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Sample records for m-1 s-1 pa-1

  1. Target-specific M1 inputs to infragranular S1 pyramidal neurons

    Science.gov (United States)

    Fanselow, Erika E.; Simons, Daniel J.

    2016-01-01

    The functional role of input from the primary motor cortex (M1) to primary somatosensory cortex (S1) is unclear; one key to understanding this pathway may lie in elucidating the cell-type specific microcircuits that connect S1 and M1. Recently, we discovered that a subset of pyramidal neurons in the infragranular layers of S1 receive especially strong input from M1 (Kinnischtzke AK, Simons DJ, Fanselow EE. Cereb Cortex 24: 2237–2248, 2014), suggesting that M1 may affect specific classes of pyramidal neurons differently. Here, using combined optogenetic and retrograde labeling approaches in the mouse, we examined the strengths of M1 inputs to five classes of infragranular S1 neurons categorized by their projections to particular cortical and subcortical targets. We found that the magnitude of M1 synaptic input to S1 pyramidal neurons varies greatly depending on the projection target of the postsynaptic neuron. Of the populations examined, M1-projecting corticocortical neurons in L6 received the strongest M1 inputs, whereas ventral posterior medial nucleus-projecting corticothalamic neurons, also located in L6, received the weakest. Each population also possessed distinct intrinsic properties. The results suggest that M1 differentially engages specific classes of S1 projection neurons, thereby regulating the motor-related influence S1 exerts over subcortical structures. PMID:27334960

  2. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  3. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.

    Science.gov (United States)

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter; Schulze, Tobias

    2017-01-01

    Introduction . Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P 1-5 ) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  4. ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties.

    Science.gov (United States)

    Wang, Fang; Liang, Yong-Ju; Wu, Xing-Ping; Su, Xiao-Dong; Fu, Li-Wu

    2012-03-01

    S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

  5. vacA s1m1 genotype and cagA EPIYA-ABC pattern are predominant among Helicobacter pylori strains isolated from Mexican patients with chronic gastritis.

    Science.gov (United States)

    Atrisco-Morales, Josefina; Martínez-Santos, Verónica I; Román-Román, Adolfo; Alarcón-Millán, Judit; De Sampedro-Reyes, José; Cruz-Del Carmen, Iván; Martínez-Carrillo, Dinorah N; Fernández-Tilapa, Gloria

    2018-03-01

    Virulent genotypes of Helicobacter pylori vacA s1m1/cagA + /babA2 + have been associated with severe gastric diseases. VacA, CagA and BabA are polymorphic proteins, and their association with the disease is allele-dependent. The aims of this work were: (i) to determine the prevalence of H. pylori by type of chronic gastritis; (ii) to describe the frequency of cagA, babA2 and vacA genotypes in strains from patients with different types of chronic gastritis; (iii) to characterize the variable region of cagA alleles. A total of 164 patients with chronic gastritis were studied. Altogether, 50 H. pylori strains were isolated, and the status of cagA, babA2 and vacA genotypes was examined by PCR. cagA EPIYA segment identification was performed using PCR and sequencing of cagA fragments of six randomly selected strains.Results/Key findings. The overall prevalence of H. pylori was 30.5 %. Eighty percent of the isolated strains were vacA s1m1, and the cagA and babA2 genes were detected in 74 and 32 % of the strains, respectively. The most frequent genotypes were vacA s1m1/cagA + /babA2 - and vacA s1m1/cagA + /babA2 + , with 40 % (20/50) and 28 % (14/50), respectively. In cagA + , the most frequent EPIYA motif was -ABC (78.4 %), and EPIYA-ABCC and -ABCCC motifs were found in 10.8 % of the strains. A modified EPIYT-B motif was found in 66.6 % of the sequenced strains. H. pylori strains carrying vacA s1m1, cagA + and babA2 - genotypes were the most prevalent in patients with chronic gastritis from the south of Mexico. In the cagA + strains, the EPIYA-ABC motif was the most common.

  6. Enhancement of motor learning by focal intermittent theta burst stimulation (iTBS) of either the primary motor (M1) or somatosensory area (S1) in healthy human subjects.

    Science.gov (United States)

    Platz, Thomas; Adler-Wiebe, Marija; Roschka, Sybille; Lotze, Martin

    2018-01-01

    Motor rehabilitation after brain damage relies on motor re-learning as induced by specific training. Non-invasive brain stimulation (NIBS) can alter cortical excitability and thereby has a potential to enhance subsequent training-induced learning. Knowledge about any priming effects of NIBS on motor learning in healthy subjects can help to design targeted therapeutic applications in brain-damaged subjects. To examine whether complex motor learning in healthy subjects can be enhanced by intermittent theta burst stimulation (iTBS) to primary motor or sensory cortical areas. Eighteen young healthy subjects trained eight different arm motor tasks (arm ability training, AAT) once a day for 5 days using their left non-dominant arm. Except for day 1 (baseline), training was performed after applying an excitatory form of repetitive transcranial magnetic stimulation (iTBS) to either (I) right M1 or (II) S1, or (III) sham stimulation to the right M1. Subjects were randomly assigned to conditions I, II, or III. A principal component analysis of the motor behaviour data suggested eight independent motor abilities corresponding to the 8 trained tasks. AAT induced substantial motor learning across abilities with generalisation to a non-trained test of finger dexterity (Nine-Hole-Peg-Test, NHPT). Participants receiving iTBS (to either M1 or S1) showed better performance with the AAT tasks over the period of training compared to sham stimulation as well as a bigger improvement with the generalisation task (NHPT) for the trained left hand after training completion. Priming with an excitatory repetitive transcranial magnetic stimulation as iTBS of either M1 or S1 can enhance motor learning across different sensorimotor abilities.

  7. Complete sequences of IncHI1 plasmids carrying blaCTX-M-1 and qnrS1 in equine Escherichia coli provide new insights into plasmid evolution

    DEFF Research Database (Denmark)

    Dolejska, Monika; Villa, Laura; Minoia, Marco

    2014-01-01

    OBJECTIVES: To determine the structure of two multidrug-resistant IncHI1 plasmids carrying blaCTX-M-1 in Escherichia coli isolates disseminated in an equine clinic in the Czech Republic. METHODS: A complete nucleotide sequencing of 239 kb IncHI1 (pEQ1) and 287 kb IncHI1/X1 (pEQ2) plasmids was per...... highlight the structure and evolution of IncHI1 from equine E. coli. A plasmid-mediated sugar metabolic element could play a key role in strain fitness, contributing to the successful dissemination and maintenance of these plasmids in the intestinal microflora of horses....

  8. PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Takashi Takeshita

    Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

  9. Expression and biological activity of the cystine knot bioinsecticide PA1b (Pea Albumin 1 Subunit b.

    Directory of Open Access Journals (Sweden)

    Vanessa Eyraud

    Full Text Available The PA1b (Pea Albumin 1, subunit b peptide is an entomotoxin extract from Legume seeds with lethal activity on several insect pests, such as mosquitoes, some aphids and cereal weevils. This 37 amino-acid cysteine-rich peptide has been, until now, obtained by biochemical purification or chemical synthesis. In this paper, we present our results for the transient production of the peptide in Nicotiana benthamiana by agro-infiltration, with a yield of about 35 µg/g of fresh leaves and maximum production 8 days after infiltration. PA1b is part of the PA1 gene which, after post-translational modifications, encodes two peptides (PA1b and PA1a. We show that transforming tobacco with the PA1b cDNA alone does not result in production of the toxin and, in fact, the entire cDNA is necessary, raising the question of the role of PA1a. We constructed a PA1-cassette, allowing for the quick "cut/paste" of different PA1b mutants within a conserved PA1 cDNA. This cassette enabled us to produce the six isoforms of PA1b which exist in pea seeds. Biological tests revealed that all the isoforms display similar activity, with the exception of one which is inactive. The lack of activity in this isoform led us to conclude that the amphiphilic nature of the peptide is necessary for activity. The possible applications of this expression system for other cysteine-rich biomolecules are discussed.

  10. PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation*

    Science.gov (United States)

    Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C.; Simons, S. Stoney

    2013-01-01

    Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (Amax), the potency of agonists (EC50), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses Amax, increases the EC50, and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC50, and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene. PMID:23161582

  11. PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation.

    Science.gov (United States)

    Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C; Simons, S Stoney

    2013-01-04

    Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (A(max)), the potency of agonists (EC(50)), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene.

  12. Rapid and efficient purification method for small, hydrophobic, cationic bacteriocins : Purification of lactococcin B and pediocin PA-1

    NARCIS (Netherlands)

    Venema, Koen; Chikindas, Michael L.; Seegers, Jos F.M.L.; Haandrikman, Alfred J.; Leenhouts, Kees J.; Venema, Gerard; Kok, Jan

    The bacteriocins lactococcin B and pediocin PA 1 were purified by ethanol precipitation, preparative isoelectric focusing, and ultrafiltration. The procedure reproducibly leads to high final yields in comparison to the generally low yields obtained by column chromatography. Specifically, during

  13. Production of biosurfactants from Pseudomonas aeruginosa PA 1 isolated in oil environments

    Directory of Open Access Journals (Sweden)

    L.M. Santa Anna

    2002-04-01

    Full Text Available The potential production of rhamnolipid-type biosurfactants is assessed based on the development of a fermentative process with a strain of Pseudomonas aeruginosa PA1, which was isolated from oil production wastewater in the Northeast of Brazil. These production of molecules using different carbon (n-hexadecane, paraffinic oil, glycerol and babassu oil and nitrogen sources (NaNO3, (NH42SO4 and CH4N2O was studied. The best results were obtained when using glycerol as substrate. A C/N ratio of 60/1 and use of sodium nitrate as nitrogen source resulted in higher production of the rhamnolipid, expressed by rhamnose (3.16 g/L and by the yield in relation to biomass (Yp/x = 0.70 g/g. Additionally, physical-chemical characteristics of the spent broth with and without cells were studied, providing a low critical micelle concentration of 19 mg/L and toxicity values of 13 and 13.8 mg/L using two test organisms, the micro crustacean Daphnia similis and the bacterium Vibrio fisheri (Microtox, respectively.

  14. Rapid and Efficient Purification Method for Small, Hydrophobic, Cationic Bacteriocins: Purification of Lactococcin B and Pediocin PA-1

    OpenAIRE

    Venema, K.; Chikindas, M. L.; Seegers, J.; Haandrikman, A. J.; Leenhouts, K. J.; Venema, G.; Kok, J.

    1997-01-01

    The bacteriocins lactococcin B and pediocin PA-1 were purified by ethanol precipitation, preparative isoelectric focusing, and ultrafiltration. The procedure reproducibly leads to high final yields in comparison to the generally low yields obtained by column chromatography. Specifically, during isoelectric focusing no loss of activity occurs. The method, in general, should be applicable to small, hydrophobic, cationic bacteriocins.

  15. Improved antimicrobial activities of synthetic-hybrid bacteriocins designed from enterocin E50-52 and pediocin PA-1.

    Science.gov (United States)

    Tiwari, Santosh Kumar; Sutyak Noll, Katia; Cavera, Veronica L; Chikindas, Michael L

    2015-03-01

    Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Heterologous Coproduction of Enterocin A and Pediocin PA-1 by Lactococcus lactis: Detection by Specific Peptide-Directed Antibodies

    Science.gov (United States)

    Martínez, José M.; Kok, Jan; Sanders, Jan W.; Hernández, Pablo E.

    2000-01-01

    Antibodies against enterocin A were obtained by immunization of rabbits with synthetic peptides PH4 and PH5 designed, respectively, on the N- and C-terminal amino acid sequences of enterocin A and conjugated to the carrier protein KLH. Anti-PH4-KLH antibodies not only recognized enterocin A but also pediocin PA-1, enterocin P, and sakacin A, three bacteriocins which share the N-terminal class IIa consensus motif (YGNGVXC) that is contained in the sequence of the peptide PH4. In contrast, anti-PH5-KLH antibodies only reacted with enterocin A because the amino acid sequences of the C-terminal parts of class IIa bacteriocins are highly variable. Enterocin A and/or pediocin PA-1 structural and immunity genes were introduced in Lactococcus lactis IL1403 to achieve (co)production of the bacteriocins. The level of production of the two bacteriocins was significantly lower than that obtained by the wild-type producers, a fact that suggests a low efficiency of transport and/or maturation of these bacteriocins by the chromosomally encoded bacteriocin translocation machinery of IL1403. Despite the low production levels, both bacteriocins could be specifically detected and quantified with the anti-PH5-KLH (anti-enterocin A) antibodies isolated in this study and the anti-PH2-KLH (anti-pediocin PA-1) antibodies previously generated (J. M. Martínez, M. I. Martínez, A. M. Suárez, C. Herranz, P. Casaus, L. M. Cintas, J. M. Rodríguez, and P. E. Hernández, Appl. Environ. Microbiol. 64:4536–4545, 1998). In this work, the availability of antibodies for the specific detection and quantification of enterocin A and pediocin PA-1 was crucial to demonstrate coproduction of both bacteriocins by L. lactis IL1403(pJM04), because indicator strains that are selectively inhibited by each bacteriocin are not available. PMID:10919819

  17. Curvature of super Diff(S1)/S1

    International Nuclear Information System (INIS)

    Oh, P.; Ramond, P.

    1987-01-01

    Motivated by the work of Bowick and Rajeev, we calculate the curvature of the infinite-dimensional flag manifolds Diff(S 1 )/S 1 and Super Diff(S 1 )/S 1 using standard finite-dimensional coset space techniques. We regularize the infinite by ζ-function regularization and recover the conformal and superconformal anomalies respectively for a specific choice of the torsion. (orig.)

  18. Enantioselective degradation and unidirectional chiral inversion of 2-phenylbutyric acid, an intermediate from linear alkylbenzene, by Xanthobacter flavus PA1

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yishan; Han, Ping [School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Li, Xiao-yan; Shih, Kaimin [Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Gu, Ji-Dong, E-mail: jdgu@hkucc.hku.hk [School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong (China); The Swire Institute of Marine Science, The University of Hong Kong, Shek O, Cape d' Aguilar, Hong Kong (China)

    2011-09-15

    Highlights: {yields} We isolated a Xanthobacter flavus strain PA1 utilizing the racemic 2-PBA and the single enantiomers as the sole source of carbon and energy. {yields} Both (R) and (S) forms of enantiomers can be degraded in a sequential manner in which the (S) disappeared before the (R) form. {yields} The biochemical degradation pathway involves an initial oxidation of the alkyl side chain before aromatic ring cleavage. - Abstract: Microbial degradation of the chiral 2-phenylbutyric acid (2-PBA), a metabolite of surfactant linear alkylbenzene sulfonates (LAS), was investigated using both racemic and enantiomer-pure compounds together with quantitative stereoselective analyses. A pure culture of bacteria, identified as Xanthobacter flavus strain PA1 isolated from the mangrove sediment of Hong Kong Mai Po Nature Reserve, was able to utilize the racemic 2-PBA as well as the single enantiomers as the sole source of carbon and energy. In the presence of the racemic compounds, X. flavus PA1 degraded both (R) and (S) forms of enantiomers to completion in a sequential manner in which the (S) enantiomer disappeared much faster than the (R) enantiomer. When the single pure enantiomer was supplied as the sole substrate, a unidirectional chiral inversion involving (S) enantiomer to (R) enantiomer was evident. No major difference was observed in the degradation intermediates with either of the individual enantiomers when used as the growth substrate. Two major degradation intermediates were detected and identified as 3-hydroxy-2-phenylbutanoic acid and 4-methyl-3-phenyloxetan-2-one, using a combination of liquid chromatography-mass spectrometry (LC-MS), and {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR) spectroscopy. The biochemical degradation pathway follows an initial oxidation of the alkyl side chain before aromatic ring cleavage. This study reveals new evidence for enantiomeric inversion catalyzed by pure culture of environmental bacteria and emphasizes the

  19. "Lactococcus lactis" productores de pediocina PA-1 y enterococos aislados de leche materna como agentes bioconservantes en quesos

    OpenAIRE

    Reviriego Herráez, Carlota

    2008-01-01

    Producción heteróloga de pediocina PA-1 en cepas de Lactococcus lactis. Empleo como cultivos bioprotectores para la elaboración de quesos.Mediante diversas estrategias (intercambio de líderes, utilización del operón completo de la pediocina, integración cromosómica y obtención de un vector de grado alimentario) y diversos vectores (de diferente número de copias, selección mediante diferentes antibióticos, vector integrativo y vector de grado alimentario) se consiguió la producción de pediocin...

  20. m=1” coatings

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.; Klinkby, Esben Bryndt; Beaucour, J.

    For neutrons the critical angle of Ni is defined as m=1. If one needs a coating with reflectivity above m=1, people have traditionally used Ni58 or Ni-based multilayers. The reason to use Ni is the high neutron scattering density and the fact that it is easy to coat Ni using magnetron sputtering....... For a neutron guide the cost of shielding around the guide is a substantial part of the total cost of the guide. We are therefore looking at other materials than Ni for m=1 coatings. Both Be and diamond have the same or higher neutron scattering density than Ni, and have a much smaller absorption cross section....... Because of the lower absorption cross section, and because of fewer emitted gamma ray photons when a neutron is absorbed, these coatings are producing much less gamma radiation and therefore reduce the shielding costs. Be is frequently used in a wide range of science and technology applications. The only...

  1. Predicting Trainability of M1 Crewmen

    Science.gov (United States)

    1982-10-01

    Load Main Gun Clear Main Gun LOAD/UNLOAD M250 GRENADE LAUNCHER ON M1 TANK* Load Grenade Launcher Unload Grenade Launcher PREPARE GUNNER’S STATION...Clear Main Gun LOAD/UNLOAD M250 GRENADE LAUNCHER ON Ml TANK* Load Grenade Launcher Unload Grenade Lauacher PREPARE GUNNER’S STATION FOR OPERATION ON Ml

  2. Superstring field theories on super-flag manifolds: superdiff S1/S1 and superdiff S1/super S1

    International Nuclear Information System (INIS)

    Zhao Zhiyong; Wu, Ke; Saito, Takesi

    1987-01-01

    We generalize the geometric approach of Bowick and Rajeev [BR] to superstring field theories. The anomaly is identified with nonvanishing of the Ricci curvature of the super-flag manifold. We explicitly calculate the curvatures of superdiff S 1 /S 1 and superdiff S 1 /superS 1 using super-Toeplitz operator techniques. No regularization is needed in this formalism. The critical dimension D=10 is rediscovered as a result of vanishing curvature of the product bundle over the super-flag manifold. (orig.)

  3. Current Status of TRR-1/M1

    International Nuclear Information System (INIS)

    Sittichai, Chaiyut

    2000-01-01

    In 1961, the first Thai Research Reactor, TRR-1, having power of 1 MW was established. It was located at Office of Atomic Energy for Peace (OAEP) in Bangkok. TRR-1 was completely commissioned in June 1962. Plate typed high-enriched uranium (HEU) and U 3 O 8 -Al were used as fuel. Light water used as moderator and coolant. During 1975-1977, TRR-1 was shut down for modification. The reactor core and control system were disassembled and replaced by TRIGA Mark III. It is a circular hexagonal core typed reactor designed by General Atomics Company (GA). Afterwards, TRR-1 was officially renamed to Thai Research Reactor 1/Modification 1 (TRR-1/M1). TRR-1/M1 is a multipurpose reactor with nominal power of 2 MW. This swimming pool typed reactor uses low-enriched uranium (LEU) as fuel and light water as coolant and moderator. To date, the reactor has been operated with core No.12 that released power 1135 MWD to serve the user. The reactor has been serving for various kinds of utilization, for example, to produce radioisotope, neutron beam experiments and reactor physics experiments. This report explains in detail regarding operational experience and current status of this reactor, for example, reactor operation and reactor utilization. (author)

  4. Design, Synthesis, and Biological Evaluation of 68Ga-DOTA-PA1 for Lung Cancer: A Novel PET Tracer for Multiple Somatostatin Receptor Imaging.

    Science.gov (United States)

    Liu, Fei; Liu, Teli; Xu, Xiaoxia; Guo, Xiaoyi; Li, Nan; Xiong, Chiyi; Li, Chun; Zhu, Hua; Yang, Zhi

    2018-02-05

    Most of the radiolabeled somatostatin analogues (SSAs) are specific for subtype somatostatin receptor 2 (SSTR 2 ). Lack of ligands targeting other subtypes of SSTRs, especially SSTR 1, SSTR 3 , and SSTR 5 , limited their applications in tumors of low SSTR 2 expression, including lung tumor. In this study, we aimed to design and synthesize a positron emission tomography (PET) radiotracer targeting multi-subtypes of SSTRs for PET imaging. PA1 peptide and its conjugate with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator or fluorescein isothiocyanate (FITC) at the N-terminal of the lysine position were synthesized. 68 Ga was chelated to DOTA-PA1 to obtain 68 Ga-DOTA-PA1 radiotracer. The stability, lipophilicity, binding affinity, and binding specificity of 68 Ga-DOTA-PA1 and FITC-PA1 were evaluated by various in vitro experiments. Micro-PET imaging of 68 Ga-DOTA-PA1 was performed in nude mice bearing A549 lung adenocarcinoma, as compared with 68 Ga-DOTA-(Tyr3)-octreotate ( 68 Ga-DOTA-TATE). Histological analysis of SSTR expression in A549 tumor tissues and human tumor tissues was conducted using immunofluorescence staining and immunohistochemical assay. 68 Ga-DOTA-PA1 had high radiochemical yield and radiochemical purity of over 95% and 99%, respectively. The radiotracer was stable in vitro in different buffers over a 2 h incubation period. Cell uptake of 68 Ga-DOTA-PA1 was 1.31-, 1.33-, and 1.90-fold that of 68 Ga-DOTA-TATE, which has high binding affinity only for SSTR 2 , after 2 h incubation in H520, PG, and A549 lung cancer cell lines, respectively. Micro-PET images of 68 Ga-DOTA-PA1 showed that the PET imaging signal correlated with the total expression of SSTRs, instead of SSTR 2 only, which was measured by Western blotting and immunofluorescence analysis in mice bearing A549 tumors. In summary, a novel PET radiotracer, 68 Ga-DOTA-PA1, targeting multi-subtypes of SSTRs, was successfully synthesized and was confirmed to be useful for PET

  5. "m=1" coatings for neutron guides

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over...... the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and thermal neutrons and when a neutron is absorbed it emits a lot of gamma rays, some with energies above 9 Me...... of diamond coatings to show the potential for using these coatings in neutron guides....

  6. E-ELT M1 test facility

    Science.gov (United States)

    Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, P.; Sedghi, B.; Mueller, M.

    2012-09-01

    During the advanced design phase of the European Extremely Large Telescope (E-ELT) several critical components have been prototyped. During the last year some of them have been tested in dedicated test stands. In particular, a representative section of the E-ELT primary mirror has been assembled with 2 active and 2 passive segments. This test stand is equipped with complete prototype segment subunits, i.e. including support mechanisms, glass segments, edge sensors, position actuators as well as additional metrology for monitoring. The purpose is to test various procedures such as calibration, alignment and handling and to study control strategies. In addition the achievable component and subsystem performances are evaluated, and interface issues are identified. In this paper an overview of the activities related to the E-ELT M1 Test Facility will be given. Experiences and test results are presented.

  7. Introduction to the m = 1 helicity source

    International Nuclear Information System (INIS)

    Platts, D.A.; Jarboe, T.R.; Wright, B.L.

    1985-01-01

    The m = 1 Helicity Source, formerly called the Kinked Z-pinch, was developed as part of the Electrode Studies program at Los Alamos. The Electrode Studies program was initiated to study the control of electrode erosion in long discharge duration spheromak sources. Erosion control is necessary to reduce plasma impurities and to obtain adequate electrode lifetimes. The first task of the Electrode Studies program is to determine, from among a variety of configurations including the coaxial one, a helicity source geometry with good prospects for erosion control. The more efficient the helicity source the easier it will be to control erosion, but the source most also be easy to diagnose and modify if it is to be a useful test bed. The various erosion control techniques which have been proposed will require extensive experimentation to evaluate and optimize. Proposed techniques include, using refractory metals, profiling of the electrodes and magnetic fields, and various gas injection schemes including porous electrodes. It is considered necessary to do these experiments on an optimized helicity source so that the electrode geometries and plasma properties will be relevant. Therefore the present Electrode Studies program is aimed at developing an improved helicity source design

  8. Supplemental Table S1.xls

    Indian Academy of Sciences (India)

    S1_at, 4, 4, 11.8, 4, 4, 4, 4, 0.0019, 1.13, NC, 4.4, 0.126, 1.03, NC, 5.2, -1.18, 0.0282 ...... pyruvate, phosphate dikinase, chloroplast precursor, putative, expressed ...... LOC_Os09g28160.1|11, phosphate carrier protein, mitochondrial precursor, ...

  9. Infinitely many N=1 dualities from m+1m=1

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Prarit; Intriligator, Kenneth; Song, Jaewon [Department of Physics, University of California,San Diego, La Jolla, CA 92093 (United States)

    2015-10-06

    We discuss two infinite classes of 4d supersymmetric theories, T{sub N}{sup (m)} and U{sub N}{sup (m)}, labelled by an arbitrary non-negative integer, m. The T{sub N}{sup (m)} theory arises from the 6d, A{sub N−1} type N=(2,0) theory reduced on a 3-punctured sphere, with normal bundle given by line bundles of degree (m+1,−m); the m=0 case is the N=2 supersymmetric T{sub N} theory. The novelty is the negative-degree line bundle. The U{sub N}{sup (m)} theories likewise arise from the 6d N=(2,0) theory on a 4-punctured sphere, and can be regarded as gluing together two (partially Higgsed) T{sub N}{sup (m)} theories. The T{sub N}{sup (m)} and U{sub N}{sup (m)} theories can be represented, in various duality frames, as quiver gauge theories, built from T{sub N} components via gauging and nilpotent Higgsing. We analyze the RG flow of the U{sub N}{sup (m)} theories, and find that, for all integer m>0, they end up at the same IR SCFT as SU(N) SQCD with 2N flavors and quartic superpotential. The U{sub N}{sup (m)} theories can thus be regarded as an infinite set of UV completions, dual to SQCD with N{sub f}=2N{sub c}. The U{sub N}{sup (m)} duals have different duality frame quiver representations, with 2m+1 gauge nodes.

  10. An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function.

    Science.gov (United States)

    Fatehi, M; Rowan, E G; Harvey, A L

    2002-01-01

    The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

  11. M1 transitions in the (sdg) boson model

    International Nuclear Information System (INIS)

    Kuyucak, S.; Tuebingen Univ.; Morrison, I.

    1988-01-01

    Using the 1/N expansion technique we derive expressions for β → g, γ → g and γ → γ M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character. (orig.)

  12. M1 transitions in the (sdg) boson model

    Energy Technology Data Exchange (ETDEWEB)

    Kuyucak, S.; Morrison, I.

    1988-03-03

    Using the 1/N expansion technique we derive expressions for ..beta.. -> g, ..gamma.. -> g and ..gamma.. -> ..gamma.. M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character.

  13. Stochasticity and the m = 1 mode in tokamaks

    International Nuclear Information System (INIS)

    Izzo, R.; Monticello, D.A.; Stodiek, W.; Park, W.

    1986-05-01

    It has recently been proposed that stochasticity resulting from toroidal coupling could lead to a saturation of the m = 1 internal mode in tokamaks. We present results from the nonlinear evolution of the m = 1 mode with toroidal coupling that show that stochasticity is not enough to cause saturation of the m = 1 mode

  14. PA-1, a Versatile Anaerobe Obtained in Pure Culture, Catabolizes Benzenoids and Other Compounds in Syntrophy with Hydrogenotrophs, and P-2 plus Wolinella sp. Degrades Benzenoids

    Science.gov (United States)

    Barik, Sudhakar; Brulla, W. J.; Bryant, M. P.

    1985-01-01

    Methanogenic enrichments catabolizing 13 mM phenylacetate or 4 mM phenol were established at 37°C, using a 10% inoculum from a municipal anaerobic digester. By using agar roll tubes of the basal medium plus 0.1% yeast extract-25 mM fumarate, a hydrogenotrophic lawn of Wolinella succinogenes and phenol or phenylacetate, strains P-2 and PA-1, respectively, were isolated in coculture with W. succinogenes. With the lawn deleted, PA-1 was isolated in pure culture. Strain P-2 is apparently a new species of anaerobic, motile, gram-negative, spindle-shaped, small rod that as yet has been grown only in coculture with W. succinogenes. It used phenol, hydrocinnamate, benzoate, and phenylacetate as energy sources. Product recovery by the coculture, per mole of phenol and 4.4 mol of fumarate used, included 2.03, 0.12, 0.08, and 3.23 mol, respectively, of acetate, propionate, butyrate, and succinate. Carbon recovery was 75% and H recovery was 80%, although CO2 and a few other possible products were not determined. That P-2 is an obligate proton-reducing acetogen and possible pathways for its degradation of phenol are discussed. Strain PA-1 is apparently a new species of anaerobic, motile, relatively small, gram-negative rod. It utilized compounds such as phenylacetate, hydrocinnamate, benzoate, phenol, resorcinol, gallate, 4-aminophenol, 2-aminobenzoate, pyruvate, Casamino Acids, and aspartate as energy sources in coculture with W. succinogenes. Per mole of phenylacetate and 1.44 mol of fumarate used, 1.04, 0.53, and 0.78 mol of acetate, propionate, and succinate, respectively, were recovered from the coculture. Only about 50% of the carbon and H were recovered. In coculture with Methanospirillum hungatei, 0.96 mol of acetate and 0.25 mol of methane were recovered per mol of pyruvate used; 0.90 mol of acetate and 0.33 mol of methane, per mol of fumarate used; 0.93 mol of acetate and 0.54 mol of methane, per mol of aspartate used; and 1.71 mol of acetate and 0.57 mol of methane

  15. Characterization of a periplasmic S1-like nuclease coded by the Mesorhizobium loti symbiosis island

    International Nuclear Information System (INIS)

    Pimkin, Maxim; Miller, C. Glenn; Blakesley, Lauryn; Oleykowski, Catherine A.; Kodali, Nagendra S.; Yeung, Anthony T.

    2006-01-01

    DNA sequences encoding hypothetical proteins homologous to S1 nuclease from Aspergillus oryzae are found in many organisms including fungi, plants, pathogenic bacteria, and eukaryotic parasites. One of these is the M1 nuclease of Mesorhizobium loti which we demonstrate herein to be an enzymatically active, soluble, and stable S1 homolog that lacks the extensive mannosyl-glycosylation found in eukaryotic S1 nuclease homologs. We have expressed the cloned M1 protein in M. loti and purified recombinant native M1 to near homogeneity and have also isolated a homogeneous M1 carboxy-terminal hexahistidine tag fusion protein. Mass spectrometry and N-terminal Edman degradation sequencing confirmed the protein identity. The enzymatic properties of the purified M1 nuclease are similar to those of S1. At acidic pH M1 is 25 times more active on single-stranded DNA than on double-stranded DNA and 3 times more active on single-stranded DNA than on single-stranded RNA. At neutral pH the RNase activity of M1 exceeds the DNase activity. M1 nicks supercoiled RF-I plasmid DNA and rapidly cuts the phosphodiester bond across from the nick in the resultant relaxed RF-II plasmid DNA. Therefore, M1 represents an active bacterial S1 homolog in spite of great sequence divergence. The biochemical characterization of M1 nuclease supports our sequence alignment that reveals the minimal 21 amino acid residues that are necessarily conserved for the structure and functions of this enzyme family. The ability of M1 to degrade RNA at neutral pH implies previously unappreciated roles of these nucleases in biological systems

  16. M1 transitions in the (sdg) boson model

    Science.gov (United States)

    Kuyucak, S.; Morrison, I.

    1988-03-01

    Using the {1}/{N} expansion technique we derive expressions for β→g, γ→g and γ→γ M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character.

  17. Symbiotic nature of the object M1-77

    International Nuclear Information System (INIS)

    Kondrt'eva, L.N.

    2004-01-01

    Many year spectral observations show, that the object M1-77 is the symbiotic system, which consists of a M-giant and a B-star. An emission spectra arises from an envelope, which was formed from a giant's extended atmosphere, and now is ionized by the hotter component. Some spectral changes were registered in M1-77: the forbidden lines intensities increase relatively to that of Hα. It is connected with the decrease of hydrogen emission. (author)

  18. Investigation of aflatoxin M1 degradation in milk

    Directory of Open Access Journals (Sweden)

    Smajlović Ahmed

    2012-01-01

    Full Text Available Aflatoxin M1 is a highly toxic 4-hydroxylated metabolite of aflatoxins B1 and B2. It is one of the most potent hepatocarcinogens, mutagens, teratogens and immunosuppressors. Feed is often contaminated with aflatoxigenic moulds and aflatoxins with a high possibility of contaminating milk and dairy products with aflatoxin M1. Samples of artificially contaminated milk were exposed to the effects of physical conditions (temperature of -18oC and for microwaves in a microwave oven, time (during the period from 1 to 12 months and a combination of the above mentioned conditions. Following this, levels of aflatoxin M1 degradation were established by using the ELISA method. An insignificant decrease in concentration of toxin was observed which indicates that a temperature of -18°C does not significantly influence the concentration of aflatoxin M1 in the artificially contaminated milk. At the same time, treatment of milk with microwaves in a microwave oven showed an insignificant influence on the percentage of aflatoxin M1 absorbance.

  19. Influence of extracellular zinc on M1 microglial activation.

    Science.gov (United States)

    Higashi, Youichirou; Aratake, Takaaki; Shimizu, Shogo; Shimizu, Takahiro; Nakamura, Kumiko; Tsuda, Masayuki; Yawata, Toshio; Ueba, Tetuya; Saito, Motoaki

    2017-02-27

    Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30-60 μM ZnCl 2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia-reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory.

  20. Safety assessment for the S-1 Spheromak

    International Nuclear Information System (INIS)

    Ellis, R. Jr.; Stencel, J.R.

    1984-02-01

    The S-1 machine is part of the Magnetic Fusion Program. The goal of the Magnetic Fusion Program is to develop and demonstrate the practical application of fusion. S-1 is an experimental device which will provide an essential link in the research effort aiming at the realization of fusion power

  1. M1 transitions between superdeformed states in 195Tl

    International Nuclear Information System (INIS)

    Zheng Xing; Xingqu Chen; Xiaochun Wang

    1996-01-01

    Using a triaxial-particle-rotor model, the quadrupole and dipole transition energies, kinematic and dynamic moments of inertia, electromagnetic transition probabilities and the relative intensity of the E2 γ-transitions are calculated for superdeformed bands in 195 Tl. A strong perturbation effect of rotation on transition energies and M1 and E2 transitions of superdeformed states is investigated. The total M1 transitions, enhanced by internal conversion, are expected to compete strongly with the E2 γ-ray at low spins in the superdeformed 195 Tl nucleus. (author)

  2. M1-transitions in the MIT bag model

    International Nuclear Information System (INIS)

    Hackman, R.H.; Deshpande, N.G.; Dicus, D.A.; Teplitz, V.L.

    1977-03-01

    In the MIT bag model, the M1-transitions of low lying hadrons are investigated. The following calculations are performed: 32 hadron masses are recomputed with a choice of bag parameters designed to give the correct values for the proton magnetic moment, μ/sub p/, and several masses, M/sub rho/ M/sub ω/ M/sub Δ/ M/sub Ω/, and M/sub D/; (2) eta, eta', eta/sub c/ mixing is computed in an untrustworthy approximation; and the widths for 38 M1-transitions are computed

  3. Genetic analysis of rice semidwarf mutant Tad-M-1

    International Nuclear Information System (INIS)

    Wang Naiyuan; Yang Rencui

    1995-01-01

    This paper dealed with the inheritance of the rice semidwarf of Tad-M-,a mutant line bred from traditional indica rice Variety Tadukan by radiation. The results indicated that semidwarf of Tad-M-1 was controlled by one pair of recessive gene, which was nonallelic to sd-1 gene of variety Aijiaonante and sd-g gene of variety Xinguiai and allelic to the semidwarf gene of Yunnan japonica variety Xueheaizao and Sichuan indica variety Yizila.The possible uses of Tad-M-1 in rice breeding was also discussed

  4. Limited similarity between plasmids encoding CTX-M-1 β-lactamase in Escherichia coli from humans, pigs, cattle, organic poultry layers and horses in Denmark

    DEFF Research Database (Denmark)

    Jakobsen, Lotte; Bortolaia, Valeria; Bielak, Eliza Maria

    2015-01-01

    in Denmark between 2006 and 2010. In total, 65 CTX-M-1-producing isolates from patients (n=22), pigs (n=21), cattle (n=4), organic poultry layers (n=3) and horses (n=15) were typed by pulsed-field gel electrophoresis (PFGE). Plasmids harbouring blaCTX-M-1 were characterised by S1 PFGE, PCR-based replicon...

  5. Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons.

    Science.gov (United States)

    Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

    2017-01-06

    The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals.

  6. assessing aflatoxin m1 levels among lactating mothers' in damaturu ...

    African Journals Online (AJOL)

    userpc

    1Department of Microbiology Ahmadu Bello University Zaria, Kaduna State. ... Aflatoxin M1 (AFM1) is a biomarker of aflatoxin B1 exposure in breast milk, a possible risk factor for infant early ..... Mycotoxins in food and feed: present status and ...

  7. Analytic theory of the nonlinear M = 1 tearing mode

    International Nuclear Information System (INIS)

    Hazeltine, R.D.; Meiss, J.D.; Morrison, P.J.

    1985-09-01

    Numerical studies show that the m = 1 tearing mode continues to grow exponentially well into the nonlinear regime, in contrast with the slow, ''Rutherford,'' growth of m > 1 modes. We present a single helicity calculation which generalizes that of Rutherford to the case when the constant-psi approximation is invalid. As in that theory, the parallel current becomes an approximate flux function when the island size, W, exceeds the linear tearing layer width. However for the m = 1 mode, W becomes proportional to deltaB, rather than (deltaB)/sup 1/2/ above this critical amplitude. This implies that the convective nonlinearity in Ohm's law, which couples the m = 0 component to the m = 1 component, dominates the resistive diffusion term. The balance between the inductive electric field and this convective nonlinearity results in exponential growth. Assuming the form of the perturbed fields to be like that of the linear mode, we find that the growth occurs at 71% of the linear rate

  8. Theory of the m=1 kink mode in toroidal plasmas

    International Nuclear Information System (INIS)

    Blank, J.H. de.

    1990-01-01

    The work in this thesis addresses the stability problems arising in tokamak experiments. In part I of this thesis the internal m=1 kink instability in tokamak plasmas is considered within the confines of ideal magnetohydrodynamics (ideal MHD), in which model the pressure is considered to be isotropic, while state is assumed. Because irreversible processes are disregarded, there is an energy principle. By extremizing the energy associated with infinitesimal perturbations of the plasma, a normal mode is obtained. The m=n=1 mode is resonant at the q=1 surface, and therefore, equilibria with a broad region where q#approx = # 1 are expected to be particularly unstable. The m=1 instability is computed for these q profiles. In Part II of this thesis, the internal m=1 kink instability is considered in a stationary rotating tokamak plasma, in which the particle velocity distribution is allowed to be non-thermal. In a tokamak plasma that is intensely heated by neutron beams or radiofrequent waves, these features, which cannot be described with ideal MHD, may become important, especially in the cases with high m=1 growth rates found in Part I. The energy principle of a generalized fluid theory is applied in these cases, without specifying the equation of state of the plasma. Therefore the resulting energy functional for the m=1 mode is incomplete and not direct applicable, however, the result makes clear that a kinetic description of the plasma is required only to a first approximation, and can therefore be applied analytically. The guiding center approximation is applied, which neglects finite gyroradius effects and collisions. Application of the dispersion relation, that is obtained from kinetic theory, shows that compared to the ideal MHD case, growth rates are strongly reduced due to Landau damping while the stability boundaries are not changed. (author). 72 refs.; 11 figs

  9. The Global S$_1$ Ocean Tide

    Science.gov (United States)

    Ray, Richard D.; Egbert, G. D.

    2003-01-01

    The small S$_1$ ocean tide is caused primarily by diurnal atmospheric pressure loading. Its excitation is therefore unlike any other diurnal tide. The global character of $S-1$ is here determined by numerical modeling and by analysis of Topex/Poseidon satellite altimeter data. The two approaches yield reasonably consistent results, and large ( $ greater than $l\\cm) amplitudes in several regions are further confirmed by comparison with coastal tide gauges. Notwithstanding their excitation differences, S$-1$ and other diurnal tides are found to share several common features, such as relatively large amplitudes in the Arabian Sea, the Sea of Okhotsk, and the Gulf of Alaska. The most noticeable difference is the lack of an S$-1$ Antarctic Kelvin wave. These similarities and differences can be explained in terms of the coherences between near-diurnal oceanic normal modes and the underlying tidal forcings. While gravitational diurnal tidal forces excite primarily a 28-hour Antarctic-Pacific mode, the S$_1$ air tide excites several other near-diurnal modes, none of which has large amplitudes near Antarctica.

  10. Quadrupole decay strength of the M1 scissors mode

    Science.gov (United States)

    Beck, T.; Beller, J.; Derya, V.; Gayer, U.; Isaak, J.; Löher, B.; Mertes, L.; Pietralla, N.; Ries, P.; Romig, C.; Savran, D.; Scheck, M.; Tornow, W.; Weller, H. R.; Werner, V.; Zweidinger, M.

    2015-10-01

    The E2/M1 multipole mixing ratio δ1→2 of the 1sc +→21+ transition of Gd was determined using results from high-statistics photon scattering. This provides a possibility for a new approach on the search of Jsc + members of the rotational band built on the scissors mode. By application of Alaga's rule, which is justifiable as 156Gd is a well-deformed rotor with good K quantum number, a transition strength of B (E 2 ;2sc +→01+)=0.034 (13 ) W.u. is estimated.

  11. Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

    Directory of Open Access Journals (Sweden)

    Meyyammai Swaminathan

    2014-06-01

    Full Text Available Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM, comparable to that of acetylcholine (Ki = 59 µM. Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

  12. PEMBUATAN PROGRAM INTERFACE UNTUK PENGONTROLAN RV-M1

    Directory of Open Access Journals (Sweden)

    Endra Endra

    2007-10-01

    Full Text Available Article explores the making of interface of RV-M1 hand robot control that replaced the cosiprog program,a program that is able to help student in Mecatronica-1 Practice, and able to control the hand robot by localnetwork by two user or more. The used methods were literature study, and field study, that is design method. Theresearch result are control of hand robot on X,Y,Z axis and point to point, the use of local network to control thehand robot, save certain position, and use several user to control the robot.Keywords: interface program, robot, local network

  13. S1 photocathode image converter tubes

    International Nuclear Information System (INIS)

    Gex, F.; Bauduin, P.; Hammes, C.; Horville, P.; Fleurot, N.; Nail, M.

    1984-08-01

    The S1 photocathode was the first cathode available for practical applications; in spite of this its mechanism of photoemission has remained enigmatic. S1 semi-transparent photocathode is the only one that can be used to study the 1.06 μm neodynium laser pulses of less than 10 ps duration. This recent application and the difficulties to manufacture stable and sensitive S1 photocathode at this wavelength gave rise to new researches which aim is to have a better knowledge of this structure. We first review the recent results obtained at the Paris Observatory (research sponsored by the CEA) and report on the lifetime in the 1-μm range of the photocathodes processed four years ago. In a second part we will try to analyse the researches which have been investigated during these last ten years in different laboratories to determine the role of the main constituants (silver particles, Co oxydes) and their contributions to photoemission in order to improve the sensitivity and the stability of S1 photocathode

  14. E1 and M1 strength functions at low energy

    Science.gov (United States)

    Schwengner, Ronald; Massarczyk, Ralph; Bemmerer, Daniel; Beyer, Roland; Junghans, Arnd R.; Kögler, Toni; Rusev, Gencho; Tonchev, Anton P.; Tornow, Werner; Wagner, Andreas

    2017-09-01

    We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  15. E1 and M1 strength functions at low energy

    Directory of Open Access Journals (Sweden)

    Schwengner Ronald

    2017-01-01

    Full Text Available We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  16. A S=1 underscreened Kondo lattice model

    International Nuclear Information System (INIS)

    Perkins, N.B.; Nunez-Regueiro, M.D.; Iglesias, J.R.; Coqblin, B.

    2006-01-01

    The underscreened Kondo lattice model presented here includes both an intra-site Kondo exchange interaction J K between the conduction band and localized 5f electrons described by S=1 spins, and an inter-site exchange f-f interaction J H . We write both localized and itinerant spins in a Fermionic representation, and then use a mean-field approximation. We obtain a coexistence of Kondo effect and magnetism which can account for the behavior of some Uranium compounds

  17. Presence of moulds and aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Janković Vesna V.

    2009-01-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk or dairy products as a direct result of the cattle's ingestion of feed contaminated with aflatoxin B1 (AFB1. This study comprises mycological and mycotoxicological investigations of 23 milk samples (raw, infant food, pasteurized, whey and yoghurt. The mycological testing showed dominant presence of genus Geotrichum. G. candidum was found in 9 samples, with the highest contamination in the raw milk samples. The contamination level of AM1 is defined by using direct competitive enzyme- -linked immunosorbent assay (ELISA. AFM1 was found in 9 samples. AFM1 levels were lower than the recommended limits. However, as AFM1 is considered a probable human carcinogen (2B type, it is necessary to achieve a low level of AFM1 in milk. Therefore, cows' feed samples from various cowsheds are supposed to be evaluated routinely for aflatoxin, and kept away from fungal contamination as much as possible.

  18. Interference effects in Moessbauer spectra of M1-transitions

    International Nuclear Information System (INIS)

    Peregudov, V.N.

    1980-01-01

    The purpose of the study is the calculation of interference effects in Moessbauer spectra of the (γ, e) reaction. Two channels of the inelastic (γ, e) reaction are considered: resonance gamma radiation absorption by nucleus accompanied by internal conversion and photo absorption by atomic electrons. The case of M1 nuclear transition multipolarity is considered. The expression for angular dependence coefficients of interference member is obtained. General expression for (γ, e) reaction cross section is obtained in a long-wave approximation for the case when the specimen is placed in longitudinal magnetic field involving superfine nuclear level splitting. The results of disperse amplitudes calculation for 93 Kr, 119 Sn, 129 I, 149 Sm, 151 Eu, 169 Tm, 183 W, 193 Ir, 197 Au nuclei are verified. The calculations show that maximum interference effect in the (γ, e) reaction should be expected for 169 Tm isotope [ru

  19. Excitation of M1 resonances by medium energy protons

    International Nuclear Information System (INIS)

    Crawley, G.M.; Djalali, C.; Marty, N.

    1983-01-01

    The results of 201 MeV (p,p') studies of ΔL=0 spin-flip transitions at very forward angles are discussed. The reasons for making comparisons between (p,p'), (p,n) and electromagnetic measurements of M1 transitions are outlined. After presenting some of the experimental and theoretical uncertainties, a summary of the results on the Zr isotopes plus other nuclei to mass 140 is given. Results from 48 Ca, the N=28 nuclei 50 Ti, 51 V, 52 Cr and 54 Fe are discussed and compared with (p,n) and electromagnetic measurements. In the Ni isotopes, the T 0 and T 0 +1 components of the 1 + spin-flips transition were observed both in (p,p') and in (p,n) reactions

  20. Thai Research Reactor (TRR-1/M1) Neutron Beam Measurements

    International Nuclear Information System (INIS)

    Ratanatongchai, Wichian

    2009-07-01

    Full text: Neutron beam tube of neutron radiography facility at Thai Research Reactor (TRR-1/M1) Thailand Institute of Nuclear Technology (public organization) is a divergent beam. The rectangular open-end of the beam tube is 16 cm x 17 cm while the inner-end is closed to the reactor core. The neutron beam size was measured using 20 cm x 40 cm neutron imaging plate. The measurement at the position 100 cm from the end of the collimator has shown that the beam size was 18.2 cm x 19.0 cm. Gamma ray in neutron the beam was also measured by the identical position using industrial X ray film. The area of gamma ray was 27.8 cm x 31.1 cm with the highest intensity found to be along the neutron beam circumference

  1. Aflatoxin M1 Contamination in Ice-Cream

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-06-01

    Full Text Available Aflatoxin M1 (AFM1 is the hydroxylated metabolite of aflatoxin B1 (AFB1 that it can be found in milk and dairy products. In this study, ELISA (Enzyme Linked Immunosorbent Assay technique was used for detection of AFM1 in ice-cream in Guilan province (Northern Iran. A total of 90 ice-cream samples was randomly obtained from different supermarkets. In 62 of the 90 ice-cream samples examined (68.88%, the presence of AFM1 was detected in concentrations between 8.4 -147.7 ng/l. The mean level of AFM1 in positive samples was 40.36 ng/l. AFM1 levels in 11 samples (12.22% were higher than the maximum tolerance limit (50 ng/l accepted by ISIRI, European Community and Codex Alimentarius.

  2. Physics at 1034 cm-2 s-1

    International Nuclear Information System (INIS)

    Diebold, R.; Wagner, R.

    1984-01-01

    Most of the detector studies at Snowmass-84 have rightfully concentrated on detailed studies of individual interactions - their rates, signatures, and backgrounds. Depending on the physics and the detector components, there seems to be agreement that general-purpose detectors will likely be able to accept luminosities up to 10 32-33 cm -2 s -1 . The purpose of this paper is to show how the physics reach of the SSC is extended by going to a luminosity of 10 34 cm -2 s -1 , to take a first look at what sort of detector could be used at this luminosity, and to discuss how one might trigger on interesting events in the presence of many overlapping minimum bias events. We will assume that the SSC turns on at 10 31 or 10 32 cm -2 s -1 , with an increase of luminosity to 10 33 over a period of a few years as the machine and detectors become better understood. Thus, the lower mass scale will have been explored and we can set our thresholds high when running 10 34

  3. Collider baseline parameters: Milestone M1.5

    CERN Document Server

    Schulte, Daniel

    2016-01-01

    The deliverable D1.1 provided a preliminary specification of the layout and target operation parameters for the FCC-hh hadron collider concept. It serves as the basis for the studies in all work packages. Tis milestone summarises the outcome of the first studies of this design. The goal of the FCC hadron collider is to provide proton-proton collisions at a centre-of-mass energy of 100 TeV. The machine is compatible with ion beam operation. Assuming a nominal dipole field of 16 T, such a machine is based on a perimeter of 100 km. The machine is designed to accommodate two main proton experiments that are operated simultaneously. The machine delivers a peak luminosity of 5-30 x 1034 cm-2s-1. The layout allows for two additional special-purpose experiments.

  4. Reduction of Aflatoxin M1 in Milk Using Kefir Starter

    Directory of Open Access Journals (Sweden)

    Siavash Kamyar

    2017-11-01

    Full Text Available Background: Mycotoxins naturally occur in foods. Aflatoxins can cause serious health problems in consumers. Nowadays, biological detoxification method is considered to decrease the aflatoxins level in foods. The aim of this study was to evaluate the effect of kefir starter microorganisms to decrease the aflatoxin M1 (AFM1 levels in milk. Methods: The study was carried out at Shabestar branch, Islamic Azad University in 2016. AFM1 at three levels 150, 200 and 250 ng/L was added to milk samples. Then a pool of lactic acid bacteria (LAB, yeasts and full kefir starter culture was added to milk samples. After cool storage of samples in 4 °C for 7 d, all samples were collected and the level of AFM1 determined by HPLC method. All samples were prepared in triplicate. Results: The highest reduction percentage of AFM1 was observed in yeast (65.33%-68.89% and LAB pool (65%. Samples with full kefir starter showed the reduction percent range of 11.67-34.66% that was lower in compare with other treatment groups. Conclusion: These findings support the ability of LAB and yeasts to bind to aflatoxins in foods. Kefir drink in countries with high contamination by AFM1 in milk can be a safe dairy product choice for consumers.

  5. Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

    Science.gov (United States)

    Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

    2014-07-01

    The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. The S-1 Spheromak Control System

    International Nuclear Information System (INIS)

    Mathe, P.; Mika, R.; Oliaro, G.

    1983-01-01

    The use of a CAMAC based DEC LSI-11/23 microcomputer to perform all control functions for the S-1 Spheromak is described. The system monitors and controls the three coil systems, Toroidal, Poloidal, and Equilibrium field coils and their associated power sources, the water cooling system, the personnel and machine safety system, the machine and diagnostic timing system and the control room display and operator interface. Future requirements include control of the vacuum system, the gas injection system and interface to the PPPL Data Acquisition System DEC10. The computer is connected to five remotely located CAMAC crates by a fiber-optic serial highway operating at five megahertz. These crates contain interface modules required to control the S-1 experiment. These modules include: D/A and A/D converters, fast transient digitizers, timing modules, temperature sensing modules, CRT alphanumeric display drivers, watchdog timers, and relay and TTL parallel I/O ports. The computer itself resides in crate number0 and consists of an LSI-11/23 with hardware floating post processor, memory management, 256K bytes of memory, four RS-232 serial ports and a 30 megabyte hard disk with a one megabyte floppy disk backup. The majority of software is written in FORTRAN with a few speed critical programs written in PDP-11 MACRO assembly language. The software simulates a sequential state machine which allows easily changeable logic since all logic is represented by standard Boolean Fortran statements. The RSX-11/m operating system allows multiple tasks to be active simultaneously. This provides computing time for operator interactions, editing of critical machine parameters, data analysis and transmission of data to other computers while still maintaining the scan activity which constantly monitors machine parameters

  7. High-definition transcranial direct-current stimulation of the right M1 further facilitates left M1 excitability during crossed facilitation.

    Science.gov (United States)

    Cabibel, Vincent; Muthalib, Makii; Teo, Wei-Peng; Perrey, Stephane

    2018-04-01

    The crossed-facilitation (CF) effect refers to when motor-evoked potentials (MEPs) evoked in the relaxed muscles of one arm are facilitated by contraction of the opposite arm. The aim of this study was to determine whether high-definition transcranial direct-current stimulation (HD-tDCS) applied to the right primary motor cortex (M1) controlling the left contracting arm [50% maximum voluntary isometric contraction (MVIC)] would further facilitate CF toward the relaxed right arm. Seventeen healthy right-handed subjects participated in an anodal and cathodal or sham HD-tDCS session of the right M1 (2 mA for 20 min) separated by at least 48 h. Single-pulse transcranial magnetic stimulation (TMS) was used to elicit MEPs and cortical silent periods (CSPs) from the left M1 at baseline and 10 min into and after right M1 HD-tDCS. At baseline, compared with resting, CF (i.e., right arm resting, left arm 50% MVIC) increased left M1 MEP amplitudes (+97%) and decreased CSPs (-11%). The main novel finding was that right M1 HD-tDCS further increased left M1 excitability (+28.3%) and inhibition (+21%) from baseline levels during CF of the left M1, with no difference between anodal and cathodal HD-tDCS sessions. No modulation of CSP or MEP was observed during sham HD-tDCS sessions. Our findings suggest that CF of the left M1 combined with right M1 anodal or cathodal HD-tDCS further facilitated interhemispheric interactions during CF from the right M1 (contracting left arm) toward the left M1 (relaxed right arm), with effects on both excitatory and inhibitory processing. NEW & NOTEWORTHY This study shows modulation of the nonstimulated left M1 by right M1 HD-tDCS combined with crossed facilitation, which was probably achieved through modulation of interhemispheric interactions.

  8. Random Walks on Homeo( S 1)

    Science.gov (United States)

    Malicet, Dominique

    2017-12-01

    In this paper, we study random walks {g_n=f_{n-1}\\ldots f_0} on the group Homeo ( S 1) of the homeomorphisms of the circle, where the homeomorphisms f k are chosen randomly, independently, with respect to a same probability measure {ν}. We prove that under the only condition that there is no probability measure invariant by {ν}-almost every homeomorphism, the random walk almost surely contracts small intervals. It generalizes what has been known on this subject until now, since various conditions on {ν} were imposed in order to get the phenomenon of contractions. Moreover, we obtain the surprising fact that the rate of contraction is exponential, even in the lack of assumptions of smoothness on the f k 's. We deduce various dynamical consequences on the random walk ( g n ): finiteness of ergodic stationary measures, distribution of the trajectories, asymptotic law of the evaluations, etc. The proof of the main result is based on a modification of the Ávila-Viana's invariance principle, working for continuous cocycles on a space fibred in circles.

  9. Global magnetic fluctuations in S-1 spheromak plasmas and relaxation toward a minimum-energy state

    International Nuclear Information System (INIS)

    Janos, A.; Hart, G.W.; Yamada, M.

    1986-01-01

    Globally coherent modes have been observed during formation in the S-1 Spheromak plasma. These modes play an important role in flux conversion and plasma relaxation toward a minimum-energy state. A significant finding is the temporal progression through the n = 5, 4, 3, 2; m = 1 mode sequence as q rises through rational fractions m/n. Peak amplitudes of the modes relative to the unperturbed field are typically less than 5%, while amplitudes as high as 20% have been observed

  10. Effect of closed shells on the multipole mixing parameter δ(E2/M1)

    International Nuclear Information System (INIS)

    Morozov, V.A.

    1992-01-01

    The behavior of the magnitude and sign of the mixing parameter δ(E2/M1) in even-even nuclei has been studied in a number of papers. The most extensive data has been given for transitions of the type 3 γ + , 2 γ + , 2 β + →2 g + . The data on δ are relatively scarce for mixed transitions in odd nuclei with magic or semimagic cores. However, certain conclusions can be drawn about the behavior of δ in transitions in odd nuclei near magic numbers, and also in transitions in even-even nuclei when passing through quasishells: (1) the absolute value of the reduced mixing parameter in transitions between particle and cluster-vibrational states in odd nuclei decreases as a closed shell is approached; (2) δ has the same sign for transitions between particle and cluster-vibrational levels in nuclei with Z=83 and 85 and N=83, 85, and 87; (3) in odd nuclei the sign of δ is positive for transitions between positive-parity states s 1/2 -d 3/2 in Cd, Sm, and Tl isotopes and is negative for transitions between negative-parity states f 7/2 π and h 9/2 π in Sm, Gd, Bi, and At isotopes, independently of whether these transitions are neutron or proton transitions; (4) the removal of ±2 nucleons in an even shell from a magic core (and in certain nuclei a larger number of pairs of nucleons) does not lead to a change in sign of δ in transitions producing an odd nucleus; (5) the closure of quasishells at N=96 and 104 in even-even nuclei is associated with an increase in the absolute value of δ(E2/M1)/E γ , but the sign of δ does not change

  11. Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis

    International Nuclear Information System (INIS)

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-01-01

    Highlights: ► The effect of a newly developed S1P 1 -selective antagonist on angiogenic responses. ► S1P 1 is a critical component of VEGF-related angiogenic responses. ► S1P 1 -selective antagonist showed in vitro activity to inhibit angiogenesis. ► S1P 1 -selective antagonist showed in vivo activity to inhibit angiogenesis. ► The efficacy of S1P 1 -selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P 1 ) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P 1 and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P 1 -selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P 1 antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P 1 is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  12. Supplementary data Fig. S1 Fig. S1. FE-SEM images of the ...

    Indian Academy of Sciences (India)

    微软用户

    Fig. S3. Cycling behavior of V2O5 nanomaterials recorded by CV at 20 mV·s-1 scan rate. Page 4. 4. Fig. S4. Fig. S4. Cycling behavior of V2O5 nanomaterials electrodes of galvanostatic charge and discharge profiles recorded by GCD at a current density of 1 A·g-1. Page 5. 5. Fig. S5. Fig. S5. Cycling behavior of V2O5 ...

  13. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling.

    Science.gov (United States)

    Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

    2015-01-01

    Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  14. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  15. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Shoichi Fukui

    2018-01-01

    Full Text Available ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA.MethodsPeripheral blood mononuclear cells (PBMCs were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55% were anticitrullinated protein antibody (ACPA positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range. There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001. The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028 and significantly greater numbers of OCs in vitro (p = 0.005 than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

  16. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization[S

    Science.gov (United States)

    Lee, Mi-Hye; Appleton, Kathryn M.; El-Shewy, Hesham M.; Sorci-Thomas, Mary G.; Thomas, Michael J.; Lopes-Virella, Maria F.; Luttrell, Louis M.; Hammad, Samar M.; Klein, Richard L.

    2017-01-01

    HDL normally transports about 50–70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration. PMID:27881715

  17. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.

    Science.gov (United States)

    Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Sorci-Thomas, Mary G; Thomas, Michael J; Lopes-Virella, Maria F; Luttrell, Louis M; Hammad, Samar M; Klein, Richard L

    2017-02-01

    HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

  18. Chemical and genetic tools to explore S1P biology.

    Science.gov (United States)

    Cahalan, Stuart M

    2014-01-01

    The zwitterionic lysophospholipid Sphingosine 1-Phosphate (S1P) is a pleiotropic mediator of physiology and pathology. The synthesis, transport, and degradation of S1P are tightly regulated to ensure that S1P is present in the proper concentrations in the proper location. The binding of S1P to five G protein-coupled S1P receptors regulates many physiological systems, particularly the immune and vascular systems. Our understanding of the functions of S1P has been aided by the tractability of the system to both chemical and genetic manipulation. Chemical modulators have been generated to affect most of the known components of S1P biology, including agonists of S1P receptors and inhibitors of enzymes regulating S1P production and degradation. Genetic knockouts and manipulations have been similarly engineered to disrupt the functions of individual S1P receptors or enzymes involved in S1P metabolism. This chapter will focus on the development and utilization of these chemical and genetic tools to explore the complex biology surrounding S1P and its receptors, with particular attention paid to the in vivo findings that these tools have allowed for.

  19. Sphingosine-1-Phosphate (S1P) Lyase Inhibition Causes Increased Cardiac S1P Levels and Bradycardia in Rats.

    Science.gov (United States)

    Harris, Christopher M; Mittelstadt, Scott; Banfor, Patricia; Bousquet, Peter; Duignan, David B; Gintant, Gary; Hart, Michelle; Kim, Youngjae; Segreti, Jason

    2016-10-01

    Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function. The S1PL inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile was used to determine the relationship in rats between drug concentration, S1P levels in select tissues, and circulating lymphocytes. Repeated oral doses of the S1PL inhibitor fully depleted circulating lymphocytes after 3 to 4 days of treatment in rats. Full lymphopenia corresponded to increased levels of S1P of 100- to 1000-fold in lymph nodes, 3-fold in blood (but with no change in plasma), and 9-fold in cardiac tissue. Repeated oral dosing of the S1PL inhibitor in telemeterized, conscious rats resulted in significant bradycardia within 48 hours of drug treatment, comparable in magnitude to the bradycardia induced by 3 mg/kg fingolimod. These results suggest that S1PL inhibition modulates cardiac function and does not provide immune suppression with an improved cardiovascular safety profile over fingolimod in rats. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Modification of barley powdery mildew resistance controlled by the gene M1-a212

    International Nuclear Information System (INIS)

    Torp, J.; Joergensen, J.H.

    1989-01-01

    Full text: The barley line Sultan 5 carries resistance gene M1-a12. Seeds were treated with EMS or NaN 3 . Among 10381 M 1 -spike progenies inoculated with M1-a12 a-virulent isolates of Erysiphe graminis, 25 segregated for less resistant infection type. Among 10 mutants analyzed, 9 had mutant allels of M1-a12 and one had a recessive mutant gene in a different locus acting as a ''suppressor'' of M1-a12. (author)

  1. An S=1/2 impurity spin in the antiferromagnetic S=1 bond-alternating chain

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Nobuyuki [Gifu National College of Technology, Dept. of Fundamental Science, Gifu (Japan); Hikihara, Toshiya [National Inst. for Materials Science, Computational Material Research Group, Tsukuba, Ibaraki (Japan); Kaburagi, Makoto [Kobe Univ., Faculty of Cross-Cultural Studies, Kobe, Hyogo (Japan); Tonegawa, Takashi [Fukui Univ. of Technology, Dept. of Mechanical Engineering, Fukui (Japan)

    2002-06-01

    We explore low-lying excited states as well as the ground state of the antiferromagnetic S=1 bond-alternating chain with an S=1/2 impurity spin. For the case where the ground-state phase of the host system is the Haldane phase, we review a numerical analysis of the electron-spin-resonance experimental results on the NENP: Cu{sup 2+} system. For the case where the ground-state phase of the host system is the dimer phase, on the other hand, we calculate, using the exact-diagonalization method, the dependences of the energy differences between the ground and low-lying excited states upon both the impurity-host exchange constant and the single-ion-type anisotropy constant, and also calculate, using the density-matrix renormalization-group method, the external-magnetic-field dependence of the impurity-spin magnetization in the ground state. In these calculations, we keep the NTENP: Cu{sup 2+} system in mind to choose the value of the bond-alternation parameter. We find that a few low-lying excited states which are expected from the valence-bond-solid picture appear as the impurity states in the energy gap between the singlet ground and triplet first-excited states (the dimer gap). Furthermore, for certain values of the above constants, we find that the impurity-spin magnetization shows a clear jump at a magnetic field which is in the dimer-gap region or in the magnetization-plateau region of the host system, and also that the impurity-spin magnetization has a magnetic-field region where it decreases as a function of the magnetic field. (author)

  2. Shaping the landscape: Metabolic regulation of S1P gradients

    Science.gov (United States)

    Olivera, Ana; Allende, Maria Laura; Proia, Richard L.

    2012-01-01

    Sphingosine-1-phosphate (S1P) is a lipid that functions as a metabolic intermediate and a cellular signaling molecule. These roles are integrated when compartments with differing extracellular S1P concentrations are formed that serve to regulate functions within the immune and vascular systems, as well as during pathologic conditions. Gradients of S1P concentration are achieved by the organization of cells with specialized expression of S1P metabolic pathways within tissues. S1P concentration gradients underpin the ability of S1P signaling to regulate in vivo physiology. This review will discuss the mechanisms that are necessary for the formation and maintenance of S1P gradients, with the aim of understanding how a simple lipid controls complex physiology. PMID:22735358

  3. Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.

    Science.gov (United States)

    Tsai, Hsing-Chuan; Han, May H

    2016-07-01

    Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.

  4. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling

    Directory of Open Access Journals (Sweden)

    Eunjung Moon

    2015-01-01

    Full Text Available Initial and recurrent stroke produces central nervous system (CNS damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  5. Structural basis for the inhibition of M1 family aminopeptidases by the natural product actinonin: Crystal structure in complex with E. coli aminopeptidase N.

    Science.gov (United States)

    Ganji, Roopa Jones; Reddi, Ravikumar; Gumpena, Rajesh; Marapaka, Anil Kumar; Arya, Tarun; Sankoju, Priyanka; Bhukya, Supriya; Addlagatta, Anthony

    2015-05-01

    Actinonin is a pseudotripeptide that displays a high affinity towards metalloproteases including peptide deformylases (PDFs) and M1 family aminopeptidases. PDF and M1 family aminopeptidases belong to thermolysin-metzincin superfamily. One of the major differences in terms of substrate binding pockets between these families is presence (in M1 aminopeptidases) or absence (in PDFs) of an S1 substrate pocket. The binding mode of actinonin to PDFs has been established previously; however, it is not clear how the actinonin, without a P1 residue, would bind to the M1 aminopeptidases. Here we describe the crystal structure of Escherichia coli aminopeptidase N (ePepN), a model protein of the M1 family aminopeptidases in complex with actinonin. For comparison we have also determined the structure of ePepN in complex with a well-known tetrapeptide inhibitor, amastatin. From the comparison of the actinonin and amastatin ePepN complexes, it is clear that the P1 residue is not critical as long as strong metal chelating head groups, like hydroxamic acid or α-hydroxy ketone, are present. Results from this study will be useful for the design of selective and efficient hydroxamate inhibitors against M1 family aminopeptidases. © 2015 The Protein Society.

  6. Characterization of IncN plasmids carrying blaCTX-M-1 and qnr genes in Escherichia coli and Salmonella from animals, the environment and humans

    DEFF Research Database (Denmark)

    Dolejska, Monika; Villa, Laura; Hasman, Henrik

    2013-01-01

    were compared using restriction fragment length polymorphism (RFLP), plasmid multilocus sequence typing (pMLST) and hybridization with repN, qnrS1, qnrB19 or blaCTX-M-1 probes. Plasmids pKT58A and pHHA45 were sequenced using the 454-Genome Sequencer FLX platform on a library constructed from plasmid...... DNA purified from the respective E. coli transformants.Results Three types of IncN plasmids carrying blaCTX-M-1, qnrS1 and qnrB19 genes were identified in strains isolated from the Czech Republic, Poland, Slovakia, Denmark, Italy and the Netherlands, corresponding to pMLST sequence type (ST) 1, ST3...

  7. Behavior of 14C aflatoxin M1 during camembert cheese making.

    Science.gov (United States)

    Fremy, J M; Roiland, J C; Gaymard, A

    1990-01-01

    Camembert cheeses are made from raw milk spiked with aflatoxin M1. Three aflatoxin M1 levels (7.5 micrograms/L, 3 micrograms/L, and 0.3 micrograms/L) are used. In curds 35.6, 47.1, and 57.7% of aflatoxin M1, respectively, are recovered, and in wheys 64.4, 52.9, and 42.3%, respectively, are recovered. During the first 15 days of storage, the aflatoxin M1 content of different cheeses decreases 25, 55, and 75%, respectively. A similar experiment is made with milk contaminated with 14C labeled aflatoxin M1. The same results are obtained, except for the behavior of aflatoxin M1 in cheese; the same 14C activity is recovered during storage for 30 days.

  8. Sphingosine-1-Phosphate (S1P) Signaling in Neural Progenitors.

    Science.gov (United States)

    Callihan, Phillip; Alqinyah, Mohammed; Hooks, Shelley B

    2018-01-01

    Sphingosine-1-phosphate (S1P) and its receptors are important in nervous system development. Reliable in vitro human model systems are needed to further define specific roles for S1P signaling in neural development. We have described S1P-regulated signaling, survival, and differentiation in a human embryonic stem cell-derived neuroepithelial progenitor cell line (hNP1) that expresses functional S1P receptors. These cells can be further differentiated to a neuronal cell type and therefore represent a good model system to study the role of S1P signaling in human neural development. The following sections describe in detail the culture and differentiation of hNP1 cells and two assays to measure S1P signaling in these cells.

  9. Representations of Nets of C*-Algebras over S 1

    Science.gov (United States)

    Ruzzi, Giuseppe; Vasselli, Ezio

    2012-11-01

    In recent times a new kind of representations has been used to describe superselection sectors of the observable net over a curved spacetime, taking into account the effects of the fundamental group of the spacetime. Using this notion of representation, we prove that any net of C*-algebras over S 1 admits faithful representations, and when the net is covariant under Diff( S 1), it admits representations covariant under any amenable subgroup of Diff( S 1).

  10. FoxM1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma by targeting Snai1

    OpenAIRE

    Yu, Chun-Peng; Yu, Shui; Shi, Lei; Wang, Song; Li, Zi-Xiang; Wang, Yan-Hua; Sun, Cheng-Jian; Liang, Jun

    2017-01-01

    Forkhead box protein M1 (FoxM1) is aberrantly expressed in several types of human malignancy, and serves an important role in tumor metastasis. Epithelial-mesenchymal transition (EMT) of cancer cells has been associated cancer metastasis; however, the implication of FoxM1 in EMT and its putative roles in the regulation of cancer metastasis remain to be elucidated. In the present study, the expression of FoxM1, Snai1 and E-cadherin in hepatocellular carcinoma (HCC) cell lines with various meta...

  11. Exit Strategies: S1P Signaling and T Cell Migration.

    Science.gov (United States)

    Baeyens, Audrey; Fang, Victoria; Chen, Cynthia; Schwab, Susan R

    2015-12-01

    Whereas the role of sphingosine 1-phosphate receptor 1 (S1PR1) in T cell egress and the regulation of S1P gradients between lymphoid organs and circulatory fluids in homeostasis are increasingly well understood, much remains to be learned about S1P signaling and distribution during an immune response. Recent data suggest that the role of S1PR1 in directing cells from tissues into circulatory fluids is reprised again and again, particularly in guiding activated T cells from non-lymphoid tissues into lymphatics. Conversely, S1P receptor 2 (S1PR2), which antagonizes migration towards chemokines, confines cells within tissues. Here we review the current understanding of the roles of S1P signaling in activated T cell migration. In this context, we outline open questions, particularly regarding the shape of S1P gradients in different tissues in homeostasis and inflammation, and discuss recent strategies to measure S1P. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. S1P and the birth of platelets

    Science.gov (United States)

    Galvani, Sylvain; Rafii, Shahin; Nachman, Ralph

    2012-01-01

    Recent work has highlighted the multitude of biological functions of sphingosine 1-phosphate (S1P), which include roles in hematopoietic cell trafficking, organization of immune organs, vascular development, and neuroinflammation. Indeed, a functional antagonist of S1P1 receptor, FTY720/Gilenya, has entered the clinic as a novel therapeutic for multiple sclerosis. In this issue of the JEM, Zhang et al. highlight yet another function of this lipid mediator: thrombopoiesis. The S1P1 receptor is required for the growth of proplatelet strings in the bloodstream and the shedding of platelets into the circulation. Notably, the sharp gradient of S1P between blood and the interstitial fluids seems to be essential to ensure the production of platelets, and S1P appears to cooperate with the CXCL12–CXCR4 axis. Pharmacologic modulation of the S1P1 receptor altered circulating platelet numbers acutely, suggesting a potential therapeutic strategy for controlling thrombocytopenic states. However, the S1P4 receptor may also regulate thrombopoiesis during stress-induced accelerated platelet production. This work reveals a novel physiological action of the S1P/S1P1 duet that could potentially be harnessed for clinical translation. PMID:23166370

  13. Mitochondrial lineage M1 traces an early human backflow to Africa.

    Science.gov (United States)

    González, Ana M; Larruga, José M; Abu-Amero, Khaled K; Shi, Yufei; Pestano, José; Cabrera, Vicente M

    2007-07-09

    The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA) sequences and 261 partial sequences belonging to haplogroup M1 was carried out. The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

  14. Mitochondrial lineage M1 traces an early human backflow to Africa

    Directory of Open Access Journals (Sweden)

    Pestano José

    2007-07-01

    Full Text Available Abstract Background The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA sequences and 261 partial sequences belonging to haplogroup M1 was carried out. Results The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. Conclusion This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

  15. Emissions in potassium vapour under 4S1/2-7S1/2 two-photon nsec excitation

    International Nuclear Information System (INIS)

    Pentaris, D.; Chatzikyriakos, G.; Armyras, A.; Efthimiopoulos, T.

    2010-01-01

    The two-photon excitation of 4S 1/2 -7S 1/2 transition of potassium atoms is studied. Several coherent emissions and processes are possible, such as parametric four-wave (PFWM), parametric six-wave (PSWM) mixing and competition with the stimulated hyper Raman (SHRS) and the amplified spontaneous emission (ASE). The radiations at the transitions 6P 3/2,1/2 -4S 1/2 , 6S 1/2 -4P 3/2,1/2 and 5P 3/2,1/2 -4S 1/2 are emitted only in the forward direction (indicating a parametric process), while the radiation at the transition 4P 3/2,1/2 -4S 1/2 is emitted in the forward and in the backward direction, indicating an ASE process.

  16. Properties of M1-M2-Si-Al-O-N glasses (M1 = La or Nd, M2 = Y or Er)

    Energy Technology Data Exchange (ETDEWEB)

    Pomeroy, M.J.; Nestor, E.; Hampshire, S. [Limerick Univ. (Ireland). Materials and Surface Science Inst.; Ramesh, R. [Littelfuse Ireland, Dundalk, Co. Louth (Ireland)

    2002-07-01

    Mixed lanthanide cation oxynitride glasses have been prepared in the M1 - M2 - Si-Al-O-N systems where M1 = La or Nd and M2 = Y or Er. The densities ({rho}), Young's moduli (E), microhardnesses (H{sub v}), glass transition temperatures (T{sub g}), dilatometric softening temperatures (T{sub dil}) and coefficients of thermal expansion (CTE) of 13 glasses were determined. The molar volume values (MV) calculated from density data, E, H{sub v}, T{sub g}, T{sub dil} and CTE values were all found to vary linearly with the effective cation field strength arising from the M1 and M2 modifier cations. Least squares intercept and slope values are presented which correlate each property to effective cation field strength together with error values which arise from glass and specimen preparation and measurement inconsistencies. These linear correlations clearly indicate that the overall glass structure remains the same for each of the thirteen glasses with only the modifier cation(s) having any influence. This influence appears to be a cross-linking effect, the strength of which increases as the effective cation field strength of the M1, M2 modifiers increases. (orig.)

  17. Alterations of M1 and M4 acetylcholine receptors in the genetically dystonic (dtsz) hamster and moderate antidystonic efficacy of M1 and M4 anticholinergics.

    Science.gov (United States)

    Hamann, Melanie; Plank, Jagoda; Richter, Franziska; Bode, Christoph; Smiljanic, Sinisa; Creed, Meaghan; Nobrega, José N; Richter, Angelika

    2017-08-15

    Striatal cholinergic dysfunction has been suggested to play a critical role in the pathophysiology of dystonia. In the dt sz hamster, a phenotypic model of paroxysmal dystonia, M1 antagonists exerted moderate antidystonic efficacy after acute systemic administration. In the present study, we examined the effects of the M4 preferring antagonist tropicamid and whether long-term systemic or acute intrastriatal injections of the M1 preferring antagonist trihexyphenidyl are more effective in mutant hamsters. Furthermore, M1 and M4 receptors were analyzed by autoradiography and immunohistochemistry. Tropicamide retarded the onset of dystonic attacks, as previously observed after acute systemic administration of trihexyphenidyl. Combined systemic administration of trihexyphenidyl (30mg/kg) and tropicamide (15mg/kg) reduced the severity in acute trials and delayed the onset of dystonia during long-term treatment. In contrast, acute striatal microinjections of trihexyphenidyl, tropicamid or the positive allosteric M4 receptor modulator VU0152100 did not exert significant effects. Receptor analyses revealed changes of M1 receptors in the dorsomedial striatum, suggesting that the cholinergic system is involved in abnormal striatal plasticity in dt sz hamsters, but the pharmacological data argue against a crucial role on the phenotype in this animal model. However, antidystonic effects of tropicamide after systemic administration point to a novel therapeutic potential of M4 preferring anticholinergics for the treatment of dystonia. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Comparison of clinicopathological parameters with FoxM1 expression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sezen Kocarslan

    2014-01-01

    Conclusion: This study showed that FoxM1 have a progressive oncogenic role in ccRRC. Our results suggested that higher expression of FoxM1 in tumor tissues predicts a locally aggressive behavior and poor outcome of patients with ccRCC, but not in patient with non-ccRCC.

  19. 12 CFR Appendix M1 to Part 226 - Generic Repayment Estimates

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Generic Repayment Estimates M1 Appendix M1 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... rounded down to the nearest whole year if the estimate contains a fractional year less than 0.5, and...

  20. Nanometre-accurate form measurement machine for E-ELT M1 segments

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.

    2015-01-01

    To enable important scientific discoveries, ESO has defined a new ground-based telescope: the European Extremely Large Telescope (E-ELT). The baseline design features a telescope with a 39-m-class primary mirror (M1), making it the largest and most powerful telescope in the world. The M1 consists of

  1. 78 FR 13897 - Final Revision and Publication of the 2012 Form M-1, Notice

    Science.gov (United States)

    2013-03-01

    ... DEPARTMENT OF LABOR Employee Benefits Security Administration RIN 1210-AB51 Final Revision and Publication of the 2012 Form M-1, Notice AGENCY: Employee Benefits Security Administration, Department of... revisions to the Form M-1, Report for Multiple Employer Welfare Arrangements (MEWAs) and Certain Entities...

  2. [Appearance of aflatoxin M1 during the manufacture of Camembert cheese].

    Science.gov (United States)

    Frémy, J M; Roiland, J C

    1979-01-01

    Several classic cheese making of camembert are made from raw milk spiked with Aflatoxin M1. Three Aflatoxin levels 7.5 microgram/l, 3 microgram/l are used. In respective curds 35.6, 47.1 and 57.7% of Aflatoxin M1 are recovered and 64.4, 52.9 and 42.3% in respective whey. During the first 15 days of storage the Aflatoxin M1 content of different cheeses decrease respectively 25, 55, 75%. A similar experience is made with a milk contamined in Aflatoxin M1 C14 labelled. Same results are recovered, except about behaviour of Aflatoxin M1 in cheese: a same C14 activity is recovered during storage for 30 days.

  3. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Science.gov (United States)

    Chen, Yen-Po; Chen, Ming-Ju

    2013-01-01

    Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8) CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  4. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Directory of Open Access Journals (Sweden)

    Yen-Po Chen

    Full Text Available Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8 CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  5. Different expression of FoxM1 in human benign and malignant pleural effusion.

    Science.gov (United States)

    Tang, Zhonghao; Li, Hongqing; Zhu, Huili; Bai, Chunxue

    2015-01-01

    The aims of this study were as follows: to analyze the forkhead box M1 (FoxM1) expression in benign and malignant pleural effusion by reverse transcription-polymerase chain reaction assay (RT-PCR); to explore the role of FoxM1 in formation and progress in malignant pleural effusion, and whether there is significant difference in expression level of FoxM1 between benign and malignant pleural effusion; to seek a gene marker diagnostically useful to identify benign and malignant pleural effusion in diagnosis and treatment of pleural effusion; and to collect expression level data of FoxM1 in 23 malignant pleural effusion samples (17 adenocarcinoma samples, four squamous carcinoma samples and two small cell lung carcinoma samples) and 15 benign pleural effusion samples (11 inflammatory pleural effusions, two transudates, two tuberculous pleural effusions) by RT-PCR. Among all 38 samples, average FoxM1 expression level of benign pleural effusions is (235.09 ± 59.99), while malignant pleural effusions (828.77 ± 109.76). Among 23 malignant samples, average FoxM1 expression level is (529.27 ± 75.85) in samples without cytological diagnostic evidence, while (1,218.12 ± 167.21) in samples with cytological diagnostic evidence. Differences of FoxM1 expression level between benign pleural effusions and malignant ones have statistical significance. There is an area of 0.881 under the receiver-operating characteristic curve, which verifies the accuracy of using FoxM1 expression level as diagnostic index to identify benign and malignant pleural effusions. According to our study, diagnostic sensitivity and specificity for FoxM1 expression level at 418.1 were 82.6 and 86.7 %, respectively, while 47.8 and 100 %, respectively, at 768.7. FoxM1 expression level in malignant pleural effusions is significantly higher than in benign ones. This study provides a new approach in clinical diagnosis, with FoxM1 as a specific molecule marker to identify benign and malignant pleural

  6. [Family of ribosomal proteins S1 contains unique conservative domain].

    Science.gov (United States)

    Deriusheva, E I; Machulin, A V; Selivanova, O M; Serdiuk, I N

    2010-01-01

    Different representatives of bacteria have different number of amino acid residues in the ribosomal proteins S1. This number varies from 111 (Spiroplasma kunkelii) to 863 a.a. (Treponema pallidum). Traditionally and for lack of this protein three-dimensional structure, its architecture is represented as repeating S1 domains. Number of these domains depends on the protein's length. Domain's quantity and its boundaries data are contained in the specialized databases, such as SMART, Pfam and PROSITE. However, for the same object these data may be very different. For search of domain's quantity and its boundaries, new approach, based on the analysis of dicted secondary structure (PsiPred), was used. This approach allowed us to reveal structural domains in amino acid sequences of S1 proteins and at that number varied from one to six. Alignment of S1 proteins, containing different domain's number, with the S1 RNAbinding domain of Escherichia coli PNPase elicited a fact that in family of ribosomal proteins SI one domain has maximal homology with S1 domain from PNPase. This conservative domain migrates along polypeptide chain and locates in proteins, containing different domain's number, according to specified pattern. In this domain as well in the S1 domain from PNPase, residues Phe-19, Phe-22, His-34, Asp-64 and Arg-68 are clustered on the surface and formed RNA binding site.

  7. Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

    Science.gov (United States)

    Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

    2014-08-01

    Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Techniques used detection and quantification of aflatoxin M1 in milk

    OpenAIRE

    Adriana Frizzarin; Keila Maria Roncato Duarte

    2012-01-01

    Aflatoxin is a group of toxic substances produced by fungi, mainly Aspergillus flavus and Aspergillus parasiticus. It can be developed in agriculture products such as grains or processed food, when environment conditions of humidity and air humidity are favorable. Aflatoxins can be presented as several forms. In Milk, are called M1 and M2, resulting from aflatoxins B1 and B2 metabolism. Aflatoxin M1 (AFM1) is classified as a possible carcinogen to humans, so the occurrence of aflatoxin M1 in ...

  9. Attenuation of cocaine's reinforcing and discriminative stimulus effects via muscarinic M1 acetylcholine receptor stimulation

    DEFF Research Database (Denmark)

    Thomsen, Morgane; Conn, P Jeffrey; Lindsley, Craig

    2010-01-01

    substituted for cocaine and enhanced its discriminative stimulus. Conversely, muscarinic agonists blunted cocaine discrimination and abolished cocaine self-administration with varying effects on food-maintained behavior. Specifically, increasing selectivity for the M(1) subtype (oxotremorine ...'s abuse-related effects, whereas non-M(1)/M(4) receptors probably contribute to undesirable effects of muscarinic stimulation. These data provide the first demonstration of anticocaine effects of systemically applied, M(1) receptor agonists and suggest the possibility of a new approach to pharmacotherapy...

  10. Triaxiality and alternating M1 strengths in f-p-g shell nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Tabor, S L; Johnson, T D; Holcombe, J W; Womble, P C; Doring, J; Nazarewicz, W [Florida State Univ., Tallahassee, FL (United States). Dept. of Physics

    1992-08-01

    The appearance of alternating patterns in B(M1) strengths in f-p-g shell nuclei is surveyed. The M1 alternations in a sequence of N= 41 isotones, in conjunction with particle-rotor model calculations, is shown to provide information about changing {gamma} deformation. In addition to other odd-A nuclei, several odd-odd nuclei are shown to exhibit alternating B(M1) values and signature inversion. alternations have also been reported in a 4 quasiparticle band in {sup 86}Zr, where they have been interpreted in terms of the interacting boson model. (author). 15 refs., 1 tab., 6 figs.

  11. Fine structure of the giant M1 resonance in 90Zr.

    Science.gov (United States)

    Rusev, G; Tsoneva, N; Dönau, F; Frauendorf, S; Schwengner, R; Tonchev, A P; Adekola, A S; Hammond, S L; Kelley, J H; Kwan, E; Lenske, H; Tornow, W; Wagner, A

    2013-01-11

    The M1 excitations in the nuclide 90Zr have been studied in a photon-scattering experiment with monoenergetic and linearly polarized beams from 7 to 11 MeV. More than 40 J(π)=1+ states have been identified from observed ground-state transitions, revealing the fine structure of the giant M1 resonance with a centroid energy of 9 MeV and a sum strength of 4.17(56) μ(N)(2). The result for the total M1 strength and its fragmentation are discussed in the framework of the three-phonon quasiparticle-phonon model.

  12. Quantum effective potential in S1xR3

    International Nuclear Information System (INIS)

    Denardo, G.; Spallucci, E.; Doebner, H.D.

    1981-07-01

    The functional integral formulation of quantum field theory is applied to the study of the vacuum state in spacetimes with S 1 xR 3 topology. Such a global spacetime structure can be physically realized both in flat and in curved spacetime. In the first case one deals with finite temperature quantum field theories (if S 1 is time-like) or with field theories in a spacetime with a compact space dimension (if S 1 is spacelike). When curvature is present, a S 1 time-like dimension is induced by the Wick rotation whenever the metric is endowed with an event horizon, and this leads to the thermal nature of the vacuum in these cases. We shall take into account here only conformally flat spacetimes. Finally we discuss in some details the topological restoration of a spontaneously broken symmetry and the strictly related problem of the mass dynamical generation. (author)

  13. MESSAGE 2 space experiment with Rhodospirillum rubrum S1H

    Data.gov (United States)

    National Aeronautics and Space Administration — R. rubrum S1H inoculated on solid agar rich media was sent to the ISS in October 2003 (MESSAGE-part 2 experiment). After 10 days flight R. rubrum cultures returned...

  14. S = -1 and S = -2 few-body hypernuclei

    International Nuclear Information System (INIS)

    Gibson, B.F.

    1997-01-01

    The S = -1 and S = -2 few-body bound states are the focus of this discussion. Implications for the understanding of the baryon-baryon interaction are examined. Octet-octet coupling effects not found in conventional, non-strange nuclei are highlighted. TJNAF wave function tests for the S = -1 sector are noted. The need to identify S = -2 hypernuclei to explore the S = -2 strong interaction and to test model predictions is emphasized

  15. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    Energy Technology Data Exchange (ETDEWEB)

    Bayes, R. [Univ. of Glasgow, Scotland (United Kingdom); Berg, J. S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blackmore, V. [Imperial College, London (United Kingdom); Hunt, C. [Imperial College, London (United Kingdom); Liu, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pasternak, J. [Imperial College, London (United Kingdom); Rogers, C. T. [Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Rutherford Appleton Lab. (RAL)

    2015-10-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  16. M1 chimerism following mutagen treatment of seeds in rice and some other cereals

    International Nuclear Information System (INIS)

    Kawai, T.

    1983-01-01

    Articles reporting on M 1 chimerism following treatment of seed with mutagen in cereals were mostly published in the 1960's. Rice is a good material for making such studies because of its relatively large number of seeds per panicle, rather easily identifiable tillering and panicle branching systems and uniform growth after seedling transplanting. The present article summarizes results of studies on M 1 chimerism in rice and some other cereals which may serve as reference information in discussing M 1 chimerism of those plant species showing different development patterns, as dicotyledonous plants, following treatment of seed with mutagen. Studies on M 1 chimerism provide not only knowledge of the sporophyte development but also basic information for developing methods of harvesting M 2 seed which provide the maximum numbers of mutants of different origins in a limited number of M 2 plants. (author)

  17. Techniques used detection and quantification of aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-02-01

    Full Text Available Aflatoxin is a group of toxic substances produced by fungi, mainly Aspergillus flavus and Aspergillus parasiticus. It can be developed in agriculture products such as grains or processed food, when environment conditions of humidity and air humidity are favorable. Aflatoxins can be presented as several forms. In Milk, are called M1 and M2, resulting from aflatoxins B1 and B2 metabolism. Aflatoxin M1 (AFM1 is classified as a possible carcinogen to humans, so the occurrence of aflatoxin M1 in milk of lactating cows is a public health issue, and because of its importance several techniques are used for its detection and quantification. These techniques include the physical-chemical as thin layer chromatography and high performance liquid chromatography and the biological techniques including immunoassays such as RIA and ELISA. This review aimed to present the techniques used to quantify aflatoxins M1 and M2 in milk and dairy products.

  18. Addendum to 'Half coalescence of the m=1, n=1 magnetic island in tokamaks'

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.

    1985-01-01

    As an addendum to our previous work concerning the half-coalescence instability of an m=1, n=1 magnetic island in tokamaks, the potential energy is given for an arbitrary shape of the separatrix. (orig.)

  19. Inelastic electron scattering, fine structure of M1 giant resonances and Gamow-Teller states

    International Nuclear Information System (INIS)

    Richter, A.

    1983-01-01

    Recent progress in obtaining detailed fine structure distributions of magnetic giant resonances in nuclei using high resolution inelastic electron scattering at low energy is discussed. Specific examples chosen are the medium heavy nuclei 40 42 44 48 Ca in which M1 excitations are due to neutron spin-flip transitions and the N=28 isotones 50 Ti, 52 Cr and 54 Fe where in addition also proton excitations contribute to the measured M1 strength. It is found that the M1 strength is very fragmented and considerably quenched in comparison to predictions of shell model calculations in a model space that includes up to 2p-2h excitations. Finally, the old problem of M1 strength in 208 Pb is revisited and the results of a form factor measurement of a recently discovered low lying Jsup(π)=1 + state by nuclear resonance fluorescence are presented. (Auth.)

  20. The mutual dependence of M1 fertility and M2 mutations in rice

    International Nuclear Information System (INIS)

    Gopinathan Nair, V.

    1982-01-01

    The mutual dependence of M 1 fertility and M 2 mutations in rice was studied after treatment with gamma rays and EMS. The frequency of chlorophyll mutations increased with decrease in seed fertility when M 1 ears were selected at random. However, at the lowest fertility class the mutation frequency was low. This reduction is attributed to the elimination of mutants in the high sterility class. The mutation yield can therefore be significantly enhanced by selecting M 1 ears of low fertility. The segregation ratio of mutants increased as fertility decreased. Mutation spectrum was however not influenced by M 1 fertility. This makes selection for fertility quite ineffective in altering the mutation spectrum. (author)

  1. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    International Nuclear Information System (INIS)

    Bayes, R.; Berg, J. S.; Blackmore, V.; Hunt, C.; Liu, A.; Pasternak, J.; Rogers, C. T.

    2015-01-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  2. 76 FR 799 - Publication of Year 2010 Form M-1 With Electronic Filing Option, Notice

    Science.gov (United States)

    2011-01-06

    ... DEPARTMENT OF LABOR Employee Benefits Security Administration Publication of Year 2010 Form M-1 With Electronic Filing Option, Notice AGENCY: Employee Benefits Security Administration, Department of... Employer Welfare Arrangements and Certain Entities Claiming Exception. It is generally identical to the...

  3. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2014-05-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  4. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-11-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  5. Emergence and oscillation of cosmic space by joining M1-branes

    International Nuclear Information System (INIS)

    Sepehri, Alireza; Rahaman, Farook; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-01-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  6. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    OpenAIRE

    Adriana Frizzarin; Thiago Pereira Motta; Thamires Martins; Livia Castelani; Heloisa Solda de Azevedo; Cláudia Rodrigues Pozzi

    2012-01-01

    Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, preg...

  7. Toroidal effects on the non-linearly saturated m = 1 island in tokamaks

    International Nuclear Information System (INIS)

    Avinash, K.; Haas, F.A.; Thyagaraja, A.

    1990-01-01

    This paper investigates the influence of toroidal effects (due to the coupling of various poloidal harmonics) on the non-linear saturation of the m=1 island. Bounds are obtained relating the aspect ratio, the shear at the q=1 surface and the saturated island width. Provided these bounds are satisfied, then we find that the cylindrical m=1 island theory is valid for toroidal geometry. (author)

  8. Emergence and oscillation of cosmic space by joining M1-branes

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza [Shahid Bahonar University, Faculty of Physics, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Rahaman, Farook [Jadavpur University, Department of Mathematics, Kolkata, West Bengal (India); Capozziello, Salvatore [Universita di Napoli Federico II, Dipartimento di Fisica ' ' E. Pancini' ' , Naples (Italy); Gran Sasso Science Institute (INFN), L' Aquila (Italy); Tomsk State Pedagogical University, Tomsk (Russian Federation); INFN Sezione di Napoli, Naples (Italy); Ali, Ahmed Farag [Benha University, Department of Physics, Faculty of Science, Benha (Egypt); Pradhan, Anirudh [G L A University, Department of Mathematics, Institute of Applied Sciences and Humanities, Mathura, Uttar Pradesh (India)

    2016-05-15

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  9. Chimerism in M1 plants of Vicia faba, Capsicum annuum and Linum usitatissimum

    International Nuclear Information System (INIS)

    Hermelin, T.; Brunner, H.; Daskalov, S.; Nakai, H.

    1983-01-01

    One important task of our group at IAEA is to develop procedures aiming to improve sampling of M 2 seeds to facilitate the recovery of a maximum number of induced mutations in crop plants. Results from studies on three species are reported in this paper. Seeds have been mutagen treated and the chimeric M 1 plants were progeny tested in M 2 . The position of the M 2 seeds on the M 1 plants has been recorded

  10. The Evaluation of Aflatoxin M1 Level in Collected Raw Milk for Pasteurized Dairy

    Directory of Open Access Journals (Sweden)

    Ehsan Sadeghi

    2013-03-01

    Full Text Available Background: Aflatoxins are fungal toxins that have carcinogenic, cellular mutations and malformation effects. Aflatoxin M1 resists pasteurization, autoclave and the other methods that make foodstuff healthy. This study aims to determine the contents of aflatoxin M1 in raw milk of milk factories in Kermanshah province.Materials and Methods: This research is carried out through the descriptive-cross sectional method. Among the raw milk received by four pasteurized milk factories in Kermanshah, coded by (A, B, C, D labels, six samples, totally 320 samples (80 samples from each factory, were taken within four seasons. The concentration of aflatoxin M1 was examined by Enzyme-Linked Immunosorbent Assay (ELISA. The mean difference was analyzed statistically through t-test using SPSS software. Results: The content of aflatoxin was higher than Codex standard (0.5 µg/l in 295 samples. The total mean was 1.21, which exceeds two times the Codex standard. The highest and lowest contents of aflatoxin M1 were observed in “Factory D” in spring and in “Factory A” in autumn, respectively. There was a significant difference between contamination of aflatoxin M1 and different seasons (p< 0.05.Conclusion: High content of aflatoxin M1 in raw milk is worrying. Measuring the content of aflatoxin M1 is essential to reduce the toxin entering the daily food of animals and the other related factors. The considerable difference of aflatoxin M1 content between Factory D and Factory A can be attributed to the amount of the local milk and the industrial milk received by the factories.

  11. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

    Science.gov (United States)

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

    2015-01-01

    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio. © International & American Associations for Dental Research 2014.

  12. The effect of proton correlations in the M1 scattering strengths of even calcium isotopes

    International Nuclear Information System (INIS)

    Chaves, L.; Poves, A.

    1986-01-01

    The proton correlations are evaluated in Ca isotopes using the wave functions obtained in an extended shell model calculation in the [1dsub(3/2), 1fsub(7/2), 1fsub(5/2)] valence space. The inclusion of 2p-2h correlations in M1 scattering strengths and magnetic moments improves the agrreement with the experimental data. The M1 strength in 40 Ca is correctly reproduced. (orig.)

  13. FoxM1 is a general target for proteasome inhibitors.

    Directory of Open Access Journals (Sweden)

    Uppoor G Bhat

    2009-08-01

    Full Text Available Proteasome inhibitors are currently in the clinic or in clinical trials, but the mechanism of their anticancer activity is not completely understood. The oncogenic transcription factor FoxM1 is one of the most overexpressed genes in human tumors, while its expression is usually halted in normal non-proliferating cells. Previously, we established that thiazole antibiotics Siomycin A and thiostrepton inhibit FoxM1 and induce apoptosis in human cancer cells. Here, we report that Siomycin A and thiostrepton stabilize the expression of a variety of proteins, such as p21, Mcl-1, p53 and hdm-2 and also act as proteasome inhibitors in vitro. More importantly, we also found that well-known proteasome inhibitors such as MG115, MG132 and bortezomib inhibit FoxM1 transcriptional activity and FoxM1 expression. In addition, overexpression of FoxM1 specifically protects against bortezomib-, but not doxorubicin-induced apoptosis. These data suggest that negative regulation of FoxM1 by proteasome inhibitors is a general feature of these drugs and it may contribute to their anticancer properties.

  14. [Recombinant human gapM1 expressed in Pichia pastoris and its anti-diabetic effect].

    Science.gov (United States)

    Mei, Xiang; Du, Renqian; Li, Xi; Huang, Haiyan; Yu, Min; Tang, Qiqun

    2009-08-01

    Adiponectin is an adipokine predominantly synthesized and secreted by adipocytes in the white adipose tissue, and it can lower the blood glucose level and increase free fatty acid oxidation. In the current study, we developed the globular domain of adiponectin (gapM1) to treat type II diabetes. In both flask and fermentor, we cultivated Pichia pastoris expressing recombinant gapM1 and established the purification procedure by using gel filtration and anion exchange chromatography. To evaluate the biological activity of recombinant gapM1, we used rat type II diabetes model fed high-fat diet in combination with low-dose STZ (Streptozocin) induction. We purified 200 mg gapM1 with purity of 96% from 10 liters of supernatant. The recombinant gapM1 significantly lowered blood glucose (34.2%), serum triglyceride (79.6%) and total cholesterol (62.1%) in type II diabetes induced rat. Therefore, the recombinant human gapM1 is successfully expressed in Pichia pastoris and effectively treated type II diabetes in rat models.

  15. The improvement of M1 polarization in macrophages by glycopeptide derived from Ganoderma lucidum.

    Science.gov (United States)

    Sun, Li-Xin; Lin, Zhi-Bin; Lu, Jie; Li, Wei-Dong; Niu, Yan-Dong; Sun, Yu; Hu, Chen-Yang; Zhang, Guo-Qiang; Duan, Xin-Suo

    2017-06-01

    Ganoderma lucidum (Fr.) Karst (Ganodermataceae) is a medicinal mushroom that has been extensively used in China for centuries to promote longevity and improve vigor without significant adverse effects. There is continuous interest in the bioactive properties of G. lucidum in view of its newly developed popularity in other regions besides Asia, such as Europe. Glycopeptide derived from G. lucidum (Gl-PS) is one of the main effective components isolated from this mushroom. The Gl-PS has been demonstrated pleiotropic with many bioactivities including immunomodulatory and antitumor effects. Macrophages are important cells involved in innate and adaptive immunity. Classically activated macrophages (M1) and alternatively activated macrophages (M2), with their different roles, display distinct cytokine profiles: M1 preferentially produces TNF-α, IL-6, and IL-12; conversely, M2 generates more IL-10 and arginase. Gl-PS might have the potential to promote macrophage M1 polarization by lipopolysaccharide (LPS). In this study, LPS was used to induce the M1 polarization. It was shown that the level of the TNF-α, IL-6, and IL-12 were increased and the IL-10 and arginase I were decreased in the polarized M1 macrophages after application of Gl-PS compared to the control. The results indicated the potential of Gl-PS to promote M1 polarization vs M2, with the health beneficial understanding of the bioactivities of Gl-PS.

  16. AP4M1 is abnormally expressed in oxygen-glucose deprived hippocampal neurons.

    Science.gov (United States)

    Zhang, J; Cheng, X Y; Sheng, G Y

    2014-03-20

    AP4M1 mutations have been suggested to be associated with autosomal recessive cerebral palsy syndrome. But the pathogenic mechanism remains uncertain. The purpose of this study is to investigate whether and how AP4M1 expression is changed in injured neurons. Primary cultured hippocampal neurons were prepared for this experiment. They were subjected to oxygen-glucose deprivation (OGD) leading to apoptosis, mimicking brain ischemia. Neuron-specific enolase (NSE) was labeled immunofluorescently to confirm that the purity of neuron was higher than 90%. Real-time PCR and western blotting were performed to measure the gene expression. AP4M1 was labeled with MAP2 or Tau-1 to observe the distribution. We found that the AP4M1 protein levels immediately after the procedure were similar between the OGD group and the sham group. However, down-regulation was observed 12h after the reperfusion, and became more notable at 24h. The real-time PCR showed similar results, except that the down-regulation of mRNA was able to be detected immediately after the OGD. Immunofluorescent labeling revealed AP4M1 distributed in the dendrites of normal neurons, but it redistributed to the axons after the OGD procedure. In conclusion, AP4M1 is not only down-regulated at both the mRNA and protein levels, but also redistributed from dendrites to axons in oxygen-glucose deprived hippocampal neurons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Search for weak M 1 transitions in 48Ca with inelastic proton scattering

    Science.gov (United States)

    Mathy, M.; Birkhan, J.; Matsubara, H.; von Neumann-Cosel, P.; Pietralla, N.; Ponomarev, V. Yu.; Richter, A.; Tamii, A.

    2017-05-01

    Background: The quenching of spin-isospin modes in nuclei is an important field of research in nuclear structure. It has an impact on astrophysical reaction rates and on fundamental processes like neutrinoless double-β decay. Gamow-Teller (GT) and spin-flip M 1 strengths are quenched. Concerning the latter, the Jπ=1+ resonance in the doubly magic nucleus 48Ca, dominated by a single transition, serves as a reference case. Purpose: The aim of the present work is to search for weak M 1 transitions in 48Ca with a high-resolution (p ,p') experiment at 295 MeV and forward angles including 0∘ and a comparison with results from a similar study using backward-angle electron scattering at low momentum transfers in order to estimate their contribution to the total B (M 1 ) strength in 48Ca. Methods: The spin-M 1 cross sections of individual peaks in the spectra are deduced with a multipole decomposition analysis (MDA) and converted to reduced spin-M 1 transition strengths by using the unit cross-section method. For a comparison with electron-scattering results, corresponding reduced B (M 1 ) transition strengths are extracted following the approach outlined in Birkhan et al. [Phys. Rev. C 93, 041302(R) (2016), 10.1103/PhysRevC.93.041302]. Results: In total, 30 peaks containing a M 1 contribution are found in the excitation energy region 7-13 MeV. The resulting B (M 1 ) strength distribution compares well to the electron-scattering results considering different factors limiting the sensitivity in both experiments and the enhanced importance of mechanisms breaking the proportionality of nuclear cross sections and electromagnetic matrix elements for weak transitions as studied here. The total strength of 1.14(7) μN2 deduced assuming a nonquenched isoscalar part of the (p ,p') cross sections agrees with the (e ,e') result of 1.21(13) μN2. A bin-wise analysis above 10 MeV provides an upper limit of 1.51(17) μN2. Conclusions: The present results confirm the previous electron

  18. β-adrenergic-stimulated macrophages: Comprehensive localization in the M1–M2 spectrum

    Science.gov (United States)

    Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.

    2016-01-01

    β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1–M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1–M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1–M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1–M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1–M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

  19. Learning stage-dependent effect of M1 disruption on value-based motor decisions.

    Science.gov (United States)

    Derosiere, Gerard; Vassiliadis, Pierre; Demaret, Sophie; Zénon, Alexandre; Duque, Julie

    2017-11-15

    The present study aimed at characterizing the impact of M1 disruption on the implementation of implicit value information in motor decisions, at both early stages (during reinforcement learning) and late stages (after consolidation) of action value encoding. Fifty subjects performed, over three consecutive days, a task that required them to select between two finger responses according to the color (instruction) and to the shape (implicit, undisclosed rule) of an imperative signal: considering the implicit rule in addition to the instruction allowed subjects to earn more money. We investigated the functional contribution of M1 to the implementation of the implicit rule in subjects' motor decisions. Continuous theta burst stimulation (cTBS) was applied over M1 either on Day 1 or on Day 3, producing a temporary lesion either during reinforcement learning (cTBS Learning group) or after consolidation of the implicit rule, during decision-making (cTBS Decision group), respectively. Interestingly, disrupting M1 activity on Day 1 improved the reliance on the implicit rule, plausibly because M1 cTBS increased dopamine release in the putamen in an indirect way. This finding corroborates the view that cTBS may affect activity in unstimulated areas, such as the basal ganglia. Notably, this effect was short-lasting; it did not persist overnight, suggesting that the functional integrity of M1 during learning is a prerequisite for the consolidation of implicit value information to occur. Besides, cTBS over M1 did not impact the use of the implicit rule when applied on Day 3, although it did so when applied on Day 2 in a recent study where the reliance on the implicit rule declined following cTBS (Derosiere et al., 2017). Overall, these findings indicate that the human M1 is functionally involved in the consolidation and implementation of implicit value information underlying motor decisions. However, M1 contribution seems to vanish as subjects become more experienced in using

  20. Targeting the S1P/S1PR1 axis mitigates cancer-induced bone pain and neuroinflammation.

    Science.gov (United States)

    Grenald, Shaness A; Doyle, Timothy M; Zhang, Hong; Slosky, Lauren M; Chen, Zhoumou; Largent-Milnes, Tally M; Spiegel, Sarah; Vanderah, Todd W; Salvemini, Daniela

    2017-09-01

    Metastatic bone pain is the single most common form of cancer pain and persists as a result of peripheral and central inflammatory, as well as neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P). Intriguingly, de novo sphingolipid biosynthesis was increased as shown by the elevations of dihydro-ceramides and dihydro-S1P. We next identified the S1P receptor subtype 1 (S1PR1) as a novel target for therapeutic intervention. Intrathecal or systemic administration of the competitive and functional S1PR1 antagonists, TASP0277308 and FTY720/Fingolimod, respectively, attenuated cancer-induced spontaneous flinching and guarding. Inhibiting CIBP by systemic delivery of FTY720 did not result in antinociceptive tolerance over 7 days. FTY720 administration enhanced IL-10 in the lumbar ipsilateral spinal cord of CIBP animals and intrathecal injection of an IL-10 neutralizing antibody mitigated the ability of systemic FTY720 to reverse CIBP. FTY720 treatment was not associated with alterations in bone metabolism in vivo. Studies here identify a novel mechanism to inhibit bone cancer pain by blocking the actions of the bioactive metabolites S1P and dihydro-S1P in lumbar spinal cord induced by bone cancer and support potential fast-track clinical application of the FDA-approved drug, FTY720, as a therapeutic avenue for CIBP.

  1. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

    Science.gov (United States)

    Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

    2017-10-01

    Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. Improved E-ELT subsystem and component specifications, thanks to M1 test facility

    Science.gov (United States)

    Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, Pablo; Sedghi, B.; Kornweibel, N.

    2014-07-01

    During the last 2 years ESO has operated the "M1 Test Facility", a test stand consisting of a representative section of the E-ELT primary mirror equipped with 4 complete prototype segment subunits including sensors, actuators and control system. The purpose of the test facility is twofold: it serves to study and get familiar with component and system aspects like calibration, alignment and handling procedures and suitable control strategies on real hardware long before the primary mirror (hereafter M1) components are commissioned. Secondly, and of major benefit to the project, it offered the possibility to evaluate component and subsystem performance and interface issues in a system context in such detail, that issues could be identified early enough to feed back into the subsystem and component specifications. This considerably reduces risk and cost of the production units and allows refocusing the project team on important issues for the follow-up of the production contracts. Experiences are presented in which areas the results of the M1 Test Facility particularly helped to improve subsystem specifications and areas, where additional tests were adopted independent of the main test facility. Presented are the key experiences of the M1 Test Facility which lead to improved specifications or identified the need for additional testing outside of the M1 Test Facility.

  3. First case report of M1 macrophage polarization in an untreated symptomatic patient with toxoplasmosis.

    Science.gov (United States)

    De Luca, Graziano; Di Lisio, Chiara; Lattanzio, Giuseppe; D'Antuono, Tommaso; Liberatore, Marcella; Aiello, Francesca Bianca

    2018-03-27

    In immunocompetent patients, acute toxoplasmosis is usually asymptomatic. We identified M1 macrophages in a case of symptomatic acute Toxoplasma gondii infection that resolved without treatment. M1 macrophages have been demonstrated in animal models of toxoplasmosis, but not in humans. A 63-year-old woman presented with laterocervical and axillary bilateral lymphadenopathy. Her anamnesis defined an episode of high fever and prolonged asthenia 4 months previously, which suggested an infectious disease. Following laboratory, radiological, and pathological analyses, she was diagnosed with toxoplasmosis. Immunohistochemical analyses were performed on lymph node sections. More than 50% of the macrophages in the lymph node microgranulomas were M1 macrophages, defined by CD68 + /p-Stat1 + staining, and the presence of T helper 1 lymphocytes indicated an immune response known to induce M1 macrophage polarization. Activated endothelial cells were found only in inflamed areas. No therapy was administered before or after diagnosis, and the lymphadenopathy resolved after a follow-up of 5 months. This is the first report to demonstrate the presence of M1 macrophages in human toxoplasmosis. Our findings contribute to the understanding of the pathogenesis of toxoplasmosis, and encourage further studies on the role of macrophage polarization in human toxoplasmosis.

  4. Dopaminergic mesocortical projections to M1: role in motor learning and motor cortex plasticity

    Directory of Open Access Journals (Sweden)

    Jonas Aurel Hosp

    2013-10-01

    Full Text Available Although the architecture of a dopaminergic (DA system within the primary motorcortex (M1 was well characterized anatomically, its functional significance remainedobscure for a long time. Recent studies in rats revealed that the integrity ofdopaminergic fibers in M1 is a prerequisite for successful acquisition of motor skills.This essential contribution of DA for motor learning is plausible as it modulates M1circuitry at multiple levels thereby promoting plastic changes that are required forinformation storage: at the network level, DA increases cortical excitability andenhances the stability of motor maps. At the cellular level, DA induces the expressionof learning related genes via the transcription factor c-fos. At the level of synapses,DA is required for the formation of long-term potentiation (LTP, a mechanism thatlikely is a fingerprint of a motor memory trace within M1. Dopaminergic fibersinnervating M1 originate within the midbrain, precisely the ventral tegmental area(VTA and the medial portion of substantia nigra (SN. Thus, they could be part of themeso-cortico-limibic pathway – a network that provides information about saliencyand motivational value of an external stimulus and is commonly referred as

  5. In vivo analysis of the Notch receptor S1 cleavage.

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    2009-08-01

    Full Text Available A ligand-independent cleavage (S1 in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control.

  6. Diff(S1)/SL(2,R) and Teichmueller space

    International Nuclear Information System (INIS)

    Nag, S.; Verjovsky, A.

    1988-08-01

    It is shown that the unique homogeneous Kaehler metric carried by M=Diff(S 1 )/SL(2,R) induces the Weil-Petersson metric on the Teichmueller space. This is via our identification of M as a holomorphic submanifold of universal Teichmueller space T(1). The identification was obtained simply by noting that every diffeomorphism of S 1 is a quasisymmetric homeomorphism. Our computations allow us also to prove that every T(G), G any infinite Fuchsian group, projects out of M transversely. This last assertion is related to the ''fractal'' nature of G-invariant quasicircles. (author). 12 refs

  7. Nonlinear ω*-stabilization of the m = 1 mode in tokamaks

    International Nuclear Information System (INIS)

    Rogers, B.; Zakharov, L.

    1995-08-01

    Earlier studies of sawtooth oscillations in Tokamak Fusion Test Reactor supershots (Levinton et al, Phys. Rev. Lett. 72, 2895 (1994); Zakharov, et al, Plasma Phys. and Contr. Nucl. Fus. Res., Proc. 15th Int. Conf., Seville 1994, Vienna) have found an apparent contradiction between conventional linear theory and experiment: even in sawtooth-free discharges, the theory typically predicts instability due to a nearly ideal m = 1 mode. Here, the nonlinear evolution of such mode is analyzed using numerical simulations of a two-fluid magnetohydrodynamic (MHD) model. We find the mode saturates nonlinearly at a small amplitude provided the ion and electron drift-frequencies ω* i,e are somewhat above the linear stability threshold of the collisionless m = 1 reconnecting mode. The comparison of the simulation results to m = 1 mode activity in TFTR suggests additional, stabilizing effects outside the present model are also important

  8. Analysis of experimental air-detritiation data using TSOAK-M1

    International Nuclear Information System (INIS)

    Land, R.H.; Maroni, V.A.; Minkoff, M.

    1980-01-01

    A computer code (TSOAK-M1) has been developed which permits the determination of tritium reaction (T 2 to HTO)/adsorption/release and instrument correction parameters from enclosure (building) detritiation test data. The code is based on a simplified model which treats each parameter as a normalized time-independent constant throughout the data-unfolding steps. TSOAK-M1 was used to analyze existing small-cubicle test data with good success, and the resulting normalized parameters were employed to evaluate hypothetical reactor-building detritiation scenarios. It was concluded from the latter evaluation that the complications associated with moisture formation, adsorption, and release, particularly in terms of extended cleanup times, may not be as great as was previously thought. It is recommended that the validity of the TSOAK-M1 model be tested using data from detritiation tests conducted on large experimental enclosures (5 to 10 m 3 ) and, if possible, actual facility buildings

  9. PERUBAHAN KARAKTER KUANTITATIF MUCUNA PRURIENS GENERASI M1 PASCA IRRADIASI SINAR GAMMA CO-60

    Directory of Open Access Journals (Sweden)

    Yustinus Ulung Anggraito

    2015-02-01

    Full Text Available Koro benguk (Mucuna pruriens berpotensi sebagai bahan substitusi kedelai. Keragaman genetik koro benguk termasuk kategori rendah, sehingga perlu ditingkatkan keragaman genetiknya terutama pada faktor-faktor produksi. Tujuan penelitian adalah mendapatkan informasi mutasi mikro pada koro benguk generasi M1 setelah diradiasi dengan sinar gamma dari Cobalt-60. Benih koro benguk diperoleh dari Balai Pengembangan Perbenihan Tanaman Pangan dan Hortikultura (BP2TPH Ngipiksari, Sleman, Yogyakarta. Radiasi sinar gamma dilakukan di PAIR BATAN Pasar Jumat, Jakarta. Dosis radiasi gamma yang digunakan adalah 0; 25 Gy, 50 Gy; 100 Gy; 150 Gy, 200 Gy, dan 250 Gy. Eksperimen dilakukan menggunakan Rancangan Acak Kelompok (RAK. Parameter yang diamati adalah umur berbunga, jumlah polong, jumlah biji, berat 100 biji tanaman generasi M1. Data dianalisis menggunakan Anava, dilanjutkan dengan Uji Beda Nyata Duncan (DMRT. Hasil penelitian menunjukkan bahwa peningkatan dosis radiasi sinar gamma akan memperpanjang hari munculnya bunga dan berat biji, namun menurunkan jumlah polong dan jumlah biji pada tanaman generasi M1.

  10. Application of commercial RIA kit in investigating milk contamination with M1 aflatoxin

    International Nuclear Information System (INIS)

    Fukal, L.

    1988-01-01

    Measured were samples of commercially sold milk produced by two Czech dairies and samples of unprocessed cow's milk from three farms. The determination of aflatoxin M 1 in liquid milk was carried out with a RIA-test-aflatoxin M 1 B 1 kit. The range of the calibration curve of the kit is 0.06 to 2.0 μg/l. In samples of commercially sold milk a higher share of aflatoxin M 1 free samples was found (93%) and 7% samples contained 0.050 to 0.1 μg aflatoxin/l. The dilution effect was manifest in commercially sold milk. On the other hand in 7% samples of raw milk aflatoxin concentration exceeded the limits set by hygiene inspection bodies for consumption by infants. The detected aflatoxin concentrations are compared with data from abroad. (E.S.). 2 tabs., 13 refs

  11. Mission hazard assessment for STARS Mission 1 (M1) in the Marshall Islands area

    Energy Technology Data Exchange (ETDEWEB)

    Outka, D.E.; LaFarge, R.A.

    1993-07-01

    A mission hazard assessment has been performed for the Strategic Target System Mission 1 (known as STARS M1) for hazards due to potential debris impact in the Marshall Islands area. The work was performed at Sandia National Laboratories as a result of discussion with Kwajalein Missile Range (KMR) safety officers. The STARS M1 rocket will be launched from the Kauai Test Facility (KTF), Hawaii, and deliver two payloads to within the viewing range of sensors located on the Kwajalein Atoll. The purpose of this work has been to estimate upper bounds for expected casualty rates and impact probability or the Marshall Islands areas which adjoin the STARS M1 instantaneous impact point (IIP) trace. This report documents the methodology and results of the analysis.

  12. First evidence for spin-flip M1 strength in 40Ar

    International Nuclear Information System (INIS)

    Li, T.C.; Rainovski, G.; Pietralla, N.; Ahn, T.; Costin, A.; Tonchev, A.P.; Ahmed, M.W.; Blackston, M.A.; Parpottas, Y.; Perdue, B.A.; Tornow, W.; Weller, H.R.; Angell, C.; Keeter, K.J.; Li, J.; Mikhailov, S.; Wu, Y.K.; Lisetskiy, A.

    2006-01-01

    The 40 Ar(γ→,γ ' ) photon scattering reaction was used to search for spin-flip M1 strength in 40 Ar. The nearly monochromatic, linearly polarized photon beam of HIγS, in an energy region from 7.7 to 11 MeV, was employed in this study. 28 dipole excitations were observed. The azimuthal intensity asymmetry indicated that all of these states were E1 except for the state at E x =9.757 MeV. Shell-model calculations were used to interpret this state as one fragment of the spin-flip M1 strength in 40 Ar

  13. Molecular cloning of S1 glycoprotein gene of infectious bronchitis ...

    African Journals Online (AJOL)

    In vitro protein expression is an important method of obtaining large amounts of viral proteins to investigate their biological properties. The S1 glycoprotein of infectious bronchitis virus, due to its effective immune-dominant role is an appropriate candidate for production of recombinant vaccine against infectious bronchitis ...

  14. Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

    Science.gov (United States)

    Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

    2016-01-15

    Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Chromospheric Evaporation in an M1.8 Flare Observed by the Extreme-ultraviolet Imaging Spectrometer on Hinode

    Science.gov (United States)

    Doschek, G. A.; Warren, H. P.; Young, P. R.

    2013-04-01

    We discuss observations of chromospheric evaporation for a complex flare that occurred on 2012 March 9 near 03:30 UT obtained from the Extreme-ultraviolet Imaging Spectrometer (EIS) on board the Hinode spacecraft. This was a multiple event with a strong energy input that reached the M1.8 class when observed by EIS. EIS was in raster mode and fortunately the slit was almost at the exact location of a significant energy input. Also, EIS obtained a full-CCD spectrum of the flare, i.e., the entire CCD was readout so that data were obtained for about the 500 lines identified in the EIS wavelength ranges. Chromospheric evaporation characterized by 150-200 km s-1 upflows was observed in multiple locations in multi-million degree spectral lines of flare ions such as Fe XXII, Fe XXIII, and Fe XXIV, with simultaneous 20-60 km s-1 upflows in million degree coronal lines from ions such as Fe XII-Fe XVI. The behavior of cooler, transition region ions such as O VI, Fe VIII, He II, and Fe X is more complex, but upflows were also observed in Fe VIII and Fe X lines. At a point close to strong energy input in space and time, the flare ions Fe XXII, Fe XXIII, and Fe XXIV reveal an isothermal source with a temperature close to 14 MK and no strong blueshifted components. At this location there is a strong downflow in cooler active region lines from ions such as Fe XIII and Fe XIV, on the order of 200 km s-1. We speculate that this downflow may be evidence of the downward shock produced by reconnection in the current sheet seen in MHD simulations. A sunquake also occurred near this location. Electron densities were obtained from density sensitive lines ratios from Fe XIII and Fe XIV. Atmospheric Imaging Assembly (AIA) observations from the Solar Dynamics Observatory are used with JHelioviewer to obtain a qualitative overview of the flare. However, AIA data are not presented in this paper. In summary, spectroscopic data from EIS are presented that can be used for predictive tests of

  16. Design of an E-ELT M1 segment measurement machine with nanometer accuracy

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.; te Voert, M.J.A.

    2014-01-01

    The baseline design of the European Extremely Large Telescope features a telescope with a 39-meter-class primary mirror (M1), consisting of 798 hexagonal segments. A measurement machine design is presented based on a non-contact single-point scanning technique, capable of measuring the form error of

  17. Transient analysis of an M/M/1 queue with multiple vacations

    Directory of Open Access Journals (Sweden)

    Kaliappan Kalidass

    2014-05-01

    Full Text Available In this paper, we have obtained explicit expressions for the time dependent probabilities of the M/M/1  queue with server vacations under a multiple vacation scheme. The corresponding steady state probabilities have been obtained. We also obtain the time dependent performance measures of the systems

  18. Study the Effect of Processing of Commercial Kashk Making on Aflatoxin M1 Residue

    Directory of Open Access Journals (Sweden)

    B Hajimohammadi

    2016-03-01

    Full Text Available Introduction: Aflatoxin M1 (AFM1 is a highly toxic compound which is stable during milk processing, and Storage. Hence, it may be found as contaminant in milk and dairy products with hazardous effects for human beings. In this regard, several studies have demonstrated the potential of process to remove Aflatoxin M1 from dairy product. Therefore, the aims of this study were to assess the ability commercial kashk making to reduce Aflatoxin M1 artificially contaminated milk using a natural process of kashk making. Methods: In this study the commercial cheese from cow's milk (skim milk which was contaminated artificially at a level of 0.25 micrograms per liter of aflatoxin M1 was produced at three replications, and the effects of kashk making process on the AFM1 contents were investigated. The HPLC method was used to determine the presence and levels of AFM1. Results: In the commercial kashk production in same concentration between initial milk and commercial kashk caused losses of AFM1 about 91%. These losses were found to be statistically significant (P <0.052 in same concentration between initial milk and commercial kashk. Conclusion: The results of this work demonstrate that the processing of commercial kashk could help to reduce harmful effects of AFM1 humans through consumption of contaminated milk or dairy products.

  19. A Busy period analysis for the state dependent M/M/1/K queue

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; Boxma, Onno

    2010-01-01

    In this paper, we study the transient behavior of a state dependent M/M/1/K queue during the busy period. We derive in closed-form the joint transform of the length of the busy period, the number of customers served during the busy period, and the number of losses during the busy period. For two

  20. Nonlinear calculation of the M=1 internal kink instability in current carrying stellarators

    International Nuclear Information System (INIS)

    Wakatani, M.

    1978-02-01

    Nonlinear properties of the m = 1 internal kink mode are shown in a low β current carrying stellarator. The effects of the external helical magnetic fields are considered through a rotational transform and the magnetic surface is assumed to be circular. Magnetic surfaces inside the iota sub(h) + iota sub(σ) = 1 surface shift and deform non-circularly, while magnetic surfaces outside the iota sub(h) + iota sub(σ) = 1 are not disturbed, where iota sub(h) is a rotational transform due to helical magnetic fields and iota sub(σ) is due to a plasma current. Many higher harmonics are excited after the fundamental mode saturates. When the external helical magnetic fields are lowered, the m = 1 tearing mode similar to that in a low β tokamak grows and magnetic islands appear near the iota sub(h) + iota sub(σ) = 1 surface. For adequate helical magnetic fields, the current carrying stellarator becomes stable against both the m = 1 internal kink mode and the m = 1 tearing mode, without lowering the rotational transform. (auth.)

  1. Effect of Pressure Anisotropy on the m = 1 Small Wavelength Modes in Z-Pinches

    Science.gov (United States)

    Faghihi, M.

    1987-05-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m = 1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (rΣB2)' = 0.

  2. Homocysteine elicits an M1 phenotype in murine macrophages through an EMMPRIN-mediated pathway.

    Science.gov (United States)

    Winchester, Lee J; Veeranki, Sudhakar; Givvimani, Srikanth; Tyagi, Suresh C

    2015-07-01

    Hyperhomocysteinemia (HHcy) is associated with inflammatory diseases and is known to increase the production of reactive oxygen species (ROS), matrix metalloproteinase (MMP)-9, and inducible nitric oxide synthase, and to decrease endothelial nitric oxide production. However, the impact of HHcy on macrophage phenotype differentiation is not well-established. It has been documented that macrophages have 2 distinct phenotypes: the "classically activated/destructive" (M1), and the "alternatively activated/constructive" (M2) subtypes. We hypothesize that HHcy increases M1 macrophage differentiation through extracellular matrix metalloproteinase inducer (EMMPRIN), a known inducer of matrix metalloproteinases. murine J774A.1 and Raw 264.7 macrophages were treated with 100 and 500 μmol/L Hcy, respectively, for 24 h. Samples were analyzed using Western blotting and immunocytochemistry. Homocysteine treatment increased cluster of differentiation 40 (CD40; M1 marker) in J774A.1 and Raw 264.7 macrophages. MMP-9 was induced in both cell lines. EMMPRIN protein expression was also increased in both cell lines. Blocking EMMPRIN function by pre-treating cells with anti-EMMPRIN antibody, with or without Hcy, resulted in significantly lower expression of CD40 in both cell lines by comparison with the controls. A DCFDA assay demonstrated increased ROS production in both cell lines with Hcy treatment when compared with the controls. Our results suggest that HHcy results in an increase of the M1 macrophage phenotype. This effect seems to be at least partially mediated by EMMPRIN induction.

  3. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    have calculated the forbidden transition (M1 and E2) parameters such as transition energies, log- arithmic weighted ... Keywords. Forbidden transitions; transition energies; logarithmic weighted oscillator strengths; .... optimizing the energy function based on the non-relativistic Hamiltonian of an atom,. HNR = N. ∑ j=1. (12∇ ...

  4. Advances in thermal control and performance of the MMT M1 mirror

    Science.gov (United States)

    Gibson, J. D.; Williams, G. G.; Callahan, S.; Comisso, B.; Ortiz, R.; Williams, J. T.

    2010-07-01

    Strategies for thermal control of the 6.5-meter diameter borosilicate honeycomb primary (M1) mirror at the MMT Observatory have included: 1) direct control of ventilation system chiller setpoints by the telescope operator, 2) semiautomated control of chiller setpoints, using a fixed offset from the ambient temperature, and 3) most recently, an automated temperature controller for conditioned air. Details of this automated controller, including the integration of multiple chillers, heat exchangers, and temperature/dew point sensors, are presented here. Constraints and sanity checks for thermal control are also discussed, including: 1) mirror and hardware safety, 2) aluminum coating preservation, and 3) optimization of M1 thermal conditions for science acquisition by minimizing both air-to-glass temperature differences, which cause mirror seeing, and internal glass temperature gradients, which cause wavefront errors. Consideration is given to special operating conditions, such as high dew and frost points. Precise temperature control of conditioned ventilation air as delivered to the M1 mirror cell is also discussed. The performance of the new automated controller is assessed and compared to previous control strategies. Finally, suggestions are made for further refinement of the M1 mirror thermal control system and related algorithms.

  5. TSOAK-M1: an examination of its model and methods

    International Nuclear Information System (INIS)

    Edgell, D.H.

    1983-05-01

    Fusion facilities will contain a sizable inventory of tritium fuel that will be vulnerable to release. Once released, molecular tritium begins converting into tritiated water which is 10000 times more hazardous and tends to adsorb onto surfaces. The rate of conversion and adsorption/desorption must be accurately known to estimate cleanup times and radiation hazards realistically. Argonne National Laboratory developed a computer code, TSOAK-M1, to determine the conversion/ adsorption/desorption parameters and to model cleanups. The Canadian Fusion Fuels Technology Project examined the program for reliability and potential applications. TSOAK-M1 assumes a pseudo second order radiolytic conversion where a first order surface reaction seems more appropriate. This difference in order should be investigated to accurately determine the reaction law. TSOAK-M1 determines the model parameters from experimental data using an optimization routine. However the data used is judged insufficient. More data is needed where the conversion of molecular tritium to tritiated water has a significant effect due to adsorption/desorption. SOAKER, an improved version of the TSOAK-M1 model, which combines first and second order reactions has been implemented in Wang BASIC. Once the reaction law and the parameters have been accurately determined the program could be a useful tool in the study and design of decontamination systems

  6. Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

    African Journals Online (AJOL)

    Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

  7. First Observation of the M1 Transition psi -> gamma eta(c)(2S)

    NARCIS (Netherlands)

    Ablikim, M.; Achasov, M. N.; Ambrose, D. J.; An, F. F.; An, Q.; An, Z. H.; Bai, J. Z.; Ban, Y.; Becker, J.; Berger, N.; Bertani, M.; Bian, J. M.; Boger, E.; Bondarenko, O.; Boyko, I.; Briere, R. A.; Bytev, V.; Cai, X.; Calcaterra, A.; Cao, G. F.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, Y.; Chen, Y. B.; Cheng, H. P.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; Ding, W. M.; Ding, Y.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Fang, J.; Fang, S. S.; Fava, L.; Feldbauer, F.; Feng, C. Q.; Ferroli, R. B.; Fu, C. D.; Fu, J. L.; Gao, Y.; Geng, C.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y. P.; Han, Y. L.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, M.; He, Z. Y.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, H. M.; Hu, J. F.; Hu, T.; Huang, B.; Huang, G. M.; Huang, J. S.; Huang, X. T.; Huang, Y. P.; Hussain, T.; Ji, C. S.; Ji, Q.; Ji, X. B.; Ji, X. L.; Jia, L. K.; Jiang, L. L.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jing, F. F.; Kalantar-Nayestanaki, N.; Kavatsyuk, M.; Kuehn, W.; Lai, W.; Lange, J. S.; Leung, J. K. C.; Li, C. H.; Li, Cheng; Li, Cui; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, K.; Li, Lei; Li, N. B.; Li, Q. J.; Li, S. L.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, X. R.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Liao, X. T.; Liu, B. J.; Liu, B. J.; Liu, C. L.; Liu, C. X.; Liu, C. Y.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H.; Liu, H. B.; Liu, H. H.; Liu, H. M.; Liu, H. W.; Liu, J. P.; Liu, K. Y.; Liu, Kai; Liu, Kun; Liu, P. L.; Liu, S. B.; Liu, X.; Liu, X. H.; Liu, Y.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H.; Lu, G. R.; Lu, H. J.; Lu, J. G.; Lu, Q. W.; Lu, X. R.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lv, M.; Ma, C. L.; Ma, F. C.; Ma, H. L.; Ma, Q. M.; Ma, S.; Ma, T.; Ma, X. Y.; Ma, Y.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, H.; Mao, Y. J.; Mao, Z. P.; Messchendorp, J. G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Morales, C. Morales; Motzko, C.; Muchnoi, N. Yu.; Nefedov, Y.; Nicholson, C.; Nikolaev, I. B.; Ning, Z.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Park, J. W.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Ping, J. L.; Ping, R. G.; Poling, R.; Prencipe, E.; Pun, C. S. J.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, X. S.; Qin, Y.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Rong, G.; Ruan, X. D.; Sarantsev, A.; Schaefer, B. D.; Schulze, J.; Shao, M.; Shen, C. P.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, X. Y.; Spataro, S.; Spruck, B.; Sun, D. H.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. D.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Thorndike, E. H.; Tian, H. L.; Toth, D.; Ullrich, M.; Varner, G. S.; Wang, B.; Wang, B. Q.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q.; Wang, Q. J.; Wang, S. G.; Wang, X. F.; Wang, X. L.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wei, D. H.; Weidenkaff, P.; Wen, Q. G.; Wen, S. P.; Werner, M.; Wiedner, U.; Wu, L. H.; Wu, N.; Wu, S. X.; Wu, W.; Wu, Z.; Xia, L. G.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, G. M.; Xu, H.; Xu, Q. J.; Xu, X. P.; Xu, Y.; Xu, Z. R.; Xue, F.; Xue, Z.; Yan, L.; Yan, W. B.; Yan, Y. H.; Yang, H. X.; Yang, T.; Yang, Y.; Yang, Y. X.; Ye, H.; Ye, M.; Ye, M. H.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yu, L.; Yu, S. P.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. G.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, L.; Zhang, S. H.; Zhang, T. R.; Zhang, X. J.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. S.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, H. S.; Zhao, J. W.; Zhao, K. X.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, X. H.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, Y. H.; Zheng, Z. P.; Zhong, B.; Zhong, J.; Zhou, L.; Zhou, X. K.; Zhou, X. R.; Zhu, C.; Zhu, K.; Zhu, K. J.; Zhu, S. H.; Zhu, X. L.; Zhu, X. W.; Zhu, Y. M.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Zuo, J. X.

    2012-01-01

    Using a sample of 106 x 10(6) psi(3686) events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium S-wave spin-triplet and the radially excited S-wave spin-singlet states: psi(3686) -> gamma

  8. The complex structures on the coadjoint orbit spaces of Diff(S1) and on Bers' universal Teichmueller space are compatible

    International Nuclear Information System (INIS)

    Nag, S.; Verjovsky, A.

    1988-08-01

    Precisely two coadjoint orbit spaces of the group of string reparametrizations carry in a natural way the structure of infinite dimensional, holomorphically homogeneous complex manifolds. These are M 1 =Diff(S 1 )/Rot(S 1 ) and M 2 =Diff(S 1 )/Mo-barb(S 1 ). M 2 can be naturally considered as (embedded in) the classical univeral Teichmueller space T(Δ), simply by noting that a diffeomorphism of S 1 is a quasi-symmetric homeomorphism. T(Δ) is itself a homomorphically homogeneous complex Banach manifold. We prove that the inclusion of M 2 in T(Δ) is complex analytic. Every Teichmueller space of finite or infinite dimension is contained canonically and holomorphically in T(Δ). Our result thus appears to connect the loop space approach to bosonic string theory with the sum-over moduli (Polyakov path integral) approach. (author). 12 refs

  9. [A case of breast cancer with multiple hepatic metastasis successfully treated with S-1/PTX and S-1 chemotherapy].

    Science.gov (United States)

    Hashimoto, Masakazu; Moriyuki, Toshio; Kuranishi, Fumito; Niitsu, Hiroaki; Fujikuni, Nobuaki; Iwako, Hiroshi; Kuroda, Yoshinori

    2010-06-01

    The case is a woman in her 50's. A total glandectomy was performed for her breast cancer on August 8, 1998, and subsequently chemotherapy(5'-DFUR, CMF, uracil.tegafur, CEF, and docetaxel)as well as radiation therapy and surgical resection have been performed for local recurrence. With multiple hepatic metastasis recognized in September, 2007, chemotherapy combined with S-1/paclitaxel(PTX)has been performed. In view of the side effects such as reduction in appetite and leukocyte, the dosage has been reduced as of the second course of treatment. With the disappearance of hepatic metastasis on CT, 6 courses of S-1monotherapy have been performed after completing 6 courses of chemotherapy combined with S-1/ PTX. As of March, 2009, the therapeutic effect shows that continuous CR and outpatient follow-up have been performed while maintaining QOL. Since any chemotherapy after thirdline treatment for recurrent breast cancer has not been established yet, chemotherapy combined with S-1/PTX is considered to be one of the regimens and therefore, the second and thirdphase clinical tests ahead are expected to bring better outcomes.

  10. S1-sensitive sites in DNA after γ-irradiation

    International Nuclear Information System (INIS)

    Martin-Bertram, H.

    1981-01-01

    DNA from γ-irradiated T 1 bacteriophages was analyzed for 'single-stranded' sites by cleavage with S1 nuclease from Aspergillus oryzae as lesion probe. The ratio of 'S1-sensitive sites' to the amount of radiation-induced single-strand breaks was about one. Presumably these 'denatured' sites were associated with single-strand breaks. The subsequent check for the persistence of 'single-stranded' sites within the DNA molecule by thermokinetics demonstrated a strong affinity of the nuclease to its substrate, the single-stranded lesion, and a perfect excision. It is assumed that the direct absorption of radiation energy in the DNA gives rise to the formation of such bulky lesions. (Auth.)

  11. Saturn V First Stage (S-1C) At MSFC

    Science.gov (United States)

    1960-01-01

    This small group of unidentified officials is dwarfed by the gigantic size of the Saturn V first stage (S-1C) at the shipping area of the Manufacturing Engineering Laboratory at Marshall Space Flight Center in Huntsville, Alabama. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

  12. Osmo-, thermo- and ethanol- tolerances of Saccharomyces cerevisiae S1

    Directory of Open Access Journals (Sweden)

    Sandrasegarampillai Balakumar

    2012-03-01

    Full Text Available Saccharomyces cerevisiae S1, which is a locally isolated and improved strain showed viability at 40, 45 and 50ºC and produced ethanol at 40, 43 and 45ºC. When the cells were given heat shock at 45ºC for 30min and grown at 40ºC, 100% viability was observed for 60h, and addition of 200gl-1 ethanol has led to complete cell death at 30h. Heat shock given at 45ºC (for 30min has improved the tolerance to temperature induced ethanol shock leading to 37% viability at 30h. when the cells were subjected to ethanol (200gl-1 for 30 min and osmotic shock (sorbitol 300gl-1, trehalose contents in the cells were increased. The heat shocked cells showed better viability in presence of added ethanol. Soy flour supplementation has improved the viability of S. cerevisiae S1 to 80% in presence of 100gl-1 added ethanol and to 60% in presence of 300gl-1 sorbitol. In presence of sorbitol (200gl-1 and ethanol (50gl-1 at 40ºC, 46% viability was retained by S. cerevisiae S1 at 48h and it was improved to 80% by soy flour supplementation.

  13. Gutzwiller approach for elementary excitations in S = 1 antiferromagnetic chains

    International Nuclear Information System (INIS)

    Liu, Zheng-Xin; Zhou, Yi; Ng, Tai-Kai

    2014-01-01

    In a previous paper (Liu et al 2012 Phys. Rev. B 85 195144), a variational Monte Carlo method (based on Gutzwiller projected states) was generalized to S = 1 systems. This method provided very good trial ground states for the gapped phases of an S = 1 bilinear-biquadratic (BLBQ) Heisenberg chain. In this paper, we extend the approach to study the low-lying elementary excitations in S = 1 chains. We calculate the one-magnon and two-magnon excitation spectra of the BLBQ Heisenberg chain and the results agree very well with recent data in the literature. In our approach, the difference of the excitation spectrum between the Haldane phase and the dimer phase (such as the even/odd size effect) can be understood from their different topologies of the corresponding mean field theory. We especially study the Takhtajan–Babujian critical point. Despite the fact that the ‘elementary excitations’ are spin-1 magnons, which are different from the spin-1/2 spinons in Bethe solution, we show that the excitation spectrum, critical exponent (η=0.74) and central charge (c = 1.45) calculated from our theory agree well with the Bethe ansatz solution and conformal field theory predictions. (paper)

  14. Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

    International Nuclear Information System (INIS)

    Morimoto, Shigefumi; Kitada, Noriaki; Anami, Setsuko

    2008-01-01

    Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. At hospitals giving priority to chemotherapy, it became clear that appropriate treatment was promoted by decreasing. The individual target dosage on the basis of daily medical examination. (author)

  15. Calibration of GEO 600 for the S1 science run

    International Nuclear Information System (INIS)

    Hewitson, M; Grote, H; Heinzel, G; Strain, K A; Ward, H; Weiland, U

    2003-01-01

    In 2002, the interferometric gravitational wave detector GEO 600 took part in a coincident science run (S1) with other detectors world-wide. When completed, GEO will employ a dual-recycling scheme which will allow its peak sensitivity to be tuned over a range of frequencies in the detection band. Still in the commissioning phase, GEO was operated as a power-recycled Michelson for the duration of S1. The accurate calibration of the sensitivity of GEO to gravitational waves is a critical step in preparing GEO data for exchange with other detectors forming a world-wide detector network. An online calibration scheme has been developed to perform real-time calibration of the power-recycled GEO detector. This scheme will later be extended to cover the more complex case of the dual-recycled interferometer in which multiple output signals will need to be combined to optimally recover a calibrated strain channel. This report presents an outline of the calibration scheme that was used during S1. Also presented are results of detector characterization work that arises naturally from the calibration work

  16. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    International Nuclear Information System (INIS)

    Zhirnov, O.P.; Manykin, A.A.; Rossman, J.S.; Klenk, H.D.

    2016-01-01

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  17. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-12-01

    Full Text Available Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, pregnant women and elderly. The objective of this study was to detect the presence of B1 aflatoxin in feed supplied to dairy cows and the presence of M1 aflatoxin in milk. Samples were collected from complete diet (corn silage and concentrate from a batch of 15 lactating cows from a dairy farm in the Campinas region. Two samples of diets were collected directly into the troughs in intervals of 24 hours at every 15 days, totalizing a period of 45 days. Milk samples of those cows were collected 24 hours after diet collection, directly from sample valves in the glass jars.. B1 and M1 aflatoxins were detected by the technique of High Performance Liquid Chromatography after extraction and purification on immunoaffinity columns. From the 40 samples of diets evaluated, 40% were contaminated with B1 aflatoxin, and the levels found ranged from 1.93 to 43.78μg/Kg. One sample showed result higher than the maximum recommended for grain and animal feed in Brazil (20μg/Kg. From the 75 milk samples analyzed, the presence of M1 aflatoxin was detected in 13.3% with levels ranging from 0.03 to 0.16μg/L, not exceeding the maximum permitted for marketing in the country of 0.5μg/L, however 80% of contaminated samples had values above the maximum permissible levels of 0.05μg/L, value found among countries with abundant milk production... The presence of aflatoxins highlights the importance of monitoring the production, the storage and the importance of handling food and

  18. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Manykin, A.A. [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Rossman, J.S. [School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom); Klenk, H.D. [Institute of Virology, Philipps University, Marburg 35037 (Germany)

    2016-05-15

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  19. Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages

    Directory of Open Access Journals (Sweden)

    Sanjima Pal

    2016-06-01

    Full Text Available Any chronic, inflammatory, autoimmune disease (e.g. arthritis associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I–IV induced auto-reactive M1 type monocyte/macrophage model.

  20. CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Olusiji A. Akinrinmade

    2017-09-01

    Full Text Available To date, no curative therapy is available for the treatment of most chronic inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, or autoimmune disorders. Current treatments require a lifetime supply for patients to alleviate clinical symptoms and are unable to stop the course of disease. In contrast, a new series of immunotherapeutic agents targeting the Fc γ receptor I (CD64 have emerged and demonstrated significant clinical potential to actually resolving chronic inflammation driven by M1-type dysregulated macrophages. This subpopulation plays a key role in the initiation and maintenance of a series of chronic diseases. The novel recombinant M1-specific immunotherapeutics offer the prospect of highly effective treatment strategies as they have been shown to selectively eliminate the disease-causing macrophage subpopulations. In this review, we provide a detailed summary of the data generated, together with the advantages and the clinical potential of CD64-based targeted therapies for the treatment of chronic inflammatory diseases.

  1. B(M1) values in the band-crossing of shears bands in 197Pb

    Science.gov (United States)

    Krücken, R.; Cooper, J. R.; Beausang, C. W.; Novak, J. R.; Dewald, A.; Klug, T.; Kemper, G.; von Brentano, P.; Carpenter, M.; Wiedenhöver, I.

    We present details of the band crossing mechanism of shears bands using the example of 197Pb. Absolute reduced matrix elements B(M1) were determined by means of a RDM lifetime measurement in one of the shears bands in 197Pb. The experiment was performed using the New Yale Plunger Device (NYPD) in conjunction with the Gammasphere array. Band mixing calculations on the basis of the semi-classical model of the shears mechanism are used to describe the transition matrix elements B(M1) and energies throughout the band-crossing regions. Good agreement with the data was obtained and the detailed composition of the states in the shears band are discussed.

  2. Observation of the M1 giant resonance by resonance averaging in 106Pd

    International Nuclear Information System (INIS)

    Kopecky, J.

    1987-01-01

    An investigation of capture of 2 keV and 24 keV neutrons in a 105 Pd target resulted in resonance-averaged intensities of primary gamma rays with energies between 5.2 and 9.5 MeV. From these intensities the gamma ray strength functions have been evaluated for E1, M1 and E2 radiation and compared with predictions of the giant resonance theory. The inclusion of an energy dependent spreading width for the E1 giant resonance is necessary. The energy distribution of M1 reduced strength is consistent with an interpretation of a broad resonance around 8.8 MeV. E2 data agrees satisfactorily with the giant extrapolation. (orig.)

  3. IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Serkan I. Göktuna

    2014-06-01

    Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

  4. Prototyping the E-ELT M1 local control system communication infrastructure

    Science.gov (United States)

    Argomedo, J.; Kornweibel, N.; Grudzien, T.; Dimmler, M.; Andolfato, L.; Barriga, P.

    2016-08-01

    The primary mirror of the E-ELT is composed of 798 hexagonal segments of about 1.45 meters across. Each segment can be moved in piston and tip-tilt using three position actuators. Inductive edge sensors are used to provide feedback for global reconstruction of the mirror shape. The E-ELT M1 Local Control System will provide a deterministic infrastructure for collecting edge sensor and actuators readings and distribute the new position actuators references while at the same time providing failure detection, isolation and notification, synchronization, monitoring and configuration management. The present paper describes the prototyping activities carried out to verify the feasibility of the E-ELT M1 local control system communication architecture design and assess its performance and potential limitations.

  5. Efficacy of magnetoacustoradiation treatment of experimental M-1, PC-1 tumors

    International Nuclear Information System (INIS)

    Chizh, D.V.; Krutilina, N.I.

    2011-01-01

    The urgency of the struggle against malignant tumors is determined by a stable growth of cancer incidence, high level of disability and morbidity, the cost and difficulty of treatment. The influence of low-frequency ultrasound and alternating magnetic field on transplanted tumors of sarcoma M-1 and alveolar liver cancer PC-1 together with radiation therapy at a SFD of 5 Gy and 20 Gy was investigated in the experiments on animals. It was established that the influence of the above physical factors inhibited sarcoma M-1 and alveolar liver cancer PC-1 growth, prolonged the life and survival of the animals of the investigated groups when compared to the intact controls, which definitely expanded the ideas about the capabilities of ultrasound and magnetic fields in cancer treatment.

  6. Design and optimization of selective azaindole amide M1 positive allosteric modulators.

    Science.gov (United States)

    Davoren, Jennifer E; O'Neil, Steven V; Anderson, Dennis P; Brodney, Michael A; Chenard, Lois; Dlugolenski, Keith; Edgerton, Jeremy R; Green, Michael; Garnsey, Michelle; Grimwood, Sarah; Harris, Anthony R; Kauffman, Gregory W; LaChapelle, Erik; Lazzaro, John T; Lee, Che-Wah; Lotarski, Susan M; Nason, Deane M; Obach, R Scott; Reinhart, Veronica; Salomon-Ferrer, Romelia; Steyn, Stefanus J; Webb, Damien; Yan, Jiangli; Zhang, Lei

    2016-01-15

    Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. The effect of gamma and fast neutron irradiations on M1 seedling growth in soybean

    International Nuclear Information System (INIS)

    Hassan, S.; Mohammad, T.; Khan, S.

    1985-01-01

    Seeds of three varieties of soybean, i.e. Bragg, Hodgson and Lee-74, having a moisture content of 11-13% were irradiated with doses of gamma, 100,200,300,400 and 500 Gray and fast neutron, 5,10,20,25 and 30 Gray, to study the effect on M1 seedling growth. The parameters studied were germination, seedling height and epicotyl length. Growth inhibition was found to increase with increasing radiation doses and the effect on germination was observed only at higher doses. Among early assessable M1 parameters for radio-sensitivity, epicotyl length has proved to be most sensitive, and hence most useful. The Relative Biological Effectiveness (RBE) values for the three varieties differed slightly for epicotyl length and the difference was more pronounced for seedling height. A dose range of 150-300 Gray of gamma rays and 10-15 Gray of fast neutron might prove useful for efficient induced mutation. (authors)

  8. Scissors and unique-parity modes of M1 excitation in deformed nuclei

    International Nuclear Information System (INIS)

    Otsuka, T.

    1989-01-01

    In this paper the possible modes of M1 excitation in deformed even-even nuclei are studied in terms of the particle-number-conserved Nilsson + BCS formalism with the standard parameters. The spurious motion with respect to the rotation is removed. In addition to the Scissors mode, the Unique-Parity Spin and Normal-Parity Spin modes are suggested, although the latter may be fragmented to a large extent. The Scissors mode carries most of the orbital strength, while the others the spin strength. The proton Unique-Parity (i.e. Oh 11/12 ) Spin mode for 164 Dy is obtained just below Ex = 3 MeV with B(M1) ∼ 0.2 μ 2 N ) in the sum rule limit. This is in a good agreement to the recent experimental data

  9. Forbidden Raman scattering processes. I. General considerations and E1--M1 scattering

    International Nuclear Information System (INIS)

    Harney, R.C.

    1979-01-01

    The generalized theory of forbidden Raman scattering processes is developed in terms of the multipole expansion of the electromagnetic interaction Hamiltonian. Using the general expressions, the theory of electric dipole--magnetic dipole (E1--M1) Raman scattering is derived in detail. The 1 S 0 → 3 P 1 E1--M1 Raman scattering cross section in atomic magnesium is calculated for two applicable laser wavelengths using published f-value data. Since resonantly enhanced cross sections larger than 10 -29 cm 2 /sr are predicted it should be possible to experimentally observe this scattering phenomenon. In addition, by measuring the frequency dependence of the cross section near resonance, it may be possible to directly determine the relative magnitudes of the Axp and AxA contributions to the scattering cross section. Finally, possible applications of the effect in atomic and molecular physics are discussed

  10. Theoretical expression of the internal conversion coefficient of a M1 transition between two atomic states

    International Nuclear Information System (INIS)

    Attallah, F.; Chemin, J.F.; Scheurer, J.N.; Karpeshin, F.; Harston, M.

    1997-01-01

    We have established a general relation for the expression of the internal conversion of an M 1 transition a 1s electronic state to an empty ns electronic bound state. Under the hypothesis that the density of the electron level ρ n satisfies the condition ρ n Γ >> 1 (where Γ is the total width of the excited atomic state) a calculation in the first order gives a relation for the internal conversion coefficient.This relation shows that the internal conversion coefficient takes a resonant character when the nuclear energy transition is smaller than the binding energy of the 1s electron. An application of this relation to an M 1 transition in the case of the ion 125 T e with a charge state Q = 45 and an 1s electron binding energy E B 45 = 35.581 KeV gives the value for the internal conversion coefficient R = 5.7

  11. Status and perspectives of the M1 scissors mode in nuclei

    International Nuclear Information System (INIS)

    Richter, A.

    1988-07-01

    The present status of the M1 scissors mode which is now known in deformed nuclei ranging from 46 Ti to 238 U is summarized. Particular emphasis is placed on a discussion of the structure, the excitation energy, the transition strength, the form factor and the spin to orbit ratio in the strength of the mode. Finally it is demonstrated how strongly this mode contributes to the magnetic dipole polarizability of nuclei. (orig.)

  12. Magnetic susceptibility and M1 transitions in /sup 208/Pb. [Sum rules

    Energy Technology Data Exchange (ETDEWEB)

    Traini, M; Lipparini, E; Orlandini, G; Stringari, S [Dipartimento di Matematica e Fisica, Universita di Trento, Italy

    1979-04-16

    M1 transitions in /sup 208/Pb are studied by evaluating energy-weighted and inverse energy-weighted sum-rules. The role of the nuclear interaction is widely discussed. It is shown that the nuclear potential increases the energy-weighted sum rule and lowers the inverse energy-weighted sum rule, with respect to the prediction of the pure shell model. Values of strengths and excitation energies are compared with experimental results and other theoretical calculations.

  13. Measurement of Aflatoxin M1 in Raw and Pasteurized Cow Milk Samples by HPLC

    Directory of Open Access Journals (Sweden)

    afshin Nazari

    2007-10-01

    Full Text Available Nazari A1, Noroozi H2, Movahedi M3, Khaksarian M1 1. Instructor, Department of Physiology, Faculty of Medicine, Lorestan University of Medical Sciences 2. Assistant Professor, Department of Mycology, Faculty of Medicine, Iran University of Medical Sciences 3. Assistant Professor, Department of Genetic Epidemiology, Faculty of Medicine, Lorestan University of Medical Sciences Abstract Background: Aflatoxin M1 is a hydroxylated form of aflatoxin B1 which is produced by Aspergillus flavus. This toxin is produced when cows or other ruminants eat foods contaminated with these mycotoxins and then excrete them in the milk. The toxin is a potent liver and kidney carcinogenetic agent. Materials and methods: Forty two raw cows milk samples from local sources of milk collection and forty samples of commercial pasteurized market milk from Khorramabad, Lorestan, Iran were collected in summer and winter season of 2005. Twenty-one cow milk samples and 20 pasteurized milk samples in each season were analyzed for the presence of aflatoxin M1 (AFM1 by HPLC immunoaffinity columns. Results: Four of 21 raw milk samples in summer showed AFM1 levels between 0.017-0.046 ng/ml and all samples (100% in winter showed the presence of AFM1 levels between 0.003-0.041ng/ ml. AFM1 was detected in 55% of market pasteurized cow milk samples ranging from 0.017 to 0.533 ng/ml in summer and 100% ranging from 0.005-0.0054 ng/ml in winter.,Only one of all milk samples of pasteurized milk in summer had toxin level (0.533 ng/ml more than the maximum permissive limit (0.5 ng/ml. No significant difference was observed among mean contamination level of raw and pasteurized cow milk in two seasons. Key words: Aflatoxin M1, raw milk, pasteurized milk, Khoramabad, HPLC

  14. Presynaptic M1 muscarinic receptor modulates spontaneous release of acetylcholine from rat basal forearm slices

    International Nuclear Information System (INIS)

    Suzuki, T.; Fujimoto, LK.; Oohata, H.; Kawashima, K.

    1988-01-01

    Spontaneous release of (ACh) from rat basal forebrain slices in the presence of cholinesterase inhibitor was directly determined using a specific radioimmunoassay for ACh. The release was calcium dependent. A consistent amount of ACh release was observed throughout the experiment. Atropine (10- 8 to 10- 5 M) and pirenzepine (10- 7 to 10- 5 M) enhanced spontaneous ACh release. These findings indicate the presence of an M 1 muscarenic autoreceptor that modulates spontaneous release of ACh in the rat forebrain

  15. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

    Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

  16. Effect of gamma rays on growth and survival of three mustard varieties in M1 generation

    International Nuclear Information System (INIS)

    Kamala, T.; Rao, R.N.B.

    1982-01-01

    Effects of gamma radiation on germination, survival percentage, seedling height, leaf length and breadth, and growth rate in three mustard varieties were studied in M 1 generation. Seeds were exposed to 15, 30, 45, 60 and 80 Kr doses for the study. Germinations and survival percentages and seedling height showed dose-dependent decrease, while growth rate, leaf length and breadth increased at 60, 45 and 30 Kr and decreased at 80 Kr, though varietal differences were observed. (M.G.B.)

  17. Enhanced Macrophage M1 Polarization and Resistance to Apoptosis Enable Resistance to Plague.

    Science.gov (United States)

    Pachulec, Emilia; Abdelwahed Bagga, Rym Ben; Chevallier, Lucie; O'Donnell, Hope; Guillas, Chloé; Jaubert, Jean; Montagutelli, Xavier; Carniel, Elisabeth; Demeure, Christian E

    2017-09-15

    Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined. SEG MPs exhibit a stronger bactericidal activity with higher nitric oxide production, a more proinflammatory polarized cytokine response, and a higher resistance to Y. pestis-induced apoptosis. This response was not specific to Y. pestis and involved a reduced sensitivity to M2 polarization/signal transducer and activator of transcription 6 activation and inhibition of caspase 8. The enhanced M1 profile was inducible in C57BL/6 MPs in vitro, and when transferred to susceptible C57BL/6 mice, these MPs significantly increased survival of bubonic plague. MPs can develop an enhanced functional profile beyond the prototypic M1, characterized by an even more potent proinflammatory response coordinated with resistance to killing. This programming plays a key role in the plague-resistance phenotype and may be similarly significant in other highly lethal infections, suggesting that orienting the MP response may represent a new therapeutic approach. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. Current status of the Thai Research Reactor (TRR-1/M1)

    International Nuclear Information System (INIS)

    Chueinta, Siripone; Julanan, Mongkol; Charncanchee, Decharchai

    2006-01-01

    The first Thai Research Reactor, TRR-1 went critical on 27 October 1962 at the maximum power of 1 MW. It was located at Office of Atoms for Peace (OAP) in Bangkok. Since then, TRR-1 was continuously operated and eventually shut down in 1975. Plate type, high-enriched uranium (HEU) and U 3 O 8 A1 cladding were used as the reactor fuel. Light water was used as moderator and coolant as well. In 1975, because of the problem from fuel supplier and also to supporting the Treaty of Non Proliferation of Nuclear Weapon or NPT, TRR-1 was shut down for modification. The reactor core and control system were disassembled and replaced by TRIGA Mark III. A new core was a hexagonal core shape designed by General Atomics (GA). Afterwards, TRR-1 was officially renamed to the Thai Research Reactor-1/Modification 1 (TRR-1/M1). TRR-1/M1 is a multipurpose swimming pool type reactor with nominal power of 2 MW. The TRR-1/M1 uses uranium enriched at 20% in U-235 (LEU) and ZrH alloy as fuel. Light water is also used as coolant and moderator. At present, the reactor is operating with core No.14. The reactor has been serving for various kinds of utilization namely, radioisotope production, neutron activation analysis, beam experiments and reactor physics experiments. (author)

  19. Surface Termination of M1 Phase and Rational Design of Propane Ammoxidation Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Guliants, Vadim [Univ. of Cincinnati, OH (United States)

    2015-02-16

    This final report describes major accomplishments in this research project which has demonstrated that the M1 phase is the only crystalline phase required for propane ammoxidation to acrylonitrile and that a surface monolayer terminating the ab planes of the M1 phase is responsible for their activity and selectivity in this reaction. Fundamental studies of the topmost surface chemistry and mechanism of propane ammoxidation over the Mo-V-(Te,Sb)-(Nb,Ta)-O M1 and M2 phases resulted in the development of quantitative understanding of the surface molecular structure – reactivity relationships for this unique catalytic system. These oxides possess unique catalytic properties among mixed metal oxides, because they selectively catalyze three alkane transformation reactions, namely propane ammoxidation to acrylonitrile, propane oxidation to acrylic acid and ethane oxidative dehydrogenation, all of considerable economic significance. Therefore, the larger goal of this research was to expand this catalysis to other alkanes of commercial interest, and more broadly, demonstrate successful approaches to rational design of improved catalysts that can be applied to other selective (amm)oxidation processes.

  20. Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy.

    Science.gov (United States)

    Antonicelli, L; Ruello, M L; Monsalve, R I; González, R; Fava, G; Bonifazi, F

    2010-10-01

    Epidemic asthma outbreaks are potentially a very high-risk medical situation in seaport towns where large volumes of soybean are loaded and unloaded Airborne allergen assessment plays a pivotal role in evaluating the resulting environmental pollution. The aim of this study was to measure the airborne Gly m 1 allergen level in the seaport of Ancona in order assess the soybean-specific allergenic risk for the city. Allergen and PM10 were evaluated at progressive distances from the port area. Allergen analysis was performed by monoclonal antibody-based immunoassay on the sampled filters. Daily meteorological data were obtained from the local meteorological station. For estimating the assimilative capacity of the atmosphere, an approach based on dispersive ventilation coefficient was tried. The allergen concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne Gly m 1 was not coupled with the presence of the soy-carrying ships in the port. A statistically significant relationship between airborne allergen, PM10 and local meteorological parameters quantifies the association with the atmospheric condition. Airborne Gly m 1 is part of the atmospheric dust of Ancona. The low level of this allergen seems consistent with the absence of asthma epidemic outbreak.

  1. Energetic M1 transitions as a probe of nuclear collectivity at high temperatures

    International Nuclear Information System (INIS)

    Baktash, C.

    1987-01-01

    At ORNL, we have recently utilized the Spin Spectrometer setup to investigate the differential effects of increasing spin and excitation energy on nuclear shape and collectivity in 158 Yb. Along the yrast line of this and other N = 88 nuclei, weakly prolate shapes gradually give way to triaxial, and then finally to non-collective oblate shapes as the spin approaches 40 h-bar. However, above the yrast line, large deformation and collectivity once again sets in. This is evidenced by the emergence of a broad quadrupole structure (E/sub γ/ ≅ 1.2 MeV) in the continuum gamma-ray spectra that grows with increasing temperature. The short (sub ps) lifetimes of these transitions attest to the collective nature of these structures. The emergence and growth of the quadrupole structure at high excitation energies is closely correlated with the appearance of energetic (E/sub γ/ ≅ 2.5 MeV), fast M1 transitions which form another broad structure in the continuum spectra. From the centroid of the M1 bump, a quadrupole deformation parameter of 0.35 is inferred. Because of this sensitivity, these energetic M1 transitions provide a unique probe of nuclear shape in the excitation energy range of ≅ 3 to 10 MeV. 6 refs., 2 figs

  2. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results.

  3. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results.

  4. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    International Nuclear Information System (INIS)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results

  5. Interaction of integrin β4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement.

    Science.gov (United States)

    Ni, Xiuqin; Epshtein, Yulia; Chen, Weiguo; Zhou, Tingting; Xie, Lishi; Garcia, Joe G N; Jacobson, Jeffrey R

    2014-06-01

    We previously reported sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF) augment endothelial cell (EC) barrier function and attenuate murine acute lung inury (ALI). While the mechanisms underlying these effects are not fully understood, S1P and HGF both transactivate the S1P receptor, S1PR1 and integrin β4 (ITGB4) at membrane caveolin-enriched microdomains (CEMs). In the current study, we investigated the roles of S1PR2 and S1PR3 in S1P/HGF-mediated EC signaling and their associations with ITGB4. Our studies confirmed ITGB4 and S1PR2/3 are recruited to CEMs in human lung EC in response to either S1P (1 µM, 5 min) or HGF (25 ng/ml, 5 min). Co-immunoprecipitation experiments identified an S1P/HGF-mediated interaction of ITGB4 with both S1PR2 and S1PR3. We then employed an in situ proximity ligation assay (PLA) to confirm a direct ITGB4-S1PR3 association induced by S1P/HGF although a direct association was not detectable between S1PR2 and ITGB4. S1PR1 knockdown (siRNA), however, abrogated S1P/HGF-induced ITGB4-S1PR2 associations while there was no effect on ITGB4-S1PR3 associations. Moreover, PLA confirmed a direct association between S1PR1 and S1PR2 induced by S1P and HGF. Finally, silencing of S1PR2 significantly attenuated S1P/HGF-induced EC barrier enhancement as measured by transendothelial resistance while silencing of S1PR3 significantly augmented S1P/HGF-induced barrier enhancement. These results confirm an important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4. Our findings elucidate novel mechanisms of EC barrier regulation that may ultimately lead to new therapeutic targets for disorders characterized by increased vascular permeability including ALI. © 2013 Wiley Periodicals, Inc.

  6. Comparative genomics of Streptococcus pyogenes M1 isolates differing in virulence and propensity to cause systemic infection in mice

    NARCIS (Netherlands)

    Fiebig, A.; Loof, T.G.; Babbar, A.; Itzeg, A.; Koehorst, J.J.; Schaap, P.J.; Nitsche-Schmitz, D.P.

    2015-01-01

    Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to

  7. Chromospheric evaporation flows and density changes deduced from Hinode/EIS during an M1.6 flare

    Science.gov (United States)

    Gömöry, P.; Veronig, A. M.; Su, Y.; Temmer, M.; Thalmann, J. K.

    2016-04-01

    Aims: We study the response of the solar atmosphere during a GOES M1.6 flare using spectroscopic and imaging observations. In particular, we examine the evolution of the mass flows and electron density together with the energy input derived from hard X-ray (HXR) in the context of chromospheric evaporation. Methods: We analyzed high-cadence sit-and-stare observations acquired with the Hinode/EIS spectrometer in the Fe xiii 202.044 Å (log T = 6.2) and Fe xvi 262.980 Å (log T = 6.4) spectral lines to derive temporal variations of the line intensity, Doppler shifts, and electron density during the flare. We combined these data with HXR measurements acquired with RHESSI to derive the energy input to the lower atmosphere by flare-accelerated electrons. Results: During the flare impulsive phase, we observe no significant flows in the cooler Fe xiii line but strong upflows, up to 80-150 km s-1, in the hotter Fe xvi line. The largest Doppler shifts observed in the Fe xvi line were co-temporal with the sharp intensity peak. The electron density obtained from a Fe xiii line pair ratio exhibited fast increase (within two minutes) from the pre-flare level of 5.01 × 109 cm-3 to 3.16 × 1010 cm-3 during the flare peak. The nonthermal energy flux density deposited from the coronal acceleration site to the lower atmospheric layers during the flare peak was found to be 1.34 × 1010 erg s-1 cm-2 for a low-energy cut-off that was estimated to be 16 keV. During the decline flare phase, we found a secondary intensity and density peak of lower amplitude that was preceded by upflows of ~15 km s-1 that were detected in both lines. The flare was also accompanied by a filament eruption that was partly captured by the EIS observations. We derived Doppler velocities of 250-300 km s-1 for the upflowing filament material. Conclusions: The spectroscopic results for the flare peak are consistent with the scenario of explosive chromospheric evaporation, although a comparatively low value of the

  8. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  9. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Science.gov (United States)

    Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

  10. Quenched Approximation to ΔS = 1 K Decay

    International Nuclear Information System (INIS)

    Christ, Norman H.

    2005-01-01

    The importance of explicit quark loops in the amplitudes contributing to ΔS = 1, K meson decays raises potential ambiguities when these amplitudes are evaluated in the quenched approximation. Using the factorization of these amplitudes into short- and long-distance parts provided by the standard low-energy effective weak Hamiltonian, we argue that the quenched approximation can be conventionally justified if it is applied to the long-distance portion of each amplitude. The result is a reasonably well-motivated definition of the quenched approximation that is close to that employed in the RBC and CP-PACS calculations of these quantities

  11. Local carbon diffusion coefficient measurement in the S-1 spheromak

    International Nuclear Information System (INIS)

    Mayo, R.M.; Levinton, F.M.; Meyerhofer, D.D.; Chu, T.K.; Paul, S.F.; Yamada, M.

    1988-10-01

    The local carbon diffusion coefficient was measured in the S - 1 spheromak by detecting the radial spread of injected carbon impurity. The radial impurity density profile is determined by the balance of ionization and diffusion. Using measured local electron temperature T/sub e/ and density n/sub e/, the ionization rate is determined from which the particle diffusion coefficient is inferred. The results found in this work are consistent with Bohm diffusion. The absolute magnitude of D/sub /perpendicular// was determined to be (4/approximately/6) /times/ D/sub Bohm/. 25 refs., 13 figs., 2 tabs

  12. [S1 Herpes zoster localization: acute urinary retention in woman].

    Science.gov (United States)

    Vella, Marco; Mastrocinque, Giuseppe; Romeo, Salvatore; Giammanco, Giovanni; Melloni, Darwin

    2011-01-01

    Acute urinary retention in women is rare. The varicella-zoster virus causes inflammatory lesions of the sensory-root ganglions, meninges and, less frequently, spinal cord. Herpes zoster has been reported to affect, although rarely, lower urinary tract innervations, and acute urinary retention can be thought to occur in the presence of sacral dermatome involvement. Usually it is located in S2-4 dermatome and the prognosis for acute urinary retention is benign resolving in about 20 days. We present a case in which the S1 dermatome was involved and acute urinary retention developed. After 10 days of specific therapy and self-catheterization the problem resolved.

  13. Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase.

    Directory of Open Access Journals (Sweden)

    Evgeny V Berdyshev

    Full Text Available BACKGROUND: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P induces migration of human pulmonary artery endothelial cells (HPAECs through the activation of S1P(1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs and S1P lyase (S1PL, that regulate intracellular S1P accumulation, in HPAEC motility. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino-4-(p-Chlorophenyl Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1P(int, and attenuated S1P(ext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1P(int and potentiated motility of HPAECs to S1P(ext or serum. S1P(ext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting "inside-out" signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs. Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1P(ext or 4-deoxypyridoxine-dependent endothelial cell motility. CONCLUSIONS/SIGNIFICANCE: These results suggest S1P(ext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL.

  14. Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

    Science.gov (United States)

    Berdyshev, Evgeny V.; Gorshkova, Irina; Usatyuk, Peter; Kalari, Satish; Zhao, Yutong; Pyne, Nigel J.; Pyne, Susan; Sabbadini, Roger A.; Garcia, Joe G. N.; Natarajan, Viswanathan

    2011-01-01

    Background Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility. Methodology/Principal Findings Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino)-4-(p-Chlorophenyl) Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1Pint, and attenuated S1Pext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1Pint and potentiated motility of HPAECs to S1Pext or serum. S1Pext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting “inside-out” signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs). Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1Pext or 4-deoxypyridoxine-dependent endothelial cell motility. Conclusions/Significance These results suggest S1Pext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL. PMID:21304987

  15. LCLS-S1 optical transition radiation monitor

    International Nuclear Information System (INIS)

    Berg, W.J.; Yang, B.; Erwin, L.L.; Shoaf, S.E.

    2008-01-01

    Argonne National Laboratory has developed a high- resolution optical transition radiation (OTR) imaging monitor for the Linac Coherent Light Source (LCLS) injection linac at SLAC. The imaging station,OTR-S1, will be located at the S1 spectrometer with a beam energy of 135 MeV. The system will be used to acquire 2-D transverse beam distributions of the accelerated photocathode-gun-generated electron beam. We anticipate an average beam current of 0.2 to 1 nC and nominal beam spot size of 130 mum (sigmax), 100 mum (sigmay). The imaging system was designed for a field of view x/y: 10 times 7.5 mm. The spatial resolution of ∼12 microns was verified over the central 5times4 mm region in the visible. A 12-bit digital camera acquires the image and a Mac-based digital frame-capturing system was employed for the initial lab-based performance testing of the device. We report on system development, testing methods, and data analysis.

  16. Complete genome sequence of Rhodospirillum rubrum type strain (S1).

    Science.gov (United States)

    Munk, A Christine; Copeland, Alex; Lucas, Susan; Lapidus, Alla; Del Rio, Tijana Glavina; Barry, Kerrie; Detter, John C; Hammon, Nancy; Israni, Sanjay; Pitluck, Sam; Brettin, Thomas; Bruce, David; Han, Cliff; Tapia, Roxanne; Gilna, Paul; Schmutz, Jeremy; Larimer, Frank; Land, Miriam; Kyrpides, Nikos C; Mavromatis, Konstantinos; Richardson, Paul; Rohde, Manfred; Göker, Markus; Klenk, Hans-Peter; Zhang, Yaoping; Roberts, Gary P; Reslewic, Susan; Schwartz, David C

    2011-07-01

    Rhodospirillum rubrum (Esmarch 1887) Molisch 1907 is the type species of the genus Rhodospirillum, which is the type genus of the family Rhodospirillaceae in the class Alphaproteobacteria. The species is of special interest because it is an anoxygenic phototroph that produces extracellular elemental sulfur (instead of oxygen) while harvesting light. It contains one of the most simple photosynthetic systems currently known, lacking light harvesting complex 2. Strain S1(T) can grow on carbon monoxide as sole energy source. With currently over 1,750 PubMed entries, R. rubrum is one of the most intensively studied microbial species, in particular for physiological and genetic studies. Next to R. centenum strain SW, the genome sequence of strain S1(T) is only the second genome of a member of the genus Rhodospirillum to be published, but the first type strain genome from the genus. The 4,352,825 bp long chromosome and 53,732 bp plasmid with a total of 3,850 protein-coding and 83 RNA genes were sequenced as part of the DOE Joint Genome Institute Program DOEM 2002.

  17. Relationship between pattern of ischemic manifestation and hemodynamics in symptomatic M1 stenosis

    International Nuclear Information System (INIS)

    Tokumitsu, Naoki; Sako, Kazuhiro; Aizawa, Shizuka; Shirai, Wakako

    2002-01-01

    The mechanism through which ischemic manifestations develop in patients with middle cerebral artery (MCA) stenosis is still uncertain. It may cause ischemic symptoms through both embolic and hemodynamic mechanisms. In this study, we compared the findings from cerebral angiograms with single photon emission computed tomography (SPECT) in patients with M1 stenosis to determine the pathogenesis of ischema. At our hospital from 1994 to 2000, 14 patients (12 males and 2 females; mean age, 60.9; range, 31 to 85 years) with angiographically demonstrated symptomatic M1 stenosis were enrolled in this study. In 10, their stenotic lesion was located at the proximal site of the perforating arteries and for the other 4, stenosis was found at the distal site. Nine presented with transient ischemic attack (TIA) and 5 with completed stroke for an initial episode. The discrepancy in regional cerebral blood flow (rCBF) was evaluated in relation to the site and degree of stenosis, type of ischemic presentation, and frequency of ischemic events. There was no significant difference in CBF between the patients with stenosis involving the proximal site and those with distal stenosis; but the cortical CBF decreased significantly in those with severe stenosis compared with moderate stenosis. The cortical CBF of those who had a complete stroke is similar to that of the patients with TIA; but CBF of BGA decreased significantly in those with a complete stroke. The single ischemic event group showed a significant decrease in cortical CBF. On the other hand, the group with multiple ischemic events exhibited normal hemodynamics. We concluded that multiple ischemic events that occurred in M1 stenosis are caused by an embolic mechanism. (author)

  18. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.

    Science.gov (United States)

    Farias, L H S; Rodrigues, A P D; Coêlho, E C; Santos, M F; Sampaio, S C; Silva, E O

    2017-09-01

    American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.

  19. Mice in Bion-M 1 Space Mission: Training and Selection

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Popova, Anfisa; Boyle, Richard; Alberts, Jeffrey; Shenkman, Boris; Vinogradova, Olga; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Darya; Soldatov, Pavel; Nemirovskaya, Tatyana; Ilyin, Eugeniy; Sychev, Vladimir

    2014-01-01

    After a 16-year hiatus, Russia has resumed its program of biomedical research in space, with the successful 30-day flight of the Bion-M 1 biosatellite (April 19–May 19, 2013). The principal species for biomedical research in this project was the mouse. This paper presents an overview of the scientific goals, the experimental design and the mouse training/selection program. The aim of mice experiments in the Bion-M 1 project was to elucidate cellular and molecular mechanisms, underlying the adaptation of key physiological systems to long-term exposure in microgravity. The studies with mice combined in vivo measurements, both in flight and post-flight (including continuous blood pressure measurement), with extensive in vitro studies carried out shortly after return of the mice and in the end of recovery study. Male C57/BL6 mice group housed in space habitats were flown aboard the Bion-M 1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control groups were used to account for housing effects and possible seasonal differences. Mice training included the co-adaptation in housing groups and mice adaptation to paste food diet. The measures taken to co-adapt aggressive male mice in housing groups and the peculiarities of “space” paste food are described. The training program for mice designated for in vivo studies was broader and included behavioral/functional test battery and continuous behavioral measurements in the home-cage. The results of the preliminary tests were used for the selection of homogenous groups. After the flight, mice were in good condition for biomedical studies and displayed signs of pronounced disadaptation to Earth's gravity. The outcomes of the training program for the mice welfare are discussed. We conclude that our training program was effective and that male mice can be successfully employed in space biomedical research. PMID:25133741

  20. Ethics control of vertebrate animals experiments in biosatellite BION-M1 project

    Science.gov (United States)

    Ilyin, Eugene

    During April 19-May 19, 2013 it was realized 30-days flight of Russian biosatellite Bion-M1. The main goal of this flight was to study effects of microgravity upon behavior and structural-functional state of different physiological systems of vertebrates. The folloving species were accommodated aboard of biosatellite: 45 mice C57bl/6, 8 Mongolian gerbils Meriones unguiculatus, 15 lizards, i.e. geckos Chondrodctylus turneri Gray, and fish Oreochromis mossambicus. The selection and traing of mice for the flight and ground-based control experiments was carried out at the Research Institute of Mitoengineering by Moscow State University. The protocols for animals care and reserch were revised and adopted by Bioethics Commission of above mentioned institute (decision on November 01, 2013, N35). The final version of Bion-M1 Scientific Reseach Program and protocols for separate experiments were discussed and adopted by Biomedical Ethics Commission of Institute of Biomedical Problems (decision on April 4, 2014, N317). The IMBP Commission has a status of Physiological Section of Russian Bioethics Committee by Russian Commision for UNESCO affairs and follows the Russian Bioethical Guidelines for Experiments in Aerospace and Naval Medicine and other national and international rules including COSPAR International Policy and Guidelines for Animal Care and Use in Space-born Research. Because US-scientists were the main partners in mice investigations the decision of IMBP Biomedical Commission related to Bion-M1 project was sended for information to Institutional Animal Care and Use Committee of NASA Ames Research Center. Postflight estimation of mice was done by Russian veterinary with the participation of NASA Chief veterinary.

  1. Aflatoxin M1 level in pasteurized and sterilized milk of Babol city

    Directory of Open Access Journals (Sweden)

    Hashemi S J

    2007-11-01

    Full Text Available Background: Aflatoxins are severe toxic secondary metabolites found in most plant products. When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin is metabolized by liver and is excreted as Aflatoxin M1 (AFM1 via milk. Aflatoxins are acute toxic compounds, immunosuppressive, mutagen, tratogen and carcinogen."nMethods: During the winter of 2006, pasteurized and sterilized (ultra high temperature (UHT milk packages were collected from supermarkets in Babol city. 78 pasteurized and 33 sterilized milk, totally 111 samples were tested for AFM1 by competitive Enzyme Linked Immunosorbent Assay (ELISA. Solid phase in plastic micro wells coated whit anti-Aflatoxin M1 antibodies. We added 100 microliter skimmed milk and Aflatoxin M1 standard solutions in each well. In each plate, we appointed seven wells for standards. Plates were incubated at 20-25 centigrade for 45 min. Each well was washed four times by washing buffer 20X concentration. Then 100 micro liter conjugated solution (100X was added to each well, and the plate was incubated at 20-25 centigrade for 15 min. After that, the wells were washed. After adding the substrates to wells, we incubated the plate at 20-25 centigrade in a dark place for 15 min. The reaction was stopped by stop solution. After one hour, light absorption was read at 450 nm by ELISA reader."nResults: AFM1 were detected in 100% of all samples. 100% of samples were above of European community regulations (50ng/l. AFM1 contamination mean levels pasteurized and sterilized milk were 230.5 and 221.66 respectively. Therefore more than four fold levels European community. There is not a significant relationship between AFM1 contamina-tion level and different months of winter applying statistical test."nConclusion: The results showed the need for introducing safety limits for AFM1 levels in child milk under Food Legislative liable of Iran. Aflatoxin M1 contamination is a serious problem for public health

  2. Observation of the m = 1 mode by microwave transmission measurements in the Tore Supra tokamak

    International Nuclear Information System (INIS)

    Giruzzi, G.; Segui, J.L.; Pecquet, A.L.; Gil, C.

    1991-06-01

    Microwave transmission measurements in the Tore Supra tokamak exhibit low-frequency oscillations of the transmitted power, associated to the presence of a saturated m = 1, n = 1 mode, as observed by soft X-ray diagnostics. It is shown that these oscillations are related to refraction effects, and specifically to modulations of the electron density profile due to a rotating magnetic island. An analytical solution of the ray equations in the presence of a rotating density perturbation is found, explaining the frequency spectrum of the oscillations

  3. Effect of pressure anisotropy on the m=1 small wavelength modes in Z-pinches

    Energy Technology Data Exchange (ETDEWEB)

    Faghihi, M. (Royal Inst. of Tech., Stockholm, Sweden. Dept. of Plasma Physics and Fusion Research)

    1987-05-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m=1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (r{SIGMA}B{sup 2})' {le} 0, where {SIGMA} = 1 - (P{sub parallel} - P{sub perpendicular} {sub to})/B/sup 2/. It cannot be fulfilled without violation of the fire hose stability condition {SIGMA} {ge} 0.

  4. Effects of pressure anisotropy on the M=1 small wavelength modes in Z-pinches

    International Nuclear Information System (INIS)

    Faghihi, M.

    1986-05-01

    A new model is used to investigate the effect of the pressure anisotropy on the internal kink (m=1) mode instability in a Z-pinch. A normal mode analysis of perturbed motion of an incompressible, collision- less and cylindrical plasma is performed. A comparison of the derived stability criterion with that of ideal MHD is made. The conclusion is that the stability criterion (rSigmaB/sp2/) ' 0, where Sigma=1-(P/sb/(parall)-P/sb/(perpend)/ B/sp/2. (author)

  5. Effect of pressure anisotropy on the m=1 small wavelength modes in Z-pinches

    International Nuclear Information System (INIS)

    Faghihi, M.

    1987-01-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m=1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (rΣB 2 )' ≤ 0, where Σ = 1 - (P parallel - P perpendicular to )/B 2 . It cannot be fulfilled without violation of the fire hose stability condition Σ ≥ 0. (orig.)

  6. Asymmetric Mach-Zehnder Interferometer Based Biosensors for Aflatoxin M1 Detection.

    Science.gov (United States)

    Chalyan, Tatevik; Guider, Romain; Pasquardini, Laura; Zanetti, Manuela; Falke, Floris; Schreuder, Erik; Heideman, Rene G; Pederzolli, Cecilia; Pavesi, Lorenzo

    2016-01-06

    In this work, we present a study of Aflatoxin M1 detection by photonic biosensors based on Si₃N₄ Asymmetric Mach-Zehnder Interferometer (aMZI) functionalized with antibodies fragments (Fab'). We measured a best volumetric sensitivity of 10⁴ rad/RIU, leading to a Limit of Detection below 5 × 10(-7) RIU. On sensors functionalized with Fab', we performed specific and non-specific sensing measurements at various toxin concentrations. Reproducibility of the measurements and re-usability of the sensor were also investigated.

  7. The M/M/1 queue with inventory, lost sale and general lead times

    DEFF Research Database (Denmark)

    Saffari, Mohammad; Asmussen, Søren; Haji, Rasoul

    We consider an M/M/1 queueing system with inventory under the (r,Q) policy and with lost sales, in which demands occur according to a Poisson process and service times are exponentially distributed. All arriving customers during stockout are lost. We derive the stationary distributions of the joint...... queue length (number of customers in the system) and on-hand inventory when lead times are random variables and can take various distributions. The derived stationary distributions are used to formulate long-run average performance measures and cost functions in some numerical examples....

  8. Nuclear critical opalescence and the M1 form factors of 12C and 13C

    International Nuclear Information System (INIS)

    Delorme, J.; Figureau, A.; Guichon, P.

    1981-01-01

    It is shown that core polarization by the nuclear pion field has opposite effects on the M1 form factors of 12 C(15.11 MeV) and 13 C(g.s.). New data on 13 C are found to agree with this prediction and a common interpretation of the experiments is shown to be possible for the two nuclei in terms of critical opalescence. Discrimination from alternative explanations of the observed anomalies should await further experiments, especially photopion reactions. (orig.)

  9. Relaxation phenomena in the high temperature S-1 spheromak

    International Nuclear Information System (INIS)

    Ono, Y.; Ellis, R.A. Jr.; Janos, A.C.; Levinton, F.M.; Mayo, R.M.; Motley, R.W.; Ueda, Y.; Yamada, M.

    1988-06-01

    Operation of the S-1 device in a high current density (j/n/sub e/ ≥ 2 /times/ 10 -14 A/center dot/m) regime has created high electron temperature spheromaks (50eV ≤ T/sub e/ ≤ 130eV). The mechanisms and causes of the periodic relaxation events often observed in these hotter spheromak plasmas were made clear. Also, a relationship between the MHD relaxation cycle and confinement characteristics was revealed for the first time. Resistive loss at the outer edge of the plasma causes a departure from the initial force-free minimum-energy Taylor state to a MHD profile unstable to low-n ideal MHD modes; a relaxation event then returns the configuration to nearly a Taylor state. 11 refs., 5 figs

  10. Confinement and power balance in the S-1 spheromak

    Energy Technology Data Exchange (ETDEWEB)

    Levinton, F.M.; Meyerhofer, D.D.; Mayo, R.M.; Janos, A.C.; Ono, Y.; Ueda, Y.; Yamada, M.

    1989-07-01

    The confinement and scaling features of the S-1 spheromak have been investigated using magnetic, spectroscopic, and Thomson scattering data in conjunction with numerical modeling. Results from the multipoint Thomson scattering diagnostic shows that the central beta remains constant (/beta//sub to/ /approximately/ 5%) as the plasma current density increases from 0.68--2.1 MA/m/sup 2/. The density is observed to increase slowly over this range, while the central electron temperature increases much more rapidly. Analysis of the global plasma parameters shows a decrease in the volume average beta and energy confinement as the total current is increased. The power balance has been modeled numerically with a 0-D non-equilibrium time-dependent coronal model and is consistent with the experimental observations. 20 refs., 12 figs., 2 tabs.

  11. Confinement and power balance in the S-1 spheromak

    International Nuclear Information System (INIS)

    Levinton, F.M.; Meyerhofer, D.D.; Mayo, R.M.; Janos, A.C.; Ono, Y.; Ueda, Y.; Yamada, M.; Rochester Univ., NY; Los Alamos National Lab., NM; Princeton Univ., NJ

    1989-07-01

    The confinement and scaling features of the S-1 spheromak have been investigated using magnetic, spectroscopic, and Thomson scattering data in conjunction with numerical modeling. Results from the multipoint Thomson scattering diagnostic shows that the central beta remains constant (β to ∼ 5%) as the plasma current density increases from 0.68--2.1 MA/m 2 . The density is observed to increase slowly over this range, while the central electron temperature increases much more rapidly. Analysis of the global plasma parameters shows a decrease in the volume average beta and energy confinement as the total current is increased. The power balance has been modeled numerically with a 0-D non-equilibrium time-dependent coronal model and is consistent with the experimental observations. 20 refs., 12 figs., 2 tabs

  12. Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock.

    Science.gov (United States)

    Gazit, Salomé L; Mariko, Boubacar; Thérond, Patrice; Decouture, Benoit; Xiong, Yuquan; Couty, Ludovic; Bonnin, Philippe; Baudrie, Véronique; Le Gall, Sylvain M; Dizier, Blandine; Zoghdani, Nesrine; Ransinan, Jessica; Hamilton, Justin R; Gaussem, Pascale; Tharaux, Pierre-Louis; Chun, Jerold; Coughlin, Shaun R; Bachelot-Loza, Christilla; Hla, Timothy; Ho-Tin-Noé, Benoit; Camerer, Eric

    2016-09-30

    Sphingosine-1-phosphate (S1P) signaling is essential for vascular development and postnatal vascular homeostasis. The relative importance of S1P sources sustaining these processes remains unclear. To address the level of redundancy in bioactive S1P provision to the developing and mature vasculature. S1P production was selectively impaired in mouse platelets, erythrocytes, endothelium, or smooth muscle cells by targeted deletion of genes encoding sphingosine kinases -1 and -2. S1P deficiency impaired aggregation and spreading of washed platelets and profoundly reduced their capacity to promote endothelial barrier function ex vivo. However, and in contrast to recent reports, neither platelets nor any other source of S1P was essential for vascular development, vascular integrity, or hemostasis/thrombosis. Yet rapid and profound depletion of plasma S1P during systemic anaphylaxis rendered both platelet- and erythrocyte-derived S1P essential for survival, with a contribution from blood endothelium observed only in the absence of circulating sources. Recovery was sensitive to aspirin in mice with but not without platelet S1P, suggesting that platelet activation and stimulus-response coupling is needed. S1P deficiency aggravated vasoplegia in this model, arguing a vital role for S1P in maintaining vascular resistance during recovery from circulatory shock. Accordingly, the S1P2 receptor mediated most of the survival benefit of S1P, whereas the endothelial S1P1 receptor was dispensable for survival despite its importance for maintaining vascular integrity. Although source redundancy normally secures essential S1P signaling in developing and mature blood vessels, profound depletion of plasma S1P renders both erythrocyte and platelet S1P pools necessary for recovery and high basal plasma S1P levels protective during anaphylactic shock. © 2016 American Heart Association, Inc.

  13. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness

    International Nuclear Information System (INIS)

    Young, Nicholas; Van Brocklyn, James R.

    2007-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of five G-protein-coupled receptors, termed S1P 1-5 . S1P stimulates growth and invasiveness of glioma cells, and high expression levels of the enzyme that forms S1P, sphingosine kinase-1, correlate with short survival of glioma patients. In this study we examined the mechanism of S1P stimulation of glioma cell proliferation and invasion by either overexpressing or knocking down, by RNA interference, S1P receptor expression in glioma cell lines. S1P 1 , S1P 2 and S1P 3 all contribute positively to S1P-stimulated glioma cell proliferation, with S1P 1 being the major contributor. Stimulation of glioma cell proliferation by these receptors correlated with activation of ERK MAP kinase. S1P 5 blocks glioma cell proliferation, and inhibits ERK activation. S1P 1 and S1P 3 enhance glioma cell migration and invasion. S1P 2 inhibits migration through Rho activation, Rho kinase signaling and stress fiber formation, but unexpectedly, enhances glioma cell invasiveness by stimulating cell adhesion. S1P 2 also potently enhances expression of the matricellular protein CCN1/Cyr61, which has been implicated in tumor cell adhesion, and invasion as well as tumor angiogenesis. A neutralizing antibody to CCN1 blocked S1P 2 -stimulated glioma invasion. Thus, while S1P 2 decreases glioma cell motility, it may enhance invasion through induction of proteins that modulate glioma cell interaction with the extracellular matrix

  14. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-01-01

    Highlights: ► MH7A cells and CD4 + T cells expressed S1P1 and RANKL. ► S1P increased RANKL expression in MH7A cells and CD4 + T cells. ► The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-κB ligand (RANKL) in RA synoviocytes and CD4 + T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4 + T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4 + T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-α in MH7A cells and CD4 + T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4 + T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  15. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  16. Contamination levels of aflatoxin M1 in bulk raw milk of Chaloos and Ramsar

    Directory of Open Access Journals (Sweden)

    A.R Barami

    2012-02-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk as a direct result of the ingestion of feed contaminated with aflatoxin B1 by cattle. This study was conducted to investigate the contamination rate of raw milk whit aflatoxin M1 in Chaloos and Ramsar raw milk collection centers. Two hundred bulk raw milk samples were collected during winter (January and February and summer (June and July seasons. The milk samples were analyzed by ELISA method for the presence of AFM1. During the winter, AFM1 was detected in 100% and 59/79% of the bulk raw milk samples in Ramsar and Chaloos, respectively; however, during summer 83/52% and 50/1 of the samples was found as positive in Ramsar and Chaloos, respectively. Furthermore, 45% of Ramsar and 30% of Chaloos bulk milk samples showed higher contamination level of AFM1 than maximum tolerance limit (50 ng/l accepted by National Standard as well as European Union. Although, the difference between the contamination rate in samples obtained during summer and winter seasons was not statistically significantly, (p

  17. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J; Lowther, Jonathan; Stack, Colin M; Golding, Sarah J; Skinner-Adams, Tina S; Trenholme, Katharine R; Teuscher, Franka; Donnelly, Sheila M; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; Degori, Ross; Buckle, Ashley M; Gardiner, Donald L; Whisstock, James C; Dalton, John P

    2009-02-24

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH(2)]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite.

  18. Process economics and safety considerations for the oxidative dehydrogenation of ethane using the M1 catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Baroi, Chinmoy; Gaffney, Anne M.; Fushimi, Rebecca

    2017-12-01

    Olefins or unsaturated hydrocarbons play a vital role as feedstock for many industrially significant processes. Ethylene is the simplest olefin and a key raw material for consumer products. Oxidative Dehydrogenation (ODH) is one of the most promising new routes for ethylene production that can offer a significant advantage in energy efficiency over the conventional steam pyrolysis process. This study is focused on the ODH chemistry using the mixed metal oxide MoVTeNbOx catalysts, generally referred to as M1 for the key phase known to be active for dehydrogenation. Using performance results from the patent literature a series of process simulations were conducted to evaluate the effect of feed composition on operating costs, profitability and process safety. The key results of this study indicate that the ODH reaction can be made safer and more profitable without use of an inert diluent and furthermore by replacing O2 with CO2 as an oxidant. Modifications of the M1 catalyst composition in order to adopt these changes are discussed.

  19. E2 and M1 transition strengths in heavy deformed nuclei revisited

    International Nuclear Information System (INIS)

    Draayer, J.P.; Popa, G.; Hirsch, J.G.; Vargas, C.E.

    2003-01-01

    An update on the status of pseudo-SU(3) shell-model calculations in strongly deformed nuclei in the rare earth region is presented. Representative results for energy levels as well as E2 (quadrupole) and M1 (scissors) transitions strengths in 162 Dy (even-even) and 163 Dy (odd-mass) are given. The calculations use realistic single-particle energies and quadrupole-quadrupole and pairing interaction strengths fixed from systematics. The strengths of rotor-like terms included in the Hamiltonian- all small relative to the other terms in the interaction were adjusted to give an overall best fit to the energy spectra. The results present a paradox: for even-even nuclei (integer angular momentum) non-zero pseudo-spin configurations seems to be unimportant while for the odd-mass systems (half-integer angular momentum) pseudo-spin mixing is essential as spin-flip couplings appear to dominate the M1 transition strengths. (Author)

  20. Microscopic description of low-lying M1 excitations in odd-mass actinide nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Tabar, Emre, E-mail: etabar@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Yakut, Hakan, E-mail: hyakut@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Kuliev, Ali Akbar [Azerbaijan National Academy of Aviation, Baku (Azerbaijan)

    2017-01-15

    A restoration method of a broken symmetry which allows self-consistent determination of the separable effective restoration forces is now adapted to odd-mass nuclei in order to restore violated rotational invariance (RI-) of the Quasiparticle Phonon Nuclear Model (QPNM) Hamiltonian. Because of the self-consistency of the method, these effective forces contain no arbitrary parameters. Within RI-QPNM, the properties of the low-lying magnetic dipole excitations in odd-mass deformed {sup 229–233}Th and {sup 233–239}U nuclei have been investigated for the first time. It has been shown that computed fragmentation of the M1 strengths below 4 MeV in these nuclei is much stronger than that in neighboring doubly even {sup 228–232}Th and {sup 232–238}U nuclei. For {sup 235}U the summed M1 strength in the energy range 1.5–2.8 MeV is in agreement with the relevant experimental data where the missing strength was extracted by means of a fluctuation analysis.

  1. Development of Neutron Imaging System for Neutron Tomography at Thai Research Reactor TRR-1/M1

    Science.gov (United States)

    Wonglee, S.; Khaweerat, S.; Channuie, J.; Picha, R.; Liamsuwan, T.; Ratanatongchai, W.

    2017-09-01

    The neutron imaging is a powerful non-destructive technique to investigate the internal structure and provides the information which is different from the conventional X-ray/Gamma radiography. By reconstruction of the obtained 2-dimentional (2D) images from the taken different angle around the specimen, the tomographic image can be obtained and it can provide the information in more detail. The neutron imaging system at Thai Research Reactor TRR-1/M1 of Thailand Institute of Nuclear Technology (Public Organization) has been developed to conduct the neutron tomography since 2014. The primary goal of this work is to serve the investigation of archeological samples, however, this technique can also be applied to various fields, such as investigation of industrial specimen and others. This research paper presents the performance study of a compact neutron camera manufactured by Neutron Optics such as speed and sensitivity. Furthermore, the 3-dimentional (3D) neutron image was successfully reconstructed at the developed neutron imaging system of TRR-1/M1.

  2. Detection of aflatoxin M1 in raw and commercial pasteurized milk in Urmia, Iran.

    Science.gov (United States)

    Tajik, Hossein; Rohani, Seyed Mehdi Razavi; Moradi, Mehran

    2007-11-15

    During the years 2005 and 2006, samples of raw and of pasteurized milk (72 samples each) were collected randomly from various parts of Urmia city in Iran for the detection of aflatoxin M1. Aflatoxin M1 levels were assessed by Enzyme Linked Immuno Sorbent Assay (ELISA). There was a high incidence of AFM1 (100%), in both raw and pasteurized milk samples. The AFM1 levels in 6.25% of samples were higher than the maximum tolerance limit accepted by European Union (50 ng L(-1)), while the observed mean ofAFM1 was lower than those proposed for European diets. Maximum level ofAFM1 in raw and pasteurized samples were 91.8 and 28.5 ng L(-1), while minimum levels were 4.3 and 5.1 ng L(-1), respectively. The levels ofAFM1 in total samples indicated that feeds for cows in this region were contaminated with AFB1 in such a level that appears to be a serious public health problem at the moment. Therefore, there is a need to limit exposure to aflatoxins by imposing regulatory limits.

  3. Aflatoxin M1 contamination of raw and pasteurized milk produced in Sanandaj, Iran

    Directory of Open Access Journals (Sweden)

    Mafakheri, Sh.

    2010-07-01

    Full Text Available This study was conducted to evaluate and compare the levels of aflatoxin M1 in raw and pasteurized milk samples during different seasons by Enzyme- Linked Immuno Sorbent Assay in Sanandaj, Iran. In 257 (94.49% out of 272 milk samples the presence of aflatoxin M1 was detected in concentrations ranging between 0.007 and 115.930 ng/l. AFM1 level in 12 (4.4% of positive samples were higher than the maximum tolerance limit (50 ng/l accepted by Iran and European Union countries. Statistical evaluations showed that the differences between raw and pasteurized samples were not significant (p<0.05. There was no significant difference between spring and summer but the differences between other seasons were statistically significant. Winter samples with 22.35 ng/l and summer samples with 5.14 ng/l had the highest and lowest concentration, respectively (p<0.05. Since contamination of milk with aflatoxin is a potential risk for human health, milk and milk products should be controlled periodically for Aflatoxin contamination.

  4. Nonlinear dynamics of the m=1 kink-tearing instability in a modified magnetohydrodynamic model

    International Nuclear Information System (INIS)

    Wang, X.; Bhattacharjee, A.

    1995-01-01

    A theory is given for the nonlinear dynamical evolution of the collisionless m=1 kink-tearing instability, including the effects of electron inertia and electron pressure gradient in a generalized Ohm's law. It is demonstrated that electron pressure gradients can cause near-explosive growth in the nonlinear regime of a thin m=1 island. This near-explosive phase is followed by a rapid decay phase as the island width becomes comparable to the radius of the sawtooth region. An island equation is derived for the entire nonlinear evolution of the instability, extending recent work on the subject [X. Wang and A. Bhattacharjee, Phys. Rev. Lett. 70, 1627 (1993)] to include the effects of both electron inertia and electron pressure gradient. Comparisons are made with experimental data from present-day tokamaks. It is suggested that the present model not only accounts for fast sawtooth crashes, but also provides possible explanations for the problems of sudden onset and incomplete reconnection that have been, heretofore, unexplained features of observations. copyright 1995 American Institute of Physics

  5. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J.; Lowther, Jonathan; Stack, Colin M.; Golding, Sarah J.; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Teuscher, Franka; Donnelly, Sheila M.; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; DeGori, Ross; Buckle, Ashley M.; Gardiner, Donald L.; Whisstock, James C.; Dalton, John P.

    2009-01-01

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH2]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite. PMID:19196988

  6. Meiotic chromosome behaviours in M1 generation of bread wheat irradiated by gamma-rays

    International Nuclear Information System (INIS)

    Watanabe, Y.; Takato, S.

    1982-01-01

    Growing plants of bread wheat (Triticum aestivum L. 2 n=6x=42, AABBDD) were subjected to acute or chronic irradiation by gamma-rays from 60Co and meiotic chromosome behaviours of PMCS in M 1 generation were cytologically compared. Both acute and chronic irradiations produced different types of chromosomal aberrations at the meiotic stages. Among them, translocation type was the most frequent, followed by univalent type. A mixed type, i. e. translocation accompanying one or more univalents was often detected. Even normal type which lacked translocation and univalent included laggards and briclges without exception. Other meiotic abnormalities such as deletion, iso-chromosome and micronuclei were observed frequently in both treatments. Dose dependency of translocation frequency was not recognized in this experiment. In chronic irradiation, different chromosome numbers and meiotic behaviours were found not only among florets of a spike but also among anthers of a floret. A number of plants with aneuploid-like grass types occurred at a high frequency in M 1 , especially with low exposure

  7. Compressional effects in nonneutral plasmas, a shallow water analogy and m=1 instability

    International Nuclear Information System (INIS)

    Finn, J.M.; Del-Castillo-Negrete, D.; Barnes, D.C.

    1999-01-01

    Diocotron instabilities form an important class of ExB shear flow instabilities which occur in nonneutral plasmas. The case of a single-species plasma confined in a cylindrical Penning trap, with an axisymmetric, hollow (nonmonotonic) density profile is studied. According to the standard linear theory, the m=1, k z =0 diocotron mode is always stable. On the other hand, experiments by Driscoll [Phys. Rev. Lett. 64, 645 (1990)] show a robust exponential growth of m=1 diocotron perturbations in hollow density profiles. The apparent contradiction between these experimental results and linear theory has been an outstanding problem in the theory of nonneutral plasmas. A new instability mechanism due to the radial variation of the equilibrium plasma length is proposed in this paper. This mechanism involves the compression of the plasma parallel to the magnetic field and implies the conservation of the line integrated density. The predicted growth rate, frequency, and mode structure are in reasonable agreement with the experiment. The effect of a linear perturbation of the plasma length is also shown to give instability with a comparable growth rate. The conservation of the line integrated density in the plasma is analogous to the conservation of the potential vorticity in the shallow water equations used in geophysical fluid dynamics. In particular, there is an analog of Rossby waves in nonneutral plasmas. copyright 1999 American Institute of Physics

  8. Quadrupole decay strength of the M1 scissors mode of {sup 156}Gd

    Energy Technology Data Exchange (ETDEWEB)

    Beck, T.; Beller, J.; Gayer, U.; Mertes, L.; Pai, H.; Pietralla, N.; Ries, P.; Romig, C.; Werner, V.; Zweidinger, M. [IKP, TU Darmstadt (Germany); Derya, V. [IKP, Universitaet zu Koeln (Germany); Isaak, J.; Loeher, B.; Savran, D. [EMMI, GSI, Darmstadt (Germany); FIAS, Frankfurt (Germany); Scheck, M. [IKP, TU Darmstadt (Germany); School of Engineering, UWS, Paisley (United Kingdom); SUPA, Glasgow (United Kingdom); Tornow, W.; Weller, H.R. [Duke University, Durham (United States)

    2015-07-01

    The isovector low-lying J{sup π}{sub K}=1{sup +}{sub 1} scissors mode of deformed nuclei has been studied extensively in (e,e{sup '}) and (γ,γ{sup '}) experiments over the last 30 years with the main focus on strong M1 transitions to the ground state band. In the framework of the semiclassical two-rotor-model it has its origin in quadrupole deformation. A considerable E2 matrix element between the rotational band of the scissors mode and the ground band is predicted which has not been addressed experimentally. A photon-scattering experiment with linearly-polarized quasi monoenergetic vector (γ)-rays has been performed at the High Intensity vector (γ)-ray Source (HIvector (γ)S) at Duke University, Durham, NC, exploiting the γ{sup 3} setup. We have measured an E2/M1-multipole mixing ratio for the 1{sup +}{sub sc}→2{sup +}{sub 1} transition for the first time. The Alaga rule is applicable and delivers a first estimate of the transition strength B(E2:2{sup +}{sub sc}→0{sup +}{sub 1}). A candidate for a 2{sup +}{sub sc}→2{sup +}{sub 1} transition is discussed.

  9. Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases.

    Science.gov (United States)

    Felder, Christian C; Goldsmith, Paul J; Jackson, Kimberley; Sanger, Helen E; Evans, David A; Mogg, Adrian J; Broad, Lisa M

    2018-01-25

    The cholinergic signalling system has been an attractive pathway to seek targets for modulation of arousal, cognition, and attention which are compromised in neurodegenerative and neuropsychiatric diseases. The acetylcholine muscarinic receptor M1 and M4 subtypes which are highly expressed in the central nervous system, in cortex, hippocampus and striatum, key areas of cognitive and neuropsychiatric control, have received particular attention. Historical muscarinic drug development yielded first generation agonists with modest selectivity for these two receptor targets over M2 and M3 receptors, the major peripheral sub-types hypothesised to underlie the dose-limiting clinical side effects. More recent compound screening and medicinal chemistry optimization of orthosteric and allosteric agonists, and positive allosteric modulators binding to sites distinct from the highly homologous acetylcholine binding pocket have yielded a collection of highly selective tool compounds for preclinical validation studies. Several M1 selective ligands have progressed to early clinical development and in time will hopefully lead to useful therapeutics for treating symptoms of Alzheimer's disease and related disorders. Copyright © 2018. Published by Elsevier Ltd.

  10. The sphingosine 1-phosphate receptor S1P(2) triggers hepatic wound healing

    NARCIS (Netherlands)

    Serriere-Lanneau, Valerie; Teixeira-Clerc, Fatima; Li, Liying; Schippers, Marlies; de Wries, Willie; Julien, Boris; Tran-Van-Nhieu, Jeanne; Manin, Sylvie; Poelstra, Klaas; Chun, Jerold; Carpentier, Stephane; Levade, Thierry; Mallat, Ariane; Lotersztajn, Sophie

    Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK1 and 2). We previously showed that S1P receptors (S1P(1), S1P(2), and S1P(3)) are expressed in hepatic myofibroblasts (hMF), a population of cells that triggers matrix remodeling during liver injury. Here

  11. Role of sphingosine 1-phosphate (S1P and effects of fingolimod, an S1P receptor 1 functional antagonist in lymphocyte circulation and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Kenji Chiba

    2014-11-01

    Full Text Available Sphingosine 1-phosphate (S1P, a multi-functional phospholipid mediator, is generated from sphingosine by sphingosine kinases and binds to five known G protein-coupled S1P receptors (S1P1, S1P2, S1P3, S1P4, and S1P5. It is widely accepted that S1P receptor 1 (S1P1 plays an essential role in lymphocyte egress from the secondary lymphoid organs (SLO and thymus, because lymphocyte egress from these organs to periphery is at extremely low levels in mice lacking lymphocytic S1P1. Fingolimod hydrochloride (FTY720 is a first-in-class, orally active S1P1 functional antagonist which was discovered by chemical modification of a natural product, myriocin. Since FTY720 has a structure closely related to sphingosine, the phosphorylated FTY720 (FTY720-P is converted by sphingosine kinases and binds 4 types of S1P receptors. FTY720-P strongly induces down-regulation of S1P1 by internalization and degradation of this receptor and acts as a functional antagonist at S1P1. Consequently, FTY720 inhibits S1P1-dependent lymphocyte egress from the SLO and thymus to reduce circulating lymphocytes including autoreactive Th17 cells, and is highly effective in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. In relapsing remitting MS patients, oral FTY720 shows a superior efficacy when compared to intramuscular interferon-β-1a. Based on these data, it is presumed that modulation of the S1P-S1P1 axis provides an effective therapy for autoimmune diseases including MS.

  12. Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardioprotection.

    Science.gov (United States)

    Yung, Bryan S; Brand, Cameron S; Xiang, Sunny Y; Gray, Charles B B; Means, Christopher K; Rosen, Hugh; Chun, Jerold; Purcell, Nicole H; Brown, Joan Heller; Miyamoto, Shigeki

    2017-02-01

    Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P 1 , S1P 2 , and S1P 3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to G q . We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD. The S1P receptor subtypes and G proteins that regulate RhoA activation and downstream responses in the heart have not been determined. Using siRNA or pertussis toxin to inhibit different G proteins in NRVMs we established that S1P regulates RhoA activation through Gα 13 but not Gα 12 , Gα q , or Gα i . Knockdown of the three major S1P receptors using siRNA demonstrated a requirement for S1P 3 in RhoA activation and subsequent phosphorylation of PKD, and this was confirmed in studies using isolated hearts from S1P 3 knockout (KO) mice. S1P treatment reduced infarct size induced by ischemia/reperfusion in Langendorff perfused wild-type (WT) hearts and this protection was abolished in the S1P 3 KO mouse heart. CYM-51736, an S1P 3 -specific agonist, also decreased infarct size after ischemia/reperfusion to a degree similar to that achieved by S1P. The finding that S1P 3 receptor- and Gα 13 -mediated RhoA activation is responsible for protection against ischemia/reperfusion suggests that selective targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma.

    Science.gov (United States)

    Rodriguez, A M; Graef, A J; LeVine, D N; Cohen, I R; Modiano, J F; Kim, J-H

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs. S1P/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA). Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used. This was a retrospective case series and in vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography/mass spectrometry. S1P signaling was evaluated by intracellular Ca(2+) mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining. Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1 , decreased S1P1 protein expression and induced apoptosis of HSA cells. S1P/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  14. Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

    Science.gov (United States)

    Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2014-01-01

    Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

  15. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors.

    Science.gov (United States)

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott

    2016-01-27

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

  16. Activation of multiple G-proteins by muscarinic M1 and M2 receptors

    Czech Academy of Sciences Publication Activity Database

    Michal, Pavel; El-Fakahany, E. E.; Doležal, Vladimír

    2006-01-01

    Roč. 27, č. S1 (2006), s. 404-404 ISSN 1671-4083. [World Congress of Pharmacology /15./. 02.07.2006-07.07.2006, Beijing] R&D Projects: GA ČR(CZ) GP305/05/P209; GA ČR(CZ) GA305/05/0452; GA MŠk(CZ) LC554 Grant - others:NIH(US) NS25743 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic receptors * multiple G-protein coupling Subject RIV: ED - Physiology

  17. Cytogenetic effects in bone marrow cells of mice exposed on the biosatellite "BION-M1"

    Science.gov (United States)

    Dorozhkina, Olga; Ivanov, Alexander

    In studies of cytogenetic damage in blood lymphocytes of astronauts, conducted in recent years, have shown an increase in the frequency of chromosomal damage bound, as believe, with influence on an organism of astronauts of space radiation (B.S. Fedorenko, G.P. Snigireva, 2004). However, in recent years published evidence that both acute and chronic stress induce chromosomal aberrations and modified genome sensitivity to mutagens of different nature, including to ionizing radiation (F.I. Ingel et al, 2005 ). This question is especially actual for space biology and medicine due to a number of specific features of space flights, when the interaction of factors more pronounced than in normal terrestrial conditions. In experiment "BION - M1" by anaphase method was determined level of chromosomal aberrations in bone marrow cells of tibia of mice. Flight duration biosatellite "BION - M1" was 30 days in Earth orbit. Euthanasia of experimental animals was carried out at intervals of 15-20 minutes by method of cervical dislocation after 12 hours from the moment of landing satellite. Level of chromosomal aberrations in vivarium-housed control mice was 1,75 ± 0,6% and 1,8 ± 0,45%, while the mitotic index 1,46 ± 0,09% and 1,53 ± 0,05%. Differences are not significant. The maintenance of animals in experiment with the onboard equipment (ground experiment) led to some increase in aberrant mitoses (2,3 ± 0,4%) and to decrease in a mitotic index (1,37 ± 0,02%). In the flight experiment "BION - M1" statistically significant increase of level of chromosomal aberrations (29,7 ± 4,18%) and a decrease in the mitotic index (0,74 ± 0,07%). Since the mouse is a suitable experimental model , also had several ground experiments on research of combined effect of irradiation and other stress factors specific to space flight, with marked tendency to increase the level of aberrant mitoses under the combined action of radiation and stress exposure group housing male mice. Statistically

  18. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

    Science.gov (United States)

    Zhao, Lan-Xue; Ge, Yan-Hui; Xiong, Cai-Hong; Tang, Ling; Yan, Ying-Hui; Law, Ping-Yee; Qiu, Yu; Chen, Hong-Zhuan

    2018-03-06

    M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

  19. Forkhead Box M1 Is Regulated by Heat Shock Factor 1 and Promotes Glioma Cells Survival under Heat Shock Stress*

    Science.gov (United States)

    Dai, Bingbing; Gong, Aihua; Jing, Zhitao; Aldape, Kenneth D.; Kang, Shin-Hyuk; Sawaya, Raymond; Huang, Suyun

    2013-01-01

    The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G2-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance. PMID:23192351

  20. Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor.

    Science.gov (United States)

    Onuma, Takashi; Tanabe, Kumiko; Kito, Yuko; Tsujimoto, Masanori; Uematsu, Kodai; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Doi, Tomoaki; Nagase, Kiyoshi; Akamatsu, Shigeru; Tokuda, Haruhiko; Ogura, Shinji; Iwama, Toru; Kozawa, Osamu; Iida, Hiroki

    2017-08-01

    Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gαi and GTP-bound Gα13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. [Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes].

    Science.gov (United States)

    Bao, X H; Li, H X; Tao, J; Li, X M; Yang, Y N; Ma, Y T; Chen, B D

    2016-05-24

    To study the role and mechanism of sphingosine-1-phosphate (S1P)/ sphingosine-1-phosphate receptor 1(S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes. Neonatal rat cardiomyocytes were isolated and cultured, then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy. Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning. Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected: (1) IPost group (hypoxia+ postconditioning); (2) IPost+ S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost); (3) IPost+ W-146+ S1P group (cells in IPost+ W-146+ S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min); (4) IPost+ PD98059+ S1P group (cells in IPost+ S1P group were pretreated with MAPK antagonist PD98059 (125 μmol/L) for 20 min); (5) IPost+ LY-294002+ S1P group (cells in IPost+ S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min). Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot. (1)Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90±4.49)% group compared with normal control group (7.97±2.18)%, which could be significantly reduced in IPost group (15.90±1.77)% (all PS1P and IPost+ S1P+ LY-294002 groups than in IPost and IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 group (all PS1P and IPost+ S1P+ LY-294002 group than in IPost and IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 group (all PS1P+ W-146 and IPost+ S1P+ PD98059 groups. p-ERK1/2 and p-Akt levels in IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 were similar as in IPost group. S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and

  2. On the GI/M/1 Queue with Vacations and Multiple Service Phases

    Directory of Open Access Journals (Sweden)

    Jianjun Li

    2017-01-01

    Full Text Available This paper considers a GI/M/1 queue with vacations and multiple service phases. Whenever the system becomes empty, the server takes a vacation, causing the system to move to vacation phase 0. If the server returns from a vacation to find no customer waiting, another vacation begins. Otherwise, the system jumps from phase 0 to some service phase i with probability qi,  i=1,2,…,N. Using the matrix geometric solution method and semi-Markov process, we obtain the distributions of the stationary system size at both arrival and arbitrary epochs. The distribution of the stationary waiting time of an arbitrary customer is also derived. In addition, we present some performance measures such as mean waiting time of an arbitrary customer, mean length of the type-i cycle, and mean number of customers in the system at the end of phase 0. Finally, some numerical examples are presented.

  3. Optimization of an M/M/1/N Feedback Queue with Retention of Reneged Customers

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2014-01-01

    Full Text Available Customer impatience has become a threat to the business world. Firms employ various customer retention strategies to retain their impatient (or reneged customers. Customer retention mechanisms may help to retain some or all impatient customers. Further, due to unsatisfactory service, customers may rejoin a queue immediately after departure. Such cases are referred to as feedback customers. Kumar and Sharma take this situation into account and study an M/M/1/N feedback queuing system with retention of reneged customers. They obtain only a steady-state solution for this model. In this paper, we extend the work of Kumar and Sharma by performing an economic analysis of the model. We develop a model for the costs incurred and perform the appropriate optimization. The optimum system capacity and optimum service rate are obtained. (original abstract

  4. Atomic spectroscopy with twisted photons: Separation of M 1 -E 2 mixed multipoles

    Science.gov (United States)

    Afanasev, Andrei; Carlson, Carl E.; Solyanik, Maria

    2018-02-01

    We analyze atomic photoexcitation into the discrete states by twisted photons, or photons carrying extra orbital angular momentum along their direction of propagation. From the angular momentum and parity considerations, we are able to relate twisted-photon photoexcitation amplitudes to their plane-wave analogs, independently of the details of the atomic wave functions. We analyze the photoabsorption cross sections of mixed-multipolarity E 2 -M 1 transitions in ionized atoms and found fundamental differences coming from the photon topology. Our theoretical analysis demonstrates that it is possible to extract the relative transition rates of different multipolar contributions by measuring the photoexcitation rate as a function of the atom's position (or impact parameter) with respect to the optical vortex center. The proposed technique for separation of multipoles can be implemented if the target's atom position is resolved with subwavelength accuracy; for example, with Paul traps. Numerical examples are presented for Boron-like highly charged ions.

  5. Occurrence of Aflatoxin M1 in Dairy Products in Southern Italy

    Directory of Open Access Journals (Sweden)

    Giovanna Barbuti

    2008-12-01

    Full Text Available A screening survey of the presence of aflatoxin M1 (AFM1 was carried out on 265 samples of cheese made from cow, buffalo, goat, sheep, sheep-goat milk collected in the Apulia region (Southern Italy. Selected samples included unripened, medium and long-term ripened cheeses. AFM1 was found in 16.6% of the analyzed samples. The highest positive incidence was for medium and long-term ripened cheeses, especially those made from sheep-goat milk, while buffalo cheeses tested consistently negative. Our results show that the level of contamination by AFM1 in dairy products from Apulia Region are lower than in other Italian and European regions. Moreover, it is important to underline that a common European norm concerning the AFM1 threshold limits for dairy products is still lacking.

  6. Radiative rates for E1, E2, M1 and M2 transitions in Fe X

    International Nuclear Information System (INIS)

    Aggarwal, K.M.; Keenan, F.P.

    2004-01-01

    Energies of the 54 levels belonging to the (1s 2 2s 2 2p 6 ) 3s 2 3p 5 , 3s3p 6 , 3s 2 3p 4 3d and 3s3p 5 3d configurations of Fe X have been calculated using the GRASP code of Dyall and colleagues (1989). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Comparisons are made with results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 3%, whereas results for other parameters are probably accurate to better than 20% . Additionally, the agreement between measured and calculated lifetimes is better than 10%. (authors)

  7. E2 and M1 Transition Probabilities in Odd Mass Hg Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Berg, V; Baecklin, A; Fogelberg, B; Malmskog, S G

    1969-10-15

    L- and M-subshell ratios have been measured for the 39.5 keV transition in {sup 193}Hg and the 37.1 and 16.2 keV transitions in {sup 195}Hg yielding 0.38 {+-} 0.12 , <0.02 and 0.08 {+-} 0.03 per cent E2, respectively. The half-lives of the 39.5 keV level in {sup 193}Hg and the 53.3 and 37.1 keV levels in {sup 195}Hg have been measured by the delayed coincidence method, yielding values of 0.63 {+-} 0.03, 0.72 {+-} 0.03 and <0.05 nsec respectively. A systematic compilation of reduced E2 and M1 transition probabilities in odd mass Pt, Hg and Pb nuclei is given and compared to theoretical predictions.

  8. Aflatoxin M1 in buffalo and cow milk in Afyonkarahisar, Turkey.

    Science.gov (United States)

    Kara, Recep; Ince, Sinan

    2014-01-01

    Potential hazardous human exposure to aflatoxin M1 (AFM1) via consumption of milk and milk products has been demonstrated by many researchers. The aim of this study was to investigate the presence of this mycotoxin in buffalo and cow milk samples in the city of Afyonkarahisar, Turkey. For this purpose, 126 buffalo and 124 cow milk samples were collected from dairy farms in Afyonkarahisar province. AFM1 levels were determined by high-performance liquid chromatography with tandem mass spectrometric detection. Although AFM1 was not detected in cow milk samples, AFM1 was found above the limit of detection (milk samples. The results of this study indicated the importance of continuous surveillance of commonly consumed milk or milk product samples for AFM1 contamination in Turkey.

  9. Mutagenesis in yam, Discorea rotundata: Clonal evaluation of M1V3 yam plants

    International Nuclear Information System (INIS)

    Nwachukwu, E.C.; Mbanso, E.N.; Ene, L.S.O.

    1997-01-01

    Ten thousand plants of M 1 V 3 population of the white guinea yam, Dioscorea rotundata Poir, were evaluated. There was no consistent trends in variations in plant height, number of branches, branching heights and number of leaves of the treated tubers. However, plant height were lower in the irradiated than in the control. The coefficients of variations (C.V.) were higher in the irradiated than in the control populations, indicating wider variations in the former population. Based on yield performance, 110 tubers were selected for preliminary yield trials, Considering that diplontic selection may occur in the irradiated micro-tubers, the experiment will also be carried out using nodal cultures in vitro. (author). 2 tabs

  10. The MCNP Simulation of a PGNAA System at TRR-1/M1

    Science.gov (United States)

    Sangaroon, S.; Ratanatongchai, W.; Picha, R.; Khaweerat, S.; Channuie, J.

    2017-06-01

    The prompt-gamma neutron activation analysis system (PGNAA) has been installed at Thai Research Reactor-1/Modified 1 (TRR-1/M1) since 1999. The purpose of the system is for elemental and isotopic analyses. The system mainly consists of a series of the moderator and collimator, neutron and gamma-ray shielding and the HPGe detector. In this work, the condition of the system is carried out based on the Monte Carlo method using Monte Carlo N-Particle transport code and the experiment. The flux ratios (Φthermal/Φepithermal and Φthermal/Φfast) and thermal neutron flux have been obtained. The simulated prompt gamma rays of the Portland cement sample have been carried out. The simulation provides significant contribution in upgrading the PGNAA station to be available in various applications.

  11. M1 transitions between low-lying states in the sdg-IBM-2

    Science.gov (United States)

    Casperson, Robert; Werner, Volker

    2006-10-01

    The interplay between collective and single-particle degrees of freedom for nuclei in the A=90 region have recently been under investigation. In Molybdenum and Ruthenium nuclei, collective symmetric and mixed-symmetric structures have been identified, while in Zirconium, underlying shell-structure plays an enhanced role. Collective symmetric structures appear when protons and neutrons are in phase, whereas mixed-symmetric structures occur when they are not. The one-phonon 2^+ mixed-symmetric state was identified from strong M1 transitions to the 2^+1 state. Similar transitions were observed between higher-spin states, and are predicted by the shell model. These phenomena will be investigated within the sdg Interacting Boson Model 2 in order to obtain a better understanding about the structure of the states involved, and results from first model calculations will be presented. Work supported by US DOE under grant number DE-FG02-91ER-40609.

  12. An Automatic Detection Method of Nanocomposite Film Element Based on GLCM and Adaboost M1

    Directory of Open Access Journals (Sweden)

    Hai Guo

    2015-01-01

    Full Text Available An automatic detection model adopting pattern recognition technology is proposed in this paper; it can realize the measurement to the element of nanocomposite film. The features of gray level cooccurrence matrix (GLCM can be extracted from different types of surface morphology images of film; after that, the dimension reduction of film can be handled by principal component analysis (PCA. So it is possible to identify the element of film according to the Adaboost M1 algorithm of a strong classifier with ten decision tree classifiers. The experimental result shows that this model is superior to the ones of SVM (support vector machine, NN and BayesNet. The method proposed can be widely applied to the automatic detection of not only nanocomposite film element but also other nanocomposite material elements.

  13. Low pressure injection sequence sensitivity study of the M1 module of MEDICI

    International Nuclear Information System (INIS)

    Corradini, M.L.; Moses, G.A.; Norkus, J.K.; Welzbacker, R.T.

    1985-01-01

    In order to assess the consequences of a PWR containment failure and the ensuing radiological source term following a severe reactor accident, it is necessary to understand the ex-vessel behavior of the molten core. The M1 module of MEDICI models the dynamic fuel-coolant mixing, energetic interaction, and ejection of fuel and coolant from the reactor cavity following such an accident. A sensitivity study of the low pressure injection sequence was performed utilizing a Box-Behnken statistical design to treat five sets of input variables considered to be significant in the mixing and steam explosion processes. The low pressure injection sequence was studied in which the molten corium is modeled as a pour stream entering the cavity without entraining or sweeping out fuel or coolant

  14. The frequency of occurrence of aflatoxin M1 in milk on the territory of Vojvodina

    Directory of Open Access Journals (Sweden)

    Polovinski-Horvatović Miroslava S.

    2009-01-01

    Full Text Available Aflatoxin is one of the most common mycotoxins which can be found in milk. It represents a natural metabolite of aflatoxin B1 that occurs as a result of animal metabolism and the body's attempt to detoxificate it. It is excreted in milk, feces and urine of animals that consumed contaminated feed with aflatoxin B1. The carry-over from feed to milk depends on many factors, ranging from 0.3 to 6.2%. Aflatoxin M1 is in the first group of carcinogens according to the IRAC classification from 2002, but it is considered to have only 10% of carcinogenicity from its precursor aflatoxin B1. Legislation in member countries of European Union for this mycotoxin in milk intended for people is 0.05 μg/l, while the rest of the countries that also have legislation for this mycotoxin allow the concentration that is ten times higher, and that is 0.5 μg/l. In this paper, we have tried to provide on insight into the quality of milk, food often consumed by children, from the standpoint of mycotoxicology, and to compare the obtained data with data available from literature, from countries in the region that have similar climatic and agricultural conditions. From a total of 65 samples of processed milk, aflatoxin M1 was found in 18 samples and none of the samples exceeded the level of 0.05 μg/l, which is allowed by the legislation of the European Union.

  15. Phenotype and molecular analysis of M1 generation of stylosanthes irradiated by 60Co

    International Nuclear Information System (INIS)

    Zhang Weili; Liu Fengmin

    2012-01-01

    The seeds of Stylosanthes guianensis SW. ‘Reyan No.13’ were irradiated by 60 Co at 0, 325, 487 and 974 Gy. Phenotype and molecular variations of Stylosanthes M 1 generations were studied. Germination percentage, plant height, leaf length and stem diameter of M 1 seedlings were determined using SRAP-PCR. Results showed that biological character indices of treatments were significantly lower than that of control (CK). Irradiation inhibited plant growth. Growth indices of 974 Gy treatment, except leaf length, were significantly lower than CK and other two treatments. Eight effective primers selected from 24 primers combination were used for SRAP-PCR. SRAP analysis revealed that the 57 of 88 DNA fragments were amplified showing polymorphisms. The average percentage of polymorphic bands was 64.77%. The effects of 60 Coγ irradiation on DNA variation of seedlings were varied from different treatments. Numbers of polymorphic bands changed after irradiation. Coefficient of variation was in direct proportion to irradiation doses. Variation rates of 325 Gy, 487 Gy and 974 Gy treatments were 22.0%, 38.1% and 41.5%, respectively. The Nei’s genetic similarity coefficient of all treatments was ranged from 0.585 to 0.780 by software NTSYSpc 2.1 based on SRAP results and the average Nei's coefficient was 0.678. The Nei’s genetic similarity coefficient of 974 Gy treatment was 0.585 and variation degree was highest among all treatments, 487 Gy treatment was second and 325 Gy treatment was the lowest one. Based on present bands, four irradiated treatments were classified into two major groups by UPGMA cluster analysis. Group 1 included CK, 325 Gy and 487 Gy treatment and group 2 included 974 Gy. SRAP analysis determined variation of Stylosanthes after irradiation and the results of SRAP analysis were consistent with their biological indexes in some extent

  16. Single-channel ground airborne radio system (SINCGARS) based remote control for the M1 Abrahms

    Science.gov (United States)

    Urda, Joseph R.

    1995-04-01

    Remote control of the Ml Abrahms Main Battle Tank through a minefield breach operation will remove the vehicle crew from the inherent hazard. A successful remote control system will provide automotive control yet not impair normal operation. This requires a minimum of physical parts, and an unobtrusive installation. Most importantly, a system failure must not impair the regular operation as a manned system. The system itself need not be complex. A minefield breach only requires simple control of automotive function and a mine plow interface. Control hardware for the Ml-Al can be reduced to two linear actuators, an electrical interface for the engine control unit, an interface for the mine plow, and the associated cables. Communication between vehicle control and operator control takes place over the vehicles organic radio (typically SINCGARS). This helps reduce the number of special purpose components for the remote control device. The device is currently awaiting an automotive safety test to prepare for its safety release. Because of the specific nature of the MDL-STD 1553-B data bus the device will not control an M1-A2 Main Battle Tank. The architecture will allow control of the M1-A2 through the 1553-B data bus however the physical hardware has not been constructed. The control scheme will not change. The communication interface will provide greater flexibility when interfacing to the vehicle tactical radio. Operational utility will be determined by U.S. Army Training and Doctrine Command personnel. The obvious benefit is that if a remote tank is lost during a minefield breach the crew is saved.

  17. In Vivo Measurements in Mice in the Bion-M 1 Mission

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Custaud, Marc-Antoine; Popova, Anfisa; Borovik, Anatoliy; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Daria; Vinogradova, Olga

    The main aim of BION-M 1 mission was to reveal morphological, biochemical and molecular mechanisms of adaptation to prolonged exposure in microgravity. Besides that functional state and behavior were assessed in vivo using test battery, home cage observations and implantable telemetry in space-flown mice (SF), control mice from the ground replica of the flight experiment (GC) and in mice kept in vivarium (SFV and GCV). Blood pressure and heart rate were monitored continuously in a subgroup of mice using implantable telemetry throughout the flight as well as before and after it. After 30-days flight aboard BION-M 1 biosatellite SF mice have gained more weight than GC, SFV or GCV mice (11%). SF mice displayed pronounced motor impairment upon examination shortly after landing. 1 day after the flight mice were less active and more anxious in the open-field test, less coordinated in the Rotarod and aerial drop test and had less grip force compared to both control and pre-flight values. Exercise performance was greatly reduced after 30-days flight and recovered by day 7 post-flight. Before the flight mice were trained to perform a simple task using positively reinforced free operant conditioning approach. After the flight performance in the same task was preserved, however learning ability was impaired. Mice displayed drastic reduction of heart rate during launch and reentry acceleration periods. Heart rate (by 8-10%) and, to a lesser extent blood pressure (by 5%) were elevated during the 30-days flight. After return heart rate in SF mice remained elevated throughout the 7-days observation period with no apparent recovery. In summary, mice display pronounced disadaptation to 1g after 30-days exposure in microgravity with different physiological systems having different recovery dynamics. Of particular interest, hemodynamic reactions in mice closely resemble reactions in larger organisms, implying that factors that govern the cardiovascular system adaptation to

  18. Proteoglycan biosynthesis in murine monocytic leukemic (M1) cells before and after differentiation

    International Nuclear Information System (INIS)

    McQuillan, D.J.; Yanagishita, M.; Hascall, V.C.; Bickel, M.

    1989-01-01

    Murine monocytic leukemic (M1) cells were cultured in the presence of [ 3 H]glucosamine and [ 35 S]sulfate. Labeled proteoglycans were purified by anion exchange chromatography and characterized by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in combination with chemical and enzymatic degradation. M1 cells synthesize a single predominant species of proteoglycan which distributes almost equally between the cell and medium after 17 h labeling. The cell-associated proteoglycan has an overall size of about 135 kDa and contains three to five chondroitin sulfate chains (28-31 kDa each) attached to a chondroitinase-generated core protein of 28 kDa. The synthesis and subsequent secretion of this proteoglycan was enhanced 4-5-fold in cells induced to differentiate into macrophages. This was not a phenomenon of arrest in the G0/G1 stage of the cell cycle, since density inhibited undifferentiated cells arrested at this stage did not increase proteoglycan synthesis. The chondroitin sulfate chains contained exclusively chondroitin 4- and 6-sulfate; however, the ratio of these two disaccharides differed between the medium- and cell-associated proteoglycans, and changed during progression of the cells into a fully differentiated phenotype. Pulse-chase kinetics indicate the presence of two distinct pools of proteoglycan; one that is secreted very rapidly from the cell after a approximately 1-h lag, and a second pool that is turned over in the cell with a half-time of approximately 3.5 h. Subtle differences in the glycosylation patterns of the medium- and cell-associated species are consistent with synthesis of two pools. Papain digestion suggests that the chondroitin sulfate chains are clustered on a small protease resistant peptide. The data suggest that this proteoglycan is similar to the serglycin proteoglycan family

  19. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

    Science.gov (United States)

    Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

    2014-05-01

    Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

  20. Matrix quantum mechanics on S1/Z2

    Directory of Open Access Journals (Sweden)

    P. Betzios

    2018-03-01

    Full Text Available We study Matrix Quantum Mechanics on the Euclidean time orbifold S1/Z2. Upon Wick rotation to Lorentzian time and taking the double-scaling limit this theory provides a toy model for a big-bang/big crunch universe in two dimensional non-critical string theory where the orbifold fixed points become cosmological singularities. We derive the MQM partition function both in the canonical and grand canonical ensemble in two different formulations and demonstrate agreement between them. We pinpoint the contribution of twisted states in both of these formulations either in terms of bi-local operators acting at the end-points of time or branch-cuts on the complex plane. We calculate, in the matrix model, the contribution of the twisted states to the torus level partition function explicitly and show that it precisely matches the world-sheet result, providing a non-trivial test of the proposed duality. Finally we discuss some interesting features of the partition function and the possibility of realising it as a τ-function of an integrable hierarchy.

  1. Matrix quantum mechanics on S1 /Z2

    Science.gov (United States)

    Betzios, P.; Gürsoy, U.; Papadoulaki, O.

    2018-03-01

    We study Matrix Quantum Mechanics on the Euclidean time orbifold S1 /Z2. Upon Wick rotation to Lorentzian time and taking the double-scaling limit this theory provides a toy model for a big-bang/big crunch universe in two dimensional non-critical string theory where the orbifold fixed points become cosmological singularities. We derive the MQM partition function both in the canonical and grand canonical ensemble in two different formulations and demonstrate agreement between them. We pinpoint the contribution of twisted states in both of these formulations either in terms of bi-local operators acting at the end-points of time or branch-cuts on the complex plane. We calculate, in the matrix model, the contribution of the twisted states to the torus level partition function explicitly and show that it precisely matches the world-sheet result, providing a non-trivial test of the proposed duality. Finally we discuss some interesting features of the partition function and the possibility of realising it as a τ-function of an integrable hierarchy.

  2. Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

    Science.gov (United States)

    Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

    2016-08-01

    Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice. Copyright © 2016 the American Physiological Society.

  3. Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis.

    Science.gov (United States)

    Dai, Lan; Liu, Yixuan; Xie, Lei; Wu, Xia; Qiu, Lihua; Di, Wen

    2017-09-26

    Sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) signaling pathway has been implicated in a variety of pathological processes of ovarian cancer. However, the function of this axis in ovarian cancer angiogenesis remains incompletely defined. Here we provided the first evidence that SphK1/S1P/S1PR 1/3 pathway played key roles in ovarian cancer angiogenesis. The expression level of SphK1, but not SphK2, was closely correlated with the microvascular density (MVD) of ovarian cancer tissue. In vitro , the angiogenic potential and angiogenic factor secretion of ovarian cancer cells could be attenuated by SphK1, but not SphK2, blockage and were restored by the addition of S1P. Moreover, in these cells, we found S1P stimulation induced the angiogenic factor secretion via S1PR 1 and S1PR 3 , but not S1PR 2 . Furthermore, inhibition of S1PR 1/3 , but not S1PR 2 , attenuated the angiogenic potential and angiogenic factor secretion of the cells. in vivo , blockage of SphK or S1PR 1/3 could attenuate ovarian cancer angiogenesis and inhibit angiogenic factor expression in mouse models. Collectively, the current study showed a novel role of SphK1/S1P/S1PR 1/3 axis within the ovarian cancer, suggesting a new target to block ovarian cancer angiogenesis.

  4. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    Science.gov (United States)

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  5. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

    Science.gov (United States)

    Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

    2015-06-01

    Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

  6. HLA-B27M1M2 and high immune responsiveness to Shigella flexneri in post-dysenteric arthritis

    NARCIS (Netherlands)

    van Bohemen, C. G.; Nabbe, A. J.; Landheer, J. E.; Grumet, F. C.; Mazurkiewicz, E. S.; Dinant, H. J.; Lionarons, R. J.; van Bodegom, P. C.; Zanen, H. C.

    1986-01-01

    The heterogeneous HLA-B27 antigen is closely associated with post-infectious or reactive arthritis (ReA) and is comprised of two serologically defined variants: B27M1+M2+ and B27M1+M2-. An outbreak of dysentery (n = 120) caused by a Shigella flexneri 2a strain, which possessed cell envelope antigens

  7. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase.

    Science.gov (United States)

    Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani; Zhao, Yutong; Natarajan, Viswanathan

    2017-01-01

    Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. . Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs.

    Science.gov (United States)

    Ren, Kun; Lu, Yan-Ju; Mo, Zhong-Cheng; -Liu, Xing; Tang, Zhen-Li; Jiang, Yue; Peng, Xiao-Shan; Li, Li; Zhang, Qing-Hai; Yi, Guang-Hui

    2017-05-01

    Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway.

  9. Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein

    DEFF Research Database (Denmark)

    Schimmel, Joost; Eifler, Karolin; Sigurdsson, Jón Otti

    2014-01-01

    Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during cell......-cycle progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M...... relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression....

  10. Identification of the yeast gene encoding the tRNA m1G methyltransferase responsible for modification at position 9.

    Science.gov (United States)

    Jackman, Jane E; Montange, Rebecca K; Malik, Harmit S; Phizicky, Eric M

    2003-05-01

    Methylation of tRNA at the N-1 position of guanosine to form m(1)G occurs widely in nature. It occurs at position 37 in tRNAs from all three kingdoms, and the methyltransferase that catalyzes this reaction is known from previous work of others to be critically important for cell growth in Escherichia coli and the yeast Saccharomyces cerevisiae. m(1)G is also widely found at position 9 in eukaryotic tRNAs, but the corresponding methyltransferase was unknown. We have used a biochemical genomics approach with a collection of purified yeast GST-ORF fusion proteins to show that m(1)G(9) formation of yeast tRNA(Gly) is associated with ORF YOL093w, named TRM10. Extracts lacking Trm10p have undetectable levels of m(1)G(9) methyltransferase activity but retain normal m(1)G(37) methyltransferase activity. Yeast Trm10p purified from E. coli quantitatively modifies the G(9) position of tRNA(Gly) in an S-adenosylmethionine-dependent fashion. Trm10p is responsible in vivo for most if not all m(1)G(9) modification of tRNAs, based on two results: tRNA(Gly) purified from a trm10-Delta/trm10-Delta strain is lacking detectable m(1)G; and a primer extension block occurring at m(1)G(9) is removed in trm10-Delta/trm10-Delta-derived tRNAs for all 9 m(1)G(9)-containing species that were testable by this method. There is no obvious growth defect of trm10-Delta/trm10-Delta strains. Trm10p bears no detectable resemblance to the yeast m(1)G(37) methyltransferase, Trm5p, or its orthologs. Trm10p homologs are found widely in eukaryotes and many archaea, with multiple homologs in several metazoans, including at least three in humans.

  11. Absolute M1 and E2 Transition Probabilities in 233U

    International Nuclear Information System (INIS)

    Malmskog, S.G.; Hoejeberg, M.

    1967-08-01

    Using the delayed coincidence technique, the following half lives have been determined for different excited states in 233 U: T 1/2 (311.9 keV level) = (1.20 ± 0.15) x 10 -10 sec, T 1/2 (340.5 keV level) = (5.2 ± 1.0) x 10 -11 sec, T 1/2 (398.6 keV level) = (5.5 ± 2.0) x 10 -11 sec and T 1/2 (415.8 keV level) -11 sec. From these half life determinations, together with earlier known electron intensities and conversion coefficients, 22 reduced B(Ml) and B(E2) transition probabilities (including 9 limits) have been deduced. The rotational transitions give information on the parameters δ and (g K - g R ) . The experimental M1 and E2 transition rates between members of different bands have been analysed in terms of the predictions of the Nilsson model, taking also pairing correlations and Coriolis coupling effects into account

  12. Contamination profile of aflatoxin M1 residues in milk supply chain of Sindh, Pakistan

    Directory of Open Access Journals (Sweden)

    Sana Jawaid

    2015-01-01

    Full Text Available Aflatoxin M1 (AFM1 is a potent carcinogen, teratogen and mutagen found in the milk when lactating animals consume feed contaminated with aflatoxin B1 (AFB1. In the present study, the contamination of AFM1 was evaluated in the milk supply chain of the province of Sindh, Pakistan. For the broader profiling of targeted toxin, enzyme-linked immunosorbent assay (ELISA was used for the determination of AFM1 in both branded and non-branded milk samples. The results showed that 96.43% of samples (81 out of 84 were contaminated with AFM1 in the range of 0.01–0.76 μg/L. The average contamination level was 0.38 μg/L. The determined values of AFM1 in the collected milk samples were above the standard limit of the European Commission while 70% of the samples exceeded levels established by United States regulations. According to these results, the estimated daily intake of AFM1 for adults was determined as 3.1 ng/kg of body weight per day.

  13. Pancreatic Resections for Advanced M1-Pancreatic Carcinoma: The Value of Synchronous Metastasectomy

    Directory of Open Access Journals (Sweden)

    S. K. Seelig

    2010-01-01

    Materials and Methods. From January 1, 2004 to December, 2007 a total of 20 patients with pancreatic malignancies were retrospectively evaluated who underwent pancreatic surgery with synchronous resection of hepatic, adjacent organ, or peritoneal metastases for proven UICC stage IV periampullary cancer of the pancreas. Perioperative as well as clinicopathological parameters were evaluated. Results. There were 20 patients (9 men, 11 women; mean age 58 years identified. The primary tumor was located in the pancreatic head (n=9, 45%, in pancreatic tail (n=9, 45%, and in the papilla Vateri (n=2, 10%. Metastases were located in the liver (n=14, 70%, peritoneum (n=5, 25%, and omentum majus (n=2, 10%. Lymphnode metastases were present in 16 patients (80%. All patients received resection of their tumors together with metastasectomy. Pylorus preserving duodenopancreatectomy was performed in 8 patients, distal pancreatectomy in 8, duodenopancreatectomy in 2, and total pancreatectomy in 2. Morbidity was 45% and there was no perioperative mortality. Median postoperative survival was 10.7 months (2.6–37.7 months which was not significantly different from a matched-pair group of patients who underwent pancreatic resection for UICC adenocarcinoma of the pancreas (median survival 15.6 months; P=.1. Conclusion. Pancreatic resection for M1 periampullary cancer of the pancreas can be performed safely in well-selected patients. However, indication for surgery has to be made on an individual basis.

  14. CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages.

    Science.gov (United States)

    Zhang, Yang; Li, Xiang-Xiang; Ma, Yuan; Xu, Jie; Zhao, Li-Na; Qian, Xue-Feng; Zhang, Xian-Feng; Shi, Jin-Fang; Han, Qing-Zhen

    2017-12-04

    Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.

  15. Rates of E1, E2, M1, and M2 transitions in Ni II

    Science.gov (United States)

    Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

    2016-03-01

    Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

  16. Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development

    Directory of Open Access Journals (Sweden)

    Silvia Marchese

    2018-05-01

    Full Text Available Aflatoxins are fungal metabolites found in feeds and foods. When the ruminants eat feedstuffs containing Aflatoxin B1 (AFB1, this toxin is metabolized and Aflatoxin M1 (AFM1 is excreted in milk. International Agency for Research on Cancer (IARC classified AFB1 and AFM1 as human carcinogens belonging to Group 1 and Group 2B, respectively, with the formation of DNA adducts. In the last years, some epidemiological studies were conducted on cancer patients aimed to evaluate the effects of AFB1 and AFM1 exposure on cancer cells in order to verify the correlation between toxin exposure and cancer cell proliferation and invasion. In this review, we summarize the activation pathways of AFB1 and AFM1 and the data already reported in literature about their correlation with cancer development and progression. Moreover, considering that few data are still reported about what genes/proteins/miRNAs can be used as damage markers due to AFB1 and AFM1 exposure, we performed a bioinformatic analysis based on interaction network and miRNA predictions to identify a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation.

  17. Absolute M1 and E2 Transition Probabilities in 2{sup 33}U

    Energy Technology Data Exchange (ETDEWEB)

    Malmskog, S G; Hoejeberg, M

    1967-08-15

    Using the delayed coincidence technique, the following half lives have been determined for different excited states in {sup 233}U: T{sub 1/2} (311.9 keV level) = (1.20 {+-} 0.15) x 10{sup -10} sec, T{sub 1/2} (340.5 keV level) = (5.2 {+-} 1.0) x 10{sup -11} sec, T{sub 1/2} (398.6 keV level) = (5.5 {+-} 2.0) x 10{sup -11} sec and T{sub 1/2} (415.8 keV level) < 3 x 10{sup -11}sec. From these half life determinations, together with earlier known electron intensities and conversion coefficients, 22 reduced B(Ml) and B(E2) transition probabilities (including 9 limits) have been deduced. The rotational transitions give information on the parameters {delta} and (g{sub K} - g{sub R}) . The experimental M1 and E2 transition rates between members of different bands have been analysed in terms of the predictions of the Nilsson model, taking also pairing correlations and Coriolis coupling effects into account.

  18. Monitoring of aflatoxin M1 in raw cow milk in Croatia during winter 2015

    Directory of Open Access Journals (Sweden)

    Nina Bilandžić

    2016-01-01

    Full Text Available A total of 548 raw milk samples were collected in the western, central and eastern regions of Croatia during February and March 2015. Aflatoxin M1 (AFM1 concentrations were quantified by the enzyme immunoassay method. The method limits of detection (LOD and quantification (LOQ were 22.2 and 34.2 ng/kg, respectively. The mean AFM1 levels measured in the three regions were (ng/kg as follows: western 3.69, central 3.11 and eastern 4.14. In total, the 548 samples analysed concentrations were below the LOD value and accordingly below the European Union maximum residue level (EU MRL of 50 ng/kg. The results suggest an absence of use of contaminated with aflatoxin B1 supplementary feedstuff for lactating cows in winter 2015. Such results might be related to the improved storage conditions for feed as well as to the enhanced and more stringent feed control system for mycotoxins in Croatia.

  19. Aflatoxin M1 in Pasteurized Milk in Babol city, Mazandaran Province, Iran.

    Science.gov (United States)

    Sefidgar, Saa; Mirzae, M; Assmar, M; Naddaf, Sr

    2011-01-01

    Aflatoxin M(1) (AFM(1)) is the metabolite of aflatoxin B1 (AFB(1)) and is found in milk when lactating animals are fed with contaminated feedstuff. The presence of AFM(1) in milk, pose a major risk for humans especially kids as it can have immunosuppressive, mutagenic, teratogenic and carcinogenic effects. The present study is aimed to investigate the occurrence of AFM(1) in subsidized pasteurized milk in Babol, Mazandaran Province, Iran. Some 72 pasteurized milk packages were collected from supermarkets in various districts of city during January to March 2006. Milk samples were centrifuged and amounts of 100 μl of skimmed milk were tested for AFM(1) contamination by competitive ELISA. All the samples (100%) exhibited contamination with AFM(1). The contamination levels means in January, February, and March were 227.85, 229.64, and 233.1ng/l, respectively. The amount of AFM(1) in all the samples were above 50ng/l, the threshold set by the European community regulations. Monitoring of AFM(1) level should be part of quality control procedures in dairy factories, particularly the ones providing infant's milk. Production of safer and healthier milk and other dairy products with minimum AFM(1) level can be achieved by adopting prophylactic measures including control of humidity and water content of feedstuff, which favors mould production.

  20. Aflatoxin M1 in milk by immunoaffinity column cleanup with TLC/HPLC determination

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    Shundo Luzia

    2006-01-01

    Full Text Available During 2002 and 2003, a total of 107 samples of raw, pasteurized and ultrahigh treated temperature (UHT milk commercialized in the cities of São Paulo and Marília (SP were analyzed for the presence of aflatoxin M1 (AFM1. AFM1 was detected in 79 (73.8% of milk samples, ranging from <0.02 to 0.26 mug/L.The samples were analyzed using an immunoaffinity column for cleanup and a thin layer chromatography for determining AFM1. The parameters, such as recovery, repeatibility, detection and quantification limit were evaluated to optimize this method (in-house. Based on spiked samples, the recovery values ranged from 85.83 to 73.86% at levels of 0.010-0.50 mug/L, respectively, and the relative standard deviation for repeatibility ranged from 7.73 to 2.08%. The quantification limit was 0.02 mug/L. The results of some samples analyzed by this method demonstrated a satisfatory correlation when compared with High Performance Liquid Chromatography (HPLC. In conclusion, immunoaffinity column cleanup gave excellent results for recovery, sensibility and sample through put. Despite the high rate of occurrence of AFM1 in samples in both cities, the contamination level could not be considered a serious public health hazard, according to Brazilian legislation.

  1. A survey of aflatoxin M1 in cow milk in Southern Iran

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    Majid Hashemi

    2016-10-01

    Full Text Available The competitive enzyme-linked immunosorbent assay technique was used to evaluate aflatoxin M1 (AFM1 levels in 168 samples of raw milk (135 samples and 33 samples from bulk tanks of farms and milk collection centers, respectively and 12 samples of pasteurized milk in Fars province, Southern Iran. AFM1 was found in 55.56% of the samples with a mean concentration of 21.31 ng/L. The concentration of AFM1 in raw milk samples from farms was significantly (p < 0.05 lower than that in samples from collection centers and pasteurized milk. The concentration of AFM1 was not influenced by season, location, or type of farm. The concentrations of AFM1 in all samples were lower than the Iranian national standard limit (100 ng/L, but in 30% of raw cow milk samples they were higher than the maximum tolerance limit accepted by the European Union (50 ng/L; therefore, more effort is needed to control AFM1 levels in milk produced in Southern Iran.

  2. Development of an Electrochemical Biosensor for the Detection of Aflatoxin M1 in Milk

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    Jean-Louis Marty

    2010-10-01

    Full Text Available We have developed an electrochemical immunosensor for the detection of ultratrace amounts of aflatoxin M1 (AFM1 in food products. The sensor was based on a competitive immunoassay using horseradish peroxidase (HRP as a tag. Magnetic nanoparticles coated with antibody (anti-AFM1 were used to separate the bound and unbound fractions. The samples containing AFM1 were incubated with a fixed amount of antibody and tracer [AFM1 linked to HRP (conjugate] until the system reached equilibrium. Competition occurs between the antigen (AFM1 and the conjugate for the antibody. Then, the mixture was deposited on the surface of screen-printed carbon electrodes, and the mediator [5-methylphenazinium methyl sulphate (MPMS] was added. The enzymatic response was measured amperometrically. A standard range (0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, 0.3, 0.4 and 0.5 ppb of AFM1-contaminated milk from the ELISA kit was used to obtain a standard curve for AFM1. To test the detection sensitivity of our sensor, samples of commercial milk were supplemented at 0.01, 0.025, 0.05 or 0.1 ppb with AFM1. Our immunosensor has a low detection limit (0.01 ppb, which is under the recommended level of AFM1 [0.05 µg L-1 (ppb], and has good reproducibility.

  3. Distribution and stability of Aflatoxin M1 during processing and ripening of traditional white pickled cheese.

    Science.gov (United States)

    Oruc, H H; Cibik, R; Yilmaz, E; Kalkanli, O

    2006-02-01

    The distribution of aflatoxin M(1) (AFM(1)) has been studied between curd, whey, cheese and pickle samples of Turkish white pickled cheese produced according to traditional techniques and its stability studied during the ripening period. Cheeses were produced in three cheese-making trials using raw milk that was artificially contaminated with AFM(1) at the levels of 50, 250 and 750 ng/l and allowed to ripen for three months. AFM(1) determinations were carried out at intervals by LC with fluorescence detection after immunoaffinity column clean-up. During the syneresis of the cheese a proportionately high concentration of AFM(1) remained in curd and for each trial the level was 3.6, 3.8 and 4.0 times higher than levels in milk. At the end of the ripening, the distribution of AFM(1) for cheese/whey + brine samples was 0.9, 1.0 and 1.3 for first, second and third spiking respectively indicating that nearly half of the AFM(1) remained in cheese. It has been found that only 2-4% of the initial spiking of AFM(1) transferred into the brine solution. During the ripening period AFM(1) levels remained constant suggesting that AFM(1) was quite stable during manufacturing and ripening.

  4. Distribution of radiative strength with excitation energy: the E1 and M1 giant resonances

    International Nuclear Information System (INIS)

    Brown, G.E.; Speth, J.

    1979-01-01

    Calculations of the giant dipole resonance in the particle-hole model, employing empirical values for the unperturbed particle and hole energies, have been unsuccessful in pushing the dipole state to a sufficiently high energy. it is argued that unperturbed levels correspondign to an effective mass of m*/m approx. 0.6 to 0.7 should be employed. The couplings of particles and holes to vibrations are the crucial ingredients in these considerations. More generally, it is argued that the effective mass relevant to excitations near the Fermi surface is that corresponding to empirical single-particle levels, m*/m greater than or equal to 1.0. For particle-hole excitations above the Fermi surface, it is a decreasing function of excitation energy, reaching the above values 0.6 to 0.7 for E greater than or equal to 2 dirac constant/b omega, dirac constant/sub omega/ being the shell spacing. This has the consequence of spreading out the M1 strength. A new interpretation of experimental strengths is proposed

  5. CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

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    Paula Mota

    2010-01-01

    Full Text Available Lung cancer is considered an environment-related disease that develops as a consequence of exposure to mutagenic agents, namely those present in tobacco. The CYP1A1 gene codifies the phase I enzyme aryl hydrocarbon hydroxilase (AHH belonging to the cytochrome P450 system that plays a major role in the bio-activation of tobacco procarcinogenes. Two CYP1A1 polymorphisms, m1 (T6235C transition and m2 (A4889G transition, are associated with greater enzymatic activity and have been described as genetic susceptibility factors for lung cancer.The aim of this study was to verify if this association holds true in blood samples of 175 lung cancer patients and 217 non-cancer patients from Portugal's midlands region. The samples were studied by restriction fragment length polymorphism (RFLP assay.The allelic frequencies of the mutant alleles were 0.12 for allele C and 1.14 for allele G in the control population. The results were not statistically different from those alleles in the patient population. There was also no statistically significant difference in genotype distribution in lung cancer patients and controls even when combining high risk genotypes. In our control sample, as in other populations of different ethnic origin, both polymorphisms also seem to be in linkage disequilibrium. We conclude that in this sample of the Portuguese population, CYP1A1 m1 and m2 polymorphisms are too rare to be of clinical relevance, and do not seem to be associated with susceptibility to lung cancer. Resumo: O cancro do pulmão é considerado uma doença relacionada com o meio ambiente, consequência da exposição a agentes mutagénicos, nomeadamente os presentes no fumo do tabaco. O gene CYP1A1 codifica a enzima aril hidrocarboneto hidroxilase (AHH, da fase I, do sistema multienzimático do citocromo P450, que desempenha uma função preponderante na bioactivação dos procarcinogénios do tabaco. Dois polimorfismos do CYP1A1, m1 (transi

  6. Development of an impedimetric aptasensor for the determination of aflatoxin M1 in milk.

    Science.gov (United States)

    Istamboulié, Georges; Paniel, Nathalie; Zara, Lorena; Reguillo Granados, Lucia; Barthelmebs, Lise; Noguer, Thierry

    2016-01-01

    An aptasensor was designed for the determination of aflatoxin M1 (AFM1) in milk based on DNA-aptamer recognition and electrochemical impedance spectroscopy detection. A hexaethyleneglycol-modified 21-mer oligonucleotide was immobilized on a carbon screen-printed electrode through carbodiimide immobilization, after diazonium activation of the sensing surface. Cyclic voltammetry and electrochemical impedance spectroscopy in the presence of ferri/ferrocyanide redox probe were used to characterize each step of the aptasensor development. Aptamer-AFM1 interaction induced an increase in electron-transfer resistance, allowing the determination of AFM1 in buffer in the range 2-150 ng/L (LOD=1.15 ng/L). Application to milk analysis showed that a preliminary treatment was mandatory. A simple filtration through a 0.2 µm PTFE membrane allowed determination of AFM1 in milk for concentrations ranging from 20 to 1000 ng/kg. These performances are compatible with the AFM1 levels set in European Union for milk and dairy products for adults (50 ng/kg) and infants (25 ng/kg). Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Aflatoxin M1 levels in raw milk, pasteurised milk and infant formula

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    Sharaf S. Omar

    2016-06-01

    Full Text Available The incidence of contamination of aflatoxin M1 (AFM1 in milk samples collected from the Jordanian market was investigated by using the competitive enzyme linked immunosorbent assay (ELISA technique. A total of 175 samples were collected during 2014-2015. All tested samples were contaminated with various levels of AFM1 ranging from 9.71 to 288.68 ng/kg. The concentration of AFM1 in 66% of fresh milk samples was higher than the maximum tolerance limit accepted by the European Union (50 ng/kg and 23% higher than the maximum tolerance limit accepted by the US (500 ng/kg. Percentages of contaminated raw cow, sheep, goat and camel milk exceeding the European tolerance limit were 60, 85, 75 and 0%, respectively. Of AFM1 contaminated pasteurised cow milk samples, 12% exceeded the European tolerance limit with a range of contamination between 14.60 and 216.78 ng/kg. For infant formula samples, the average concentration of AFM1 was 120.26 ng/kg (range from 16.55 to 288.68 ng/kg, the concentration of AFM1 in 85% of infant formula samples was higher than the maximum tolerance limit accepted by the European Union and the US (25 ng/kg.

  8. Genomic Comparison among Lethal Invasive Strains of Streptococcus pyogenes Serotype M1

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    Gabriel R. Fernandes

    2017-10-01

    Full Text Available Streptococcus pyogenes, also known as group A Streptococcus (GAS, is a human pathogen that causes diverse human diseases including streptococcal toxic shock syndrome (STSS. A GAS outbreak occurred in Brasilia, Brazil, during the second half of the year 2011, causing 26 deaths. Whole genome sequencing was performed using Illumina platform. The sequences were assembled and genes were predicted for comparative analysis with emm type 1 strains: MGAS5005 and M1 GAS. Genomics comparison revealed one of the invasive strains that differ from others isolates and from emm 1 reference genomes. Also, the new invasive strain showed differences in the content of virulence factors compared to other isolated in the same outbreak. The evolution of contemporary GAS strains is strongly associated with horizontal gene transfer. This is the first genomic study of a Streptococcal emm 1 outbreak in Brazil, and revealed the rapid bacterial evolution leading to new clones. The emergence of new invasive strains can be a consequence of the injudicious use of antibiotics in Brazil during the past decades.

  9. Reduction of Aflatoxin M1 Levels during Ethiopian Traditional Fermented Milk (Ergo Production

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    Tsige Shigute

    2018-01-01

    Full Text Available In this study, the reduction of aflatoxin M1 (AFM1 levels during lab-scale ergo production was investigated through determination of the residual levels of AFM1 using Enzyme Linked Immunosorbent Assay. The results showed gradual and incubation time dependent reduction of AFM1 level in the raw milk samples being fermented to ergo. The maximum reductions of 57.33 and 54.04% were recorded in AFM1 in natural and LAB inoculums initiated fermentations, respectively, in 5 days of incubation. Although a significant difference (P=0.05 in the AFM1 decrease in the two types of fermentations was recorded, such findings could vary with milk samples depending on initial load of the microorganisms as determined by hygienic conditions. However, the level of AFM1 in control (sterilized samples showed only a 5.5% decrease during the entire period of incubation. Microbiological investigation showed increasing LAB counts with incubation time. A gradual decrease in pH of the milk samples was observed during fermentation. Considering the fact that both viable and dead bacterial cells could remove AFM1 during ergo production, the mechanism is proposed as predominantly involving noncovalent binding of the toxin with the chemical components of the bacterial cell wall.

  10. Medical students who decompress during the M-1 year outperform those who fail and repeat it: A study of M-1 students at the University of Illinois College of Medicine at Urbana-Champaign 1988–2000

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    Freund Gregory G

    2005-05-01

    Full Text Available Abstract Background All medical schools must counsel poor-performing students, address their problems and assist them in developing into competent physicians. The objective of this study was to determine whether students with academic deficiencies in their M-1 year graduate more often, spend less time to complete the curriculum, and need fewer attempts at passing USMLE Step 1 and Step 2 by entering the Decompressed Program prior to failure of the M-1 year than those students who fail the M-1 year and then repeat it. Method The authors reviewed the performance of M-1 students in the Decompressed Program and compared their outcomes to M-1 students who failed and fully repeated the M-1 year. To compare the groups upon admission, t-Tests comparing the Cognitive Index of students and MCAT scores from both groups were performed. Performance of the two groups after matriculation was also analyzed. Results Decompressed students were 2.1 times more likely to graduate. Decompressed students were 2.5 times more likely to pass USMLE Step 1 on the first attempt than the repeat students. In addition, 46% of those in the decompressed group completed the program in five years compared to 18% of the repeat group. Conclusion Medical students who decompress their M-1 year prior to M-1 year failure outperform those who fail their first year and then repeat it. These findings indicate the need for careful monitoring of M-1 student performance and early intervention and counseling of struggling students.

  11. Sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis is involved in liver fibrosis-associated angiogenesis.

    Science.gov (United States)

    Yang, Le; Yue, Shi; Yang, Lin; Liu, Xin; Han, Zhen; Zhang, Yuanyuan; Li, Liying

    2013-07-01

    Sphingosine kinase (SphK)/sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) axis is involved in multiple biological processes, including liver fibrosis. Angiogenesis is an important pathophysiological process closely associated with liver fibrosis; however, the functional role of SphK/S1P/S1PR in this process remains incompletely defined. Bile duct ligation or carbon tetrachloride was used to induce liver fibrosis in mice. Human fibrotic samples were obtained from livers of patients undergoing liver transplantation. S1P levels in the liver were examined by HPLC. Expression of angiogenic markers, including angiopoietin 1, CD31, vascular cell adhesion molecule-1, and von Willebrand factor, was characterized by immunofluorescence, real-time RT-PCR, and Western blot in the fibrotic liver and primary mouse hepatic stellate cells (HSCs). SphK inhibitor (SKI) or S1PR antagonists were administered intraperitoneally in mice. S1P levels in the liver were closely correlated with mRNA expression of angiogenic markers. Ang1 is expressed in activated HSCs of the fibrotic liver and in primary HSCs. In HSCs, by using specific antagonists or siRNAs, we demonstrated S1P stimulation induced Ang1 expression via S1PR1 and S1PR3. In vivo, S1P reduction by SKI inhibited angiogenesis in fibrotic mice. Furthermore, S1PR1/3 antagonist significantly blocked upregulation of angiogenic markers in the injured liver, and attenuated the extent of liver fibrosis, while S1PR2 antagonist had no effect on angiogenesis, supporting the key role of S1PR1 and S1PR3 in angiogenesis underlying liver fibrosis process. SphK1/S1P/S1PR1/3 axis plays a crucial role in the angiogenic process required for fibrosis development, which may represent an effective therapeutic strategy for liver fibrosis. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

    Science.gov (United States)

    Yang, Weiwei; Li, Qinghua; Pan, Zhifang

    2014-01-01

    Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

  13. Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

    Science.gov (United States)

    Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

  14. Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages Regulates Glucose Intolerance in Obesity

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    Donghyun Kim

    2017-07-01

    Full Text Available IRF5 is a signature transcription factor that induces M1 macrophage polarization. However, little is known regarding cytosolic proteins that induce IRF5 activation for M1 polarization. Here, we report the interaction between ubiquitin E3 ligase Pellino-1 and IRF5 in the cytoplasm, which increased nuclear translocation of IRF5 by K63-linked ubiquitination in human and mouse M1 macrophages. LPS and/or IFN-γ increased Pellino-1 expression, and M1 polarization was attenuated in Pellino-1-deficient macrophages in vitro and in vivo. Defective M1 polarization in Pellino-1-deficient macrophages improved glucose intolerance in mice fed a high-fat diet. Furthermore, macrophages in adipose tissues from obese humans exhibited increased Pellino-1 expression and IRF5 nuclear translocation compared with nonobese subjects, and these changes are associated with insulin resistance index. This study demonstrates that cytosolic Pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-γ receptor-IRF5 axis during M1 polarization.

  15. BION-M 1: First continuous blood pressure monitoring in mice during a 30-day spaceflight

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Popova, Anfisa; Lloret, Jean-Christophe; Aubry, Patrick; Borovik, Anatoliy; Tsvirkun, Daria; Vinogradova, Olga; Ilyin, Eugeniy; Gauquelin-Koch, Guillemette; Gharib, Claude; Custaud, Marc-Antoine

    2017-05-01

    Animals are an essential component of space exploration and have been used to demonstrate that weightlessness does not disrupt essential physiological functions. They can also contribute to space research as models of weightlessness-induced changes in humans. Animal research was an integral component of the 30-day automated Russian biosatellite Bion-M 1 space mission. The aim of the hemodynamic experiment was to estimate cardiovascular function in mice, a species roughly 3000 times smaller than humans, during prolonged spaceflight and post-flight recovery, particularly, to investigate if mice display signs of cardiovascular deconditioning. For the first time, heart rate (HR) and blood pressure (BP) were continuously monitored using implantable telemetry during spaceflight and recovery. Decreased HR and unchanged BP were observed during launch, whereas both HR and BP dropped dramatically during descent. During spaceflight, BP did not change from pre-flight values. However, HR increased, particularly during periods of activity. HR remained elevated after spaceflight and was accompanied by increased levels of exercise-induced tachycardia. Loss of three of the five mice during the flight as a result of the hardware malfunction (unrelated to the telemetry system) and thus the limited sample number constitute the major limitation of the study. For the first time BP and HR were continuously monitored in mice during the 30-day spaceflight and 7-days of post-flight recovery. Cardiovascular deconditioning in these tiny quadruped mammals was reminiscent of that in humans. Therefore, the loss of hydrostatic pressure in space, which is thought to be the initiating event for human cardiovascular adaptation in microgravity, might be of less importance than other physiological mechanisms. Further experiments with larger number of mice are needed to confirm these findings.

  16. Wingspan stent for symptomatic M1 stenosis of middle cerebral artery

    International Nuclear Information System (INIS)

    Guo Xinbin; Ma Nan; Hu Xiaobo; Guan Sheng; Fan Yimu

    2011-01-01

    Objective: Stent placement for intracranial atherosclerotic stenosis has become an alternative treatment technique; however, stent placement for middle cerebral artery (MCA) stenosis remains a technical and clinical challenge. Our purpose was to assess the safety and feasibility of Wingspan stent for patients with symptomatic M1 stenosis, and its initial effect on prevention of ischemic events. Methods: Fifty-three cases with recurrent symptomatic MCA stenosis resistant to medical therapy treated by self-expanding stent were reviewed retrospectively (average 58 ± 18.5 years old, 19 women). All patients underwent angioplasty and stenting with the Gateway balloon–Wingspan stent system, and advised follow-up with DSA or TCD at 6th month. Results: Patients had an average stenosis ratio of 76.5 ± 15.4% prior to the treatment. Of the 53 patients, the technical success rate was 98.1% as a whole (52/53). The mean degree of stenosis reduced from (76.5 ± 15.4)% to (18.2 ± 11.3)%. Complications associated with the procedure include subarachnoid hemorrhage (1.89%) and occlusion (3.78%) occurred. During a follow-up of 6 months, there was no recurrence of transient ischemic attack or stroke in 52 cases with successful stenting. Cerebral hemodynamics of MCA using transcranial Doppler monitoring were at normal level (<120 cm/s) in 41 follow-up patients. The follow up angiography at 6 month post-procedure was conducted in 32 patients and showed good patency in stented vessels. Conclusions: Wingspan stent for symptomatic stenosis of middle cerebral artery is a safe and feasible procedure. It improves clinical outcome in the intermediate follow up, but its long-term effect remains to be further evaluated.

  17. Lactobacillus kefiranofaciens M1 isolated from milk kefir grains ameliorates experimental colitis in vitro and in vivo.

    Science.gov (United States)

    Chen, Y P; Hsiao, P J; Hong, W S; Dai, T Y; Chen, M J

    2012-01-01

    Lactobacillus kefiranofaciens M1, isolated from and identified in Taiwanese milk kefir grain, has demonstrated immune-modulating activity. In the present study, we further investigated the effects of Lb. kefiranofaciens M1 on intestinal epithelial cells in vitro and on dextran sodium sulfate (DSS)-induced colitis in vivo. The possible mechanisms regarding the cytokine products and intestinal epithelial barrier restoration as well as the putative receptor for the protective effects of Lb. kefiranofaciens M1 were investigated. In vitro results indicated that Lb. kefiranofaciens M1 could strengthen the epithelial barrier function in vitro by increasing the transepithelial electrical resistance (TEER) and significantly upregulated the level of the chemokine CCL-20 at both the apical and basolateral sites. The in vivo effects of Lb. kefiranofaciens M1 on the regulation of intestinal physiology indicate that this strain could ameliorate DSS-induced colitis with a significant attenuation of the bleeding score and colon length shortening. Production of proinflammatory cytokines was decreased and that of the antiinflammatory cytokine IL-10 was increased in the DSS-treated mice given Lb. kefiranofaciens M1. The putative receptor for the protective effects of Lb. kefiranofaciens M1 was toll-like receptor 2 (TLR2), which was involved in probiotic-induced cytokine production in vitro and in attenuation of the bleeding score and colon length shortening in vivo. In this study, the kefir lactobacillus Lb. kefiranofaciens M1 clearly demonstrated an anticolitis effect. Based on these results, Lb. kefiranofaciens M1 has the potential to be applied in fermented dairy products as an alternative therapy for intestinal disorders. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  18. Endothelial and Smooth Muscle Cell Interaction via FoxM1 Signaling Mediates Vascular Remodeling and Pulmonary Hypertension.

    Science.gov (United States)

    Dai, Zhiyu; Zhu, Maggie M; Peng, Yi; Jin, Hua; Machireddy, Narsa; Qian, Zhijian; Zhang, Xianming; Zhao, You-Yang

    2018-04-17

    Angioproliferative vasculopathy is a hallmark of pulmonary arterial hypertension (PAH). However, little is known how endothelial cell (EC) and smooth muscle cell (SMC) crosstalk regulates the angioproliferative vascular remodeling. We aimed to investigate the role of EC and SMC interaction and underlying signaling pathways in PH development. SMC-specific Foxm1 or Cxcr4 knockout mice, EC-specific Foxm1 or Egln1 knockout mice, as well as EC-specific Egln1/Cxcl12 double knockout mice were used to assess the role of FoxM1 on SMC proliferation and PH. Lung tissues and cells from PAH patients were employed to validate clinical relevance. FoxM1 inhibitor Thiostrepton was used in Sugen 5416/hypoxia- and monocrotaline-challenged rats. FoxM1 expression was markedly upregulated in lungs and pulmonary arterial SMCs of idiopathic PAH patients and 4 discrete PH rodent models. Mice with SMC- (but not EC-) specific deletion of Foxm1 were protected from hypoxia- or Sugen 5416/hypoxia-induced PH. The upregulation of FoxM1 in SMCs induced by multiple EC-derived factors (PDGF-B, CXCL12, ET-1 and MIF) mediated SMC proliferation. Genetic deletion of endothelial Cxcl12 in Egln1Tie2Cre mice or loss of its cognate receptor Cxcr4 in SMCs in hypoxia-treated mice inhibited FoxM1 expression, SMC proliferation and PH. Accordingly, pharmacological inhibition of FoxM1 inhibited severe PH in both Sugen 5416/hypoxia and monocrotaline-challenged rats. Multiple factors derived from dysfunctional ECs induced FoxM1 expression in SMCs and activated FoxM1-dependent SMC proliferation which contributes to pulmonary vascular remodeling and PH. Thus, targeting FoxM1 signaling represents a novel strategy for treatment of IPAH.

  19. E2,M1 multipole mixing ratios in even--even nuclei, A greater than or equal to 152

    International Nuclear Information System (INIS)

    Krane, K.S.

    1975-01-01

    A survey is presented of E2,M1 mixing ratios of gamma-ray transitions in even-even nuclei with mass numbers A greater than or equal to 152. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. The cutoff date for the literature was June 1975. Based on an average of the experimental results from the literature, a recommended value of the E2,M1 mixing ratio for each transition is included

  20. Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1-phosphate (S1P)/S1P3 signaling axis.

    Science.gov (United States)

    Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji

    2015-10-01

    Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-β is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF-β/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1-phosphate (S1P)/S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF-β/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3(-/-) mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13(+) chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3(-/-) mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-β type II receptor-dependent manner, and S1P3 was found to be required for TGF-β-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3.

    Science.gov (United States)

    Lee, Hui Min; Lo, Kwok-Wai; Wei, Wenbin; Tsao, Sai Wah; Chung, Grace Tin Yun; Ibrahim, Maha Hafez; Dawson, Christopher W; Murray, Paul G; Paterson, Ian C; Yap, Lee Fah

    2017-05-01

    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  2. Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

    Science.gov (United States)

    Patmanathan, Sathya Narayanan; Johnson, Steven P; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R; Herr, Deron R; Murray, Paul G; Yap, Lee Fah; Paterson, Ian C

    2016-05-10

    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.

  3. Progress toward measuring the 6S1/2 5D3/2 magnetic-dipole transition moment in Ba+

    Science.gov (United States)

    Williams, Spencer; Jayakumar, Anupriya; Hoffman, Matthew; Blinov, Boris; Fortson, Norval

    2015-05-01

    We report the latest results from our effort to measure the magnetic-dipole transition moment (M1) between the 6S1 / 2 and 5D3 / 2 manifolds in Ba+. We describe a new technique for calibrating view-port birefringence and how we will use it to enhance the M1 signal. To access the transition moment we use a variation of a previously proposed technique that allows us to isolate the magnetic-dipole coupling from the much larger electric-quadrupole coupling in the transition rates between particular Zeeman sub-levels. Knowledge of M1 is crucial for a parity-nonconservation experiment in the ion where M1 will be a leading source of systematic errors. No measurement of this M1 has been made in Ba+, however, there are three calculations that predict it to be 80 ×10-5μB, 22 ×10-5μB, and 17 ×10-5μB. A precise measurement may help resolve this theoretical discrepancy which originates from their different estimations of many-body effects. Supported by NSF Grant No. 09-06494F.

  4. Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

    2017-08-01

    Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

  5. Sphingosine 1-Phosphate (S1P) Carrier-dependent Regulation of Endothelial Barrier

    Science.gov (United States)

    Wilkerson, Brent A.; Grass, G. Daniel; Wing, Shane B.; Argraves, W. Scott; Argraves, Kelley M.

    2012-01-01

    Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to promote endothelial cell (EC) barrier function. In plasma, S1P is associated with both high density lipoproteins (HDL) and albumin, but it is not known whether the carriers impart different effects on S1P signaling. Here we establish that HDL-S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1, and involve persistent activation of Akt and endothelial NOS (eNOS), as well as activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1 protein levels were found to be higher in response to HDL-S1P treatment as compared with albumin-S1P, and this effect was not associated with increased S1P1 mRNA or dependent on de novo protein synthesis. Several pieces of evidence indicate that long term EC barrier enhancement activity of HDL-S1P is due to specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with cells treated with albumin-S1P. Second, the long term barrier-promoting effects of HDL-S1P were abrogated by treatment with the recycling blocker, monensin. Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched microdomains were higher after treatment with HDL-S1P as compared with albumin-S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC-dependent EC barrier function. PMID:23135269

  6. Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhengming; Zhou, Jun; Zhang, Yingtao [Developmental Therapeutics Program, Karmanos Cancer Institute, Detroit, MI (United States); Bepler, Gerold, E-mail: beplerg@karmanos.org [Developmental Therapeutics Program, Karmanos Cancer Institute, Detroit, MI (United States)

    2011-09-23

    Highlights: {yields} Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. {yields} The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. {yields} The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. {yields} C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. {yields} The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy. -- Abstract: Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its function is indispensible in cell proliferation and DNA repair. It also serves as a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'-difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic explanation remains to be determined. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90 kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change resulting from covalent labeling by gemcitabine. It is specific to gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable in human tumor xenografts in mice treated with gemcitabine. Among mutations of seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the conformational change, while N427A, C787A, and C790A diminished it. C444A was unique since it was able to alter the conformation even in absence of gemcitabine treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine-induced conformational change of RRM1, and this stabilized RRM1

  7. Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

    International Nuclear Information System (INIS)

    Chen, Zhengming; Zhou, Jun; Zhang, Yingtao; Bepler, Gerold

    2011-01-01

    Highlights: → Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. → The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. → The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. → C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. → The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy. -- Abstract: Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its function is indispensible in cell proliferation and DNA repair. It also serves as a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'-difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic explanation remains to be determined. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90 kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change resulting from covalent labeling by gemcitabine. It is specific to gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable in human tumor xenografts in mice treated with gemcitabine. Among mutations of seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the conformational change, while N427A, C787A, and C790A diminished it. C444A was unique since it was able to alter the conformation even in absence of gemcitabine treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine-induced conformational change of RRM1, and this stabilized RRM1 conformation has the potential to serve as a specific

  8. detection of aflatoxin M1 contamination in milk for Syrian market using ELISA

    International Nuclear Information System (INIS)

    Ghanem, I.; Orfi, M.

    2008-01-01

    Aflatoxin M1 (AFM1) is the hydroxylated metabolite of a biotransformation process of Aflatoxin B1 (AFB1) which is produced in food and feed by the fungi Aspergillus flavus and A. paraciticus. AFM1 has been shown to be excreted in milk following exposure to AFB1 contaminated feed. Since milk is consumed in large quantities by human populations, particularly among infants and young children the occurrence of AFM1 in this product is constitutes and health hazard since it is carcinogenic and has been listed as Class 2B carcinogen. The occurrence of AFM1 in milk samples from the Syrian market was investigated by the competitive ELISA technique. A total of 126 samples consisting of fresh cow milk (74), locally processed pasteurized cow milk (10), sheep milk (23), goat milk (11) and powdered milk and infant formula (8) showed that the incidence of contamination, i.e. above the detection limit of the ELISA assay, was 80%. 18% of the tested samples contained higher than the acceptable level of AFM1 adopted in Syria, which is 200 ng/kg; whereas, 17% and 54% of all tested samples contained AFM1 higher than the acceptable level in the US, (500 ng/kg) and in the European Union (50 ng/kg), respectively. The range of contamination with AFM1 was higher in cow milk samples than in sheep milk and goat milk samples. 30% of the analyzed cow fresh milk samples contained levels of AFM1 exceeding that of the European Communities (Codex Alimentarius) recommended limits (50 ng/l); whereas, 13% of the analyzed sheep milk samples (23) exceeded the latter limit, and only 9% of the analyzed goat milk samples exceeded same limit. Pasteurized milk, which is collected from various locations, showed particularly high level of contamination, with 80% and 50% of tested samples showing levels of contamination higher than the European and US acceptable levels, respectively. Powdered milk and infant formula, which are imported and only dispensed locally, were free of contamination. The above result

  9. Bion M1. Peculiarities of life activities of microbes in 30-day spaceflight

    Science.gov (United States)

    Viacheslav, Ilyin; Korshunov, Denis; Morozova, Julia; Voeikova, Tatiana; Tyaglov, Boris; Novikova, Liudmila; Krestyanova, Irina; Emelyanova, Lydia

    The aim of this work was to analyze the influence of space flight factors ( SFF) to microorganism strains , exposed inside unmanned spacecraft Bion M-1 during the 30- day space flight. Objectives of the work - the study of the influence of the SFF exchange chromosomal DNA in crosses microorganisms of the genus Streptomyces; the level of spontaneous phage induction of lysogenic strains fS31 from Streptomyces lividans 66 and Streptomyces coelicolor A3 ( 2 ) on the biosynthesis of the antibiotic tylosin strain of Streptomyces fradiae; survival electrogenic bacteria Shewanella oneidensis MR- 1 is used in the microbial fuel cell As a result of this work it was found that the SFF affect the exchange of chromosomal DNA by crossing strains of Streptomyces. Was detected polarity crossing , expressed in an advantageous contribution chromosome fragment of one of the parent strains in recombinant offspring. This fact may indicate a more prolonged exposure of cells in microgravity and , as a consequence, the transfer of longer fragments of chromosomal DNA This feature is the transfer of genetic material in microgravity could lead to wider dissemination and horizontal transfer of chromosomal and plasmid DNA of symbiotic microflora astronauts and other strains present in the spacecraft. It was shown no effect on the frequency of recombination PCF and the level of mutation model reversion of auxotrophic markers to prototrophy It was demonstrated that PCF increase the level of induction of cell actinophage fS31 lysogenic strain of S. lividans 66, but did not affect the level of induction of this phage cells S. coelicolor A3 ( 2). It is shown that the lower the level of synthesis PCF antibiotic aktinorodina (actinorhodin) in lysogenic strain S. coelicolor A3 ( 2). 66 Strains of S. lividans and S. coelicolor A3 ( 2 ) can be used as a biosensor for studying the effect on microorganisms PCF It is shown that the effect of the PCF reduces synthesis of tylosin and desmicosyn S. fradiae at

  10. Effect of 60Co gamma radiation on the performance of two soybean varieties in M1 and M2 generations

    International Nuclear Information System (INIS)

    Miah, M.A.; Rahman, L.

    1982-01-01

    Seed of two soybean varieties Bragg and Improved Pelican were treated with gamma-rays at 0, 11, 29, 47 and 65 Kr doses. Percentage of seedling emergence in both varieties in M 1 generation was not so seriously affected as in M 1 generation. The plant height of Bragg after one month of sowing was less influenced than Improved Pelican. Plant height of both the varieties decreased with increase in radiation doses; except 11 Kr in Bragg in both generations. Similar results were also obtained in plant height at harvest except that Improved Pelican in M 1 generation produced taller plants at 29 Kr than at 11 Kr level. Days required to harvest increased at higher doses in comparison to control, except 11 Kr for Improved Pelican and 29 Kr for Bragg in M 1 generation. (author)

  11. Targeting the SphK1/S1P/S1PR1 Axis That Links Obesity, Chronic Inflammation, and Breast Cancer Metastasis.

    Science.gov (United States)

    Nagahashi, Masayuki; Yamada, Akimitsu; Katsuta, Eriko; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P; Hait, Nitai C; Allegood, Jeremy C; Tsuchida, Junko; Yuza, Kizuki; Nakajima, Masato; Abe, Manabu; Sakimura, Kenji; Milstien, Sheldon; Wakai, Toshifumi; Spiegel, Sarah; Takabe, Kazuaki

    2018-04-01

    Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here, we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates cancer pathogenesis. A high-fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors. Targeting the SphK1/S1P/S1PR1 axis with FTY720/fingolimod attenuated key proinflammatory cytokines, macrophage infiltration, and tumor progression induced by obesity. S1P produced in the lung premetastatic niche by tumor-induced SphK1 increased macrophage recruitment into the lung and induced IL6 and signaling pathways important for lung metastatic colonization. Conversely, FTY720 suppressed IL6, macrophage infiltration, and S1P-mediated signaling pathways in the lung induced by a high-fat diet, and it dramatically reduced formation of metastatic foci. In tumor-bearing mice, FTY720 similarly reduced obesity-related inflammation, S1P signaling, and pulmonary metastasis, thereby prolonging survival. Taken together, our results establish a critical role for circulating S1P produced by tumors and the SphK1/S1P/S1PR1 axis in obesity-related inflammation, formation of lung metastatic niches, and breast cancer metastasis, with potential implications for prevention and treatment. Significance: These findings offer a preclinical proof of concept that signaling by a sphingolipid may be an effective target to prevent obesity-related breast cancer metastasis. Cancer Res; 78(7); 1713-25. ©2018 AACR . ©2018 American Association for Cancer Research.

  12. A Prokaryotic S1P Lyase Degrades Extracellular S1P In Vitro and In Vivo: Implication for Treating Hyperproliferative Disorders

    Science.gov (United States)

    Huwiler, Andrea; Bourquin, Florence; Kotelevets, Nataliya; Pastukhov, Oleksandr; Capitani, Guido; Grütter, Markus G.; Zangemeister-Wittke, Uwe

    2011-01-01

    Sphingosine-1-phosphate (S1P) regulates a broad spectrum of fundamental cellular processes like proliferation, death, migration and cytokine production. Therefore, elevated levels of S1P may be causal to various pathologic conditions including cancer, fibrosis, inflammation, autoimmune diseases and aberrant angiogenesis. Here we report that S1P lyase from the prokaryote Symbiobacterium thermophilum (StSPL) degrades extracellular S1P in vitro and in blood. Moreover, we investigated its effect on cellular responses typical of fibrosis, cancer and aberrant angiogenesis using renal mesangial cells, endothelial cells, breast (MCF-7) and colon (HCT 116) carcinoma cells as disease models. In all cell types, wild-type StSPL, but not an inactive mutant, disrupted MAPK phosphorylation stimulated by exogenous S1P. Functionally, disruption of S1P receptor signaling by S1P depletion inhibited proliferation and expression of connective tissue growth factor in mesangial cells, proliferation, migration and VEGF expression in carcinoma cells, and proliferation and migration of endothelial cells. Upon intravenous injection of StSPL in mice, plasma S1P levels rapidly declined by 70% within 1 h and then recovered to normal 6 h after injection. Using the chicken chorioallantoic membrane model we further demonstrate that also under in vivo conditions StSPL, but not the inactive mutant, inhibited tumor cell-induced angiogenesis as an S1P-dependent process. Our data demonstrate that recombinant StSPL is active under extracellular conditions and holds promise as a new enzyme therapeutic for diseases associated with increased levels of S1P and S1P receptor signaling. PMID:21829623

  13. Evaluation of different glycoforms of honeybee venom major allergen phospholipase A2 (Api m 1) produced in insect cells

    DEFF Research Database (Denmark)

    Blank, Simon; Seismann, Henning; Plum, Melanie

    2011-01-01

    Allergic reactions to hymenoptera stings are one of the major reasons for IgE-mediated anaphylaxis. However, proper diagnosis using venom extracts is severely affected by molecular cross-reactivity. In this study recombinant honeybee venom major allergen phospholipase A2 (Api m 1) was produced......-derived recombinant Api m 1 with defined CCD phenotypes might provide further insights into hymenoptera venom IgE reactivities and contribute to an improved diagnosis of hymenoptera venom allergy....

  14. A novel M1 PAM VU0486846 exerts efficacy in cognition models without displaying agonist activity or cholinergic toxicity.

    Science.gov (United States)

    Rook, Jerri M; Bertron, Jeanette L; Cho, Hyekyung P; Garcia-Barrantes, Pedro M; Moran, Sean P; Maksymetz, James T; Nance, Kellie D; Dickerson, Jonathan W; Remke, Daniel H; Chang, Sichen; Harp, Joel; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

    2018-04-27

    Selective activation of the M1 subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M1 ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M1, leading to agonist actions in the prefrontal cortex (PFC) that impairs cognitive function, induces behavioral convulsions, and results in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M1 PAM, VU0486846. VU0486846 possesses only weak agonist activity in M1-expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427 and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [3H]-NMS binding at theorthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M1 PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M1 PAM activity (EC50s > 100 nM) and pure-PAM activity in native tissues display robust pro-cognitive efficacy without AEs mediated by excessive activation of M1. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.

  15. Effect of heat-inactivated kefir-isolated Lactobacillus kefiranofaciens M1 on preventing an allergic airway response in mice.

    Science.gov (United States)

    Hong, Wei-Sheng; Chen, Yen-Po; Dai, Ting-Yeu; Huang, I-Nung; Chen, Ming-Ju

    2011-08-24

    In this study, we assessed the anti-asthmatic effects of heat-inactivated Lactobacillus kefiranofaciens M1 (HI-M1) and its fermented milk using different feeding procedures and at various dosage levels. The possible mechanisms whereby HI-M1 has anti-allergic asthmatic effects were also evaluated. Ovalbumin (OVA)-allergic asthma mice that have been orally administrated the HI-M1 samples showed strong inhibition of production of T helper cell (Th) 2 cytokines, pro-inflammatory cytokines, and Th17 cytokines in splenocytes and bronchoalveolar fluid compared to control mice. An increase in regulatory T cell population in splenocytes in the allergic asthma mice after oral administration of H1-M1 was also observed. In addition, all of the features of the asthmatic phenotype, including specific IgE production, airway inflammation, and development of airway hyperresponsiveness, were depressed in a dose-dependent manner by treatment. These findings support the possibility that oral feeding of H1-M1 may be an effective way of alleviating asthmatic symptoms in humans.

  16. Selective replication of oncolytic virus M1 results in a bystander killing effect that is potentiated by Smac mimetics.

    Science.gov (United States)

    Cai, Jing; Lin, Yuan; Zhang, Haipeng; Liang, Jiankai; Tan, Yaqian; Cavenee, Webster K; Yan, Guangmei

    2017-06-27

    Oncolytic virotherapy is a treatment modality that uses native or genetically modified viruses that selectively replicate in and kill tumor cells. Viruses represent a type of pathogen-associated molecular pattern and thereby induce the up-regulation of dozens of cytokines via activating the host innate immune system. Second mitochondria-derived activator of caspases (Smac) mimetic compounds (SMCs), which antagonize the function of inhibitor of apoptosis proteins (IAPs) and induce apoptosis, sensitize tumor cells to multiple cytokines. Therefore, we sought to determine whether SMCs sensitize tumor cells to cytokines induced by the oncolytic M1 virus, thus enhancing a bystander killing effect. Here, we report that SMCs potentiate the oncolytic effect of M1 in vitro, in vivo, and ex vivo. This strengthened oncolytic efficacy resulted from the enhanced bystander killing effect caused by the M1 virus via cytokine induction. Through a microarray analysis and subsequent validation using recombinant cytokines, we identified IL-8, IL-1A, and TRAIL as the key cytokines in the bystander killing effect. Furthermore, SMCs increased the replication of M1, and the accumulation of virus protein induced irreversible endoplasmic reticulum stress- and c-Jun N-terminal kinase-mediated apoptosis. Nevertheless, the combined treatment with M1 and SMCs had little effect on normal and human primary cells. Because SMCs selectively and significantly enhance the bystander killing effect and the replication of oncolytic virus M1 specifically in cancer cells, this combined treatment may represent a promising therapeutic strategy.

  17. Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

    Science.gov (United States)

    Yue, Meng; Li, Shiquan; Yan, Guoqiang; Li, Chenyao; Kang, Zhenhua

    2018-01-01

    Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

  18. Effects of selective activation of M1 and M4 muscarinic receptors on object recognition memory performance in rats.

    Science.gov (United States)

    Galloway, Claire R; Lebois, Evan P; Shagarabi, Shezza L; Hernandez, Norma A; Manns, Joseph R

    2014-01-01

    Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M1 and M4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M1 or M4 receptors to improve memory performance in individuals with impaired memory.

  19. Bioimaging of M1 cells using ceramic nanophosphors: Synthesis and toxicity assay of Y2O3 nanoparticles

    International Nuclear Information System (INIS)

    Venkatachalam, N; Soga, K; Tsuji, T; Okumura, Y; Fukuda, R

    2009-01-01

    Er 3+ doped Y 2 O 3 nanoparticles were synthesized by enzymatic and polymer-assisted homogeneous co-precipitation methods. Resultant particle size is about 30-40 nm with narrow size distribution whereas the particle size is smaller than those acquired by conventional homogeneous and alkali precipitation methods. The particles shows bright green (550 nm) and red (660 nm) upconversion (UC) as well as near infrared (NIR) fluorescence (1550 nm) under 980 nm excitation. Bioimaging of M1 cells using the nanoparticles were successfully attempted. It is observed that 0.5 mg/ml of nanoparticles is the nominal concentration for bioimaging of M1 cells under the physiological conditions. The cellular uptake of nanoparticles is evidenced from bright field, UC and NIR fluorescence images of live M1 cells. Our studies suggest that lower concentration of nanoparticles is sufficient for imaging when the particles are taken in the M1 cells and also the concentration can keep the cells alive. Further it was demonstrated that under the physiological conditions, Y 2 O 3 nanoparticles emit UC and NIR fluorescence in M1 cells even after the surface modification with PEG-b-PAAc polymer. Moreover, surface modified nanoparticles shows lower toxic effect in M1 cells while compare to bare nanoparticles.

  20. Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

    Science.gov (United States)

    Quint, Patrick; Ruan, Ming; Pederson, Larry; Kassem, Moustapha; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

    2013-01-01

    Normal bone turnover requires tight coupling of bone resorption and bone formation to preserve bone quantity and structure. With aging and during several pathological conditions, this coupling breaks down, leading to either net bone loss or excess bone formation. To preserve or restore normal bone metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed that osteoclasts produce the chemokine sphingosine 1-phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) cell chemotaxis. S1P treatment of mesenchymal (skeletal) cells activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1P receptors, S1PR1 and S1PR2, coordinately promoted migration through activation of the JAK/STAT3 and FAK/PI3K/AKT signaling pathways, respectively. These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways. PMID:23300082

  1. Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration.

    Science.gov (United States)

    Westwood, Melissa; Al-Saghir, Khiria; Finn-Sell, Sarah; Tan, Cherlyn; Cowley, Elizabeth; Berneau, Stéphane; Adlam, Daman; Johnstone, Edward D

    2017-12-01

    Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH) 2 D 3 . QPCR and immunolocalisation were used to demonstrate EVT S1P receptor expression. EVTs express S1P receptors 1, 2 and 3. S1P inhibited EVT migration. This effect was abolished in the presence of the specific S1PR2 inhibitor, JTE-013 (p S1P alone) whereas treatment with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is regulated by vitamin D; here we found that treatment with 1,25(OH) 2 D 3 for 48 or 72 h reduces S1PR2 (4-fold; S1P did not inhibit the migration of cells exposed to 1,25(OH) 2 D 3 (p S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα 12/13 to activate Rho and thereby acts as potent inhibitor of EVT migration. Importantly, expression of S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data suggest that vitamin D deficiency, which is known to be associated with PE, may contribute to the impaired trophoblast migration that underlies this condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Chemical and Biological Properties of S-1-Propenyl-l-Cysteine in Aged Garlic Extract.

    Science.gov (United States)

    Kodera, Yukihioro; Ushijima, Mitsuyasu; Amano, Hirotaka; Suzuki, Jun-Ichiro; Matsutomo, Toshiaki

    2017-03-31

    S-1-Propenyl-l-cysteine (S1PC) is a stereoisomer of S-1-Propenyl-l-cysteine (SAC), an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE). The existence of S1PC in garlic preparations has been known since the 1960's. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88-100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important, pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC.

  3. Chemical and Biological Properties of S-1-Propenyl-ʟ-Cysteine in Aged Garlic Extract

    Directory of Open Access Journals (Sweden)

    Yukihioro Kodera

    2017-03-01

    Full Text Available S-1-Propenyl-ʟ-cysteine (S1PC is a stereoisomer of S-1-Propenyl-ʟ-cysteine (SAC, an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE. The existence of S1PC in garlic preparations has been known since the 1960’s. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88–100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important, pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC.

  4. Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.

    Directory of Open Access Journals (Sweden)

    Kaipeng Huang

    Full Text Available The accumulation of glomerular extracellular matrix (ECM is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1-sphingosine 1- phosphate (S1P signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG and simultaneously inhibited S1P2 receptor-mediated FN overproduction. Further, BBR also obviously suppressed the activation of NF-κB induced by HG, which was accompanied by reduced S1P2 receptor and FN expression. Taken together, our findings suggest that BBR reduces FN expression by acting on the S1P2 receptor in the mesangium under diabetic condition. The role of BBR in S1P2 receptor expression regulation could closely associate with its inhibitory effect on NF-κB activation.

  5. A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

    Science.gov (United States)

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-02-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. © 2016 Yamamoto, Yako, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  6. Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia

    Science.gov (United States)

    Wang, I-Ching; Zhang, Yufang; Snyder, Jonathan; Sutherland, Mardi J.; Burhans, Michael S.; Shannon, John M.; Park, Hyun Jung; Whitsett, Jeffrey A.; Kalinichenko, Vladimir V.

    2010-01-01

    Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation, differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibits lung maturation and causes respiratory failure after birth. However, the role of Foxm1 during postnatal lung morphogenesis remains unknown. In the present study, Foxm1 expression was detected in epithelial cells of conducting and peripheral airways and changing dynamically with lung maturation. To discern the biological role of Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant or FoxM1-ΔN) under the control of lung epithelial-specific SPC promoter was produced. Expression of the FoxM1-ΔN transgene during embryogenesis caused epithelial hyperplasia, inhibited lung sacculation and expression of the type II epithelial marker, pro-SPC. Expression of FoxM1-ΔN mutant during the postnatal period did not influence alveologenesis but caused focal airway hyperplasia and increased proliferation of Clara cells. Likewise, expression of FoxM1-ΔN mutant in conducting airways with Scgb1a1 promoter was sufficient to induce Clara cell hyperplasia. Furthermore, FoxM1-ΔN cooperated with activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1 altered lung sacculation, induced proliferation in the respiratory epithelium and accelerated lung tumor growth, indicating that precise regulation of Foxm1 is critical for normal lung morphogenesis and development of lung cancer. PMID:20816795

  7. Correlation of Acute M1 Middle Cerebral Artery Thrombus Location with Endovascular Treatment Success and Clinical Outcome.

    Science.gov (United States)

    Pavabvash, Seyedmehdi; Taleb, Shayandokht; Majidi, Shahram; Qureshi, Adnan I

    2017-01-01

    The location of the arterial occlusion can help with prognostication and treatment triage of acute stroke patients. We aimed to determine the effects of M1 distance-to-thrombus on angiographic recanalization success rate and clinical outcome following endovascular treatment of acute M1 occlusion. All acute ischemic stroke patients with M1 segment middle cerebral artery (MCA) occlusion on admission CT angiography (CTA) who underwent endovascular treatment were analyzed. The distance between thrombus origin and internal carotid artery (ICA) bifurcation was measured on admission CTA. The modified thrombolysis in cerebral infarction (mTICI) grades 2 b (>50% of distal branch filling) and 3 (complete) were considered as successful recanalization. Favorable outcome was defined by 3-month follow-up modified Rankin scale (mRs) score ≤2. Successful recanalization was achieved in 24 (71%) of 34 consecutive patients included in this study. The M1 distance-to-thrombus was shorter among patients with successful recanalization (5.4 ± 5.4 mm) versus those without (11.3 ± 7.6 mm, p = 0.015). The successful recanalization rate was higher among patients with M1 distance-to-thrombus ≤6 mm (odds ratio: 8, 95% confidence interval: 1.37-46.81, p = 0.023) compared with those with distance-to-thrombus >6 mm. There was no significant correlation between M1 distance-to-thrombus and 3-month mRs (rho: 0.131, p = 0.461); however, the distance-to-thrombus negatively correlated with admission National Institutes of Health Stroke Scale (NIHSS) scores (rho: -0.350, p=0.043). On the other hand, successful recanalization and admission NIHSS score were the only independent predictors of favorable outcome. Shorter distance of M1 thrombus from ICA bifurcation is associated with higher rate of successful recanalization following endovascular treatment.

  8. Correlation of Acute M1 Middle Cerebral Artery Thrombus Location with Endovascular Treatment Success and Clinical Outcome

    Science.gov (United States)

    Pavabvash, Seyedmehdi; Taleb, Shayandokht; Majidi, Shahram; Qureshi, Adnan I.

    2017-01-01

    Purpose The location of the arterial occlusion can help with prognostication and treatment triage of acute stroke patients. We aimed to determine the effects of M1 distance-to-thrombus on angiographic recanalization success rate and clinical outcome following endovascular treatment of acute M1 occlusion. Methods All acute ischemic stroke patients with M1 segment middle cerebral artery (MCA) occlusion on admission CT angiography (CTA) who underwent endovascular treatment were analyzed. The distance between thrombus origin and internal carotid artery (ICA) bifurcation was measured on admission CTA. The modified thrombolysis in cerebral infarction (mTICI) grades 2b (>50% of distal branch filling) and 3 (complete) were considered as successful recanalization. Favorable outcome was defined by 3-month follow-up modified Rankin scale (mRs) score ≤2. Results Successful recanalization was achieved in 24 (71%) of 34 consecutive patients included in this study. The M1 distance-to-thrombus was shorter among patients with successful recanalization (5.4 ± 5.4 mm) versus those without (11.3 ± 7.6 mm, p = 0.015). The successful recanalization rate was higher among patients with M1 distance-to-thrombus ≤6 mm (odds ratio: 8, 95% confidence interval: 1.37–46.81, p = 0.023) compared with those with distance-to-thrombus >6 mm. There was no significant correlation between M1 distance-to-thrombus and 3-month mRs (rho: 0.131, p = 0.461); however, the distance-to-thrombus negatively correlated with admission National Institutes of Health Stroke Scale (NIHSS) scores (rho: −0.350, p=0.043). On the other hand, successful recanalization and admission NIHSS score were the only independent predictors of favorable outcome. Conclusion Shorter distance of M1 thrombus from ICA bifurcation is associated with higher rate of successful recanalization following endovascular treatment. PMID:28243346

  9. A new and efficient culture method for porcine bone marrow-derived M1- and M2-polarized macrophages.

    Science.gov (United States)

    Gao, Jiye; Scheenstra, Maaike R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P

    2018-06-01

    Macrophages play an important role in the innate immune system as part of the mononuclear phagocyte system (MPS). They have a pro-inflammatory signature (M1-polarized macrophages) or anti-inflammatory signature (M2-polarized macrophages) based on expression of surface receptors and secretion of cytokines. However, very little is known about the culture of macrophages from pigs and more specific about the M1 and M2 polarization in vitro. Porcine monocytes or mononuclear bone marrow cells were used to culture M1- and M2-polarized macrophages in the presence of GM-CSF and M-CSF, respectively. Surface receptor expression was measured with flow cytometry and ELISA was used to quantify cytokine secretion in response to LPS and PAM 3 CSK 4 stimulation. Human monocyte-derived macrophages were used as control. Porcine M1- and M2-polarized macrophages were cultured best using porcine GM-CSF and murine M-CSF, respectively. Cultures from bone marrow cells resulted in a higher yield M1- and M2-polarized macrophages which were better comparable to human monocyte-derived macrophages than cultures from porcine monocytes. Porcine M1-polarized macrophages displayed the characteristic fried egg shape morphology, lower CD163 expression and low IL-10 production. Porcine M2-polarized macrophages contained the spindle-like morphology, higher CD163 expression and high IL-10 production. Porcine M1- and M2-polarized macrophages can be most efficiently cultured from mononuclear bone marrow cells using porcine GM-CSF and murine M-CSF. The new culture method facilitates more refined studies of porcine macrophages in vitro, important for both porcine and human health since pigs are increasingly used as model for translational research. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Overexpression of the polycystin-1 (PC-1) C-tail enhances sensitivity of M-1 cells to ouabain

    Science.gov (United States)

    Jansson, Kyle; Magenheimer, Brenda S.; Maser, Robin L.; Calvet, James P.; Blanco, Gustavo

    2014-01-01

    Cells derived from renal cysts of patients with autosomal dominant polycystic kidney disease (ADPKD) are abnormally sensitive to ouabain, responding to physiological ouabain concentrations with enhanced proliferation and increased forskolin-induced transepithelial fluid secretion. This requires activation of the epidermal growth factor receptor (EGFR), Src kinase, and the extracellular regulated kinases MEK and ERK. Here, we have determined if the ADPKD phenotype obtained in mouse cortical collecting duct cells by stable overexpression of the C-terminal domain of polycystin-1 (PC-1 C-tail) also elicits the ADPKD-like response to ouabain in the cells. M-1 C20 cells expressing the PC-1 C-tail, and M-1 C17 cells, lacking expression of this construct, were treated with physiological concentrations of ouabain, and cell proliferation, activation of the EGFR-Src-MEK-ERK pathway, forskolin-induced transepithelial Cl− secretion, and the sensitivity of the Na,K-ATPase to ouabain were explored. M-1 C20 cells responded to ouabain with increased cell proliferation and ERK phosphorylation. Ouabain also augmented forskolin-induced and cystic fibrosis transmembrane conductance regulator (CFTR)-mediated apical secretion of Cl− in M-1 C20 cells. These effects required activation of EGFR, Src and MEK. In contrast, ouabain had no significant effects on M-1 C17 cells. Interestingly, approximately 20 % of the Na,K-ATPase from M-1 C20 cells presented an abnormally increased sensitivity to ouabain. Overexpression of PC-1 C-tail in M-1 C20 cells is associated with a ouabain sensitive phenotype and an increased ability of the cells to proliferate and secrete anions upon ouabain stimulation. This phenotype mimics the ouabain sensitivity of ADPKD cells and may help promote their cystogenic potential. PMID:23784065

  11. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

    International Nuclear Information System (INIS)

    Genin, Marie; Clement, Francois; Fattaccioli, Antoine; Raes, Martine; Michiels, Carine

    2015-01-01

    Tumor associated macrophages (TAMs) are present in high density in solid tumors. TAMs share many characteristics with alternatively activated macrophages, also called M2. They have been shown to favor tumor development and a role in chemoresistance has also been suggested. Here, we investigated the effects of M2 in comparison to M1 macrophages on cancer cell sensitivity to etoposide. We set up a model of macrophage polarization, starting from THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate). Once differentiated (M0 macrophages), they were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). To mimic the communication between cancer cells and TAMs, M0, M1 or M2 macrophages and HepG2 or A549 cancer cells were co-cultured during respectively 16 (HepG2) or 24 (A549) hours, before etoposide exposure for 24 (HepG2) or 16 (A549) hours. After the incubation, the impact of etoposide on macrophage polarization was studied and cancer cell apoptosis was assessed by western-blot for cleaved caspase-3 and cleaved PARP-1 protein, caspase activity assay and FACS analysis of Annexin V and PI staining. mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages, which provide a new, easy and well-characterized model of polarized human macrophages. Etoposide-induced cancer cell apoptosis was markedly reduced in the presence of THP-1 M2 macrophages, while apoptosis was increased in cells co-cultured with M1 macrophages. On the other hand, etoposide did not influence M1 or M2 polarization. These results evidence for the first time a clear protective effect of M2 on the contrary to M1 macrophages on etoposide-induced cancer cell apoptosis

  12. Three-fold increase of M1 strength in 40Ar at 10 MeV excitation energy

    Science.gov (United States)

    Tornow, Werner; Finch, Sean; Krishichayan, Fnu; Tonchev, Anton

    2017-09-01

    We reexamined the excitation energy region of 40Ar around 9.8 MeV with the goal of determining the known M1 strength located at 9.76 MeV more accurately. The physics motivation was based on the fact that i) the neutrino-nucleus interaction cross section is proportional to the M1 strength of a nucleus, ii) DUNE, the Deep Underground Neutrino Experiment at SURF will be using liquid argon as detector medium, iii) the energy spectrum of supernova neutrinos is peaked at approximately 10 MeV. Mono-energetic and linearly polarized photons of 9.88 MeV were produced via Compton backscattering of 548 nm FEL photons from 543 MeV electrons at the High-Intensity γ-ray Source (HI γS) facility at TUNL. The 1.25 cm diameter photon beam with energy spread of 300 keV (FWHM) interacted with argon gas contained in a high-pressure cell. The cell was viewed with HPGe detectors placed at 90o relative to the incident photon beam in the horizontal and vertical planes to distinguish between E1 and M1 de-excitation γ-rays. Our re-measurement provided an increase in M1 strength by a factor of approximately 3, mostly due to the discovery that the known level in 40Ar at 9.84 MeV is of M1 character and not of E1 character, as previously thought. In addition to the already known M1 state at 9.76 MeV, we observed weaker M1 states at 9.70, 9.81, 9.87, and 9.89 MeV.

  13. Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

    Science.gov (United States)

    Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

    2017-12-01

    Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

  14. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.

    Science.gov (United States)

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction.

  15. Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

    Science.gov (United States)

    Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

    2013-07-18

    The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

  16. Theoretical descriptions of novel triplet germylenes M1-Ge-M2-M3 (M1 = H, Li, Na, K; M2 = Be, Mg, Ca; M3 = H, F, Cl, Br).

    Science.gov (United States)

    Kassaee, Mohamad Zaman; Ashenagar, Samaneh

    2018-02-06

    In a quest to identify new ground-state triplet germylenes, the stabilities (singlet-triplet energy differences, ΔE S-T ) of 96 singlet (s) and triplet (t) M 1 -Ge-M 2 -M 3 species were compared and contrasted at the B3LYP/6-311++G**, QCISD(T)/6-311++G**, and CCSD(T)/6-311++G** levels of theory (M 1  = H, Li, Na, K; M 2  = Be, Mg, Ca; M 3  = H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M 3  = F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M 3  = Cl or Br). Triplets with M 1  = K (i.e., the K-Ge-M 2 -M 3 series) seem to be more stable than the corresponding triplets with M 1  = H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M 3  = Cl behave similarly to those with M 3  = Br. Conversely, triplets with M 3  = H show similar stabilities and linearities to those with M 3  = F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M 1 -Ge-M 2 -M 3 become more stable as the electropositivities of the α-substituents (M 1 and M 2 ) and the electronegativity of the β-substituent (M 3 ) increase.

  17. Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review.

    Science.gov (United States)

    Mahajan-Thakur, Shailaja; Bien-Möller, Sandra; Marx, Sascha; Schroeder, Henry; Rauch, Bernhard H

    2017-11-17

    The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.

  18. The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁ and hypertension (S1P₃ in rat.

    Directory of Open Access Journals (Sweden)

    Ryan M Fryer

    Full Text Available Sphingosine-1-phospate (S1P and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1P(X receptor agonist produces modest hypertension in patients (2-3 mmHg in 1-yr trial as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes responsible is controversial, likely dependent upon the cardiovascular response in question (e.g. bradycardia, hypertension, and perhaps even species-dependent since functional differences in rodent, rabbit, and human have been suggested. Thus, we characterized the S1P receptor subtype specificity for each compound in vitro and, in vivo, the cardiovascular effects of FTY720 and the more selective S1P₁,₅ agonist, BAF312, were tested during acute i.v. infusion in anesthetized rats and after oral administration for 10 days in telemetry-instrumented conscious rats. Acute i.v. infusion of FTY720 (0.1, 0.3, 1.0 mg/kg/20 min or BAF312 (0.5, 1.5, 5.0 mg/kg/20 min elicited acute bradycardia in anesthetized rats demonstrating an S1P₁ mediated mechanism-of-action. However, while FTY720 (0.5, 1.5, 5.0 mg/kg/d elicited dose-dependent hypertension after multiple days of oral administration in rat at clinically relevant plasma concentrations (24-hr mean blood pressure = 8.4, 12.8, 16.2 mmHg above baseline vs. 3 mmHg in vehicle controls, BAF312 (0.3, 3.0, 30.0 mg/kg/d had no significant effect on blood pressure at any dose tested suggesting that hypertension produced by FTY720 is mediated S1P₃ receptors. In summary, in vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1P₁ receptors mediate bradycardia while hypertension is mediated by S1P₃ receptor activation.

  19. [A case report of the combination therapy with S-1 plus CDDP intraperitoneal chemotherapy for CY positive cancer patient].

    Science.gov (United States)

    Ishii, Yasushi; Iwasaki, Yoshiki; Ohashi, Manabu; Iwanaga, Tomohiro; Ohinata, Ryouki; Takahashi, Keiichi; Matsumoto, Hiroshi; Yamaguchi, Tatsurou; Nakano, Daisuke

    2011-11-01

    A male patient in his 50s underwent distal gastrectomy for gastric cancer. In operation, there was no peritoneal dissemination. But peritoneal lavage cytology revealed positive peritoneal dissemination. Thus, we set an intraperitoneal infuser port to this patient. On specimen, a type-3 tumor was located in the gastric lesser of antrum to angle. Microscopic examination of specimens revealed a signet ring cell carcinoma and poorly differentiated adenocarcinoma under serosa, and positive of lymph node metastasis. The diagnosis was pT4N2M1P0CY1H0, Stage IV( Japanese classification of gastric carcinoma The 14 Edition). CDDP was administered through the infuser port (on day 7, a first dose of 60 mg/m2 and 30 mg/m2 for second) combined with oral administration of S-1 (100 mg/body) for two weeks, with one week of drug withdrawal. This chemotherapy was repeated for 11 courses. After that, peritoneal lavage cytology became negative. S-1 oral administration was continued for four years, and this patient has been well for five years and six months after the surgery. Therefore, it is suggested that intraperitoneal chemotherapy with cisplatin is an effective treatment for microscopical peritoneal dissemination.

  20. Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

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    Chan-on W

    2015-04-01

    Full Text Available Waraporn Chan-on,1 Nguyen Thi Bich Huyen,2 Napat Songtawee,3 Wilasinee Suwanjang,1 Supaluk Prachayasittikul,3 Virapong Prachayasittikul2 1Center for Research and Innovation, 2Department of Clinical Microbiology and Applied Technology, 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand Purpose: Fork head box M1 (FoxM1 is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA. A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ and nitroxoline (NQ, represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells.Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl-5-(3-carboxymethoxyphenyl-(4-sulfophenyl-2H-tetrazolium (MTS assay. Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction.Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment

  1. Divorcing the Late Upper Palaeolithic demographic histories of mtDNA haplogroups M1 and U6 in Africa

    Directory of Open Access Journals (Sweden)

    Pennarun Erwan

    2012-12-01

    Full Text Available Abstract Background A Southwest Asian origin and dispersal to North Africa in the Early Upper Palaeolithic era has been inferred in previous studies for mtDNA haplogroups M1 and U6. Both haplogroups have been proposed to show similar geographic patterns and shared demographic histories. Results We report here 24 M1 and 33 U6 new complete mtDNA sequences that allow us to refine the existing phylogeny of these haplogroups. The resulting phylogenetic information was used to genotype a further 131 M1 and 91 U6 samples to determine the geographic spread of their sub-clades. No southwest Asian specific clades for M1 or U6 were discovered. U6 and M1 frequencies in North Africa, the Middle East and Europe do not follow similar patterns, and their sub-clade divisions do not appear to be compatible with their shared history reaching back to the Early Upper Palaeolithic. The Bayesian Skyline Plots testify to non-overlapping phases of expansion, and the haplogroups’ phylogenies suggest that there are U6 sub-clades that expanded earlier than those in M1. Some M1 and U6 sub-clades could be linked with certain events. For example, U6a1 and M1b, with their coalescent ages of ~20,000–22,000 years ago and earliest inferred expansion in northwest Africa, could coincide with the flourishing of the Iberomaurusian industry, whilst U6b and M1b1 appeared at the time of the Capsian culture. Conclusions Our high-resolution phylogenetic dissection of both haplogroups and coalescent time assessments suggest that the extant main branching pattern of both haplogroups arose and diversified in the mid-later Upper Palaeolithic, with some sub-clades concomitantly with the expansion of the Iberomaurusian industry. Carriers of these maternal lineages have been later absorbed into and diversified further during the spread of Afro-Asiatic languages in North and East Africa.

  2. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

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    Marianne Quiding-Järbrink

    Full Text Available BACKGROUND: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. METHODOLOGY/PRINCIPAL FINDINGS: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. CONCLUSIONS/SIGNIFICANCE: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.

  3. Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti-Inflammatory M2 State

    Directory of Open Access Journals (Sweden)

    Laura Dugo

    2017-01-01

    Full Text Available Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γ for M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2 consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

  4. The M1 muscarinic receptor and its second messenger coupling in human neuroblastoma cells and transfected murine fibroblast cells

    International Nuclear Information System (INIS)

    Mei, Lin.

    1989-01-01

    The data of this study indicate that pirenzepine (PZ)-high affinity muscarinic receptors (mAChRs) are coupled to the hydrolysis of inositol lipids and not to the adenylate cyclase system in human neuroblastoma SH-SY5Y cells. The maximal carbachol(CCh)-stimulated [ 3 H]IP 1 accumulation in the SH-SY5Y cells was decreased in the presence of 1μg/ml pertussis toxin, suggesting that a pertussis toxin sensitive G-protein may be involved in the coupling. Several cell clones which express only M 1 mAChR were generated by transfecting the murine fibroblast B82 cells with the cloned rat genomic m 1 gene. The transfected B82 cells (cTB10) showed specific [ 3 H](-)QNB binding activity. The mAChRs in these cells are of the M 1 type defined by their high affinity for PZ and low affinity for AF-DX 116 and coupled to hydrolysis of inositol lipids, possibly via a pertussis toxin sensitive G protein. The relationship between the M 1 mAChR density and the receptor-mediated hydrolysis of inositol lipids was studied in 7 clones. The M 1 mAChR densities in these cells characterized by [ 3 H](-)MQNB binding ranged from 12 fmol/10 6 cells in LK3-1 cells to 260 fmol/10 6 cells in the LK3-8 cells

  5. S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis.

    Science.gov (United States)

    Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing

    2017-12-15

    Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.

  6. Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function.

    Science.gov (United States)

    Josipovic, Ivana; Pflüger, Beatrice; Fork, Christian; Vasconez, Andrea E; Oo, James A; Hitzel, Juliane; Seredinski, Sandra; Gamen, Elisabetta; Heringdorf, Dagmar Meyer Zu; Chen, Wei; Looso, Mario; Pullamsetti, Soni Savai; Brandes, Ralf P; Leisegang, Matthias S

    2018-03-01

    Sphingosine-1-Phosphate (S1P) is a potent signaling lipid. The effects of S1P are mediated by the five S1P receptors (S1PR). In the endothelium S1PR1 is the predominant receptor and thus S1PR1 abundance limits S1P signaling. Recently, lncRNAs were identified as a novel class of molecules regulating gene expression. Interestingly, the lncRNA NONHSAT004848 (LISPR1, Long intergenic noncoding RNA antisense to S1PR1), is closely positioned to the S1P1 receptors gene and in part shares its promoter region. We hypothesize that LISPR1 controls endothelial S1PR1 expression and thus S1P-induced signaling in endothelial cells. In vitro transcription and translation as well as coding potential assessment showed that LISPR1 is indeed noncoding. LISPR1 was localized in both cytoplasm and nucleus and harbored a PolyA tail at the 3'end. In human umbilical vein endothelial cells, as well as human lung tissue, qRT-PCR and RNA-Seq revealed high expression of LISPR1. S1PR1 and LISPR1 were downregulated in human pulmonary diseases such as COPD. LISPR1 but also S1PR1 were induced by inflammation, shear stress and statins. Knockdown of LISPR1 attenuated endothelial S1P-induced migration and spheroid outgrowth of endothelial cells. LISPR1 knockdown decreased S1PR1 expression, which was paralleled by an increase of the binding of the transcriptional repressor ZNF354C to the S1PR1 promoter and a reduction of the recruitment of RNA Polymerase II to the S1PR1 5'end. This resulted in attenuated S1PR1 expression and attenuated S1P downstream signaling. Collectively, the disease relevant lncRNA LISPR1 acts as a novel regulatory unit important for S1PR1 expression and endothelial cell function. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Systematics of the excitation of M1 resonances in medium heavy nuclei by 200 MeV proton inelastic scattering

    International Nuclear Information System (INIS)

    Djalali, C.; Marty, N.; Morlet, M.

    1982-01-01

    In a series of seventeen nuclei ranging from 51 V to 140 Ca, broad resonance structures are observed at energies between 8 and 10 MeV, nearly mass independent. These resonances have very forward peaked angular distributions which imply that they are populated by an angular momentum transfer of zero. This together with the observed excitation energies suggests an M1 character for these resonances. In 51 V, 58 Ni, 60 Ni, 62 Ni, a sharp peak located at an excitation energy above the threshold for neutron emission is interpreted as a part of the T 0+1 component of the M1 resonances. Cross-sections are given for all the M1 resonances. For 58 Ni, 90 Zr, 92 Mo, 120 Sn and 140 Ca, an ''attenuation'' factor for the cross-sections is extracted in a OWIA calculation assuming simple shell model structures for these resonances

  8. Roles of transmembrane segment M1 of Na(+),K (+)-ATPase and Ca (2+)-ATPase, the gatekeeper and the pivot

    DEFF Research Database (Denmark)

    Einholm, Anja P.; Andersen, Jens Peter; Vilsen, Bente

    2007-01-01

    In this review we summarize mutagenesis work on the structure-function relationship of transmembrane segment M1 in the Na(+),K(+)-ATPase and the sarco(endo)plasmic reticulum Ca(2+)-ATPase. The original hypothesis that charged residues in the N-terminal part of M1 interact with the transported...... cations can be rejected. On the other hand hydrophobic residues in the middle part of M1 turned out to play crucial roles in Ca(2+) interaction/occlusion in Ca(2+)-ATPase and K(+) interaction/occlusion in Na(+),K(+)-ATPase. Leu(65) of the Ca(2+)-ATPase and Leu(99) of the Na(+),K(+)-ATPase, located...... of the extracytoplasmic gate in both the Ca(2+)-ATPase and the Na(+),K(+)-ATPase. Udgivelsesdato: 2007-Dec...

  9. Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal Tokomak with circular cross sections

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.

    1976-01-01

    A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the Tokomak with circular cross sections. One includes the resistive and diamagnetic effects in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, one obtains a system of two coupled equations for the harmonic amplitudes. When the shear is finite on q=1, the toroidal coupling is negligible. In the opposite limit, one can explain: the experimental behaviour of the (m=1, n=1) mode before the internal disruption; the simultaneous observation of the modes (m=1, n=1) and [de

  10. Effective Lagrangians, Watson's theorem and the E2/M1 mixing ratio in the excitation of the Delta resonance

    International Nuclear Information System (INIS)

    Davidson, R.M.

    1992-01-01

    The author investigates theoretical uncertainties and model dependence in the extraction of the nucleon-delta(1232) electromagnetic transition amplitudes from the multipole data base. The starting point is an effective Lagrangian incorporating chiral symmetry, which includes at the tree level the pseudovector Born terms, leading t-channel vector meson exchanges, and s and u channel delta exchanges. The nucleon-delta magnetic dipole (M1) and electric quadrupole (E2) transition amplitudes are expressed in terms of two independent gauge couplings at the γNΔ vertex. After unitarizing the tree level amplitude, the gauge couplings are fitted to various multipole data sets, thus determining E2 and M1. Although there is much sensitivity to the method used to unitarize the amplitude, the author extracts the E2/M1 ratio to be negative, with a magnitude around 1.5%. 11 refs., 3 figs

  11. Disturbed mitochondrial function restricts glutamate uptake in the human Müller glia cell line, MIO-M1

    DEFF Research Database (Denmark)

    Vohra, Rupali; Gurubaran, Iswariyaraja Sridevi; Henriksen, Ulrik

    2017-01-01

    Using the human Müller cell line, MIO-M1, the aim was to study the impact of mitochondrial inhibition in Müller glia through antimycin A treatment. MIO-M1 cell survival, levels of released lactate, mitochondrial function, and glutamate uptake were studied in response to mitochondrial inhibition...... and glucose restriction. Lactate release decreased in response to glucose restriction. Combined glucose restriction and blocked mitochondrial activity decreased survival and caused collapse of the respiratory chain measured by oxygen consumption rate and extracellular acidification rate. Mitochondrial...... inhibition caused impaired glutamate uptake and decreased mRNA expression of the glutamate transporter, EAAT1. Over all, we show important roles of mitochondrial activity in MIO-M1 cell function and survival....

  12. Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.

    Science.gov (United States)

    Panarese, Joseph D; Cho, Hykeyung P; Adams, Jeffrey J; Nance, Kellie D; Garcia-Barrantes, Pedro M; Chang, Sichen; Morrison, Ryan D; Blobaum, Anna L; Niswender, Colleen M; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

    2016-08-01

    This Letter describes the continued chemical optimization of the VU0453595 series of M1 positive allosteric modulators (PAMs). By surveying alternative 5,6- and 6,6-heterobicylic cores for the 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one core of VU453595, we found new cores that engendered not only comparable or improved M1 PAM potency, but significantly improved CNS distribution (Kps 0.3-3.1). Moreover, this campaign provided fundamentally distinct M1 PAM chemotypes, greatly expanding the available structural diversity for this valuable CNS target, devoid of hydrogen-bond donors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Task-specificity of unilateral anodal and dual-M1 tDCS effects on motor learning.

    Science.gov (United States)

    Karok, Sophia; Fletcher, David; Witney, Alice G

    2017-01-08

    Task-specific effects of transcranial direct current stimulation (tDCS) on motor learning were investigated in 30 healthy participants. In a sham-controlled, mixed design, participants trained on 3 different motor tasks (Purdue Pegboard Test, Visuomotor Grip Force Tracking Task and Visuomotor Wrist Rotation Speed Control Task) over 3 consecutive days while receiving either unilateral anodal over the right primary motor cortex (M1), dual-M1 or sham stimulation. Retention sessions were administered 7 and 28 days after the end of training. In the Purdue Pegboard Test, both anodal and dual-M1 stimulation reduced average completion time approximately equally, an improvement driven by online learning effects and maintained for about 1 week. The Visuomotor Grip Force Tracking Task and the Visuomotor Wrist Rotation Speed Control Task were associated with an advantage of dual-M1 tDCS in consolidation processes both between training sessions and when testing at long-term retention; both were maintained for at least 1 month. This study demonstrates that M1-tDCS enhances and sustains motor learning with different electrode montages. Stimulation-induced effects emerged at different learning phases across the tasks, which strongly suggests that the influence of tDCS on motor learning is dynamic with respect to the functional recruitment of the distributed motor system at the time of stimulation. Divergent findings regarding M1-tDCS effects on motor learning may partially be ascribed to task-specific consequences and the effects of offline consolidation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

    Science.gov (United States)

    Jiao, Xiaodong; Yu, Wenlong; Qian, Jianxin; Chen, Ying; Wei, Peilian; Fang, Wenzheng; Yu, Guanzhen

    2018-05-18

    A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro. ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens. The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

  15. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Directory of Open Access Journals (Sweden)

    Senthilkumar Pitchalu Kasthurinaidu

    Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  16. Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

    Science.gov (United States)

    Tsuji, Takashi; Suzuki, Keisuke; Nakamura, Tsuyoshi; Goto, Taiji; Sekiguchi, Yukiko; Ikeda, Takuya; Fukuda, Takeshi; Takemoto, Toshiyasu; Mizuno, Yumiko; Kimura, Takako; Kawase, Yumi; Nara, Futoshi; Kagari, Takashi; Shimozato, Takaichi; Yahara, Chizuko; Inaba, Shinichi; Honda, Tomohiro; Izumi, Takashi; Tamura, Masakazu; Nishi, Takahide

    2014-08-01

    We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. The Armys M-1 Abrams, M-2/M-3 Bradley, and M-1126 Stryker: Background and Issues for Congress

    Science.gov (United States)

    2016-04-05

    the Army John McHugh , urging instead the limited production of 70 M-1A2SEPv2 tanks per year from FY2013 to FY2017. 32 Congress subsequently decided...House Members sent a letter to Secretary of the Army McHugh expressing concern over the Army’s failure to fund production of the M-1A2. Congress...John McHugh by Rep. Sander Levin and Rep. Mike Rogers, May 6, 2011. 33 See CRS Reports: CRS Report R43323, Defense: FY2014 Authorization and

  18. E2,M1 multipole mixing ratios in even-even nuclei, 58< or =A< or =150

    International Nuclear Information System (INIS)

    Krane, K.S.

    1977-01-01

    A survey is presented of E2,M1 multipole mixing ratios of gamma-ray transitions in even-even nuclei in the mass range 58< or =A< or =150. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. A set of recommended values of the mixing ratios is included based on averages of results from various studies. The survey includes data available in the literature up to December 1976

  19. E2,M1 Multipole mixing ratios in odd-mass nuclei, 59< or =A< or =149

    International Nuclear Information System (INIS)

    Krane, K.S.

    1977-01-01

    A survey is presented of the E2,M1 mxing ratios of gamma-ray transitions in odd-mass nuclei with 59< or =A< or =149. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. A set of recommended values of the mixing ratios is included, based on averages of results from various studies. The survey includes data available in the literature up to September 1976

  20. Achievements and Prospects in Electrochemical-Based Biosensing Platforms for Aflatoxin M1 Detection in Milk and Dairy Products

    Directory of Open Access Journals (Sweden)

    Ana-Maria Gurban

    2017-12-01

    Full Text Available Aflatoxins, which are mainly produced by Aspergillus flavus and parasiticus growing on plants and products stored under inappropriate conditions, represent the most studied group of mycotoxins. Contamination of human and animal milk with aflatoxin M1, the hydroxylated metabolite of aflatoxin B1, is an important health risk factor due to its carcinogenicity and mutagenicity. Due to the low concentration of this aflatoxin in milk and milk products, the analytical methods used for its quantification have to be highly sensitive, specific and simple. This paper presents an overview of the analytical methods, especially of the electrochemical immunosensors and aptasensors, used for determination of aflatoxin M1.

  1. Photosynthetic behaviour of Arabidopsis thaliana (Pa-1 accession ...

    African Journals Online (AJOL)

    The growth reduction observed in many plants caused by salinity is often associated with a decrease in their photosynthetic capacity. This effect could be associated with the partial stomatal closure and/or the non-stomatal limitation which involves the decrease in ribulose-1,5-bisphosphate carboxylase oxygenase ...

  2. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment.

    Directory of Open Access Journals (Sweden)

    Al Shaimaa Hasan

    Full Text Available Cardiosphere-derived cells (CDCs, one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1 into a regulatory anti-inflammatory phenotype (M2. Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages, but decreased the expression of CD86 (a marker for M1 macrophages 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair.

  3. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment

    Science.gov (United States)

    Hasan, Al Shaimaa; Luo, Lan; Yan, Chen; Zhang, Tian-Xia; Urata, Yoshishige; Goto, Shinji; Mangoura, Safwat A.; Abdel-Raheem, Mahmoud H.; Zhang, Shouhua; Li, Tao-Sheng

    2016-01-01

    Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages), but decreased the expression of CD86 (a marker for M1 macrophages) 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair. PMID:27764217

  4. Large low-energy M1 strength for ^{56,57}Fe within the nuclear shell model.

    Science.gov (United States)

    Brown, B Alex; Larsen, A C

    2014-12-19

    A strong enhancement at low γ-ray energies has recently been discovered in the γ-ray strength function of ^{56,57}Fe. In this work, we have for the first time obtained theoretical γ decay spectra for states up to ≈8  MeV in excitation for ^{56,57}Fe. We find large B(M1) values for low γ-ray energies that provide an explanation for the experimental observations. The role of mixed E2 transitions for the low-energy enhancement is addressed theoretically for the first time, and it is found that they contribute a rather small fraction. Our calculations clearly show that the high-ℓ(=f) diagonal terms are most important for the strong low-energy M1 transitions. As such types of 0ℏω transitions are expected for all nuclei, our results indicate that a low-energy M1 enhancement should be present throughout the nuclear chart. This could have far-reaching consequences for our understanding of the M1 strength function at high excitation energies, with profound implications for astrophysical reaction rates.

  5. HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis

    Science.gov (United States)

    Harrington, Willie; Bond, Vincent; Huang, Ming Bo; Powell, Michael; Lillard, James; Manne, Upender; Bumpers, Harvey

    2010-01-01

    CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1α, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis. PMID:20383296

  6. Selective incorporation of vRNP into influenza A virions determined by its specific interaction with M1 protein

    Energy Technology Data Exchange (ETDEWEB)

    Chaimayo, Chutikarn [Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 (United States); Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Hayashi, Tsuyoshi; Underwood, Andrew; Hodges, Erin [Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 (United States); Takimoto, Toru, E-mail: toru_takimoto@urmc.rochester.edu [Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 (United States)

    2017-05-15

    Influenza A viruses contain eight single-stranded, negative-sense RNA segments as viral genomes in the form of viral ribonucleoproteins (vRNPs). During genome replication in the nucleus, positive-sense complementary RNPs (cRNPs) are produced as replicative intermediates, which are not incorporated into progeny virions. To analyze the mechanism of selective vRNP incorporation into progeny virions, we quantified vRNPs and cRNPs in the nuclear and cytosolic fractions of infected cells, using a strand-specific qRT-PCR. Unexpectedly, we found that cRNPs were also exported to the cytoplasm. This export was chromosome region maintenance 1 (CRM1)-independent unlike that of vRNPs. Although both vRNPs and cRNPs were present in the cytosol, viral matrix (M1) protein, a key regulator for viral assembly, preferentially bound vRNPs over cRNPs. These results indicate that influenza A viruses selectively uptake cytosolic vRNPs through a specific interaction with M1 during viral assembly. - Highlights: •Influenza cRNPs are exported from the nucleus of an infected cell via a CRM1-independent pathway. •Influenza A viruses selectively incorporate cytosolic vRNPs through a specific interaction with M1 during viral assembly. •M1 dissociates from vRNP export complex after nuclear export, and is re-associated with vRNPs at the plasma membrane.

  7. Differential effects of m1 and m2 receptor antagonists in perirhinal cortex on visual recognition memory in monkeys.

    Science.gov (United States)

    Wu, Wei; Saunders, Richard C; Mishkin, Mortimer; Turchi, Janita

    2012-07-01

    Microinfusions of the nonselective muscarinic antagonist scopolamine into perirhinal cortex impairs performance on visual recognition tasks, indicating that muscarinic receptors in this region play a pivotal role in recognition memory. To assess the mnemonic effects of selective blockade in perirhinal cortex of muscarinic receptor subtypes, we locally infused either the m1-selective antagonist pirenzepine or the m2-selective antagonist methoctramine in animals performing one-trial visual recognition, and compared these scores with those following infusions of equivalent volumes of saline. Compared to these control infusions, injections of pirenzepine, but not of methoctramine, significantly impaired recognition accuracy. Further, similar doses of scopolamine and pirenzepine yielded similar deficits, suggesting that the deficits obtained earlier with scopolamine were due mainly, if not exclusively, to blockade of m1 receptors. The present findings indicate that m1 and m2 receptors have functionally dissociable roles, and that the formation of new visual memories is critically dependent on the cholinergic activation of m1 receptors located on perirhinal cells. Published by Elsevier Inc.

  8. Immunocytochemical demonstration of M1 muscarinic acetylcholine receptors at the presynaptic and postsynaptic membranes of rat diaphragm endplates

    Czech Academy of Sciences Publication Activity Database

    Malomouzh, A. I.; Arkhipova, S. S.; Nikolsky, E. E.; Vyskočil, František

    2011-01-01

    Roč. 60, č. 1 (2011), s. 185-188 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110905; GA ČR GA202/09/0806 Institutional research plan: CEZ:AV0Z50110509 Keywords : skeletal muscle * M1 muscarinic receptor Subject RIV: ED - Physiology Impact factor: 1.555, year: 2011

  9. Calculation of the single lepton SUSY analysis limits in the cMSSM m0-m1/2 plane

    CERN Document Server

    Megas, Efstathios

    2014-01-01

    The goal of the summer student project was the calculation of the single lepton SUSY analysis limits in the cMSSM $m_0$-$m_{1/2}$ plane. To this end, the analysis code, the production of the ntuples and a familarization with the higgs combination tool was needed.

  10. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

    2003-01-01

    Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects ...

  11. Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats.

    Science.gov (United States)

    Cheng, Tse-Chou; Lin, Chian-Shiung; Hsu, Chih-Chieh; Chen, Li-Jen; Cheng, Kai-Chun; Cheng, Juei-Tang

    2009-11-20

    Curcumin, an active principle contained in rhizome of Curcuma longa, has been mentioned to show merit for diabetes through its anti-oxidative and anti-inflammatory properties. In the present study, we found that curcumin caused a concentration-dependent increase of glucose uptake into skeletal muscle isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block muscarinic M-1 cholinoceptor (M(1)-mAChR). In radioligand binding assay, the binding of [(3)H]-pirenzepine was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PI3K pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide 3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was markedly reduced. In Western blotting analysis, the membrane protein level of glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade of M(1)-mAChR or PLC-PI3K pathway in a same manner. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals for increase of glucose uptake into skeletal muscle through PLC-PI3-kinase pathway.

  12. Activation of muscarinic M-1 cholinoceptors by curcumin to increase contractility in urinary bladder isolated from Wistar rats.

    Science.gov (United States)

    Cheng, Tse-Chou; Lu, Chih-Cheng; Chung, Hsien-Hui; Hsu, Chih-Chieh; Kakizawa, Nozomi; Yamada, Shizuo; Cheng, Juei-Tang

    2010-04-05

    Curcumin is an active principle contained in rhizome of Curcuma longa, and it has been recently mentioned to show affinity to muscarinic M-1 cholinoceptors (M(1)-mAChR). In the present study, we found that curcumin caused a concentration-dependent increase of muscle tone in urinary bladder isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block M(1)-mAChR. In radioligand-binding assay, specific binding of [(3)H]-oxotremorine (OXO-M) in the rat bladder homogenates was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PKC pathway, either U73122 (phospholipase C inhibitor) or chelerythrine (protein kinase C inhibitor), curcumin-stimulated contraction in urinary bladder was markedly reduced. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals to increase of muscle tone in urinary bladder through PLC-PKC pathway.

  13. Selective incorporation of vRNP into influenza A virions determined by its specific interaction with M1 protein

    International Nuclear Information System (INIS)

    Chaimayo, Chutikarn; Hayashi, Tsuyoshi; Underwood, Andrew; Hodges, Erin; Takimoto, Toru

    2017-01-01

    Influenza A viruses contain eight single-stranded, negative-sense RNA segments as viral genomes in the form of viral ribonucleoproteins (vRNPs). During genome replication in the nucleus, positive-sense complementary RNPs (cRNPs) are produced as replicative intermediates, which are not incorporated into progeny virions. To analyze the mechanism of selective vRNP incorporation into progeny virions, we quantified vRNPs and cRNPs in the nuclear and cytosolic fractions of infected cells, using a strand-specific qRT-PCR. Unexpectedly, we found that cRNPs were also exported to the cytoplasm. This export was chromosome region maintenance 1 (CRM1)-independent unlike that of vRNPs. Although both vRNPs and cRNPs were present in the cytosol, viral matrix (M1) protein, a key regulator for viral assembly, preferentially bound vRNPs over cRNPs. These results indicate that influenza A viruses selectively uptake cytosolic vRNPs through a specific interaction with M1 during viral assembly. - Highlights: •Influenza cRNPs are exported from the nucleus of an infected cell via a CRM1-independent pathway. •Influenza A viruses selectively incorporate cytosolic vRNPs through a specific interaction with M1 during viral assembly. •M1 dissociates from vRNP export complex after nuclear export, and is re-associated with vRNPs at the plasma membrane.

  14. Activation of M1 macrophages in sepsis-induced acute kidney injury in response to heparin-binding protein.

    Directory of Open Access Journals (Sweden)

    Li Xing

    Full Text Available In the early stage of sepsis, M1 macrophages result in the production of inflammatory mediators and AKI. Heparin-binding protein (HBP have been shown to play important roles in sepsis-induced AKI. In this study, we investigate the association of HBP with M1 macrophages in sepsis-induced AKI.Male C57BL6 mice were subjected to cecal ligation and puncture (CLP or sham surgery. Biochemical and histological renal damage was assessed. Macrophage infiltration was assessed by immunohistochemistry. RT-PCR was used to investigate the expression of heparin-binding protein (HBP, the inducible nitric oxide synthase (iNOS and arginase 1 (Arg-1 mRNAs. Western blots were performed to assay the tissue levels of HBP, tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6.High levels of HBP were obviously detected 24 h after sepsis-induced AKI. Heparin inhibited HBP expression during sepsis-induced AKI. The suppression of HBP expression by heparin injection after the establishment of sepsis-induced AKI resulted in a reduction in renal injury severity accompanied with a significant repression of M1 macrophage activation and expression of TNF-α and IL-6.HBP plays an important role in the initial inflammatory reaction associated with sepsis-induced AKI, presumably by activating M1 macrophages and suppressing TNF-α and IL-6 secretion.

  15. Allosteric modulation by persistent binding of xanomeline of the interaction of competitive ligands with the M1 muscarinic acetylcholine receptor

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; Tuček, Stanislav; El-Fakahany, E. E.

    2002-01-01

    Roč. 301, č. 3 (2002), s. 1033-1041 ISSN 0022-3565 R&D Projects: GA ČR GP305/01/D119 Grant - others:NIH(US) NS25743 Institutional research plan: CEZ:AV0Z5011922 Keywords : xanomeline * M(1) muscarinic acetylcholine receptor Subject RIV: FH - Neurology Impact factor: 3.991, year: 2002

  16. Design, Engineering and Application of an Amyloidogenic Protein, SBAFP-m1, for use in Nanotechnological Applications

    Science.gov (United States)

    Peralta, Maria del Refugio

    Nanotechnology relies on collaborations across scientific disciplines such as physics, engineering, chemistry and biology. In nanotechnology, researchers manipulate molecules on the nanometer scale for various applications, ranging from tissue engineering, nanowire synthesis, and alternative energy devices. By utilizing various biological scaffolds, namely amyloid fibrils, the work of nanometer molecular control can be achieved through the use of self-assembly systems. Here, a systematic design scheme was developed to engineer protein based amyloid fibrils and was successfully applied to the design of two, unique self-assembled monomers, SBAFP-m1 and RGAFP-m1, from naturally occurring ice binding proteins found in insects and plants. A highly idealized, in-register dimer interface was designed and experimentally synthesized and demonstrated to form micron long amyloid fibrils (Chapter 2). The strength and resistance of the designer amyloid fibrils formed by SBAFP-m1 were probed in Chapter 3. Most notably, the ultimate tensile strength of SBAFP-m1 fibrils was experimentally determined to be 2.1 +/- 1.7 GPa, on par with that of naturally occurring amyloid fibrils in literature and steel. The fibrils were found to maintain their beta-sheet structure over a wide range of temperatures, from - 80 °C to 90 °C. Fibrils were resistant to common protein denaturants like 8M urea, 2.5 M guanidine hydrochloride, 2.5 M NaCl, organic solvents (methanol, ethanol, isopropanol and acetone), and across the pH range two to 11. SBAFP-m1 was mutated to add a 5x cysteine tag to the N-terminus, allowing for gold nanoparticle conjugation along the fibril axis (Chapter 4). The gold-conjugated fibrils were then enhanced with silver to produce nanowires. Various attempts to selectively synthesize heterogeneous fibrils from SBAFP-m1 mutants were attempted in Chapter 5. An attempt to de-stabilize the homogeneous fibril assembly through unfavorable homogeneous protein interactions was not

  17. Identification of the GST-T1 and GST-M1 null genotypes using high resolution melting analysis.

    Science.gov (United States)

    Drobná, Zuzana; Del Razo, Luz Maria; Garcia-Vargas, Gonzalo; Sánchez-Ramírez, Blanca; González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Loomis, Dana; Stýblo, Miroslav

    2012-01-13

    Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved in the phase II detoxification pathways for xenobiotics as well as in the metabolism of endogenous compounds. Polymorphisms in these genes have been linked to an increased susceptibility to carcinogenesis and associated with risk factors that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1 null genotypes have been shown to be responsible for interindividual variations in the metabolism of arsenic, a known human carcinogen. To assess the specific GST genotypes in the Mexican population chronically exposed to arsenic, we have developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a LightCycler480 instrument. This method is based on analysis of the PCR product melting curve that discriminates PCR products according to their lengths and base sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and β-globin, an internal control, to produce amplicons of different length were designed and combined with LightCycler480 High Resolution Melting Master Mix containing ResoLight, a completely saturating DNA dye. Data collected from melting curve analysis were evaluated using LightCycler480 software to determine specific melting temperatures of individual melting curves representing target genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1 and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype frequencies which differ from those of the Chihuahua population. In addition, 14 individuals have been identified as carriers of the double null genotype, i.e., null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be used in an

  18. Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury.

    Science.gov (United States)

    Yang, Xiaodong; Xu, Shaoqing; Qian, Yiwei; Xiao, Qin

    2017-08-01

    Microglia are the primary cells that exert immune function in the central nervous system (CNS), and accumulating evidence suggests that microglia act as key players in the initiation of neurodegenerative diseases. It is now well recognized that microglia have functional plasticity and dual phenotypes, proinflammatory M1 and anti-inflammatory M2 phenotypes. Inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for the treatment of neuroinflammation-related diseases. Resveratrol has been demonstrated to exert anti-inflammatory effects by suppressing M1 microglia activation. However, the role of resveratrol in regulating microglia polarization and the molecular mechanisms involved have not been fully clarified. In this study, we tested whether resveratrol could suppress microglia activation by promoting microglia polarization toward the M2 phenotype via PGC-1α by measuring M1 and M2 markers in vitro and in vivo. Our study demonstrated that resveratrol reduced inflammatory damage and promoted microglia polarization to the M2 phenotype in LPS-induced neuroinflammation. In addition, resveratrol ameliorated LPS-induced sickness behavior in mice. The promoting effects of resveratrol on M2 polarization were attenuated by knocking down PGC-1α. PGC-1α not only suppressed LPS-evoked M1 marker expression by inhibition of NF-κB activity but also increased M2 marker expression by coactivation of the STAT6 and STAT3 pathways. We propose that overexpression PGC-1α by resveratrol could be a potential therapeutic approach to suppress neuroinflammation by regulating microglia polarization. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis.

    Science.gov (United States)

    Mahmood, Dler Faieeq Darweesh; Abderrazak, Amna; Couchie, Dominique; Lunov, Oleg; Diderot, Vimala; Syrovets, Tatiana; Slimane, Mohamed-Naceur; Gosselet, Fabien; Simmet, Thomas; Rouis, Mustapha; El Hadri, Khadija

    2013-07-01

    Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 µg/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/ml or IL-4/IL-13 (10 ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. Copyright © 2013 Wiley Periodicals, Inc.

  20. Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Mathew Jobin

    2009-04-01

    Full Text Available Abstract Acetylcholine (ACh, the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. Previous reports from our laboratory on streptozotocin (STZ induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax and affinity (Kd of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

  1. Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

    International Nuclear Information System (INIS)

    Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.

    1982-01-01

    The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

  2. The XXX spin s quantum chain and the alternating s1, s2 chain with boundaries

    International Nuclear Information System (INIS)

    Doikou, Anastasia

    2002-01-01

    The integrable XXX spin s quantum chain and the alternating s 1 , s 2 (s 1 -s 2 =1/2) chain with boundaries are considered. The scattering of their excitations with the boundaries via the Bethe ansatz method is studied, and the exact boundary S matrices are computed in the limit s,s 1,2 →∞. Moreover, the connection of these models with the SU(2) Principal Chiral, WZW and the RSOS models is discussed

  3. Targeting S1P in Inflammatory bowel disease: new avenues for modulating intestinal leukocyte migration.

    Science.gov (United States)

    Danese, Silvio; Furfaro, Federica; Vetrano, Stefania

    2017-07-28

    Sphingosine 1 phosphate (S1P) is a bioactive lipid mediator involved in the regulation of several cellular processes though the activation of a G protein-coupled receptor family known as the S1P receptors (S1PRs). Advances in the understanding of the biological activities mediated by S1PRs have sparked great interest in the S1P/S1PRs axes as new therapeutic targets for the modulation of several cellular processes. In particular, S1P/ S1PR1 axis has been identified as key regulator for the lymphocyte migration from lymph nodes. The blockade of this axis is emerging as a new therapeutic approach to control the aberrant leukocytes migration into the mucosa in inflammatory bowel disease (IBD). This review briefly summarizes the current evidence coming from clinical studies and discusses the future prospects of S1P inhibitors for treatment of inflammatory bowel disease. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. Spectroscopic properties of the S1 state of linear carotenoids after excess energy excitation

    Science.gov (United States)

    Kuznetsova, Valentyna; Southall, June; Cogdell, Richard J.; Fuciman, Marcel; Polívka, Tomáš

    2017-09-01

    Properties of the S1 state of neurosporene, spheroidene and lycopene were studied after excess energy excitation in the S2 state. Excitation of carotenoids into higher vibronic levels of the S2 state generates excess vibrational energy in the S1 state. The vibrationally hot S1 state relaxes faster when carotenoid is excited into the S2 state with excess energy, but the S1 lifetime remains constant regardless of which vibronic level of the S2 state is excited. The S∗ signal depends on excitation energy only for spheroidene, which is likely due to asymmetry of the molecule, facilitating conformations responsible for the S∗ signal.

  5. Pathophysiological Consequences of a Break in S1P1-Dependent Homeostasis of Vascular Permeability Revealed by S1P1 Competitive Antagonism.

    Science.gov (United States)

    Bigaud, Marc; Dincer, Zuhal; Bollbuck, Birgit; Dawson, Janet; Beckmann, Nicolau; Beerli, Christian; Fishli-Cavelti, Gina; Nahler, Michaela; Angst, Daniela; Janser, Philipp; Otto, Heike; Rosner, Elisabeth; Hersperger, Rene; Bruns, Christian; Quancard, Jean

    2016-01-01

    Homeostasis of vascular barriers depends upon sphingosine 1-phosphate (S1P) signaling via the S1P1 receptor. Accordingly, S1P1 competitive antagonism is known to reduce vascular barrier integrity with still unclear pathophysiological consequences. This was explored in the present study using NIBR-0213, a potent and selective S1P1 competitive antagonist. NIBR-0213 was tolerated at the efficacious oral dose of 30 mg/kg BID in the rat adjuvant-induced arthritis (AiA) model, with no sign of labored breathing. However, it induced dose-dependent acute vascular pulmonary leakage and pleural effusion that fully resolved within 3-4 days, as evidenced by MRI monitoring. At the supra-maximal oral dose of 300 mg/kg QD, NIBR-0213 impaired lung function (with increased breathing rate and reduced tidal volume) within the first 24 hrs. Two weeks of NIBR-0213 oral dosing at 30, 100 and 300 mg/kg QD induced moderate pulmonary changes, characterized by alveolar wall thickening, macrophage accumulation, fibrosis, micro-hemorrhage, edema and necrosis. In addition to this picture of chronic inflammation, perivascular edema and myofiber degeneration observed in the heart were also indicative of vascular leakage and its consequences. Overall, these observations suggest that, in the rat, the lung is the main target organ for the S1P1 competitive antagonism-induced acute vascular leakage, which appears first as transient and asymptomatic but could lead, upon chronic dosing, to lung remodeling with functional impairments. Hence, this not only raises the question of organ specificity in the homeostasis of vascular barriers, but also provides insight into the pre-clinical evaluation of a potential safety window for S1P1 competitive antagonists as drug candidates.

  6. First-line chemotherapy with S-1 alone or S-1 plus cisplatin for elderly patients with advanced gastric cancer: a multicenter propensity score matched study.

    Science.gov (United States)

    Makiyama, Akitaka; Kunieda, Kenji; Noguchi, Masaaki; Kajiwara, Takeshi; Tamura, Takao; Takeda, Koji; Sugiyama, Junko; Minashi, Keiko; Moriwaki, Toshikazu; Sugimoto, Naotoshi; Nagase, Michitaka; Negoro, Yuji; Tsuda, Takashi; Shimodaira, Hideki; Okano, Naohiro; Tsuji, Akihito; Sakai, Daisuke; Yanagihara, Kazuhiro; Ueda, Shinya; Tamura, Shingo; Otsu, Satoshi; Honda, Takuya; Matsushita, Yuzo; Okuno, Tatsuya; Kashiwada, Tomomi; Nozaki, Akira; Ebi, Masahide; Okuda, Hiroyuki; Shimokawa, Mototsugu; Hironaka, Shuichi; Hyodo, Ichinosuke; Baba, Eishi; Boku, Narikazu; Muro, Kei; Esaki, Taito

    2018-01-20

    Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability. In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors. PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients' characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p strategy and explore applicability of the geriatric assessment for these patients.

  7. QED based on self-energy: The relativistic 2S1/2 → 1S1/2+1γ decay rates of hydrogenlike atoms

    International Nuclear Information System (INIS)

    Barut, A.O.; Salamin, Y.I.

    1989-07-01

    Within the framework of the recently advanced formulation of QED based on self-energy, we calculate the relativistic rates of the 2S 1/2 → 1S 1/2 +1γ transition in the hydrogen isoelectronic sequence for values of Z ranging between 1 and 92. We compare our results with those of Johnson (Phys. Rev. Lett. 29, 1123 (1972)) and Parpia and Johnson (Phys. Rev. A 26, 1142 (1982)) and find them to be in good agreement with both. (author). 12 refs, 1 tab

  8. QED based on self-energy: The relativistic 2S1/2→1S1/2+1γ decay rates of hydrogenlike atoms

    International Nuclear Information System (INIS)

    Barut, A.O.; Salamin, Y.I.

    1991-01-01

    Within the framework of the recently advanced formulation of QED based on self-energy, we calculate the relativistic rates of the 2S 1/2 →1S 1/2 +1γ transition in the hydrogen isoelectronic sequence for values of Z ranging between 1 and 92. We compare our results with those of Johnson [Phys. Rev. Lett. 29, 1123 (1972)] and Parpia and Johnson [Phys. Rev. A 26, 1142 (1982)], analytically and numerically. Although the two approaches are quite different, the formulas for decay rates are shown to be equivalent

  9. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    International Nuclear Information System (INIS)

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui; Xiao, Gengfu

    2011-01-01

    Highlights: → Successfully selected specific PreS1-interacting peptides by using phage displayed library. → Alignment of the positive phage clones revealed a consensus PreS1 binding motif. → A highly enriched peptide named P7 had a strong binding ability for PreS1. → P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX n HX m HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  10. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Xiao, Gengfu, E-mail: xiaogf@wh.iov.cn [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)

    2011-09-09

    Highlights: {yields} Successfully selected specific PreS1-interacting peptides by using phage displayed library. {yields} Alignment of the positive phage clones revealed a consensus PreS1 binding motif. {yields} A highly enriched peptide named P7 had a strong binding ability for PreS1. {yields} P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX{sub n}HX{sub m}HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  11. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells.

    Science.gov (United States)

    Mendoza, Alejandra; Fang, Victoria; Chen, Cynthia; Serasinghe, Madhavika; Verma, Akanksha; Muller, James; Chaluvadi, V Sai; Dustin, Michael L; Hla, Timothy; Elemento, Olivier; Chipuk, Jerry E; Schwab, Susan R

    2017-06-01

    Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P 1 receptor (S1P 1 R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer's patches into lymph. Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P 1 R on T cells, and that the requirement for S1P 1 R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival.

  12. Proto-planetary nebulae. I. The extreme bipolar nebulae M2-9 and M1-91

    International Nuclear Information System (INIS)

    Goodrich, R.W.

    1991-01-01

    Results are presented on a long-slit optical spectroscopy measurements of the prototype bipolar planetary nebula M2-9 and the M1-91 bipolar nebula, performed in order to determine the nature of the morphology of the wings of these two nebulae. It is concluded that the overall bipolar morphologies of these nebulae might be due to the orbital motions of binaries, with the orbital angular momentum vector defining the axis of the nebula. Secondary symmetries in the nebulae, such as the point-symmetric knots in M1-91, could be due to other symmetries, such as the rotation axis of one of the individual stars or the polar axis of the accretion disk. 39 refs

  13. Cytoplasm localization of aminopeptidase M1 and its functional activity in root hair cells and BY-2 cells.

    Science.gov (United States)

    Lee, Ok Ran; Cho, Hyung-Taeg

    2012-12-01

    Aminopeptidase M1 (APM1) was the first M1 metallopeptidase family member identified in Arabidopsis, isolated by its affinity for the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). A loss-of-function mutation showed various developmental defects in cell division and auxin transport. APM1 was shown to be localized in endomembrane structures, the cytoplasm, and the plasma membrane. These previous results suggested that APM1 has diverse functional roles in different cell and tissue types. Here we report that APM1 localized to the cytoplasm, and its over-expression in the root hair cell caused longer root hair phenotypes. Treatment of aminopeptidase inhibitors caused internalization of auxin efflux PIN-FORMED proteins in root hair cells and suppressed short root hair phenotype of PIN3 overexpression line (PIN3ox). APM1 also localized to the cytoplasm in tobacco BY-2 cells, its over-expression had little effect on auxin transport in these cells.

  14. Determination of aflatoxins B1 and M1 in animal feeds and liquid milk using thin layer chromatography

    International Nuclear Information System (INIS)

    Njue, W.; Gitu, L.; Kaberia, F.

    1996-01-01

    Animal feed samples were collected from feeding troughs and analysed for levels of aflatoxins B 1 , a toxic and carcinogenic mycotoxin. When aflatoxin B 1 is consumed by dairy cattle some of it is hydroxylated to form aflatoxin M 1 , which can appear in milk. Since aflatoxin M 1 , is also toxic and carcinogenic, it was determined in liquid milk. The determinations were carried out using thin-layer chromatography. Some of the feed samples were found to contain concentrations of aflatoxin B 1 that were above maximum tolerated values in foods and feeds in various countries. Brewers grain and used poultry feed contained 133.4 ppb, while the barley husks had a maximum value of 27.4 ppb. The details of the experimental results and analytical methods used are presented.(author)

  15. Cosméticos Contém 1g: um caso de empreendedorismo e inovação

    OpenAIRE

    Guimarães,Liliane de Oliveira; Cardoza,Guillermo

    2005-01-01

    Este caso de ensino descreve a fundação e a expansão da Contém 1g, uma empresa brasileira do setor de higiene pessoal, perfumaria e cosméticos. Fundada em 1984 como empresa têxtil, seu proprietário redirecionou o negócio e iniciou a produção de perfumes em 1994. A história empresarial da Contém 1g é marcada pelo lançamento de novos produtos e pela utilização, a partir de determinado momento, de um sistema híbrido de vendas: venda direta e franquia. A decisão de expandir o negócio é o ponto de...

  16. Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

    Science.gov (United States)

    Seely, Jeffrey S; Kaufman, Matthew T; Ryu, Stephen I; Shenoy, Krishna V; Cunningham, John P; Churchland, Mark M

    2016-11-01

    Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1) and primary motor cortex (M1). All V1 datasets were 'simplest' (there were relatively few degrees of freedom) along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

  17. Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.

    Science.gov (United States)

    Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping

    2014-09-01

    Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Molybdenum emission from impurity-induced m= 1 snake-modes on the Alcator C-Mod tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Delgado-Aparicio, L. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); MIT - Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Bitter, M.; Gates, D.; Hill, K.; Pablant, N. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); Granetz, R.; Reinke, M.; Podpaly, Y.; Rice, J. [MIT - Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Beiersdorfer, P. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Sugiyama, L. [MIT - Laboratory for Nuclear Science, Cambridge, Massachusetts 02139 (United States)

    2012-10-15

    A suite of novel high-resolution spectroscopic imaging diagnostics has facilitated the identification and localization of molybdenum impurities as the main species during the formation and lifetime of m= 1 impurity-induced snake-modes on Alcator C-Mod. Such measurements made it possible to infer, for the first time, the perturbed radiated power density profiles from which the impurity density can be deduced.

  19. Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Seely

    2016-11-01

    Full Text Available Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1 and primary motor cortex (M1. All V1 datasets were 'simplest' (there were relatively few degrees of freedom along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

  20. Unexpected expansion of tRNA substrate recognition by the yeast m1G9 methyltransferase Trm10.

    Science.gov (United States)

    Swinehart, William E; Henderson, Jeremy C; Jackman, Jane E

    2013-08-01

    N-1 Methylation of the nearly invariant purine residue found at position 9 of tRNA is a nucleotide modification found in multiple tRNA species throughout Eukarya and Archaea. First discovered in Saccharomyces cerevisiae, the tRNA methyltransferase Trm10 is a highly conserved protein both necessary and sufficient to catalyze all known instances of m1G9 modification in yeast. Although there are 19 unique tRNA species that contain a G at position 9 in yeast, and whose fully modified sequence is known, only 9 of these tRNA species are modified with m1G9 in wild-type cells. The elements that allow Trm10 to distinguish between structurally similar tRNA species are not known, and sequences that are shared between all substrate or all nonsubstrate tRNAs have not been identified. Here, we demonstrate that the in vitro methylation activity of yeast Trm10 is not sufficient to explain the observed pattern of modification in vivo, as additional tRNA species are substrates for Trm10 m1G9 methyltransferase activity. Similarly, overexpression of Trm10 in yeast yields m1G9 containing tRNA species that are ordinarily unmodified in vivo. Thus, yeast Trm10 has a significantly broader tRNA substrate specificity than is suggested by the observed pattern of modification in wild-type yeast. These results may shed light onto the suggested involvement of Trm10 in other pathways in other organisms, particularly in higher eukaryotes that contain up to three different genes with sequence similarity to the single TRM10 gene in yeast, and where these other enzymes have been implicated in pathways beyond tRNA processing.

  1. Screening the Medicines for Malaria Venture "Malaria Box" against the Plasmodium falciparum aminopeptidases, M1, M17 and M18.

    Directory of Open Access Journals (Sweden)

    Alessandro Paiardini

    Full Text Available Malaria is a parasitic disease that remains a global health burden. The ability of the parasite to rapidly develop resistance to therapeutics drives an urgent need for the delivery of new drugs. The Medicines for Malaria Venture have compounds known for their antimalarial activity, but not necessarily the molecular targets. In this study, we assess the ability of the "MMV 400" compounds to inhibit the activity of three metalloaminopeptidases from Plasmodium falciparum, PfA-M1, PfA-M17 and PfM18 AAP. We have developed a multiplex assay system to allow rapid primary screening of compounds against all three metalloaminopeptidases, followed by detailed analysis of promising compounds. Our results show that there were no PfM18AAP inhibitors, whereas two moderate inhibitors of the neutral aminopeptidases PfA-M1 and PfA-M17 were identified. Further investigation through structure-activity relationship studies and molecular docking suggest that these compounds are competitive inhibitors with novel binding mechanisms, acting through either non-classical zinc coordination or independently of zinc binding altogether. Although it is unlikely that inhibition of PfA-M1 and/or PfA-M17 is the primary mechanism responsible for the antiplasmodial activity reported for these compounds, their detailed characterization, as presented in this work, pave the way for their further optimization as a novel class of dual PfA-M1/PfA-M17 inhibitors utilising non-classical zinc binding groups.

  2. Computational Modeling with Fluid-Structure Interaction of the Severe M1 Stenosis Before and After Stenting

    OpenAIRE

    Park, Soonchan; Lee, Sang-Wook; Lim, Ok Kyun; Min, Inki; Nguyen, Minhtuan; Ko, Young Bae; Yoon, Kyunghwan; Suh, Dae Chul

    2013-01-01

    Purpose Image-based computational models with fluid-structure interaction (FSI) can be used to perform plaque mechanical analysis in intracranial artery stenosis. We described a process in FSI study applied to symptomatic severe intracranial (M1) stenosis before and after stenting. Materials and Methods Reconstructed 3D angiography in STL format was transferred to Magics for smoothing of vessel surface and trimming of branch vessels and to HyperMesh for generating tetra volume mesh from trian...

  3. How well do we know the quantum numbers of possible anti p p → M1M2 states

    International Nuclear Information System (INIS)

    Lanou, R.E.

    1979-01-01

    Information is available to completely analyze the p anti p → ππ reaction, allowing more global, large-scale, phenomenological analyses which combine the two experimental data sets in an energy independent, amplitude analysis which also includes pion-nucleon data. It would appear from the preliminary analyses of p anti p → M 1 M 2 angular distributions and polarizations the T-region may indeed contain some very interesting activity

  4. Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway.

    Science.gov (United States)

    Dong, Guang-Zhi; Jeong, Ji Hye; Lee, Yu-Ih; Lee, So Yoon; Zhao, Hui-Yuan; Jeon, Raok; Lee, Hwa Jin; Ryu, Jae-Ha

    2017-04-01

    Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds 1 and 7 inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (1) from Alpinia officinarum (lesser galangal) and platyphyllenone (7) from Alnus japonica inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.

  5. Operation of TRR-1/M1 for 25 years and lessons learned in management of safety and safety culture

    International Nuclear Information System (INIS)

    Keinmeesuke, Sirichai

    2002-01-01

    The first Thai Research Reactor, TRR-1, was installed and put into operation in 1962. In 1975 the reactor was converted to a 2 MW TRIGA Mark III by replacing of the reactor core and the control system. The renamed TRR-1/M1 research reactor went critical again in November 1977. TRR-1/M1 has been operated safely for 25 years with its main utilization in research, isotope production and training. Safety management and safety culture have been implemented for 25 years both in the legislation level and the operation level. There was no nuclear incident and there were a few radiological incidents during the 25 years of operation of TRR-1/M1. The lessons learned from the incident events such as the release of N-16 and Ar-41, the release of radioactive Bromine gave valued opportunities to improve our operation procedure, safety procedure and safety culture. All type of activities with respect to safety culture such as individual awareness, commitment, motivation, supervision and responsibility have been seriously reviewed and being set as normal practices. (author)

  6. Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia

    Directory of Open Access Journals (Sweden)

    Conceição Bettencourt

    2017-11-01

    Full Text Available Abstract Background Autosomal recessive hereditary spastic paraplegia (HSP due to AP4M1 mutations is a very rare neurodevelopmental disorder reported for only a few patients. Methods We investigated a Greek HSP family using whole exome sequencing (WES. Results A novel AP4M1A frameshift insertion, and a very rare missense variant were identified in all three affected siblings in the compound heterozygous state (p.V174fs and p.C319R; the unaffected parents were carriers of only one variant. Patients were affected with a combination of: (a febrile seizures with onset in the first year of life (followed by epileptic non-febrile seizures; (b distinctive facial appearance (e.g., coarse features, bulbous nose and hypomimia; (c developmental delay and intellectual disability; (d early-onset spastic weakness of the lower limbs; and (e cerebellar hypoplasia/atrophy on brain MRI. Conclusions We review genotype-phenotype correlations and discuss clinical overlaps between different AP4-related diseases. The AP4M1 belongs to a complex that mediates vesicle trafficking of glutamate receptors, being likely involved in brain development and neurotransmission.

  7. Problems of concurrent radiotherapy with S-1 for T2 glottic carcinoma

    International Nuclear Information System (INIS)

    Higashino, Masaaki; Kawata, Ryo; Suzuki, Norio; Ichihara, Takahiro; Terada, Tetsuya

    2016-01-01

    The aim of this study was to investigate the effectiveness and problems of concurrent radiotherapy with S-1 for T2 glottic carcinoma. The study included 48 patients (22 patients for radiotherapy alone (RT group), 26 patients for radiotherapy concurrent with S-1 (S-1 group) who underwent initial treatment as outpatients for T2 glottic carcinoma at Osaka Medical College. Six of the 26 patients of the S-1 group were suspected to have local recurrence, but 5 of them had necrosis and one had dysplasia. Three patients suffered bilateral vocal cord paralysis and underwent tracheostomy. On the other hand, 4 of the 22 patients of the RT group suffered local recurrence and one patient suffered unilateral vocal cord paralysis. The local control rate of the S-1 group was significantly higher than that of the RT group. In the S-1 group, 5 patients with laryngeal function disorder tended to develop upper and arytenoid cartilage. The local control rate of radiotherapy for T2 glottic carcinoma was improved by concurrent S-1. In the S-1 group, there was no local recurrence, but some cases suffered laryngeal dysfunction, so efforts should be made to preserve laryngeal function. (author)

  8. Genome Sequence of Bacillus pumilus S-1, an Efficient Isoeugenol-Utilizing Producer for Natural Vanillin

    Science.gov (United States)

    Su, Fei; Hua, Dongliang; Zhang, Zhaobin; Wang, Xiaoyu; Tang, Hongzhi; Tao, Fei; Tai, Cui; Wu, Qiulin; Wu, Geng; Xu, Ping

    2011-01-01

    Bacillus pumilus S-1 is an efficient isoeugenol-utilizing producer of natural vanillin. The genome of B. pumilus S-1 contains the epoxide hydrolase and six candidate monooxygenases that make it possible to explore the mechanism involved in conversion of isoenguenol to vanillin in the B. pumilus strain. PMID:22038964

  9. Interaction of avian infectious bronchitis virus S1 protein with heat ...

    African Journals Online (AJOL)

    The interaction between S1 and HSP47 was verified by colocalization experiment and co-immunoprecipitation of HeLa cell lysates expressing both proteins. The mapping studies localized the critical S1 sequences for this interaction to amino acids 340-470. Based on these results, we speculate that HSP47 is a functional ...

  10. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

    Science.gov (United States)

    Fang, Chao; Bian, Ganlan; Ren, Pan; Xiang, Jie; Song, Jun; Yu, Caiyong; Zhang, Qian; Liu, Ling; Chen, Kun; Liu, Fangfang; Zhang, Kun; Wu, Chunfeng; Sun, Ruixia; Hu, Dan; Ju, Gong; Wang, Jian

    2018-02-08

    Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

  11. To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling.

    Science.gov (United States)

    Chew, Wee Siong; Wang, Wei; Herr, Deron R

    2016-11-01

    Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and disease states, such as cardiovascular development, immune function, hypoxic responses, and cancer. The therapeutic potential of targeting this system took center stage when it was demonstrated that the immune modulator, fingolimod (FTY720/Gilenya), exerts it lymphopenic effect by acting on S1P receptors, primarily on S1P receptor 1 (S1P 1 ). In 2010, fingolimod became the first oral medication approved for the treatment of multiple sclerosis (MS). Since then, second-generation S1P receptor modulators have been under development in an effort to provide improved safety and efficacy profiles for MS, and to broaden their use to other autoimmune indications. Beyond the development of S1P 1 -modulators, there has been considerable effort in targeting other components of the S1P signaling pathway for the treatment of other diseases, such as cardiovascular disease, sepsis, and cancer. This manuscript provides an overview of the clinical and preclinical development of drugs targeting S1P signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Winther, Stine Braendegaard; Österlund, Pia; Berglund, Åke

    2017-01-01

    to select which older patients should receive therapy. Methods: The NORDIC 9 trial is a Nordic multicenter randomized phase II study comparing full dose monotherapy (S-1 30 mg/m2 twice daily days 1-14 every 3 weeks, followed by second line irinotecan 250-350 mg/m2 iv day 1 every 3 weeks or 180-250 mg/m2 iv...... day 1 every 2 weeks) with reduced dose combination therapy (S-1 20 mg/m2 days 1-14 + oxaliplatin 100 mg/m2 iv day 1 every 3 weeks, followed by second line S-1 20 mg/m2 days 1-14 + irinotecan 180 mg/m2 day 1 every 3 week) for older patients (≥70 years) with mCRC who are not candidates for full...... chance for tailored treatment strategies in these patients. Trial registration: EU Clinical Trial Register, EudraCT no. 2014-000394-39. Registered 05 May 2014....

  13. CTX-M-1 β-lactamase expression in Escherichia coli is dependent on cefotaxime concentration, growth phase and gene location

    DEFF Research Database (Denmark)

    Kjeldsen, Thea S. B.; Overgaard, Martin; Nielsen, Søren S.

    2015-01-01

    blaCTX-M-1 mRNA expression and CTX-M-1 protein levels were dependent on cefotaxime concentration, growth phase and gene location. These results provide insight into the expression of cephalosporin resistance in CTX-M-1-producing E. coli, improving our understanding of the relationship between ant...

  14. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury

    Directory of Open Access Journals (Sweden)

    Huiying Liu

    2016-12-01

    Full Text Available Background Acute lung injury and acute respiratory distress syndrome (ALI/ARDS is a severe clinical syndrome with mortality rate as high as 30–40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs exhibit make it possible to regulate the homeostatic control of S1P. Methods By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. Results It was found that the down-regulation of TNF-α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. Discussions The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1

  15. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury.

    Science.gov (United States)

    Liu, Huiying; Zhang, Zili; Li, Puyuan; Yuan, Xin; Zheng, Jing; Liu, Jinwen; Bai, Changqing; Niu, Wenkai

    2016-01-01

    Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30-40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P. By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. It was found that the down-regulation of TNF- α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their possible synergistic mechanism.

  16. Estimates of epistatic and pleiotropic effects of casein alpha s1 (CSN1S1) and thyroglobulin (TG) genetic markers on beef heifer performance traits enhanced by selection

    Science.gov (United States)

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for two years to equalize CSN1S1 and TG genetic marker frequencies to evaluate the epista...

  17. The clinical significance of detection of serum Pre-S1 antigen

    International Nuclear Information System (INIS)

    Jiang Xuehua; Huang Zhuqing; Han Yi; Gong Shoujun

    2003-01-01

    To study the clinical significance of detection of serum Pre-S 1 Ag, the serum Pre-S 1 Ag, HBV-marks and HBV-DNA were detected in 338 patients with hepatitis B. The positive rate and the relationship between them were analyzed and compared. In 338 patients, the positive rate of serum Pre-S 1 Ag, HBeAg, HBV-DNA was 63.02%, 48.52%, 68.05% respectively, and the co-positive rate of Pre-S 1 Ag with HBV-DNA, HBeAg was 78.56%, 81.17% respectively. There was a significant correlation between Pre-S 1 Ag, HBeAg and HBV-DNA (P 1 Ag could well reflect the reproductive status of hepatitis B virus, and so it could be used as the clinical marker of the reproductive status of hepatitis B virus

  18. Mixing between the 23S1 and 13D1 Ds

    International Nuclear Information System (INIS)

    Yuan Ling; Chen Bing; Zhang Ailin

    2013-01-01

    Mixing between the 2 3 S 1 and 1 3 D 1 D s is studied within the 3 P 0 model. If mixing between these two 1 - states exists, D s1 * (2700)± and D sJ * (2860)± could be interpreted as the two orthogonal mixed states with mixing angle θ≈-80° in the case of a special β for each meson. However, in the case of a universal β for all mesons, D s1 * (2700)± could be interpreted as the mixed state of 2 3 S 1 and 1 3 D 1 with mixing angle 12° < θ < 21° but D s * J (2860) ± seems difficult to interpret as the orthogonal partner of D s1 * (2700) ± . (authors)

  19. Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA.

    Science.gov (United States)

    Pereira, Carina F; Read, Eliot K C; Wise, Helen M; Amorim, Maria J; Digard, Paul

    2017-08-01

    Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted with cellular NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1 polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1 facilitates late viral gene expression by acting as an adaptor between viral mRNAs and the cellular nuclear export machinery to promote their nuclear export. IMPORTANCE Influenza A virus is a major pathogen of a wide variety of mammalian and avian species that threatens public health and food security. A fuller understanding of the virus life cycle is important to aid control strategies. The virus has a small genome that encodes relatively few proteins that are often multifunctional. Here, we characterize a new function for the NS1 protein, showing that, as well as

  20. Electrical dipole polarizability and spin M1 strength from {sup 48}Ca(p,p') data under 0; Elektrische Dipol-Polarisierbarkeit und Spin-M1-Staerke aus {sup 48}Ca(p,p')-Daten unter 0

    Energy Technology Data Exchange (ETDEWEB)

    Birkhan, Jonny Hubertus

    2016-07-01

    In this thesis, proton scattering data on the nucleus {sup 48}Ca at very forward angles had been analysed. The data stem from a measurement campaign which was launched at the Research Centre of Nuclear Physics at Osaka, Japan, in the past. One of the two objectives of this analysis was to extract a value for the static electric dipole polarisability from the isovector giant dipole resonance (IVGDR). The second objective was to extract the total electromagnetic M1 strength B(M1) of the spin-flip transition which excites the prominent 1{sup +} state at an excitation energy of E{sub x}=10.22 MeV. The polarisability was calculated from the distribution of photo-absorption cross sections within an energy range from E{sub x}=11 MeV to E{sub x}=26 MeV. The photo-absorption cross sections had been deduced from the distribution of E1 cross sections by the method of virtual photons. For this purpose the experimental cross sections had been deconvoluted by a multipole deconvolution into an E1 part and a background part. Then, the best estimate of the polarisability is given by α{sub D}=(1.36±0.14) fm{sup 3}. If a E3 model was included into the multipole decomposition of the (p,p') data the result increased up to α{sub D}=(1.50±0.09) fm{sup 3}. The deviation between these two results is mainly due to the fact that the multipole decomposition is very sensitive on the background function. Assuming that the the IVGDR of the nuclei {sup 48}Ca and {sup 40}Ca have approximately the same structure, estimates for the polarisability of the nucleus {sup 48}Ca could be drawn from {sup 40}Ca(γ,abs) data. Additionally, data from a {sup 48}Ca(e,e'n) measurement were used to estimate the polarisability of the nucleus {sup 48}Ca. Its polarisability seems to fall within the range of α{sub D}=(1.50±0.09) fm{sup 3} and α{sub D}=(1.69±0.03) fm{sup 3}. Beside this, it could be shown by the {sup 40}Ca data that a significant contribution to the polarisability has to be expected

  1. ApolipoproteinA1-75 G/A (M1- polymorphism and Lipoprotein(a; Anti- vs. Pro-Atherogenic properties

    Directory of Open Access Journals (Sweden)

    Ranganath L

    2007-08-01

    Full Text Available Abstract Background ApolipoproteinA1(apoA1 is the major apoprotein constituent of high-density-lipoprotein(HDL. The relationship of apoA1 -75 bp(M1- allele polymorphism with lipoprotein phenotype and cardiovascular diseae (CVD remain unclear. Overnight fasting blood samples were collected from a cohort of high-risk Omani population, 90 non-diabetic subjects and 149 type 2 diabetes mellitus (T2DM subjects for genotype and phenotype studies. Results The M1+ and M1- alleles frequencies were 0.808 and 0.192 for M1+ and M1-, respectively, comparable to the frequency of apoA1 (M1+ and M1- amongst a healthy Omani population, 0.788 and 0.212, respectively. The frequencies of the hetero- and homozygous subjects for the MspI polymorphism at -75 (M1- of the apoA1 gene were in Hardy-Weinberg equilibrium. The mean Lp(a concentration was significantly higher(P = 0.02 in subjects carrying M1- allele compared to M1+ allele of the APOA1 gene with an odd ratio of 2.3(95% CI, 1.13–14.3, irrespective of gender and the diabetic status. Conclusion ApolipoproteinA1-75 G/A (M1- polymorphism is relatively common and is positively associated with Lp(a and therefore, may confer a potential risk for cardiovascular disease (CVD.

  2. [A recent trial of chemo-radiation with S-1 against gastric cancer].

    Science.gov (United States)

    Saikawa, Yoshiro; Kiyota, Tsuyoshi; Nakamura, Rieko; Wada, Norihito; Yoshida, Masashi; Kubota, Tetsuro; Kumai, Koichiro; Shigematsu, Naoyuki; Kubo, Atsushi; Kitajima, Masaki

    2006-06-01

    A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer.

  3. Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Okita Yoshihiro

    2010-02-01

    Full Text Available Abstract Background The combination of gemcitabine (GEM and S-1, an oral 5-fluorouracil (5-FU derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. Methods Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed. Results The maximum concentration (Cmax, the area under the curve from the drug administration to the infinite time (AUCinf, and the elimination half-life (T1/2 of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax were not significantly different between S-1 administration with and without GEM. Conclusion There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.

  4. An engineered S1P chaperone attenuates hypertension and ischemic injury.

    Science.gov (United States)

    Swendeman, Steven L; Xiong, Yuquan; Cantalupo, Anna; Yuan, Hui; Burg, Nathalie; Hisano, Yu; Cartier, Andreane; Liu, Catherine H; Engelbrecht, Eric; Blaho, Victoria; Zhang, Yi; Yanagida, Keisuke; Galvani, Sylvain; Obinata, Hideru; Salmon, Jane E; Sanchez, Teresa; Di Lorenzo, Annarita; Hla, Timothy

    2017-08-15

    Endothelial dysfunction, a hallmark of vascular disease, is restored by plasma high-density lipoprotein (HDL). However, a generalized increase in HDL abundance is not beneficial, suggesting that specific HDL species mediate protective effects. Apolipoprotein M-containing HDL (ApoM + HDL), which carries the bioactive lipid sphingosine 1-phosphate (S1P), promotes endothelial function by activating G protein-coupled S1P receptors. Moreover, HDL-bound S1P is limiting in several inflammatory, metabolic, and vascular diseases. We report the development of a soluble carrier for S1P, ApoM-Fc, which activated S1P receptors in a sustained manner and promoted endothelial function. In contrast, ApoM-Fc did not modulate circulating lymphocyte numbers, suggesting that it specifically activated endothelial S1P receptors. ApoM-Fc administration reduced blood pressure in hypertensive mice, attenuated myocardial damage after ischemia/reperfusion injury, and reduced brain infarct volume in the middle cerebral artery occlusion model of stroke. Our proof-of-concept study suggests that selective and sustained targeting of endothelial S1P receptors by ApoM-Fc could be a viable therapeutic strategy in vascular diseases. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. A structural insight into the P1S1 binding mode of diaminoethylphosphonic and phosphinic acids, selective inhibitors of alanine aminopeptidases

    Energy Technology Data Exchange (ETDEWEB)

    Węglarz-Tomczak, Ewelina; Berlicki, Łukasz; Pawełczak, Małgorzata; Nocek, Bogusław; Joachimiak, Andrzej; Mucha, Artur

    2016-07-01

    N0 -substituted 1,2-diaminoethylphosphonic acids and 1,2-diaminoethylphosphinic dipeptides were explored to unveil the structural context of the unexpected selectivity of these inhibitors of M1 alanine aminopeptidases (APNs) versus M17 leucine aminopeptidase (LAP). The diaminophosphonic acids were obtained via aziridines in an improved synthetic procedure that was further expanded for the phosphinic pseudodipeptide system. The inhibitory activity, measured for three M1 and one M17 metalloaminopeptidases of different sources (bacterial, human and porcine), revealed several potent compounds (e.g., Ki ¼ 65 nM of 1u for HsAPN). Two structures of an M1 representative (APN from Neisseria meningitidis) in complex with N-benzyl-1,2-diaminoethylphosphonic acid and N-cyclohexyl-1,2- diaminoethylphosphonic acid were determined by the X-ray crystallography. The analysis of these structures and the models of the phosphonic acid complexes of the human ortholog provided an insight into the role of the additional amino group and the hydrophobic substituents of the ligands within the S1 active site region.

  6. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    International Nuclear Information System (INIS)

    Kasamatsu, Atsushi; Uzawa, Katsuhiro; Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki; Endo-Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Takiguchi, Yuichi; Tanzawa, Hideki

    2015-01-01

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  7. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kasamatsu, Atsushi, E-mail: kasamatsua@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Uzawa, Katsuhiro, E-mail: uzawak@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Endo-Sakamoto, Yosuke; Ogawara, Katsunori [Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Shiiba, Masashi; Takiguchi, Yuichi [Medical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Tanzawa, Hideki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan)

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  8. miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages

    Directory of Open Access Journals (Sweden)

    Fei Huang

    2017-10-01

    Full Text Available The Notch pathway plays critical roles in the differentiation and polarized activation of macrophages; however, the downstream molecular mechanisms underlying Notch activity in macrophages remain elusive. Our previous study has identified a group of microRNAs that mediate Notch signaling to regulate macrophage activation and tumor-associated macrophages (TAMs. In this study, we demonstrated that miR-148a-3p functions as a novel downstream molecule of Notch signaling to promote the differentiation of monocytes into macrophages in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF. Meanwhile, miR-148a-3p promoted M1 and inhibited M2 polarization of macrophages upon Notch activation. Macrophages overexpressing miR-148a-3p exhibited enhanced ability to engulf and kill bacteria, which was mediated by excessive production of reactive oxygen species (ROS. Further studies using reporter assay and Western blotting identified Pten as a direct target gene of miR-148a-3p in macrophages. Macrophages overexpressing miR-148a-3p increased their ROS production through the PTEN/AKT pathway, likely to defend against bacterial invasion. Moreover, miR-148a-3p also enhanced M1 macrophage polarization and pro-inflammatory responses through PTEN/AKT-mediated upregulation of NF-κB signaling. In summary, our data establish a novel molecular mechanism by which Notch signaling promotes monocyte differentiation and M1 macrophage activation through miR-148a-3p, and suggest that miR-148a-3p-modified monocytes or macrophages are potential new tools for the treatment of inflammation-related diseases.

  9. NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage.

    Science.gov (United States)

    Tang, Li-li; Wu, Yuan-bo; Fang, Chuan-qin; Qu, Ping; Gao, Zong-liang

    2016-01-15

    Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage. Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay. Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A. Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Use of 3-(4-hydroxyphenyl)propionic acid as electron donating compound in a potentiometric aflatoxin M1-immunosensor

    International Nuclear Information System (INIS)

    Rameil, Steffen; Schubert, Peter; Grundmann, Peter; Dietrich, Richard; Maertlbauer, Erwin

    2010-01-01

    We developed a potentiometric aflatoxin M 1 -immunosensor which utilizes 3-(4-hydroxyphenyl)propionic acid (p-HPPA) as electron donating compound for horseradish peroxidase (HRP; EC 1.11.1.7). The assay system consists of a polypyrrole-surface-working electrode coated with a polyclonal anti-M 1 antibody (pAb-AFM 1 ), a Ag/AgCl reference electrode and a HRP-aflatoxin B 1 conjugate (HRP-AFB 1 conjugate). To optimize the potentiometric measuring system p-HPPA as well as related compounds serving as electron donating compounds were compared. Also the influence of different buffer systems, varying pH and substrate concentrations on signal intensity was investigated. Our results suggest that reaction conditions that favor the formation of Pummerer's type ketones lead to an increase in signal intensity rather than formation of fluorescent dye. Comparison with commercial ready-to-use HRP electron donating compounds such as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), o-phenylenediamine (OPD) or 3,3',5,5'-tetramethylbenzidine (TMB) showed that only 34%, 77% and 49% of the signal intensity of p-HPPA were reached, respectively. The optimized assay had a detection limit of 40 pg mL -1 and allowed detection of 500 pg mL -1 (FDA action limit) aflatoxin M 1 (AFM 1 ) in pasteurized milk and UHT-milk containing 0.3-3.8% fat within 10 min without any sample treatment. The working range was between 250 and 2000 pg mL -1 AFM 1 .

  11. Including α s1 casein gene information in genomic evaluations of French dairy goats.

    Science.gov (United States)

    Carillier-Jacquin, Céline; Larroque, Hélène; Robert-Granié, Christèle

    2016-08-04

    Genomic best linear unbiased prediction methods assume that all markers explain the same fraction of the genetic variance and do not account effectively for genes with major effects such as the α s1 casein polymorphism in dairy goats. In this study, we investigated methods to include the available α s1 casein genotype effect in genomic evaluations of French dairy goats. First, the α s1 casein genotype was included as a fixed effect in genomic evaluation models based only on bucks that were genotyped at the α s1 casein locus. Less than 1 % of the females with phenotypes were genotyped at the α s1 casein gene. Thus, to incorporate these female phenotypes in the genomic evaluation, two methods that allowed for this large number of missing α s1 casein genotypes were investigated. Probabilities for each possible α s1 casein genotype were first estimated for each female of unknown genotype based on iterative peeling equations. The second method is based on a multiallelic gene content approach. For each model tested, we used three datasets each divided into a training and a validation set: (1) two-breed population (Alpine + Saanen), (2) Alpine population, and (3) Saanen population. The α s1 casein genotype had a significant effect on milk yield, fat content and protein content. Including an α s1 casein effect in genetic and genomic evaluations based only on male known α s1 casein genotypes improved accuracies (from 6 to 27 %). In genomic evaluations based on all female phenotypes, the gene content approach performed better than the other tested methods but the improvement in accuracy was only slightly better (from 1 to 14 %) than that of a genomic model without the α s1 casein effect. Including the α s1 casein effect in a genomic evaluation model for French dairy goats is possible and useful to improve accuracy. Difficulties in predicting the genotypes for ungenotyped animals limited the improvement in accuracy of the obtained estimated breeding values.

  12. UGT74S1 is the key player in controlling secoisolariciresinol diglucoside (SDG) formation in flax.

    Science.gov (United States)

    Fofana, Bourlaye; Ghose, Kaushik; McCallum, Jason; You, Frank M; Cloutier, Sylvie

    2017-02-02

    Flax lignan, commonly known as secoisolariciresinol (SECO) diglucoside (SDG), has recently been reported with health-promoting activities, including its positive impact in metabolic diseases. However, not much was reported on the biosynthesis of SDG and its monoglucoside (SMG) until lately. Flax UGT74S1 was recently reported to sequentially glucosylate SECO into SMG and SDG in vitro. However, whether this gene is the only UGT achieving SECO glucosylation in flax was not known. Flax genome-wide mining for UGTs was performed. Phylogenetic and gene duplication analyses, heterologous gene expression and enzyme assays were conducted to identify family members closely related to UGT74S1 and to establish their roles in SECO glucosylation. A total of 299 different UGTs were identified, of which 241 (81%) were duplicated. Flax UGTs diverged 2.4-153.6 MYA and 71% were found to be under purifying selection pressure. UGT74S1, a single copy gene located on chromosome 7, displayed no evidence of duplication and was deemed to be under positive selection pressure. The phylogenetic analysis identified four main clusters where cluster 4, which included UGT74S1, was the most diverse. The duplicated UGT74S4 and UGT74S3, located on chromosomes 8 and 14, respectively, were the most closely related to UGT74S1 and were differentially expressed in different tissues. Heterologous expression levels of UGT74S1, UGT74S4 and UGT74S3 proteins were similar but UGT74S4 and UGT74S3 glucosylation activity towards SECO was seven fold less than UGT74S1. In addition, they both failed to produce SDG, suggesting neofunctionalization following their divergence from UGT74S1. We showed that UGT74S1 is closely related to two duplicated genes, UGT74S4 and UGT74S3 which, unlike UGT74S1, failed to glucosylate SMG into SDG. The study suggests that UGT74S1 may be the key player in controlling SECO glucosylation into SDG in flax although its closely related genes may also contribute to a minor extent in supplying

  13. Transient solution of an M/M/1 vacation queue with a waiting server and impatient customers

    Directory of Open Access Journals (Sweden)

    Sherif I. Ammar

    2017-07-01

    Full Text Available Recently, Ammar [1] has discussed the transient behavior of a multiple vacations queue with impatient customers. In this paper, a similar technique is used to derive a new elegant explicit solution for an M/M/1 vacation queue with impatient customers and a waiting server, where the server is allowed to take a vacation whenever the system is empty after waiting for a random period of time. If the server does not return from the vacation before the expiry of the customer impatience time, the customer abandons the system forever. Moreover, the formulas of mean and variance expressed in terms of the obtained possibilities for this model.

  14. Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Eskerod, O

    1995-01-01

    stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p basal and vagally stimulated PGE2 output increased significantly (p ...The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion...... sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p basal and vagally...

  15. Involvement of Striatal Cholinergic Interneurons and M1 and M4 Muscarinic Receptors in Motor Symptoms of Parkinson's Disease.

    Science.gov (United States)

    Ztaou, Samira; Maurice, Nicolas; Camon, Jeremy; Guiraudie-Capraz, Gaëlle; Kerkerian-Le Goff, Lydia; Beurrier, Corinne; Liberge, Martine; Amalric, Marianne

    2016-08-31

    Over the last decade, striatal cholinergic interneurons (ChIs) have reemerged as key actors in the pathophysiology of basal-ganglia-related movement disorders. However, the mechanisms involved are still unclear. In this study, we address the role of ChI activity in the expression of parkinsonian-like motor deficits in a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) lesion model using optogenetic and pharmacological approaches. Dorsal striatal photoinhibition of ChIs in lesioned ChAT(cre/cre) mice expressing halorhodopsin in ChIs reduces akinesia, bradykinesia, and sensorimotor neglect. Muscarinic acetylcholine receptor (mAChR) blockade by scopolamine produces similar anti-parkinsonian effects. To decipher which of the mAChR subtypes provides these beneficial effects, systemic and intrastriatal administration of the selective M1 and M4 mAChR antagonists telenzepine and tropicamide, respectively, were tested in the same model of Parkinson's disease. The two compounds alleviate 6-OHDA lesion-induced motor deficits. Telenzepine produces its beneficial effects by blocking postsynaptic M1 mAChRs expressed on medium spiny neurons (MSNs) at the origin of the indirect striatopallidal and direct striatonigral pathways. The anti-parkinsonian effects of tropicamide were almost completely abolished in mutant lesioned mice that lack M4 mAChRs specifically in dopamine D1-receptor-expressing neurons, suggesting that postsynaptic M4 mAChRs expressed on direct MSNs mediate the antiakinetic action of tropicamide. The present results show that altered cholinergic transmission via M1 and M4 mAChRs of the dorsal striatum plays a pivotal role in the occurrence of motor symptoms in Parkinson's disease. The striatum, where dopaminergic and cholinergic systems interact, is the pivotal structure of basal ganglia involved in pathophysiological changes underlying Parkinson's disease. Here, using optogenetic and pharmacological approaches, we investigated the involvement of striatal

  16. DFT study on oxidation of HS(CH2) m SH ( m = 1-8) in oxidative desulfurization

    Science.gov (United States)

    Song, Y. Z.; Song, J. J.; Zhao, T. T.; Chen, C. Y.; He, M.; Du, J.

    2016-06-01

    Density functional theory was employed for calculation of HS(CH2) m SH ( m = 1-8) and its derivatives at B3LYP method at 6-31++g ( d, p) level. Using eigenvalues of LUMO and HOMO for HS(CH2) m SH, the standard electrode potentials were estimated by a stepwise multiple regression techniques (MLR), and obtained as E° = 1.500 + 7.167 × 10-3 HOMO-0.229 LUMO with high correlation coefficients of 0.973 and F values of 43.973.

  17. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

    2003-01-01

    (EPS) at therapeutically relevant doses. In the present study, we examined whether the xanomeline-induced functional dopamine antagonism found in rodent studies could also be observed in nonhuman primates. In addition, we studied whether the lack of EPS observed in rodents also applies to primates......Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects...

  18. Influence of the projection of BCS functions on the M1 and E2 transitions in rare earths

    International Nuclear Information System (INIS)

    Fellah, M.; Hammann, T.F.

    1975-01-01

    E2 and M1 transition probabilities for odd-mass rare earth nuclei, have been calculated using both the usual BCS wave functions and the strict particle conserving, projected BCS functions. The blocking effect has been exactly and systematically taken into account. The influence of the Coriolis interaction has been studied using the first order perturbation theory. Allowance has been made for the β and γ vibrations. The unphysical effects, due to particle fluctuation in the BCS theory, are not always negligible, but are in most cases, less important than the Coriolis effect [fr

  19. Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia.

    Science.gov (United States)

    Setty, Bhuvana A; Yeager, Nicholas D; Bajwa, Rajinder P

    2011-09-01

    Severe congenital neutropenia is an autosomal recessive disorder characterized by maturation arrest at the promyelocyte/myelocyte phase in the bone marrow, absolute neutrophil count ELA-2 have been described. We report the case of a premature male infant with congenital neutropenia, associated with multiple infections, refractory to treatment with granulocyte colony stimulating factor who subsequently underwent matched sibling donor stem-cell transplant. He was found to be heterozygous for the M1V variant of the ELA-2 gene that we postulate to be causative for his severe neutropenia Copyright © 2011 Wiley-Liss, Inc.

  20. Safety Analysis Report for Packaging (SARP): USA/9507/BLF (ERDA--AL), Model AL-M1

    International Nuclear Information System (INIS)

    Watkins, R.A.; Bertram, R.E.; Blauvelt, R.K.; Edling, D.A.; Flanagan, T.M.; Griffin, J.F.; Rhinehammer, T.B.

    1977-01-01

    The SARP includes structural integrity, thermal resistance, radiation shielding and radiological safety, nuclear criticality safety, and quality control of three insulated drum shipping containers identified as USA/9507/BLF (ERDA-AL), also called AL-M1, configurations 1, 3, and 5. Complete physical and technical descriptions of the packages are presented. Each package consists of an inner container centered within an insulated steel drum. The contents are plutonium-239 and uranium-235 in configurations-1 and -3. The configuration-5 package is intended for shipment of up to 100,000 Ci of tritiated water immobilized on a sorbent such as molecular sieve

  1. Crystallization and preliminary crystallographic study of the yeast Malassezia sympodialis allergen Mala s 1

    International Nuclear Information System (INIS)

    Vilhelmsson, Monica; Hallberg, B. Martin; Rasool, Omid; Zargari, Arezou; Scheynius, Annika; Achour, Adnane

    2006-01-01

    Crystals of the M. sympodialis allergen Mala s 1 have been obtained using the hanging-drop vapour-diffusion method. A diffraction data set has been collected from native crystals to 1.35 Å resolution. The opportunistic yeast Malassezia sympodialis can act as an allergen and elicit specific IgE- and T-cell reactivity in patients with atopic eczema. The first identified major allergen from M. sympodialis, Mala s 1, is present on the cell surface of the yeast. Recombinant Mala s 1 was expressed in Escherichia coli, purified and refolded in a soluble form. Crystals of Mala s 1 were obtained in 25% PEG 8K, 0.2 M (NH 4 ) 2 SO 4 . Crystals belong to space group P2 1 2 1 2, with unit-cell parameters a = 44.4, b = 163.7, c = 50.6 Å, and diffract to 1.35 Å resolution

  2. Crystal growth and magneto-transport behavior of PdS1

    Science.gov (United States)

    Cao, Lin; Lv, Yang-Yang; Chen, Si-Si; Li, Xiao; Zhou, Jian; Yao, Shu-Hua; Chen, Y. B.; Lu, Minghui; Chen, Yan-Feng

    2018-04-01

    PdS is theoretically proposed to novel topological material with eight-band fermions. Here, PdS1-δ crystals were successfully grown from KI as solvent by modified flux method. The single crystalline quality and compositional homogeneity of grown PdS1-δ are characterized by X-ray diffraction and energy dispersion spectroscopy. Temperature dependent electrical transport property of PdS1-δ demonstrates a semiconductor-like behavior. Analysis of temperature-dependent resistance indicates that there is variable-range-hopping behavior at low temperature. The clear negative MR of PdS1-δ single crystals is measured at the low temperature (interaction between conducting carriers and localized moments. however, the magneto-transport results have not shown the clues of topological feature of PdS.

  3. BASE-A space experiment with Rhodospirillum rubrum S1H

    Data.gov (United States)

    National Aeronautics and Space Administration — R. rubrum S1H inoculated on solid minimal media was sent to the ISS in September 2006 (BASE-A experiment). After 10 days flight R. rubrum cultures returned back to...

  4. Preparation of (S)-1-Halo-2-octanols Using Ionic Liquids and Biocatalysts.

    Science.gov (United States)

    Oromí-Farrús, Mireia; Eras, Jordi; Sala, Núria; Torres, Mercè; Canela, Ramon

    2009-10-23

    Preparation of (S)-1-chloro-2-octanol and (S)-1-bromo-2-octanol was carried out by the enzymatic hydrolysis of halohydrin palmitates using biocatalysts. Halohydrin palmitates were prepared by various methods from palmitic acid and 1,2-octanediol. A tandem hydrolysis was carried out using lipases from Candida antarctica (Novozym 435), Rhizomucor miehei (Lipozyme IM), and "resting cells" from a Rhizopus oryzae strain that was not mycotoxigenic. The influence of the enzyme and the reaction medium on the selective hydrolysis of isomeric mixtures of halohydrin esters is described. Novozym 435 allowed preparation of (S)-1-chloro-2-octanol and (S)-1-bromo-2-octanol after 1-3 h of reaction at 40 degrees C in [BMIM][PF(6)].

  5. Study of gamma-ray induced variability on F1M1-F3M3 distant tomato hybrids

    International Nuclear Information System (INIS)

    Siromeatnicov, Iulia; Cotenco, Eugenia; Ciobanu, Renata

    2013-01-01

    The outcome of the evaluation of the gamma radiation's action, the growth and development tomato plant has shown that the coefficient of variation of plant height character is on the rise with increasing doses of gamma radiation. The hybrid combination F 1 M 1 (L.hpriz.1998) irradiated with dose 150 Gy variant presented superior value a towards scrutiny for plant height of the characters, number of flowers and fruits per bunch, number of fruits per plant and fruit mass of. The character F 2 M 2 generation plant height registered diminished value compared to F 1 M 1 generation. The highest value was recorded at the hybrid combination F 2 M 2 L.hpriz.1998 200 Gy treated dose. The evaluation research has highlighted that at the doses 100 Gy, 150 Gy, 200 Gy, have confirmed an increase in characters of reproductive system: the number of flowers and fruits per bunch, number of fruits per plant, fruit mass and reduction of the characters waist and height of placing of the first inflorescences plant. Similar aspects with some differences as low as hybrid combination Lhpi1998 in relation to the radiation doses used under study were confirmed in the case F 3 M 3 . (authors)

  6. A Study on the Occurrence of Aflatoxin M1 in Raw and Pasteurized Milk Produced in Rafsanjan, Iran

    Directory of Open Access Journals (Sweden)

    FaAkrami Mohajeri Akrami Mohajeri

    2015-12-01

    Full Text Available Introduction: Aflatoxins, known as causative factors of hepatic and extra-hepatic carcinogenesis within humans, are extremely teratogenic, mutagenic, toxic, and carcinogenic compounds. Materials & Methods: This study was undertaken to determine the occurrence of aflatoxin M1 (AFM1 in 40 raw milk and 47 pasteurized milk samples collected during spring and winter. In order to analyze the samples, the Enzyme-linked Immunosorbent Assay (ELISA procedure was used. The statistical methods used in this study were based on normal confidence intervals and analysis of variance (ANOVA. Results: Aflatoxin M1 was detected in 97.5% of the raw milk ranging from 6.52 to 68.17 ng/l and 95.7% of the pasteurized milk, ranging from 0.8 to 58.13 ng/l. Toxin levels in 10% of the raw milk and 2.1% of the pasteurized milk samples exceeded the Iranian national standard limit i.e. 50 ng/l.  Due to seasonal variations, mean concentration of AFM1 in the samples collected in winter was significantly (P < 0.03 higher than those collected in the summer. Conclusion: Large amount of AFM1 in milk samples might be a potential hazard for the public health. Reducing the levels of AF