice from diabetes development.

    Science.gov (United States)

    Mori, Yoshiko; Kodaka, Tetsuro; Kato, Takako; Kanagawa, Edith M; Kanagawa, Osami

    2009-11-01

    IFN-gamma signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN-gamma signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN-gamma receptor-deficient (IFN-gammaR(-/-)) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN-gamma is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the T(h)1/T(h)17 balance between IFN-gammaR(-/-) NOD and wild-type NOD mice. There is also no difference in the total numbers and percentages of regulatory T (Treg) cells in the lymph node CD4(+) T-cell populations between IFN-gammaR(-/-) NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-gammaR are resistant to the suppressive effect of Treg cells, both in vivo and in vitro. Therefore, it is likely that CFA-mediated protection against diabetes development depends on a change in the balance between Treg cells and pathogenic T cells, and IFN-gamma signaling seems to control the susceptibility of pathogenic T cells to the inhibitory activity of Treg cells.

  6. Nucleotide-oligomerizing domain-1 (NOD1) receptor activation induces pro-inflammatory responses and autophagy in human alveolar macrophages.

    Science.gov (United States)

    Juárez, Esmeralda; Carranza, Claudia; Hernández-Sánchez, Fernando; Loyola, Elva; Escobedo, Dante; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Torres, Martha; Sada, Eduardo

    2014-09-25

    Nucleotide-binding oligomerizing domain-1 (NOD1) is a cytoplasmic receptor involved in recognizing bacterial peptidoglycan fragments that localize to the cytosol. NOD1 activation triggers inflammation, antimicrobial mechanisms and autophagy in both epithelial cells and murine macrophages. NOD1 mediates intracellular pathogen clearance in the lungs of mice; however, little is known about NOD1's role in human alveolar macrophages (AMs) or its involvement in Mycobacterium tuberculosis (Mtb) infection. AMs, monocytes (MNs), and monocyte-derived macrophages (MDMs) from healthy subjects were assayed for NOD1 expression. Cells were stimulated with the NOD1 ligand Tri-DAP and cytokine production and autophagy were assessed. Cells were infected with Mtb and treated with Tri-DAP post-infection. CFUs counting determined growth control, and autophagy protein recruitment to pathogen localization sites was analyzed by immunoelectron microscopy. NOD1 was expressed in AMs, MDMs and to a lesser extent MNs. Tri-DAP stimulation induced NOD1 up-regulation and a significant production of IL1β, IL6, IL8, and TNFα in AMs and MDMs; however, the level of NOD1-dependent response in MNs was limited. Autophagy activity determined by expression of proteins Atg9, LC3, IRGM and p62 degradation was induced in a NOD1-dependent manner in AMs and MDMs but not in MNs. Infected AMs could be activated by stimulation with Tri-DAP to control the intracellular growth of Mtb. In addition, recruitment of NOD1 and the autophagy proteins IRGM and LC3 to the Mtb localization site was observed in infected AMs after treatment with Tri-DAP. NOD1 is involved in AM and MDM innate responses, which include proinflammatory cytokines and autophagy, with potential implications in the killing of Mtb in humans.

  7. Activation of nucleotide oligomerization domain 2 (NOD2 by human cytomegalovirus initiates innate immune responses and restricts virus replication.

    Directory of Open Access Journals (Sweden)

    Arun Kapoor

    Full Text Available Nucleotide-binding oligomerization domain 2 (NOD2 is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.

  8. Coordination compounds of cobalt(II), nickel(II), copper(II), and zinc(II) with pantothenic acid

    Energy Technology Data Exchange (ETDEWEB)

    Shabilalov, A.A.; Yunuskhodzhaev, A.N.; Khodzhaev, O.F.; Azizov, M.A.

    1986-11-01

    The compounds Ni(PANA - H)/sub 2/ x 4H/sub 2/O (PANA stands for pantothenic acid, and - H indicates a deprotonated ligand), Cu(PANA - H)/sub 2/ x 2H/sub 2/O, Zn(PANA - H)/sub 2/ x H/sub 2/O, Co(PANA - H)Cl x H/sub 2/O, and Ni(PANA - H)Cl x 3H/sub 2/O have been synthesized on the basis of pantothenic acid and Co(II), Ni(II), Cu(II), and Zn(II) salts in aqueous media. The compounds have been identified by elemental and x-ray diffraction analysis. Some physicochemical properties (solubility, melting point, molar conductivity) of the compounds obtained have been studied. The structure of the compounds isolated has been established on the basis of an analysis of their IR, ESR, and electronic spectra, as well as derivatograms.

  9. THE COORDINATION COMPOUNDS OF COBALT (II, III) WITH DITHIOCARBAMIC ACID DERIVATIVES — MODIFICATORS OF HYDROLYTIC ENZYMES ACTIVITY

    OpenAIRE

    L. D. Varbanets; О. V. Matselyukh; N. А. Nidyalkova; Е. V. Аvdiyuk; А. V. Gudzenko; I. I. Seifullina; G. N. Маsаnоvets; N. V. Khitrich

    2013-01-01

    Chloride, bromide and isothiocyanate complexes of cobalt(II) with N-substituted thiocarbamoyl-N?-pentamethylenesulfenamides (1)–(12), and also complexes of cobalt(II, Ш) with derivatives of morpholine-4-carbodithioic acid (13)–(18) have been used as modificators of enzymes of hydrolytic action — Bacillus thurin-giensis ІМВ В-7324 peptidases, Bacillus subtilis 147 and Aspergillus flavus var. oryzae 80428 amylases, Eupenicillium erubescens 248 and Cryptococcus albidus 1001 rhamnosidases. It was...

  10. Solvent induced synthesis, structure and properties of coordination polymers based on 5-hydroxyisophthalic acid as linker and 1,10-phenanthroline as auxiliary ligand

    Science.gov (United States)

    Kariem, Mukaddus; Yawer, Mohd; Sheikh, Haq Nawaz

    2015-11-01

    Three new coordination polymers [Mn(hip)(phen) (H2O)]n (1), [Co(hip)(phen) (H2O)]n (2), and [Cd(hip) (phen) (H2O)]n (3) (H2hip=5-hydroxyisophthalic acid; phen=1,10-phenanthroline) have been synthesized by solvo-hydrothermal method using diethyl formamide-water (DEF-H2O) as solvent system. Single-crystal X-ray diffraction analysis reveals that all three coordination polymers 1, 2 and 3 crystallize in monoclinic space group P2/n. Metal ions are inter-connected by hydroxyisophthalate anions forming zig-zag 1D chain. 1D chains are further inter-connected by hydrogen bonding and π-π stacking interactions leading to 3D supramolecular architecture. Hydrogen-bonding and π-π stacking provide thermal stability to polymers. Compounds 1 and 2 are paramagnetic at room temperature and variable temperature magnetic moment measurements revealed weak ferromagnetic interactions between metal ions at low temperature. Compound 3 exhibits excellent photoluminescence with large Stokes shift.

  11. Cofactor Balance by Nicotinamide Nucleotide Transhydrogenase (NNT) Coordinates Reductive Carboxylation and Glucose Catabolism in the Tricarboxylic Acid (TCA) Cycle*♦

    Science.gov (United States)

    Gameiro, Paulo A.; Laviolette, Laura A.; Kelleher, Joanne K.; Iliopoulos, Othon; Stephanopoulos, Gregory

    2013-01-01

    Cancer and proliferating cells exhibit an increased demand for glutamine-derived carbons to support anabolic processes. In addition, reductive carboxylation of α-ketoglutarate by isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) was recently shown to be a major source of citrate synthesis from glutamine. The role of NAD(P)H/NAD(P)+ cofactors in coordinating glucose and glutamine utilization in the tricarboxylic acid (TCA) cycle is not well understood, with the source(s) of NADPH for the reductive carboxylation reaction remaining unexplored. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial enzyme that transfers reducing equivalents from NADH to NADPH. Here, we show that knockdown of NNT inhibits the contribution of glutamine to the TCA cycle and activates glucose catabolism in SkMel5 melanoma cells. The increase in glucose oxidation partially occurred through pyruvate carboxylase and rendered NNT knockdown cells more sensitive to glucose deprivation. Importantly, knocking down NNT inhibits reductive carboxylation in SkMel5 and 786-O renal carcinoma cells. Overexpression of NNT is sufficient to stimulate glutamine oxidation and reductive carboxylation, whereas it inhibits glucose catabolism in the TCA cycle. These observations are supported by an impairment of the NAD(P)H/NAD(P)+ ratios. Our findings underscore the role of NNT in regulating central carbon metabolism via redox balance, calling for other mechanisms that coordinate substrate preference to maintain a functional TCA cycle. PMID:23504317

  12. A New Approach to Non-Coordinating Anions: Lewis Acid Enhancement of Porphyrin Metal Centers in a Zwitterionic Metal$-$Organic Framework

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jacob A. [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry; Petersen, Brenna M. [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry; Kormos, Attila [Hungarian Academy of Sciences, Budapest (Hungary); Echeverría, Elena [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Physics and Astronomy; Chen, Yu-Sheng [Univ. of Chicago, Argonne, IL (United States). ChemMatCARS, Center for Advanced Radiation Sources; Zhang, Jian [Univ. of Nebraska, Lincoln, NE (United States). Dept. of Chemistry

    2017-02-28

    Here, we describe a new strategy to generate non-coordinating anions using zwitterionic metal–organic frameworks (MOFs). By assembly of anionic inorganic secondary building blocks (SBUs) ([In(CO2)4]$-$) with cationic metalloporphyrin-based organic linkers, we prepared zwitterionic MOFs in which the complete internal charge separation effectively prevents the potential binding of the counteranion to the cationic metal center. We demonstrate the enhanced Lewis acidity of MnIII- and FeIII-porphyrins in the zwitterionic MOFs in three representative electrocyclization reactions: [2 + 1] cycloisomerization of enynes, [3 + 2] cycloaddition of aziridines and alkenes, and [4 + 2] hetero-Diels–Alder cycloaddition of aldehydes with dienes. Lastly, this work paves a new way to design functional MOFs for tunable chemical catalysis.

  13. Two novel penetrating coordination polymers based on flexible S-containing dicarboxylate acid with sensing properties towards Fe3+ and Cr2O72- ions

    Science.gov (United States)

    Chen, Zhiwei; Mi, Xiuna; Wang, Suna; Lu, Jing; Li, Yunwu; Li, Dacheng; Dou, Jianmin

    2018-05-01

    Two new coordination polymers (CPs), namely, {[Zn(L)(bpp)]·DMF}n (1) and {[Zn(L)(bpe)]·DMF}n (2) (L = 2,2'-[benzene-1,3-diylbis(methanediylsulfanediyl)]dibenzoic acid, bpp= 1,3-bis(4-pyridyl)propane, bpe = 1,2-Bis(4-pyridyl)ethylene, DMF = N,N-Dimethylformamide), have been solvothermally synthesized and fully characterized. Complex 1 displays a 2D→2D three-fold"false" interpenetrating structure while complex 2 possesses a novel 3-D 4-connected structure with fascinating self-penetrating moieties. The luminescence studies reveal that these complexes exhibited excellent selectivity for Fe3+ and Cr2O72- ions in DMF. The sensing mechanism was investigated through PXRD, XPS , EDS mapping measurements, and discussed in details.

  14. Three PbII coordination polymers based on 2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylic acid: Syntheses, crystal structures, and fluorescent properties

    International Nuclear Information System (INIS)

    Yu, Xiao-Yang; Xin, Rui; Gao, Wei-Ping; Wang, Na; Zhang, Xiao; Yang, Yan-Yan; Qu, Xiao-Shu

    2013-01-01

    Three lead coordination polymers, [PbCl(C 10 H 6 N 3 O 4 )(H 2 O)·H 2 O] n (1), [Pb(C 10 H 6 N 3 O 4 ) 2 (H 2 O)] n (2) and [Pb 3 (C 10 H 5 N 3 O 4 ) 3 ] n (3) (C 10 H 7 N 3 O 4 =2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylic acid), have been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction. In 1, Cl anions connected neighboring wave-like 2D layers, which are constructed with left- and right-handed helical chains, into a 3D network structure with a (6 3 )(6 5 ·8) topology. In 2, Pb cations are linked into a 3D 6 6 network with left- and right-handed helixes by μ 2 -bridging C 10 H 6 N 3 O 4 − ligands. In 3, C 10 H 5 N 3 O 4 2− ligands link Pb 6 O 12 clusters into a 3D (4 12 ·6 3 ) network. Their fluorescent properties were also investigated. - Graphical abstract: Three 3D lead compounds based on 2-(pyridin-2-yl)-1H-imidazole-4,5-dicarboxylic acid have been hydrothermally synthesized. Four new coordination modes of the organic ligand are first reported. Display Omitted - Highlights: • Three new Pb(II) complexes have been synthesized and characterized. • Left- and right-handed helical chains can be found in the 3D networks of 1 and 2. • Pb 6 O 12 clusters are connected into (4 12 ·6 3 ) network in 3

  15. Ebselen protects against behavioral and biochemical toxicities induced by 3-nitropropionic acid in rats: correlations between motor coordination, reactive species levels, and succinate dehydrogenase activity.

    Science.gov (United States)

    Wilhelm, Ethel A; Bortolatto, Cristiani F; Jesse, Cristiano R; Luchese, Cristiane

    2014-12-01

    The protective effect of ebselen was investigated against 3-nitropropionic acid (3-NP)-induced behavioral and biochemical toxicities in rats. Ebselen (10 or 25 mg/kg, intragastrically) was administered to rats 30 min before 3-NP (20 mg/kg, intraperitoneally) once a day for a period of 4 days. Locomotor activity, motor coordination, and body weight gain were determined. The striatal content of reactive oxygen species (ROS), reduced glutathione (GSH), ascorbic acid (AA), and protein carbonyl as well as catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) activities was determined 24 h after the last dose of 3-NP. Na(+)/ K(+)-ATPase, succinate dehydrogenase (SDH), and δ-aminolevulinic dehydratase (δ-ALA-D) activities were also determined. The results demonstrated that ebselen at a dose of 25 mg/kg, but not at 10 mg/kg, protected against (1) a decrease in locomotor activity, motor coordination impairment, and body weight loss; (2) striatal oxidative damage, which was characterized by an increase in ROS levels, protein carbonyl content, and GR activity, an inhibition of CAT and GPx activities, and a decrease in GSH levels; and (3) an inhibition of SDH and Na(+)/K(+)-ATPase activities, induced by 3-NP. GST activity and AA levels were not modified by ebselen or 3-NP. Ebselen was not effective against the inhibition of δ-ALA-D activity induced by 3-NP. The results revealed a significant correlation between SDH activity and ROS levels, and SDH activity and latency to fall (rotarod test). The present study highlighted the protective effect of ebselen against 3-NP-induced toxicity in rats.

  16. The Maize MID-COMPLEMENTING ACTIVITY homolog CELL NUMBER REGULATOR13/NARROW ODD DWARF, coordinates organ growth and tissue patterning

    Science.gov (United States)

    Organogenesis occurs from cell division, expansion and differentiation. How these cellular processes are coordinated remains elusive. The maize leaf provides an excellent system to study cellular differentiation because it has several different tissues and cell types. The narrow odd dwarf (nod) mut...

  17. Two novel alkaline earth coordination polymers constructed from cinnamic acid and 1,10-phenanthroline: synthesis and structural and thermal properties.

    Science.gov (United States)

    Bendjellal, Nassima; Trifa, Chahrazed; Bouacida, Sofiane; Boudaren, Chaouki; Boudraa, Mhamed; Merazig, Hocine

    2018-02-01

    In coordination chemistry and crystal engineering, many factors influence the construction of coordination polymers and the final frameworks depend greatly on the organic ligands used. The diverse coordination modes of N-donor ligands have been employed to assemble metal-organic frameworks. Carboxylic acid ligands can deprotonate completely or partially when bonding to metal ions and can also act as donors or acceptors of hydrogen bonds; they are thus good candidates for the construction of supramolecular architectures. We synthesized under reflux or hydrothermal conditions two new alkaline earth(II) complexes, namely poly[(1,10-phenanthroline-κ 2 N,N')bis(μ-3-phenylprop-2-enoato-κ 3 O,O':O)calcium(II)], [Ca(C 10 H 7 O 2 ) 2 (C 10 H 8 N 2 )] n , (1), and poly[(1,10-phenanthroline-κ 2 N,N')(μ 3 -3-phenylprop-2-enoato-κ 4 O:O,O':O')(μ-3-phenylprop-2-enoato-κ 3 O,O':O)barium(II)], [Ba(C 10 H 7 O 2 ) 2 (C 10 H 8 N 2 )] n , (2), and characterized them by FT-IR and UV-Vis spectroscopies, thermogravimetric analysis (TGA) and single-crystal X-ray diffraction analysis, as well as by powder X-ray diffraction (PXRD) analysis. Complex (1) features a chain topology of type 2,4 C4, where the Ca atoms are connected by O and N atoms, forming a distorted bicapped trigonal prismatic geometry. Complex (2) displays chains of topology type 2,3,5 C4, where the Ba atom is nine-coordinated by seven O atoms of bridging/chelating carboxylate groups from two cinnamate ligands and by two N atoms from one phenanthroline ligand, forming a distorted tricapped prismatic arrangement. Weak C-H...O hydrogen bonds and π-π stacking interactions between phenanthroline ligands are responsible to the formation of a supramolecular three-dimensional network. The thermal decompositions of (1) and (2) in the temperature range 297-1173 K revealed that they both decompose in three steps and transform to the corresponding metal oxide.

  18. 3-Methylindole-Based Tripodal Tetraphosphine Ruthenium Complexes in N2 Coordination and Reduction and Formic Acid Dehydrogenation

    Directory of Open Access Journals (Sweden)

    Fenna F. van de Watering

    2017-10-01

    Full Text Available The ruthenium(II complexes RuCl2L1H, RuCl2L1CF3, RuCl2L1OMe and RuCl2L2H were synthesized from [Ru(η6-benzeneCl(μ-Cl]2 and the corresponding tripodal tris-3-methylindolephosphine-based ligands L1H, L1CF3, L1OMe, and L2H. Stoichiometric reduction of these complexes with KC8 yielded the corresponding ruthenium(0 dinitrogen complexes. The latter complexes were studied in the N2 reduction with chlorosilanes and KC8, yielding stoichiometric amounts of the silylamines. The synthesized ruthenium(II complexes are also active catalysts for the formic acid dehydrogenation reaction.

  19. THE COORDINATION COMPOUNDS OF COBALT (II, III WITH DITHIOCARBAMIC ACID DERIVATIVES — MODIFICATORS OF HYDROLYTIC ENZYMES ACTIVITY

    Directory of Open Access Journals (Sweden)

    L. D. Varbanets

    2013-02-01

    Full Text Available Chloride, bromide and isothiocyanate complexes of cobalt(II with N-substituted thiocarbamoyl-N?-pentamethylenesulfenamides (1–(12, and also complexes of cobalt(II, Ш with derivatives of morpholine-4-carbodithioic acid (13–(18 have been used as modificators of enzymes of hydrolytic action — Bacillus thurin-giensis ІМВ В-7324 peptidases, Bacillus subtilis 147 and Aspergillus flavus var. oryzae 80428 amylases, Eupenicillium erubescens 248 and Cryptococcus albidus 1001 rhamnosidases. It was shown that cobalt (II, Ш compounds influence differently on the activity of enzymes tested, exerted both inhibitory and stimulatory action. It gives a possibility to expect that manifestation of activity by complex molecule depends on ligand and anion presence — Cl–, Br– or NCS–. The high activating action of cobalt(II complexes with N-substituted thiocarbamoyl-N?-pentamethylenesulphenamides (1–(12 on elastase and fibrinolytic activity of peptidases compared to tris(4-morpholinecarbodithioatocobalt(ІІІ (14 and products of its interaction with halogens (15–(17, causes inhibitory effect that is probably due to presence of a weekly S–N link, which is easy subjected to homolytic breaking. The studies of influences of cobalt(II complexes on activity of C. аlbidus and E. еrubescens ?-Lrhamnosidases showed, that majority of compounds inhibits of its activity, at that the most inhibitory effect exerts to C. аlbidus enzyme.To sum up, it is possible to state that character of influence of cobalt(II complexes with N-substituted thiocarbamoyl-N?-pentamethylenesulphenamides, and also cobalt(II, Ш complexes with derivatives of morpholine-4-carbodithioic acid varies depending on both strain producer and enzyme tested. The difference in complex effects on enzymes tested are due to peculiarities of building and functional groups of their active centers, which are also responsible for binding with modificators.

  20. NOD2/CARD15: geographic differences in the Spanish population and clinical applications in Crohn's disease.

    Science.gov (United States)

    Barreiro-de-Acosta, M; Mendoza, J L; Lana, R; Domínguez-Muñoz, J E; Díaz-Rubio, M

    2010-05-01

    Crohn's disease (CD) is a genetically complex disease in which both genetic susceptibility and environmental factors play key roles in the development of the disorder. NOD2/CARD15 mutations are associated with CD. NOD2 encodes for a protein that is an intracellular receptor for a bacterial product (muramyl dipeptide), though the exact functional consequences of these mutations remain the subject of debate. NOD2/CARD15 mutations are associated with ileal CD, with stricturing behavior, and possibly with a more complicated course of CD. NOD2/CARD15 mutations associated with CD have demonstrated heterogeneity across ethnicities and populations throughout the world, with regional variations across Europe and Spain. However, "NOD2/CARD15 testing" is not yet ready for use in the clinical setting. One of the reasons is that we know that these genetic variants increase the risk of disease only marginally, and many healthy individuals carry the risk alleles, at present it is not recommended to screen first-degree relatives, because we do not have the ability to prevent the disease at the present time.

  1. Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

    Science.gov (United States)

    Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

    2005-03-01

    Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

  2. The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity

    DEFF Research Database (Denmark)

    Damgaard, Rune Busk; Nachbur, Ueli; Yabal, Monica

    2012-01-01

    Nucleotide-binding and oligomerization domain (NOD)-like receptors constitute a first line of defense against invading bacteria. X-linked Inhibitor of Apoptosis (XIAP) is implicated in the control of bacterial infections, and mutations in XIAP are causally linked to immunodeficiency in X-linked l......Nucleotide-binding and oligomerization domain (NOD)-like receptors constitute a first line of defense against invading bacteria. X-linked Inhibitor of Apoptosis (XIAP) is implicated in the control of bacterial infections, and mutations in XIAP are causally linked to immunodeficiency in X......-linked lymphoproliferative syndrome type-2 (XLP-2). Here, we demonstrate that the RING domain of XIAP is essential for NOD2 signaling and that XIAP contributes to exacerbation of inflammation-induced hepatitis in experimental mice. We find that XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly...... signaling. We conclude that XIAP and LUBAC constitute essential ubiquitin ligases in NOD2-mediated inflammatory signaling and propose that deregulation of NOD2 signaling contributes to XLP-2 pathogenesis....

  3. NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans.

    Science.gov (United States)

    Juárez, Esmeralda; Carranza, Claudia; Hernández-Sánchez, Fernando; León-Contreras, Juan C; Hernández-Pando, Rogelio; Escobedo, Dante; Torres, Martha; Sada, Eduardo

    2012-04-01

    A role for the nucleotide-binding oligomerization domain 2 (NOD2) receptor in pulmonary innate immune responses has recently been explored. In the present study, we investigated the role that NOD2 plays in human alveolar macrophage innate responses and determined its involvement in the response to infection with virulent Mycobacterium tuberculosis. Our results showed that NOD2 was expressed in human alveolar macrophages, and significant amounts of IL-1β, IL-6, and TNF-α were produced upon ligand recognition with muramyldipeptide (MDP). NOD2 ligation induced the transcription and protein expression of the antimicrobial peptide LL37 and the autophagy enzyme IRGM in alveolar macrophages, demonstrating a novel function for this receptor in these cells. MDP treatment of alveolar macrophages improved the intracellular growth control of virulent M. tuberculosis; this was associated with a significant release of TNF-α and IL-6 and overexpression of bactericidal LL37. In addition, the autophagy proteins IRGM, LC3 and ATG16L1 were recruited to the bacteria-containing autophagosome after treatment with MDP. In conclusion, our results suggest that NOD2 can modulate the innate immune response of alveolar macrophages and play a role in the initial control of respiratory M. tuberculosis infections. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Recognition of Lipopolysaccharide and Activation of NF-κB by Cytosolic Sensor NOD1 in Teleost Fish

    Directory of Open Access Journals (Sweden)

    Dekun Bi

    2018-06-01

    Full Text Available Lipopolysaccharide (LPS is the major component of the outer membrane of Gram-negative bacteria. This molecule can induce strong immune response and various biological effects. In mammals, TLR4 can recognize LPS and induce inflammatory response. However, the innate receptor in fish for recognizing LPS remains ambiguous. LPS can invade the cytoplasm via outer membrane vesicles produced by Gram-negative bacteria and could be detected by intracellular receptor caspase-11 in mammals, so, there may also exist the intracellular receptors that can recognize LPS in fish. NOD1 is a member of NOD-like receptors family and can recognize the iE-DAP in the cytoplasm in mammals. In fish, NOD1 can also respond to infection of Gram-negative bacteria and may play an important role in the identification of bacterial components. In this study, to study whether NOD1 is a recognition receptor for LPS, we detected the expression of NOD1 and several cytokines at transcript levels to determine whether LPS can induce inflammatory response in teleost fish and NOD1 can respond to LPS. Then, we perform the binding analysis between NOD1 and ultrapure LPS by using Streptavidin pulldown assay and enzyme-linked immunosorbent assay to prove that NOD1 can be combined with LPS, and using dual luciferase reporter gene assay to verify the signal pathways activated by NOD1. Next, through cell viability analysis, we proved that LPS-induced cytotoxicity can be mediated by NOD1 in fish. The results showed that NOD1 can identify LPS and activate the NF-κB signal pathway by recruiting RIPK2 and then promoting the expression of inflammatory cytokines to induce the resistance of organism against bacterial infection.

  5. Enantioseparation of dansyl amino acids and dipeptides by chiral ligand exchange capillary electrophoresis based on Zn(II)-L-hydroxyproline complexes coordinating with γ-cyclodextrins.

    Science.gov (United States)

    Mu, Xiaoyu; Qi, Li; Qiao, Juan; Yang, Xinzheng; Ma, Huimin

    2014-10-10

    A chiral ligand exchange capillary electrophoresis (CLE-CE) method using Zn(II) as the central ion and L-4-hydroxyproline as the chiral ligand coordinating with γ-cyclodextrin (γ-CD) was developed for the enantioseparation of amino acids (AAs) and dipeptides. The effects of various separation parameters, including the pH of the running buffer, the ratio of Zn(II) to L-4-hydroxyproline, the concentration of complexes and cyclodextrins (CDs) were systematically investigated. After optimization, it has been found that eight pairs of labeled AAs and six pairs of labeled dipeptides could be baseline-separated with a running electrolyte of 100.0mM boric acid, 5.0mM ammonium acetate, 3.0mM Zn(II), 6.0mM L-hydroxyproline and 4.0mM γ-CD at pH 8.2. The quantitation of AAs and dipeptides was conducted and good linearity (r(2)≥0.997) and favorable repeatability (RSD≤3.6%) were obtained. Furthermore, the proposed method was applied in determining the enantiomeric purity of AAs and dipeptides. Meanwhile, the possible enantiorecognition mechanism based on the synergistic effect of chiral metal complexes and γ-CD was explored and discussed briefly. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. A family of entangled coordination polymers constructed from a flexible V-shaped long bicarboxylic acid and auxiliary N-donor ligands: Luminescent sensing

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jun [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi' an 710127 (China); College of Chemistry and Environmental Engineering, Sichuan University of Science & Engineering, Zigong 643000 (China); Bai, Chao [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi' an 710127 (China); Hu, Huai-Ming, E-mail: ChemHu1@NWU.EDU.CN [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi' an 710127 (China); Yuan, Fei; Xue, Gang-Lin [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi' an 710127 (China)

    2017-05-15

    Eight Zn(II)-based coordination polymers, namely, [Zn{sub 2}L{sub 2}(2,2’-bipy)]{sub n}·nH{sub 2}O (1), [Zn{sub 2}L{sub 2}(phen)]{sub n}·nH{sub 2}O (2), [ZnL(phen)(H{sub 2}O)]{sub n} (3), [Zn{sub 3}L{sub 3}(4,4’-bipy)]{sub n} (4), [Zn{sub 2}L{sub 2}(4,4’-bipy){sub 2}]{sub n} [Zn{sub 2}L{sub 2}(H{sub 2}O){sub 2}]{sub n}·2nH{sub 2}O (5), [Zn{sub 4}L{sub 4}(bpp){sub 2}]{sub n} (6), [ZnL(bbi){sub 0.5}]{sub n} (7), [ZnL(bpz)]{sub n} (8) (H{sub 2}L=4,4’-([1,2-phenylenebis-(methylene)]bis(oxy))dibenzoic acid, 2,2’-bipy =2,2’-bipyridine, phen =1,10-phenanthroline, 4,4’-bpy=4,4’-bipyridine, bpp =1,3-bis(4-pyridyl)propane, bbi=1,4-bis(imidazol-1-yl)butane, bpz=3,3′,5,5′-tetramethyl-4,4′-bipyrazole), have been hydrothermally synthesized and structurally characterized. 1–8 display various coordination motifs with different entangled forms and conformations due to the effect of the assistant N-donor ligands. The photoluminescent properties of compounds 1–8 in solid state were studied. Interestingly, 3 exhibits highly efficient luminescent sensing for Cu{sup 2+} cations and CrO{sub 4}{sup 2-} anions, as well as detection ability for the different organic solvents and nitro explosives. These results indicated that it could be utilized as a multi-responsive luminescent sensor. Furthermore, compound 3 also shows good chemical resistance to both acidity and alkalinity solutions with pH ranging from 2 to 13. Thus, multi-photofunctionality and fluorescent response to pH have been combined in the 3, which is the first example in the Zn-based hybrid materials. - Graphical abstract: Eight new Zn(II)-based coordination polymers constructed from a flexible V-shaped long bicarboxylic acid and different N-donor ligands have been hydrothermally synthesized through fixing the metal salts and the solvent systems. The photoluminescent properties of complexes 1−8 in solid state were studied. Interestingly, 3 exhibits highly efficient luminescent sensing for Cu{sup 2

  7. A family of entangled coordination polymers constructed from a flexible V-shaped long bicarboxylic acid and auxiliary N-donor ligands: Luminescent sensing

    International Nuclear Information System (INIS)

    Wang, Jun; Bai, Chao; Hu, Huai-Ming; Yuan, Fei; Xue, Gang-Lin

    2017-01-01

    Eight Zn(II)-based coordination polymers, namely, [Zn 2 L 2 (2,2’-bipy)] n ·nH 2 O (1), [Zn 2 L 2 (phen)] n ·nH 2 O (2), [ZnL(phen)(H 2 O)] n (3), [Zn 3 L 3 (4,4’-bipy)] n (4), [Zn 2 L 2 (4,4’-bipy) 2 ] n [Zn 2 L 2 (H 2 O) 2 ] n ·2nH 2 O (5), [Zn 4 L 4 (bpp) 2 ] n (6), [ZnL(bbi) 0.5 ] n (7), [ZnL(bpz)] n (8) (H 2 L=4,4’-([1,2-phenylenebis-(methylene)]bis(oxy))dibenzoic acid, 2,2’-bipy =2,2’-bipyridine, phen =1,10-phenanthroline, 4,4’-bpy=4,4’-bipyridine, bpp =1,3-bis(4-pyridyl)propane, bbi=1,4-bis(imidazol-1-yl)butane, bpz=3,3′,5,5′-tetramethyl-4,4′-bipyrazole), have been hydrothermally synthesized and structurally characterized. 1–8 display various coordination motifs with different entangled forms and conformations due to the effect of the assistant N-donor ligands. The photoluminescent properties of compounds 1–8 in solid state were studied. Interestingly, 3 exhibits highly efficient luminescent sensing for Cu 2+ cations and CrO 4 2- anions, as well as detection ability for the different organic solvents and nitro explosives. These results indicated that it could be utilized as a multi-responsive luminescent sensor. Furthermore, compound 3 also shows good chemical resistance to both acidity and alkalinity solutions with pH ranging from 2 to 13. Thus, multi-photofunctionality and fluorescent response to pH have been combined in the 3, which is the first example in the Zn-based hybrid materials. - Graphical abstract: Eight new Zn(II)-based coordination polymers constructed from a flexible V-shaped long bicarboxylic acid and different N-donor ligands have been hydrothermally synthesized through fixing the metal salts and the solvent systems. The photoluminescent properties of complexes 1−8 in solid state were studied. Interestingly, 3 exhibits highly efficient luminescent sensing for Cu 2+ cations and CrO 4 2- anions, as well as detection ability for the different organic solvents and nitro explosives, in which indicates it could be

  8. 'You sit in fear': understanding perceptions of nodding syndrome in post-conflict northern Uganda.

    Science.gov (United States)

    Buchmann, Kristine

    2014-01-01

    Nodding syndrome, a disabling epidemic epileptic encephalopathy, has affected an estimated 1,834 children in northern Uganda, with reports of as many as 3,000. Etiology is unknown and children are being treated symptomatically but inconsistently with anti-epileptic drugs. This qualitative study comprised 10 semi-structured interviews with caregivers of affected children and five focus group discussions with 23 participants; relatives, teachers, and religious leaders. Data collection and participant observation were carried out from July to September 2012 in Kitgum and Pader districts. The material was coded through inductive thematic analysis. Nodding syndrome has brought signs of discrimination in school admission procedures, founded in a fear of transmission. The suffering and loss caused by nodding syndrome is collective, and participants felt that nodding syndrome was viewed as a threat to the Acholi only, and that interventions had therefore been delayed. Multiple theories of causation exist, most commonly that the disease is caused by chemicals from bombs or that food aid distributed in IDP camps had expired or been poisoned.A feeling of uncertainty was present in all focus group discussions, fueled by the fact that results of investigations were not being shared with the communities. It was especially agonizing that CDC results had been given to the Ugandan government in 2010 but not to the public. The definitive fear is that the disease will be the end of the Acholi. This study provided insight into the perceptions of communities affected by an unknown emerging disease. Families of affected children are grieving not only their child's illness; it is a loss of social value and of lineage. The loss and suffering involved with nodding syndrome should be seen in the context of the wider suffering of a society disrupted by violent conflict. The memory of war is omnipresent and is also how nodding syndrome is understood.

  9. Type 1 diabetes in NOD mice unaffected by mast cell deficiency.

    Science.gov (United States)

    Gutierrez, Dario A; Fu, Wenxian; Schonefeldt, Susann; Feyerabend, Thorsten B; Ortiz-Lopez, Adriana; Lampi, Yulia; Liston, Adrian; Mathis, Diane; Rodewald, Hans-Reimer

    2014-11-01

    Mast cells have been invoked as important players in immune responses associated with autoimmune diseases. Based on in vitro studies, or in vivo through the use of Kit mutant mice, mast cells have been suggested to play immunological roles in direct antigen presentation to both CD4(+) and CD8(+) T cells, in the regulation of T-cell and dendritic cell migration to lymph nodes, and in Th1 versus Th2 polarization, all of which could significantly impact the immune response against self-antigens in autoimmune disease, including type 1 diabetes (T1D). Until now, the role of mast cells in the onset and incidence of T1D has only been indirectly tested through the use of low-specificity mast cell inhibitors and activators, and published studies reported contrasting results. Our three laboratories have generated independently two strains of mast cell-deficient nonobese diabetic (NOD) mice, NOD.Cpa3(Cre/+) (Heidelberg) and NOD.Kit(W-sh/W-sh) (Leuven and Boston), to address the effects of mast cell deficiency on the development of T1D in the NOD strain. Our collective data demonstrate that both incidence and progression of T1D in NOD mice are independent of mast cells. Moreover, analysis of pancreatic lymph node cells indicated that lack of mast cells has no discernible effect on the autoimmune response, which involves both innate and adaptive immune components. Our results demonstrate that mast cells are not involved in T1D in the NOD strain, making their role in this process nonessential and excluding them as potential therapeutic targets. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. Nd(III) and Dy(III) coordination compounds based on 1H-tetrazolate-5-acetic acid ligands: Synthesis, crystal structures and catalytic properties

    Energy Technology Data Exchange (ETDEWEB)

    Li Qiaoyun; Chen Dianyu; He Minghua [Jiangsu Laboratory of Advanced Functional Materials, Department of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu 215500, Jiangsu (China); Yang Gaowen, E-mail: ygwsx@126.com [Jiangsu Laboratory of Advanced Functional Materials, Department of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu 215500, Jiangsu (China); Shen Lei; Zhai Chun; Shen Wei; Gu Kun; Zhao Jingjing [Jiangsu Laboratory of Advanced Functional Materials, Department of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu 215500, Jiangsu (China)

    2012-06-15

    Reactions of 1H-tetrazolate-5-acetic acid(H{sub 2}tza) with Nd(NO{sub 3}){sub 3}{center_dot}6H{sub 2}O or Dy(NO{sub 3}){sub 3}{center_dot}6H{sub 2}O with the presence of KOH under solvothermal conditions, produced two new coordination compounds, [M{sub 2}(tza){sub 3}(H{sub 2}O){sub 6}]{center_dot}2H{sub 2}O [M=Nd(1), Dy(2)]. Both compounds were structurally characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. Compounds 1 and 2 reveal 1D structures via bridging tza as linker. Furthermore, the compounds 1 and 2 showed a specific and good catalytic behavior for the polymerization of styrene, and the polymerization showed controlled characteristics. - Graphical Abstract: Two new coordination compounds, [M{sub 2}(tza){sub 3}(H{sub 2}O){sub 6}]{center_dot}2H{sub 2}O [M=Nd(1), Dy(2)] have been synthesis. 1 and 2 reveal 1D structures via bridging tza as linker, and showed a specific and good catalytic behavior for the polymerization of styrene. Highlights: Black-Right-Pointing-Pointer we have reported two novel compounds formed by H{sub 2}tza and Nd(III) or Dy(III). Black-Right-Pointing-Pointer Compounds 1 and 2 were found to have catalysis property for the photo-polymerization of styrene. Black-Right-Pointing-Pointer The high molecular weight polymers with narrow molecular weight distributions were obtained.

  11. Poisson Coordinates.

    Science.gov (United States)

    Li, Xian-Ying; Hu, Shi-Min

    2013-02-01

    Harmonic functions are the critical points of a Dirichlet energy functional, the linear projections of conformal maps. They play an important role in computer graphics, particularly for gradient-domain image processing and shape-preserving geometric computation. We propose Poisson coordinates, a novel transfinite interpolation scheme based on the Poisson integral formula, as a rapid way to estimate a harmonic function on a certain domain with desired boundary values. Poisson coordinates are an extension of the Mean Value coordinates (MVCs) which inherit their linear precision, smoothness, and kernel positivity. We give explicit formulas for Poisson coordinates in both continuous and 2D discrete forms. Superior to MVCs, Poisson coordinates are proved to be pseudoharmonic (i.e., they reproduce harmonic functions on n-dimensional balls). Our experimental results show that Poisson coordinates have lower Dirichlet energies than MVCs on a number of typical 2D domains (particularly convex domains). As well as presenting a formula, our approach provides useful insights for further studies on coordinates-based interpolation and fast estimation of harmonic functions.

  12. Cd(II)-coordination polymers based on tetracarboxylic acid and diverse bis(imidazole) ligands: Synthesis, structural diversity and photoluminescence properties

    Energy Technology Data Exchange (ETDEWEB)

    Arıcı, Mürsel, E-mail: marici@ogu.edu.tr [Department of Chemistry, Faculty of Arts and Sciences, Eskişehir Osmangazi University, 26480 Eskişehir (Turkey); Yeşilel, Okan Zafer [Department of Chemistry, Faculty of Arts and Sciences, Eskişehir Osmangazi University, 26480 Eskişehir (Turkey); Taş, Murat [Department of Science Education, Education Faculty, Ondokuz Mayıs University, 55139 Samsun (Turkey)

    2017-01-15

    Three new Cd(II)-coordination polymers, namely, ([Cd{sub 2}(μ{sub 6}-ao{sub 2}btc)(μ-1,5-bipe){sub 2}]·2H{sub 2}O){sub n} (1), ([Cd{sub 2}(μ{sub 6}-ao{sub 2}btc)(μ-1,4-bix){sub 2}]{sub n}·2DMF) (2) and ([Cd{sub 2}(μ{sub 8}-abtc)(μ-1,4-betix)]·DMF·H{sub 2}O){sub n} (3) (ao{sub 2}btc=di-oxygenated form of 3,3′,5,5′-azobenzenetetracarboxylate, 1,5-bipe: 1,5-bis(imidazol-1yl)pentane, 1,4-bix=1,4-bis(imidazol-1ylmethyl)benzene, 1,4-betix=1,4-bis(2-ethylimidazol-1ylmethyl)benzene) were synthesized with 3,3′,5,5′-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1–3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the rare sqc27 topology. When semi-flexible substituted bis(imidazole) linker was used, 3D framework of complex 3 was obtained with the paddlewheel Cd{sub 2}(CO{sub 2}){sub 4}-type binuclear SBU. Moreover, thermal and photoluminescence properties of the complexes were determined in detailed. - Graphical abstract: In this study, three novel Cd(II)-coordination polymers were synthesized with 3,3′,5,5′-azobenzenetetracarboxylic acid and flexible, semi-flexible and semi-flexible substituted bis(imidazole) linkers. They were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction, powder X-ray diffractions (PXRD) and thermal analyses (TG/DTA). Complexes 1–3 exhibited structural diversities depending on flexible, semi-flexible and semi-flexible substituted bis(imidazole) ligands. Complex 1 was 2D structure with 3,6L18 topology. Complex 2 had a 3D pillar-layered framework with the rare sqc27 topology. When semi

  13. Expressão dos genes nodC, nodW e nopP em Bradyrhizobium japonicum estirpe CPAC 15 avaliada por RT-qPCR Expression of nodC, nodW and nopP genes in Bradyrhizobium japonicum CPAC 15 strain evaluated by RT-qPCR

    Directory of Open Access Journals (Sweden)

    Simone Bortolan

    2009-11-01

    Full Text Available O objetivo deste trabalho foi avaliar a expressão, por RT-qPCR, dos genes de nodulação nodC e nodW e do gene nopP da estirpe CPAC 15, que provavelmente atuam na infecção das raízes da soja. Foram realizados dois experimentos. No primeiro, a expressão dos genes foi avaliada nas células após a incubação com genisteína por 15 min, 1, 4 e 8 horas. Os resultados revelaram que os três genes apresentaram maior expressão imediatamente após o contato com o indutor (15 min. No segundo experimento, a bactéria foi cultivada na presença de indutores (genisteína ou exsudatos de sementes de soja por 48 horas. A expressão dos três genes foi maior na presença de genisteína, com valores de expressão para nodC, nodW e nopP superiores ao controle. Os resultados obtidos confirmam a funcionalidade dos três genes na estirpe CPAC 15, com ênfase para o nopP, cuja funcionalidade em Bradyrhizobium japonicum foi descrita pela primeira vez.The objective of this work was to evaluate, by RT-qPCR, the expression of the nodC and nodW nodulation genes and of the nopP gene of the CPAC 15 strain, which probably play a role in the infection of soybean roots. Two experiments were done. In the first, the gene expression was evaluated in cells after incubation with genistein for 15 min, 1, 4 and 8 hours. Results showed that the three genes showed higher expression immediately after contact with the inducer (15 min. In the second experiment, the bacterium was grown in the presence of inducers (genistein or soybean seed exudates for 48 hours. The expression of the three genes was greater when induced by genistein, and the expression of nodC, nodW and nopP had higher values than the control. The results confirm the functionality of the three genes in the CPAC 15 strain, with an emphasis on the nopP, whose functionality in Bradyrhizobium japonicum was described for the first time.

  14. Synthesis and characterization of new coordination polymer with l-proline amino acid ligand, new precursor for preparation of pure phase lead(II) oxide nanoparticles via thermal decomposition

    Czech Academy of Sciences Publication Activity Database

    Varzdar, S.; Hashemi, L.; Morsali, A.; Dušek, Michal

    2017-01-01

    Roč. 14, č. 11 (2017), s. 2255-2261 ISSN 1735-207X Institutional support: RVO:68378271 Keywords : coordination polymer * nanoparticle * lead(II) oxide * proline amino acid Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 1.407, year: 2016

  15. Seven new Zn(II)/Cd(II) coordination polymers with 2-(hydroxymethyl)-1H-benzo[d]imidazole-5-carboxylic acid: Synthesis, structures and properties

    Science.gov (United States)

    Wang, Xin-Fang; Zhou, Sheng-Bin; Du, Ceng-Ceng; Wang, Duo-Zhi; Jia, Dianzeng

    2017-08-01

    Using a new simi-rigid multitopic ligand 2-(hydroxymethyl)-1H-benzo[d]imidazole-5-carboxylic acid (H2L), seven new coordination polymers [Zn3(L)2(μ2-OH)2]n (1), {[Zn2(HL)2(H2O)2]·SiF6}n (2), [Zn(HL)(SCN)]n (3), {[Zn2(HL)2(SO4)]·(4,4‧-bpy)}n (4) [4,4‧-bpy =4,4‧-bipyridine], {[Zn(HL)2]·2H2O}n (5), {[Cd(HL)2]·2H2O}n (6) and [Cd2(HL)2(H2O)2(SO4)]n (7) have been successfully obtained from H2L ligand under solvothermal conditions and structurally characterized by single-crystal X-ray diffraction, elemental analysis, thermogravimetric analysis, powder X-ray diffraction and IR spectroscopy. In addition, UV-vis diffuse-reflectance spectra demonstrate wide band gaps. Complex 1 features a 3D topological net of {412·63} with the stoichiometry (6-c), contains 1D channels with the accessible solvent volume of 42.1%. 3, 4, 5 and 6 have a 1D chain structure, 5 and 6 further assemble to form 2D sheet and 3D supramolecular frameworks by hydrogen-bonding interactions, respectively. Complexes 2 and 7 possess a 2D layered structure, and the 2D supramolecular network of 2 can be rationalized to be four-connected {44·62} topological sql network with the dinuclear units, while 7 shows a 3-nodal 2D net with a point symbol of {63}. Moreover, the fluorescent emission, fluorescence lifetimes of 1-7 have been investigated and discussed. Interesting enough, complex 1 showed high efficiency for catalyzing the Knoevenagel condensation reaction between 4-substituted aromatic aldehydes and malononitrile as selective heterogeneous catalyst. The CPs combining catalytic and fluorescent properties could further meet the requirement as a multifunctional material. Seven new Zn(II)/Cd(II) coordination polymers with simi-rigid multitopic ligand, [(2-(hydroxymethyl)-1H-benzo[d]imidazole-5-carboxylic acid) (H2L)] have been successfully obtained and structurally characterized by single-crystal X-ray diffraction, elemental analysis, thermogravimetric analysis, powder X-ray diffraction and IR

  16. Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose Concentrations In Vitro and in Islets Transplanted to Diabetic NOD Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Eva Ludvigsen

    2011-01-01

    Full Text Available Somatostatin acts via five receptors (sst1-5. We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

  17. Creation of Optically Pure Crystals from a Meso-Type Gold(I) Metalloligand with d- and l-Amino Acids: A Coordination Trick.

    Science.gov (United States)

    Itai, Takuma; Kojima, Tatsuhiro; Kuwamura, Naoto; Konno, Takumi

    2017-11-21

    A unique example of a coordination system that creates optically pure crystals from a meso compound with d- and l-amino acids is reported. The 1:1 reaction of a newly prepared meso digold(I) complex, [Au 2 (dcpe)(d-Hpen)(l-Hpen)] ([H 2 1]), with Co(OAc) 2 under aerobic conditions yielded a cationic Au I 2 Co III trinuclear complex, [Au 2 Co(dcpe)(d-pen)(l-pen)] + [2] + , in which [1] 2- acts as a hexadentate-N 2 ,O 2 ,S 2 metalloligand to a Co III center. Similar reactions with M(OAc) 2 (M=Ni and Zn) produced analogous but neutral Au I 2 M II complexes, [Au 2 M(dcpe)(d-pen)(l-pen)] ([3 M ]). Complexes [2] + and [3 M ] are chiral (C vs. A) at the octahedral Co III and M II centers due to the arrangement of the N 2 ,O 2 ,S 2 donor set. In addition, through spontaneous resolution, [3 M ] gave optically pure C-[3 M ] and A-[3 M ] crystals, showing the creation of homochirality from meso-[1] 2- and achiral M 2+ through crystallization. Such a phenomenon was not observed for [2] + , which gave a racemic compound containing both C-[2] + and A-[2] + . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Vibrational spectroscopic investigation and normal coordinate analysis of the fibrate hypolipidemic agent 5-(2,5-dimethylphenoxy)-2,2-dimethyl pentanoic acid (Gemfibrozil)

    Science.gov (United States)

    Priya, M. Siva; Benitta, T. Asenath; James, C.

    2011-03-01

    Colorless crystals of 5-(2,5-dimethylphenoxy)-2,2-dimethyl pentanoic acid were grown by slow evaporation method and the FT-IR and FT-Raman spectra of the sample were recorded in the region 4000-450 cm -1 and 4000-50 cm -1 respectively. Molecular structure is optimized with the help of B3LYP/6-31G (d) density functional theory method. Stability of the molecule arising from hyperconjugation and charge delocalization is confirmed by the natural bond orbital analysis (NBO). The results show that electron density (ED) in the σ ∗ antibonding orbitals and E (2) energies confirms the occurrence of intra-molecular charge transfer (ICT) within the molecule. The assignments of the vibrational spectra have been carried out with the help of Normal coordinate analysis following the scaled quantum mechanical force field (SQMFF) methodology. Mulliken population analysis on atomic charges is also calculated. The calculated HOMO and LUMO energy gap shows that charge transfer occurs within the molecule.

  19. Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice.

    Science.gov (United States)

    Yu, Shiguang; Sharp, Gordon C; Braley-Mullen, Helen

    2006-01-01

    The role of inflammatory cells in thyroid epithelial cell (thyrocyte) hyperplasia is unknown. Here, we demonstrate that thyrocyte hyperplasia in IFN-gamma-/- NOD.H-2h4 mice has an autoimmune basis. After chronic exposure to increased dietary iodine, 60% of IFN-gamma-/- mice had severe thyrocyte hyperplasia with minimal or moderate lymphocyte infiltration, and thyroid dysfunction with reduced serum T4. All mice produced anti-thyroglobulin autoantibody. Some wild-type NOD.H-2h4 mice had isolated areas of thyrocyte hyperplasia with predominantly lymphocytic infiltration, whereas IL-4-/- and 50% of wild-type NOD.H-2h4 mice developed lymphocytic thyroiditis but no thyrocyte hyperplasia. Both thyroid infiltrating inflammatory cells and environmental factors (iodine) were required to induce thyrocyte hyperplasia. Splenocytes from IFN-gamma-/- mice with thyrocyte hyperplasia, but not splenocytes from naïve IFN-gamma-/- mice, induced hyperplasia in IFN-gamma-/- NOD.H-2h4.SCID mice. These results may provide clues for understanding the mechanisms underlying development of epithelial cell hyperplasia not only in thyroids but also in other tissues and organs.

  20. Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.

    Science.gov (United States)

    Canning, Peter; Ruan, Qui; Schwerd, Tobias; Hrdinka, Matous; Maki, Jenny L; Saleh, Danish; Suebsuwong, Chalada; Ray, Soumya; Brennan, Paul E; Cuny, Gregory D; Uhlig, Holm H; Gyrd-Hansen, Mads; Degterev, Alexei; Bullock, Alex N

    2015-09-17

    RIPK2 mediates pro-inflammatory signaling from the bacterial sensors NOD1 and NOD2, and is an emerging therapeutic target in autoimmune and inflammatory diseases. We observed that cellular RIPK2 can be potently inhibited by type II inhibitors that displace the kinase activation segment, whereas ATP-competitive type I inhibition was only poorly effective. The most potent RIPK2 inhibitors were the US Food and Drug Administration-approved drugs ponatinib and regorafenib. Their mechanism of action was independent of NOD2 interaction and involved loss of downstream kinase activation as evidenced by lack of RIPK2 autophosphorylation. Notably, these molecules also blocked RIPK2 ubiquitination and, consequently, inflammatory nuclear factor κB signaling. In monocytes, the inhibitors selectively blocked NOD-dependent tumor necrosis factor production without affecting lipopolysaccharide-dependent pathways. We also determined the first crystal structure of RIPK2 bound to ponatinib, and identified an allosteric site for inhibitor development. These results highlight the potential for type II inhibitors to treat indications of RIPK2 activation as well as inflammation-associated cancers. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Prior Knowledge Facilitates Mutual Gaze Convergence and Head Nodding Synchrony in Face-to-face Communication.

    Science.gov (United States)

    Thepsoonthorn, C; Yokozuka, T; Miura, S; Ogawa, K; Miyake, Y

    2016-12-02

    As prior knowledge is claimed to be an essential key to achieve effective education, we are interested in exploring whether prior knowledge enhances communication effectiveness. To demonstrate the effects of prior knowledge, mutual gaze convergence and head nodding synchrony are observed as indicators of communication effectiveness. We conducted an experiment on lecture task between lecturer and student under 2 conditions: prior knowledge and non-prior knowledge. The students in prior knowledge condition were provided the basic information about the lecture content and were assessed their understanding by the experimenter before starting the lecture while the students in non-prior knowledge had none. The result shows that the interaction in prior knowledge condition establishes significantly higher mutual gaze convergence (t(15.03) = 6.72, p < 0.0001; α = 0.05, n = 20) and head nodding synchrony (t(16.67) = 1.83, p = 0.04; α = 0.05, n = 19) compared to non-prior knowledge condition. This study reveals that prior knowledge facilitates mutual gaze convergence and head nodding synchrony. Furthermore, the interaction with and without prior knowledge can be evaluated by measuring or observing mutual gaze convergence and head nodding synchrony.

  2. Nodding syndrome in Kitgum District, Uganda: association with conflict and internal displacement.

    Science.gov (United States)

    Landis, Jesa L; Palmer, Valerie S; Spencer, Peter S

    2014-11-04

    To test for any temporal association of Nodding syndrome with wartime conflict, casualties and household displacement in Kitgum District, northern Uganda. Data were obtained from publicly available information reported by the Ugandan Ministry of Health (MOH), the Armed Conflict Location & Event Data (ACLED) Project of the University of Sussex in the UK, peer-reviewed publications in professional journals and other sources. Reports of Nodding syndrome began to appear in 1997, with the first recorded cases in Kitgum District in 1998. Cases rapidly increased annually beginning in 2001, with peaks in 2003-2005 and 2008, 5-6 years after peaks in the number of wartime conflicts and deaths. Additionally, peaks of Nodding syndrome cases followed peak influxes 5-7 years earlier of households into internal displacement camps. Peaks of Nodding syndrome reported by the MOH are associated with, but temporally displaced from, peaks of wartime conflicts, deaths and household internment, where infectious disease was rampant and food insecurity rife. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. "But Everything Is against Us Here": Some Thoughts on Noddings and on Exposing Our Educational Present

    Science.gov (United States)

    Ramaekers, Stefan

    2013-01-01

    Noddings's radical choice for a particular stance in life is both what makes "Happiness and Education" a thought-provoking book and what also leads me to have some reservations. First, I briefly outline some of these reservations and focus on what I think are two important difficulties "Happiness and Education" faces:…

  4. NOD mouse model for Sjögren's syndrome: lack of longitudinal stability

    NARCIS (Netherlands)

    Lodde, B. M.; Mineshiba, F.; Kok, M. R.; Wang, J.; Zheng, C.; Schmidt, M.; Cotrim, A. P.; Kriete, M.; Tak, P. P.; Baum, B. J.

    2006-01-01

    OBJECTIVES: The non-obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjögren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno-associated

  5. Genotyping for NOD2 genetic variants and crohn disease: a metaanalysis

    DEFF Research Database (Denmark)

    Yazdanyar, Shiva; Weischer, Maren; Nordestgaard, Børge

    2009-01-01

    BACKGROUND: Arg702Trp, Gly908Arg, and Leu1007fsinsC variants of the NOD2 gene (nucleotide-binding oligomerization domain containing 2; alias, CARD15) influence the risk of Crohn disease. METHODS: We conducted a systematic review to examine whether Arg702Trp, Gly908Arg, and Leu1007fsinsC are equally...

  6. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis...

  7. For Whom the Bell Tolls (and Nods): Spit-acular Saliva

    Czech Academy of Sciences Publication Activity Database

    Shaw, D.K.; Kotsyfakis, Michalis; Pedra, J. H. F.

    2016-01-01

    Roč. 3, č. 2 (2016), s. 40-50 E-ISSN 2196-3045 Institutional support: RVO:60077344 Keywords : tick-borne diseases * tick saliva * innate immune signaling * toll-like receptor (TLR) * nod-like receptor (NLR) Subject RIV: EC - Immunology

  8. Effect of early-life gut mucosal compromise on disease progression in NOD mice

    DEFF Research Database (Denmark)

    Bendtsen, Katja M.; Hansen, Camilla HF; Krych, Lukasz

    2017-01-01

    Disease expression in spontaneous nonobese diabetic (NOD) mice depends on environmental stimuli such as stress, diet, and gut microbiota composition. We evaluated a brief, early-life gut intervention in which pups were weaned to low-dose dextran sulfate sodium (DSS). We hypothesized that the mucus...

  9. A Nod to disease vectors: mitigation of pathogen sensing by arthropod saliva

    Czech Academy of Sciences Publication Activity Database

    Sakhon, O. S.; Severo, M. S.; Kotsyfakis, Michalis; Pedra, J. H. F.

    2013-01-01

    Roč. 4, OCT 2013 (2013), a308 ISSN 1664-302X Institutional support: RVO:60077344 Keywords : nod-like receptors * inflammasome * vector-borne pathogens * vector-borne diseases * arthropod saliva * salivary proteins Subject RIV: EC - Immunology Impact factor: 3.941, year: 2013

  10. An exploration of caregiver burden for children with nodding syndrome (lucluc) in Northern Uganda.

    Science.gov (United States)

    Nakigudde, Janet; Mutamba, Byamah Brian; Bazeyo, William; Musisi, Seggane; James, Okello

    2016-07-22

    Caregivers of patients with chronic illnesses are often uncompensated for work that is physically demanding, time consuming and emotionally and economically draining. This is particularly true for caregivers of children with nodding syndrome, an emergent neurological disorder of unknown etiology in resource poor settings in Africa. We aimed to explore perceptions of caregivers regarding challenges that a typical caregiver faces when caring for a child with nodding syndrome. We used a qualitative exploratory study design with focus group discussions and in-depth interviews to collect data. We analyzed data using the qualitative analysis software package of NVivo and thematic query building. Emergent themes centered on burden of care with emotional agony as the most prominent. Subthemes reflecting the burden of care giving included child and caregiver safety concerns, burnout, social isolation and rejection, and homicidal ideation. Caregivers also complained of physical and financial constraints associated with the care of children with nodding syndrome. The findings point to a high burden of care for caregivers of children with nodding syndrome and suggests the need to incorporate community-based psychosocial and mental health care services for the caregivers of affected children into the national health system response.

  11. Prevention of early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    Czech Academy of Sciences Publication Activity Database

    Funda, David P.; Fundová, Petra; Hansen, A. K.; Buschard, K.

    2014-01-01

    Roč. 9, č. 4 (2014) E-ISSN 1932-6203 R&D Projects: GA ČR GA310/09/1640; GA MZd(CZ) NS10340 Institutional support: RVO:61388971 Keywords : gliadin * diabetes * diabetes 1 type * NOD mice Subject RIV: EC - Immunology Impact factor: 3.234, year: 2014

  12. MRI findings in people with epilepsy and nodding syndrome in an ...

    African Journals Online (AJOL)

    Background: Onchocerciasis has been implicated in the pathogenesis of epilepsy. The debate on a potential causal relationship between Onchocerca volvulus and epilepsy has taken a new direction in the light of the most recent epidemic of nodding syndrome. Objective: To document MRI changes in people with different ...

  13. The NOD2 Single Nucleotide Polymorphism rs72796353 (IVS4+10 A>C) Is a Predictor for Perianal Fistulas in Patients with Crohn's Disease in the Absence of Other NOD2 Mutations.

    Science.gov (United States)

    Schnitzler, Fabian; Friedrich, Matthias; Wolf, Christiane; Stallhofer, Johannes; Angelberger, Marianne; Diegelmann, Julia; Olszak, Torsten; Tillack, Cornelia; Beigel, Florian; Göke, Burkhard; Glas, Jürgen; Lohse, Peter; Brand, Stephan

    2015-01-01

    A previous study suggested an association of the single nucleotide polymorphism (SNP) rs72796353 (IVS4+10 A>C) in the NOD2 gene with susceptibility to Crohn's disease (CD). However, this finding has not been confirmed. Given that NOD2 variants still represent the most important predictors for CD susceptibility and phenotype, we evaluated the association of rs72796353 with inflammatory bowel disease (IBD) susceptibility and the IBD phenotype. Genomic DNA from 2256 Caucasians, including 1073 CD patients, 464 patients with ulcerative colitis (UC), and 719 healthy controls, was genotyped for the NOD2 SNP rs72796353 and the three main CD-associated NOD2 mutations rs2066844, rs2066845, and rs2066847. Subsequently, IBD association and genotype-phenotype analyses were conducted. In contrast to the strong associations of the NOD2 SNPs rs2066844 (p=3.51 x 10(-3)), rs2066845 (p=1.54 x 10(-2)), and rs2066847 (p=1.61 x 10(-20)) with CD susceptibility, no significant association of rs72796353 with CD or UC susceptibility was found. However, in CD patients without the three main CD-associated NOD2 mutations, rs72796353 was significantly associated with the development of perianal fistulas (p=2.78 x 10(-7), OR 5.27, [95% CI 2.75-10.12] vs. NOD2 wild-type carriers). Currently, this study represents the largest genotype-phenotype analysis of the impact of the NOD2 variant rs72796353 on the disease phenotype in IBD. Our data demonstrate that in CD patients the IVS4+10 A>C variant is strongly associated with the development of perianal fistulas. This association is particularly pronounced in patients who are not carriers of the three main CD-associated NOD2 mutations, suggesting rs72796353 as additional genetic marker for the CD disease behaviour.

  14. Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

    International Nuclear Information System (INIS)

    Lee, Y.S.; Kim, D.; Lee, E.K.; Kim, S.; Choi, C.S.; Jun, H.S.

    2015-01-01

    Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

  15. Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.S.; Kim, D.; Lee, E.K. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Kim, S. [Komipharm International Co. Ltd., 3188, Seongnam-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-827 (Korea, Republic of); Choi, C.S. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Endocrinology, Internal Medicine, Gachon University Gil Medical Center, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Jun, H.S., E-mail: hsjun@gachon.ac.kr [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of)

    2015-04-15

    Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

  16. Insights into the diversity of NOD-like receptors: Identification and expression analysis of NLRC3, NLRC5 and NLRX1 in rainbow trout.

    Science.gov (United States)

    Álvarez, Claudio A; Ramírez-Cepeda, Felipe; Santana, Paula; Torres, Elisa; Cortés, Jimena; Guzmán, Fanny; Schmitt, Paulina; Mercado, Luis

    2017-07-01

    Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are efficient soluble intracellular sensors that activate defense mechanisms against pathogens. In teleost fish, the involvement of NLRs in the immune response is not well understood. However, recent work has evidenced the expression of different NLRs in response to some pathogen associated molecular patterns (PAMPs). In the present work, the cDNA sequence encoding three new NOD-like receptors were identified in Oncorhynchus mykiss, namely OmNLRC3, OmNLRC5 and OmNLRX1. Results showed that their sequences coded for proteins of 1135, 836 and 1010 amino acids, respectively. The deduced protein sequences of all receptors showed characteristic domains of this receptor family, such as leucine rich repeats and NACHT domain. Phylogenetic analysis revealed a high degree of identity with other NOD-like receptors and they are clustered into different families. Transcript expression analysis indicated that OmNLRs are constitutively expressed in liver, spleen, intestine, gill, skin and brain. OmNLR expression was upregulated in kidney and gills from rainbow trout in response to LPS. In order to give new insights into the function of these new NLR members, an in vitro model of immune stimulation was established using the rainbow trout cell line RTgill-W1. Expression analysis revealed that RTgill-W1 overexpressed proinflammatory cytokines in response to LPS and poly I:C alongside with a differential overexpression of OmNLRC3, OmNLRC5 and OmNLRX1. The expression of OmNLRC5 was further verified at the protein level by immunofluorescence. Finally, the effect of the overexpressed cytokines on the OmNLR expression by RTgill-W1 cells was assessed, suggesting a regulatory mechanism on OmNLRC3 expression. Overall, results suggest that O. mykiss NOD-like receptors could play a key role in the defense mechanisms of teleost through PAMP recognition. Future studies will focus on gills which could be related with a key

  17. Direct bacterial killing in vitro by recombinant Nod2 is compromised by Crohn's disease-associated mutations.

    Directory of Open Access Journals (Sweden)

    Laurent-Herve Perez

    2010-06-01

    Full Text Available A homeostatic relationship with the intestinal microflora is increasingly appreciated as essential for human health and wellbeing. Mutations in the leucine-rich repeat (LRR domain of Nod2, a bacterial recognition protein, are associated with development of the inflammatory bowel disorder, Crohn's disease. We investigated the molecular mechanisms underlying disruption of intestinal symbiosis in patients carrying Nod2 mutations.In this study, using purified recombinant LRR domains, we demonstrate that Nod2 is a direct antimicrobial agent and this activity is generally deficient in proteins carrying Crohn's-associated mutations. Wild-type, but not Crohn's-associated, Nod2 LRR domains directly interacted with bacteria in vitro, altered their metabolism and disrupted the integrity of the plasma membrane. Antibiotic activity was also expressed by the LRR domains of Nod1 and other pattern recognition receptors suggesting that the LRR domain is a conserved anti-microbial motif supporting innate cellular immunity.The lack of anti-bacterial activity demonstrated with Crohn's-associated Nod2 mutations in vitro, supports the hypothesis that a deficiency in direct bacterial killing contributes to the association of Nod2 polymorphisms with the disease.

  18. Two new coordination polymers constructed by naphthalene-1,4-dicarboxylic acid and 2,4-diamino-6-methyl-triazine

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yamin, E-mail: liyamin@henu.edu.cn [Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004 (China); Xiao, Changyu [Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004 (China); Zhang, Xudong [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Xu, Yanhui [Department of Medical Imaging, Bethune Medical Non-Commissioned Officer' s, College, Shijiazhuang, Hebei 050081 (China); Li, Junrui; Lun, Huijie; Chen, Qi [Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004 (China)

    2013-08-15

    Two new transition metal coordination complexes, ([MnO(nda)](H{sub 2}dmt)(H{sub 2}O)){sub n} (1), [Ag{sub 5}(nda){sub 2.5}(dmt)]{sub n} (2), (H{sub 2}nda=naphthalene-1,4-dicarboxylic acid, dmt=2,4-diamine-6-methyl-1,3,5-triazine) have been hydrothermally synthesized by the reactions of H{sub 2}nda and dmt with the homologous MnCl{sub 2}·4H{sub 2}O and AgNO{sub 3}, respectively, and characterized by single-crystal X-ray diffraction, IR spectra, elemental analysis, thermogravimetric analysis (TGA). The compound 1 exhibits a 3D network comprising 1D metal chain (MnO(CO{sub 2}){sub 2}){sub n} connected by the ligand nda{sup 2−}, featuring a four-connected uninodal diamond -like topology. In compound 2, it is firstly observed that decanuclear silver units as secondary building units to construct 3D network by the ligands dmt and nda{sup 2−}, with a rare 2-nodal (3,8)-connected tfz-d topology ((4{sup 3}){sub 2}(4{sup 6}.6{sup 18}.8{sup 4})). The interactions within each Mn(II)—Mn(II) pair of compound 1 are antiferromagnetic (g=2.07, J=−1.42(1) cm{sup −1}, zj′=−0.73(2) cm{sup −1}). In addition, compound 2 exhibits photoluminescent property at about 472 nm (λ{sub ex}=394 nm). - Graphical abstract: Two new transition metal coordination complexes 1–2 have been hydrothermally synthesized and characterized by single-crystal X-ray diffraction, IR spectra, elemental analysis thermogravimetric analysis (TGA). Highlights: • The compound 1 exhibits a 3D network with four-connected uninodal diamond-like topology. • The first 3D network of 2 with a rare tfz-d topology consists of decanuclear silver clusters as secondary building units. • The magnetic measurement indicates the compound 1 shows antiferromagnetic interactions. • The photoluminescent property of 2 has been measured.

  19. Coordination cycles

    Czech Academy of Sciences Publication Activity Database

    Steiner, Jakub

    -, č. 274 (2005), s. 1-26 ISSN 1211-3298 Institutional research plan: CEZ:AV0Z70850503 Keywords : coordination * crises * cycles and fluctuations Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp274.pdf

  20. Coordination cycles

    Czech Academy of Sciences Publication Activity Database

    Steiner, Jakub

    2008-01-01

    Roč. 63, č. 1 (2008), s. 308-327 ISSN 0899-8256 Institutional research plan: CEZ:AV0Z70850503 Keywords : global games * coordination * crises * cycles and fluctuations Subject RIV: AH - Economics Impact factor: 1.333, year: 2008

  1. Synthesis, characterization and metal coordination of a potential β-lactamase inhibitor: 5-Methyl-2-phenoxymethyl-3-H-imidazole-4-carboxylic acid (PIMA

    Directory of Open Access Journals (Sweden)

    Chiara Romagnoli

    2017-12-01

    Full Text Available Among relevant metal ions in biological systems, zinc and iron play a key role as active partners of the catalytic machinery. In particular, the inhibition of metal enzymes that are involved in physiological and pathological processes has been deeply investigated for the rational design of selective and efficient drugs based on chelators. Since imidazole histidine residue is one of the most versatile sites in proteins, especially in enzymes acting in the presence of metal ions as cofactors, in this work the synthesis and characterization of a new imidazole derivative, namely 5-methyl-2-phenoxymethyl-3-H-imidazole-4-carboxylic acid (PIMA is reported. PIMA was designed as metallo-β-lactamase inhibitor thanks to its similarity with penicillin V, a β-lactam antibiotic inactivated by metallo-β-lactamase, for which there are no commercially available inhibitors. The evaluation of PIMA coordinating ability toward iron, zinc, and gallium, these latter selected as a non-paramagnetic probe for iron, is performed by theoretical DFT calculations and in solution by experimental techniques, i.e. potentiometry, UV–vis and NMR spectroscopy. PIMA exhibits an efficient metal chelating ability; the prevailing species in physiological condition are ML3 for Fe3+ and Ga3+ and ML2 for Zn2+, in which chelation is due to deprotonated carboxylic oxygen and imidazole nitrogen in the N,O donor set. The demonstrated ability of PIMA to chelate zinc ion, combined with its structure similarity with penicillin V, supports further exploration of this imidazole-4-carboxylate as metallo-β-lactamase inhibitor.

  2. Three two-dimensional coordination polymers constructed from transition metals and 2,3-norbornanedicarboxylic acid: Hydrothermal synthesis, crystal structures and photocatalytic properties

    Science.gov (United States)

    Zhang, Jia; Wang, Chong-Chen

    2017-02-01

    Three novel coordination polymers based on transition metals like Co(II), Cu(II) and Mn(II), namely [Co2(bpy)2(nbda)2(H2O)2]·2H2O (denoted as BUC-1), [Cu2(bpy)2(nbda)2(H2O)2]·2H2O (BUC-2), [Mn2(bpy)2(nbda)2(H2O)2]·2H2O (BUC-3), (where bpy = 4,4‧-bipyridine, H2nbda = 2,3-norbornanedicarboxylic acid, BUC = Beijing University of Civil Engineering and Architecture), were synthesized under hydrothermal conditions, and characterized by CNH elemental analyses (EA), Fourier Transform infrared spectroscopy (FTIR), and single crystal X-ray diffraction (SCXRD). BUC 1-3 were isostructural and crystallized in the monoclinic space group C2/c, in which the corresponding metal atoms were linked by typical bidentate bpy ligands into two adjacent 1D [M1(bpy)]n2n+ and [M2(bpy)]n2n+ (M = Co(II), Cu(II), Mn(II)), further joined by versatile nbda2- ligands into 2D [M2(bpy)2(nbda)2]n sheets. Finally, three-dimensional supramolecular frameworks were constructed with the aid of the intermolecular hydrogen bonding interactions. BUC 1-3 exhibited different photocatalytic degradation ability to decompose methylene blue (MB) and methyl orange (MO) under UV light irradiation. Additionally, a possible photocatalytic mechanism HOMO-LUMO was proposed and discussed, which was further confirmed by radicals trapping experiments using isopropanol as radical scavenger.

  3. Synthesis, Structure and Properties of Two Novel 2D Zinc(II) Coordination Polymers based on Fluconazole and Benzene Carboxylic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Ganghong; Tang, Jingniu; Xu, Wenjia; Liang, Peng; Huang, Zhongjing [Guangxi University for Nationalities, Nanning (China)

    2013-12-15

    The design and synthesis of coordination polymers have aroused great interest owing to their intriguing aesthetic structures and potential applications in nonlinear optics, gas storage, ion exchange, luminescence, magnetism and catalysis. Self-assembly of bridging organic ligands (connectors) and multi-connected metal ions can give rise to various types of interesting coordination polymers. Since metal ion Zn(II) with d{sup 10} electronic configuration permits a variety of coordination numbers and geometries which are not dependent on ligand field stabilization but on ligand size and charge, it is well suited for the construction of various coordination polymers. Its borderline hardness allows the coordination of N, O and S donor atoms.

  4. Lactase persistence, NOD2 status and Mycobacterium avium subsp. paratuberculosis infection associations to Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Elguezabal Natalia

    2012-06-01

    Full Text Available Abstract Background Inflammatory Bowel Disease (IBD, which includes both Crohn’s disease (CD and ulcerative colitis (UC, is caused by a complex interplay involving genetic predisposition, environmental factors and an infectious agent. Mycobacterium avium subsp. paratuberculosis (MAP is a promising pathogen candidate since it produces a chronic intestinal inflammatory disease in ruminants that resembles CD in humans. MAP is a ubiquitous microorganism, although its presence in the food chain, especially in milk from infected animals, is what made us think that there could be an association between lactase persistence (LP and IBD. The LCT mutation has brought adaptation to dairy farming which in turn would have increased exposure of the population to infection by MAP. NOD2 gene mutations are highly associated to CD. Methods In our study, CD and UC patients and controls from the North of Spain were genotyped for the lactase gene (LCT and for three NOD-2 variants, R702W, G908R and Cins1007fs. MAP PCR was carried out in order to assess MAP infection status and these results were correlated with LCT and NOD2 genotypes. Results As for LP, no association was found with IBD, although UC patients were less likely to present the T/T−13910 variant compared to controls, showing a higher C-allele frequency and a tendency to lactase non-persistence (LNP. NOD2 mutations were associated to CD being the per-allele risk higher for the Cins1007fs variant. MAP infection was more extended among the healthy controls (45.2% compared to CD patients (21.38% and UC patients (19.04% and this was attributed to therapy. The Asturian CD cohort presented higher levels of MAP prevalence (38.6% compared to the Basque CD cohort (15.5%, differences also attributed to therapy. No interaction was found between MAP infection and LCT or NOD2 status. Conclusions We conclude that LP is not significantly associated with IBD, but that MAP infection and NOD2 do show not mutually

  5. Rhizobia with 16S rRNA and nifH similar to Mesorhizobium huakuii but Novel recA, glnII, nodA and nodC genes are symbionts of New Zealand Carmichaelinae.

    Directory of Open Access Journals (Sweden)

    Heng Wee Tan

    Full Text Available New Zealand became geographically isolated about 80 million years ago and this separation gave rise to a unique native flora including four genera of legume, Carmichaelia, Clianthus and Montigena in the Carmichaelinae clade, tribe Galegeae, and Sophora, tribe Sophoreae, sub-family Papilionoideae. Ten bacterial strains isolated from NZ Carmichaelinae growing in natural ecosystems grouped close to the Mesorhizobium huakuii type strain in relation to their 16S rRNA and nifH gene sequences. However, the ten strains separated into four groups on the basis of their recA and glnII sequences: all groups were clearly distinct from all Mesorhizobium type strains. The ten strains separated into two groups on the basis of their nodA sequences but grouped closely together in relation to nodC sequences; all nodA and nodC sequences were novel. Seven strains selected and the M. huakuii type strain (isolated from Astragalus sinicus produced functional nodules on Carmichaelia spp., Clianthus puniceus and A. sinicus but did not nodulate two Sophora species. We conclude that rhizobia closely related to M. huakuii on the basis of 16S rRNA and nifH gene sequences, but with variable recA and glnII genes and novel nodA and nodC genes, are common symbionts of NZ Carmichaelinae.

  6. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball

    Overview From a technical perspective, CMS has been in “beam operation” state since 6th November. The detector is fully closed with all components operational and the magnetic field is normally at the nominal 3.8T. The UXC cavern is normally closed with the radiation veto set. Access to UXC is now only possible during downtimes of LHC. Such accesses must be carefully planned, documented and carried out in agreement with CMS Technical Coordination, Experimental Area Management, LHC programme coordination and the CCC. Material flow in and out of UXC is now strictly controlled. Access to USC remains possible at any time, although, for safety reasons, it is necessary to register with the shift crew in the control room before going down.It is obligatory for all material leaving UXC to pass through the underground buffer zone for RP scanning, database entry and appropriate labeling for traceability. Technical coordination (notably Stephane Bally and Christoph Schaefer), the shift crew and run ...

  7. Four coordination polymers based on 5-tert-butyl isophthalic acid and rigid bis(imidazol-1yl)benzene linkers: Synthesis, luminescence detection of acetone and optical properties

    International Nuclear Information System (INIS)

    Arıcı, Mürsel; Zafer Yeşilel, Okan; Büyükgüngör, Orhan

    2017-01-01

    detection of acetone. Moreover, thermal and optical properties of the complexes were also studied. - Highlights: • Four new 2D and 3D coordination polymers with 5-tert-butyl isophthalic acid and rigid bis(imidazol-1yl)benzene linkers. • The structural diversity depending on ligands and coordination number of metal centers. • Fluorescent sensor for the detection of acetone.

  8. Four coordination polymers based on 5-tert-butyl isophthalic acid and rigid bis(imidazol-1yl)benzene linkers: Synthesis, luminescence detection of acetone and optical properties

    Energy Technology Data Exchange (ETDEWEB)

    Arıcı, Mürsel, E-mail: marici@ogu.edu.tr [Department of Chemistry, Faculty of Arts and Sciences, Eskişehir Osmangazi University, 26480 Eskişehir (Turkey); Zafer Yeşilel, Okan [Department of Chemistry, Faculty of Arts and Sciences, Eskişehir Osmangazi University, 26480 Eskişehir (Turkey); Büyükgüngör, Orhan [Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University, 55139 Samsun (Turkey)

    2017-05-15

    methanol could be used as a fluorescent sensor for the detection of acetone. Moreover, thermal and optical properties of the complexes were also studied. - Highlights: • Four new 2D and 3D coordination polymers with 5-tert-butyl isophthalic acid and rigid bis(imidazol-1yl)benzene linkers. • The structural diversity depending on ligands and coordination number of metal centers. • Fluorescent sensor for the detection of acetone.

  9. A cluster of coregulated genes determines TGF-β–induced regulatory T-cell (Treg) dysfunction in NOD mice

    Science.gov (United States)

    D'Alise, Anna Morena; Ergun, Ayla; Hill, Jonathan A.; Mathis, Diane; Benoist, Christophe

    2011-01-01

    Foxp3+ regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4+ T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility. PMID:21543717

  10. A cluster of coregulated genes determines TGF-beta-induced regulatory T-cell (Treg) dysfunction in NOD mice.

    Science.gov (United States)

    D'Alise, Anna Morena; Ergun, Ayla; Hill, Jonathan A; Mathis, Diane; Benoist, Christophe

    2011-05-24

    Foxp3(+) regulatory T cells (Tregs) originate in the thymus, but the Treg phenotype can also be induced in peripheral lymphoid organs or in vitro by stimulation of conventional CD4(+) T cells with IL-2 and TGF-β. There have been divergent reports on the suppressive capacity of these TGF-Treg cells. We find that TGF-Tregs derived from diabetes-prone NOD mice, although expressing normal Foxp3 levels, are uniquely defective in suppressive activity, whereas TGF-Tregs from control strains (B6g7) or ex vivo Tregs from NOD mice all function normally. Most Treg-typical transcripts were shared by NOD or B6g7 TGF-Tregs, except for a small group of differentially expressed genes, including genes relevant for suppressive activity (Lrrc32, Ctla4, and Cd73). Many of these transcripts form a coregulated cluster in a broader analysis of T-cell differentiation. The defect does not map to idd3 or idd5 regions. Whereas Treg cells from NOD mice are normal in spleen and lymph nodes, the NOD defect is observed in locations that have been tied to pathogenesis of diabetes (small intestine lamina propria and pancreatic lymph node). Thus, a genetic defect uniquely affects a specific Treg subpopulation in NOD mice, in a manner consistent with a role in determining diabetes susceptibility.

  11. NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Blandine C Mercier

    Full Text Available Pattern recognition receptors (PRR, like Toll-like receptors (TLR and NOD-like receptors (NLR, are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR. This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-κB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions.

  12. Postnatal events in intestinal gene expression and splenic cell composition is altered in NOD mice

    DEFF Research Database (Denmark)

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Kristensen, Matilde Bylov

    2013-01-01

    microbiota seems to play an important role in the development and control of T1D. We hypothesized that NOD mice in the perinatal period respond differently than mice not prone to develop T1D (C57/Bl6), and we investigated the differences in postnatal expression of genes in gut, spleen, liver and pancreas......Evidence suggests that colonisation pattern of the gut in the early postnatal period is highly correlated with the risk of developing type 1 diabetes (T1D). We have recently shown that colonization in SPF mice accelerates gut maturation and that at postnatal day (PND) 1, in comparison with germ...... free mice, certain chemokines, including Cxcl2 encoding macrophage inflammatory protein (MIP)-2 and involved in attraction of neutrophils was downregulated in the gut epithelium. The non-obese diabetes (NOD) mouse is widely used as a model for studying the pathogenesis of T1D. The neonatal gut...

  13. Purification, crystallization and preliminary crystallographic characterization of the caspase-recruitment domain of human Nod1

    International Nuclear Information System (INIS)

    Srimathi, Thiagarajan; Robbins, Sheila L.; Dubas, Rachel L.; Seo, Jang-Hoon; Park, Young Chul

    2006-01-01

    The caspase-recruitment domain of the cytosolic pathogen receptor Nod1 was crystallized. X-ray diffraction data were collected to 1.9 Å resolution. The caspase-recruitment domain (CARD) is known to play an important role in apoptosis and inflammation as an essential protein–protein interaction domain. The CARD of the cytosolic pathogen receptor Nod1 was overexpressed in Escherichia coli and purified by affinity chromatography and gel filtration. The purified CARD was crystallized at 277 K using the microseeding method. X-ray diffraction data were collected to 1.9 Å resolution. The crystals belong to space group P3 1 or P3 2 , with unit-cell parameters a = b = 79.1, c = 80.9 Å. Preliminary analysis indicates that there is one dimeric CARD molecule in the asymmetric unit

  14. Physical growth, puberty and hormones in adolescents with Nodding Syndrome; a pilot study.

    Science.gov (United States)

    Piloya-Were, Theresa; Odongkara-Mpora, Beatrice; Namusoke, Hanifa; Idro, Richard

    2014-11-28

    Nodding syndrome is an epidemic symptomatic generalized epilepsy syndrome of unknown cause in Eastern Africa. Some patients have extreme short stature. We hypothesized that growth failure in nodding syndrome is associated with specific endocrine dysfunctions. In this pilot study, we examined the relationship between serum hormone levels and stature, bone age and sexual development. We recruited ten consecutive children, 13 years or older, with World Health Organization defined nodding syndrome and assessed physical growth, bone age, development of secondary sexual characteristics and serum hormone levels. Two children with incomplete results were excluded. Of the eight remaining, two had severe stunting (height for age Z [HAZ] scorebone age was delayed by a median 3(range 0-4) years. Serum growth hormone levels were normal in all eight but the two patients with severe stunting and one with moderate stunting had low levels of Somatomedin C (Insulin like Growth Factor [IGF1]) and/or IGF binding protein 3 (IGFBP3), mediators of growth hormone function. A linear relationship was observed between serum IGF1 level and HAZ score. With the exception of one child, all were either pre-pubertal or in early puberty (Tanner stages 1 and 2) and in the seven, levels of the gonadotrophins (luteinising and follicle stimulating hormone) and the sex hormones (testosterone/oestrogen) were all within pre-pubertal ranges or ranges of early puberty. Thyroid function, prolactin, adrenal, and parathyroid hormone levels were all normal. Patients with nodding syndrome may have dysfunctions in the pituitary growth hormone and pituitary gonadal axes that manifest as stunted growth, delayed bone age and puberty. Studies are required to determine if such endocrine dysfunction is a primary manifestation of the disease or a secondary consequence of chronic ill health and malnutrition and if so, whether targeted interventions can improve outcome.

  15. Coordinating controls

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-07-15

    While physics Laboratories are having to absorb cuts in resources, the machines they rely on are becoming more and more complex, requiring increasingly sophisticated systems. Rather than being a resourceful engineer or physicist able to timber together solutions in his 'backyard', the modern controls specialist has become a professional in his own right. Because of possible conflicts between increasing sophistication on one hand and scarcer resources on the other, there was felt a need for more contacts among controls specialists to exchange experiences, coordinate development and discuss 'family problems', away from meetings where the main interest is on experimental physics.

  16. Coordinated unbundling

    DEFF Research Database (Denmark)

    Timmermans, Bram; Zabala-Iturriagagoitia, Jon Mikel

    2013-01-01

    Public procurement for innovation is a matter of using public demand to trigger innovation. Empirical studies have demonstrated that demand-based policy instruments can be considered to be a powerful tool in stimulating innovative processes among existing firms; however, the existing literature has...... not focused on the role this policy instrument can play in the promotion of (knowledge-intensive) entrepreneurship. This paper investigates this link in more detail and introduces the concept of coordinated unbundling as a strategy that can facilitate this purpose. We also present a framework on how...

  17. Coordinating controls

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    While physics Laboratories are having to absorb cuts in resources, the machines they rely on are becoming more and more complex, requiring increasingly sophisticated systems. Rather than being a resourceful engineer or physicist able to timber together solutions in his 'backyard', the modern controls specialist has become a professional in his own right. Because of possible conflicts between increasing sophistication on one hand and scarcer resources on the other, there was felt a need for more contacts among controls specialists to exchange experiences, coordinate development and discuss 'family problems', away from meetings where the main interest is on experimental physics

  18. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball

    2010-01-01

    Operational Experience At the end of the first full-year running period of LHC, CMS is established as a reliable, robust and mature experiment. In particular common systems and infrastructure faults accounted for <0.6 % CMS downtime during LHC pp physics. Technical operation throughout the entire year was rather smooth, the main faults requiring UXC access being sub-detector power systems and rack-cooling turbines. All such problems were corrected during scheduled technical stops, in the shadow of tunnel access needed by the LHC, or in negotiated accesses or access extensions. Nevertheless, the number of necessary accesses to the UXC averaged more than one per week and the technical stops were inevitably packed with work packages, typically 30 being executed within a few days, placing a high load on the coordination and area management teams. It is an appropriate moment for CMS Technical Coordination to thank all those in many CERN departments and in the Collaboration, who were involved in CMS techni...

  19. RUN COORDINATION

    CERN Multimedia

    Christophe Delaere

    2013-01-01

    The focus of Run Coordination during LS1 is to monitor closely the advance of maintenance and upgrade activities, to smooth interactions between subsystems and to ensure that all are ready in time to resume operations in 2015 with a fully calibrated and understood detector. After electricity and cooling were restored to all equipment, at about the time of the last CMS week, recommissioning activities were resumed for all subsystems. On 7 October, DCS shifts began 24/7 to allow subsystems to remain on to facilitate operations. That culminated with the Global Run in November (GriN), which   took place as scheduled during the week of 4 November. The GriN has been the first centrally managed operation since the beginning of LS1, and involved all subdetectors but the Pixel Tracker presently in a lab upstairs. All nights were therefore dedicated to long stable runs with as many subdetectors as possible. Among the many achievements in that week, three items may be highlighted. First, the Strip...

  20. RUN COORDINATION

    CERN Multimedia

    C. Delaere

    2013-01-01

    Since the LHC ceased operations in February, a lot has been going on at Point 5, and Run Coordination continues to monitor closely the advance of maintenance and upgrade activities. In the last months, the Pixel detector was extracted and is now stored in the pixel lab in SX5; the beam pipe has been removed and ME1/1 removal has started. We regained access to the vactank and some work on the RBX of HB has started. Since mid-June, electricity and cooling are back in S1 and S2, allowing us to turn equipment back on, at least during the day. 24/7 shifts are not foreseen in the next weeks, and safety tours are mandatory to keep equipment on overnight, but re-commissioning activities are slowly being resumed. Given the (slight) delays accumulated in LS1, it was decided to merge the two global runs initially foreseen into a single exercise during the week of 4 November 2013. The aim of the global run is to check that we can run (parts of) CMS after several months switched off, with the new VME PCs installed, th...

  1. Identification and Antioxidant Activity of the Extracts of Eugenia uniflora Leaves. Characterization of the Anti-Inflammatory Properties of Aqueous Extract on Diabetes Expression in an Experimental Model of Spontaneous Type 1 Diabetes (NOD Mice

    Directory of Open Access Journals (Sweden)

    Nayara Simon Gonzalez Schumacher

    2015-10-01

    Full Text Available Medical and folklore reports suggest that Eugenia uniflora (E. uniflora is a functional food that contains numerous compounds in its composition, with anti-inflammatory, antioxidant and anti-diabetic effects. In the present study, we investigated the best solvents (water, ethanol and methanol/acetone for extracting bioactive compounds of E. uniflora leaves, assessing total phenols and the antioxidant activity of the extracts by 2,2-Diphenyl-1-picrylhydrazyl (DPPH, Ferric Reducing Antioxidant Power (FRAP, 2,2′-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS and Oxygen Radical Absorbance Capacity (ORAC assays, identifying hydrolysable tannins and three phenolic compounds (ellagic acid, gallic acid and rutin present in the leaves. In addition, we evaluated the incidence of diabetes, degree of insulitis, serum insulin, hepatic glutathione and tolerance test glucose in non-obese diabetic (NOD mice. Our results suggest that the aqueous extract presents antioxidant activity and high total phenols, which were used as a type 1 diabetes mellitus (DM-1 treatment in NOD mice. We verified that the chronic consumption of aqueous extract reduces the inflammatory infiltrate index in pancreatic islets, maintaining serum insulin levels and hepatic glutathione, and reducing serum lipid peroxidation as well as the risk for diabetes.

  2. Identification and Antioxidant Activity of the Extracts of Eugenia uniflora Leaves. Characterization of the Anti-Inflammatory Properties of Aqueous Extract on Diabetes Expression in an Experimental Model of Spontaneous Type 1 Diabetes (NOD Mice).

    Science.gov (United States)

    Schumacher, Nayara Simon Gonzalez; Colomeu, Talita Cristina; de Figueiredo, Daniella; Carvalho, Virginia de Campos; Cazarin, Cinthia Baú Betim; Prado, Marcelo Alexandre; Meletti, Laura Maria Molina; Zollner, Ricardo de Lima

    2015-10-09

    Medical and folklore reports suggest that Eugenia uniflora (E. uniflora) is a functional food that contains numerous compounds in its composition, with anti-inflammatory, antioxidant and anti-diabetic effects. In the present study, we investigated the best solvents (water, ethanol and methanol/acetone) for extracting bioactive compounds of E. uniflora leaves, assessing total phenols and the antioxidant activity of the extracts by 2,2-Diphenyl-1-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and Oxygen Radical Absorbance Capacity (ORAC) assays, identifying hydrolysable tannins and three phenolic compounds (ellagic acid, gallic acid and rutin) present in the leaves. In addition, we evaluated the incidence of diabetes, degree of insulitis, serum insulin, hepatic glutathione and tolerance test glucose in non-obese diabetic (NOD) mice. Our results suggest that the aqueous extract presents antioxidant activity and high total phenols, which were used as a type 1 diabetes mellitus (DM-1) treatment in NOD mice. We verified that the chronic consumption of aqueous extract reduces the inflammatory infiltrate index in pancreatic islets, maintaining serum insulin levels and hepatic glutathione, and reducing serum lipid peroxidation as well as the risk for diabetes.

  3. TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

    Science.gov (United States)

    Zheng, Shasha; Hedl, Matija; Abraham, Clara

    2015-02-15

    Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

  4. NOD1CARD Might Be Using Multiple Interfaces for RIP2-Mediated CARD-CARD Interaction: Insights from Molecular Dynamics Simulation.

    Directory of Open Access Journals (Sweden)

    Jitendra Maharana

    Full Text Available The nucleotide-binding and oligomerization domain (NOD-containing protein 1 (NOD1 plays the pivotal role in host-pathogen interface of innate immunity and triggers immune signalling pathways for the maturation and release of pro-inflammatory cytokines. Upon the recognition of iE-DAP, NOD1 self-oligomerizes in an ATP-dependent fashion and interacts with adaptor molecule receptor-interacting protein 2 (RIP2 for the propagation of innate immune signalling and initiation of pro-inflammatory immune responses. This interaction (mediated by NOD1 and RIP2 helps in transmitting the downstream signals for the activation of NF-κB signalling pathway, and has been arbitrated by respective caspase-recruitment domains (CARDs. The so-called CARD-CARD interaction still remained contradictory due to inconsistent results. Henceforth, to understand the mode and the nature of the interaction, structural bioinformatics approaches were employed. MD simulation of modelled 1:1 heterodimeric complexes revealed that the type-Ia interface of NOD1CARD and the type-Ib interface of RIP2CARD might be the suitable interfaces for the said interaction. Moreover, we perceived three dynamically stable heterotrimeric complexes with an NOD1:RIP2 ratio of 1:2 (two numbers and 2:1. Out of which, in the first trimeric complex, a type-I NOD1-RIP2 heterodimer was found interacting with an RIP2CARD using their type-IIa and IIIa interfaces. However, in the second and third heterotrimer, we observed type-I homodimers of NOD1 and RIP2 CARDs were interacting individually with RIP2CARD and NOD1CARD (in type-II and type-III interface, respectively. Overall, this study provides structural and dynamic insights into the NOD1-RIP2 oligomer formation, which will be crucial in understanding the molecular basis of NOD1-mediated CARD-CARD interaction in higher and lower eukaryotes.

  5. Modelando a coordenação de fosfato com o sítio ativo das fosfatases ácidas púrpuras Modeling the coordination of phosphate to the active site of purple acid phosphatases

    OpenAIRE

    Marcos Aires de Brito; Ademir Neves; Luiz R. Zilli

    1997-01-01

    We present a new binuclear complex, Fe2III(BBPMP)(OH)(O2 P(OPh)2) ClO4.CH3OH, 3, where BBPMP is the anion of 2,6-bis(2-hydroxybenzyl)(2-pyridylmethyl) aminomethyl-4-methylphenol, as a suitable model for the chromophoric site of purple acid phosphatases coordinated to phosphate. The complex was obtained by the reaction of complex 2, Fe2III(BBPMP)(O2P(OPh) 2)2 ClO4.H2O, in CH3CN with one equivalent of triethylamine. Based on the chromophoric properties of the model complex, lmax = 560 nm/ e = 4...

  6. Defining proximity relationships in the tertiary structure of the dopamine transporter. Identification of a conserved glutamic acid as a third coordinate in the endogenous Zn(2+)-binding site

    DEFF Research Database (Denmark)

    Løland, Claus Juul; Norregaard, L; Gether, U

    1999-01-01

    , high affinity Zn(2+)-binding site. To achieve further insight into the tertiary organization of hDAT, we set out to identify additional residues involved in Zn(2+) binding and subsequently to engineer artificial Zn(2+)-binding sites. Ten aspartic acids and glutamic acids, predicted...

  7. Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice.

    Science.gov (United States)

    Bodin, Johanna; Kocbach Bølling, Anette; Wendt, Anna; Eliasson, Lena; Becher, Rune; Kuper, Frieke; Løvik, Martinus; Nygaard, Unni Cecilie

    2015-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1 mg/l), a mixture of phthalates (DEHP 1 mg/l, DBP 0.2 mg/l, BBP 10 mg/l and DiBP 20 mg/l) or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4) from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function.

  8. Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice

    Directory of Open Access Journals (Sweden)

    Johanna Bodin

    2015-01-01

    Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA accelerates the spontaneous development of diabetes in non-obese diabetic (NOD mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1 mg/l, a mixture of phthalates (DEHP 1 mg/l, DBP 0.2 mg/l, BBP 10 mg/l and DiBP 20 mg/l or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4 from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function.

  9. Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice.

    Science.gov (United States)

    Hänninen, Arno; Toivonen, Raine; Pöysti, Sakari; Belzer, Clara; Plovier, Hubert; Ouwerkerk, Janneke P; Emani, Rohini; Cani, Patrice D; De Vos, Willem M

    2017-12-21

    Intestinal microbiota is implicated in the pathogenesis of autoimmune type 1 diabetes in humans and in non-obese diabetic (NOD) mice, but evidence on its causality and on the role of individual microbiota members is limited. We investigated if different diabetes incidence in two NOD colonies was due to microbiota differences and aimed to identify individual microbiota members with potential significance. We profiled intestinal microbiota between two NOD mouse colonies showing high or low diabetes incidence by 16S ribosomal RNA gene sequencing and colonised the high-incidence colony with the microbiota of the low-incidence colony. Based on unaltered incidence, we identified a few taxa which were not effectively transferred and thereafter, transferred experimentally one of these to test its potential significance. Although the high-incidence colony adopted most microbial taxa present in the low-incidence colony, diabetes incidence remained unaltered. Among the few taxa which were not transferred, Akkermansia muciniphila was identified. As A. muciniphila abundancy is inversely correlated to the risk of developing type 1 diabetes-related autoantibodies, we transferred A. muciniphila experimentally to the high-incidence colony. A. muciniphila transfer promoted mucus production and increased expression of antimicrobial peptide Reg3γ , outcompeted Ruminococcus torques from the microbiota, lowered serum endotoxin levels and islet toll-like receptor expression, promoted regulatory immunity and delayed diabetes development. Transfer of the whole microbiota may not reduce diabetes incidence despite a major change in gut microbiota, but single symbionts such as A. muciniphila with beneficial metabolic and immune signalling effects may reduce diabetes incidence when administered as a probiotic. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly

  10. Human T-cell responses to oral streptococci in human PBMC-NOD/SCID mice.

    Science.gov (United States)

    Salam, M A; Nakao, R; Yonezawa, H; Watanabe, H; Senpuku, H

    2006-06-01

    We investigated cellular and humoral immune responses to oral biofilm bacteria, including Streptococcus mutans, Streptococcus anginosus, Streptococcus sobrinus, and Streptococcus sanguinis, in NOD/SCID mice immunized with human peripheral blood mononuclear cells (hu-PBMC-NOD/SCID mice) to explore the pathogenicity of each of those organisms in dental and oral inflammatory diseases. hu-PBMC-NOD/SCID mice were immunized by intraperitoneal injections with the whole cells of the streptococci once a week for 3 weeks. FACS analyses were used to determine the percentages of various hu-T cell types, as well as intracellular cytokine production of interleukin-4 and interferon-gamma. Serum IgG and IgM antibody levels in response to the streptococci were also determined by enzyme-linked immunosorbent assay. S. anginosus induced a significant amount of the proinflammatory cytokine interferon-gamma in CD4(+) and CD8(+) T cells in comparison with the other streptococci. However, there was no significant differences between the streptococci in interleukin-4 production by CD4(+) and CD8(+) T cells after inoculation. Further, S. mutans significantly induced human anti-S. mutans IgG, IgG(1), IgG(2), and IgM antibodies in comparison with the other organisms. In conclusion, S. anginosus up-regulated Th1 and Tc1 cells, and S. mutans led to increasing levels of their antibodies, which was associated with the induction of Th2 cells. These results may contribute to a better understanding of human lymphocyte interactions to biofilm bacteria, along with their impact on dental and mucosal inflammatory diseases, as well as endocarditis.

  11. Cd (II) and holodirected lead (II) 3D-supramolecular coordination polymers based on nicotinic acid: Structure, fluorescence property and photocatalytic activity

    Science.gov (United States)

    Etaiw, Safaa El-din H.; Abd El-Aziz, Dina M.; Marie, Hassan; Ali, Elham

    2018-05-01

    Two new supramolecular coordination polymers namely {[Cd(NA)2(H2O)]}, SCP 1 and {[Pb(NA)2]}, SCP 2, (NA = nicotinate ligand) were synthesized by self-assembly method and structurally characterized by different analytical and spectroscopic methods. Single-crystal X-ray diffraction showed that SCP 1 extend in three dimensions containing bore structure where the 3D- network is constructed via interweaving zigzag chains. The Cd atom coordinates to (O4N2) atoms forming distorted-octahedral configuration. The structure of SCP 2 extend down the projection of the b-axis creating parallel zigzag 1D-chains connected by μ2-O2 atoms and H-bonds forming a holodirected lead (II) hexagonal bi-pyramid configuration. SCP 2 extend to 3D-network via coordinate and hydrogen bonds. The thermal stability, photoluminescence properties, photocatalytic activity for the degradation of methylene blue dye (MB) under UV-irradiation and sunlight irradiation were also studied.

  12. Are NOD2 polymorphisms linked to a specific disease endophenotype of Crohn's disease?

    DEFF Research Database (Denmark)

    Jensen, Stina Rikke; Nielsen, Ole Haagen; Pedersen, Susanne Brix

    2011-01-01

    is not yet clarified. The enhanced number of pathogenic E. coli in the ileal mucosa of CD as compared to healthy controls may result from a genetically based failure in one of the intestinal bacteria sensing systems, like NOD2, making the ileal epithelium more prone to colonization with microbes harboring...... specific properties such as AIEC. Increasing the focus on defining subgroups of patients with similar disease initiations, mechanisms of action, and manifestations in CD may be pivotal for the development and implementation of future individualized treatment strategies of benefit for the single patient...

  13. Penetrance of NOD2/CARD15 genetic variants in the general population

    DEFF Research Database (Denmark)

    Yazdanyar, Shiva; Kamstrup, Pia R; Tybjaerg-Hansen, Anne

    2010-01-01

    In case-control studies of Europeans, heterozygosity for Arg702Trp(rs2066844), Gly908Arg(rs2066845) and Leu1007fsinsC(rs5743293) on the NOD2/CARD15 gene is associated with a 2-fold greater risk of Crohn disease, whereas homozygosity or compound heterozygosity is associated with a 17-fold greater ...... risk. However, the importance of these genetic variants if identified in particular individuals within the general population is unknown. We undertook this study to estimate the penetrance of these variants in the general population....

  14. Toll-like receptors and NOD-like receptors in rheumatic diseases.

    LENUS (Irish Health Repository)

    McCormack, William J

    2012-02-01

    The past 10 years have seen the description of families of receptors that drive proinflammatory cytokine production in infection and tissue injury. Two major classes have been examined in the context of inflammatory joint disease--the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs such as TLR2 and TLR4 are being implicated in the pathology of rheumatoid arthritis, ankylosing spondylitis, lyme arthritis and osteoarthritis. Nalp3 has been identified as a key NLR for IL-1beta production and has been shown to have a particular role in gout. These findings present new therapeutic opportunities, possibly allowing for the replacement of biologics with small molecule inhibitors.

  15. NOD2/CARD15 genotype, cardiovascular disease and cancer in 43 600 individuals from the general population

    DEFF Research Database (Denmark)

    Yazdanyar, S.; Nordestgaard, B.G.

    2010-01-01

    from two large Danish general population cohorts followed for 31 years: the Copenhagen City Heart Study (n = 10 597) and the Copenhagen General Population Study (n = 32 999). We examined the risk of cardiovascular disease (2743 and 3890, respectively, in the two studies) and cancer (2144 and 3241......, respectively) by NOD2/CARD15 genotype using Cox and logistic regressions in both studies. To maximize statistical power, the three NOD2/CARD15 genetic variants were analysed together as follows: noncarriers for all three variants, heterozygotes for one of the three variants and homozygotes for one of the three...... variants pooled with compound heterozygotes for two variants. Results. Multifactorially adjusted hazard ratios for cardiovascular disease and cancer in NOD2/CARD15 heterozygotes or homozygotes/compound heterozygotes versus noncarries did not differ from 1.0 in the Copenhagen City Heart Study...

  16. Identification and Functional Characterisation of Nod Factor Receptor (NFR) Paralogs in Lotus japonicus

    DEFF Research Database (Denmark)

    Vestergaard, Gitte; Radutoiu, Elena Simona; Stougaard, Jens

    an important missing link in plant-bacterial communication. This picture changed with the cloning of LysM-domain containing receptor-like kinases (LysM-RLKs) in different legume species. In Lotus japonicus, two LysM-RLKs, Nod Factor Receptor 1 (NFR1) and Nod Factor Receptor 5 (NFR5), are believed to bind Nod...... using the sequences of NFR1 and NFR5. Microsattelite markers were developed from each TAC clone containing the LysM-RLK, permitting us to locate the genes on a genetic map of Lotus japonicus. In order to get more insight into the function of these genes an inverse genetic approach using RNAi has been...

  17. A novel mutation in the NOD2 gene associated with Blau syndrome: a Norwegian family with four affected members

    DEFF Research Database (Denmark)

    Milman, N; Ursin, K; Rødevand, E

    2009-01-01

    BACKGROUND: Blau syndrome is a chronic granulomatous disease with an autosomal dominant trait characterized by the triad granulomatous dermatitis, arthritis, and uveitis. It is caused by mutations in the NOD2 gene, also termed the CARD15 gene. OBJECTIVE: To report a novel mutation in the NOD2 gen...... with an autosomal dominant heritage. Most likely the mutation has arisen de novo in the proband. Genetic counselling and antenatal diagnostics should be available to the involved families....... associated with Blau syndrome. METHODS AND RESULTS: The proband was a 68-year-old ethnic Norwegian male who had uveitis and arthritis since 10 years of age followed by lifelong recurrent arthritis and chronic eye involvement. Genetic analysis showed a heterozygous c.1814 C>A, T605N mutation in NOD2 that has...

  18. Application of SGT1-Hsp90 chaperone complex for soluble expression of NOD1 LRR domain in E. coli

    International Nuclear Information System (INIS)

    Hong, Tae-Joon; Hahn, Ji-Sook

    2016-01-01

    NOD1 is an intracellular sensor of innate immunity which is related to a number of inflammatory diseases. NOD1 is known to be difficult to express and purify for structural and biochemical studies. Based on the fact that Hsp90 and its cochaperone SGT1 are necessary for the stabilization and activation of NOD1 in mammals, SGT1 was chosen as a fusion partner of the leucine-rich repeat (LRR) domain of NOD1 for its soluble expression in Escherichia coli. Fusion of human SGT1 (hSGT1) to NOD1 LRR significantly enhanced the solubility, and the fusion protein was stabilized by coexpression of mouse Hsp90α. The expression level of hSGT1-NOD1 LRR was further enhanced by supplementation of rare codon tRNAs and exchange of antibiotic marker genes. - Highlights: • The NOD1 LRR domain was solubilized by SGT1 fusion in E. coli. • The coexpression of HSP90 stabilized the SGT1-NOD1 LRR fusion protein. • Several optimizations could enhance the expression level of the fusion protein.

  19. ‘You sit in fear’: understanding perceptions of nodding syndrome in post-conflict northern Uganda

    Directory of Open Access Journals (Sweden)

    Kristine Buchmann

    2014-10-01

    Full Text Available Background: Nodding syndrome, a disabling epidemic epileptic encephalopathy, has affected an estimated 1,834 children in northern Uganda, with reports of as many as 3,000. Etiology is unknown and children are being treated symptomatically but inconsistently with anti-epileptic drugs. Design: This qualitative study comprised 10 semi-structured interviews with caregivers of affected children and five focus group discussions with 23 participants; relatives, teachers, and religious leaders. Data collection and participant observation were carried out from July to September 2012 in Kitgum and Pader districts. The material was coded through inductive thematic analysis. Results: Nodding syndrome has brought signs of discrimination in school admission procedures, founded in a fear of transmission. The suffering and loss caused by nodding syndrome is collective, and participants felt that nodding syndrome was viewed as a threat to the Acholi only, and that interventions had therefore been delayed. Multiple theories of causation exist, most commonly that the disease is caused by chemicals from bombs or that food aid distributed in IDP camps had expired or been poisoned.A feeling of uncertainty was present in all focus group discussions, fueled by the fact that results of investigations were not being shared with the communities. It was especially agonizing that CDC results had been given to the Ugandan government in 2010 but not to the public. The definitive fear is that the disease will be the end of the Acholi. Conclusions: This study provided insight into the perceptions of communities affected by an unknown emerging disease. Families of affected children are grieving not only their child's illness; it is a loss of social value and of lineage. The loss and suffering involved with nodding syndrome should be seen in the context of the wider suffering of a society disrupted by violent conflict. The memory of war is omnipresent and is also how nodding

  20. CP-25 Alleviates Experimental Sjögren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets.

    Science.gov (United States)

    Gu, Fang; Xu, Shixia; Zhang, Pengying; Chen, Xiaoyun; Wu, Yujing; Wang, Chun; Gao, Mei; Si, Min; Wang, Xinming; Heinrich, Korner; Wu, Huaxun; Wei, Wei

    2018-04-17

    Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune illness of the moisture-producing glands such as salivary glands that is characterized by various immune abnormalities. The aetiology of pSS remains unclear and there is no curative agent. In this study, we investigated the putative therapeutic effects on a NOD/Ltj mouse model of Sjögren's syndrome-like disorders of an ester derivative of paeoniflorin, paeoniflorin-6'O-benzene (termed CP-25). Our study showed that CP-25 alleviated effectively clinical manifestations in NOD/Ltj mice resulting, for example, in increased salivary flow and reduced histopathological scores. Furthermore, CP-25 decreased lymphocyte viability in NOD/Ltj mice and attenuated the infiltration of Th1 cells and Th2 cells into the salivary glands of NOD/Ltj mice. In the spleen on NOD/Ltj mice, CP-25 skewed the ratio of Th17 and regulatory T cells towards regulatory T cells. After treatment, concentrations of anti-La/SSB and IgG antibodies were reduced and the titre of the inflammatory cytokines IFN-γ, IL-4, IL-6 and IL-17A in the serum on NOD/Ltj mice was alleviated. Thus, we define CP-25 as a novel compound that is a potent therapeutic agent for pSS by modulating T lymphocyte subsets. Future studies will validate the use of CP-25 as a therapeutic strategy for the treatment of pSS. © 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  1. Effect of dietary gluten on dendritic cells and innate immune subsets in BALB/c and NOD mice.

    Directory of Open Access Journals (Sweden)

    Jesper Larsen

    Full Text Available The innate immune system is known to play an important role in oral tolerance to dietary antigens. This is important in development of celiac disease (CD but may also be important in type 1 diabetes (T1D, and could potentially explain the reduced incidence of T1D in mice receiving a gluten-free (GF diet. The direct in vivo effect of gluten on innate cells, and particularly dendritic cells (DC is not sufficiently clarified. Therefore, we wished to investigate the innate cell populations of spontaneous diabetic NOD mice and healthy BALB/c mice kept on a GF or a standard (STD gluten containing diet. We studied, by flow cytometry and reverse transcription-quantitative polymerase chain reaction (qRT-PCR, if dietary gluten induces changes in the activation of DCs and distribution of selected innate cells in lymphoid, pancreatic and intestinal tissues in BALB/c and NOD mice. We found that a GF diet increased the percentage of macrophages in BALB/c spleen and of CD11c+ DCs in BALB/c and NOD spleen. Strictly gluten-free (SGF diet increased the percentage of CD103+ DCs in BALB/c mice and decreased percentages of CD11b+ DCs in mesenteric and pancreatic lymph nodes in BALB/c mice. SGF diet in BALB/c mice also decreased DC expression of CD40, CCR7 and MHC-II in pancreatic lymph nodes. In conclusion, GF diet changes the composition of the innate immune system in BALB/c and NOD mice and increases expression of DC activation markers in NOD mice. These results contribute to the explanation of the low diabetes incidence in GF NOD mice. This mechanism may be important in development of type 1 diabetes, celiac disease and non-celiac gluten sensitivity.

  2. Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.

    Directory of Open Access Journals (Sweden)

    Ayelet Kaminitz

    Full Text Available BACKGROUND: Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff and regulatory T cells (Treg to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice. PRINCIPAL FINDINGS: Both effector (CD25(-, FoxP3(- and suppressor (CD25(+, FoxP3(+ CD4(+ T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP trangeneess. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL in both strains. The effector and suppressor CD4(+ subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4(+CD25(- T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice. CONCLUSION: These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis.

  3. miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu; Wang, Chengxiao; Liu, Ying; Tang, Liwei; Zheng, Mingxia [Department of Pediatrics, Jiangwan Hospital of Shanghai, Shanghai 200434 (China); Xu, Chundi [Department of Pediatrics, Ruijin affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025 (China); Song, Jian, E-mail: jiansongkxy@126.com [Department of Gastroenterology, Jiangwan Hospital of Shanghai, Shanghai 200434 (China); Meng, Xiaochun [Department of Pediatrics, Jiangwan Hospital of Shanghai, Shanghai 200434 (China)

    2013-08-16

    Highlights: •NOD2 is a target gene of miR-122. •miR-122 inhibits LPS-induced apoptosis by suppressing NOD2 in HT-29 cells. •miR-122 reduces the expression of pro-inflammatory cytokines (TNF-α and IFN-γ). •miR-122 promotes the release of anti-inflammatory cytokines (IL-4 and IL-10). •NF-κB signaling pathway is involved in inflammatory response induced by LPS. -- Abstract: Crohn’s disease (CD) is one of the two major types of inflammatory bowel disease (IBD) thought to be caused by genetic and environmental factors. Recently, miR-122 was found to be deregulated in association with CD progression. However, the underlying molecular mechanisms remain unclear. In the present study, the gene nucleotide-binding oligomerization domain 2 (NOD2/CARD15), which is strongly associated with susceptibility to CD, was identified as a functional target of miR-122. MiR-122 inhibited LPS-induced apoptosis by suppressing NOD2 in HT-29 cells. NOD2 interaction with LPS initiates signal transduction mechanisms resulting in the activation of nuclear factor κB (NF-κB) and the stimulation of downstream pro-inflammatory events. The activation of NF-κB was inhibited in LPS-stimulated HT-29 cells pretreated with miR-122 precursor or NOD2 shRNA. The expression of the pro-inflammatory cytokines TNF-α and IFN-γ was significantly decreased, whereas therelease of the anti-inflammatory cytokines IL-4 and IL-10 was increased in LPS-stimulated HT-29 cells pretreated with miR-122 precursor, NOD2 shRNA or the NF-κB inhibitor QNZ. Taken together, these results indicate that miR-122 and its target gene NOD2 may play an important role in the injury of intestinal epithelial cells induced by LPS.

  4. Utilization of mixed ligands to construct diverse Ni(II)-coordination polymers based on terphenyl-2,2′,4,4′-tetracarboxylic acid and varied N-donor co-ligands

    International Nuclear Information System (INIS)

    Wang, Chao; Zhao, Jun; Xia, Liang; Wu, Xue-Qian; Wang, Jian-Fang; Dong, Wen-Wen; Wu, Ya-Pan

    2016-01-01

    Three new coordination polymers, namely, {[Ni(H 2 L)(bix)(H 2 O) 2 ]·2h 2 O} n (1), {[Ni(HL)(Hdpa)(H 2 O) 2 ]·H 2 O} n (2), {[Ni(L) 0.5 (bpp)(H 2 O)]·H 2 O} n (3) (H 4 L=terphenyl-2,2′,4,4′-tetracarboxylic acid; bix=1,4-bis(imidazol-1-ylmethyl)benzene; dpa =4,4′-dipyridylamine; bpp=1,3-bis(4-pyridyl)propane), based on rigid H 4 L ligand and different N-donor co-ligands, have been synthesized under hydrothermal conditions. Compound 1 features a 3D 4-connected 6 6 -dia-type framework with H 4 L ligand adopts a μ 2 -bridging mode with two symmetry-related carboxylate groups in μ 1 -η 1 :η 0 monodentate mode. Compound 2 displays a 1D [Ni(HL)(Hdpa)] n ribbon chains motif, in which the H 4 L ligand adopts a μ 2 -bridging mode with two carboxylate groups in μ 1 -η 1 :η 1 and μ 1 -η 1 :η 0 monodentate modes, while 3 possesses a (4,4)-connected 3D frameworks with bbf topology, with H 4 L ligand displays a μ 4 -bridging coordination mode. The H 4 L ligand displays not only different deprotonated forms but also diverse coordination modes and conformations. The structural diversities among 1–3 have been carefully discussed, and the roles of N-donor co-ligands in the self-assembly of coordination polymers have been well documented. - Graphical abstract: Three nickel coordination polymers with different architectures based on mixed ligand system were synthesized and structurally characterized. Topology analyses indicate that 1 shows the 4-connected 6 6 -dia net, 1D ribbon chains for 2 and 3D (4,4)-connected bbf network for 3. Display Omitted - Highlights: • Three Ni-based coordination polymers with distinct features have been prepared. • Compound 1 features a 3D 4-connected 66-dia-type framework, 2 displays a 1D [Ni(HL)(Hdpa)] n ribbon chains motif, while 3 possesses a (4,4)-connected 3D frameworks with bbf topology. • The “mixed ligand assembled” strategy is significant potential for network design.

  5. Utilization of mixed ligands to construct diverse Ni(II)-coordination polymers based on terphenyl-2,2′,4,4′-tetracarboxylic acid and varied N-donor co-ligands

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chao [College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, Hubei Provincial Collaborative Innovation Center for New Energy Microgrid, China Three Gorges University, Yichang 443002 (China); Zhao, Jun, E-mail: junzhao08@126.com [College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, Hubei Provincial Collaborative Innovation Center for New Energy Microgrid, China Three Gorges University, Yichang 443002 (China); State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 35002 (China); Xia, Liang [College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, Hubei Provincial Collaborative Innovation Center for New Energy Microgrid, China Three Gorges University, Yichang 443002 (China); State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 35002 (China); Wu, Xue-Qian; Wang, Jian-Fang; Dong, Wen-Wen; Wu, Ya-Pan [College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, Hubei Provincial Collaborative Innovation Center for New Energy Microgrid, China Three Gorges University, Yichang 443002 (China)

    2016-06-15

    Three new coordination polymers, namely, {[Ni(H_2L)(bix)(H_2O)_2]·2h_2O}{sub n} (1), {[Ni(HL)(Hdpa)(H_2O)_2]·H_2O}{sub n} (2), {[Ni(L)_0_._5(bpp)(H_2O)]·H_2O}{sub n} (3) (H{sub 4}L=terphenyl-2,2′,4,4′-tetracarboxylic acid; bix=1,4-bis(imidazol-1-ylmethyl)benzene; dpa =4,4′-dipyridylamine; bpp=1,3-bis(4-pyridyl)propane), based on rigid H{sub 4}L ligand and different N-donor co-ligands, have been synthesized under hydrothermal conditions. Compound 1 features a 3D 4-connected 6{sup 6}-dia-type framework with H{sub 4}L ligand adopts a μ{sub 2}-bridging mode with two symmetry-related carboxylate groups in μ{sub 1}-η{sup 1}:η{sup 0} monodentate mode. Compound 2 displays a 1D [Ni(HL)(Hdpa)]{sub n} ribbon chains motif, in which the H{sub 4}L ligand adopts a μ{sub 2}-bridging mode with two carboxylate groups in μ{sub 1}-η{sup 1}:η{sup 1} and μ{sub 1}-η{sup 1}:η{sup 0} monodentate modes, while 3 possesses a (4,4)-connected 3D frameworks with bbf topology, with H{sub 4}L ligand displays a μ{sub 4}-bridging coordination mode. The H{sub 4}L ligand displays not only different deprotonated forms but also diverse coordination modes and conformations. The structural diversities among 1–3 have been carefully discussed, and the roles of N-donor co-ligands in the self-assembly of coordination polymers have been well documented. - Graphical abstract: Three nickel coordination polymers with different architectures based on mixed ligand system were synthesized and structurally characterized. Topology analyses indicate that 1 shows the 4-connected 6{sup 6}-dia net, 1D ribbon chains for 2 and 3D (4,4)-connected bbf network for 3. Display Omitted - Highlights: • Three Ni-based coordination polymers with distinct features have been prepared. • Compound 1 features a 3D 4-connected 66-dia-type framework, 2 displays a 1D [Ni(HL)(Hdpa)]{sub n} ribbon chains motif, while 3 possesses a (4,4)-connected 3D frameworks with bbf topology. • The “mixed ligand assembled

  6. A two-dimensional bismuth coordination polymer with tartaric acid: synthesis, characterization and thermal decomposition to Bi.sub.2./sub.O.sub.3./sub. nanoparticles

    Czech Academy of Sciences Publication Activity Database

    Ahadiat, G.; Tabatabaee, M.; Gholivand, K.; Zare, K.; Dušek, Michal; Kučeráková, Monika

    2017-01-01

    Roč. 16, č. 1 (2017), s. 7-16 ISSN 1024-1221 R&D Projects: GA ČR(CZ) GA15-12653S; GA MŠk LO1603 EU Projects: European Commission(XE) CZ.2.16/3.1.00/24510 Institutional support: RVO:68378271 Keywords : bismuth coordination polymer * tartrate ligand * thermal decomposition * alpha-Bi 2 O 3 nanoparticles Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 0.565, year: 2016

  7. Increased expression of TACI on NOD B cells results in germinal centre reaction anomalies, enhanced plasma cell differentiation and immunoglobulin production.

    Science.gov (United States)

    Banday, Viqar S; Thyagarajan, Radha; Sundström, Mia; Lejon, Kristina

    2016-11-01

    B cells have an important pathogenic role in the development of type 1 diabetes in the non-obese diabetic (NOD) mouse. We have previously reported that NOD mice display an increased percentage of TACI high -expressing B cells compared with C57BL/6 mice and this trait is linked to chromosomes 1 and 8. In this paper the genetic association of the transmembrane activator, calcium modulator and cyclophilin ligand interactor (TACI) trait was confirmed using double congenic NOD.B6C1/Idd22 mice. TACI ligation by a proliferation-inducing ligand (APRIL) has been shown to influence plasma cell differentiation, immunoglobulin production and isotype switch. Hence, the functional consequence of the up-regulation of TACI on NOD B cells was analysed both in vitro and in vivo. NOD B cells stimulated with APRIL showed an enhanced plasma cell differentiation and class switch to IgG and IgA compared with B cells from C57BL/6 mice. Moreover, flow cytometry analyses revealed that germinal centre B cells in NOD failed to down-regulate TACI. Availability of the TACI ligand B-cell activating factor (BAFF) has been shown to be a limiting factor in the germinal centre reaction. In line with this, upon immunization with 4-hydroxy-3-nitrophenylacetyl hapten-conjugated hen egg lysozyme, NOD mice produced higher titres of low-affinity antibodies compared with C57BL/6 mice. This observation was supported by the detection of increased levels of BAFF in NOD germinal centres after immunization compared with C57BL/6 by immunofluorescence. Our results support the hypothesis that increased TACI expression on NOD B cells contributes to the pathogenesis of type 1 diabetes in the NOD mouse. © 2016 John Wiley & Sons Ltd.

  8. Nodding syndrome—a new hypothesis and new direction for research

    Directory of Open Access Journals (Sweden)

    Robert Colebunders

    2014-10-01

    Full Text Available Nodding syndrome (NS is an unexplained neurological illness that mainly affects children aged between 5 and 15 years. NS has so far been reported from South Sudan, northern Uganda, and Tanzania, but in spite of extensive investigations, the aetiology remains unknown. We hypothesize that blackflies (Diptera: Simuliidae infected with Onchocerca volvulus microfilariae may also transmit another pathogen. This may be a novel neurotropic virus or an endosymbiont of the microfilariae, which causes not only NS, but also epilepsy without nodding. This hypothesis addresses many of the questions about NS that researchers have previously been unable to answer. An argument in favour of the hypothesis is the fact that in Uganda, the number of new NS cases decreased (with no new cases reported since 2013 after ivermectin coverage was increased and with the implementation of a programme of aerial spraying and larviciding of the large rivers where blackflies were breeding. If confirmed, our hypothesis will enable new strategies to control NS outbreaks.

  9. Polyinosine-polycytidylic acid promotes excessive iodine intake induced thyroiditis in non-obese diabetic mice via Toll-like receptor 3 mediated inflammation.

    Science.gov (United States)

    Shi, Ya-nan; Liu, Feng-hua; Yu, Xiu-jie; Liu, Ze-bing; Li, Qing-xin; Yuan, Ji-hong; Zang, Xiao-yi; Li, Lan-ying

    2013-02-01

    Excessive iodine intake and viral infection are recognized as both critical factors associated with autoimmune thyroid diseases. Toll-like receptors (TLRs) have been reported to play an important role in autoimmune and inflammatory disorders. In this study, we aimed to clarify the possible mechanism of TLR3 involved in polyinosine-polycytidylic acid (poly(I:C)) promoting excessive iodine intake induced thyroiditis in non-obese diabetic (NOD) mice. Both NOD and BALB/c mice were randomly assigned to four groups: control group (n = 5), high iodine intake (HI) group (n = 7), poly(I:C) group (n = 7) and combination of excessive iodine and poly(I:C) injection (HIP) group (n = 7). After 8 weeks, mice were weighed and blood samples were collected. All the mice were sacrificed before dissection of spleen and thyroid gland. Then, thyroid histology, thyroid secreted hormone, expression of CD3(+) cells and TLR3 as well as inflammatory mRNA level were evaluated. Both NOD and BALB/c mice from HI and HIP group represented goiter and increasing thyroid relative weight. Thyroid histology evidence indicated that only HIP group of NOD mice showed severe thyroiditis with lymphocytes infiltration in majority of thyroid tissue, severe damage of follicles and general fibrosis. Immunofluorescence staining results displayed a large number of CD3(+) cells in HIP NOD mice. Real-time polymerase chain reaction (PCR) results suggested interferon (IFN)-α increased over 30 folds and IFN-γ expression was doubled compared with control group, but interleukin (IL)-4 remained unchanged in HIP group of NOD mice thyroid. Meanwhile, over one third decrease of blood total thyroxine (TT4) and increased thyroid-stimulating hormone (TSH) was observed in HIP group of NOD mice. Only HIP group of NOD mice represented significantly elevation of TLR3 expression. Poly(I:C) enhanced excessive dietary iodine induced thyroiditis in NOD mice through increasing TLR3 mediated inflammation.

  10. Use of ionizing radiation in the regulation of amino acid synthesis of micro organisms. Part of a coordinated programme on radiation microbiology

    International Nuclear Information System (INIS)

    Hall, A.N.

    1976-05-01

    The effects of ionizing radiations on the production of glutamic acid (from glucose) by Corynebacterium glutamicum was investigated. Experiments were carried out with resting cell systems and with growing cultures of C. glutamicum. The growing cultures produced optimum yields of glutamic acid (25-30% of theoretical) in culture medium containing 1,0μg/l of biotin. The yield was virtually zero when 25μg/l of biotin was supplied. Resting cells from a medium containing growth-limiting concentrations of biotin (1μg/l) gave good yield of glutamic acid (approximately 27%), while cells harvested from a biotin-rich medium produced only traces of glutamate. Pre-irradiated cells of C. glutamicum produced less glutamic acid than unirradiated cells, and continuously irradiated (3,03 and 4,76 rad/h resting cells accumulated less glutamic acid than the corresponding unirradiated controls. Considerable increase in the glutamate produced by C. glutamicum during growth in the presence of 25μg/l of biotin was induced by continuously irradiating the cultures from the time of inoculation. The increases in the actual concentration of glutamate and in the precentage yield vary from approximately 2-fold to 4-fold. A dose rate of 4.0 krad/h was the most effective of the ones tested

  11. Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice

    NARCIS (Netherlands)

    K. Buschard (Karsten); A.K. Hansen; K. Jensen (Karen); D.J. Lindenbergh-Kortleve (Dicky); L.F. de Ruiter (Lilian); T.C. Krohn (Thomas); M.R. Hufeldt (Majbritt); F.K. Vogensen (Finn); B. Aasted (Bent); T. Osterbye (Thomas); B.O. Roep (Bart); C.J. de Haar (Colin); E.E.S. Nieuwenhuis (Edward)

    2011-01-01

    textabstractBackground: Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. Methods: The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice

  12. Structural requirements of acylated Gly-l-Ala-d-Glu analogs for activation of the innate immune receptor NOD2.

    Science.gov (United States)

    Gobec, Martina; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner; Jakopin, Žiga

    2016-06-30

    The fragment of bacterial peptidoglycan muramyl dipeptide (MDP) has long been known for its adjuvant activity, however the underlying mechanism of this action has only recently been elucidated. It is ascribed to its agonist action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). In spite of the pressing need for novel adjuvants for human use, this discovery is hampered, by not knowing the structural requirements underlying the immunostimulatory activity. We have investigated how minor modifications of hit compound acyl Gly-L-Ala-D-Glu derivative I modulate the molecular recognition by NOD2. A series of novel desmuramyldipeptides has been designed and synthesized leading to the identification of compound 16, in which the sugar moiety is replaced by a 6-phenylindole moiety, that exhibits the strongest NOD2 activation to date sans the carbohydrate moiety. The results have enabled a deeper understanding of the structural requirements of desmuramylpeptides for NOD2 activation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. An "Ideal" Home for Care: Nel Noddings, Thomas Hill Green, and an Ontological Support for a Phenomenology of Care

    Science.gov (United States)

    Decoste, Jordan; Boyd, Dwight

    2009-01-01

    This paper is grounded in a deep appreciation of Nel Noddings' "ethics of care" as an important contribution to moral philosophy and moral education. We seek to offer some philosophical reflections that have the potential to strengthen this important alternative to mainstream ethics and to how moral education might be conceived and practiced…

  14. From signal to form: Nod factor as a morhogenetic signal molecule to induce symbiotic responses in legume root hairs

    NARCIS (Netherlands)

    Esseling, J.J.

    2004-01-01

    In this thesis, research is presented which contributes to a better understanding of nod factor (NF) induced signalling in Iegume root hairs, leading to a successful symbiosis. We mainly use root hairs of the model Iegume Medicago truncatula ('barrel medic') as an experimental system. In the

  15. Chronic Myelogenous Leukemia Cells Contribute to the Stromal Myofibroblasts in Leukemic NOD/SCID Mouse In Vivo

    Directory of Open Access Journals (Sweden)

    Ryosuke Shirasaki

    2012-01-01

    Full Text Available We recently reported that chronic myelogenous leukemia (CML cells converted into myofibroblasts to create a microenvironment for proliferation of CML cells in vitro. To analyze a biological contribution of CML-derived myofibroblasts in vivo, we observed the characters of leukemic nonobese diabetes/severe combined immunodeficiency (NOD/SCID mouse. Bone marrow nonadherent mononuclear cells as well as human CD45-positive cells obtained from CML patients were injected to the irradiated NOD/SCID mice. When the chimeric BCR-ABL transcript was demonstrated in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML-derived myofibroblasts composed with the bone marrow-stroma, which produced significant amounts of human vascular endothelial growth factor A. When the parental CML cells were cultured with myofibroblasts separated from CML cell-engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly. These observations indicate that CML cells make an adequate microenvironment for their own proliferation in vivo.

  16. NOD2 Down-Regulates Colonic Inflammation by IRF4-Mediated Inhibition of K63-Linked Polyubiquitination of RICK and TRAF6

    Science.gov (United States)

    Watanabe, Tomohiro; Asano, Naoki; Meng, Guangxun; Yamashita, Kouhei; Arai, Yasuyuki; Sakurai, Toshiharu; Kudo, Masatoshi; Fuss, Ivan J; Kitani, Atsushi; Shimosegawa, Tooru; Chiba, Tsutomu; Strober, Warren

    2014-01-01

    It is well established that polymorphisms of the nucleotide-binding oligomerization domain 2 (NOD2) gene, a major risk factor in Crohn's disease (CD), lead to loss of NOD2 function. However, a molecular explanation of how such loss of function leads to increased susceptibility to CD has remained unclear. In a previous study exploring this question we reported that activation of NOD2 in human dendritic cells by its ligand, muramyl dipeptide (MDP) negatively regulates Toll-like receptor (TLR)-mediated inflammatory responses. Here we show that NOD2 activation results in increased interferon regulatory factor 4 (IRF4) expression and binding to TNF receptor associated factor 6 (TRAF6) and receptor interacting serine-threonine kinase (RICK). We then show that such binding leads to IRF4-mediated inhibition of Lys63-linked polyubiquitination of TRAF6 and RICK and thus to down-regulation of NF-κB activation. Finally, we demonstrate that protection of mice from the development of experimental colitis by MDP or IRF4 administration is accompanied by similar IRF4-mediated effects on polyubiquitination of TRAF6 and RICK in colonic lamina propria mononuclear cells. These findings thus define a mechanism of NOD2-mediated regulation of innate immune responses to intestinal microflora that could explain the relation of NOD2 polymorphisms and resultant NOD2 dysfunction to CD. PMID:24670424

  17. Genetic deletion of the bacterial sensor NOD2 improves murine Crohn’s disease-like ileitis independent of functional dysbiosis

    Energy Technology Data Exchange (ETDEWEB)

    Corridoni, D.; Rodriguez-Palacios, A.; Di Stefano, G.; Di Martino, L.; Antonopoulos, D. A.; Chang, E. B.; Arseneau, K. O.; Pizarro, T. T.; Cominelli, F.

    2016-11-16

    Although genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn’s disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 have been conducted using healthy (ileitis/colitis-free) mouse strains. Here, we evaluated the effects of Nod2 deletion in a murine model of spontaneous ileitis, i.e., the SAMP1Yit/Fc (SAMP) strain, which closely resembles CD. Remarkably, Nod2 deletion improved both chronic cobblestone ileitis (by 50% assessed, as the % of abnormal mucosa at 24 wks of age), as well as acute dextran sodium sulfate (DSS) colitis. Mechanistically, Th2 cytokine production and Th2-transcription factor activation (i.e., STAT6 phosphorylation) were reduced. Microbiologically, the effects of Nod2 deletion appeared independent of fecal microbiota composition and function, assessed by 16S rRNA and metatranscriptomics. Our findings indicate that pharmacological blockade of NOD2 signaling in humans could improve health in Th2-driven chronic intestinal inflammation.

  18. Ribosomal protein-Mdm2-p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation.

    Science.gov (United States)

    Liu, Yong; He, Yizhou; Jin, Aiwen; Tikunov, Andrey P; Zhou, Lishi; Tollini, Laura A; Leslie, Patrick; Kim, Tae-Hyung; Li, Lei O; Coleman, Rosalind A; Gu, Zhennan; Chen, Yong Q; Macdonald, Jeffrey M; Graves, Lee M; Zhang, Yanping

    2014-06-10

    The tumor suppressor p53 has recently been shown to regulate energy metabolism through multiple mechanisms. However, the in vivo signaling pathways related to p53-mediated metabolic regulation remain largely uncharacterized. By using mice bearing a single amino acid substitution at cysteine residue 305 of mouse double minute 2 (Mdm2(C305F)), which renders Mdm2 deficient in binding ribosomal proteins (RPs) RPL11 and RPL5, we show that the RP-Mdm2-p53 signaling pathway is critical for sensing nutrient deprivation and maintaining liver lipid homeostasis. Although the Mdm2(C305F) mutation does not significantly affect growth and development in mice, this mutation promotes fat accumulation under normal feeding conditions and hepatosteatosis under acute fasting conditions. We show that nutrient deprivation inhibits rRNA biosynthesis, increases RP-Mdm2 interaction, and induces p53-mediated transactivation of malonyl-CoA decarboxylase (MCD), which catalyzes the degradation of malonyl-CoA to acetyl-CoA, thus modulating lipid partitioning. Fasted Mdm2(C305F) mice demonstrate attenuated MCD induction and enhanced malonyl-CoA accumulation in addition to decreased oxidative respiration and increased fatty acid accumulation in the liver. Thus, the RP-Mdm2-p53 pathway appears to function as an endogenous sensor responsible for stimulating fatty acid oxidation in response to nutrient depletion.

  19. Targeted delivery of antigen to intestinal dendritic cells induces oral tolerance and prevents autoimmune diabetes in NOD mice.

    Science.gov (United States)

    Chen, Yulin; Wu, Jie; Wang, Jiajia; Zhang, Wenjing; Xu, Bohui; Xu, Xiaojun; Zong, Li

    2018-03-15

    The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice. A targeting NP delivery system was developed to encapsulate H6P, and the ability of this system to protect and facilitate H6P delivery to gut DCs was assessed. NOD mice were immunised with H6P-loaded targeting NPs orally once a week for 7 weeks and the onset of diabetes was assessed by monitoring blood glucose levels. H6P-loaded targeting NPs protected the encapsulated H6P from degradation in the gastrointestinal tract environment and significantly increased the uptake of H6P by DCs in the gut Peyer's patches (4.1 times higher uptake compared with the control H6P solution group). Oral vaccination with H6P-loaded targeting NPs induced antigen-specific T cell tolerance and prevented diabetes in 100% of NOD mice. Immune deviation (T helper [Th]1 to Th2) and CD4 + CD25 + FOXP3 + regulatory T cells were found to participate in the induction of immune tolerance. In this study, we successfully induced antigen-specific T cell tolerance and prevented the onset of diabetes in NOD mice. To our knowledge, this is the first attempt at delivering antigen to gut DCs using targeting NPs to induce T cell tolerance.

  20. Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy.

    Science.gov (United States)

    Sales-Marques, Carolinne; Cardoso, Cynthia Chester; Alvarado-Arnez, Lucia Elena; Illaramendi, Ximena; Sales, Anna Maria; Hacker, Mariana de Andréa; Barbosa, Mayara Garcia de Mattos; Nery, José Augusto da Costa; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes; Pacheco, Antonio Guilherme; Moraes, Milton Ozório

    2017-07-01

    The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations. Here, in a prospective approach, both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan-Meier survival curves, and the genetic effect was estimated by the Cox proportional-hazards regression model. In a sample including 447 leprosy patients, we confirmed that gender (male), and high bacillary clinical forms are risk factors for leprosy reactions. From the 15 single nucleotide polymorphisms (SNPs) at the 8 candidate genes genotyped (TNF/LTA, IFNG, IL10, TLR1, NOD2, SOD2, and IL6) we observed statistically different survival curves for rs751271 at the NOD2 and rs2069845 at the IL6 genes (log-rank p-values = 0.002 and 0.023, respectively), suggesting an influence on the amount of time before developing leprosy reactions. Cox models showed associations between the SNPs rs751271 at NOD2 and rs2069845 at IL6 with leprosy reactions (HRGT = 0.45, p = 0.002; HRAG = 1.88, p = 0.0008, respectively). Finally, IL-6 and IFN-γ levels were confirmed as high, while IL-10 titers were low in the sera of reactional patients. Rs751271-GT genotype-bearing individuals correlated (p = 0.05) with lower levels of IL-6 in sera samples, corroborating the genetic results. Although the experimental size may be considered a limitation of the study, the findings confirm the association of classical variables such as sex and clinical forms with leprosy, demonstrating the consistency of the results. From the results, we conclude that SNPs at the NOD2 and IL6 genes are associated with leprosy reactions as an outcome. NOD2 also has a clear functional pro-inflammatory link that is coherent with the exacerbated responses observed in these patients.

  1. A series of coordination polymers constructed from R-isophthalic acid (R=–SO{sub 3}H, –NO{sub 2}, and –OH) and N-donor ligands: Syntheses, structures and fluorescence properties

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yong-Hong, E-mail: zhou21921@sina.com [School of Chemistry and Material Science, Huaibei Normal University, Huaibei 235000 (China); Zhou, Xu-Wan; Zhou, Su-Rong [School of Chemistry and Material Science, Huaibei Normal University, Huaibei 235000 (China); Tian, Yu-Peng; Wu, Jie-Ying [Department of Chemistry and Chemical Technology, Anhui University, Hefei 230039 (China)

    2017-01-15

    Six novel Zn(II), Cd(II), and Cu(II) mixed-ligand coordination complexes, namely, [Zn{sub 2}Na(sip){sub 2}(bpp){sub 3}(Hbpp)(H{sub 2}O){sub 2}]·8H{sub 2}O (1), [Cd{sub 3}(sip){sub 2}(nbi){sub 6}(H{sub 2}O){sub 2}]·7H{sub 2}O (2), [Zn(sip)(nbi){sub 2}(H{sub 2}O)]·Hnbi·3H{sub 2}O (3), [Cd(hip)(nbi){sub 2}(H{sub 2}O)]·nbi·5H{sub 2}O (4), [Cd{sub 2}(nip){sub 2}(nbi){sub 2}(H{sub 2}O){sub 2}]·DMF (5), and [Cu(nip)(nbi)(H{sub 2}O){sub 2}]·H{sub 2}O (6) (H{sub 3}sip=5-sulfoisophthalic acid, H{sub 2}hip=5-hydroxylisophthalic acid, H{sub 2}nip=5-nitroisophthalic acid, bpp=1,3-bis(4-pyridyl)propane, and nbi=6-nitrobenzimidazole) have been synthesized hydrothermally by the self-assembly of R-isophthalic acid (R=–SO{sub 3}H, –NO{sub 2}, and –OH) and N-donor ligands. Single crystal X-ray analyses reveal that two Zn(II) ions and one Na(I) ion of complex 1 are linked through O atoms to generate a 1D linear chain. Then the 2D supramolecular architectures are constructed via intermolecular interactions. In complex 2, the Cd1 ions are connected by bridging carboxyl groups from sip{sup 3−} anions to form 1D double chain, which are further connected by Cd2 ions to afford 2D layer structure. The adjacent 2D layers are further linked via hydrogen-bonding interactions to give 3D supramolecular network. Compounds 3–5 show 1D chain structures, which are assembled into 2D or 3D supramolecular frameworks via weak interactions. In compound 6, the Cu(II) ions are bridged by the nip{sup 2−} ligands to form 48-membered ring, which is assembled into 1Dchain via the π-π stacking interaction. In addition, the thermal stabilities and fluorescence properties of these compounds have also been studied. - Graphical abstract: A series of Cd(II)/Zn(II)/ Cu(II) coordination polymers based on R-isophthalic acid (R=–SO{sub 3}H, –NO{sub 2}, and –OH) and N-donor ligands have been synthesized under hydrothermal conditions and structurally characterized. Photoluminescent properties

  2. Synthesis, coordination and biological aspects of organotin(IV derivatives of 4-[(2,4-dinitrophenylamino]-4-oxo-2-butenoic acid and 2-{[(2,4-dinitrophenylamino]carbonyl}benzoic acid

    Directory of Open Access Journals (Sweden)

    KHADIJA SHAHID

    2009-02-01

    Full Text Available New series of organotin(IV complexes of aniline derivatives, R2SnL2 and R3SnL [where R = Me, n-Bu, Ph, n-Oct] have been synthesized by the reaction of HL1 and HL2 with respective organotin halides or oxides. Experimental details for the preparation and characterization (including elemental analysis, IR and multinuclear NMR (1H-, 13C- and 119Sn- spectra in CDCl3 and EI mass spectra of both series are provided. The binding sites of the ligands were identified by means of FTIR spectroscopic measurements. It was found that in all cases the organotin(IV moiety reacts with the oxygen of COO– group to form new complexes. In the diorganotin complexes, the COO– group is coordinated to the organotin(IV centres in a bidentate manner in the solid state. The 119Sn NMR data and the nJ(13C‑119/117Sn coupling constant support the tetrahedral coordination geometry of the organotin complexes in non-coordinating solvents. Biological activities (antibacterial, antifungal, cytotoxicity, antileishmanial and insecticidal of these compounds are also reported.

  3. Three coordination polymers based on a star-like geometry 4, 4', 4'' -nitrilotribenzoic acid ligand and their framework dependent luminescent properties

    Science.gov (United States)

    Hu, Zhiyong; Zhao, Meng; Su, Jian; Xu, Shasha; Hu, Lei; Liu, Hui; Zhang, Qiong; Zhang, Jun; Wu, Jieying; Tian, Yupeng

    2018-02-01

    Three novel coordination polymers, [Zn(μ2-HTCA)(Phen)]n (1), {[Cd(μ3-HTCA)(Phen)]·2H2O}n (2), [Mn(μ2-HTCA)(Phen)(H2O)]n (3) were prepared by hydrothermal synthesis from the 4, 4', 4''-nitrilotribenzoicacid (H3TCA) and 1, 10-phenanthroline monohydrate (Phen) with different transition metal salts, which were characterized by elemental analysis, IR spectra, powder and single-crystal X-ray diffraction and thermogravimetric analysis. The photophysical properties of the complexes were investigated by solid-state diffuse reflectance spectra, photoluminescent properties, lifetime and quantum yield. For these complexes, it was found that the band gaps follow the order: 3 < 2 < 1 < 2.80 eV, fluorescence intensity order: 1 > H3TCA > 2 > 3; quantum yield order: H3TCA > 1 > 2 > 3; while the lifetime order: 1 > 2 > H3TCA > 3.

  4. NOD-Like Receptors: A Tail from Plants to Mammals Through Invertebrates.

    Science.gov (United States)

    Pontillo, Alessandra; Crovella, Sergio

    2017-01-01

    NOD Like Receptors (NLRs) are the most abundant cytoplasmic immune receptors in plants and animals and they similarly act sensing pathogen invasion and activating immune response. Despite the fact that plant and mammals NLRs share homology.; with some protein structure differences.; for signalling pathway.; divergent evolution of the receptors has been hypothesized. Next generation genome sequencing has contributed to the description of NLRs in phyla others than plants and mammals and leads to new knowledge about NLRs evolution along phylogeny. Full comprehension of NLR-mediated immune response in plant could contribute to the understanding of animal NLRs physiology and/or pathology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Transmaternal bisphenol A exposure accelerates diabetes type 1 development in NOD mice.

    Science.gov (United States)

    Bodin, Johanna; Bølling, Anette Kocbach; Becher, Rune; Kuper, Frieke; Løvik, Martinus; Nygaard, Unni Cecilie

    2014-02-01

    Diabetes mellitus type 1 is an autoimmune disease with a genetic predisposition that is triggered by environmental factors during early life. Epidemiological studies show that bisphenol A (BPA), an endocrine disruptor, has been detected in about 90% of all analyzed human urine samples. In this study, BPA was found to increase the severity of insulitis and the incidence of diabetes in female non obese diabetic (NOD) mice offspring after transmaternal exposure through the dams' drinking water (0, 0.1, 1, and 10mg/l). Both the severity of insulitis in the pancreatic islets at 11 weeks of age and the diabetes prevalence at 20 weeks were significantly increased for female offspring in the highest exposure group compared to the control group. Increased numbers of apoptotic cells, a reduction in tissue resident macrophages and an increase in regulatory T cells were observed in islets prior to insulitis development in transmaternally exposed offspring. The detectable apoptotic cells were identified as mostly glucagon producing alpha-cells but also tissue resident macrophages and beta-cells. In the local (pancreatic) lymph node neither regulatory T cell nor NKT cell populations were affected by maternal BPA exposure. Maternal BPA exposure may have induced systemic immune changes in offspring, as evidenced by alterations in LPS- and ConA-induced cytokine secretion in splenocytes. In conclusion, transmaternal BPA exposure, in utero and through lactation, accelerated the spontaneous diabetes development in NOD mice. This acceleration appeared to be related to early life modulatory effects on the immune system, resulting in adverse effects later in life.

  6. An Epidemiologic Investigation of Potential Risk Factors for Nodding Syndrome in Kitgum District, Uganda.

    Directory of Open Access Journals (Sweden)

    Jennifer L Foltz

    Full Text Available Nodding Syndrome (NS, an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda.In December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations.Surveillance identified 224 cases; most (95% were 5-15-years-old (range = 2-27. Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0·6-46. The case-control investigation (n = 49 case/village control pairs showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR1 = 14·4 (2·7, 78·3], exposure to munitions [AOR1 = 13·9 (1·4, 135·3], and consumption of crushed roots [AOR1 = 5·4 (1·3, 22·1] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84% and controls (75%.NS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5- to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies.

  7. Five new Zn(II) and Cd(II) coordination polymers constructed by 3,5-bis-oxyacetate-benzoic acid: Syntheses, crystal structures, network topologies and luminescent properties

    International Nuclear Information System (INIS)

    Jiang Xianrong; Yuan Hongyan; Feng Yunlong

    2012-01-01

    Five Zn(II) and Cd(II) coordination polymers, [Zn 2 (BOABA)(bpp)(OH)]·0.5H 2 O (1), [Cd 3 (BOABA) 2 (bpp) 2 (H 2 O) 6 ]·2H 2 O (2), [Cd 3 (BOABA) 2 (2,2′-bipy) 3 (H 2 O) 4 ]·5.5H 2 O (3), [CdNa(BOABA)(H 2 O)] 2 ·H 2 O (4) and [Cd 2 (BOABA)(bimb)Cl(H 2 O) 2 ]·H 2 O (5) (H 3 BOABA=3,5-bis-oxyacetate-benzoic acid, bpp=1,3-bi(4-pyridyl)propane, 2,2′-bipy=2,2′-bipyridine, bimb=1,4-bis(imidazol-1′-yl)butane), have been solvothermally synthesized and characterized by single-crystal X-ray diffraction, elemental analyses, IR spectra and TG analyses. 1 is an uninodal 4-connected 2D square grid network based on binuclear zinc clusters. 2 is 2D wavelike layer structure and further linked by hydrogen bonds into the final 3D (5,6,6)-connected topology network. 3 is 3-connected 2D topology network and the 2,2′-bipy ligands decorate in two different types. 4 is a (4,8)-connected 2D topology network with heterocaryotic {Cd 2 Na 2 } clusters and BOABA 3– ligands. 5 can be rationalized as a (3,10)-connected 3D topology network with tetranuclear {Cd 4 Cl 2 } clusters and BOABA 3– ligands. Meanwhile, photoluminescence studies revealed that these five coordination polymers display strong fluorescent emission bands in the solid state at room temperature. - Graphical abstract: Five new d 10 metal(II) coordination polymers based on H 3 BOABA ligand were obtained and characterized. They display different topological structures and luminescent properties. Highlights: ► Five d 10 metal(II) polymers based on 3,5-bis-oxyacetate-benzoic acid were obtained. ► The polymers were structurally characterized by single-crystal X-ray diffraction. ► Polymers 1–5 display different topological structures. ► They show strong fluorescent emission bands in the solid state.

  8. Coordination polymers with the chiral ligand N-p-tolylsulfonyl-L-glutamic acid: Influence of metal ions and different bipyridine ligands on structural chirality

    International Nuclear Information System (INIS)

    He Rong; Song Huihua; Wei Zhen; Zhang Jianjun; Gao Yuanzhe

    2010-01-01

    Four new polymers, namely [Ni(-tsgluO)(2,4'-bipy) 2 (H 2 O) 2 ] n .5nH 2 O (1), [Co(-tsgluO)(2,4'-bipy) 2 (H 2 O) 2 ] n .5nH 2 O (2), [Ni(-tsgluO)(4,4'-bipy)] n .0.5nH 2 O (3), and [Co(-tsgluO)(4,4'-bipy)] n .0.5nH 2 O (4), where tsgluO 2- =(+)-N-p-tolylsulfonyl-L-glutamate dianion, 2,4'-bipy=2,4'-bipyridine, and 4,4'-bipy=4,4'-bipyridine, have been prepared and structurally characterized. Compounds 1 and 2 are isostructural and mononuclear, and crystallize in the acentric monoclinic space group Cc, forming 1D chain structures. Compound 3 is also mononuclear, but crystallizes in the chiral space group P2 1 , forming a homochiral 2D architecture. In contrast to the other complexes, compound 4 crystallizes in the space group P-1 and is composed of binuclear [Co 2 O 6 N 2 ] n 4- units, which give rise to a 2D bilayer framework. Moreover, compounds 1, 2, and 4 self-assemble to form 3D supramolecular structures through π-π stacking and hydrogen-bonding interactions, while compound 3 is further hydrogen-bonded to form 3D frameworks. We have demonstrated the influence of the central metal and bipyridine ligands on the framework chirality of the coordination complexes. - Graphical abstract: Four novel polymers based on a chiral ligand were prepared and structurally characterized; it represents the first series of investigations about the effect of central metals and bipyridine ligands on framework chirality.

  9. Synthesis, characterization, and thermochemistry of the solid state coordination compound Zn(Nic){sub 2} . H{sub 2}O(s) (Nic = nicotinic acid)

    Energy Technology Data Exchange (ETDEWEB)

    Di Youying [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong (China)], E-mail: yydi@lcu.edu.cn; Hong Yuanping; Kong Yuxia; Yang Weiwei [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong (China); Tan Zhicheng [Thermochemistry Laboratory, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023 (China)

    2009-01-15

    A novel compound, viz. zinc nicotinate monohydrate, was synthesized by the method of room temperature solid phase synthesis. The techniques of FT-IR chemical and elemental analyses and X-ray powder diffraction were applied to characterise the structure and composition of the complex. In accordance with Hess' law, a thermochemical cycle was designed and the enthalpy change of the solid phase reaction of nicotinic acid with hydrated zinc acetate was determined to be {delta}{sub r}H{sub m}{sup 0}=(46.71{+-}0.21)kJ.mol{sup -1} by use of an isoperibol solution-reaction calorimeter. The standard molar enthalpy of formation of the title complex Zn(Nic){sub 2} . H{sub 2}O(s) was calculated as -(1062.3 {+-} 2.0) kJ . mol{sup -1} by use of the enthalpies of dissolution and other auxiliary thermodynamic data.

  10. Synthesis, structure and sensing behavior of a Cd-coordination polymer based on 1,10-phenanthroline and 2-aminoterephthalic acid

    Science.gov (United States)

    Meng, Xing; Wang, Hai-Feng; Chen, He; Zhou, Zi-Yan; Wang, Hai-Ning

    The reaction of 2-aminoterephthalic acid and 1,10-phenanthroline with Cd(NO3)2ṡ4H2O under solvothermal conditions leads to the formation of [Cd(2-aip)(phen)]ṡ0.5C2H5OH ( 1). In the compound, dimetallic cluster [Cd2(COO)4] exists and is linked by 2-aip ligands to stretch into a 2D flat layer. These layers are lined parallel to each other via N-HṡṡṡOCO hydrogen bond interactions, generating a 3D supramolecular architecture. The sensing property has been investigated. The experimental results show that the compound can be used as a luminescent probe to detect Co2+ and organic small molecules acetone.

  11. Discovery of Nanomolar Desmuramylpeptide Agonists of the Innate Immune Receptor Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Possessing Immunostimulatory Properties.

    Science.gov (United States)

    Gobec, Martina; Tomašič, Tihomir; Štimac, Adela; Frkanec, Ruža; Trontelj, Jurij; Anderluh, Marko; Mlinarič-Raščan, Irena; Jakopin, Žiga

    2018-04-12

    Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants, and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis, and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date. Compound 9 augmented pro-inflammatory cytokine release from human peripheral blood mononuclear cells in synergy with lipopolysaccharide. Furthermore, it was able to induce ovalbumin-specific IgG titers in a mouse model of adjuvancy. These findings provide deeper insights into the structural requirements of desmuramylpeptides for NOD2-activation and highlight the potential use of NOD2 agonists as adjuvants for vaccines.

  12. Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report.

    Science.gov (United States)

    Dziedzic, Magdalena; Marjańska, Agata; Bąbol-Pokora, Katarzyna; Urbańczyk, Anna; Grześk, Elżbieta; Młynarski, Wojciech; Kołtan, Sylwia

    2017-07-27

    Pediatric autoinflammatory diseases are rare and still poorly understood conditions resulting from defective genetic control of innate immune system, inter alia from anomalies of NOD2 gene. The product of this gene is Nod2 protein, taking part in maintenance of immune homeostasis. Clinical form of resultant autoinflammatory condition depends on NOD2 genotype; usually patients with NOD2 defects present with Blau syndrome, NOD2-associated autoinflammatory disease (NAID) or Crohn's disease. We present the case of a 7-year-old girl with co-existing symptoms of two rare diseases, Blau syndrome and NAID. Overlapping manifestations of two syndromes raised a significant diagnostic challenge, until next-generation molecular test (NGS) identified presence of three pathogenic variants of NOD2 gene: P268S, IVS8 +158 , 1007 fs, and established the ultimate diagnosis. Presence of multiple genetical abnormalities resulted in an ambiguous clinical presentation with overlapping symptoms of Blau syndrome and NAID. Final diagnosis of autoinflammatory disease opened new therapeutic possibilities, including the use of biological treatments.

  13. Mechanisms of Mycobacterium avium-induced resistance against insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice: role of Fas and Th1 cells.

    Science.gov (United States)

    Martins, T C; Aguas, A P

    1999-02-01

    NOD mice spontaneously develop autoimmune diabetes. One of the manipulations that prevent diabetes in NOD mice is infection with mycobacteria or immunization of mice with mycobacteria-containing adjuvant. Infection of NOD mice with Mycobacterium avium, done before the mice show overt diabetes, results in permanent protection of the animals from diabetes and this protective effect is associated with increased numbers of CD4+ T cells and B220+ B cells. Here, we investigate whether the M. avium-induced protection of NOD mice from diabetes was associated with changes in the expression of Fas (CD95) and FasL by immune cells, as well as alterations in cytotoxic activity, interferon-gamma (IFN-gamma) and IL-4 production and activation of T cells of infected animals. Our data indicate that protection of NOD mice from diabetes is a Th1-type response that is mediated by up-regulation of the Fas-FasL pathway and involves an increase in the cytotoxicity of T cells. These changes are consistent with induction by the infection of regulatory T cells with the ability of triggering deletion or anergy of peripheral self-reactive lymphocytes that cause the autoimmune disease of NOD mice.

  14. Antibody repertoires in humanized NOD-scid-IL2Rγ(null mice and human B cells reveals human-like diversification and tolerance checkpoints in the mouse.

    Directory of Open Access Journals (Sweden)

    Gregory C Ippolito

    Full Text Available Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγ(null engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH and light (IGK and IGL genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγ(null mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3 repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential D(H-J(H pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by

  15. Elevated systemic glutamic acid level in the non-obese diabetic mouse is Idd linked and induces beta cell apoptosis.

    Science.gov (United States)

    Banday, Viqar Showkat; Lejon, Kristina

    2017-02-01

    Although type 1 diabetes (T1D) is a T-cell-mediated disease in the effector stage, the mechanism behind the initial beta cell assault is less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in patients with T1D before disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD mice. Serum glutamic acid levels from a (NOD×B6)F 2 cohort (n = 182) were measured. By genome-wide and Idd region targeted microsatellite mapping, genetic association was detected for six regions including Idd2, Idd4 and Idd22. In silico analysis of potential enzymes and transporters located in and around the mapped regions that are involved in glutamic acid metabolism consisted of alanine aminotransferase, glutamic-oxaloacetic transaminase, aldehyde dehydrogenase 18 family, alutamyl-prolyl-tRNA synthetase, glutamic acid transporters GLAST and EAAC1. Increased EAAC1 protein expression was observed in lysates from livers of NOD mice compared with B6 mice. Functional consequence of the elevated glutamic acid level in NOD mice was tested by culturing NOD. Rag2 -/- Langerhans' islets with glutamic acid. Induction of apoptosis of the islets was detected upon glutamic acid challenge using TUNEL assay. Our results support the notion that a dysregulated metabolome could contribute to the initiation of T1D. We suggest that targeting of the increased glutamic acid in pre-diabetic patients could be used as a potential therapy. © 2016 John Wiley & Sons Ltd.

  16. Effect of dietary gluten on dendritic cells and innate immune subsets in BALB/c and NOD mice

    DEFF Research Database (Denmark)

    Larsen, Jesper; Weile, Christian; Antvorskov, Julie Christine

    2015-01-01

    containing diet. We studied, by flow cytometry and reverse transcription-quantitative polymerase chain reaction (qRT-PCR), if dietary gluten induces changes in the activation of DCs and distribution of selected innate cells in lymphoid, pancreatic and intestinal tissues in BALB/c and NOD mice. We found......-free (GF) diet. The direct in vivo effect of gluten on innate cells, and particularly dendritic cells (DC) is not sufficiently clarified. Therefore, we wished to investigate the innate cell populations of spontaneous diabetic NOD mice and healthy BALB/c mice kept on a GF or a standard (STD) gluten......The innate immune system is known to play an important role in oral tolerance to dietary antigens. This is important in development of celiac disease (CD) but may also be important in type 1 diabetes (T1D), and could potentially explain the reduced incidence of T1D in mice receiving a gluten...

  17. New coordination polymers from 1D chain, 2D layer to 3D framework constructed from 1,2-phenylenediacetic acid and 1,3-bis(4-pyridyl)propane flexible ligands

    International Nuclear Information System (INIS)

    Xin Lingyun; Liu Guangzhen; Wang Liya

    2011-01-01

    The hydrothermal reactions of Cd, Zn, or Cu(II) acetate salts with H 2 PHDA and BPP flexible ligands afford three new coordination polymers, including [Cd(PHDA)(BPP)(H 2 O)] n (1), [Zn(PHDA)(BPP)] n (2), and [Cu 2 (PHDA) 2 (BPP)] n (3) (H 2 PHDA=1,2-phenylenediacetic acid, BPP=1,3-bis(4-pyridyl)propane). The single-crystal X-ray diffractions reveal that all three complexes feature various metal carboxylate subunits extended further by the BPP ligands to form a diverse range of structures, displaying a remarked structural sensitivity to metal(II) cation. Complex 1 containing PHDA-bridged binuclear cadmium generates 1D double-stranded chain, complex 2 results in 2D→2D interpenetrated (4,4) grids, and complex 3 displays a 3D self-penetrated framework with 4 8 6 6 8 rob topology. In addition, fluorescent analyses show that both 1 and 2 exhibit intense blue-violet photoluminescence in the solid state. - Graphical Abstract: We show diverse supramolecular frameworks based on the same ligands (PHDA and BPP) and different metal acetate salts including 1D double-stranded chain, 2D → 2D twofold interpenetrated layer, and 3D self-penetration networks. Highlights: → Three metal(II = 2 /* ROMAN ) coordination polymers were synthesized using H 2 PHDA and BPP. → The diversity of structures show a remarked sensitivity to metal(II) center. → Complexes show the enhancement of fluorescence compared to that of free ligand.

  18. Comparative Geometrical Analysis of Leucine-Rich Repeat Structures in the Nod-Like and Toll-Like Receptors in Vertebrate Innate Immunity

    Directory of Open Access Journals (Sweden)

    Norio Matsushima

    2015-08-01

    Full Text Available The NOD-like receptors (NLRs and Toll-like receptors (TLRs are pattern recognition receptors that are involved in the innate, pathogen pattern recognition system. The TLR and NLR receptors contain leucine-rich repeats (LRRs that are responsible for ligand interactions. In LRRs short β-strands stack parallel and then the LRRs form a super helical arrangement of repeating structural units (called a coil of solenoids. The structures of the LRR domains of NLRC4, NLRP1, and NLRX1 in NLRs and of TLR1-5, TLR6, TLR8, TLR9 in TLRs have been determined. Here we report nine geometrical parameters that characterize the LRR domains; these include four helical parameters from HELFIT analysis. These nine parameters characterize well the LRR structures in NLRs and TLRs; the LRRs of NLR adopts a right-handed helix. In contrast, the TLR LRRs adopt either a left-handed helix or are nearly flat; RP105 and CD14 also adopt a left-handed helix. This geometrical analysis subdivides TLRs into four groups consisting of TLR3/TLR8/TLR9, TLR1/TLR2/TRR6, TLR4, and TLR5; these correspond to the phylogenetic tree based on amino acid sequences. In the TLRs an ascending lateral surface that consists of loops connecting the β-strand at the C-terminal side is involved in protein, protein/ligand interactions, but not the descending lateral surface on the opposite side.

  19. (15)N NMR spectroscopy unambiguously establishes the coordination mode of the diimine linker 2-(2'-pyridyl)pyrimidine-4-carboxylic acid (cppH) in Ru(ii) complexes.

    Science.gov (United States)

    Battistin, Federica; Balducci, Gabriele; Demitri, Nicola; Iengo, Elisabetta; Milani, Barbara; Alessio, Enzo

    2015-09-21

    We investigated the reactivity of three Ru(ii) precursors -trans,cis,cis-[RuCl2(CO)2(dmso-O)2], cis,fac-[RuCl2(dmso-O)(dmso-S)3], and trans-[RuCl2(dmso-S)4] - towards the diimine linker 2-(2'-pyridyl)pyrimidine-4-carboxylic acid (cppH) or its parent compound 4-methyl-2-(2'-pyridyl)pyrimidine ligand (mpp), in which a methyl group replaces the carboxylic group on the pyrimidine ring. In principle, both cppH and mpp can originate linkage isomers, depending on how the pyrimidine ring binds to ruthenium through the nitrogen atom ortho (N(o)) or para (N(p)) to the group in position 4. The principal aim of this work was to establish a spectroscopic fingerprint for distinguishing the coordination mode of cppH/mpp also in the absence of an X-ray structural characterization. By virtue of the new complexes described here, together with the others previously reported by us, we successfully recorded {(1)H,(15)N}-HMBC NMR spectra at natural abundance of the (15)N isotope on a consistent number of fully characterized Ru(ii)-cppH/mpp compounds, most of them being stereoisomers and/or linkage isomers. Thus, we found that (15)N NMR chemical shifts unambiguously establish the binding mode of cppH and mpp - either through N(o) or N(p)- and can be conveniently applied also in the absence of the X-ray structure. In fact, coordination of cppH to Ru(ii) induces a marked upfield shift for the resonance of the N atoms directly bound to the metal, with coordination induced shifts (CIS) ranging from ca.-45 to -75 ppm, depending on the complex, whereas the unbound N atom resonates at a frequency similar to that of the free ligand. Similar results were found for the complexes of mpp. This work confirmed our previous finding that cppH has no binding preference, whereas mpp binds exclusively through N(p). Interestingly, the two cppH linkage isomers trans,cis-[RuCl2(CO)2(cppH-κN(p))] (5) and trans,cis-[RuCl2(CO)2(cppH-κN(o))] (6) were easily obtained in pure form by exploiting their different

  20. Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance.

    Science.gov (United States)

    Zhang, Chengliang; Gui, Ling; Xu, Yanjiao; Wu, Tao; Liu, Dong

    2013-08-01

    Andrographolide, an active component in traditional anti-diabetic herbal plants, is a diterpenoid lactone isolated from Andrographis paniculata because of its potent anti-inflammatory and hypoglycemic effects. However, the effect of andrographolide on the development of diabetes in autoimmune non-obese diabetic (NOD) mice remains unknown. This study aimed to investigate the protective effects of andrographolide on the development of autoimmune diabetes and clarify the underlying mechanism. NOD mice were randomly divided into four groups and administered with water and andrographolide at 50, 100, and 150mg/kg body weight for four weeks. ICR mice were also selected as the control group. Oral glucose tolerance and histopathological insulitis were examined. Th1/Th2/Th17 cytokine secretion was determined by ELISA. The transcriptional profiles of T-bet, GATA3, and RORγt in the pancreatic lymphatic node samples derived from the NOD mice were detected by RT-PCR. After four weeks of oral supplementation, andrographolide significantly inhibited insulitis, delayed the onset, and suppressed the development of diabetes in 30-week-old NOD mice in a dose dependent manner. This protective status was correlated with a substantially decreased production of interferon (IFN)-γ and interleukin (IL)-2, increased IL-10 and transforming growth factor (TGF)-β, and a reduced IL-17. Andrographolide also increased GATA3 mRNA expression but decreased T-bet and RORγt mRNA expressions. Our results suggested that andrographolide prevented type 1 diabetes by maintaining Th1/Th2/Th17 homeostasis. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. The Role of NOD Mice in Type 1 Diabetes Research: Lessons from the Past and Recommendations for the Future

    OpenAIRE

    Yi-Guang Chen; Clayton E. Mathews; John P. Driver

    2018-01-01

    For more than 35 years, the NOD mouse has been the primary animal model for studying autoimmune diabetes. During this time, striking similarities to the human disease have been uncovered. In both species, unusual polymorphisms in a major histocompatibility complex (MHC) class II molecule confer the most disease risk, disease is caused by perturbations by the same genes or different genes in the same biological pathways and that diabetes onset is preceded by the presence of circulating autorea...

  2. Corrigendum: ‘You sit in fear’: understanding perceptions of nodding syndrome in post-conflict northern Uganda

    OpenAIRE

    Publishing, Co-Action

    2015-01-01

    Background Nodding syndrome, a disabling epidemic epileptic encephalopathy, has affected an estimated 1,834 children in northern Uganda, with reports of as many as 3,000. Etiology is unknown and children are being treated symptomatically but inconsistently with anti-epileptic drugs. Design This qualitative study comprised 10 semi-structured interviews with caregivers of affected children and five focus group discussions with 23 participants; relatives, teachers, and religious leaders. Data co...

  3. Suppressing effect of low-dose ionizing radiation on incidence of type I diabetes of NOD mice

    International Nuclear Information System (INIS)

    Nomura, T.; Makino, N.; Oda, T.; Sakai, K.

    2002-01-01

    In the present study we examined the effects of 0.5 Gy of ionizing radiation, given acutely or chronically, on the incidence of type I diabetes in non-obese diabetic mice was examined. NOD mice are characterized by a progressive loss of insulin-producing cells in the pancreas by autoimmune mechanisms. The results suggest that the suppressive effects on the onset of he diabetes by the low dose irradiation are explain by the induction of the antioxidative activity

  4. Overexpression of thioredoxin in islets transduced by a lentiviral vector prolongs graft survival in autoimmune diabetic NOD mice

    Directory of Open Access Journals (Sweden)

    Sytwu Huey-Kang

    2009-08-01

    Full Text Available Abstract Pancreatic islet transplantation is considered an appropriate treatment to achieve insulin independence in type I diabetic patients. However, islet isolation and transplantation-induced oxidative stress and autoimmune-mediated destruction are still the major obstacles to the long-term survival of graft islets in this potential therapy. To protect islet grafts from inflammatory damage and prolong their survival, we transduced islets with an antioxidative gene thioredoxin (TRX using a lentiviral vector before transplantation. We hypothesized that the overexpression of TRX in islets would prolong islet graft survival when transplanted into diabetic non-obese diabetic (NOD mice. Methods Islets were isolated from NOD mice and transduced with lentivirus carrying TRX (Lt-TRX or enhanced green fluorescence protein (Lt-eGFP, respectively. Transduced islets were transplanted under the left kidney capsule of female diabetic NOD mice, and blood glucose concentration was monitored daily after transplantation. The histology of the islet graft was assessed at the end of the study. The protective effect of TRX on islets was investigated. Results The lentiviral vector effectively transduced islets without altering the glucose-stimulating insulin-secretory function of islets. Overexpression of TRX in islets reduced hydrogen peroxide-induced cytotoxicity in vitro. After transplantation into diabetic NOD mice, euglycemia was maintained for significantly longer in Lt-TRX-transduced islets than in Lt-eGFP-transduced islets; the mean graft survival was 18 vs. 6.5 days (n = 9 and 10, respectively, p Conclusion We successfully transduced the TRX gene into islets and demonstrated that these genetically modified grafts are resistant to inflammatory insult and survived longer in diabetic recipients. Our results further support the concept that the reactive oxygen species (ROS scavenger and antiapoptotic functions of TRX are critical to islet survival after

  5. NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

    Science.gov (United States)

    Jiang, Zhaozhao; Fortune, Sarah M.; Coulombe, Francois; Behr, Marcel A.; Fitzgerald, Katherine A.; Sassetti, Christopher M.; Kelliher, Michelle A.

    2009-01-01

    While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNα and IFNβ, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds to bacterial peptidoglycan, and this event requires membrane damage that is actively inflicted by the bacterium. Unexpectedly, this recognition triggers the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This response is only partially impaired by the loss of Irf3 and therefore, differs fundamentally from those stimulated by bacterial DNA, which depend entirely on this transcription factor. This difference appears to result from the unusual peptidoglycan produced by mycobacteria, which we show is a uniquely potent agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system. PMID:19578435

  6. A series of coordination polymers constructed from R-isophthalic acid (R=-SO3H, -NO2, and -OH) and N-donor ligands: Syntheses, structures and fluorescence properties

    Science.gov (United States)

    Zhou, Yong-Hong; Zhou, Xu-Wan; Zhou, Su-Rong; Tian, Yu-Peng; Wu, Jie-Ying

    2017-01-01

    Six novel Zn(II), Cd(II), and Cu(II) mixed-ligand coordination complexes, namely, [Zn2Na(sip)2(bpp)3(Hbpp)(H2O)2]·8H2O (1), [Cd3(sip)2(nbi)6(H2O)2]·7H2O (2), [Zn(sip)(nbi)2(H2O)]·Hnbi·3H2O (3), [Cd(hip)(nbi)2(H2O)]·nbi·5H2O (4), [Cd2(nip)2(nbi)2(H2O)2]·DMF (5), and [Cu(nip)(nbi)(H2O)2]·H2O (6) (H3sip=5-sulfoisophthalic acid, H2hip=5-hydroxylisophthalic acid, H2nip=5-nitroisophthalic acid, bpp=1,3-bis(4-pyridyl)propane, and nbi=6-nitrobenzimidazole) have been synthesized hydrothermally by the self-assembly of R-isophthalic acid (R=-SO3H, -NO2, and -OH) and N-donor ligands. Single crystal X-ray analyses reveal that two Zn(II) ions and one Na(I) ion of complex 1 are linked through O atoms to generate a 1D linear chain. Then the 2D supramolecular architectures are constructed via intermolecular interactions. In complex 2, the Cd1 ions are connected by bridging carboxyl groups from sip3- anions to form 1D double chain, which are further connected by Cd2 ions to afford 2D layer structure. The adjacent 2D layers are further linked via hydrogen-bonding interactions to give 3D supramolecular network. Compounds 3-5 show 1D chain structures, which are assembled into 2D or 3D supramolecular frameworks via weak interactions. In compound 6, the Cu(II) ions are bridged by the nip2- ligands to form 48-membered ring, which is assembled into 1Dchain via the π-π stacking interaction. In addition, the thermal stabilities and fluorescence properties of these compounds have also been studied.

  7. Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice.

    Science.gov (United States)

    McLachlan, Sandra M; Lesage, Sylvie; Collin, Roxanne; Banuelos, Bianca; Aliesky, Holly A; Rapoport, Basil

    2017-04-01

    Thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) develop spontaneously in NOD.H2h4 mice, a phenotype enhanced by dietary iodine. NOD.H2h4 mice were derived by introducing the major histocompatibility class (MHC) molecule I-Ak from B10.A(4R) mice to nonobese diabetic (NOD) mice. Apart from I-Ak, the genes responsible for the NOD.H2h4 phenotype are unknown. Extending serendipitous observations from crossing BALB/c to NOD.H2h4 mice, thyroid autoimmunity was investigated in both genders of the F1, F2, and the second-generation backcross of F1 to NOD.H2h4 (N2). Medium-density linkage analysis was performed on thyroid autoimmunity traits in F2 and N2 progeny. TgAb develop before TPOAb and were measured after 8 and 16 weeks of iodide exposure; TPOAb and thyroiditis were studied at 16 weeks. TgAb, TPOAb, and thyroiditis, absent in BALB/c and F1 mice, developed in most NOD.H2h4 and in more N2 than F2 progeny. No linkages were observed in F2 progeny, probably because of the small number of autoantibody-positive mice. In N2 progeny (equal numbers of males and females), a chromosome 17 locus is linked to thyroiditis and TgAb and is suggestively linked to TPOAb. This locus includes MHC region genes from B10.A(4R) mice (such as I-Ak and Tnf, the latter involved in thyrocyte apoptosis) and genes from NOD mice such as Satb1, which most likely plays a role in immune tolerance. In conclusion, MHC and non-MHC genes, encoded within the chromosome 17 locus from both B10.A(4R) and NOD strains, are most likely responsible for the Hashimoto disease-like phenotype of NOD.H2h4 mice. Copyright © 2017 Endocrine Society.

  8. Structures of NodZ α1,6-fucosyltransferase in complex with GDP and GDP-fucose

    Energy Technology Data Exchange (ETDEWEB)

    Brzezinski, Krzysztof [Argonne National Laboratory, Argonne, IL 60439 (United States); Polish Academy of Sciences, 61-704 Poznan (Poland); Dauter, Zbigniew [Argonne National Laboratory, Argonne, IL 60439 (United States); Jaskolski, Mariusz, E-mail: mariuszj@amu.edu.pl [Polish Academy of Sciences, 61-704 Poznan (Poland); A. Mickiewicz University, 60-780 Poznan (Poland); Argonne National Laboratory, Argonne, IL 60439 (United States)

    2012-02-01

    Crystal structures of the bacterial α1,6-fucosyltransferase NodZ in complex with GDP and GDP-fucose are presented. Rhizobial NodZ α1,6-fucosyltransferase (α1,6-FucT) catalyzes the transfer of the fucose (Fuc) moiety from guanosine 5′-diphosphate-β-l-fucose to the reducing end of the chitin oligosaccharide core during Nod-factor (NF) biosynthesis. NF is a key signalling molecule required for successful symbiosis with a legume host for atmospheric nitrogen fixation. To date, only two α1,6-FucT structures have been determined, both without any donor or acceptor molecule that could highlight the structural background of the catalytic mechanism. Here, the first crystal structures of α1,6-FucT in complex with its substrate GDP-Fuc and with GDP, which is a byproduct of the enzymatic reaction, are presented. The crystal of the complex with GDP-Fuc was obtained through soaking of native NodZ crystals with the ligand and its structure has been determined at 2.35 Å resolution. The fucose residue is exposed to solvent and is disordered. The enzyme–product complex crystal was obtained by cocrystallization with GDP and an acceptor molecule, penta-N-acetyl-l-glucosamine (penta-NAG). The structure has been determined at 1.98 Å resolution, showing that only the GDP molecule is present in the complex. In both structures the ligands are located in a cleft formed between the two domains of NodZ and extend towards the C-terminal domain, but their conformations differ significantly. The structures revealed that residues in three regions of the C-terminal domain, which are conserved among α1,2-, α1,6- and protein O-fucosyltransferases, are involved in interactions with the sugar-donor molecule. There is also an interaction with the side chain of Tyr45 in the N-terminal domain, which is very unusual for a GT-B-type glycosyltransferase. Only minor conformational changes of the protein backbone are observed upon ligand binding. The only exception is a movement of the loop

  9. The machinery of Nod-like receptors: refining the paths to immunity and cell death.

    Science.gov (United States)

    Saleh, Maya

    2011-09-01

    One of the fundamental aspects of the innate immune system is its capacity to discriminate between self and non-self or altered self, and to quickly respond by eliciting effector mechanisms that act in concert to restore normalcy. This capacity is determined by a set of evolutionarily conserved pattern recognition receptors (PRRs) that sense the presence of microbial motifs or endogenous danger signals, including tissue damage, cellular transformation or metabolic perturbation, and orchestrate the nature, duration and intensity of the innate immune response. Nod-like receptors (NLRs), a group of intracellular PRRs, are particularly essential as evident by the high incidence of genetic variations in their genes in various diseases of homeostasis. Here, I overview the signaling mechanisms of NLRs and discuss the mounting evidence of evolutionary conservation between their pathways and the cell death machinery. I also describe their effector functions that link the sensing of danger to the induction of inflammation, autophagy or cell death. © 2011 John Wiley & Sons A/S.

  10. Nodding syndrome since 2012: recent progress, challenges and recommendations for future research.

    Science.gov (United States)

    Colebunders, R; Post, R; O'Neill, S; Haesaert, G; Opar, B; Lakwo, T; Laudisoit, A; Hendy, A

    2015-02-01

    We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics. © 2014 John Wiley & Sons Ltd.

  11. Nod-like receptor protein 1 inflammasome mediates neuron injury under high glucose.

    Science.gov (United States)

    Meng, Xian-Fang; Wang, Xiao-Lan; Tian, Xiu-Juan; Yang, Zhi-Hua; Chu, Guang-Pin; Zhang, Jing; Li, Man; Shi, Jing; Zhang, Chun

    2014-04-01

    Diabetic encephalopathy is one of the most common complications of diabetes. Inflammatory events during diabetes may be an important mechanism of diabetic encephalopathy. Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein (ASC), and caspase 1 or 5, which functions to switch on the inflammatory process and the release of inflammatory factors. The present study hypothesized that the formation and activation of NLRP1 inflammasome turns on neuroinflammation and neuron injury during hyperglycemia. The results demonstrated that the levels of interleukin-1 beta (IL-1β) were increased in the cortex of streptozocin (STZ)-induced diabetic rats. The levels of mature IL-1β and IL-18 were also elevated in culture medium of neurons treated with high glucose (50 mM). The expression of three essential components of the NLRP1 inflammasome complex, namely, NLRP1, ASC, and caspase 1, was also upregulated in vivo and in vitro under high glucose. Silencing the ASC gene prevented the caspase-1 activation, and inhibiting caspase 1 activity blocked hyperglycemia-induced release of inflammatory factors and neuron injury. Moreover, we found that pannexin 1 mediated the actvitation of NLRP1 inflammasome under high glucose. These results suggest that hyperglycemia induces neuroinflammation through activation of NLRP1 inflammasome, which represents a novel mechanism of diabetes-associated neuron injury.

  12. Five new Zn(II) and Cd(II) coordination polymers constructed by 3,5-bis-oxyacetate-benzoic acid: Syntheses, crystal structures, network topologies and luminescent properties

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Xianrong; Yuan Hongyan [Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, Institute of Physical Chemistry, Zhejiang Normal University, Jinhua, Zhejiang 321004 (China); Feng Yunlong, E-mail: sky37@zjnu.edu.cn [Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, Institute of Physical Chemistry, Zhejiang Normal University, Jinhua, Zhejiang 321004 (China)

    2012-07-15

    Five Zn(II) and Cd(II) coordination polymers, [Zn{sub 2}(BOABA)(bpp)(OH)]{center_dot}0.5H{sub 2}O (1), [Cd{sub 3}(BOABA){sub 2}(bpp){sub 2}(H{sub 2}O){sub 6}]{center_dot}2H{sub 2}O (2), [Cd{sub 3}(BOABA){sub 2}(2,2 Prime -bipy){sub 3}(H{sub 2}O){sub 4}]{center_dot}5.5H{sub 2}O (3), [CdNa(BOABA)(H{sub 2}O)]{sub 2}{center_dot}H{sub 2}O (4) and [Cd{sub 2}(BOABA)(bimb)Cl(H{sub 2}O){sub 2}]{center_dot}H{sub 2}O (5) (H{sub 3}BOABA=3,5-bis-oxyacetate-benzoic acid, bpp=1,3-bi(4-pyridyl)propane, 2,2 Prime -bipy=2,2 Prime -bipyridine, bimb=1,4-bis(imidazol-1 Prime -yl)butane), have been solvothermally synthesized and characterized by single-crystal X-ray diffraction, elemental analyses, IR spectra and TG analyses. 1 is an uninodal 4-connected 2D square grid network based on binuclear zinc clusters. 2 is 2D wavelike layer structure and further linked by hydrogen bonds into the final 3D (5,6,6)-connected topology network. 3 is 3-connected 2D topology network and the 2,2 Prime -bipy ligands decorate in two different types. 4 is a (4,8)-connected 2D topology network with heterocaryotic {l_brace}Cd{sub 2}Na{sub 2}{r_brace} clusters and BOABA{sup 3-} ligands. 5 can be rationalized as a (3,10)-connected 3D topology network with tetranuclear {l_brace}Cd{sub 4}Cl{sub 2}{r_brace} clusters and BOABA{sup 3-} ligands. Meanwhile, photoluminescence studies revealed that these five coordination polymers display strong fluorescent emission bands in the solid state at room temperature. - Graphical abstract: Five new d{sup 10} metal(II) coordination polymers based on H{sub 3}BOABA ligand were obtained and characterized. They display different topological structures and luminescent properties. Highlights: Black-Right-Pointing-Pointer Five d{sup 10} metal(II) polymers based on 3,5-bis-oxyacetate-benzoic acid were obtained. Black-Right-Pointing-Pointer The polymers were structurally characterized by single-crystal X-ray diffraction. Black-Right-Pointing-Pointer Polymers 1-5 display different

  13. Self-assembled coordination nanoparticles from nucleotides and lanthanide ions with doped-boronic acid-fluorescein for detection of cyanide in the presence of Cu2+ in water.

    Science.gov (United States)

    Kulchat, Sirinan; Chaicham, Anusak; Ekgasit, Sanong; Tumcharern, Gamolwan; Tuntulani, Thawatchai; Tomapatanaget, Boosayarat

    2012-01-30

    The sensor molecule, F-oBOH, containing boronic acid-linked hydrazide and fluorescein moieties was synthesized. For anion sensing applications, F-oBOH was studied in aqueous media. Unfortunately, F-oBOH was found to be hydrolyzed in water. Therefore, a new strategy was developed to prevent the hydrolysis of F-oBOH by applying self-assembly coordination nanoparticles network (F-oBOH-AMP/Gd(3+) CNPs). Interestingly, the nanoparticles network displayed the enhancement of fluorescent signal after adding Cu(2+) following by CN(-). The network, therefore, possessed a high selectivity for detection of CN(-) compared to other competitive anions in the presence of Cu(2+). Cyanide ion could promote the Cu(2+) binding to F-oBOH incorporated in AMP/Gd(3+) CNPs to give the opened-ring form of spirolactam resulting in the fourfold of fluorescence enhancement compared to Cu(2+) complexation without CN(-). Additionally, the log K value of F-oBOH-AMP/Gd(3+) CNPs⊂Cu(2+) toward CN(-) was 3.97 and the detection limits obtained from naked-eye and spectrofluorometry detections were 20μM and 4.03μM, respectively. The proposed method was demonstrated to detect CN(-) in drinking water with high accuracy. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Syntheses, crystal structures and fluorescent properties of Cd(II), Hg(II) and Ag(I) coordination polymers constructed from 1H-1,2,4-triazole-1-acetic acid

    International Nuclear Information System (INIS)

    Ding Degang; Xie Lixia; Fan Yaoting; Hou Hongwei; Xu Yan

    2009-01-01

    Three new d 10 coordination polymers, namely [Cd(taa)Cl] n 1, [Hg(taa)Cl] n 2, and [Ag 1.5 (taa)(NO 3 ) 0.5 ] n 3 (taa=1H-1,2,4-triazole-1-acatate anion) have been prepared and characterized by elemental analysis, IR, and single crystal X-ray diffraction. Compound 1 consists of two-dimensional layers constructed by carboxyl-linked helical chains, which are further linked through carboxyl group to generate a unique 3D open framework. Topological analysis reveals that the structure of 1 can be classified as an unprecedented (3,8)-connected network with the Schlaefli symbol (4.5 2 ) 2 (4 2 .5 8 .6 14 .7 3 .8). Compound 2 manifests a doubly interpenetrated decorated α-polonium cubic network with the Schlaefli symbol of (4 10 .6 2 .8 3 ). Compound 3 consists of 2D puckered layers made up of Ag centers and taa - bridges. In addition, all of these compounds are photoluminescent in the solid state with spectra that closely resemble those of the ligand precursor. - Graphical abstract: Three new compounds based on 1H-1,2,4-triazole-1-acetic acid and Cd(II), Hg(II) and Ag(I) salts display luminescent properties and may be potential candidates for luminescent materials.

  15. New coordination polymers from 1D chain, 2D layer to 3D framework constructed from 1,2-phenylenediacetic acid and 1,3-bis(4-pyridyl)propane flexible ligands

    Science.gov (United States)

    Xin, Ling-Yun; Liu, Guang-Zhen; Wang, Li-Ya

    2011-06-01

    The hydrothermal reactions of Cd, Zn, or Cu(II) acetate salts with H 2PHDA and BPP flexible ligands afford three new coordination polymers, including [Cd(PHDA)(BPP)(H 2O)] n(1), [Zn(PHDA)(BPP)] n(2), and [Cu 2(PHDA) 2(BPP)] n(3) (H 2PHDA=1,2-phenylenediacetic acid, BPP=1,3-bis(4-pyridyl)propane). The single-crystal X-ray diffractions reveal that all three complexes feature various metal carboxylate subunits extended further by the BPP ligands to form a diverse range of structures, displaying a remarked structural sensitivity to metal(II) cation. Complex 1 containing PHDA-bridged binuclear cadmium generates 1D double-stranded chain, complex 2 results in 2D→2D interpenetrated (4,4) grids, and complex 3 displays a 3D self-penetrated framework with 4 86 68 rob topology. In addition, fluorescent analyses show that both 1 and 2 exhibit intense blue-violet photoluminescence in the solid state.

  16. Modular construction, magnetic property, and luminescent sensing of 3D Mn(II) and Cd(II) coordination polymers based on p-terphenyl-2,2″,5″,5‴-tetracarboxylate acid

    Science.gov (United States)

    Fan, Liming; Zhang, Yujuan; Wang, Jiang; Zhao, Li; Wang, Xiaoqing; Hu, Tuoping; Zhang, Xiutang

    2018-04-01

    Two 3D modular designed coordination polymers, namely, {[H2N(CH3)2]2[Mn(TPT)]}n (1), and {[Cd(TPT)0.5(bib)]·0.5H2O}n (2) (H4TPT = p-terphenyl-2,2″,5″,5‴-tetracarboxylate acid, and bib = 1,3-bis((imidazol-1-yl) benzene) have been synthesized and structural characterized by EA, IR, TG, PXRD. Single-crystal X-ray diffraction analyses reveal that complex 1 is a 3D 4-connected {42.63.8}-sra net with the tiling modular being [42.62.82] = [4a.4b.62.8a.8b] (transitivity is 2451). While complex 2 is a 3D (4,4)-connected {64.82}{66}2-bbf net with tiling modular is [6.82]+[63.8] = [6 c.8a.8b]+[6a.6b.6 c.8a] (transitivity is 2352). The variable-temperature susceptibility of 1 has been investigated. Besides, complex 2 exhibits highly sensitive sensing of FeIII ions in DMF solution.

  17. Quantitative analysis of protein and gene expression in salivary glands of Sjogren's-like disease NOD mice treated by bone marrow soup.

    Directory of Open Access Journals (Sweden)

    Kaori Misuno

    Full Text Available BACKGROUND: Bone marrow cell extract (termed as BM Soup has been demonstrated to repair irradiated salivary glands (SGs and restore saliva secretion in our previous study. In the present study, we aim to investigate if the function of damaged SGs in non-obese diabetic (NOD mice can be restored by BM Soup treatment and the molecular alterations associated with the treatment. METHODS: Whole BM cells were lysed and soluble intracellular contents ("BM Soup" were injected I.V. into NOD mice. Tandem mass tagging with 2-D liquid chromatography-mass spectrometry was used to quantify proteins in the submandibular glands (SMGs between untreated and BM Soup-treated mice. Quantitative PCR was used to identify genes with altered expression in the treated mice. RESULTS BM SOUP: restored salivary flow rates to normal levels and significantly reduced the focus scores of SMGs in NOD mice. More than 1800 proteins in SMG cells were quantified by the proteomic approach. Many SMG proteins involved in inflammation and apoptosis were found to be down-regulated whereas those involved in salivary gland biology and development/regeneration were up-regulated in the BM Soup-treated mice. qPCR analysis also revealed expression changes of growth factors and cytokines in the SMGs of the treated NOD mice. CONCLUSION: BM Soup treatment is effective to restore the function of damaged SGs in NOD mice. Through gene/protein expression analysis, we have found that BM Soup treatment might effectuate via inhibiting apoptosis, focal adhesion and inflammation whereas promoting development, regeneration and differentiation of the SG cells in NOD mice. These findings provide important insights on the potential mechanisms underlying the BM Soup treatment for functional restoration of damaged SGs in NOD mice. Additional studies are needed to further confirm the identified target genes and their related signaling pathways that are responsible for the BM Soup treatment.

  18. Quantitative Analysis of Protein and Gene Expression in Salivary Glands of Sjogren’s-Like Disease NOD Mice Treated by Bone Marrow Soup

    Science.gov (United States)

    Misuno, Kaori; Khalili, Saeed; Huang, Junwei; Liu, Younan

    2014-01-01

    Background Bone marrow cell extract (termed as BM Soup) has been demonstrated to repair irradiated salivary glands (SGs) and restore saliva secretion in our previous study. In the present study, we aim to investigate if the function of damaged SGs in non-obese diabetic (NOD) mice can be restored by BM Soup treatment and the molecular alterations associated with the treatment. Methods Whole BM cells were lysed and soluble intracellular contents (“BM Soup”) were injected I.V. into NOD mice. Tandem mass tagging with 2-D liquid chromatography-mass spectrometry was used to quantify proteins in the submandibular glands (SMGs) between untreated and BM Soup-treated mice. Quantitative PCR was used to identify genes with altered expression in the treated mice. Results BM Soup restored salivary flow rates to normal levels and significantly reduced the focus scores of SMGs in NOD mice. More than 1800 proteins in SMG cells were quantified by the proteomic approach. Many SMG proteins involved in inflammation and apoptosis were found to be down-regulated whereas those involved in salivary gland biology and development/regeneration were up-regulated in the BM Soup-treated mice. qPCR analysis also revealed expression changes of growth factors and cytokines in the SMGs of the treated NOD mice. Conclusion BM Soup treatment is effective to restore the function of damaged SGs in NOD mice. Through gene/protein expression analysis, we have found that BM Soup treatment might effectuate via inhibiting apoptosis, focal adhesion and inflammation whereas promoting development, regeneration and differentiation of the SG cells in NOD mice. These findings provide important insights on the potential mechanisms underlying the BM Soup treatment for functional restoration of damaged SGs in NOD mice. Additional studies are needed to further confirm the identified target genes and their related signaling pathways that are responsible for the BM Soup treatment. PMID:24489858

  19. Quantitative analysis of protein and gene expression in salivary glands of Sjogren's-like disease NOD mice treated by bone marrow soup.

    Science.gov (United States)

    Misuno, Kaori; Tran, Simon D; Khalili, Saeed; Huang, Junwei; Liu, Younan; Hu, Shen

    2014-01-01

    Bone marrow cell extract (termed as BM Soup) has been demonstrated to repair irradiated salivary glands (SGs) and restore saliva secretion in our previous study. In the present study, we aim to investigate if the function of damaged SGs in non-obese diabetic (NOD) mice can be restored by BM Soup treatment and the molecular alterations associated with the treatment. Whole BM cells were lysed and soluble intracellular contents ("BM Soup") were injected I.V. into NOD mice. Tandem mass tagging with 2-D liquid chromatography-mass spectrometry was used to quantify proteins in the submandibular glands (SMGs) between untreated and BM Soup-treated mice. Quantitative PCR was used to identify genes with altered expression in the treated mice. restored salivary flow rates to normal levels and significantly reduced the focus scores of SMGs in NOD mice. More than 1800 proteins in SMG cells were quantified by the proteomic approach. Many SMG proteins involved in inflammation and apoptosis were found to be down-regulated whereas those involved in salivary gland biology and development/regeneration were up-regulated in the BM Soup-treated mice. qPCR analysis also revealed expression changes of growth factors and cytokines in the SMGs of the treated NOD mice. BM Soup treatment is effective to restore the function of damaged SGs in NOD mice. Through gene/protein expression analysis, we have found that BM Soup treatment might effectuate via inhibiting apoptosis, focal adhesion and inflammation whereas promoting development, regeneration and differentiation of the SG cells in NOD mice. These findings provide important insights on the potential mechanisms underlying the BM Soup treatment for functional restoration of damaged SGs in NOD mice. Additional studies are needed to further confirm the identified target genes and their related signaling pathways that are responsible for the BM Soup treatment.

  20. Symbiotic Burkholderia Species Show Diverse Arrangements of nif/fix and nod Genes and Lack Typical High-Affinity Cytochrome cbb3 Oxidase Genes.

    Science.gov (United States)

    De Meyer, Sofie E; Briscoe, Leah; Martínez-Hidalgo, Pilar; Agapakis, Christina M; de-Los Santos, Paulina Estrada; Seshadri, Rekha; Reeve, Wayne; Weinstock, George; O'Hara, Graham; Howieson, John G; Hirsch, Ann M

    2016-08-01

    Genome analysis of fourteen mimosoid and four papilionoid beta-rhizobia together with fourteen reference alpha-rhizobia for both nodulation (nod) and nitrogen-fixing (nif/fix) genes has shown phylogenetic congruence between 16S rRNA/MLSA (combined 16S rRNA gene sequencing and multilocus sequence analysis) and nif/fix genes, indicating a free-living diazotrophic ancestry of the beta-rhizobia. However, deeper genomic analysis revealed a complex symbiosis acquisition history in the beta-rhizobia that clearly separates the mimosoid and papilionoid nodulating groups. Mimosoid-nodulating beta-rhizobia have nod genes tightly clustered in the nodBCIJHASU operon, whereas papilionoid-nodulating Burkholderia have nodUSDABC and nodIJ genes, although their arrangement is not canonical because the nod genes are subdivided by the insertion of nif and other genes. Furthermore, the papilionoid Burkholderia spp. contain duplications of several nod and nif genes. The Burkholderia nifHDKEN and fixABC genes are very closely related to those found in free-living diazotrophs. In contrast, nifA is highly divergent between both groups, but the papilionoid species nifA is more similar to alpha-rhizobia nifA than to other groups. Surprisingly, for all Burkholderia, the fixNOQP and fixGHIS genes required for cbb3 cytochrome oxidase production and assembly are missing. In contrast, symbiotic Cupriavidus strains have fixNOQPGHIS genes, revealing a divergence in the evolution of two distinct electron transport chains required for nitrogen fixation within the beta-rhizobia.

  1. Explicitly computing geodetic coordinates from Cartesian coordinates

    Science.gov (United States)

    Zeng, Huaien

    2013-04-01

    This paper presents a new form of quartic equation based on Lagrange's extremum law and a Groebner basis under the constraint that the geodetic height is the shortest distance between a given point and the reference ellipsoid. A very explicit and concise formulae of the quartic equation by Ferrari's line is found, which avoids the need of a good starting guess for iterative methods. A new explicit algorithm is then proposed to compute geodetic coordinates from Cartesian coordinates. The convergence region of the algorithm is investigated and the corresponding correct solution is given. Lastly, the algorithm is validated with numerical experiments.

  2. Immuno-inhibitory PD-L1 can be induced by a peptidoglycan/NOD2 mediated pathway in primary monocytic cells and is deficient in Crohn's patients with homozygous NOD2 mutations.

    Science.gov (United States)

    Hewitt, Rachel E; Pele, Laetitia C; Tremelling, Mark; Metz, Andrew; Parkes, Miles; Powell, Jonathan J

    2012-05-01

    Peptidoglycan (PGN) is a ubiquitous bacterial membrane product that, despite its well known pro-inflammatory properties, has also been invoked in immuno-tolerance of the gastrointestinal tract. PGN-induced mucosal IL-10 secretion and downregulation of Toll like receptors are potential mechanisms of action in the gut but there are few data on tolerogenic adaptive immune responses and PGN. Here, using blood-derived mononuclear cells, we showed that PGN induced marked cell surface expression of PD-L1 but not PD-L2 or CD80/CD86, and specifically in the CD14(+) monocytic fraction. This was reproduced at the gene level with rapid induction (<4 h) and, unlike for LPS stimulation, was still sustained at 24 h. Using transfected and native muramyl dipeptide (MDP), which is a cleavage product of PGN and a specific NOD2 agonist, in assays with wild type cells or those from patients with Crohn's disease carrying the Leu1007 frameshift mutation of NOD2, we showed that (i) both NOD2 dependent and independent signalling (appearing TLR2 mediated) occurred for PGN upregulation of PD-L1 (ii) upregulation is lost in response to MDP in patients with the homozygous mutation and (iii) PD-L1 upregulation was unaffected in patients with heterozygous mutations as previously reported for cytokine responses to MDP. The uptake of PGN and its cleavage products by the intestinal mucosa is well recognised and further work should consider PD-L1 upregulation as one potential mechanism of the commensal flora-driven intestinal immuno-tolerance. Indeed, recent work has shown that loss of PD-L1 signalling in the gut breaks CD8(+) T cell tolerance to self antigen and leads to severe autoimmune enteritis. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Simulation in 3 dimensions of a cycle 18 months for an BWR type reactor using the Nod3D program; Simulacion en 3 dimensiones de un ciclo de 18 meses para un reactor BWR usando el programa Nod3D

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, N.; Alonso, G. [ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico)]. E-mail: nhm@nuclear.inin.mx; Valle, E. del [IPN, ESFM, 07738 Mexico D.F. (Mexico)

    2004-07-01

    The development of own codes that you/they allow the simulation in 3 dimensions of the nucleus of a reactor and be of easy maintenance, without the consequent payment of expensive use licenses, it can be a factor that propitiates the technological independence. In the Department of Nuclear Engineering (DIN) of the Superior School of Physics and Mathematics (ESFM) of the National Polytechnic Institute (IPN) a denominated program Nod3D has been developed with the one that one can simulate the operation of a reactor BWR in 3 dimensions calculating the effective multiplication factor (kJJ3, as well as the distribution of the flow neutronic and of the axial and radial profiles of the power, inside a means of well-known characteristics solving the equations of diffusion of neutrons numerically in stationary state and geometry XYZ using the mathematical nodal method RTN0 (Raviart-Thomas-Nedelec of index zero). One of the limitations of the program Nod3D is that it doesn't allow to consider the burnt of the fuel in an independent way considering feedback, this makes it in an implicit way considering the effective sections in each step of burnt and these sections are obtained of the code Core Master LEND. However even given this limitation, the results obtained in the simulation of a cycle of typical operation of a reactor of the type BWR are similar to those reported by the code Core Master LENDS. The results of the keJ - that were obtained with the program Nod3D they were compared with the results of the code Core Master LEND, presenting a difference smaller than 0.2% (200 pcm), and in the case of the axial profile of power, the maxim differs it was of 2.5%. (Author)

  4. Muramyl dipeptide (MDP) induces reactive oxygen species (ROS) generation via the NOD2/COX-2/NOX4 signaling pathway in human umbilical vein endothelial cells (HUVECs).

    Science.gov (United States)

    Kong, Ling-Jun; Liu, Xiao-Qian; Xue, Ying; Gao, Wei; Lv, Qian-Zhou

    2018-03-20

    Vascular endothelium dysfunction caused by oxidative stress accelerates the pathologic process of cardiovascular diseases. NOD2, an essential receptor of innate immune system, has been demonstrated to play a critical role in atherosclerosis. Here, the aim of our study was to investigate the effect and underlying molecular mechanism of muramyl dipeptide (MDP) on NOX4-mediated ROS generation in human umbilical vein endothelial cells (HUVECs). 2,7-dichlorofluorescein diacetate staining was to measure the intracellular ROS level and showed MDP promoted ROS production in a time- and dose-dependent manner. The mRNA and protein levels of NOX4 and COX-2 were detected by real-time PCR and western blot. Small interfering RNA (siRNA) was used to silence NOD2 or COX-2 gene expression and investigate the mechanism of NOD2-mediated signaling pathway in HUVECs. Data showed that MDP induced NOX4 and COX-2 expression in a time- and dose-dependent manner. NOD2 knock-down suppressed up-regulation of COX-2 and NOX4 in HUVECs treated with MDP. Furthermore, silence of COX-2 in HUVECs down-regulated the NOX4 expression after MDP stimulation. Collectively, we indicated that NOD2 played a leading role in MDP-induced COX-2/NOX4/ROS signaling pathway in HUVECs, which was a novel regulatory mechanism in the progress of ROS generation.

  5. NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway

    Science.gov (United States)

    Watanabe, Tomohiro; Asano, Naoki; Fichtner-Feigl, Stefan; Gorelick, Peter L.; Tsuji, Yoshihisa; Matsumoto, Yuko; Chiba, Tsutomu; Fuss, Ivan J.; Kitani, Atsushi; Strober, Warren

    2010-01-01

    Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular epithelial cell protein known to play a role in host defense at mucosal surfaces. Here we show that a ligand specific for NOD1, a peptide derived from peptidoglycan, initiates an unexpected signaling pathway in human epithelial cell lines that results in the production of type I IFN. Detailed analysis revealed the components of the signaling pathway. NOD1 binding to its ligand triggered activation of the serine-threonine kinase RICK, which was then able to bind TNF receptor–associated factor 3 (TRAF3). This in turn led to activation of TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε) and the subsequent activation of IFN regulatory factor 7 (IRF7). IRF7 induced IFN-β production, which led to activation of a heterotrimeric transcription factor complex known as IFN-stimulated gene factor 3 (ISGF3) and the subsequent production of CXCL10 and additional type I IFN. In vivo studies showed that mice lacking the receptor for IFN-β or subjected to gene silencing of the ISGF3 component Stat1 exhibited decreased CXCL10 responses and increased susceptibility to Helicobacter pylori infection, phenotypes observed in NOD1-deficient mice. These studies thus establish that NOD1 can activate the ISGF3 signaling pathway that is usually associated with protection against viral infection to provide mice with robust type I IFN–mediated protection from H. pylori and possibly other mucosal infections. PMID:20389019

  6. Diabetes-Resistant NOR Mice Are More Severely Affected by Streptozotocin Compared to the Diabetes-Prone NOD Mice: Correlations with Liver and Kidney GLUT2 Expressions

    Directory of Open Access Journals (Sweden)

    S. Kahraman

    2015-01-01

    Full Text Available Nonobese Diabetic (NOD mice are susceptible strains for Type 1 diabetes development, and Nonobese Diabetes-Resistant (NOR mice are defined as suitable controls for NOD mice in non-MHC-related research. Diabetes is often accelerated in NOD mice via Streptozotocin (STZ. STZ is taken inside cells via GLUT2 transmembrane carrier proteins, the major glucose transporter isoforms in pancreatic beta cells, liver, kidneys, and the small intestine. We observed severe adverse effects in NOR mice treated with STZ compared to NOD mice that were made diabetic with a similar dose. We suggested that the underlying mechanism could be differential GLUT2 expressions in pancreatic beta cells, yet immunofluorescent and immunohistochemical studies revealed similar GLUT2 expression levels. We also detected GLUT2 expression profiles in NOD and NOR hepatic and renal tissues by western blot analysis and observed considerably higher GLUT2 expression levels in liver and kidney tissues of NOR mice. Although beta cell GLUT2 expression levels are frequently evaluated as a marker predicting STZ sensitivity in animal models, we report here very different diabetic responses to STZ in two different animal strains, in spite of similar initial GLUT2 expressions in beta cells. Furthermore, use of NOR mice in STZ-mediated experimental diabetes settings should be considered accordingly.

  7. Type 1 Diabetes Prone NOD Mice Have Diminished Cxcr1 mRNA Expression in Polymorphonuclear Neutrophils and CD4+ T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    Karine Haurogné

    Full Text Available In humans, CXCR1 and CXCR2 are two homologous proteins that bind ELR+ chemokines. Both receptors play fundamental roles in neutrophil functions such as migration and reactive oxygen species production. Mouse Cxcr1 and Cxcr2 genes are located in an insulin-dependent diabetes genetic susceptibility locus. The non obese diabetic (NOD mouse is a spontaneous well-described animal model for insulin-dependent type 1 diabetes. In this disease, insulin deficiency results from the destruction of insulin-producing beta cells by autoreactive T lymphocytes. This slow-progressing disease is dependent on both environmental and genetic factors. Here, we report descriptive data about the Cxcr1 gene in NOD mice. We demonstrate decreased expression of mRNA for Cxcr1 in neutrophils and CD4+ lymphocytes isolated from NOD mice compared to other strains, related to reduced NOD Cxcr1 gene promoter activity. Looking for Cxcr1 protein, we next analyze the membrane proteome of murine neutrophils by mass spectrometry. Although Cxcr2 protein is clearly found in murine neutrophils, we did not find evidence of Cxcr1 peptides using this method. Nevertheless, in view of recently-published experimental data obtained in NOD mice, we argue for possible Cxcr1 involvement in type 1 diabetes pathogenesis.

  8. Double negative (CD3+ 4- 8- TCR alphabeta splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Beverly Duncan

    2010-07-01

    Full Text Available Double negative CD3(+4(-8(- TCR alphabeta splenic cells (DNCD3 can suppress the immune responses to allo and xenografts, infectious agents, tumors, and some autoimmune disorders. However, little is known about their role in autoimmune diabetes, a disease characterized by the reduction of insulin production subsequent to destruction of pancreatic beta-cells by a polyclonal population of self-reactive T-cells. Herein, we analyzed the function and phenotype of DNCD3 splenic cells in young NOD mice predisposed to several autoimmune disorders among which, the human-like autoimmune diabetes.DNCD3 splenic cells from young NOD mice (1 provided long-lasting protection against diabetes transfer in NOD/Scid immunodeficient mice, (2 proliferated and differentiated in the spleen and pancreas of NOD/Scid mice and pre-diabetic NOD mice into IL-10-secreting T(R-1 like cells in a Th2-like environment, and (3 their anti-diabetogenic phenotype is CD3(+(CD4(-CD8(-CD28(+CD69(+CD25(low Foxp3(- iCTLA-4(-TCR alphabeta(+ with a predominant Vbeta13 gene usage.These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4(+CD25(high Foxp3(+T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes.

  9. Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice.

    Directory of Open Access Journals (Sweden)

    Aude Aumeunier

    Full Text Available BACKGROUND: Infections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. METHODS AND FINDINGS: Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL-10 and transforming growth factor (TGF-beta and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. CONCLUSIONS/SIGNIFICANCE: These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses

  10. Autophosphorylation is essential for the in vivo function of the Lotus japonicus Nod factor receptor 1 and receptor-mediated signalling in cooperation with Nod factor receptor 5

    DEFF Research Database (Denmark)

    Madsen, Esben B; Antolín-Llovera, Meritxell; Grossmann, Christina

    2011-01-01

    and cloning of downstream components, little is known about the activation and signalling mechanisms of the Nod-factor receptors themselves. Here we show that both receptor proteins localize to the plasma membrane, and present evidence for heterocomplex formation initiating downstream signalling. Expression...... of NFR1 and NFR5 in Nicotiana benthamiana and Allium ampeloprasum (leek) cells caused a rapid cell-death response. The signalling leading to cell death was abrogated using a kinase-inactive variant of NFR1. In these surviving cells, a clear interaction between NFR1 and NFR5 was detected in vivo through...

  11. The curvature coordinate system

    DEFF Research Database (Denmark)

    Almegaard, Henrik

    2007-01-01

    The paper describes a concept for a curvature coordinate system on regular curved surfaces from which faceted surfaces with plane quadrangular facets can be designed. The lines of curvature are used as parametric lines for the curvature coordinate system on the surface. A new conjugate set of lin...

  12. Coordinate measuring machines

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    This document is used in connection with three exercises of 2 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercises concern three aspects of coordinate measuring: 1) Measuring and verification of tolerances on coordinate measuring machines, 2) Traceabilit...... and uncertainty during coordinate measurements, 3) Digitalisation and Reverse Engineering. This document contains a short description of each step in the exercise and schemes with room for taking notes of the results.......This document is used in connection with three exercises of 2 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercises concern three aspects of coordinate measuring: 1) Measuring and verification of tolerances on coordinate measuring machines, 2) Traceability...

  13. Syntheses, structures and photoluminescent properties of Zn(Ⅱ)/Co(Ⅱ) coordination polymers based on flexible tetracarboxylate ligand of 5,5′-(butane-1,4-diyl)-bis(oxy)-di isophthalic acid

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yan-Peng [Inner Mongolia Key Lab Chem & Phys Rare Earth Mat, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021 (China); Department of Chemistry and Chemical Engineering, Ordos College of Inner Mongolia University, Ordos 017000 (China); Department of Chemistry and Chemical Engineering, Ordos Applied Technology College, Ordos 017000 (China); Guo, Le [Department of Chemistry and Chemical Engineering, Ordos College of Inner Mongolia University, Ordos 017000 (China); Department of Chemistry and Chemical Engineering, Ordos Applied Technology College, Ordos 017000 (China); Dong, Wei; Jia, Min; Zhang, Jing-Xue; Sun, Zhong [Inner Mongolia Key Lab Chem & Phys Rare Earth Mat, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021 (China); Chang, Fei, E-mail: ndchfei@imu.edu.cn [Inner Mongolia Key Lab Chem & Phys Rare Earth Mat, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021 (China)

    2016-08-15

    Three new mixed-ligand metal-organic frameworks based on 5,5′-(butane-1,4- diyl)-bis(oxy)-diisophthalic acid and transitional metal cations with the help of two ancillary bridging N-donor pyridyl and imidazole linkers, [Zn(L){sub 0.5}(4,4′-bpy)]·2(H{sub 2}O) (1), [M(L){sub 0.5}(bib)]·4(H{sub 2}O) (M = Zn (2), Co (3)), (4,4′-bpy=4,4′–bipyridine, bib=1,4-bis (1H-imidazol-1-yl)-butane), have been synthesized under solvothermal conditions. Their structures and properties were determined by single-crystal and powder X-ray diffraction analyses, IR spectra, elemental analyses and thermogravimetric analyses (TGA). Compounds 1–3 display a 3D 3-fold interpenetrated frameworks linked by the L{sup 4−} ligands, ancillary N-donor linkers and the free water molecules in the crystal lattice. Topological analysis reveals that 1–3 are a (4,4)-connected bbf topology net with the (6{sup 4}·8{sup 2})(6{sup 6}) topology. The effects of the L{sup 4−} anions, the N-donor ligands, and the metal ions on the structures of the coordination polymers have been discussed. Furthermore, luminescence properties and thermogravimetric properties of these compounds were investigated. - Graphical abstract: Three new compounds of MOFs have been prepared and characterized. The luminescence properties and thermogravimetric properties of compounds were investigated. Display Omitted.

  14. Simulation in 3 dimensions of a cycle 18 months for an BWR type reactor using the Nod3D program

    International Nuclear Information System (INIS)

    Hernandez, N.; Alonso, G.; Valle, E. del

    2004-01-01

    The development of own codes that you/they allow the simulation in 3 dimensions of the nucleus of a reactor and be of easy maintenance, without the consequent payment of expensive use licenses, it can be a factor that propitiates the technological independence. In the Department of Nuclear Engineering (DIN) of the Superior School of Physics and Mathematics (ESFM) of the National Polytechnic Institute (IPN) a denominated program Nod3D has been developed with the one that one can simulate the operation of a reactor BWR in 3 dimensions calculating the effective multiplication factor (kJJ3, as well as the distribution of the flow neutronic and of the axial and radial profiles of the power, inside a means of well-known characteristics solving the equations of diffusion of neutrons numerically in stationary state and geometry XYZ using the mathematical nodal method RTN0 (Raviart-Thomas-Nedelec of index zero). One of the limitations of the program Nod3D is that it doesn't allow to consider the burnt of the fuel in an independent way considering feedback, this makes it in an implicit way considering the effective sections in each step of burnt and these sections are obtained of the code Core Master LEND. However even given this limitation, the results obtained in the simulation of a cycle of typical operation of a reactor of the type BWR are similar to those reported by the code Core Master LENDS. The results of the keJ - that were obtained with the program Nod3D they were compared with the results of the code Core Master LEND, presenting a difference smaller than 0.2% (200 pcm), and in the case of the axial profile of power, the maxim differs it was of 2.5%. (Author)

  15. β-cell-specific IL-2 therapy increases islet Foxp3+Treg and suppresses type 1 diabetes in NOD mice.

    Science.gov (United States)

    Johnson, Mark C; Garland, Alaina L; Nicolson, Sarah C; Li, Chengwen; Samulski, R Jude; Wang, Bo; Tisch, Roland

    2013-11-01

    Interleukin-2 (IL-2) is a critical cytokine for the homeostasis and function of forkhead box p3-expressing regulatory T cells (Foxp3(+)Tregs). Dysregulation of the IL-2-IL-2 receptor axis is associated with aberrant Foxp3(+)Tregs and T cell-mediated autoimmune diseases such as type 1 diabetes. Treatment with recombinant IL-2 has been reported to enhance Foxp3(+)Tregs and suppress different models of autoimmunity. However, efficacy of IL-2 therapy is dependent on achieving sufficient levels of IL-2 to boost tissue-resident Foxp3(+)Tregs while avoiding the potential toxic effects of systemic IL-2. With this in mind, adeno-associated virus (AAV) vector gene delivery was used to localize IL-2 expression to the islets of NOD mice. Injection of a double-stranded AAV vector encoding IL-2 driven by a mouse insulin promoter (dsAAVmIP-IL2) increased Foxp3(+)Tregs in the islets but not the draining pancreatic lymph nodes. Islet Foxp3(+)Tregs in dsAAVmIP-IL2-treated NOD mice exhibited enhanced fitness marked by increased expression of Bcl-2, proliferation, and suppressor function. In contrast, ectopic IL-2 had no significant effect on conventional islet-infiltrating effector T cells. Notably, β-cell-specific IL-2 expression suppressed late preclinical type 1 diabetes in NOD mice. Collectively, these findings demonstrate that β-cell-specific IL-2 expands an islet-resident Foxp3(+)Tregs pool that effectively suppresses ongoing type 1 diabetes long term.

  16. Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice.

    Directory of Open Access Journals (Sweden)

    Karsten Buschard

    Full Text Available BACKGROUND: Ethanol ('alcohol' is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. METHODS: The study included cellular in vitro tests using α-galactosylceramide (αGalCer, and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. RESULTS: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05. CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05, whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. CONCLUSION: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.

  17. Structures of NodZ α1,6-fucosyltransferase in complex with GDP and GDP-fucose.

    Science.gov (United States)

    Brzezinski, Krzysztof; Dauter, Zbigniew; Jaskolski, Mariusz

    2012-02-01

    Rhizobial NodZ α1,6-fucosyltransferase (α1,6-FucT) catalyzes the transfer of the fucose (Fuc) moiety from guanosine 5'-diphosphate-β-L-fucose to the reducing end of the chitin oligosaccharide core during Nod-factor (NF) biosynthesis. NF is a key signalling molecule required for successful symbiosis with a legume host for atmospheric nitrogen fixation. To date, only two α1,6-FucT structures have been determined, both without any donor or acceptor molecule that could highlight the structural background of the catalytic mechanism. Here, the first crystal structures of α1,6-FucT in complex with its substrate GDP-Fuc and with GDP, which is a byproduct of the enzymatic reaction, are presented. The crystal of the complex with GDP-Fuc was obtained through soaking of native NodZ crystals with the ligand and its structure has been determined at 2.35 Å resolution. The fucose residue is exposed to solvent and is disordered. The enzyme-product complex crystal was obtained by cocrystallization with GDP and an acceptor molecule, penta-N-acetyl-L-glucosamine (penta-NAG). The structure has been determined at 1.98 Å resolution, showing that only the GDP molecule is present in the complex. In both structures the ligands are located in a cleft formed between the two domains of NodZ and extend towards the C-terminal domain, but their conformations differ significantly. The structures revealed that residues in three regions of the C-terminal domain, which are conserved among α1,2-, α1,6- and protein O-fucosyltransferases, are involved in interactions with the sugar-donor molecule. There is also an interaction with the side chain of Tyr45 in the N-terminal domain, which is very unusual for a GT-B-type glycosyltransferase. Only minor conformational changes of the protein backbone are observed upon ligand binding. The only exception is a movement of the loop located between strand βC2 and helix αC3. In addition, there is a shift of the αC3 helix itself upon GDP

  18. Prevention of diabetes in NOD mice by repeated exposures to a contact allergen inducing a sub-clinical dermatitis

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Buschard, Karsten; Hansen, Axel Jacob Kornerup

    2010-01-01

    Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect...... of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two...

  19. Gluten-free but also gluten-enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes

    DEFF Research Database (Denmark)

    Funda, D.P.; Kaas, A.; Tlaskalova-Hogenova, H.

    2008-01-01

    BACKGROUND: Environmental factors such as nutrition or exposure to infections play a substantial role in the pathogenesis of type 1 diabetes (T1D). We have previously shown that gluten-free, non-purified diet largely prevented diabetes in non-obese diabetic (NOD) mice. In this study we tested...... hypothesis that early introduction of gluten-enriched (gluten+) diet may increase diabetes incidence in NOD mice. METHODS: Standard, gluten-free, gluten+ modified Altromin diets and hydrolysed-casein-based Pregestimil diet were fed to NOD females and diabetes incidence was followed for 310 days. Insulitis...... score and numbers of gut mucosal lymphocytes were determined in non-diabetic animals. RESULTS: A significantly lower diabetes incidence (p diet (5.9%, n = 34) and Pregestimil diet (10%, n = 30) compared to mice on the standard Altromin diet (60.6%, n...

  20. Candidate chromosome 1 disease susceptibility genes for Sjogren’s syndrome xerostomia are narrowed by novel NOD.B10 congenic mice

    Science.gov (United States)

    Mongini, Patricia K. A.; Kramer, Jill M.; Ishikawa, Tomo-o; Herschman, Harvey; Esposito, Donna

    2014-01-01

    Sjogren’s syndrome (SS) is characterized by salivary gland leukocytic infiltrates and impaired salivation (xerostomia). Cox-2 (Ptgs2) is located on chromosome 1 within the span of the Aec2 region. In an attempt to demonstrate that COX-2 drives antibody-dependent hyposalivation, NOD.B10 congenic mice bearing a Cox-2flox gene were generated. A congenic line with non-NOD alleles in Cox-2-flanking genes failed manifest xerostomia. Further backcrossing yielded disease-susceptible NOD.B10 Cox-2flox lines; fine genetic mapping determined that critical Aec2 genes lie within a 1.56 to 2.17 Mb span of DNA downstream of Cox-2. Bioinformatics analysis revealed that susceptible and non-susceptible lines exhibit non-synonymous coding SNPs in 8 protein-encoding genes of this region, thereby better delineating candidate Aec2 alleles needed for SS xerostomia. PMID:24685748

  1. Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR and Inflammation: Focus on the Gastrointestinal (GI Tract

    Directory of Open Access Journals (Sweden)

    Evagelia Spanou

    2017-05-01

    Full Text Available The fundamental role of human Toll-like receptors (TLRs and NOD-like receptors (NLRs, the two most studied pathogen recognition receptors (PRRs, is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR/NLR gene mutations and susceptibility to inflammatory, autoimmune, and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms. We briefly review the impact of TLR4 and NOD1/NOD2 and their genetic variability in the process of inflammation, tumorigenesis and DNA repair, focusing in the gastrointestinal tract. We also review the available data on new therapeutic strategies utilizing TLR/NLR agonists and antagonists for cancer, allergic diseases, viral infections and vaccine development against both infectious diseases and cancer.

  2. Three phylogenetic groups of nodA and nifH genes in Sinorhizobium and Mesorhizobium isolates from leguminous trees growing in Africa and Latin America.

    Science.gov (United States)

    Haukka, K; Lindström, K; Young, J P

    1998-02-01

    The diversity and phylogeny of nodA and nifH genes were studied by using 52 rhizobial isolates from Acacia senegal, Prosopis chilensis, and related leguminous trees growing in Africa and Latin America. All of the strains had similar host ranges and belonged to the genera Sinorhizobium and Mesorhizobium, as previously determined by 16S rRNA gene sequence analysis. The restriction patterns and a sequence analysis of the nodA and nifH genes divided the strains into the following three distinct groups: sinorhizobia from Africa, sinorhizobia from Latin America, and mesorhizobia from both regions. In a phylogenetic tree also containing previously published sequences, the nodA genes of our rhizobia formed a branch of their own, but within the branch no correlation between symbiotic genes and host trees was apparent. Within the large group of African sinorhizobia, similar symbiotic gene types were found in different chromosomal backgrounds, suggesting that transfer of symbiotic genes has occurred across species boundaries. Most strains had plasmids, and the presence of plasmid-borne nifH was demonstrated by hybridization for some examples. The nodA and nifH genes of Sinorhizobium teranga ORS1009T grouped with the nodA and nifH genes of the other African sinorhizobia, but Sinorhizobium saheli ORS609T had a totally different nodA sequence, although it was closely related based on the 16S rRNA gene and nifH data. This might be because this S. saheli strain was originally isolated from Sesbania sp., which belongs to a different cross-nodulation group than Acacia and Prosopis spp. The factors that appear to have influenced the evolution of rhizobial symbiotic genes vary in importance at different taxonomic levels.

  3. TNF{alpha} and IL-1{beta} are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Wenwen; Zheng, Xuexing [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Liu, Shue [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Ouyang, Hongsheng [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Levitt, Roy C.; Candiotti, Keith A. [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Hao, Shuanglin, E-mail: shao@med.miami.edu [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer LPS induces proinflammatory cytokine release in HAPI cells. Black-Right-Pointing-Pointer JNK pathway is dependent on TLR4 signaling to release cytokines. Black-Right-Pointing-Pointer NF-{kappa}B pathway is dependent on Nod1 signaling to release cytokines. -- Abstract: A growing body of evidence recently suggests that glial cell activation plays an important role in several neurodegenerative diseases and neuropathic pain. Microglia in the central nervous system express toll-like receptor 4 (TLR4) that is traditionally accepted as the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4 signaling pathways to induce the production of proinflammatory molecules. In the present studies, we verified the LPS signaling pathways using cultured highly aggressively proliferating immortalized (HAPI) microglial cells. We found that HAPI cells treated with LPS upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-{kappa}B (pNF-{kappa}B), TNF{alpha} and IL-1{beta}. Silencing TLR4 with siRNA reduced the expression of pJNK, TNF{alpha} and IL-1{beta}, but not pNF-{kappa}B in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNF{alpha} and IL-1{beta}. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-{kappa}B. Inhibition of NF-{kappa}B also reduced the expression of TNF{alpha} and IL-1{beta}. Nod1 ligand, DAP induced the upregulation of pNF-{kappa}B which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-{kappa}B is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-{kappa}B pathways is involved in the expression of TNF{alpha} and IL-1{beta}.

  4. A NodD-like protein activates transcription of genes involved with naringenin degradation in a flavonoid-dependent manner in Herbaspirillum seropedicae.

    Science.gov (United States)

    Wassem, R; Marin, A M; Daddaoua, A; Monteiro, R A; Chubatsu, L S; Ramos, J L; Deakin, W J; Broughton, W J; Pedrosa, F O; Souza, E M

    2017-03-01

    Herbaspirillum seropedicae is an associative, endophytic non-nodulating diazotrophic bacterium that colonises several grasses. An ORF encoding a LysR-type transcriptional regulator, very similar to NodD proteins of rhizobia, was identified in its genome. This nodD-like gene, named fdeR, is divergently transcribed from an operon encoding enzymes involved in flavonoid degradation (fde operon). Apigenin, chrysin, luteolin and naringenin strongly induce transcription of the fde operon, but not that of the fdeR, in an FdeR-dependent manner. The intergenic region between fdeR and fdeA contains several generic LysR consensus sequences (T-N 11 -A) and we propose a binding site for FdeR, which is conserved in other bacteria. DNase I foot-printing revealed that the interaction with the FdeR binding site is modified by the four flavonoids that stimulate transcription of the fde operon. Moreover, FdeR binds naringenin and chrysin as shown by isothermal titration calorimetry. Interestingly, FdeR also binds in vitro to the nod-box from the nodABC operon of Rhizobium sp. NGR234 and is able to activate its transcription in vivo. These results show that FdeR exhibits two features of rhizobial NodD proteins: nod-box recognition and flavonoid-dependent transcription activation, but its role in H. seropedicae and related organisms seems to have evolved to control flavonoid metabolism. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  5. The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.

    Directory of Open Access Journals (Sweden)

    Wouter Beumer

    Full Text Available Two major dendritic cell (DC subsets have been described in the pancreas of mice: The CD11c+ CD8α- DCs (strong CD4+ T cell proliferation inducers and the CD8α+ CD103+ DCs (T cell apoptosis inducers. Here we analyzed the larger subset of CD11c+ CD8α- DCs isolated from the pancreas of pre-diabetic NOD mice for genome-wide gene expression (validated by Q-PCR to elucidate abnormalities in underlying gene expression networks. CD11c+ CD8α- DCs were isolated from 5 week old NOD and control C57BL/6 pancreas. The steady state pancreatic NOD CD11c+ CD8α- DCs showed a reduced expression of several gene networks important for the prime functions of these cells, i.e. for cell renewal, immune tolerance induction, migration and for the provision of growth factors including those for beta cell regeneration. A functional in vivo BrdU incorporation test showed the reduced proliferation of steady state pancreatic DC. The reduced expression of tolerance induction genes (CD200R, CCR5 and CD24 was supported on the protein level by flow cytometry. Also previously published functional tests on maturation, immune stimulation and migration confirm the molecular deficits of NOD steady state DC. Despite these deficiencies NOD pancreas CD11c+ CD8α- DCs showed a hyperreactivity to LPS, which resulted in an enhanced pro-inflammatory state characterized by a gene profile of an enhanced expression of a number of classical inflammatory cytokines. The enhanced up-regulation of inflammatory genes was supported by the in vitro cytokine production profile of the DCs. In conclusion, our data show that NOD pancreatic CD11c+ CD8α- DCs show various deficiencies in steady state, while hyperreactive when encountering a danger signal such as LPS.

  6. Regional transit coordination guidebook.

    Science.gov (United States)

    2009-01-01

    Constant growth in rural areas and extensive suburban development have contributed to increasingly more people needing seamless and adequate public transportation into and from nearby cities. Coordinating existing services or determining the need for...

  7. Supercritical Airfoil Coordinates

    Data.gov (United States)

    National Aeronautics and Space Administration — Rectangular Supercritical Wing (Ricketts) - design and measured locations are provided in an Excel file RSW_airfoil_coordinates_ricketts.xls . One sheet is with Non...

  8. Developmental coordination disorder

    Science.gov (United States)

    Developmental coordination disorder can lead to: Learning problems Low self-esteem resulting from poor ability at sports and teasing by other children Repeated injuries Weight gain as a result of not wanting to participate ...

  9. Environmental Compliance Issue Coordination

    Science.gov (United States)

    An order to establish the Department of Energy (DOE) requirements for coordination of significant environmental compliance issues to ensure timely development and consistent application of Departmental environmental policy and guidance

  10. Data Management Coordinators (DMC)

    Science.gov (United States)

    The Regional Data Management Coordinators (DMCs) were identified to serve as the primary contact for each region for all Water Quality Framework activities. They will facilitate and communicate information to the necessary individuals at the region and tra

  11. Association of NOD2 and IL23R with Inflammatory Bowel Disease in Puerto Rico

    Science.gov (United States)

    Ballester, Veroushka; Guo, Xiuqing; Vendrell, Roberto; Haritunians, Talin; Klomhaus, Alexandra M.; Li, Dalin; McGovern, Dermot P. B.; Rotter, Jerome I.; Torres, Esther A.; Taylor, Kent D.

    2014-01-01

    The Puerto Rico population may be modeled as an admixed population with contributions from three continents: Sub-Saharan Africa, Ancient America, and Europe. Extending the study of the genetics of inflammatory bowel disease (IBD) to an admixed population such as Puerto Rico has the potential to shed light on IBD genes identified in studies of European populations, find new genes contributing to IBD susceptibility, and provide basic information on IBD for the care of US patients of Puerto Rican and Latino descent. In order to study the association between immune-related genes and Crohn’s disease (CD) and ulcerative colitis (UC) in Puerto Rico, we genotyped 1159 Puerto Rican cases, controls, and family members with the ImmunoChip. We also genotyped 832 subjects from the Human Genome Diversity Panel to provide data for estimation of global and local continental ancestry. Association of SNPs was tested by logistic regression corrected for global continental descent and family structure. We observed the association between Crohn’s disease and NOD2 (rs17313265, 0.28 in CD, 0.19 in controls, OR 1.5, p = 9×10−6) and IL23R (rs11209026, 0.026 in CD, 0.0.071 in controls, OR 0.4, p = 3.8×10−4). The haplotype structure of both regions resembled that reported for European populations and “local” continental ancestry of the IL23R gene was almost entirely of European descent. We also observed suggestive evidence for the association of the BAZ1A promoter SNP with CD (rs1200332, 0.45 in CD, 0.35 in controls, OR 1.5, p = 2×10−6). Our estimate of continental ancestry surrounding this SNP suggested an origin in Ancient America for this putative susceptibility region. Our observations underscored the great difference between global continental ancestry and local continental ancestry at the level of the individual gene, particularly for immune-related loci. PMID:25259511

  12. Association of NOD2 and IL23R with inflammatory bowel disease in Puerto Rico.

    Directory of Open Access Journals (Sweden)

    Veroushka Ballester

    Full Text Available The Puerto Rico population may be modeled as an admixed population with contributions from three continents: Sub-Saharan Africa, Ancient America, and Europe. Extending the study of the genetics of inflammatory bowel disease (IBD to an admixed population such as Puerto Rico has the potential to shed light on IBD genes identified in studies of European populations, find new genes contributing to IBD susceptibility, and provide basic information on IBD for the care of US patients of Puerto Rican and Latino descent. In order to study the association between immune-related genes and Crohn's disease (CD and ulcerative colitis (UC in Puerto Rico, we genotyped 1159 Puerto Rican cases, controls, and family members with the ImmunoChip. We also genotyped 832 subjects from the Human Genome Diversity Panel to provide data for estimation of global and local continental ancestry. Association of SNPs was tested by logistic regression corrected for global continental descent and family structure. We observed the association between Crohn's disease and NOD2 (rs17313265, 0.28 in CD, 0.19 in controls, OR 1.5, p = 9×10-6 and IL23R (rs11209026, 0.026 in CD, 0.0.071 in controls, OR 0.4, p = 3.8×10-4. The haplotype structure of both regions resembled that reported for European populations and "local" continental ancestry of the IL23R gene was almost entirely of European descent. We also observed suggestive evidence for the association of the BAZ1A promoter SNP with CD (rs1200332, 0.45 in CD, 0.35 in controls, OR 1.5, p = 2×10-6. Our estimate of continental ancestry surrounding this SNP suggested an origin in Ancient America for this putative susceptibility region. Our observations underscored the great difference between global continental ancestry and local continental ancestry at the level of the individual gene, particularly for immune-related loci.

  13. Coordinating Work with Groupware

    DEFF Research Database (Denmark)

    Pors, Jens Kaaber; Simonsen, Jesper

    2003-01-01

    One important goal of employing groupware is to make possible complex collaboration between geographically distributed groups. This requires a dual transformation of both technology and work practice. The challenge is to re­duce the complexity of the coordination work by successfully inte....... Using the CSCW frame­work of coordination mechanisms, we have elicited six general factors influencing the integration of the groupware application in two situations....

  14. Luminescent lanthanide coordination polymers

    Energy Technology Data Exchange (ETDEWEB)

    Ma, L.; Evans, O.R.; Foxman, B.M.; Lin, W.

    1999-12-13

    One-dimensional lanthanide coordination polymers with the formula Ln(isonicotinate){sub 3}(H{sub 2}O){sub 2} (Ln = Ce, Pr, Nd, Sm, Eu, Tb; 1a-f) were synthesized by treating nitrate or perchlorate salts of Ln(III) with 4-pyridinecarboxaldehyde under hydro(solvo)thermal conditions. Single-crystal and powder X-ray diffraction studies indicate that these lanthanide coordination polymers adopt two different structures. While Ce(III), Pr(III), and Nd(III) complexes adopt a chain structure with alternating Ln-(carboxylate){sub 2}-Ln and Ln-(carboxylate){sub 4}-Ln linkages, Sm(III), Eu(III), and Tb(III) complexes have a doubly carboxylate-bridged infinite-chain structure with one chelating carboxylate group on each metal center. In both structures, the lanthanide centers also bind to two water molecules to yield an eight-coordinate, square antiprismatic geometry. The pyridine nitrogen atoms of the isonicotinate groups do not coordinate to the metal centers in these lanthanide(III) complexes; instead, they direct the formation of Ln(III) coordination polymers via hydrogen bonding with coordinated water molecules. Photoluminescence measurements show that Tb(isonicotinate){sub 3}(H{sub 2}O){sub 2} is highly emissive at room temperature with a quantum yield of {approximately}90%. These results indicate that highly luminescent lanthanide coordination polymers can be assembled using a combination of coordination and hydrogen bonds. Crystal data for 1a: monoclinic space group P2{sub 1}/c, a = 9.712(2) {angstrom}, b = 19.833(4) {angstrom}, c = 11.616(2) {angstrom}, {beta} = 111.89(3){degree}, Z = 4. Crystal data for 1f: monoclinic space group C2/c, a = 20.253(4) {angstrom}, b = 11.584(2) {angstrom}, c = 9.839(2) {angstrom}, {beta} = 115.64(3){degree}, Z = 8.

  15. Coordinate-invariant regularization

    International Nuclear Information System (INIS)

    Halpern, M.B.

    1987-01-01

    A general phase-space framework for coordinate-invariant regularization is given. The development is geometric, with all regularization contained in regularized DeWitt Superstructures on field deformations. Parallel development of invariant coordinate-space regularization is obtained by regularized functional integration of the momenta. As representative examples of the general formulation, the regularized general non-linear sigma model and regularized quantum gravity are discussed. copyright 1987 Academic Press, Inc

  16. MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset.

    Directory of Open Access Journals (Sweden)

    Hannelie Korf

    Full Text Available Macrophages contribute in the initiation and progression of insulitis during type 1 diabetes (T1D. However, the mechanisms governing their recruitment into the islets as well as the manner of retention and activation are incompletely understood. Here, we investigated a role for macrophage migration inhibitory factor (MIF and its transmembrane receptor, CD74, in the progression of T1D. Our data indicated elevated MIF concentrations especially in long-standing T1D patients and mice. Additionally, NOD mice featured increased MIF gene expression and CD74+ leukocyte frequencies in the pancreas. We identified F4/80+ macrophages as the main immune cells in the pancreas expressing CD74 and showed that MIF antagonism of NOD macrophages prevented their activation-induced cytokine production. The physiological importance was highlighted by the fact that inhibition of MIF delayed the onset of autoimmune diabetes in two different diabetogenic T cell transfer models. Mechanistically, macrophages pre-conditioned with the MIF inhibitor featured a refractory capacity to trigger T cell activation by keeping them in a naïve state. This study underlines a possible role for MIF/CD74 signaling pathways in promoting macrophage-mediated inflammation in T1D. As therapies directed at the MIF/CD74 pathway are in clinical development, new opportunities may be proposed for arresting T1D progression.

  17. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice.

    Science.gov (United States)

    Krych, Ł; Nielsen, D S; Hansen, A K; Hansen, C H F

    2015-01-01

    Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3(+) regulatory T cells, CD11b(+) dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24-7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.

  18. Differences in the Expression of TLR-2, NOD2, and NF-κB in Placenta Between Twins.

    Science.gov (United States)

    Szylberg, Łukasz; Bodnar, Magdalena; Lebioda, Anna; Krepska, Patrycja; Kowalewski, Adam; Bręborowicz, Grzegorz; Marszałek, Andrzej

    2018-05-23

    Dizygotic twins share the same type of genetic relationship as non-twin siblings. Whereas monozygotic (MZ) twins are considered to have identical genetic material, they still differ. There is a number of reasons for early MZ twin discordance, including differences in the in utero environment, stochasticity, genetic mosaicism, and epigenetic factors. During gestation, the efficient innate immune system is of utmost importance. Our study was based on immunohistochemical evaluation of the differences in innate immune protein expression (TLR-2, NOD2, and NF-κB) in the 95 placentas between twins. Our study revealed statistical significant differences between diamniotic-dichorionic and monoamniotic-dichorionic twins. Monoamniotic-monochorionic twins exhibited no significant differences in protein expressions. To identify epigenetic factors causing the differences between twins, we made a series of comparisons with clinical data. The study revealed more cases with infections, miscarriages, in vitro fertilization, and premature rupture of membranes within the group with higher differences level of NF-κB, NOD2 and TLR-2 between twins. In case of twin-to-twin transfusion syndrome, there were no significant differences in innate immune protein expressions between twins. These results show that dissimilar genetic material and separate in utero environment promote discordance in innate immune protein expressions between twins. Moreover, additional blood flow between twins may be favorable in life-threatening conditions ensuring similar microenvironment.

  19. Synergistic reversal of type 1 diabetes in NOD mice with anti-CD3 and interleukin-1 blockade

    DEFF Research Database (Denmark)

    Ablamunits, Vitaly; Henegariu, Octavian; Hansen, Jakob Bondo

    2012-01-01

    (ab')(2) fragments of anti-CD3 mAb with or without IL-1 receptor antagonist (IL-1RA), or anti-IL-1ß mAb. We studied the reversal of diabetes and effects of treatment on the immune system. Mice that received a combination of anti-CD3 mAb with IL-1RA showed a more rapid rate of remission of diabetes than......Inflammatory cytokines are involved in autoimmune diabetes: among the most prominent is interleukin (IL)-1ß. We postulated that blockade of IL-1ß would modulate the effects of anti-CD3 monoclonal antibody (mAb) in treating diabetes in NOD mice. To test this, we treated hyperglycemic NOD mice with F...... arginase expression in macrophages and dendritic cells, and had delayed adoptive transfer of diabetes. After 1 month, there were increased concentrations of IgG1 isotype antibodies and reduced intrapancreatic expression of IFN-¿, IL-6, and IL-17 despite normal splenocyte cytokine secretion. These studies...

  20. Magnetic Coordinate Systems

    Science.gov (United States)

    Laundal, K. M.; Richmond, A. D.

    2017-03-01

    Geospace phenomena such as the aurora, plasma motion, ionospheric currents and associated magnetic field disturbances are highly organized by Earth's main magnetic field. This is due to the fact that the charged particles that comprise space plasma can move almost freely along magnetic field lines, but not across them. For this reason it is sensible to present such phenomena relative to Earth's magnetic field. A large variety of magnetic coordinate systems exist, designed for different purposes and regions, ranging from the magnetopause to the ionosphere. In this paper we review the most common magnetic coordinate systems and describe how they are defined, where they are used, and how to convert between them. The definitions are presented based on the spherical harmonic expansion coefficients of the International Geomagnetic Reference Field (IGRF) and, in some of the coordinate systems, the position of the Sun which we show how to calculate from the time and date. The most detailed coordinate systems take the full IGRF into account and define magnetic latitude and longitude such that they are constant along field lines. These coordinate systems, which are useful at ionospheric altitudes, are non-orthogonal. We show how to handle vectors and vector calculus in such coordinates, and discuss how systematic errors may appear if this is not done correctly.

  1. Non-traditional Oxidants in Preparative Coordination Chemistry

    Science.gov (United States)

    Kukushkin, Vadim Yu; Kukushkin, Yurii N.

    1986-10-01

    The application of nitrosonium and arenediazonium salts, carbenium, silver(I), and mercury(II) ions, protic acids, and amine oxides as oxidants in preparative coordination chemistry is examined. Specific examples illustrate which problems in the field of the synthesis and reactions of coordination compounds can be solved with the aid of these oxidants. The bibliography includes 158 references.

  2. synthesis and optical properties of self-assembled coordination ...

    African Journals Online (AJOL)

    The coordination chemistry of the phenylmalonic acid and 4-1H- amino- 1,2,4- triazole with Zn(II) ions has been investigated. The coordination polymer was synthesized by slow evaporation method and characterized by FT-infrared spectroscopy, ultraviolet-visible measurements, scanning electron microscopy, Electron ...

  3. Role of N-glycosylation sites and CXC motifs in trafficking of Medicago trunculata Nod Factor Perception protein to the plasma membrane.

    NARCIS (Netherlands)

    Lefebvre, B.; Klaus-Heisen, D.; Pietraszewska-Bogiel, A.; Hervé, M.; Camut, S.; Auriac, M.C.; Gasciolli, V.; Nurisso, A.; Gadella, T.W.; Cullimore, J.

    2012-01-01

    The lysin motif receptor like kinase, NFP, is a key protein in the legume Medicago truncatula for the perception of lipochitooligosaccharidic Nod Factors, which are secreted bacterial signals essential for establishing the nitrogen-fixing legume-rhizobia symbiosis. Predicted structural and genetic

  4. Resveratrol given intraperitoneally does not inhibit growth of high-risk t(4;11) acute lymphoblastic leukemia cells in NOD/SCID mouse model

    Science.gov (United States)

    The efficacy of the phytochemical resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL line SEM. SEM cells were injected into the tail vein and engraftment was monitored by ...

  5. Nonobese Diabetic (NOD Mice Lack a Protective B-Cell Response against the “Nonlethal” Plasmodium yoelii 17XNL Malaria Protozoan

    Directory of Open Access Journals (Sweden)

    Mirian Mendoza

    2016-01-01

    Full Text Available Background. Plasmodium yoelii 17XNL is a nonlethal malaria strain in mice of different genetic backgrounds including the C57BL/6 mice (I-Ab/I-Enull used in this study as a control strain. We have compared the trends of blood stage infection with the nonlethal murine strain of P. yoelii 17XNL malaria protozoan in immunocompetent Nonobese Diabetic (NOD mice prone to type 1 diabetes (T1D and C57BL/6 mice (control mice that are not prone to T1D and self-cure the P. yoelii 17XNL infection. Prediabetic NOD mice could not mount a protective antibody response to the P. yoelii 17XNL-infected red blood cells (iRBCs, and they all succumbed shortly after infection. Our data suggest that the lack of anti-P. yoelii 17XNL-iRBCs protective antibodies in NOD mice is a result of parasite-induced, Foxp3+ T regulatory (Treg cells able to suppress the parasite-specific antibody secretion. Conclusions. The NOD mouse model may help in identifying new mechanisms of B-cell evasion by malaria parasites. It may also serve as a more accurate tool for testing antimalaria therapeutics due to the lack of interference with a preexistent self-curing mechanism present in other mouse strains.

  6. The NOD2 3020insC Mutation in Women with Breast Cancer from the Bydgoszcz Region in Poland. First Results

    Directory of Open Access Journals (Sweden)

    Janiszewska Hanna

    2006-01-01

    Full Text Available Abstract The frameshift NOD2 gene mutation 3020insC is predominantly associated with Crohn's disease, but predisposes to many types of common cancers as well. We studied the frequency of this mutant NOD2 allele in 148 breast cancer women from the Bydgoszcz region in Poland. The NOD2 mutation was present in 8.8% of the patients. The mean age at breast cancer diagnosis of the mutation carriers was 43 years. We did not find any mutation in patients diagnosed with breast cancer after the age of 50 years. There was no association of the NOD2 mutation with a strong family history of breast cancer. On the contrary, the mutation frequency (11.4% was two times higher in women from families with a single case of breast cancer and with aggregation of other common types of cancer, especially digestive tract cancers. Low risk of breast cancer in the mutation carriers seems to be confirmed by finding the 3020insC mutation in three healthy parents of probands aged 73, 74 and 83 years, from three separate families.

  7. A 200 bp region of the pea ENOD12 promoter is sufficient for nodule-specific and nod factor induced expression

    DEFF Research Database (Denmark)

    Vijn, I; Christiansen, H; Lauridsen, P

    1995-01-01

    ENOD12 is one of the first nodulin genes expressed upon inoculation with Rhizobium and also purified Nod factors are able to induce ENOD12 expression. The ENOD12 gene family in pea (Pisum sativum) has two members. A cDNA clone representing PsENOD12A [26] and a PsENOD12B genomic clone [7] have been...

  8. Liposome-mediated transfer of IL-1 receptor antagonist gene to dispersed islet cells does not prevent recurrence of disease in syngeneically transplanted NOD mice

    DEFF Research Database (Denmark)

    Saldeen, J; Sandler, S; Bendtzen, K

    2000-01-01

    transplanted non-obese diabetic (NOD) mice. NOD mouse islet cells were transfected using liposome-mediated gene transfer with a human IL-1ra cDNA construct and transplanted two days later to prediabetic NOD mice. Graft infiltration and destruction were monitored three, five and eight days posttransplantation...... by histology and determination of insulin and cytokine content. IL-1ra gene transfer resulted in transient expression of IL-1ra protein in islet cells in vitro as assessed by ELISA and of IL-1ra mRNA in transplanted islets as revealed by RT-PCR. However, both control and IL-1ra transfected NOD grafts exhibited......IL-1beta is cytotoxic to pancreatic beta-cells in vitro but its role in the vicinity of beta-cells in vivo is unknown. We explored whether liposome-mediated transfer of the interleukin 1 receptor antagonist (IL-1ra) gene to islet cells might prevent recurrence of disease in syngeneically...

  9. [Binocular coordination during reading].

    Science.gov (United States)

    Bassou, L; Granié, M; Pugh, A K; Morucci, J P

    1992-01-01

    Is there an effect on binocular coordination during reading of oculomotor imbalance (heterophoria, strabismus and inadequate convergence) and of functional lateral characteristics (eye preference and perceptually privileged visual laterality)? Recordings of the binocular eye-movements of ten-year-old children show that oculomotor imbalances occur most often among children whose left visual perceptual channel is privileged, and that these subjects can present optomotor dissociation and manifest lack of motor coordination. Close binocular motor coordination is far from being the norm in reading. The faster reader displays saccades of differing spatial amplitude and the slower reader an oculomotor hyperactivity, especially during fixations. The recording of binocular movements in reading appears to be an excellent means of diagnosing difficulties related to visual laterality and to problems associated with oculomotor imbalance.

  10. The NOD3 software package: A graphical user interface-supported reduction package for single-dish radio continuum and polarisation observations

    Science.gov (United States)

    Müller, Peter; Krause, Marita; Beck, Rainer; Schmidt, Philip

    2017-10-01

    Context. The venerable NOD2 data reduction software package for single-dish radio continuum observations, which was developed for use at the 100-m Effelsberg radio telescope, has been successfully applied over many decades. Modern computing facilities, however, call for a new design. Aims: We aim to develop an interactive software tool with a graphical user interface for the reduction of single-dish radio continuum maps. We make a special effort to reduce the distortions along the scanning direction (scanning effects) by combining maps scanned in orthogonal directions or dual- or multiple-horn observations that need to be processed in a restoration procedure. The package should also process polarisation data and offer the possibility to include special tasks written by the individual user. Methods: Based on the ideas of the NOD2 package we developed NOD3, which includes all necessary tasks from the raw maps to the final maps in total intensity and linear polarisation. Furthermore, plot routines and several methods for map analysis are available. The NOD3 package is written in Python, which allows the extension of the package via additional tasks. The required data format for the input maps is FITS. Results: The NOD3 package is a sophisticated tool to process and analyse maps from single-dish observations that are affected by scanning effects from clouds, receiver instabilities, or radio-frequency interference. The "basket-weaving" tool combines orthogonally scanned maps into a final map that is almost free of scanning effects. The new restoration tool for dual-beam observations reduces the noise by a factor of about two compared to the NOD2 version. Combining single-dish with interferometer data in the map plane ensures the full recovery of the total flux density. Conclusions: This software package is available under the open source license GPL for free use at other single-dish radio telescopes of the astronomical community. The NOD3 package is designed to be

  11. Quantifying linguistic coordination

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Tylén, Kristian

    task (Bahrami et al 2010, Fusaroli et al. 2012) we extend to linguistic coordination dynamical measures of recurrence employed in the analysis of sensorimotor coordination (such as heart-rate (Konvalinka et al 2011), postural sway (Shockley 2005) and eye-movements (Dale, Richardson and Kirkham 2012......). We employ nominal recurrence analysis (Orsucci et al 2005, Dale et al 2011) on the decision-making conversations between the participants. We report strong correlations between various indexes of recurrence and collective performance. We argue this method allows us to quantify the qualities...

  12. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition.

    Directory of Open Access Journals (Sweden)

    Ellen Li

    Full Text Available We tested the hypothesis that Crohn's disease (CD-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum-associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1-V3 and V3-V5, were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R and the ATG16L1 risk allele (T300A. The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR assays were conducted to measure the relative frequencies of the Clostridium coccoides - Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤ 0.05 with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides--E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These

  13. Inflammatory bowel diseases phenotype, C. difficile and NOD2 genotype are associated with shifts in human ileum associated microbial composition.

    Science.gov (United States)

    Li, Ellen; Hamm, Christina M; Gulati, Ajay S; Sartor, R Balfour; Chen, Hongyan; Wu, Xiao; Zhang, Tianyi; Rohlf, F James; Zhu, Wei; Gu, Chi; Robertson, Charles E; Pace, Norman R; Boedeker, Edgar C; Harpaz, Noam; Yuan, Jeffrey; Weinstock, George M; Sodergren, Erica; Frank, Daniel N

    2012-01-01

    We tested the hypothesis that Crohn's disease (CD)-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum-associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA) gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1-V3 and V3-V5), were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD) undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R) and the ATG16L1 risk allele (T300A). The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR) assays were conducted to measure the relative frequencies of the Clostridium coccoides - Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤ 0.05) with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides--E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These results indicate

  14. Gluten-free but also gluten-enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes.

    Science.gov (United States)

    Funda, David P; Kaas, Anne; Tlaskalová-Hogenová, Helena; Buschard, Karsten

    2008-01-01

    Environmental factors such as nutrition or exposure to infections play a substantial role in the pathogenesis of type 1 diabetes (T1D). We have previously shown that gluten-free, non-purified diet largely prevented diabetes in non-obese diabetic (NOD) mice. In this study we tested hypothesis that early introduction of gluten-enriched (gluten+) diet may increase diabetes incidence in NOD mice. Standard, gluten-free, gluten+ modified Altromin diets and hydrolysed-casein-based Pregestimil diet were fed to NOD females and diabetes incidence was followed for 310 days. Insulitis score and numbers of gut mucosal lymphocytes were determined in non-diabetic animals. A significantly lower diabetes incidence (p gluten-free diet (5.9%, n = 34) and Pregestimil diet (10%, n = 30) compared to mice on the standard Altromin diet (60.6%, n = 33). Surprisingly, gluten+ diet also prevented diabetes incidence, even at the level found with the gluten-free diet (p gluten+, gluten-free, Pregestimil) diets, did that slightly later compared to those on the standard diet. Lower insulitis score compared to control mice was found in non-diabetic NOD mice on the gluten-free, and to a lesser extent also gluten+ and Pregestimil diets. No substantial differences in the number of CD3(+), TCR-gammadelta(+), and IgA(+) cells in the small intestine were documented. Gluten+ diet prevents diabetes in NOD mice at the level found with the non-purified gluten-free diet. Possible mechanisms of the enigmatic, dual effect of dietary gluten on the development of T1D are discussed. 2007 John Wiley & Sons, Ltd

  15. NSC23766, a Known Inhibitor of Tiam1-Rac1 Signaling Module, Prevents the Onset of Type 1 Diabetes in the NOD Mouse Model

    Directory of Open Access Journals (Sweden)

    Rajakrishnan Veluthakal

    2016-07-01

    Full Text Available Background/Aims: Type 1 diabetes (T1D is characterized by absolute insulin deficiency due to destruction of pancreatic β-cells by cytokines (e.g., interleukin-1β; IL-1β released by invading immune cells. The mechanisms by which these cytokines induce β-cell dysfunction remain poorly understood. Recent evidence suggests that excessive generation of reactive oxygen species (ROS by the phagocyte-like NADPH oxidase2 (Nox2, along with significantly low levels of antioxidants in β-cells, drive them toward oxidative damage. Rac1, a small G-protein, is one of the members of Nox2 holoenzyme. We recently reported that NSC23766, a known inhibitor of Rac1, significantly attenuated cytokine-induced Nox2 activation and ROS generation in pancreatic islet β-cells in vitro. Herein, we determined the effects of NSC23766 (2.5 mg/kg/day, i.p/daily on the development of diabetes in the NOD mouse, a model for T1D. Methods: Two groups of experimental animals (Balb/c and NOD mice received NSC23766, while the two control groups received equal volume of saline. Body weights and blood glucose were measured every week for 34 weeks. Rac1 activation in pancreatic islets was measured by GLISA activation assay. Rac1 and CHOP expression was determined by Western Blotting. Results: Our findings indicate that administration of NSC23766 significantly prevented the development of spontaneous diabetes in the NOD mice. Furthermore, NSC23766 markedly suppressed Rac1 expression and activity and the endoplasmic reticulum stress (CHOP expression in NOD islets. Conclusions: Our findings provide the first evidence implicating the role of Tiam1-Rac1-Nox2 signaling pathway in the onset of spontaneous diabetes in the NOD mouse model.

  16. Spectroscopic Studies of a Three-dimensional, Five-coordinated Copper(Ⅱ) Complex via Hydrogen Bonds: [Cu(PDA)(H2O)2](H2PDA=Pyridine-2,6-dicarboxylic Acid)

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A new copper(Ⅱ) complex [Cu(PDA)(H2O)2] was synthesized and its structure was determined. Cu(Ⅱ) is five-coordinated in a tetragonal pyramid geometry. The two coordinating water molecules are different and the two Cu-O bond lengths differ by nearly 0.02 nm. The whole crystal is linked to form a three-dimensional network by means of hydrogen bonds. The X-band ESR spectrum shows three different g tensors with a well-resolved hyperfine structure in the gz signal, giving the ESR parameters gx=2.05, gy=2.065 and gz=2.29. The covalency of the coordinate bonds and the deviation from tetragonal pyramid geometry for the complex are discussed based on the ESR spectra.

  17. Is the glass half full or half empty? A qualitative exploration on treatment practices and perceived barriers to biomedical care for patients with nodding syndrome in post-conflict northern Uganda.

    Science.gov (United States)

    Mwaka, Amos Deogratius; Okello, Elialilia S; Abbo, Catherine; Odwong, Francis Okot; Olango, Willy; Etolu, John Wilson; Oriyabuzu, Rachel; Lagoro, David Kitara; Mutamba, Byamah Brian; Idro, Richard; Opar, Bernard Toliva; Aceng, Jane Ruth; Lukwago, Assuman; Neema, Stella

    2015-08-29

    Nodding syndrome has increasingly become an issue of public health concern internationally. The etiology of the disorder is still unknown and there are yet no curative treatments. We explored perceptions about treatment practices and barriers to health seeking for nodding syndrome in Pader and Kitgum districts in northern Uganda in order to provide data necessary for informing policy on treatment adherence and rehabilitations. We used focus group discussions and individual interviews to gain deep insights into help-seeking and treatment practices for nodding syndrome. Purposive sampling was used to identify information-rich participants that included village health teams, community members not directly affected with nodding syndrome, district leaders, healthcare professionals, and caregivers of children affected with nodding syndrome. We used qualitative content analysis to analyze data and presented findings under distinct categories and themes. Caregivers and communities sought care from multiple sources including biomedical facilities, traditional healers, traditional rituals from shrines, and spiritual healing. Nodding syndrome affected children reportedly have showed no enduring improvement with traditional medicines, traditional rituals, and prayers. A substantial minority of participants reported minimal improvements in symptoms of convulsions with use of western medicines. Challenges involved in health seeking included; (1) health system factors e.g. long distances to facilities, frequent unavailability of medicines, few healthcare providers, and long waiting times; (2) contextual and societal challenges e.g. lack of money for transport and medical bills, overburdening nature of the illness that does not allow time for other activities, and practical difficulties involved in transporting the physically deformed and mentally retarded children to the health facilities. Help-seeking for nodding syndrome is pluralistic and include use of traditional and

  18. Dimensions of Organizational Coordination

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Aldewereld, Huib; Dignum, Virginia

    2013-01-01

    be supported to include organizational objectives and constraints into their reasoning processes by considering two alternatives: agent reasoning and middleware regulation. We show how agents can use an organizational specification to achieve organizational objectives by delegating and coordinating...... their activities with other agents in the society, using the GOAL agent programming language and the OperA organizational model....

  19. Reusability of coordination programs

    NARCIS (Netherlands)

    F. Arbab (Farhad); C.L. Blom (Kees); F.J. Burger (Freek); C.T.H. Everaars (Kees)

    1996-01-01

    textabstractIsolating computation and communication concerns into separate pure computation and pure coordination modules enhances modularity, understandability, and reusability of parallel and/or distributed software. This can be achieved by moving communication primitives (such as SendMessage and

  20. [Civilian-military coordination].

    Science.gov (United States)

    de Montravel, G

    2002-01-01

    Current humanitarian emergencies create complex, mutidimensional situations that stimulate simultaneous responses from a wide variety of sources including governments, non-governmental organizations (NGO), United Nations agencies, and private individuals. As a result, it has become essential to establish a coherent framework in which each actor can contribute promptly and effectively to the overall effort. This is the role of the United Nations Office for the Coordination of Humanitarian Affairs. Regardless of the circumstances and level of coordination, cooperation and collaboration between humanitarian and military personnel, it is necessary to bear in mind their objectives. The purpose of humanitarian action is to reduce human suffering. The purpose of military intervention is to stop warfare. The author of this article will discuss the three major obstacles to civilian-military coordination (strategic, tactical, and operational). Operations cannot be conducted smoothly and differences cannot be ironed out without mutual respect between the two parties, an explicit definition of their respective duties and responsibilities, a clear understanding of their cultural differences, and the presence of an organization and facilities for coordination and arbitrage by a neutral referee.

  1. Coordination of hand shape.

    Science.gov (United States)

    Pesyna, Colin; Pundi, Krishna; Flanders, Martha

    2011-03-09

    The neural control of hand movement involves coordination of the sensory, motor, and memory systems. Recent studies have documented the motor coordinates for hand shape, but less is known about the corresponding patterns of somatosensory activity. To initiate this line of investigation, the present study characterized the sense of hand shape by evaluating the influence of differences in the amount of grasping or twisting force, and differences in forearm orientation. Human subjects were asked to use the left hand to report the perceived shape of the right hand. In the first experiment, six commonly grasped items were arranged on the table in front of the subject: bottle, doorknob, egg, notebook, carton, and pan. With eyes closed, subjects used the right hand to lightly touch, forcefully support, or imagine holding each object, while 15 joint angles were measured in each hand with a pair of wired gloves. The forces introduced by supporting or twisting did not influence the perceptual report of hand shape, but for most objects, the report was distorted in a consistent manner by differences in forearm orientation. Subjects appeared to adjust the intrinsic joint angles of the left hand, as well as the left wrist posture, so as to maintain the imagined object in its proper spatial orientation. In a second experiment, this result was largely replicated with unfamiliar objects. Thus, somatosensory and motor information appear to be coordinated in an object-based, spatial-coordinate system, sensitive to orientation relative to gravitational forces, but invariant to grasp forcefulness.

  2. Block coordination copolymers

    Science.gov (United States)

    Koh, Kyoung Moo; Wong-Foy, Antek G; Matzger, Adam J; Benin, Annabelle I; Willis, Richard R

    2012-11-13

    The present invention provides compositions of crystalline coordination copolymers wherein multiple organic molecules are assembled to produce porous framework materials with layered or core-shell structures. These materials are synthesized by sequential growth techniques such as the seed growth technique. In addition, the invention provides a simple procedure for controlling functionality.

  3. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Krych, Lukasz; Nielsen, Dennis Sandris

    2012-01-01

    , a glycopeptide antibiotic specifically directed against Gram-positive bacteria, could influence immune homeostasis and the development of diabetic symptoms in the NOD mouse model for diabetes. Methods: Accordingly, one group of mice received vancomycin from birth until weaning (day 28), while another group...... lower for the neonatally treated group compared with the untreated group, whereas the insulitis score and blood glucose levels were significantly lower for the mice treated as adults compared with the other groups. Mucosal inflammation was investigated by intracellular cytokine staining of the small...... genera of Gram-positive and Gram-negative microbes while, interestingly, one single species, Akkermansia muciniphila, became dominant. Conclusions/interpretation: The early postnatal period is a critical time for microbial protection from type 1 diabetes and it is suggested that the mucolytic bacterium A...

  4. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice

    DEFF Research Database (Denmark)

    Krych, Lukasz; Nielsen, Dennis Sandris; Hansen, Axel Kornerup

    2015-01-01

    Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link...... measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3(+) regulatory T cells, CD11b......(+) dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24-7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all...

  5. Nod factor supply under water stress conditions modulates cytokinin biosynthesis and enhances nodule formation and N nutrition in soybean.

    Science.gov (United States)

    Prudent, Marion; Salon, Christophe; Smith, Donald L; Emery, R J Neil

    2016-09-01

    Nod factors (NF) are molecules produced by rhizobia which are involved in the N 2 -fixing symbiosis with legume plants, enabling the formation of specific organs called nodules. Under drought conditions, nitrogen acquisition by N 2 -fixation is depressed, resulting in low legume productivity. In this study, we evaluated the effects of NF supply on nitrogen acquisition and on cytokinin biosynthesis of soybean plants grown under drought. NF supply to water stressed soybeans increased the CK content of all organs. The profile of CK metabolites also shifted from t-Z to cis-Z and an accumulation of nucleotide and glucoside conjugates. The changes in CK coincided with enhanced nodule formation with sustained nodule specific activity, which ultimately increased the total nitrogen fixed by the plant.

  6. Coordination failure caused by sunspots

    DEFF Research Database (Denmark)

    Beugnot, Julie; Gürgüç, Zeynep; Øvlisen, Frederik Roose

    2012-01-01

    on the efficient equilibrium, we consider sunspots as a potential reason for coordination failure. We conduct an experiment with a three player 2x2x2 game in which coordination on the efficient equilibrium is easy and should normally occur. In the control session, we find almost perfect coordination on the payoff......-dominant equilibrium, but in the sunspot treatment, dis-coordination is frequent. Sunspots lead to significant inefficiency, and we conclude that sunspots can indeed cause coordination failure....

  7. Neuropsychiatric perspectives on nodding syndrome in northern Uganda: a case series study and a review of the literature.

    Science.gov (United States)

    Musisi, S; Akena, D; Nakimuli-Mpungu, E; Abbo, C; Okello, J

    2013-06-01

    Nodding Syndrome (NS), previously called Nodding Disease, is a chronic and debilitating illness affecting thousands of children aged 3-18 years in post-conflict Northern Uganda and South Sudan. Characterised by malnutrition, stunted growth, mental retardation and seizures, some researchers have designated it as epilepsy. With reports appearing in Northern Uganda in1997, NS reached epidemic proportions around 2000-2003 when people were moved into Internally Displaced People's (IDP) camps. Investigations for infections (onchocerciasis) and toxins have been inconclusive as to cause, treatment or outcome. No study has addressed the possible relationship of NS to childhood war-trauma experiences. To explore a possible relationship of exposure to prolonged war-trauma and the emergence of epidemic NS in Northern Uganda. This study was a case-series descriptive psychiatric naturalistic field observations of NS cases from homesteads in Northern Uganda and psychiatric investigations and treatment of NS cases referred to Mulago National Referral and Teaching Hospital. Detailed Psychiatric clinical evaluations and field observations revealed that NS children had been exposed to severe war-related psychological and physical trauma as well as non-specific CNS insults including untreated CNS infections/infestations and malnutrition possibly causing seizures. Many children suffered post-traumatic stress disorder (PTSD) and depression. NS could present as an association of childhood complex PTSD, (called Developmental Trauma Disorder), occurring in the chronically war-traumatised children of Northern Uganda, complicated by severe prolonged depression with its characteristic symptoms of psychomotor retardation, anxiety, anhedonia and anorexia. This, coupled with food shortages, resulted in malnutrition, wasting and stunted growth with severe avitaminoses. Many children had seizures. All this calls for multi-disciplinary treatment approaches.

  8. The Effects of Alpha Interferon on the Development of Autoimmune Thyroiditis in the NOD H2h4 Mouse

    Directory of Open Access Journals (Sweden)

    Yael Oppenheim

    2003-01-01

    Full Text Available Alpha interferon (αIFN therapy is known to induce thyroid autoimmunity in up to 40% of patients. The mechanism is unknown, but Th1 switching has been hypothesized. The aim of our study was to examine whether αIFN accelerated the development of thyroiditis in genetically susceptible mice. We took advantage of NOD-H2h4, a genetically susceptible animal model, which develops thyroiditis when fed a high iodine diet. Six to eight week old male NOD H2h4 mice were injected with mouse αIFN (200 units or with saline three times a week for 8 weeks. All mice drank iodinated water (0.15%. Mice were sacrificed after 8 weeks of injection. Their thyroids were examined for histology and blood was tested for antithyroglobulin antibody levels. T4 and glucose levels were also assessed. In the IFN-injected group, 6/13 (46.2% developed thyroiditis and/or thyroid antibodies while in the saline-injected group, only 4/13 (30.8% developed thyroiditis and/or thyroid antibodies (p=0.4. The grade of thyroiditis was not different amongst the two groups. None of the mice developed clinical thyroiditis or diabetes mellitus. Our results showed that αIFN treatment did not accelerate thyroiditis in this mouse model. This may imply that αIFN induces thyroiditis in a non-genetically dependent manner, and this would not be detected in a genetically susceptible mouse model if the effect were small. Alternatively, it is possible that αIFN did not induce thyroiditis in mice because, unlike in humans, in mice αIFN does not induce Th1 switching.

  9. Four coordination polymers based on 5-tert-butyl isophthalic acid and rigid bis(imidazol-1yl)benzene linkers: Synthesis, luminescence detection of acetone and optical properties

    Science.gov (United States)

    Arıcı, Mürsel; Zafer Yeşilel, Okan; Büyükgüngör, Orhan

    2017-05-01

    Four coordination polymers including, [Co(μ-Htbip)2(μ-dib)]n (1), [Co(μ-tbip)(μ-dmib)0.5]n (2), [Zn2(μ-tbip)(μ3-tbip)(μ-dmib)1.5]n (3) and [Cd(μ3-tbip)(μ-dib)0.5 (H2O)]n (4) (tbip: 5-tert-butylisophthalate, dib: 1,4-bis(imidazol-1yl)benzene, dmib: 1,4-bis(imidazol-1yl)-2,5-dimethylbenzene), were hydrothermally synthesized and characterized by elemental analysis, IR spectra, single crystal and powder X-ray diffraction and thermal analysis (TG/DTA). The structural diversity is observed depending on ligands and coordination number of metal centers in the synthesized complexes. The tbip ligand displayed five different coordination modes in its complexes. In 1 and 2, complex 1 is 3D framework with the dia topology while complex 2 has 2D structure with the sql topology depending on coordination geometries of Co ions. Complex 3 is 3D framework with the fsh 4,6-conn topology and complex 4 has 2D 4-connected sql topology. Photoluminescent properties of complex 3 dispersed in various organic solvents were investigated and the results showed that 3 dispersed in methanol could be used as a fluorescent sensor for the detection of acetone. Moreover, thermal and optical properties of the complexes were also studied.

  10. Improving Project Manufacturing Coordination

    Directory of Open Access Journals (Sweden)

    Korpivaara Ville

    2014-09-01

    Full Text Available The objective of this research is to develop firms’ project manufacturing coordination. The development will be made by centralizing the manufacturing information flows in one system. To be able to centralize information, a deep user need assessment is required. After user needs have been identified, the existing system will be developed to match these needs. The theoretical background is achieved through exploring the literature of project manufacturing, development project success factors and different frameworks and tools for development project execution. The focus of this research is rather in customer need assessment than in system’s technical expertise. To ensure the deep understanding of customer needs this study is executed by action research method. As a result of this research the information system for project manufacturing coordination was developed to respond revealed needs of the stakeholders. The new system improves the quality of the manufacturing information, eliminates waste in manufacturing coordination processes and offers a better visibility to the project manufacturing. Hence it provides a solid base for the further development of project manufacturing.

  11. Universal mechatronics coordinator

    Science.gov (United States)

    Muir, Patrick F.

    1999-11-01

    Mechatronic systems incorporate multiple actuators and sensor which must be properly coordinated to achieve the desired system functionality. Many mechatronic systems are designed as one-of-a-kind custom projects without consideration for facilitating future system or alterations and extensions to the current syste. Thus, subsequent changes to the system are slow, different, and costly. It has become apparent that manufacturing processes, and thus the mechatronics which embody them, need to be agile in order to more quickly and easily respond to changing customer demands or market pressures. To achieve agility, both the hardware and software of the system need to be designed such that the creation of new system and the alteration and extension of current system is fast and easy. This paper describes the design of a Universal Mechatronics Coordinator (UMC) which facilitates agile setup and changeover of coordination software for mechatronic systems. The UMC is capable of sequencing continuous and discrete actions that are programmed as stimulus-response pairs, as state machines, or a combination of the two. It facilitates the modular, reusable programing of continuous actions such as servo control algorithms, data collection code, and safety checking routines; and discrete actions such as reporting achieved states, and turning on/off binary devices. The UMC has been applied to the control of a z- theta assembly robot for the Minifactory project and is applicable to a spectrum of widely differing mechatronic systems.

  12. The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007 fs Mutation and may be Explained by Age at Diagnosis: A Meta-Analysis and Case-Only Study

    Directory of Open Access Journals (Sweden)

    M. Ellen Kuenzig

    2017-07-01

    Interpretation: The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007 fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction.

  13. Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4+CD25+ regulatory T cells

    International Nuclear Information System (INIS)

    Jin, Yulan; Purohit, Sharad; Chen, Xueqin; Yi, Bing; She, Jin-Xiong

    2012-01-01

    Highlights: ► This is the first study to provide direct evidence of the role of Stat5b in NOD mice. ► Over-expression of wild type Stat5b transgene protects NOD mice against diabetes. ► This protection may be mediated by the up-regulation of CD4 + CD25 + Tregs. -- Abstract: The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4 + T cells and especially CD8 + T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4 + and CD8 + T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-γ, TNF-α and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4 + CD25 + regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4 + CD25 + regulatory T cells.

  14. Coordinator, Translation Services | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Coordinator, Translation Services coordinates the overall operations of the ... services in IDRC by acting as the main resource person for internal clients ... all operational issues in order to ensure good quality products delivered on time.

  15. A radiolabeled antibody targeting CD123+ leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

    Directory of Open Access Journals (Sweden)

    Jeffrey V. Leyton

    2015-01-01

    Full Text Available Radioimmunotherapy (RIT with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS peptides and labeled with the Auger electron-emitter, 111In (111In-NLS-CSL360 was studied in the prevalent NOD/SCID mouse AML engraftment assay. Significant decreases in CD123+ leukemic cells and impairment of leukemic stem cell self-renewal were achieved with high doses of RIT. However, NOD/SCID mice were very radiosensitive to these doses. At low non-toxic treatment doses, 111In-NLS-CSL360 demonstrated a trend towards improved survival associated with decreased spleen/body weight ratio, an indicator of leukemia burden, and almost complete eradication of leukemia from the bone marrow in some mice.

  16. Several classical mouse inbred strains, including DBA/2, NOD/Lt, FVB/N, and SJL/J, carry a putative loss-of-function allele of Gpr84.

    Science.gov (United States)

    Perez, Carlos J; Dumas, Aline; Vallières, Luc; Guénet, Jean-Louis; Benavides, Fernando

    2013-01-01

    G protein-coupled receptor 84 (GPR84) is a 7-transmembrane protein expressed on myeloid cells that can bind to medium-chain free fatty acids in vitro. Here, we report the discovery of a 2-bp frameshift deletion in the second exon of the Gpr84 gene in several classical mouse inbred strains. This deletion generates a premature stop codon predicted to result in a truncated protein lacking the transmembrane domains 4-7. We sequenced Gpr84 exon 2 from 58 strains representing different groups in the mouse family tree and found that 14 strains are homozygous for the deletion. Some of these strains are DBA/1J, DBA/2J, FVB/NJ, LG/J, MRL/MpJ, NOD/LtJ, and SJL/J. However, the deletion was not found in any of the wild-derived inbred strains analyzed. Haplotype analysis suggested that the deletion originates from a unique mutation event that occurred more than 100 years ago, preceding the development of the first inbred strain (DBA), from a Mus musculus domesticus source. As GPR84 ostensibly plays a role in the biology of myeloid cells, it could be relevant 1) to consider the existence of this Gpr84 nonsense mutation in several mouse strains when choosing a mouse model to study immune processes and 2) to consider reevaluating data obtained using such strains.

  17. Recursive Advice for Coordination

    DEFF Research Database (Denmark)

    Terepeta, Michal Tomasz; Nielson, Hanne Riis; Nielson, Flemming

    2012-01-01

    Aspect-oriented programming is a programming paradigm that is often praised for the ability to create modular software and separate cross-cutting concerns. Recently aspects have been also considered in the context of coordination languages, offering similar advantages. However, introducing aspects...... challenging. This is important since ensuring that a system does not contain errors is often equivalent to proving that some states are not reachable. In this paper we show how to solve these challenges by applying a successful technique from the area of software model checking, namely communicating pushdown...

  18. Effect of iodide on Fas, Fas-ligand and Bcl-w mRNA expression in thyroid of NOD mice pretreated with methimazole

    Directory of Open Access Journals (Sweden)

    L.H.B. Boechat

    2002-03-01

    Full Text Available Nonobese diabetic (NOD mice and a derived strain, NOD.H.2h4, have been used as a model for experimental spontaneous thyroiditis and thyroiditis induced by iodide excess after a goiter-inducing period. Some authors have proposed that iodide, given after methimazole or propylthiouracil, is capable of inducing apoptosis in thyroid cells and that anti-thyroid drugs can modulate the expression of apoptosis components such as Fas and its ligand (Fas-L. Here we evaluated the effect of potassium iodide (20 µg/animal for 4 days, ip given to NOD mice at the 10th week of life after exposure to methimazole (1 mg/ml in drinking water from the 4th to the 10th week of life. Fas, Fas-L and Bcl-w expression were analyzed semiquantitatively by RT-PCR immediately after potassium iodide administration (group MI44D or at week 32 (MI32S. Control groups were added at 10 (C10 and 32 weeks (C32, as well as a group that received only methimazole (CM10. An increase in the expression of Fas-L and Bcl-w (P<0.01, ANOVA was observed in animals of group MI44D, while Fas was expressed at higher levels (P = 0.02 in group C32 (72.89 ± 47.09 arbitrary units when compared to group C10 (10.8 ± 8.55 arbitrary units. Thus, the analysis of Fas-L and Bcl-w expression in the MI44D group and Fas in group C32 allowed us to detect two different patterns of expression of these apoptosis components in thyroid tissue of NOD mice.

  19. Higher susceptibility of NOD/LtSz-scid Il2rg−/− NSG mice to xenotransplanted lung cancer cell lines

    International Nuclear Information System (INIS)

    Kanaji, Nobuhiro; Tadokoro, Akira; Susaki, Kentaro; Yokokura, Saki; Ohmichi, Kiyomi; Haba, Reiji; Watanabe, Naoki; Bandoh, Shuji; Ishii, Tomoya; Dobashi, Hiroaki; Matsunaga, Takuya

    2014-01-01

    No lung cancer xenograft model using non-obese diabetic (NOD)-scid Il2rg −/− mice has been reported. The purpose of this study is to select a suitable mouse strain as a xenogenic host for testing tumorigenicity of lung cancer. We directly compared the susceptibility of four immunodeficient mouse strains, c-nu, C.B-17 scid, NOD-scid, and NOD/LtSz-scid Il2rg −/− (NSG) mice, for tumor formation from xenotransplanted lung cancer cell lines. Various numbers (10 1 –10 5 cells/head) of two lung cancer cell lines, A549 and EBC1, were subcutaneously inoculated and tumor sizes were measured every week up to 12 weeks. When 10 4 EBC1 cells were inoculated, no tumor formation was observed in BALB/c-nu or C.B-17 scid mice. Tumors developed in two of the five NOD-scid mice (40%) and in all the five NSG mice (100%). When 10 3 EBC1 cells were injected, no tumors developed in any strain other than NSG mice, while tumorigenesis was achieved in all the five NSG mice (100%, P=0.0079) within 9 weeks. NSG mice similarly showed higher susceptibility to xenotransplantation of A549 cells. Tumor formation was observed only in NSG mice after inoculation of 10 3 or fewer A549 cells (40% vs 0% in 15 NSG mice compared with others, respectively, P=0.0169). We confirmed that the engrafted tumors originated from inoculated human lung cancer cells by immunohistochemical staining with human cytokeratin and vimentin. NSG mice may be the most suitable strain for testing tumorigenicity of lung cancer, especially if only a few cells are available

  20. Innate immune receptors in human airway smooth muscle cells: activation by TLR1/2, TLR3, TLR4, TLR7 and NOD1 agonists.

    Directory of Open Access Journals (Sweden)

    Anne Månsson Kvarnhammar

    Full Text Available BACKGROUND: Pattern-recognition receptors (PRRs, including Toll-like receptors (TLRs, NOD-like receptors (NLRs and RIG-I-like receptors (RLRs, recognize microbial components and trigger a host defense response. Respiratory tract infections are common causes of asthma exacerbations, suggesting a role for PRRs in this process. The present study aimed to examine the expression and function of PRRs on human airway smooth muscle cells (HASMCs. METHODS: Expression of TLR, NLR and RLR mRNA and proteins was determined using real-time RT-PCR, flow cytometry and immunocytochemistry. The functional responses to ligand stimulation were investigated in terms of cytokine and chemokine release, cell surface marker expression, proliferation and proteins regulating the contractile state. RESULTS: HASMCs expressed functional TLR2, TLR3, TLR4, TLR7 and NOD1. Stimulation with the corresponding agonists Pam3CSK4, poly(I:C, LPS, R-837 and iE-DAP, respectively, induced IL-6, IL-8 and GM-CSF release and up-regulation of ICAM-1 and HLA-DR, while poly(I:C also affected the release of eotaxin and RANTES. The proliferative response was slightly increased by LPS. Stimulation, most prominently with poly(I:C, down-regulated myosin light chain kinase and cysteinyl leukotriene 1 receptor expression and up-regulated β2-adrenoceptor expression. No effects were seen for agonist to TLR2/6, TLR5, TLR8, TLR9, NOD2 or RIG-I/MDA-5. CONCLUSION: Activation of TLR2, TLR3, TLR4, TLR7 and NOD1 favors a synthetic phenotype, characterized by an increased ability to release inflammatory mediators, acquire immunomodulatory properties by recruiting and interacting with other cells, and reduce the contractile state. The PRRs might therefore be of therapeutic use in the management of asthma and infection-induced disease exacerbations.

  1. Effects of total glucosides of peony on AQP-5 and its mRNA expression in submandibular glands of NOD mice with Sjogren's syndrome.

    Science.gov (United States)

    Wu, G-L; Pu, X-H; Yu, G-Y; Li, T-Y

    2015-01-01

    The aim of this study was to observe the effects of total glucosides of peony (TGP) on pathological change, Aquaporin-5 (AQP-5) and its mRNA expression in submandibular glands of non-obese diabetic (NOD) mice with Sjogren's Syndrome, to investigate its regulation on secretion of salivary glands. 40 NOD mice were randomly divided into model group, TGP group, hydroxychloroquine group, combination group (n = 10). For TGP group, the mice were intragastrically administrated with 0.4 ml TGP dilution per day in accordance with 300 g/kg dose; for hydroxychloroquine group, the mice were intragastrically administrated with 0.4 ml hydroxychloroquine per day in accordance with 60 mg/kg dose; for the combination group, the mice were intragastrically administrated with 0.4 ml TGP dilution and 0.4 ml hydroxychloroquine. 8 weeks later, the mice were sacrificed, and submandibular glands were collected by anatomy. Pathological changes of submandibular gland were observed under a light microscope; AQP-5 protein in submandibular glands was detected by immunohistochemical staining; and AQP-5 mRNA expression in submandibular glands was detected by RT-PCR. The lymphocytic infiltration score of model mice was significantly higher than that of other groups. The pathological morphology and score of NOD mice were significantly improved after administration, and the combination group was superior to the hydroxychloroquine group and TGP group (p TGP group and the combination group were higher than the hydroxychloroquine group (p TGP may improve pathological damage of submandibular glands of NOD mouse with Sjogren's syndrome by upregulating AQP-5 and its mRNA expression in submandibular glands.

  2. Nod factor effects on root hair-specific transcriptome of Medicago truncatula: focus on plasma membrane transport systems and reactive oxygen species networks

    OpenAIRE

    Isabelle eDAMIANI; Alice eDRAIN; Marjorie eGUICHARD; Sandrine eBALZERGUE; Sandrine eBALZERGUE; Alexandre eBOSCARI; Jean-Christophe eBOYER; Véronique eBRUNAUD; Véronique eBRUNAUD; Sylvain eCOTTAZ; Sylvain eCOTTAZ; Corinne eRANCUREL; Martine eDa Rocha; Cécile eFIZAMES; Sebastien eFORT

    2016-01-01

    Root hairs are involved in water and nutrient uptake, and thereby in plant autotrophy. In legumes, they also play a crucial role in establishment of rhizobial symbiosis. To obtain a holistic view of Medicago truncatula genes expressed in root hairs and of their regulation during the first hours of the engagement in rhizobial symbiotic interaction, a high throughput RNA sequencing on isolated root hairs from roots challenged or not with lipochitooligosaccharides Nod factors (NF) for 4 h or 20 ...

  3. Nod Factor Effects on Root Hair-Specific Transcriptome of Medicago truncatula: Focus on Plasma Membrane Transport Systems and Reactive Oxygen Species Networks.

    OpenAIRE

    Damiani , Isabelle; Drain , Alice; Guichard , Marjorie; Balzergue , Sandrine; Boscari , Alexandre; Boyer , Jean-Christophe; Brunaud , Véronique; Cottaz , Sylvain; Rancurel , Corinne; Da Rocha , Martine; Fizames , Cécile; Fort , Sébastien; Gaillard , Isabelle; MAILLOL , Vincent; Danchin , Etienne G J

    2015-01-01

    International audience; Root hairs are involved in water and nutrient uptake, and thereby in plant autotrophy. In legumes, they also play a crucial role in establishment of rhizobial symbiosis. To obtain a holistic view of Medicago truncatula genes expressed in root hairs and of their regulation during the first hours of the engagement in rhizobial symbiotic interaction, a high throughput RNA sequencing on isolated root hairs from roots challenged or not with lipochitooligosaccharides Nod fac...

  4. NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

    Science.gov (United States)

    Jiao, Delong; Wong, Chun-Kwok; Qiu, Huai-Na; Dong, Jie; Cai, Zhe; Chu, Man; Hon, Kam-Lun; Tsang, Miranda Sin-Man; Lam, Christopher Wai-Kei

    2016-01-01

    The skin of patients with atopic dermatitis (AD) has a unique predisposition for colonization by Staphylococcus aureus (S. aureus), which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll-like receptor 2 (TLR2) ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions. Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil–fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway by which S. aureus contributes to the pathophysiology of AD. PMID:26388234

  5. The INCA trial (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Casper, Markus; Mengel, Martin; Fuhrmann, Christine; Herrmann, Eva; Appenrodt, Beate; Schiedermaier, Peter; Reichert, Matthias; Bruns, Tony; Engelmann, Cornelius; Grünhage, Frank; Lammert, Frank

    2015-03-08

    Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP. The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (INCA trial is first in the field of hepatology aimed at rapidly transferring and validating information on individual genetic risk into clinical decision algorithms. German Clinical Trials Register DRKS00005616 . Registered 22 January 2014. EU Clinical Trials Register EudraCT 2013-001626-26 . Registered 26 January 2015.

  6. Comparative expression profile of NOD1/2 and certain acute inflammatory cytokines in thermal-stressed cell culture model of native and crossbred cattle

    Science.gov (United States)

    Bhanuprakash, V.; Singh, Umesh; Sengar, Gyanendra Singh; Raja, T. V.; Sajjanar, Basavraj; Alex, Rani; Kumar, Sushil; Alyethodi, R. R.; Kumar, Ashish; Sharma, Ankur; Kumar, Suresh; Bhusan, Bharat; Deb, Rajib

    2017-05-01

    Thermotolerance depends mainly on the health and immune status of the animals. The variation in the immune status of the animals may alter the level of tolerance of animals exposed to heat or cold stress. The present study was conducted to investigate the expression profile of two important nucleotide binding and oligomerization domain receptors (NLRs) (NOD1 and NOD2) and their central signalling molecule RIP2 gene during in vitro thermal-stressed bovine peripheral blood mononuclear cells (PBMCs) of native (Sahiwal) and crossbred (Sahiwal X HF) cattle. We also examined the differential expression profile of certain acute inflammatory cytokines in in vitro thermal-stressed PBMC culture among native and its crossbred counterparts. Results revealed that the expression profile of NOD1/2 positively correlates with the thermal stress, signalling molecule and cytokines. Present findings also highlighted that the expression patterns during thermal stress were comparatively superior among indigenous compared to crossbred cattle which may add references regarding the better immune adaptability of Zebu cattle.

  7. LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations.

    Directory of Open Access Journals (Sweden)

    Patrick Marcinek

    Full Text Available In recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control of intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1 responses. In this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in Indian population by genotyping four variants in NOD2 (rs9302752A/G, LRRK2 (rs1873613A/G, RIPK2 (rs40457A/G and rs42490G/A. The LRRK2 locus is associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotypes were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes confer protection in paucibacillary and leprosy patients. The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was observed to contribute towards increased risk whereas haplotypes AA was observed to confer protective role. Our results indicate that a possible shared mechanisms underlying the development of these two clinical forms of the disease as hypothesized. Our findings confirm and validates the role of gene variants involved in NOD2-mediated signalling pathways that play a role in immunological control of intracellular bacteria M. leprae.

  8. IL-27 Induced by Select Candida spp. via TLR7/NOD2 Signaling and IFN-β Production Inhibits Fungal Clearance

    Science.gov (United States)

    Patin, Emmanuel C.; Jones, Adam V.; Thompson, Aiysha; Clement, Mathew; Liao, Chia-Te; Griffiths, James S.; Wallace, Leah E.; Bryant, Clare E.; Lang, Roland; Rosenstiel, Philip; Humphreys, Ian R.; Taylor, Philip R.

    2016-01-01

    Candida spp. elicit cytokine production downstream of various pathogen recognition receptors, including C-type lectin-like receptors, TLRs, and nucleotide oligomerization domain (NOD)–like receptors. IL-12 family members IL-12p70 and IL-23 are important for host immunity against Candida spp. In this article, we show that IL-27, another IL-12 family member, is produced by myeloid cells in response to selected Candida spp. We demonstrate a novel mechanism for Candida parapsilosis–mediated induction of IL-27 in a TLR7-, MyD88-, and NOD2-dependent manner. Our data revealed that IFN-β is induced by C. parapsilosis, which in turn signals through the IFN-α/β receptor and STAT1/2 to induce IL-27. Moreover, IL-27R (WSX-1)–deficient mice systemically infected with C. parapsilosis displayed enhanced pathogen clearance compared with wild-type mice. This was associated with increased levels of proinflammatory cytokines in the serum and increased IFN-γ and IL-17 responses in the spleens of IL-27R–deficient mice. Thus, our data define a novel link between C. parapsilosis, TLR7, NOD2, IFN-β, and IL-27, and we have identified an important role for IL-27 in the immune response against C. parapsilosis. Overall, these findings demonstrate an important mechanism for the suppression of protective immune responses during infection with C. parapsilosis, which has potential relevance for infections with other fungal pathogens. PMID:27259855

  9. First field trial of Virtual Network Operator oriented network on demand (NoD) service provisioning over software defined multi-vendor OTN networks

    Science.gov (United States)

    Li, Yajie; Zhao, Yongli; Zhang, Jie; Yu, Xiaosong; Chen, Haoran; Zhu, Ruijie; Zhou, Quanwei; Yu, Chenbei; Cui, Rui

    2017-01-01

    A Virtual Network Operator (VNO) is a provider and reseller of network services from other telecommunications suppliers. These network providers are categorized as virtual because they do not own the underlying telecommunication infrastructure. In terms of business operation, VNO can provide customers with personalized services by leasing network infrastructure from traditional network providers. The unique business modes of VNO lead to the emergence of network on demand (NoD) services. The conventional network provisioning involves a series of manual operation and configuration, which leads to high cost in time. Considering the advantages of Software Defined Networking (SDN), this paper proposes a novel NoD service provisioning solution to satisfy the private network need of VNOs. The solution is first verified in the real software defined multi-domain optical networks with multi-vendor OTN equipment. With the proposed solution, NoD service can be deployed via online web portals in near-real time. It reinvents the customer experience and redefines how network services are delivered to customers via an online self-service portal. Ultimately, this means a customer will be able to simply go online, click a few buttons and have new services almost instantaneously.

  10. NodHex3D: An application for solving the neutron diffusion equations in hexagonal-Z geometry and steady state

    International Nuclear Information System (INIS)

    Esquivel E, J.; Del Valle G, E.

    2014-10-01

    The system called NodHex3D is a graphical application that allows the solution of the neutron diffusion equation. The system considers fuel assemblies of hexagonal cross section. This application arose from the idea of expanding the development of neutron own codes, used primarily for academic purposes. The advantage associated with the use of NodHex3D, is that the kernel configuration and fuel batches is dynamically without affecting directly the base source code of the solution of the neutron diffusion equation. In addition to the kernel configuration to use, specify the values for the cross sections for each batch of fuel used, these values are: diffusion coefficient, removal cross section, absorption cross section, fission cross section and dispersion cross section. Important also, considering that the system is able to perform calculations for various energy groups. As evidence of the operation of NodHex3D, was proposed to model three-dimensional core of a nuclear reactor VVER-1000, based on the reference problem AER-FCM-101. The configuration of the reactor core consists of fuel assemblies (25 batches), composed of seven distinct materials, one of which reflector material, vacuum boundary conditions on the surface delimiting the reactor core. The diffusion equation for two energy groups solves, obtaining the value of the effective neutron multiplication factor. The obtained results are compared to those documented in the reference problem and by 3-DNT codes. (Author)

  11. Oral administration of Lactococcus lactis-expressing heat shock protein 65 and tandemly repeated IA2P2 prevents type 1 diabetes in NOD mice.

    Science.gov (United States)

    Liu, Kun-Feng; Liu, Xiao-Rui; Li, Guo-Liang; Lu, Shi-Ping; Jin, Liang; Wu, Jie

    2016-06-01

    Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of insulin-secreting β cells upon autoreactive T cell attack. Oral administration of autoantigens is an attractive approach to treating T1DM, but an effective carrier should be used in order to protect antigens. Lactococcus lactis, a safe engineering strain, was used for this task in the present study. Two recombinant L. lactis expressing protein HSP65-6IA2P2 were used and be investigated the effects and mechanisms against T1DM in NOD mice. Our findings demonstrate that recombinant L. lactis strains can successfully both deliver antigens to intestinal mucosa and maintain the epitopes for a long time in NOD mice. Oral administration of recombinant L. lactis could prevent hyperglycemia, improve glucose tolerance, and reduce insulitis by inhibiting antigen-specific proliferation of T cells, augmenting regulatory immune reactions, and balancing ratios of Th17/Tregs and Th1/Th2. These results prove that orally administrated L. lactis expressing HSP65-6IA2P2 is an effective approach for the prevention of T1DM in NOD mice. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  12. Mechanical signaling coordinates the embryonic heartbeat

    Science.gov (United States)

    Chiou, Kevin K.; Rocks, Jason W.; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E.; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F.; Prosser, Benjamin L.; Discher, Dennis E.; Liu, Andrea J.

    2016-01-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts—consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  13. Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses.

    Directory of Open Access Journals (Sweden)

    Muhammad Shafique

    Full Text Available INTRODUCTION: RSV infection remains a serious threat to newborns and the elderly. Currently, there is no vaccine available to prevent RSV infection. A mucosal RSV vaccine would be attractive as it could induce mucosal as well as systemic antibodies, capable of protecting both the upper and lower respiratory tract. Previously, we reported on a virosomal RSV vaccine for intramuscular injection with intrinsic adjuvant properties mediated by an incorporated lipophilic Toll-like receptor 2 (TLR2 ligand. However, it has not been investigated whether this virosomal RSV vaccine candidate would be suitable for use in mucosal immunization strategies and if additional incorporation of other innate receptor ligands, like NOD2-ligand, could further enhance the immunogenicity and protective efficacy of the vaccine. OBJECTIVE: To explore if intranasal (IN immunization with a virosomal RSV vaccine, supplemented with TLR2 and/or NOD2-ligands, is an effective strategy to induce RSV-specific immunity. METHODS: We produced RSV-virosomes carrying TLR2 (Pam3CSK4 and/or NOD2 (L18-MDP ligands. We tested the immunopotentiating properties of these virosomes in vitro, using TLR2- and/or NOD2-ligand-responsive murine and human cell lines, and in vivo by assessing induction of protective antibody and cellular responses upon IN immunization of BALB/c mice. RESULTS: Incorporation of Pam3CSK4 and/or L18-MDP potentiates the capacity of virosomes to activate (antigen-presenting cells in vitro, as demonstrated by NF-κB induction. In vivo, incorporation of Pam3CSK4 in virosomes boosted serum IgG antibody responses and mucosal antibody responses after IN immunization. While L18-MDP alone was ineffective, incorporation of L18-MDP in Pam3CSK4-carrying virosomes further boosted mucosal antibody responses. Finally, IN immunization with adjuvanted virosomes, particularly Pam3CSK4/L18-MDP-adjuvanted-virosomes, protected mice against infection with RSV, without priming for enhanced

  14. Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igμnull mice after polyclonal B cell reconstitution

    Directory of Open Access Journals (Sweden)

    Sercarz Eli E

    2011-07-01

    Full Text Available Abstract Background Non Obese Diabetic mice lacking B cells (NOD.Igμnull mice do not develop diabetes despite their susceptible background. Upon reconstitution of B cells using a chimera approach, animals start developing diabetes at 20 weeks of age. Methods We have used the spectratyping technique to follow the T cell receptor (TCR V beta repertoire of NOD.Igμnull mice following B cell reconstitution. This technique provides an unbiased approach to understand the kinetics of TCR expansion. We have also analyzed the TCR repertoire of reconstituted animals receiving cyclophosphamide treatment and following tissue transplants to identify common aggressive clonotypes. Results We found that B cell reconstitution of NOD.Igμnull mice induces a polyclonal TCR repertoire in the pancreas 10 weeks later, gradually diversifying to encompass most BV families. Interestingly, these clonotypic BV expansions are mainly confined to the pancreas and are absent from pancreatic lymph nodes or spleens. Cyclophosphamide-induced diabetes at 10 weeks post-B cell reconstitution reorganized the predominant TCR repertoires by removing potential regulatory clonotypes (BV1, BV8 and BV11 and increasing the frequency of others (BV4, BV5S2, BV9, BV16-20. These same clonotypes are more frequently present in neonatal pancreatic transplants under the kidney capsule of B-cell reconstituted diabetic NOD.Igμnull mice, suggesting their higher invasiveness. Phenotypic analysis of the pancreas-infiltrating lymphocytes during diabetes onset in B cell reconstituted animals show a predominance of CD19+ B cells with a B:T lymphocyte ratio of 4:1. In contrast, in other lymphoid organs (pancreatic lymph nodes and spleens analyzed by FACS, the B:T ratio was 1:1. Lymphocytes infiltrating the pancreas secrete large amounts of IL-6 and are of Th1 phenotype after CD3-CD28 stimulation in vitro. Conclusions Diabetes in NOD.Igμnull mice appears to be caused by a polyclonal repertoire of T cell

  15. Network Coordinator Report

    Science.gov (United States)

    Himwich, Ed; Strand, Richard

    2013-01-01

    This report includes an assessment of the network performance in terms of lost observing time for the 2012 calendar year. Overall, the observing time loss was about 12.3%, which is in-line with previous years. A table of relative incidence of problems with various subsystems is presented. The most significant identified causes of loss were electronics rack problems (accounting for about 21.8% of losses), antenna reliability (18.1%), RFI (11.8%), and receiver problems (11.7%). About 14.2% of the losses occurred for unknown reasons. New antennas are under development in the USA, Germany, and Spain. There are plans for new telescopes in Norway and Sweden. Other activities of the Network Coordinator are summarized.

  16. Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer.

    Science.gov (United States)

    Huhn, Stefanie; da Silva Filho, Miguel I; Sanmuganantham, Tharmila; Pichulik, Tica; Catalano, Calogerina; Pardini, Barbara; Naccarati, Alessio; Polakova-Vymetálkova, Veronika; Jiraskova, Katerina; Vodickova, Ludmila; Vodicka, Pavel; Löffler, Markus W; Courth, Lioba; Wehkamp, Jan; Din, Farhat V N; Timofeeva, Maria; Farrington, Susan M; Jansen, Lina; Hemminki, Kari; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael; Dunlop, Malcolm G; Weber, Alexander N R; Försti, Asta

    2018-01-01

    Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.

  17. Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation.

    Directory of Open Access Journals (Sweden)

    Nan Wang

    Full Text Available Type I diabetes (T1D, mediated by autoreactive T cell destruction of insulin-producing islet beta cells, has been treated with bone marrow-derived hematopoietic stem cell (BM-HSC transplantation. Older non-obese diabetic (NOD mice recipients (3m, at disease-onset stage receiving syngeneic BM-HSC progressed more rapidly to end-stage diabetes post-transplantation than younger recipients (4-6w, at disease-initiation stage. FACS analyses showed a higher percentage and absolute number of regulatory T cells (Treg and lower proportion of proliferating T conventional cells (Tcon in pancreatic lymph nodes from the resistant mice among the younger recipients compared to the rapid progressors among the older recipients. Treg distribution in spleen, mesenteric lymph nodes (MLN, blood and thymus between the two groups was similar. However, the percentage of thymic Tcon and the proliferation of Tcon in MLN and blood were lower in the young resistants. These results suggest recipient age and associated disease stage as a variable to consider in BM-HSC transplantation for treating T1D.

  18. Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation.

    Science.gov (United States)

    Kahn, Joy; Byk, Tamara; Jansson-Sjostrand, Lottie; Petit, Isabelle; Shivtiel, Shoham; Nagler, Arnon; Hardan, Izhar; Deutsch, Varda; Gazit, Zulma; Gazit, Dan; Karlsson, Stefan; Lapidot, Tsvee

    2004-04-15

    A major limitation to clinical stem cell-mediated gene therapy protocols is the low levels of engraftment by transduced progenitors. We report that CXCR4 overexpression on human CD34+ progenitors using a lentiviral gene transfer technique helped navigate these cells to the murine bone marrow and spleen in response to stromal-derived factor 1 (SDF-1) signaling. Cells overexpressing CXCR4 exhibited significant increases in SDF-1-mediated chemotaxis and actin polymerization compared with control cells. A major advantage of CXCR4 overexpression was demonstrated by the ability of transduced CD34+ cells to respond to lower, physiologic levels of SDF-1 when compared to control cells, leading to improved SDF-1-induced migration and proliferation/survival, and finally resulting in significantly higher levels of in vivo repopulation of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice including primitive CD34+/CD38(-/low) cells. Importantly, no cellular transformation was observed following transduction with the CXCR4 vector. Unexpectedly, we documented lack of receptor internalization in response to high levels of SDF-1, which can also contribute to increased migration and proliferation by the transduced CD34+ cells. Our results suggest CXCR4 overexpression for improved definitive human stem cell motility, retention, and multilineage repopulation, which could be beneficial for in vivo navigation and expansion of hematopoietic progenitors.

  19. Coordinating Group report

    International Nuclear Information System (INIS)

    1994-01-01

    In December 1992, western governors and four federal agencies established a Federal Advisory Committee to Develop On-site Innovative Technologies for Environmental Restoration and Waste Management (the DOIT Committee). The purpose of the Committee is to advise the federal government on ways to improve waste cleanup technology development and the cleanup of federal sites in the West. The Committee directed in January 1993 that information be collected from a wide range of potential stakeholders and that innovative technology candidate projects be identified, organized, set in motion, and evaluated to test new partnerships, regulatory approaches, and technologies which will lead to improve site cleanup. Five working groups were organized, one to develop broad project selection and evaluation criteria and four to focus on specific contaminant problems. A Coordinating Group comprised of working group spokesmen and federal and state representatives, was set up to plan and organize the routine functioning of these working groups. The working groups were charged with defining particular contaminant problems; identifying shortcomings in technology development, stakeholder involvement, regulatory review, and commercialization which impede the resolution of these problems; and identifying candidate sites or technologies which could serve as regional innovative demonstration projects to test new approaches to overcome the shortcomings. This report from the Coordinating Group to the DOIT Committee highlights the key findings and opportunities uncovered by these fact-finding working groups. It provides a basis from which recommendations from the DOIT Committee to the federal government can be made. It also includes observations from two public roundtables, one on commercialization and another on regulatory and institutional barriers impeding technology development and cleanup

  20. NOD2/CARD15: geographic differences in the Spanish population and clinical applications in Crohn's disease NOD2/CARD15: diferencias geográficas en la población española y su aplicación clínica en la enfermedad de Crohn

    Directory of Open Access Journals (Sweden)

    M. Barreiro-de-Acosta

    2010-05-01

    Full Text Available Crohn's disease (CD is a genetically complex disease in which both genetic susceptibility and environmental factors play key roles in the development of the disorder. NOD2/CARD15 mutations are associated with CD. NOD2 encodes for a protein that is an intracellular receptor for a bacterial product (muramyl dipeptide, though the exact functional consequences of these mutations remain the subject of debate. NOD2/CARD15 mutations are associated with ileal CD, with stricturing behavior, and possibly with a more complicated course of CD. NOD2/CARD15 mutations associated with CD have demonstrated heterogeneity across ethnicities and populations throughout the world, with regional variations across Europe and Spain. However, "NOD2/CARD15 testing" is not yet ready for use in the clinical setting. One of the reasons is that we know that these genetic variants increase the risk of disease only marginally, and many healthy individuals carry the risk alleles, At present it is not recommended to screen first-degree relatives, because we do not have the ability to prevent the disease at the present time.La enfermedad de Crohn (EC es una enfermedad compleja desde el punto de vista de la genética puesto que para el desarrollo de la enfermedad se tiene que producir una interacción entre factores genéticos y ambientales. Las mutaciones del gen NOD2/CARD15 se han asociado con la susceptibilidad a padecer la EC. El gen NOD2/CARD15 codifica una proteína que actúa como un receptor intracelular de la proteína dipeptidomuramil que se encuentran en la pared de cubierta de algunas bacterias. Actualmente se desconoce cuál es el papel exacto de estas mutaciones en el funcionamiento de la proteína NOD2/CARD15. Estas mutaciones se han asociado con la localización en intestino delgado de la enfermedad, el comportamiento fibroestenosante y con un curso más grave de la enfermedad. Las tres mutaciones asociadas con la EC presentan una distribución desigual entre las

  1. Coordination chemistry and bioactivity of Ni2+, Cu2+, and Zn2+ complexes containing a bidentate NS ligand, β-N-phenyldithiocarbazic acid, and the crystal structure of β-hydroxy-β-phenylmethylene α-phenylimine

    International Nuclear Information System (INIS)

    Tarafder, M.T.H.; Ahmed Faizal Shamsuddin; Grouse, Karen A.; Yamin, B.M.; Ali, A.M.; Fun, H.-K.

    2003-07-01

    A bidentate ligand (PhDTCH) with NS donor sequence was prepared from the reaction between carbon disulfide and phenylhydrazine in ethanol. Complexes of this ligand with Ni(II), Cu(II) and Zn(II) were synthesized and characterized by elemental analyses, and various physicochemical techniques. The metal complexes were all four coordinated. In an attempt to resolve the crystal structure of PhDTCH, an ethanolic solution, after leaving for a few days gave bright crystals of PhD6, β-hydroxy-β-phenylmethylene α-phenylimine, the crystal structure of which has been resolved. The crystal packing indicated that it is monoclinic with a space group of P21/n. All of the compounds were tested against different bacteria and fungi, and also against leukemic cell lines. All of the compounds showed weak biological properties compared to standard drugs. (author)

  2. Coordinates in relativistic Hamiltonian mechanics

    International Nuclear Information System (INIS)

    Sokolov, S.N.

    1984-01-01

    The physical (covariant and measurable) coordinates of free particles and covariant coordinates of the center of inertia are found for three main forms of relativistic dynamics. In the point form of dynamics, the covariant coordinates of two directly interacting particles are found, and the equations of motion are brought to the explicitly covariant form. These equations are generalized to the case of interaction with an external electromagnetic field

  3. Exposure to perfluoroundecanoic acid (PFUnDA accelerates insulitis development in a mouse model of type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Johanna Bodin

    Full Text Available Perfluoralkylated substances (PFAS are classified as persistent, bioaccumulative and toxic substances and are widespread environmental contaminants. Humans are exposed through food, drinking water and air. We have previously reported that bisphenol A accelerates spontaneous diabetes development in non-obese diabetic (NOD mice and observed in the present study that perfluoroundecanoic acid, PFUnDA, increased insulitis development, a prerequisite for diabetes development in NOD mice. We exposed NOD mice to PFUnDA in drinking water (3, 30 and 300 μg/l at mating, during gestation and lactation and until 30 weeks of age. After 300 μg/l PFUnDA exposure, we report (i increased pancreatic insulitis, (ii increased number of apoptotic cells in pancreatic islets prior to insulitis and (iii decreased phagocytosis in peritoneal macrophages. There was also a trend of decreased number of tissue resident macrophages in pancreatic islets prior to insulitis after exposure to 300 μg/l, and altered cytokine secretion in activated splenocytes after exposure to 3 μg/l PFUnDA. Although insulitis is a prerequisite for autoimmune diabetes, the accelerated insulitis was not associated with accelerated diabetes development. Instead, the incidence of diabetes tended to be reduced in the animals exposed to 3 and 30 μg/l PFUnDA, suggesting a non-monotonic dose response. The effects of PFUnDA exposure on increased apoptosis in pancreas and reduced macrophage function as well as accelerated insulitis development in NOD mice, may also be relevant for human insulitis. Further observational autoimmune diabetes clinical cohort studies and animal experiments for PFUnDA as well as other PFASs are therefore encouraged. Keywords: Perfluoralkylated substances, PFUnDA, T1DM, Diabetes, NOD mice, Insulitis

  4. Calculating the Response of NMR Shielding Tensor .sigma.(31P) and 2J(31P,13C) Coupling Constants in Nucleic Acid Phosphate to Coordination of the Mg2+Cation

    Czech Academy of Sciences Publication Activity Database

    Benda, Ladislav; Schneider, Bohdan; Sychrovský, Vladimír

    2011-01-01

    Roč. 115, č. 11 (2011), s. 2385-2395 ISSN 1089-5639 R&D Projects: GA AV ČR IAA400550701; GA ČR GAP205/10/0228 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520701 Keywords : nucleic acids * phosphate * NMR Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.946, year: 2011

  5. Molecular role of TGF-beta, secreted from a new type of CD4+ suppressor T cell, NY4.2, in the prevention of autoimmune IDDM in NOD mice.

    Science.gov (United States)

    Han, H S; Jun, H S; Utsugi, T; Yoon, J W

    1997-06-01

    A new type of CD4+ T cell clone (NY4.2) isolated from pancreatic islet-infiltrated lymphocytes of acutely diabetic non-obese diabetic (NOD) mice prevents the development of insulin-dependent diabetes mellitus (IDDM) in NOD mice, as well as the recurrence of autoimmune diabetes in syngeneic islet-transplanted NOD mice. It has been demonstrated that the cytokine TGF-beta, secreted from the cells of this clone, is the substance which prevents autoimmune IDDM. This investigation was initiated to determine the molecular role TGF-beta plays in the prevention of autoimmune IDDM by determining its effect on IL-2-induced signal transduction in Con A-activated NOD mouse splenocytes and HT-2 cells. First, we determined whether TGF-beta, secreted from NY4.2 T cells, inhibits IL-2-dependent T cell proliferation in HT-2 cells (IL-2-dependent T cell line) and NOD splenocytes. We found that TGF-beta suppresses IL-2-dependent T cell proliferation. Second, we determined whether TGF-beta inhibits the activation of Janus kinases (JAKs), as well as signal transducers and activators of transcription (STAT) proteins, involved in an IL-2-induced signalling pathway that normally leads to the proliferation of T cells. We found that TGF-beta inhibited tyrosine phosphorylation of JAK1, JAK3, STAT3 and STAT5 in Con A blasts from NOD splenocytes and HT-2 cells. Third, we examined whether TGF-beta inhibits the cooperation between STAT proteins and mitogen-activated protein kinase (MAPK), especially extracellular signal-regulated kinase 2 (ERK2). We found that TGF-beta inhibited the association of STAT3 and STAT5 with ERK2 in Con A blasts from NOD splenocytes and HT-2 cells. On the basis of these observations, we conclude that TGF-beta may interfere with signal transduction via inhibition of the IL-2-induced JAK/STAT pathway and inhibition of the association of STAT proteins with ERK2 in T cells from NOD splenocytes, resulting in the inhibition of IL-2-dependent T cell proliferation. TGF

  6. A three-dimensional coordination polymer based on 1,2,3-triazole-4,5-dicarboxylic acid (H{sub 3}tda): ([Cd{sub 12}(tda){sub 8}(H{sub 2}O){sub 11}] · (H{sub 2}O)6.25){sub n}

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xin-Hui, E-mail: iamxhzhou@njupt.edu.cn; Chen, Qiang [Nanjing University of Posts and Telecommunications, Key Laboratory for Organic Electronics and Information Displays and Institute of Advanced Materials, National Jiangsu Syngerstic Innovation Center for Advanced Materials (SICAM) (China)

    2017-03-15

    The title coordination polymer ([Cd{sub 12}(tda){sub 8}(H{sub 2}O){sub 11}] · (H{sub 2}O){sub 6.25}){sub n} (H{sub 3}tda = 1,2,3-triazole-4,5-dicarboxylic acid), has been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction. Complex crystallizes in orthorhombic sp. gr. Pmn2{sub 1} with Z = 4. The Cd{sub 2} unit doublebridged by one carboxylate oxygen atom and two neighboring nitrogen atoms from the tda{sup 3–} ligands are linked by the tda{sup 3–}ligands to lead to the 2D (4,4) network in the ac plane. The almost coplanar Cd{sub 2}(μ{sub 5}-tda){sub 2} unit comprised of two Cd ions double-bridged by two tda{sup 3–} ligands through the neighboring nitrogen atoms is connected with the other four Cd{sub 2}(μ{sub 5}-tda){sub 2} units form the undulating 2D network in the ac plane. The (4,4) networks and undulating 2D networks are alternatively connected along the b axis by the tda{sup 3–} ligands coordinating to the Cd ions to form the 3D framework.

  7. Synthesis, crystal structure and luminescent properties of one 3D Cd(II) coordination polymer [Cd(H3BPTC)2(bpy)]n (H4BPTC = 1,1'-biphenyl-2,2',6,6'-tetracarboxylic acid, bpy = 4,4'-bipyridine).

    Science.gov (United States)

    Mei, Chong-Zhen; Shan, Wen-Wen; Liu, Bing-Tao

    2011-10-15

    A new 3D metal-organic coordination polymer [Cd(H(3)BPTC)(2)(bpy)](n) (1) (H(4)BPTC = 1,1'-biphenyl-2,2',6,6'-tetracarboxylic acid, bpy =4,4'-bipyridine) has been synthesized and characterized by single X-ray diffraction and IR spectroscopy. The one-dimensional metal-organic chains of the title complex, namely [Cd(H(3)BPTC)(2)](n), are held together through hydrogen bonding and bridging "second" ligand 4,4'-bpy to give a three-dimensional metal-organic network. The thermal stability of complex 1 was studied by thermal gravimetric (TG) and differential thermal analysis (DTA). Compound 1 exhibits photoluminescence with an emission maximum at ca. 380 nm upon excitation at ca. 251 nm. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Coordination of Conditional Poisson Samples

    Directory of Open Access Journals (Sweden)

    Grafström Anton

    2015-12-01

    Full Text Available Sample coordination seeks to maximize or to minimize the overlap of two or more samples. The former is known as positive coordination, and the latter as negative coordination. Positive coordination is mainly used for estimation purposes and to reduce data collection costs. Negative coordination is mainly performed to diminish the response burden of the sampled units. Poisson sampling design with permanent random numbers provides an optimum coordination degree of two or more samples. The size of a Poisson sample is, however, random. Conditional Poisson (CP sampling is a modification of the classical Poisson sampling that produces a fixed-size πps sample. We introduce two methods to coordinate Conditional Poisson samples over time or simultaneously. The first one uses permanent random numbers and the list-sequential implementation of CP sampling. The second method uses a CP sample in the first selection and provides an approximate one in the second selection because the prescribed inclusion probabilities are not respected exactly. The methods are evaluated using the size of the expected sample overlap, and are compared with their competitors using Monte Carlo simulation. The new methods provide a good coordination degree of two samples, close to the performance of Poisson sampling with permanent random numbers.

  9. Coordination in continuously repeated games

    NARCIS (Netherlands)

    Weeren, A.J.T.M.; Schumacher, J.M.; Engwerda, J.C.

    1995-01-01

    In this paper we propose a model to describe the effectiveness of coordination in a continuously repeated two-player game. We study how the choice of a decision rule by a coordinator affects the strategic behavior of the players, resulting in more or less cooperation. Our model requires the analysis

  10. Coordinated Transportation: Problems and Promise?

    Science.gov (United States)

    Fickes, Michael

    1998-01-01

    Examines the legal, administrative, and logistical barriers that have prevented the wide acceptance of coordinating community and school transportation services and why these barriers may be breaking down. Two examples of successful implementation of coordinated transportation are examined: employing a single system to serve all transportation…

  11. Bare coordination: the semantic shift

    NARCIS (Netherlands)

    de Swart, Henriette; Le Bruyn, Bert

    2014-01-01

    This paper develops an analysis of the syntax-semantics interface of two types of split coordination structures. In the first type, two bare singular count nouns appear as arguments in a coordinated structure, as in bride and groom were happy. We call this the N&N construction. In the second type,

  12. A two-dimensional bilayered Cd(II) coordination polymer with a three-dimensional supramolecular architecture incorporating 1,2-bis(pyridin-4-yl)ethene and 2,2'-(diazenediyl)dibenzoic acid.

    Science.gov (United States)

    Liu, Lei-Lei; Zhou, Yan; Li, Ping; Tian, Jiang-Ya

    2014-02-01

    In poly[[μ2-1,2-bis(pyridin-4-yl)ethene-κ(2)N:N'][μ2-2,2'-(diazenediyl)dibenzoato-κ(3)O,O':O'']cadmium(II)], [Cd(C14H8N2O4)(C12H10N2)]n, the asymmetric unit contains one Cd(II) cation, one 2,2'-(diazenediyl)dibenzoate anion (denoted L(2-)) and one 1,2-bis(pyridin-4-yl)ethene ligand (denoted bpe). Each Cd(II) centre is six-coordinated by four O atoms of bridging/chelating carboxylate groups from three L(2-) ligands and by two N atoms from two bpe ligands, forming a distorted octahedron. The Cd(II) cations are bridged by L(2-) and bpe ligands to give a two-dimensional (4,4) layer. The layers are interlinked through bridging carboxylate O atoms from L(2-) ligands, generating a two-dimensional bilayered structure with a 3(6)4(13)6(2) topology. The bilayered structures are further extended to form a three-dimensional supramolecular architecture via a combination of hydrogen-bonding and aromatic stacking interactions.

  13. Nod-Like Receptor Protein-3 Inflammasome Plays an Important Role during Early Stages of Wound Healing

    Science.gov (United States)

    Weinheimer-Haus, Eileen M.; Mirza, Rita E.; Koh, Timothy J.

    2015-01-01

    The Nod-like receptor protein (NLRP)-3 inflammasome/IL-1β pathway is involved in the pathogenesis of various inflammatory skin diseases, but its biological role in wound healing remains to be elucidated. Since inflammation is typically thought to impede healing, we hypothesized that loss of NLRP-3 activity would result in a downregulated inflammatory response and accelerated wound healing. NLRP-3 null mice, caspase-1 null mice and C57Bl/6 wild type control mice (WT) received four 8 mm excisional cutaneous wounds; inflammation and healing were assessed during the early stage of wound healing. Consistent with our hypothesis, wounds from NLRP-3 null and caspase-1 null mice contained lower levels of the pro-inflammatory cytokines IL-1β and TNF-α compared to WT mice and had reduced neutrophil and macrophage accumulation. Contrary to our hypothesis, re-epithelialization, granulation tissue formation, and angiogenesis were delayed in NLRP-3 null mice and caspase-1 null mice compared to WT mice, indicating that NLRP-3 signaling is important for early events in wound healing. Topical treatment of excisional wounds with recombinant IL-1β partially restored granulation tissue formation in wounds of NLRP-3 null mice, confirming the importance of NLRP-3-dependent IL-1β production during early wound healing. Despite the improvement in healing, angiogenesis and levels of the pro-angiogenic growth factor VEGF were further reduced in IL-1β treated wounds, suggesting that IL-1β has a negative effect on angiogenesis and that NLRP-3 promotes angiogenesis in an IL-1β-independent manner. These findings indicate that the NLRP-3 inflammasome contributes to the early inflammatory phase following skin wounding and is important for efficient healing. PMID:25793779

  14. Multipole structure and coordinate systems

    International Nuclear Information System (INIS)

    Burko, Lior M

    2007-01-01

    Multipole expansions depend on the coordinate system, so that coefficients of multipole moments can be set equal to zero by an appropriate choice of coordinates. Therefore, it is meaningless to say that a physical system has a nonvanishing quadrupole moment, say, without specifying which coordinate system is used. (Except if this moment is the lowest non-vanishing one.) This result is demonstrated for the case of two equal like electric charges. Specifically, an adapted coordinate system in which the potential is given by a monopole term only is explicitly found, the coefficients of all higher multipoles vanish identically. It is suggested that this result can be generalized to other potential problems, by making equal coordinate surfaces adapt to the potential problem's equipotential surfaces

  15. Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

    Science.gov (United States)

    Bai, Xue; Zhang, Xiangjian; Chen, Linyu; Zhang, Jian; Zhang, Lan; Zhao, Xumeng; Zhao, Ting; Zhao, Yuan

    2014-08-01

    Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Naringenin (NG) has gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigate the potential neuroprotective role of NG and the underlying mechanisms. Focal cerebral ischemia in male Sprague-Dawley rats was induced by permanent middle cerebral artery occlusion (pMCAO) and NG was pre-administered intragastrically once daily for four consecutive days before surgery. Neurological deficit, brain water content and infarct volume were measured at 24 h after stroke. Immunohistochemistry, Western blot and RT-qPCR were used to explore the anti-inflammatory potential of NG in the regulation of NOD2, RIP2 and NF-κB in ischemic cerebral cortex. Additionally, the activities of MMP-9 and claudin-5 were analyzed to detect NG's influence on blood-brain barrier. Compared with pMCAO and Vehicle groups, NG noticeably improved neurological deficit, decreased infarct volume and edema at 24 h after ischemic insult. Consistent with these results, our data also indicated that NG significantly downregulated the expression of NOD2, RIP2, NF-κB and MMP-9, and upregulated the expression of claudin-5 (P < 0.05). The results provided a neuroprotective profile of NG in cerebral ischemia, this effect was likely exerted by down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

  16. Apoptosis of purified CD4+ T cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic NOD mice.

    Directory of Open Access Journals (Sweden)

    Ayelet Kaminitz

    Full Text Available BACKGROUND: Regulatory T cells (Treg play a significant role in immune homeostasis and self-tolerance. Excessive sensitivity of isolated Treg to apoptosis has been demonstrated in NOD mice and humans suffering of type 1 diabetes, suggesting a possible role in the immune dysfunction that underlies autoimmune insulitis. In this study the sensitivity to apoptosis was measured in T cells from new onset diabetic NOD females, comparing purified subsets to mixed cultures. PRINCIPAL FINDINGS: Apoptotic cells are short lived in vivo and death occurs primarily during isolation, manipulation and culture. Excessive susceptibility of CD25(+ T cells to spontaneous apoptosis is characteristic of isolated subsets, however disappears when death is measured in mixed splenocyte cultures. In variance, CD25(- T cells display balanced sensitivity to apoptosis under both conditions. The isolation procedure removes soluble factors, IL-2 playing a significant role in sustaining Treg viability. In addition, pro- and anti-apoptotic signals are transduced by cell-to-cell interactions: CD3 and CD28 protect CD25(+ T cells from apoptosis, and in parallel sensitize naïve effector cells to apoptosis. Treg viability is modulated both by other T cells and other subsets within mixed splenocyte cultures. Variations in sensitivity to apoptosis are often hindered by fast proliferation of viable cells, therefore cycling rates are mandatory to adequate interpretation of cell death assays. CONCLUSIONS: The sensitivity of purified Treg to apoptosis is dominated by cytokine deprivation and absence of cell-to-cell interactions, and deviate significantly from measurements in mixed populations. Balanced sensitivity of naïve/effector and regulatory T cells to apoptosis in NOD mice argues against the concept that differential susceptibility affects disease evolution and progression.

  17. Autoreactive effector/memory CD4+ and CD8+ T cells infiltrating grafted and endogenous islets in diabetic NOD mice exhibit similar T cell receptor usage.

    Directory of Open Access Journals (Sweden)

    Ramiro Diz

    Full Text Available Islet transplantation provides a "cure" for type 1 diabetes but is limited in part by recurrent autoimmunity mediated by β cell-specific CD4(+ and CD8(+ T cells. Insight into the T cell receptor (TCR repertoire of effector T cells driving recurrent autoimmunity would aid the development of immunotherapies to prevent islet graft rejection. Accordingly, we used a multi-parameter flow cytometry strategy to assess the TCR variable β (Vβ chain repertoires of T cell subsets involved in autoimmune-mediated rejection of islet grafts in diabetic NOD mouse recipients. Naïve CD4(+ and CD8(+ T cells exhibited a diverse TCR repertoire, which was similar in all tissues examined in NOD recipients including the pancreas and islet grafts. On the other hand, the effector/memory CD8(+ T cell repertoire in the islet graft was dominated by one to four TCR Vβ chains, and specific TCR Vβ chain usage varied from recipient to recipient. Similarly, islet graft- infiltrating effector/memory CD4(+ T cells expressed a limited number of prevalent TCR Vβ chains, although generally TCR repertoire diversity was increased compared to effector/memory CD8(+ T cells. Strikingly, the majority of NOD recipients showed an increase in TCR Vβ12-bearing effector/memory CD4(+ T cells in the islet graft, most of which were proliferating, indicating clonal expansion. Importantly, TCR Vβ usage by effector/memory CD4(+ and CD8(+ T cells infiltrating the islet graft exhibited greater similarity to the repertoire found in the pancreas as opposed to the draining renal lymph node, pancreatic lymph node, or spleen. Together these results demonstrate that effector/memory CD4(+ and CD8(+ T cells mediating autoimmune rejection of islet grafts are characterized by restricted TCR Vβ chain usage, and are similar to T cells that drive destruction of the endogenous islets.

  18. Addition of HO-nucleophiles to free and coordinated nitriles

    International Nuclear Information System (INIS)

    Bokach, Nadejda A; Kukushkin, Vadim Yu

    2005-01-01

    The review surveys data on the addition of HO-nucleophiles (water, oximes, hydroxylamines, hydroxamic acids, alcohols) to nitriles. Main methods for C≡N bond activation in nucleophilic addition reactions are discussed. Particular attention is given to activation of nitriles through coordination to metal centres.

  19. NodHex3D: An application for solving the neutron diffusion equations in hexagonal-Z geometry and steady state; NodHex3D: Una aplicacion para solucionar las ecuaciones de difusion de neutrones en geometria hexagonal-Z y estado estacionario

    Energy Technology Data Exchange (ETDEWEB)

    Esquivel E, J. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Del Valle G, E., E-mail: jaime.esquivel@inin.gob.mx [IPN, Escuela Superior de Fisica y Matematicas, Av. IPN s/n, Edificio 9, Col. San Pedro Zacatenco, 07738 Mexico D. F. (Mexico)

    2014-10-15

    The system called NodHex3D is a graphical application that allows the solution of the neutron diffusion equation. The system considers fuel assemblies of hexagonal cross section. This application arose from the idea of expanding the development of neutron own codes, used primarily for academic purposes. The advantage associated with the use of NodHex3D, is that the kernel configuration and fuel batches is dynamically without affecting directly the base source code of the solution of the neutron diffusion equation. In addition to the kernel configuration to use, specify the values for the cross sections for each batch of fuel used, these values are: diffusion coefficient, removal cross section, absorption cross section, fission cross section and dispersion cross section. Important also, considering that the system is able to perform calculations for various energy groups. As evidence of the operation of NodHex3D, was proposed to model three-dimensional core of a nuclear reactor VVER-1000, based on the reference problem AER-FCM-101. The configuration of the reactor core consists of fuel assemblies (25 batches), composed of seven distinct materials, one of which reflector material, vacuum boundary conditions on the surface delimiting the reactor core. The diffusion equation for two energy groups solves, obtaining the value of the effective neutron multiplication factor. The obtained results are compared to those documented in the reference problem and by 3-DNT codes. (Author)

  20. Keep Meaning in Conversational Coordination

    Directory of Open Access Journals (Sweden)

    Elena Clare Cuffari

    2014-12-01

    Full Text Available Coordination is a widely employed term across recent quantitative and qualitative approaches to intersubjectivity, particularly approaches that give embodiment and enaction central explanatory roles. With a focus on linguistic and bodily coordination in conversational contexts, I review the operational meaning of coordination in recent empirical research and related theorizing of embodied intersubjectivity. This discussion articulates what must be involved in treating linguistic meaning as dynamic processes of coordination. The coordination approach presents languaging as a set of dynamic self-organizing processes and actions on multiple timescales and across multiple modalities that come about and work in certain domains (those jointly constructed in social, interactive, high-order sense-making. These processes go beyond meaning at the level that is available to first-person experience. I take one crucial consequence of this to be the ubiquitously moral nature of languaging with others. Languaging coordinates experience, among other levels of behavior and event. Ethical effort is called for by the automatic autonomy-influencing forces of languaging as coordination.

  1. Coordinating distributed work : Exploring situated coordination with gaming-simulation

    NARCIS (Netherlands)

    van Laere, J.

    2003-01-01

    Organizational work has become more and more distributed nowadays. Information and communication technologies (ICT) provide opportunities to improve coordination of distributed work, but in practice many organizations struggle with integrating new organizational structures, new work practices and

  2. The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007fs Mutation and may be Explained by Age at Diagnosis: A Meta-Analysis and Case-Only Study.

    Science.gov (United States)

    Kuenzig, M Ellen; Yim, Jeff; Coward, Stephanie; Eksteen, Bertus; Seow, Cynthia H; Barnabe, Cheryl; Barkema, Herman W; Silverberg, Mark S; Lakatos, Peter L; Beck, Paul L; Fedorak, Richard; Dieleman, Levinus A; Madsen, Karen; Panaccione, Remo; Ghosh, Subrata; Kaplan, Gilaad G

    2017-07-01

    NOD2 and smoking are risk factors for Crohn's disease. We meta-analyzed NOD2-smoking interactions in Crohn's disease (Phase 1), then explored the effect of age at diagnosis on NOD2-smoking interactions (Phase 2). Phase 1: MEDLINE and EMBASE were searched for studies (n=18) providing data on NOD2 and smoking in Crohn's disease. NOD2-smoking interactions were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) calculated using random effects models. Phase 2: A case-only study compared the proportion of smokers and carriers of the 1007fs variant across ages at diagnosis (≤16, 17-40, >40years). Phase 1: Having ever smoked was less common among carriers of the 1007fs variant of NOD2 (OR 0.74, 95%CI:0.66-0.83). There was no interaction between smoking and the G908R (OR 0.96, 95%CI:0.82-1.13) or the R702W variant (OR 0.89, 95%CI:0.76-1.05). Phase 2: The proportion of patients (n=627) carrying the 1007fs variant decreased with age at diagnosis (≤16years: 15%; 17-40: 12%; >40: 3%; p=0.003). Smoking was more common in older patients (≤16years: 4%; 17-40: 48%; >40: 71%; psmoking interaction in Crohn's disease is specific to the 1007fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Intratibial injection of human multiple myeloma cells in NOD/SCID IL-2Rγ(null mice mimics human myeloma and serves as a valuable tool for the development of anticancer strategies.

    Directory of Open Access Journals (Sweden)

    Julia Schueler

    Full Text Available BACKGROUND: We systematically analyzed multiple myeloma (MM cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice and validated the response of the resulting xenografts to antimyeloma agents. DESIGN AND METHODS: Using flow cytometry and near infrared fluorescence in-vivo-imaging, growth kinetics of MM cell lines L363 and RPMI8226 and patient bone marrow cells were investigated with use of a murine subcutaneous bone implant, intratibial and intravenous approach in NOD/SCID, NOD/SCID treated with CD122 antibody and NOD/SCID IL-2Rγ(null mice (NSG. RESULTS: Myeloma growth was significantly increased in the absence of natural killer cell activity (NSG or αCD122-treated NOD/SCID. Comparison of NSG and αCD122-treated NOD/SCID revealed enhanced growth kinetics in the former, especially with respect to metastatic tumor sites which were exclusively observed therein. In NSG, MM cells were more tumorigenic when injected intratibially than intravenously. In NOD/SCID in contrast, the use of juvenile long bone implants was superior to intratibial or intravenous cancer cell injection. Using the intratibial NSG model, mice developed typical disease symptoms exclusively when implanted with human MM cell lines or patient-derived bone marrow cells, but not with healthy bone marrow cells nor in mock-injected animals. Bortezomib and dexamethasone delayed myeloma progression in L363- as well as patient-derived MM cell bearing NSG. Antitumor activity could be quantified via flow cytometry and in vivo imaging analyses. CONCLUSIONS: Our results suggest that the intratibial NSG MM model mimics the clinical situation of the disseminated disease and serves as a valuable tool in the development of novel anticancer strategies.

  4. The coordinate transforming in geography information system

    International Nuclear Information System (INIS)

    Zhao Xiang; Chen Gang

    2003-01-01

    The coordinate transforming of geography information system includes two kinds of transforming, map projection and coordinate-transforming. This paper proposed a arithmetic of coordinate-transforming, it implement the transforming between the longitude-latitude coordinate and the screen coordinate and apply it in the GIS. The preferable effect was made. (authors)

  5. Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4{sup +}CD25{sup +} regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Yulan; Purohit, Sharad [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); Department of Pathology, Medical College of Georgia, Georgia Health Sciences University, GA (United States); Chen, Xueqin; Yi, Bing [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); She, Jin-Xiong, E-mail: jshe@georgiahealth.edu [Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, GA (United States); Department of Pathology, Medical College of Georgia, Georgia Health Sciences University, GA (United States)

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer This is the first study to provide direct evidence of the role of Stat5b in NOD mice. Black-Right-Pointing-Pointer Over-expression of wild type Stat5b transgene protects NOD mice against diabetes. Black-Right-Pointing-Pointer This protection may be mediated by the up-regulation of CD4{sup +}CD25{sup +} Tregs. -- Abstract: The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4{sup +} T cells and especially CD8{sup +} T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4{sup +} and CD8{sup +} T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-{gamma}, TNF-{alpha} and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4{sup +}CD25{sup +} regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4{sup +}CD25{sup +} regulatory T cells.

  6. Who matters in coordination problems?

    Czech Academy of Sciences Publication Activity Database

    Sákovics, J.; Steiner, Jakub

    2012-01-01

    Roč. 102, č. 7 (2012), s. 3439-3461 ISSN 0002-8282 Institutional support: RVO:67985998 Keywords : coordination problem s * heterogeneous agents Subject RIV: AH - Economics Impact factor: 2.792, year: 2012

  7. Coordination Processes in International Organisations

    DEFF Research Database (Denmark)

    Nedergaard, Peter

    2008-01-01

    The EU is not a member of the International Labour Organisation (ILO), but relatively elaborate EU coordination takes place anyway. This paper addresses two research questions: 1) How is it possible to evaluate the coordination of the EU in its specific observable configuration in the ILO?, and 2......-à-vis their principals, the Member States. The Commission is the leading agent in the phase leading up to the Conference; the Presidency then takes over. On the one hand, due to the Treaty obligations and their interpretations by the Court of Justice, both the Presidency and the Commission are kept within tight limits...... by the principals. On the other hand, both before and during the Conference, the Member States accept the so-called discursive coordination of the Commission, which seems to be of great (but often neglected) importance. Owing to the organisational set-up in which coordination takes place, the EU is able...

  8. Hall effect in noncommutative coordinates

    International Nuclear Information System (INIS)

    Dayi, Oemer F.; Jellal, Ahmed

    2002-01-01

    We consider electrons in uniform external magnetic and electric fields which move on a plane whose coordinates are noncommuting. Spectrum and eigenfunctions of the related Hamiltonian are obtained. We derive the electric current whose expectation value gives the Hall effect in terms of an effective magnetic field. We present a receipt to find the action which can be utilized in path integrals for noncommuting coordinates. In terms of this action we calculate the related Aharonov-Bohm phase and show that it also yields the same effective magnetic field. When magnetic field is strong enough this phase becomes independent of magnetic field. Measurement of it may give some hints on spatial noncommutativity. The noncommutativity parameter θ can be tuned such that electrons moving in noncommutative coordinates are interpreted as either leading to the fractional quantum Hall effect or composite fermions in the usual coordinates

  9. Future in actinoids coordination chemistry

    International Nuclear Information System (INIS)

    Kitazawa, Takafumi

    2006-01-01

    Actinoids coordination chemistry is concerned with spent nuclear fuel reprocessing, specifically with solid-state chemistry of nuclear fuels, separation process with radioactive substances, and geological disposal of high-level radioactive substances. In the 21st century, accumulation of minor actinides, Np, Am, Cm, and others will be realized according with the present program of nuclear energy development. The present article briefly introduces general properties of actinide elements, followed by their coordination chemistry compared with rare earths coordination chemistry. Special facility needed to treat actinoids as well as their chemistry is briefly explained, together with the specific experimental apparatus such as X-ray Absorption Fine Structure (XAFS) and time-resolved laser-induced fluorescence spectrometry (TRLFS) with synchrotron radiation facilities. The effect of coordination with actinoids in the environment chemistry is important in underground disposal of high-level radioactive wastes. For theoretical analysis of the results with actinoids chemistry, relativistic calculation is needed. (S. Ohno)

  10. The influence of iron coordination compounds on producing capacity of some crops

    International Nuclear Information System (INIS)

    Rakhimova, M.M.; Yusupov, Z.N.; Nurmatov, T.M.; Dzhafarov, M.I.

    1993-01-01

    Present article is devoted to influence of iron coordination compounds on producing capacity of some crops. The influence of aqueous solutions of iron coordination compounds with anions of acetic and ethylen diamin disuccinic acids on germinative energy and germination of cotton crops and grapes was studied in laboratory conditions. The conducted researches shown that application of iron coordination compounds improves the growth, fruiting and the quality of studied crops.

  11. Coordination theory and collaboration technology

    CERN Document Server

    Olson, Gary M; Smith, John B

    2001-01-01

    The National Science Foundation funded the first Coordination Theory and Collaboration Technology initiative to look at systems that support collaborations in business and elsewhere. This book explores the global revolution in human interconnectedness. It will discuss the various collaborative workgroups and their use in technology. The initiative focuses on processes of coordination and cooperation among autonomous units in human systems, in computer and communication systems, and in hybrid organizations of both systems. This initiative is motivated by three scientific issues which have been

  12. Path integrals in curvilinear coordinates

    International Nuclear Information System (INIS)

    Prokhorov, L.V.

    1984-01-01

    Integration limits are studied for presenting the path integral curvilinear coordinates. For spherical (and topoloqically equivalent) coordinates it is shown that in formulas involving classical action in the exponent integration over all variables should be carried out within infinite limits. Another peculiarity is associated with appearance of the operator q which provides a complete definition of the wave functions out of the physical region. arguments are given upporting the validity of the cited statament in the general case

  13. Different Dimensional and Structural Variations in Coordination Compounds of Cadmium, Manganese and Nickel Constructed from the Ligand 2,2'-Bipyidine-3,3',6,6'-tetracarboxylic Acid (H{sub 4}bptc)

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Jing; Yang, Tiantian; Fu, Lulu; Luo, Ya; Wu, Jiashou [Yangtze Univ., Jingzhou (China)

    2013-09-15

    The reactions of hydrated CdCl{sub 2}, MnCl{sub 2}, and NiCl{sub 2} with 2,2'-bipyidine-3,3',6,6'-tetracarboxylic acid (H{sub 4}bptc) afforded the mononuclear [Cd{sup II}(H{sub 2}bptc)(H{sub 2}O){sub 3}]·H{sub 2}O (1), linear [Cd(H{sub 2}bptc)(H{sub 2}O)]·3H{sub 2}O{sub n} (2), 3-D hetero-bimetallic [NaCd(Hbptc)(H{sub 2}O)] (3), layer [Mn(H{sub 2}bptc)(H{sub 2}O)]n (4) and a dinuclear compound [Ni{sub 2}(H{sub 2}bptc)-(H{sub 2}O){sub 2}]·6H{sub 2}O (5). These compounds have been characterized by elemental analysis, IR, and their structures have been determined by X-ray crystallography. The thermal stabilities of 1-3 were measured by thermogravimetric analysis (TGA) and their solid state luminescence properties together with the free ligand H{sub 4}bptc were investigated at room temperature.

  14. Anti-idiotypic antibody specific to GAD65 autoantibody prevents type 1 diabetes in the NOD mouse.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Overt autoantibodies to the smaller isoform of glutamate decarboxylase (GAD65Ab are a characteristic in patients with Type 1 diabetes (T1D. Anti-idiotypic antibodies (anti-Id directed to GAD65Ab effectively prevent the binding of GAD65 to GAD65Ab in healthy individuals. Levels of GAD65Ab-specific anti-Id are significantly lower in patients with T1D, leading to overt GAD65Ab in these patients. To determine the possible protective role of GAD65Ab-specific anti-Id in T1D pathogenesis, we developed the monoclonal anti-Id MAb 8E6G4 specifically targeting human monoclonal GAD65Ab b96.11. MAb 8E6G4 was demonstrated as a specific anti-Id directed to the antigen binding site of b96.11. MAb 8E6G4 recognized human antibodies in sera from healthy individuals, T2D patients, and T1D patients as established by ELISA. We confirmed these MAb 8E6G4-bound human antibodies to contain GAD65Ab by testing the eluted antibodies for binding to GAD65 in radioligand binding assays. These findings confirm that GAD65Ab are present in sera of individuals, who test GAD65Ab-negative in conventional detection assays. To test our hypothesis that GAD65Ab-specific anti-Id have an immune modulatory role in T1D, we injected young Non Obese Diabetic (NOD mice with MAb 8E6G4. The animals were carefully monitored for development of T1D for 40 weeks. Infiltration of pancreatic islets by mononuclear cells (insulitis was determined to establish the extent of an autoimmune attack on the pancreatic islets. Administration of MAb 8E6G4 significantly reduced the cumulative incidence rate of T1D and delayed the time of onset. Insulitis was significantly less severe in animals that received MAb 8E6G4 as compared to control animals. These results support our hypothesis that anti-Id specific to GAD65Ab have a protective role in T1D.

  15. Inibição da expressão de ciclooxigenase 2 em feridas cutâneas de camundongos NOD submetidos à terapia a laser de baixa intensidade Inhibition of cyclooxygenase 2 expression in NOD mice cutaneous wound by low-level laser therapy

    Directory of Open Access Journals (Sweden)

    Carolina de Lourdes Julião Vieira Rocha

    2012-09-01

    Full Text Available CONTEXTO: A terapia a laser de baixa intensidade (LLLT tem sido relatada como importante moduladora da cicatrização de feridas cutâneas aumentando a proliferação fibroblástica associada ao aumento da expressão da citocina fator transformador de crescimento- β2 (TGF-βB2. OBJETIVO: No presente estudo foram avaliados os efeitos da LLLT sobre a expressão da enzima ciclooxigenase 2 (COX2 no sítio do reparo tecidual utilizando o modelo experimental com camundongos diabéticos não obesos (NOD para estudar a cicatrização de feridas cutâneas. MÉTODOS: Foram utilizados 30 camundongos NOD, destes 14 ficaram diabéticos e foram divididos em dois grupos: o grupo I (n=7 foi submetido a um procedimento cirúrgico de feridas cutâneas e o grupo II (n=7 foi submetido a um procedimento cirúrgico de feridas cutâneas e tratados com LLLT. O grupo II foi submetido à LLLT nos seguintes parâmetros: 15 mW de potência, dose de 3,8 J/cm² e tempo de aplicação de 20 segundos. Após sete dias do ato cirúrgico e após aplicação do laser, os animais foram eutanasiados com sobredose de anestesia e amostras das feridas foram colhidas para posterior análise histopatológica, histomorfométrica e imuno-histoquímica. RESULTADOS: A LLLT promoveu a inibição da expressão da COX2 em feridas cutâneas de camundongos diabéticos. CONCLUSÃO: Em conjunto, os resultados sugeriram que a LLLT é capaz de modular negativamente a expressão da enzima COX2 contribuindo para o controle da resposta inflamatória em feridas cutâneas de camundongos NOD.BACKGROUND: Low-level laser therapy (LLLT has been reported to modulate the healing of wounds by inducing an increase in fibroblast number associated with increased expression of the cytokine transforming growth factor-β2 (TGF-β2. OBJECTIVE: In the present study, the effect of LLLT on expression of COX2 at the site of tissue repair was evaluated, using an experimental model with non obese diabetic mice (NOD to study

  16. Regulatory CD8{sup +} T cells induced by exposure to all-trans retinoic acid and TGF-{beta} suppress autoimmune diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Minoru [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Yasuda, Hisafumi, E-mail: yasuda@med.kobe-u.ac.jp [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Abe, Yasuhisa; Sasaki, Hirotomo; Shimizu, Mami; Arai, Takashi; Okumachi, Yasuyo; Moriyama, Hiroaki; Hara, Kenta; Yokono, Koichi; Nagata, Masao [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-03-26

    Antigen-specific regulatory CD4{sup +} T cells have been described but there are few reports on regulatory CD8{sup +} T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8{sup +} T cells from 8.3-NOD transgenic mice. CD8{sup +} T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-{beta}, and all-trans retinoic acid (ATRA) for 5 days. CD8{sup +} T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-{beta} and ATRA had low Foxp3{sup +} expression (1.7 {+-} 0.9% and 3.2 {+-} 4.5%, respectively). In contrast, CD8{sup +} T cells induced by exposure to IGRP, SpDCs, TGF-{beta}, and ATRA showed the highest expression of Foxp3{sup +} in IGRP-reactive CD8{sup +} T cells (36.1 {+-} 10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8{sup +} T cells cultured with IGRP, SpDCs, TGF-{beta}, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8{sup +} T cells suppressed the proliferation of diabetogenic CD8{sup +} T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-{beta} induces CD8{sup +}Foxp3{sup +} T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

  17. Basicity and ionization constants of some molybdenum(6) complex acids

    International Nuclear Information System (INIS)

    Fedorov, A.A.

    1975-01-01

    Coordination of the Mo(6) ions of the malic, trioxyglutaric, glucaric and mucic acids changes their acidity. Complex Mo(6) acids are stronger then corresponding oxyacids. It was demonstrated that complexes of Mo(6) with malic, trioxyglutaric, glutaric, mucic acids and mannitol were behaving as polybasic acids during titration. Sequential ionization constants of the complex acids were determined

  18. Three coordination compounds based on benzene tetracarboxylate ...

    Indian Academy of Sciences (India)

    YUNLONG WU

    nescence, considerable attention has been focused on the construction of coordination .... measurements were performed on ground powder samples at .... Figure 2. (a) Coordination environment of Co1 ion in compound 2. (b) Coordination.

  19. Managing interteam coordination within and between organizations

    NARCIS (Netherlands)

    de Vries, Thomas Arend

    2015-01-01

    To accomplish complex tasks and effectively respond to environmental contingencies, teams must coordinate task-related issues with other teams (i.e., interteam coordination). Regrettably, interteam coordination is often complicated by misunderstandings that can arise from differences in teams’

  20. Motor coordination uses external spatial coordinates independent of developmental vision.

    Science.gov (United States)

    Heed, Tobias; Röder, Brigitte

    2014-07-01

    The constraints that guide bimanual movement coordination are informative about the processing principles underlying movement planning in humans. For example, symmetry relative to the body midline benefits finger and hand movements independent of hand posture. This symmetry constraint has been interpreted to indicate that movement coordination is guided by a perceptual code. Although it has been assumed implicitly that the perceptual system at the heart of this constraint is vision, this relationship has not been tested. Here, congenitally blind and sighted participants made symmetrical and non-symmetrical (that is, parallel) bimanual tapping and finger oscillation movements. For both groups, symmetrical movements were executed more correctly than parallel movements, independent of anatomical constraints like finger homology and hand posture. For the blind, the reliance on external spatial factors in movement coordination stands in stark contrast to their use of an anatomical reference frame in perceptual processing. Thus, the externally coded symmetry constraint evident in bimanual coordination can develop in the absence of the visual system, suggesting that the visual system is not critical for the establishment of an external-spatial reference frame in movement coordination. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Cold Responsive Gene Expression Profiling of Sugarcane and Saccharum spontaneum with Functional Analysis of a Cold Inducible Saccharum Homolog of NOD26-Like Intrinsic Protein to Salt and Water Stress.

    Directory of Open Access Journals (Sweden)

    Jong-Won Park

    Full Text Available Transcriptome analysis of sugarcane hybrid CP72-1210 (cold susceptible and Saccharum spontaneum TUS05-05 (cold tolerant using Sugarcane Assembled Sequences (SAS from SUCEST-FUN Database showed that a total of 35,340 and 34,698 SAS genes, respectively, were expressed before and after chilling stress. The analysis revealed that more than 600 genes are differentially expressed in each genotype after chilling stress. Blast2Go annotation revealed that the major difference in gene expression profiles between CP72-1210 and TUS05-05 after chilling stress are present in the genes related to the transmembrane transporter activity. To further investigate the relevance of transmembrane transporter activity against abiotic stress tolerance, a S. spontaneum homolog of a NOD26-like major intrinsic protein gene (SspNIP2 was selected for functional analysis, of which expression was induced after chilling stress in the cold tolerant TUS05-05. Quantitative real-time PCR showed that SspNIP2 expression was increased ~2.5 fold at 30 minutes after cold treatment and stayed induced throughout the 24 hours of cold treatment. The amino acid sequence analysis of the cloned SspNIP2 confirmed the presence of six transmembrane domains and two NPA (Asn-Pro-Ala motifs, signature features of major intrinsic protein families. Amino acid analysis confirmed that four amino acids, comprising the ar/R (aromatic residue/arginine region responsible for the substrate specificity among MIPs, are conserved among monocot silicon transporters and SspNIP2. Salinity stress test on SspNIP2 transgenic tobacco plants resulted in more vigorous transgenic lines than the non-transgenic tobacco plants, suggesting some degree of tolerance to salt stress conferred by SspNIP2. SspNIP2-transgenic plants, exposed to 2 weeks of water stress without irrigation, developed various degrees of water stress symptom. The water stress test confirmed that the SspNIP2 transgenic lines had lower evapotranspiration

  2. Coordination Networks Based on Boronate and Benzoxaborolate Ligands

    Directory of Open Access Journals (Sweden)

    Saad Sene

    2016-05-01

    Full Text Available Despite the extensive range of investigations on boronic acids (R-B(OH2, some aspects of their reactivity still need to be explored. This is the case for the coordination chemistry of boronate anions (R-B(OH3−, which has only recently been started to be studied. The purpose of this review is to summarize some of the key features of boronate ligands (and of their cyclic derivatives, benzoxaborolates in materials: (i coordination properties; (ii spectroscopic signatures; and (iii emerging applications.

  3. The architecture of metal coordination groups in proteins.

    Science.gov (United States)

    Harding, Marjorie M

    2004-05-01

    A set of tables is presented and a survey given of the architecture of metal coordination groups in a representative set of protein structures from the Protein Data Bank [Bernstein et al. (1977), J. Mol. Biol. 112, 535-542; Berman et al. (2000), Nucleic Acids Res. 28, 235-242]. The structures have been determined to a resolution of 2.5 A or better; the metals considered are Ca, Mg, Mn, Fe, Cu, Zn, Na and K, with particular emphasis on Ca and Zn and the exclusion of haem groups and Fe/S clusters; the proteins are a representative set in which none has more than 30% sequence identity with any other. In them the metal is coordinated by several donor groups from different amino-acid residues in the protein chain and often also by water or other small molecules. The tables, for approximately 600 metal coordination groups, include information on the conformations of the protein chain in the region around the metal and reliability indicators. They illustrate the wide variety of coordination numbers, chelate-loop sizes and other properties and the different characteristics of different metals. They show that glycine has a particular significance in the position adjacent to a donor residue, especially in Ca coordination groups. They also show that metal coordination does not appear to lead to significant distortions of the torsion angles phi, psi from their normally allowed values. Very few metal coordination groups occur more than once in the representative set and when they do they are usually related in fold and function; they have similar but not necessarily identical conformations. However, individual chelate loops, for example Zn(-C-X-X'-C-), in which both cysteines are coordinated to Zn through S, and X and X' are any amino acids, are repeated frequently in many different and unrelated proteins. Not all chelate loops with the same composition have the same conformation, but for smaller loops there are usually one or two strongly preferred and well defined

  4. Federal interagency radiation policy coordination

    International Nuclear Information System (INIS)

    Young, A.L.

    1984-01-01

    The author discusses Federal interagency radiation policy coordination. The Committee on Interagency Radiation Research and Policy Coordination (CIRRPC) is explained as being dedicated to the success and forward motion of enhanced radiation research and policy coordination. Both CIRRPC and the Science Panel are staffed with Federal employees. Their expertise includes many and various radiation disciplines including cytogenetics, dosimetry, epidemiology, genetics, health physics, nuclear medicine, radiology, radiation carcinogenesis, and risk assessment. Ten scientific and technical issues in their preliminary order are presented: radioepidemiological tables; de minimis radiation levels; radon progeny health effects; occupational exposure registry; measurement, recording, and control of radiation; food irradiation; use of radiation in science, industry, and medicine; nonionizing radiation; and remedial actions

  5. An argument for VP coordination: scene-setting coordination and ...

    African Journals Online (AJOL)

    This article demonstrates the properties of this curious construction type and proposes the first analysis to date. It is argued that this is an instance of VP coordination and that this configuration allows the possibility of high merger of direct objects in a constrained fashion. Southern African Linguistics and Applied Language ...

  6. Evaluating the Relational Coordination instrument

    DEFF Research Database (Denmark)

    Edwards, Kasper; Lundstrøm, Sanne Lykke

    2014-01-01

    consistency, interrater agreement and reliability, structural validity, content validity. However as relational coordination is being used as a diagnostics tool it is important to examine further if the instrument can measure changes. Indeed we need to know how precise and sensitive the instrument is when....... We distinguish between statistical and clinical significance. Statistical significance is calculated using T-test. Clinical significance is the minimal amount of change in relational coordination score that is not considered noise. Sensitivity of the instrument i.e. the ability of the instrument...

  7. Cation coordination in oxychloride glasses

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J A [Energy Technology Division, Argonne National Laboratory, Argonne, IL (United States); Holland, D [Physics Department, Warwick University, Coventry (United Kingdom); Bland, J [Physics Department, University of Liverpool, PO Box 147, Liverpool (United Kingdom); Johnson, C E [Physics Department, Northern Illinois University, DeKalb, IL (United States); Thomas, M F [Physics Department, University of Liverpool, PO Box 147, Liverpool (United Kingdom)

    2003-02-19

    Glasses containing mixtures of cations and anions of nominal compositions [Sb{sub 2}O{sub 3}]{sub x} - [ZnCl{sub 2}]{sub 1-x} where x = 0.25, 0.50, 0.75, and 1.00, have been studied by means of neutron diffraction and Raman and Moessbauer spectroscopy. There is preferential bonding within the system with the absence of Sb-Cl bonds. Antimony is found to be threefold coordinated to oxygen, and zinc fourfold coordinated. The main contributing species are of the form [Sb(OSb){sub 2}(OZn)] and [Zn(ClZn){sub 2}(OSb){sub 2}].

  8. Cation coordination in oxychloride glasses

    International Nuclear Information System (INIS)

    Johnson, J A; Holland, D; Bland, J; Johnson, C E; Thomas, M F

    2003-01-01

    Glasses containing mixtures of cations and anions of nominal compositions [Sb 2 O 3 ] x - [ZnCl 2 ] 1-x where x = 0.25, 0.50, 0.75, and 1.00, have been studied by means of neutron diffraction and Raman and Moessbauer spectroscopy. There is preferential bonding within the system with the absence of Sb-Cl bonds. Antimony is found to be threefold coordinated to oxygen, and zinc fourfold coordinated. The main contributing species are of the form [Sb(OSb) 2 (OZn)] and [Zn(ClZn) 2 (OSb) 2

  9. Bare coordination: the semantic shift

    OpenAIRE

    de Swart, Henriette; Le Bruyn, Bert

    2014-01-01

    This paper develops an analysis of the syntax-semantics interface of two types of split coordination structures. In the first type, two bare singular count nouns appear as arguments in a coordinated structure, as in bride and groom were happy. We call this the N&N construction. In the second type, the determiner shows agreement with the first conjunct, while the second conjunct is bare, as in the Spanish example el hornero y hornera cobraban en panes (‘thesg.m bakersg.m and bakersg.f werepl p...

  10. The NOD2 p.Leu1007fsX1008 mutation (rs2066847 is a stronger predictor of the clinical course of Crohn's disease than the FOXO3A intron variant rs12212067.

    Directory of Open Access Journals (Sweden)

    Fabian Schnitzler

    Full Text Available Very recently, a sub-analysis of genome-wide association scans revealed that the non-coding single nucleotide polymorphism (SNP rs12212067 in the FOXO3A gene is associated with a milder course of Crohn's disease (CD (Cell 2013;155:57-69. The aim of our study was to evaluate the clinical value of the SNP rs12212067 in predicting the severity of CD by correlating CD patient genotype status with the most relevant complications of CD such as stenoses, fistulas, and CD-related surgery.We genotyped 550 CD patients for rs12212067 (FOXO3A and the three common CD-associated NOD2 mutations rs2066844, rs2066847, and rs2066847 and performed genotype-phenotype analyses.No significant phenotypic differences were found between the wild-type genotype TT of the FOXO3A SNP rs12212067 and the minor genotypes TG and GG independently from NOD2 variants. The allele frequency of the minor G allele was 12.7%. Age at diagnosis, disease duration, body mass index, surgery rate, stenoses, fistula, need for immunosuppressive therapy, and disease course were not significantly different. In contrast, the NOD2 mutant p.Leu1007fsX1008 (rs2066847 was highly associated with penetrating CD (p = 0.01, the development of fistulas (p = 0.01 and stenoses (p = 0.01, and ileal disease localization (p = 0.03. Importantly, the NOD2 SNP rs2066847 was a strong separator between an aggressive and a mild course of CD (p = 2.99×10(-5, while the FOXO3A SNP rs12212067 did not separate between mild and aggressive CD behavior in our cohort (p = 0.35. 96.2% of the homozygous NOD2 p.Leu1007fsX1008 carriers had an aggressive disease behavior compared to 69.3% of the patients with the NOD2 wild-type genotype (p = 0.007.In clinical practice, the NOD2 variant p.Leu1007fsX1008 (rs2066847, in particular in homozygous form, is a much stronger marker for a severe clinical phenotype than the FOXO3A rs12212067 SNP for a mild disease course on an individual patient level despite

  11. The NOD2 p.Leu1007fsX1008 mutation (rs2066847) is a stronger predictor of the clinical course of Crohn's disease than the FOXO3A intron variant rs12212067.

    Science.gov (United States)

    Schnitzler, Fabian; Friedrich, Matthias; Wolf, Christiane; Angelberger, Marianne; Diegelmann, Julia; Olszak, Torsten; Beigel, Florian; Tillack, Cornelia; Stallhofer, Johannes; Göke, Burkhard; Glas, Jürgen; Lohse, Peter; Brand, Stephan

    2014-01-01

    Very recently, a sub-analysis of genome-wide association scans revealed that the non-coding single nucleotide polymorphism (SNP) rs12212067 in the FOXO3A gene is associated with a milder course of Crohn's disease (CD) (Cell 2013;155:57-69). The aim of our study was to evaluate the clinical value of the SNP rs12212067 in predicting the severity of CD by correlating CD patient genotype status with the most relevant complications of CD such as stenoses, fistulas, and CD-related surgery. We genotyped 550 CD patients for rs12212067 (FOXO3A) and the three common CD-associated NOD2 mutations rs2066844, rs2066847, and rs2066847 and performed genotype-phenotype analyses. No significant phenotypic differences were found between the wild-type genotype TT of the FOXO3A SNP rs12212067 and the minor genotypes TG and GG independently from NOD2 variants. The allele frequency of the minor G allele was 12.7%. Age at diagnosis, disease duration, body mass index, surgery rate, stenoses, fistula, need for immunosuppressive therapy, and disease course were not significantly different. In contrast, the NOD2 mutant p.Leu1007fsX1008 (rs2066847) was highly associated with penetrating CD (p = 0.01), the development of fistulas (p = 0.01) and stenoses (p = 0.01), and ileal disease localization (p = 0.03). Importantly, the NOD2 SNP rs2066847 was a strong separator between an aggressive and a mild course of CD (p = 2.99×10(-5)), while the FOXO3A SNP rs12212067 did not separate between mild and aggressive CD behavior in our cohort (p = 0.35). 96.2% of the homozygous NOD2 p.Leu1007fsX1008 carriers had an aggressive disease behavior compared to 69.3% of the patients with the NOD2 wild-type genotype (p = 0.007). In clinical practice, the NOD2 variant p.Leu1007fsX1008 (rs2066847), in particular in homozygous form, is a much stronger marker for a severe clinical phenotype than the FOXO3A rs12212067 SNP for a mild disease course on an individual patient level despite its

  12. Unusual metal coordination chemistry from an amino-amide derivative of 4-nitrophenol, a surprising ligand

    DEFF Research Database (Denmark)

    McGinley, John; McKee, Vickie; Toftlund, Hans

    2009-01-01

    The simple ligand N-(2-aminoethyl)-2-hydroxy-5-nitrobenzamide () exhibits several coordination modes depending on the reaction conditions, acting as a zwitterion on its own or being ionic in the presence of acid and depending on the concentration of metal present in a reaction, it can coordinate...... to the metal in either a 1:1 or a 1:2 metal:ligand mode. Furthermore, the role of solvent plays an important role in these complexation reactions with both four and six coordinate copper complexes being obtained using water as solvent but only six coordinate copper complexes obtained using acetonitrile...

  13. Two novel Pb(II) coordination polymers (CPs) based on 4-(4-oxopyridin-1(4H)-yl) and 3-(4-oxopyridin-1(4H)-yl) phthalic acid: Band gaps, structures, and their photoelectrocatalytic properties in CO2-saturated system

    Science.gov (United States)

    Yan, Zhi Shuo; Long, Ji Ying; Gong, Yun; Lin, Jian Hua

    2018-05-01

    Based on 4-(4-oxopyridin-1(4H)-yl) phthalic acid (H2L1) and 3-(4-oxopyridin-1(4H)-yl) phthalic acid (H2L2), two novel Pb(II) coordination polymers (CPs) formulated as [Pb4Cl4·(L1)2·H2O]n (CP 1), [Pb3Cl4·L2·H2O]n (CP 2) were solvothermally synthesized and characterized by single-crystal X-ray diffraction. The two novel Pb(II) CPs (CPs 1 and 2) possessed different structures. Density functional theory (DFT) calculations revealed the two CPs had different band structures yet the characteristic of semiconductors in common. Their valence band (VB) and conduction band (CB) positions were determined by Mott-Schottky and UV-visible diffuse reflectance analyses. The photoelectrocatalytic performance of the two CPs towards CO2 reduction were tested by photocurrent responses at various applied potentials. And the E =-1.4 V vs SCE (-0.74 V vs NHE) was selected as the required potential according to the regulation of photocurrent responses at various tested potentials in CO2-saturated system. The photoelectrocatalytic performance of CP 2 was superior to that of CP 1 owing to the well-matched CB position of CP 2 and CO2 reduction potentials at the required potential of -1.4 V vs SCE (-0.74 V vs NHE). In addition, the photoelectrolytic experiment were performed 1 h in the CO2-saturated 0.2 M Na2SO4 solution at the required potential of -1.4 V vs SCE (-0.74 V vs NHE) with and without illumination, and we initially demonstrated the influence of visible light in the CO2-saturated photoelectrocatalytic measurement system and the reason of stability in 1 h chronoamperometry.

  14. Expression of TLR-2, TLR-4, NOD2 and pNF-kappaB in a neonatal rat model of necrotizing enterocolitis.

    Directory of Open Access Journals (Sweden)

    Aurelie Le Mandat Schultz

    Full Text Available BACKGROUND: The etiology of necrotizing enterocolitis (NEC results from a combination of several risk factors that act synergistically and occurs in the same circumstances as those which lead to innate immunity activation. Pattern recognition molecules could be an important player in the initiation of an exaggerated inflammatory response leading to intestinal injury in NEC. METHODOLOGY/PRINCIPAL FINDINGS: We specifically evaluated intestinal epithelial cell (IEC expression of Toll-like receptor 2 (TLR-2, TLR-4, NOD2 and phosphorylated NF-kappaB (pNF-kappaB after mucosal injury in a rat model of NEC induced by prematurity, systemic hypoxia, and a rich protein formula. In the control group (group 1, neonatal rats were full-term and breast-fed; in the experimental groups, rat pups were preterm at day 21 of gestation and rat-milk fed (group 2 or hand-gavaged with a protein rich formula after a hypoxia-reoxygenation procedure (group 3. Morphological mucosal changes in the small bowel were scored on hematoxylin- and eosin-stained sections. Immunohistochemistry was performed on frozen tissue sections using anti TLR-2 and active pNF-kappaB p65 antibodies. Real-time RT-PCR was performed to assess mRNA expression of NOD2, TLR-2 and TLR-4. Proliferation and apoptosis were studied in paraffin sections using anti Ki-67 and caspase-3 antibodies, respectively. The combination of immaturity, protein rich formula and a hypoxia-reoxygenation procedure induces pathological mucosal damage consistent with NEC. There was an overexpression of TLR-2, and pNF-kappaB in IECs that was correlated with the severity of mucosal damage, together with an increase of apoptotic IECs and markedly impaired proliferation. In addition, these immunological alterations appeared before severe mucosal damage. TLR-2 mRNA were also increased in NEC together with TLR-4 mRNA using real-time RT-PCR whereas NOD2 expression was unchanged. CONCLUSIONS/SIGNIFICANCE: These results show that this

  15. 47 CFR 95.1113 - Frequency coordinator.

    Science.gov (United States)

    2010-10-01

    ... SERVICES Wireless Medical Telemetry Service (WMTS) General Provisions § 95.1113 Frequency coordinator. (a) The Commission will designate a frequency coordinator(s) to manage the usage of the frequency bands for the operation of medical telemetry devices. (b) The frequency coordinator shall (1) Review and...

  16. 29 CFR 42.8 - Coordination plan.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Coordination plan. 42.8 Section 42.8 Labor Office of the Secretary of Labor COORDINATED ENFORCEMENT § 42.8 Coordination plan. (a) Based upon, among other things, the... coordination plan concerning farm labor-related responsibilities of the Department, including migrant housing...

  17. Service Coordination Policies and Models: National Status.

    Science.gov (United States)

    Harbin, Gloria L.; Bruder, M.; Mazzarella, C.; Gabbard, G.; Reynolds, C.

    This report discusses the findings of a study that investigated state coordination of early intervention services for infants, toddlers, and young children with disabilities. State Part C coordinators participated in a survey that sought their perceptions of values under girding service coordination, approach to service coordination, policies,…

  18. The symbiotic biofilm of Sinorhizobium fredii SMH12, necessary for successful colonization and symbiosis of Glycine max cv Osumi, is regulated by Quorum Sensing systems and inducing flavonoids via NodD1.

    Directory of Open Access Journals (Sweden)

    Francisco Pérez-Montaño

    Full Text Available Bacterial surface components, especially exopolysaccharides, in combination with bacterial Quorum Sensing signals are crucial for the formation of biofilms in most species studied so far. Biofilm formation allows soil bacteria to colonize their surrounding habitat and survive common environmental stresses such as desiccation and nutrient limitation. This mode of life is often essential for survival in bacteria of the genera Mesorhizobium, Sinorhizobium, Bradyrhizobium, and Rhizobium. The role of biofilm formation in symbiosis has been investigated in detail for Sinorhizobium meliloti and Bradyrhizobium japonicum. However, for S. fredii this process has not been studied. In this work we have demonstrated that biofilm formation is crucial for an optimal root colonization and symbiosis between S. fredii SMH12 and Glycine max cv Osumi. In this bacterium, nod-gene inducing flavonoids and the NodD1 protein are required for the transition of the biofilm structure from monolayer to microcolony. Quorum Sensing systems are also required for the full development of both types of biofilms. In fact, both the nodD1 mutant and the lactonase strain (the lactonase enzyme prevents AHL accumulation are defective in soybean root colonization. The impairment of the lactonase strain in its colonization ability leads to a decrease in the symbiotic parameters. Interestingly, NodD1 together with flavonoids activates certain quorum sensing systems implicit in the development of the symbiotic biofilm. Thus, S. fredii SMH12 by means of a unique key molecule, the flavonoid, efficiently forms biofilm, colonizes the legume roots and activates the synthesis of Nod factors, required for successfully symbiosis.

  19. Porous coordination polymer with flexibility imparted by coordinatively changeable lithium ions on the pore surface.

    Science.gov (United States)

    Xie, Lin-Hua; Lin, Jian-Bin; Liu, Xiao-Min; Wang, Yu; Zhang, Wei-Xiong; Zhang, Jie-Peng; Chen, Xiao-Ming

    2010-02-01

    Solvothermal reactions of equimolar zinc acetate, lithium acetate, and 1,3,5-benzenetricarboxylic acid (H(3)btc) in different mixed solvents yielded isostructural three-dimensional frameworks [LiZn(btc)(cG)].lG [cG and lG denote coordinated and lattice guests, respectively; cG = (nmp)(0.5)(H(2)O)(0.5), lG = (EtOH)(0.5) (1a); cG = H(2)O, lG = EtOH (1b); nmp = N-methyl-2-pyrrolidone] with one-dimensional channels occupied by guest molecules and solvent-coordinated, extrusive Li(+) ions. Thermogravimetry analyses and powder X-ray diffraction measurements revealed that both 1a and 1b can lose all lattice and coordinated guests to form a desolvated phase [LiZn(btc)] (MCF-27, 1) and almost retains the original framework structure. Gas adsorption measurements on 1 confirmed its permanent porosity but suggested a structural transformation from 1a/1b to 1. It is noteworthy that only 1a can undergo a single-crystal to single-crystal (SCSC) transformation into 1 upon desolvation. The crystal structure of 1 revealed that the Li(+) ions were retracted into the channel walls via complementary coordination to the carboxylate oxygen atoms in the framework rather than being exposed on the pore surface. Single-crystal X-ray diffraction analyses were also performed for N(2)- and CO(2)-loaded samples of 1, revealing that the framework remained unchanged when the gases were adsorbed. Although the gas molecules could not be modeled, the residue electrons inside the channels demonstrated that the retracted Li(+) ions still behave as the primary interacting site for CO(2) molecules. Nevertheless, solvent molecules such as H(2)O can readily compete with the framework oxygen atom to retrieve the extrusive Li(+) ions, accompanying the reverse structural transformation, i.e., from 1 to 1a/1b.

  20. U.S. CWMD Coordination

    Science.gov (United States)

    2012-12-11

    coordination. For example, it conducted joint vehicle inspection training for Pakistani Customs and Border Guard personnel at a US- Mexico border...biological material, including such hazards as: anthrax, botulism, cholera , Ebola virus hemorrhagic fever, E. coli, Plague, and smallpox 79

  1. Collective coordinates on symplectic manifolds

    International Nuclear Information System (INIS)

    Razumov, A.V.; Taranov, A.Yu.

    1981-01-01

    For an arbitrary Lie group of canonical transformations on a symplectic manifold collective coordinates are introduced. They describe a motion of the dynamical system as a whole under the group transformations. Some properties of Lie group of canonical transformations are considered [ru

  2. Motivic amplitudes and cluster coordinates

    International Nuclear Information System (INIS)

    Golden, J.K.; Goncharov, A.B.; Spradlin, M.; Vergu, C.; Volovich, A.

    2014-01-01

    In this paper we study motivic amplitudes — objects which contain all of the essential mathematical content of scattering amplitudes in planar SYM theory in a completely canonical way, free from the ambiguities inherent in any attempt to choose particular functional representatives. We find that the cluster structure on the kinematic configuration space Conf n (ℙ 3 ) underlies the structure of motivic amplitudes. Specifically, we compute explicitly the coproduct of the two-loop seven-particle MHV motivic amplitude A 7,2 M and find that like the previously known six-particle amplitude, it depends only on certain preferred coordinates known in the mathematics literature as cluster X-coordinates on Conf n (ℙ 3 ). We also find intriguing relations between motivic amplitudes and the geometry of generalized associahedrons, to which cluster coordinates have a natural combinatoric connection. For example, the obstruction to A 7,2 M being expressible in terms of classical polylogarithms is most naturally represented by certain quadrilateral faces of the appropriate associahedron. We also find and prove the first known functional equation for the trilogarithm in which all 40 arguments are cluster X-coordinates of a single algebra. In this respect it is similar to Abel’s 5-term dilogarithm identity

  3. Co-ordinated Classroom Lectures.

    Science.gov (United States)

    Harmon, Darell Boyd

    From a series of lectures, a selection of eight are oriented principally toward the biologically developing child, and the physiological operations in visual process. The numbered lectures are--(1) The Coordinated Classroom, its Philosophy and Principles, (2) An Outline of a Biological Point of View, (3) The Evolution of Structure--despite man's…

  4. Henry Taube and Coordination Chemistry

    Science.gov (United States)

    dropdown arrow Site Map A-Z Index Menu Synopsis Henry Taube and Coordination Chemistry Resources with Professor of Chemistry, Emeritus, at Stanford University, received the 1983 Nobel Prize in Chemistry " there from 1940-41. "I became deeply interested in chemistry soon after I came to Berkeley,"

  5. Possibility of extending space-time coordinates

    International Nuclear Information System (INIS)

    Wang Yongcheng.

    1993-11-01

    It has been shown that one coordinate system can describe a whole space-time region except some supersurfaces on which there are coordinate singularities. The conditions of extending a coordinate from real field to complex field are studied. It has been shown that many-valued coordinate transformations may help us to extend space-time regions and many-valued metric functions may make one coordinate region to describe more than one space-time regions. (author). 11 refs

  6. Imaging dynamics of CD11c+ cells and Foxp3+ cells in progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes

    DEFF Research Database (Denmark)

    Schmidt-Christensen, Anja; Hansen, Lisbeth; Ilegems, Erwin

    2013-01-01

    the endocrine pancreas during initiation and progression of insulitis in the NOD mouse. Individual, ACE-transplanted islets of Langerhans were longitudinally and repetitively imaged by stereomicroscopy and two-photon microscopy to follow fluorescently labelled leucocyte subsets. Results We demonstrate that......, in spite of the immune privileged status of the eye, the ACE-transplanted islets develop infiltration and beta cell destruction, recapitulating the autoimmune insulitis of the pancreas, and exemplify this by analysing reporter cell populations expressing green fluorescent protein under the Cd11c or Foxp3......Aims/hypothesis The aim of this study was to visualise the dynamics and interactions of the cells involved in autoimmune-driven inflammation in type 1 diabetes. Methods We adopted the anterior chamber of the eye (ACE) transplantation model to perform non-invasive imaging of leucocytes infiltrating...

  7. Implication of TLR- but not of NOD2-signaling pathways in dendritic cell activation by group B Streptococcus serotypes III and V.

    Directory of Open Access Journals (Sweden)

    Paul Lemire

    Full Text Available Group B Streptococcus (GBS is an important agent of life-threatening invasive infection. It has been previously shown that encapsulated type III GBS is easily internalized by dendritic cells (DCs, and that this internalization had an impact on cytokine production. The receptors underlying these processes are poorly characterized. Knowledge on the mechanisms used by type V GBS to activate DCs is minimal. In this work, we investigated the role of Toll-like receptor (TLR/MyD88 signaling pathway, the particular involvement of TLR2, and that of the intracellular sensing receptor NOD2 in the activation of DCs by types III and V GBS. The role of capsular polysaccharide (CPS, one of the most important GBS virulence factors in bacterial-DC interactions was evaluated using non-encapsulated mutants. Despite differences in the role of CPS between types III and V GBS in bacterial internalization and intracellular survival, no major differences were observed in their capacity to modulate release of cytokines by DC. For both serotypes, CPS had a minor role in this response. Production of cytokines by DCs was shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize GBS and become activated mostly through TLR signaling. Yet, GBS-infected TLR2-/- DCs only showed a partial reduction in the production of IL-6 and CXCL1 compared to control DCs. Surprisingly, CXCL10 release by type III or type V GBS-infected DCs was MyD88-independent. No differences in DC activation were observed between NOD2-/- and control DCs. These results demonstrate the involvement of various receptors and the complexity of the cytokine production pathways activated by GBS upon DC infection.

  8. An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rγnull mice allows HIV replication and development of anti-HIV immune responses.

    Directory of Open Access Journals (Sweden)

    Maneesh Singh

    Full Text Available Cord blood hematopoietic progenitor cells (CB-HPCs transplanted immunodeficient NOD/LtsZ-scidIL2Rγ(null (NSG and NOD/SCID/IL2Rγ(null (NOG mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials.

  9. Association of NOD1, CXCL16, STAT6 and TLR4 gene polymorphisms with Malaysian patients with Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Kek Heng Chua

    2016-03-01

    Full Text Available Crohn’s disease (CD is a prominent type of inflammatory bowel disease (IBD that can affect any part of the gastrointestinal tract. CD is known to have higher prevalence in the Western countries, but the number of cases has been increasing in the past decades in Asia, including Malaysia. Therefore, there is a need to investigate the underlining causes of CD that may shed light on its prevention and treatment. In this study, genetic polymorphisms in NOD1 (rs2075820, CXCL16 (rs2277680, STAT6 (rs324015 and TLR4 (rs4986791 genes were examined in a total of 335 individuals (85 CD patients and 250 healthy controls with PCR-RFLP approach. There was no significant association observed between NOD1 rs2075820 and STAT6 rs324015 with the onset of CD in the studied cohort. However, the G allele of CXCL16 rs2277680 was found to have a weak association with CD patients (P = 0.0482; OR = 1.4310. The TLR4 rs4986791 was also significantly associated to CD. Both the homozygous C genotype (P = 0.0029; OR = 0.3611 and C allele (P = 0.0069; OR = 0.4369 were observed to confer protection against CD. On the other hand, the heterozygous C/T genotype was a risk genotype (P = 0.0015; OR = 3.1392. Further ethnic-stratified analysis showed that the significant associations in CXCL16 rs2277680 and TLR4 rs4986791 were accounted by the Malay cohort. In conclusion, the present study reported two CD-predisposing loci in the Malay CD patients. However, these loci were not associated to the onset of CD in Chinese and Indian patients.

  10. Numeric kinetic energy operators for molecules in polyspherical coordinates

    International Nuclear Information System (INIS)

    Sadri, Keyvan; Meyer, Hans-Dieter; Lauvergnat, David; Gatti, Fabien

    2012-01-01

    Generalized curvilinear coordinates, as, e.g., polyspherical coordinates, are in general better adapted to the resolution of the nuclear Schrödinger equation than rectilinear ones like the normal mode coordinates. However, analytical expressions of the kinetic energy operators (KEOs) for molecular systems in polyspherical coordinates may be prohibitively complicated for large systems. In this paper we propose a method to generate a KEO numerically and bring it to a form practicable for dynamical calculations. To examine the new method we calculated vibrational spectra and eigenenergies for nitrous acid (HONO) and compare it with results obtained with an exact analytical KEO derived previously [F. Richter, P. Rosmus, F. Gatti, and H.-D. Meyer, J. Chem. Phys. 120, 6072 (2004)]. In a second example we calculated π→π* photoabsorption spectrum and eigenenergies of ethene (C 2 H 4 ) and compared it with previous work [M. R. Brill, F. Gatti, D. Lauvergnat, and H.-D. Meyer, Chem. Phys. 338, 186 (2007)]. In this ethene study the dimensionality was reduced from 12 to 6 by freezing six internal coordinates. Results for both molecules show that the proposed method for obtaining an approximate KEO is reliable for dynamical calculations. The error in eigenenergies was found to be below 1 cm −1 for most states calculated.

  11. On coordinates and coordinate transformation in Einstein's theory of gravitation

    International Nuclear Information System (INIS)

    Chou Peiyuan

    1983-01-01

    This investigation is a further exposition of the significance of coordinates and their transformation in Einstein's theory of gravitation. The author considers the static axisymmetric field as an example, starts with its metric in the cylindrical coordinates, transforms this metric and the field equations into the Weyl-Levi-Civita system of coordinates, and supplements them with the harmonic condition. Both of the field equations and the harmonic condition are then transformed back to the original Cartesian system. Solutions for the static fields of an infinite plane with uniform surface density and an infinite rod with uniform linear density of matter, and of a body with spherical symmetry, are obtained again to show the necessity of the harmonic condition in their solutions. The fact that under the harmonic condition the solutions of the field equations for these problems contain their corresponding Newtonian potentials as approximations, is a strong support to the argument that the harmonic condition should be a physical supplement to Einstein's theory of gravitation. (Auth.)

  12. [Pr2(pdc3(Hpdc(H2O4]n·n(H3hp·8n(H2O, a One-Dimensional Coordination Polymer Containing PrO6N3 Tri-Capped Trigonal Prisms and PrO8N Mono-Capped Square Anti-Prisms (H2pdc = Pyridine 2,6-Dicarboxylic Acid, C7H5NO4; 3hp = 3-Hydroxy Pyridine, C5H5NO

    Directory of Open Access Journals (Sweden)

    Shahzad Sharif

    2012-08-01

    Full Text Available The synthesis, structure and some properties of the one-dimensional coordination polymer, [Pr2(pdc3(Hpdc]n·n(H3hp·8n(H2O, (H2pdc = pyridine 2,6-dicarboxylic acid, C7H5NO4; 3hp = 3-hydroxypyridine, C5H5NO are described. One of the Pr3+ ions is coordinated by two O,N,O-tridentate pdc2− ligands and one tridentate Hpdc− anion to generate a fairly regular PrO6N3 tri-capped trigonal prism, with the N atoms acting as the caps. The second Pr3+ ion is coordinated by one tridentate pdc2− dianion, four water molecules and two monodentate bridging pdc2− ligands to result in a PrO8N coordination polyhedron that approximates to a mono-capped square-anti-prism. The ligands bridge the metal-atom nodes into a chain, which extends in the [100] direction. The H3hp+ cation and uncoordinated water molecules occupy the inter-chain regions and an N–HLO and numerous O–HLO hydrogen bonds consolidate the structure. The H3hp+ species appears to intercalate between pendant pdc rings to consolidate the polymeric structure. Crystal data: 1 (C33H43N5O29Pr2, Mr = 1255.54, triclinic,  (No. 2, Z = 2, a = 13.2567(1 Å, b = 13.6304(2 Å, c = 13.6409(2 Å, α = 89.695(1°, β = 63.049(1°, γ = 86.105(1°, V = 2191.16(5 Å3, R(F = 0.033, wR(F2 = 0.084.

  13. TURNAROUND COORDINATOR. YES OR NOT?

    Directory of Open Access Journals (Sweden)

    Martin HROMÁDKA

    2013-12-01

    Full Text Available Both low cost carriers ‘fresh wind’ and liberalisation of ground handling market makes airlines to be cost-wise in every single field. Thus, ground handling contract are cutting down in terms of their costs. Handling companies struggle with pressure being put from the market environment, they rush 25 minutes turnaround with couple of people. This can be potentially dangerous from the safety point of view. One of possible solutions seems to be introducing turnaround coordinator, person who would supervise the ramp handling procedures. This paper discusses the role of turnaround coordinator within the aircraft turnaround process. Duties and responsibilities of this person are described. However, not every airport is staffing this position. The survey shows that smaller airports pay much more attention to this issue than the big ones.

  14. A coordination language for databases

    DEFF Research Database (Denmark)

    Li, Ximeng; Wu, Xi; Lluch Lafuente, Alberto

    2017-01-01

    We present a coordination language for the modeling of distributed database applications. The language, baptized Klaim-DB, borrows the concepts of localities and nets of the coordination language Klaim but re-incarnates the tuple spaces of Klaim as databases. It provides high-level abstractions...... and primitives for the access and manipulation of structured data, with integrity and atomicity considerations. We present the formal semantics of Klaim-DB and develop a type system that avoids potential runtime errors such as certain evaluation errors and mismatches of data format in tables, which are monitored...... in the semantics. The use of the language is illustrated in a scenario where the sales from different branches of a chain of department stores are aggregated from their local databases. Raising the abstraction level and encapsulating integrity checks in the language primitives have benefited the modeling task...

  15. Coordinating talk and practical action

    DEFF Research Database (Denmark)

    Oshima, Sae; Streeck, Jürgen

    2015-01-01

    This paper investigates how talk and practical action are coordinated during one type of activity involving professional communication: the service-assessment sequence in hair salons. During this activity, a practical inspection of the haircut must be coupled with sequentially produced verbal acts....... Our analysis of four examples reveals that there is no fixed relationship between the organization of talk and practical action. Instead, people manipulate this relationship on a moment-by-moment basis, often coordinating the two into a single, integral package, or relying on one stream of action...... to achieve progress in the other. These findings imply that some multimodal activities that are brought into alignment may have their own, separate and independent procedural logic and sequencing patterns and that these can be brought into play to create or deal with constraints in each other....

  16. Improving Channel Coordination Through Franchising

    OpenAIRE

    Rajiv Lal

    1990-01-01

    In this paper, we explore the role of franchising arrangements in improving coordination between channel members. In particular we focus on two elements of the franchising contract, namely, the royalty structure and the monitoring technology. We begin with a simple analysis where a manufacturer distributes its product through a retailer and the retail demand is affected by the retail price and the service provided by the retailer. In this context we show that neither royalty payments nor moni...

  17. Coordination in the European Union

    OpenAIRE

    Martin Feldstein

    2013-01-01

    This paper examines the sources of current conflict within the EU and the EMU. The topics discussed include the recent ECB policy of bond buying (the OMT policy), the attempts to advance the "European Project" of stronger political union (the fiscal compact, the banking union, and the proposals for budget supervision). Contrary to the claims of the European leadership, the progress that has been made has been by individual countries and not by coordinated action. The special problems of Franc...

  18. Coordination strategies of crew management

    Science.gov (United States)

    Conley, Sharon; Cano, Yvonne; Bryant, Don

    1991-01-01

    An exploratory study that describes and contrasts two three-person flight crews performing in a B-727 simulator is presented. This study specifically attempts to delineate crew communication patterns accounting for measured differences in performance across routine and nonroutine flight patterns. The communication patterns in the two crews evaluated indicated different modes of coordination, i.e., standardization in the less effective crew and planning/mutual adjustment in the more effective crew.

  19. Monetary and Fiscal Policy Coordination

    OpenAIRE

    Hanif, Muhammad N.; Arby, Muhammad Farooq

    2003-01-01

    Macroeconomic policies are meant to achieve non-inflationary, stable growth. There are two major groups of policy instruments to achieve the purpose; one is related to monetary conditions and the other to fiscal conditions. Monetary instruments are employed by the central bank and fiscal instruments are employed by ministry of finance. The objectives and implications of policy measures taken by the two institutions often conflict with each other and thus call for policy coordination for effec...

  20. Inorganic, coordination and organometallic compounds

    International Nuclear Information System (INIS)

    Jursik, F.

    1978-01-01

    Separation of cations and anions of inorganic, coordination and metalloorganic compounds by the method of liquid column chromatography is considered. Common scheme of multicomponent cation mixture is suggesteed. Separation conditions, adsrbents, eluents, pH value solution concenstration, elution rate are also suggested. Separation of rare earth elements Cs, Be, Cd, Te, Th, U, Mo, Re, V, Ru, Zr, In compounds is considered as an example of liquid column chromatography application. Data on column chromatography application are summarized in a table

  1. Porphyrin coordination polymer nanospheres and nanorods

    Science.gov (United States)

    Wang, Zhongchun; Shelnutt, John A.; Medforth, Craig J.

    2012-12-04

    A porphyrin coordination polymer nanostructure comprising a network of pyridyl porphyrin molecules and coordinating metal ions coordinatively bound through the pyridyl groups. In some embodiments, the porphyrins are metalloporphyrins. A variety of nanostructures are formed by the network polymer, including nanospheres, polygonal nanostructures, nanorods, and nanofibers, depending on a variety of factors including coordination metal ion, porphyrin type, metal of the metalloporphyrin, and degree of agitation during nanostructure formation. Reduction of coordinating metal ions may be used to form metal nanoparticles on the coordination polymer nanostructure.

  2. Rare earth niobate coordination polymers

    Science.gov (United States)

    Muniz, Collin N.; Patel, Hiral; Fast, Dylan B.; Rohwer, Lauren E. S.; Reinheimer, Eric W.; Dolgos, Michelle; Graham, Matt W.; Nyman, May

    2018-03-01

    Rare-earth (RE) coordination polymers are infinitely tailorable to yield luminescent materials for various applications. Here we described the synthesis of a heterometallic rare-earth coordination compound ((CH3)2SO)3(RE)NbO(C2O4)3((CH3)2SO) = dimethylsulfoxide, DMSO, (C2O2= oxalate), (RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb). The structure was obtained from single crystal X-ray diffraction of the La analogue. The Nb˭O and DMSO terminal-bonding character guides assembly of an open framework structure with noncentrosymmetric RE-coordination geometry, and large spacing between the RE centers. A second structure was observed by PXRD for the smaller rare earths (Dy, Ho, Er, Yb); this structure has not yet been determined. The materials were further characterized using FTIR, and photoluminescence measurements. Characteristic excitation and emission transitions were observed for RE = Nd, Sm, Eu, and Tb. Quantum yield (QY) measurements were performed by exciting Eu and Tb analoges at 394 nm (QY 66%) and 464 nm (QY 71%) for Eu; and 370 nm (QY=40%) for Tb. We attribute the high QY and bright luminescence to two main structure-function properties of the system; namely the absence of water in the structure, and absence of concentration quenching.

  3. Lewis Acidic Ionic Liquids.

    Science.gov (United States)

    Brown, Lucy C; Hogg, James M; Swadźba-Kwaśny, Małgorzata

    2017-08-21

    Until very recently, the term Lewis acidic ionic liquids (ILs) was nearly synonymous with halometallate ILs, with a strong focus on chloroaluminate(III) systems. The first part of this review covers the historical context in which these were developed, speciation of a range of halometallate ionic liquids, attempts to quantify their Lewis acidity, and selected recent applications: in industrial alkylation processes, in supported systems (SILPs/SCILLs) and in inorganic synthesis. In the last decade, interesting alternatives to halometallate ILs have emerged, which can be divided into two sub-sections: (1) liquid coordination complexes (LCCs), still based on halometallate species, but less expensive and more diverse than halometallate ionic liquids, and (2) ILs with main-group Lewis acidic cations. The two following sections cover these new liquid Lewis acids, also highlighting speciation studies, Lewis acidity measurements, and applications.

  4. Multisites Coordination in Shared Multicast Trees

    National Research Council Canada - National Science Library

    Dommel, H-P; Garcia-Luna-Aceves, J. J

    1999-01-01

    .... The protocol supports Internet-wide coordination for large and highly interactive groupwork, relying on transmission of coordination directives between group members across a shared end-to-end multicast tree...

  5. International Coordination of Lunar Polar Volatiles Exploration

    Science.gov (United States)

    Gruener, J. E.; Suzuki, N. H.; Carpenter, J. D.

    2015-10-01

    The International Space Exploration Coordination Group (ISECG) has established a study team to coordinate the worldwide interest in lunar polar volatiles, and in particular water ice, in an effort to stimulate cooperation and collaboration.

  6. The Imperative for Improved Global Economic Coordination

    OpenAIRE

    Stiglitz, Joseph E.

    2009-01-01

    While global coordination is absolutely essential, success in achieving it may prove difficult because economic globalization has outpaced political globalization. If we are to succeed, we will have to manage coordination better than we have in the past.

  7. Dreams: a framework for distributed synchronous coordination

    NARCIS (Netherlands)

    Proença, J.; Clarke, D.; Vink, de E.P.; Arbab, F.

    2012-01-01

    Synchronous coordination systems, such as Reo, exchange data via indivisible actions, while distributed systems are typically asynchronous and assume that messages can be delayed or get lost. To combine these seemingly contradictory notions, we introduce the Dreams framework. Coordination patterns

  8. Reusable coordinator modules for massively concurrent applications

    NARCIS (Netherlands)

    F. Arbab (Farhad); C.L. Blom (Kees); F.J. Burger (Freek); C.T.H. Everaars (Kees)

    1998-01-01

    htmlabstractIsolating computation and communication concerns into separate pure computation and pure coordination modules enhances modularity, understandability and reusability of parallel and/or distributed software. MANIFOLD is a pure coordination language that encourages this separation. We use

  9. Coordinator, Evaluation Unit | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Job Summary The Evaluation Unit Coordinator is expected to: ... with Centre policies and procedures and disseminates information to Unit staff on changes ... Coordinates the planning and organization of technical and administrative meetings ...

  10. Process Coordination & Policy Officer | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Such liaison aims to ensure that the operational aspects and requirements are taken into account. ... Business Process Coordination and Change Management ... plan and coordinating the update of the Division's work plan by all managers; ...

  11. Modeling Coordination Problems in a Music Ensemble

    DEFF Research Database (Denmark)

    Frimodt-Møller, Søren R.

    2008-01-01

    This paper considers in general terms, how musicians are able to coordinate through rational choices in a situation of (temporary) doubt in an ensemble performance. A fictitious example involving a 5-bar development in an unknown piece of music is analyzed in terms of epistemic logic, more...... to coordinate. Such coordination can be described in terms of Michael Bacharach's theory of variable frames as an aid to solve game theoretic coordination problems....

  12. Parenting Coordinators' Practices Recommendations: A Qualitative Study

    OpenAIRE

    Hirsch, Barbara Phyllis

    2016-01-01

    This qualitative study used a phenomenological approach to understand the experiences of seven parenting coordinators in using parenting coordination practices that they have found to be effective and would recommend to other parenting coordinators to achieve the following goals: educating parents, increasing the quality of parenting and co-parenting, managing conflict, and involving children and other family members in the process of parenting coordination. Data were collected with semi-str...

  13. A Dynamic Coordination Mechanism Using Adjustable Autonomy

    NARCIS (Netherlands)

    Neef, R.M.; Vecht, B. van der; Dignum, F.; Meyer, J.J.C.

    2008-01-01

    Agents in an organization need to coordinate their actions in order to reach the organizational goals. This research describes the relation between types of coordination and the autonomy of actors. In an experimental setting we show that there is not one best way to coordinate in all situations. The

  14. A Dynamic Coordination Mechanism Using Adjustable Autonomy

    NARCIS (Netherlands)

    Vecht, B. van der; Dignum, F.; Meyer, J.J.C.; Neef, R.M.

    2007-01-01

    Agents in an organization need to coordinate their actions in order to reach the organizational goals. This research describes the relation between types of coordination and the autonomy of actors. In an experimental setting we show that there is not one best way to coordinate in all situations. The

  15. 45 CFR 1310.23 - Coordinated transportation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Coordinated transportation. 1310.23 Section 1310... START PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.23 Coordinated transportation. (a) Each agency providing transportation services must make reasonable efforts to coordinate transportation...

  16. The unified coordination language UnCL.

    NARCIS (Netherlands)

    F.S. de Boer (Frank); J.V. Guillen Scholten (Juan); J.F. Jacob (Joost)

    2005-01-01

    textabstractIn this paper we show how to use a (subset) of UML as an Unified Coordination Language (UnCL) that is based on a separation of concerns between coordination and computation. As such UnCL provides a general language for the coordination of, in particular, object-oriented applications. The

  17. A Note on the Dipole Coordinates

    OpenAIRE

    Kageyama, Akira; Sugiyama, Tooru; Watanabe, Kunihiko; Sato, Tetsuya

    2004-01-01

    A couple of orthogonal coordinates for dipole geometry are proposed for numerical simulations of plasma geophysics in the Earth's dipole magnetic field. These coordinates have proper metric profiles along field lines in contrast to the standard dipole coordinate system that is commonly used in analytical studies for dipole geometry.

  18. Optimization of strong and weak coordinates

    NARCIS (Netherlands)

    Swart, M.; Bickelhaupt, F.M.

    2006-01-01

    We present a new scheme for the geometry optimization of equilibrium and transition state structures that can be used for both strong and weak coordinates. We use a screening function that depends on atom-pair distances to differentiate strong coordinates from weak coordinates. This differentiation

  19. 47 CFR 27.57 - International coordination.

    Science.gov (United States)

    2010-10-01

    ... COMMUNICATIONS SERVICES Technical Standards § 27.57 International coordination. (a) WCS operations in the border areas shall be subject to coordination with those countries and provide protection to non-U.S... 47 Telecommunication 2 2010-10-01 2010-10-01 false International coordination. 27.57 Section 27.57...

  20. 40 CFR 109.6 - Coordination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Coordination. 109.6 Section 109.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS CRITERIA FOR STATE, LOCAL AND REGIONAL OIL REMOVAL CONTINGENCY PLANS § 109.6 Coordination. For the purposes of coordination...