WorldWideScience

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

  1. 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

  2. Experimental Conditions: SE18_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available liver and brain by Orbitrap MS and automated search engine Lipid Search SE18_S1 Mouse liver SE18_S1_M1 34.1...phy. SE18_MS1 Preparation of lipid extract and ESI negative detection by LC-MS analysis SE18_DS1 Identification of phospholipids with Lipid Search default ...

  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

    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 (S1P1–5) 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 S1P1. In contrast, M1-polarized macrophages significantly downregulated S1P4. 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. [Determination of virginiamycin M1 and S1 residues in livestock and poultry products by liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Qiu, Yuanjin; Yang, Fang; Liu, Zhengcai; Lin, Yonghui; Liu, Suzhen

    2012-05-01

    A liquid chromatography-tandem mass spectrometry method was established for the determination of virginiamycin M1 and S1 residues in livestock and poultry products. The sample was extracted by methanol-acetonitrile solution (1:1, v/v). The supernatant was diluted with 0.01 mol/L ammonium dihydrogen phosphate solution, then purified and concentrated on an Oasis HLB cartridge. The separation of virginiamycin M1 and S1 was performed on a Luna C18 column with the mobile phases acetonitrile and 5 mmol/L ammonium acetate aqueous solution (containing 0.1% (v/v) formic acid) in a gradient elution mode. The identification and quantification of the drugs were carried out by positive electrospray ionization (ESI + ) in the multiple reaction monitoring (MRM) mode using external standard method. The calibration curves showed good linearity in the range of 0.15-10.0 microg/L with correlation coefficients (r2) above 0. 999. The limits of quantities (LOQs) were both 0.25 microg/kg. The average recoveries of the two drugs spiked at 0.25, 0.5 and 2.5 microg/kg levels in different matrices were between 71.2% and 98.4%, and the relative standard deviations (RSDs) were between 3.6% and 15.4%. The method is simple, rapid, sensitive and accurate. It is suitable for the confirmation and quantification of virginiamycin M1 and S1 residues in livestock and poultry products.

  5. Determination of virginiamycin M1 and S1 residues in livestock and poultry products by liquid chromatographytandem mass spectrometry%液相色谱-串联质谱法检测畜禽产品中维吉尼亚霉素M1S1残留

    Institute of Scientific and Technical Information of China (English)

    邱元进; 杨方; 刘正才; 林永辉; 刘素珍

    2012-01-01

    A liquid chromatography-tandem mass spectrometry method was established for the determination of virginiamycin Ml and SI residues in livestock and poultry products. The sample was extracted by methanol-acetonitrile solution (1: 1, v/v). The supernatant was diluted with 0. 01 mol/L ammonium dihydrogen phosphate solution, then purified and concentrated on an Oasis HLB cartridge. The separation of virginiamycin Ml and SI was performed on a Luna C18 column with the mobile phases acetonitrile and 5 mmol/L ammonium acetate aqueous solution (containing 0. 1 % (v/v) formic acid) in a gradient elution mode. The identification and quantification of the drugs were carried out by positive electrospray ionization (ESI + ) in the multiple reaction monitoring (MRM) mode using external standard method. The calibration curves showed good linearity in the range of 0. 15 - 10. 0 pug/L with correlation coefficients (r2) above 0. 999. The limits of quantities (LOQs) were both 0. 25μg/kg. The average recoveries of the two drugs spiked at 0. 25, 0. 5 and 2. 5μg/kg levels in different matrices were between 71.2% and 98.4%, and the relative standard deviations (RSDs) were between 3.6% and 15. 4%. The method is simple, rapid, sensitive and accurate. It is suitable for the confirmation and quantification of virginiamycin Ml and SI residues in livestock and poultry products.%建立了畜禽产品中维吉尼亚霉素M1S1药物残留检测的液相色谱-串联质谱分析方法.样品以甲醇-乙腈溶液(1:1,V/v)提取,上清液经0.01 mol/L磷酸二氢铵溶液稀释后,Oasis HLB固相萃取小柱净化,Luna C18色谱柱分离,以乙腈和含0.1%(体积分数)甲酸的5 mmol/L乙酸铵水溶液作为流动相进行梯度洗脱,电喷雾正离子模式电离(ESI+).多反应监测(MRM)模式检测,外标法定量.该方法对两物质线性范围均为0.15~10.O μg/L,相关系数r2均大于0.999;定量下限均为0.25 μg/kg.在不同基质中,0.25、0.50、2.5 μg/kg 3个添加

  6. Complete sequences of IncHI1 plasmids carrying blasub>CTX-M-1sub> 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...

  7. Rapid Determination of Virginiamycin and Residues in Poultry and Swine Tissues Using Liquid Chromatography-Tandem Mass Spectrometry%HPLC-MS/MS快速测定家禽和猪组织中维吉尼亚霉素M1S1残留量

    Institute of Scientific and Technical Information of China (English)

    曹文卿; 林黎明; 张鸿伟; 王凤美; 许辉; 杨桂朋

    2012-01-01

    建立了快速测定动物组织中维吉尼亚霉素M1S1残留量的高效液相色谱-质谱/质谱(HPLC-MS/MS)方法.样品采用乙腈提取,经冷冻脱脂和氯化钠溶液盐析净化,用甲醇-甲酸铵溶液定容,经SDB-C8色谱柱分离后,采用多反应监测(MRM)正离子模式检测.监测离子对分别为M1:m/z 526.3/355.1、526.3/337.2;S1:824.5/290.1、824.5/205.1.其中526.3/355.1和824.5/205.1分别用于M1S1的外标法定量.维吉尼亚霉素M1S1在0.5~10.0 μg·kg-1范围内线性关系良好,回收率为86%~118%,RSD为2.0% ~ 10.1%,检出限和定量下限分别为0.3μg· kg-1和0.5 μg· kg-1.实验结果表明,该方法准确度高、省时、操作简单、成本低、重现性好,结果可靠.

  8. Data of evolutionary structure change: 1PA1A-2PA5B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1PA1A-2PA5B 1PA1 2PA5 A B ----KLEFMEMEKEFEQIDKSG--SWAAIYQDIRHEASD...IFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWPDFGVPESPASFLNFLFKVRESGSLSPE---HGPVVVHDSAGIGRSGTFCLADTCLLLMDKR...HHHH-------------HHHHH - 0 1PA...1 A 1PA1A IDKSG--SWAAI...ne>ILE CA 308 2PA5 B 2PA

  9. Strategies for improved rhamnolipid production by Pseudomonas aeruginosa PA1.

    Science.gov (United States)

    Soares Dos Santos, Alexandre; Pereira, Nei; Freire, Denise M G

    2016-01-01

    Rhamnolipids are biosurfactants with potential for diversified industrial and environmental uses. The present study evaluated three strategies for increasing the production of rhamnolipid-type biosurfactants produced by Pseudomonas aeruginosa strain PA1. The influence of pH, the addition of P. aeruginosa spent culture medium and the use of a fed-batch process were examined. The culture medium adjusted to pH 7.0 was the most productive. Furthermore, the pH of the culture medium had a measurable effect on the ratio of synthesized mono- and dirhamnolipids. At pH values below 7.3, the proportion of monorhamnolipids decreased from 45 to 24%. The recycling of 20% of the spent culture medium in where P. aeruginosa was grown up to the later stationary phase was responsible for a 100% increase in rhamnolipid volumetric productivity in the new culture medium. Finally, the use of fed-batch operation under conditions of limited nitrogen resulted in a 3.8-fold increase in the amount of rhamnolipids produced (2.9 g L(-1)-10.9 g L(-1)). These results offer promising pathways for the optimization of processes for the production of rhamnolipids.

  10. Processing of FENDL-PA/1.1

    Energy Technology Data Exchange (ETDEWEB)

    Mann, F.M.; Lessor, D.E.; Carter, L.L.

    1994-02-01

    The Fusion Evaluated Nuclear Data Library (FENDL) is an evaluated nuclear data library based upon the best evaluations from the world community. The library is maintained by the Nuclear Data Section of the International Atomic Energy Agency (IAEA). However, before the data can be used in computer codes, it must be processed into the appropriate format. The library containing the transmutation (or activation) cross sections that are part of FENDL is designated as FENDL-PA (P designating pointwise). The evaluations in Version 1.1 of this activation library were selected in the following two steps. For the most important reactions ({approximately}250), consultants to the IAEA compared evaluations submitted for consideration with experimental data. These evaluations included those from ENDF/B, JEF, BROND, JENDL, as well as ``complete`` activation libraries, such as EAF and REAC. The consultants then chose the ``best`` evaluation for each of the reactions. The evaluations for the remaining ({approximately}12,000) reactions were taken from EAF-3. The pointwise FENDL-PA/1.1 activation library was processed into two formats. Continuous energy format as used by the Monte Carlo neutron/photon transport code MCNP. ASCII 175 group multigroup format as used by the transmutation code REAC*2/3.

  11. Orion Launch Abort System (LAS) Propulsion on Pad Abort 1 (PA-1)

    Science.gov (United States)

    Jones, Daniel S.

    2015-01-01

    This presentation provides a concise overview of the highly successful Orion Pad Abort 1 (PA-1) flight test, and the three rocket motors that contributed to this success. The primary purpose of the Orion PA-1 flight was to help certify the Orion Launch Abort System (LAS), which can be utilized in the unlikely event of an emergency on the launchpad or during mission vehicle ascent. The PA-1 test was the first fully integrated flight test of the Orion LAS, one of the primary systems within the Orion Multi-Purpose Crew Vehicle (MPCV). The Orion MPCV is part of the architecture within the Space Launch System (SLS), which is being designed to transport astronauts beyond low-Earth orbit for future exploration missions. Had the Orion PA-1 flight abort occurred during launch preparations for a real human spaceflight mission, the PA-1 LAS would have saved the lives of the crew. The PA-1 flight test was largely successful due to the three solid rocket motors of the LAS: the Attitude Control Motor (ACM); the Jettison Motor (JM); and the Abort Motor (AM). All three rocket motors successfully performed their required functions during the Orion PA-1 flight test, flown on May 6, 2010 at the White Sands Missile Range in New Mexico, culminating in a successful demonstration of an abort capability from the launchpad.

  12. The Orion Pad Abort 1 (PA-1) Flight Test: A Propulsion Success

    Science.gov (United States)

    Jones, Daniel S.

    2015-01-01

    This poster provides a concise overview of the highly successful Orion Pad Abort 1 (PA-1) flight test, and the three rocket motors that contributed to this success. The primary purpose of the Orion PA-1 flight was to help certify the Orion Launch Abort System (LAS), which can be utilized in the unlikely event of an emergency on the launchpad or during mission vehicle ascent. The PA-1 test was the first fully integrated flight test of the Orion LAS, one of the primary systems within the Orion Multi-Purpose Crew Vehicle (MPCV). The Orion MPCV is part of the architecture within the Space Launch System (SLS), which is being designed to transport astronauts beyond low-Earth orbit for future exploration missions. Had the Orion PA-1 flight abort occurred during launch preparations for a real human spaceflight mission, the PA-1 LAS would have saved the lives of the crew. The PA-1 flight test was largely successful due to the three solid rocket motors of the LAS: the Attitude Control Motor (ACM); the Jettison Motor (JM); and the Abort Motor (AM). All three rocket motors successfully performed their required functions during the Orion PA-1 flight test, flown on May 6, 2010 at the White Sands Missile Range in New Mexico, culminating in a successful demonstration of an abort capability from the launchpad.

  13. 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.

  14. Pea Albumin 1 Subunit b (PA1b), a Promising Bioinsecticide of Plant Origin.

    OpenAIRE

    Corinne Royer; Vanessa Eyraud; Lamis Karaki; Frédéric Gressent; Pedro Da Silva

    2011-01-01

    International audience; PA1b (Pea Albumin 1, subunit b) is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus), the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications); it can withstand man...

  15. 广谱抗菌肽——片球菌素pediocin PA-1%Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

    Institute of Scientific and Technical Information of China (English)

    吕燕妮

    2011-01-01

    Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industrys. This antimicrobial peptide is the most extensively studied class Ⅱa bacteriocin, and it has been sufficiently well characterized to be used as a food biopreservative. This review focuses on the progress that have been made in the elucidations of its structure and mode of action, includes an overview of its applications in food systems. In the future, protein engineering, genetic engineering and chemical synthesis may lead to the development of new antimicrobial peptides with improved properties, based on some features of the pediocin PA-1 molecule.%片球菌素PA-1是一种广谱的乳酸菌细菌素,它对食品工业中的腐败菌单核细胞增生李斯特氏菌有强烈的抑制作用,是Ⅱa类细菌素中研究最深入的一种抗菌肽,具有很好的作为食品生物防腐剂开发的应用前景。对近年来关于片球菌素PA-1的结构、作用方式及在食品中的应用作一综述,并对其未来的应用前景,在蛋白质工程、基因工程和化学合成方面进行性质改进做出了展望。

  16. Pea Albumin 1 Subunit b (PA1b, a Promising Bioinsecticide of Plant Origin

    Directory of Open Access Journals (Sweden)

    Corinne Royer

    2011-12-01

    Full Text Available PA1b (Pea Albumin 1, subunit b is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus, the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications; it can withstand many steps of extraction and purification without losing its activity; and it is present in a seed regularly consumed by humans and mammals without any known toxicity or allergenicity. The potential of this peptide to limit pest damage has stimulated research concerning its host range, its mechanism of action, its three-dimensional structure, the natural diversity of PA1b and its structure–function relationships.

  17. Pea Albumin 1 subunit b (PA1b), a promising bioinsecticide of plant origin.

    Science.gov (United States)

    Gressent, Frédéric; Da Silva, Pedro; Eyraud, Vanessa; Karaki, Lamis; Royer, Corinne

    2011-12-01

    PA1b (Pea Albumin 1, subunit b) is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus), the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications); it can withstand many steps of extraction and purification without losing its activity; and it is present in a seed regularly consumed by humans and mammals without any known toxicity or allergenicity. The potential of this peptide to limit pest damage has stimulated research concerning its host range, its mechanism of action, its three-dimensional structure, the natural diversity of PA1b and its structure-function relationships.

  18. Data of evolutionary structure change: 1K9PA-1CNPA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1K9PA-1CNPA 1K9P 1CNP A A -ACPLDQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQ...D>1K9P A 1K9PA IGSKL-QDAEI 1CNP A 1CNPA VAL CA 413 -13.432999610900879 15.65699958801269...5 50.41999816894531 rallel> 0.11400000005960464 0.9580000042915344 <

  19. Expression of lactococcin A and pediocin PA-1 in heterologous hosts

    NARCIS (Netherlands)

    Chikindas, M.L.; Venema, K.; Ledeboer, A.M.; Venema, G.; Kok, Jan

    Pediocin PA-1 production, immunity and secretion are specified by a cluster of four genes in Pediococcus acidilactici PAC1.0. The production by, secretion of, and immunity to lactococcin A of Lactococcus lactis are also determined by four genes. Here, expression of the pediocin operon in Lactococcus

  20. Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

    NARCIS (Netherlands)

    Rodriguez, JM; Martinez, MI; Kok, J

    2002-01-01

    Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries. This antimicrobial peptide is the most extensively studied class IIa (or pediocin family)

  1. Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

    NARCIS (Netherlands)

    Rodriguez, JM; Martinez, MI; Kok, J

    2002-01-01

    Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries. This antimicrobial peptide is the most extensively studied class IIa (or pediocin family) ba

  2. Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

    NARCIS (Netherlands)

    Rodriguez, JM; Martinez, MI; Kok, J

    2002-01-01

    Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries. This antimicrobial peptide is the most extensively studied class IIa (or pediocin family) ba

  3. Pediocin PA-1 and a pediocin producing Lactobacillus plantarum strain do not change the HMA rat microbiota

    DEFF Research Database (Denmark)

    Bernbom, Nete; Jelle, N.B.; Brogren, C.-H.

    2009-01-01

    The bacteriocin pediocin PA-1 has potential use as a food biopreservative, and understanding its effect on the commensal gut microbiota is important for assessment of consumer risks associated with the use of biopreservative cultures. Effects of ingested (i) pediocin PA-1 producing Lactobacillus...... in the faeces after ingestion. Pediocin PA-1 did not mediate changes of the rat microbiota, and a biological assay indicated that the bacteriocin was degraded or inactivated during passage through the intestine....

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

    Science.gov (United States)

    Eyraud, Vanessa; Karaki, Lamis; Rahioui, Isabelle; Sivignon, Catherine; Da Silva, Pedro; Rahbé, Yvan; Royer, Corinne; Gressent, Frédéric

    2013-01-01

    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.

  5. 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.

  6. Pseudomonas aeruginosa bacteriophage PA1Ø requires type IV pili for infection and shows broad bactericidal and biofilm removal activities.

    Science.gov (United States)

    Kim, Shukho; Rahman, Marzia; Seol, Sung Yong; Yoon, Sang Sun; Kim, Jungmin

    2012-09-01

    We isolated a new lytic Pseudomonas aeruginosa phage that requires type IV pili for infection. PA1Ø has a broad bactericidal spectrum, covering Gram-positive and Gram-negative bacteria, and can eradicate biofilm cells. PA1Ø may be developed as a therapeutic agent for biofilm-related mixed infections with P. aeruginosa and Staphylococcus aureus.

  7. Chimeras of mature pediocin PA-1 fused to the signal peptide of enterocin P permits the cloning, production, and expression of pediocin PA-1 in Lactococcus lactis.

    Science.gov (United States)

    Martín, María; Gutiérrez, Jorge; Criado, Raquel; Herranz, Carmen; Cintas, Luis M; Hernández, Pablo E

    2007-12-01

    Chimeras of pediocin PA-1 (PedA-1), a bacteriocin produced by Pediococcus acidilactici PLBH9, fused to the signal peptide of enterocin P (EntP), a sec-dependent bacteriocin produced by Enterococcus faecium P13, permitted the production of PedA-1 in Lactococcus lactis. Chimeric genes encoding the EntP signal peptide (SP(entP)) fused to mature PedA-1 (pedA), with or without its immunity gene (pedB), were cloned into the expression vector pMG36c to generate the recombinant plasmids pMPP9 (SP(entP):pedA) and pMPP14i (SP(entP):pedA + pedB). Transformation of competent L. lactis subsp. lactis IL1403, L. lactis subsp. cremoris NZ9000, and L. lactis subsp. lactis DPC5598 with the recombinant plasmids has permitted the detection and quantitation of PedA-1 and the coproduction of nisin A and PedA-1 in supernatants of producer cells with specific anti-PedA-1 antibodies and a noncompetitive indirect enzyme-linked immunosorbent assay. Recombinant L. lactis hosts carrying pMPP9 or pMPP14i displayed antimicrobial activity, suggesting that mature PedA-1 fused to SP(EntP) is the minimum requirement for the synthesis, processing, and secretion of biologically active PedA-1 in L. lactis. However, the production and antimicrobial activity of the PedA-1 produced by L. lactis was lower than that produced by the P. acidilactici control strains.

  8. GSM(m,1)(m=1,2)模型的数值解%Numeriacl Solution of GSM (m, 1)(m= 1,2)Model

    Institute of Scientific and Technical Information of China (English)

    吴强; 刘炳琪

    2001-01-01

    The prediction accuracy can be improved by using the spline function to correct the residue of GM (m,1)(m=1,2). Numerical Solution of GSM (m,1)(m=1,2)Modle is given.%本文用样条函数对GM(m,1)(m=1,2)模型的残差序列进行插值拟合,得到GSM(m,1)(m=1,2)模型的数值解.

  9. 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

    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 isoe

  10. 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

  11. Fusion expression of pedA gone to obtain biologically active pediocin PA-1 in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Shan-na LIU; Ye HAN; Zhi-jiang ZHOU

    2011-01-01

    Two heterologous expression systems using thioredoxin (trxA) as a gene fusion part in Eschenchia coli weredeveloped to produce recombinant pediocin PA-1. Pediocin PA-1 structural gene pedA was isolated from Pediococcusacidi/actici PA003 by the method of polymerase chain reaction (PCR), then cloned into vector pET32a(+), and expressedas thioredoxin-PedA fusion protein in the host strain E. coil BL21 (DE3). The fusion protein was in the form of inclusionbody and was refolded before purification by nickel-iminodiacetic acid (Ni-IDA) agarose resin column. Biological activity ofrecombinant pediocin PA-1 was analyzed after cleavage of the fusion protein by enterokinase. Agar diffusion test re-vealed that 512-arbitrary unit (AU) recombinant pediocin PA-1 was obtained from 1 ml culture medium of E. coli(pPA003PED1) using Listeda monocytogenes as the indicator strain. Thioredoxin-PedA fusion gene was further clonedinto pET20b(+). Thioredoxin-PedA fusion protein was detected in both the periplasmic and cytoplasmic spaces. Therecombinant pediocin PA-1 from the soluble fraction attained 384 AU from 1 ml culture medium of E. coli (pPA003PED2).Therefore, biologically active pediocin PA-1 could be obtained by these two hybrid gene expression methods.

  12. 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.

  13. Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Promotes Murine Hair Growth and Human Dermal Papilla Cell Gene Expression.

    Science.gov (United States)

    Wakame, Koji; Okawa, Hiroshi; Komatsu, Ken-Ich; Nakata, Akifumi; Sato, Keisuke; Ingawa, Hiroyuki; Kohchi, Chie; Nishizawa, Takashi; Soma, Gen-Ichiro

    2016-07-01

    The lipopolysaccharide (LPS)-like compound derived from Pantoea agglomerans (immunopotentiator from Pantoea agglomerans 1 (IP-PA1)) has been used not only as dietary supplement or cosmetic for humans, but also by Japanese veterinarians as an anti-tumor, anti-allergy, "keep a fine coat of fur" and hair growth-promoting functional food for dogs and cats. In the present study, we focused on the hair growth-promoting effects of IP-PA1 on a hair-shaved animal model and its mechanism of action. We also investigated its potential on gene expression after stimulating human dermal papilla cells with IP-PA1. The hair on the back of a C3H/HeN mouse was shaved and IP-PA1 was orally administered or applied to the skin. The status of hair growth was observed and recorded for 14 days. Skin was collected and histological tissue examination was performed with respect to hair growth status using hematoxylin and eosin staining. After IP-PA1 administration (2 and 10 μg/ml) to human dermal papilla cell culture system for 24 h, fibroblast growth factor-7 (FGF-7) and vascular endothelial growth factor (VEGF) mRNA expression were measured using real-time polymerase chain reaction (PCR) analysis. IP-PA1, when given orally, showed a tendency to promote hair growth in mice. In addition, skin application also significantly promoted hair growth, while histopathological examinations further demonstrated hair elongation from dermal papilla cells. In the human dermal papilla cell culture system, significant FGF-7 and VEGF mRNA expressions were observed (p<0.05). An underlying mechanism of gene expression by which IP-PA1 promotes hair growth was suggested to be different from that of medicine and traditional hair tonics, such as minoxidil and adenosine. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Santa Anna L.M.

    2002-01-01

    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.

  15. Pediocin PA-1, a Bacteriocin from Pediococcus acidilactici PAC1.0, Forms Hydrophilic Pores in the Cytoplasmic Membrane of Target Cells

    NARCIS (Netherlands)

    Chikindas, Michael L.; García-Garcerá, Maria J.; Driessen, Arnold J.M.; Ledeboer, Aat M.; Nissen-Meyer, Jon; Nes, Ingolf F.; Abee, Tjakko; Konings, Wilhelmus; Venema, Gerhardus

    1993-01-01

    Pediocin PA-1 is a bacteriocin which is produced by Pediococcus acidilactici PAC1.0. We demonstrate that pediocin PA-1 kills sensitive Pediococcus cells and acts on the cytoplasmic membrane. In contrast to its lack of impact on immune cells, pediocin PA-1 dissipates the transmembrane electrical

  16. Pediocin PA-1, a Bacteriocin from Pediococcus acidilactici PAC1.0, Forms Hydrophilic Pores in the Cytoplasmic Membrane of Target Cells

    NARCIS (Netherlands)

    Chikindas, Michael L.; García-Garcerá, Maria J.; Driessen, Arnold J.M.; Ledeboer, Aat M.; Nissen-Meyer, Jon; Nes, Ingolf F.; Abee, Tjakko; Konings, Wilhelmus; Venema, Gerhardus

    1993-01-01

    Pediocin PA-1 is a bacteriocin which is produced by Pediococcus acidilactici PAC1.0. We demonstrate that pediocin PA-1 kills sensitive Pediococcus cells and acts on the cytoplasmic membrane. In contrast to its lack of impact on immune cells, pediocin PA-1 dissipates the transmembrane electrical pote

  17. Enhanced production of pediocin PA-1 in wild nisin- and non-nisin-producing Lactococcus lactis strains of dairy origin

    NARCIS (Netherlands)

    Reviriego, C.; Fernandez, L.; Kuipers, O. P.; Kok, J.; Rodriguez, J. M.

    In this work, heterologous production of pediocin PA-1 in Lactococcus lactis ESI 153 and ESI 515 (Nis+), two strains selected because of their technological properties for cheesemaking, was achieved after transformation with plasmids pMC117, pRK119 and pCNC1, which contain the complete pediocin

  18. Microcin V Production in Lactobacillus plantarum LB-B1 Using Heterologous Leader Peptide from Pediocin PA-1.

    Science.gov (United States)

    Ma, Xiayin; Wang, Guohong; Li, Dan; Hao, Yanling

    2016-03-01

    Lactobacillus strains producing bacteriocins have attracted highly attention as probiotic cultures in animal nutrition since the use of antibiotics was forbidden in the livestock industry. Lactobacillus plantarum LB-B1 isolated from the fermented dairy product can produce pediocin PA-1, which has a strong inhibition of Listeria but hardly any influence on Gram-negative spoilage agents. In this work, L. plantarum LB-B1 was selected as the host to express microcin V using the leader peptide of pediocin PA-1. Well-diffusion assay combined with Tricine-SDS-polyacrylamide gel showed that microcin V could be successfully expressed and secreted in L. plantarum LB-B1. Meanwhile, the production of microcin V did not affect the secretion of pediocin PA-1. It is worthwhile noted that the supernatant from L. plantarum 8148-ColV had a more effective inhibition of Listeria than that from the control strain L. plantarum 8148. Furthermore, this supernatant also unexpectedly produced antibacterial activity against Staphylococcus aureus. Taken altogether, these results suggested that pediocin PA-1 and microcin V in the supernatant could generate synergistic effect, which not only enhanced the antibacterial ability but also expanded the antibacterial spectrum. Therefore, the recombinant strain has a great potential application as a probiotic to reduce the level of enteric pathogens in livestock industry.

  19. Simple and rapid purification of pediocin PA-1 from Pediococcus pentosaceous NCDC 273 suitable for industrial application.

    Science.gov (United States)

    Vijay Simha, B; Sood, S K; Kumariya, Rashmi; Garsa, Anita Kumari

    2012-10-12

    The use of pediocins as food additives or drugs requires a simple and rapid method by which large quantities of homogeneous pediocin are produced at industrial level. Two centrifugation steps required during initial stages of purification i.e. separation of cells from fermentation broth and collection of precipitates after ammonium sulphate precipitation are the major bottlenecks for their large scale purification. In the present work, pediocin production by a new a dairy strain, Pediococcus pentosaceous NCDC 273 (identical to pediocin PA-1 at nucleotide sequence level), was found to be optimum at initial pH of 6.0 and 7.0 of basal MRS supplemented with 20 g/l of glucose or lactose at 20 and 24 h, respectively. Immobilization of cells through entrapment in alginate-xanthan gum gel beads with chitosan coating resulted in negligible cell release during fermentation. Thus, the cell free extract was directly collected through decantation, avoiding the need of centrifugation step at this stage. Subsequent ammonium sulphate precipitation at isoelectric point of pediocin PA-1 (8.85), using magnetic stirrer at high speed (approx. 1200 rpm), resulted in forceful deposition of precipitates on the wall of precipitation beaker allowing their collection using a spatula, avoiding centrifugation step at this stage also. Further purification using cation-exchange chromatography resulted in yield of 134.4% with more than 320 fold purification with the specific activity of 19×10⁵ AU/mg. The collection of single peak of pediocin at 41.9min in RP-HPLC, overlapping with standard pediocin PA-1, resulted in yield of 1.15 μg from 20 μl of sample applied. The overlapping of RP-HPLC peak and SDS-PAGE band corresponding to 4.6 kDa, confirmed the purity and identity of pediocin 273 as pediocin PA-1.

  20. M$_1$ - M* correlation in galaxy clusters

    CERN Document Server

    Trevese, D; Appodia, B

    1994-01-01

    Photographic F band photometry of a sample of 36 Abell clusters has been used to study the relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M^*. Clusters appear segregated in the M_1-M^* plane according to their Rood \\& Sastry class. We prove on a statistical basis that on average, going from early to late RS classes, M_1 becomes brighter while M^* becomes fainter. The result agrees with the predictions of galactic cannibalism models, never confirmed by previous analyses.

  1. 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

  2. New mode of action for a knottin protein bioinsecticide: pea albumin 1 subunit b (PA1b) is the first peptidic inhibitor of V-ATPase.

    Science.gov (United States)

    Chouabe, Christophe; Eyraud, Vanessa; Da Silva, Pedro; Rahioui, Isabelle; Royer, Corinne; Soulage, Christophe; Bonvallet, Robert; Huss, Markus; Gressent, Frédéric

    2011-10-21

    PA1b (for pea albumin 1 subunit b) is a plant bioinsecticide lethal to several pests that are important in agriculture or human health. PA1b belongs to the inhibitory cystine knot family or knottin family. Originating from a plant (the garden pea) commonly eaten by humans without any known toxic or allergic effects, PA1b is a candidate for transgenic applications and is one of the most promising biopesticides for pest control. Using whole-cell patch-clamp techniques on Sf9 PA1b-sensitive lepidopteran insect cells, we discovered that PA1b reversibly blocked ramp membrane currents in a dose-dependent manner (EC(50) = 0.52 μM). PA1b had the same effect as bafilomycin, a specific inhibitor of the vacuolar proton pump (V-type H(+)-ATPase), and the PA1b-sensitive current depended on the internal proton concentration. Biochemical assays on purified V-ATPase from the lepidopteran model Manduca sexta showed that PA1b inhibited the V(1)V(0)-type H(+)-ATPase holoenzyme activity (IC(50) ∼ 70 nM) by interacting with the membrane-bound V(0) part of the V-ATPase. V-ATPase is a complex protein that has been studied increasingly because of its numerous physiological roles. In the midgut of insects, V-ATPase activity is essential for energizing nutrient absorption, and the results reported in this work explain the entomotoxic properties of PA1b. Targeting V-ATPase is a promising means of combating insect pests, and PA1b represents the first peptidic V-ATPase inhibitor. The search for V-ATPase inhibitors is currently of great importance because it has been demonstrated that V-ATPase plays a role in so many physiological processes.

  3. Characterization of Compass M-1 signals

    NARCIS (Netherlands)

    Hauschild, A.; Montenbruck, O.; Sleewaegen, J.-M.; Huisman, L.; Teunissen, P.J.G.

    2011-01-01

    An analysis of observations from China’s first medium earth orbit satellite Compass M-1 is presented, with main focus on the first orbit and clock solution for this satellite. The orbit is computed from laser ranging measurements. Based on this orbit solution, the apparent clock offset is estimated

  4. Analytic closures for M1 neutrino transport

    Science.gov (United States)

    Murchikova, E. M.; Abdikamalov, E.; Urbatsch, T.

    2017-08-01

    Carefully accounting for neutrino transport is an essential component of many astrophysical studies. Solving the full transport equation is too expensive for most realistic applications, especially those involving multiple spatial dimensions. For such cases, resorting to approximations is often the only viable option for obtaining solutions. One such approximation, which recently became popular, is the M1 method. It utilizes the system of the lowest two moments of the transport equation and closes the system with an ad hoc closure relation. The accuracy of the M1 solution depends on the quality of the closure. Several closures have been proposed in the literature and have been used in various studies. We carry out an extensive study of these closures by comparing the results of M1 calculations with precise Monte Carlo calculations of the radiation field around spherically symmetric protoneutron star models. We find that no closure performs consistently better or worse than others in all cases. The level of accuracy that a given closure yields depends on the matter configuration, neutrino type and neutrino energy. Given this limitation, the maximum entropy closure by Minerbo on average yields relatively accurate results in the broadest set of cases considered in this work.

  5. M1 muscarinic receptor activation mediates cell death in M1-HEK293 cells.

    Science.gov (United States)

    Graham, E Scott; Woo, Kerhan K; Aalderink, Miranda; Fry, Sandie; Greenwood, Jeffrey M; Glass, Michelle; Dragunow, Mike

    2013-01-01

    HEK293 cells have been used extensively to generate stable cell lines to study G protein-coupled receptors, such as muscarinic acetylcholine receptors (mAChRs). The activation of M1 mAChRs in various cell types in vitro has been shown to be protective. To further investigate M1 mAChR-mediated cell survival, we generated stable HEK293 cell-lines expressing the human M1 mAChR. M1 mAChRs were efficiently expressed at the cell surface and efficiently internalised within 1 h by carbachol. Carbachol also induced early signalling cascades similar to previous reports. Thus, ectopically expressed M1 receptors behaved in a similar fashion to the native receptor over short time periods of analysis. However, substantial cell death was observed in HEK293-M1 cells within 24 h after carbachol application. Death was only observed in HEK cells expressing M1 receptors and fully blocked by M1 antagonists. M1 mAChR-stimulation mediated prolonged activation of the MEK-ERK pathway and resulted in prolonged induction of the transcription factor EGR-1 (>24 h). Blockade of ERK signalling with U0126 did not reduce M1 mAChR-mediated cell-death significantly but inhibited the acute induction of EGR-1. We investigated the time-course of cell death using time-lapse microscopy and xCELLigence technology. Both revealed the M1 mAChR cytotoxicity occurs within several hours of M1 activation. The xCELLigence assay also confirmed that the ERK pathway was not involved in cell-death. Interestingly, the MEK blocker did reduce carbachol-mediated cleaved caspase 3 expression in HEK293-M1 cells. The HEK293 cell line is a widely used pharmacological tool for studying G-protein coupled receptors, including mAChRs. Our results highlight the importance of investigating the longer term fate of these cells in short term signalling studies. Identifying how and why activation of the M1 mAChR signals apoptosis in these cells may lead to a better understanding of how mAChRs regulate cell-fate decisions.

  6. "m=1" coatings for neutron guides

    OpenAIRE

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt; Kapaklis, V.; Wilkens, H.; Rats, D.; Hjörvarsson, B.; Kirstein, O.; Bentley, Philip

    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 therm...

  7. Cloning, expression, and nucleotide sequence of genes involved in production of pediocin PA-1, and bacteriocin from Pediococcus acidilactici PAC1.0.

    Science.gov (United States)

    Marugg, J D; Gonzalez, C F; Kunka, B S; Ledeboer, A M; Pucci, M J; Toonen, M Y; Walker, S A; Zoetmulder, L C; Vandenbergh, P A

    1992-01-01

    The production of pediocin PA-1, a small heat-stable bacteriocin, is associated with the presence of the 9.4-kbp plasmid pSRQ11 in Pediococcus acidilactici PAC1.0. It was shown by subcloning of pSRQ11 in Escherichia coli cloning vectors that pediocin PA-1 is produced and, most probably, secreted by E. coli cells. Deletion analysis showed that a 5.6-kbp SalI-EcoRI fragment derived from pSRQ11 is required for pediocin PA-1 production. Nucleotide sequence analysis of this 5.6-kbp fragment indicated the presence of four clustered open reading frames (pedA, pedB, pedC, and pedD). The pedA gene encodes a 62-amino-acid precursor of pediocin PA-1, as the predicted amino acid residues 19 to 62 correspond entirely to the amino acid sequence of the purified pediocin PA-1. Introduction of a mutation in pedA resulted in a complete loss of pediocin production. The pedB and pedC genes, encoding proteins of 112 and 174 amino acid residues, respectively, are located directly downstream of the pediocin structural gene. Functions could not be assigned to their gene products; mutation analysis showed that the PedB protein is not involved in pediocin PA-1 production. The mutation analysis further revealed that the fourth gene, pedD, specifying a relatively large protein of 724 amino acids, is required for pediocin PA-1 production in E. coli. The predicted pedD protein shows strong similarities to several ATP-dependent transport proteins, including the E. coli hemolysin secretion protein HlyB and the ComA protein, which is required for competence induction for genetic transformation in Streptococcus pneumoniae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1514784

  8. "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......V. Materials like diamond and Be have higher neutron scattering density than Ni, have smaller absorption cross section and when a neutron is absorbed they emit much less gamma ray and at lower energies. We present results, both theoretically and experimentally, comparing Ni with Be and preliminary results...

  9. Simultaneous bioremediation and biodetection of mercury ion through surface display of carboxylesterase E2 from Pseudomonas aeruginosa PA1.

    Science.gov (United States)

    Yin, Kun; Lv, Min; Wang, Qiaoning; Wu, Yixuan; Liao, Chunyang; Zhang, Weiwei; Chen, Lingxin

    2016-10-15

    Mercury is a toxic heavy metal and presents significant threats to organisms and natural ecosystems. Recently, the mercury remediation as well as its detection by environmental-friendly biotechnology has received increasing attention. In this study, carboxylesterase E2 from mercury-resistant strain Pseudomonas aeruginosa PA1 has been successfully displayed on the outer membrane of Escherichia coli Top10 bacteria to simultaneously adsorb and detect mercury ion (Hg(2+)). The transmission electron microscopy analysis shows that Hg(2+) can be absorbed by carboxylesterase E2 and accumulated on the outer membrane of surface-displayed E. coli bacteria. The adsorption of Hg(2+) followed a physicochemical, equilibrated and saturatable mechanism, which well fits the traditional Langmuir adsorption model. The surface-displayed system can be regenerated through regulating pH values. As its activity can be inhibited by Hg(2+), carboxylesterase E2 has been used to detect the concentration of Hg(2+) in water samples. The developed surface display system will be of great potential in the simultaneous bioremediation and biodetection of environmental mercury pollution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The interaction of the bioinsecticide PA1b (Pea Albumin 1 subunit b) with the insect V-ATPase triggers apoptosis.

    Science.gov (United States)

    Eyraud, Vanessa; Balmand, Séverine; Karaki, Lamis; Rahioui, Isabelle; Sivignon, Catherine; Delmas, Agnès F; Royer, Corinne; Rahbé, Yvan; Da Silva, Pedro; Gressent, Frédéric

    2017-07-07

    PA1b (Pea Albumin 1, subunit b) peptide is an entomotoxin, extracted from Legume seeds, with a lethal activity towards several insect pests, such as mosquitoes, some aphids and cereal weevils. This toxin acts by binding to the subunits c and e of the plasma membrane H(+)-ATPase (V-ATPase) in the insect midgut. In this study, two cereal weevils, the sensitive Sitophilus oryzae strain WAA42, the resistance Sitophilus oryzae strain ISOR3 and the insensitive red flour beetle Tribolium castaneum, were used in biochemical and histological experiments to demonstrate that a PA1b/V-ATPase interaction triggers the apoptosis mechanism, resulting in insect death. Upon intoxication with PA1b, apoptotic bodies are formed in the cells of the insect midgut. In addition, caspase-3 enzyme activity occurs in the midgut of sensitive weevils after intoxication with active PA1b, but not in the midgut of resistant weevils. These biochemical data were confirmed by immuno-histochemical detection of the caspase-3 active form in the midgut of sensitive weevils. Immuno-labelling experiments also revealed that the caspase-3 active form and V-ATPase are close-localized in the insect midgut. The results concerning this unique peptidic V-ATPase inhibitor pave the way for the utilization of PA1b as a promising, more selective and eco-friendly insecticide.

  11. Cancer risks posed by aflatoxin M1.

    Science.gov (United States)

    Hsieh, D P; Cullen, J M; Hsieh, L S; Shao, Y; Ruebner, B H

    1985-01-01

    The suspect milk-borne carcinogen, aflatoxin M1 (AFM), was produced and isolated from the rice culture of the fungus Aspergillus flavus NRRL3251 for confirmation and determination of the potency of its carcinogenicity in the male adult Fischer rat. The carcinogen was mixed into an agar-based, semisynthetic diet at 0, 0.5, 5, and 50 ppb (microgram/kg) and was fed to groups of animals continuously for 19-21 months. Aflatoxin B1 (AFB), of which AFM is a metabolite, at 50 ppb was used as a positive control. Hepatocarcinogenicity of AFM was detected at 50 ppb, but not at 5 or 0.5 ppb, with a potency of 2-10% that of AFB. A low incidence of intestinal adenocarcinomas was found in the AFM 50 ppb group, but not in any other groups. At 0.5 ppb, the action level enforced by the U.S.A. Food and Drug Administration, AFM induced no liver lesions in the rats but stimulated the animals' growth. On the average, the rats in the 0.5 ppb group weighed 11% (p less than 0.001) more than those in the control group. This increased growth was associated with increased feed intake. Based on the biological activity of AFM at the relevant low doses and the estimated level of human exposure to AFM through consumption of milk, the cancer risk posed by this contaminant for human adults is assessed to be very low. For infants, further studies are warranted because milk constitutes the major ingredient of the infant diet and because infant animals have been shown to be more sensitive to the carcinogenicity of AFB than adult animals.

  12. Helicobacter pylori vacA s1a and s1b alleles from clinical isolates from different regions of Chile show a distinct geographic distribution

    Institute of Scientific and Technical Information of China (English)

    MI Díaz; A Kirberg; E Hebel; J Fierro; R Bravo; F Siegel; G Leon; G Klapp; A Venegas; A Valdivia; P Martínez; JL Palacios; P Harris; J Novales; E Garrido; D Valderrama; C Shilling

    2005-01-01

    AIM: To establish the most common vacA alleles in Helicobacter pylori(H pylori) strains isolated from Chilean patients and its relationship with gastritis and gastroduodenal ulcers.METHODS: Two hundred and forty five H pylori clinical isolates were obtained from 79 biopsies from Chilean infected patients suffering from gastrointestinal diseases. An average of 2-3 strains per patient was isolated and the vacA genotype was analyzed by PCR and 3% agarose electrophoresis. Some genotypes were checked by DNA sequencing.RESULTS: The most prevalent vacA genotype inChilean patients was s1b m1 (76%), followed by s1a m1 (21%). In contrast, the s2 m2 genotype was scarcely represented (3%).The s1b m1 genotype was found most frequently linked to gastropathies (P<0.05) rather than ulcers. Ulcers were found more commonly in male and older patients. Curiously, patients living in cities located North and far South of Santiago, the capital and largest Chilean city, carried almost exclusively strains with the s1b m1 genotype. In contrast, patients from Santiago and cities located South of Santiago carried strains with either one or both s1a m1 and s1b m1 genotypes.Regarding the s2 m2 genotype, comparison with GenBank sequences revealed that Chilean s2 sequence was identical to those of Australian, American, and Colombian strains but quite different from those of Alaska and India.CONCLUSION: Differences in geographic distribution of the s and m vaccA alleles in Chile and a relationship of s1b m1 genotype with gastritis were found. Sequence data in part support a hispanic origin for the vacA genotype.Asymmetric distribution of genotypes s1b m1 and s2 m2recedes H Pyloristrain distribution in Spain and Portugal.

  13. Heterologous Processing and Export of the Bacteriocins Pediocin PA-1 and Lactococcin A in Lactococcus Lactis : A Study with Leader Exchange

    NARCIS (Netherlands)

    Chikindas, M.; Emond, E.; Haandrikman, A.J.; Kok, J.; Leenhouts, K.; Pandian, S.; Venema, Gerhardus; Venema, K.

    2010-01-01

    The bacteriocins pediocin PA-1 and lactococcin A are synthesized as precursors carrying N-terminal extensions with a conserved cleavage site preceded by two glycine residues in positions -2 and -1. Each bacteriocin is translocated through the cytoplasmic membrane by an integral membrane protein of

  14. The conformational flexibility of the antibiotic virginiamycin M(1).

    Science.gov (United States)

    Dang, Jason; Metzger, Robert P; Brownlee, Robert T C; Ng, Chai Ann; Bergdahl, Mikael; Separovic, Frances

    2005-07-01

    The antibiotic virginiamycin is a combination of two molecules, virginiamycin M(1) (VM1) and virginiamycin S(1) (VS1) or analogues, which function synergistically by binding to bacterial ribosomes and inhibiting bacterial protein synthesis. Both VM1 and VS1 dissolve poorly in water and are soluble in more hydrophobic solvents. We have recently reported that the 3D conformation of VM1 in CDCl(3) solution differs markedly from the conformation bound to a VM1 binding enzyme and to 50S ribosomes as found by X-ray crystallographic studies. We now report the results of further NMR studies and subsequent molecular modeling of VM1 dissolved in CD(3)CN/H(2)O and compare the structure with that in CD(3)OD and CDCl(3). The conformations of VM1 in CD(3)CN/H(2)O, CD(3)OD and CDCl(3) differ substantially from one another and from the bound form, with the aqueous form most like the bound structure. We propose that the flexibility of the VM1 molecule in response to environmental conditions contributes to its effectiveness as an antibiotic.

  15. On the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, complex orthogonal design

    CERN Document Server

    Li, Yuan

    2011-01-01

    Complex orthogonal designs (CODs) are used to construct space-time block codes. COD $\\mathcal{O}_z$ with parameter $[p, n, k]$ is a $p\\times n$ matrix, where nonzero entries are filled by $\\pm z_i$ or $\\pm z^*_i$, $i = 1, 2,..., k$, such that $\\mathcal{O}^H_z \\mathcal{O}_z = (|z_1|^2+|z_2|^2+...+|z_k|^2)I_{n \\times n}$. Adams et al. in "The final case of the decoding delay problem for maximum rate complex orthogonal designs," IEEE Trans. Inf. Theory, vol. 56, no. 1, pp. 103-122, Jan. 2010, first proved the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, COD. Combining with the previous result that decoding delay should be an integer multiple of $\\binom{2m}{m-1}$, they solved the final case $n \\equiv 2 \\pmod 4$ of the decoding delay problem for maximum rate complex orthogonal designs. In this paper, we give another proof of the nonexistence of COD with parameter $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd. Our new proof is based on the uniqueness of $[\\binom{2m}{m-1}, 2m-1, \\binom{...

  16. E1M1 and E1E2 transition probabilities in one-electron ions

    Energy Technology Data Exchange (ETDEWEB)

    Labzowsky, L.N. [Institute of Physics, St. Petersburg State University, Uljanovskaya 1, Petrodvorets, 198904 St. Petersburg (Russian Federation) and Petersburg Nuclear Physics Institute, Gatchina, 188350 St. Petersburg (Russian Federation)]. E-mail: leonti@landau.phys.spbu.ru; Shonin, A.V. [Institute of Physics, St. Petersburg State University, Uljanovskaya 1, Petrodvorets, 198904 St. Petersburg (Russian Federation)

    2004-12-06

    The quantum electrodynamical (QED) theory of the two-photon transitions in hydrogenlike ions is presented. The emission probability for 2s1/2->2{gamma}(E1)+1s1/2 transitions is calculated and compared to the results of the previous calculations. The emission probabilities 2p1/2->{gamma}(E1)+{gamma}(E2)+1s1/2 and 2p1/2->{gamma}(E1)+{gamma}(M1)+1s1/2 are also calculated for the nuclear charge Z values 1=

  17. The conformation of acetylated virginiamycin M1 and virginiamycin M1 in explicit solvents.

    Science.gov (United States)

    Ng, Chai Ann; Zhao, Wen; Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2007-05-01

    The three-dimensional structure of acetylated virginiamycin M(1) (acetylated VM1) in chloroform and in a water/acetonitrile mixture (83:17 v/v) have been established through 2D high resolution NMR experiments and molecular dynamics modeling and the results compared with the conformation of the antibiotic VM1 in the same and other solvents. The results indicated that acetylation of the C-14 OH group of VM1 caused it to rotate about 90 degrees from the position it assumed in non-acetylated VM1. The conformation of both VM1 and acetylated VM1 appear to flatten in moving from a nonpolar to polar solvent. However, the acetylated form has a more hydrophobic nature. The acetylated VM1 in chloroform and in water/acetonitrile solution had a similar configuration to that of VM1 bound to 50S ribosomes and to the Vat(D) active sites as previously determined by X-ray crystallography. Docking studies of VM1 to the 50S ribosomal binding site and the Vat(D) gave conformations very similar to those derived from X-ray crystallographic studies. The docking studies with acetylated VM1 suggested the possibility of a hydrogen bond from the acetyl carbonyl group oxygen of acetylated VM1 to the 2' hydroxyl group of ribose of adenosine 2538 at the ribosomal VM1 binding site. No hydrogen bonds between acetylated VM1 and the Vat(D) active sites were found; the loss of this binding interaction partly accounts for the release of the product from the active site.

  18. Aflatoxin M1 in raw milk and binding of aflatoxin by lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Aflatoxin M1 in raw milk and binding of aflatoxin by lactic acid bacteria

    2010-12-01

    Full Text Available Aflatoxin M1 (AFM1 is potential human carcinogen. Its presence in milk and dairy products represents risk for human health. Therefore, this study was carried out in order to determine thedegree of microbiological contamination by mold, and the potential presence of aflatoxin M1 in 60 raw milk samples, randomly taken from individual producers from different regions of the continental Croatia. The most common genera isolated fungi were Geotrichum (78.3 %, Aspergillus (32.4 % and Penicillium (27.0 %. From total of 60 studied milk samples, 86.66 % were positive for the presence of aflatoxin M1, and 6.66 % of samples were above the prescribed limits. Lactic acid bacteria used in fermented dairy products as a starter culture may play a role in reduction of aflatoxin in foods and nutrients. In this paper the ability of lactic acid bacteria: Lactobacillus rhamnosus GG (ATCC 53103, Lactobacillus delbrueckii S1 and Lactobacillus plantarum A1 to bind aflatoxin M1 was investigated. Standard strain L. rhamnosus GG (ATCC 53103 and L. delbrueckii S1 can significantly (P50 % compared to L. plantarum A1, which binds AFM1 between 18.7 to 28.7 %.

  19. Qualification Lab Testing on M1 Abrams Engine Oil Filters

    Science.gov (United States)

    2016-11-01

    UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K. Rutta U.S...the originator. UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K...TITLE AND SUBTITLE Qualification Lab Testing on M1 Abrams Engine Oil Filter 5a. CONTRACT NUMBER W56HZV-15-C-0030 5b. GRANT NUMBER 5c. PROGRAM

  20. Develop Efficient Leak Proof M1 Abrams Plenum Seal

    Science.gov (United States)

    2014-05-07

    UNCLASSIFIED UNCLASSIFIED ER-GLSV11389-001.docx Develop Efficient Leak Proof M1 Abrams Plenum Seal SBIR Phase I: Topic A13-061...Leak Proof M1 Abrams Plenum Seal Christian Muehfeld Steve Pennala Great Lakes Sound & Vibration, Inc. 47140 North Main Street Houghton, MI 49931 ER...061. The purpose of this report is to show the feasibility of developing an efficient, leak proof plenum seal for the M1 Abrams . It also shows the

  1. Main: S1FSORPL21 [PLACE

    Lifescience Database Archive (English)

    Full Text Available S1FSORPL21 S000215 19-August-2004 (last modified) kehi S1F binding site (S1 site) i...in downregulating RPL21 promoter activity (Lagrange et al., 1993); See S000211 (SITE1SORPS1), S000166 (S2FSOR

  2. Genomic Characterization of Campylobacter jejuni strain M1

    DEFF Research Database (Denmark)

    Friis, Carsten; Wassenaar, Gertrude Maria; Javed, Muhammad A.

    2010-01-01

    publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core...

  3. FoxM1 Regulates Mammary Luminal Cell Fate

    Directory of Open Access Journals (Sweden)

    Janai R. Carr

    2012-06-01

    Full Text Available Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.

  4. On (2m + 1)-variable symmetric Boolean functions with submaximum algebraic immunity 2m-1

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    All (2m +1)-variable symmetric Boolean functions with submaximal algebraic immunity 2m-1 are described and constructed. The total number of such Boolean functions is 32 ·22m-3 +3m-2 · 24 - 2 for m≥2.

  5. Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs.

    Science.gov (United States)

    Rook, Jerri M; Abe, Masahito; Cho, Hyekyung P; Nance, Kellie D; Luscombe, Vincent B; Adams, Jeffrey J; Dickerson, Jonathan W; Remke, Daniel H; Garcia-Barrantes, Pedro M; Engers, Darren W; Engers, Julie L; Chang, Sichen; Foster, Jarrett J; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Conn, P Jeffrey; Lindsley, Craig W

    2017-01-10

    Both historical clinical and recent preclinical data suggest that the M1 muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M1 activation. Efforts then shifted to focus on selective activation of M1 via either allosteric agonists or positive allosteric modulators (PAMs). While M1 PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M1 ago-PAMs. Our data demonstrate that closely related M1 PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M1 PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M1 responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M1 PAMs.

  6. Broad analgesic activity of a novel, selective M1 agonist.

    Science.gov (United States)

    Wood, Michael W; Martino, Giovanni; Coupal, Martin; Lindberg, Mattias; Schroeder, Patricia; Santhakumar, Vijayaratnam; Valiquette, Manon; Sandin, Johan; Widzowski, Daniel; Laird, Jennifer

    2017-09-01

    Although the muscarinic receptor family has long been a source of potentially compelling targets for small molecule drug discovery, it was difficult to achieve agonist selectivity within the family. A new class of M1 muscarinic agonists has emerged, and these compounds have been characterized as agonists that activate the receptor at an allosteric site. Members of this class of M1 agonists have been shown to be selective across the muscarinic receptors. However, upon introduction of a novel pharmacologic mechanism, it is prudent to ensure that no new off-target activities have arisen, particularly within the context of in vivo experiments. Reported here, is the in vitro and in vivo characterization of a novel M1 agonist tool compound, PPBI, and demonstrations that the primary biological effects of PPBI are mediated through M1. PPBI reverses d-amphetamine locomotor activity, but fails to do so in transgenic mice that do not express M1. PPBI also reverses a natural deficit in a rat cognition model at a level of exposure which also activates cortical circuitry. Most notably, PPBI is analgesic in a variety of rat and mouse models and the analgesic effect of PPBI is reversed by an M1-preferring antagonist and an M1-selective toxin. Finally, the pharmacokinetic/pharmacodynamic measures of PPBI are compared across multiple endpoints which highlights that activity in models of psychosis and pain require higher exposures than that required in the cognition model. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. 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...

  8. Selectivity of oxomemazine for the M1 muscarinic receptors.

    Science.gov (United States)

    Lee, S W; Woo, C W; Kim, J G

    1994-12-01

    The binding characteristics of pirenzepine and oxomemazine to muscarinic receptor were studied to evaluate the selectivity of oxomemazine for the muscarinic receptor subtypes in rat cerebral microsomes. Equilibrium dissociation constant (KD) of (-)-[3H]quinuclidinyl benzilate([3H]QNB) determined from saturation isotherms was 64 pM. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki = 16 nM, M1 receptor) and low (Ki = 400 nM, M3 receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with about 20-fold difference in the affinity for high (Ki = 84 nM, OH receptor) and low (Ki = 1.65 microM, OL receptor) affinity sites. The percentage populations of M1 and M3 receptors to the total receptors were 61:39, and those of OH and OL receptors 39:61, respectively. Both pirenzepine and oxomemazine increased the KD value for [3H]QNB without affecting the binding site concentrations and Hill coefficient for the [3H]QNB binding. Oxomemazine had a 10-fold higher affinity at M1 receptors than at M3 receptors, and pirenzepine a 8-fold higher affinity at OH receptors than at OL receptors. Analysis of the shallow competition binding curves of oxomemazine for M1 receptors and pirenzepine for OL receptors yielded that 69% of M1 receptors were of OH receptors and the remaining 31% of OL receptors, and that 29% of OL receptors were of M1 receptors and 71% of M3 receptors. However, M3 for oxomemazine and OH for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could be classified as a selective drug for M1 receptors and also demonstrate that rat cerebral microsomes contain three different subtypes of M1, M3 and the other site which is different from M1, M2 and M3 receptors.

  9. M1.3--a small scaffold for DNA origami .

    Science.gov (United States)

    Said, Hassan; Schüller, Verena J; Eber, Fabian J; Wege, Christina; Liedl, Tim; Richert, Clemens

    2013-01-07

    The DNA origami method produces programmable nanoscale objects that form when one long scaffold strand hybridizes to numerous oligonucleotide staple strands. One scaffold strand is dominating the field: M13mp18, a bacteriophage-derived vector 7249 nucleotides in length. The full-length M13 is typically folded by using over 200 staple oligonucleotides. Here we report the convenient preparation of a 704 nt fragment dubbed "M1.3" as a linear or cyclic scaffold and the assembly of small origami structures with just 15-24 staple strands. A typical M1.3 origami is large enough to be visualized by TEM, but small enough to show a cooperativity in its assembly and thermal denaturation that is reminiscent of oligonucleotide duplexes. Due to its medium size, M1.3 origami with globally modified staples is affordable. As a proof of principle, two origami structures with globally 5'-capped staples were prepared and were shown to give higher UV-melting points than the corresponding assembly with unmodified DNA. M1.3 has the size of a gene, not a genome, and may function as a model for gene-based nanostructures. Small origami with M1.3 as a scaffold may serve as a workbench for chemical, physical, and biological experiments.

  10. Surface properties of new virginiamycin M(1) derivatives.

    Science.gov (United States)

    Nott, Katherine; Paquot, Michel; Dufour, Samuel; Eeman, Marc; Deleu, Magali

    2009-03-01

    Three kinds of derivatives of the M(1) factor of virginiamycin have been synthesised: esters with long chain fatty acids, oximes with modified polar amino acids and bis-derivatives with both the ester and oxime function. The study of the surface tension time dependence of M(1) and its derivatives has shown that it is necessary to enhance simultaneously the hydrophobicity and the hydrophilicity of M(1) to render M(1) surface-active. A structure/function relationship study of the surface-active bis-derivatives has shown that enhancing the hydrophobicity of the molecule led to slower adsorption kinetics, higher stability of the monolayers formed and a better capacity to penetrate a membrane model. The repulsive electrostatic forces due to the presence of charges on the amino acids linked to M(1) lead to higher surface tensions, a greater molecular area at the interface and lower penetration into a membrane model. This study has demonstrated that modifying systematically the hydrophobicity and hydrophilicity of a non surface-active molecule allows the production of surface-active derivatives.

  11. Genomic characterization of Campylobacter jejuni strain M1.

    Directory of Open Access Journals (Sweden)

    Carsten Friis

    Full Text Available Campylobacter jejuni strain M1 (laboratory designation 99/308 is a rarely documented case of direct transmission of C. jejuni from chicken to a person, resulting in enteritis. We have sequenced the genome of C. jejuni strain M1, and compared this to 12 other C. jejuni sequenced genomes currently publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core genome comprised 1,295 gene families, or about two-thirds of the gene content of the average of the sequenced C. jejuni genomes. Various comparison and visualization tools were applied to the 13 C. jejuni genome sequences, including a species pan- and core genome plot, a BLAST Matrix and a BLAST Atlas. Trees based on 16S rRNA sequences and on the total gene families in each genome are presented. The findings are discussed in the background of the proven virulence potential of M1.

  12. 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.

  13. PA1b, a plant peptide, induces intracellular [Ca2+] in- crease via Ca2+ influx through the L-type Ca2+ channel and triggers secretion in pancreatic β cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitutes the cystine-knot structure. Using microfluorometry and patch clamp techniques, we found that PA1b significantly elevated the intracellular calcium level ([Ca2+ ]i) and elicited membrane capacitance increase in the primary rat pancreatic β cells. The PA1b effect on [Ca2+]i elevation was abolished in the absence of extracellular Ca2+ or in the presence of L-type Ca2+ channel blocker, ni- modipine. Interestingly, we found that PA1b significantly depolarized membrane potential, which could lead to the opening of voltage-dependent L-type Ca2+ channels and influx of extracellular Ca2+, and then evoke robust secretion. In this study we identified the plant peptide PA1b which is capable of affecting the excitability and function of mammalian pancreatic β cell.

  14. PA1b, a plant peptide, induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel and triggers secretion in pancreatic β cells

    Institute of Scientific and Technical Information of China (English)

    HU ZhiTao; DUN XinPeng; ZHANG Ming; ZHU HongLiang; XIE Li; WU ZhengXing; CHEN ZhengWang; XU Tao

    2007-01-01

    Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitutes the cystine-knot structure. Using microfluorometry and patch clamp techniques, we found that PA1b significantly elevated the intracellular calcium level ([Ca2+]i) and elicited membrane capacitance increase in the primary rat pancreatic β cells. The PA1b effect on [Ca2+]i elevation was abolished in the absence of extracellular Ca2+ or in the presence of L-type Ca2+ channel blocker, nimodipine. Interestingly, we found that PA1b significantly depolarized membrane potential, which could lead to the opening of voltage-dependent L-type Ca2+ channels and influx of extracellular Ca2+, and then evoke robust secretion. In this study we identified the plant peptide PA1b which is capable of affecting the excitability and function of mammalian pancreatic β cell.

  15. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  16. Theory of the M = 1 Kink Mode in Toroidal Plasma

    NARCIS (Netherlands)

    de Blank, H. J.; Schep, T. J.

    1991-01-01

    The energy principle of ideal magnetohydrodynamics (MHD) is used to study the ideal MHD stability of the m = 1 internal kink mode in a toroidal plasma. The equilibrium configurations that are considered allow for a broad region where the safety factor q is close to unity. This region may extend to t

  17. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  18. Characterization of leucocin B-KM432Bz from Leuconostoc pseudomesenteroides isolated from boza, and comparison of its efficiency to pediocin PA-1.

    Directory of Open Access Journals (Sweden)

    Kahina Maya Makhloufi

    Full Text Available A bacteriocin-producing bacterium was isolated from boza and identified as Leuconostoc pseudomesenteroides KM432Bz. The antimicrobial peptide was purified and shown to be identical to other class IIa bacteriocins: leucocin A from Leuconostoc gelidum UAL-187 and Leuconostoc pseudomesenteroides QU15 and leucocin B from Leuconostoc carnosum Ta11a. The bacteriocin was named leucocin B-KM432Bz. Leucocin B-KM432Bz gene cluster encodes the bacteriocin precursor (lcnB, the immunity protein (lcnI and the dedicated export machinery (lcnD and lcnE. A gene of unknown and non-essential function (lcnC, which is interrupted by an insertion sequence of the IS30 family, is localized between lcnB and lcnD. The activity of leucocin B-KM432Bz requires subunit C of the EII(t Man mannose permease, which is the receptor for entry into target cells. The determination of the minimum inhibitory concentrations revealed the lowest values for leucocin B-KM432Bz over Listeria strains, with 4 to 32 fold better efficiency than pediocin PA-1.

  19. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Hoblit, S. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.]|[Univ. of Virginia, Charlottesville, VA (United States). Dept. of Physics; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-10-01

    New high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. The E2/M1 mixing ratio for the n {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  20. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Sandorfi, A.M. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-08-01

    The properties of the transition from the nucleon to the {Delta}(1232) serve as a benchmark for models of nucleon structure. To first order, N {r_arrow} {Delta} photo-excitation is dominated by a simple M1 quark spin-flip transition. At higher order, small L = 2 components in the N and {Delta} wavefunctions allow this excitation to proceed via an electric quadrupole transition. Since Nucleon models differ greatly on the mechanisms used to generate these L = 2 components,, the ratio of E2/M1 transitions (EMR) provides a sensitive test for structure models. Here, new high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. Compton scattering has provided two important new constraints on the photo-pion amplitude. The E2/M1 mixing ratio for the N {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  1. Effect of the radial plasma nonuniformity on the propagation of guided m = + 1 and m = - 1 modes in helicon discharges

    Science.gov (United States)

    Aliev, Yu. M.; Krämer, M.

    2016-10-01

    Theoretical as well as numerical analyses of the full set of Maxwell's equations is carried out to study non-axisymmetric ( m ≠ 0 ) guided modes in radially nonuniform helicon (HE) discharges. Unlike the axisymmetric (m = 0) modes, these modes reveal a non-reciprocal behavior with respect to the azimuthal direction. We develop the conditions for propagation and non-propagation of the various modes in the helicon parameter range, thereby focussing on the important role of the radial density gradient. Three types of modes occurring in different parameter ranges are described, i.e., the helicon (HE) mode, the electrostatic (ES) or Trivelpiece-Gould mode, and the locally coupled (LC) mode that is characterized by mode coupling (MC) in a certain region of the plasma density profile. In contrast to m = + 1 modes, the parameter range of m = - 1 modes is much more restricted as rather high densities are needed for the propagation of the helicon and LC modes. An important issue of the investigations is the rf power coupling and absorption via the various modes. Computations based on a simple antenna-plasma model show that the axial wavenumber of the antenna determines decisively which type of mode is excited. In case of LC mode excitation, the dominant role of the MC layer for the absorption is demonstrated. Finally, the rf power coupling to helicon modes is studied. The density limit for m = - 1 helicon mode propagation and the narrow magnetic field profiles of these modes are the main reasons why the rf power absorption in helicon discharges occurs via m = + 1 helicon modes.

  2. Identification of benzoxazole analogs as novel, S1P(3) sparing S1P(1) agonists.

    Science.gov (United States)

    Deng, Guanghui; Meng, Qinghua; Liu, Qian; Xu, Xuesong; Xu, Qiongfeng; Ren, Feng; Guo, Taylor B; Lu, Hongtao; Xiang, Jia-Ning; Elliott, John D; Lin, Xichen

    2012-06-15

    A novel series of benzoxazole-derived S1P(1) agonists were designed based on scaffold hopping molecular design strategy combined with computational approaches. Extensive SAR studies led to the discovery of compound 17d as a selective S1P(1) agonist (over S1P(3)) with high CNS penetration and favorable DMPK properties. 17d also demonstrated in vivo pharmacological efficacy to reduce blood lymphocyte in mice after oral administration.

  3. Electrochemical immunochip sensor for aflatoxin M1 detection.

    Science.gov (United States)

    Parker, Charlie O; Lanyon, Yvonne H; Manning, Mary; Arrigan, Damien W M; Tothill, Ibtisam E

    2009-07-01

    An investigation into the fabrication, electrochemical characterization, and development of a microelectrode array (MEA) immunosensor for aflatoxin M(1) is presented in this paper. Gold MEAs (consisting of 35 microsquare electrodes with 20 microm x 20 microm dimensions and edge-to-edge spacing of 200 microm) together with on-chip reference and counter electrodes were fabricated using standard photolithographic methods. The MEAs were then characterized by cyclic voltammetry, and the behavior of the on-chip electrodes were evaluated. The microarray sensors were assessed for their applicability to the development of an immunosensor for the analysis of aflatoxin M(1) directly in milk samples. Following the sensor surface silanization, antibodies were immobilized by cross-linking with 1,4-phenylene diisothiocyanate (PDITC). Surface characterization was conducted by electrochemistry, fluorescence microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). A competitive enzyme linked immunosorbent assay (ELISA) assay format was developed on the microarray electrode surface using the 3,3,5',5'-tetramethylbenzidine dihyrochloride (TMB)/H(2)O(2) electrochemical detection scheme with horseradish peroxidase (HRP) as the enzyme label. The performance of the assay and the microarray sensor were characterized in pure buffer conditions before applying to the milk samples. With the use of this approach, the detection limit for aflatoxin M(1) in milk was estimated to be 8 ng L(-1), with a dynamic detection range of 10-100 ng L(-1), which meets present legislative limits of 50 ng L(-1). The milk interference with the sensor surface was also found to be minimal. These devices show high potential for development of a range of new applications which have previously only been detected using elaborate instrumentation.

  4. A review of aflatoxin M1 in liquid milk

    OpenAIRE

    2015-01-01

    Mycotoxins continue to pose a health concern via human exposure to contaminated food. Aflatoxin M1 (AFM1), the hydroxylated metabolite of aflatoxin B1 (AFB1), may be found in the milk of dairy cattle and other mammals. In humans, AFM1 is excreted through the feces, urine, and in the case of lactating mothers, also in breast milk after consumption of aflatoxin contaminated food. Concentration of AFM1 in milk is a function of several factors, namely: animal type, milking day, milk yield, season...

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. [The BION-M1 project: overview and first results].

    Science.gov (United States)

    Sychev, V N; Ilyin, E A; Yarmanova, E N; Rakov, D V; Ushakov, I B; Kirilin, A N; Orlov, O I; Grigoriev, A I

    2014-01-01

    Biosatellite BION-M1 was launched on April 19 and landed on May 19, 2013. The mission program was largely a continuation of the earlier flown 11 BION projects, FOTON-M2 and FOTON-M3. The biosatellite was inhabited by a great variety of living organisms used for experiments and studies in gravitational physiology, gravitational biology, biotechnology, astrobiology and radiation biology, dosimetry and spectrometry. This was the first time in the history of national biology and physiology when male mice C57bl/6 were chosen for a long-term space experiment focused upon molecular biology investigations. Unfortunately, because of technical failures during the flight a part of the animals were lost. However, the major objectives were attained through reconsideration of biomaterial division among investigators and completion of virtually the total scope of investigations.

  10. Restless legs syndrome mimicking S1 radiculopathy.

    Science.gov (United States)

    Zambelis, Th; Wolgamuth, B R; Papoutsi, S N; Economou, N T

    2016-01-01

    Α case of a chronic idiopathic form of a severe type of Restless Legs Syndrome (RLS), which developed during pregnancy and persisted after this, misdiagnosed for 34 years as radiculopathy S1, is reported. In spite of the thorough clinical and laboratory investigation, in addition to constant changes of the therapeutic approach, the diagnosis of S1 radiculopathy could not be confirmed, resulting in a chronic clinical course; the latter was characterized by relapses and remissions not attributed or linked in any way to the treatment (various types of). In fact, it was due to a routine workup in a sleep clinic, where the patient was referred because of a coincident chronic insomnia (Restless Legs Syndrome is a known and important cause of insomnia/chronic insomnia), which resulted in a proper diagnosis and treatment of this case. With the use of Restless Legs Syndrome appropriate treatment (Pramipexole 0.18 mg taken at bedtime, a dopaminergic agent and Level A recommended drug for Restless Legs Syndrome) an excellent response and immediate elimination of symptoms was achieved. Restless Legs Syndrome may present with a variety of symptoms (with the most prominent shortly being reported with the acronym URGE: Urge to move the legs usually associated with unpleasant leg sensations, Rest induces symptoms, Getting active brings relief, Evening and night deteriorate symptoms); given the fact that Restless Legs Syndrome presents with a great variety and heterogeneity of symptoms (mostly pain, dysesthesia and paresthesia), which may occur in several other diseases (the so called "RLS mimics"), proper diagnosis of Restless Legs Syndrome usually fails. Restless Legs Syndrome misinterpreted as S1 radiculopathy, to the best of our knowledge, has not been reported yet in the literature. Here, case history, clinical course and common RLS mimics are presented. Different forms of Restless Legs Syndrome manifestations, which are commonly -as in this case- misinterpreted due to their

  11. 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.

  12. Unstable $m=1$ modes of counter-rotating Keplerian discs

    CERN Document Server

    Gulati, Mamta; Sridhar, S

    2012-01-01

    We study the linear $m=1$ counter-rotating instability in a two-component, nearly Keplerian disc. Our goal is to understand these \\emph{slow} modes in discs orbiting massive black holes in galactic nuclei. They are of interest not only because they are of large spatial scale--and can hence dominate observations--but also because they can be growing modes that are readily excited by accretion events. Self-gravity being nonlocal, the eigenvalue problem results in a pair of coupled integral equations, which we derive for a two-component softened gravity disc. We solve this integral eigenvalue problem numerically for various values of mass fraction in the counter-rotating component. The eigenvalues are in general complex, being real only in the absence of the counter-rotating component, or imaginary when both components have identical surface density profiles. Our main results are as follows: (i) the pattern speed appears to be non negative, with the growth (or damping) rate being larger for larger values of the ...

  13. The m=1 amplituhedron and cyclic hyperplane arrangements

    CERN Document Server

    Karp, Steven N

    2016-01-01

    The (tree) amplituhedron A(n,k,m) is the image in the Grassmannian Gr(k,k+m) of the totally nonnegative part of Gr(k,n), under a (map induced by a) linear map which is totally positive. It was introduced by Arkani-Hamed and Trnka in 2013 in order to give a geometric basis for the computation of scattering amplitudes in N=4 supersymmetric Yang-Mills theory. When k+m=n, the amplituhedron is isomorphic to the totally nonnegative Grassmannian, and when k=1, the amplituhedron is a cyclic polytope. While the case m=4 is most relevant to physics, the amplituhedron is an interesting mathematical object for any m. In this paper we study it in the case m=1. We start by taking an orthogonal point of view and define a related "B-amplituhedron" B(n,k,m), which we show is isomorphic to A(n,k,m). We use this reformulation to describe the amplituhedron in terms of sign variation. We then give a cell decomposition of the amplituhedron A(n,k,1) using the images of a collection of distinguished cells of the totally nonnegative ...

  14. Abundances of Planetary Nebula M1-42

    CERN Document Server

    Pottasch, S R; Roellig, T L

    2007-01-01

    The spectra of the planetary nebula M1-42 is reanalysed using spectral measurements made in the mid-infrared with the Spitzer Space Telescope. The aim is to determine the chemical composition of this object. We also make use of ISO, IUE and ground based spectra. Abundances determined from the mid- and far-infrared lines, which are insensitive to electron temperature, are used as the basis for the determination of the composition, which are found to substantially differ from earlier results. High values of neon, argon and sulfur are found. They are higher than in other PN, with the exception of NGC6153, a nebula of very similar abundances. The high values of helium and nitrogen found indicate that the second dredge-up and hot bottom burning has occurred in the course of evolution and that the central star was originally more massive than 4Msun. The present temperature and luminosity of the central star is determined and at first sight may be inconsistent with such a high mass.

  15. Thermoelectric waste heat recovery from an M1 Abrams tank

    Science.gov (United States)

    Stokes, C. David; Thomas, Peter M.; Baldasaro, Nicholas G.; Mantini, Michael J.; Venkatasubramanian, Rama; Barton, Michael D.; Cardine, Christopher V.; Walker, Grayson W.

    2012-06-01

    The addition of advanced sensors, targeting systems and electronic countermeasures to military vehicles has created a strategic need for additional electric power. By incorporating a thermoelectric (TE) waste heat recovery system to convert available exhaust heat to electricity, increased electric power needs can be met without reducing the energy efficiency of the vehicle. This approach allows existing vehicles to be upgraded without requiring a complete re-design of the engine and powertrain to support the integration of advanced electronic sensors and systems that keep the performance at the state of the art level. RTI has partnered with General Dynamics Land Systems and Creare, Inc. under an Army Research Lab program to develop a thermoelectric exhaust waste heat recovery system for the M1 Abrams tank. We have designed a reduced-scale system that was retrofitted to the tank and generated 80W of electric power on the vehicle operating on a test track by capturing a portion of the exhaust heat from the Honeywell/Lycoming AGT-1500 gas turbine engine.

  16. Integrable KdV Hierarchies on $T^2=S^1\\times S^1$

    CERN Document Server

    Sedra, M B

    2007-01-01

    Following our previous works on extended higher spin symmetries on the torus we focus in the present contribution to make a setup of the integrable KdV hierarchies on $T^{2} = S^{1} \\times S^{1}$. Actually two particular systems are considered, namely the KdV and the Burgers non linear integrable model associated to currents of conformal weights (2, 2) and (1, 1) respectively. One key steps towards proving the integrability of these systems is to find their Lax pair operators. This is explicitly done and a mapping between the two systems is discussed.

  17. MANAJEMEN PEMBELAJARAN S1 KEPERAWATAN STIKES YOGYAKARTA

    Directory of Open Access Journals (Sweden)

    Teti Indriati Kastuti

    2014-10-01

    Full Text Available Penelitian ini bertujuan untuk mendeskripsikan manajemen pembelajaran dilihat dari segi pe-rencanaan, pelaksanaan, dan evaluasi kurikulum di S1 Keperawatan STIKES Yogyakarta. Penelitian ini merupakan penelitian deskriptif dengan pendekatan kualitatif. Subjek penelitian adalah Pembantu Ketua I, III, dosen, kepala bagain akademik, perpustakaan, laboratorium, dan mahasiswa. Data peneli-tian dikumpulkan melalui wawancara, observasi, dan studi dokumentasi. Dianalisis secara kualitatif dengan menggunakan teknik analisis interaktif model Miles dan Huberman. Hasil penelitian bahwa perencanaan pembelajaran: 1 rumusan kompetensi pendukung dan lainnya tidak terjabarkan dalam elemen kompetensi; 2 proses pembelajaran memerlukan team teaching. Pelaksanaan pembelajaran: 1 pembinaan motivasi belajar mahasiswa masih ada dosen yang mengajar berdasarkan mood; 2 bahan ajar dimanfaatkan dengan baik untuk mencapai tujuan instruksional pembelajaran; 3 bimbing-an dan konseling pada saat pengisian KRS; 4 masih ada dosen yang mengganti jadwal. Evaluasi pembelajaran: 1 penamaan mata kuliah IKD 1 dan 2, yang menunjukkan prerequisite, kenyataannya tidak berhubungan; 2 evaluasi dosen  sebatas pelaksanaan administratif. Kata kunci: manajemen, kurikulum, pembelajaran, keperawatan

  18. Modulation of Effects of Intermittent Theta Burst Stimulation Applied Over Primary Motor Cortex (M1) by Conditioning Stimulation of the Opposite M1

    Science.gov (United States)

    Ragert, Patrick; Camus, Mickael; Vandermeeren, Yves; Dimyan, Michael A.; Cohen, Leonardo G.

    2009-01-01

    The excitability of the human primary motor cortex (M1) as tested with transcranial magnetic stimulation (TMS) depends on its previous history of neural activity. Homeostatic plasticity might be one important physiological mechanism for the regulation of corticospinal excitability and synaptic plasticity. Although homeostatic plasticity has been demonstrated locally within M1, it is not known whether priming M1 could result in similar homeostatic effects in the homologous M1 of the opposite hemisphere. Here, we sought to determine whether down-regulating excitability (priming) in the right (R) M1 with 1-Hz repetitive transcranial magnetic stimulation (rTMS) changes the excitability-enhancing effect of intermittent theta burst stimulation (iTBS) applied over the homologous left (L) M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design with real or sham R M1 1-Hz TMS stimulation always preceding L M1 iTBS or sham by about 10 min. The primary outcome measure was corticospinal excitability in the L M1, as measured by recruitment curves (RCs). Secondary outcome measures included pinch force, simple reaction time, and tapping speed assessed in the right hand. The main finding of this study was that preconditioning R M1 with 1-Hz rTMS significantly decreased the excitability-enhancing effects of subsequent L M1 iTBS on RCs. Application of 1-Hz rTMS over R M1 alone and iTBS over L M1 alone resulted in increased RC in L M1 relative to sham interventions. The present findings are consistent with the hypothesis that homeostatic mechanisms operating across hemispheric boundaries contribute to regulate motor cortical function in the primary motor cortex. PMID:19474173

  19. Main: S1FBOXSORPS1L21 [PLACE

    Lifescience Database Archive (English)

    Full Text Available S1FBOXSORPS1L21 S000223 10-May-1998 (last modified) kehi S1F box conserved both in ...e element; Might play a role in downregulating RPS1 and RPL21 promoter activity (Lagrange et al., 1993); See S000211 (SITE1SOR...PS1), S000215 (S1FSORPL21); S1F; S1F box; S1F-box; S1; plastid protein; RPS1; RPL21; leaf; negative; spinach (Spinacia oleracea) ATGGTA ...

  20. The TNM 8 M1b and M1c classification for non-small cell lung cancer in a cohort of patients with brain metastases.

    Science.gov (United States)

    Nieder, C; Hintz, M; Oehlke, O; Bilger, A; Grosu, A L

    2017-09-01

    According to the recent TNM 8 classification, patients with metastatic non-small cell lung cancer (NSCLC) and single extrathoracic metastasis should be classified as stage M1b, while those with 2 or more metastases comprise stage M1c. The purpose of this study was to analyze the impact of this classification in patients with brain metastases. This retrospective study included 172 patients treated with individualized approaches. Actuarial survival was calculated. Uni- and multivariate analyses were performed. Thirty patients (17%) were staged as M1b. Those with squamous cell cancer were more likely to harbor M1b disease (29%, adenocarcinoma 14%, other histology 17%, p = 0.16). Median survival was 5.4 months (8.0 months in case of M1b disease and 4.5 months in case of M1c disease, p = 0.001). Multivariate analysis confirmed the role of M1b stage. M1b patients managed with upfront surgery or radiosurgery had significantly longer median survival than those who received whole-brain irradiation (21.0 vs. 3.5 months, p = 0.0001) and the potential to survive beyond 5 years. We found the M1b classification to provide clinically relevant information. The multivariate analysis suggested that patients with M1b disease, better performance status and younger age have better survival.

  1. Experimental Conditions: SE37_S18_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S18 PSEUDO: Unlabeled and labeled Medicago samples for metabolite annotation using ShiftedIonsFind...17_M1), and for Medicago samples labeled by 13C (S05_M1), 15N (S07_M1), 28O (S10_M1), and 34S (S13_M1) are used. SE37_DS4 Labeled peak search by ShiftedIonsFinder ...

  2. 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.

  3. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Zhang

    Full Text Available Tumor-associated macrophages (TAMs represent an important cellular subset within the glioblastoma (WHO grade IV microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo.

  4. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo

    Science.gov (United States)

    Kahn, Suzana A.; Azad, Tej D.; Gholamin, Sharareh; Xu, Chelsea Y.; Liu, Jie; Achrol, Achal S.; Richard, Chase; Sommerkamp, Pia; Schoen, Matthew Kenneth; McCracken, Melissa N.; Majeti, Ravi; Weissman, Irving; Mitra, Siddhartha S.; Cheshier, Samuel H.

    2016-01-01

    Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo. PMID:27092773

  5. 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.

  6. 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.

  7. Cohomology of the Schro¨dinger Algebra S (1)

    Institute of Scientific and Technical Information of China (English)

    Yue Zhu WU; Xiao Qing YUE; Lin Sheng ZHU

    2014-01-01

    We explicitly compute the first and second cohomology groups of the Schr¨odinger algebra S(1) with coeffi cients in the trivial module and the finite-dimensional irreducible modules. We also show that the first and second cohomology groups of S(1) with coeffi cients in the universal enveloping algebras U (S (1)) (under the adjoint action) are infinite dimensional.

  8. Fast-timing study of the l -forbidden 1 /2+→3 /2+ M 1 transition in 129Sn

    Science.gov (United States)

    Licǎ, R.; Mach, H.; Fraile, L. M.; Gargano, A.; Borge, M. J. G.; Mǎrginean, N.; Sotty, C. O.; Vedia, V.; Andreyev, A. N.; Benzoni, G.; Bomans, P.; Borcea, R.; Coraggio, L.; Costache, C.; De Witte, H.; Flavigny, F.; Fynbo, H.; Gaffney, L. P.; Greenlees, P. T.; Harkness-Brennan, L. J.; Huyse, M.; Ibáñez, P.; Judson, D. S.; Konki, J.; Korgul, A.; Kröll, T.; Kurcewicz, J.; Lalkovski, S.; Lazarus, I.; Lund, M. V.; Madurga, M.; Mǎrginean, R.; Marroquín, I.; Mihai, C.; Mihai, R. E.; Morales, A. I.; Nácher, E.; Negret, A.; Page, R. D.; Pakarinen, J.; Pascu, S.; Paziy, V.; Perea, A.; Pérez-Liva, M.; Picado, E.; Pucknell, V.; Rapisarda, E.; Rahkila, P.; Rotaru, F.; Swartz, J. A.; Tengblad, O.; Van Duppen, P.; Vidal, M.; Wadsworth, R.; Walters, W. B.; Warr, N.; IDS Collaboration

    2016-04-01

    The levels in 129Sn populated from the β- decay of 129In isomers were investigated at the ISOLDE facility of CERN using the newly commissioned ISOLDE Decay Station (IDS). The lowest 1 /2+ state and the 3 /2+ ground state in 129Sn are expected to have configurations dominated by the neutron s1 /2 (l =0 ) and d3 /2 (l =2 ) single-particle states, respectively. Consequently, these states should be connected by a somewhat slow l -forbidden M 1 transition. Using fast-timing spectroscopy we have measured the half-life of the 1 /2+ 315.3-keV state, T1 /2= 19(10) ps, which corresponds to a moderately fast M 1 transition. Shell-model calculations using the CD-Bonn effective interaction, with standard effective charges and g factors, predict a 4-ns half-life for this level. We can reconcile the shell-model calculations to the measured T1 /2 value by the renormalization of the M 1 effective operator for neutron holes.

  9. Targeting sphingosine 1-phosphate (S1P) levels and S1P receptor functions for therapeutic immune interventions.

    Science.gov (United States)

    Gräler, Markus H

    2010-01-01

    Sphingosine 1-phosphate (S1P) is an important regulator of many different immune functions including lymphocyte circulation, antigen presentation, and T cell development. It stimulates five G protein-coupled receptors designated S1P(1-5), which are also expressed by immune cells. S1P receptors couple to different heterotrimeric G proteins including G alpha i, q, and 12/13, and elicit cellular signalling events by activating the small GTPases Rac and Rho and protein kinases Akt, ERK, and JNK, and by inducing cellular calcium flux and inhibiting cAMP accumulation, amongst others. S1P is the exit signal for lymphocytes leaving lymphoid organs and present in blood and lymph at high nanomolar concentrations due to the S1P-producing activity of sphingosine kinases (SK). The S1P-degrading enzyme S1P-lyase maintains low amounts of S1P in lymphoid organs. Disrupting this concentration difference by S1P receptor agonists and antagonists like FTY720, SEW2871, and VPC23019, by an anti-S1P antibody, or by inhibiting the S1P-lyase has therapeutic potential for autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis and for many other disorders like cancer, fibrosis, inflammation, macular degeneration, diabetic retinopathy, and glaucoma. This report aims to provide a brief overview of concepts, approaches, pharmaceutical compounds, and targets that are currently used to modulate S1P-driven immune functions.

  10. 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.

  11. Resonating Valence Bond states for low dimensional S=1 antiferromagnets

    Science.gov (United States)

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

    2014-03-01

    We study S = 1 spin liquid states in low dimensions. We show that the resonating-valence-bond (RVB) picture of S = 1 / 2 spin liquid state can be generalized to S = 1 case. For S = 1 system, a many-body singlet (with even site number) can be decomposed into superposition of products of two-body singlets. In other words, the product states of two-body singlets, called the singlet pair states (SPSs), are over complete to span the Hilbert space of many-body singlets. Furthermore, we generalized fermionic representation and the corresponding mean field theory and Gutzwiller projected stats to S = 1 models. We applied our theory to study 1D anti-ferromagnetic bilinear-biquadratic model and show that both the ground states (including the phase transition point) and the excited states can be understood excellently well within the framework. Our method can be applied to 2D S = 1 antiferromagnets.

  12. Main: O2F2BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available coxin, the maize b-32 genes and the AP-1 pseudopalindrome; O2; opaque-2; be2S1; seed; Brazil nut tree (Bertholletia excelsa) GCCACCTCAT ... ...O2F2BE2S1 S000163 17-May-1998 (last modified) kehi opaque-2 recognition site F2 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

  13. 26 CFR 1.414(s)-1 - Definition of compensation.

    Science.gov (United States)

    2010-04-01

    ... prior regulation provisions of § 1.414(s)-1T. (See § 1.414(s)-1T as contained in the CFR edition revised... to the extent necessary to satisfy the requirements of 29 CFR 2530.204-2(d) (regarding double... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of compensation. 1.414(s)-1 Section...

  14. Association between CYP1A1m1 gene polymorphism and primary open-angle glaucoma.

    Science.gov (United States)

    Costa, N B; Silva, C T X; Frare, A B; Silva, R E; Moura, K K V O

    2014-12-04

    The CYP1A1 gene is related to the generation of secondary metabolites that are capable of inducing DNA damage. The CYP1A1m1 polymorphism has been examined in many studies, and is located in a region near loci that have been linked to glaucoma, including the locus GLC1I. As a result, this polymorphism has been related to several diseases that are influenced by exposure to xenobiotic as well as primary open-angle glaucoma. We compared the prevalence of the CYP1A1m1 polymorphism in 152 Brazilian patients, 100 patients with primary open-angle glaucoma, and 52 normal controls using restriction fragment length polymorphism analysis. The frequency of the homozygous wild-type (w1/w1) CYP1A1 gene among patients with primary open-angle glaucoma (N = 100) was 16%, for genotype w1/m1, the frequency was 77%, and for m1/m1 it was 7%. Among the control group (N = 52), the frequency of the homozygous wild-type (w1/w1) CYP1A1 gene was 54%, the frequency of w1/m1 was 46%, and the frequency of m1/m1 was 0%. The presence of the CYP1A1m1 polymorphism may interfere with xenobiotic metabolism and exacerbate direct or indirect damage to the optic nerve. These CYP1A1m1 polymorphisms may be risk factors for primary open-angle glaucoma.

  15. Main: O2F3BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available quences of be2S1 promoter; F3 is hybrid of A/G box; O2; opaque-2; be2S1; seed; Brazil nut tree (Bertholletia excelsa) TCCACGTACT ... ...O2F3BE2S1 S000164 17-May-1998 (last modified) kehi opaque-2 recognition site F3 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

  16. Main: O2F1BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available quences of be2S1 promoter; F1 is hybrid C/G box; O2; opaque-2; be2S1; F1; seed; Brazil nut tree (Bertholletia excelsa); TCCACGTCGA ... ...O2F1BE2S1 S000162 17-May-1998 (last modified) kehi opaque-2 recognition site F1 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

  17. SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs).

    Science.gov (United States)

    Kuduk, Scott D; Beshore, Douglas C

    2014-01-01

    There is mounting evidence from preclinical and early proof-of-concept studies suggesting that selective modulation of the M1 muscarinic receptor is efficacious in cognitive models of Alzheimer's disease (AD). A number of nonselective M1 muscarinic agonists have previously shown positive effects on cognitive function in AD patients, but were limited due to cholinergic adverse events thought to be mediated by pan activation of the M2 to M5 sub-types. Thus, there is a need to identify selective activators of the M1 receptor to evaluate their potential in cognitive disorders. One strategy to confer selectivity for M1 is the identification of allosteric agonists or positive allosteric modulators, which would target an allosteric site on the M1 receptor rather than the highly conserved orthosteric acetylcholine binding site. BQCA has been identified as a highly selective carboxylic acid M1 PAM and this review focuses on an extensive lead optimization campaign undertaken on this compound.

  18. Inhibition of skeletal muscle S1-myosin ATPase by peroxynitrite.

    Science.gov (United States)

    Tiago, Teresa; Simão, Sónia; Aureliano, Manuel; Martín-Romero, Francisco Javier; Gutiérrez-Merino, Carlos

    2006-03-21

    Exposure of myosin subfragment 1 (S1) to 3-morpholinosydnonimine (SIN-1) produced a time-dependent inhibition of the F-actin-stimulated S1 Mg(2+)-ATPase activity, reaching 50% inhibition with 46.7 +/- 8.3 microM SIN-1 for 8.7 microM S1, that is, at a SIN-1/S1 molar ratio of approximately 5.5. The inhibition was due to the peroxynitrite produced by SIN-1 decomposition because (1) decomposed SIN-1 was found to have no effect on S1 ATPase activity, (2) addition of SIN-1 in the presence of superoxide dismutase and catalase fully prevented inhibition by SIN-1, and (3) micromolar pulses of chemically synthesized peroxynitrite produced inhibition of F-actin-stimulated S1 Mg(2+)-ATPase activity. In parallel, SIN-1 produced the inhibition of the nonphysiological Ca(2+)-dependent and K(+)/EDTA-dependent S1 ATPase activity of S1 and, therefore, suggested that the inhibition of F-actin-stimulated S1 Mg(2+)-ATPase activity is produced by the oxidation of highly reactive cysteines of S1 (Cys(707) and Cys(697)), located close to the catalytic center. This point was further confirmed by the titration of S1 cysteines with 5,5'-dithiobis(2-nitrobenzoic acid) and by the parallel decrease of Cys(707) labeling by 5-(iodoacetamido)fluorescein, and it was reinforced by the fact that other common protein modifications produced by peroxynitrite, for example, protein carbonyl and nitrotyrosine formation, were barely detected at the concentrations of SIN-1 that produced more than 50% inhibition of the F-actin-stimulated S1 Mg(2+)-ATPase activity. Differential scanning calorimetry of S1 (untreated and treated with different SIN-1 concentrations) pointed out that SIN-1, at concentrations that generate micromolar peroxynitrite fluxes, impaired the ability of ADP.V(1) to induce the intermediate catalytic transition state and also produced the partial unfolding of S1 that leads to an enhanced susceptibility of S1 to trypsin digestion, which can be fully protected by 2 mM GSH.

  19. An Upper Bound on the Strongly Forbidden $6S_{1/2} \\leftrightarrow 5D_{3/2}$ Magnetic Dipole Transition Moment in {Ba}$^{+}$

    CERN Document Server

    Williams, Spencer R; Hoffman, Matthew R; Blinov, Boris B; Fortson, E N

    2016-01-01

    We report the results from our first-generation experiment to measure the magnetic-dipole transition moment (M1) between the $6S_{1/2}$ and $5D_{3/2}$ manifolds in Ba$^{+}$. Knowledge of M1 is crucial for the proposed parity-nonconservation experiment in the ion \\cite{Fortson93}, where M1 will be a leading source of systematic error. To date, no measurement of M1 has been made in Ba$^{+}$, and moreover, the sensitivity of the moment to electron-electron correlations has confounded accurate theoretical predictions. A precise measurement may help to resolve the theoretical discrepancies while providing essential information for planning a future PNC measurement in Ba$^{+}$. We demonstrate our technique for measuring M1 - including a method for calibrating for stress-induced birefringence introduced by the scientific apparatus - and place an upper bound of $\\mathrm{M1} < 93 \\pm 39 \\times 10^{-5} \\mu_{B}$.

  20. M1 Protein Allows Group A Streptococcal Survival in Phagocyte Extracellular Traps through Cathelicidin Inhibition

    OpenAIRE

    Lauth, Xavier; von Köckritz-Blickwede, Maren; McNamara, Case W; Myskowski, Sandra; Zinkernagel, Annelies S.; Beall, Bernard; Ghosh, Partho; Richard L Gallo; Nizet, Victor

    2009-01-01

    M1 protein contributes to Group A Streptococcus (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance...

  1. Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation.

    Science.gov (United States)

    Xiang, D; Liu, C-C; Wang, M-J; Li, J-X; Chen, F; Yao, H; Yu, B; Lu, L; Borjigin, U; Chen, Y-X; Zhong, L; Wangensteen, K J; He, Z-Y; Wang, X; Hu, Y-P

    2014-05-22

    Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocytes in recipient livers. In this study, we analyzed the application of FoxM1, a cell-cycle regulator, to enhance the proliferation capacity of hepatocytes. The non-viral sleeping beauty (SB) transposon vector carrying FoxM1 gene was constructed for delivering FoxM1 into the hepatocytes. The proliferation capacities of hepatocytes with FoxM1 expression were examined both in vivo and in vitro. Results indicated that the hepatocytes with FoxM1 expression had a higher proliferation rate than wild-type (WT) hepatocytes in vitro. In comparison with WT hepatocytes, the hepatocytes with FoxM1 expression had an enhanced level of liver repopulation in the recipient livers at both sub-acute injury (fumaryl acetoacetate hydrolase (Fah)(-/-) mice model) and acute injury (2/3 partial hepatectomy mice model). Importantly, there was no increased risk of tumorigenicity with FoxM1 expression in recipients even after serial transplantation. In conclusion, expression of FoxM1 in hepatocytes enhanced the capacity of liver repopulation without inducing tumorigenesis. FoxM1 gene delivered by non-viral SB vector into hepatocytes may be a viable approach to promote therapeutic repopulation after hepatocyte transplantation.

  2. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    Directory of Open Access Journals (Sweden)

    G. Karina Chimal-Ramírez

    2016-01-01

    Full Text Available Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1 and protumoral (M2 activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli.

  3. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    Science.gov (United States)

    Chimal-Ramírez, G. Karina; Espinoza-Sánchez, Nancy Adriana; Chávez-Sánchez, Luis; Arriaga-Pizano, Lourdes

    2016-01-01

    Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1) and protumoral (M2) activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli. PMID:27376091

  4. Experimental Conditions: SE37_S19_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S19 PSEUDO: Unlabeled and labeled Medicago samples for flavonoid annotation using ShiftedIonsFinde...03_M1) and for a blank sample (S16_M1 to S16_M3) are used. Import file name is unlabeling SE37_DS5 Flavonoid like peak search by ShiftedIonsFinder ...

  5. Radioiodinated ganglioside G/sub M1/: A potential tracer for neurological studies

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.; Gallagher, P.; Magistretti, P.L.; Ghidoni, R.

    1985-05-01

    Ganglioside G/sub M1/ is a glycosphingolipid which appears to be involved in the regeneration of damaged neuronal tissue. In addition, it is being investigated clinically in the treatment of various neuropathies. If labeled with the appropriate isotope, G/sub M1/ might be useful as a probe of these processes, particularly if it accumulates preferentially in cerebral infarcts. The G/sub M1/ -tyr derivative was labeled with I-125 in 75% yield using the Iodogen method and at micellar concentration was isolated using gel chromatography. Binding of I-125 (G/sub M1/ -tyr) to rat neuronal membranes was measured at concentrations of 5,50, and 500 nM. The amount bound (8,26, and 158 pmol/gm membrane) was similar to that reported for H-3(G/sub M1/). The biodistribution of I-125(G/sub M1/ -tyr) in mice at both micellar and monomeric concentrations was also similar to that of H-3(G/sub M1/). However, at monomeric concentrations, thyroid uptake of I-125 was about 10 times higher than at micellar concentrations, suggesting differential dehalogenation of the two forms. Initial studies in the gerbil stroke model suggest that the uptake of I-125(G/sub M1/ -tyr) in damaged brain is twice that in normal tissue.

  6. CONDITIONAL INVOLVEMENT OF MUSCARINIC M(1) RECEPTORS IN VAGALLY MEDIATED CONTRACTION OF GUINEA-PIG BRONCHI

    NARCIS (Netherlands)

    TENBERGE, REJ; ROFFEL, AF; ZAAGSMA, J

    The involvement of ganglionic muscarinic M(1) receptors in vagally induced bronchoconstriction in guinea-pig airways is controversial. Therefore, we studied the effects of the M(1)-selective muscarinic receptor antagonist pirenzepine on vagus nerve (VNS, preganglionic) and electrical field

  7. A note on predicting recessions in the euro area using real M1

    OpenAIRE

    Jens Boysen-Hogrefe

    2012-01-01

    Real M1 is a renowned leading indicator used to forecast real economic activity. This note provides evidence that real M1 is also a suitable recession indicator that gave a clear and early signal for the Great Recession as long as changes in money demand are controlled for.

  8. Analytical Method (M): SE37_S18_M1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE37_S18_M1 This is a pseudo metadata prepared for integrated analyses of multiple ...datasets. The raw data obtained from LC-Orbitarp MS analyses for Medicago samples and a blank sample (S17_M1

  9. 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,...

  10. Experimental Conditions: SE19_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE19_S2_M1_D1 SE19 Grobal triacylglycerol analysis in mouse liver and white adipose... tissue (WAT) by high resolution LC/ESI-QTOF MS/MS SE19_S2 Mouse white adipose tissue (WAT) SE19_S2_M1 20 ug

  11. FoxM1 is required for execution of the mitotic programme and chromosome stability

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Brás, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, H.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  12. FoxM1 is required for execution of the mitotic programme and chromosome stability.

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Bras, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, J.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  13. 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

  14. Localization on $AdS_2\\times S^1$

    CERN Document Server

    David, Justin R; Gupta, Rajesh Kumar; Narain, Kumar

    2016-01-01

    Conformal symmetry relates the metric on $AdS_2 \\times S^{1}$ to that of $S^3$. This implies that under a suitable choice of boundary conditions for fields on $AdS_2$ the partition function of conformal field theories on these spaces must agree which makes $AdS_2 \\times S^{1}$ a good testing ground to study localization on non-compact spaces. We study supersymmetry on $AdS_2\\times S^1$ and determine the localizing Lagrangian for ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2\\times S^1$. We evaluate the partition function of ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2 \\times S^1$ using localization, where the radius of $S^1$ is $q$ times that of $AdS_2$. With boundary conditions on $AdS_2\\times S^1$ which ensure that all the physical fields are normalizable and lie in the space of square integrable wave functions in $AdS_2$, the result for the partition function precisely agrees with that of the theory on the $q$-fold covering of $S^3$.

  15. Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ehlert, F.J.; Tran, L.P. (Univ. of California, Irvine (USA))

    1990-12-01

    The distribution of subtypes of the muscarinic receptor in homogenates of the rat brain was investigated by measuring the competitive inhibition of the binding (3H)N-methylscopolamine by pirenzepine and AF-DX 116 (11((2-((diethylamino)methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one). In most brain regions, the competitive binding curves for AF-DX 116 and pirenzepine were consistent with a two-site model. The dissociation constant of pirenzepine for its high-affinity site (M1 receptor) was approximately 10(-8) M, whereas the dissociation constant of AF-DX 116 for its high affinity site (M2 receptor) was approximately 10(-7) M. In many regions, particularly those in the forebrain, the sum of the densities of the M1 and M2 binding sites was substantially less than 100% of the total sites, indicating the existence of a third population of sites lacking high affinity for both pirenzepine and AF-DX 116. We have designated these latter sites as non-M1, non-M2 muscarinic receptors. In general, the densities of the M1 and non-M1, non-M2 binding sites were highest in cerebral cortex, corpus striatum and hippocampus, intermediate in thalamus and hypothalamus, and lowest in midbrain, medulla-pons and cerebellum, whereas the M2 binding site had a relatively low, uniform density throughout the brain. The binding capacity of (3H)N-methylquinuclidinyl benzilate was estimated to be 20 to 30% lower than that of (3H)quinuclidinyl benzilate in various regions of the forebrain, but not in more caudal regions of the brain where the two radioligands had approximately the same binding capacities.

  16. Epson EMP-S1投影机的升级产品EMP-S1H

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    EMP-S1是Epson公司推出的1款颇具影响力的经济型投影机,2004年5月Epson推出了EMP-S1的升级产品EMP-S1H。EMP.S1H在原有EMP-S1投影机的基础上亮度提高到了1400流明,同时对比度也提高到500:1,对比度的提高使图像层次感更好,影像更富有质感。

  17. The luminosity function of cluster galaxies relations among M$_{1}$, M* and the morphological type

    CERN Document Server

    Trevese, D; Appodia, B

    1996-01-01

    A study of the luminosity function of 36 Abell clusters of galaxies has been carried out using photographic plates obtained with the Palomar 1.2 m Schmidt telescope. The relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M* has been analyzed. A positive correlation between M* and M_1 is found. However clusters appear segregated in the M_1-M* plane according to their Rood & Sastry class in such a way that on average M_1 becomes brighter while M* becomes fainter going from late to early Rood & Sastry and also Bautz & Morgan classes. Also a partial correlation analysis involving the magnitude M_10 of the 10th brightest galaxy, shows a negative intrinsic correlation between M_1 and M*. These results agree with the cannibalism model for the formation of brightest cluster members, and provide new constraints for theories of cluster formation and evolution.

  18. 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.

  19. Assignment of Isodoublet of 23S1 Meson Nonet

    Institute of Scientific and Technical Information of China (English)

    FENG Xue-Chao; JIANG Feng-Chun

    2007-01-01

    Inserting the masses of some states, which have been established in the experiments or the theory of lattice QCD, we investigate the mass of the isodoublet of the 23S1 meson nonet. The agreement results, 1567 ± 22.6 MeV and 1576.8 MeV, are given by two different approaches. We suggest that the assignment of 23S1 meson nonet should be re-examined in future experiments.

  20. Exploration of FoxM1 and downstream related target molecule expression in cervical cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Yi-Chong Yuan; QiongYang

    2016-01-01

    Objective:To study the expression of FoxM1 and downstream related target molecules in cervical cancer tissue.Methods:Cervical cancer tissue and normal cervical tissue were collected to detect the expression of FoxM1, proliferation-related genes (CDK6 and CDK8) and angiogenesis-related genes (VEGFA, VEGFB and VEGFC); Hela cells were cultured and transfected with FoxM1 siRNA, and then expression of CDK6, CDK8, VEGFA, VEGFB and VEGFC were detected.Results:mRNA contents of FoxM1, CDK6, CDK8, VEGFA, VEGFB and VEGFC in cervical cancer tissue were significantly higher than those in normal cervical tissue; mRNA content of FoxM1 was positively correlated with mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC; mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC of FoxM1-siRNA group were significantly lower than those of negative control-siRNA group.Conclusion:FoxM1 expression abnormally increases in cervical cancer tissue, and its downstream target genes include CDK6, CDK8, VEGFA, VEGFB and VEGFC.

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

    CERN Document Server

    Sepehri, Alireza; 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 this model could explain the oscillation of universe between contraction and expansion branches? We try to address this issue in the framework of 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 removes these states, $M1$...

  2. Enzyme-linked immunosorbent assay for determination of aflatoxin M1 based on magnetic nanoparticles

    Science.gov (United States)

    Atanasova, M. K.; Ivanova, N. V.; Godjevargova, T. I.

    2017-02-01

    A sensitive enzyme immunoassay with magnetic nanoparticles (Method A) for the quantitative determination of aflatoxin M1 in milk was developed. This immunoassay was based on the immobilization of monoclonal antibody (mAb) on the modified magnetic nanoparticles (MNPs-NH2). It was observed that for each mg of the MNPs, 25 µg of antibody was immobilized. Both aflatoxin M1 in the sample and aflatoxin M1-BSA-peroxidase conjugate competed for the immobilized antibody. The proposed Method A was compared with other method (B). The Method B was based on the immobilization of aflatoxin M1-BSA conjugate on the MNPs-NH2, which competed with the aflatoxin M1 in the sample for binding to the added mAb. The binding of mAb to the aflatoxin M1-BSA-MNPs-NH2 was detected using a target secondary IgG-peroxidase antibody. The analytical characteristics of the two methods were compared. Real milk samples were investigated for present of aflatoxin M1. Two methods were based on the use of MNPs as a solid support for covalently immunoreagents immobilization. A comfortable separation of bound and free fraction of the tracer can be performed only through a simple collection of the MNPs by a permanent magnet. The application of MNPs helps to eliminate non-specific binding and to retain higher activity of bound biomolecules. The development of a MNPs-based ELISA for determination of aflatoxin M1 has a great potential to supersede the traditional ELISA for aflatoxin M1 diagnosis.

  3. Bounds on Subspace Codes Based on Subspaces of Type (m,1 in Singular Linear Space

    Directory of Open Access Journals (Sweden)

    You Gao

    2014-01-01

    Full Text Available The Sphere-packing bound, Singleton bound, Wang-Xing-Safavi-Naini bound, Johnson bound, and Gilbert-Varshamov bound on the subspace codes n+l,M,d,(m,1q based on subspaces of type (m,1 in singular linear space Fq(n+l over finite fields Fq are presented. Then, we prove that codes based on subspaces of type (m,1 in singular linear space attain the Wang-Xing-Safavi-Naini bound if and only if they are certain Steiner structures in Fq(n+l.

  4. 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

    and ST8, respectively. Related plasmids circulating in human and animal isolates were identified. Complete nucleotide sequences of the ST1 pHHA45 plasmid carrying blaCTX-M-1, isolated from E. coli from pigs in Denmark, and the ST3 pKT58A plasmid harbouring qnrS1, identified in E. coli from a water bird......Objectives The aim of the study was to characterize a collection of Escherichia coli and Salmonella harbouring qnr and blaCTX-M-1 genes on IncN plasmids isolated from humans, food-producing, companion and wild animals, and the environment from six European countries.Methods Nineteen IncN plasmids...... 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...

  5. Locations of All Shotpoints, USGS Cruise M1-98-GM (GOM98SHTALLG.SHP)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — All shotpoint locations from multichannel seismics survey, USGS cruise M1-98-GM. During June 1998 and April 1999, the U.S. Geological Survey (USGS) conducted two...

  6. Aflatoxin M1 levels in raw milk, pasteurized milk and infant formula

    National Research Council Canada - National Science Library

    Omar, Sharaf Shareef

    2016-01-01

    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...

  7. 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.

  8. Coiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Case; Zinkernagel, Annelies S.; Macheboeuf, Pauline; Cunningham, Madeleine W.; Nizet, Victor; Ghosh, Partho (UO-HSC); (UCSD)

    2008-07-21

    Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the -3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.

  9. Presence of Aflatoxin M1 in Raw Milk for Human Consumption in Palestinian

    Directory of Open Access Journals (Sweden)

    Ibrahim Mahmoud AL ZUHEIR

    2012-09-01

    Full Text Available The absences or insufficient food control program result in the occurrence of mycotoxin in milk and milk products, which poses a serious risk for humans and can be a public health concern. This study was conducted to highlight the occurrence of aflatoxin M1 in Palestine raw milk collected at farms from Tulkarm, Nablus and Jenin. Aflatoxin M1 was determined by direct competitive ELISA technique. 85 % (34 of 40 of the total examined raw milk samples tested were positive. The aflatoxin M1 contamination levels were between 3 - 80 ppt with a mean of 29.57 ppt. There was a high incidence rate with 92 % (11 of 12 and the highest means of contaminated with aflatoxin M1 in the samples tested in Tulkarm city (P ≤ 0.05. 20 % of the analyzed samples (8 of 40 exceeded the maximum permissible limit (50 ppt in European Codex, with a range of 2 - 80 ppt.

  10. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Nuo XU; Xin ZHANG; Xun WANG; Hai-yan GE; Xiao-ying WANG; David GARFIELD; Ping YANG; Yuan-lin SONG; Chun-xue BAI

    2012-01-01

    Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC),and the underlying mechanism remains unclear.FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients.In this study,we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms.Methods:Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used.mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis.RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells,and lentiviral infection was used to overexpress FoxM1 in H292 cells.MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells.Results:Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentrationdependent manners,while gefrtinib (1 μmol/L) downregulated in H292 cells.In SPC-A-1 cells treated with gefitinib (1 μmol/L),the expression of several downstream targets of FoxM1,including survivin,cyclin B1,SKP2,PLK1,Aurora B kinase and CDC25B,were significantly upregulated.Overexpression of FoxM1 increased the resistance in H292 cells,while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro.FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

  11. q-differential operator representation of the quantum superalgebra Uq(sl(M+1|N+1))

    CERN Document Server

    Kimura, K

    1996-01-01

    A representation of the quantum superalgebra Uq(sl(M+1|N+1)) is constructed based on the q-differential operators acting on the coherent states parameterized by coordinates. These coordinates correspond to the local ones of the flag manifold. This realization provides us with a guide to construct the free field realization for the quantum affine superalgebra Uq^(sl(M+1|N+1)) at arbitrary level.

  12. 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.

  13. 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.

  14. 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.

  15. 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.)

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

    Science.gov (United States)

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

    2016-05-01

    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.

  17. 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.

  18. Optical illusion alters M1 excitability after mirror therapy: a TMS study.

    Science.gov (United States)

    Läppchen, C H; Ringer, T; Blessin, J; Seidel, G; Grieshammer, S; Lange, R; Hamzei, F

    2012-11-01

    The contralesional primary motor cortex (M1) has been suggested to be involved in the motor recovery after mirror therapy, but whether the ipsilesional M1 is influenced by the contralesional M1 via transcallosal interhemispheric inhibition (IHI) is still unclear. The present study investigated the change of IHI as well as the intracortical inhibition and intracortical facilitation of both M1 induced by training in a mirror with the use of transcranial magnetic stimulation (TMS). In this 2 × 2 factorial design (time × group), healthy subjects exercised standardized motor skills with their right hand on four consecutive days. Either a mirror (mirror group) or a board (control group) was positioned between their hands. Before and after training TMS was applied along with training tests of both hands. Tests were the same motor skills exercised daily by both groups. Tests of the untrained left hand improved significantly more in the mirror group than in the control group after training (P = 0.02) and showed a close correlation with an increase of intracortical inhibition of M1(left). IHI did not show any difference between investigation time points and groups. The present study confirms the previous suggestion of the involvement of the "contralesional" left-side (ipsilateral to the hand behind the mirror) M1 after mirror therapy, which is not mediated by IHI. Even with the same motor skill training (both groups performed same motor skills) but with different visual information, different networks are involved in training-induced plasticity.

  19. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.

    Science.gov (United States)

    Tang, Yu; Le, Weidong

    2016-03-01

    One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

  20. Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor.

    Science.gov (United States)

    Vachal, Petr; Toth, Leslie M; Hale, Jeffrey J; Yan, Lin; Mills, Sander G; Chrebet, Gary L; Koehane, Carol A; Hajdu, Richard; Milligan, James A; Rosenbach, Mark J; Mandala, Suzanne

    2006-07-15

    Novel series of sphingosine-1-phosphate (S1P) receptor agonists were developed through a systematic SAR aimed to achieve high selectivity for a single member of the S1P family of receptors, S1P1. The optimized structure represents a highly S1P1-selective and efficacious agonist: S1P1/S1P2, S1P1/S1P3, S1P1/S1P4>10,000-fold, S1P1/S1P5>600-fold, while EC50 (S1P1) effect.

  1. Improvement of S-1 photocathode shelf life stability. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Fitts, R.W.

    1977-03-01

    The purpose of this program was to stabilize sensitivity of S-1 photocathodes in C73435AG high speed image converters. Variations in bulb pre- and post-heating and in aging were investigated using partial tube assemblies consisting of the cathode bulb half of the standard tube. Successful processing of stable S-1 photocathodes in partial tubes led to adapting the schedules to complete tube assemblies. Five tubes processed on this contract yielded high but unstable photocathode sensitivity. Continued testing of tubes being made to fill customer orders shows that control of tube heating and cooling, together with careful control of evaporated cesium, can yield stable S-1 photocathodes. Additional experimentation is required to optimize a schedule yielding consistently stable photocathodes.

  2. The Plasmodium falciparum malaria M1 alanyl aminopeptidase (PfA-M1: insights of catalytic mechanism and function from MD simulations.

    Directory of Open Access Journals (Sweden)

    Peter M Jones

    Full Text Available Malaria caused by several species of Plasmodium is major parasitic disease of humans, causing 1-3 million deaths worldwide annually. The widespread resistance of the human parasite to current drug therapies is of major concern making the identification of new drug targets urgent. While the parasite grows and multiplies inside the host erythrocyte it degrades the host cell hemoglobin and utilizes the released amino acids to synthesize its own proteins. The P. falciparum malarial M1 alanyl-aminopeptidase (PfA-M1 is an enzyme involved in the terminal stages of hemoglobin digestion and the generation of an amino acid pool within the parasite. The enzyme has been validated as a potential drug target since inhibitors of the enzyme block parasite growth in vitro and in vivo. In order to gain further understanding of this enzyme, molecular dynamics simulations using data from a recent crystal structure of PfA-M1 were performed. The results elucidate the pentahedral coordination of the catalytic Zn in these metallo-proteases and provide new insights into the roles of this cation and important active site residues in ligand binding and in the hydrolysis of the peptide bond. Based on the data, we propose a two-step catalytic mechanism, in which the conformation of the active site is altered between the Michaelis complex and the transition state. In addition, the simulations identify global changes in the protein in which conformational transitions in the catalytic domain are transmitted at the opening of the N-terminal 8 Å-long channel and at the opening of the 30 Å-long C-terminal internal chamber that facilitates entry of peptides to the active site and exit of released amino acids. The possible implications of these global changes with regard to enzyme function are discussed.

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

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    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.

  4. M1 contributes to the intrinsic but not the extrinsic components of motor-skills.

    Science.gov (United States)

    Romei, Vincenzo; Thut, Gregor; Ramos-Estebanez, Ciro; Pascual-Leone, Alvaro

    2009-10-01

    Procedural skills consist of several components that can be simultaneously acquired. During a motor-learning task we can distinguish between how a "movement" is performed (intrinsic component) and the spatial-related (extrinsic) component of this movement. The intrinsic movement component is thought to be supported by motor loops, including primary motor cortex (M1) as assessed with neuroimaging studies. Here we want to test further whether M1 makes a critical contribution to the movement rather than spatial-related component of skill-learning. To this purpose, we used repetitive Transcranial Magnetic Stimulation (rTMS) and the serial reaction time (SRT) task. Twenty right-handed participants performed the SRT-task starting with their left or right hand. After this learning session, participants switched to the untrained hand by performing original (spatial-related) and mirror-ordered (movement-based) sequences. rTMS was applied to M1 ipsi- or contralateral to the transfer-hand and both sequences were retested. Results revealed rTMS-interference with motor-skill transfer of mirror-ordered but not original sequences, showing that M1 is critically involved in the retrieval/transformation of the intrinsic but not the extrinsic movement coordinates. rTMS-interference in the mirror-condition consisted of both (i) disruption and (ii) release of motor-skill transfer depending on the stimulated hemisphere and on transfer-hand. The pattern of results suggests (i) contralateral (right) M1 involvement in retrieval/transformation of motor information during left-hand reproduction of previously acquired right-hand motor-skills; and (ii) modulatory interactions of inhibitory nature from the dominant (left) to the non-dominant (right) M1 in the same transfer-condition. These results provide further evidence that M1 is essential to intrinsic movement-based skill-learning and novel insight on models of motor-learning and hemispheric specialization, suggesting the involvement of

  5. Neoglycolipid analogues of ganglioside G sub M1 as functional receptors of cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Pacuszka, T.; Bradley, R.M.; Fishman, P.H. (National Inst. of Health, Bethesda, MD (United States))

    1991-03-12

    The authors synthesized several lipid analogues of ganglioside G{sub M1} by attaching its oligosaccharide moiety (G{sub M1}OS) to aminophospholipids, aliphatic amines, and cholesteryl hemisuccinate. They incubated G{sub M1}-deficient rat glioma C6 cells with each of the derivatives as well as native G{sub M1} and assayed the cells for their ability to bind and respond to cholera toxin. On the basis of the observed increase in binding of {sup 125}I-labeled cholera toxin, it was apparent that the cells took up and initially incorporated most of the derivatives into the plasma membrane. In the case of the aliphatic amine derivatives, the ability to generate new toxin binding sites was dependent on chain length; whereas the C{sub 10} derivative was ineffective, C{sub 12} and higher analogues were effective. Increased binding was dependent on both the concentration of the neoglycolipid in the medium and the time of exposure. Cells pretreated with the various derivatives accumulated cyclic AMP in response to cholera toxin, but there were differences in their effectiveness. The cholesterol and long-chain aliphatic amine derivatives were more effective than native G{sub M1}, whereas the phospholipid derivatives were less effective. The distance between G{sub M1}OS and the phospholipid also appeared to influence its functional activity. The results indicate that although G{sub M1}OS provides the recognition site for the binding of cholera toxin, the nature of the lipid moiety plays an important role in the action of the toxin.

  6. Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis.

    Science.gov (United States)

    Chen, Fang-Yuan; Zhou, Juan; Guo, Ning; Ma, Wang-Ge; Huang, Xin; Wang, Huan; Yuan, Zu-Yi

    2015-11-27

    Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.

  7. Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway.

    Science.gov (United States)

    Park, Y-H; Kim, S-U; Kwon, T-H; Kim, J-M; Song, I-S; Shin, H-J; Lee, B-K; Bang, D-H; Lee, S-J; Lee, D-S; Chang, K-T; Kim, B-Y; Yu, D-Y

    2016-07-07

    The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.

  8. In situ production of pediocin PA-1 like bacteriocin by different genera of lactic acid bacteria in soymilk fermentation and evaluation of sensory properties of the fermented soy curd.

    Science.gov (United States)

    Devi, Sundru Manjulata; Ramaswamy, Asha Mysore; Halami, Prakash M

    2014-11-01

    The lactic acid bacteria (LAB) are found to produce bacteriocins with enhanced nutritive properties in the fermented foods. In the present study, the ability of LAB cultures (Pediococcus acidilactici NCIM 5424, Enterococcus faecium NCIM 5423 and Lactobacillus plantarum Acr2) to produce pediocin PA-1 like bacteriocin was evaluated during soymilk fermentation. The isolates E. faecium NCIM 5423 and Lb. plantarum Acr2 were able to produce bacteriocin as well as ferment soymilk within 6 h of incubation. Upon plating the cultures E. faecium NCIM 5423 and Lb. plantarum Acr2 in soymilk were found to be viable even after 15 days of storage at 4 °C. No significant variation was observed in the viable counts of E. faecium NCIM 5423 and Lb. plantarum Acr2 (P>0.05). The effect of crude bacteriocin on Listeria cells was evidenced through scanning electron microscope (SEM) photographs wherein cell membrane damage was observed. On co-cultivation of E. faecium NCIM 5423 and Lb. plantarum Acr2 individually with Listeria monocytogenes ScottA a decrease in the Listeria count was observed within 24 h of incubation. However, during co-cultivation of ScottA with P. acidilactici NCIM 5424, no significant difference was observed in the viable counts (P>0.05). The pH, titratable acidity, pediocin activity, anti-oxidant property and sensory attributes for E. faecium NCIM 5423 were studied. It was observed that E. faecium NCIM 5423 fermented soymilk had an acceptable sensory score during storage period. Hence, such culture can be an ideal starter for development of functional foods with longer shelf life.

  9. Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning

    Science.gov (United States)

    Chan, Wilson; Singh, Sanmeet; Keshav, Taj; Dewan, Ramita; Eberly, Christian; Maurer, Robert; Nunez-Parra, Alexia; Araneda, Ricardo C.

    2017-01-01

    The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1−/− and the M1/M3−/− knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing. PMID:28210219

  10. Dynamic Changes of Microglia/Macrophage M1 and M2 Polarization in Theiler's Murine Encephalomyelitis.

    Science.gov (United States)

    Herder, Vanessa; Iskandar, Cut Dahlia; Kegler, Kristel; Hansmann, Florian; Elmarabet, Suliman Ahmed; Khan, Muhammad Akram; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner; Beineke, Andreas

    2015-11-01

    Microglia and macrophages play a central role for demyelination in Theiler's murine encephalomyelitis (TME) virus infection, a commonly used infectious model for chronic-progressive multiple sclerosis. In order to determine the dynamic changes of microglia/macrophage polarization in TME, the spinal cord of Swiss Jim Lambert (SJL) mice was investigated by gene expression profiling and immunofluorescence. Virus persistence and demyelinating leukomyelitis were confirmed by immunohistochemistry and histology. Electron microscopy revealed continuous myelin loss together with abortive myelin repair during the late chronic infection phase indicative of incomplete remyelination. A total of 59 genes out of 151 M1- and M2-related genes were differentially expressed in TME virus-infected mice over the study period. The onset of virus-induced demyelination was associated with a dominating M1 polarization, while mounting M2 polarization of macrophages/microglia together with sustained prominent M1-related gene expression was present during the chronic-progressive phase. Molecular results were confirmed by immunofluorescence, showing an increased spinal cord accumulation of CD16/32(+) M1-, arginase-1(+) M2- and Ym1(+) M2-type cells associated with progressive demyelination. The present study provides a comprehensive database of M1-/M2-related gene expression involved in the initiation and progression of demyelination supporting the hypothesis that perpetuating interaction between virus and macrophages/microglia induces a vicious circle with persistent inflammation and impaired myelin repair in TME.

  11. Reverse phase liquid chromatographic determination and confirmation of aflatoxin M1 in cheese.

    Science.gov (United States)

    Hisada, K; Terada, H; Yamamoto, K; Tsubouchi, H; Sakabe, Y

    1984-01-01

    A systematic method is proposed for determination and confirmation of aflatoxin M1 in cheese by liquid chromatography (LC). A sample of cheese is extracted with chloroform, cleaned up on 2 silica gel columns followed by a Sep-Pak C18 cartridge, and chromatographed on a 5 microns octadecyl silica column with fluorometric detection. The sample extract or standard is treated with n-hexane-trifluoroacetic acid (TFA) (4 + 1) for 30 min at 40 degrees C. Analysis by LC with TFA-treatment of the extract provides quantitative data. Multiple assays of 5 samples of Gouda cheese spiked with aflatoxin M1 at levels of 0.5, 0.1, and 0.05 ng/g showed average recoveries of 93.2, 91.6, and 92.4%, with coefficients of variation of 2.63, 3.97, and 4.52%, respectively. Assay of 5 naturally contaminated cheeses resulted in 0.051-0.448 ng/g of aflatoxin M1. Limit of quantitation is about 0.01 ng/g. The identity of aflatoxin M1 is confirmed by treating aflatoxin M1 or the M2a derivative with TFA-methanol (or ethanol) (3 + 1). The TFA-methanol reaction products of M2a could be detected quantitatively.

  12. Anomalous Dispersion of the S1 Lamb Mode

    Directory of Open Access Journals (Sweden)

    Faiz Ahmad

    2013-01-01

    Full Text Available The S1 mode of the Lamb spectrum of an isotropic plate exhibits negative group velocity in a narrow frequency domain. This anomalous behavior is explained analytically by examining the slope of each mode first in its initial state and then near its turning points.

  13. Emerging role of S-1 in gastric cancer

    Directory of Open Access Journals (Sweden)

    Eriseld Krasniqi

    2015-01-01

    Full Text Available Gastric cancer remains one of the most important malignancies worldwide in terms of incidence and mortality. The treatment is based on the combination of local surgery and radiation therapy as well as systemic chemotherapy and targeted molecules. Fluoropyrimidines and particularly 5-fluorouracil (FU represent still the backbone for gastric cancer chemotherapy and new molecular versions of this molecule have been brought to clinical practice in order to improve benefits and reduce adverse effects. S-1 is an oral prodrug of 5-FU, which has demonstrated high effectiveness for gastric cancer treatment and a favorable safety profile. Currently, there are geographic differences in the treatment of gastric cancer and in the use of S-1, which is a mainstay of gastric cancer management in Eastern countries, but is not part of the standard care in the rest of the world. In this review, we gathered data from phase I, II, and III trials of S-1 in gastric cancer, in order to define its real benefit-risk ratio and assess whether geographic differences in S-1 use are justified by unchangeable factors.

  14. Spin diffusion in anisotropic Heisenberg chains: S{>=}1/2

    Energy Technology Data Exchange (ETDEWEB)

    Huber, D.L., E-mail: huber@src.wisc.edu [Physics Department, University of Wisconsin-Madison, 1150 University Avenue, Madison WI 53706 (United States)

    2012-11-01

    In this paper, we investigate spin diffusion in Heisenberg chains with uniaxial nearest-neighbor interactions. The approach followed is based on an analysis of the infinite-temperature longitudinal spin density and spin current correlation functions. For S=1/2, exact results are presented for the time-dependent correlation functions in the XY limit. Away from this limit, the second and fourth moments of the Fourier transform of the spin density correlation function provide information about spin dynamics for arbitrary values of the spin. The moments are used in an assessment of the accuracy of the Gaussian approximation for the spin diffusion constant for S=1/2. The general behavior of the Gaussian approximation when S>1/2 is discussed, and numerical results for the spin diffusion constant are presented for S=1/2, 1, 3/2, 2 and in the classical limit. A moment-based criterion for the boundary in reciprocal space between diffusive and non-diffusive dynamics that applies to arbitrary values of the spin is presented.

  15. 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.

  16. E1, M1, E2 transition energies and probabilities of W$^{54+}$ ions

    CERN Document Server

    Ding, Xiao-bin; Liu, Jia-xin; Koike, Fumihiro; Murakami, Izumi; Kato, Daiji; Sakaue, Hiroyuki A; Nakamura, Nobuyuki; Dong, Chen-zhong

    2016-01-01

    A comprehensive theoretical study of the E1, M1, E2 transitions of Ca-like tungsten ions is presented. Using multi-configuration Dirac-Fock (MCDF) method with a restricted active space treatment, the wavelengths and probabilities of the M1 and E2 transitions between the multiplets of the ground state configuration ([Ne]3s$^{2}$3p$^{6}$3d$^{2}$) and of the E1 transitions between [Ne]3s$^{2}$3p$^{5}$3d$^{3}$ and [Ne]3s$^{2}$3p$^{6}$3d$^{2}$ have been calculated. The results are in reasonable agreement with available experimental data. The present E1 and M1 calculations are compared with previous theoretical values. For E2 transitions, the importance of electron correlation from 3s and 3p orbitals is pointed out. Several strong E1 transitions are predicted, which have potential advantage for plasma diagnostics.

  17. M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.

    Science.gov (United States)

    Nissen, Christoph; Power, Ann E; Nofzinger, Eric A; Feige, Bernd; Voderholzer, Ulrich; Kloepfer, Corinna; Waldheim, Bernhard; Radosa, Marc-Philipp; Berger, Mathias; Riemann, Dieter

    2006-11-01

    Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.

  18. 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

    Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine's discriminative stimulus....... More importantly, we tested the hypothesis that muscarinic receptor agonists with varied receptor subtype selectivity can blunt cocaine's discriminative stimulus and reinforcing effects; we hypothesized a critical role for the M(1) and/or M(4) receptor subtypes in this modulation. Mice were trained...... to discriminate cocaine from saline, or to self-administer intravenous cocaine chronically. The nonselective muscarinic antagonists scopolamine and methylscopolamine, the nonselective muscarinic agonists oxotremorine and pilocarpine, the M(1)/M(4)-preferring agonist xanomeline, the putative M(1)-selective agonist...

  19. Nonlinear {omega}*-stabilization of the m = 1 mode in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, B. [Univ. of Maryland, College Park, MD (United States). Inst. for Plasma Research; Zakharov, L. [Princeton Univ., NJ (United States). Plasma Physics Lab.

    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 {omega}*{sub 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.

  20. M1 AFLATOXIN, TOTAL BACTERIAL COUNT AND SOMATIC CELL COUNT IN ORGANIC AND CONVENTIONAL MILK

    Directory of Open Access Journals (Sweden)

    M. Trevisani

    2009-09-01

    Full Text Available Comparative quality evaluation of organic and conventional milk produced in similar environmental condition was performed. Bulk-tank milk was sampled once a week during 30 weeks from 10 organic and 10 conventional dairy farms where aflatoxin M1 level was previous tested during 11 months on bulk-tank milk from tanker at the processing plant. Somatic Cells and Total Microbial Counts did not show differences that can be related to the organic production system, suggesting an effect induced by farm size and technical factors. Higher level of Aflatoxin M1 was found in organic than conventional milk.

  1. Spatially frustrated S = 1 Heisenberg antiferromagnet with single ion anisotropy

    Science.gov (United States)

    Pires, A. S. T.

    2016-10-01

    Using the SU(3) Schwinger boson formalism, I study the S = 1 square lattice Heisenberg antiferromagnet, at zero temperature, with spatially anisotropic nearest-neighbor couplings frustrated by a next-nearest neighbor interaction and single ion anisotropy. The phase diagram at zero temperature is presented. My calculations show two magnetically ordered phases separated by a quantum-disordered region for all values of the anisotropy.

  2. The Global S_1 Tide in Earth's Nutation

    Science.gov (United States)

    Schindelegger, Michael; Einšpigel, David; Salstein, David; Böhm, Johannes

    2016-05-01

    Diurnal S_1 tidal oscillations in the coupled atmosphere-ocean system induce small perturbations of Earth's prograde annual nutation, but matching geophysical model estimates of this Sun-synchronous rotation signal with the observed effect in geodetic Very Long Baseline Interferometry (VLBI) data has thus far been elusive. The present study assesses the problem from a geophysical model perspective, using four modern-day atmospheric assimilation systems and a consistently forced barotropic ocean model that dissipates its energy excess in the global abyssal ocean through a parameterized tidal conversion scheme. The use of contemporary meteorological data does, however, not guarantee accurate nutation estimates per se; two of the probed datasets produce atmosphere-ocean-driven S_1 terms that deviate by more than 30 μ as (microarcseconds) from the VLBI-observed harmonic of -16.2+i113.4 μ as. Partial deficiencies of these models in the diurnal band are also borne out by a validation of the air pressure tide against barometric in situ estimates as well as comparisons of simulated sea surface elevations with a global network of S_1 tide gauge determinations. Credence is lent to the global S_1 tide derived from the Modern-Era Retrospective Analysis for Research and Applications (MERRA) and the operational model of the European Centre for Medium-Range Weather Forecasts (ECMWF). When averaged over a temporal range of 2004 to 2013, their nutation contributions are estimated to be -8.0+i106.0 μ as (MERRA) and -9.4+i121.8 μ as (ECMWF operational), thus being virtually equivalent with the VLBI estimate. This remarkably close agreement will likely aid forthcoming nutation theories in their unambiguous a priori account of Earth's prograde annual celestial motion.

  3. Recent Development of QCD Factorization for B-> M1 M2

    CERN Document Server

    Yang, Deshan

    2010-01-01

    After briefly introducing the framework of QCD factorization for B-> M1 M2 in the language of the Soft-Collinear Effective Theory, we firstly address the recent efforts on higher-order radiative corrections in QCD factorization. Then we discuss some phenomenologies in B-> V V within the framework of QCD factorization.

  4. 26 CFR 31.3306(m)-1 - American vessel and aircraft.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false American vessel and aircraft. 31.3306(m)-1... vessel and aircraft. (a) The term “American vessel” means any vessel which is documented (that is....) (b) The term “American aircraft” means any aircraft registered under the laws of the United States...

  5. M1 corticospinal mirror neurons and their role in movement suppression during action observation.

    Science.gov (United States)

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N; Kraskov, Alexander

    2013-02-04

    Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation, a property first shown for mirror neurons in monkey premotor cortex. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. A fluorescence anisotropy assay for the muscarinic M1 G-protein-coupled receptor.

    Science.gov (United States)

    Huwiler, Kristin G; De Rosier, Therese; Hanson, Bonnie; Vogel, Kurt W

    2010-06-01

    In the search for new chemical entities that interact with G-proteincoupled receptors (GPCRs), assays that quantify efficacy and affinity are employed. Traditional methods for measuring affinity involve radiolabeled ligands. To address the need for homogeneous biochemical fluorescent assays to characterize orthosteric ligand affinity and dissociation rates, we have developed a fluorescence anisotropy (FA) assay for the muscarinic M1 receptor that can be conducted in a 384-well plate. We used membranes from a muscarinic M1 cell line optimized for high-throughput functional assays and the previously characterized fluorescent antagonist BODIPY FL pirenzepine. The affinities of reference compounds were determined in the competitive FA assay and compared with those obtained with a competitive filter-based radioligand-binding assay using [(3)H] N-methylscopolamine. The IC(50) values produced from the FA assay were well-correlated with the radioligand-binding K(i) values (R(2) = 0.98). The dissociation of the BODIPY FL pirenzepine was readily monitored in real time using the FA assay and was sensitive to the presence of the allosteric modulator gallamine. This M1 FA assay offers advantages over traditional radioligandbinding assays as it eliminates radioactivity while allowing investigation of orthosteric or allosteric muscarinic M1 ligands in a homogeneous format.

  7. Stereospecific reduction of virginiamycin M1 as the virginiamycin resistance pathway in Streptomyces virginiae.

    Science.gov (United States)

    Lee, C K; Minami, M; Sakuda, S; Nihira, T; Yamada, Y

    1996-03-01

    In a cell extract of Streptomyces virginiae, virginiamycin M1 was inactivated in the presence of NADPH, while virginiamycin S remained intact. The inactivated product of virginiamycin M1 was isolated, and structure analysis revealed that the inactivation involves reduction of a C-16 carbonyl group leading to the formation of 16-dihydrovirginiamycin M1. Acetonide and benzylidene acetal derivatives were synthesized from the two hydroxyl groups on C-14 and C-16, and the C-16 stereochemistry was determined by 13C nuclear magnetic resonance spectroscopy. Two methyl groups of the acetonide derivative gave 13C signals of 20.1 and 30.1 ppm, indicating that the relative stereochemistry of the C-14 and C-16 hydroxy groups is syn. Furthermore, irradiation of the benzylidene methine proton gave clear nuclear Overhauser effect enhancement of the C-14 or C-16 methine protons, indicating that H-14 and H-16 were in an axial configuration. From the (14S) absolute configuration of natural virginiamycin M1 and the syn relative configuration for the C-14 and C-16 hydroxyl groups of the inactivated product, the C-16 absolute configuration of the inactivated product was thus identified as R.

  8. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  9. Molecular mechanisms that regulate the macrophage M1/M2 polarization balance

    Directory of Open Access Journals (Sweden)

    Nan eWang

    2014-11-01

    Full Text Available As an essential component of innate immunity, macrophages have multiple functions in both inhibiting or promoting cell proliferation and tissue repair. Diversity and plasticity are hallmarks of macrophages. Classical M1 and alternative M2 activation of macrophages, mirroring the Th1–Th2 polarization of T cells, represent two extremes of a dynamic changing state of macrophage activation. M1-type macrophages release cytokines that inhibit the proliferation of surrounding cells and damage contiguous tissue, and M2-type macrophages release cytokines that promote the proliferation of contiguous cells and tissue repair. M1-M2 polarization of macrophage is a tightly controlled process entailing a set of signaling pathways, transcriptional and posttranscriptional regulatory networks. An imbalance of macrophage M1-M2 polarization is often associated with various diseases or inflammatory conditions. Therefore identification of the molecules associated with the dynamic changes of macrophage polarization and understanding their interactions is crucial for elucidating the molecular basis of disease progression and designing novel macrophage-mediated therapeutic strategies.

  10. 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

  11. Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype

    Science.gov (United States)

    Xue, Nina; Zhou, Qin; Ji, Ming; Jin, Jing; Lai, Fangfang; Chen, Ju; Zhang, Mengtian; Jia, Jing; Yang, Huarong; Zhang, Jie; Li, Wenbin; Jiang, Jiandong; Chen, Xiaoguang

    2017-01-01

    Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage. PMID:28045028

  12. Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

    Science.gov (United States)

    Jiang, Xingwei; Yu, Jiahui; Shi, Qingzhu; Xiao, Yan; Wang, Wei; Chen, Guojiang; Zhao, Zhi; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Wang, Lili; Li, Yan; Han, Gencheng

    2015-10-01

    Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

  13. Experimental Conditions: SE18_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available liver and brain by Orbitrap MS and automated search engine Lipid Search SE18_S2 Mouse brain SE18_S2_M1 10.8...phy. SE18_MS1 Preparation of lipid extract and ESI negative detection by LC-MS analysis SE18_DS1 Identification of phospholipids with Lipid Search default ...

  14. 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.; Voert, M.J.A. te

    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

  15. Experimental Conditions: SE37_S16_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S16 Blank (80% methanol) SE37_S16_M1 0mg [MassBase ID] MDLC1_43484 SE37_MS1 Metabolites extraction... with 80% methanol and analysis by LC-Orbitrap-MS SE37_DS1 Peak extraction for unlabeled data 6|ITMS 2 ...

  16. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  17. Aflatoxin M1 in white cheese and butter consumed in Istanbul, Turkey.

    Science.gov (United States)

    Aycicek, Hasan; Yarsan, Ender; Sarimehmetoglu, Belgin; Cakmak, Omer

    2002-10-01

    We studied the occurrence of Aflatoxin M1 (AFM1) in 183 sample of white cheese and butter in Istanbul, Turkey in 2001. The incidence of AFM1 in white cheese and butter samples was as high as 65 and 81, respectively. The particularly high AFM,concentrations imply that more importance should be given to routine analysis of these dairy products.

  18. Effects on Variations in M1 Generation of Durum Wheat (T. durum Thell by Induced Mutagen

    Directory of Open Access Journals (Sweden)

    O. Bilgin

    2005-01-01

    Full Text Available In this research conducted ın Department of Field Crops, Tekirdağ Agricultural Faculty, TrakyaUniversity, the effect of six different gamma ray doses on plant growth in M1 generations derived from twodurum wheat cultivars was investigated.In the experiment, 10 plants in each pot (17 x 40 cm containing 5 kgsoil were grown with three replicates. Total 30 plants for each treatment were used. In M1 generation, numberof leaves, number of roots, seedling height, seedling weight, leaf weight and germination rate were determined.Application of 100-200 gray gamma ray doses did not have any inhibitory effect on investigated characters inseedling growth of M1 generation. On the other hand, 400-500 gray doses significantly inhibited the plantgrowth. 100-200 gray doses did not affect the seed germination rate whereas germination rate decreased with400-500 gray gamma ray applications. At 600 gray dose, only one seed remained viably, rest of them could notsurvive. It was generally observed the highest variations at 300-400 gray gamma doses in M1 plants.

  19. 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.

  20. Search for ammonia in comet C/2012 S1 (ISON)

    Science.gov (United States)

    Faggi, S.; Codella, C.; Tozzi, G. P.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Brucato, J. R.; Bolli, P.; Massi, F.; Tofani, G.

    2015-12-01

    Comets are uniquely pristine bodies providing unique insights about the formation of our Solar System. In this work, we focus on a dynamically new comet as it enters the inner Solar System for the first time after residing for billion of years in the Oort Cloud. Such comets are particularly important because they are thought to be not differentiated by solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH3(1,1) emission at 23.7 GHz towards comet C/2012 S1 (ISON) using a new dual-feed K band receiver mounted on the Medicina 32-m antenna. We observed the comet close to its perihelion, from 25 to 29 November 2013, when its heliocentric distance changed from 0.25 AU to 0.03 AU. We derive an upper limit of Q(NH3) of about 2.5×1029 mol s-1 on 26 November, that is consistent with the last peak of water production rate of ∼2×1030 mol s-1 within the last few days before the perihelion.

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

    Science.gov (United States)

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

    2016-05-01

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Increased SMA-M1 coherence in Parkinson's disease - Pathophysiology or compensation?

    Science.gov (United States)

    Pollok, Bettina; Kamp, Daniel; Butz, Markus; Wojtecki, Lars; Timmermann, Lars; Südmeyer, Martin; Krause, Vanessa; Schnitzler, Alfons

    2013-09-01

    Parkinson's disease (PD) is a common neurodegenerative disorder owing to loss of dopaminergic cells. Akinesia - one of the core symptoms of PD - is associated with exaggerated oscillations at beta frequency (13-30 Hz) within the subthalamic nucleus (STN). Thus, enhanced oscillations below 30 Hz are assumed to represent a pathophysiological marker of PD. However, recent data suggest that OFF medication exaggerated beta oscillations within basal ganglia (BG) cortical networks may serve for the compensation of BG dysfunctions. The STN is functionally connected to mesial prefrontal areas like the supplementary motor area (SMA). But, it is still not fully understood how enhanced beta oscillations within the BG exert dominance over the primary motor cortex (M1) thereby yielding motor impairment. The present study, therefore, investigates the effect of dopaminergic state on SMA-M1 functional connectivity using Magnetoencephalography (MEG). MEG data were recorded in 7 patients suffering from PD with preponderance of akinesia during isometric contraction of the right forearm and during rest. Coherence as a measure of functional connectivity between M1 and SMA was calculated OFF and ON medication and correlated with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) and with disease duration. During rest a significant positive correlation between disease duration and SMA-M1 coherence was found ON but not OFF medication. Conversely, during isometric contraction SMA-M1 coherence and UPDRS III were inversely correlated OFF but not ON medication explaining more than 80% of variance. The results favor the hypothesis that OFF medication exaggerated cortical coherence at beta frequency represents a compensatory mechanism rather than a pathophysiological marker per se. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Balancing the excitability of M1 circuitry during movement observation without overt replication

    Directory of Open Access Journals (Sweden)

    Pablo eArias

    2014-09-01

    Full Text Available Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE, and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: i electric cervicomedullary stimulation, to test spinal excitability, ii paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition SICI and intracortical facilitation ICF and iii continuous theta-burst stimulation (cTBS, to modulate the excitability of M1cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.

  4. Immunohistochemical localisation of cholinergic muscarinic receptor subtype 1 (M1r) in the guinea pig and human enteric nervous system.

    Science.gov (United States)

    Harrington, A M; Hutson, J M; Southwell, B R

    2007-07-01

    Little is known regarding the location of cholinergic muscarinic receptor 1 (M1r) in the ENS, even though physiological data suggest that M1rs are central to cholinergic neurotransmission. This study localised M1rs in the ENS of the guinea pig ileum and human colon using fluorescence immunohistochemistry and RT-PCR in human colon. Double labelling using antibodies against neurochemical markers was used to identify neuron subytpes bearing M1r. M1r immunoreactivity (IR) was present on neurons in the myenteric and submucosal ganglia. The two antibodies gave similar M1r-IR patterns and M1r-IR was abolished upon antibody preabsorption. M1r-IR was present on cholinergic and nNOS-IR nerve cell bodies in both guinea pig and human myenteric neurons. Presynaptic M1r-IR was present on NOS-IR and VAChT-IR nerve fibres in the circular muscle in the human colon. In the submucosal ganglia, M1r-IR was present on a population of neurons that contained cChAT-IR, but did not contain NPY-IR or calretinin-IR. M1r-IR was present on endothelial cells of blood vessels in the submucosal plexus. The localisation of M1r-IR in the guinea pig and human ENS shown in this study agrees with physiological studies. M1r-IR in cholinergic and nitrergic neurons and nerve fibres indicate that M1rs have a role in both cholinergic and nitrergic transmission. M1r-IR present in submucosal neurons suggests a role in mediating acetylcholine's effect on submucosal sensory and secretomotor/vasodilator neurons. M1r-IR present on blood vessel endothelial cells suggests that M1rs may also mediate acetylcholine's direct effect on vasoactivation.

  5. The Reaction Dynamics of the Reactions Ba+CmH2m+1Br(m=1,2,3,4,5)

    Institute of Scientific and Technical Information of China (English)

    韩克利; 郑锡光; 张瑞勤; 孙本繁; 何国钟; 楼南泉

    1994-01-01

    The internal energy distributions of the nascent BaBr products formed in the reactions ofBa+BrR(R=CH3,C2H5,C3H7,C4H9,C5H11) under the single collision condition have been first studied bylaser-induced fluorescence method.With computer simulations of the experimental spectra,we obtained thevibrational distributions of the BaBr products,and found that the vibrational excitation and reaction cross-section increase with the number of the carbon atoms in the alkyl radical R.The quasitriatomic LEPS poten-tial of the Ba+CH3 reaction has been deduced reversely from the experimental results.The dynamics of thereactions Ba+BrR have been studied by the classical trajectory calculations based on the model LEPS poten-tials.It is concluded that the mass factor and the C-Br bond strength are the major factors affecting the rela-tionship between vibrational excitation and reaction cross-section with the number of the carbon atoms in thealkyl radical R.Furthermore,we obtained all the LEPS potentials of the reactive systems Ba+CmH2m+1 andconfirmed its reliability with ab initio calculations.

  6. [A comparative study of S-1 plus cisplatin and S-1 plus weekly cisplatin for unresectable gastric cancer].

    Science.gov (United States)

    Kemmochi, Takeshi; Egawa, Tomohisa; Sato, Aya; Umakoshi, Tomoko; Ito, Yasuhiro; Nagashima, Atsushi; Makino, Hiroyuki; Yamamuro, Wataru

    2012-11-01

    Clinical efficacy and safety were analyzed in patients with unresectable gastric cancer receiving S-1 plus CDDP(CS) therapy or S-1 plus weekly CDDP (w-CS) therapy as first-line treatment between April 2007 and December 2010. Fifteen patients received CS therapy and 17 received w-CS therapy. CS therapy was used according to the SPIRITS regimen, and w-CS therapy of S-1 80 mg/(m2·day) was administered for 2 weeks followed by a 1-week rest, with CDDP 20 mg/m2 being injected intravenously on days 1 and 8. In the CS therapy group and w-CS therapy group, the overall response rates were 33.3% and 70.1%, the median overall survival periods were 135 and 174 days (p=0.113), and the median follow- up times were 196 and 352 days (p=0.196), respectively. The w-CS therapy group showed less adverse events than did the CS therapy group. This study suggested that the w-CS regimen is a useful treatment modality showing clinical efficacy and safety for unresectable gastric cancer.

  7. 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

  8. FRET-Based Detection of M1 Muscarinic Acetylcholine Receptor Activation by Orthosteric and Allosteric Agonists

    Science.gov (United States)

    Markovic, Danijela; Holdich, Jonathan; Al-Sabah, Suleiman; Mistry, Rajendra; Krasel, Cornelius; Mahaut-Smith, Martyn P.; Challiss, R. A. John

    2012-01-01

    Background and Objective Muscarinic acetylcholine receptors (mAChRs) are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M1 mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET). Methods Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M1 mAChR, respectively. The optimized FRET receptor construct (M1-cam5) was expressed stably in HEK293 cells. Results The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gαq/11 proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M1 FRET (FEYFP/FECFP) that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine. Conclusion The M1 FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a valuable molecular reagent for

  9. FRET-based detection of M1 muscarinic acetylcholine receptor activation by orthosteric and allosteric agonists.

    Directory of Open Access Journals (Sweden)

    Danijela Markovic

    Full Text Available BACKGROUND AND OBJECTIVE: Muscarinic acetylcholine receptors (mAChRs are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M(1 mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET. METHODS: Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M(1 mAChR, respectively. The optimized FRET receptor construct (M(1-cam5 was expressed stably in HEK293 cells. RESULTS: The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gα(q/11 proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M(1 FRET (F(EYFP/F(ECFP that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine. CONCLUSION: The M(1 FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a

  10. QCD corrections to inclusive $\\Delta S=1,2$ transitions

    OpenAIRE

    Jamin, Matthias

    1994-01-01

    The talk summarises a calculation of the two-point functions for $\\Delta S=1$ current-current and QCD-penguin operators, as well as for the $\\Delta S=2$ operator, at the next-to-leading order. The size of the gluonic corrections to current-current operators is large, providing a qualitative understanding of the observed enhancement in $\\Delta I=1/2$ transitions. In the $\\Delta S=2$ sector the QCD corrections are quite moderate ($\\approx -20\\%$). This work has been done in collaboration with A...

  11. New probe of M1 and E1 strengths in GDR regions

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, T. [Japan Atomic Energy Agency and National Astronomical Observatory in Japan (Japan); Ogata, K. [RCNP, Osaka University (Japan); Miyamoto, S.; Mochizuki, T.; Horikawa, K.; Amano, S. [University of Hyogo (Japan); Imazaki, K.; Li, D.; Izawa, Y. [Institute for Laser Technology (Japan); Chiba, S. [Tokyo Institute of Technology (Japan)

    2014-05-02

    The M1 strengths (or level density of 1{sup +} states) are of importance for estimation of interaction strengths between neutrinos and nuclei for the study of the supernova neutrino-process. In 1957, Agodi predicted theoretically angular distribution of neutrons emitted from states excited via dipole transitions with linearly polarized gamma-ray beam at the polar angle of θ=90° should be followed by a simple function, a + b cos(2φ), where φ, is azimuthal angel. However, this theoretical prediction has not been verified over the wide mass region except for light nuclei as deuteron. We have measured neutron angular distributions with (polarized gamma, n) reactions on Au, Nal, and Cu. We have verified the Agodi's prediction for the first time over the wide mass region. This suggests that (polarized gamma, n) reactions may be useful tools to study M1 strengths in giant resonance regions.

  12. 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.

  13. 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.

  14. Extended M1 sum rule for excited symmetric and mixed-symmetry states in nuclei

    CERN Document Server

    Smirnova, N A; Leviatan, A; Ginocchio, J N; Fransen, C

    2002-01-01

    A generalized M1 sum rule for orbital magnetic dipole strength from excited symmetric states to mixed-symmetry states is considered within the proton-neutron interacting boson model of even-even nuclei. Analytic expressions for the dominant terms in the B(M1) transition rates from the first and second $2^+$ states are derived in the U(5) and SO(6) dynamic symmetry limits of the model, and the applicability of a sum rule approach is examined at and in-between these limits. Lastly, the sum rule is applied to the new data on mixed-symmetry states of 94Mo and a quadrupole d-boson ratio $nd(0^+_1)/nd(2^+_2) \\approx 0.6$ is obtained in a largely parameter-independent way

  15. M=1 and 2 gravitational instabilities in gaseous disks; 1, diffuse gas

    CERN Document Server

    Junqueira, S

    1996-01-01

    We report the results of self-gravitating simulations of spiral galaxies, modeled by stellar and gaseous components, developed to investigate in particular the role of dissipation in the evolution of galaxy disks. The gas disk is simulated by the Beam-Scheme method, where it is considered as a self-gravitating fluid. The results suggest that the gravitational coupling between the stars and gas plays a fundamental role in the formation and dissolution of stellar bars, depending on the gaseous mass concentration and on the degree of dissipation. In addition we remark that initially concentrated gas disks can be unstable to the one-armed (m=1) spiral perturbations, which may explain the lopsided features observed in the gas distribution of the late-type isolated galaxies. The development of the m=1 feature slows down the radial gas flows towards the center, since the large-scale gravity torques are then much weaker.

  16. Cholinergic impact on neuroplasticity drives muscarinic M1 receptor mediated differentiation into neurons.

    Science.gov (United States)

    Benninghoff, Jens; Rauh, Werner; Brantl, Victor; Schloesser, Robert J; Moessner, Rainald; Möller, Hans-Jürgen; Rujescu, Dan

    2013-04-01

    Increasing evidence indicates that canonical neurotransmitters act as regulatory signals during neuroplasticity. Here, we report that muscarinic cholinergic neurotransmission stimulates differentiation of adult neural stem cells in vitro. Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in culture with basic fibroblast growth factor (BFGF) and epidermal growth factor (EGF). Carbachol (CCh), an analog of acetylcholine (ACh) significantly enhanced de novo differentiation into neurons on bFGF- and EGF-deprived stem cells as shown by the percentage of TUJ1 positive cells. By contrast, pirenzepine (PIR), a muscarinic M1 receptor antagonist, reduced the generation of neurons. Activation of cholinergic signaling drives the de novo differentiation of uncommitted stem cells into neurons. These effects appear to be predominantly mediated via the muscarinic M1 receptor subtype.

  17. Commercial scale demonstration enhanced oil recovery by miceller-polymer flooding. M-1 project: facilities report

    Energy Technology Data Exchange (ETDEWEB)

    Knight, B.L. (ed.)

    1977-04-01

    ERDA and Marathon Oil Company contracted together for a commercial scale demonstration of enhanced oil recovery by the Maraflood (TM) oil recovery process. This M-1 Project is located within Sections 15, 16, 21 and 22, T6N, R13W, Crawford County, Illinois, encompassing approximately 407 acres of Robinson Sand reservoir developed in the first decade of the century. The area covers portions of several waterfloods developed on 10-acre spacing in the 1950's that were approaching their economic limit. This report describes all M-1 Project facilities, how they were prepared or constructed, their purpose and how they operate: (1) wells (drilling and completion); (2) production facility; (3) injection facility; and (4) various service systems required during project development and/or operation. (48 fig, 7 tables) (DLC).

  18. 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.

  19. THE BULK INPUT M[X]/M/1 QUEUE WITH WORKING VACATIONS

    Institute of Scientific and Technical Information of China (English)

    Xiuli XU; Mingxin LIU; Xiaohua ZHAO

    2009-01-01

    In this paper, we analyze a bulk input M[X]/M/1 queue with multiple working vacations. A quasi upper triangle transition probability matrix of two-dimensional Markov chain in this model is obtained, and with the matrix analysis method, highly complicated probability generating function(PGF) of the stationary queue length is firstly derived, from which we got the stochastic decomposition result for the stationary queue length which indicates the evident relationship with that of the classical M[X]/M/1 queue without vacation. It is important that we find the upper and the lower bounds of the stationary waiting time in the Laplace transform order using the properties of the conditional Erlang distribution. Furthermore, we gain the mean queue length and the upper and the lower bounds of the mean waiting time.

  20. Formation of Polyhydroxyalkanoate Blends by Pseudomonas pseudoalcaligenes M1-2 from Various Carbon Sources

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Pseudomonas pseudoalcaligenes strain M1-2 isolated from oil-contaminated soil collected from an oilfield in northern China was found to be able to synthesize a blend of polyhydroxyalkanoates (PHAs) containing monomers of 3-hydroxybutyrate (C4), 3-hydroxyvalerate (C5), 3-hydroxyheptanoate (C7), 3-hydroxyoctanoate (C8), 3-hydroxynonanoate (C9), 3-hydroxydecanoate (C10) and 3-hydroxydodecanoate (C12) from various carbon sources.The hydroxyalkanoate (HA) monomer composition varied both quantitatively and qualitatively, depending on the carbon sources used.The presence of octanoate in substrates of myristic acid or tridecanoate promoted the synthesis of HB monomer in the blend.Concentration of octanoate was also found to significantly affect the PHB content in the blend.A PHA biosynthesis pathway in Pseudomonas pseudoalcaligens M1-2 was proposed.

  1. Modulating activity of M1 receptor to the reaction of ileal smooth muscle.

    Science.gov (United States)

    Glaza, Izabela; Szadujkis-Szadurski, Leszek; Szadujkis-Szadurski, Rafał; Gajdus, Marta; Olkowska, Joanna

    2011-08-03

    The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M(1) type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M(1) type, pirenzepine. Testing was conducted on tissues isolated from rat's intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963) in Kenakin modification (2006). The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC(50) was calculated for carbachol, amounting to 2.44×10(-6) [M/l]. The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M(1) type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M(1) type receptors occur not only presynaptically, but also postsynaptically.

  2. Modulating activity of M1 receptor to the reaction of ileal smooth muscle

    Directory of Open Access Journals (Sweden)

    Izabela Glaza

    2011-08-01

    Full Text Available Background:The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M1 type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M1 type, pirenzepine.Material/Methods:Testing was conducted on tissues isolated from rat’s intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg. Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963 in Kenakin modification (2006.Results:The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC50 was calculated for carbachol, amounting to 2.44×10–6 [M/l].Conclusions:The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M1 type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M1 type receptors occur not only presynaptically, but also postsynaptically.

  3. Role of M1 receptor in regulation of gastric fundus smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    Marta Gajdus

    2011-09-01

    Full Text Available Background:The subject of this study is determination of the influence of drugs on gastric fundus smooth muscle contraction induced by activation of muscarinic receptors M1. Experiments tested interactions between a receptor agonist, carbachol and muscarinic receptor antagonists, atropine and pirenzepine.Material/Methods:Testing was conducted on tissues isolated from rat’s stomach. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg. The stomach was dissected, and later the gastric fundus was isolated. Tissue was placed in a dish for insulated organs with 20 ml in capacity, filled with Krebs fluid. Results contained in the study are average values ± SE. In order to determine statistical significance, the principles of receptor theory were used (Kenakin modification.Results:According to tests, carbachol, in concentrations ranging between 10–8 M to 10–4 M, in a dosage-dependent way induces gastric fundus smooth muscle contraction. Presented results indicate that carbachol meets the conditions posed to full agonists. On the other hand, atropine, a non-selective muscarinic receptor antagonist, causes a concentration-dependent shift of concentration-effect curve (for carbachol to the right, maintaining maximum reaction. According to analysis of the curve determined, we can deduce that atropine meets the conditions posed to competitive antagonists. The use of pirenzepine, a competitive receptor agonist M1, causes shift of concentration-effect curve (for carbachol to the right, maintaining maximum reaction.Conclusions:From the testing conducted on the preparation of the gastric fundus we can deduce that atropine causes shift of concentration-effect curves for carbachol to the right. A similar effect is released by pirenzepine, selectively blocking muscarinic receptors of M1 type. The results indicate that in the preparation of the gastric fundus smooth muscle, M1 type

  4. Role of M1 receptor in regulation of gastric fundus smooth muscle contraction.

    Science.gov (United States)

    Gajdus, Marta; Szadujkis-Szadurska, Katarzyna; Szadujkis-Szadurski, Leszek; Glaza, Izabela; Szadujkis-Szadurski, Rafał; Olkowska, Joanna

    2011-09-14

    The subject of this study is determination of the influence of drugs on gastric fundus smooth muscle contraction induced by activation of muscarinic receptors M1. Experiments tested interactions between a receptor agonist, carbachol and muscarinic receptor antagonists, atropine and pirenzepine. Testing was conducted on tissues isolated from rat's stomach. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). The stomach was dissected, and later the gastric fundus was isolated. Tissue was placed in a dish for insulated organs with 20 ml in capacity, filled with Krebs fluid. Results contained in the study are average values ± SE. In order to determine statistical significance, the principles of receptor theory were used (Kenakin modification). According to tests, carbachol, in concentrations ranging between 10(-8) M to 10(-4) M, in a dosage-dependent way induces gastric fundus smooth muscle contraction. Presented results indicate that carbachol meets the conditions posed to full agonists. On the other hand, atropine, a non-selective muscarinic receptor antagonist, causes a concentration-dependent shift of concentration-effect curve (for carbachol) to the right, maintaining maximum reaction. According to analysis of the curve determined, we can deduce that atropine meets the conditions posed to competitive antagonists. The use of pirenzepine, a competitive receptor agonist M1, causes shift of concentration-effect curve (for carbachol) to the right, maintaining maximum reaction. From the testing conducted on the preparation of the gastric fundus we can deduce that atropine causes shift of concentration-effect curves for carbachol to the right. A similar effect is released by pirenzepine, selectively blocking muscarinic receptors of M1 type. The results indicate that in the preparation of the gastric fundus smooth muscle, M1 type receptors occur also postsynaptically.

  5. "5M1E"法在生产管理中的运用

    Institute of Scientific and Technical Information of China (English)

    刘秋香

    2010-01-01

    人(man)、机械(machine)、材料(material)、方法(method)、环境(enviroment)、管理(manage)这几个主要环节实行全面质量管理,称为"5M1E"法.在生产管理中应用该法,可以达到提升人品质、提升产品品质,提高员工士气.

  6. Radiationless transitions to atomic M 1,2,3 shells - Results of relativistic theory

    Science.gov (United States)

    Chen, M. H.; Crasemann, B.; Mark, H.

    1983-01-01

    Radiationless transitions filling vacancies in atomic M1, M2, and M3 subshells have been calculated relativistically with Dirac-Hartree-Slater wave functions for ten elements with atomic numbers 67-95. Results are compared with those of nonrelativistic calculations and experiment. Relativistic effects are found to be significant. Limitations of an independent-particle model for the calculation of Coster-Kronig rates are noted.

  7. Study of Mutagenic Effects of M1 Generation of Maize Seeds Irradiated by Heavy Ions

    Institute of Scientific and Technical Information of China (English)

    LUOHong-bing; ZHAOKui; GUOJi-yu; SUILi; NIMei-nan; MEIJun-ping; LUXiu-qin; ZHOUPing; KONGFu-quan; ZHANGGen-fa

    2003-01-01

    In order to study M1 biological effects induced by heavy ion irradiation on maize seeds, the embryos of dry maize seeds are irradiated with 7Li and 12C ions. The experiment is performed at the heavy ion scanning tube of the HI-13 tandem accelerator. The beam goes through a thickness of 25μm. Then the maize seeds are irradiated in the air uniformly.

  8. Cellular stress response in human Müller cells (MIO-M1) after bevacizumab treatment.

    Science.gov (United States)

    Matsuda, Monique; Krempel, Paloma Gava; Marquezini, Mônica Valeria; Sholl-Franco, Alfred; Lameu, Amanda; Monteiro, Mário Luiz R; Miguel, Nádia Campos de Oliveira

    2017-07-01

    Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely used in the treatment of retinal vascular diseases. However, due to the essential role Müller cell derived-VEGF plays in the maintenance of retinal neurons and glial cells, cell viability is likely to be affected by VEGF inhibition. We therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Müller cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium only. Cell viability was determined with the trypan blue exclusion test and MTT assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin content were quantified by immunohistochemistry. Gene expression was evaluated by real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25 and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3 mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with structural protein abnormalities, with decreased GFAP and vimentin content and upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not significantly affect MIO-M1 cell viability, it led to metabolic and molecular changes (apoptosis, autophagy and structural abnormalities) suggestive of significant cellular toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Marcin Poreba

    Full Text Available BACKGROUND: Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. METHODOLOGY/PRINCIPAL FINDINGS: To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. CONCLUSIONS/SIGNIFICANCE: This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment.

  10. Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

    Science.gov (United States)

    Poreba, Marcin; McGowan, Sheena; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Gardiner, Donald L.; Whisstock, James C.; To, Joyce; Salvesen, Guy S.; Dalton, John P.; Drag, Marcin

    2012-01-01

    Background Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. Methodology/Principal Findings To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. Conclusions/Significance This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment. PMID:22359643

  11. A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages

    Science.gov (United States)

    Deng, Huimin; Li, Zhengchao; Tan, Yafang; Guo, Zhaobiao; Liu, Yangyang; Wang, Ye; Yuan, Yuan; Yang, Ruifu; Bi, Yujing; Bai, Yang; Zhi, Fachao

    2016-01-01

    Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B. fragilis, ZY-312, was shown to possess admirable properties, including tolerance to simulated gastric fluid, intestinal fluid and ox bile, and good safety (MOI = 100, 200) and adherent ability (MOI = 100) to LoVo cells. Isolate ZY-312 cell lysate promoted phagocytosis of fluorescent microspheres and pathogenic bacteria in bone marrow-derived macrophage (BMDM) cells. Gene expression of IL-12, iNOS and IL-1β in BMDM cells was increased after treatment with ZY-312, indicating the induction of M1 macrophages, consistent with enhanced secretion of NO. Cell surface expression of CD80 and CD86 was also increased. This study is the first to demonstrate that B. fragilis enhances the phagocytic functions of macrophages, polarising them to an M1 phenotype. Our findings provide insight into the close relationship between B. fragilis and the innate immune system. PMID:27381366

  12. Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.

    Science.gov (United States)

    Zhang, Jun; Chen, Liang; Sun, Yunyun; Li, Yuanhai

    2017-03-17

    Tramadol is an analgesic drug and relieves pain through activating μ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).

  13. Muscarinic M1 receptors regulate propofol modulation of GABAergic transmission in rat ventrolateral preoptic neurons.

    Science.gov (United States)

    Zhang, Yu; Yu, Tian; Liu, Yang; Qian, Kun; Yu, Bu-Wei

    2015-04-01

    GABAergic neurons within the ventrolateral preoptic area (VLPO) play an important role in sleep-wakefulness regulation. Propofol, a widely used systemic anesthetic, has lately been reported to excite noradrenaline (NA)-inhibited type of VLPO neurons. Present study tested if acetylcholine system takes part in the propofol modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat VLPO neurons using a conventional whole-cell patch clamp technique. Propofol reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that propofol acts presynaptically to decrease the probability of spontaneous GABA release. The propofol action on GABAergic mIPSC frequency was completely blocked by atropine, a nonselective muscarinic acetylcholine (mACh) receptor antagonist, and pirenzepine, a selective M1 receptor antagonist. These results suggest that propofol acts on M1 receptors on GABAergic nerve terminals projecting to VLPO neurons to inhibit spontaneous GABA release. The M1 receptor-mediated modulation of GABAergic transmission onto VLPO neurons may contribute to the regulation of loss of consciousness induced by propofol.

  14. Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain.

    Science.gov (United States)

    Wang, Q; Zengin, A; Ying, W; Newell, K A; Wang, P; Yeo, W; Wong, P T-H; Yenari, M A; Huang, X-F

    2008-06-26

    Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [(3)H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [(3)H]pirenzepine binding, predominantly in the prefrontal cortex (171%, Ppirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [(3)H]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors.

  15. The mechanism of the anticancer function of M1 macrophages and their use in the clinic

    Institute of Scientific and Technical Information of China (English)

    Xing-Qing Pan

    2012-01-01

    M1-type macrophages are capable of inducing lysis in various types of cancer cells,but the mechanism of action is unclear.It has been noted that an "unknown protein" produced together with protease by activated macrophages is responsible for this action.Activated M1 macrophages have been recently reported to produce family 18 chitinases,all of which have been named chitotriosidase.Our experiments have demonstrated that family 18 chitinases work together with proteases and can damage various cancer cells both in vitro and in vivo.Thus,in this article,we suggest that the 50-kDa chitotriosidase is the reported "unknown protein".In addition,we discuss how to properly stimulate activated M1 macrophages to produce 50-kDa chitotriosidases and proteases for destroying cancer cells.Because family 19 chitinase has recently been reported to kill cancer cells,we also discuss the possibility of directly using human family 18 chitotriosidase and the humanized plant family 19 chitinase for cancer treatment.

  16. The detection of C60 in the well-characterized planetary nebula M1-11

    CERN Document Server

    Otsuka, Masaaki; Hyung, S; Sargent, B A; Meixner, M; Tajitsu, A; Yanagisawa, K

    2013-01-01

    We performed multiwavelength observations of the young planetary nebula (PN) M1-11 and obtained its elemental abundances, dust mass, and the evolutionary status of the central star. The AKARI/IRC, VLT/VISIR, and Spitzer/IRS spectra show features due to carbon-rich dust, such as the 3.3, 8.6, and 11.3 um features due to polycyclic aromatic hydrocarbons (PAHs), a smooth continuum attributable to amorphous carbon, and the broad 11.5 and 30 um features often ascribed to SiC and MgS, respectively. We also report the presence of an unidentified broad feature at 16-22 um, similar to the feature found in Magellanic Cloud PNe with either C-rich or O-rich gas-phase compositions. We identify for the first time in M1-11 spectral lines at 8.5 (blended with PAH), 17.3, and 18.9 um that we attribute to the C60 fullerene. This identification is strengthened by the fact that other Galactic PNe in which fullerenes are detected, have similar central stars, similar gas-phase abundances, and a similar dust composition to M1-11. T...

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

    Energy Technology Data Exchange (ETDEWEB)

    Guliants, Vadim

    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.

  18. Aflatoxin M1 in raw milk in Qazvin Province, Iran: a seasonal study.

    Science.gov (United States)

    Fallah, Aziz A; Barani, Afshin; Nasiri, Zeinab

    2015-01-01

    Occurrence of aflatoxin M1 (AFM1) was determined in 254 samples of raw milk obtained from dairy cow farms of Qazvin Province, Iran. Aflatoxin M1 analysis was carried out by using the competitive enzyme-linked immunosorbent assay technique for screening and high-performance liquid chromatography with fluorescence detection for confirmatory purposes. The limit of detection and quantification of the confirmatory method were 0.003 and 0.01 µg/l, respectively. Aflatoxin M1 was detected in 204 analysed samples (80.3%), ranging from 0.011 to 0.321 μg/l, and 144 samples (56.7%) had levels above the Iranian national standard limit of 0.050 μg/l. Considering the seasonal variability, the occurrence and levels of AFM1 in samples obtained in winter were significantly higher (P < 0.05) than those obtained in summer. The results of this survey indicate the usefulness of a monitoring programme to supervise food safety for consumers.

  19. 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.

  20. Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors

    NARCIS (Netherlands)

    Schueller, Ulrich; Zhao, Qing; Godinho, Susana A.; Heine, Vivi M.; Medema, Rene H.; Pellman, David; Rowitch, David H.

    2007-01-01

    The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G(2)/M transition of the cell cycle. Here we define specific functions of FoxM1 during brain development by the investigation of FoxM1 loss-of-function mutations in the

  1. 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.

  2. 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

  3. The S1 ← S0 fluorescence excitation spectrum and structure of propanal in the S1 excited electronic state.

    Science.gov (United States)

    Godunov, I A; Yakovlev, N N; Terentiev, R V; Maslov, D V; Abramenkov, A V

    2016-06-01

    We have obtained and analyzed the S1 ← S0 fluorescence excitation spectra of jet-cooled propanal-h1 (CH3CH2CHO) and -d1 (CH3CH2CDO). Using the results of theoretical studies of the structure of propanal molecule in the S1 lowest excited singlet electronic state, we have assigned the bands of both spectra to the vibronic transitions of the cis conformer (in the S0 ground electronic state) to the 1 and 3 conformers (in the S1 state) differed by the angle of the C2H5 ethyl group rotation around the central C-C bond. The origins of the 1 ← cis and 3 ← cis electronic transitions have been observed at 29 997 and 30 075 cm(-1) for propanal-h1 and at 30 040 and 30 115 cm(-1) for propanal-d1, respectively. The high activity of torsional (C2H5 ethyl groups) and inversional (CCHO/CCDO carbonyl fragments) vibrations and the intensity distribution of the bands in torsional sequences (passing through maximum) are in agreement with the theoretical prediction that the S1 ← S0 electronic excitation of the cis conformer causes (after geometrical relaxation) the pyramidalization of carbonyl fragments and the rotation of ethyl groups around the central C-C bond. A number of energy levels have been found for torsional and inversional vibrations, and also fundamentals of ν10 (CCO bend) and ν13 (CCC bend) for the both 1 and 3 conformers of propanal-h1 and -d1 have been found. Then the "experimental" potential functions of inversion for the pair of the 1 and 3 conformers have been determined. The heights of potential barriers to inversion and the angle values corresponding to the minima of potential functions of inversion are 900 cm(-1) and 35° for propanal-h1 and 820 cm(-1) and 34° for propanal-d1, respectively.

  4. A Search for Dilepton Signatures from Minimal Low Energy Supergravity in $\\overline{p}p$ Collisions at $\\sqrt{s} = 1.8 TeV$

    CERN Document Server

    Abbott, B

    2001-01-01

    We report on a search for supersymmetry using the DØ detector. The 1994-96 data sample of $\\sqrt{s}=1.8$ TeV $\\bar{p}p$ collisions was analyzed for events containing two leptons ($e$ or $\\mu$), two or more jets, and missing transverse energy. Assuming minimal supergravity, with free parameters $m_0$, $m_{1/2}$ and $\\tan\\beta$, various thresholds were employed to optimize the search. No excess of events was observed. We present exclusion contours in the $(m_0, m_{1/2})$ plane for $\\tan\\beta=2-6$.

  5. Production of a monoclonal antibody against aflatoxin M1 and its application for detection of aflatoxin M1 in fortified milk

    Directory of Open Access Journals (Sweden)

    Umarphorn Chadseesuwan

    2016-10-01

    Full Text Available Aflatoxin M1 (AFM1 is a toxic metabolite of the fungal product aflatoxin found in milk. For food safety concern, maximum residual limits of AFM1 in milk and dairy products have been differently enforced in many countries. A suitable detection method is required to screen a large number of product samples for the AFM1 contamination. In this study, monoclonal antibodies (MAbs against AFM1 were generated using a conventional somatic cell fusion technique. After screening, five MAbs (AFM1-1, AFM1-3, AFM1-9, AFM1-11, and AFM1-17 were obtained that showed cross-reactivity with aflatoxin B1 (AFB1 and aflatoxin G1 (AFG1 but with no other tested compounds. An indirect competitive enzyme-linked immunosorbent assay (ELISA using a partially purified MAb and antigen-coated plates yielded the best sensitivity with the 50% inhibition concentration (IC50 and the limit of detection (LOD values of 0.13 ng/mL and 0.04 ng/mL, respectively. This indirect competitive ELISA was used to quantify the amount of fortified AFM1 in raw milk. The precision and accuracy in terms of % coefficient of variation (CV and % recovery of the detection was investigated for both intra- (n = 6 and inter- (n = 12 variation assays. The % CV was found in the range of 3.50–15.8% and 1.32–7.98%, respectively, while the % recovery was in the range of 92–104% and 100–103%, respectively. In addition, the indirect ELISA was also used to detect AFM1 fortified in processed milk samples. The % CV and % recovery values were in the ranges of 0.1–33.0% and 91–109%, respectively. Comparison analysis between the indirect ELISA and high performance liquid chromatography was also performed and showed a good correlation with the R2 of 0.992 for the concentration of 0.2–5.0 ng/mL. These results indicated that the developed MAb and ELISA could be used for detection of AFM1 in milk samples.

  6. 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.

  7. Transitive Lie groups on S^1\\times S^{2m}

    Science.gov (United States)

    Gorbatsevich, Vladimir V.

    2007-10-01

    The structure of Lie groups acting transitively on the direct product of a circle and an even-dimensional sphere is described. For products of two spheres of dimension >1 a similar problem has already been solved by other authors. The minimal transitive Lie groups on S^1 and S^{2m} are also indicated. As an application of these results, the structure of the automorphism group of one class of geometric structures, generalized quadrangles (a special case of Tits buildings) is considered. A conjecture put forward by Kramer is proved: the automorphism group of a connected generalized quadrangle of type (1,2m) always contains a transitive subgroup that is the direct product of a compact simple Lie group and a one-dimensional Lie group. Bibliography: 16 titles.

  8. Dynamical instability in the S =1 Bose-Hubbard model

    Science.gov (United States)

    Asaoka, Rui; Tsuchiura, Hiroki; Yamashita, Makoto; Toga, Yuta

    2016-01-01

    We study the dynamical instabilities of superfluid flows in the S =1 Bose-Hubbard model. The time evolution of each spin component in a condensate is calculated based on the dynamical Gutzwiller approximation for a wide range of interactions, from a weakly correlated regime to a strongly correlated regime near the Mott-insulator transition. Owing to the spin-dependent interactions, the superfluid flow of the spin-1 condensate decays at a different critical momentum from a spinless case when the interaction strength is the same. We furthermore calculate the dynamical phase diagram of this model and clarify that the obtained phase boundary has very different features depending on whether the average number of particles per site is even or odd. Finally, we analyze the density and spin modulations that appear in association with the dynamical instability. We find that spin modulations are highly sensitive to the presence of a uniform magnetic field.

  9. Inverse Supersymmetry Breaking in S1 × R3

    Directory of Open Access Journals (Sweden)

    Vasilis Oikonomou

    2010-03-01

    Full Text Available In this paper, we study the influence of hard supersymmetry breaking terms in a N = 1, d = 4 supersymmetric model, in S1 × R3 spacetime topology. It is shown that when the radius of the compact dimension is large supersymmetry is unbroken, and dynamically breaks as the radius decreases. We point out that this resembles the inverse symmetry breaking of continuous symmetries at finite temperature (however, in the case of supersymmetry, the role of the temperature is played by the compact dimension’s radius. Furthermore, we also find a universality in the dependence of the critical length Lc as a function of a coupling g3, after comparing all cases.

  10. S-1 project. Volume I. Architecture. 1979 annual report

    Energy Technology Data Exchange (ETDEWEB)

    1979-01-01

    The US Navy is one of the world's largest users of digital computing equipment having a procurement cost of at least $50,000, and is the single largest such computer customer in the Department of Defense. Its projected acquisition plan for embedded computer systems during the first half of the 80s contemplates the installation of over 10,000 such systems at an estimated cost of several billions of dollars. This expenditure, though large, is dwarfed by the 85 billion dollars which DOD is projected to spend during the next half-decade on computer software, the near-majority of which will be spent by the Navy; the life-cycle costs of the 700,000+ lines of software for a single large Navy weapons systems application (e.g., AEGIS) have been conservatively estimated at most of a billion dollars. The S-1 Project is dedicated to realizing potentially large improvements in the efficiency with which such very large sums may be spent, so that greater military effectiveness may be secured earlier, and with smaller expenditures. The fundamental objectives of the S-1 Project's work are first to enable the Navy to be able to quickly, reliably and inexpensively evaluate at any time what is available from the state-of-the-art in digital processing systems and what the relevance of such systems may be to Navy data processing applications: and second to provide reference prototype systems to support possible competitive procurement action leading to deployment of such systems.

  11. Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.

    Science.gov (United States)

    Li, Zhen; Chen, Weirong; Hale, Jeffrey J; Lynch, Christopher L; Mills, Sander G; Hajdu, Richard; Keohane, Carol Ann; Rosenbach, Mark J; Milligan, James A; Shei, Gan-Ju; Chrebet, Gary; Parent, Stephen A; Bergstrom, James; Card, Deborah; Forrest, Michael; Quackenbush, Elizabeth J; Wickham, L Alexandra; Vargas, Hugo; Evans, Rose M; Rosen, Hugh; Mandala, Suzanne

    2005-10-06

    A class of 3,5-diphenyl-1,2,4-oxadiazole based compounds have been identified as potent sphingosine-1-phosphate-1 (S1P1) receptor agonists with minimal affinity for the S1P2 and S1P3 receptor subtypes. Analogue 26 (S1P1 IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P3 receptor agonism is not a component of immunosuppressive efficacy.

  12. 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.

  13. Effect of pirenzepine, a muscarinic M1 receptor antagonist, on amygdala kindling in rat.

    Science.gov (United States)

    Eşkazan, E; Aker, R; Onat, F; Köseoğlu, S; Gören, M Z; Hasanoğlu, A

    1999-11-01

    Kindling, an animal model of complex partial seizures with secondary generalization, is performed by daily application of low-intensity electrical brain stimulation. The purpose of this study was to investigate the role of muscarinic M1 receptors on amygdala kindling in the rat. Bipolar nichrome stimulation and recording electrodes were stereotaxically implanted into the right and left basolateral amygdala. Extradural recording electrodes were also placed bilaterally in the skull over the cortex. Amygdala stimulation was applied twice daily at the current intensity of afterdischarge threshold. Seizure intensity was graded by using Racine's standard five-stage scale. In the first group of experiments, saline or pirenzepine (10, 25, 50 and 100 nmol), a muscarinic M1 receptor antagonist, was injected intracerebroventricularly 1 h before the electrical stimulation. In the second group of experiments, rats were kindled to full stage 5 seizures. After a recovery period, 50 nmol of pirenzepine was administered intracerebroventricularly to kindled animals. In the first group of experiments, none of the animals pretreated with the doses of 50 and 100 nmol of pirenzepine reached a stage 5 seizure. Pirenzepine significantly retarded kindling seizure development and increased the total number of stimulations required to reach the first stage 5 seizure. Afterdischarge duration was also reduced in the pirenzepine 10 nmol group as compared with that in the saline-pretreated group. In the second group, seizure stage and afterdischarge duration were not affected by pirenzepine in fully-kindled animals. The findings of this study suggest that muscarinic M1 receptors may have a critical role in the development of kindling epileptic activity, but not in already kindled seizures.

  14. Spatio-kinematics of the optical nebula M1-92 with HST/STIS

    Science.gov (United States)

    Ramos-Medina, J.; Sánchez-Contreras, C.; Sahai, R.; Bujarrabal, V.; Castro-Carrizo, A.; Morris, M.

    2014-04-01

    We report optical long-slit spectroscopy with HST/STIS of the well known pre-Planetary Nebula (pPN) M1-92 (a.k.a. Minkowski's footprint). Complementary long-slit echelle spectra obtained with Keck II+ESI have been also used. We have used our high-angular (~0.1arcsec) resolution spectra to characterize the spatio-kinematic structure of the optical nebula of this object. From the analysis of the Halpha two-dimensional profile we identify several distinct nebular components at different spatial scales. The blue-shifted absorption component of the broad 'P cygni'-like profile of the Halpha emission is spatially and spectrally resolved and is found to be composed of not one but two different features centered at Vlsr~-600 and -200 km/s. To assist in the interpretation of the data, we have used a simple spatio-kinematic model which has allowed us to describe the main properties of the fast, bipolar winds (expanding with velocities of up to ~700 km/s) running inside the reflection lobes of M1-92 and that produce the absorptions. At the nebula center, we also discover an equatorially extended H-alpha emitting region that is expanding at moderate velocity (~300 km/s) in the direction perpendicular to the lobes. We have estimated the column density of the inner post-AGB winds and other physical parameters that have helped improving our understanding of the evolutionary history of M1-92.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tokumitsu, Naoki; Sako, Kazuhiro; Aizawa, Shizuka; Shirai, Wakako [Nayoro City Hospital, Hokkaido (Japan)

    2002-07-01

    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)

  16. ISSR Analysis of M_1 Generation of Gladiolus hybridus Hort Treated by EMS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Gladiolus hybridus Hort is one of famous cutting flowers,being famous of big size,bright color,various shapes and long bloom period.New species should be cultivated in order to meet consumers' needs.Mutagenic breeding is a shortcut to cultivate new species of flowers.In this study,corm bud of G.hybridus Hort was treated with different concentrations of EMS.Then M 1 generation was analyzed by ISSR.Results showed that EMS was a very effective mutagenic agent for the corm bud of G.hybridus Hort.With the increa...

  17. 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

  18. Daniel Hertz SA M1落地式音箱

    Institute of Scientific and Technical Information of China (English)

    许成文

    2011-01-01

    Daniel Hertz SA M1落地式音箱在箱体结构上取经典造型。毫无疑问,Daniel Hertz的SAM1落地式音箱甫一亮相干市场,便已经奠定了它作为一代经典作品的基础——这不仅使其采用最经典的前障板布局和单元配置,在更大的程度上还包括它的综合技术内涵。

  19. THE DETECTION OF C60 IN THE WELL-CHARACTERIZED PLANETARY NEBULA M1-11

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Masaaki; Kemper, F. [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 10617, Taiwan (China); Hyung, S. [School of Science Education (Astronomy), Chungbuk National University, CheongJu, Chungbuk 361-763 (Korea, Republic of); Sargent, B. A.; Meixner, M. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Tajitsu, A. [Subaru Telescope, NAOJ, 650 North A' ohoku Place, Hilo, HI 96720 (United States); Yanagisawa, K., E-mail: otsuka@asiaa.sinica.edu.tw [Okayama Astrophysical Observatory (OAO), NAOJ, Kamogata, Okayama 719-0232 (Japan)

    2013-02-10

    We performed multiwavelength observations of the young planetary nebula (PN) M1-11 and obtained its elemental abundances, dust mass, and the evolutionary status of the central star. The AKARI/IRC, VLT/VISIR, and Spitzer/IRS spectra show features due to carbon-rich dust, such as the 3.3, 8.6, and 11.3 {mu}m features due to polycyclic aromatic hydrocarbons (PAHs), a smooth continuum attributable to amorphous carbon, and the broad 11.5 and 30 {mu}m features often ascribed to SiC and MgS, respectively. We also report the presence of an unidentified broad feature at 16-22 {mu}m, similar to the feature found in Magellanic Cloud PNe with either C-rich or O-rich gas-phase compositions. We identify for the first time in M1-11 spectral lines at 8.5 (blended with PAH), 17.3, and 18.9 {mu}m that we attribute to the C{sub 60} fullerene. This identification is strengthened by the fact that other Galactic PNe in which fullerenes are detected have similar central stars, similar gas-phase abundances, and a similar dust composition to M1-11. The weak radiation field due to the relatively cool central stars in these PNe may provide favorable conditions for fullerenes to survive in the circumstellar medium. Using the photoionization code CLOUDY, combined with a modified blackbody, we have fitted the {approx}0.1-90 {mu}m spectral energy distribution (SED) and determined the dust mass in the nebula to be {approx}3.5 Multiplication-Sign 10{sup -4} M {sub Sun }. Our chemical abundance analysis and SED model suggest that M1-11 is perhaps a C-rich PN with C/O ratio in the gas phase of +0.19 dex, and that it evolved from a 1-1.5 M {sub Sun} star.

  20. Scaled-energy spectroscopy of helium \\|M\\|=1 Rydberg atoms in a static electric field

    Science.gov (United States)

    Kips, Annemieke; Vassen, Wim; Hogervorst, Wim; Dando, Paul A.

    1998-10-01

    We present scaled-energy spectra on helium Rydberg atoms in a static electric field. \\|M\\|=1 states were studied in excitation from the 2 1S0 metastable state. Spectra were recorded for ɛ=-2.940(4), ɛ=-2.350(4), both below the saddle point, and ɛ=-1.760(4), above the saddle point. Closed-orbit theory was applied to interpret the spectra. A recent extension to closed-orbit theory, incorporating core effects, was used. This significantly improved agreement between experiment and theory.

  1. Enhancement of M1 Transition Rates at High Spin in 90Mo

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-Guang; YANG Chun-Xiang; LI Guang-Sheng; PENG Zhao-Hua; WEN Shu-Xian; HAN Guang-Bing; LI Cheng-Po; LU Shao-Jun; WU Shao-Yong; YUAN Guan-Jun

    2001-01-01

    High spin states in 90Mo have been populated through the 59Co (35C1,2p2n) 90Mo reaction at a beam energy of116 Me V. Level lifetimes of the positive-parity decay sequence are measured by using the Doppler shift attenuationmethod. It is observed that the M1 transition strengths show a substantial enhancement at high spin. Thisbehaviour may be related to occupation of high Ω orbitals by a pair of g9/2 protons. A deformed, oblate, shapeis suggested above the 13+ state.

  2. 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.

  3. AN M/M/1/N FEEDBACK QUEUING SYSTEM WITH REVERSE BALKING

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2015-06-01

    Full Text Available In this paper we develop an M/M/1/N feedback queuing system with reverse balking. Reverse balking is a type of customer behavior according to which an arriving customer joins a system with high probability if he encounters large system size and vice-versa. This behavior of a customer can be observed in many businesses such as investment. Feedback customer in queuing literature refers to a customer who is unsatisfied with incomplete, partial or unsatisfactory service. We derive the steady-state solution of the model and obtain some important measures of performance. Sensitivity analysis of the model is also performed with respect to the parameters involved.

  4. E1M1 and E1E2 transition probabilities in one-electron ions

    Science.gov (United States)

    Labzowsky, L. N.; Shonin, A. V.

    2004-12-01

    The quantum electrodynamical (QED) theory of the two-photon transitions in hydrogenlike ions is presented. The emission probability for 2s→2γ(E1)+1s transitions is calculated and compared to the results of the previous calculations. The emission probabilities 2p→γ(E1)+γ(E2)+1s and 2p→γ(E1)+γ(M1)+1s are also calculated for the nuclear charge Z values 1⩽Z⩽100. This is the first calculation of the two latter probabilities. The results are given in two different gauges.

  5. STS-34 crewmembers sit in M1-13 APC during emergency egress training at KSC

    Science.gov (United States)

    1989-01-01

    STS-34 crewmembers sit in M1-13 Armored Personnel Carrier (APC) during emergency egress training at KSC's shuttle landing facility (SLF) prior to terminal countdown demonstration test (TCDT) activities. Wearing launch and entry suits (LESs), are (from left) Mission Specialist (MS) Ellen S. Baker, MS Shannon W. Lucid, Commander Donald E. Williams (right side, in back), MS Franklin R. Chang-Diaz, and Pilot Michael J. McCulley (holding headset). View provided by KSC with alternate number KSC-89PC-871.

  6. 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 joi...... 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....

  7. 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.

  8. M1-46: A Case Study on Multiple-Shell Planetary Nebula Formation

    Science.gov (United States)

    Guerrero, M. A.; Manchado, A.; Stanghellini, L.; Herrero, A.

    1996-06-01

    We discuss in detail the evolutionary path of the multiple-shell planetary nebula M1-46, in the light of our new observations. The velocities of the halo and main nebula correspond to a dynamical time lap between the shells of about 6.8 x 104 yr. By means of a non-LTE analysis of the central star's spectrum, we derived a stellar temperature of Teff = 45,000 K, which, coupled to the visual magnitude and an appropriate bolometric correction, gives a stellar luminosity of 5370 Lsun. The mass of the central star has been evaluated to be 0.6 Msun, and its interpulse time on the asymptotic giant branch is 7.6 x 104 yr. The agreement between the observed intershell time lap and the evolutionary interpulse time lap points to the fact that the formation of this planetary nebula could be ascribed to the gasping mass loss associated with the thermal pulses at the thermally pulsating asymptotic giant branch. The high-resolution spatially resolved observations reveal the presence of different kinematical components in the main nebula which cannot be understood in a homogeneous expanding shell scenario. As regards the chemical abundances, M1-46 has the typical abundances of a type II planetary nebula. No definite abundance gradient between the shells is found.

  9. 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

  10. 新加坡M1与Vodafone达成漫游协议

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    为了让经常旅游的客户能够更方便有效地使用数据业务。新加坡M1用户推出了数据漫游业务。用户在Vodafone的网络上进行数据漫游时,将只需支付本地数据资费,从而节省了60%的数据使用费。这一优惠目前可以在8个有Vodafone网络运营的国家实现,今年早些时候将有超过30个国家可以享受到这项服务,包括一些很流行的漫游目的地,如香港、法国、英国、澳大利亚和德国。随着数据漫游资费的推出,M1成为新加坡第一个提供在Vodafone网络上的单一数据漫游资费的移动运营商。

  11. 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.

  12. Determination of aflatoxin M1 levels in Iranian white and cream cheese.

    Science.gov (United States)

    Fallah, Aziz A; Jafari, Tina; Fallah, Ali; Rahnama, Mohammad

    2009-08-01

    A screening survey on the occurrence of aflatoxin M1 (AFM1) was accomplished on 210 cheese samples composed of white cheese (116 samples) and cream cheese (94 samples) purchased from popular markets in central part of Iran (Esfahan and Yazd provinces). The quantitative analysis of AFM1 levels in the samples was performed by using the competitive enzyme-linked immunosorbent assay (ELISA) technique. Aflatoxin M1 at measurable level (50 ng/kg) was detected in 161 (76.6%) samples, consisting of 93 (80.1%) white and 68 (72.3%) cream cheese samples. The concentration of AFM1 in the samples ranged from 52.1 to 785.4 ng/kg. Comparing to legal regulation (250 ng/kg) accepted by some of the countries, 24.2% of the samples exceeded the accepted limit. Among these, the AFM1 levels in 28.4% of white and 19.1% of cream cheese samples were not in accordance with the safety limit. The results indicated that contamination of the samples with AFM1 in such a level appear to be a potential hazard for public health. This paper represents the data of the first survey on the occurrence of AFM1 in cheeses consumed in central part of Iran.

  13. Pirenzepine Promotes the Dimerization of Muscarinic M1 Receptors through a Three-step Binding Process*

    Science.gov (United States)

    Ilien, Brigitte; Glasser, Nicole; Clamme, Jean-Pierre; Didier, Pascal; Piemont, Etienne; Chinnappan, Raja; Daval, Sandrine B.; Galzi, Jean-Luc; Mely, Yves

    2009-01-01

    Ligand binding to G protein-coupled receptors is a complex process that involves sequential receptor conformational changes, ligand translocation, and possibly ligand-induced receptor oligomerization. Binding events at muscarinic acetylcholine receptors are usually interpreted from radioligand binding studies in terms of two-step ligand-induced receptor isomerization. We report here, using a combination of fluorescence approaches, on the molecular mechanisms for Bodipy-pirenzepine binding to enhanced green fluorescent protein (EGFP)-fused muscarinic M1 receptors in living cells. Real time monitoring, under steady-state conditions, of the strong fluorescence energy transfer signal elicited by this interaction permitted a fine kinetic description of the binding process. Time-resolved fluorescence measurements allowed us to identify discrete EGFP lifetime species and to follow their redistribution upon ligand binding. Fluorescence correlation spectroscopy, with EGFP brightness analysis, showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. Finally, all these experimental data could be quantitatively reconciled into a three-step mechanism, with four identified receptor conformational states. Fast ligand binding to a peripheral receptor site initiates a sequence of conformational changes that allows the ligand to access to inner regions of the protein and drives ligand-receptor complexes toward a high affinity dimeric state. PMID:19451648

  14. Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor.

    Science.gov (United States)

    Tahtaoui, Chouaib; Parrot, Isabelle; Klotz, Philippe; Guillier, Fabrice; Galzi, Jean-Luc; Hibert, Marcel; Ilien, Brigitte

    2004-08-12

    Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains. Copyright 2004 American Chemical Society

  15. Pirenzepine promotes the dimerization of muscarinic M1 receptors through a three-step binding process.

    Science.gov (United States)

    Ilien, Brigitte; Glasser, Nicole; Clamme, Jean-Pierre; Didier, Pascal; Piemont, Etienne; Chinnappan, Raja; Daval, Sandrine B; Galzi, Jean-Luc; Mely, Yves

    2009-07-17

    Ligand binding to G protein-coupled receptors is a complex process that involves sequential receptor conformational changes, ligand translocation, and possibly ligand-induced receptor oligomerization. Binding events at muscarinic acetylcholine receptors are usually interpreted from radioligand binding studies in terms of two-step ligand-induced receptor isomerization. We report here, using a combination of fluorescence approaches, on the molecular mechanisms for Bodipy-pirenzepine binding to enhanced green fluorescent protein (EGFP)-fused muscarinic M1 receptors in living cells. Real time monitoring, under steady-state conditions, of the strong fluorescence energy transfer signal elicited by this interaction permitted a fine kinetic description of the binding process. Time-resolved fluorescence measurements allowed us to identify discrete EGFP lifetime species and to follow their redistribution upon ligand binding. Fluorescence correlation spectroscopy, with EGFP brightness analysis, showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. Finally, all these experimental data could be quantitatively reconciled into a three-step mechanism, with four identified receptor conformational states. Fast ligand binding to a peripheral receptor site initiates a sequence of conformational changes that allows the ligand to access to inner regions of the protein and drives ligand-receptor complexes toward a high affinity dimeric state.

  16. Molecular Probes for Muscarinic Receptors: Derivatives of the M1-Antagonist Telenzepine

    Science.gov (United States)

    Karton, Yishai; Baumgold, Jesse; Handen, Jeffrey S.; Jacobson, Kenneth A.

    2012-01-01

    Functionalized congeners of the M1-selective muscarinic antagonist telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno[3,4–b][1,5]benzodiazepin-10-one) were developed and found to bind to the receptor with affinities (Ki values) in approximately the nanomolar range. The derivatives contain a 10-aminodecyl group, which provides a nucleophilic functionality for further derivatization. The attachment of a spacer chain to the distal piperazinyl nitrogen was based on previous findings of enhanced affinity at muscarinic receptors in an analogous series of alkylamino derivatives of pirenzepine [J. Med. Chem. (1991) 34, 2133–2145]. The telenzepine derivatives contain prosthetic groups for radioiodination, protein cross-linking, photoaffinity labeling, and fluorescent labeling and biotin for avidin complexation. The affinity for muscarinic receptors in rat forebrain (mainly m1 subtype) was determined in competitive binding assays vs [3H]-N-methylscopolamine. A (p-aminophenyl)-acetyl derivative for photoaffinity labeling had a Ki value of 0.29 nM at forebrain muscarinic receptors (16-fold higher affinity than telenzepine). A biotin conjugate displayed a Ki value of 0.60 nM at m2-receptors and a 5-fold selectivity versus forebrain. The high affinity of these derivatives makes them suitable for the characterization of muscarinic receptors in pharmacological and spectroscopic studies, for peptide mapping, and for histochemical studies. PMID:1520727

  17. 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

    2017-05-01

    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.

  18. 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.

  19. 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.

  20. The Truth-Telling Motor Cortex: Response Competition in M1 Discloses Deceptive Behaviour

    Directory of Open Access Journals (Sweden)

    Aviad A. Hadar

    2011-05-01

    Full Text Available Recent studies have suggested that circuits associated with response conflict and response inhibition are strongly implicated in deception. Using single-pulse transcranial magnetic stimulation (TMS, we examined whether conflict between competing responses in primary motor cortex (M1 can be used for discriminating between intentionally false and true facial recognition. Participants used little finger and thumb key-presses to lie or tell the truth regarding their familiarity with a series of famous and nonfamous faces. Single-pulse TMS was administered to M1 at three intervals prior to response execution in order to evoke motor evoked potentials (MEPs in both Abductor Digiti Minimi (ADM and first dorsal interosseous (FDI of the right hand. As predicted, we found that the MEP of the nonresponding digit was greater than the MEP of the responding digit when participants prepared to engage in deception, while a mirror-reversed pattern was observed for truth telling. This effect did not interact with the stimulation interval suggesting consistent activation of the motor plan representing the truth throughout the response preparation process. We discuss these results with reference to models of response selection and procedures for the detection of deception.

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

    Science.gov (United States)

    Tabar, Emre; Yakut, Hakan; Kuliev, Ali Akbar

    2017-01-01

    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 229-233Th and 233-239U 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 228-232Th and 232-238U nuclei. For 235U 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.

  2. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets.

    Science.gov (United States)

    Fuchs, Ann-Kathrin; Syrovets, Tatiana; Haas, Karina A; Loos, Cornelia; Musyanovych, Anna; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

    2016-04-01

    Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.

  3. Selecting against S1P3 enhances the acute cardiovascular tolerability of 3-(N-benzyl)aminopropylphosphonic acid S1P receptor agonists.

    Science.gov (United States)

    Hale, Jeffrey J; Doherty, George; Toth, Leslie; Mills, Sander G; Hajdu, Richard; Keohane, Carol Ann; Rosenbach, Mark; Milligan, James; Shei, Gan-Ju; Chrebet, Gary; Bergstrom, James; Card, Deborah; Forrest, Michael; Sun, Shu-Yu; West, Sarah; Xie, Huijuan; Nomura, Naomi; Rosen, Hugh; Mandala, Suzanne

    2004-07-01

    Structurally modified 3-(N-benzylamino)propylphosphonic acid S1P receptor agonists that maintain affinity for S1P1, and have decreased affinity for S1P3 are efficacious, but exhibit decreased acute cardiovascular toxicity in rodents than do nonselective agonists.

  4. Involvement of an Arginine Triplet in M1 Matrix Protein Interaction with Membranes and in M1 Recruitment into Virus-Like Particles of the Influenza A(H1N1)pdm09 Virus

    Science.gov (United States)

    Moncorgé, Olivier; Panthu, Baptiste; Prchal, Jan; Décimo, Didier; Ohlmann, Théophile; Lina, Bruno; Favard, Cyril; Decroly, Etienne; Ottmann, Michèle; Roingeard, Philippe; Muriaux, Delphine

    2016-01-01

    The influenza A(H1N1)pdm09 virus caused the first influenza pandemic of the 21st century. In this study, we wanted to decipher the role of conserved basic residues of the viral M1 matrix protein in virus assembly and release. M1 plays many roles in the influenza virus replication cycle. Specifically, it participates in viral particle assembly, can associate with the viral ribonucleoprotein complexes and can bind to the cell plasma membrane and/or the cytoplasmic tail of viral transmembrane proteins. M1 contains an N-terminal domain of 164 amino acids with two basic domains: the nuclear localization signal on helix 6 and an arginine triplet (R76/77/78) on helix 5. To investigate the role of these two M1 basic domains in influenza A(H1N1)pdm09 virus molecular assembly, we analyzed M1 attachment to membranes, virus-like particle (VLP) production and virus infectivity. In vitro, M1 binding to large unilamellar vesicles (LUVs), which contain negatively charged lipids, decreased significantly when the M1 R76/77/78 motif was mutated. In cells, M1 alone was mainly observed in the nucleus (47%) and in the cytosol (42%). Conversely, when co-expressed with the viral proteins NS1/NEP and M2, M1 was relocated to the cell membranes (55%), as shown by subcellular fractionation experiments. This minimal system allowed the production of M1 containing-VLPs. However, M1 with mutations in the arginine triplet accumulated in intracellular clusters and its incorporation in VLPs was strongly diminished. M2 over-expression was essential for M1 membrane localization and VLP production, whereas the viral trans-membrane proteins HA and NA seemed dispensable. These results suggest that the M1 arginine triplet participates in M1 interaction with membranes. This R76/77/78 motif is essential for M1 incorporation in virus particles and the importance of this motif was confirmed by reverse genetic demonstrating that its mutation is lethal for the virus. These results highlight the molecular

  5. A Method for Measuring the $6S_{1/2} \\leftrightarrow 5D_{3/2}$ Magnetic Dipole Transition Moment in {Ba}$^{+}$

    CERN Document Server

    Williams, Spencer R; Hoffman, Matthew R; Blinov, Boris B; Fortson, E N

    2013-01-01

    We propose a method for measuring the magnetic dipole (M1) transition moment of the $6S_{1/2} \\big(\\mathrm{m}=-1/2\\big)\\leftrightarrow 5D_{3/2}\\big(\\mathrm{m}=-1/2\\big)$ transition in single trapped Ba$^{+}$ by exploiting different symmetries in the electric quadrupole (E2) and M1 couplings between the states. The technique is adapted from a previously proposed method for measuring atomic parity nonconservation in a single trapped ion [Norval Fortson, Phys. Rev. Lett. \\textbf{70}, 17 (1993)]. Knowledge of M1 is crucial for any parity nonconservation measurement in Ba$^{+}$, as laser coupling through M1 can mimic the parity-violating signal. The magnetic moment for the transition has been calculated by atomic theory and found to be dominated by electron-electron correlation effects [B.K. Sahoo et. al., Phys. Rev. A \\textbf{74}, 6 (2006)]. To date the value has not been verified experimentally. This proposed measurement is therefore an essential step toward a parity nonconservation experiment in the ion that wi...

  6. Involvement of Sphingosine 1-Phosphate (S1P) Receptor Type 1 and Type 4 in Migratory Response of Mouse T Cells toward S1P

    Institute of Scientific and Technical Information of China (English)

    Hirofumi Matsuyuki; Yasuhiro Maeda; Kazuhiro Yano; Kunio Sugahara; Kenji Chiba; Takayuki Kohno; Yasuyuki Igarashi

    2006-01-01

    Sphingosine 1-phosphate (S1P), a pleiotropic lysophospholipid, regulates signal transduction pathway via Gprotein-coupled receptors termed S1P1-5 in several types of the cells including lymphocytes. Higher levels of S1P4 mRNA as well as S1P1 mRNA are expressed in lymphoid tissues such as the spleen, thymus, lymph nodes, and Payer's patches. In contrast to S1P1 that plays an essential role in lymphocyte egress, little is known about the role of S1P4 in immune system. In this study, we found that S1P at 10 to 100 nM significantly induced the cell migration and the significant levels of S1P1 and S1P4 mRNA were expressed in mouse CD4 T cells, D10.G4.1 mouse Th2 cells,and EL-4.IL-2 mouse thymoma cells. In D10.G4.1 and EL-4.IL-2 cells, S1P-induced migration was almost completely inhibited by pretreatment with pertussis toxin, Clostoridium difficile toxin B, and (S)-enantiomer of FTY720-phosphate, a potent agonist at S1P1 and S1P4. The members of the Rho family small GTPase, Cdc42 and Rac were activated by S1P stimulation in these cells. The transfection with dominant negative or constitutively active forms of Cdc42 and Rac revealed that the activation of both Cdc42 and Rac is essential for S1P-induced migration of these cells. The immunoprecipitation assays using CHO cells co-expressing both S1P4 and S1P1 receptors indicated that S1P4 and S1P1 are associated on the cell surface. These results suggest that the association of S1P4 and S1P1 plays an important role in migratory response of mouse T cells toward S1P.

  7. Confinement on $R^{3}\\times S^{1}$: continuum and lattice

    CERN Document Server

    Ogilvie, Michael C

    2014-01-01

    There has been substantial progress in understanding confinement in a class of four-dimensional SU(N) gauge theories using semiclassical methods. These models have one or more compact directions, and much of the analysis is based on the physics of finite-temperature gauge theories. The topology $R^{3}\\times S^{1}$ has been most often studied, using a small compactification circumference $L$ such that the running coupling $g^{2}\\left(L\\right)$ is small. The gauge action is modified by a double-trace Polyakov loop deformation term, or by the addition of periodic adjoint fermions. The additional terms act to preserve $Z(N)$ symmetry and thus confinement. An area law for Wilson loops is induced by a monopole condensate. In the continuum, the string tension can be computed analytically from topological effects. Lattice models display similar behavior, but the theoretical analysis of topological effects is based on Abelian lattice duality rather than on semiclassical arguments. In both cases the key step is reducin...

  8. Will Comet ISON (C/2012 S1) Survive Perihelion?

    Science.gov (United States)

    Knight, Matthew M.; Walsh, Kevin J.

    2013-10-01

    On 2013 November 28 Comet ISON (C/2012 S1) will pass by the Sun with a perihelion distance of 2.7 solar radii. Understanding the possible outcomes for the comet's response to such a close passage by the Sun is important for planning observational campaigns and for inferring ISON's physical properties. We present new numerical simulations and interpret them in context with the historical track record of comet disruptions and of sungrazing comet behavior. Historical data suggest that sizes below ~200 m are susceptible to destruction by sublimation driven mass loss, while we find that for ISON's perihelion distance, densities lower than 0.1 g cm-3 are required to tidally disrupt a retrograde or non-spinning body. Such low densities are substantially below the range of the best-determined comet nucleus densities, though dynamically new comets such as ISON have few measurements of physical properties. Disruption may occur for prograde rotation at densities up to 0.7 g cm-3, with the chances of disruption increasing for lower density, faster prograde rotation, and increasing elongation of the nucleus. Given current constraints on ISON's nucleus properties and the typically determined values for these properties among all comets, we find tidal disruption to be unlikely unless other factors (e.g., spin-up via torquing) affect ISON substantially. Whether or not disruption occurs, the largest remnant must be big enough to survive subsequent mass loss due to sublimation in order for ISON to remain a viable comet well after perihelion.

  9. Will Comet ISON (C/2012 S1) Survive Perihelion?

    CERN Document Server

    Knight, Matthew M

    2013-01-01

    On 2013 November 28 Comet ISON (C/2012 S1) will pass by the Sun with a perihelion distance of 2.7 solar radii. Understanding the possible outcomes for the comet's response to such a close passage by the Sun is important for planning observational campaigns and for inferring ISON's physical properties. We present new numerical simulations and interpret them in context with the historical track record of comet disruptions and of sungrazing comet behavior. Historical data suggest that sizes below ~200 m are susceptible to destruction by sublimation driven mass loss, while we find that for ISON's perihelion distance, densities lower than 0.1 g cm^-3 are required to tidally disrupt a retrograde or non-spinning body. Such low densities are substantially below the range of the best-determined comet nucleus densities, though dynamically new comets such as ISON have few measurements of physical properties. Disruption may occur for prograde rotation at densities up to 0.7 g cm^-3, with the chances of disruption increas...

  10. The human Müller cell line MIO-M1 expresses opsins.

    Science.gov (United States)

    Hollborn, Margrit; Ulbricht, Elke; Rillich, Katja; Dukic-Stefanovic, Sladjana; Wurm, Antje; Wagner, Lysann; Reichenbach, Andreas; Wiedemann, Peter; Limb, Gloria Astrid; Bringmann, Andreas; Kohen, Leon

    2011-01-01

    To determine whether the human Müller cell line Moorfields/Institute of Ophthalmology-Müller 1 (MIO-M1) expresses opsins. The gene expression of opsins was determined by reverse-transcription PCR (RT-PCR). The presence of opsin proteins was determined by western blotting and immunocytochemistry. The light sensitivity of the cells was examined with imaging experiments using the calcium-sensitive dye Fluo-4. MIO-M1 cells express glial (glutamine synthase [GLUL], vimentin [VIM], glial fibrillary acidic protein [GFAP], cellular retinaldehyde-binding protein [RLBP1], glial high-affinity glutamate transporter [SLCA1], aquaporin-4 [AQP4], inwardly rectifying potassium channel Kir4.1 [Kir4.1]), neuronal (Thy-1 cell surface antigen [THY1], heavy neurofilament polypeptide [NEFH], microtubule-associated protein 2 [MAP2], neurogenic differentiation 1 [NEUROD1], neuronal nuclei [NEUN]), and neural progenitor markers (Nestin [NES], paired-type homeobox transcription factor [PAX6], neurogenic locus notch homolog 1 [NOTCH1]). The cells contain mRNA for the following opsins: blue opsin (OPN1SW), rhodopsin (OPN2), panopsin (OPN3), melanopsin (OPN4), neuropsin (OPN5), and peropsin (RRH), as well as for the transducins (guanine nucleotide binding protein [GNAZ], alpha transducing activity polypeptide 1 [GNAT1], alpha transducing activity polypeptide 2 [GNAT2]). The presence of blue opsin and melanopsin was confirmed with immunocytochemistry and western blotting. The immunoreactivity and mRNA of red-green opsin were found in some but not all cultures, while the immunoreactivity for rhodopsin was absent in all cultures investigated. Repetitive stimulation with 480 nm light evoked slow and fast transient calcium responses in the majority of cells investigated, while irradiation with 600 nm light was ineffective. The human Müller cell line MIO-M1 expresses opsins. This suggests immortalized Müller cells could be used as a cellular source to produce human opsins for their potential

  11. State-dependent and timing-dependent bidirectional associative plasticity in the human SMA-M1 network.

    Science.gov (United States)

    Arai, Noritoshi; Müller-Dahlhaus, Florian; Murakami, Takenobu; Bliem, Barbara; Lu, Ming-Kuei; Ugawa, Yoshikazu; Ziemann, Ulf

    2011-10-26

    The supplementary motor area (SMA-proper) plays a key role in the preparation and execution of voluntary movements. Anatomically, SMA-proper is densely reciprocally connected to primary motor cortex (M1), but neuronal coordination within the SMA-M1 network and its modification by external perturbation are not well understood. Here we modulated the SMA-M1 network using MR-navigated multicoil associative transcranial magnetic stimulation in healthy subjects. Changes in corticospinal excitability were assessed by recording motor evoked potential (MEP) amplitude bilaterally in a hand muscle. We found timing-dependent bidirectional Hebbian-like MEP changes during and for at least 30 min after paired associative SMA-M1 stimulation. MEP amplitude increased if SMA stimulation preceded M1 stimulation by 6 ms, but decreased if SMA stimulation lagged M1 stimulation by 15 ms. This associative plasticity in the SMA-M1 network was highly topographically specific because paired associative stimulation of pre-SMA and M1 did not result in any significant MEP change. Furthermore, associative plasticity in the SMA-M1 network was strongly state-dependent because it required priming by near-simultaneous M1 stimulation to occur. We conclude that timing-dependent bidirectional associative plasticity is demonstrated for the first time at the systems level of a human corticocortical neuronal network. The properties of this form of plasticity are fully compatible with spike-timing-dependent plasticity as defined at the cellular level. The necessity of priming may reflect the strong interhemispheric connectivity of the SMA-M1 network. Findings are relevant for better understanding reorganization and potentially therapeutic modification of neuronal coordination in the SMA-M1 network after cerebral lesions such as stroke.

  12. Sphingosine 1 Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Osteoblast Migration Through S1P Activation of Complementary Kinase Pathways

    DEFF Research Database (Denmark)

    Quint, Patrick; Ruan, Ming; Pederson, Larry

    2013-01-01

    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) stem cell (MSC) chemotaxis. S1P treatment of MSC activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1...... metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed osteoclasts produce the chemokine sphingosine 1 phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts...

  13. Irreducible Modular Representations of the Reflection Group G(m,1,n

    Directory of Open Access Journals (Sweden)

    José O. Araujo

    2015-01-01

    Full Text Available In an article published in 1980, Farahat and Peel realized the irreducible modular representations of the symmetric group. One year later, Al-Aamily, Morris, and Peel constructed the irreducible modular representations for a Weyl group of type Bn. In both cases, combinatorial methods were used. Almost twenty years later, using a geometric construction based on the ideas of Macdonald, first Aguado and Araujo and then Araujo, Bigeón, and Gamondi also realized the irreducible modular representations for the Weyl groups of types An and Bn. In this paper, we extend the geometric construction based on the ideas of Macdonald to realize the irreducible modular representations of the complex reflection group of type G(m,1,n.

  14. 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.

  15. Occurrence of aflatoxin M(1) in dairy products in southern Italy.

    Science.gov (United States)

    Montagna, Maria Teresa; Napoli, Christian; De Giglio, Osvalda; Iatta, Roberta; Barbuti, Giovanna

    2008-12-01

    A screening survey of the presence of aflatoxin M(1) (AFM(1)) 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. AFM(1) 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 AFM(1) 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 AFM(1) threshold limits for dairy products is still lacking.

  16. Excretion of Aflatoxin M1 in milk of goats fed diet contaminated by Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Gianni Battacone

    2010-01-01

    Full Text Available An experiment was carried out to study the excretion of aflatoxin M1(AFM1 in milk of three goats fed a single dose (0.8mg/head of pure aflatoxin B1 (AFB1. The values of AFM1 concentration excreted in milk was highly variable among goats, even if the pattern of excretion over time was very similar among the three animals. AFM1 was first detected at the milking performed 1h after the AFB1 administration. The highest values of AFM1 concentration in milk were reached 3 and 6h after the AFB1 intake. The trend of clearance of AFM1 in milk over time was expressed by a decreasing exponential equation. AFM1 concentration was below the EU maximum allowed level (50 ng/L in milk collected 36 h after the AFB1 administration.

  17. Robinson-Schensted-Knuth Correspondence and Weak Polynomial Identities of M1,1(E)

    Institute of Scientific and Technical Information of China (English)

    Onofrio Mario Di Vincenzo; Roberto La Scala

    2005-01-01

    In this paper, it is proved that the ideal Iω of the weak polynomial identities of the superalgebra M1,1(E) is generated by the p roper polynomials [x1,x2, x3] and [x2,x1][xa,x1][x4, x1]. This is proved for any infinite field F of characteristic different a basis and the dimension of any multihomogeneous component of the quotient algebra B/(B ∩ Iw). We also compute the Hilbert series of this algebra. One of the main tools of this paper is a variant we found of the Robinson-Schensted-Knuth correspondence defined for single semistandard tableaux of double shape.

  18. Solvent affects the conformation of virginiamycin M1 (pristinamycin IIA, streptogramin A).

    Science.gov (United States)

    Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2004-10-21

    The streptogramins are antibiotics which act by binding two different components at separate nearby sites on the bacterial 50S ribosome, inhibiting protein synthesis. The first component, a macrolactone, is common to many of the streptogramin antibiotics and, thus, is referred to by many names including virginiamycin M1(VM1), pristinamycin IIA, ostreogrycin A and streptogramin A. X-Ray crystallographic studies of VM1 bound to ribosomes and to a deactivating enzyme show a different conformation to that of VM1 in chloroform solution. We now report the results of high resolution 2D NMR experiments that show that the conformation of VM1 in dimethyl sulfoxide and methanol differs from both that in chloroform solution and in the bound form. The 3D structure and the 1H NMR and 13C NMR chemical shifts of VM1 in dimethyl sulfoxide and methanol are described.

  19. RAPD Analysis of M1 Generation of Gladiolus hybridus Hort Treated by EMS

    Institute of Scientific and Technical Information of China (English)

    WANG Jingang; GUO Ying; CHE Daidi; LIU Shenkui; YANG Chuanpin

    2009-01-01

    Gladiolus hybridus Hort is one of the world's famous cutting flowers. It is very popular because of the big size, bright color, various shape, and long period of bloom. New species should be cultivated in order to meet the consumers' need of asking for the new. Among the technologies of cultivating new species of flowers, mutagenic breeding is a shortcut. This study treated corm bud of G. hybridus Hort with EMS of different consistency. Then M1 after treated was analyzed by RAPD. The result showed that EMS was a very effective mutagenic agent for the corm bud of G. hybridus Hort. With the increase of consistency, the mutagenic range increased first, then decreased, among which 0.6% EMS treatment had the biggest influence. However, with the same EMS consistency, there was not close relevancy between the amount of mutagenic agent and the divergence of plant's genomes, which offered a molecular basis for selecting plants with good mutation.

  20. 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.

  1. 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.

  2. The M/M/1 Queue with Controlled Multiple Working Vacations

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-bo; FENG Ping-hua

    2013-01-01

    In this paper,we study an M/M/1 queue with multiple working vacations under following Bernoulli control policy:at the instants of the completion of a service in vacation,the server will interrupt the vacation and enter regular busy period with probabiiity1-p (if there are customers in the queue) or continue the vacation with probability p.For this model,we drive the analytic expression of the stationary queue length and demonstrate stochastic decomposition structures of the stationary queue length and waiting time,also we obtain the additional queue length and the additional delay of this model.The results we got agree with the corresponding results for working vacation model with or without vacation interruption if we set p =0 or p =1,respectively.

  3. Detection of Aflatoxin M1 in Milk from Qom (Aried and Semiaried Province of Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Dakhili

    2016-06-01

    Full Text Available Background: Aflatoxins are secondary metabolites fungal When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin hydrolyzed and changed to the aflatoxin M1 and transmit to the milk consumers. Methods: seventy milk samples from different milk producers who were selling their milk to the dairy plant during two season in winter and summer and investigated by Enzyme Linked Immuno Sorbent Assay (ELISA. Results: AFM1 was found in 100% of the milk samples in winter. About 15% of the samples had AFM1 greater than the maximum tolerance limit (50ng/l accepted by European Union. Mean concentrations of AFM1 in Winter, Summer were 122, 53 ng/L, respectively. Mean concentrations of AFM1 in winter and Summer samples were significantly higher (P<0.05. Conclusion: these results show that the important of periodically monitoring the occurrence of AFM1 in raw milk and dairy products in Qom province.

  4. Fluid queues driven by an M/M/1/N queue

    Directory of Open Access Journals (Sweden)

    R. B. Lenin

    2000-01-01

    Full Text Available In this paper, we consider fluid queue models with infinite buffer capacity which receives and releases fluid at variable rates in such a way that the net input rate of fluid into the buffer (which is negative when fluid is flowing out of the buffer is uniquely determined by the number of customers in an M/M/1/N queue model (that is, the fluid queue is driven by this Markovian queue with constant arrival and service rates. We use some interesting identities of tridiagonal determinants to find analytically the eigenvalues of the underlying tridiagonal matrix and hence the distribution function of the buffer occupancy. For specific cases, we verify the results available in the literature.

  5. Scaled-energy spectroscopy of a |M|=1 Rydberg barium atom in an electric field

    Institute of Scientific and Technical Information of China (English)

    Wang Lei; Quan Wei; Shen Li; Yang Hai-Feng; Shi Ting-Yun; Liu Xiao-Jun; Liu Hong-Ping; Zhan Ming-Sheng

    2009-01-01

    We observe strong energy-dependent quantum defects in the scaled-energy Stark spectra for |M|=1 Rydberg states of barium atoms at three scaled energies: ε= -2.000, ε= -2.500 and ε=-3.000. In an attempt to explain the observations, theoretical calculations of closed orbit theory based on a model potential including core effect are performed for non-hydrogenic atoms. While such a potential has been uniformly successful for alkali atoms with a single valence electron, it fails to match experimental results for barium atoms in the 6snp Rydberg states with two valence electrons. Our study points out that this discrepancy is due to the strong perturbation from the 5d8p state, which voids the simple approximation for constant quantum defects of principle quantum number n.

  6. Remarks on the BRST-cohomology for $c_M > 1$ matter coupled to ``Liouville gravity"

    CERN Document Server

    Bilal, Adel

    1992-01-01

    We describe the (chiral) BRST-cohomology of matter with central charge $10$) and ghost-numbers 0 or $-1$ (for $r<0$). The (chiral) ground ring is isomorphic to a subring of the $c_M =1$ theory which is $(xy)^n,\\ n=0,1,2,\\ldots$, and there are {\\it no} non-trivial currents acting on the ground ring. In case b) there is no non-trivial relative cohomology for non-zero ghost numbers and, for zero ghost number, the cohomology groups are isomorphic to a $(D-1)$-dimensional on-shell ``transverse" Fock space. The only exceptions are at level 1 for vanishing matter momentum and $p_L=Q_L(1+r)$ with $r=\\pm 1$, where one has one more ghost-number zero and a ghost-number $r$ cohomology state. All these results follow quite easily from the existing literature.

  7. BRST cohomology ring in $\\widehat{c}_{M}$ $<$ 1 NSR string theory

    CERN Document Server

    Panda, S; Panda, Sudhakar; Roy, Shibaji

    1995-01-01

    The full cohomology ring of the Lian-Zuckerman type operators (states) in {\\hat c_M}<1 Neveu-Schwarz-Ramond (NSR) string theory is argued to be generated by three elements x, y and w in analogy with the corresponding results in the bosonic case. The ground ring generators x and y are non-invertible and belong to the Ramond sector whereas the higher ghost number operators are generated by an invertible element w with ghost number one less than that of the ground ring generators and belongs to either Neveu-Schwarz (NS) or Ramond (R) sector depending on whether we consider (even, even) or (odd, odd) series coupled to 2d supergravity. We explicitly construct these operators (states) and illustrate our result with an example of pure Liouville supergravity.

  8. The Matrix protein M1 from influenza C virus induces tubular membrane invaginations in an in vitro cell membrane model

    Science.gov (United States)

    Saletti, David; Radzimanowski, Jens; Effantin, Gregory; Midtvedt, Daniel; Mangenot, Stéphanie; Weissenhorn, Winfried; Bassereau, Patricia; Bally, Marta

    2017-01-01

    Matrix proteins from enveloped viruses play an important role in budding and stabilizing virus particles. In order to assess the role of the matrix protein M1 from influenza C virus (M1-C) in plasma membrane deformation, we have combined structural and in vitro reconstitution experiments with model membranes. We present the crystal structure of the N-terminal domain of M1-C and show by Small Angle X-Ray Scattering analysis that full-length M1-C folds into an elongated structure that associates laterally into ring-like or filamentous polymers. Using negatively charged giant unilamellar vesicles (GUVs), we demonstrate that M1-C full-length binds to and induces inward budding of membrane tubules with diameters that resemble the diameter of viruses. Membrane tubule formation requires the C-terminal domain of M1-C, corroborating its essential role for M1-C polymerization. Our results indicate that M1-C assembly on membranes constitutes the driving force for budding and suggest that M1-C plays a key role in facilitating viral egress. PMID:28120862

  9. Sequence Characterization of matrix protein (M1 in influenza A viruses (H1, H3 and H5

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2011-10-01

    Full Text Available This study brings the analysis of amino acid sequences of matrix protein (M1 from the influenza virus A (H1N1, H3N2 and H5N1 during 2007-2208. 741 sequences of M1 were compared, of them, H1N1 388; H3N2 251 and H5N1 102. Even though, the M1 is relatively conserved among the influenza A viruses, we found some variations in the M1 among the viruses, H1N1, H3N2 and H5N1. The nuclear localization signal at amino acid 101 to 105 is RKLKR for H1N1 and H3N2, but for H5N1 is KKLKR. All differences of amino acid in M1 of H1, H3 and H5 were listed. 80 sequences of M1 of H1N1 H3N2 and H5N1 were used for phylogenetic analysis. There is no reasontantment found in the M1 among these subtypes. Further study is needed to study the differences of the function of M1 among H1N1, H3N2 and H5N1. The M1 of H5N1 may contribute to the high pathogenesis to this virus.

  10. Seasonal milk contamination by aflatoxin m1, organophosphates and carbamates in Paraná – Brazil

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Crispim de Oliveira Ramos

    2016-08-01

    Full Text Available Aiming to evaluate the milk contamination in the dairy production systems (DPS for mycotoxins and chemical residues of organophosphates and carbamates it was made a study encompassing 96 DPS in three regions of Parana state. There were collected samples of milk, water and food and they were evaluated for chemical residues in all samples and aflatoxin only for food and milk. Mycotoxins in food (aflatoxin B1, B2, G1, G2, zearalenone and ochratoxin were detected by the method of thin layer chromatography – TLC and for the determination of aflatoxin M1 was used an immunoassay kit competitive ELISA Ridascreen®. The residues of organophosphates and carbamates were performed by colorimetric method qualitatively. There were evaluated the differences between regions, periods and the sources of mycotoxin contamination. Carbamates and organophosphates were screened for their presence in milk and the sources of food and water. Then it was estimated the contributions of each mycotoxin for milk contamination, as well as their respective contaminated food. Differences were found between periods (p < 0,05 for milk contamination with aflatoxin M1 – AFM1. For carbamates and organophosphates were found different contamination sources (p < 0,01. For the carbamates the source were pesticides used to parasitic herd control and for the organophosphates pesticides used in agriculture. For food sources contamination resulting in the AFM1 contamination it was detected that aflatoxin B1 – AFB1 was the main source. The aflatoxin G1 – AFG1 showed a strong correlation (p < 0,01 with AFB1 levels suggesting causal relationship is a function of fungal strains producing both at the same time. It was also found the prevalence of aflatoxin contamination in 70% of contaminated samples and its predominant presence in relation to other mycotoxins in all kinds of foods analyzed. By identifying the checkpoints of contamination can be proposed the inclusion of practical

  11. 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.

  12. 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

  13. The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew.

    Science.gov (United States)

    Cottriall, C L; McBrien, N A

    1996-06-01

    To determine the efficacy of the M1-selective muscarinic antagonist, pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew. Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either pirenzepine (17.7 mumol; n = 9) or vehicle control (n = 6). Control groups (n = 6) were used to assess the effects of MD, injection regimen, and drug effects. In sham-injected and saline-injected MD tree shrews, 12 days of MD produced-13.2 D +/- 0.8 D and -14.1 D +/- 0.5 D of axial myopia, respectively. In pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only -2.1 D +/- 1.4 D. The significant reduction in myopia in pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm +/- 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm +/- 0.02 mm and 0.29 mm +/- 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in pirenzepine-injected MD tree shrews (P Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia. Control experiments demonstrated that pirenzepine did not cause a significant reduction in amplitude of carbachol-induced accommodation. Findings demonstrate that chronic administration of the M1-selective muscarinic antagonist, pirenzepine, prevents experimentally induced myopia in this mammalian model by a nonaccommodative mechanism.

  14. Paracoccin Induces M1 Polarization of Macrophages via Interaction with TLR4

    Science.gov (United States)

    Freitas, Mateus S.; Oliveira, Aline F.; da Silva, Thiago A.; Fernandes, Fabrício F.; Gonçales, Relber A.; Almeida, Fausto; Roque-Barreira, Maria C.

    2016-01-01

    The fungal human pathogen Paracoccidioides brasiliensis contains paracoccin (PCN), a multi-domain protein that has lectin and N-acetyl-glucosaminidase activities, which account for its effects on the growth and morphogenesis of the fungus and on the activation of host macrophages through its interaction with TLR N-glycans. With the purpose of detailing the knowledge on the effects of PCN on macrophages, we used recombinant PCN expressed in Pichia pastoris (p-rPCN) to stimulate isolated murine peritoneal macrophages. The activation of these cells manifested through the release of high levels of inflammatory mediators, such as nitric oxide, TNF-α, IL-12p40, and IL-6. Furthermore, peritoneal macrophages stimulated with p-rPCN increased the relative expression of STAT1, SOCS3, and iNOS2 mRNA (M1 polarization markers). However, the expression of Arginase-1, Ym-1, and FIZZ1 (M2 polarization markers) remained at basal levels. Interestingly, the observed M1 macrophages’ polarization triggered by p-rPCN was abolished in cells obtained from knockout Toll-like receptor-4 mice. In this case, the p-rPCN-induced production of pro-inflammatory mediators was blocked too. These results demonstrate that the classical activation of macrophages induced by paracoccin depends on TLR4. Taken together, the results of our study indicate that paracoccin acts as a TLR agonist able to modulate immunity and exerts biological activities that favor its applicability as an immunotherapeutic agent to combat systemic fungal infections. PMID:27458431

  15. Composition of breccia matrices from the Manson M-1 drill core

    Science.gov (United States)

    Kracher, A.; Anderson, R. R.; Koeberl, C.

    1994-07-01

    Eleven drill cores were recently recovered from the Manson, Iowa, impact structure. Core M-1, which was drilled at the edge of the large central uplift, contains three major impact rock types: sedimentary clast breccia, melt matrix breccia, and fragmental breccia. Breccia matrices from different depths in the M-1 core were investigated by defocused beam electron probe microanalysis. To obtain average compositions, matrix areas free of lithic and mineral clasts were covered with an orthogonal grid of analyses points. Variations in composition have two main causes: differences in source lithology and postimpact processes. With increasing depth distinct changes in composition can be observed. All compositions are highly feldspathic and surprisingly low in SiO2 for putative source lithologies of mostly granitic composition. Within the lithological units containing melt matrix breccia increasing recrystallization can be observed with depth. Compositions in this interval are marginally corundum normative and not as high in normative feldspar as other matrices. The thoroughly recrystallized matrices from the lowest intervals of the melt matrix breccia are more feldpathic, higher in Na/K ratio, and not corundum normative. Unlike the chemical variation between rock types, we tentatively ascribe the chemical changes within the melt matrix breccia to reaction of matrix with clasts. In particular, quartz clasts in breccias with highly recrystallized matrices develop fringes of K-spar, cpx, and ilmenite. The formation of these minerals is presumably accompanied by complementary changes in matrix composition. Factor analysis on data sets of individual melt matrix analyses provides further clues to the influence of source lithology and post impact processes respectively in the chemical makeup of the breccia matrices. The most significant factors are a mafic component and a plagioclase component.

  16. Distant and new mutations in CTX-M-1 beta-lactamase affect cefotaxime hydrolysis.

    Science.gov (United States)

    Pérez-Llarena, Francisco José; Kerff, Frédéric; Abián, Olga; Mallo, Susana; Fernández, María Carmen; Galleni, Moreno; Sancho, Javier; Bou, Germán

    2011-09-01

    The CTX-M β-lactamases are an increasingly prevalent group of extended-spectrum β-lactamases (ESBL). Point mutations in CTX-M β-lactamases are considered critical for enhanced hydrolysis of cefotaxime. In order to clarify the structural determinants of the activity against cefotaxime in CTX-M β-lactamases, screening for random mutations was carried out to search for decreased activity against cefotaxime, with the CTX-M-1 gene as a model. Thirteen single mutants with a considerable reduction in cefotaxime MICs were selected for biochemical and stability studies. The 13 mutated genes of the CTX-M-1 β-lactamase were expressed, and the proteins were purified for kinetic studies against cephalothin and cefotaxime (as the main antibiotics). Some of the positions, such as Val103Asp, Asn104Asp, Asn106Lys, and Pro107Ser, are located in the (103)VNYN(106) loop, which had been described as important in cefotaxime hydrolysis, although this has not been experimentally confirmed. There are four mutations located close to catalytic residues-Thr71Ile, Met135Ile, Arg164His, and Asn244Asp-that may affect the positioning of these residues. We show here that some distant mutations, such as Ala219Val, are critical for cefotaxime hydrolysis and highlight the role of this loop at the top of the active site. Other distant substitutions, such as Val80Ala, Arg191, Ala247Ser, and Val260Leu, are in hydrophobic cores and may affect the dynamics and flexibility of the enzyme. We describe here, in conclusion, new residues involved in cefotaxime hydrolysis in CTX-M β-lactamases, five of which are in positions distant from the catalytic center.

  17. 乳品中黄曲霉毒素M1检测方法研究进展%Review on detection methods of aflatoxin M1 in dairy products

    Institute of Scientific and Technical Information of China (English)

    黄亚伟; 魏光; 王若兰; 罗莉

    2014-01-01

    Aflatoxin M1 is the metabolite of aflatoxin B1 after being intaken by animals. It mainly appears in animals’ milk and urine. Aflatoxin M1 is very toxic, ingestion of which by dairy will produce a great harm to the human body. This paper focused on the toxicity, hazards, and detection methods of aflatoxin M1 in dairy. The main characteristics and scope of the detection methods were analyzed and summarized, and the develop-ment of detection of aflatoxin M1 were also reasonably prospected.%黄曲霉毒素M1是动物摄入黄曲霉毒素B1后的代谢产物,主要分布在动物的乳汁、尿液中。黄曲霉毒素 M1毒性很大,经乳制品摄入会对人体产生巨大的危害。本文主要对乳品中黄曲霉毒素 M1毒性、危害、检测方法进行综述。对主要检测方法的特性及适用范围进行分析与概括,并且对未来黄曲霉毒素M1的检测方法的发展进行了合理展望。

  18. 叉头框蛋白 M1在乳腺癌的进展及治疗耐药中的作用%The role of FoxM1 in the development and treatment of breast cancer

    Institute of Scientific and Technical Information of China (English)

    李蕙颖(综述); 耿敬姝(审校)

    2016-01-01

    FoxM1 is a specific transcription factor related to proliferation .Previous studies have found that FoxM1 can enhance the proliferation ,metastasis and invasion of cancer cells ,and play a crucial role in canc-er.Recent studies indicate that the abnormal expression of FoxM 1 plays an important role in breast cancer ,and its overexpression is negatively correlated with the overall survival of patients .For the early diagnosis of breast canc-er,clinical prognosis and study on combination therapy provides a new direction .This article reviews the relation-ship between FoxM1 and breast cancer .%叉头框蛋白质M1(Forkhead box protein M1,FoxM1)是一种特异性的与增殖相关的转录因子。既往研究发现,FoxM1具有增强癌细胞增殖、转移和侵袭的功能,在肿瘤的发生发展中扮演着至关重要的角色。近年来研究表明,FoxM1的异常表达在乳腺癌的发生及发展中起着重要的作用,且其过表达与肿瘤患者的总生存期的关系呈负相关,为乳腺癌的早期诊断、临床预后及联合治疗提供了新的研究方向,本文就FoxM1与乳腺癌的关系做一综述。

  19. The preparation of milkpowder contaminated with aflatoxin M1. Investigations of the homogeneity and stability of the product

    NARCIS (Netherlands)

    Egmond; H.P.van; Sizoo; E.A.

    1984-01-01

    Ten behoeve van BCR werd een hoeveelheid melkpoeder bereid, langs natuurlijke weg besmet met aflatoxine M1 op een niveau van ca. 1 mug/kg. Onderzoek naar de homogeniteit van het materiaal wees uit dat aflatoxine M1 homogeen verdeeld was over de geproduceerde melkpoeder. Voorts bleek dat beware

  20. Observations of Post-flare Plasma Dynamics during an M1.0 Flare in AR11093 by SDO/AIA

    CERN Document Server

    Srivastava, Abhishek K

    2011-01-01

    We observe the motion of cool and hot plasma in a multi-stranded post flare loop system that evolved in the decay phase of a two ribbon M1.0 class flare in AR 11093 on 7 August 2010 using SDO/AIA 304 \\AA\\ and 171 \\AA\\ filters. The moving intensity feature and its reflected counterpart are observed in the loop system at multi-temperature. The observed hot counterpart of the plasma that probably envelopes the cool confined plasma, moves comparatively faster ($\\sim$34 km s$^{-1}$) to the later (29 km s$^{-1}$) in form of the spreaded intensity feature. The propagating plasma and intensity reflect from the region of another footpoint of the loop. The subsonic speed of the moving plasma and associated intensity feature may be most likely evolved in the post flare loop system through impulsive flare heating processes. Complementing our observations of moving multi-temperature intensity features in the post flare loop system and its reflection, we also attempt to solve two-dimensional ideal magnetohydrodynamic equat...

  1. Nuclear export of the influenza virus ribonucleoprotein complex: Interaction of Hsc70 with viral proteins M1 and NS2.

    Science.gov (United States)

    Watanabe, Ken; Shimizu, Teppei; Noda, Saiko; Tsukahara, Fujiko; Maru, Yoshiro; Kobayashi, Nobuyuki

    2014-01-01

    The influenza virus replicates in the host cell nucleus, and the progeny viral ribonucleoprotein complex (vRNP) is exported to the cytoplasm prior to maturation. NS2 has a nuclear export signal that mediates the nuclear export of vRNP by the vRNP-M1-NS2 complex. We previously reported that the heat shock cognate 70 (Hsc70) protein binds to M1 protein and mediates vRNP export. However, the interactions among M1, NS2, and Hsc70 are poorly understood. In the present study, we demonstrate that Hsc70 interacts with M1 more strongly than with NS2 and competes with NS2 for M1 binding, suggesting an important role of Hsc70 in the nuclear export of vRNP.

  2. F-box protein FBXL2 inhibits gastric cancer proliferation by ubiquitin-mediated degradation of forkhead box M1.

    Science.gov (United States)

    Li, Liang-qing; Pan, Dun; Chen, Hui; Zhang, Lin; Xie, Wen-jun

    2016-02-01

    F-box/LRR-repeat protein 2 (FBXL2), a component of Skp-Cullin-F box (SCF) ubiquitin E3 ligase, has been shown to inhibit tumorigenesis by targeting and ubiquitinating several oncoproteins. However, its role in gastric cancer remains poorly understood. Here, by tandem mass spectrometry, we show that FBXL2 interacts with forkhead box M1 (FoxM1) transcription factor. As a result, FBXL2 promotes ubiquitination and degradation of FoxM1 in gastric cancer cells. Furthermore, overexpression of FBXL2 inhibits, while its deficiency promotes cell proliferation and invasion. Expression levels of cell-cycle regulators (Cdc25B and p27), which are down-stream target effectors of FoxM1, are also regulated by FBXL2. Therefore, our results uncover a previous unknown network involving FBXL2 and FoxM1 in the regulation of gastric cancer growth.

  3. Targeting Rac1 signaling inhibits streptococcal M1 protein-induced CXC chemokine formation, neutrophil infiltration and lung injury.

    Directory of Open Access Journals (Sweden)

    Songen Zhang

    Full Text Available Infections with Streptococcus pyogenes exhibit a wide spectrum of infections ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome (STSS. The M1 serotype of Streptococcus pyogenes is most commonly associated with STSS. In the present study, we hypothesized that Rac1 signaling might regulate M1 protein-induced lung injury. We studied the effect of a Rac1 inhibitor (NSC23766 on M1 protein-provoked pulmonary injury. Male C57BL/6 mice received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein-induced neutrophil infiltration, edema formation and tissue injury in the lung. M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1 protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition markedly decreased M1 protein-evoked formation of CXC chemokines in the lung. Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. We conclude that these novel results suggest that Rac1 signaling is a significant regulator of neutrophil infiltration and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be a potent strategy to attenuate streptococcal M1 protein-triggered acute lung damage.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Dose Measurements on the BION-M1 satellite applying passive detector packages

    Science.gov (United States)

    Stradi, Andrea; Berger, Thomas; Kodaira, Satoshi; Kubancak, Jan; Palfalvi, Jozsef K.; Ambrozova, Iva; Tolochek, Raisa; Shurshakov, Vyacheslav; Szabo, Julianna

    A passive detector package was developed in the past years in the Centre for Energy Research, Hungarian Academy of Science to detect cosmic ray particles, to determine their flux and dose. It consists of thermoluminescent detectors (TLD) and plastic solid state nuclear track detectors (SSNTD). In the frame of a scientific co-operation between the Institute for Biomedical Problems (IBMP) fourteen packages were flow within the new BION-M1 satellite program together with biological samples and detector packages from other participants. Two packages were located outside and the rest ones inside the recoverable capsule. Comparing to the previous BION and similar FOTON experiments, (all together 17 successful ones), this flight was a “champion” with the highest altitude (575 km), orbital inclination (64.9°) and flight duration (30 days). The external exposure provided a unique possibility to study not only the elevated level of cosmic rays but also the behavior of the detector packages in extreme circumstances as low temperature and pressure. The paper will summarize the construction of the detector packages, the calibration and evaluation processes, as well as, the linear energy transfer (LET) spectra, the absorbed dose and the mean quality factor. These quantities will be compared taking into consideration their location inside and outside the capsule and to the results of other participants. Also some comparison of results to the previous BION and FOTON flights and contemporary measurements on the ISS will be presented.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. DETECTION OF AFLATOXIN M1 IN BULK-TANK MILK AND SHEEP CHEESE

    Directory of Open Access Journals (Sweden)

    F. Cossu

    2011-01-01

    Full Text Available The Aflatoxin M1 (AFM1 content in 118 bulk-tank sheep milk samples was evaluated using an ELISA commercial kit. During a lactation, three bulk-tank milk samples were collected from each of 40 semi-extensive farms, selected on the basis of high level of concentrate supplementation as risk factor for exposure to Aflatoxin B1 (AFB1. The AFM1 content was also determined in 38 sheep cheese samples collected from a dairy plant where the farms enrolled in the survey shipped the milk. In the three sampling the concentrate supplementation recorded in the farms ranged between (mean±sd 492.2±257.7 and 397.7±214.3. AFM1 was detected in 1 bulk-tank sheep milk sample (0.8% at concentrations as little as 5.2 ng/L while in 117 it was not detectable (<5 ng/L. AFM1 was also detected in 5 (13.2% out of 38 samples of ripened sheep cheese at levels (mean±sd of 58.1±7.8 ng/Kg. A very low AFM1 content in bulk mik and cheese was observed, as the result of the implementation of good agricultural and good farming practices.

  9. Enhanced spectrofluorimetric determination of aflatoxin M1 in liquid milk after magnetic solid phase extraction

    Science.gov (United States)

    Hashemi, Mahdi; Taherimaslak, Zohreh; Rashidi, Somayeh

    2014-07-01

    A simple and sensitive method using magnetic solid phase extraction (MSPE) followed by spectrofluorimetric detection has been developed for separation and determination of aflatoxin M1 (AFM1) in liquid milk. The method is based on the extraction of AFM1 on the modified magnetic nanoparticles (MMNPs) and subsequent derivatization of extracted AFM1 to AFM1 hemi-acetal derivative (AFM2a) by reaction with trifluoroacetic acid (TFA) for spectrofluorimetric detection. Magnetic nanoparticles (MNPs) coated by 3-(trimethoxysilyl)-1-propantiol (TMSPT) and modified with 2-amino-5-mercapto-1,3,4-thiadiazole (AMT) were used as adsorbent in MSPE procedure. Influential parameters affecting the extraction efficiency were investigated and optimized. Under the optimum conditions the calibration curve for AFM1 determination showed good linearity in the range 0.030-10.0 μg L-1 (R2 = 0.9991). The repeatability and reproducibility (RSD%) for 0.050 μg L-1 of AFM1 were 4.5% and 5.3%, respectively and limit of detection limit (S/N = 3) was estimated to be 0.010 μg L-1. The developed method was successfully applied for extraction of AFM1 from spiked liquid milk and natural contaminated liquid milk. The good spiked recoveries ranging from 91.6% to 96.1% were obtained. The results demonstrated that the developed method is simple, inexpensive, accurate and remarkably free from interference effects.

  10. Microwave Emission of Supra-arcade Structure associated with M1.6 Limb Flare

    CERN Document Server

    Kim, Sujin; Shibasaki, Kiyoto; Reznikova, Veronika

    2012-01-01

    We have investigated a supra-arcade structure, associated with an M1.6 flare, which occurred on the south-east limb on 4th of November 2010. It is observed in microwaves at 17 GHz with the Nobeyama Radioheliograph (NoRH), soft X-rays in the range of 8-20 keV with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI), and EUV with the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO). As reported by Reeves & Golub (2011), the supra-arcade structure is observed predominantly in the AIA 131 {\\AA} channel, which contains a hot 11 MK component from Fe XIX (Boerner et al. 2011). While this hot flare plasma lasts over the decay phase of the flare, it shows some interesting characteristics in microwaves and soft X-rays: 1) In the supra-arcade structure, the brightness temperature (TB) of the microwave emission increases gradually up to 2\\times10^4 K, and 2) two soft X-ray sources appear: one cospatial with the supra-arcade structure and another above the post-flare arcade...

  11. Green pigment from Bacillus cereus M(1)(16) (MTCC 5521): production parameters and antibacterial activity.

    Science.gov (United States)

    Banerjee, Debopam; Chatterjee, Sandipan; Banerjee, U C; Guha, Arun K; Ray, Lalitagauri

    2011-07-01

    A bacterial strain, Bacillus cereus M(1)(16) (MTCC 5521), isolated and identified in our laboratory produces a green pigment when grown in nutrient broth at stationary condition. Optimum fermentation parameters for maximum pigment production are pH 7.0, temperature 30°C, time of incubation 72 h and inoculum volume 1% from 20 h grown cell suspension. Magnesium ion enhances pigment production whereas calcium and zinc ions inhibit the process. The pigment is better extracted from the fermented broth with chloroform in comparison with diethyl ether, ethyl acetate, and butanol. The extracted crude pigment consists of three fractions as revealed from thin layer chromatogram on silica gel GF254 using ethyl acetate and hexane (1:1) solvent system. The major fraction C(3) shows antibacterial activity against different gram positive bacteria. The proposed structure of C(3) is 9-methyl-1,4,5,8-tetra-azaphenanthrene obtained by elemental analysis, GC-MS, and NMR spectra studies.

  12. Development of ultrasensitive direct chemiluminescent enzyme immunoassay for determination of aflatoxin M1 in milk.

    Science.gov (United States)

    Vdovenko, Marina M; Lu, Chuan-Chen; Yu, Feng-Yih; Sakharov, Ivan Yu

    2014-09-01

    A direct competitive chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) for detecting aflatoxin M1 (AFM1) was developed. To improve the sensitivity of the assay, a mixture of 3-(10'-phenothiazinyl)-propane-1-sulfonate (SPTZ) and 4-morpholinopyridine (MORPH) was used to enhance peroxidase-induced CL. The concentrations of the coating anti-AFM1 antibody and the conjugate of AFB1 with horseradish peroxidase the conditions of the chemiluminescent assay were varied to optimise the condition of the chemiluminescent assay. The lower detection limit values and dynamic working range of CL-ELISA of AFM1 were 0.001 ng mL(-1) and 0.002-0.0075 ng mL(-1), respectively. A 20-fold dilution of milk samples prevented a matrix effect of the milk and allowed measurement of AFM1 at concentrations below than the maximum acceptable limit. Values of recovery within and between assays were 81.5-117.6% and 86-110.6%, respectively. The results of using the developed CL-ELISA to analyse samples of six brands of milk that were purchased in Taiwan revealed that AFM1 was absent from all studied samples.

  13. Enzyme-assisted extraction for the HPLC determination of aflatoxin M1 in cheese.

    Science.gov (United States)

    Pietri, Amedeo; Fortunati, Paola; Mulazzi, Annalisa; Bertuzzi, Terenzio

    2016-02-01

    The extraction of aflatoxin M1 (AFM1) from cheese is generally carried out using chlorinated organic solvents. In this study, two innovative methods were developed, based on an enzyme-assisted (EA) extraction using proteolytic enzymes (pepsin or pepsin-pancreatin). After purification through an immunoaffinity column, AFM1 is determined by HPLC-FLD. A comparison between the new EA methods and an established chloroform (CH) method was carried out on 24 cheese samples. The results showed that the extraction efficiency of the EA methods was independent of ripening time of cheese, whereas the CH method was not able to fully recover AFM1 from ripened cheeses. The simpler (pepsin) of the two methods has been adopted by our laboratory for routine analysis of AFM1 in cheese. In comparison with the CH method, the pepsin-HCl (P-HCl) method is simpler, avoiding solvent evaporation, dissolution and partition in a separating funnel; moreover, it gives higher recoveries, comparable LOD and LOQ and more accurate results.

  14. Cloning and Expression of Bile Salt Hydrolase Gene from Lactobacillus plantarum M1-UVS29

    Institute of Scientific and Technical Information of China (English)

    Yu Chang-qing; Li Rong

    2015-01-01

    We cloned and expressed bile salt hydrolase gene ofLactobacillus plantarum M1-UVS29 inLactococcus lactis NZ9000 successfully. Gene-specific primers for amplification ofL. plantarum bsh were designed by using sequence which availabled from GenBank. The production of PCR amplicon was confirmed by sequencing and cloned into pMD18-T vector, and then recombined into expression vector pNZ8148 and yielding vector pNZ8148-BSH. pNZ8148-BSH was transferred intoLactococcus lactis NZ9000. Sequencing indicated that the clonedbsh fragment contained 995 nucleotides, and shared 99.3% sequence homology withbsh gene fromL. plantarum MBUL10. Clonedbsh fragment was successfully transduced into NICE expression system and confirmed by PCR and restriction digest. Recombinant BSH protein was analyzed by SDS-PAGE. The molecular weight of BSH protein was approximately 37 ku. Activity of the expressed protein was 0.77 µmol• min-1. The successfully expressed proteins by genetic engineering technology made the function of lactic acid bacteria be abundant and laid the foundation for further researches into cholesterol-lowering lactic acid bacterium food and probiotics.

  15. Indication for joint replacement and glutathione s-transferases M1 and T1 genotypes.

    Science.gov (United States)

    Klein, Torsten; Selinski, Silvia; Blaszkewicz, Meinolf; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    In most patients with osteoarthritis (OA), therapy-resistant pain is the indication for hip or knee replacement. Glutathione S-transferases, particularly glutathione S-transferase M1 (GSTM1), are involved in metabolism of highly reactive metabolites that may be generated by inflammatory processes. In total, 148 patients with indication for hip or knee replacement and 129 patients of the same hospital without indication for joint replacement were genotyped for GSTM1 and GSTT1 and interviewed by a newly developed questionnaire for occupational and nonoccupational risk factors of hip and/or knee osteoarthritis. Mean age was 70.9 yr in OA cases and 67.4 yr in controls. The frequency of GSTM1 negative in the OA case group was (45%) in the lower range compared to values in Caucasian general population (approximately 50%), whereas the frequency in the controls was normal (51%). The frequency of GSTT1 negative genotype in OA cases and controls was normal. The normal distribution of the GSTM1 negative genotype in patients with indication for hip or knee replacement indicates that the role GSTM1 in these patients is different from that in other aseptic inflammatory diseases such as ozone-related inflammatory reactions of the respiratory tract.

  16. Miners compensated for pneumoconiosis and glutathione s-transferases M1 and T1 genotypes.

    Science.gov (United States)

    Zimmermann, Anna; Ebbinghaus, Rainer; Prager, Hans-Martin; Blaszkewicz, Meinolf; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    Chronic inhalation of quartz-containing dust produces reversible inflammatory changes in lungs resulting in irreversible fibrotic changes termed pneumoconiosis. Due to the inflammatory process in the lungs, highly reactive substances are released that may be detoxified by glutathione S-transferases. Therefore, 90 hard coal miners with pneumoconiosis as a recognized occupational disease (in Germany: Berufskrankheit BK 4101) were genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) according to standard methods. Furthermore, occupational exposure and smoking habits were assessed by questionnaire. Changes in a chest x-ray were classified according to ILO classification 2000. Of the investigated hard coal miners 43% were GSTM1 negative whereas 57% were GSTM1 positive. The arithmetic mean of the age at time of investigation was 74.2 yr (range: 42-87 yr). Seventy-four percent of the hard coal miners reported being ever smokers, while 26% denied smoking. All hard coal miners provided pneumoconiosis-related changes in the chest x-ray. The observed frequency of GSTM1 negative hard coal miners was not different from frequencies reported for general Caucasian populations and in agreement with findings reported for Chinese coal miners. In contrast, in a former study, 16 of 19 German hard coal miners (84%) with urinary bladder cancer displayed a GSTM1 negative genotype. The outcome of this study provides evidence that severely occupationally exposed Caucasian hard coal miners do not present an elevated level of GSTM1 negative individuals.

  17. Purification and characterization of virginiamycin M1 reductase from Streptomyces virginiae.

    Science.gov (United States)

    Suzuki, N; Lee, C K; Nihira, T; Yamada, Y

    1998-11-01

    Virginiamycin M1 (VM1), produced by Streptomyces virginiae, is a polyunsaturated macrocyclic lactone antibiotic belonging to the virginiamycin A group. S. virginiae possesses an activity which stereospecifically reduces a 16-carbonyl group of VM1, resulting in antibiotically inactive 16R-dihydroVM1. The corresponding VM1 reductase was purified to homogeneity from crude extracts of S. virginiae in five steps, with 5,650-fold purification and 23% overall yield. The N-terminal amino acid sequence was determined to be MAIKLVIA. The purified enzyme showed an apparent Mr of 73,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an Mr of 280,000 by native molecular sieve high-performance liquid chromatography, indicating the tetrameric nature of the native enzyme. NADPH served as a coenzyme for the reduction, with a Km value of 0.13 mM, but NADH did not support the reaction, even at a concentration of 5 mM, indicating the NADPH-specific nature of the enzyme. The Km for VM1 was determined to be 1.5 mM in the presence of 2 mM NADPH. In the reverse reaction, only 16R-dihydroVM1, not the 16S-epimer, served as a substrate, with a less than 0.1% overall reaction rate compared to that of the forward reaction, confirming that the VM1 reductase participates solely in VM1 inactivation in vivo.

  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. [Cytogenetic investigations of bone marrow cells from mice exposed onboard biosatellite "Bion-M1"].

    Science.gov (United States)

    Dorozhkina, O V; Ivanov, A A

    2015-01-01

    The results of studying the mitotic activities and chromosomal aberrations in bone marrow cells from C57/BL6N mice with the help of the anaphase technique in 12 hours after completion of the 30-day "Bion-M1" mission and ground-based experiment using flight equipment are presented. A statistically reliable decline of the mitotic activity (0.74%) was found in cells taken from the space flown animals. In the ground-based experiment, a statistically reliable downward trend in proliferative activity (1.37%) was revealed after the comparison with groups of vivarium control (1.46-1.53%). In both experiments mice increased the number of initial mitotic phases (prophase + metaphase) relative to the sum of anaphases and telophases. The number of aberrant mitoses grew reliably in the group of flight animals by 29.7%, whereas in the ground-based experiment an upward trend was insignificant as their number increased up to 2.3% only. In the vivarium controls aberrant mitoses constituted 1.75-1.8%. An increase in chromosomal aberrations was largely due to such abnormalities as fragments. These findings seem to have been a result of summation of the effects of radiation and other stressful factors in space flight.

  20. THE M/M/1 QUEUE WITH WORKING VACATIONS AND VACATION INTERRUPTIONS

    Institute of Scientific and Technical Information of China (English)

    Jihong LI; Naishuo TIAN

    2007-01-01

    In this paper,we study the M/M/1 queue with working vacations and vacation interruptions.The working vacation is introduced recently,during which the server can still provide service on the original ongoing work at a lower rate.Meanwhile,we introduce a new policy:the server can come back from the vacation to the normal working level once some indices of the system,such as the number of customers,achieve a certain value in the vacation period.The server may come back from the vacation without completing the vacation.Such policy is called vacation interruption.We connect the above mentioned two policies and assume that if there are customers in the system after a service completion during the vacation period,the server will come back to the normal working level.In terms of the quasi birth and death process and matrix-geometric solution method,we obtain the distributions and the stochastic decomposition structures for the number of customers and the waiting time and provide some indices of systems.

  1. Glutathione s-transferase M1 and T1 genetic polymorphisms in Iranian patients with glaucoma

    Directory of Open Access Journals (Sweden)

    Fatemeh Kazemi Safa

    2014-05-01

    Full Text Available Objective(s:Glaucoma is the second leading cause of blindness and it is related to oxidative stress based on numerous studies. Glutathione S-transferases (GSTs are members of multigenic family, which have important role in cells as an antioxidant. In the present study, we examined the polymorphism of GSTT1 and GSTM1 deletion genotypes (T0M1, T1M0, and T0M0 in 100 Glaucoma patients (41with primary open angle glaucoma (PCAG, and 59 with primary closed angle glaucoma (POAG compared to 100 healthy subjects. Materials and Methods: GSTM1and GSTT1 polymorphisms were determined by multiplex polymerase chain reaction. Results: GSTM1 and GSTT1 null deletions genotypes were determined in 22 (53.7% and 7 (17.1% patients with PCAG and 34 (34% and 15 (15% in healthy subjects[VAIO1] . Comparison between patients and healthy subjects regarding GSTM1 and GSTT1 genotypes revealed increase of GSTM1 null deletions genotypes in patients with PCAG (P=0.03. Conclusion: It was concluded that the increased frequencies of GSTM1 null in patients with PCAG could be a risk factor for incidence of PCAG in the Iranian population.  

  2. Seasonal patterns of aflatoxin M1 contamination in commercial pasteurised milk from different areas in Thailand.

    Science.gov (United States)

    Suriyasathaporn, Witaya; Nakprasert, Watinee

    2012-01-01

    Aflatoxin M1 (AFM1) levels were determined in pasteurised milk from five commercial trademarks produced in different areas in Thailand. One hundred and twenty milk samples were collected from local markets in Chiang Mai province, Thailand, to evaluate AFM1 concentrations using immunoaffinity columns and high-performance liquid chromatography with fluorescence detection. The overall median AFM1 level was 0.023 µg L(-1) ranging from 0.004 to 0.293 µg L(-1). All trademarks had average AFM1 concentrations lower than 0.05 µg L(-1), with those in Trademarks 3 to 5 being higher than Trademarks 1 and 2 (P < 0.01). All trademarks had different seasonal patterns of AFM1, even though operating in the same area. However, only Trademark 3 showed significant differences of AFM1 levels between seasons. The results suggested that farm management factors, rather than environment factors, were likely to be the main cause of AFM1 contamination in dairy products.

  3. Rapid and specific gray matter changes in M1 induced by balance training.

    Science.gov (United States)

    Taubert, Marco; Mehnert, Jan; Pleger, Burkhard; Villringer, Arno

    2016-06-01

    Training-induced changes in cortical structure can be observed non-invasively with magnetic resonance imaging (MRI). While macroscopic changes were found mainly after weeks to several months of training in humans, imaging of motor cortical networks in animals revealed rapid microstructural alterations after a few hours of training. We used MRI to test the hypothesis of immediate and specific training-induced alterations in motor cortical gray matter in humans. We found localized increases in motor cortical thickness after 1h of practice in a complex balancing task. These changes were specific to motor cortical effector representations primarily responsible for balance control in our task (lower limb and trunk) and these effects could be confirmed in a replication study. Cortical thickness changes (i) linearly increased across the training session, (ii) occurred independent of alterations in resting cerebral blood flow and (iii) were not triggered by repetitive use of the lower limbs. Our findings show that motor learning triggers rapid and specific gray matter changes in M1.

  4. Occurrence of aflatoxin M1 in raw milk of five dairy species in Ahvaz, Iran.

    Science.gov (United States)

    Rahimi, E; Bonyadian, M; Rafei, M; Kazemeini, H R

    2010-01-01

    During November 2007 to December 2008, 311 samples of raw milk from cow, water buffalo, camel, sheep, and goat were collected in the Ahvaz (southwest Iran). All of the samples were analyzed for presence of aflatoxin M1 (AFM1) by competitive ELISA technique. AFM1 was found in 42.1% of the samples by average concentration of 43.3+/-43.8 ng/kg. The incidence rates of AFM1 in raw cow, water buffalo, camel, sheep, and goat milks were, 78.7%, 38.7%, 12.5%, 37.3%, and 27.1%, respectively. The concentration of AFM1 in all of the samples were lower than Iranian national standard and FDA limit (500 ng/l), but in 36% of raw cow milk, 8% water buffalo milk, 3.9% sheep milk, and 5.7% raw goat milk samples were higher than maximum tolerance limit accepted by European union/Codex Alimentarius Commission (50 ng/l). The results showed that the milk of camel, goat, and sheep is safe respect to AFM1 contamination in this area.

  5. Repeatability of ellipsometric data in cholera toxin G M1-ELISA structures

    Science.gov (United States)

    Castro, Leon G.; Thompson, Daniel W.; Tiwald, Thomas; Berberov, Emil M.; Woollam, John A.

    2007-04-01

    The need for repeated measurements in a wide range of biological testing due to statistical variations is well known. In this paper, we discuss a specific example in which the measurement probe is a spectroscopic ellipsometer. Repeatable results are needed in a wide range of applications such as drug testing, immunoassays and other tests for disease, and fundamental biomaterial research. The present paper seeks to help reduce the non-meaningful causes of lack of repeatability by identifying a large number of externally controllable factors. Another goal of this work was to quantify the effects of many of these factors on ellipsometric measurements. By exploiting the sensitivity of spectroscopic ellipsometry to ultrathin layers, improved ways to detect and quantitatively differentiate biological events can be explored. This initial work was motivated from an interest to distinguish one disease from another or discern effects of one drug from another using the high surface sensitivity of spectroscopic ellipsometry. In this paper, we investigate the example biological system of cholera toxin (CT) in an ELISA structure with monosialoganglioside (G M1).

  6. Binding of aflatoxin M1 to different protein fractions in ovine and caprine milk.

    Science.gov (United States)

    Barbiroli, A; Bonomi, F; Benedetti, S; Mannino, S; Monti, L; Cattaneo, T; Iametti, S

    2007-02-01

    The affinity of aflatoxin M1 toward the main milk protein fractions in ewe and goat milk was investigated by using an ELISA. This study took into account the possible effects of common dairy processes such as ultrafiltration, acidic or rennet curding, and production of ricotta from acidic or rennet whey. Treatments that allowed the separation of casein from whey proteins under conditions that do not alter the physical or chemical status of the proteins (such as ultracentrifugation) were used as a reference. None of the treatments used in typical dairy processes caused significant release of the toxin, in spite of the relevant changes they induced in the interactions among proteins. Only the combined heat and acidic treatment used for production of ricotta cheese altered the structure of whey proteins to the point where they lost their ability to bind the toxin. This study also showed that, regardless of the physical state of the sample, a commercial electronic nose device, in combination with appropriate statistical tools, was able to discriminate among different levels of sample contamination.

  7. Nonlinear phase of the compressional m=1 diocotron instability: Saturation and analogy with geophysical fluid dynamics

    Science.gov (United States)

    Delzanno, G. L.; Finn, J. M.; Lapenta, G.

    2002-12-01

    The nonlinear dynamics of a Penning trap plasma, including the effect of the finite length and end curvature of the plasma column, is studied. A new cylindrical particle-in-cell code, called KANDINSKY, has been implemented by using a new interpolation scheme. The principal idea is to calculate the volume of each cell from a particle volume, in the same manner as is done for the cell charge. With this new method, the density is conserved along streamlines and artificial sources of compressibility are avoided. The code has been validated with a number of tests. The code is then used to compare the dynamics of three different models: the standard Euler or drift-Poisson model, the modified drift-Poisson model [J. Finn et al. Phys. Plasmas 6, 3744 (1999); Phys. Rev. Lett. 84, 2401 (2000)] with compressional effects, and the quasigeostrophic model of geophysical fluid dynamics in the limit of the γ-plane approximation. The results of this investigation show that Penning traps can be used to simulate geophysical fluids. Moreover, the results for the m=1 diocotron instability reproduce qualitatively the experiments [C. F. Driscoll, Phy. Rev. Lett. 64, 645 (1990); C. F. Driscoll et al. Phys. Fluids B 2, 1359 (1990)]: The instability turns the plasma "inside-out" resulting at the end in a stable, monotonic profile.

  8. Loss of Forkhead box M1 promotes erythropoiesis through increased proliferation of erythroid progenitors.

    Science.gov (United States)

    Youn, Minyoung; Wang, Nan; LaVasseur, Corinne; Bibikova, Elena; Kam, Sharon; Glader, Bertil; Sakamoto, Kathleen M; Narla, Anupama

    2017-05-01

    Forkhead box M1 (FOXM1) belongs to the forkhead/winged-helix family of transcription factors and regulates a network of proliferation-associated genes. Its abnormal upregulation has been shown to be a key driver of cancer progression and an initiating factor in oncogenesis. FOXM1 is also highly expressed in stem/progenitor cells and inhibits their differentiation, suggesting that FOXM1 plays a role in the maintenance of multipotency. However, the exact molecular mechanisms by which FOXM1 regulates human stem/progenitor cells are still uncharacterized. To understand the role of FOXM1 in normal hematopoiesis, human cord blood CD34(+) cells were transduced with FOXM1 short hairpin ribonucleic acid (shRNA) lentivirus. Knockdown of FOXM1 resulted in a 2-fold increase in erythroid cells compared to myeloid cells. Additionally, knockdown of FOXM1 increased bromodeoxyuridine (BrdU) incorporation in erythroid cells, suggesting greater proliferation of erythroid progenitors. We also observed that the defective phosphorylation of FOXM1 by checkpoint kinase 2 (CHK2) or cyclin-dependent kinases 1/2 (CDK1/2) increased the erythroid population in a manner similar to knockdown of FOXM1. Finally, we found that an inhibitor of FOXM1, forkhead domain inhibitor-6 (FDI-6), increased red blood cell numbers through increased proliferation of erythroid precursors. Overall, our data suggest a novel function of FOXM1 in normal human hematopoiesis. Copyright© Ferrata Storti Foundation.

  9. Detection of aflatoxin M1 in human breast milk and raw cow's milk in Istanbul, Turkey.

    Science.gov (United States)

    Keskin, Yaşar; Başkaya, Ruhtan; Karsli, Seher; Yurdun, Türkan; Ozyaral, Oğuz

    2009-04-01

    This survey was undertaken to determine the extent of aflatoxin M1 (AFM1) contamination in human breast milk and raw cow's milk in Istanbul, Turkey. Samples of human and raw cow's milk were collected randomly and analyzed for AFM1 using an enzyme-linked immunosorbent assay and high-performance liquid chromatography with fluorescence detection in which the samples were cleaned up with immunoaffinity columns. In this study, AFM, was detected in 8 (13.1%) of 61 human breast milk samples examined (mean +/- SD level, 5.68 +/- 0.62 ng/liter; range, 5.10 to 6.90 ng/liter) and 20 (33.3%) of 60 raw cow's milk samples examined (range, 5.40 to 300.20 ng/liter). Five (8.3%) of the positive raw cow's milk samples had AFM1 levels (153.52 +/- 100.60 ng/liter; range, 61.20 to 300.20 ng/liter) that were higher than the maximum tolerance limit (0.05 ppb) stipulated by regulations in Turkey and some other countries.

  10. 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.

  11. First observation of the M1 transition $\\psi^\\prime\\to \\gamma\\eta_c^\\prime$

    CERN Document Server

    Ablikim, M; 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 million $\\psi^\\prime$ 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: $\\psi^\\prime\\to\\gamma\\eta_c^\\prime$. Analyses of the processes $\\psi^\\prime\\to \\gamma\\eta_c^\\prime$ with $\\eta_c^\\prime\\to \\K_S^0 K\\pi$ and $K^+K^-\\pi^0$ gave an $\\eta_c^\\prime$ signal with a statistical significance of greater than 10 standard deviations under a wide range of assumptions about the signal and background properties. The data are used to obtain measurements of the $\\eta_c^\\prime$ mass ($M(\\eta_c^\\prime)=3637.6\\pm 2.9_\\mathrm{stat}\\pm 1.6_\\mathrm{sys}$ MeV/$c^2$), width ($\\Gamma(\\eta_c^\\prime)=16.9\\pm 6.4_\\mathrm{stat}\\pm 4.8_\\mathrm{sys}$ MeV), and the product branching fraction ($\\BR(\\psi^\\prime\\to \\gamma\\eta_c^\\prime)\\times \\BR(\\eta_c^\\prime\\to K\\bar K\\pi) = (1.30\\pm 0.20_\\mathrm{stat}\\pm 0.30_\\mathrm{sys})\\tim...

  12. The aflatoxin M1 crisis in the Serbian dairy sector: the year after.

    Science.gov (United States)

    Miocinovic, Jelena; Keskic, Tanja; Miloradovic, Zorana; Kos, Andrea; Tomasevic, Igor; Pudja, Predrag

    2017-03-01

    During the last 3 years, high aflatoxin M1 (AFM1) concentrations in milk and dairy products occurred in Serbia. It resulted in periodical change of the official regulations regarding maximum levels (MLs) of AFM1 as set by the Serbian Government. The aim of this study was to compare the occurrence of AFM1 in raw milk and dairy products during 2015 and also to determine whether there were some differences in AFM1 level among seasons. The AFM1 level exceeded the European Union ML in 29.3% of raw milk and 4.2% of milk product samples. The highest level of AFM1 in raw milk was found during the autumn season, while during the rest of the 2015, it was significantly lower. Although the improvement of dairy products safety was evident in 2015 when compared to 2013 and 2014, the cause of high concentrations in raw milk remained unresolved yet. This study indicates that dairy plants introduced control measures and refused reception of too high contaminated raw milk.

  13. Assessment of aflatoxin M1 in maternal breast milk in Eastern Turkey.

    Science.gov (United States)

    Atasever, Meryem; Yildirim, Yeliz; Atasever, Mustafa; Tastekin, Ayhan

    2014-04-01

    Breastfeeding may be considered as a risk factor for aflatoxin M1 (AFM1) exposure in early infancy. Hence, AFM1 levels in maternal breast milk (MBM) and the correlation between moldy cheese consumption of lactating mothers and infant exposure to AFM1 were investigated in this study. MBM samples from 73 lactating women randomly selected in hospitals located in Eastern Turkey were analysed for the presence of AFM1 using competitive ELISA. Out of 73 lactating mothers, 44 of them had the habit of cheese consumption (at least once a week), while remaining 29 had no such habit. AFM1 was detected in MBM of 18 out of 73 samples (24.6%); 12 MBM of 44 lactating mothers with moldy cheese consumption habit (27.2%) and 6 MBM of 29 mothers with no such habit (20.6%) with the range of 1.3-6.0 ng/l. None of the samples exceeded the limit set by EU and Turkish legislations. Moldy cheese consumption habit of lactating mothers exhibited no significant correlation with the presence of AFM1 in their milk (p>0.05). The results indicated that the relative risk of infant AFM1 exposure via MBM of moldy cheese consuming mother was not higher than MBM of mothers with no such habit.

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. Ramsey Number of K2,s+1 vs. K1,n%关于K2,s+1 VS,K1,n的Ramsey数

    Institute of Scientific and Technical Information of China (English)

    秦大伟; 沈大鹏

    2007-01-01

    It is shown that the Ramsey number r(K2,s+1, K1,n) ≤ n + √sn+ (s + 3)/2 + o(1) for large n, and r(K2,s+1, K1,n)∈{(q-1)2/s+1,-(q-1)2/s+2},wheren: (q-1)2/s-q+2 and q is a prime power such that s|(q - 1).

  16. The SphKs/S1P/S1PR1 axis in immunity and cancer: more ore to be mined.

    Science.gov (United States)

    Jin, Lei; Liu, Wei-Ren; Tian, Meng-Xin; Fan, Jia; Shi, Ying-Hong

    2016-04-29

    Over the past two decades, huge amounts of research were launched to understand the functions of sphingosine. Many pathways were uncovered that convey the relative functions of biomacromolecules. In this review, we discuss the recent advances of the role of the SphKs/S1P/S1PR1 axis in immunity and cancer. Finally, we investigate the therapeutic potential of new drugs that target S1P signaling in cancer therapy.

  17. Hypothalamic S1P/S1PR1 axis controls energy homeostasis in Middle-Aged Rodents: the reversal effects of physical exercise

    Science.gov (United States)

    Silva, Vagner Ramon Rodrigues; Katashima, Carlos Kiyoshi; Bueno Silva, Carla G.; Lenhare, Luciene; Micheletti, Thayana Oliveira; Camargo, Rafael Ludemann; Ghezzi, Ana Carolina; Camargo, Juliana Alves; Assis, Alexandre Moura; Tobar, Natalia; Morari, Joseane; Razolli, Daniela S.; Moura, Leandro Pereira; Pauli, José Rodrigo; Cintra, Dennys Esper; Velloso, Lício Augusto; Saad, Mario J.A; Ropelle, Eduardo Rochete

    2017-01-01

    Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process. PMID:28039439

  18. Structural damage and functional reorganization in ipsilesional m1 in well-recovered patients with subcortical stroke.

    Science.gov (United States)

    Zhang, Jing; Meng, Liangliang; Qin, Wen; Liu, Ningning; Shi, Fu-Dong; Yu, Chunshui

    2014-03-01

    Both structural atrophy and functional reorganization of the primary motor cortex (M1) have been reported in patients with subcortical infarctions affecting the motor pathway. However, the relationship between structural impairment and functional reorganization in M1 remains unclear. Twenty-six patients exhibiting significant recovery after subcortical infarctions were investigated using multimodal MRI techniques. Structural impairment was assessed via cortical thickness, and functional reorganization was analyzed using task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity. Compared with healthy controls, patients with stroke exhibited reduced cortical thickness in the ipsilesional M1; however, this region exhibited increased task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity in these patients. Patients with stroke demonstrated increased task-evoked activation in another ipsilesional M1 region, in which increased amplitude of low-frequency fluctuation and resting-state functional connectivity were observed. The structural and functional changes in M1 were located selectively in the ipsilesional hemisphere. We provide convincing evidence that indicates extensive functional reorganization in the ipsilesional M1 of patients with chronic subcortical infarctions, including the structurally impaired M1 region.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance.

    Science.gov (United States)

    Ye, Lifang; Liang, Shu; Guo, Chao; Yu, Xizhong; Zhao, Juan; Zhang, Hao; Shang, Wenbin

    2016-12-01

    Insulin resistance is associated with a chronic inflammation in adipose tissue which is propagated by a phenotypic switch in adipose tissue macrophage (ATM) polarization. This study aimed to investigate whether berberine, the major alkaloid of rhizoma coptidis, can improve insulin resistance through inhibiting ATM activation and inflammatory response in adipose tissue. High-fat-diet induced obese mice were administered oral with berberine (50mg/kg/day) for 14days. ATMs were analysed using FACS and insulin resistance was evaluated. Expressions of pro-inflammatory cytokines and activation of inflammatory pathways were detected. The chemotaxis of macrophages was measured. Glucose consumption and insulin signalling of adipocytes were examined. Berberine significantly decreased F4/80(+)/CD11c(+)/CD206(-) cells in the stromal vascular fraction from adipose tissue and improved glucose tolerance in obsess mice. In addition, berberine reduced the elevated levels of serum TNF-α, IL-6 and MCP-1 and the expressions of TNF-α, IL-6 and MCP-1 and attenuated the phosphorylation of JNK and IKKβ and the expression of NF-κB p65 in the obese adipose tissue, Raw264.7 macrophages and 3T3-L1 adipocytes, respectively. The phosphorylation of IRS-1 (Ser307) was inhibited by berberine in adipose tissue and cultured adipocytes. The phosphorylation of AKT (Ser473) was increased in berberine-treated adipose tissue. Conditioned medium from adipocytes treated with berberine reduced the number of infiltrated macrophages. Berberine partly restored the impaired glucose consumption and the activation of IRS-1 (Ser307) in adipocytes induced by the activation of macrophages. Our findings imply that berberine improves insulin resistance by inhibiting M1 macrophage activation in adipose tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Transport of Aflatoxin M1 in human intestinal Caco-2/TC7 cells

    Directory of Open Access Journals (Sweden)

    Francesca eCaloni

    2012-06-01

    Full Text Available Aflatoxin M1 (AFM1 is a hydroxylated metabolite of aflatoxin B1 (AFB1. After it is formed, it is secreted in the milk of mammals.Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions of the intestinal Caco-2/TC7 clone grown on microporous filter supports. These inserts allowed for the separation of the apical and basolateral compartments which correspond to the in vivo lumen and the interstitial space/vascular systems of intestinal mucosa respectively.In this study, the Caco-2/TC7 cells were treated with different AFM1 concentrations (10-10,000 ng/kg for short (40 minutes and long periods of time (48 hours. The AFM1 influx/efflux transport and effects on tight junctions were evaluated by measuring trans-epithelial electrical resistance and observing tight junction protein (Zonula occludens-1 and occludin localization.The results showed that: i when introduced to the apical and basolateral compartments, AFM1 was poorly absorbed by the Caco-2/TC7 cells but its transport across the cell monolayer occurred very quickly (Papp value of 105.10 ± 7.98 cm/s x 10-6. ii The integrity of tight junctions was not permanently compromised after exposure to the mycotoxin. Viability impairment or barrier damage did not occur either.The present results contribute to the evaluation of human risk exposure to AFM1, although the AFM1 transport mechanism need to be clarified.

  2. The Hotspot for (Global) One Health in Primary Food Production: Aflatoxin M1 in Dairy Products.

    Science.gov (United States)

    Frazzoli, Chiara; Gherardi, Paola; Saxena, Navneet; Belluzzi, Giancarlo; Mantovani, Alberto

    2016-01-01

    One Health involves the multifaceted environment-animal-human web: nevertheless, the role of toxicological issues has yet to be fully explored in this context. Aflatoxin B1 (AFB1) contamination of feeds is a risk for the health of several farm animals, including fishes; milk is the only food of animal origin where a significant feed-food carry over may occur. The main AFB1-related compound present in milk is the hydroxy-metabolite aflatoxin M1 (AFM1). Besides contamination of raw milk, AFM1 is of concern for the whole dairy chain; AFM1 may also contaminate the milk of several other ruminants used for milk/dairy production. In a One Health perspective, milk represents a sentinel matrix for AFB1 vulnerability of the agro-food system, that is crucial in a phase when food/nutritional security becomes a global issue and climatic changes may affect agricultural productions. In the global setting, food chain exposure to long-term toxicants, such as AFM1, is a growing concern for economically developing countries, whereas global trade and climatic change makes AFM1 an emerging hot issue in economically developed countries as well. We critically review the state of the art on AFM1 risk assessment and risk management using two scenarios as case studies: a European Union country where the health system aims at ensuring a high-level protection of food chain (Italy) and the world's largest (and economically developing) producer of dairy products by volume (India). The case studies are used to provide building blocks for a global One Health framework.

  3. NST and IRIS multi-wavelength observations of an M1.0 class solar flare

    Science.gov (United States)

    Vargas Domínguez, Santiago; Sadykov, Viacheslav; Kosovichev, Alexander; Sharykin, Ivan; Struminsky, Alexei; Zimovets, Ivan

    2015-08-01

    Although solar flares are the most energetic events in the Solar System and have direct impact in the interplanetary space and ultimately in our planet, there are still many unresolved issues concerning their generation, the underlying processes of particle acceleration involved, the effect at different layer in the solar atmosphere, among others. This work presents new coordinated observations from the New Solar Telescope (NST) and the space telescope IRIS that acquired simultaneous observations of an M1.0 class flare occurred on 12 June, 2014 in active region NOAA 12087. NST filtergrams using the TiO filter, together with chromospheric data from the Halpha line allow us to study the evolution of the event from the first signs of the intensification of the intensity in the region. We focused on a small portion where the intensity enhancement in Halpha (blue and red wings) seems to be triggered, and discovered a rapid expansion of a flux-rope structure near the magnetic neutral line, in the sequence of high-resolution photospheric images. IRIS observations evidenced strong emission of the chromospheric and transition region lines during the flare. Jet-like structures are detected before the initiation of the flare in chromospheric lines and strong non-thermal emission in the transition region at the beginning of the impulsive phase. Evaporation flows with velocities up to 50 km/s occurred in the hot chromospheric plasma. We interpreted the result in terms of the “gentle” evaporation that occurs after accelerated particles heat the chromosphere.

  4. Aflatoxin M1 contamination of human breast milk in Isfahan, Iran

    Science.gov (United States)

    Jafarian-Dehkordi, Abbas; Pourradi, Nasibeh

    2013-01-01

    Background: During the last decades there has been great attention paid to aflatoxins. They are highly toxic, immunosuppressive, mutagenic, teratogenic, and carcinogenic compounds. Aflatoxin M1 (AFM1), a hydroxylated metabolite of aflatoxin B1 (AFB1), is formed in the liver and excreted into the breast milk. It is considered to cause certain hygienic risks for infant health. The aim of this study was to evaluate the presence of the AFM1 in the breast milk using AFM1 in milk as a biomarker for exposure to aflatoxin B1 and determine the level of AFM1 contamination in the lactating mothers in Isfahan, Iran. Materials and Methods: This study was carried out on 80 lactating women randomly selected from two urban health centers. Mother's milk samples and information on food intake were collected from the participants using structured food-frequency questionnaire. Breast milk samples were tested for AFM1 by a competitive ELISA technique. Results: Our findings showed that only one sample was contaminated with AFM1 with concentrations of 6.8 ng/L. However, the AFM1 level in this sample was lower than the maximum tolerable limit (25 ng/L) accepted by the European Communities and Codex Alimentarius. Conclusion: Although the concentration of AFM1 in none of the samples was higher than the acceptable level, the presence of AFM1 in only one of them confirms the need for developing strategies to reduce exposure to aflatoxin in foods and to carry out biological monitoring of aflatoxins as a food quality control measure routinely. PMID:24524032

  5. Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

    Science.gov (United States)

    Yan, Shushan; Wang, Zengfang; Wang, Zengyan; Duan, Quanhong; Wang, Xiaochen; Li, Jun; Sun, Beicheng

    2016-08-01

    Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

  6. Deletion of Forkhead Box M1 transcription factor from respiratory epithelial cells inhibits pulmonary tumorigenesis.

    Directory of Open Access Journals (Sweden)

    I-Ching Wang

    Full Text Available The Forkhead Box m1 (Foxm1 protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1(-/- mice prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA/butylated hydroxytoluene (BHT. Decreased lung tumorigenesis in epFoxm1(-/- mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2alpha (TOPO-2alpha, a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2alpha mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2alpha promoter region, indicating that TOPO-2alpha is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2alpha expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy.

  7. 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.

  8. Aflatoxin B1 and M1 Degradation by Lac2 from Pleurotus pulmonarius and Redox Mediators

    Science.gov (United States)

    Loi, Martina; Fanelli, Francesca; Zucca, Paolo; Liuzzi, Vania C.; Quintieri, Laura; Cimmarusti, Maria T.; Monaci, Linda; Haidukowski, Miriam; Logrieco, Antonio F.; Sanjust, Enrico; Mulè, Giuseppina

    2016-01-01

    Laccases (LCs) are multicopper oxidases that find application as versatile biocatalysts for the green bioremediation of environmental pollutants and xenobiotics. In this study we elucidate the degrading activity of Lac2 pure enzyme form Pleurotus pulmonarius towards aflatoxin B1 (AFB1) and M1 (AFM1). LC enzyme was purified using three chromatographic steps and identified as Lac2 through zymogram and LC-MS/MS. The degradation assays were performed in vitro at 25 °C for 72 h in buffer solution. AFB1 degradation by Lac2 direct oxidation was 23%. Toxin degradation was also investigated in the presence of three redox mediators, (2,2′-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid]) (ABTS) and two naturally-occurring phenols, acetosyringone (AS) and syringaldehyde (SA). The direct effect of the enzyme and the mediated action of Lac2 with redox mediators univocally proved the correlation between Lac2 activity and aflatoxins degradation. The degradation of AFB1 was enhanced by the addition of all mediators at 10 mM, with AS being the most effective (90% of degradation). AFM1 was completely degraded by Lac2 with all mediators at 10 mM. The novelty of this study relies on the identification of a pure enzyme as capable of degrading AFB1 and, for the first time, AFM1, and on the evidence that the mechanism of an effective degradation occurs via the mediation of natural phenolic compounds. These results opened new perspective for Lac2 application in the food and feed supply chains as a biotransforming agent of AFB1 and AFM1. PMID:27563923

  9. S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13)

    Institute of Scientific and Technical Information of China (English)

    Kensuke Matsumoto; Akira Kitanaka; Makiko Uemura; Fusako Waki; Tetsuya Fukumoto; Hiroaki Ohnishi; Yoshitsugu Kubota; Toshihiko Ishida

    2011-01-01

    Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration,and that hematological adverse events were relatively rare. PPyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-Ⅱ inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia.

  10. S-1 monotherapy versus S-1 combination therapy in gemcitabine-refractory advanced pancreatic cancer: A meta-analysis (PRISMA) of randomized control trials.

    Science.gov (United States)

    Zhong, Sheng; Qie, Shuai; Yang, Liu; Yan, Qi; Ge, Linna; Wang, Zhongfeng

    2017-07-01

    Pancreatic cancer (PC) is one of the most lethal digestive system tumors. Most new cases are diagnosed based on metastasis or local aggression and are known as "advanced PC." Recently, studies investigating S-1 have indicated that it has a better clinical curative effect on PC. We conducted a meta-analysis to evaluate the efficacy and safety of S-1 monotherapy compared with S-1 combination regimens in patients with gemcitabine (GEM)-refractory PC. Trials published between 1978 and 2016 were identified by an electronic search of public databases (Medline, Embase, and the Cochrane Library). All prospective studies were independently identified by 2 authors for inclusion. The response rate (RR), progression-free and overall survival (PFS and OS, respectively), and the primary toxicities were extracted for the meta-analysis. Four randomized controlled trials consisting of 623 patients were included in the analysis, among which 315 patients underwent S-1 monotherapy and 308 patients underwent S-1 combination therapy. The pooled data showed a significantly higher response rate and longer PFS in the S-1 combination group than in the S-1 monotherapy group (RR, 1.75; 95% confidence interval [CI], 1.19-2.57; P = .005 and hazard ration [HR], 0.75; 95% CI, 0.62-0.91; P = .005). There were no significant differences in OS or adverse events. Compared with the S-1 monotherapy group, the S-1 combination group had a higher response rate and longer PFS. Both groups had few adverse events, which were balanced between the groups. The subgroup analysis suggested that S-1 combination regimens with leucovorin or irinotecan (CPT-11) provided promising efficacy. These promising combination regimens should be considered for patients with advanced PC who choose S-1 as their second-line therapy.

  11. A prokaryotic S1P lyase degrades extracellular S1P in vitro and in vivo: implication for treating hyperproliferative disorders.

    Directory of Open Access Journals (Sweden)

    Andrea Huwiler

    Full Text Available 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.

  12. HDL-associated ApoM is anti-apoptotic by delivering sphingosine 1-phosphate to S1P1 & S1P3 receptors on vascular endothelium.

    Science.gov (United States)

    Ruiz, Mario; Okada, Hiromi; Dahlbäck, Björn

    2017-02-08

    High-density Lipoprotein (HDL) attenuates endothelial cell apoptosis induced by different cell-death stimuli such as oxidation or growth factor deprivation. HDL is the main plasma carrier of the bioactive lipid sphingosine 1-phosphate (S1P), which it is a signaling molecule that promotes cell survival in response to several apoptotic stimuli. In HDL, S1P is bound to Apolipoprotein M (ApoM), a Lipocalin that is only present in around 5% of the HDL particles. The goal of this study is to characterize ApoM-bound S1P role in endothelial apoptosis protection and the signaling pathways involved. Human umbilical vein endothelial cells (HUVEC) cultures were switched to serum/grow factor deprivation medium to induce apoptosis and the effect caused by the addition of ApoM and S1P analyzed. The addition of HDL(+ApoM) or recombinant ApoM-bound S1P promoted cell viability and blocked apoptosis, whereas HDL(-ApoM) had no protective effect. Remarkably, S1P exerted a more potent anti-apoptotic effect when carried by ApoM as compared to albumin, or when added as free molecule. Mechanistically, cooperation between S1P1 and S1P3 was required for the HDL/ApoM/S1P-mediated anti-apoptotic ability. Furthermore, AKT and ERK phosphorylation was also necessary to achieve the anti-apoptotic effect of the HDL/ApoM/S1P complex. Altogether, our results indicate that ApoM and S1P are key elements of the anti-apoptotic activity of HDL and promote optimal endothelial function.

  13. 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 Birk

    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...... 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....

  14. 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.

  15. 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.

  16. The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts

    NARCIS (Netherlands)

    Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend

    2016-01-01

    Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). Th

  17. Evolutionary Trajectories of Beta-Lactamase CTX-M-1 Cluster Enzymes: Predicting Antibiotic Resistance

    Science.gov (United States)

    Novais, Ângela; Comas, Iñaki; Baquero, Fernando; Cantón, Rafael; Coque, Teresa M.; Moya, Andrés; González-Candelas, Fernando; Galán, Juan-Carlos

    2010-01-01

    Extended-spectrum beta-lactamases (ESBL) constitute a key antibiotic-resistance mechanism affecting Gram-negative bacteria, and also an excellent model for studying evolution in real time. A shift in the epidemiology of ESBLs is being observed, which is characterized by the explosive diversification and increase in frequency of the CTX-M-type β-lactamases in different settings. This provides a unique opportunity for studying a protein evolutionary radiation by the sequential acquisition of specific mutations enhancing protein efficiency and fitness concomitantly. The existence of driver antibiotic molecules favoring protein divergence has been investigated by combining evolutionary analyses and experimental site-specific mutagenesis. Phylogenetic reconstruction with all the CTX-M variants described so far provided a hypothetical evolutionary scenario showing at least three diversification events. CTX-M-3 was likely the enzyme at the origin of the diversification in the CTX-M-1 cluster, which was coincident with positive selection acting on several amino acid positions. Sixty-three CTX-M-3 derivatives containing all combinations of mutations under positively selected positions were constructed, and their phenotypic efficiency was evaluated. The CTX-M-3 diversification process can only be explained in a complex selective landscape with at least two antibiotics (cefotaxime and ceftazidime), indicating the need to invoke mixtures of selective drivers in order to understand the final evolutionary outcome. Under this hypothesis, we found congruent results between the in silico and in vitro analyses of evolutionary trajectories. Three pathways driving the diversification of CTX-M-3 towards the most complex and efficient variants were identified. Whereas the P167S pathway has limited possibilities of further diversification, the D240G route shows a robust diversification network. In the third route, drift may have played a role in the early stages of CTX-M-3 evolution

  18. 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

  19. Tracklines of Multichannel Seismics Survey Collected During USGS Cruise M1-98-GM (GOM98LINE.SHP)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Shapefile showing tracklines of Multichannel Seismics Survey Collected During USGS Cruise M1-98-GM. This cruise was to the Mississippi Canyon region of the Gulf of...

  20. Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M1 exhibits improved potency against MRSA.

    Science.gov (United States)

    Hoang, N H; Huong, N L; Shrestha, A; Sohng, J K; Yoon, Y J; Park, J W

    2013-11-01

    A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M1 was created by feeding virginiamycin M1 into a culture of recombinant Streptomyces venezuelae. Its chemical structure was spectroscopically elucidated, and this streptogramin A analogue showed twofold higher antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) compared with its parent molecule virginiamycin M1. Docking studies using the model of streptogramin A acetyltransferase (VatA) suggested that the newly generated analogue binds tighter with overall lower free energy compared with the parent molecule virginiamycin M1. This hypothesis was validated experimentally through the improvement of efficacy of the new analogue against MRSA strains. The biotransformation approach presented herein could have a broad application in the production of reduced macrocyclic molecules.

  1. Complete genome sequence of Streptococcus pyogenes M1 476, isolated from a patient with streptococcal toxic shock syndrome.

    Science.gov (United States)

    Miyoshi-Akiyama, Tohru; Watanabe, Shinya; Kirikae, Teruo

    2012-10-01

    Here, we report the completely annotated genome sequence of Streptococcus pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome (STSS) during pregnancy. The genome sequence will provide new insights into the mechanisms underlying STSS.

  2. Complete Genome Sequence of Streptococcus pyogenes M1 476, Isolated from a Patient with Streptococcal Toxic Shock Syndrome

    OpenAIRE

    Miyoshi-Akiyama, Tohru; WATANABE, Shinya; Kirikae, Teruo

    2012-01-01

    Here, we report the completely annotated genome sequence of Streptococcus pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome (STSS) during pregnancy. The genome sequence will provide new insights into the mechanisms underlying STSS.

  3. Aflatoxin M1 in samples of "minas" cheese commercialized in the city of Belo Horizonte - Minas Gerais/Brazil Aflotoxina M1 em amostras de queijo "minas" comercializada na cidade de Belo Horizonte - Minas Gerais/ Brasil

    Directory of Open Access Journals (Sweden)

    Guilherme PRADO

    2000-12-01

    Full Text Available Milk products such as cheeses may be contaminated by aflatoxin M1 when dairy cattle have consumed feeds contaminated with aflatoxin B1. Samples of "Minas" cheeses (fresh, canastra and standard were collected by the Inspection Service in the Mercado Central in Belo Horizonte city, Minas Gerais - Brazil. A purified extract was obtained by extraction with dichloromethane followed by a washing with n-hexane and immunoaffinity column purification. The quantification of aflatoxin M1 was done by high performance liquid chromatography (HPLC using a fluorescence detector. Recoveries were about 75%. In 56 of the 75 samples (74.7%, the presence of aflatoxin M1 was detected in concentrations ranging between 0.02 and 6.92ng/g of cheese. In the positive cases ( > or = 0.02ng/g the mean contamination level of aflatoxin M1 was 0.08ng/g in fresh cheese, 0.36ng/g in canastra cheese and 0.62ng/g in standard cheese. No aflatoxin M1 maximum tolerance level in cheese has been established in Brazil.Produtos derivados de leite, como queijo, podem estar contaminados com aflatoxina M1 quando o gado leiteiro consome ração contaminada com aflatoxina B1. Amostras de queijo "Minas" ( frescal, canastra e padrão foram coletados pela Vigilância Sanitária de Minas Gerais - Brasil. Foi obtido um extrato purificado através de extração com diclorometano, seguido de lavagem com n-hexano e purificação em coluna de imunoafinidade. A quantificação da aflatoxina M1 foi feita por cromatografia líquida de alta eficiência (CLAE usando detetor de fluorescência. Os valores de recuperação foram em torno de 75%. A presença de aflatoxina M1 foi detectada em 56 das 75 amostras (74,7% e a faixa de concentração observada foi 0,02 a 6,92ng/g de queijo. Dentre os valores positivos ( > ou = 0,02ng/g a média de contaminação de aflatoxina M1 foi 0,08ng/g para queijo frescal, 0,36ng/g para queijo canastra e 0,62ng/g para queijo padrão. O Brasil não apresenta nível de toler

  4. FoxM1和ADAM17在乳腺癌中的表达及其临床意义%Expression and clinical significance of FoxM1 and ADAM17 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    张艳; 乔炜超; 孙影; 张雪鹏

    2016-01-01

    目的:探讨叉头框蛋白M1(FoxM1)与ADAM17在乳腺癌中的表达、相关性及临床意义。方法采用免疫组织化学法检测2014年6月~2015年12月华北理工大学附属医院浸润性乳腺癌(乳腺癌组)62例、乳腺纤维腺瘤(乳腺纤维腺瘤组)33例和正常乳腺组织(对照组)31例中FoxM1和ADAM17的表达,分析两者之间的关系以及其与乳腺癌临床病理特征的相关性。结果 FoxM1和ADAM17在对照组、乳腺纤维腺瘤组、乳腺癌组中的染色指数分别为0.49±0.11、2.13±0.25、9.58±0.95和0.56±0.17、1.87±0.22、9.40±1.17。乳腺癌组FoxM1和ADAM17表达显著高于乳腺纤维腺瘤组,乳腺纤维腺瘤组FoxM1、ADAM17表达高于对照组,差异均有统计学意义(P0.05)。FoxM1和ADAM17在乳腺癌中的表达呈正相关(r=0.68,P0.05) , but it was associated with the metastasis of axillary lymph nodes (P< 0.05). Correlation analysis showed that the expression of FoxM1 and ADAM17 in breast cancer was positively correlated (r=0.68, P<0.05). Conclusion There is high level of FoxM1 and ADAM17 in inva-sive carcinoma, and a positive correlation between them. Positive expression of FoxM1 and ADAM17 is positive associ-ation with axillary lymph node metastasis, but not with age and tumor size in patients with invasive carcinoma of the breast.

  5. Effect of S1P5 on proliferation and migration of human esophageal cancer cells

    OpenAIRE

    Hu, Wei-Min; Li, Li; Jing, Bao-Qian; Zhao, Yong-Sheng; Wang, Chao-Li; Feng, Li; Xie, Yong-En

    2010-01-01

    AIM: To investigate the sphingosine 1-phosphate (S1P) receptor expression profile in human esophageal cancer cells and the effects of S1P5 on proliferation and migration of human esophageal cancer cells.

  6. 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....

  7. Moesin controls clathrin-mediated S1PR1 internalization in T cells.

    Directory of Open Access Journals (Sweden)

    Akira Nomachi

    Full Text Available The lipid mediator sphingosine 1-phosphate (S1P regulates a wide range of cellular activities, including vascular maturation, angiogenesis, and immune-cell trafficking. Among the five known receptors for S1P (S1PR1-S1PR5, S1PR1 is a critical regulator of lymphocyte trafficking: its signaling is required for lymphocyte egress from lymphoid organs, while its down-modulation by agonist-induced internalization is a prerequisite for lymphocyte entry into lymphoid organs from the bloodstream. Despite the importance of S1PR1 down-regulation in determining lymphocyte behavior, the molecular mechanism of its internalization in lymphocytes has not been defined. Here we show that agonist-induced S1PR1 internalization in T cells occurs via clathrin-mediated endocytosis and is regulated by moesin, an ezrin-radixin-moesin (ERM family member. In S1P-stimulated T cells, S1PR1 relocalized within clathrin-coated vesicles (CCVs and early endosomes, and S1PR1 internalization was blocked when clathrin was pharmacologically inhibited. Stimulating moesin-deficient T cells with S1P failed to induce S1PR1 internalization and CCV formation. Furthermore, treating moesin-deficient mice with FTY720, an S1P receptor agonist known to internalize S1PR1, caused delayed lymphopenia, and lymphocytes isolated from FTY720-treated moesin-deficient mice still responded to S1P ex vivo in chemotaxis assays. These results reveal a novel role for moesin in regulating clathrin-dependent S1PR1 internalization through CCV formation.

  8. 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.

  9. 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. PMID:26539121

  10. Excitation of internal m = 1 mode during application of resonant magnetic perturbations on J-TEXT tokamak

    Science.gov (United States)

    Li, Jianchao; Hu, Qiming; Ding, Yonghua; Zhang, Xiaoqing; Yu, Qingquan; Yang, Zhoujun; Chen, Zhipeng; Li, Da; Rao, Bo; Wang, Nengchao; Zhuang, Ge; the J-TEXT Team

    2017-08-01

    The excitation of internal m = 1 mode during application of resonant magnetic perturbations (RMPs) is observed on J-TEXT tokamak. It is found that the sawtooth oscillation disappears after RMPs penetration, and subsequently an internal m = 1 mode with a frequency around 2 kHz appears, were m and n are the poloidal and toroidal mode numbers, respectively. In addition, the internal m = 1 mode often coexists with a rotating m/n = 2/1 tearing mode, and its frequency increases by about 0.5 kHz when the 2/1 tearing mode is locked by RMPs. The bispectrum analysis proves that the m = 1 mode interacts with the rotating 2/1 tearing mode, which implies the mode coupling between these two modes. The frequency of m = 1 mode increases for higher electron density. These results reveal that, the internal m = 1 mode can be excited by RMPs and coexist with both locked and rotating 2/1 mode due to toroidal mode coupling.

  11. Bivariate flow cytometric analysis of DNA content versus immunopositivity for ribonucleotide reductase M1 subunit in the cell cycle.

    Science.gov (United States)

    Mangiarotti, R; Bottone, M G; Danova, M; Pellicciari, C

    1998-06-01

    Ribonucleotide reductase (RR) is a cytoplasmatic enzyme catalyzing the reduction of all four ribonucleotides to their corresponding deoxyribonucleotides. Its activity strongly correlates to the rate of DNA synthesis. By using a specific monoclonal antibody against the large M1 subunit of RR, we assessed the expression of M1-RR versus DNA content by dual-parameter flow cytometry. The aim of this paper was to compare the variations in the immunopositivity for M1-RR during the cell cycle to the positivity for other cell cycle markers identifying either proliferating cells (Ki-67 and PCNA) or quiescent cells (statin). To do this, normal human embryonic fibroblasts in different growth conditions as well as several other mammalian cell lines (rat C6 glioma cells; mouse 3T3 fibroblasts and B16 melanoma cells; human epithelial EUE cells and mammary carcinoma MCF-7 cells) were used. The expression of M1-RR antigen was found to correlate positively with the expression of Ki-67 and PCNA, and negatively with the expression of statin. During early G1 phase, M1-RR becomes detectable by specific antibodies relatively later compared to PCNA and Ki-67; therefore, the lack of immunopositivity for M1-RR cannot be taken as an absolute indication of cell quiescence in G0.

  12. 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.

  13. 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.

  14. The fork head box M1 effects on human colon cancer cells malignant phenotype%叉头框转录因子 M1对人结肠癌细胞恶性表型的影响

    Institute of Scientific and Technical Information of China (English)

    冒晓蓓; 陈龙邦; 刘小北; 徐凯; 褚晓源; 郁红菊; 薛利军; 陈亚楠; 任丽丽; 戴婷婷

    2014-01-01

    Objective The invasion and metastasis of colon cancer often leads to treatment failure and mortality in patients . Our research is to investigate the influence of FoxM 1 to malignant human colon cancer line . Methods In two human colon cancer lines, the protein and mRNA expression levels of FoxM 1 were analyzed with the application of RT-PCR and Western blot , from which high-expressed HT-29 and low-expressed HCT-116 were determined.The expression of FoxM1 was down-regulated by RNA interfering in HT-29 and up-regulated by constructing overexpression transgenic line in HCT-116.The proliferation of the above cells was assayed by healing method;while the metastasis and invasion ability were examined by Transwell chamber assay . Results Two colon cancer lines were selected with high-expression or low-expression of FoxM1 separately named HT-29 and HCT-116.Application of PEX-2-FoxM1 raised after HCT-116 cells express FoxM1, cell scratches in HCT-116 experimetal group ([70.92 ±1.48]%) compared with HCT-116 control group([16.92 ±4.05]%)and HCT-116 blank control group([16.66 ±2.63]%) will markedly enhance its capabil-ity of healing (P<0.05), Transwell Chambers in membrane cells in HCT-116 experimetal group (186.0 ±6.8) compared with HCT-116 control group(42.0 ±2.0) and HCT-116 blank control grou (37.0 ± 2.2)was increased (P<0.05).On the other hand, the applied pG-PH-shFoxM1 can reduce FoxM1 expression in HT-29 cell, cell scrat-ches healing ability in HT-29 experimetal group ( [ 10 .37 ± 3.86]%) compared with HT-29 control group([34.63 ±2.35]%)and HT-29 blank control group([67.36 ±2.61]%) decreased significantly (P<0.05), Transwell Chambers in membrane cells in HT-29 experimetal group (53.0 ±1.8)compared with HT-29 control group(95.0 ±2.2)and HT-29 blank control grou(118.0 ±4.0) was also reduced (P<0.05). Conclusion The expression of FoxM1 is in close relation to the invasion and metastasis of CRC .The fact that the siRNA interfering FoxM1 could effectively

  15. Determination of aspergillus flavus toxin M1 in milk by resonance light scattering%共振光散射法检测牛奶中黄曲霉毒素M1

    Institute of Scientific and Technical Information of China (English)

    黄明元; 刘倩楠; 李兰芳

    2013-01-01

    目的:建立一种基于大分子物质环糊精的共振散射光色谱差异测定牛奶中残余黄曲霉毒素M1的新型检测方法.方法:β-环糊精与黄曲霉毒素M1结合后,不同浓度黄曲霉毒素M1与环糊精形成的包合物存在不同强度的共振散射光光谱,用共振瑞利散射光对黄曲霉毒素M1进行检测.结果:在波长为335 nm处共振光散射增强强度与黄曲霉毒素M1的浓度呈线性关系.在pH =4.0~5.0时,包合物形成的最佳温度为60℃,静置时间为1h,方法的检出限为0.38 ng/ml;线性范围为0ng/nd~8.0 ng/ml,线性相关系数r=0.992回收率为85%~ 108%.结论:本方法可简便,快速地测定牛奶中的黄曲霉毒素M1,结果可靠.%objective:A new method for determination of residual aspergillus flavus toxin M1 in milk was established based on macromolecular material cyclodextrin and resonance light scattering spectrum difference.Methods:After combination of beta cyclodextrin and aspergillus flavus toxin M1,clathrate formed by different concentrations of aspergillus flavus toxin M1 and cyclodextrin showed resonance scattering light spectrum had various intensity,then resonance rayleigh scattering light was used to detect aspergillus flavus toxin M1.Results:At the wavelength of 335 nm,the intensity of resonance light scattering was linear with concentration of aspergillus flavus toxin M1.When the pH value was 4.0 ~ 5.0,the optimum temperature of inclusion formation was 60 ℃ and the standing time was 1 h.The detection limit of the method was 0.38 ng/ml,the linear range was 0 ng/ml ~ 8.0 ng/ml with correlation coefficient of r =0.992 and recovery of 85 % ~ 108%.Conclusion:The method is simple and fast in determining aspergillus flavus toxin M1 in milk,with reliable results.

  16. 替米沙坦对小鼠巨噬细胞 M1/M2亚型极化的影响%Effect of Telmisartan on mice macrophage M1/M2 polarization

    Institute of Scientific and Technical Information of China (English)

    邢亦明; 胡泽平; 王邦宁; 周青; 汪渊

    2016-01-01

    Objective To investigate the effect of Telmisartan on the M1 /M2 polarization of mice macrophage . Methods Mice macrophage was induced to M1 /M2 polarization by LPS +IFN-γand IL-4 respectively, and tested by immunofluorescence.Meanwhile cells were treated with 0.1,1,10 μmol /L Telmisartan,blank control group and vehicle control group were established at the same time .The biomarkers iNOS and Arg Ⅰ were tested by Western blot, and the cytokines IL-6 and IL-10 were tested by ELISA assay.Results The biomarker iNOS and IL-6,secre-ted by M1 macrophage, were apparently increased in the macrophages induced by LPS +IFN-γ.However, after be-ing treated with Telmisartan,the expressions of iNOS and IL-6 were obviously decreased(P <0.05), as the concen-tration higher the expression lower .While, the expression of Arg I and IL-10, which represented the M2 macro-phage, increased ( P <0.05).Conclusion Telmisartan can inhibit the M1 polarization of mice macrophage RAW264.7 induced by LPS and IFN-γand transform M1 macrophage polarization to M2 macrophage polarization.%目的探讨替米沙坦对小鼠巨噬细胞 M1/M2亚型极化的影响。方法分别用脂多糖(LPS)联合干扰素-γ(IFN-γ)和白介素-4(IL-4)诱导小鼠巨噬细胞 M1/M2型极化,用免疫荧光法检测极化结果。在 M1型巨噬细胞中分别加入0.1、1、10μmol/L 替米沙坦,同时设立空白对照组及溶剂对照组,Western blot 法检测各组巨噬细胞亚型标志物诱导性一氧化氮合酶(iNOS)和精氨酸酶Ⅰ(Arg Ⅰ)的表达情况, ELISA 法检测各组培养液上清中 IL-6、IL-10表达情况。结果在 LPS +IFN-γ诱导的小鼠巨噬细胞中 M1型巨噬细胞标志物 iNOS、IL-6的表达水平明显升高,替米沙坦干预后,各干预组 M1型巨噬细胞标志物 iNOS、IL-6的表达水平下降(P <0.05),随着替米沙坦浓度的增加而降低,而代表 M2型巨噬细胞标志物的 Arg

  17. 叉头框转录因子M1在甲状腺乳头状癌组织中的表达及意义%Expression and Significance of Forkhead Box M1 in Papillary Thyroid Carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴文艺; 张丽婷; 王朝阳; 邱建龙; 朱世泽

    2013-01-01

    目的 探讨叉头框转录因子M1(FoxM1)在人类甲状腺乳头状癌组织中的表达及其意义.方法 利用实时荧光定量PCR、Western blot检测20例甲状腺乳头状癌组织及相应的20例癌旁正常甲状腺组织和20例甲状腺腺瘤组织中FoxM1 mRNA和蛋白的表达水平并进行统计学分析.结果 FoxM1 mRNA及蛋白表达在甲状腺乳头状癌组织中显著高于癌旁正常甲状腺组织及甲状腺腺瘤组织(均P< 0.01),癌旁正常甲状腺组织和甲状腺腺瘤组织比较差异无统计学意义(P>0.05),甲状腺乳头状癌有淋巴结转移组高于无淋巴结转移组(P<0.01),包膜侵犯组高于包膜无侵犯组(P<0.01).FoxM1 mRNA及蛋白表达与患者的性别、年龄、肿瘤大小及TNM分期均无关(P>0.05).结论 FoxM1 mRNA及蛋白的异常表达可能与甲状腺乳头状癌的发生发展、淋巴结转移、包膜侵犯有关,有望成为甲状腺乳头状癌诊治中的一个新的标志物.%Objective To investigate the expression and clinical significance of forkhead box M1(FoxM1) in human papillary thyroid carcinoma. Methods Quantitative real-time PCR and Western blot was performed to detect the mRNA and protein expressions of FoxM1 in papillary thyroid carcinoma tissues (20 cases), adjacent normal tissues ( 20 cases), and thyroid adenoma (20 cases); statistical analyze was performed. Results The expressions of FoxM1 mRNA and protein in papillary thyroid carcinoma were significantly higher than that in adjacent normal tissues (P 0.05). The expressions of FoxM1 mRNA and protein were higher in the group with lymph node metastasis than those without lymph node metastasis (P 0.05). Conclusion The abnormal expression of FoxM1 may be associated with the oncogenesis and progress of papillary thyroid carcinoma and lymph node metastasis, capsule invasion, which is expected to become a new marker for diagnosis and treatment of papillary thyroid carcinoma.

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

    Science.gov (United States)

    Fiebig, Anne; Loof, Torsten G; Babbar, Anshu; Itzek, Andreas; Koehorst, Jasper J; Schaap, Peter J; Nitsche-Schmitz, D Patric

    2015-09-01

    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 sequence the whole genome of isolates 5448 and AP1 for comparative analysis. Strain 5448 is known to acquire inactivating mutations in the CovRS two-component system during mouse infection, producing hypervirulent progeny such as 5448AP. Isolates AP1 and 5448AP, more than 5448, caused disseminating infections that became systemic and lethal. SF370 was not pathogenic. Phages caused gross genetic differences and increased the gene content of AP1 by 8% as compared to 5448 and SF370. Each of six examined M1 genomes contained two CRISPR-Cas systems. Phage insertion destroyed a type II CRISPR-Cas system in AP1 and other strains of serotypes M1, M3, M6 and M24, but not in M1 strains 5448, SF370, MGAS5005, A20 or M1 476. A resulting impaired defence against invading genetic elements could have led to the wealth of phages in AP1. AP1 lacks genetic features of the MGAS5005-like clonal complex including the streptodornase that drives selection for hypervirulent clones with inactivated CovRS system. Still, inactivating mutations in covS were a common genetic feature of AP1 and the MGAS5005-like isolate 5448AP. Abolished expression of the cysteine proteinase SpeB, due to CovRS inactivation could be a common cause for hypervirulence of the two isolates. Moreover, an additional protein H-coding gene and a mutation in the regulator gene rofA distinguished AP1 form other M1 isolates. In conclusion, hypervirulence of S. pyogenes M1 in mice is not limited to the MGAS5005-like genotype. Copyright © 2015 Elsevier GmbH. All rights reserved.

  19. Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    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

  20. Effect of alphas1-casein ( CSN1S1) genotype on milk CSN1S1 content in Malagueña and Murciano-Granadina goats.

    Science.gov (United States)

    Caravaca, Francisco; Amills, Marcel; Jordana, Jordi; Angiolillo, Antonella; Agüera, Pastora; Aranda, Cristina; Menéndez-Buxadera, Alberto; Sánchez, Alfonso; Carrizosa, Juan; Urrutia, Baltasar; Sànchez, Armand; Serradilla, Juan Manuel

    2008-11-01

    There is substantial evidence showing that the polymorphism of the goat alphas1-casein (CSN1S1) gene has a major effect on milk protein, casein and fat content as well as on cheese yield. However, its influence on the synthesis rate of CSN1S1 has been less studied, with measurements only available in French breeds. In this article, we have measured milk CSN1S1 content in 89 Malagueña and 138 Murciano-Granadina goats with 305 and 460 phenotypic registers, respectively. In the Malagueña breed, average values of CSN1S1 content estimated for BB, BF, EE and FF genotypes were 6.94+/-0.38, 5.36+/-0.22, 4.58+/-0.13 and 3.98+/-0.27 g/l, respectively, being all significantly different (Pgene polymorphism on the synthesis rate of the corresponding protein.

  1. Pre-flare Coronal Jet and Evolutionary Phases of a Solar Eruptive Prominence Associated with the M1.8 Flare: SDO and RHESSI Observations

    Science.gov (United States)

    Joshi, Bhuwan; Kushwaha, Upendra; Veronig, Astrid M.; Cho, K.-S.

    2016-12-01

    We investigate the triggering, activation, and ejection of a solar eruptive prominence that occurred in a multi-polar flux system of active region NOAA 11548 on 2012 August 18 by analyzing data from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory, the Reuven Ramaty High Energy Solar Spectroscopic Imager, and the Extreme Ultraviolet Imager/Sun Earth Connection Coronal and Heliospheric Investigation on board the Solar Terrestrial Relation Observatory. Prior to the prominence activation, we observed striking coronal activities in the form of a blowout jet, which is associated with the rapid eruption of a cool flux rope. Furthermore, the jet-associated flux rope eruption underwent splitting and rotation during its outward expansion. These coronal activities are followed by the prominence activation during which it slowly rises with a speed of ˜12 km s-1 while the region below the prominence emits gradually varying EUV and thermal X-ray emissions. From these observations, we propose that the prominence eruption is a complex, multi-step phenomenon in which a combination of internal (tether-cutting reconnection) and external (i.e., pre-eruption coronal activities) processes are involved. The prominence underwent catastrophic loss of equilibrium with the onset of the impulsive phase of an M1.8 flare, suggesting large-scale energy release by coronal magnetic reconnection. We obtained signatures of particle acceleration in the form of power-law spectra with hard electron spectral index (δ ˜ 3) and strong HXR footpoint sources. During the impulsive phase, a hot EUV plasmoid was observed below the apex of the erupting prominence that ejected in the direction of the prominence with a speed of ˜177 km s-1. The temporal, spatial, and kinematic correlations between the erupting prominence and the plasmoid imply that the magnetic reconnection supported the fast ejection of prominence in the lower corona.

  2. Haemophilus ducreyi-induced interleukin-10 promotes a mixed M1 and M2 activation program in human macrophages.

    Science.gov (United States)

    Li, Wei; Katz, Barry P; Spinola, Stanley M

    2012-12-01

    During microbial infection, macrophages are polarized to classically activated (M1) or alternatively activated (M2) cells in response to microbial components and host immune mediators. Proper polarization of macrophages is critical for bacterial clearance. To study the role of macrophage polarization during Haemophilus ducreyi infection, we analyzed a panel of macrophage surface markers in skin biopsy specimens of pustules obtained from experimentally infected volunteers. Lesional macrophages expressed markers characteristic of both M1 and M2 polarization. Monocyte-derived macrophages (MDM) also expressed a mixed M1 and M2 profile of surface markers and cytokines/chemokines upon infection with H. ducreyi in vitro. Endogenous interleukin 10 (IL-10) produced by infected MDM downregulated and enhanced expression of several M1 and M2 markers, respectively. Bacterial uptake, mediated mainly by class A scavenger receptors, and activation of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathways were required for H. ducreyi-induced IL-10 production in MDM. Compared to M1 cells, IL-10-polarized M2 cells displayed enhanced phagocytic activity against H. ducreyi and similar bacterial killing. Thus, IL-10-modulated macrophage polarization may contribute to H. ducreyi clearance during human infection.

  3. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

    Directory of Open Access Journals (Sweden)

    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.

  4. Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model.

    Science.gov (United States)

    Ghoshal, A; Rook, J M; Dickerson, J W; Roop, G N; Morrison, R D; Jalan-Sakrikar, N; Lamsal, A; Noetzel, M J; Poslusney, M S; Wood, M R; Melancon, B J; Stauffer, S R; Xiang, Z; Daniels, J S; Niswender, C M; Jones, C K; Lindsley, C W; Conn, P J

    2016-01-01

    Schizophrenia patients exhibit deficits in signaling of the M1 subtype of muscarinic acetylcholine receptor (mAChR) in the prefrontal cortex (PFC) and also display impaired cortical long-term depression (LTD). We report that selective activation of the M1 mAChR subtype induces LTD in PFC and that this response is completely lost after repeated administration of phencyclidine (PCP), a mouse model of schizophrenia. Furthermore, discovery of a novel, systemically active M1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of selective potentiation of M1 on induction of LTD and behavioral deficits in PCP-treated mice. Interestingly, VU0453595 fully restored impaired LTD as well as deficits in cognitive function and social interaction in these mice. These results provide critical new insights into synaptic changes that may contribute to behavioral deficits in this mouse model and support a role for selective M1 PAMs as a novel approach for the treatment of schizophrenia.

  5. Dissolution and transport of 2,4-DNT and 2,6-DNT from M1 propellant in soil.

    Science.gov (United States)

    Dontsova, Katerina M; Pennington, Judith C; Hayes, Charolett; Simunek, Jiri; Williford, Clint W

    2009-10-01

    Live-fire training exercises can result in particulate propellant contamination on military training ranges and can potentially contaminate ground water. This study was conducted to evaluate dissolution of the 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) from the propellant formulation, M1 (87.6% nitrocellulose, 7.3% 2,4-DNT, 0.57% 2,6-DNT, 1.06% diphenylamine, 3.48% dibutyl phthalate) and their subsequent transport in soil. Batch dissolution studies were followed by saturated column transport experiments. Neat, dissolved 2,4-DNT, and M1 in solid and dissolved forms were used as influent to columns filled with Plymouth loamy sand (mesic, coated Typic Quartzipsamments) from Camp Edwards, MA. Dissolution rates and other fate and transport parameters were determined using the HYDRUS-1D code. M1 dissolution was limited by DNT diffusion from the interior of the pellet, resulting in an exponential decrease in dissolution rate with time. The HYDRUS-1D model accurately described release and transport of 2,4- and 2,6-DNT from M1 propellant. Dissolution rates for M1 in the stirred reactor and column studies were similar, indicating that batch dissolution rates are potentially useful to represent field conditions.

  6. Cost-effectiveness analysis of gemcitabine, S-1 and gemcitabine plus S-1 for treatment of advanced pancreatic cancer based on GEST study.

    Science.gov (United States)

    Zhou, Jing; Zhao, Rongce; Wen, Feng; Zhang, Pengfei; Tang, Ruilei; Du, Zedong; He, Xiaofeng; Zhang, Jian; Li, Qiu

    2015-04-01

    Gemcitabine (GEM) alone, S-1 alone and gemcitabine plus S-1 (GS) have shown a marginal clinical benefit for the treatment of advanced pancreatic cancer. However, there is no clearly defined optimal cost-effectiveness treatment. The objective of this study was to assess the cost-effectiveness of GEM alone, S-1 alone and GS for the treatment of advanced pancreatic cancer based on GEST study for public payers. A decision model compared GEM alone, S-1 alone and GS. Primary base case data were identified using the GEST study and the literatures. Costs were estimated from West China Hospital, Sichuan University, China, and incremental cost-effectiveness ratios (ICERs) were calculated. Survival benefits were reported in quality-adjusted life-months (QALMs). Sensitive analyses were performed by varying potentially modifiable parameters of the model. The base case analysis showed that the GEM cost $21,912 and yielded survival of 6.93 QALMs, S-1 cost $19,371 and yielded survival of 7.90 QALMs and GS cost $22,943 and yielded survival of 7.46 QALMs in the entire treatment. The one-way sensitivity analyses showed that the ICER of S-1 was driven mostly by the S-1 group utility score of stable state compared with GEM, and the GEM group utility score of progressed state played a key role on the ICER of GS compared with GEM. S-1 represents an attractive cost-effective treatment for advanced pancreatic cancer, given the favorable cost per QALM and improvement in clinical efficacy, especially the limited available treatment options.

  7. Post-marketing Safety Evaluation of S-1 in Patients with Inoperable or Recurrent Breast Cancer: Especially in Patients Treated with S-1 + Trastuzumab

    OpenAIRE

    Saito, Yuki; Oshitanai, Risa; Terao, Mayako; Terada, Mizuho; Tsuda, Banri; Okamura, Takuho; Suzuki, Yasuhiro; Tokuda, Yutaka

    2011-01-01

    Objective The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients. Methods A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Resu...

  8. Post-marketing safety evaluation of S-1 in patients with inoperable or recurrent breast cancer: especially in patients treated with S-1 + trastuzumab.

    Science.gov (United States)

    Saito, Yuki; Oshitanai, Risa; Terao, Mayako; Terada, Mizuho; Tsuda, Banri; Okamura, Takuho; Suzuki, Yasuhiro; Tokuda, Yutaka

    2011-09-01

    The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients. A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. At least one adverse drug reaction was encountered by 858 patients, with an overall incidence of 63.0% (858/1361). The incidence of Grade 3 or higher adverse drug reactions in a descending order was 14.7% (200/1361). In this study, the most common combination drug was trastuzumab. The overall incidence of adverse drug reactions was 63.5% (431/679 patients) in patients treated with S-1 alone, and 55.9% (66/118 patients) in patients treated with S-1 + trastuzumab. Monotherapy with S-1 or combination therapy with S-1 + trastuzumab was well tolerated for inoperable or recurrent breast cancer patients.

  9. 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...

  10. Different roles for M1 and M2 receptors within perirhinal cortex in object recognition and discrimination.

    Science.gov (United States)

    Bartko, Susan J; Winters, Boyer D; Saksida, Lisa M; Bussey, Timothy J

    2014-04-01

    Recognition and discrimination of objects and individuals are critical cognitive faculties in both humans and non-human animals, and cholinergic transmission has been shown to be essential for both of these functions. In the present study we focused on the role of M1 and M2 muscarinic receptors in perirhinal cortex (PRh)-dependent object recognition and discrimination. The selective M1 antagonists pirenzepine and the snake toxin MT-7, and a selective M2 antagonist, AF-DX 116, were infused directly into PRh. Pre-sample infusions of both pirenzepine and AF-DX 116 significantly impaired object recognition memory in a delay-dependent manner. However, pirenzepine and MT-7, but not AF-DX 116, impaired oddity discrimination performance in a perceptual difficulty-dependent manner. The findings indicate distinct functions for M1 and M2 receptors in object recognition and discrimination.

  11. Association between aflatoxin M1 excreted in human urine samples with the consumption of milk and dairy products.

    Science.gov (United States)

    Mohd Redzwan, Sabran; Rosita, Jamaluddin; Mohd Sokhini, Abdul Mutalib; Nurul Aqilah, Abdul Rahman

    2012-12-01

    This study aimed to find the association between urinary aflatoxin M(1) level and milk and dairy products consumption. Of 160 morning urine samples collected, aflatoxin M(1) was detected in 61.3 % samples (n = 98) [mean ± SD = 0.0234 ± 0.0177 ng/mL; range = 0-0.0747 ng/mL]. Of these positive samples, 67.3 % (n = 66) had levels above the limit of detection. Respondents with intake of milk and dairy products above median (67.79 g/day) had significantly high level of AFM(1) compared to those with low intake. A significant and positive association (φ = 0.286) was found between milk and dairy products consumption and urinary aflatoxin M(1) level.

  12. Observation of M1 resonance in sup 2 sup 0 sup 6 Pb using a highly linear polarized photon beam

    CERN Document Server

    Ohgaki, H; Noguchi, T; Sugiyama, S; Mikado, T; Yamada, K; Suzuki, R; Ohdaira, T; Sei, N; Yamazaki, T

    1999-01-01

    More than twenty M1 states were discovered in sup 2 sup 0 sup 6 Pb from 6.5 to 8.1 MeV with a high-resolution NRF experiment that used a highly linear-polarized photon beam generated by laser-Compton backscattering. The total reduced transition probability of sigma B(M1 arrow up) = 17.4+-5.6 mu sup 2 sub N agreed well with QPM calculation (16.1 mu sup 2 sub N) and previous tagged photon experiment (19 +- 2 mu sup 2 sub N). A fine structure of two bumps at 7.2 and 7.9 MeV which was reproduced reasonably by the QPM calculation was clearly observed in the isovector M1 strength distribution.

  13. Disturbed mitochondrial function restricts glutamate uptake in the human Müller glia cell line, MIO-M1.

    Science.gov (United States)

    Vohra, Rupali; Gurubaran, Iswariyaraja Sridevi; Henriksen, Ulrik; Bergersen, Linda Hildegaard; Rasmussen, Lene Juel; Desler, Claus; Skytt, Dorte Marie; Kolko, Miriam

    2017-09-01

    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. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  14. 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.

  15. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Science.gov (United States)

    Kasthurinaidu, Senthilkumar Pitchalu; Ramasamy, Thirumurugan; Ayyavoo, Jayachitra; Dave, Dhvani Kirtikumar; Adroja, Divya Anantray

    2015-01-01

    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. 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.

  17. Age-related peculiarities of inotropic response of rat myocardium to selective block of M1-cholinoreceptors.

    Science.gov (United States)

    Zefirov, T L; Ziyatdinova, N I; Zefirov, A L

    2013-10-01

    In vitro effect of M1-cholinoreceptor blockade on the cardiac inotropic function was examined in rats aging 1, 3, 6, 8, and 20 weeks. In 1- and 3-week old rat pups, the sympathetic control of the heart has not developed, the age of 7-8 weeks being pubertal. Adult 20-week rats were used as the controls. In rats of all age groups, preliminary blockade of M1-cholinoreceptors did not prevent the inhibitory effect of carbacholine on contractility of the atrial and ventricular myocardium. The inhibitory effect of pirenzepine on the contractile force of ventricular myocardium was revealed in 6-week rats.

  18. Learning from the other limb's experience: sharing the 'trained' M1 representation of the motor sequence knowledge.

    Science.gov (United States)

    Gabitov, Ella; Manor, David; Karni, Avi

    2016-01-01

    Participants were scanned during the untrained-hand performance of a motor sequence, intensively trained a day earlier, and also a similarly constructed but novel, untrained sequence. The superior performance levels for the trained, compared to the untrained sequence, were associated with a greater magnitude of activity within the primary motor cortex (M1), bilaterally, for the trained sequence. The differential responses in the 'trained' M1, ipsilateral to the untrained hand, were positively correlated with experience-related differences in the functional connectivity between the 'trained' M1 and (1) its homologue and (2) the dorsal premotor cortex (PMd) within the contralateral hemisphere. No significant correlation was evident between experience-related differences in M1 - M1 and M1 - PMd connectivity measures. These results suggest that the transfer of sequence-specific information between the two primary motor cortices is predominantly mediated by excitatory mechanisms driven by the 'trained' M1 via two independent neural pathways. Following unimanual training on a novel sequence of movements, sequence-specific performance may improve overnight not only in the trained hand, but also in the hand afforded no actual physical experience. It is not clear, however, how transfer to the untrained hand is achieved. In the present study, we examined whether and how interaction between the two primary motor cortices contributes to the performance of a sequence of movements, extensively trained the day before, by the untrained hand. Accordingly, we studied participants during the untrained-hand performance of a finger-to-thumb opposition sequence (FOS), intensively trained a day earlier (T-FOS), and a similarly constructed, but novel, untrained FOS (U-FOS). Changes in neural signals driven by task performance were assessed using functional magnetic resonance imaging. To minimize potential differences as a result of the rate of sequence execution per se, participants

  19. Temporal Evolution of Chromospheric Evaporation: Case Studies of the M1.1 Flare on 2014 September 6 and X1.6 Flare on 2014 September 10

    Science.gov (United States)

    Tian, Hui; Young, Peter R.; Reeves, Katharine K.; Chen, Bin; Liu, Wei; McKillop, Sean

    2015-10-01

    With observations from the Interface Region Imaging Spectrograph, we track the complete evolution of ˜11 MK evaporation flows in an M1.1 flare on 2014 September 6 and an X1.6 flare on 2014 September 10. These hot flows, as indicated by the blueshifted Fe xxi 1354.08 Å line, evolve smoothly with a velocity decreasing exponentially from ˜200 km s-1 to almost stationary within a few minutes. We find a good correlation between the flow velocity and energy deposition rate as represented by the hard X-ray flux observed with the Reuven Ramaty High Energy Solar Spectroscopic Imager, or time derivative of the soft X-ray flux observed with the Geostationary Operational Environmental Satellites and the HINODE X-ray Telescope, which is in general agreement with models of nonthermal electron heating. The maximum blueshift of Fe xxi appears approximately at the same time as or slightly after the impulsive enhancement of the ultraviolet continuum and the Mg ii 2798.8 Å line emission, demonstrating that the evaporation flow is closely related to heating of the lower chromosphere. Finally, while the hot Fe xxi 1354.08 Å line is entirely blueshifted with no obvious rest component, cool chromospheric and transition region lines like Si iv 1402.77 Å are often not entirely redshifted but just reveal an obvious red wing enhancement at the ribbons, suggesting that the speed of chromospheric condensation might be larger than previously thought.

  20. Chisholm-Caianiello-Fubini Identities for S=1 Barut-Muzinich-Williams Matrices

    CERN Document Server

    Cabral, M de G Caldera

    2013-01-01

    The formulae of the relativistic products are found S=1 Barut-Muzinich-Williams matrices. They are analogs of the well-known Chisholm-Caianiello-Fubini identities. The obtained results can be useful in the higher-order calculations of the high-energy processes with S=1 particles in the framework of the 2(2S+1) Weinberg formalism, which recently attracted attention again. PACS numbers: 02.90.+p, 11.90.+t, 12.20.Ds

  1. Discovery of a novel series of potent S1P1 agonists.

    Science.gov (United States)

    Crosignani, Stefano; Bombrun, Agnes; Covini, David; Maio, Maurizio; Marin, Delphine; Quattropani, Anna; Swinnen, Dominique; Simpson, Don; Sauer, Wolfgang; Françon, Bernard; Martin, Thierry; Cambet, Yves; Nichols, Anthony; Martinou, Isabelle; Burgat-Charvillon, Fabienne; Rivron, Delphine; Donini, Cristina; Schott, Olivier; Eligert, Valerie; Novo-Perez, Laurence; Vitte, Pierre-Alain; Arrighi, Jean-François

    2010-03-01

    The discovery of a novel series of S1P1 agonists is described. Starting from a micromolar HTS positive, iterative optimization gave rise to several single-digit nanomolar S1P1 agonists. The compounds were able to induce internalization of the S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing.

  2. Orally administered S-1 suppresses circulating endothelial cell counts in metastatic breast cancer patients.

    OpenAIRE

    2013-01-01

    [Background]S-1 is an oral cytotoxic preparation that contains tegafur. Gamma-butyrolactone (GBL) is a metabolite of tegafur that is known to suppress vascular endothelial growth factor (VEGF)-mediated angiogenic activity. The aim of this study was to determine the change in circulating endothelial cell (CEC) counts, GBL levels, and angiogenesis-related factors during S-1 administration in metastatic breast cancer (MBC) patients. [Methods]Patients with HER2-negative MBC were eligible. S-1 was...

  3. S1←S0 vibronic spectra and structure of cyclopropanecarboxaldehyde molecule in the S1 lowest excited singlet electronic state

    Science.gov (United States)

    Godunov, I. A.; Yakovlev, N. N.; Terentiev, R. V.; Maslov, D. V.; Bataev, V. A.; Abramenkov, A. V.

    2016-11-01

    The S1←S0 vibronic spectra of gas-phase absorption at room temperature and fluorescence excitation of jet-cooled cyclopropanecarboxaldehyde (CPCA, c-C3H5CHO)were obtained and analyzed. In addition, the quantum chemical calculation (CASPT2/cc-pVTZ)was carried out for CPCA in the ground (S0) and lowest excited singlet (S1) electronic states. As a result, it was proved that the S1←S0 electronic excitation of the CPCA conformers (syn and anti) causes (after geometrical relaxation) significant structural changes, namely, the carbonyl fragments become non-planar and the cyclopropyl groups rotate around the central C-C bond. As a consequence, the potential energy surface of CPCA in the S1 state has six minima, 1ab, 2ab, and 3ab, corresponding to three pairs of mirror symmetry conformers: a and b. It was shown that vibronic bands of experimental spectra can be assigned to the 2(S1)←syn(S0) electronic transition with the origin at 30,481 cm-1. A number of fundamental vibrational frequencies for the 2 conformer of CPCA were assigned. In addition, several inversional energy levels for the 2 conformer were found and the 2a↔2b potential function of inversion was determined. The experimental barrier to inversion and the equilibrium angle between the CH bond and the CCO plane were calculated as 570 cm-1 and 28°, respectively.

  4. Benzyl butyl phthalate promotes breast cancer stem cell expansion via SPHK1/S1P/S1PR3 signaling

    Science.gov (United States)

    Chuang, Hsiao-Li; Chang, Yi-Chih; Chen, Hung-Sheng; Lee, Jau-Nan; Tsai, Eing-Mei

    2016-01-01

    Understanding the regulatory mechanisms unique to breast cancer stem cells (BCSCs) is required to control breast cancer metastasis. We found that phthalates promote BCSCs in human breast cancer cell cultures and xenograft tumors. A toxic phthalate, benzyl butyl phthalate (BBP), activated aryl hydrocarbon receptor in breast cancer cells to stimulate sphingosine kinase 1 (SPHK1)/sphingosine 1-phosphate (S1P)/sphingosine-1-phosphate receptor 3 (S1PR3) signaling and enhance formation of metastasis-initiating BCSCs. BBP induced histone modifications in S1PR3 in side population (SP) cells, but not in non-SP cells. SPHK1 or S1PR3 knockdown in breast cancer cells effectively reduced tumor growth and lung metastasis in vivo. Our findings suggest S1PR3 is a determinant of phthalate-driven breast cancer metastasis and a possible therapeutic target for regulating BCSC populations. Furthermore, the association between breast carcinogenesis and environmental pollutants has important implications for public health. PMID:27129165

  5. Effect of S1P5 on proliferation and migration of human esophageal cancer cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the sphingosine 1phosphate (S1P) receptor expression profile in human esophageal cancer cells and the effects of S1P5 on proliferation and migration of human esophageal cancer cells. METHODS: S1P receptor expression profile in human esophageal squamous cell carcinoma cell line Eca109 was detected by semiquantitative reverse trans cription polymerase chain reaction. Eca109 cells were stably transfected with S1P5EGFP or controlEGFP constructs. The relation between the responses of cell prol...

  6. Intersystem crossing rates of S1 state keto-amino cytosine at low excess energy

    Science.gov (United States)

    Lobsiger, Simon; Etinski, Mihajlo; Blaser, Susan; Frey, Hans-Martin; Marian, Christel; Leutwyler, Samuel

    2015-12-01

    The amino-keto tautomer of supersonic jet-cooled cytosine undergoes intersystem crossing (ISC) from the v = 0 and low-lying vibronic levels of its S1(1ππ∗) state. We investigate these ISC rates experimentally and theoretically as a function of S1 state vibrational excess energy Eexc. The S1 vibronic levels are pumped with a ˜5 ns UV laser, the S1 and triplet state ion signals are separated by prompt or delayed ionization with a second UV laser pulse. After correcting the raw ISC yields for the relative S1 and T1 ionization cross sections, we obtain energy dependent ISC quantum yields QISC corr = 1 % -5%. These are combined with previously measured vibronic state-specific decay rates, giving ISC rates kISC = 0.4-1.5 ṡ 109 s-1, the corresponding S1⇝S0 internal conversion (IC) rates are 30-100 times larger. Theoretical ISC rates are computed using SCS-CC2 methods, which predict rapid ISC from the S1; v = 0 state with kISC = 3 ṡ 109 s-1 to the T1(3ππ∗) triplet state. The surprisingly high rate of this El Sayed-forbidden transition is caused by a substantial admixture of 1nOπ∗ character into the S1(1ππ∗) wave function at its non-planar minimum geometry. The combination of experiment and theory implies that (1) below Eexc = 550 cm-1 in the S1 state, S1⇝S0 internal conversion dominates the nonradiative decay with kIC ≥ 2 ṡ 1010 s-1, (2) the calculated S1⇝T1 (1ππ∗⇝3ππ∗) ISC rate is in good agreement with experiment, (3) being El-Sayed forbidden, the S1⇝T1 ISC is moderately fast (kISC = 3 ṡ 109 s-1), and not ultrafast, as claimed by other calculations, and (4) at Eexc ˜ 550 cm-1 the IC rate increases by ˜50 times, probably by accessing the lowest conical intersection (the C5-twist CI) and thereby effectively switching off the ISC decay channels.

  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. Effects of the spin-orbit and tensor interactions on the M1 and E2 excitations in light nuclei

    CERN Document Server

    Fayache, M S; Zamick, L; Von Neumann-Cosel, P; Richter, A

    1996-01-01

    The effects of varying the spin-orbit and tensor components of a realistic interaction on M1 excitation rates and B(E2)'s are studied on nuclei in the 0p and 1s-0d shells. Not only the total M1 but also the spin and orbital parts separately are studied. The single-particle energies are first calculated with the same interaction that is used between the valence nucleons. Later this stringent condition is relaxed somewhat and the 1s level is raised relative to 0d. For nuclei up to ^{28}Si, much better results i.e stronger B(M1) rates are obtained by increasing the strength of the spin-orbit interaction relative to the free value. This is probably also true for ^{32}S, but ^{36}Ar presents some difficulties. The effects of weakening the tensor interaction are also studied. On a more subtle level, the optimum spin-orbit interaction in the lower half of the s-d shell, as far as M1 excitations are concerned, is substantially larger than the difference E(J=3/2^+)_1-E(J=5/2^+)_1=5.2~MeV in ^{17}O. A larger spin-orbit...

  9. Diagonalization of transfer matrix of supersymmetry $u_q(\\hat{sl}(m+1|n+1))$ chain with a boundary

    CERN Document Server

    Kojima, Takeo

    2012-01-01

    We study the supersymmetry $U_q(\\hat{sl}(M+1|N+1))$ analogue of the supersymmetric t-J model with a boundary, in the framework of the algebraic analysis method. We diagonalize the commuting transfer matrix by using the bosonization of the vertex operator associated with the quantum affine supersymmetry.

  10. Occurrence of aflatoxins M(1) and M(2) in milk commercialized in Ribeirão Preto-SP, Brazil.

    Science.gov (United States)

    Garrido, N S; Iha, M H; Santos Ortolani, M R; Duarte Fávaro, R M

    2003-01-01

    Aflatoxins are toxic metabolites found in foods and feeds. When ruminants eat foodstuffs containing aflatoxins B(1) and B(2), these toxins are metabolized and excreted as aflatoxin M(1) and M(2) in milk. The aim was to determine the incidence of these aflatoxins in commercial milk collected from supermarkets in Ribeirão Preto-SP, Brazil, and consisting of 60 ultrahigh temperature (UHT) milk samples and 79 pasteurized milk samples. The milk samples were analysed according to method 986.16 of AOAC International. None of the milk samples analysed were contaminated with aflatoxin M(2), and aflatoxin M(1) was detected in 29 (20.9%) of samples in the range 50-240 ng l(-1). The results show that despite a high occurrence of aflatoxin M(1) in commercial pasteurized and UHT milk sold in Ribeirão Preto in 1999 and 2000, the contamination level of these toxins could not be considered a serious public health problem according to MERCOSUR Technical Regulations. However, levels in 20.9% of the milk samples exceeded the concentration of 50 ng l(-1) permitted by the European Union. Although it is not necessary to continue monitoring the incidence and levels of aflatoxins M(1) and M(2) in milk samples, surveillance could be appropriate.

  11. Structural changes in steel 10Kh9K3V1M1FBR due to creep

    Science.gov (United States)

    Kipelova, A. Yu.; Belyakov, A. N.; Skorobogatykh, V. N.; Shchenkova, I. A.; Kaibyshev, R. O.

    2010-09-01

    The evolution of microstructure in steel 10Kh9K3V1M1FBR during creep and in aging at 600 - 650°C is studied. The results are compared with data for steel P91. The role of cobalt in growth in the long-term strength is considered.

  12. Preparation of three spray-dried milkpowder reference materials for aflatoxin M1 analysis, including packaging and homogeneity control

    NARCIS (Netherlands)

    Egmond; H.P.van; Sizoo; E.A.

    1984-01-01

    Ten behoeve van BCR werden drie partijen melkpoeder bereid, langs natuurlijke weg besmet met aflatoxine M1 op niveau's van 0, ca. 0.3 en ca. 0.9 mug/kg. Van elke partij werden ca. 300 eenheden van elk 25 gram afgevuld in laminaatverpakkingen, die onder N2 werden afgesloten. Onderzoek na afv

  13. Aflatoxin M1 contamination of milk and ice cream in Abeokuta and Odeda local governments of Ogun State, Nigeria.

    Science.gov (United States)

    Atanda, Olusegun; Oguntubo, Adenike; Adejumo, Oloyede; Ikeorah, John; Akpan, Iyang

    2007-07-01

    A survey was undertaken to determine the aflatoxin M(1) contamination of milk and some locally produced dairy products in Abeokuta and Odeda local governments of Ogun State, Nigeria. Samples of human and cow milk, yoghurt, "wara", ice cream and "nono" were collected randomly within the local governments and analysed for aflatoxin M(1) using the two-dimensional TLC. Aflatoxin M(1) contamination in the range of 2.04-4.00 microg l(-1) was noticed only in milk and ice cream. In particular, samples of human milk, cow milk and ice cream recorded high scores of 4.0 microg l(-1), 2.04 microg l(-1) and 2.23 microg l(-1), respectively in Abeokuta local governments and a score of 4.0 microg l(-1) for cow milk in Odeda local government. This indicates a high level contamination in the local governments since the weighted mean concentration of aflatoxin M1 in milk for African diet is 0.002 microg l(-1). Therefore the concentration of AFB1 in feeds which is transformed to AFM1 in milk should be reduced by good manufacturing and good storage practices. Furthermore, there is need for stringent quality control during processing and distribution of these products.

  14. Role of Microglial M1/M2 Polarization in Relapse and Remission of Psychiatric Disorders and Diseases

    Directory of Open Access Journals (Sweden)

    Yutaka Nakagawa

    2014-11-01

    Full Text Available Psychiatric disorders such as schizophrenia and major depressive disorder were thought to be caused by neurotransmitter abnormalities. Patients with these disorders often experience relapse and remission; however the underlying molecular mechanisms of relapse and remission still remain unclear. Recent advanced immunological analyses have revealed that M1/M2 polarization of macrophages plays an important role in controlling the balance between promotion and suppression in inflammation. Microglial cells share certain characteristics with macrophages and contribute to immune-surveillance in the central nervous system (CNS. In this review, we summarize immunoregulatory functions of microglia and discuss a possible role of microglial M1/M2 polarization in relapse and remission of psychiatric disorders and diseases. M1 polarized microglia can produce pro-inflammatory cytokines, reactive oxygen species, and nitric oxide, suggesting that these molecules contribute to dysfunction of neural network in the CNS. Alternatively, M2 polarized microglia express cytokines and receptors that are implicated in inhibiting inflammation and restoring homeostasis. Based on these aspects, we propose a possibility that M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases. Consequently, a target molecule skewing M2 polarization of microglia may provide beneficial therapies for these disorders and diseases in the CNS.

  15. Finite-beta effects on the nonlinear evolution of the (m = 1; n = 1) mode in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, J.A.; Carreras, B.A.; Hicks, H.R.; Lynch, V.E.; Rothe, K.E.

    1982-01-01

    The stability and evolution of ISX-B-like plasmas are numerically studied using a reduced set of resistive magnetohydrodynamic (MHD) equations. For a sequence of equilibria stable to ideal modes, the n = 1 mode changes from a tearing branch to a pressure-driven branch as ..beta../sup p/ is increased. When this mode is unstable at low beta, it is just the (m = 1;n = 1) tearing mode. Higher n modes also become linearly unstable with increasing ..beta../sub p/; they are essentially pressure driven and have a ballooning character. For low values of beta the instability is best described as a ..beta../sub p/ distortion of the (m = 1;n = 1) tearing mode. This mode drives many other helicities through toroidal and nonlinear couplings. As ..beta../sub p/ is increased, the growth of the m = 1 island slows down in time, going from exponential to linear before reconnection occurs. If ..beta../sub p/ is large enough, the island saturates without reconnection. A broad spectrum of other modes, driven by the (m = 1;n = 1) instability, is produced. These results agree with some observed features of MHD activity in ISX-B.

  16. 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.

  17. 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.

  18. Research on detection results of aflatoxin M1 enzyme-linked immune sorbent assay detection kit%黄曲霉毒素M1 ELISA试剂盒的检测效果研究

    Institute of Scientific and Technical Information of China (English)

    李平; 谢体波; 易重任; 魏丽丽; 王大敏; 张建宇; 欧翔; 陈芳; 罗先坤

    2015-01-01

    目的:为验证本公司生产的黄曲霉毒素 M1酶联免疫法(ELISA)检测试剂盒的检测效果。方法用ELISA检测试剂盒对牛奶、酸奶、奶粉和干酪等4种样品中黄曲霉毒素M1的残留量进行检测,并与高效液相色谱荧光检测法进行对照。结果该试剂盒对4种样品的最低检测限分别为0.039、0.192、0.306、0.199μg/kg(L),试剂盒板内板间变异系数均小于5%;对4种样品做加标回收试验,其回收率均在93%~120%之间,变异系数均小于10%;该方法与高效液相色谱法检测实际样品的阴、阳性判断结果一致。结论该方法稳定、可靠、灵敏,可满足食品中黄曲霉毒素M1残留快速检测的需要。%Objective To verify the test effect of aflatoxin M1 enzyme-linked immune sorbent assay (ELISA) detection kit developed by Beijing Kwinbon biotechnology company. Methods The method of ELISA was used to detect the residues of aflatoxin M1 in milk, yoghurt, milk powder and cheese, and compared with high performance liquid chromatography (HPLC). Results The results showed that the minimum detection limitation of the kit for the 4 kinds of samples were 0.039, 0.192, 0.306, and 0.199 μg/kg (L), the coefficient of variation was less than 5%. The recovery of the method was in the range of 93%~120%, and the coefficient of variation was less than 10%. The judgments of positive and negative by ELISA were the same as those of HPLC. Conclusion This method was efficient, reliable and sensitive, and could meet the fast-test for the determination of aflatoxin M1 residues in food.

  19. M1 Site Splitting Due to Next Nearest Neighbor Effects and Ferric Iron in Tetrahedral Site in Clinopyroxene Megacrysts

    Institute of Scientific and Technical Information of China (English)

    李一良; 李玉芝; 等

    1998-01-01

    It is well known that in pyroxene structure,there are two metal sites,M1 and M2.Generally speaking,Ferrous iron in each of these sites would normally be expected to give rise to a doublet,However,anomalies have been found in the relative areas of the peaks in the room temperature spectra of some clinopyroxene(CPX)when the above assignment is followed.According to the calculation of Next Nearest Neighbor configurations of divalent cations in M1,we found that the four configurations of M1 can be divided into two groups.One group is 3Ca configuration that increases with the content of Ca(p.f.u);the other group is made up of three No-3Ca configurations that decrease with the content of Ca.The two groups contribute to the spectrum structure of M1.so in this study we fit two doublets for ferrous iron in M1.Though there were several reports on Fe3+ in tetrahedral site previously,it was not sure that Fe3+ occupies the T site is a universal fact in CPX,despite of the content of Al.We found that the Fe3+ in the T site fitted by Moessbauer spectroscopy is negatively correlated to the Si content in the T site and positively correlated to the Fe3+ in the T site estimated on the supposition that Fe3+ and Al occupy the T site randomly.If it is true.it is important in the modeling of ion exchange geobarometries and geothermomeries.

  20. M1 and M2 macrophage recruitment during tendon regeneration induced by amniotic epithelial cell allotransplantation in ovine.

    Science.gov (United States)

    Mauro, Annunziata; Russo, Valentina; Di Marcantonio, Lisa; Berardinelli, Paolo; Martelli, Alessandra; Muttini, Aurelio; Mattioli, Mauro; Barboni, Barbara

    2016-04-01

    Recently, we have demonstrated that ovine amniotic epithelial cells (oAECs) allotransplanted into experimentally induced tendon lesions are able to stimulate tissue regeneration also by reducing leukocyte infiltration. Amongst leukocytes, macrophages (Mφ) M1 and M2 phenotype cells are known to mediate inflammatory and repairing processes, respectively. In this research it was investigated if, during tendon regeneration induced by AECs allotransplantation, M1Mφ and M2Mφ phenotype cells are recruited and differently distributed within the lesion site. Ovine AECs treated and untreated (Ctr) tendons were explanted at 7, 14, and 28 days and tissue microarchitecture was analyzed together with the distribution and quantification of leukocytes (CD45 positive), Mφ (CD68 pan positive), and M1Mφ (CD86, and IL12b) and M2Mφ (CD206, YM1 and IL10) phenotype related markers. In oAEC transplanted tendons CD45 and CD68 positive cells were always reduced in the lesion site. At day 14, oAEC treated tendons began to recover their microarchitecture, contextually a reduction of M1Mφ markers, mainly distributed close to oAECs, and an increase of M2Mφ markers was evidenced. CD206 positive cells were distributed near the regenerating areas. At day 28 oAECs treated tendons acquired a healthy-like structure with a reduction of M2Mφ. Differently, Ctr tendons maintained a disorganized morphology throughout the experimental time and constantly showed high values of M1Mφ markers. These findings indicate that M2Mφ recruitment could be correlated to tendon regeneration induced by oAECs allotransplantation. Moreover, these results demonstrate oAECs immunomodulatory role also in vivo and support novel insights into their allogeneic use underlying the resolution of tendon fibrosis.

  1. 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.

  2. 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 S1P1 receptor (S1P1R) 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 S1P1R on T cells, and that the requirement for S1P1R 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.

  3. 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.

  4. M/M/1/m系统算子的本征值特性(m=5,6)%The Characteristics of Eigenvalue of M/M/1/m(m =5,6)

    Institute of Scientific and Technical Information of China (English)

    盖平; 高超; 唐慧; 赵立杰

    2010-01-01

    研究了m=5,6时,M/M/1/m算子本征值特性:m=6时相应本征值的代数重为1;m=5,6时,相应的系统算子的非零本征值相互交替;m=6时的最大非零本征值比m=5时更靠近0点.这种特性延续了m=1,2,3,4,5时相应的特性.另外给出了m=5,6时,相应的po(t)图像.

  5. The Lattice Path for Embedded Markov Chain of M/M/1 Queuing System%M/M/1排队系统嵌入Markov链瞬态解的格路径算法

    Institute of Scientific and Technical Information of China (English)

    刘海宁; 屈明双

    2009-01-01

    在定义了生灭过程状态转移的单格与升降格和降升格的基础上,证明了M/M/1排队系统{X(t)t≥0}的嵌入Markov链{X(n)n≥0}的转移概率弱收敛于系统的瞬态解,并利用随机游动的格路径算法求出了该链的转移概率P(i,j,n)的显式算法表达式,从而达到确定M/M/1排队系统{X(t)t≥0}瞬态解的转移概率的目的.

  6. Comparison of HPLC and ELISA Method in Detection of Aflatoxin M1 in Milk%HPLC与ELISA法测定牛奶中黄曲霉毒素M1的比较研究

    Institute of Scientific and Technical Information of China (English)

    胡宏灿; 韩飞; 林悦楷; 卢任杰

    2013-01-01

    The method for detecting aflatoxin Ml in milk was studied by comparison of HPLC and ELISA method. The recovery rates of HPLC were 68%-85% and the recovery rates of ELISA were 97%-109%. Detection results of HPLC and ELISA had good correlation. ELISA method had low cost, rapid detection, it could be used for preliminary screening of aflatoxin Ml. HPLC method was accurate but it had high cost of testing, it is suitable for conclusive evidence of aflatoxin Ml residue.%对HPLC法和ELISA法检测牛奶样品中黄曲霉毒素M1(AFM1)残留量进行了比较,探讨了牛奶中黄曲霉毒素M1的最佳检测方法.结果显示,对于已知加标样品(阳性),HPLC法回收率为68%~85%;ELISA法回收率为97%~109%,HPLC法和ELISA法具有良好的相关性.ELISA法检验成本较低、检测迅速,但可能出现少量的假阳性和假阴性,故可用于待测样品的初筛;HPLC法检测结果准确,但检测费用较高,适用于黄曲霉毒素M1残留的确证.

  7. M/M/1/m系统算子的本征值特性(m=7,8)%The Characteristics of Eigenvalue of M/M/1/m(m = 7,8)

    Institute of Scientific and Technical Information of China (English)

    王伟华; 高超

    2011-01-01

    研究了m=7,8时,M/M/1/m算子本征值特性:相应本征值的代数重为1;m=7,8时,相应的系统算子的非零本征值相互交替;m=8时的最大非零本征值比m=7时更靠近0点.这种特性延续了m=1,2,3,4,5,6时相应的特性.另外给出了m=7,8时,相应的p0(t)图像.%In this paper, studying the characteristic of eigenvalue of M/M/1/m operator,as m = 7, 8. The eigenvalue of every model is simple; The non-zero eigenvalue of the two operator of the system alternate each other. And the maximal nonzero eigenvalue of the latter operator is approximating to zero point. Moreover, the graphs of P0(t) are given, as m = 7, 8.

  8. 牛奶中黄曲霉毒素M1的来源和控制途径%Sources and Ways to Control Aflatoxin M1 in Dairy Milk

    Institute of Scientific and Technical Information of China (English)

    熊江林; 王艳明; 刘建新

    2012-01-01

    Ayatoxins are toxic fungal metabolites found in foods and feeds. Aflatoxins from environment mainly include four subtypes: aflatoxin B1, B2, G1 and aflatoxin G2. Aflatoxin M1, carcinogenic metabolite of aflatoxin B1 in animal body, can be excreted through cow's milk and cause safety issue in dairy milk. In this review article, the sources and conversion of aflatoxin M1 were first discussed. Maximum residue limit (MRL), regulated by main countries and organizations in the world, was compared. Discussion was also made on the detection methods and the possible ways to control aflatoxin M1 in cow milk%黄曲霉毒素(AFs)是存在于食物或饲料中真菌的有毒代谢物,天然产生的AFs主要有AFB1、AFB2、AFG1和AFG2,而AFM1则是AFB1经动物体内转化而来,具有致癌性,可通过牛奶排出,引起牛奶的安全问题.本文综述了牛奶中AFM1的来源与转化,主要国家和组织对奶中AFM1的限量,奶中AFM1的检测方法和控制途径.

  9. Pan-STARRS 1 observations of the unusual active Centaur P/2011 S1(Gibbs)

    CERN Document Server

    Lin, H W; Lacerda, P; Ip, W H; Holman, M; Protopapas, P; Chen, W P; Burgett, W S; Chambers, K C; Flewelling, H; Huber, M E; Jedicke, R; Kaiser, N; Magnier, E A; Metcalfe, N; Price, P A

    2014-01-01

    P/2011 S1 (Gibbs) is an outer solar system comet or active Centaur with a similar orbit to that of the famous 29P/Schwassmann-Wachmann 1. P/2011 S1 (Gibbs) has been observed by the Pan-STARRS 1 (PS1) sky survey from 2010 to 2012. The resulting data allow us to perform multi-color studies of the nucleus and coma of the comet. Analysis of PS1 images reveals that P/2011 S1 (Gibbs) has a small nucleus $< 4$ km radius, with colors $g_{P1}-r_{P1} = 0.5 \\pm 0.02$, $r_{P1}-i_{P1} = 0.12 \\pm 0.02$ and $i_{P1}-z_{P1} = 0.46 \\pm 0.03$. The comet remained active from 2010 to 2012, with a model-dependent mass-loss rate of $\\sim100$ kg s$^{-1}$. The mass-loss rate per unit surface area of P/2011 S1 (Gibbs) is as high as that of 29P/Schwassmann-Wachmann 1, making it one of the most active Centaurs. The mass-loss rate also varies with time from $\\sim 40$ kg s$^{-1}$ to 150 kg s$^{-1}$. Due to its rather circular orbit, we propose that P/2011 S1 (Gibbs) has 29P/Schwassmann-Wachmann 1-like outbursts that control the outgass...

  10. Expression and purification of the Bordella Pertussis toxin S1 subunit mutant in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Xiao L. Zhang; Quan M. Zou

    2007-01-01

    Bordella pertussis is the causative agent of whooping cough.Traditional vaccines against this disease are inherently reactogenic, thus research is currentlly focussed on the production of less reactive,acellular vaccines.Expression of candidate antigens for these vaccines in Escherichia coli would be preferable. Pertussis toxin S1 subunit plays a critical role in the bacterium-host interplay.The mutant(rS1) containing two key amino acids substitution(Arg9-Lys/Glu129-Gly)is nontoxin and immunogenic and while retaining the protective epitopes. In this study, the immunoprotective S1 fragment of pertussis toxin fusion was verified by restriction endonuclease analysis and Western immunoblotting. Escherichia coli carrying the recombinant plasmid(pQE-rS1)produced a 26 kDa protein that was recognized by antibodies specific to the S1. Expressed rS1 in E. coli was purified from the inclusion bodies. The N-terminal 6 histidines could easily be captured by Ni-NTA affinity chromatography. Then, the rS1 of interest was purified to 92% homogeneity. Antisera generated against the purified S1 mutant protein recognized the native toxin indicating that some, if not all, of the native epitope were conserved. Thus, this vaccine preparation is potentially applicable for the production of novel vaccines against B. pertussis infection.

  11. Evoked heart rate and blood pressure in an S1-S2 paradigm

    NARCIS (Netherlands)

    Koers, G; Gaillard, A.W K; Mulder, G.

    1997-01-01

    Phasic changes in heart rate (HR) and blood pressure (BP) in an S1-S2 paradigm were studied in three experiments. In each experiment, a memory search task was performed at S1. The outcome of this task indicated whether a fast or a delayed response had to be given after S2. Besides this response

  12. To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient

    Institute of Scientific and Technical Information of China (English)

    Andrew; Hsu; Jen-Fu; Lee; Daniel; E; Cramer; Menq-Jer; Lee

    2011-01-01

    Most hematopoietic stem progenitor cells (HSPCs) reside in bone marrow (BM), but a small amount of HSPCs have been found to circulate between BM and tissues through blood and lymph. Several lines of evidence suggest that sphingosine-1-phosphate (S1P) gradient triggers HSPC egression to blood circulation after mobilization from BM stem cell niches. Stem cells also visit certain tissues. After a temporary 36 h short stay in local tissues, HSPCs go to lymph in response to S1P gradient between lymph and tissue and eventually enter the blood circulation. S1P also has a role in the guidance of the primitive HSPCs homing to BM in vivo, as S1P analogue FTY720 treatment can improve HSPC BM homing and engraftment. In stress conditions, various stem cells or progenitor cells can be attracted to local injured tissues and participate in local tissue cell differentiation and tissue rebuilding through modulation the expression level of S1P1, S1P2 or S1P3 receptors. Hence, S1P is important for stem cells circulation in blood system to accomplish its role in body surveillance and injury recovery.

  13. S1xS2-INDEX THEORY ON PRODUCT SPACE

    Institute of Scientific and Technical Information of China (English)

    ZHONGCHENGKUI; ZHAOPEIHAO; SHIKE

    1999-01-01

    A new index is constructed by use of the canonical representation of S1 x S1 group over a product space. This index satisfies the general properties of the usual index but does not satifsy the dimension property. As an application, two abstract critical point theorems are given.

  14. Vacuum Structure of Twisted Scalar Field Theories on $M^{D-1} \\otimes S^{1}$

    CERN Document Server

    Hatanaka, H; Ohnishi, K; Sakamoto, M

    2001-01-01

    We study scalar field theories on M^{D-1} \\otimes S^1, which allow to impose twisted boundary conditions for the S^1 direction, in detail and report several interesting properties overlooked so far. One of characteristic features is the appearance of critical radii of the circle S^1. A phase transition can occur at the classical level or can be caused by quantum effects. Radiative corrections can restore broken symmetries or can break symmetries for small radius. A surprising feature is that the translational invariance for the S^1 direction can spontaneously be broken. A particular class of coordinate-dependent vacuum configurations is clarified and the O(N) \\phi^4 model on M^{D-1}\\otimes S^1 is extensively studied, as an illustrative example.

  15. S1P and LPA trigger Schwann cell actin changes and migration.

    Science.gov (United States)

    Barber, Siân C; Mellor, Harry; Gampel, Alex; Scolding, Neil J

    2004-06-01

    The processes by which a Schwann cell (SC) migrates towards, wraps around and, in some cases, myelinates an axon are incompletely understood. The complex morphological rearrangements involved in these events require fundamental changes in the actin cytoskeleton. Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are two modulators of the actin cytoskeleton, and receptors for these signalling lipids are expressed on SCs at the time of differentiation. Previous work has revealed a role for LPA in SC survival, morphology and differentiation, but the effects of S1P have received less attention. Here we show that S1P and LPA both cause major rearrangements to the actin cytoskeleton in primary rat SCs and the SCL4.1/F7 rat SC line. S1P and LPA caused formation of lamellipodia and a circular geodesic actin network. We also show that S1P and LPA increased cell migration. The small GTPases RhoA and Rac1 were both activated by S1P/LPA treatment, but the actin rearrangements were dependent on Rac1 and not RhoA. These effects of S1P/LPA could be mimicked by SCL4.1/F7 cell-conditioned medium, which was found to contain S1P. Reduction in cellular synthesis of S1P by adding the sphingosine kinase inhibitor dimethyl sphingosine during medium conditioning reduced the ability of conditioned medium to cause actin rearrangements. These results support a role for S1P as an autocrine signal regulating the actin cytoskeleton during Schwann cell development.

  16. An anatomical update on the morphologic variations of S1 and S2.

    Science.gov (United States)

    Karachalios, Theofilos; Zibis, Aristides H; Zintzaras, Elias; Bargiotas, Konstantinos; Karantanas, Apostolos H; Malizos, Konstantinos N

    2010-10-11

    Although percutaneous fixation with iliosacral screws has been shown to be a safe and reproducible method for sacroiliac dislocation and sacral fractures, it is a technically demanding technique, and one of its contraindications is sacral anatomical variations and dysmorphism. The incidence and pattern of S1 and S2 anatomical variations were evaluated in 61 patients (35 women and 26 men) using magnetic resonance imaging of the sacrum in an attempt to explore the possible existence of groups of individuals in whom percutaneous sacroiliac fixation is difficult due to local anatomy. S1 and S2 dimensions in both the transverse and coronal planes were recorded and evaluated. In each individual, S1 and S2 dimensions both in the coronal and transverse planes were proportional, with S2 dimensions being 80% of those of S1 on average. Patients were separated into 4 groups based on the S1 and S2 body size and the asymmetry of dimensions in the transverse and coronal planes. In 48 patients (78.6%), dimensions in both planes were symmetrical despite the varying size of the S1 and S2 body. In 2 patients (3.3%) there was a combination of large transverse plane and small coronal plane dimensions, with large S1 and S2 body size. In 9 patients (14.8%), coronal plane dimensions were disproportionately smaller compared to those of the transverse plane, with a varying size of S1 and S2 body making effective sacroiliac screw insertion a difficult task. Thus, a preoperative imaging study, preferably computed tomography scan, of S1 and S2 body size and coronal plane dimensions and an intraoperative fluoroscopic control of S1 and S2 dimensions on the coronal plane are suggested for safe sacroiliac screw fixation.

  17. Improved energy of the 21.5 keV M1 + E2 nuclear transition in {sup 151}Eu

    Energy Technology Data Exchange (ETDEWEB)

    Inoyatov, A.Kh. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); National University, Institute of Applied Physics, Tashkent (Uzbekistan); Kovalik, A. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Nuclear Physics Institute of the ASCR, Rez near Prague (Czech Republic); Filosofov, D.V.; Perevoshchikov, L.L. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Rysavy, M. [Nuclear Physics Institute of the ASCR, Rez near Prague (Czech Republic); Baimukhanova, A. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Institute of Nuclear Physics, Almaty (Kazakhstan)

    2016-05-15

    Using internal conversion electron spectroscopy, improved energy 21 541.5±0.5 eV was determined for the 21.5 keV M1+E2 nuclear transition in {sup 151}Eu populated in the electron capture decay of {sup 151}Gd. This value was found to agree well with the present adopted value but is much more accurate. A value of 0.0305±0.0011 derived for the E2 admixture parameter vertical stroke δ(E2/M1) vertical stroke from the measured conversion electron line intensities corresponds to the present adopted value. A possible effect of nuclear structure on the multipolarity of the 21.5 keV transition was also investigated. (orig.)

  18. Short-ranged potential effects on the recurrence spectra of lithium M = 1 atoms in parallel electric and magnetic fields

    Institute of Scientific and Technical Information of China (English)

    Wang Wen-Peng; Li Hong-Yun; Wang Shu-Bao; Lin Sheng-Lu

    2008-01-01

    This paper presents recurrence spectra of highly excited lithium atoms with M = 1 state in parallel electric and magnetic fields at a fixed scaled energy ε = -0.03. Short-ranged potentials including ionic core potential and centrifugal barrier are taken into account. Their effects on the states and photo-absorption spectrum are analysed in detail. This demonstrates that the geometric features of classical orbits are of special importance for modulations of the spectral pattern. Thus the weak polarization as well as the reduction of correlation of electrons induced by short-ranged potentials give rise to the recurrence spectra of lithium M = 1 atoms more compact than that of the M = 0 one, which is in good agreement with the experimental prediction.

  19. Semi-implicit scheme for treating radiation under M1 closure in general relativistic conservative fluid dynamics codes

    CERN Document Server

    Sdowski, Aleksander; Tchekhovskoy, Alexander; Zhu, Yucong

    2012-01-01

    A numerical scheme is described for including radiation in multi-dimensional general-relativistic conservative fluid dynamics codes. In this method, a covariant form of the M1 closure scheme is used to close the radiation moments, and the radiative source terms are treated semi-implicitly in order to handle both optically thin and optically thick regimes. The scheme has been implemented in a conservative general relativistic radiation hydrodynamics code KORAL. The robustness of the code is demonstrated on a number of test problems, including radiative relativistic shock tubes, static radiation pressure supported atmosphere, shadows, beams of light in curved spacetime, and radiative Bondi accretion. The advantages of M1 closure relative to other approaches such as Eddington closure and flux-limited diffusion are discussed, and its limitations are also highlighted.

  20. Genetic Polymorphisms Analysis of Glutathione S-transferase M1 and T1 in Children with Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    王军; 张利; 冯建飞; 王宏; 朱绍先; 胡豫; 李玉香

    2004-01-01

    Summary: The relationship between glutathione S-transferases (GSTs) M1, T1 genotype and childhood acute lymphoblastic leukemia (ALL) was investigated. GSTM1 and GSTT1 genotypes in genomic DNA from 67 children with ALL and 146 healthy controls were analyzed by using the multiplex polymerase chain reaction (PCR). The frequencies of GSTM1, M1-T1 null genotypes in ALL children were significantly higher than in the healthy controls (76.12 % versus 52.74 %, OR=2.856, P<0.001;50. 74 % versus 24. 66 %, OR=3. 148, P<0.001, respectively). However,there was no significant relationship between GSTT1 null genotype and ALL of children (61.19 %versus 49.32 %, OR=1. 621, P>0.05). It was suggested that GSTM1 null genotype might be a risk genotype of childhood ALL, while there as no correlation between GSTT1 null genotype and childhood ALL.

  1. The M1 family of vertebrate aminopeptidases: role of evolutionarily conserved tyrosines in the enzymatic mechanism of aminopeptidase B.

    Science.gov (United States)

    Cadel, Sandrine; Darmon, Cécile; Pernier, Julien; Hervé, Guy; Foulon, Thierry

    2015-02-01

    Aminopeptidase B (Ap-B), a member of the M1 family of Zn(2+)-aminopeptidases, removes basic residues at the NH2-terminus of peptides and is involved in the in vivo proteolytic processing of miniglucagon and cholecystokinin-8. M1 enzymes hydrolyze numerous different peptides and are implicated in many physiological functions. As these enzymes have similar catalytic mechanisms, their respective substrate specificity and/or catalytic efficiency must be based on subtle structural differences at or near the catalytic site. This leads to the hypothesis that each primary structure contains a consensus structural template, strictly necessary for aminopeptidase activity, and a specific amino acid environment localized in or outside the catalytic pocket that finely tunes the substrate specificity and catalytic efficiency of each enzyme. A multiple sequence alignment of M1 peptidases from vertebrates allowed to identify conserved tyrosine amino acids, which are members of this catalytic backbone. In the present work, site-directed mutagenesis and 3D molecular modeling of Ap-B were used to specify the role of four fully (Y281, Y229, Y414, and Y441) and one partially (Y409) conserved residues. Tyrosine to phenylalanine mutations allowed confirming the influence of the hydroxyl groups on the enzyme activity. These groups are implicated in the reaction mechanism (Y414), in substrate specificity and/or catalytic efficiency (Y409), in stabilization of essential amino acids of the active site (Y229, Y409) and potentially in the maintenance of its structural integrity (Y281, Y441). The importance of hydrogen bonds is verified by the Y229H substitution, which preserves the enzyme activity. These data provide new insights into the catalytic mechanism of Ap-B in the M1 family of aminopeptidases. Copyright © 2015 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  2. Downregulation of cystathionine β-synthase/hydrogen sulfide contributes to rotenone-induced microglia polarization toward M1 type.

    Science.gov (United States)

    Du, Chenchen; Jin, Mengmeng; Hong, Yu; Li, Qian; Wang, Xian-Hui; Xu, Jin-Min; Wang, Fen; Zhang, Ye; Jia, Jia; Liu, Chun-Feng; Hu, Li-Fang

    2014-08-22

    Microglia-mediated neuroinflammation is implicated in the pathogenesis of several neurodegenerative disorders. Microglia can be activated and polarized to exert pro- or anti-inflammatory roles in response to specific stimulus. Rotenone is an environmental toxin that has been shown to activate microglia and neuroinflammation. However, the effects and mechanisms of rotenone on microglia polarization are poorly studied. In the present study, we demonstrated that rotenone enhanced the levels of M1 phenotypic genes including TNF-α, iNOS and COX-2/PGE2 but reduced that of M2 markers such as Ym1/2 and IL-10 in mouse primary and immortalized microglia. Moreover, the transcription and protein expression of cystathionine-β-synthase (CBS), as well as hydrogen sulfide (H2S) production were decreased in rotenone-treated primary microglia. Elevating endogenous H2S via CBS over-expression in immortalized microglia not only reduced the expression of pro-inflammatory M1 genes, but also enhanced the anti-inflammatory M2 marker IL-10 production in response to rotenone stimulation as compared to vector-transfected cells. Similarly, pretreatment with H2S donor NaHS (50, 100 and 500μmol/L) attenuated the increases of M1 gene expression triggered by rotenone treatment, and enhanced the M2 gene Ym1/2 expression in mouse primary microglia. In addition, we observed reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine reversed the down-regulation of CBS and H2S generation caused by rotenone in microglia. NaHS pretreatment also decreased the ROS formation in rotenone-stimulated microglia. Taken together, these results reveal that probably via triggering ROS formation, rotenone suppressed the CBS-H2S pathway and thus promoted microglia polarization toward M1 pro-inflammatory phenotype.

  3. 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.

    2013-01-01

    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. PMID:23793893

  4. Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy

    Directory of Open Access Journals (Sweden)

    Wang Yujuan

    2012-11-01

    Full Text Available Abstract Background Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy. Case presentation We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively

  5. Exploration of the orthosteric/allosteric interface in human M1 muscarinic receptors by bitopic fluorescent ligands.

    Science.gov (United States)

    Daval, Sandrine B; Kellenberger, Esther; Bonnet, Dominique; Utard, Valérie; Galzi, Jean-Luc; Ilien, Brigitte

    2013-07-01

    Bitopic binding properties apply to a variety of muscarinic compounds that span and simultaneously bind to both the orthosteric and allosteric receptor sites. We provide evidence that fluorescent pirenzepine derivatives, with the M1 antagonist fused to the boron-dipyrromethene [Bodipy (558/568)] fluorophore via spacers of varying lengths, exhibit orthosteric/allosteric binding properties at muscarinic M1 receptors. This behavior was inferred from a combination of functional, radioligand, and fluorescence resonance energy transfer binding experiments performed under equilibrium and kinetic conditions on enhanced green fluorescent protein-fused M1 receptors. Although displaying a common orthosteric component, the fluorescent compounds inherit bitopic properties from a linker-guided positioning of their Bodipy moiety within the M1 allosteric vestibule. Depending on linker length, the fluorophore is allowed to reach neighboring allosteric domains, overlapping or not with the classic gallamine site, but distinct from the allosteric indolocarbazole "WIN" site. Site-directed mutagenesis, as well as molecular modeling and ligand docking studies based on recently solved muscarinic receptor structures, further support the definition of two groups of Bodipy-pirenzepine derivatives exhibiting distinct allosteric binding poses. Thus, the linker may dictate pharmacological outcomes for bitopic molecules that are hardly predictable from the properties of individual orthosteric and allosteric building blocks. Our findings also demonstrate that the fusion of a fluorophore to an orthosteric ligand is not neutral, as it may confer, unless carefully controlled, unexpected properties to the resultant fluorescent tracer. Altogether, this study illustrates the importance of a "multifacet" experimental approach to unravel and validate bitopic ligand binding mechanisms.

  6. Dynamic Regulation of Quaternary Organization of the M1 Muscarinic Receptor by Subtype-selective Antagonist Drugs*

    Science.gov (United States)

    Pediani, John D.; Ward, Richard J.; Godin, Antoine G.; Marsango, Sara

    2016-01-01

    Although rhodopsin-like G protein-coupled receptors can exist as both monomers and non-covalently associated dimers/oligomers, the steady-state proportion of each form and whether this is regulated by receptor ligands are unknown. Herein we address these topics for the M1 muscarinic acetylcholine receptor, a key molecular target for novel cognition enhancers, by using spatial intensity distribution analysis. This method can measure fluorescent particle concentration and assess oligomerization states of proteins within defined regions of living cells. Imaging and analysis of the basolateral surface of cells expressing some 50 molecules·μm−2 human muscarinic M1 receptor identified a ∼75:25 mixture of receptor monomers and dimers/oligomers. Both sustained and shorter term treatment with the selective M1 antagonist pirenzepine resulted in a large shift in the distribution of receptor species to favor the dimeric/oligomeric state. Although sustained treatment with pirenzepine also resulted in marked up-regulation of the receptor, simple mass action effects were not the basis for ligand-induced stabilization of receptor dimers/oligomers. The related antagonist telenzepine also produced stabilization and enrichment of the M1 receptor dimer population, but the receptor subtype non-selective antagonists atropine and N-methylscopolamine did not. In contrast, neither pirenzepine nor telenzepine altered the quaternary organization of the related M3 muscarinic receptor. These data provide unique insights into the selective capacity of receptor ligands to promote and/or stabilize receptor dimers/oligomers and demonstrate that the dynamics of ligand regulation of the quaternary organization of G protein-coupled receptors is markedly more complex than previously appreciated. This may have major implications for receptor function and behavior. PMID:27080256

  7. Dynamic Regulation of Quaternary Organization of the M1 Muscarinic Receptor by Subtype-selective Antagonist Drugs.

    Science.gov (United States)

    Pediani, John D; Ward, Richard J; Godin, Antoine G; Marsango, Sara; Milligan, Graeme

    2016-06-17

    Although rhodopsin-like G protein-coupled receptors can exist as both monomers and non-covalently associated dimers/oligomers, the steady-state proportion of each form and whether this is regulated by receptor ligands are unknown. Herein we address these topics for the M1 muscarinic acetylcholine receptor, a key molecular target for novel cognition enhancers, by using spatial intensity distribution analysis. This method can measure fluorescent particle concentration and assess oligomerization states of proteins within defined regions of living cells. Imaging and analysis of the basolateral surface of cells expressing some 50 molecules·μm(-2) human muscarinic M1 receptor identified a ∼75:25 mixture of receptor monomers and dimers/oligomers. Both sustained and shorter term treatment with the selective M1 antagonist pirenzepine resulted in a large shift in the distribution of receptor species to favor the dimeric/oligomeric state. Although sustained treatment with pirenzepine also resulted in marked up-regulation of the receptor, simple mass action effects were not the basis for ligand-induced stabilization of receptor dimers/oligomers. The related antagonist telenzepine also produced stabilization and enrichment of the M1 receptor dimer population, but the receptor subtype non-selective antagonists atropine and N-methylscopolamine did not. In contrast, neither pirenzepine nor telenzepine altered the quaternary organization of the related M3 muscarinic receptor. These data provide unique insights into the selective capacity of receptor ligands to promote and/or stabilize receptor dimers/oligomers and demonstrate that the dynamics of ligand regulation of the quaternary organization of G protein-coupled receptors is markedly more complex than previously appreciated. This may have major implications for receptor function and behavior. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. In-field evaluation of clinoptilolite feeding efficacy on the reduction of milk aflatoxin M1 concentration in dairy cattle

    OpenAIRE

    Katsoulos, Panagiotis D.; Karatzia, Maria A.; Boscos, Constantinos; Wolf, Petra; Karatzias, Harilaos

    2016-01-01

    Background Clinoptilolite is a natural zeolite with high adsorption capacity for polar mycotoxins such as aflatoxins. The efficacy of clinoptilolite in ameliorating the toxic effects of aflatoxicosis has been proven in monogastric animals, but there is no such evidence for ruminants. The aim of this study was to evaluate, under field conditions, whether the dietary administration of clinoptilolite in dairy cows could reduce the concentration of aflatoxin M1 (AFM1) in bulk-tank milk, in farms ...

  9. A scheme for radiation pressure and photon diffusion with the M1 closure in RAMSES-RT

    OpenAIRE

    Rosdahl, J.; Teyssier, Romain

    2015-01-01

    We describe and test an updated version of radiation-hydrodynamics in the RAMSES code, that includes three new features: (i) radiation pressure on gas, (ii) accurate treatment of radiation diffusion in an unresolved optically thick medium, and (iii) relativistic corrections that account for Doppler effects and work done by the radiation to first order in v/c. We validate the implementation in a series of tests, which include a morphological assessment of the M1 closure for the Eddington tenso...

  10. Gamma-Rays and E0 and M1+E0 Transitions in $^{152}Tb \\to ^{152}$Gd Decay

    CERN Document Server

    Adam, J; Honusek, M; Kalinnikov, V G; Mrazek, J; Pronskikh, V S; Caloun, P; Lebedev, N A; Stegailov, V I; Tsoupko-Sitnikov, V M

    2001-01-01

    The decay of ^{152}Tb has been investigated by means of measurements of single gamma-spectra. The 704 transitions were observed, of which 347 were identified to the decay of ^{152}Tb for the first time. Using the more precise and full data about intensities of gamma-transitions and previously reported conversion electron intensities the E0 or M1+E0 multipolarities were established for several transitions.

  11. 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.

  12. Active vitamin D prevents podocyte injury via regulation of macrophage M1 and M2 phenotype in diabetic nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    郭银凤

    2014-01-01

    Objective To investigate the effect of active vitamin D(VD)on macrophage M1 and M2 phenotype and its role in protecting podocyte impairment in diabetic nephropathy(DN).Methods Diabetes mellitus rats were established by intraperitoneal injection with streptozocin.Rats were randomly divided into four groups:normal-1(NC-1,n=8),normal-2(NC-2,n=8,normal rats treated with calcitriol 0.1μg·kg-1·d-1by gavages),

  13. A Study on the Occurrence of Aflatoxin M1 in Raw and Pasteurized Milk Produced in Rafsanjan, Iran

    OpenAIRE

    FaAkrami Mohajeri Akrami Mohajeri; Asieh Amiri; Hossein Khorramdel Azad; Zahra Ahmadi; Zahra Asadollahi; Mohsen Rezaeian; Fallah, Aziz A.; Seyed Razi Ghalebi

    2015-01-01

    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...

  14. FoxM1 Promotes Stemness and Radio-Resistance of Glioblastoma by Regulating the Master Stem Cell Regulator Sox2.

    Science.gov (United States)

    Lee, Yeri; Kim, Kang Ho; Kim, Dong Geon; Cho, Hee Jin; Kim, Yeonghwan; Rheey, Jinguen; Shin, Kayoung; Seo, Yun Jee; Choi, Yeon-Sook; Lee, Jung-Il; Lee, Jeongwu; Joo, Kyeung Min; Nam, Do-Hyun

    2015-01-01

    Glioblastoma (GBM) is the most aggressive and most lethal brain tumor. As current standard therapy consisting of surgery and chemo-irradiation provides limited benefit for GBM patients, novel therapeutic options are urgently required. Forkhead box M1 (FoxM1) transcription factor is an oncogenic regulator that promotes the proliferation, survival, and treatment resistance of various human cancers. The roles of FoxM1 in GBM remain incompletely understood, due in part to pleotropic nature of the FoxM1 pathway. Here, we show the roles of FoxM1 in GBM stem cell maintenance and radioresistance. ShRNA-mediated FoxM1 inhibition significantly impeded clonogenic growth and survival of patient-derived primary GBM cells with marked downregulation of Sox2, a master regulator of stem cell phenotype. Ectopic expression of Sox2 partially rescued FoxM1 inhibition-mediated effects. Conversely, FoxM1 overexpression upregulated Sox2 expression and promoted clonogenic growth of GBM cells. These data, with a direct binding of FoxM1 in the Sox2 promoter region in GBM cells, suggest that FoxM1 regulates stemness of primary GBM cells via Sox2. We also found significant increases in FoxM1 and Sox2 expression in GBM cells after irradiation both in vitro and in vivo orthotopic tumor models. Notably, genetic or a small-molecule FoxM1 inhibitor-mediated FoxM1 targeting significantly sensitized GBM cells to irradiation, accompanying with Sox2 downregulation. Finally, FoxM1 inhibition combined with irradiation in a patient GBM-derived orthotopic model significantly impeded tumor growth and prolonged the survival of tumor bearing mice. Taken together, these results indicate that the FoxM1-Sox2 signaling axis promotes clonogenic growth and radiation resistance of GBM, and suggest that FoxM1 targeting combined with irradiation is a potentially effective therapeutic approach for GBM.

  15. Higher Levels of Aflatoxin M1 Contamination and Poorer Composition of Milk Supplied by Informal Milk Marketing Chains in Pakistan.

    Science.gov (United States)

    Aslam, Naveed; Tipu, Muhammad Yasin; Ishaq, Muhammad; Cowling, Ann; McGill, David; Warriach, Hassan Mahmood; Wynn, Peter

    2016-12-05

    The present study was conducted to observe the seasonal variation in aflatoxin M1 and nutritional quality of milk along informal marketing chains. Milk samples (485) were collected from three different chains over a period of one year. The average concentrations of aflatoxin M1 during the autumn and monsoon seasons (2.60 and 2.59 ppb) were found to be significantly higher (standard error of the difference, SED = 0.21: p = 0.003) than in the summer (1.93 ppb). The percentage of added water in milk was significantly lower (SED = 1.54: p marketing chain. There was no difference (p = 0.178) in concentration of aflatoxin M1 in milk collected from the farmers (2.12 ppb), small collectors (2.23 ppb), large collectors (2.36 ppb) and retailers (2.58 ppb). The high levels of contamination found in this study, which exceed the standards set by European Union (0.05 ppb) and USFDA (0.5 ppb), demand radical intervention by regulatory authorities and mass awareness of the consequences for consumer health and safety.

  16. A Genetic Switch to Hypervirulence Reduces Colonization Phenotypes of the Globally Disseminated Group A Streptococcus M1T1 Clone

    Science.gov (United States)

    Hollands, Andrew; Pence, Morgan A.; Timmer, Anjuli M.; Osvath, Sarah R.; Turnbull, Lynne; Whitchurch, Cynthia B.; Walker, Mark J.; Nizet, Victor

    2010-01-01

    Background The recent resurgence of invasive group A streptococcal disease has been paralleled by the emergence of the M1T1 clone. Recently, invasive disease initiation to has been linked to mutations in the covR/S two-compnent regulator. Here we investigate if a fitness cost is associated with covS mutation that counterbalances hypervirulence. Methods Wild-type M1T1 GAS and an isogenic covS mutant derived from animal passage were compared for adherence to human laryngeal epithelial cells, keratinocytes or fibronectin, biofilm formation, and binding to intact mouse skin. Targeted mutagenesis of capsule expression from both strains was performed for analysis of its unique contribution to the observed phenotypes. Results The covS mutant bacteria showed reduced capacity to bind to epithelial cell layers as a consequence of increased capsule expression. The covS mutant strain also had reduced capacity to bind fibronectin and to form biofilms on plastic and epithelial cell layers. A defect in skin adherence of the covS mutant strain was demonstrated in a murine model. Conclusions Reduced colonization capacity provides a potential explanation as to why the covS mutation conferring hypervirulence has not become fixed in the globally-disseminated M1T1 GAS clone, but rather may arise anew under innate immune selection in individual patients. PMID:20507231

  17. Genetic switch to hypervirulence reduces colonization phenotypes of the globally disseminated group A streptococcus M1T1 clone.

    Science.gov (United States)

    Hollands, Andrew; Pence, Morgan A; Timmer, Anjuli M; Osvath, Sarah R; Turnbull, Lynne; Whitchurch, Cynthia B; Walker, Mark J; Nizet, Victor

    2010-07-01

    The recent resurgence of invasive group A streptococcal disease has been paralleled by the emergence of the M1T1 clone. Recently, invasive disease initiation has been linked to mutations in the covR/S 2-component regulator. We investigated whether a fitness cost is associated with the covS mutation that counterbalances hypervirulence. Wild-type M1T1 group A Streptococcus and an isogenic covS-mutant strain derived from animal passage were compared for adherence to human laryngeal epithelial cells, human keratinocytes, or fibronectin; biofilm formation; and binding to intact mouse skin. Targeted mutagenesis of capsule expression of both strains was performed for analysis of its unique contribution to the observed phenotypes. The covS-mutant bacteria showed reduced capacity to bind to epithelial cell layers as a consequence of increased capsule expression. The covS-mutant strain also had reduced capacity to bind fibronectin and to form biofilms on plastic and epithelial cell layers. A defect in skin adherence of the covS-mutant strain was demonstrated in a murine model. Reduced colonization capacity provides a potential explanation for why the covS mutation, which confers hypervirulence, has not become fixed in the globally disseminated M1T1 group A Streptococcus clone, but rather may arise anew under innate immune selection in individual patients.

  18. Implications for Damage Recognition during Dpo4-Mediated Mutagenic Bypass of m1G and m3C Lesions

    Energy Technology Data Exchange (ETDEWEB)

    Rechkoblit, Olga; Delaney, James C.; Essigmann, John M.; Patel, Dinshaw J. (MIT); (MSKCC)

    2012-05-08

    DNA is susceptible to alkylation damage by a number of environmental agents that modify the Watson-Crick edge of the bases. Such lesions, if not repaired, may be bypassed by Y-family DNA polymerases. The bypass polymerase Dpo4 is strongly inhibited by 1-methylguanine (m1G) and 3-methylcytosine (m3C), with nucleotide incorporation opposite these lesions being predominantly mutagenic. Further, extension after insertion of both correct and incorrect bases, introduces additional base substitution and deletion errors. Crystal structures of the Dpo4 ternary extension complexes with correct and mismatched 3'-terminal primer bases opposite the lesions reveal that both m1G and m3C remain positioned within the DNA template/primer helix. However, both correct and incorrect pairing partners exhibit pronounced primer terminal nucleotide distortion, being primarily evicted from the DNA helix when opposite m1G or misaligned when pairing with m3C. Our studies provide insights into mechanisms related to hindered and mutagenic bypass of methylated lesions and models associated with damage recognition by repair demethylases.

  19. Differential effects of M1 muscarinic receptor blockade and nicotinic receptor blockade in the dorsomedial striatum on response reversal learning

    Science.gov (United States)

    Tzavos, Arianna; Jih, Jane; Ragozzino, Michael E.

    2011-01-01

    The present studies determined whether blockade of M1-like muscarinic or nicotinic cholinergic receptors in the dorsomedial striatum affects acquisition or reversal learning of a response discrimination. Testing occurred in a modified cross-maze across two consecutive sessions. In the acquisition phase, a rat learned to turn to the left or to the right. In the reversal learning phase, a rat learned to turn in the opposite direction as required during acquisition. Experiment 1 investigated the effects of the M1-like muscarinic receptor antagonist, pirenzepine infused into the dorsomedial striatum on acquisition and reversal learning. Experiment 2 examined the effects of the nicotinic cholinergic antagonist, mecamylamine injected into the dorsomedial striatum on acquisition and reversal learning. Bilateral injections of pirenzepine at 10 µg, but not 1 µg, selectively impaired reversal learning. Analysis of the errors indicated that pirenzepine treatment did not impair the initial shift, but increased reversions back to the original response choice following the initial shift. Bilateral injections of mecamylamine, 6 or 18 µg, did not affect acquisition or reversal learning. The results suggest that activation of M1 muscarinic cholinergic receptors, but not nicotinic cholinergic receptors, in the dorsomedial striatum is important for facilitating the flexible shifting of response patterns. PMID:15302131

  20. [Determination of virginiamycin M1, in feeds by ultra high performance liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Huang, Yonghui

    2011-10-01

    A comprehensive analytical method based on ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of virginiamycin M1 in feeds. The sample was extracted twice by ultrasonic extraction with ace-tonitrile-0.2% (v/v) formic acid (8:2, v/v). The chromatographic separation was achieved with a BEH C18 column and acetonitrile-0. 3% (v/v) formic acid (35: 65, v/v) as the mobile phase. The identification and quantification of the analyte were carried out on electrospray ionization MS/MS in a multiple reaction monitoring (MRM) mode. The correlation coefficient (r) of virginiamycin M1 was 0. 999 5 in the linear range of 0. 3 -226. 6 microg/L. The detection limit (S/ N = 3) and quantification limit (S/N = 10) of virginiamycin M1 were 2 microg/kg and 7 microg/kg, respectively. The average spiked recoveries were in the range of 82. 6% to 102. 7% with the relative standard deviations (RSDs) of 0.9% - 10.5%. The results demonstrate that the proposed method is simple, sensitive, repeatable and suitable for the testing of virginiamycin M, in feeds.

  1. Higher Levels of Aflatoxin M1 Contamination and Poorer Composition of Milk Supplied by Informal Milk Marketing Chains in Pakistan

    Science.gov (United States)

    Aslam, Naveed; Tipu, Muhammad Yasin; Ishaq, Muhammad; Cowling, Ann; McGill, David; Warriach, Hassan Mahmood; Wynn, Peter

    2016-01-01

    The present study was conducted to observe the seasonal variation in aflatoxin M1 and nutritional quality of milk along informal marketing chains. Milk samples (485) were collected from three different chains over a period of one year. The average concentrations of aflatoxin M1 during the autumn and monsoon seasons (2.60 and 2.59 ppb) were found to be significantly higher (standard error of the difference, SED = 0.21: p = 0.003) than in the summer (1.93 ppb). The percentage of added water in milk was significantly lower (SED = 1.54: p < 0.001) in summer (18.59%) than in the monsoon season (26.39%). There was a significantly different (SED = 2.38: p < 0.001) mean percentage of water added by farmers (6.23%), small collectors (14.97%), large collectors (27.96%) and retailers (34.52%). This was reflected in changes in milk quality along the marketing chain. There was no difference (p = 0.178) in concentration of aflatoxin M1 in milk collected from the farmers (2.12 ppb), small collectors (2.23 ppb), large collectors (2.36 ppb) and retailers (2.58 ppb). The high levels of contamination found in this study, which exceed the standards set by European Union (0.05 ppb) and USFDA (0.5 ppb), demand radical intervention by regulatory authorities and mass awareness of the consequences for consumer health and safety. PMID:27929386

  2. Higher Levels of Aflatoxin M1 Contamination and Poorer Composition of Milk Supplied by Informal Milk Marketing Chains in Pakistan

    Directory of Open Access Journals (Sweden)

    Naveed Aslam

    2016-12-01

    Full Text Available The present study was conducted to observe the seasonal variation in aflatoxin M1 and nutritional quality of milk along informal marketing chains. Milk samples (485 were collected from three different chains over a period of one year. The average concentrations of aflatoxin M1 during the autumn and monsoon seasons (2.60 and 2.59 ppb were found to be significantly higher (standard error of the difference, SED = 0.21: p = 0.003 than in the summer (1.93 ppb. The percentage of added water in milk was significantly lower (SED = 1.54: p < 0.001 in summer (18.59% than in the monsoon season (26.39%. There was a significantly different (SED = 2.38: p < 0.001 mean percentage of water added by farmers (6.23%, small collectors (14.97%, large collectors (27.96% and retailers (34.52%. This was reflected in changes in milk quality along the marketing chain. There was no difference (p = 0.178 in concentration of aflatoxin M1 in milk collected from the farmers (2.12 ppb, small collectors (2.23 ppb, large collectors (2.36 ppb and retailers (2.58 ppb. The high levels of contamination found in this study, which exceed the standards set by European Union (0.05 ppb and USFDA (0.5 ppb, demand radical intervention by regulatory authorities and mass awareness of the consequences for consumer health and safety.

  3. Uptake, elimination and fish bioconcentration factors for the persistent hexa- and nonachlorobornanes- M1 and P-50

    Energy Technology Data Exchange (ETDEWEB)

    Maruya, K. [Skidaway Inst. of Oceanography, Savannah, GA (United States); Warttinger, U. [Fachhochschule fuer Technik und Gestaltung, Mannheim (Germany)

    2004-09-15

    Knowledge of the uptake and elimination kinetics of chlorobornane (toxaphene) residue congeners by aquatic organisms is key to understanding their environmental fate. Most work to date has focused on a select few octa- and nonachlorinated congeners that are globally distributed and persistent. However, recent evidence suggests that lower chlorinated toxaphene residue congeners, such as 2-exo, 5-endo, 6-exo, 8c, 9b, 10a-hexachlorobornane (aka Hx-Sed; B6-923 or M1), are also detected in polar regions and thus may survive long range transport. In this study, we followed the uptake and elimination of M1 by a model fish and compared rates with that for 2- endo,3-exo,5-endo,6-exo,8,8,9,10,10-nonachlorobornane (aka B9-1679 or P-50), a known persistent congener. From these experiments, we estimated the steady state bioconcentration factor (BCF) for M1 and compared our value with reported modeled and field-based values for toxaphene congeners with a similar degree of chlorination.

  4. Echinacea purpurea Extract Polarizes M1 Macrophages in Murine Bone Marrow-Derived Macrophages Through the Activation of JNK.

    Science.gov (United States)

    Fu, Aikun; Wang, Yang; Wu, Yanping; Chen, Hongliang; Zheng, Shasha; Li, Yali; Xu, Xin; Li, Weifen

    2017-09-01

    Echinacea purpurea is an indigenous North American purple cone flower used by North Americans for treatment of various infectious diseases and wounds. This study investigated the effect of polysaccharide enriched extract of Echinacea purpurea (EE) on the polarization of macrophages. The results showed that 100 µg/mL of EE could markedly activate the macrophage by increasing the expression of CD80, CD86, and MHCII molecules. Meanwhile, EE upregulated the markers of classically activated macrophages (M1) such as CCR7 and the production of IL-1β, IL-6, IL-12p70, TNF-αand NO. The functional tests showed that EE enhanced the phagocytic and intracellular bactericidal activity of macrophage against ST. Furthermore, we demonstrated that JNK are required for EE-induced NO and M1-related cytokines production. Together, these results demonstrated that EE can polarize macrophages towards M1 phenotype, which is dependent on the JNK signaling pathways. J. Cell. Biochem. 118: 2664-2671, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. 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

    2017-03-03

    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.

  6. Contribution of Secreted NADase and Streptolysin O to the Pathogenesis of Epidemic Serotype M1 Streptococcus pyogenes Infections.

    Science.gov (United States)

    Zhu, Luchang; Olsen, Randall J; Lee, Jessica D; Porter, Adeline R; DeLeo, Frank R; Musser, James M

    2017-03-01

    Streptococcus pyogenes secretes many toxins that facilitate human colonization, invasion, and dissemination. NADase (SPN) and streptolysin O (SLO) are two toxins that play important roles in pathogenesis. We previously showed that increased production of SPN and SLO in epidemic serotype M1 and M89 S. pyogenes strains is associated with rapid intercontinental spread and enhanced virulence. The biological functions of SPN and SLO have been extensively studied using eukaryotic cell lines, but the relative contribution of each of these two toxins to pathogenesis of epidemic M1 or M89 strains remains unexplored. Herein, using a genetically representative epidemic M1 strain and a panel of isogenic mutant derivative strains, we evaluated the relative contributions of SPN and SLO toxins to virulence in mouse models of necrotizing myositis, bacteremia, and skin and soft tissue infection. We found that isogenic mutants lacking SPN, SLO, and both toxins are equally impaired in ability to cause necrotizing myositis. In addition, mutants lacking either SPN or SLO are significantly attenuated in the bacteremia and soft tissue infection models, and the mutant strain lacking production of both toxins is further attenuated. The mutant strain lacking both SPN and SLO production is severely attenuated in ability to resist killing by human polymorphonuclear leukocytes. We conclude that both SPN and SLO contribute significantly to S. pyogenes pathogenesis in these virulence assays. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Macrophages Undergo M1-to-M2 Transition in Adipose Tissue Regeneration in a Rat Tissue Engineering Model.

    Science.gov (United States)

    Li, Zhijin; Xu, Fangfang; Wang, Zhifa; Dai, Taiqiang; Ma, Chao; Liu, Bin; Liu, Yanpu

    2016-10-01

    Macrophages are involved in the full processes of tissue healing or regeneration and play an important role in the regeneration of a variety of tissues. Although recent evidence suggests the role of different macrophage phenotypes in adipose tissue expansion, metabolism, and remodeling, the spectrum of macrophage phenotype in the adipose tissue engineering field remains unknown. The present study established a rat model of adipose tissue regeneration using a tissue engineering chamber. Macrophage phenotypes were assessed during the regenerative process in the model. Neo-adipose tissue was generated 6 weeks after implantation. Macrophages were obvious in the chamber constructs 3 days after implantation, peaked at day 7, and significantly decreased thereafter. At day 3, macrophages were predominantly M1 macrophages (CCR7+), and there were few M2 macrophages (CD206+). At day 7, the percentage of M2 macrophages significantly increased and remained stable at day 14. M2 macrophages became the predominant macrophage population at 42 days. Enzyme-linked immunosorbent assay demonstrated transition of cytokines from pro-inflammatory to anti-inflammatory, which was consistent with the transition of macrophage phenotype from M1 to M2. These results showed distinct transition of macrophage phenotypes from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 in adipose tissue regeneration in our tissue engineering model. This study provides new insight into macrophage phenotype transition in the regeneration of adipose tissue.

  8. A single amino acid at N-terminal region of the 2b protein of cucumber mosaic virus strain m1 has a pivotal role in virus attenuation.

    Science.gov (United States)

    Maneechoat, Phoowanarth; Takeshita, Minoru; Uenoyama, Misa; Nakatsukasa, Maki; Kuroda, Atsuko; Furuya, Naruto; Tsuchiya, Kenichi

    2015-02-02

    Host responses to infection by a mild strain of cucumber mosaic virus, termed CMV-m1, were re-examined in several plant species in comparison with those by a severe strain CMV-Y. Mild systemic symptoms were developed on the six plant species inoculated with CMV-m1. Virus titer in the Nicotiana benthamiana plants infected with CMV-m1 was significantly lower than those infected with CMV-Y, although infection by CMV-m1 interfered with further infection by CMV-Y in the plants. Subsequently, the attenuated virulence of CMV-m1 was analyzed by reassortment and recombination analyses between CMV-m1 and CMV-Y RNAs. The results suggested that the 2b protein of CMV-m1 (m1-2b) is involved in the formation of mild symptoms in N. benthamiana. Furthermore, site-directed mutagenesis demonstrated that Thr18 of m1-2b is responsible for formation of mild symptoms. Local RNA silencing suppressor activity of m1-2b was a little lower than that of severe strain CMV-Y. We discuss the relationship between attenuation of CMV-m1 and the features of m1-2b.

  9. 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...