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Sample records for hydrogenophaga intermedia s1

  1. Hydrogenophaga electricum sp. nov., isolated from anodic biofilms of an acetate-fed microbial fuel cell.

    PubMed

    Kimura, Zen-ichiro; Okabe, Satoshi

    2013-01-01

    A Gram-negative, non-spore-forming, rod-shaped bacterial strain, AR20(T), was isolated from anodic biofilms of an acetate-fed microbial fuel cell in Japan and subjected to a polyphasic taxonomic study. Strain AR20(T) grew optimally at pH 7.0-8.0 and 25°C. It contained Q-8 as the predominant ubiquinone and C16:0, summed feature 3 (C16:1ω7c and/or iso-C15:02OH), and C18:1ω7c as the major fatty acids. The DNA G+C content was 67.1 mol%. A neighbor-joining phylogenetic tree revealed that strain AR20(T) clustered with three type strains of the genus Hydrogenophaga (H. flava, H. bisanensis and H. pseudoflava). Strain AR20(T) exhibited 16S rRNA gene sequence similarity values of 95.8-97.7% to the type strains of the genus Hydrogenophaga. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain AR20(T) is considered a novel species of the genus Hydrogenophaga, for which the name Hydrogenophaga electricum sp. nov. is proposed. The type strain is AR20(T) (= KCTC 32195(T) = NBRC 109341(T)).

  2. Description of Hydrogenophaga laconesensis sp. nov. isolated from tube well water.

    PubMed

    Mantri, Soniya; Chinthalagiri, Mohan Rao; Gundlapally, Sathyanarayana Reddy

    2016-09-01

    A light cream color colony was isolated, using oligotrophic LB agar medium, from a water sample collected from a tube well and designated as HWB-10(T). Cells of strain HWB-10(T) were Gram-negative, motile rods, non-spore forming, positive for catalase, oxidase, nitrate reduction and esculin. The predominant fatty acids were C16:0, summed feature 4 (C16:1 ω7c/iso-C15:0 2-OH) and summed feature 7 (C18:1 ω7c, C18:1 ω9t and/or C18:1 ω12t), and the major ubiquinone was Q-8. NCBI-BLAST- and EzTaxon-based 16S rRNA gene sequence similarity search identified strain HWB-10(T) as a member of the genus Hydrogenophaga and H. atypica DSM 15342(T), H. defulvi DSM 15341(T), H. palleronii LMG2366(T) and H. taeniospiralis LMG7170(T) being the nearest phylogenetic species with a similarity (%) of 99.3, 99.1, 98.4 and 98.2, respectively, while the similarity was <98.0 % with other species of the genus. However, DNA-DNA similarities between HWB-10(T) and H. atypica DSM 15342(T) and H. defulvi DSM 15341(T) were 37.0 and 43.0 %, respectively, indicating that strain HWB-10(T) is a novel species. Further, the DNA fingerprinting, based on BOX-, ERIC-, (GTG)5- and REP-PCR amplifications, distinguished strain HWB-10(T) from its closest species, H. atypica DSM 15342(T) and H. defulvi DSM 15341(T) with similarity coefficients of 0.45 and 0.37, respectively, a value sufficient to establish the species status within the genus Hydrogenophaga. In addition, strain HWB-10(T) exhibited several phenotypic differences with its closely related species. Based on the above cumulative differentiating characteristics, strain HWB-10(T) was identified as a new species of the genus Hydrogenophaga and proposed as Hydrogenophaga laconesensis sp. nov. with strain HWB-10(T) (KTCC 42478(T) = LMG 28681(T)) as its type strain.

  3. Thalassaemia Intermedia: an Update

    PubMed Central

    Taher, Ali T.; Musallam, Khaled M.; Cappellini, Maria D.

    2009-01-01

    Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with thalassaemia intermedia (TI) has substantially increased over the past decade. TI encompasses a wide clinical spectrum of beta-thalassaemia phenotypes. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from as young as 2 years of age. A number of clinical complications commonly associated with TI are rarely seen in thalassaemia major, including extramedullary hematopoiesis, leg ulcers, gallstones, thrombosis and pulmonary hypertension. There are a number of options currently available for managing patients with TI, including transfusion therapy, iron chelation therapy, modulation of foetal haemoglobin production and haematopoietic stem cell transplantation. However, at present, there are no clear guidelines for an orchestrated optimal treatment plan. PMID:21415986

  4. Fluxacademy: From Intermedia to Interactive Education.

    ERIC Educational Resources Information Center

    Saper, Craig

    1992-01-01

    Advocates a Fluxus-based experimental pedagogy which is suited for scholarship confronted with film and electronic media. Notes that the theory explored in Fluxacademy focuses specifically on the use of intermedia for interactive education. (RS)

  5. Enhancing Transport of Hydrogenophaga flava ENV735 for Bioaugmentation of Aquifers Contaminated with Methyl tert-Butyl Ether

    PubMed Central

    Streger, Sheryl H.; Vainberg, Simon; Dong, Hailiang; Hatzinger, Paul B.

    2002-01-01

    The gasoline oxygenate methyl tert-butyl ether (MTBE) has become a widespread contaminant in groundwater throughout the United States. Bioaugmentation of aquifers with MTBE-degrading cultures may be necessary to enhance degradation of the oxygenate in some locations. However, poor cell transport has sometimes limited bioaugmentation efforts in the past. The objective of this study was to evaluate the transport characteristics of Hydrogenophaga flava ENV735, a pure culture capable of growth on MTBE, and to improve movement of the strain through aquifer solids. The wild-type culture moved only a few centimeters in columns of aquifer sediment. An adhesion-deficient variant (H. flava ENV735:24) of the wild-type strain that moved more readily through sediments was obtained by sequential passage of cells through columns of sterile sediment. Hydrophobic and electrostatic interaction chromatography revealed that the wild-type strain is much more hydrophobic than the adhesion-deficient variant. Electrophoretic mobility assays and transmission electron microscopy showed that the wild-type bacterium contains two distinct subpopulations, whereas the adhesion-deficient strain has only a single, homogeneous population. Both the wild-type strain and adhesion-deficient variant degraded MTBE, and both were identified by 16S rRNA analysis as pure cultures of H. flava. The effectiveness of surfactants for enhancing transport of the wild-type strain was also evaluated. Many of the surfactants tested were toxic to ENV735; however, one nonionic surfactant, Tween 20, enhanced cell transport in sand columns. Improving microbial transport may lead to a more effective bioaugmentation strategy for MTBE-contaminated sites where indigenous oxygenate degraders are absent. PMID:12406751

  6. Degradation of human hemoglobin by Prevotella intermedia.

    PubMed

    Guan, Su-Min; Nagata, Hideki; Shizukuishi, Satoshi; Wu, Jun-Zheng

    2006-01-01

    In this study, the ability of Prevotella intermedia, an obligate anaerobic rod, to degrade human hemoglobin was determined by SDS-PAGE and the degradation was quantified by scanning densitometry. Both bacterial cells and culture supernatants degraded hemoglobin. The hemoglobin degradation by P. intermedia was time-dependent, heat sensitive, pH related and was not influenced by iron restriction. Inhibition studies demonstrated that a cysteine protease might be involved in hemoglobin degradation and this protease might require metal ions for its activity and it might be thiol-requiring and trypsin-inducible. The results indicate that P. intermedia is capable to release heme from hemoglobin, hence provide a source of iron for its proliferation.

  7. Complete Genome Sequence of Prevotella intermedia Strain 17-2.

    PubMed

    Nambu, Takayuki; Yamane, Kazuyoshi; Maruyama, Hugo; Mashimo, Chiho; Yamanaka, Takeshi

    2015-08-20

    Prevotella intermedia, a Gram-negative black-pigmented anaerobic rod, is frequently isolated from not only periodontal pockets but also purulent infections. We report here the complete genome sequence of P. intermedia strain 17-2, which is a non-exopolysaccharide-producing variant obtained from exopolysaccharide (EPS)-producing P. intermedia strain 17 stock culture.

  8. β-Thalassemia Intermedia: A Clinical Perspective

    PubMed Central

    Musallam, Khaled M.; Taher, Ali T.; Rachmilewitz, Eliezer A.

    2012-01-01

    Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with β-thalassemia intermedia has substantially increased over the past decade. Earlier studies observed that patients with β-thalassemia intermedia experience a clinical-complications profile that is different from that in patients with β-thalassemia major. In this article, a variety of clinical morbidities are explored, and their associations with the underlying disease pathophysiology and risk factors are examined. These involve several organs and organ systems including the vasculature, heart, liver, endocrine glands, bone, and the extramedullary hematopoietic system. The effects of some therapeutic interventions on the development of clinical complications are also discussed. PMID:22762026

  9. Coaggregation of Prevotella intermedia with oral Actinomyces species.

    PubMed Central

    Nesbitt, W E; Fukushima, H; Leung, K P; Clark, W B

    1993-01-01

    Five strains of Prevotella intermedia were examined for their ability to coaggregate with various gram-positive and gram-negative species of oral bacteria. Two of the P. intermedia strains coaggregated with selected Actinomyces species, P. intermedia 27 with Actinomyces viscosus T14V and Actinomyces naeslundii ATCC 12104, PK606, PK984, and PK947, and P. intermedia 113 with Actinomyces odontolyticus WVU 1546 and Actinomyces israelii WVU 838. Exposure of both Prevotella strains but not the Actinomyces strains to heat, trypsin, or proteinase K abolished most coaggregations. All pairs were disaggregated by the addition of sodium dodecyl sulfate, but only those coaggregations involving P. intermedia 113 were reversed by the addition of 2.0 M urea. P. intermedia 27 was sensitive to periodate oxidation, whereas the partner strains were stable to this treatment. Most coaggregations occurred in the presence of saliva; however, reactions involving P. intermedia 27 were not as strong as those of buffer-suspended cells. Treatment of both P. intermedia 113 coaggregations pairs with proteinase K and the results obtained from suspensions of these pairs in saliva suggest that different surface molecules of this P. intermedia strain may mediate each of these coaggregations. These data suggest that all of these coaggregations involve either a protein or glycoprotein on the Prevotella strain, which may interact with carbohydrates or carbohydrate-containing molecules on the surface of the Actinomyces strain. PMID:8478088

  10. Legal and institutional aspects of regulating intermedia pollution

    SciTech Connect

    Entman, R.M.

    1980-05-01

    Intermedia pollution is defined here as the creation of new environmental impacts by controlling existing ones. DOE asked four questions: (1) do the major environmental laws address intermedia pollution; (2) does the Environmental Protection Agency (EPA) have rules, regulations, and procedures through which it considers intermedia questions; (3) do the legislative histories of the laws indicate whether Congress intended for the EPA to consider intermedia issues; and (4) in what ways do the existing laws and regulatory procedures exacerbate intermedia pollution. The answer to the first three questions is yes; much of this report is devoted to amplifying and qualifying that response, the rest to answering the fourth question. The report frames these issues by asking how we can control the adverse environmental i.e., intermedia, impacts of EPA itself. A case study of the intermedia implications of recently issued air-pollution standards for coal-fired power plants illustrates the themes concretely. An analysis of policy alternatives for improving intermedia pollution control concludes the study. The major problems impending good intermedia policy decisions are: conflicts among and failures fully to implement environmental laws; political pressures; tendencies of EPA to minimize the adverse environmental consequences of its own actions; uncertainties caused by the rudimentary scientific understanding of intermedia pollution; and limitations on EPA's organizational ability to handle whatever complex intermedia information it does obtain. The final chapter assesses three policy responses to these problems: do nothing new; issue an incremental prod; and a new law and EPA suffice. Evaluation of these alternatives depends on how deficient current practices are thought to be.

  11. Multiple extracellular phospholipase activities from Prevotella intermedia.

    PubMed

    Bulkacz, Jaime; Faull, Kym F

    2009-06-01

    Enzyme preparations obtained from Prevotella intermedia culture supernatants were partially purified by ammonium sulfate precipitation and ion-exchange column chromatography. Hydrolytic activities were revealed by an assay that uses silicic acid thin layer chromatography to separate the products derived from (14)C-labeled phosphatidyl-choline (PC) hydrolysis. These products were then measured by liquid scintillation spectrometry after iodine visualization. The assays revealed linearity of substrate depletion and product formation with respect to time and protein concentration up to 30 min of incubation. The products had retention times consistent with lyso-phospholipids and phosphoryl-choline. These data strongly suggests the presence of both phospholipase A (PL-A) and phospholipase C (PL-C) activities.

  12. Hydroxyurea in the management of thalassemia intermedia.

    PubMed

    Karimi, Mehran

    2009-01-01

    Hydroxyurea (HU) is an antineoplastic agent that enhances fetal hemoglobin. The clinical significance induced by this compound is well known in sickle cell disease. This clinical significance could also be expected in beta-thalassemia patients. Although studies on beta-thalassemia major patients showed significant results, but these clinical responses are expected to be more in thalassemia intermedia (TI) patients because of lesser alpha/beta globin imbalance. Studies showed that HU therapy in TI patients has significant effects on increasing Hb levels that can cause reducing blood transfusion dependency and transfusion free in some patients, decreasing skeletal deformities and splenomegaly and increasing energy state. So HU therapy could be a useful alternative to blood transfusion in some TI patients.

  13. Biodegradation of 3-methyldiphenylether (MDE) by Hydrogenophaga atypical strain QY7-2 and cloning of the methy-oxidation gene mdeABCD

    NASA Astrophysics Data System (ADS)

    Yang, Qian; Cai, Shu; Dong, Shaowei; Chen, Lulu; Chen, Jifei; Cai, Tianming

    2016-12-01

    3-Methyldiphenylether (MDE) is an important alkyl-substituted diphenyl ether compound that is widely used as an intermediate in the synthesis of pyrethroid insecticides. An efficient MDE-degrading strain QY7-2, identified as Hydrogenophaga atypical, was isolated from activated sludge for the first time. Strain QY7-2 can utilize MDE as the sole carbon and energy source and completely mineralize MDE. The degradation pathway of MDE was proposed in the strain through metabolites identification. A gene cluster involving in methy-oxidation of MDE was cloned from QY7-2 and expressed in Escherichia coli BL21 (DE3), and the products were purified by SDS-PAGE. The specific activities of the recombinant enzymes MdeAB, MdeC and MdeD were 113.8 ± 3.5, 274.5 ± 6.2 and 673.4 ± 8.7 nmol min‑1 mg‑1, respectively. These results provide the biochemical and genetic foundation of microbial degradation pathway of MDE and benefit the bioremediation of MDE-contaminated environments.

  14. Biodegradation of 3-methyldiphenylether (MDE) by Hydrogenophaga atypical strain QY7-2 and cloning of the methy-oxidation gene mdeABCD

    PubMed Central

    Yang, Qian; Cai, Shu; Dong, Shaowei; Chen, Lulu; Chen, Jifei; Cai, Tianming

    2016-01-01

    3-Methyldiphenylether (MDE) is an important alkyl-substituted diphenyl ether compound that is widely used as an intermediate in the synthesis of pyrethroid insecticides. An efficient MDE-degrading strain QY7-2, identified as Hydrogenophaga atypical, was isolated from activated sludge for the first time. Strain QY7-2 can utilize MDE as the sole carbon and energy source and completely mineralize MDE. The degradation pathway of MDE was proposed in the strain through metabolites identification. A gene cluster involving in methy-oxidation of MDE was cloned from QY7-2 and expressed in Escherichia coli BL21 (DE3), and the products were purified by SDS-PAGE. The specific activities of the recombinant enzymes MdeAB, MdeC and MdeD were 113.8 ± 3.5, 274.5 ± 6.2 and 673.4 ± 8.7 nmol min−1 mg−1, respectively. These results provide the biochemical and genetic foundation of microbial degradation pathway of MDE and benefit the bioremediation of MDE-contaminated environments. PMID:27995977

  15. Periodontal status and Prevotella intermedia antibody in acute coronary syndrome.

    PubMed

    Soejima, Hirofumi; Oe, Yoko; Nakayama, Hideki; Matsuo, Katsuhiko; Fukunaga, Takashi; Sugamura, Koichi; Kawano, Hiroaki; Sugiyama, Seigo; Shinohara, Masanori; Izumi, Yuichi; Ogawa, Hisao

    2009-11-12

    We performed periodontal examination and measured serum antibody levels against Prevotella intermedia in patients with acute coronary syndrome (ACS). Composite periodontal risk scores were significantly higher in the ACS group than in the coronary artery disease (CAD) group. Serum antibody levels were higher in the ACS group than in the CAD group and those were significantly correlated with the composite periodontal risk scores. These results provided important information about the status of P. intermedia infection in patients with ACS.

  16. Antibacterial and antibiofilm effects of iron chelators against Prevotella intermedia.

    PubMed

    Moon, Ji-Hoi; Kim, Cheul; Lee, Hee-Su; Kim, Sung-Woon; Lee, Jin-Yong

    2013-09-01

    Prevotella intermedia, a major periodontopathogen, has been shown to be resistant to many antibiotics. In the present study, we examined the effect of the FDA-approved iron chelators deferoxamine (DFO) and deferasirox (DFRA) against planktonic and biofilm cells of P. intermedia in order to evaluate the possibility of using these iron chelators as alternative control agents against P. intermedia. DFRA showed strong antimicrobial activity (MIC and MBC values of 0.16 mg ml(-1)) against planktonic P. intermedia. At subMICs, DFRA partially inhibited the bacterial growth and considerably prolonged the bacterial doubling time. DFO was unable to completely inhibit the bacterial growth in the concentration range tested and was not bactericidal. Crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that DFRA significantly decreased the biofilm-forming activity as well as the biofilm formation, while DFO was less effective. DFRA was chosen for further study. In the ATP-bioluminescent assay, which reflects viable cell counts, subMICs of DFRA significantly decreased the bioactivity of biofilms in a concentration-dependent manner. Under the scanning electron microscope, P. intermedia cells in DFRA-treated biofilm were significantly elongated compared to those in untreated biofilm. Further experiments are necessary to show that iron chelators may be used as a therapeutic agent for periodontal disease.

  17. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    PubMed

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  18. Morphometric and genetic analysis of Arcella intermedia and Arcella intermedia laevis (Amoebozoa, Arcellinida) illuminate phenotypic plasticity in microbial eukaryotes.

    PubMed

    Porfírio-Sousa, Alfredo L; Ribeiro, Giulia M; Lahr, Daniel J G

    2016-11-25

    Testate amoebae are eukaryotic microorganisms characterized by the presence of an external shell (test). The shell morphology is used as a diagnostic character, but discordance between morphological and molecular data has been demonstrated in groups of arcellinids (Amoebozoa), one of the principal groups of testate amoebae. Morphology of the test is supposed to differentiate genera and species and it is applied in ecological, monitoring and paleontological studies. However, if phenotype does not reflect genotype, conclusions in these types of studies become severely impaired. The objective of this work is to evaluate the morphometrical and morphological variation of the closely related and morphologically similar taxa Arcella intermedia laevis Tsyganov and Mazei, 2006 and Arcella intermedia (Deflandre 1928) Tsyganov and Mazei, 2006 in nature and in cultured individuals and see how these are correlated with molecular data. Our results demonstrate that phenotypic plasticity in Arcella intermedia make morphological distinctions impossible in both taxa. Arcella intermedia and Arcella intermedia laevis are molecularly identical for SSU rDNA and a mitochondrial molecular marker (NAD9/7). We conclude that morphological techniques alone cannot identify phenotypic plasticity from natural populations. More work is clearly needed to better understand the morphological, morphometric and molecular variability in these organisms.

  19. Severe thalassaemia intermedia with multiple fractures: role of transfusion therapy.

    PubMed

    Ahmad, Saqib Qayyum; Iqbal, Mudassar; Wahla, Madiha Saeed; Tarrar, Aimel Munir

    2011-11-01

    Thalassaemia intermedia includes thalassaemias with clinical severity intermediate between asymptomatic thalassaemia minor and transfusion dependent thalassaemia major. By definition patients of thalassaemia intermedia maintain a haemoglobin level of 7-10 g/dl and do not, or only occasionally, require blood transfusion. An eight-year-old girl who was a known case of thalassaemia intermedia and had been occasionally transfused presented with fever, pain and swelling over the wrists, ankles and above the right knee joint. Radiographs showed medullary widening, cortical thinning and; multiple, recent and old, partially healed fractures of metadiaphseal regions of long bones. Her fractures have been immobilized by means of back slabs. In view of her recurrent fractures and growth retardation we advised a regular transfusion-chelation regimen to our patient to suppress her ineffective dyserythropoiesis. The treatment is expected to prevent further bone fragility and fractures, as well as improve her life quality.

  20. Larval and juvenile development of Tatia intermedia (Siluriformes: Auchenipteridae).

    PubMed

    Pereira, L H A; Bialetzki, A; Bonecker, A C T

    2017-03-01

    This study describes the morphology, morphometry and meristic characters of larval and juvenile Tatia intermedia collected in the middle Tocantins River and some of its tributaries. Six larvae of T. intermedia were examined and they have a moderately elongate body, head slightly dorso-ventrally depressed with a convex snout, small and round eyes and a subterminal mouth. In five juvenile stages observed, the head and eye are relatively smaller than in the larval stage and the snout remains convex and mouth becomes terminal.

  1. Development and evaluation of new primers for PCR-based identification of Prevotella intermedia.

    PubMed

    Zhou, Yanbin; Liu, Dali; Wang, Yiwei; Zhu, Cailian; Liang, Jingping; Shu, Rong

    2014-08-01

    The aim of this study was to develop new Prevotella intermedia-specific PCR primers based on the 16S rRNA. The new primer set, Pi-192 and Pi-468, increased the accuracy of PCR-based P. intermedia identification and could be useful in the detection of P. intermedia as well as epidemiological studies on periodontal disease.

  2. Molecular cloning and functional characterization of borneol dehydrogenase from the glandular trichomes of Lavandula x intermedia.

    PubMed

    Sarker, Lukman S; Galata, Mariana; Demissie, Zerihun A; Mahmoud, Soheil S

    2012-12-15

    Several varieties of Lavandula x intermedia (lavandins) are cultivated for their essential oils (EOs) for use in cosmetic, hygiene and personal care products. These EOs are mainly constituted of monoterpenes including camphor, which contributes an off odor reducing the olfactory appeal of the oil. We have recently constructed a cDNA library from the glandular trichomes (the sites of EO synthesis) of L. x intermedia plants. Here, we describe the cloning of a borneol dehydrogenase cDNA (LiBDH) from this library. The 780 bp open reading frame of the cDNA encoded a 259 amino acid short chain alcohol dehydrogenase with a predicted molecular mass of ca. 27.5 kDa. The recombinant LiBDH was expressed in Escherichia coli, purified by Ni-NTA agarose affinity chromatography, and functionally characterized in vitro. The bacterially produced enzyme specifically converted borneol to camphor as the only product with K(m) and k(cat) values of 53 μM and 4.0 × 10(-4) s(-1), respectively. The LiBDH transcripts were specifically expressed in glandular trichomes of mature flowers indicating that like other Lavandula monoterpene synthases the expression of this gene is regulated in a tissue-specific manner. The cloning of LiBDH has far reaching implications in improving the quality of Lavandula EOs through metabolic engineering.

  3. Nucleases from Prevotella intermedia can degrade neutrophil extracellular traps.

    PubMed

    Doke, M; Fukamachi, H; Morisaki, H; Arimoto, T; Kataoka, H; Kuwata, H

    2016-08-01

    Periodontitis is an inflammatory disease caused by periodontal bacteria in subgingival plaque. These bacteria are able to colonize the periodontal region by evading the host immune response. Neutrophils, the host's first line of defense against infection, use various strategies to kill invading pathogens, including neutrophil extracellular traps (NETs). These are extracellular net-like fibers comprising DNA and antimicrobial components such as histones, LL-37, defensins, myeloperoxidase, and neutrophil elastase from neutrophils that disarm and kill bacteria extracellularly. Bacterial nuclease degrades the NETs to escape NET killing. It has now been shown that extracellular nucleases enable bacteria to evade this host antimicrobial mechanism, leading to increased pathogenicity. Here, we compared the DNA degradation activity of major Gram-negative periodontopathogenic bacteria, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We found that Pr. intermedia showed the highest DNA degradation activity. A genome search of Pr. intermedia revealed the presence of two genes, nucA and nucD, putatively encoding secreted nucleases, although their enzymatic and biological activities are unknown. We cloned nucA- and nucD-encoding nucleases from Pr. intermedia ATCC 25611 and characterized their gene products. Recombinant NucA and NucD digested DNA and RNA, which required both Mg(2+) and Ca(2+) for optimal activity. In addition, NucA and NucD were able to degrade the DNA matrix comprising NETs.

  4. β-Thalassemia Intermedia: A Bird’s-Eye View

    PubMed Central

    Haddad, Anthony; Tyan, Paul; Radwan, Amr; Mallat, Naji; Taher, Ali

    2014-01-01

    Beta-thalassemia is due to a defect in the synthesis of the beta-globin chains, leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. The spectrum of thalassemias is wide, with one end comprising thalassemia minor, which consists of a mild hypochromic microcytic anemia with no obvious clinical manifestations, while on the other end is thalassemia major, characterized by patients who present in their first years of life with profound anemia and regular transfusion requirements for survival. Along the spectrum lies thalassemia intermedia, a term developed to describe patients with manifestations that are neither mild enough nor severe enough to be classified in the spectrum’s extremes. Over the past decade, our understanding of β-thalassemia intermedia has increased tremendously with regards to molecular information as well as pathophysiology. It is now clear that β-thalassemia intermedia has a clinical presentation as well as complications associated with the disease that are different from those of β-thalassemia major. This review is designed to tackle issues related to β-thalassemia intermedia from the basic definition of the disease to paramedical issues, namely the quality of life in these patients. Genetics and pathophysiology are revisited, as well as the complications specific to this disease. These complications include effects on several organ systems, including the cardiovascular, hepatic, endocrine, renal, brain, and skeletal systems. Extramedullary hematopoiesis is also discussed in this article. Risk factors are highlighted and cutoffs are identified to minimize morbidities in β-thalassemia intermedia. Several treatment modalities are considered by shining a light on the pros and cons of each modality, as well as the role of special pharmacological agents in the progress of the disease and its morbidities. Finally, health-related quality of life is discussed in these patients with a direct comparison to the more severe

  5. CLINICAL APPLICATION OF RECOMBINANT ERYTHROPOIETIN IN BETA-THALASSAEMIA INTERMEDIA.

    PubMed

    Asadov, Ch; Alimirzoyeva, Z; Hasanova, M; Mammadova, T; Shirinova, A

    2016-06-01

    Research objective is to study the efficacy of recombinant erythropoietin (epoetin alfa) as alternative method of treatment beta-thalassemia intermedia. Study involved 58 patients with beta-thalassemia intermedia (23 women and 35 men). In all observed patients was defined levels of hemoglobin (Hb), red blood cells (RBC), erythrocyte indexes (MCV, MCH, MCHC), hemoglobin fractions (HbA, HbA2, HbF), serum ferritin, serum erythropoietin before and after administrated rEPO. All patients received rEPO during 6 month at the dose - 10000 IU subcutaneously. The majority of patients - 39 (67%) had a good response to rEPO (increase in hemoglobin level more than 20 g/l); 16 patients (28%) had a mean response (increase in Hb 10 - 20 g/l); in 3 (5%) patients occurred poor response to rEPO therapy (increase in Hb <10 g/l). After rEPO treatment of beta-thalassemia intermedia patients there was a statistically significant change in the number of RBC, levels of HbF and sEPO. The evaluation of interdependence between the indices of the baseline sEPO and increased Hb values in patients after rEPO treatment revealed the presence of the reverse direct relationship (r=-0.67). Based on the results, it can be concluded that the use of rEPO in complex therapy of beta-thalassemia intermedia leads to increased levels of Hb and consequently reducing the need for blood transfusions, and accordingly expected to prevent severe complications of blood transfusion (alloimmunization, hypersplenism, iron overload, contamination transmissible infections) facilitating normal growth and development, and a better quality of life.

  6. Thalamic Massa Intermedia Duplication in a Dysmorphic 14 month-old Toddler

    PubMed Central

    Whitehead, Matthew T

    2015-01-01

    The massa intermedia is an inconstant parenchymal band connecting the medial thalami. It may be thickened in various disease processes such as Chiari II malformation or absent in other disease states. However, the massa intermedia may also be absent in up to 30% of normal human brains. To the best of my knowledge, detailed imaging findings of massa intermedia duplication have only been described in a single case report. An additional case of thalamic massa intermedia duplication discovered on a routine brain MR performed for dysmorphic facial features is reported herein. PMID:26622932

  7. Beta-thalassemia intermedia associated with moyamoya syndrome.

    PubMed

    Göksel, Basak Karakurum; Ozdogu, Hakan; Yildirim, Tulin; Oğuzkurt, Levent; Asma, Suheyl

    2010-07-01

    Moyamoya syndrome (MMS) is a progressive disorder. We report a 19-year-old boy with beta-thalassemia who presented with a left hemiparesis. Brain MRI showed old middle cerebral artery and left frontal subcortical white matter infarcts. Brain magnetic resonance angiography and digital subtraction angiography revealed occlusion of the bilateral internal carotid arteries with a rich network of basal collateral vessels. To our knowledge this is the third report of beta-thalassemia intermedia and MMS, and the first report of a patient in Turkey. It emphasizes the potential for cerebral infarct due to anemia, protein S and thrombocytosis.

  8. The identification of genes specific to Prevotella intermedia and Prevotella nigrescens using genomic subtractive hybridization.

    PubMed

    Masakiyo, Yoshiaki; Yoshida, Akihiro; Shintani, Yasuyuki; Takahashi, Yusuke; Ansai, Toshihiro; Takehara, Tadamichi

    2010-06-01

    Prevotella intermedia and Prevotella nigrescens, which are often isolated from periodontal sites, were once considered two different genotypes of P. intermedia. Although the genomic sequence of P. intermedia was determined recently, little is known about the genetic differences between P. intermedia and P. nigrescens. The subtractive hybridization technique is a powerful method for generating a set of DNA fragments differing between two closely related bacterial strains or species. We used subtractive hybridization to identify the DNA regions specific to P. intermedia ATCC 25611 and P. nigrescens ATCC 25261. Using this method, four P. intermedia ATCC 25611-specific and three P. nigrescens ATCC 25261-specific regions were determined. From the species-specific regions, insertion sequence (IS) elements were isolated for P. intermedia. IS elements play an important role in the pathogenicity of bacteria. For the P. intermedia-specific regions, the genes adenine-specific DNA-methyltransferase and 8-amino-7-oxononanoate synthase were isolated. The P. nigrescens-specific region contained a Flavobacterium psychrophilum SprA homologue, a cell-surface protein involved in gliding motility, Prevotella melaninogenica ATCC 25845 glutathione peroxide, and Porphyromonas gingivalis ATCC 33277 leucyl-tRNA synthetase. The results demonstrate that the subtractive hybridization technique was useful for distinguishing between the two closely related species. Furthermore, this technique will contribute to our understanding of the virulence of these species.

  9. SYNCHROTRON X-RAY ABSORPTION-EDGE COMPUTED MICROTOMOGRAPHY IMAGING OF THALLIUM COMPARTMENTALIZATION IN IBERIS INTERMEDIA

    EPA Science Inventory

    Thallium (TI) is an extremely toxic metal which, due to its similarities to K, is readily taken up by plants. Thallium is efficiently hyperaccumulated in Iberis intermedia as TI(I). Distribution and compartmentalization of TI in I. intermedia is highes...

  10. Dipeptide utilization by the periodontal pathogens Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum.

    PubMed

    Takahashi, Nobuhiro; Sato, T

    2002-02-01

    Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum, which can frequently be isolated from periodontal pockets, preferentially utilize proteins and peptides as growth substrates. In this study, we determined the size of peptide that is preferentially utilized as a source of energy and material for cell growth by P. gingivalis, P. intermedia, P. nigrescens and F. nucleatum using various sizes of poly amino acids consisting of two to approximately 100 molecules of aspartate or glutamate. Resting cells of P. gingivalis, P. intermedia and P. nigrescens utilized aspartylaspartate, while cells of P. gingivalis and F. nucleatum utilized glutamylglutamate. The addition of aspartylaspartate to the culture medium increased the growth of P. gingivalis, P. intermedia and P. nigrescens, while the addition of glutamylglutamate promoted the growth of P. gingivalis and F. nucleatum. These results clearly indicate that dipeptides such as aspartylaspartate and glutamylglutamate can be utilized as growth substrates for P. gingivalis, P. intermedia, P. nigrescens and F. nucleatum.

  11. Gravi-photomorphogenesis of the moss Pottia intermedia protonemata

    NASA Astrophysics Data System (ADS)

    Demkiv, O. T.; Kyjak, N. Y.; Khorkavtsiv, Y. D.; Kit, N. A.

    The protonemata development proceeds in the process of gradual differentiation of growing apical cells and intercalar cells the shortened lateral branches of the latters being transformed into three-dimensional gametophore buds (Demkiv et al., 1991). Normal course of plant development needs favourable external conditions. Sometimes, however, external environment agents can accelerate the development of organism. So, apical protonema cells of darkgrown gravitropic P. intermedia differentiate gametophore-buds in light of low intensity (Ripetskyj, 1999). We investigate the influence of gravistimulation on bud formation in haploid and diploid P. intermedia protonema. Diploid protonema was found to react on light weaker than haploid one. Under the influence of light the darkgrown apical cells and lateral branches of haploid protonema were directly transformed into buds, while in diploid protonema at first the formation of bundles of rhizoid type filaments takes place on the tips of caulonema and buds appeared in center of such bundles. The participation of gravity in gametophore bud formation was assessed by clinorotating protonema in darkness. Being illuminated such protonema also developed buds quickly the latters being formed along all stolon. It can be suggested that at 1g the growth zone of apical cells actively attract inductors of bud formation. During clinorotation the inductors probably are transferred much more slower than under stationary state and that is why the buds arised not only at the tips of stolons but along all their length. It is known that gametophore bud formation can be stimulated by exogenous phytohormones. As M. Bopp (1980) has shown, that kinetin selectively promotes bud formation on moss protonema. Our observations have shown 0,5 -- 50 μ M of kinetin stimulate the bud formation on diploid aposporic protonema much more effectively that on haploid one. It can be concluded that the amount of endogenous cytokinins in haploid protonemal cells is

  12. Prevotella intermedia upregulates MMP-1 and MMP-8 expression in human periodontal ligament cells.

    PubMed

    Guan, Su-Min; Shu, Lei; Fu, Shan-Min; Liu, Bin; Xu, Xiu-Li; Wu, Jun-Zheng

    2009-10-01

    Prevotella intermedia, a major periodontal pathogen, plays important roles in the initiation and development of periodontitis by stimulating the release of proinflammatory cytokines, proteinases and matrix metalloproteinases (MMPs). Our previous study demonstrated that P. intermedia induced MMP-9 expression in human periodontal ligament (hPDL) cells. In this study, we examined the effects of P. intermedia on other MMPs' expression. Semi-quantitative reverse transcriptase (RT)-PCR analysis revealed that P. intermedia ATCC 25611 supernatant increased MMP-1 and MMP-8 mRNA expression in a concentration- and time-dependent manner. Enzyme-linked immunosorbent assay and Western blot results confirmed the RT-PCR results at the protein level. Cyclooxygenase inhibitor indomethacin significantly attenuated the upregulatory effects of P. intermedia on MMP-1 and MMP-8 expression. Extracellular signal-related kinase inhibitor PD98059 and c-Jun N-terminal kinase inhibitor SP600125 considerably decreased the upregulated level of MMP-1, whereas p38 inhibitor SB203580 markedly inhibited MMP-8 expression, suggesting that prostaglandin E(2) and mitogen-activated protein kinase signaling pathways are involved in P. intermedia-induced MMP-1 and MMP-8 upregulation. Our results indicate that P. intermedia might contribute to periodontal connective tissue and bone matrix destruction through upregulating MMP production.

  13. Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria.

    PubMed

    Fteita, Dareen; Könönen, Eija; Söderling, Eva; Gürsoy, Ulvi Kahraman

    2014-06-01

    Alterations in the quantity and quality of biofilms at gingival margin are considered to play a role in the initiation and development of pregnancy-related gingivitis. Prevotella intermedia sensu lato is able to consume estradiol, the major sex hormone secreted during pregnancy, in the absence of vitamin K. The aim of the study was to examine the effect of estradiol on the planktonic growth, coaggregation, polysaccharide production, and biofilm formation of the P. intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, and Prevotella pallens. In all experiments, the type strain (ATCC) and a clinical strain (AHN) of P. intermedia, P. nigrescens, and P. pallens were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol. Planktonic growth was assessed by means of the colony forming unit method, while coaggregation and biofilm formation were assessed by spectrophotometric methods. In the determination of protein and polysaccharide levels, the Bradford and phenol-sulfuric acid methods were used, respectively. P. pallens AHN 9283 and P. nigrescens ATCC 33563 increased their numbers at planktonic stage with increasing estradiol concentrations. In 48-h biofilm tests, elevated protein levels were found for both strains of P. intermedia, and the strains P. nigrescens ATCC 33563 and P. pallens AHN 9283 in the presence of estradiol. The P. intermedia strains also increased the levels of polysaccharide formation in the biofilm. Coaggregation of the P. intermedia group organisms with Fusobacterium nucleatum was enhanced only in P. intermedia AHN 8290. In conclusion, our in vitro experiments indicate that estradiol regulates planktonic growth, coaggregation, polysaccharide production, and biofilm formation characteristics of P. intermedia, P. nigrescens, and P. pallens differently. These results may, at least partly, explain the differences seen in their contribution to the pathogenesis of pregnancy-related gingivitis.

  14. Nuevos sistemas de frecuencia intermedia para el IAR

    NASA Astrophysics Data System (ADS)

    Olalde, J. C.; Perilli, D.; Larrarte, J. J.

    Se presenta el diagrama en bloques de los nuevos sistemas de Frecuencia Intermedia para los dos radiómetros instalados en el IAR. Entre las características más importantes del sistema podemos mencionar la posibilidad de conectar cualquiera de las dos antenas a los ``backend" disponibles: analizador espectral de alta resolución (META II) de 0,05 Hz, autocorrelador de 1008 canales y contínuo. Se incorporan al sistema nuevos sintetizadores de frecuencia implementados con PLL y la moderna técnica de síntesis digital directa. Por último, el conjunto del sistema es susceptible de ser configurado por las computadoras de adquisición de datos, supervisadas por otra, que entrega el estado de funcionamiento actual y evita la selección de configuraciones incorrectas por parte del usuario.

  15. Secondary Haemochromatosis in a Patient with Thalassemia Intermedia

    PubMed Central

    ROTARU, IONELA; GAMAN, AMELIA; GAMAN, G.

    2014-01-01

    Haemochromatosis is due to excessive accumulation of iron in tissues and organs impairing their function. The most common haematologic disorders that are subject to an intensive transfusion regimen bringing excess iron in the body are: thalassemia and myelodysplastic syndrome. The value of serum ferritin in these patients (indicator of iron stores condition) reaches high values. Red cell substitution bringing additional iron intake must be accompanied by administration of chelation therapy in order to prevent haemochromatosis and related complications. We present the case of a patient with thalassemia intermedia, integumentary secondary haemochromatosis, cirrhosis with haemochromatosis, and secondary diabetes, who died at the age of 33 years because of upper gastrointestinal bleeding due to the rupture of oesophageal varices. PMID:24791210

  16. Suppression of linalool acetate production in Lavandula x intermedia.

    PubMed

    Desautels, Amy; Biswas, Kamal; Lane, Alexander; Boeckelmann, Astrid; Mahmoud, Soheil S

    2009-11-01

    Linalool acetate, one of the major constituent of several essential oils, is heat-labile and decomposes upon exposure to the high injector temperature during gas chromatography. Here we report the development of an improved method for detection of this compound by gas chromatography mass spectrometry (GCMS) using cold on-column injection of the sample. By using this sensitive method, it has been demonstrated that a lavandin (L. x intermedia) mutant accumulates trace quantities of linalool acetate and camphor and higher amounts of cineole and borneol compared to its parent. This plant, which very likely carries a point mutation in one or more of the genes involved in essential oil production, provides a unique tool for investigating regulation of essential oil biogenesis in plants.

  17. Antimicrobial susceptibility pattern of Brachyspira intermedia isolates from European layers.

    PubMed

    Verlinden, Marc; Boyen, Filip; Pasmans, Frank; Garmyn, An; Haesebrouck, Freddy; Martel, An

    2011-09-01

    A broth microdilution method was used to determine the antimicrobial susceptibility of 20 Brachyspira intermedia isolates obtained from different layer flocks in Belgium and The Netherlands between 2008 and 2010. The antimicrobial agents used were tylosin, tilmicosin, tiamulin, valnemulin, doxycycline, and lincomycin. The minimal inhibitory concentration (MIC) distribution patterns of tylosin, tilmicosin, lincomycin, and doxycycline were bimodal, demonstrating acquired resistance against doxycycline in three strains, against the macrolides in two strains, and against lincomycin in one strain. The MICs of tiamulin and valnemulin showed a monomodal distribution, but with tailing toward the higher MIC values, possibly suggesting low-level acquired resistance in six isolates. Sequencing revealed a G1058C mutation in the 16S rRNA gene in all doxycycline-resistant strains. The strain resistant to tylosin, tilmicosin, and lincomycin had an A2058T mutation in the 23S rRNA gene.

  18. Microarray Bactericidal Testing of Natural Products Against Yersinia intermedia and Bacillus anthracis

    DTIC Science & Technology

    2002-01-01

    against B. anthracis and Y. intermedia in Microarray Format AC Plant Source AC Plant Source Cineole Eucalyptus globulus Carvacrol Oregano (Origanum...concentrations (Figure 1, Table 3 ). Only the AC’s thymol, eugenol and carvacrol were effective against both B. anthracis and Y. intermedia (Figures 2, 3, 7...needed for an Overnight Inocula of B. anthracis VNR1-)1 and Y. intermedia Active component MIC (mM) B.A. MIC (mM) Y.I. Carvacrol 1.2 1.0 Thymol 0.3 3.5

  19. Gravitropism in caulonemata of the moss Pottia intermedia

    NASA Technical Reports Server (NTRS)

    Chaban, C. I.; Kern, V. D.; Ripetskyj, R. T.; Demkiv, O. T.; Sack, F. D.

    1998-01-01

    The gravitropism of caulonemata of Pottia intermedia is described and compared with that of other mosses. Spore germination produces primary protonemata including caulonemata which give rise to buds that form the leafy moss plant, the gametophore. Primary caulonemata are negatively gravitropic but their growth and the number of filaments are limited in the dark. Axenic culture of gametophores results in the production of secondary caulonemata that usually arise near the leaf base. Secondary protonemata that form in the light are agravitropic. Secondary caulonemata that form when gametophores are placed in the dark for several days show strong negative gravitropism and grow well in the dark. When upright caulonemata are reorientated to the horizontal or are inverted, upward bending can be detected after 1 h and caulonemata reach the vertical within 1-2 d. Clear amyloplast sedimentation occurs 10-15 minutes after horizontal placement and before the start of upward curvature. This sedimentation takes place in a sub-apical zone. Amyloplast sedimentation also takes place along the length of upright and inverted Pottia protonemata. These results support the hypothesis that amyloplast sedimentation functions in gravitropic sensing since sedimentation occurs before gravitropism in Pottia and since the location and presence of a unique sedimentation zone is conserved in all four mosses known to gravitropic protonomata.

  20. In Vitro Effects of Polyphosphate against Prevotella intermedia in Planktonic Phase and Biofilm.

    PubMed

    Jang, Eun-Young; Kim, Minjung; Noh, Mi Hee; Moon, Ji-Hoi; Lee, Jin-Yong

    2016-02-01

    Polyphosphate (polyP) has gained a wide interest in the food industry due to its potential as a decontaminating agent. In this study, we examined the effect of sodium tripolyphosphate (polyP3; Na5P3O10) against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. The MIC of polyP3 against P. intermedia ATCC 49046 determined by agar dilution method was 0.075%, while 0.05% polyP3 was bactericidal against P. intermedia in time-kill analysis performed using liquid medium. A crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that sub-MICs of polyP3 significantly decreased biofilm formation. Under the scanning electron microscope, decreased numbers of P. intermedia cells forming the biofilms were observed when the bacterial cells were incubated with 0.025% or higher concentrations of polyP3. Assessment of biofilm viability with LIVE/DEAD staining and viable cell count methods showed that 0.05% or higher concentrations of polyP3 significantly decreased the viability of the preformed biofilms in a concentration-dependent manner. The zone sizes of alpha-hemolysis formed on horse blood agar produced by P. intermedia were decreased in the presence of polyP3. The expression of the genes encoding hemolysins and the genes of the hemin uptake (hmu) locus was downregulated by polyP3. Collectively, our results show that polyP is an effective antimicrobial agent against P. intermedia in biofilms as well as planktonic phase, interfering with the process of hemin acquisition by the bacterium.

  1. In Vitro Effects of Polyphosphate against Prevotella intermedia in Planktonic Phase and Biofilm

    PubMed Central

    Jang, Eun-Young; Kim, Minjung; Noh, Mi Hee

    2015-01-01

    Polyphosphate (polyP) has gained a wide interest in the food industry due to its potential as a decontaminating agent. In this study, we examined the effect of sodium tripolyphosphate (polyP3; Na5P3O10) against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. The MIC of polyP3 against P. intermedia ATCC 49046 determined by agar dilution method was 0.075%, while 0.05% polyP3 was bactericidal against P. intermedia in time-kill analysis performed using liquid medium. A crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that sub-MICs of polyP3 significantly decreased biofilm formation. Under the scanning electron microscope, decreased numbers of P. intermedia cells forming the biofilms were observed when the bacterial cells were incubated with 0.025% or higher concentrations of polyP3. Assessment of biofilm viability with LIVE/DEAD staining and viable cell count methods showed that 0.05% or higher concentrations of polyP3 significantly decreased the viability of the preformed biofilms in a concentration-dependent manner. The zone sizes of alpha-hemolysis formed on horse blood agar produced by P. intermedia were decreased in the presence of polyP3. The expression of the genes encoding hemolysins and the genes of the hemin uptake (hmu) locus was downregulated by polyP3. Collectively, our results show that polyP is an effective antimicrobial agent against P. intermedia in biofilms as well as planktonic phase, interfering with the process of hemin acquisition by the bacterium. PMID:26596937

  2. Prevotella intermedia induces matrix metalloproteinase-9 expression in human periodontal ligament cells.

    PubMed

    Guan, Su-Min; Shu, Lei; Fu, Shan-Min; Liu, Bin; Xu, Xiu-Li; Wu, Jun-Zheng

    2008-06-01

    Matrix metalloproteinases (MMPs) play pivotal roles in inflammatory diseases including chronic periodontitis. The effects of Prevotella intermedia, a major periodontal pathogen, on MMP-9 production in primary human periodontal ligament (hPDL) cells were examined in the present study. MMP-9 mRNA expression was measured by semiquantitative reverse transcriptase PCR and its protein secretion was assayed by gelatin zymography. Prevotella intermedia ATCC 25611 supernatant time and dose-dependently induced MMP-9 expression. In contrast, Porphyromanas gingivalis ATCC 33277 supernatants, Escherichia coli lipopolysacchride and IL-1beta exhibited no stimulatory effects on MMP-9 production in hPDL cells. Mitogen-activated protein kinases [MAPK, including extracellular signal-related kinases (ERK), c-jun N-terminal kinases (JNK) and p38] inhibitors exerted no effect on the P. intermedia-induced MMP-9 production, indicating that P. intermedia induced MMP-9 production through an MAPK-independent pathway. Our results demonstrated that P. intermedia may contribute to periodontal tissue destruction during chronic periodontitis by inducing MMP-9 production in hPDL cells.

  3. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    PubMed

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease.

  4. The effects of tetracycline, minocycline, doxycycline and ofloxacin on Prevotella intermedia biofilm.

    PubMed

    Takahashi, N; Ishihara, K; Kimizuka, R; Okuda, K; Kato, T

    2006-12-01

    Prevotella intermedia, a black-pigmented, anaerobic, gram-negative bacterium, is associated with various type of periodontitis. Antibiotic treatments via a systemic or local route have been reported as being useful for treating periodontal disease. The purpose of this study was to examine the effects of four antibiotics, tetracycline (TET), minocycline (MINO), doxycycline (DOXY) and ofloxacin (OFLX) on P. intermedia biofilms at minimum inhibitory concentrations (MIC) from one-fold to 100-fold. MICs were determined for planktonic cells. Biofilm formation was determined with the crystal violet stain method and the bioactivities in the biofilms were determined with the adenosine triphosphate (ATP) -bioluminescent assay using a 96-well culture plate. At one-fold MIC, DOXY inhibited biofilm formation by P. intermedia ATCC 25611. Other antibiotics at one-fold MIC had no effects on the biofilm formation of tested bacterial strains. In P. intermedia ATCC 25611 biofilms, all the antibiotics tested showed inhibitory activities at five- to 100-fold MICs. In the biofilms of P. intermedia strains, except ATCC 25611, treated with three tetracycline antibiotics, the bioactivities were significantly increased, indicating the difficulties involved in designing antibiotic therapy for periodontal disease.

  5. Antimicrobial susceptibility testing of Brachyspira intermedia and Brachyspira pilosicoli isolates from Australian chickens.

    PubMed

    Hampson, D J; Stephens, C P; Oxberry, S L

    2006-02-01

    Susceptibilities of predominantly Australian isolates of the pathogenic intestinal spirochaetes Brachyspira intermedia (n = 25) and Brachyspira pilosicoli (n = 17) from chickens were tested in agar dilution against four concentrations each of the antimicrobials tiamulin, lincomycin, tylosin, metronidazole, tetracycline and ampicillin. Based on available minimum inhibitory concentration (MIC) breakpoint values for Brachyspira hyodysenteriae or other Gram-negative enteric veterinary pathogens, isolates of both species generally were susceptible to tiamulin, lincomycin, metronidazole and tetracycline. Although not classed as resistant, four isolates of B. intermedia had an elevated MIC range for tiamulin (1 to 4 mg/l), 11 isolates of B. intermedia and five of B. pilosicoli had an elevated MIC range for lincomycin (10 to 50 mg/l), one isolate of B. pilosicoli had an elevated MIC range for tetracycline (10 to 20 mg/l), and one isolate of B. intermedia and five of B. pilosicoli had an elevated MIC range for ampicillin (10 to 50 mg/l). A clear lack of susceptibility to tylosin (MIC > 4 mg/l) was seen in 11 isolates each of B. intermedia and B. pilosicoli, and to ampicillin (MIC > 32 mg/l) in two isolates of B. pilosicoli. These data suggest that some resistance to common antimicrobials exists among intestinal spirochetes obtained from laying hens and supports the need of MIC data for clinical isolates before any treatment is considered.

  6. [Diversity and resistance of rhizobia isolated from Caragana intermedia in Maowusu sandland].

    PubMed

    Gao, Lifeng; Deng, Xin; Wang, Hongxin; Hu, Zhiang

    2004-01-01

    Fifteen rhizobia strains were isolated from wild shrubby legume Caragana intermedia in Maowusu sandland. A dendrogram was constructed based on esterase profiles, showing a rich diversity of these rhizobia. Many biochemical characteristics were detected, including acid or alkali production, catalase activity, utilization of sole carbon sources, and resistance to salt, acid-alkali and temperature variation. The results indicated that all the rhizobia strains isolated from Caragana intermedia could excrete H+ on YMA agar and produce catalase. 73.3% strains could tolerate NaCl stress at 3% concentration, and 80% strains could grow at 50 degrees C. Except the difference in lactose and starch utilization, rhizobia strains had no bias on the rest carbon sources. However, the difference in resistance to stress existed among strains, which might be related to the adaptation of rhizobia to diverse landscapes in Maowusu sandland. It was revealed that rhizobia nodulating Caragana intermedia could be used as a new germplasm to fix nitrogen under severe environment.

  7. Digital Distribution of Advertising for Publications (DDAP): a graphic arts prototype of electronic intermedia publishing (EIP)

    NASA Astrophysics Data System (ADS)

    Dunn, Patrice M.

    1998-01-01

    The Digital Distribution of Advertising for Publications (DDAP) is a graphic arts industry prototype of Electronic Intermedia Publishing (EIP). EIP is a strategic, multi- industrial concept that seeks to enable the capture and input of volumes of data (i.e., both raster and object oriented data -- as well as the latter's antecedent which is vector data -- color data and black-and-white data) from a multiplicity of devices; then flowing, controlling, manipulating, modifying, storing, retrieving, transmitting, and shipping, that data through an industrial process for output to a multiplicity of output devices (e.g., ink on paper, toner on paper, bits and bytes on CD ROM, Internet, Multimedia, HDTV, etc.). As the technical requirements of the print medium are among the most rigorous in the Intermedia milieu the DDAP prototype addresses some of the most challenging issues faced in Electronic Intermedia Publishing (EIP).

  8. Direct quantitative differentiation between Prevotella intermedia and Prevotella nigrescens in clinical specimens.

    PubMed

    Gmür, Rudolf; Thurnheer, Thomas

    2002-05-01

    This paper describes a quantitative fluorescent in situ hybridization (FISH) assay for the differential identification of Prevotella intermedia and Prevotella nigrescens in clinical samples, and compares its performance with less discriminatory culture and quantitative immunofluorescence (IF) assays. Fluorescence-labelled oligonucleotide probes directed to specific 16S rRNA sequences of P. intermedia, P. nigrescens, Prevotella pallens and Prevotella denticola were hybridized under stringent conditions with cultured reference strains or plaque samples from deep periodontal pockets. Probe specificity was defined with strains from multiple oral Prevotella species. The lower detection level of the assays was approximately 3x10(3) target cells per ml of plaque-sample suspension. P. intermedia, P. nigrescens, P. pallens and P. denticola were detected in plaques with prevalences of 69, 67, 0 and 28%, respectively. On average, 3.9 x 10(6) P. intermedia, 3.1 x 10(6) P. nigrescens and 5.6 x 10(5) P. denticola cells were counted per positive sample. All three species were found almost exclusively in dense mixed aggregates. Quantitative FISH data agreed satisfactorily with corresponding IF data (r=0.711). Both FISH and IF enumerations of the sum of P. intermedia and P. nigrescens markedly exceeded the c.f.u. counts of black-pigmented colonies in Porphyromonas gingivalis-free cultured subgingival plaques. The results demonstrate the validity of this new assay. Unlike established IF, culture, PCR or checkerboard DNA hybridization assays, this FISH assay differentiates quantitatively between P. intermedia and P. nigrescens, provides visual accuracy control, and offers insights into the spatial distribution of the target cells within a clinical sample.

  9. Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3.

    PubMed

    Potempa, Michal; Potempa, Jan; Kantyka, Tomasz; Nguyen, Ky-Anh; Wawrzonek, Katarzyna; Manandhar, Surya P; Popadiak, Katarzyna; Riesbeck, Kristian; Eick, Sigrun; Blom, Anna M

    2009-02-01

    Periodontitis is an inflammatory disease of the supporting structures of the teeth caused by, among other pathogens, Prevotella intermedia. Many strains of P. intermedia are resistant to killing by the human complement system, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with recombinant cysteine protease of P. intermedia (interpain A) resulted in a drastic decrease in bactericidal activity of the serum. Furthermore, a clinical strain 59 expressing interpain A was more serum-resistant than another clinical strain 57, which did not express interpain A, as determined by Western blotting. Moreover, in the presence of the cysteine protease inhibitor E64, the killing of strain 59 by human serum was enhanced. Importantly, we found that the majority of P. intermedia strains isolated from chronic and aggressive periodontitis carry and express the interpain A gene. The protective effect of interpain A against serum bactericidal activity was found to be attributable to its ability to inhibit all three complement pathways through the efficient degradation of the alpha-chain of C3 -- the major complement factor common to all three pathways. P. intermedia has been known to co-aggregate with P. gingivalis, which produce gingipains to efficiently degrade complement factors. Here, interpain A was found to have a synergistic effect with gingipains on complement degradation. In addition, interpain A was able to activate the C1 complex in serum, causing deposition of C1q on inert and bacterial surfaces, which may be important at initial stages of infection when local inflammatory reaction may be beneficial for a pathogen. Taken together, the newly characterized interpain A proteinase appears to be an important virulence factor of P. intermedia.

  10. Newly Installed S-1 Truss

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Launched October 7, 2002 aboard the Space Shuttle Orbiter Atlantis, the STS-112 mission lasted 11 days and performed three sessions of Extra Vehicular Activity (EVA). Its primary mission was to install the Starboard (S1) Integrated Truss Structure and Equipment Translation Aid (CETA) Cart to the International Space Station (ISS). The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss, attached to the S0 (S Zero) truss installed by the previous STS-110 mission, flows 637 pounds of anhydrous ammonia through three heat rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA is the first of two human-powered carts that will ride along the International Space Station's railway providing a mobile work platform for future extravehicular activities by astronauts. This is a view of the newly installed S1 Truss as photographed during the mission's first scheduled EVA. The Station's Canadarm2 is in the foreground. Visible are astronauts Piers J. Sellers (lower left) and David A. Wolf (upper right), both STS-112 mission specialists.

  11. Intermedia: A System for Linking Multimedia Documents. IRIS Technical Report 86-2.

    ERIC Educational Resources Information Center

    Yankelovich, Nicole

    "Intermedia" is a hypermedia system which was developed for use in university research and teaching. It provides a framework for object-oriented, direct manipulation editors and applications, and the capability to link together materials created with those applications. Instructors are able to construct exploratory environments for their…

  12. Composition, Cytotoxic and Antimicrobial Activities of Satureja intermedia C.A.Mey Essential Oil

    PubMed Central

    Sharifi-Rad, Javad; Sharifi-Rad, Mehdi; Hoseini-Alfatemi, Seyedeh Mahsan; Iriti, Marcello; Sharifi-Rad, Majid; Sharifi-Rad, Marzieh

    2015-01-01

    In this study, the essential oil (EO) constituents from the aerial parts of Satureja intermedia C.A.Mey were detected by GC and GC/MS. The antimicrobial activity of EO on oral pathogens and its cytotoxicity to human cancer cells were determined by the microbroth dilution method and the crystal violet staining method, respectively. Thirty-nine compounds were identified and the main EO constituents were γ-terpinene (37.1%), thymol (30.2%), p-cymene (16.2%), limonene (3.9%), α-terpinene (3.3%), myrcene (2.5%), germacrene B (1.4%), elemicine (1.1%) and carvacrol (0.5%). The S. intermedia EO showed a concentration-dependent decrease in viability of Hep-G2 (hepatocellular carcinoma) and MCF-7 (breast adenocarcinoma) human cancer cell lines (p < 0.05). Antimicrobial screening of S. intermedia EO demonstrated slight antibacterial and antifungal activities against Streptococcus mutants, S. salivarius, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and C. glabrata. Further preclinical studies are needed to assess the efficacy and safety of S. intermedia EO as a new promising anticancer agent. PMID:26247936

  13. Ectoparasites of the critically endangered insular cavy, Cavia intermedia (Rodentia: Caviidae), southern Brazil.

    PubMed

    Regolin, André Luis; Furnari, Nina; de Castro Jacinavicius, Fernando; Linardi, Pedro Marcos; de Carvalho-Pinto, Carlos José

    2015-04-01

    Cavia intermedia is a rodent species critically endangered and is found only on a 10 hectare island off the southern Brazilian coast. To identify the ectoparasites of C. intermedia, 27 specimens (14 males and 13 females), representing approximately 65% of the estimated total population, were captured and examined. A total of 1336 chewing lice of two species were collected: Gliricola lindolphoi (Amblycera: Gyropidae) and Trimenopon hispidum (Amblycera: Trimenoponidae). In addition, chiggers Arisocerus hertigi (Acari: Trombiculidae) and Eutrombicula sp. (Acari: Trombiculidae) were collected from the ears of all captured animals. This low species richness compared to those for other Cavia species is expected for island mammals. Although the results presented here are not conclusive about the relationship between C. intermedia and ectoparasites, this low species richness found might be reflected in a low level of investment by the hosts in the basal immune defense, since investments in white blood cell production by mammals are influenced by the diversity of parasites in the environment. Additionally, considering that it might result in host vulnerability to other parasites that might be introduced through exotic or migratory host species, the monitoring of C. intermedia, including parasitological and immunological assessments, is recommended as a key component of conservation efforts.

  14. Formation of Lignans(-)-Secoisolariciresinol and (-)-Matairesinol with Forsythia intermedia Cell-Free Extracts

    NASA Technical Reports Server (NTRS)

    Umezawa, Toshiaki; Davin, Laurence B.; Lewis, Norman G.

    1991-01-01

    In vivo labeling experiments of Forsythia intermedia plant tissue with [8-(C-14)]- and [9,9-(2)H2,OC(2)H3]coniferyl alcohols revealed that the lignans, (-)-secoisolariciresinol and (-)-matairesinol, were derived from two coniferyl alcohol molecules; no evidence for the formation of the corresponding (+)-enantiomers was found. Administration of (+/-)-[Ar-(H-3)] secoisolariciresinols to excised shoots of F.intermedia resulted in a significant conversion into (-)-matairesinol; again, the (+)-antipode was not detected. Experiments using cell-free extracts of F.intermedia confirmed and extended these findings. In the presence of NAD(P)H and H2O2, the cell-free extracts catalyzed the formation of (-)- secoisolariciresinol, with either [8-(C-14)]- or [9,9-(2)H2,OC(2)H3]coniferyl alcohols as substrates. The (+)- enantiomer was not formed. Finally, when either (-)-[Ar-(H-3)] or (+/-)-[Ar-(H-2)]secoisolariciresinols were used as substrates, in the presence of NAD(P), only (-)- and not (+)-matairesinol formation occurred. The other antipode, (+)-secoisolariciresinol, did not serve as a substrate for the formation of either (+)- or (-)-matairesinol. Thus, in F.intermedia, the formation of the lignan, (-)-secoisolariciresinol, occurs under strict stereochemical control, in a reaction or reactions requiring NAD(P)H and H2O2 as cofactors. This stereoselectivity is retained in the subsequent conversion into (-)-matairesinol, since (+)-secoisolariciresinol is not a substrate. These are the first two enzymes to be discovered in lignan formation.

  15. Complete Genome Sequences of the Xylose-Fermenting Candida intermedia Strains CBS 141442 and PYCC 4715

    PubMed Central

    Moreno, Antonio D.; Tellgren-Roth, Christian; Soler, Lucile; Dainat, Jacques; Olsson, Lisbeth

    2017-01-01

    ABSTRACT Sustainable biofuel production from lignocellulosic materials requires efficient and complete use of all abundant sugars in the biomass, including xylose. Here, we report on the de novo genome assemblies of two strains of the xylose-fermenting yeast Candida intermedia: CBS 141442 and PYCC 4715. PMID:28385851

  16. Prevotella falsenii sp. nov., a Prevotella intermedia-like organism isolated from monkey dental plaque.

    PubMed

    Sakamoto, Mitsuo; Kumada, Hidefumi; Hamada, Nobushiro; Takahashi, Yusuke; Okamoto, Masaaki; Bakir, Mohammad Abdul; Benno, Yoshimi

    2009-02-01

    Eight anaerobic, pigmented, non-spore-forming, Gram-negative, rod-shaped strains isolated from monkey oral cavities were characterized phenotypically and chemotaxonomically and their phylogenetic positions were determined using 16S rRNA gene sequence analysis. The 16S rRNA gene sequence analysis showed that these isolates represent a single species of the genus Prevotella. These strains were most closely related to Prevotella intermedia ATCC 25611(T), with 95.0 % 16S rRNA gene sequence similarity. The next most closely related species were Prevotella pallens and Prevotella nigrescens (92.7 and 92.1 % similarity to the respective type strains). The phenotypic and biochemical characteristics of the isolates were the same as those of P. intermedia JCM 12248(T) and P. nigrescens JCM 12250(T). The isolates could be differentiated from P. pallens JCM 11140(T) on the basis of mannose fermentation and alpha-fucosidase activity. The isolates could not be distinguished from P. intermedia or P. nigrescens using conventional biochemical tests. DNA-DNA hybridization experiments revealed the genomic distinctiveness of these eight strains with respect to P. pallens JCM 11140(T), P. intermedia JCM 12248(T) and P. nigrescens JCM 12250(T). On the basis of these data, strains 04013, 04021, 04043, 04052(T), 0406, 04113, 04111 and 04161 represent a novel Prevotella species, for which the name Prevotella falsenii sp. nov. is proposed. The type strain is 04052(T) (=JCM 15124(T) =CCUG 56137(T)).

  17. Identification and functional analysis of the gene cluster for fructan utilization in Prevotella intermedia.

    PubMed

    Fuse, Haruka; Fukamachi, Haruka; Inoue, Mitsuko; Igarashi, Takeshi

    2013-02-25

    Fructanase enzymes hydrolyze the β-2,6 and β-2,1 linkages of levan and inulin fructans, respectively. We analyzed the influence of fructan on the growth of Prevotella intermedia. The growth of P. intermedia was enhanced by addition of inulin, implying that P. intermedia could also use inulin. Based on this finding, we identified and analyzed the genes encoding a putative fructanase (FruA), sugar transporter (FruB), and fructokinase (FruK) in the genome of strain ATCC25611. Transcript analysis by RT-PCR showed that the fruABK genes were co-transcribed as a single mRNA and semi-quantitative analysis confirmed that the fruA gene was induced in response to fructose and inulin. Recombinant FruA and FruK were purified and characterized biochemically. FruA strongly hydrolyzed inulin, with slight degradation of levan via an exo-type mechanism, revealing that FruA is an exo-β-d-fructanase. FruK converted fructose to fructose-6-phosphate in the presence of ATP, confirming that FruK is an ATP-dependent fructokinase. These results suggest that P. intermedia can utilize fructan as a carbon source for growth, and that the fructanase, sugar transporter, and fructokinase proteins we identified are involved in this fructan utilization.

  18. In vitro activation of the hemolysin in Prevotella nigrescens ATCC 33563 and Prevotella intermedia ATCC 25611.

    PubMed

    Silva, Tarcília Aparecida; Noronha, Fátima Soares M; de Macêdo Farias, Luiz; Carvalho, Maria Auxiliadora R

    2004-01-01

    Hemolytic activity was evaluated in the putative periodontopathogens Prevotella intermedia and Prevotella nigrescens. Whole cells of both species present weak hemolytic activity evidenced only by solid media assays after 48 h of bacterial growth or after 5 h of interaction with erythrocytes at 37 degrees C in liquid assays. In this work we show that the use of crude extract allowed the detection of a higher hemolytic activity for P. intermedia, but surprisingly not for P. nigrescens. Incubation at 37 degrees C for 9 h, or treatment with trypsin or proteinase K, increased or exposed the hemolytic activity of P. intermedia and P. nigrescens crude extract, respectively. The activation process was inhibited by TLCK and PMSF but not by EDTA, E-64 or pepstatin A, indicating the serino-protease nature of the factor involved in activation of P. intermedia and P. nigrescens hemolysins. Both the buffer and the pH employed for cell fractionation influenced the activation of hemolysin, and the best results were obtained with Universal buffer at pH 8.0. The activated hemolysins acted optimally at pH 6.5 at 37 degrees C and the maximum hemolytic activity was detected at the early log phase of growth. The results of this study show for the first time a strong hemolytic activity for P. nigrescens and evidence of proteolytic activation of hemolysins produced by periodontopathogens.

  19. Ectoparasites of the critically endangered insular cavy, Cavia intermedia (Rodentia: Caviidae), southern Brazil

    PubMed Central

    Regolin, André Luis; Furnari, Nina; de Castro Jacinavicius, Fernando; Linardi, Pedro Marcos; de Carvalho-Pinto, Carlos José

    2015-01-01

    Cavia intermedia is a rodent species critically endangered and is found only on a 10 hectare island off the southern Brazilian coast. To identify the ectoparasites of C. intermedia, 27 specimens (14 males and 13 females), representing approximately 65% of the estimated total population, were captured and examined. A total of 1336 chewing lice of two species were collected: Gliricola lindolphoi (Amblycera: Gyropidae) and Trimenopon hispidum (Amblycera: Trimenoponidae). In addition, chiggers Arisocerus hertigi (Acari: Trombiculidae) and Eutrombicula sp. (Acari: Trombiculidae) were collected from the ears of all captured animals. This low species richness compared to those for other Cavia species is expected for island mammals. Although the results presented here are not conclusive about the relationship between C. intermedia and ectoparasites, this low species richness found might be reflected in a low level of investment by the hosts in the basal immune defense, since investments in white blood cell production by mammals are influenced by the diversity of parasites in the environment. Additionally, considering that it might result in host vulnerability to other parasites that might be introduced through exotic or migratory host species, the monitoring of C. intermedia, including parasitological and immunological assessments, is recommended as a key component of conservation efforts. PMID:25830106

  20. Development of Prevotella intermedia-specific PCR primers based on the nucleotide sequences of a DNA probe Pig27.

    PubMed

    Kim, Min Jung; Hwang, Kyung Hwan; Lee, Young-Seok; Park, Jae-Yoon; Kook, Joong-Ki

    2011-03-01

    The aim of this study was to develop Prevotella intermedia-specific PCR primers based on the P. intermedia-specific DNA probe. The P. intermedia-specific DNA probe was screened by inverted dot blot hybridization and confirmed by Southern blot hybridization. The nucleotide sequences of the species-specific DNA probes were determined using a chain termination method. Southern blot analysis showed that the DNA probe, Pig27, detected only the genomic DNA of P. intermedia strains. PCR showed that the PCR primers, Pin-F1/Pin-R1, had species-specificity for P. intermedia. The detection limits of the PCR primer sets were 0.4pg of the purified genomic DNA of P. intermedia ATCC 49046. These results suggest that the PCR primers, Pin-F1/Pin-R1, could be useful in the detection of P. intermedia as well as in the development of a PCR kit in epidemiological studies related to periodontal diseases.

  1. Contribution of hly homologs to the hemolytic activity of Prevotella intermedia.

    PubMed

    Suzuki, Naoko; Fukamachi, Haruka; Arimoto, Takafumi; Yamamoto, Matsuo; Igarashi, Takeshi

    2012-06-01

    Prevotella intermedia is a periodontal pathogen that requires iron for its growth. Although this organism has hemolytic activity, the precise nature of its hemolytic substances and their associated hemolytic actions are yet to be fully determined. In the present study, we identified and characterized several putative hly genes in P. intermedia ATCC25611 which appear to encode hemolysins. Six hly genes (hlyA, B, C, D, E, and hlyI) of P. intermedia were identified by comparing their nucleotide sequences to those of known hly genes of Bacteroides fragilis NCTC9343. The hlyA-E, and hlyI genes were overexpressed individually in the non-hemolytic Escherichia coli strain JW5181 and examined its contribution to the hemolytic activity on sheep blood agar plates. E. coli cells expressing the hlyA and hlyI genes exhibited hemolytic activity under anaerobic conditions. On the other hand, only E. coli cells stably expressing the hlyA gene were able to lyse the red blood cells when cultured under aerobic conditions. In addition, expression of the hlyA and hlyI genes was significantly upregulated in the presence of red blood cells. Furthermore, we found that the growth of P. intermedia was similar in an iron-limited medium supplemented with either red blood cells or heme. Taken together, our results indicate that the hlyA and hlyI genes of P. intermedia encode putative hemolysins that appear to be involved in the lysis of red blood cells, and suggest that these hemolysins might play important roles in the iron-dependent growth of this organism.

  2. Inhibitory effects of lactoferrin on growth and biofilm formation of Porphyromonas gingivalis and Prevotella intermedia.

    PubMed

    Wakabayashi, Hiroyuki; Yamauchi, Koji; Kobayashi, Tetsuo; Yaeshima, Tomoko; Iwatsuki, Keiji; Yoshie, Hiromasa

    2009-08-01

    Lactoferrin (LF) is an iron-binding antimicrobial protein present in saliva and gingival crevicular fluids, and it is possibly associated with host defense against oral pathogens, including periodontopathic bacteria. In the present study, we evaluated the in vitro effects of LF-related agents on the growth and biofilm formation of two periodontopathic bacteria, Porphyromonas gingivalis and Prevotella intermedia, which reside as biofilms in the subgingival plaque. The planktonic growth of P. gingivalis and P. intermedia was suppressed for up to 5 h by incubation with >or=130 microg/ml of human LF (hLF), iron-free and iron-saturated bovine LF (apo-bLF and holo-bLF, respectively), and >or=6 microg/ml of bLF-derived antimicrobial peptide lactoferricin B (LFcin B); but those effects were weak after 8 h. The biofilm formation of P. gingivalis and P. intermedia over 24 h was effectively inhibited by lower concentrations (>or=8 microg/ml) of various iron-bound forms (the apo, native, and holo forms) of bLF and hLF but not LFcin B. A preformed biofilm of P. gingivalis and P. intermedia was also reduced by incubation with various iron-bound bLFs, hLF, and LFcin B for 5 h. In an examination of the effectiveness of native bLF when it was used in combination with four antibiotics, it was found that treatment with ciprofloxacin, clarithromycin, and minocycline in combination with native bLF for 24 h reduced the amount of a preformed biofilm of P. gingivalis compared with the level of reduction achieved with each agent alone. These results demonstrate the antibiofilm activity of LF with lower iron dependency against P. gingivalis and P. intermedia and the potential usefulness of LF for the prevention and treatment of periodontal diseases and as adjunct therapy for periodontal diseases.

  3. Pi30 DNA probe may be useful for the identification of Prevotella intermedia at the species or strain level.

    PubMed

    Shin, Yong Kook; Jeong, Seung-U; Yoo, So Young; Kim, Mi-Kwang; Kim, Hwa-Sook; Kim, Byung-Ock; Kim, Do Kyung; Hwang, Ho-Keel; Kook, Joong-Ki

    2004-01-01

    Recently, we introduced a new method for the rapid screening of bacterial species-or subspecies-specific DNA probes, named the "inverted dot blot hybridization screening method." This method has subsequently been then applied to develop species-or strain-specific DNA probes for Prevotella intermedia and Prevotella nigrescens. In a previous study, the inverted dot blot hybridization data showed that a probe, Pi30, was specific for P. intermedia. In this study, the DNA probe Pi30 was evaluated by Southern blot analysis to determine if it could distinguish P. intermedia from P. nigrescens. The data showed that the probe Pi30 reacted with the genomic DNAs from the reference strains and clinical isolates of both P. intermedia and P. nigrescens, but the size of the signal bands was different. In addition, the probe Pi30 reacted with a 1.4 kbp fragment from the genomic DNAs digested with Pst I of the P. intermedia strains but not with any fragments of P. nigrescens strains. The result indicates that the probe Pi30 could be useful for the identification of P. intermedia by restriction fragment length polymorphism (RFLP) at the species or strain level.

  4. Perianesthetic development of diaphragmatic hernia in a horse with equine pituitary pars intermedia dysfunction (PPID)

    PubMed Central

    Shepard, Molly K.; Lee, Wesley L.; Eggleston, Randy B.

    2015-01-01

    A 21-year-old Thoroughbred gelding with a history of equine pituitary pars intermedia dysfunction (PPID) presented with priapism of 2 days’ duration. The horse received a caudal morphine epidural and then underwent corpus cavernosum lavage and phallectomy under general anesthesia. The patient’s recovery featured multiple unsuccessful attempts to stand and his respiratory distress persisted for several hours until he acutely developed severe colic and was euthanized. Necropsy findings revealed a pituitary adenoma of the pars intermedia, bilateral adrenal cortical hyperplasia, and diaphragmatic herniation. This report suggests that horses with PPID may present a greater risk for diaphragmatic hernia under general anesthesia or during procedures placing stress on the diaphragm, including anesthetic recovery. PMID:25565714

  5. Case series of equine pituitary pars intermedia dysfunction in a tropical climate.

    PubMed

    Spelta, C W; Axon, J E

    2012-11-01

    The clinical manifestations of equine pituitary pars intermedia dysfunction (PPID) in temperate climates are well described. The classic presentation is that of an older animal with hirsutism, laminitis, poor muscle tone, pendulous abdomen and weight loss. This case series highlights the additional clinical signs of anhidrosis and heat stress with secondary exercise intolerance that were seen as primary presenting problems in equids with PPID in the hot, humid conditions of a tropical climate. The clinical signs resolved with medical treatment for PPID.

  6. DHA suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    PubMed

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-14

    Several reports have indicated that dietary intake of DHA is associated with lower prevalence of periodontitis. In the present study, we investigated the effect of DHA on the production of proinflammatory mediators in murine macrophage-like RAW264.7 cells stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. LPS was isolated from lyophilised P. intermedia ATCC 25,611 cells using the standard hot-phenol-water protocol. Culture supernatants were collected and assayed for NO, IL-1β and IL-6. Real-time PCR analysis was carried out to detect the expression of inducible NO synthase (iNOS), IL-1β, IL-6 and haeme oxygenase-1 (HO-1) mRNA. Immunoblot analysis was carried out to quantify the expression of iNOS and HO-1 protein and concentrations of signalling proteins. DNA-binding activities of NF-κB subunits were determined using an ELISA-based assay kit. DHA significantly attenuated the production of NO, IL-1β and IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. DHA induced the expression of HO-1 in cells treated with P. intermedia LPS. Selective inhibition of HO-1 activity by tin protoporphyrin IX significantly mitigated the inhibitory effects of DHA on LPS-induced NO production. DHA significantly attenuated the phosphorylation of c-Jun N-terminal kinase induced by LPS. In addition, DHA suppressed the transcriptional activity of NF-κB by regulating the nuclear translocation and DNA-binding activity of NF-κB p50 subunit and inhibited the phosphorylation of signal transducer and activator of transcription 1. Further in vivo studies are needed to better evaluate the potential of DHA in humans as a therapeutic agent to treat periodontal disease.

  7. The era of comparable life expectancy between thalassaemia major and intermedia: Is it time to revisit the major-intermedia dichotomy?

    PubMed

    Vitrano, Angela; Calvaruso, Giuseppina; Lai, Eliana; Colletta, Grazia; Quota, Alessandra; Gerardi, Calogera; Concetta Rigoli, Luciana; Pitrolo, Lorella; Cuccia, Liana; Gagliardotto, Francesco; Filosa, Aldo; Caruso, Vincenzo; Argento, Crocetta; Campisi, Saveria; Rizzo, Michele; Prossomariti, Luciano; Fidone, Carmelo; Fustaneo, Maria; Di Maggio, Rosario; Maggio, Aurelio

    2017-01-01

    In the last few decades, the life expectancy of regularly transfused β-thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with β-thalassaemia intermedia (TI) remains unknown. Three hundred and seventy-nine patients with TM (n = 284, dead 40) and TI (n = 95, dead 13) were followed retrospectively since birth until 30 June 2015 or death. Kaplan-Meir curves showed statistically significant differences in TM and TI survival (P < 0·0001) before the introduction of iron chelation in 1965, which were no longer apparent after that date (P = 0·086), reducing the Hazard Ratio of death in TM compared to TI from 6·8 [95% confidence interval (CI) 2·6-17·5] before 1965 to 2·8 (95% CI 0·8-9·2). These findings suggest that, in the era of iron chelation therapy and improved survival for TM, the major-intermedia dichotomy needs to be revisited alongside future directions in general management and prevention for both conditions.

  8. Pituitary pars intermedia dysfunction (Equine Cushing's disease) in an onager (Equus hemionus onager).

    PubMed

    Peel, Alison J; Bouts, Tim; Flach, Edmund; Rivers, Sonja; Routh, Andrew

    2009-12-01

    Pituitary pars intermedia dysfunction (PPID), also known as Equine Cushing's disease, is most often diagnosed in older horses and ponies. To the authors' knowledge, there have been no reports of its diagnosis in captive nondomestic equids. A 13-yr old onager (Equus hemionus onager) at the Zoological Society of London (ZSL) Whipsnade Zoo showed clinical signs suggestive of PPID, including hirsutism, fat redistribution, weight loss, laminitis, and chronic infections. A dexamethasone suppression test was performed to confirm PPID. Subsequently, adenomatous hyperplasia and microadenoma of the pars intermedia were identified postmortem. Four months later, this onager's dam died suddenly, and adenomatous hyperplasia of the pars intermedia was diagnosed following necropsy. The dam had shown no clinical signs of PPID. Examination of archives identified eight other adult onagers that died or were euthanized between 1993 and 2007. The brain was not examined in four of these, but pituitary glands were described as enlarged during necropsy in three animals based on the subjective assessment of an experienced zoo and wildlife pathologist, making an overall prevalence of enlargement of 83.3%. Hyperplastic pituitary changes are positively correlated with age in domestic equids, and this may also be the case in onagers. Alternative etiologies are also discussed.

  9. Immunosuppressive effects of Prevotella intermedia on in vitro human lymphocyte activation.

    PubMed Central

    Shenker, B J; Vitale, L; Slots, J

    1991-01-01

    In this study, we have assessed four strains of Prevotella intermedia, isolated from periodontally involved lesions, for their ability to inhibit lymphocyte functions. All four strains were found to cause a dose-dependent inhibition of B- and T-cell proliferation in response to mitogens and antigens. This was reflected in altered DNA, RNA, and protein syntheses. Furthermore, P. intermedia appeared to affect the early stages of cell activation. This was ascertained by kinetic analysis in which it was determined that the extract had to be present during the first 24 h of incubation to cause suppression. Moreover, direct assessment of the early stages of cell activation indicated that release of cytokines and expression of the interleukin 2 receptor and CD69 on T cells were inhibited by P. intermedia sonic extracts. Finally, preliminary characterization of the immunosuppressive agent indicates that it has a molecular mass of approximately 50 kDa and is heat labile. It has been proposed that impaired host defense may play a pivotal role in the pathogenesis of many infections. The data presented in this paper suggest that microbially mediated immunosuppression may contribute to the pathogenesis of periodontal disease by altering the nature and consequences of host-parasite interactions. PMID:1937818

  10. AdpC is a Prevotella intermedia 17 leucine-rich repeat internalin-like protein.

    PubMed

    Iyer, Divya; Anaya-Bergman, Cecilia; Jones, Kevin; Yanamandra, Sai; Sengupta, Dipanwita; Miyazaki, Hiroshi; Lewis, Janina P

    2010-06-01

    The oral bacterium Prevotella intermedia attaches to and invades gingival epithelial cells, fibroblasts, and endothelial cells. Several genes encoding proteins that mediate both the adhesion and invasion processes are carried on the genome of this bacterium. Here, we characterized one such protein, AdpC, belonging to the leucine-rich repeat (LRR) protein family. Bioinformatics analysis revealed that this protein shares similarity with the Treponema pallidum LRR (LRR(TP)) family of proteins and contains six LRRs. Despite the absence of a signal peptide, this protein is localized on the bacterial outer membrane, indicating that it is transported through an atypical secretion mechanism. The recombinant form of this protein (rAdpC) was shown to bind fibrinogen. In addition, the heterologous host strain Escherichia coli BL21 expressing rAdpC (V2846) invaded fibroblast NIH 3T3 cells at a 40-fold-higher frequency than control E. coli BL21 cells expressing a sham P. intermedia 17 protein. Although similar results were obtained by using human umbilical vein endothelial cells (HUVECs), only a 3-fold-increased invasion of V2846 into oral epithelial HN4 cells was observed. Thus, AdpC-mediated invasion is cell specific. This work demonstrated that AdpC is an important invasin protein of P. intermedia 17.

  11. Genome sequence of Prevotella intermedia SUNY aB G8-9K-3, a biofilm forming strain with drug-resistance.

    PubMed

    Moon, Ji-Hoi; Kim, Minjung; Lee, Jae-Hyung

    Prevotella intermedia has long been known to be as the principal etiologic agent of periodontal diseases and associated with various systemic diseases. Previous studies showed that the intra-species difference exists in capacity of biofilm formation, antibiotic resistance, and serological reaction among P. intermedia strains. Here we report the genome sequence of P. intermedia SUNY aB G8-9K-3 (designated ATCC49046) that displays a relatively high antimicrobial resistant and biofilm-forming capacity. Genome sequencing information provides important clues in understanding the genetic bases of phenotypic differences among P. intermedia strains.

  12. Transcriptome Changes Associated with Anaerobic Growth in Yersinia intermedia (ATCC29909)

    PubMed Central

    Kiley, Patricia J.; Glasner, Jeremy D.; Perna, Nicole T.

    2013-01-01

    Background The yersiniae (Enterobacteriaceae) occupy a variety of niches, including some in human and flea hosts. Metabolic adaptations of the yersiniae, which contribute to their success in these specialized environments, remain largely unknown. We report results of an investigation of the transcriptome under aerobic and anaerobic conditions for Y. intermedia, a non-pathogenic member of the genus that has been used as a research surrogate for Y. pestis. Y. intermedia shares characteristics of pathogenic yersiniae, but is not known to cause disease in humans. Oxygen restriction is an important environmental stimulus experienced by many bacteria during their life-cycles and greatly influences their survival in specific environments. How oxygen availability affects physiology in the yersiniae is of importance in their life cycles but has not been extensively characterized. Methodology/Principal Findings Tiled oligonucleotide arrays based on a draft genome sequence of Y. intermedia were used in transcript profiling experiments to identify genes that change expression in response to oxygen availability during growth in minimal media with glucose. The expression of more than 400 genes, constituting about 10% of the genome, was significantly altered due to oxygen-limitation in early log phase under these conditions. Broad functional categorization indicated that, in addition to genes involved in central metabolism, genes involved in adaptation to stress and genes likely involved with host interactions were affected by oxygen-availability. Notable among these, were genes encoding functions for motility, chemotaxis and biosynthesis of cobalamin, which were up-regulated and those for iron/heme utilization, methionine metabolism and urease, which were down-regulated. Conclusions/Significance This is the first transcriptome analysis of a non-pathogenic Yersinia spp. and one of few elucidating the global response to oxygen limitation for any of the yersiniae. Thus this study

  13. Intermedia transfer factors for fifteen toxic pollutants released to air basins in California

    SciTech Connect

    McKone, T.E.; Daniels, J.I.; Chiao, F.F.; Hsieh, D.P.H.

    1993-10-01

    This report provides a summary definition of the intermedia-transfer factors (ITFs). Methods are discussed for estimating these parameters in the absence of measured values, and the estimation errors inherent in these estimation methods are considered. A detailed summary is provided of measured and estimated ITF values for fifteen air contaminants. They include: 1,3 butadiene; cadmium; cellosolve; cellosolve acetate; chloroform; di-2-ethylhexylphthalate; 1,4-dioxame; hexachlorobenzene; inorganic arsenic; inorganic lead; nickel; tetrachloroethylene; toluene; toluene-2,4-diisocyanate; and 1,3-xylene. Recommendations are made regarding the expected value and variance in these values for use in exposure models.

  14. S1P control of endothelial integrity.

    PubMed

    Xiong, Yuquan; Hla, Timothy

    2014-01-01

    Sphingosine 1-phosphate (S1P), a lipid mediator produced by sphingolipid metabolism, promotes endothelial cell spreading, vascular maturation/stabilization, and barrier function. S1P is present at high concentrations in the circulatory system, whereas in tissues its levels are low. This so-called vascular S1P gradient is essential for S1P to regulate much physiological and pathophysiological progress such as the modulation of vascular permeability. Cellular sources of S1P in blood has only recently begun to be identified. In this review, we summarize the current understanding of S1P in regulating vascular integrity. In particular, we discuss the recent discovery of the endothelium-protective functions of HDL-bound S1P which is chaperoned by apolipoprotein M.

  15. Early changes in the ultrastructure of the pars intermedia of the pituitary of Xenopus laevis after change of background color.

    PubMed

    Volcanes, B D; Weatherhead, B

    1976-01-01

    Stereological analysis of the secretory cells of the pars intermedia of Xenopus laevis over a period of 3 days following the transfer of animals from a white to a black background has revealed that significant alterations in the ultrastructural appearance of these cells can be detected 8 h after the transfer. In particular, changes in the secretory granules and the rough endoplasmic reticulum were found to correlate well with previous reports concerning the melanocyte-stimulating hormone (MSH) content and the capacity for protein synthesis of the pars intermedia.

  16. Noninvasive analysis of skin iron and zinc levels in beta-thalassemia major and intermedia

    SciTech Connect

    Gorodetsky, R.; Goldfarb, A.; Dagan, I.; Rachmilewitz, E.A.

    1985-01-01

    Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for noninvasive determination of iron and zinc in two distinct skin areas, representing predominantly dermal and epidermal tissues, in 56 patients with beta-thalassemia major and intermedia. The mean iron levels in the skin of patients with beta-thalassemia major and intermedia were elevated by greater than 200% and greater than 50%, respectively, compared with control values. The zinc levels of both skin areas examined were within the normal range. The data indicate that the rate and number of blood transfusions, which correlated well with serum ferritin levels (r . 0.8), are not the only factors that determine the amount of iron deposition in the skin (r less than 0.6). Other sources of iron intake contribute to the total iron load in the tissues, particularly in patients who are not given multiple transfusions. The noninvasive quantitation of skin levels may reflect the extent of iron deposition in major parenchymal organs. Repeated DXS examinations of the skin could monitor the clearance of iron from the tissues of patients with iron overload in the course of therapy with chelating agents.

  17. Detection of Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Prevotella nigrescens in chronic endodontic infection.

    PubMed

    Tomazinho, Luiz Fernando; Avila-Campos, Mario J

    2007-02-01

    Black-pigmented anaerobic rods such as Prevotella spp. and Porphyromonas spp. are involved in the etiology and perpetuation of endodontic infections. The aim of this study was to evaluate the prevalence of these species in chronic endodontic infections by using culture and polymerase chain reaction (PCR) techniques. Samples of 100 patients with root canals displaying chronic endodontic infections were obtained by sterilized paper points. Bacterial identification was performed by using culture and PCR techniques. By culture, in 33% of the samples, P. intermedia-P. nigrescens (75.8%), P. gingivalis (27.3%), and P. endodontalis (9.1%) were identified, and by PCR 60% of the samples harbored P. nigrescens (43.3%), P. gingivalis (43.3%), P. intermedia (31.7%), and P. endodontalis (23.3%). The presence of these black-pigmented anaerobic rods alone or in association in chronic endodontic infections seems to be frequent. PCR is a very sensitive technique for detecting DNA from bacterial cells. Culturing is only able to reveal living bacteria and is less sensitive for the identification of low numbers of bacterial cells.

  18. Cloning of a sesquiterpene synthase from Lavandula x intermedia glandular trichomes.

    PubMed

    Sarker, Lukman S; Demissie, Zerihun A; Mahmoud, Soheil S

    2013-11-01

    The essential oil (EO) of Lavandula is dominated by monoterpenes, but can also contain small amounts of sesquiterpenes, depending on species and environmental conditions. For example, the sesquiterpene 9-epi-caryophyllene can make up to 8 % of the EO in a few species, including those commercially propagated for EO production. Here, we report the cloning and functional characterization of 9-epi-caryophyllene synthase (LiCPS) from the glandular trichomes of Lavandula x intermedia, cv. Grosso. The 1,617 bp open reading frame of LiCPS, which did not encode a transit peptide, was expressed in Escherichia coli and the recombinant protein purified by Ni-NTA agarose affinity chromatography. The ca. 60 kDa recombinant protein specifically converted farnesyl diphosphate to 9-epi-caryophyllene. LiCPS also produced a few monoterpenes when assayed with the monoterpene precursor geranyl diphosphate (GPP), but--unlike most monoterpene synthases--was not able to derive detectable amounts of any products from the cis isomer of GPP, neryl diphosphate. The LiCPS transcripts accumulated in developing L. x intermedia flowers and were highly enriched in glandular trichomes, but were not detected in leaves suggesting that the transcriptional expression of this gene is spatially and developmentally regulated.

  19. Role of cin-miR2118 in drought stress responses in Caragana intermedia and Tobacco.

    PubMed

    Wu, Bi-Fei; Li, Wan-Feng; Xu, Hai-Yan; Qi, Li-Wang; Han, Su-Ying

    2015-12-10

    The miR2118 is highly conserved in leguminous plants. Its function is to regulate the expression of genes encoding the TIR-NBS-LRR resistance protein. In this study, cin-miR2118 from Caragana intermedia was functionally characterized, especially with regard to its role in drought stress resistance. Two target genes of cin-miR2118 were predicted and cloned, the occurrence of miR2118 target sequence in both genes indicated that they might be targets of cin-miR2118. We investigated the expression patterns of cin-miR2118 and its target genes in C. intermedia stems and found diverse changes in expression in response to drought stress. CiDR1 was negatively correlated with corresponding miR2118 expression while CiDR2 was positively correlated with cin-miR2118. For further study, induced tolerance was observed in the transgenic Tobacco with overexpression cin-miR2118 upon 140-min water deficiency. And the expression level of cin-miR2118 was dramatically increased under drought stress. These results reveal that cin-miR2118 exert positive effects on drought stress tolerance. In addition, our study unexpectedly found that overexpression of cin-miR2118 in Tobacco can cause phenotype changes, which suggested that cin-miR2118 may have a novel function as a growth regulator in Tobacco.

  20. In vitro sensitivity of poultry Brachyspira intermedia isolates to essential oil components and in vivo reduction of Brachyspira intermedia in rearing pullets with cinnamaldehyde feed supplementation.

    PubMed

    Verlinden, M; Pasmans, F; Mahu, M; Vande Maele, L; De Pauw, N; Yang, Z; Haesebrouck, F; Martel, A

    2013-05-01

    Cecal enteritis due to Brachyspira infections tends to be chronic in laying hens. Limited availability of antimicrobial drugs for use in laying hens emphasizes the need for alternative control measures. A broth microdilution method was used to determine the antimicrobial susceptibility of 20 Brachyspira intermedia field isolates from laying hen flocks to components of essential oils (EO). Minimal inhibitory concentration (MIC) distributions, obtained for 8 EO components, were all monomodal. Cinnamaldehyde had the lowest MIC values (40 to 80 mg/L), followed by nerolidol, capsaicin, carvacrol, and thymol (80 to 320 mg/L), eugenol (160 to 640 mg/L), and linalool (320 to 1,280 mg/L). The MIC ranges of piperine were mostly above the test range of 1,280 mg/L. In an in vivo experiment, coated trans-cinnamaldehyde was supplemented to the feed of rearing pullets. A completely randomized experimental design with 4 treatments and 3 replicates each (replicate = group of seven 1-d-old laying hen chickens) was applied. The negative and positive controls received a conventional feed during the whole trial. The positive controls were orally inoculated on 3 consecutive days (d 22, 23, and 24) with 1 mL of 1.0 × 10(8) cfu/mL of a B. intermedia field isolate. Two treatment groups (preventive and curative), identically inoculated, received the coated trans-cinnamaldehyde-supplemented feed (500 mg/kg of trans-cinnamaldehyde), the preventive group from d 1, the curative from d 25. On d 32, ceca were collected for bacteriologic Brachyspira enumeration. The mean enumeration of Brachyspira cells was decreased (P < 0.05) in the curative treated group versus the positive control group. The in vitro results of the present study demonstrate the potential of EO components as antimicrobials against poultry Brachyspira isolates, including isolates with acquired resistance for classic antimicrobial drugs. Reduction of Brachyspira colonization in young pullets was obtained, in a curative way, in

  1. CYP2S1: A short review

    SciTech Connect

    Saarikoski, Sirkku T. . E-mail: sirkku.saarikoski@ktl.fi; Rivera, Steven P.; Hankinson, Oliver; Husgafvel-Pursiainen, Kirsti

    2005-09-01

    A new member of the cytochrome P450 superfamily, CYP2S1, has recently been identified in human and mouse. In this paper, we review the data currently available for CYP2S1. The human CYP2S1 gene is located in chromosome 19q13.2 within a cluster including CYP2 family members CYP2A6, CYP2A13, CYP2B6, and CYP2F1. These genes also show the highest homology to the human CYP2S1. The gene has recently been found to harbor genetic polymorphism. CYP2S1 is inducible by dioxin, the induction being mediated by the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT) in a manner typical for CYP1 family members. In line with this, CYP2S1 has been shown to be inducible by coal tar, an abundant source of PAHs, and it was recently reported to metabolize naphthalene. This points to the involvement of CYP2S1 in the metabolism of toxic and carcinogenic compounds, similar to other dioxin-inducible CYPs. CYP2S1 is expressed in epithelial cells of a wide variety of extrahepatic tissues. The highest expression levels have been observed in the epithelial tissues frequently exposed to xenobiotics, e.g., the respiratory, gastrointestinal, and urinary tracts, and in the skin. The observed ubiquitous tissue distribution, as well as the expression of CYP2S1 throughout embryogenesis suggest that CYP2S1 is likely to metabolize important endogenous substrates; thus far, retinoic acid has been identified. In conclusion, CYP2S1 exhibits many features of interest for human health and thus warrants further investigation.

  2. Preliminary Phytochemical Screening, Quantitative Analysis of Alkaloids, and Antioxidant Activity of Crude Plant Extracts from Ephedra intermedia Indigenous to Balochistan.

    PubMed

    Gul, Rahman; Jan, Syed Umer; Faridullah, Syed; Sherani, Samiullah; Jahan, Nusrat

    2017-01-01

    The aim of this study was to evaluate the antioxidant activity, screening the phytogenic chemical compounds, and to assess the alkaloids present in the E. intermedia to prove its uses in Pakistani folk medicines for the treatment of asthma and bronchitis. Antioxidant activity was analyzed by using 2,2-diphenyl-1-picryl-hydrazyl-hydrate assay. Standard methods were used for the identification of cardiac glycosides, phenolic compounds, flavonoids, anthraquinones, and alkaloids. High performance liquid chromatography (HPLC) was used for quantitative purpose of ephedrine alkaloids in E. intermedia. The quantitative separation was confirmed on Shimadzu 10AVP column (Shampack) of internal diameter (id) 3.0 mm and 50 mm in length. The extract of the solute in flow rate of 1 ml/min at the wavelength 210 nm and methanolic extract showed the antioxidant activity and powerful oxygen free radicals scavenging activities and the IC50 for the E. intermedia plant was near to the reference standard ascorbic acid. The HPLC method was useful for the quantitative purpose of ephedrine (E) and pseudoephedrine (PE) used for 45 samples of one species collected from central habitat in three districts (Ziarat, Shairani, and Kalat) of Balochistan. Results showed that average alkaloid substance in E. intermedia was as follows: PE (0.209%, 0.238%, and 0.22%) and E (0.0538%, 0.0666%, and 0.0514%).

  3. Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria?

    PubMed

    Fteita, Dareen; Könönen, Eija; Gürsoy, Mervi; Söderling, Eva; Gürsoy, Ulvi Kahraman

    2015-12-01

    Initiation and development of pregnancy-associated gingivitis is seemingly related to the microbial shift towards specific gram-negative anaerobes in subgingival biofilms. It is known that Prevotella intermedia sensu lato is able to use estradiol as an alternative source of growth instead of vitamin K. The aim of the present study was to investigate the impact of estradiol on the bacterial dipeptidyl peptidase IV (DPPIV) enzyme activity in vitro as a virulent factor of the Prevotella intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, Prevotella pallens, and Prevotella aurantiaca. In all experiments, 2 strains of each Prevotella species were used. Bacteria were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol and were allowed to build biofilms at an air-solid interface. DPPIV activities of biofilms were measured kinetically during 20 min using a fluorometric assay. The enzyme activity was later related to the amount of protein produced by the same biofilm, reflecting the biofilm mass. Estradiol significantly increased DPPIV activities of the 8 Prevotella strains in a strain- and dose-dependent manner. In conclusion, our in vitro experiments indicate that estradiol regulates the DPPIV enzyme activity of P. intermedia, P. nigrescens, P. pallens, and P. aurantiaca strains differently. Our results may, at least partly, explain the role of estradiol to elicit a virulent state which contributes to the pathogenesis of pregnancy-related gingivitis.

  4. Differentially regulated proteins in Prevotella intermedia after oxidative stress analyzed by 2D electrophoresis and mass spectrometry.

    PubMed

    Santos, Simone G; Diniz, Cláudio G; Silva, Vânia L; Lima, Francisca L; Andrade, Hélida M; Chapeaurouge, Donat A; Perales, Jonas; Serufo, José Carlos; Carvalho, Maria Auxiliadora R; Farias, Luiz M

    2012-02-01

    Prevotella intermedia is a rod-shaped, Gram-negative anaerobic bacterium found in human indigenous microbiota that plays an important role in opportunistic infections. The successful colonization depends on the ability of anaerobes to respond to oxidative stress (OS) in oxygenated tissues as well as to resist oxidative events from the host immune system until anaerobic conditions are present at the infection site. As knowledge of the mechanisms of protection against OS in Prevotella is limited, studies are needed to clarify aspects of molecular biology, physiology and ecology of this bacterium. The aim of this study was to access the proteins differentially regulated in P. intermedia after exposure to molecular oxygen by using two-dimensional gel electrophoresis (2DE) associated with the approach of MALDI-TOF/TOF Tandem Mass Spectrometry. The identity of the protein was evaluated by database search for homologous genomic sequences of P. intermedia strain 17 (TIGR). Twenty five out of 72 proteins found were identified as up-regulated (17) or down-regulated (9). These proteins were related to a variety of metabolic process, some of which could be associated to antioxidant and redox regulatory roles. Our data indicate that OS may stimulate an adaptive response in P. intermedia whose effect on its biology may be evidenced by the increase in aerotolerance and changes in protein abundance in the oxygen adapted cells.

  5. In vitro effects of N-acetyl cysteine alone and in combination with antibiotics on Prevotella intermedia.

    PubMed

    Moon, Ji-Hoi; Jang, Eun-Young; Shim, Kyu Sang; Lee, Jin-Yong

    2015-05-01

    N-acetyl cysteine (NAC) is an antioxidant that possesses anti-inflammatory activities in tissues. In the field of dentistry, NAC was demonstrated to prevent the expression of LPS-induced inflammatory mediators in phagocytic cells and gingival fibroblasts during the inflammatory process, but the effect of NAC on oral pathogens has been rarely studied. Here, we examined the effect of NAC against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. NAC showed antibacterial activity against the planktonic P. intermedia with MIC value of 3 mg/ml and significantly decreased biofilm formation by the bacterium even at sub MIC. NAC did not affect the antibiotic susceptibility of planktonic P. intermedia, showing indifference (fractional inhibitory concentration index of 0.5-4) results against the bacterium in combination with ampicillin, ciprofloxacin, tetracycline or metronidazole. On the other hand, viability of the pre-established bacterial biofilm exposed to the antibiotics except metronidazole was increased in the presence of NAC. Collectively, NAC may be used for prevention of the biofilm formation by P. intermedia rather than eradication of the pre-established bacterial biofilm. Further studies are required to explore antibacterial and anti-biofilm activity of NAC against mixed population of oral bacteria and its modulatory effect on antibiotics used for oral infectious diseases.

  6. Preliminary Phytochemical Screening, Quantitative Analysis of Alkaloids, and Antioxidant Activity of Crude Plant Extracts from Ephedra intermedia Indigenous to Balochistan

    PubMed Central

    Jan, Syed Umer; Faridullah, Syed; Sherani, Samiullah; Jahan, Nusrat

    2017-01-01

    The aim of this study was to evaluate the antioxidant activity, screening the phytogenic chemical compounds, and to assess the alkaloids present in the E. intermedia to prove its uses in Pakistani folk medicines for the treatment of asthma and bronchitis. Antioxidant activity was analyzed by using 2,2-diphenyl-1-picryl-hydrazyl-hydrate assay. Standard methods were used for the identification of cardiac glycosides, phenolic compounds, flavonoids, anthraquinones, and alkaloids. High performance liquid chromatography (HPLC) was used for quantitative purpose of ephedrine alkaloids in E. intermedia. The quantitative separation was confirmed on Shimadzu 10AVP column (Shampack) of internal diameter (id) 3.0 mm and 50 mm in length. The extract of the solute in flow rate of 1 ml/min at the wavelength 210 nm and methanolic extract showed the antioxidant activity and powerful oxygen free radicals scavenging activities and the IC50 for the E. intermedia plant was near to the reference standard ascorbic acid. The HPLC method was useful for the quantitative purpose of ephedrine (E) and pseudoephedrine (PE) used for 45 samples of one species collected from central habitat in three districts (Ziarat, Shairani, and Kalat) of Balochistan. Results showed that average alkaloid substance in E. intermedia was as follows: PE (0.209%, 0.238%, and 0.22%) and E (0.0538%, 0.0666%, and 0.0514%). PMID:28386582

  7. Safety assessment for the S-1 Spheromak

    SciTech Connect

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

    1984-02-01

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

  8. Desarrollo curricular, conciencia ambiental y tecnologia para estudiantes de intermedia: Una investigacion en accion

    NASA Astrophysics Data System (ADS)

    Rodriguez Ramos, Teresita

    Se llevó a cabo una investigación en acción con los propósitos de 1) documentar las relaciones de las tecnologías de la información y la comunicación en las clases de ciencias de escuela intermedia como elemento de apoyo cuando se aborda el tema ambiental y sus conceptos pertinentes, a partir de las observaciones de la investigadora, así como las entrevistas y diarios reflexivos de los estudiantes de una escuela intermedia en la zona metropolitana, y luego 2) diseñar una unidad instruccional sobre el tema ambiental que integre actividades tecnologías para el curso de ciencias de la escuela intermedia según el modelo PROCIC y las observaciones que hayan iniciado los estudiantes participantes. Finalmente, se plantearon las implicaciones educativas para el currículo del Programa de Ciencias al instrumentar este modelo de unidad mediante PROCIC, e integrado la tecnología y el tema ambiental. Los hallazgos se analizaron y se categorizaron de acuerdo con las preguntas de investigación. El hallazgo principal de la investigación aborda las cuatro relaciones centrales en las que se articula la utilización de las tecnologías y sus aplicaciones en la clase de ciencias. Estas cuatro relaciones que recogen la posición de los estudiantes son: 1) Perspectiva de los estudiantes hacia la tecnología. 2) Participación de los estudiantes en los aspectos docentes. 3) Aprendizaje estudiantil sobre el ambiente, y 4) Conciencia ambiental en relación con la vida diaria. Estas relaciones ponen de manifiesto,cómo se plantea en las implicaciones, la necesidad de más investigación en acción en la sala de clases, la importancia—como tema transversal—de la conciencia ambiental mediante la tecnología al construir conocimientos significativos dentro y fuera de la escuela, asó como, valorar la investigación y la dialogicidad en la sala de clases como actividades que obligan al reexamen de la práctica didáctica en su formas curriculares de objetivos, recursos

  9. Different Water Use Strategies of Juvenile and Adult Caragana intermedia Plantations in the Gonghe Basin, Tibet Plateau

    PubMed Central

    Jia, Zhiqing; Zhu, Yajuan; Liu, Liying

    2012-01-01

    Background In a semi-arid ecosystem, water is one of the most important factors that affect vegetation dynamics, such as shrub plantation. A water use strategy, including the main water source that a plant species utilizes and water use efficiency (WUE), plays an important role in plant survival and growth. The water use strategy of a shrub is one of the key factors in the evaluation of stability and sustainability of a plantation. Methodology/Principal Findings Caragana intermedia is a dominant shrub of sand-binding plantations on sand dunes in the Gonghe Basin in northeastern Tibet Plateau. Understanding the water use strategy of a shrub plantation can be used to evaluate its sustainability and long-term stability. We hypothesized that C. intermedia uses mainly deep soil water and its WUE increases with plantation age. Stable isotopes of hydrogen and oxygen were used to determine the main water source and leaf carbon isotope discrimination was used to estimate long-term WUE. The root system was investigated to determine the depth of the main distribution. The results showed that a 5-year-old C. intermedia plantation used soil water mainly at a depth of 0–30 cm, which was coincident with the distribution of its fine roots. However, 9- or 25-year-old C. intermedia plantations used mainly 0–50 cm soil depth water and the fine root system was distributed primarily at soil depths of 0–50 cm and 0–60 cm, respectively. These sources of soil water are recharged directly by rainfall. Moreover, the long-term WUE of adult plantations was greater than that of juvenile plantations. Conclusions The C. intermedia plantation can change its water use strategy over time as an adaptation to a semi-arid environment, including increasing the depth of soil water used for root growth, and increasing long-term WUE. PMID:23029303

  10. Intraspecies Variability Affects Heterotypic Biofilms of Porphyromonas gingivalis and Prevotella intermedia: Evidences of Strain-Dependence Biofilm Modulation by Physical Contact and by Released Soluble Factors.

    PubMed

    Barbosa, Graziela Murta; Colombo, Andrea Vieira; Rodrigues, Paulo Henrique; Simionato, Maria Regina Lorenzetti

    2015-01-01

    It is well known that strain and virulence diversity exist within the population structure of Porphyromonas gingivalis. In the present study we investigate intra- and inter-species variability in biofilm formation of Porphyromonas gingivalis and partners Prevotella intermedia and Prevotella nigrescens. All strains tested showed similar hydrophobicity, except for P. gingivalis W83 which has roughly half of the hydrophobicity of P. gingivalis ATCC33277. An intraspecies variability in coaggregation of P. gingivalis with P. intermedia was also found. The association P. gingivalis W83/P. intermedia 17 produced the thickest biofilm and strain 17 was prevalent. In a two-compartment system P. gingivalis W83 stimulates an increase in biomass of strain 17 and the latter did not stimulate the growth of P. gingivalis W83. In addition, P. gingivalis W83 also stimulates the growth of P. intermedia ATCC25611 although strain W83 was prevalent in the association with P. intermedia ATCC25611. P. gingivalis ATCC33277 was prevalent in both associations with P. intermedia and both strains of P. intermedia stimulate the growth of P. gingivalis ATCC33277. FISH images also showed variability in biofilm structure. Thus, the outcome of the association P. gingivalis/P. intermedia seems to be strain-dependent, and both soluble factors and physical contact are relevant. The association P. gingivalis-P. nigrescens ATCC33563 produced larger biomass than each monotypic biofilm, and P. gingivalis was favored in consortia, while no differences were found in the two-compartment system. Therefore, in consortia P. gingivalis-P. nigrescens physical contact seems to favor P. gingivalis growth. The intraspecies variability found in our study suggests strain-dependence in ability of microorganisms to recognize molecules in other bacteria which may further elucidate the dysbiosis event during periodontitis development giving additional explanation for periodontal bacteria, such as P. gingivalis and P

  11. Intraspecies Variability Affects Heterotypic Biofilms of Porphyromonas gingivalis and Prevotella intermedia: Evidences of Strain-Dependence Biofilm Modulation by Physical Contact and by Released Soluble Factors

    PubMed Central

    Barbosa, Graziela Murta; Colombo, Andrea Vieira; Rodrigues, Paulo Henrique; Simionato, Maria Regina Lorenzetti

    2015-01-01

    It is well known that strain and virulence diversity exist within the population structure of Porphyromonas gingivalis. In the present study we investigate intra- and inter-species variability in biofilm formation of Porphyromonas gingivalis and partners Prevotella intermedia and Prevotella nigrescens. All strains tested showed similar hydrophobicity, except for P. gingivalis W83 which has roughly half of the hydrophobicity of P. gingivalis ATCC33277. An intraspecies variability in coaggregation of P. gingivalis with P. intermedia was also found. The association P. gingivalis W83/P. intermedia 17 produced the thickest biofilm and strain 17 was prevalent. In a two-compartment system P. gingivalis W83 stimulates an increase in biomass of strain 17 and the latter did not stimulate the growth of P. gingivalis W83. In addition, P. gingivalis W83 also stimulates the growth of P. intermedia ATCC25611 although strain W83 was prevalent in the association with P. intermedia ATCC25611. P. gingivalis ATCC33277 was prevalent in both associations with P. intermedia and both strains of P. intermedia stimulate the growth of P. gingivalis ATCC33277. FISH images also showed variability in biofilm structure. Thus, the outcome of the association P. gingivalis/P. intermedia seems to be strain-dependent, and both soluble factors and physical contact are relevant. The association P. gingivalis-P. nigrescens ATCC33563 produced larger biomass than each monotypic biofilm, and P. gingivalis was favored in consortia, while no differences were found in the two-compartment system. Therefore, in consortia P. gingivalis-P. nigrescens physical contact seems to favor P. gingivalis growth. The intraspecies variability found in our study suggests strain-dependence in ability of microorganisms to recognize molecules in other bacteria which may further elucidate the dysbiosis event during periodontitis development giving additional explanation for periodontal bacteria, such as P. gingivalis and P

  12. Pituitary pars intermedia dysfunction (equine Cushing’s disease) in a Thoroughbred stallion: a single report

    PubMed Central

    HATAZOE, Takashi; KAWAGUCHI, Hiroaki; HOBO, Seiji; MISUMI, Kazuhiro

    2016-01-01

    ABSTRACT Equine pituitary pars intermedia dysfunction (PPID) generally occurs in older horses showing hirsutism, delayed molting, weight loss, polydipsia, polyuria, laminitis, and reproductive disorders (in broodmares), but there have been no reports on stallions. This report presents a case of a 21-year-old Thoroughbred stallion that developed hirsutism and experienced delayed molting. There were no abnormal findings for semen quality or the stallion’s sexual desire. The horse was diagnosed with PPID based on dexamethasone suppression test and plasma levels of adrenocorticotropic hormone. It was then medicated with pergolide mesylate. Since the horse died due to humerus fracture, an autopsy was conducted, and pituitary adenoma was confirmed. No pathological findings were defined in the testicles; therefore, reproductive activity might not have been impaired. PMID:26858577

  13. Development of Loxosceles intermedia Mello-Leitão (1934) (Araneae, Sicariidae) genital tract.

    PubMed

    Margraf, A; Costa-Ayub, C L S; Okada, M A; Gomes, J R; Ortolani-Machado, C F; Soares, M A M

    2011-08-01

    We examined the post-embryonic development of the male and female genital apparatus of the brown spider, Loxosceles intermedia. The development of the genital apparatus for both sexes begins with the appearance of inner structures. In the male genital apparatus, formation of the testes occurs first, followed by differentiation of the duct, ampulla and vas deferens, and finally the formation of the genital opening and differentiation of the copulatory organ (secondary sexual characteristic). Similarly, the development of the female genital apparatus begins with the formation of the ovaries, followed by the appearance of oocytes in vitellogenesis, then the development of oviducts and uterus internus and, finally, the spermatheca. These data may be very important in further comparative studies on the development of the reproductive system of spiders.

  14. Suspensory ligament degeneration associated with pituitary pars intermedia dysfunction in horses.

    PubMed

    Hofberger, Sina; Gauff, Felicia; Licka, Theresia

    2015-03-01

    In older horses, pituitary pars intermedia dysfunction (PPID) and suspensory ligament (SL) degeneration are common. The aim of the present study was to identify histopathological changes in the SL in horses with PPID. SLs of four horses with clinical signs of PPID (17-26 years of age) were compared with SLs from four old horses (18-31 years of age) and three young horses (4-9 years of age). In horses with PPID, there was reduced longitudinal arrangement of collagen fibres in SLs, along with inclusions of cartilage, extracellular matrix and haemorrhage, as well as significant proteoglycan accumulations between SL fibres. These changes are similar to the degeneration of connective tissues in Peruvian Paso horses with SL degeneration and in humans with Cushing's disease or after long term high dose corticosteroid treatments. These findings indicate an association between degeneration of the SL and PPID.

  15. Protection against the toxic effects of Loxosceles intermedia spider venom elicited by mimotope peptides.

    PubMed

    de Moura, J; Felicori, L; Moreau, V; Guimarães, G; Dias-Lopes, C; Molina, L; Alvarenga, L M; Fernandes, P; Frézard, F; Ribeiro, R R; Fleury, C; Nguyen, C; Molina, F; Granier, C; Chávez-Olórtegui, C

    2011-10-19

    The venom of Loxosceles intermedia (Li) spiders is responsible for cutaneous lesions and other clinical manifestations. We previously reported that the monoclonal antibody LimAb7 can neutralize the dermonecrotic activity of crude Li venom. In this study, we observed that this antibody recognizes several proteins from the venom dermonecrotic fraction (DNF), including LiD1. Identifying the epitope of such a neutralizing antibody could help designing immunogens for producing therapeutic sera or vaccination approaches. To this aim, two sets of 25- and 15-mer overlapping peptides that cover the complete amino acid sequence of LiD1 were synthesized using the SPOT technique. None of them was recognized by LimAb7, suggesting that the epitope is discontinuous. Then, the screening of four peptide phage-display libraries yielded four possible epitope mimics that, however, did not show any obvious similarity with the LiD1 sequence. These mimotopes, together with a 3D model of LiD1, were used to predict with the MIMOP bioinformatic tool the putative epitope region (residues C197, Y224, W225, T226, D228, K229, R230, T232 and Y248 of LiD1) recognized by LimAb7. This analysis and the results of alanine-scanning experiments highlighted a few residues (such as W225 and D228) that are found in the active site of different SMases D and that may be important for LiD1 enzymatic activity. Finally, the only mimotope NCNKNDHLFACW that interacts with LimAb7 by SPOT and its analog NSNKNDHLFASW were used as immunogens in rabbits. The resulting antibodies could neutralize some of the biological effects induced by crude Li venom, demonstrating a mimotope-induced protection against L. intermedia venom.

  16. The Global S$_1$ Ocean Tide

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  17. Prevotella intermedia stimulates tissue-type plasminogen activator and plasminogen activator inhibitor-2 expression via multiple signaling pathways in human periodontal ligament cells.

    PubMed

    Guan, Su-Min; He, Jian-Jun; Zhang, Ming; Shu, Lei

    2011-06-01

    Prevotella intermedia is an important periodontal pathogen that induces various inflammatory and immune responses. In this study, we investigated the effects of P. intermedia on the plasminogen system in human periodontal ligament (hPDL) cells and explored the signaling pathways involved. Using semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-qPCR, we demonstrated that P. intermedia challenge increased tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-2 expression in a concentration- and time-dependent manner, but exerted no influence on urokinase-type plasminogen activator and PAI-1mRNA expression in hPDL cells. Prevotella intermedia stimulation also enhanced tPA protein secretion as confirmed by enzyme-linked immunosorbent assay. Western blot results revealed that P. intermedia treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38). ERK, JNK and protein kinase C inhibitors significantly attenuated the P. intermedia-induced tPA and PAI-2 expression. Furthermore, p38 and phosphatidylinositol 3-kinase inhibitors markedly decreased PAI-2 expression, whereas they showed no or little inhibition on tPA expression. In contrast, inhibition of protein kinase A greatly enhanced the upregulatory effect of P. intermedia on tPA and PAI-2 expression. Our results suggest that P. intermedia may contribute to periodontal tissue destruction by upregulating tPA and PAI-2 expression in hPDL cells via multiple signaling pathways.

  18. Mitogen-activated protein kinases and phosphatidylinositol 3-kinase are involved in Prevotella intermedia-induced proinflammatory cytokines expression in human periodontal ligament cells.

    PubMed

    Guan, Su-Min; Zhang, Ming; He, Jian-Jun; Wu, Jun-Zheng

    2009-08-28

    Chronic periodontitis is an inflammatory disease affecting periodontal connective tissues and alveolar bone. Proinflammatory mediators induced by periodontal pathogens play vital roles in the initiation and progression of the disease. In this study, we examined whether Prevotella intermedia induces proinflammatory cytokines expression in human periodontal ligament cells (hPDLs). The mRNA expression and protein production were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbant assay (ELISA) respectively. P. intermedia treatment dose- and time-dependently increased IL-6, IL-8 and M-CSF, but not IL-1beta and TNF-alpha mRNA expression and protein secretion. Preincubation of hPDLs with extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 kinase and phosphatidylinositol 3-kinase (PI3K) inhibitors PD98059, SP600125, SB203580 and LY294002 resulted in significant reduction in P. intermedia-induced IL-6, IL-8 and M-CSF expression. Blocking the synthesis of prostaglandin E(2) (PGE(2)) by indomethacin also abolished the stimulatory effects of P. intermedia on cytokines expression. Our results indicate that P. intermedia induces proinflammatory cytokines through MAPKs and PI3K signaling pathways, and PGE(2) is involved in the P. intermedia-induced proinflammatory cytokines upregulation.

  19. Evaluation of antioxidant potential of Lavandula x intermedia Emeric ex Loisel. 'Budrovka': a comparative study with L. angustifolia Mill.

    PubMed

    Blazeković, Biljana; Vladimir-Knezević, Sanda; Brantner, Adelheid; Stefan, Maja Bival

    2010-08-30

    A Croatian indigenous cultivar of lavandin, Lavandula x intermedia 'Budrovka' (Lamiaceae) was studied for the phenolic acids, flavonoids, anthocyanins, procyanidins and total tannins, as well as total polyphenols content, in the flower, inflorescence stalk and leaf ethanolic extracts. Antioxidant potentials on these plant part extracts were assessed by the DPPH free radical scavenging activity, iron chelating activity, reducing power, lipid peroxidation inhibition properties and total antioxidant capacity assays. All results were compared with those of Lavandula angustifolia, the only member of the Lavandula genus officially used in modern phytotherapy. Based on the results of our parallel study, we may suggest that Lavandula x intermedia 'Budrovka' is as potent an antioxidant as Lavandula angustifolia and the antioxidant activity of the Lavandula extracts is mainly due to the presence of rosmarinic acid. A good correlation was found between the polyphenol contents and antioxidant activities of the extracts.

  20. Fungal His-Tagged Nitrilase from Gibberella intermedia: Gene Cloning, Heterologous Expression and Biochemical Properties

    PubMed Central

    Gong, Jin-Song; Li, Heng; Zhu, Xiao-Yan; Lu, Zhen-Ming; Wu, Yan; Shi, Jing-Song; Xu, Zheng-Hong

    2012-01-01

    Background Nitrilase is an important member of the nitrilase superfamiliy. It has attracted substantial interest from academia and industry for its function of converting nitriles directly into the corresponding carboxylic acids in recent years. Thus nitrilase has played a crucial role in production of commercial carboxylic acids in chemical industry and detoxification of nitrile-contaminated wastes. However, conventional studies mainly focused on the bacterial nitrilase and the potential of fungal nitrilase has been far from being fully explored. Research on fungal nitrilase gene expression will advance our understanding for its biological function of fungal nitrilase in nitrile hydrolysis. Methodology/Principal Findings A fungal nitrilase gene from Gibberella intermedia was cloned through reverse transcription-PCR. The open reading frame consisted of 963 bp and potentially encoded a protein of 320 amino acid residues with a theoretical molecular mass of 35.94 kDa. Furthermore, the catalytic triad (Glu-45, Lys-127, and Cys-162) was proposed and confirmed by site-directed mutagenesis. The encoding gene was expressed in Escherichia coli Rosetta-gami (DE3) and the recombinant protein with His6-tag was purified to electrophoretic homogeneity. The purified enzyme exhibited optimal activity at 45°C and pH 7.8. This nitrilase was specific towards aliphatic and aromatic nitriles. The kinetic parameters Vmax and Km for 3-cyanopyridine were determined to be 0.81 µmol/min·mg and 12.11 mM through Hanes-Woolf plot, respectively. 3-Cyanopyridine (100 mM) could be thoroughly hydrolyzed into nicotinic acid within 10 min using the recombinant strain with the release of about 3% nicotinamide and no substrate was detected. Conclusions/Significance In the present study, a fungal nitrilase was cloned from the cDNA sequence of G. intermedia and successfully expressed in E. coli Rosetta-gami (DE3). The recombinant strain displayed good 3-cyanopyridine degradation efficiency and wide

  1. Human dental stem cells suppress PMN activity after infection with the periodontopathogens Prevotella intermedia and Tannerella forsythia

    PubMed Central

    Hieke, Cathleen; Kriebel, Katja; Engelmann, Robby; Müller-Hilke, Brigitte; Lang, Hermann; Kreikemeyer, Bernd

    2016-01-01

    Periodontitis is characterized by inflammation associated with the colonization of different oral pathogens. We here aimed to investigate how bacteria and host cells shape their environment in order to limit inflammation and tissue damage in the presence of the pathogen. Human dental follicle stem cells (hDFSCs) were co-cultured with gram-negative P. intermedia and T. forsythia and were quantified for adherence and internalization as well as migration and interleukin secretion. To delineate hDFSC-specific effects, gingival epithelial cells (Ca9-22) were used as controls. Direct effects of hDFSCs on neutrophils (PMN) after interaction with bacteria were analyzed via chemotactic attraction, phagocytic activity and NET formation. We show that P. intermedia and T. forsythia adhere to and internalize into hDFSCs. This infection decreased the migratory capacity of the hDFSCs by 50%, did not disturb hDFSC differentiation potential and provoked an increase in IL-6 and IL-8 secretion while leaving IL-10 levels unaltered. These environmental modulations correlated with reduced PMN chemotaxis, phagocytic activity and NET formation. Our results suggest that P. intermedia and T. forsythia infected hDFSCs maintain their stem cell functionality, reduce PMN-induced tissue and bone degradation via suppression of PMN-activity, and at the same time allow for the survival of the oral pathogens. PMID:27974831

  2. Human dental stem cells suppress PMN activity after infection with the periodontopathogens Prevotella intermedia and Tannerella forsythia.

    PubMed

    Hieke, Cathleen; Kriebel, Katja; Engelmann, Robby; Müller-Hilke, Brigitte; Lang, Hermann; Kreikemeyer, Bernd

    2016-12-15

    Periodontitis is characterized by inflammation associated with the colonization of different oral pathogens. We here aimed to investigate how bacteria and host cells shape their environment in order to limit inflammation and tissue damage in the presence of the pathogen. Human dental follicle stem cells (hDFSCs) were co-cultured with gram-negative P. intermedia and T. forsythia and were quantified for adherence and internalization as well as migration and interleukin secretion. To delineate hDFSC-specific effects, gingival epithelial cells (Ca9-22) were used as controls. Direct effects of hDFSCs on neutrophils (PMN) after interaction with bacteria were analyzed via chemotactic attraction, phagocytic activity and NET formation. We show that P. intermedia and T. forsythia adhere to and internalize into hDFSCs. This infection decreased the migratory capacity of the hDFSCs by 50%, did not disturb hDFSC differentiation potential and provoked an increase in IL-6 and IL-8 secretion while leaving IL-10 levels unaltered. These environmental modulations correlated with reduced PMN chemotaxis, phagocytic activity and NET formation. Our results suggest that P. intermedia and T. forsythia infected hDFSCs maintain their stem cell functionality, reduce PMN-induced tissue and bone degradation via suppression of PMN-activity, and at the same time allow for the survival of the oral pathogens.

  3. Prevotella intermedia induces severe bacteremic pneumococcal pneumonia in mice with upregulated platelet-activating factor receptor expression.

    PubMed

    Nagaoka, Kentaro; Yanagihara, Katsunori; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

    2014-02-01

    Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells.

  4. [Effects of cutting and reseeding on the ground-dwelling arthropod community in Caragana intermedia forest in desert steppe].

    PubMed

    Liu, Ren-Tao; Chai, Yong-Qing; Yang, Xin-Guo; Song, Nai-Ping; Wang, Xin-Yun; Wang, Lei

    2013-01-01

    Taking a 25-year-old Caragana intermedia forest in desert steppe as test object, an investigation was conducted on the ground-dwelling arthropod community in cutting and no-cutting stands with and without reseeding, aimed to understand the effects of cutting, reseeding and their interaction on the individual number and group richness of ground-dwelling arthropod in C. intermedia forest. There were significantly lower number and richness of ground-dwelling arthropod in the open spaces than under the shrubs in the no-cutting and no-reseeding stands. Cutting, reseeding and both of them could significantly increase the number and richness of ground-dwelling arthropod in the open spaces, but not under the shrubs, compared with no cutting or reseeding. Consequently, there were no significant differences in the distribution of ground-dwelling arthropod in the open spaces and under the shrubs in the cutting, reseeding, or cutting and reseeding stands. Further, there was a similar buffer effect between cutting and reseeding on the ground-dwelling arthropod. No significant differences were observed in the ground-dwelling arthropod distribution, between cutting stand and reseeding stand, between cutting stand and cutting and reseeding stand, and between reseeding stand and cutting and reseeding stand. It was suggested that cutting, reseeding, or both of them could significantly improve the ground-dwelling arthropod diversity especially in the open spaces, being beneficial for the restoration of degraded grassland ecosystem and the rational management on artificial C. intermedia forest in desert steppe.

  5. Defective transient endogenous spleen colony formation in S1/S1d mice.

    PubMed

    Wiktor-Jedrzejczak, W; Ahmed, A; Sharkis, S J; McKee, A; Sell, K W

    1979-04-01

    WCB6F1 mice of the genotype S1/S1d did not form transient 5-day endogenous spleen colonies following midlethal irradiation, either spontaneously or in response to postirradiation bleeding. Their hematologically normal (+/+) littermates produced colonies equivalent in number and morphologic type to a normal strain (D2B6F1), as evaluated by both macroscopic and microscopic criteria. Bone marrow cells from S1/S1d mice, when transplanted into lethally irradiated +/+ mice, were able to generate equivalent numbers of transient endogenous spleen colonies (TE-CFUs), as compared to that obtained when syngeneic +/+ marrow cells were injected into lethally irradiated +/+ recipients. A defective growth of an early class of hematopoietic progenitor cells, resulting in the clinical course of the S1/S1d anemia is suggested and confirms previous reports on the microenvironmental nature of this abnormality.

  6. A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A

    PubMed Central

    Mallorquí-Fernández, Noemí; Manandhar, Surya P.; Mallorquí-Fernández, Goretti; Usón, Isabel; Wawrzonek, Katarzyna; Kantyka, Tomasz; Solà, Maria; Thøgersen, Ida B.; Enghild, Jan J.; Potempa, Jan; Gomis-Rüth, F.Xavier

    2009-01-01

    Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defences and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and its self-processed mature form. The latter consists of a bivalved moiety made up by two subdomains. In the structure of a catalytic cysteine-to-alanine zymogen variant, the right subdomain interacts with an unusual prodomain, thus contributing to latency. Unlike the catalytic cysteine residue, already in its competent conformation in the zymogen, the catalytic histidine is swung out from its active conformation and trapped in a cage shaped by a backing helix, a zymogenic hairpin and a latency flap in the zymogen. Dramatic rearrangement of up to 20Å of these elements triggered by a tryptophan switch occurs during activation and accounts for a new activation mechanism for proteolytic enzymes. These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcus pyogenes SpeB and Porphyromonas gingivalis periodontain. PMID:17993455

  7. Histopathological findings in rabbits after experimental acute exposure to the Loxosceles intermedia (brown spider) venom

    PubMed Central

    Ospedal, Katia Zoghbi; Appel, Marcia Helena; Neto, José Fillus; Mangili, Oldemir Carlos; Veiga, Silvio Sanches; Gremski, Waldemiro

    2002-01-01

    Loxoscelism, the term used to describe envenomation with brown spiders, is characterized by a dermonecrotic lesion at the bite site. In the present investigation we submitted albino rabbits to an acute experimental envenomation protocol using Loxosceles intermedia (brown spider) venom, with in order to determine the pathogenesic features of the lesion induced by this spider, which is the cause of several accidents throughout the world. Rabbits received intradermal injections of the venom and were monitored over the first 4 h, and then at 12 h and 1, 2 and 5 days after envenomation. Histological specimens from 3 rabbits per time point were collected from euthanized animals and processed for histological examination by light microscopy. Major findings observed during the first 4 h were oedema, haemorrhage, degeneration of blood vessel walls, plasma exudation, thrombosis, neutrophil accumulation in and around blood vessels with an intensive diapedesis, a diffuse collection of inflammatory cells (polymorphonuclear leucocytes) in the dermis, and subcutaneous muscular oedema. Over the following hours and up to 5 days after envenomation the changes progressed to massive neutrophil infiltration (with no other leucocytes) into the dermis and even into subcutaneous muscle tissue, destruction of blood vessels, thrombosis, haemorrhage, myonecrosis, and coagulative necrosis on the 5th day. PMID:12657137

  8. Exploring the optimum conditions for maximizing the microbial growth of Candida intermedia by response surface methodology.

    PubMed

    Yönten, Vahap; Aktaş, Nahit

    2014-01-01

    Exploring optimum and cost-efficient medium composition for microbial growth of Candida intermedia Y-1981 yeast culture growing on whey was studied by applying a multistep response surface methodology. In the first step, Plackett-Burman (PB) design was utilized to determine the most significant fermentation medium factors on microbial growth. The medium temperature, sodium chloride and lactose concentrations were determined as the most important factors. Subsequently, the optimum combinations of the selected factors were explored by steepest ascent (SA) and central composite design (CCD). The optimum values for lactose and sodium chloride concentrations and medium temperature were found to be 18.4 g/L, 0.161 g/L, and 32.4°C, respectively. Experiments carried out at the optimum conditions revealed a maximum specific growth rate of 0.090 1/hr; 42% of total lactose removal was achieved in 24 h of fermentation time. The obtained results were finally verified with batch reactor experiments carried out under the optimum conditions evaluated.

  9. Influence of metabolic stress on the inheritance of cell determination in the moss, Pottia intermedia.

    PubMed

    Lobachevska, O; Kyjak, N; Khorkavtsiv, O; Dovgalyuk, A; Kit, N; Klyuchivska, O; Stoika, R; Ripetsky, R; Cove, D

    2005-03-01

    Epigenetically-determined apogamy in aposporous regenerants of the moss Pottia intermedia persists during vegetative propagation, the capacity of apogamy being inherited by individual aposporous protonemal cells. To test Bauer-Lazarenko's proposal that stable apogamy in mosses may be due to some self-replicating cytoplasmic factor, the effects of different metabolic stress treatments on the expression of apogamy have been tested. Chronic metabolic stress caused by long-term growth of autotrophic aposporous protonema on mineral medium with 0.25% of casamino acids and on Murashiga-Skoog (MS) medium with sucrose and phytohormones, as well as by transitory action of high kinetin concentration, have a much stronger influence on the expression of apogamy, than short-term stress treatments with RNase and Pb(2+). Apogamy has been found to be lost stably, after prolonged growth on MS medium containing kinetin and ABA. The proposal that the capacity for apogamy is related to the release of aposporous protonemal cells from a putative factor for apogamy is discussed.

  10. Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing's disease).

    PubMed

    Donaldson, Mark T; LaMonte, Bernadette H; Morresey, Peter; Smith, Gary; Beech, Jill

    2002-01-01

    Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucose concentrations and clinical signs. Prior to treatment, the most common clinical signs were laminitis, hirsutism, and abnormal body fat distribution. The median pergolide dose was 3.0 microg/kg p.o. q24h (range, 1.7-5.5 microg/kg). All horses treated with cyproheptadine were given 0.25 mg/kg p.o. q24h. After pergolide treatment, ACTH concentrations (n = 20; median = 30.4 pg/ml; range, 4.2-173) were significantly lower (P < .01) than those in horses treated with cyproheptadine (n = 7; median = 141.0 pg/ml: range, 10-1,230). Among horses treated with pergolide, there was a correlation between ACTH concentration after treatment and the duration of treatment (P < .001) and pergolide dose (P = .04). Significantly (P = .02) more owners of horses treated with pergolide (85%, 17/20) reported an improvement in clinical signs compared to owners of horses treated with cyproheptadine (28%, 2/7).

  11. A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A.

    PubMed

    Mallorquí-Fernández, Noemí; Manandhar, Surya P; Mallorquí-Fernández, Goretti; Usón, Isabel; Wawrzonek, Katarzyna; Kantyka, Tomasz; Solà, Maria; Thøgersen, Ida B; Enghild, Jan J; Potempa, Jan; Gomis-Rüth, F Xavier

    2008-02-01

    Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defenses and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and self-processed mature forms. The latter consists of a bivalved moiety made up by two subdomains. In the structure of a catalytic cysteine-to-alanine zymogen variant, the right subdomain interacts with an unusual prodomain, thus contributing to latency. Unlike the catalytic cysteine residue, already in its competent conformation in the zymogen, the catalytic histidine is swung out from its active conformation and trapped in a cage shaped by a backing helix, a zymogenic hairpin, and a latency flap in the zymogen. Dramatic rearrangement of up to 20A of these elements triggered by a tryptophan switch occurs during activation and accounts for a new activation mechanism for proteolytic enzymes. These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcus pyogenes SpeB and Porphyromonas gingivalis periodontain.

  12. Starvation response and growth in serum of Fusobacterium nucleatum, Peptostreptococcus anaerobius, Prevotella intermedia, and Pseudoramibacter alactolyticus.

    PubMed

    Brundin, Malin; Figdor, David; Sundqvist, Göran; Sjögren, Ulf

    2009-07-01

    The microbiota inhabiting the untreated root canal differ markedly from those found in post-treatment disease, yet there is limited information on the microbial characteristics distinguishing the different infections. We hypothesized that starvation survival is a key microbial property in species selection. This study analyzed starvation-survival behavior over 60 days of species representative of the untreated root canal infection: Fusobacterium nucleatum, Peptostreptococcus anaerobius, Prevotella intermedia and Pseudoramibacter alactolyticus. All species did not survive 1 day in water. In 1% serum, the 4 species could not survive beyond 2-3 weeks. They required a high initial cell density and >or=10% serum to survive the observation period. The results highlight a poor starvation-survival capacity of these 4 species compared with species prevalent in post-treatment infection, which are well equipped to endure starvation and survive in low numbers on minimal serum. These findings point to starvation-survival capacity as a selection factor for microbial participation in post-treatment disease.

  13. Biosynthesis of silver nanoparticles using Euglena gracilis, Euglena intermedia and their extract.

    PubMed

    Li, Yong; Tang, Xiaoling; Song, Wenshuang; Zhu, Lina; Liu, Xingang; Yan, Xiaomin; Jin, Chengzhi; Ren, Qingguang

    2015-02-01

    Extracellular and intracellular biosynthesis of silver nanoparticles (AgNPs) by Euglena gracilis (EG) strain and Euglena intermedia (EI) strain are reported in this study. The obtained nanoparticles showed an absorption peak approximates 420 nm in the UV-visible spectrum, corresponding to the plasmon resonance of AgNPs. According to the result of inductively coupled plasma-atomic emission spectrometer, the intakes of silver ions by EI and EG are roughly equal. The transmission electron microscope (TEM) analysis of the successful in vivo and in vitro synthesised AgNPs indicated the sizes, ranging from 6 to 24 nm and 15 to 60 nm in diameter, respectively, and a spherical-shaped polydispersal of the particles. The successful formation of AgNPs has been confirmed by energy dispersive X-ray analysis connected to the TEM. The Fourier transform infrared spectroscopy measurements reveal the presence of bioactive functional groups such as amines are found to be the capping and stabilising agents of nanoparticles. To our knowledge, this is the first report where two kinds of Euglena microalga were used as the potential source for in vivo and in vitro biosynthesis of AgNPs.

  14. Adsorption of colored pollutants from distillery spent wash by native and treated fungus: neurospora intermedia.

    PubMed

    Kaushik, Garima; Thakur, Indu Shekhar

    2013-02-01

    The native and physico-chemically treated fungal biomasses of Neurospora intermedia were used for adsorption of colored pollutants from distillery spent wash in batch systems. Experiments were conducted at varying color concentrations of the effluent (1,000-6,500 CU). The kinetics of effect of initial sorbate concentration, dose of biosorbent, temperature, and pH on adsorption were studied. Physical and chemical pretreatments of biomass resulted in an increase or decrease in color removal capacity. This effect was further studied by FTIR analysis of the dried fungal mycelium. The maximum color uptake on all the tested fungal biomass preparations was observed at pH 3.0 and temperature 30 °C, within first 4 h. The Langmuir and Freundlich adsorption models were used for the mathematical description of the biosorption equilibrium and the data showed an optimal fit to these isotherms. Kinetic parameters indicated the dominance of Lagergren pseudo first-order kinetic model for adsorption. On the basis of maximum adsorption capacity, the color removal capacity by fungal preparations was in the order of native > heat > acid, base.

  15. Genetic interactions in thalassemia intermedia: analysis of beta-mutations, alpha-genotype, gamma-promoters, and beta-LCR hypersensitive sites 2 and 4 in Italian patients.

    PubMed

    Camaschella, C; Mazza, U; Roetto, A; Gottardi, E; Parziale, A; Travi, M; Fattore, S; Bacchiega, D; Fiorelli, G; Cappellini, M D

    1995-02-01

    In order to verify the genetic factors influencing the clinical expression of beta-thalassemia we have studied 292 Italian patients, 165 with thalassemia intermedia and 127 with thalassemia major. The beta-globin gene mutations were defined in all cases. The number of alpha-globin genes and the integrity of specific control regions of the beta-globin cluster--gamma promoters and beta-Locus Control Region (beta-LCR)--were studied in selected cases. Homozygosity for mild mutations (group I) accounts for 24% of the intermedia patients and it is not represented among major patients. Forty-four percent of intermedia patients had combinations of mild/severe (group II) mutations and 32% had homozygosity or double heterozygosity for severe mutations (group III). Seventy-six percent of patients with thalassemia major were classified in group III and 24% in group II. Deletion type-alpha3.7 thalassemia, assessed in a part of the cases, was found in 5% of thalassemia major and 19.5% of intermedia patients in groups II and III. Structural analysis of gamma promoters and beta-LCR HS2 and HS4 regions, carried out in order to look for alterations associated with Hb F increase, did not reveal new mutations. Only rare polymorphic changes were observed at the HS2 and HS4 level. The -158G gamma C T change was found with an increased incidence in intermedia patients in groups II and III. A subset of 10 beta-thalassemia heterozygotes with mild intermedia phenotype resulted from coinheritance of a triplicated alpha-locus. We have been unable to find a molecular basis for the benign clinical course in approximately 20% of patients with thalassemia intermedia. Other genetic or acquired factors must be hypothesized which ameliorate the clinical condition.

  16. Restless legs syndrome mimicking S1 radiculopathy.

    PubMed

    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

  17. Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.

    PubMed

    Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M

    2012-01-01

    Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.

  18. A Novel Hyaluronidase from Brown Spider (Loxosceles intermedia) Venom (Dietrich's Hyaluronidase): From Cloning to Functional Characterization

    PubMed Central

    Ferrer, Valéria Pereira; de Mari, Thiago Lopes; Gremski, Luiza Helena; Trevisan Silva, Dilza; da Silveira, Rafael Bertoni; Gremski, Waldemiro; Chaim, Olga Meiri; Senff-Ribeiro, Andrea; Nader, Helena Bonciani; Veiga, Silvio Sanches

    2013-01-01

    Loxoscelism is the designation given to clinical symptoms evoked by Loxosceles spider's bites. Clinical manifestations include skin necrosis with gravitational spreading and systemic disturbs. The venom contains several enzymatic toxins. Herein, we describe the cloning, expression, refolding and biological evaluation of a novel brown spider protein characterized as a hyaluronidase. Employing a venom gland cDNA library, we cloned a hyaluronidase (1200 bp cDNA) that encodes for a signal peptide and a mature protein. Amino acid alignment revealed a structural relationship with members of hyaluronidase family, such as scorpion and snake species. Recombinant hyaluronidase was expressed as N-terminal His-tag fusion protein (∼45 kDa) in inclusion bodies and activity was achieved using refolding. Immunoblot analysis showed that antibodies that recognize the recombinant protein cross-reacted with hyaluronidase from whole venom as well as an anti-venom serum reacted with recombinant protein. Recombinant hyaluronidase was able to degrade purified hyaluronic acid (HA) and chondroitin sulfate (CS), while dermatan sulfate (DS) and heparan sulfate (HS) were not affected. Zymograph experiments resulted in ∼45 kDa lytic zones in hyaluronic acid (HA) and chondroitin sulfate (CS) substrates. Through in vivo experiments of dermonecrosis using rabbit skin, the recombinant hyaluronidase was shown to increase the dermonecrotic effect produced by recombinant dermonecrotic toxin from L. intermedia venom (LiRecDT1). These data support the hypothesis that hyaluronidase is a “spreading factor”. Recombinant hyaluronidase provides a useful tool for biotechnological ends. We propose the name Dietrich's Hyaluronidase for this enzyme, in honor of Professor Carl Peter von Dietrich, who dedicated his life to studying proteoglycans and glycosaminoglycans. PMID:23658852

  19. Measurement of cortisol concentration in the tears of horses and ponies with pituitary pars intermedia dysfunction.

    PubMed

    Hart, Kelsey A; Kitchings, Kalyn M; Kimura, Shune; Norton, Natalie A; Myrna, Kathern E

    2016-11-01

    OBJECTIVE To compare tear cortisol concentrations between horses and ponies with pituitary pars intermedia dysfunction (PPID) and healthy nonaged (≤ 15 years old) and aged (≥ 20 years old) horses and to determine whether serum and tear cortisol concentrations were correlated. ANIMALS 11 horses and ponies with PPID and 20 healthy control horses and ponies (11 nonaged and 9 aged). PROCEDURES Paired tear and serum samples were obtained from PPID and control animals. All animals were free of active ocular disease. Tear and serum cortisol concentrations were measured with an ELISA and chemiluminescent assay, respectively. Groups were compared with Kruskal-Wallis and Mann-Whitney U tests, and Spearman correlation analysis was used to examine relationships between tear and serum cortisol concentrations within groups. RESULTS Median tear cortisol concentration was significantly higher in PPID animals than in aged control animals, despite comparable serum cortisol concentrations in PPID and aged control animals. Median tear-to-serum cortisol concentration ratios were also significantly higher in PPID animals than in aged control animals. Serum and tear cortisol concentrations were not significantly correlated in PPID or control animals. CONCLUSIONS AND CLINICAL RELEVANCE Some horses and ponies with PPID had increased tear cortisol concentrations, compared with concentrations in healthy aged animals. Localized cortisol production in the tear film or altered cortisol binding dynamics could have contributed to this increase. Further studies are warranted to evaluate these mechanisms and to determine whether increased tear cortisol concentrations are associated with delays in corneal wound healing in horses and ponies with and without PPID.

  20. Molecular Basis of β-Thalassemia Intermedia in Erbil Province of Iraqi Kurdistan.

    PubMed

    Shamoon, Rawand P; Al-Allawi, Nasir A S; Cappellini, Maria D; Di Pierro, Elena; Brancaleoni, Valentina; Granata, Francesca

    2015-01-01

    β-Thalassemia intermedia (β-TI) is a clinical term describing a range of clinical phenotypes that are intermediate in severity between the carrier state and β-thalassemia major (β-TM). To characterize the molecular basis of β-TI in Erbil Province, Northern Iraq, 83 unrelated patients were investigated. Detection of β-globin gene mutations was carried out by reverse hybridization assay and direct gene sequencing. All patients were screened for the XmnI polymorphism by direct sequencing of HBG2 ((G)γ promoter gene). Detection of α-globin gene deletions and triplication was carried out using the reverse hybridization assay. Four main molecular patterns were identified in association with the β-TI phenotype, namely: β(+)/β(+) (38.5%), β(+)/β(0) (21.6%), β(0)/β(0) (31.3%), and β(0)/wild type (8.4%). IVS-I-6 (T > C) was the most frequently encountered mutation (55 alleles, 34.6%), followed by IVS-II-1 (G > A) and codon 8 (-AA); furthermore, we report for the first time from Iraq two β(+) mutations, -87 (C > G) and 5' untranslated region (5'UTR) +22 (G > A). The XmnI polymorphism was detected in 47.0% of patients, mainly in association with the β(0)/β(0) genotype. The α-globin gene deletions were encountered in four cases, including one case with (- -(FIL)) double gene deletion, a report that is the first from our country. The α-globin gene triplication was detected in five of the seven heterozygous β-thalassemia (β-thal) patients. Similar to other Mediterranean countries, inheritance of mild β-globin mutations was the main molecular pattern underlying β-TI in our patients followed by the ameliorating effect of the XmnI polymorphism.

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

    PubMed

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

    2014-07-01

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

  2. The functional roles of S1P in immunity.

    PubMed

    Hisano, Yu; Nishi, Tsuyoshi; Kawahara, Atsuo

    2012-10-01

    The lipid mediator sphingosine-1-phosphate (S1P) is generated within cells from sphingosine by two sphingosine kinases (SPHK1 and SPHK2). Intracellularly synthesized S1P is released into the extracellular fluid by S1P transporters, including SPNS2. Released S1P binds specifically to the G protein-coupled S1P receptors (S1PR1/S1P(1)-S1PR5/S1P(5)), which activate a diverse range of downstream signalling pathways. Recent studies have proposed that one of the central physiological functions of intercellular S1P signalling is in lymphocyte trafficking in vivo because genetic disruption of SPHK1/2, SPNS2 or S1PR1/S1P(1) in mice induces a lymphopenia phenotype. In this review, we discuss the current understanding of intercellular S1P signalling in the context of immunity.

  3. Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia and Prevotella nigrescens in endodontic lesions detected by culture and by PCR.

    PubMed

    Gomes, B P F A; Jacinto, R C; Pinheiro, E T; Sousa, E L R; Zaia, A A; Ferraz, C C R; Souza-Filho, F J

    2005-08-01

    he aim of this study was to investigate the presence of four black-pigmented bacteria, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia and Prevotella nigrescens, in endodontic infections by culture and polymerase chain reaction (PCR) analyses. Microbial samples were obtained from 50 teeth with untreated necrotic pulps (primary infection) and from 50 teeth with failing endodontic treatment (secondary infection). Microbiological strict anaerobic techniques were used for serial dilution, plating, incubation, and identification. For PCR detection, the samples were analyzed using species-specific primers of 16S rDNA and the downstream intergenic spacer region. Culture and PCR detected the test species in 13/100 and 50/100 of the study teeth, respectively. The organisms were cultured from 11/50 (22%) of primarily infected root canal samples and from 2/50 (4%) of secondary root canal samples. PCR detection identified the target species in 32/50 (64%) and 18/50 (36%) of primary and secondary infections, respectively. P. gingivalis was rarely isolated by culture methods (1%), but was the most frequently identified test species by PCR (38%). Similarly, P. endodontalis was not recovered by culture from any tooth studied, but was detected by PCR in 25% of the sampled teeth. PCR-based identification also showed higher detection rates of P. intermedia (33%) and P. nigrescens (22%) than culture (13%). In conclusion, P. gingivalis, P. endodontalis, P. intermedia, and P. nigrescens were identified more frequently in teeth with necrotic pulp than in teeth with failing endodontic treatment. Also, a higher frequency of black-pigmented species was detected by PCR than by culture.

  4. Reference gene selection for quantitative real-time PCR normalization in Caragana intermedia under different abiotic stress conditions.

    PubMed

    Zhu, Jianfeng; Zhang, Lifeng; Li, Wanfeng; Han, Suying; Yang, Wenhua; Qi, Liwang

    2013-01-01

    Quantitative real-time reverse transcription polymerase chain reaction (qPCR), a sensitive technique for gene expression analysis, depends on the stability of the reference genes used for data normalization. Caragana intermedia, a native desert shrub with strong drought-resistance, sand-fixing capacity and high forage value that is widespread in the desert land of west and northwest China, has not been investigated regarding the identification of reference genes suitable for the normalization of qPCR data. In this study, 10 candidate reference genes were analyzed in C. intermedia subjected to different abiotic (osmotic, salt, cold and heat) stresses, in two distinct plant organs (roots and leaves). The expression stability of these genes was assessed using geNorm, NormFinder and BestKeeper algorithms. The best-ranked reference genes differed across the different sets of samples, but UNK2, PP2A and SAND were the most stable across all tested samples. UNK2 and SAND would be appropriate for normalizing gene expression data for salt-treated roots, whereas the combination of UNK2, SAND and EF-1α would be appropriate for salt-treated leaves. UNK1, UNK2 and PP2A would be appropriate for PEG-treated (osmotic) roots, whereas the combination of TIP41 and PP2A was the most suitable for PEG-treated leaves. SAND, PP2A and TIP41 exhibited the most stable expression in heat-treated leaves. In cold-treated leaves, SAND and EF-1α were the most stably expressed. To further validate the suitability of the reference genes identified in this study, the expression levels of DREB1 and DREB2 (homologs of AtDREB1 and AtDREB2) were studied in parallel. This study is the first systematic analysis for the selection of superior reference genes for qPCR in C. intermedia under different abiotic stress conditions, and will benefit future studies on gene expression in C. intermedia and other species of the leguminous genus Caragana.

  5. Nocturnal activity rhythms of Lutzomyia intermedia and Lutzomyia whitmani (Diptera: Psychodidae) in a transmission area of American cutaneous leishmaniasis in Rio de Janeiro State, Brazil.

    PubMed

    Souza, Nataly A; Andrade-Coelho, Cláudia A; Peixoto, Alexandre A; Rangel, Elizabeth F

    2005-11-01

    The phlebotomine sand flies Lutzomyia (Nyssomyia) intermedia (Lutz & Neiva) and Lutzomyia (Nyssomyia) whitmani (Coutinho & Antunes) are important vectors of Leishmania (Vianna) braziliensis, the etiological agent of American cutaneous leishmaniasis. In some areas, both species occur in sympatry, and their relative roles as vectors in these areas are not clear. We studied the nocturnal activity and biting rhythms of both species in Posse, a locality in Rio de Janeiro State, Brazil. Our results show differences between the activity patterns of Lu. intermedia and Lu. whitmani that might be epidemiologically important. Although the activity profiles vary between seasons and microhabitats (peridomestic versus forest), the two species show marked differences in their tendencies to bite humans in the early morning (0400-0600 hours), with Lu. whitmani showing higher feeding rates than Lu. intermedia.

  6. Biology of the first generation of a laboratory colony of Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) (Diptera: Psychodidae).

    PubMed

    Andrade Filho, José Dilermando; Galati, Eunice A Bianchi; Falcão, Alda Lima

    2004-10-01

    The phlebotomine sand flies Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) are very close and may be involved in the transmission of Leishmania spp. Ross, 1903 in Brazil. The biology of the first laboratory-reared generations of these species, descended from insects captured in Além Paraíba (N. intermedia) and Corinto (N. neivai) in the Brazilian state of Minas Gerais, is described here. The captured females were fed on hamsters and maintained individually in rearing pots. Laboratory temperature and relative humidity were maintained at 25-26 masculineC and 80% respectively. The productivity of the first generation of N. intermedia was greater than that of N. neivai, and its development time clearly shorter, particularly for the second and third larval instars.

  7. Prevotella intermedia lipopolysaccharide stimulates release of tumor necrosis factor-alpha through mitogen-activated protein kinase signaling pathways in monocyte-derived macrophages.

    PubMed

    Kim, Sung-Jo; Choi, Eun-Young; Kim, Eun Gyung; Shin, Su-Hwa; Lee, Ju-Youn; Choi, Jeom-Il; Choi, In-Soon

    2007-11-01

    The purpose of this study was to investigate the effects of lipopolysaccharide from Prevotella intermedia, a major cause of inflammatory periodontal disease, on the production of tumor necrosis factor (TNF)-alpha and the expression of TNF-alpha mRNA in differentiated THP-1 cells, a human monocytic cell line. The potential involvement of the three main mitogen-activated protein kinase (MAPK) signaling pathways in the induction of TNF-alpha production was also investigated. Lipopolysaccharide from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. It was found that P. intermedia lipopolysaccharide can induce TNF-alpha mRNA expression and stimulate the release of TNF-alpha in differentiated THP-1 cells without additional stimuli. Treatment of the cells with P. intermedia lipopolysaccharide resulted in a simultaneous activation of three MAPKs [extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2) and p38]. Pretreatment of the cells with MAPK inhibitors effectively suppressed P. intermedia lipopolysaccharide-induced TNF-alpha production without affecting the expression of TNF-alpha mRNA. These data thus provided good evidence that the MAPK signaling pathways are required for the regulation of P. intermedia lipopolysaccharide-induced TNF-alpha synthesis at the level of translation more than at the transcriptional level.

  8. Carbon monoxide-releasing molecule-3 suppresses Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-1β in murine macrophages.

    PubMed

    Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2015-10-05

    This study was performed to analyze the effect of carbon monoxide (CO)-releasing molecule-3 (CORM-3) in alleviating the production of proinflammatory mediators in macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen associated with periodontal disease, and its possible mechanisms of action. LPS was isolated using the hot phenol-water method. Culture supernatants were assayed for nitric oxide (NO) and interleukin-1β (IL-1β). Gene expression was quantified by real-time PCR, and protein expression by immunoblotting. DNA-binding activities of NF-κB subunits were determined using an ELISA-based kit. CORM-3 suppressed the production of inducible NO synthase (iNOS)-derived NO and IL-1β at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. CORM-3 enhanced heme oxygenase-1 (HO-1) expression in cells stimulated with P. intermedia LPS, and inhibition of HO-1 activity by SnPP notably reversed the suppressive effect of CORM-3 on LPS-induced production of NO. LPS-induced phosphorylation of p38 and JNK was not affected by CORM-3. CORM-3 did not influence P. intermedia LPS-induced degradation of IκB-α. Instead, nuclear translocation of NF-κB p65 and p50 subunits was blocked by CORM-3 in LPS-treated cells. In addition, CORM-3 reduced LPS-induced p65 and p50 binding to DNA. Besides, CORM-3 significantly suppressed P. intermedia LPS-induced phosphorylation of STAT1. Overall, this study indicates that CORM-3 suppresses the production of NO and IL-1β in P. intermedia LPS-activated murine macrophages via HO-1 induction and inhibition of NF-κB and STAT1 pathways. The modulation of host inflammatory response by CORM-3 would be an attractive therapeutic approach to attenuate the progression of periodontal disease.

  9. Evolución de estrellas enanas blancas de Helio de masa baja e intermedia

    NASA Astrophysics Data System (ADS)

    Althaus, L. G.; Benvenuto, O. G.

    Numerosas observaciones realizadas particularmente en los últimos dos años parecen confirmar que las enanas blancas (EB) de helio de masa baja e intermedia son el resultado de la evolución de sistemas binarios cercanos. Con el objeto de realizar una adecuada interpretación de estos objetos son necesarios modelos de EBs de helio lo más detallado posibles. En este estudio presentamos cálculos detallados de la evolución de EBs de helio con masas entre M=0.1Msolar y M=0.5Msolar a intervalos de 0.05Msolar . Para ello, hemos tenido en cuenta los efectos de temperatura finita mediante un código de evolución estelar lo más actualizado posible. En particular, el transporte de energía es descripto en el marco del nuevo modelo para la convección turbulenta desarrollado por Canuto - Mazzitelli. Además hemos considerado la nueva ecuación de estado para plasmas de helio de Saumon et al. y nuevas opacidades radiativas OPAL. Las pérdidas por neutrinos fueron asimismo tenidas en cuenta. Excepto para las EBs más masivas, nuestros modelos iniciales están ubicados en las cercanías de la correspondiente línea de Hayashi para configuraciones de helio. Nuestros resultados muestran que existe una región prohibida en el diagrama observacional HR donde ninguna EB de helio puede encontrarse. Dicha región es para log{(L/Lsolar )}>= -0.25 and log{Teff} >= 4.45. Hemos encontrado también que los tracks evolutivos en el diagrama HR en el dominio de alta luminosidad (pre - EB) son fuertemente afectados por la eficiencia convectiva y que las pérdidas por neutrinos son importantes en los modelos más masivos. Finalmente hemos analizado la estructura de la zona convectiva externa encontrando que la teoría de Canuto - Mazzitelli conduce a un perfil convectivo muy diferente del dado por cualquier versión de la popular teoría de la mixing length. Si bién este comportamiento es decisivo en el contexto de las inestabilides pulsacionales, los radios y gravedades superficiales de

  10. Response to hydroxycarbamide in pediatric β-thalassemia intermedia: 8 years' follow-up in Egypt.

    PubMed

    El-Beshlawy, Amal; El-Ghamrawy, Mona; EL-Ela, Mona Abou; Said, Fadwa; Adolf, Sonia; Abdel-Razek, Abdel-Rahman Ahmed; Magdy, Rania Ismail; Abdel-Salam, Amina

    2014-12-01

    Hydroxycarbamide (hydroxyurea or HU) has been shown to increase fetal hemoglobin (HbF) in patients with β-thalassemia intermedia (TI). The reported effects of HU in increasing the total hemoglobin (Hb) have been inconsistent. Studies of long-term therapy with HU in pediatric TI are rather uncommon. A retrospective observational study was carried out to evaluate the clinical responses to HU in Egyptian patients with β-TI. One hundred patients; children (n = 82, mean age 9.9 ± 4.1 years) and adults (n = 18) were studied for the mean Hb, HbF%, median serum ferritin, transfusion history, and splenic size before and after HU therapy (mean dose 20.0 ± 4.2 mg/kg/day, range 10-29 mg/kg/day) over a follow-up period 4 to 96 months (mean 35.4 ± 19.2 months). Molecular studies were also done for group of patients (n = 42). The overall response rate to HU was 79 %; 46 % were minor responders (with a reduction in transfusion rate by 50 % or more and/or an increase in their total hemoglobin level by 1-2 g/dl) and 33 % major responders (becoming transfusion-free and/or having an increase in total hemoglobin level by >2 g/dl). Mean hemoglobin increased among responders from 6.9 ± 0.9 g/dl to 8.3 ± 1.4 g/dl (p < 0.001). A significant rise in mean HbF (27.0 vs. 42.5 %; p < 0.011) and a decrease in median serum ferritin (800 vs. 644 ng/ml; p < 0.001) were also observed among responders (n = 45). Transfusions stopped in 44 % of pretreatment frequently transfused responders (n = 11/25). Splenic size decreased in 37 % of patients (n = 30/81). The predominant β-thalassemia mutation was 1-6 (T > C) in 32/42 (76 %) of studied patients; 28/32 were responders. Bivariate analysis showed no predictors of response as regards sex, pediatric and adult age, splenic status, or genotype. Hydroxycarbamide is a good therapeutic modality in the management of pediatric as in adult TI patients. It can minimize the need for blood transfusion, concomitant iron overload, and blood-born viral

  11. Effects of oxidative stress on the virulence profile of Prevotella intermedia during experimental infection in gnotobiotic mice.

    PubMed

    Santos, Simone G; Diniz, Claúdio G; Silva, Vânia L; Martins, Wanderlany A; Cara, Denise C; Souza, Natalia C; Serufo, José C; Nicoli, Jacques R; Carvalho, Maria Auxiliadora R; Farias, Luiz M

    2007-03-01

    Prevotella intermedia is a component of the indigenous microbiota but is also responsible for anaerobic infections of the gastrointestinal tract and oral cavity. The aim of the present study was to investigate the influence of oxidative stress on the in vivo pathogenicity of P. intermedia. Germ-free mice were challenged intraperitoneally with parental (wt) or oxidative stress adapted (aero) strains. Bacterial virulence was evaluated by histopathology, hyperaemia and blood analysis [C-reactive protein (CRP), serum albumin and white blood cells (WBCs)], 3 and 10 days after challenge. CRP levels and WBC count were higher in animals challenged with the aero strain, and the albumin level was lower in this group, only 10 days after infection (P<0.05). Body weight gain was significantly reduced whereas hyperaemia and ratios of spleen/organ weight were increased in animals challenged with the aero strain (P<0.05). The liver of animals challenged with the aero strain showed hyperaemia, vasodilatation as well as an increase in the number of inflammatory cells and liver/organ weight ratio (P<0.05). Similar, but more discrete, alterations were observed in the small intestine of animals challenged with the aero strain. Studies on stress responses of this putative pathogen may help to better understand the aggressive potential and virulence markers of anaerobic bacteria.

  12. Phylogenetic analysis of Prevotella nigrescens, Prevotella intermedia and Porphyromonas gingivalis clinical strains reveals a clear species clustering.

    PubMed

    Kuhnert, Peter; Frey, Joachim; Lang, Niklaus P; Mayfield, Lisa

    2002-07-01

    Prevotella nigrescens, Prevotella intermedia and Porphyromonas gingivalis are oral pathogens from the family Bacteroidaceae, regularly isolated from cases of gingivitis and periodontitis. In this study, the phylogenetic variability of these three bacterial species was investigated by means of 16S rRNA (rrs) gene sequence comparisons of a set of epidemiologically and geographically diverse isolates. For each of the three species, the rrs gene sequences of 11 clinical isolates as well as the corresponding type strains was determined. Comparison of all rrs sequences obtained with those of closely related species revealed a clear clustering of species, with only a little intraspecies variability but a clear difference in the rrs gene with respect to the next related taxon. The results indicate that the three species form stable, homogeneous genetic groups, which favours an rrs-based species identification of these oral pathogens. This is especially useful given the 7% sequence divergence between Prevotella intermedia and Prevotella nigrescens, since phenotypic distinction between the two Prevotella species is inconsistent or involves techniques not applicable in routine identification.

  13. Outer membrane proteome of Prevotella intermedia 17: identification of thioredoxin and iron-repressible hemin uptake loci.

    PubMed

    Yu, Fan; Anaya, Cecilia; Lewis, Janina P

    2007-02-01

    Although hemin is an indispensable nutrient for the oral pathogen Prevotella intermedia, not much is known regarding the molecular mechanisms of hemin acquisition. The availability of the genomic sequence of the bacterium allowed us to apply proteomic approaches to identify proteins that may be mediating the hemin acquisition process. As hemin acquisition mechanisms have been shown to be induced in iron-depleted conditions, we applied proteomic approaches to detect those proteins whose expressions were affected by iron. We analyzed 40 protein spots and identified 19 such proteins. Interestingly, two proteins drastically upregulated in iron-depleted conditions, PIN0009 and PINA0611, are homologs of hemin uptake receptors in other bacteria. PIN0009 is predicted to be an outer membrane lipoprotein. It is encoded by a gene that is the first of a seven-gene genomic locus encoding proteins of a novel hemin acquisition system. The second protein, PINA0611, is a homolog of numerous TonB-dependent outer membrane receptors including outer membrane iron uptake receptors of various Gram-negative bacteria. There was also another protein, regulated by iron, that was previously demonstrated to bind hemoglobin in P. intermedia. Finally, we identified a thioredoxin-like protein that has a novel outer membrane location.

  14. A Preliminary Study of the Effects of pH upon Fluorescence in Suspensions of Prevotella intermedia.

    PubMed

    Hope, Christopher K; Billingsley, Karen; de Josselin de Jong, Elbert; Higham, Susan M

    2016-01-01

    The quantification of fluorescence in dental plaque is currently being developed as a diagnostic tool to help inform and improve oral health. The oral anaerobe Prevotella intermedia exhibits red fluorescence due to the accumulation of porphyrins. pH affects the fluorescence of abiotic preparations of porphyrins caused by changes in speciation between monomers, higher aggregates and dimers, but this phenomenon has not been demonstrated in bacteria. Fluorescence spectra were obtained from suspensions of P. intermedia that were adjusted to pHs commensurate with the range found within dental plaque. Two fluorescent motifs were identified; 410 nm excitation / 634 nm emission (peak A) and 398 nm excitation / 622 nm emission (peak B). A transition in the fluorescence spectra was observed from peak A to peak B with increasing pH which was also evident as culture age increased from 24 hours to 96 hours. In addition to these 'blue-shifts', the intensity of peak A increased with pH whilst decreasing with culture age from 24 to 96 hours. A bacterium's relationship with the local physiochemical environment at the time of image capture may therefore affect the quantification of dental plaque fluorescence.

  15. A Preliminary Study of the Effects of pH upon Fluorescence in Suspensions of Prevotella intermedia

    PubMed Central

    Hope, Christopher K.; Billingsley, Karen; de Josselin de Jong, Elbert; Higham, Susan M.

    2016-01-01

    The quantification of fluorescence in dental plaque is currently being developed as a diagnostic tool to help inform and improve oral health. The oral anaerobe Prevotella intermedia exhibits red fluorescence due to the accumulation of porphyrins. pH affects the fluorescence of abiotic preparations of porphyrins caused by changes in speciation between monomers, higher aggregates and dimers, but this phenomenon has not been demonstrated in bacteria. Fluorescence spectra were obtained from suspensions of P. intermedia that were adjusted to pHs commensurate with the range found within dental plaque. Two fluorescent motifs were identified; 410 nm excitation / 634 nm emission (peak A) and 398 nm excitation / 622 nm emission (peak B). A transition in the fluorescence spectra was observed from peak A to peak B with increasing pH which was also evident as culture age increased from 24 hours to 96 hours. In addition to these ‘blue-shifts’, the intensity of peak A increased with pH whilst decreasing with culture age from 24 to 96 hours. A bacterium’s relationship with the local physiochemical environment at the time of image capture may therefore affect the quantification of dental plaque fluorescence. PMID:27441707

  16. Identification and characterization of a cell surface protein of Prevotella intermedia 17 with broad-spectrum binding activity for extracellular matrix proteins.

    PubMed

    Yu, Fan; Iyer, Divya; Anaya, Cecilia; Lewis, Janina P

    2006-11-01

    Prevotella intermedia binds and invades a variety of host cells. This binding is most probably mediated through cell surface proteins termed adhesins. To identify proteins binding to the host extracellular matrix (ECM) component, fibronectin, and study the molecular mechanism underlying bacterial colonization, we applied proteomic approaches to perform a global investigation of P. intermedia strain 17 outer membrane proteins. 2-DE followed by Far Western Blot analysis using fibronectin as a probe revealed a 29-kDa fibronectin-binding protein, designated here AdpB. The molecular identity of the protein was determined using PMF followed by a search of the P. intermedia 17 protein database. Database searches revealed the similarity of AdpB to multiple bacterial outer membrane proteins including the fibronectin-binding protein from Campylobacter jejuni. A recombinant AdpB protein bound fibronectin as well as other host ECM components, including fibrinogen and laminin, in a saturable, dose-dependent manner. Binding of AdpB to immobilized fibronectin was also inhibited by soluble fibronectin, laminin, and fibrinogen, indicating the binding was specific. Finally, immunoelectron microscopy with anti-AdpB demonstrated the cell surface location of the protein. This is the first cell surface protein with a broad-spectrum ECM-binding abilities identified and characterized in P. intermedia 17.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

    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.

  19. NCX 4040, a nitric oxide-donating aspirin derivative, inhibits Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    PubMed

    Choi, Eun-Young; Choe, So-Hui; Hyeon, Jin-Yi; Park, Hae Ryoun; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2015-12-05

    In this study, the effects and underlying mechanisms of NCX 4040, a nitric oxide (NO)-donating aspirin derivative, on the production of proinflammatory mediators were examined using murine macrophages exposed to lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in the etiology of periodontal disease. NCX 4040 significantly reduced P. intermedia LPS-induced production of inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their mRNA expression in RAW264.7 cells. Notably, NCX 4040 was much more effective than the parental compound aspirin in reducing LPS-induced production of inflammatory mediators. NCX 4040 induced the expression of heme oxygenase-1 (HO-1) in cells treated with P. intermedia LPS, and the suppressive effect of NCX 4040 on LPS-induced NO production was significantly reversed by SnPP, a competitive HO-1 inhibitor. NCX 4040 did not influence LPS-induced phosphorylation of JNK and p38. IκB-α degradation as well as nuclear translocation and DNA-binding activities of NF-κB p65 and p50 subunits induced by P. intermedia LPS were significantly reduced by NCX 4040. Besides, LPS-induced phosphorylation of STAT1 and STAT3 was significantly down-regulated by NCX 4040. Further, NCX 4040 elevated the SOCS1 mRNA in cells stimulated with LPS. This study indicates that NCX 4040 inhibits P. intermedia LPS-induced production of NO, IL-1β and IL-6 in murine macrophages through anti-inflammatory HO-1 induction and suppression of NF-κB, STAT1 and STAT3 activation, which is associated with the activation of SOCS1 signaling. NCX 4040 could potentially be a promising tool in the treatment of periodontal disease, although further studies are required to verify this.

  20. [Variations of ground vegetation and soil properties during the growth process of artificial sand-fixing Caragana intermedia plantations in desert steppe].

    PubMed

    Liu, Ren-Tao; Chai, Yong-Qing; Xu, Kun; Zhu, Fan

    2012-11-01

    To study the variation characteristics of ground vegetation and soil properties during the growth process of Caragana intermedia plantations in desert steppe is of scientific significance in revealing the ecological effect of the plantations on the restoration of desertified grassland ecosystem. In this paper, an investigation was conducted on the ground vegetation and soil properties in 6-, 15-, 24-, and 36-yr artificial sand-fixing C. intermedia plantations in desert steppe of Ningxia, Northwest China, with the variation characteristics of the ground vegetation and soil properties during the growth process of the C. intermedia plantations analyzed. With the growth and development of the plantations, the shrub crown width, height, sprout number, and basal diameter all increased significantly, the contents of soil coarse sand and fine sand had significant decrease while those of very fine sand and clay silt were in adverse, the soil organic carbon, total N, and total P contents increased linearly, and the soil pH decreased significantly. During the growth process of the plantations, the species number and individual number of ground vegetation increased significantly, and the vegetation coverage and height presented the order of 24- > 15- > 6- > 36-yr plantation. The soil texture, bulk density, nutrient contents, and pH value were the main factors affecting the species and individual number as well as the coverage of ground vegetation in C. intermedia plantations. It was suggested that in desert steppe, the growth process of artificial sand-fixing C. intermedia plantation benefited the improvement of soil conditions and the recovery of ground vegetation, and promoted the restoration of degraded grassland ecosystem in desert steppe.

  1. S1-equivariant Chern-Weil constructions on loop space

    NASA Astrophysics Data System (ADS)

    McCauley, Thomas

    2017-02-01

    We study the existence of S1-equivariant characteristic classes on certain natural infinite rank bundles over the loop space LM of a manifold M. We discuss the different S1-equivariant cohomology theories in the literature and clarify their relationships. We attempt to use S1-equivariant Chern-Weil techniques to construct S1-equivariant characteristic classes. The main result is the construction of a sequence of S1-equivariant characteristic classes on the total space of the bundles, but these classes do not descend to the base LM. Nevertheless, we conclude by identifying a class of bundles for which the S1-equivariant first Chern class does descend to LM.

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

    SciTech Connect

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

    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.

  3. A review of the bioactivity of South African herbal teas: rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia).

    PubMed

    McKay, Diane L; Blumberg, Jeffrey B

    2007-01-01

    Rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) are popular tisanes in their native South Africa and have a growing worldwide market. Both herbal teas are used traditionally for medicinal purposes and are rich in polyphenols with rooibos a rare source of the dietary dihydrochalcones, aspalathin and nothofagin. The principal polyphenols in honeybush include the xanthone mangiferin and the flavonones hesperitin and isokuranetin. Despite their divergent phytochemical and nutrient compositions, rooibos and honeybush share potent antioxidant and antimutagenic activities in vitro. Animal model studies indicate both herbal teas possess potent antioxidant, immune-modulating and chemopreventive actions. However, human studies of rooibos are limited and of honeybush are absent. No adverse effects of rooibos or honeybush consumption as tisanes have been reported.

  4. Development of microsatellites from Fothergilla ×intermedia (Hamamelidaceae) and cross transfer to four other genera within Hamamelidaceae1

    PubMed Central

    Hatmaker, E. Anne; Wadl, Phillip A.; Mantooth, Kristie; Scheffler, Brian E.; Ownley, Bonnie H.; Trigiano, Robert N.

    2015-01-01

    Premise of the study: We developed microsatellites from Fothergilla ×intermedia to establish loci capable of distinguishing species and cultivars, and to assess genetic diversity for use by ornamental breeders and to transfer within Hamamelidaceae. Methods and Results: We sequenced a small insert genomic library enriched for microsatellites to develop 12 polymorphic microsatellite loci. The number of alleles detected ranged from four to 15 across five genera within Hamamelidaceae. Shannon’s information index ranged from 0.07 to 0.14. Conclusions: These microsatellite loci provide a set of markers to evaluate genetic diversity of natural and cultivated collections and assist ornamental plant breeders for genetic studies of five popular genera of woody ornamental plants. PMID:25909044

  5. Plasma cholesterol reduction by defatted soy ontjom (fermented with Neurospora intermedia) in rats fed a cholesterol-free diet.

    PubMed

    Matsuo, M

    2000-02-01

    To popularize defatted soy ontjom (DSB-ontjom, soy product fermented with Neurospora intermedia) as a new food, I examined the plasma cholesterol-reducing effects of DSB-ontjom and DSB in rats fed cholesterol-free diets and compared the efficiencies of these effects. DSB-ontjom greatly reduced the plasma cholesterol level and increased fecal steroid excretion as compared to DSB. DSB-ontjom was rich in pepsin-resistant protein having a high bile acid binding capacity and was abundant in isoflavone-aglycones, especially daizein. The dietary fiber (DF) of DSB-ontjom stimulated the production of short-chain fatty acids (SCFAs) by intestinal microflora. The effect of DSB-ontjom on plasma cholesterol reduction was attributed to the collaborative effects of pepsin-resistant-protein, isoflavone-aglycones and SCFA-producing DF in DSB-ontjom.

  6. Conformationally Constrained, Stable, Triplet Ground State (S = 1) Nitroxide Diradicals. Antiferromagnetic Chains of S = 1 Diradicals

    SciTech Connect

    Rajca, Andrzej; Takahashi, Masahiro; Pink, Maren; Spagnol, Gaelle; Rajca, Suchada

    2008-06-30

    Nitroxide diradicals, in which nitroxides are annelated to m-phenylene forming tricyclic benzobisoxazine-like structures, have been synthesized and characterized by X-ray crystallography, magnetic resonance (EPR and {sup 1}H NMR) spectroscopy, as well as magnetic studies in solution and in solid state. For the octamethyl derivative of benzobisoxazine nitroxide diradical, the conformationally constrained nitroxide moieties are coplanar with the m-phenylene, leading to large values of 2J (2J/k > 200 K in solution and 2J/k >> 300 K in the solid state). For the diradical, in which all ortho and para positions of the m-phenylene are sterically shielded, distortion of the nitroxide moieties from coplanarity is moderate, such that the singlet-triplet gaps remain large in both solution (2J/k > 200 K) and the solid state (2J/k {approx} 400-800 K), though an onset of thermal depopulation of the triplet ground state is detectable near room temperature. These diradicals have robust triplet ground states with strong ferromagnetic coupling and good stability at ambient conditions. Magnetic behavior of the nitroxide diradicals at low temperature is best fit to the model of one-dimensional S = 1 Heisenberg chains with intrachain antiferromagnetic coupling. The antiferromagnetic coupling between the S = 1 diradicals may be associated with the methyl nitroxide C-H {hor_ellipsis} O contacts, including nonclassical hydrogen bonds. These unprecedented organic S = 1 antiferromagnetic chains are highly isotropic, compared to those of the extensively studied Ni(II)-based chains.

  7. Ethanol and Protein from Ethanol Plant By-Products Using Edible Fungi Neurospora intermedia and Aspergillus oryzae

    PubMed Central

    Bátori, Veronika; Ferreira, Jorge A.; Taherzadeh, Mohammad J.; Lennartsson, Patrik R.

    2015-01-01

    Feasible biorefineries for production of second-generation ethanol are difficult to establish due to the process complexity. An alternative is to partially include the process in the first-generation plants. Whole stillage, a by-product from dry-mill ethanol processes from grains, is mostly composed of undegraded bran and lignocelluloses can be used as a potential substrate for production of ethanol and feed proteins. Ethanol production and the proteins from the stillage were investigated using the edible fungi Neurospora intermedia and Aspergillus oryzae, respectively. N. intermedia produced 4.7 g/L ethanol from the stillage and increased to 8.7 g/L by adding 1 FPU of cellulase/g suspended solids. Saccharomyces cerevisiae produced 0.4 and 5.1 g/L ethanol, respectively. Under a two-stage cultivation with both fungi, up to 7.6 g/L of ethanol and 5.8 g/L of biomass containing 42% (w/w) crude protein were obtained. Both fungi degraded complex substrates including arabinan, glucan, mannan, and xylan where reductions of 91, 73, 38, and 89% (w/v) were achieved, respectively. The inclusion of the current process can lead to the production of 44,000 m3 of ethanol (22% improvement), around 12,000 tons of protein-rich biomass for animal feed, and energy savings considering a typical facility producing 200,000 m3 ethanol/year. PMID:26682213

  8. Ethanol and Protein from Ethanol Plant By-Products Using Edible Fungi Neurospora intermedia and Aspergillus oryzae.

    PubMed

    Bátori, Veronika; Ferreira, Jorge A; Taherzadeh, Mohammad J; Lennartsson, Patrik R

    2015-01-01

    Feasible biorefineries for production of second-generation ethanol are difficult to establish due to the process complexity. An alternative is to partially include the process in the first-generation plants. Whole stillage, a by-product from dry-mill ethanol processes from grains, is mostly composed of undegraded bran and lignocelluloses can be used as a potential substrate for production of ethanol and feed proteins. Ethanol production and the proteins from the stillage were investigated using the edible fungi Neurospora intermedia and Aspergillus oryzae, respectively. N. intermedia produced 4.7 g/L ethanol from the stillage and increased to 8.7 g/L by adding 1 FPU of cellulase/g suspended solids. Saccharomyces cerevisiae produced 0.4 and 5.1 g/L ethanol, respectively. Under a two-stage cultivation with both fungi, up to 7.6 g/L of ethanol and 5.8 g/L of biomass containing 42% (w/w) crude protein were obtained. Both fungi degraded complex substrates including arabinan, glucan, mannan, and xylan where reductions of 91, 73, 38, and 89% (w/v) were achieved, respectively. The inclusion of the current process can lead to the production of 44,000 m(3) of ethanol (22% improvement), around 12,000 tons of protein-rich biomass for animal feed, and energy savings considering a typical facility producing 200,000 m(3) ethanol/year.

  9. Associates of poor physical and mental health-related quality of life in beta thalassemia-major/intermedia

    PubMed Central

    Azarkeivan, Azita; Hajibeigi, Bashir; Alavian, Seyed Moayed; Lankarani, Maryam Moghani; Assari, Shervin

    2009-01-01

    BACKGROUND: Using two logistic regression models, we determined the associates of poor physical and mental health related quality of life (HRQoL) among beta thalassemia patients. METHODS: In this cross-sectional study which was conducted during 2006 and 2007 in outpatient adult thalassemia clinic, Blood Transfusion Organization, Tehran, Iran, Short Form 36 (SF-36) was used for measuring HRQoL in 179 patients with beta thalassemia (major/intermedia). We determined scores higher than third quartiles of obtained PCS and MCS scores as the cutoff points of good HRQoL. Poor HRQoL was defined scores lower than first quartiles of obtained PCS and MCS scores. Two distinct logistic regression models were used to derive associated variables including demographic, clinical, and psychological factors. RESULTS: The regression models suggested that poor physical HRQoL was positively associated with somatic comorbidities (OR = 1.472, CI = 1.021-2.197, p = 0.048) and depression score (OR = 8.568, CI = 2.325-31.573, p = 0.001). The variables that were associated with poor mental HRQoL were anxiety score (OR = 9.409, CI = 1.022-89.194, p = 0.049) and depression score (OR = 20.813, CI = 4.320-100.266, p < 0.001). CONCLUSIONS: Depression is associated with both poor physical and mental HRQoL among patients with major/intermedia beta thalassemia, however somatic comorbidities and anxiety are associated with poor physical and mental HRQoL, respectively. PMID:21772908

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

    PubMed

    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.

  11. Chemical and genetic tools to explore S1P biology.

    PubMed

    Cahalan, Stuart M

    2014-01-01

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

  12. 26 CFR 1.414(s)-1 - Definition of compensation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of compensation. 1.414(s)-1 Section 1.414(s)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(s)-1 Definition...

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

    PubMed

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

    2016-10-01

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

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

    PubMed

    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.

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

    PubMed

    Tsai, Hsing-Chuan; Han, May H

    2016-07-01

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

  16. Interaction of Prevotella intermedia strain 17 leucine-rich repeat domain protein AdpF with eukaryotic cells promotes bacterial internalization.

    PubMed

    Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K; Miyazaki, Hiroshi; Lewis, Janina P

    2014-06-01

    Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells.

  17. Spatial Heterogeneity of Soil Nutrients after the Establishment of Caragana intermedia Plantation on Sand Dunes in Alpine Sandy Land of the Tibet Plateau

    PubMed Central

    Li, Qingxue; Jia, Zhiqing; Zhu, Yajuan; Wang, Yongsheng; Li, Hong; Yang, Defu; Zhao, Xuebin

    2015-01-01

    The Gonghe Basin region of the Tibet Plateau is severely affected by desertification. Compared with other desertified land, the main features of this region is windy, cold and short growing season, resulting in relatively difficult for vegetation restoration. In this harsh environment, identification the spatial distribution of soil nutrients and analysis its impact factors after vegetation establishment will be helpful for understanding the ecological relationship between soil and environment. Therefore, in this study, the 12-year-old C. intermedia plantation on sand dunes was selected as the experimental site. Soil samples were collected under and between shrubs on the windward slopes, dune tops and leeward slopes with different soil depth. Then analyzed soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), available nitrogen (AN), available phosphorus (AP) and available potassium (AK). The results showed that the spatial heterogeneity of soil nutrients was existed in C. intermedia plantation on sand dunes. (1) Depth was the most important impact factor, soil nutrients were decreased with greater soil depth. One of the possible reasons is that windblown fine materials and litters were accumulated on surface soil, when they were decomposed, more nutrients were aggregated on surface soil. (2) Topography also affected the distribution of soil nutrients, more soil nutrients distributed on windward slopes. The herbaceous coverage were higher and C. intermedia ground diameter were larger on windward slopes, both of them probably related to the high soil nutrients level for windward slopes. (3) Soil “fertile islands” were formed, and the “fertile islands” were more marked on lower soil nutrients level topography positions, while it decreased towards higher soil nutrients level topography positions. The enrichment ratio (E) for TN and AN were higher than other nutrients, most likely because C. intermedia is a leguminous

  18. Spatial Heterogeneity of Soil Nutrients after the Establishment of Caragana intermedia Plantation on Sand Dunes in Alpine Sandy Land of the Tibet Plateau.

    PubMed

    Li, Qingxue; Jia, Zhiqing; Zhu, Yajuan; Wang, Yongsheng; Li, Hong; Yang, Defu; Zhao, Xuebin

    2015-01-01

    The Gonghe Basin region of the Tibet Plateau is severely affected by desertification. Compared with other desertified land, the main features of this region is windy, cold and short growing season, resulting in relatively difficult for vegetation restoration. In this harsh environment, identification the spatial distribution of soil nutrients and analysis its impact factors after vegetation establishment will be helpful for understanding the ecological relationship between soil and environment. Therefore, in this study, the 12-year-old C. intermedia plantation on sand dunes was selected as the experimental site. Soil samples were collected under and between shrubs on the windward slopes, dune tops and leeward slopes with different soil depth. Then analyzed soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), available nitrogen (AN), available phosphorus (AP) and available potassium (AK). The results showed that the spatial heterogeneity of soil nutrients was existed in C. intermedia plantation on sand dunes. (1) Depth was the most important impact factor, soil nutrients were decreased with greater soil depth. One of the possible reasons is that windblown fine materials and litters were accumulated on surface soil, when they were decomposed, more nutrients were aggregated on surface soil. (2) Topography also affected the distribution of soil nutrients, more soil nutrients distributed on windward slopes. The herbaceous coverage were higher and C. intermedia ground diameter were larger on windward slopes, both of them probably related to the high soil nutrients level for windward slopes. (3) Soil "fertile islands" were formed, and the "fertile islands" were more marked on lower soil nutrients level topography positions, while it decreased towards higher soil nutrients level topography positions. The enrichment ratio (E) for TN and AN were higher than other nutrients, most likely because C. intermedia is a leguminous shrub.

  19. Interaction of Prevotella intermedia Strain 17 Leucine-Rich Repeat Domain Protein AdpF with Eukaryotic Cells Promotes Bacterial Internalization

    PubMed Central

    Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K.; Miyazaki, Hiroshi

    2014-01-01

    Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells. PMID:24711565

  20. S1P and the birth of platelets.

    PubMed

    Hla, Timothy; Galvani, Sylvain; Rafii, Shahin; Nachman, Ralph

    2012-11-19

    Recent work has highlighted the multitude of biological functions of sphingosine 1-phosphate (S1P), which include roles in hematopoietic cell trafficking, organization of immune organs, vascular development, and neuroinflammation. Indeed, a functional antagonist of S1P(1) receptor, FTY720/Gilenya, has entered the clinic as a novel therapeutic for multiple sclerosis. In this issue of the JEM, Zhang et al. highlight yet another function of this lipid mediator: thrombopoiesis. The S1P(1) receptor is required for the growth of proplatelet strings in the bloodstream and the shedding of platelets into the circulation. Notably, the sharp gradient of S1P between blood and the interstitial fluids seems to be essential to ensure the production of platelets, and S1P appears to cooperate with the CXCL12-CXCR4 axis. Pharmacologic modulation of the S1P(1) receptor altered circulating platelet numbers acutely, suggesting a potential therapeutic strategy for controlling thrombocytopenic states. However, the S1P(4) receptor may also regulate thrombopoiesis during stress-induced accelerated platelet production. This work reveals a novel physiological action of the S1P/S1P(1) duet that could potentially be harnessed for clinical translation.

  1. The hypothalamo-hypophyseal rat explant in vitro: endocrinological studies of the pars intermedia dopaminergic neural input.

    PubMed Central

    Davis, M D

    1986-01-01

    Short-term in vitro incubation of hypothalamo-hypophyseal tissue from young rats was undertaken to discern more clearly the functional relationship between putative dopaminergic neural projections in the pars intermedia and the secretory activity of melanophore stimulating hormone (MSH). This explant consisted of a portion of the mediobasal hypothalamus containing the dopamine neurone cell bodies of interest, with the attached pituitary neuro-intermediate lobe (n.i.l.). The n.i.l. was inserted into the end of a 1 mm diameter tube attached to a perfusion pump which allowed uninterrupted sampling of medium neighbouring the n.i.l. A 'real-time' analysis of hormone secretion was obtained by immediately and continuously bioassaying for MSH. A bipolar stimulating electrode was placed on the ventral floor of the mediobasal hypothalamus either directly on the arcuate nucleus, median eminence or infundibular stalk. Electrical stimulation for 5 min (0.1-20.0 Hz) caused a transient inhibition of basal MSH secretion, while continuous stimulation (0.1-5.0 Hz) led to a much greater, long-term, reversible inhibition. In the latter, the degree of inhibition was generally dependent on stimulation rate up to a maximum at 5 Hz. Application of the dopamine D2 receptor antagonist, 1-sulpiride (0.001-0.1 microM) to the perfusion medium not only completely and reversibly blocked the stimulus-induced inhibition of MSH release but by itself, significantly increased the basal secretion rate. Applied to the isolated n.i.l., 1-sulpiride did not alter release but did prevent the inhibitory response caused by exogenously applied dopamine (0.1 microM). The gamma-aminobutyric acid receptor antagonist, bicuculline (0.01-1.0 microM), had no effect on any of the parameters studied. In explants, cutting the infundibular stalk linking the mediobasal hypothalamus with the n.i.l., mimicked the effects of 1-sulpiride by interrupting impulse flow to the gland. Thus, electrical stimulation of hypothalamic

  2. Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity.

    PubMed

    Choi, Eun-Young; Jin, Ji-Young; Lee, Ju-Youn; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2011-03-01

    Although a range of biological and pharmacological activities of melatonin have been reported, little is known about its potential anti-inflammatory efficacy in periodontal disease. In this study, we investigated the effects of melatonin on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory reactions in the periodontium, and sought to determine the underlying mechanisms of action. Melatonin suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6) at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. P. intermedia LPS-induced NF-κB-dependent luciferase activity was significantly inhibited by melatonin. Melatonin did not reduce NF-κB transcriptional activity at the level of IκB-α degradation. Melatonin blocked NF-κB signaling through the inhibition of nuclear translocation and DNA-binding activity of NF-κB p50 subunit and suppressed STAT1 signaling. Although further research is required to clarify the detailed mechanism of action, we conclude that melatonin may contribute to blockade of the host-destructive processes mediated by these two proinflammatory mediators and could be a highly efficient modulator of host response in the treatment of inflammatory periodontal disease.

  3. Insecticidal activity of a recombinant knottin peptide from Loxosceles intermedia venom and recognition of these peptides as a conserved family in the genus.

    PubMed

    Matsubara, F H; Meissner, G O; Herzig, V; Justa, H C; Dias, B C L; Trevisan-Silva, D; Gremski, L H; Gremski, W; Senff-Ribeiro, A; Chaim, O M; King, G F; Veiga, S S

    2017-02-01

    Loxosceles intermedia venom comprises a complex mixture of proteins, glycoproteins and low molecular mass peptides that act synergistically to immobilize envenomed prey. Analysis of a venom-gland transcriptome from L. intermedia revealed that knottins, also known as inhibitor cystine knot peptides, are the most abundant class of toxins expressed in this species. Knottin peptides contain a particular arrangement of intramolecular disulphide bonds, and these peptides typically act upon ion channels or receptors in the insect nervous system, triggering paralysis or other lethal effects. Herein, we focused on a knottin peptide with 53 amino acid residues from L. intermedia venom. The recombinant peptide, named U2 -sicaritoxin-Li1b (Li1b), was obtained by expression in the periplasm of Escherichia coli. The recombinant peptide induced irreversible flaccid paralysis in sheep blowflies. We screened for knottin-encoding sequences in total RNA extracts from two other Loxosceles species, Loxosceles gaucho and Loxosceles laeta, which revealed that knottin peptides constitute a conserved family of toxins in the Loxosceles genus. The insecticidal activity of U2 -SCTX-Li1b, together with the large number of knottin peptides encoded in Loxosceles venom glands, suggests that studies of these venoms might facilitate future biotechnological applications of these toxins.

  4. An Extraordinary Accumulation of (-)-Pinoresinol in Cell-Free Extracts of Forsythia intermedia: Evidence for Enantiospecific Reduction of (+)-Pinoresinol

    NASA Technical Reports Server (NTRS)

    Katayama, Takeshi; Davin, Laurence B.; Lewis, Norman G.

    1992-01-01

    Stereoselective and enantiospecific transformation mechanisms in lignan biogenesis are only now yielding to scientific inquiry: it has been shown that soluble cell-free preparations from Forsythia intermedia catalysis the formation of the enantiomerically pure lignan, (-)-secoisolariciresinol, when incubated with coniferyl alcohol in the presence of NAD(P)H and H2O2. Surprisingly, (-)-pinoresinol also accumulates in this soluble cell-free assay mixture in greater than 96% enantiomeric excess, even though it is not the naturally occurring antipode present in Forsythia sp. But these soluble cell-free preparations do not engender stereoselective coupling; instead, racemic pinoresinols are first formed, catalysed by an H2O2-dependent peroxidase reaction. An enantiospecific NAD(P)H reductase then converts (+)- pinoresinol, and not the (-)-antipode, into (-)-secoisolariciresinol. Stereoselective syntheis of(+)-pinoresinol from E-coniferyl alcohol is, however, catalysed by an insoluble enzyme preparation in F. suspensa, obtained following removal of readily soluble and ionically bound enzymes; no exogenously supplied cofactors were required other than oxygen, although the reaction was stimulated by NAD-malate addition. Thus, the overall biochemical pathway to enantiomerically pure (-)-secoisolariciresinol has been delineated.

  5. Deferiprone versus deferoxamine in thalassemia intermedia: Results from a 5-year long-term Italian multicenter randomized clinical trial.

    PubMed

    Calvaruso, Giuseppina; Vitrano, Angela; Di Maggio, Rosario; Lai, Eliana; Colletta, Grazia; Quota, Alessandra; Gerardi, Calogera; Rigoli, Luciana Concetta; Sacco, Massimiliano; Pitrolo, Lorella; Maggio, Aurelio

    2015-07-01

    In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of deferoxamine, suggesting that this drug is an alternative option in cases in which deferoxamine and deferasirox are contraindicated.

  6. Anti-diarrhoeal therapeutic potential and safety assessment of sulphated polysaccharide fraction from Gracilaria intermedia seaweed in mice.

    PubMed

    Leódido, Ana Carolina M; Costa, Luis E C; Araújo, Thiago S L; Costa, Douglas S; Sousa, Nayara A; Souza, Luan K M; Sousa, Francisca B M; Filho, Manoel D S; Vasconcelos, Daniel F P; Silva, Felipe R P; Nogueira, Kerolayne M; Araújo, Alyne R; Barros, Francisco Clark N; Freitas, Ana Lúcia P; Medeiros, Jand Venes R

    2017-04-01

    Sulphated polysaccharides extracted from algae have been extensively studied for their diverse biological activities. Thus, the purpose of this study was to evaluate the chemical composition, the anti-diarrhoeal effect and acute toxicity of a sulphated polysaccharide fraction obtained from Gracilaria intermedia (SP-Gi). Initially, the FT-IR of SP-Gi revealed to be an agaran with sulphation at C-6 of the l-galactosyl residues. The anti-diarrhoeal activity of SP-Gi was evaluated in a castor oil-induced diarrhoea model. The effects of SP-Gi on enteropooling, Na (+)-K (+)-ATPase activity, gastrointestinal transit, and gastric emptying were then examined. Subsequently, the effect of SP-Gi on diarrhoea induced by cholera toxin (CT) and Escherichia coli was examined. In addition, an acute toxicity test was conducted in accordance with OECD guideline 423. Pre-treatment with SP-Gi reduces the total faeces, total diarrhoeal faeces, and enteropooling. SP-Gi (30mg/kg p.o.) increased Na(+)/K(+)-ATPase activity and reduced gastrointestinal transit through anticholinergic mechanisms. ELISA demonstrated that SP-Gi can interact with GM1 receptors and CT. SP-Gi reduced diarrhoea induced by E. coli and prevented weight loss in the animals. Moreover, SP-Gi did not induce any toxicity signs. These results suggest that SP-Gi is a possible candidate for the treatment of diarrhoeal illnesses.

  7. Rhizobium alkalisoli sp. nov., isolated from Caragana intermedia growing in saline-alkaline soils in the north of China.

    PubMed

    Li Lu, Yang; Chen, Wen Feng; Li Han, Li; Wang, En Tao; Chen, Wen Xin

    2009-12-01

    Three rhizobial strains (CCBAU 01393(T), CCBAU 01389 and CCBAU 03239) isolated from nodules of Caragana intermedia grown in saline-alkaline soils in the north of China had identical 16S rRNA genes that showed 99.7 and 99.5 % sequence similarities with those of Rhizobium huautlense SO2(T) and Rhizobium galegae USDA 4128(T), respectively. Phylogenies of the housekeeping genes atpD, recA and glnII confirmed their distinct position, differing from recognized Rhizobium species. SDS-PAGE of whole-cell soluble proteins and a series of phenotypic and physiological tests allowed us to differentiate the novel group from all closely related recognized Rhizobium species. The levels of DNA-DNA relatedness between strain CCBAU 01393(T) and R. huautlense SO2(T) and R. galegae USDA 4128(T) were 34.9 and 20.5 %, respectively. Therefore, we propose that strains CCBAU 01393(T), CCBAU 01389 and CCBAU 03239 represent a novel species, Rhizobium alkalisoli sp. nov., with strain CCBAU 01393(T) (=LMG 24763(T)=HAMBI 3051(T)) as the type strain. This strain could form effective nodules on Caragana microphylla, Phaseolus vulgaris and Vigna radiata.

  8. Changes in formaldehyde-induced fluorescence of the hypothalamus and pars intermedia in the frog, Rana temporaria, following background adaptation.

    PubMed

    Prasada Rao, P D

    1982-01-01

    Adaptation of the frog, Rana temporaria, to a white background for 12 hr has resulted in an intense formaldehyde-induced fluorescence (FIF) in the neurons of the preoptic recess organ (PRO), paraventricular organ (PVO), nucleus infundibularis dorsalis (NID) and their basal processes permitting visualization of the PRO- and PVO-hypophysial tracts that extend into the median eminence (ME) and pars intermedia (PI); the FIF is reduced in all the structures by 3 days. In frogs adapted to a black background, for 12 hr and 3 days, there was a general reduction in the FIF of the PRO neurons and PRO-hypophysial tract. By 12 hr black background adaptation, the PVO/NID neurons and only their adjacent basal processes show FIF which was sharply reduced by 3 days, making the PVO-hypophysial tract undetectable. In the PI fibers the fluorescence was more intense in black-adapted frogs than in white-adapted ones at both the intervals studied. The simultaneous changes in the FIF of the hypothalamic nuclei, tracts and PI suggest that the PRO and PVO/NID neurons participate in PI control through release of neurotransmitter(s) at the axonal ends.

  9. Effects of mushroom and chicory extracts on the physiology and shape of Prevotella intermedia, a periodontopathogenic bacterium.

    PubMed

    Signoretto, Caterina; Marchi, Anna; Bertoncelli, Anna; Burlacchini, Gloria; Tessarolo, Francesco; Caola, Iole; Pezzati, Elisabetta; Zaura, Egija; Papetti, Adele; Lingström, Peter; Pratten, Jonathan; Spratt, David A; Wilson, Michael; Canepari, Pietro

    2011-01-01

    Contrary to the common assumption that food has a negative impact on oral health, research has shown that several foods contain a number of components with antibacterial and antiplaque activity. These natural compounds may be useful for improving daily oral hygiene. In this study we evaluate the mode of antimicrobial action of fractions of mushroom and red chicory extracts on Prevotella intermedia, a periodontopathogenic bacterium. The minimal inhibitory concentration corresponded to 0.5x compared to the natural food concentration for both extracts. This concentration resulted in a bacteriostatic effect in mushroom extract and in a slightly bactericidal effect in chicory extract. Cell mass continued to increase even after division stopped. As regards macromolecular synthesis, DNA was almost totally inhibited upon addition of either mushroom or chicory extract, and RNA to a lesser extent, while protein synthesis continued. Cell elongation occurred after septum inhibition as documented by scanning electron microscopy and cell measurement. The morphogenetic effects are reminiscent of the mode of action of antibiotics such as quinolones or β-lactams. The discovery of an antibiotic-like mode of action suggests that these extracts can be advantageously employed for daily oral hygiene in formulations of cosmetic products such as mouthwashes and toothpastes.

  10. Current Development of Anti-Cancer Drug S-1

    PubMed Central

    Giri, Anil; Shakya, Suraj; Shakya, Sujana; Sapkota, Binaya; Pramod, KC

    2016-01-01

    S-1 is a novel oral fluoropyrimidine derivative, widely used for treating gastric, pancreatic, lung, head, neck and breast carcinomas. It is designed to enhance the clinical utility of an oral fluoropyrimidine and is associated with low gastrointestinal toxicity. S-1 consists of three pharmacological agents (at a molar ratio of 1:0.4:1)-Tegafur (FT), a prodrug of 5-Fluorouracil (5-FU), 5-Chloro-2-4-Dihydroxypyridine (CDHP), which inhibits the activity of Dihydropyrimidine Dehydrogenase (DPD) and Oxonic Acid (Oxo), which reduces Gastrointestinal (GI) toxicity of 5-FU. The present article reviews the current development of clinical study of S-1. PMID:28050491

  11. 7S(1/2) ? 9S(1/2) two-photon spectroscopy of trapped francium.

    PubMed

    Simsarian, J E; Shi, W; Orozco, L A; Sprouse, G D; Zhao, W Z

    1996-12-01

    We report on the spectroscopic measurement of the (210)Fr 9S(1/2) energy obtained by two-photon excitation of atoms confined and cooled in a magneto-optic trap. The resonant intermediate level 7P(3/2) is the upper state of the trapping transition. We have measured the energy difference between the 9S(1/2) state and the 7S(1/2) ground state to be 25 671.021 +/- 0.006 cm(-1).

  12. The complete genome sequencing of Prevotella intermedia strain OMA14 and a subsequent fine-scale, intra-species genomic comparison reveal an unusual amplification of conjugative and mobile transposons and identify a novel Prevotella-lineage-specific repeat.

    PubMed

    Naito, Mariko; Ogura, Yoshitoshi; Itoh, Takehiko; Shoji, Mikio; Okamoto, Masaaki; Hayashi, Tetsuya; Nakayama, Koji

    2016-02-01

    Prevotella intermedia is a pathogenic bacterium involved in periodontal diseases. Here, we present the complete genome sequence of a clinical strain, OMA14, of this bacterium along with the results of comparative genome analysis with strain 17 of the same species whose genome has also been sequenced, but not fully analysed yet. The genomes of both strains consist of two circular chromosomes: the larger chromosomes are similar in size and exhibit a high overall linearity of gene organizations, whereas the smaller chromosomes show a significant size variation and have undergone remarkable genome rearrangements. Unique features of the Pre. intermedia genomes are the presence of a remarkable number of essential genes on the second chromosomes and the abundance of conjugative and mobilizable transposons (CTns and MTns). The CTns/MTns are particularly abundant in the second chromosomes, involved in its extensive genome rearrangement, and have introduced a number of strain-specific genes into each strain. We also found a novel 188-bp repeat sequence that has been highly amplified in Pre. intermedia and are specifically distributed among the Pre. intermedia-related species. These findings expand our understanding of the genetic features of Pre. intermedia and the roles of CTns and MTns in the evolution of bacteria.

  13. Circumpolar diversity and geographic differentiation of mtDNA in the critically endangered Antarctic blue whale (Balaenoptera musculus intermedia).

    PubMed

    Sremba, Angela L; Hancock-Hanser, Brittany; Branch, Trevor A; LeDuc, Rick L; Baker, C Scott

    2012-01-01

    The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131° longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968±0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F(ST) = 0.032, p<0.005) and microsatellite alleles (F(ST) = 0.005, p<0.05) among the six Antarctic Areas historically used by the IWC for management of blue whales.

  14. Identification, cloning, expression and functional characterization of an astacin-like metalloprotease toxin from Loxosceles intermedia (brown spider) venom

    PubMed Central

    da Silveira, Rafael B.; Wille, Ana C. M.; Chaim, Olga M.; Appel, Marcia H.; Silva, Dilza T.; Franco, Célia R. C.; Toma, Leny; Mangili, Oldemir C.; Gremski, Waldemiro; Dietrich, Carl P.; Nader, Helena B.; Veiga, Silvio S.

    2007-01-01

    Injuries caused by brown spiders (Loxosceles genus) are associated with dermonecrotic lesions with gravitational spreading and systemic manifestations. The venom has a complex composition containing many different toxins, of which metalloproteases have been described in many different species of this genus. These toxins may degrade extracellular matrix constituents acting as a spreading factor. By using a cDNA library from an Loxosceles intermedia venom gland, we cloned and expressed a 900 bp cDNA, which encoded a signal peptide and a propeptide, which corresponded to a 30 kDa metalloprotease, now named LALP (Loxosceles astacin-like protease). Recombinant LALP was refolded and used to produce a polyclonal antiserum, which showed cross-reactivity with a 29 kDa native venom protein. CD analysis provided evidence that the recombinant LALP toxin was folded correctly, was still in a native conformation and had not aggregated. LALP addition to endothelial cell cultures resulted in de-adhesion of the cells, and also in the degradation of fibronectin and fibrinogen (this could be inhibited by the presence of the bivalent chelator 1,10-phenanthroline) and of gelatin in vitro. Sequence comparison (nucleotide and deduced amino acid), phylogenetic analysis and analysis of the functional recombinant toxin revealed that LALP is related in both structure and function to the astacin family of metalloproteases. This suggests that an astacin-like toxin is present in a animal venom secretion and indicates that recombinant LALP will be a useful tool for future structural and functional studies on venom and the astacin family. PMID:17535156

  15. Identification, cloning, expression and functional characterization of an astacin-like metalloprotease toxin from Loxosceles intermedia (brown spider) venom.

    PubMed

    da Silveira, Rafael B; Wille, Ana C M; Chaim, Olga M; Appel, Marcia H; Silva, Dilza T; Franco, Célia R C; Toma, Leny; Mangili, Oldemir C; Gremski, Waldemiro; Dietrich, Carl P; Nader, Helena B; Veiga, Silvio S

    2007-09-01

    Injuries caused by brown spiders (Loxosceles genus) are associated with dermonecrotic lesions with gravitational spreading and systemic manifestations. The venom has a complex composition containing many different toxins, of which metalloproteases have been described in many different species of this genus. These toxins may degrade extracellular matrix constituents acting as a spreading factor. By using a cDNA library from an Loxosceles intermedia venom gland, we cloned and expressed a 900 bp cDNA, which encoded a signal peptide and a propeptide, which corresponded to a 30 kDa metalloprotease, now named LALP (Loxosceles astacin-like protease). Recombinant LALP was refolded and used to produce a polyclonal antiserum, which showed cross-reactivity with a 29 kDa native venom protein. CD analysis provided evidence that the recombinant LALP toxin was folded correctly, was still in a native conformation and had not aggregated. LALP addition to endothelial cell cultures resulted in de-adhesion of the cells, and also in the degradation of fibronectin and fibrinogen (this could be inhibited by the presence of the bivalent chelator 1,10-phenanthroline) and of gelatin in vitro. Sequence comparison (nucleotide and deduced amino acid), phylogenetic analysis and analysis of the functional recombinant toxin revealed that LALP is related in both structure and function to the astacin family of metalloproteases. This suggests that an astacin-like toxin is present in a animal venom secretion and indicates that recombinant LALP will be a useful tool for future structural and functional studies on venom and the astacin family.

  16. Relationship Between Serum Hepcidin and Ferritin Levels in Patients With Thalassemia Major and Intermedia in Southern Iran

    PubMed Central

    Haghpanah, Sezaneh; Esmaeilzadeh, Masoomeh; Honar, Naser; Hassani, Fatemeh; Dehbozorgian, Javad; Rezaei, Narges; Abdollahi, Maryam; Bardestani, Marzieh; Safaei, Sanaz; Karimi, Mehran

    2015-01-01

    Background: Hepcidin is a key regulator of iron absorption in humans. It is mainly affected by hypoxia and iron stores. Objectives: The current study aimed to determine the correlation between serum hepcidin and ferritin levels in patients with Thalassemia Major (TM) and Thalassemia Intermedia (TI). Patients and Methods: The current cross-sectional study investigated 88 randomly selected patients with Thalassemia, 48 TM and 40 TI, registered at the Thalassemia Clinic of Shiraz University of Medical Sciences, a referral center for Thalassemia in Southern Iran in 2013. All patients with TI were receiving Hydroxyurea (HU) 10 - 15 mg/kg/day for at least 10 years. The serum hepcidin, ferritin levels, hemoglobin (Hb) and nucleated Red Blood Cell (RBC) of the two groups were measured. Results: No statistically significant correlation was observed between serum hepcidin and ferritin levels in any of the two groups of patients with TM (rs = 0.02, P = 0.892) or TI (rs = 0.055, P = 0.734). The median Interquartile Range (IQR) for serum hepcidin and ferritin levels were significantly higher in TM compared to TI group, (hepcidin: 87.6 (43.9) vs. 51.8 (23.4), P < 0.001; ferritin: 2208 (3761) vs. 465 (632), P < 0.001). Conclusions: There was insignificant correlation between serum hepcidin and ferritin levels in the two groups of patients with TM and TI. It seems that regulation of hepcidin in patients with Thalassemia is more affected by erythropoeitic activity than iron stores. Also, hepcidin levels were significantly higher in patients with TM than TI, possibly due to higher erythropoeitic activity in TI. In TI, it seems that low dose HU increases Hb levels and leads to transfusion-independence, but it is not high enough to suppress bone marrow activity and ineffective erythropoiesis. Consequently, serum hepcidin level decreases. PMID:26421179

  17. First description of the rs45496295 polymorphism of the C/EBPE gene in β-thalassemia intermedia patients.

    PubMed

    Mejri, Awatef; Mansri, Marwa; Hadj Fredj, Sondess; Ouali, Faida; Bibi, Amina; Hafsia, Raouf; Messaoud, Taieb; Siala, Hajer

    2016-11-01

    The C/EBPE gene, located in 14q11.2, encodes for a B/zip-type transcription factor. The C/EBPɛ is involved in terminal differentiation and functional maturity of granulocyte progenitor cells and in cell apoptosis during myeloid differentiation. A C/EBPE gene has recently been described as a candidate gene involved in clinical variability of β-thalassemia (β-thal). In this study, the C/EBPE gene was sequenced in 146 subjects divided into the severe type of β-thal major (β-TM) and moderate type of β-thal intermedia (β-TI), and a control group. The analysis identified the rs45496295 (C > T) polymorphism in the heterozygous state in 73.9% β-TI patients, which was not the case in the β-TM patients or in the control group. Thus, the T allele is consequently associated with the β-TI group (p = 10(-3)). According to the Human Splicing Finder (version 3.0, Marseille, France), the presence of the rs45496295 polymorphism leads the creation of a new intronic exotic splicing enhancer (ESE) site. Moreover, the T allele of rs45496295 is associated with a lower transfusion regimen (p = 10(-3)) and a higher pretransfusion hemoglobin (Hb) rate (p = .006). The comparison of several factors concerning T allele carriers and non-carriers showed that the T allele does not act on the Hb F rate. The T allele of rs45496295, associated with moderate type of β-thal, seems to modify the C/EBPɛ action, thereby preventing the hemolysis.

  18. Extracellular biosynthesis of silver nanoparticles using a novel and non-pathogenic fungus, Neurospora intermedia: controlled synthesis and antibacterial activity.

    PubMed

    Hamedi, Sepideh; Shojaosadati, Seyed Abbas; Shokrollahzadeh, Soheila; Hashemi-Najafabadi, Sameereh

    2014-02-01

    In the present study, the biosynthesis of silver nanoparticles (AgNPs) using Neurospora intermedia, as a new non-pathogenic fungus was investigated. For determination of biomass harvesting time, the effect of fungal incubation period on nanoparticle formation was investigated using UV-visible spectroscopy. Then, AgNPs were synthesized using both culture supernatant and cell-free filtrate of the fungus. Two different volume ratios (1:100 and 1:1) of the culture supernatant to the silver nitrate were employed for AgNP synthesis. In addition, cell-free filtrate and silver nitrate were mixed in presence and absence of light. Smallest average size and highest productivity were obtained when using equal volumes of the culture supernatant and silver nitrate solution as confirmed by UV-visible spectra of colloidal AgNPs. Comparing the UV-visible spectra revealed that using cell-free filtrate for AgNP synthesis resulted in the formation of particles with higher stability and monodispersity than using culture supernatant. The absence of light in cell-free filtrate mediated synthesis led to the formation of nanoparticles with the lowest rate and the highest monodispersity. The presence of elemental silver in all prepared samples was confirmed using EDX, while the crystalline nature of synthesized particles was verified by XRD. FTIR results showed the presence of functional groups which reduce Ag(+) and stabilize AgNPs. The presence of nitrate reductase was confirmed in the cell-free filtrate of the fungus suggesting the potential role of this enzyme in AgNP synthesis. Synthesized particles showed significant antibacterial activity against E. coli as confirmed by examining the growth curve of bacterial cells exposed to AgNPs.

  19. Expression and immunological cross-reactivity of LALP3, a novel astacin-like metalloprotease from brown spider (Loxosceles intermedia) venom.

    PubMed

    Morgon, Adriano M; Belisario-Ferrari, Matheus R; Trevisan-Silva, Dilza; Meissner, Gabriel O; Vuitika, Larissa; Marin, Brenda; Tashima, Alexandre K; Gremski, Luiza H; Gremski, Waldemiro; Senff-Ribeiro, Andrea; Veiga, Silvio S; Chaim, Olga M

    2016-01-01

    Loxosceles spiders' venom comprises a complex mixture of biologically active toxins, mostly consisting of low molecular mass components (2-40 kDa). Amongst, isoforms of astacin-like metalloproteases were identified through transcriptome and proteome analyses. Only LALP1 (Loxosceles Astacin-Like protease 1) has been characterized. Herein, we characterized LALP3 as a novel recombinant astacin-like metalloprotease isoform from Loxosceles intermedia venom. LALP3 cDNA was cloned in pET-SUMO vector, and its soluble heterologous expression was performed using a SUMO tag added to LALP3 to achieve solubility in Escherichia coli SHuffle T7 Express LysY cells, which express the disulfide bond isomerase DsbC. Protein purification was conducted by Ni-NTA Agarose resin and assayed for purity by SDS-PAGE under reducing conditions. Immunoblotting analyses were performed with specific antibodies recognizing LALP1 and whole venom. Western blotting showed linear epitopes from recombinant LALP3 that cross-reacted with LALP1, and dot blotting revealed conformational epitopes with native venom astacins. Mass spectrometry analysis revealed that the recombinant expressed protein is an astacin-like metalloprotease from L. intermedia venom. Furthermore, molecular modeling of LALP3 revealed that this isoform contains the zinc binding and Met-turn motifs, forming the active site, as has been observed in astacins. These data confirmed that LALP3, which was successfully obtained by heterologous expression using a prokaryote system, is a new astacin-like metalloprotease isoform present in L. intermedia venom.

  20. Detection and genetic characterization of β-lactamases in Prevotella intermedia and Prevotella nigrescens isolated from oral cavity infections and peritonsillar abscesses.

    PubMed

    Fernández-Canigia, Liliana; Cejas, Daniela; Gutkind, Gabriel; Radice, Marcela

    2015-06-01

    A prospective analysis on β-lactam resistance mechanisms and β-lactamase prevalence was conducted on Prevotella intermedia and Prevotella nigrescens recovered from patients with chronic periodontitis and peritonsillar abscesses. Both phenotypic and genotypic methods were performed to characterize the β-lactamases, their coding genes and their genetic contexts. Overall, β-lactamase production was observed in 64% (16/25) P. intermedia and 23.8% (5/21) P. nigrescens (p < 0.01). Besides higher β-lactamase production rates were observed in P. intermedia (8/16) than in P. nigrescens (2/16) recovered from chronic periodontitis, almost all isolates from peritonsillar abscesses were producers (8/9 and 3/3, respectively). cfxA, but not cepA and cblA, was detected in those isolates, which were previously categorized as β-lactamase producers. CfxA producing isolates displayed higher β-lactam MICs than non-producers in both species. The most frequent allele was cfxA2, followed by cfxA3 and a new allelic variant named cfxA6. The analysis of the downstream flanking region in the three cfxA variants revealed the association with mobA of Tn4555, suggesting their localization in a mobilizable element. β-lactam resistance and cfxA carriage prevalence seems to be not only related to the bacterial species but also to the infection site.

  1. [Evaluation of Drug Interaction between S-1 and Warfarin].

    PubMed

    Yamamoto, Kaori; Suzuki, Shinya; Ikegawa, Kiwako; Nomura, Hisanaga; Fuse, Nozomu; Saito, Shinichiro

    2016-01-01

    Prolonged prothrombin time is observed in patients taking warfarin (WF) with a fluoropyrimidine, such as S-1. When WF is combined with S-1, the prothrombin time-international normalized ratio (PT-INR) and dose adjustment of WF should be closely monitored. To date, no clinical data have been reported in terms of the relation between temporal variation of PT-INR and its therapeutic range. In this study, we retrospectively collected patients' clinical data including PT-INR. We identified 21 patients receiving WF therapy before the start of S-1 treatment. Patient characteristics were male/female: 18/3, median age: 69 (range 48-81) years old, cancer of gastric/lung/pancreatic/other: 8/5/4/4, and history of deep vein thrombosis (DVT)/atrial fibrillation (AF)/cerebral infarction (CI)/other: 11/6/2/2. The PT-INR of 16 patients exceeded normal upper limits after taking S-1 with WF. The median time to exceed the PT-INR upper therapeutic range is 25 (range 3-77) days. Patients receiving WF anticoagulant therapy concomitant with S-1 should have their PT-INR closely monitored and WF doses adjusted accordingly.

  2. The S=1 Underscreened Anderson Lattice model for Uranium compounds

    NASA Astrophysics Data System (ADS)

    Thomas, C.; Simões, A. S. R.; Iglesias, J. R.; Lacroix, C.; Perkins, N. B.; Coqblin, B.

    2011-01-01

    Magnetic properties of uranium and neptunium compounds showing coexistence of the Kondo effect and ferromagnetic order are investigated within the degenerate Anderson Lattice Hamiltonian, describing a 5f2 electronic configuration with S = 1 spins. Through the Schrieffer-Wolff transformation, both an exchange Kondo interaction for the S = 1 f-spins and an effective f-band term are obtained, allowing to describe the coexistence of Kondo effect and ferromagnetic ordering and a weak delocalization of the 5f-electrons. We calculate the Kondo and Curie temperatures and we can account for the pressure dependence of the Curie temperature of UTe.

  3. L5 – S1 Segmental Kinematics After Facet Arthroplasty

    PubMed Central

    Voronov, Leonard I.; Havey, Robert M.; Rosler, David M.; Sjovold, Simon G.; Rogers, Susan L.; Carandang, Gerard; Ochoa, Jorge A.; Yuan, Hansen; Webb, Scott

    2009-01-01

    Background Facet arthroplasty is a motion restoring procedure. It is normally suggested as an alternative to rigid fixation after destabilizing decompression procedures in the posterior lumbar spine. While previous studies have reported successful results in reproducing normal spine kinematics after facet replacement at L4-5 and L3-4, there are no data on the viability of facet replacement at the lumbosacral joint. The anatomy of posterior elements and the resulting kinematics at L5-S1 are distinctly different from those at superior levels, making the task of facet replacement at the lumbosacral level challenging. This study evaluated the kinematics of facet replacement at L5-S1. Methods Six human cadaveric lumbar spines (L1-S1, 46.7 ± 13.0 years) were tested in the following sequence: (1) intact (L1-S1), (2) complete laminectomy and bilateral facetectomy at L5-S1, and (3) implantation of TFAS-LS (Lumbosacral Total Facet Arthroplasty System, Archus Orthopedics, Redmond, Washington) at L5-S1 using pedicle screws. Specimens were tested in flexion (8Nm), extension (6Nm), lateral bending (LB, ± 6Nm), and axial rotation (AR, ± 5Nm). The level of significance was α = .017 after Bonferroni correction for three comparisons: (1) intact vs. destabilized, (2) destabilized vs. reconstructed, and (3) intact vs. reconstructed. Results Laminectomy-facetectomy at L5-S1 increased the L5-S1 angular range of motion (ROM) in all directions. Flexion-extension (F-E) ROM increased from 15.3 ± 2.9 to 18.7 ± 3.5 degrees (P < .017), LB from 8.2 ± 1.8 to 9.3 ± 1.6 degrees (P < .017), and AR from 3.7 ± 2.0 to 5.9 ± 1.8 degrees (P < .017). The facet arthroplasty system decreased ROM compared to the laminectomy-facetectomy condition in all tested directions (P < .017). The facet arthroplasty system restored the L5-S1 ROM to its intact levels in LB and AR (P > .017). F-E ROM after the facet arthroplasty system implantation was smaller than the intact value (10.1 ± 2.2 vs. 15.3 ± 2

  4. Excitation of nutation by the global radiational S1 tide

    NASA Astrophysics Data System (ADS)

    Schindelegger, M.; Salstein, D. A.; Einspigel, D.; Boehm, J.

    2014-12-01

    Cyclic mass redistributions in the atmosphere and oceans related to the global radiational S1 tide elicit seasonal perturbations of Earth's nutation at a level of 0.1 mas (milliarcseconds). The present study provides an up-to-date assessment of these excitation effects on the basis of 10-year surface and isobaric level data from three, previously unavailable global atmospheric reanalysis systems. We retrieve numerical values of in- and out-of-phase nutation corrections for seasonally modulated S1 variations and indicate how model improvements, specifically in terms of the representation of tidal oscillations, lead to different estimates with respect to earlier reanalyses. Motion term signals in nutation display a close agreement across all probed datasets, whereas larger disparities remain among mass term excitation estimates due to their dependency on small-scale diurnal surface pressure oscillations. A simple time-stepping model for barotropic ocean dynamics, based on the shallow water equations and driven by air pressure tide climatologies, represents an appropriate means to determine global S1 estimates of sea level heights and currents that are consistent with the respective forcing fields from each reanalysis. We address the intricacies of constructing such a model and compare our preliminary oceanic angular momentum solutions to those from more established hydrodynamic forward integrations. The combined influence of the S1 tide on Earth's nutation, associated with both atmosphere and ocean dynamics, is found to yield a rough agreement with observations from geodetic VLBI (Very Long Baseline Interferometry) measurements.

  5. Role of the cysteine protease interpain A of Prevotella intermedia in breakdown and release of haem from haemoglobin.

    PubMed

    Byrne, Dominic P; Wawrzonek, Katarzyna; Jaworska, Anna; Birss, Andrew J; Potempa, Jan; Smalley, John W

    2009-12-14

    The gram-negative oral anaerobe Prevotella intermedia forms an iron(III) protoporphyrin IX pigment from haemoglobin. The bacterium expresses a 90 kDa cysteine protease, InpA (interpain A), a homologue of Streptococcus pyogenes streptopain (SpeB). The role of InpA in haemoglobin breakdown and haem release was investigated. At pH 7.5, InpA mediated oxidation of oxyhaemoglobin to hydroxymethaemoglobin [in which the haem iron is oxidized to the Fe(III) state and which carries OH- as the sixth co-ordinate ligand] by limited proteolysis of globin chains as indicated by SDS/PAGE and MALDI (matrix-assisted laser-desorption ionization)-TOF (time-of-flight) analysis. Prolonged incubation at pH 7.5 did not result in further haemoglobin protein breakdown, but in the formation of a haemoglobin haemichrome (where the haem Fe atom is co-ordinated by another amino acid ligand in addition to the proximal histidine residue) resistant to degradation by InpA. InpA-mediated haem release from hydroxymethaemoglobin-agarose was minimal compared with trypsin at pH 7.5. At pH 6.0, InpA increased oxidation at a rate greater than auto-oxidation, producing aquomethaemoglobin (with water as sixth co-ordinate ligand), and resulted in its complete breakdown and haem loss. Aquomethaemoglobin proteolysis and haem release was prevented by blocking haem dissociation by ligation with azide, whereas InpA proteolysis of haem-free globin was rapid, even at pH 7.5. Both oxidation of oxyhaemoglobin and breakdown of methaemoglobin by InpA were inhibited by the cysteine protease inhibitor E-64 [trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane]. In summary, we conclude that InpA may play a central role in haem acquisition by mediating oxyhaemoglobin oxidation, and by degrading aquomethaemoglobin in which haem-globin affinity is weakened under acidic conditions.

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

    PubMed

    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.

  7. Interleukin 10–Dominant Immune Response and Increased Risk of Cutaneous Leishmaniasis After Natural Exposure to Lutzomyia intermedia Sand Flies

    PubMed Central

    Carvalho, Augusto M.; Cristal, Juqueline R.; Muniz, Aline C.; Carvalho, Lucas P.; Gomes, Regis; Miranda, José C.; Barral, Aldina; Carvalho, Edgar M.; de Oliveira, Camila I.

    2015-01-01

    Background. Leishmaniasis is caused by parasites transmitted to the vertebrate host by infected sand flies. During transmission, the vertebrate host is also inoculated with sand fly saliva, which exerts powerful immunomodulatory effects on the host's immune response. Methods. We conducted a prospective cohort analysis to characterize the human immune response to Lutzomyia intermedia saliva in 264 individuals, from an area for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Results. Antibodies were found in 150 individuals (56.8%); immunoglobulin G1 and G4 were the predominant subclasses. Recall responses to salivary gland sonicate showed elevated production of interleukin 10 (IL-10), interleukin 13, interferon γ, CXCL9, and CCL2 compared with controls. CD4+CD25+ T cells, including Foxp3+ cells, were the main source of IL-10. L. braziliensis replication was increased (P < .05) in macrophages cocultured with saliva-stimulated lymphocytes from exposed individuals and addition of anti–IL-10 reverted this effect. Positive correlation between antibody response to saliva and cellular response to Leishmania was not found. Importantly, individuals seropositive to saliva are 2.1 times more likely to develop CL (relative risk, 2.1; 95% confidence interval, 1.07–4.2; P < .05). Conclusions. Exposure to L. intermedia sand flies skews the human immune response, facilitating L. braziliensis survival in vitro, and increases the risk of developing CL. PMID:25596303

  8. Cumberlandian Mollusk Conservation Program. Activity 3: identification of fish hosts. [Conradilla caelata; Quadrula intermedia; Epioblasma brevidens; Epioblasma capsaeformis; Epioblasma triquetra; Quadrula cylindrica; Carunculina moesta

    SciTech Connect

    Hill, D.M.

    1986-02-01

    A key element of the Cumberlandian Mollusk Conservation Program undertaken by TVA in 1979 was the determination of fish hosts of Cumberlandian mussel species unique to the Tennessee River drainage and especially the species whose habitat would be inundated by completion of Columbia Dam on the Duck River, Tennessee. Principal emphasis was placed on the birdwing pearly mussel, Conradilla caelata and the Cumberland monkeyface, Quadrula intermedia - two federally listed endangered species with limited distributions outside the proposed inundation zone of the Duck River. Additional species studied included three species of the genus Epioblasma (E. brevidens, E. capsaeformis, and E. triquetra), Quadrula cylindrica, Villosa iris, and Carunculina moesta. Experimental glochidial infection of 55 fish species resulted in the establishment of the following mussel-fish host relationships: Conradilla caelata - Etheostoma zonale; Quadrule intermedia - Hybopsis dissimilis, Hybopsis insignis; Epioblasma brevidens - Etheostoma blennioides, Etheostoma maculatum, Etheostoma rufilineatum, Etheostoma simoterum, Percina caprodes, Cottus carolinae; Epioblasma capsaeformis - Etheostoma maculatum, Etheostoma rufilineatum, Percina sciera, Cottus carolinae; Epioblasma triquetra - Percina caprodes, Cottus carolinae; Quadrula cylindrica - Notropis galacturus, Notropis spilopterus, Hybopsis amblops; and Carunculina moesta - Lepomis cyanellus, Lepomis megalotis.

  9. Effects of fruit and vegetable low molecular mass fractions on gene expression in gingival cells challenged with Prevotella intermedia and Actinomyces naeslundii.

    PubMed

    Canesi, Laura; Borghi, Cristina; Stauder, Monica; Lingström, Peter; Papetti, Adele; Pratten, Jonathan; Signoretto, Caterina; Spratt, David A; Wilson, Mike; Zaura, Egija; Pruzzo, Carla

    2011-01-01

    Low molecular mass (LMM) fractions obtained from extracts of raspberry, red chicory, and Shiitake mushrooms have been shown to be an useful source of specific antibacterial, antiadhesion/coaggregation, and antibiofilm agent(s) that might be used for protection towards caries and gingivitis. In this paper, the effects of such LMM fractions on human gingival KB cells exposed to the periodontal pathogens Prevotella intermedia and Actinomyces naeslundii were evaluated. Expression of cytokeratin 18 (CK18) and β4 integrin (β4INT) genes, that are involved in cell proliferation/differentiation and adhesion, and of the antimicrobial peptide β2 defensin (HβD2) in KB cells was increased upon exposure to either live or heat-killed bacteria. All LMM fractions tested prevented or reduced the induction of gene expression by P. intermedia and A. naeslundii depending on the experimental conditions. Overall, the results suggested that LMM fractions could modulate the effects of bacteria associated with periodontal disease in gingival cells.

  10. The haem pigment of the oral anaerobes Prevotella nigrescens and Prevotella intermedia is composed of iron(III) protoporphyrin IX in the monomeric form.

    PubMed

    Smalley, John W; Silver, Jack; Birss, Andrew J; Withnall, Robert; Titler, Philip J

    2003-07-01

    The haem pigment of Porphyromonas gingivalis is composed of micro -oxo bishaem, [Fe(III)PPIX](2)O, but the nature of that generated by Prevotella species has not been established. Mössbauer, Raman and UV-visible spectrophotometry were used to characterize the haem pigment of Prevotella intermedia and Prevotella nigrescens. Mössbauer and Raman spectroscopy revealed the major haem species to be monomeric iron protoporphyrin IX, Fe(III)PPIX.OH (haematin). The terminal growth pH of both species on blood agar was between 5.8 and 6.0, which favours the formation and maintenance of monomeric Fe(III)PPIX.OH. Incubation of Pr. nigrescens and Pr. intermedia with oxyhaemoglobin at pH 6.5 resulted in formation of aquomethaemoglobin which was degraded to generate Fe(III)PPIX.OH which in turn became cell-associated, whilst incubation at pH 7.5 resulted in formation of [Fe(III)PPIX](2)O. It is concluded that both Prevotella species degrade oxyhaemoglobin to form [Fe(III)PPIX](2)O as an intermediate, which is converted to Fe(III)PPIX.OH through a depression in pH. The low pH encourages cell-surface deposition of insoluble Fe(III)PPIX.OH which would act as a barrier against oxygen and reactive oxygen species, and also protect against H(2)O(2) through its inherent catalase activity.

  11. Evaluation of anti-microbial activity of spore powder of Ganoderma lucidum on clinical isolates of Prevotella intermedia: A pilot study

    PubMed Central

    Nayak, Ranganath N.; Dixitraj, P. T.; Nayak, Aarati; Bhat, Kishore

    2015-01-01

    Aim: This study aimed at evaluating the anti-microbial activity of spore powder of Ganoderma lucidum on Prevotella intermedia isolated from subgingival plaque from chronic periodontitis patients. Settings and Design: Written informed consent was obtained from each subject enrolled in the study. The Institutional Ethics Committee granted the ethical clearance for the study. Materials and Methods: This study included 20 patients diagnosed with chronic periodontitis. Pooled subgingival plaque samples were collected using sterile curettes from the deepest sites of periodontal pockets. The collected samples were then transported in 1 mL of reduced transport fluid. The organisms were cultured and confirmed. These organisms were then used for minimum inhibitory concentration (MIC) procedure. Statistical Analysis: Mean of the MIC value obtained was calculated. Results: Thirteen out of the 20 clinical samples were tested that showed sensitivity at various concentrations. Five samples showed sensitivity at all concentrations. Twelve samples showed sensitivity at 8 mcg/ml. Eleven samples showed sensitivity at 4 mcg/ml, 8 samples showed sensitivity at 2 mcg/ml, and 5 samples showed sensitivity even at 1 mcg/ml. Mean MIC value of G. lucidum spore powder for P. intermedia obtained was 3.62 mcg/ml. Conclusion: G. lucidum with its multipotential bioactivity could be used as an anti-microbial, in conjunction with conventional therapy in periodontal disease. PMID:26604581

  12. The Global S_1 Tide in Earth's Nutation

    NASA Astrophysics Data System (ADS)

    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.

  13. The global S1 tide and Earth's nutation

    NASA Astrophysics Data System (ADS)

    Schindelegger, M.; Böhm, J.; Salstein, D. A.

    2015-08-01

    Diurnal S1 tidal atmospheric oscillations induced by the cyclic heating of air masses through solar radiation elicit a small contribution to Earth's prograde annual nutation at a level of 100 μas (microarcseconds). Previously published estimates of this Sun-synchronous perturbation based on angular momentum series from global geophysical fluid models have however diverged, and within the present conventional nutation theory, the effect has been instead accounted for in an empirical manner based on analyzing residual spectra of observed celestial pole offsets. This study constitutes a first, tentative reassessment of the S1 signal in nutation by resorting to modern-day atmospheric reanalyses as well as available hydrodynamic solutions for diurnal oceanic angular momentum changes that are driven by daily air pressure variations at the water surface. We elucidate the global character of the S1 tide with particular regard to Earth rotation variations and investigate to which extent atmospheric and oceanic excitation terms from various sources can be superimposed. The combined influence of the principal diurnal tide on Earth's nutation, associated with both atmosphere and ocean dynamics, is found to yield a sound agreement with its observational evidence from geodetic VLBI (Very Long Baseline Interferometry) measurements.

  14. Angular momentum budget of the radiational S1 ocean tide

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Dobslaw, Henryk; Poropat, Lea; Salstein, David; Böhm, Johannes

    2016-04-01

    The balance of diurnal S1 oceanic angular momentum (OAM) variations through torques at the sea surface and the bottom topography is validated using both a barotropic and a baroclinic numerical tide model. This analysis discloses the extent to which atmosphere-driven S1 forward simulations are reliable for use in studies of high-frequency polar motion and changes in length-of-day. Viscous and dissipative torques associated with wind stress, bottom friction, as well as internal tidal energy conversion are shown to be small, and they are overshadowed by gravitational and pressure-related interaction forces. In particular, the zonal OAM variability of S1 is almost completely balanced by the water pressure torque on the local bathymetry, whereas in the prograde equatorial case also the air pressure torque on the seafloor as well as ellipsoidal contributions from the non-spherical atmosphere and solid Earth must be taken into account. Overall, the OAM budget is well closed in both the axial and the equatorial directions, thus allowing for an identification of the main diurnal angular momentum sinks in the ocean. The physical interaction forces are found to be largest at shelf breaks and continental slopes in low latitudes, with the most dominant contribution coming from the Indonesian archipelago.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Osmo-, Thermo- and Ethanol- Tolerances of Saccharomyces cerevisiae S1

    PubMed Central

    Balakumar, Sandrasegarampillai; Arasaratnam, Vasanthy

    2012-01-01

    Saccharomyces cerevisiae S1, which is a locally isolated and improved strain showed viability at 40, 45 and 50°C and produced ethanol at 40, 43 and 45°C. When the cells were given heat shock at 45°C for 30min and grown at 40°C, 100% viability was observed for 60h, and addition of 200gL−1 ethanol has led to complete cell death at 30h. Heat shock given at 45°C (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−1sorbitol. In presence of sorbitol (200gL−1) and ethanol (50gL−1) at 40°C, 46% viability was retained by S. cerevisiae S1 at 48h and it was improved to 80% by soy flour supplementation. PMID:24031814

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

    PubMed

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

    2014-06-01

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

  18. Lama glama αS1-casein: Identification of new polymorphisms in the CSN1S1 gene.

    PubMed

    Pauciullo, A; Gauly, M; Cosenza, G; Wagner, H; Erhardt, G

    2017-02-01

    South American camelids have been poorly genetically investigated and little information is available in llamas (Lama glama) regarding the diversity of the caseins at the protein and gene level. Exon skipping and duplication events previously reported in the αS1-casein gene (CSN1S1) led us to investigate the genetic variability at this locus. Seventy-two positive clones for the αS1-casein transcripts were analyzed and randomly sequenced. The comparative analysis of the sequences revealed 2 transitions, c.366A>G and c.690T>C, at the 10th nucleotide of exon 12 and 94 bp of exon 19, respectively. These SNP are responsible for 2 amino acid changes, Ile→Val in position 86 and Tyr→His in position 194 of the mature protein. Both polymorphisms clarify the genetic events behind the protein variants A and B. This result was confirmed by isoelectric focusing analysis of llama milk samples. Quick methods based on PCR-RFLP and allele-specific PCR were set up for allelic discrimination in a population of 128 animals. Based on genotyping results, 4 haplotypes were observed and the estimated frequencies indicated B as the most common haplotype (0.629) in the investigated population. These data add knowledge to the genetic variability of a species little investigated, and open opportunity for new investigation in the field of milk protein for South American camelids, including the possibility, in the future, to select alleles with favorable characteristics.

  19. Speciation history and widespread introgression in the European short-call tree frogs (Hyla arborea sensu lato, H. intermedia and H. sarda).

    PubMed

    Gvoždík, Václav; Canestrelli, Daniele; García-París, Mario; Moravec, Jiří; Nascetti, Giuseppe; Recuero, Ernesto; Teixeira, José; Kotlík, Petr

    2015-02-01

    European tree frogs (Hyla) characterized by short temporal parameters of the advertisement call form six genetically differentiated but morphologically cryptic taxa, H. arborea sensu stricto, H. orientalis and H. molleri from across Europe to western Asia (together referred to as H. arborea sensu lato), two putative taxa within H. intermedia (Northern and Southern) from the Italian Peninsula and Sicily, and H. sarda from Sardinia and Corsica. Here, we assess species limits and phylogenetic relationships within these 'short-call tree frogs' based on mitochondrial DNA and nuclear protein-coding markers. The mitochondrial and nuclear genes show partly incongruent phylogeographic patterns, which point to a complex history of gene flow across taxa, particularly in the Balkans. To test the species limits in the short-call tree frogs and to infer the species tree, we used coalescent-based approaches. The monophyly of H. arborea sensu lato is supported by the mtDNA as well as by the all-gene species tree. The Northern and Southern lineages of H. intermedia have been connected by nuclear gene flow (despite their deep mtDNA divergence) and should be treated as conspecific. On the contrary, the parapatric taxa within H. arborea sensu lato should be considered distinct species (H. arborea, H. orientalis, H. molleri) based on the coalescent analysis, although signs of hybridization were detected between them (H. arborea×H. orientalis; H. arborea×H. molleri). A mitochondrial capture upon secondary contact appears to explain the close mtDNA relationship between the geographically remote Iberian H. molleri and H. orientalis from around the Black Sea. Introgressive hybridization occurred also between the Balkan H. arborea and northern Italian H. intermedia, and between the Minor Asiatic H. orientalis and Arabian H. felix arabica (the latter belonging to a different acoustic group/clade). Our results shed light on the species limits in the European short-call tree frogs and show

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

    PubMed

    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) <0.2 nM. In vivo experiments are consistent with S1P1 receptor agonism alone being sufficient for achieving desired lymphocyte-lowering effect.

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

    PubMed

    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. Influence of altitude, latitude and season of collection (Bergmann's rule) on the dimensions of Lutzomyia intermedia (Lutz & Neiva, 1912) (Diptera, Psychodidae, Phlebotominae).

    PubMed

    Marcondes, C B; Lozovei, A L; Falqueto, A; Brazil, R P; Galati, E; Aguiar, G; Souza, N

    1999-01-01

    The influence of altitude and latitude on some structure sizes of Lutzomyia intermedia was noted; several structures of insects collected in higher localities were greater, according to Bergmann's rule. This influence was more remarkable in two localities of the State of Espírito Santo, probably due to greater differences in altitude. Comparing insects from different latitudes, more differences were noted in comparisons of insects from low altitude localities than in those of material from higher altitudes. The small number of differences between insects collected in July and in December does not indicate a defined influence of season and temperature on the size of adults. The possible epidemiological implications of these variations are discussed.

  3. Determination of antibacterial activity of green coffee bean extract on periodontogenic bacteria like Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans: An in vitro study

    PubMed Central

    Bharath, Nagaraj; Sowmya, Nagur Karibasappa; Mehta, Dhoom Singh

    2015-01-01

    Background: The aim of this study was to evaluate the antibacterial activity of pure green coffee bean extract on periodonto pathogenic bacteria Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa). Materials and Methods: Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were used to assess the antibacterial effect of pure green coffee bean extract against periodonto pathogenic bacteria by micro dilution method and culture method, respectively. Results: MIC values of Pg, Pi and Aa were 0.2 μg/ml whereas Fn showed sensitive at concentration of 3.125 μg/ml. MBC values mirrors the values same as that of MIC. Conclusion: Antimicrobial activity of pure green coffee bean extract against Pg, Pi, Fn and Aa suggests that it could be recommended as an adjunct to mechanical therapy in the management of periodontal disease. PMID:26097349

  4. A novel ICK peptide from the Loxosceles intermedia (brown spider) venom gland: cloning, heterologous expression and immunological cross-reactivity approaches.

    PubMed

    Matsubara, Fernando Hitomi; Gremski, Luiza Helena; Meissner, Gabriel Otto; Constantino Lopes, Eduardo Soares; Gremski, Waldemiro; Senff-Ribeiro, Andrea; Chaim, Olga Meiri; Veiga, Silvio Sanches

    2013-09-01

    The venom of a Loxosceles spider is composed of a complex mixture of biologically active components, consisting predominantly of low molecular mass molecules (3-45 kDa). Transcriptome analysis of the Loxosceles intermedia venom gland revealed ESTs with similarity to the previously described LiTx peptides. Sequences similar to the LiTx3 isoform were the most abundant, representing approximately 13.9% of all ESTs and 32% of the toxin-encoding messengers. These peptides are grouped in the ICK (Inhibitor Cystine Knot) family, which contains single chain molecules with low molecular mass (3-10 kDa). Due to their high number of cysteine residues, ICK peptides form intramolecular disulfide bridges. The aims of this study were to clone and express a novel ICK peptide isoform, as well as produce specific hyperimmune serum for immunoassays. The corresponding cDNA was amplified by PCR using specific primers containing restriction sites for the XhoI and BamHI enzymes; this PCR product was then ligated in the pET-14b vector and transformed into E. coli AD494 (DE3) cells. The peptide was expressed by IPTG induction for 4 h at 30 °C and purified by affinity chromatography with Ni-NTA resin. Hyperimmune serum to the recombinant peptide was produced in rabbits and was able to specifically recognize both the purified recombinant peptide and the native form present in the venom. Furthermore, the recombinant peptide was recognized by antisera raised against L. intermedia, L. gaucho and L. laeta whole venoms. The recombinant peptide obtained will enable future studies to characterize its biological activity, as well as investigations regarding possible biotechnological applications.

  5. Molecular characterization of beta-thalassemia intermedia in patients of Italian descent and identification of three novel beta-thalassemia mutations.

    PubMed

    Murru, S; Loudianos, G; Deiana, M; Camaschella, C; Sciarratta, G V; Agosti, S; Parodi, M I; Cerruti, P; Cao, A; Pirastu, M

    1991-03-15

    In this study, we have defined by dot-blot analysis with allelic specific oligonucleotide probes or direct sequencing on amplified DNA the beta-thalassemia mutations in a large group of patients (23) of Italian descent with thalassemia intermedia. These patients had one parent with either the silent beta-thalassemia carrier phenotype or borderline-normal hemoglobin A2 (HbA2) levels (2.5% to 3.5%). Nearly all were genetic compounds for a severe beta-thalassemia mutation and a beta-thalassemia mutation associated with high residual output of beta-globin chains (beta + intervening sequence [IVS]-I-nt6, beta -87, beta -101), indicating that inheritance of a mild beta-thalassemia allele, even in a single dose, is the most common molecular mechanism producing thalassemia intermedia in the Italian population. In three cases, in whom we failed to define by dot-blot analysis the mutations, we sequenced the beta + globin gene and found three novel beta-thalassemia mutations, which are certainly very rare because they have been hitherto detected solely in a single patient. These mutations consist of: (1) a T-A substitution at position 2 of IVS-I, in a patient compound heterozygote for this mutation and the -87 promoter mutation; (2) a G-C substitution at position 844 of IVS-II, in a patient heterozygous for this mutation who showed normal sequences at the in trans beta-globin gene (The reason for the presence of clinical manifestations in a beta-thalassemia heterozygote has not been defined.); and (3) a deletion of one nucleotide (-T) at codon 126, resulting in a frameshift and readthrough of the 5' untranslated region and most likely producing an elongated Hb molecule of 156 amino acid residues, in a patient heterozygous for this mutation with normal beta-globin gene sequences at the other locus.

  6. Molecular cloning and in silico characterization of knottin peptide, U2-SCRTX-Lit2, from brown spider (Loxosceles intermedia) venom glands.

    PubMed

    Meissner, Gabriel Otto; de Resende Lara, Pedro Túlio; Scott, Luis Paulo Barbour; Braz, Antônio Sérgio Kimus; Chaves-Moreira, Daniele; Matsubara, Fernando Hitomi; Soares, Eduardo Mendonça; Trevisan-Silva, Dilza; Gremski, Luiza Helena; Veiga, Silvio Sanches; Chaim, Olga Meiri

    2016-09-01

    Inhibitor cystine knots (ICKs) are a family of structural peptides with a large number of cysteine residues that form intramolecular disulfide bonds, resulting in a knot. These peptides are involved in a variety of biological functions including predation and defense, and are found in various species, such as spiders, scorpions, sea anemones, and plants. The Loxosceles intermedia venom gland transcriptome identified five groups of ICK peptides that represent more than 50 % of toxin-coding transcripts. Here, we describe the molecular cloning of U2-Sicaritoxin-Lit2 (U2-SCRTX-Lit2), bioinformatic characterization, structure prediction, and molecular dynamic analysis. The sequence of U2-SCRTX-Lit2 obtained from the transcriptome is similar to that of μ-Hexatoxin-Mg2, a peptide that inhibits the insect Nav channel. Bioinformatic analysis of sequences classified as ICK family members also showed a conservation of cysteine residues among ICKs from different spiders, with the three dimensional molecular model of U2-SCRTX-Lit2 similar in structure to the hexatoxin from μ-hexatoxin-Mg2a. Molecular docking experiments showed the interaction of U2-SCRTX-Lit2 to its predictable target-the Spodoptera litura voltage-gated sodium channel (SlNaVSC). After 200 ns of molecular dynamic simulation, the final structure of the complex showed stability in agreement with the experimental data. The above analysis corroborates the existence of a peptide toxin with insecticidal activity from a novel ICK family in L. intermedia venom and demonstrates that this peptide targets Nav channels.

  7. Identification of genes associated with prophage-like gene transfer agents in the pathogenic intestinal spirochaetes Brachyspira hyodysenteriae, Brachyspira pilosicoli and Brachyspira intermedia.

    PubMed

    Motro, Yair; La, Tom; Bellgard, Matthew I; Dunn, David S; Phillips, Nyree D; Hampson, David J

    2009-03-02

    VSH-1 is an unusual prophage-like gene transfer agent (GTA) that has been described in the intestinal spirochaete Brachyspira hyodysenteriae. The GTA does not self-propagate, but it assembles into a virus-like particle and transfers random 7.5kb fragments of host DNA to other B. hyodysenteriae cells. To date the GTA VSH-1 has only been analysed in B. hyodysenteriae strain B204, in which 11 late function genes encoding prophage capsid, tail and lysis elements have been described. The aim of the current study was to look for these 11 genes in the near-complete genomes of B. hyodysenteriae WA1, B. pilosicoli 95/1000 and B. intermedia HB60. All 11 genes were found in the three new strains. The GTA genes in WA1 and 95/1000 were contiguous, whilst some of those in HB60 were not-although in all three strains some gene rearrangements were present. A new predicted open reading frame with potential functional importance was found in a consistent position associated with all four GTAs, located between the genes for head protein Hvp24 and tail protein Hvp53, overlapping with the hvp24 sequence. Differences in the nucleotide and predicted amino acid sequences of the GTA genes in the spirochaete strains were consistent with the overall genetic distances between the strains. Hence the GTAs in the two B. hyodysenteriae strains were considered to be strain specific variants, and were designated GTA/Bh-B204 and GTA/Bh-WA1 respectively. The GTAs in the strains of B. intermedia and B. pilosicoli were designated GTA/Bint-HB60 and GTA/Bp-95/1000 respectively. Further work is required to determine the extent to which these GTAs can transfer host genes between different Brachyspira species and strains.

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

    SciTech Connect

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

    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.

  9. Effect of anisotropy in the S=1 underscreened Kondo lattice

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher; da Rosa Simões, Acirete S.; Lacroix, Claudine; Iglesias, José Roberto; Coqblin, Bernard

    2014-12-01

    We study the effect of crystal field anisotropy in the underscreened S=1 Kondo lattice model. Starting from the two orbital Anderson lattice model and including a local anisotropy term, we show, through Schrieffer-Wolff transformation, that local anisotropy is equivalent to an anisotropic Kondo interaction (J∥≠J⊥). The competition and coexistence between ferromagnetism and Kondo effect in this effective model is studied within a generalized mean-field approximation. Several regimes are obtained, depending on the parameters, exhibiting or not coexistence of magnetic order and Kondo effect. Particularly, we show that a re-entrant Kondo phase at low temperature can be obtained. We are also able to describe phases where the Kondo temperature is smaller than the Curie temperature (TK

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

    SciTech Connect

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

    1989-07-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Magnetoelectric Behavior from S =1 /2 Asymmetric Square Cupolas

    NASA Astrophysics Data System (ADS)

    Kato, Yasuyuki; Kimura, Kenta; Miyake, Atsushi; Tokunaga, Masashi; Matsuo, Akira; Kindo, Koichi; Akaki, Mitsuru; Hagiwara, Masayuki; Sera, Masakazu; Kimura, Tsuyoshi; Motome, Yukitoshi

    2017-03-01

    Magnetoelectric properties are studied by a combined experimental and theoretical study of a quasi-two-dimensional material composed of square cupolas, Ba(TiO )Cu4(PO4 ) 4 . The magnetization is measured up to the field above the saturation, and several anomalies are observed depending on the field directions. We propose a S =1 /2 spin model with Dzyaloshinskii-Moriya interactions, which reproduces the full magnetization curves well. Elaborating the phase diagram of the model, we show that the anomalies are explained by magnetoelectric phase transitions. Our theory also accounts for the scaling of the dielectric anomaly observed in the experiments. The results elucidate the crucial role of the in-plane component of Dzyaloshinskii-Moriya interactions, which is induced by the noncoplanar buckling of a square cupola. We also predict a "hidden" phase and another magnetoelectric response, both of which appear in a nonzero magnetic field.

  13. Comparisons of absolute gravimeters (COOMET.M.G-S1)

    NASA Astrophysics Data System (ADS)

    Vinnichenko, Mr Alexander; Germak, Alessandro, Dr

    2017-01-01

    This report describes the results of the RMO supplementary comparison COOMET.M.G-S1 (also known as bilateral comparison COOMET 634/UA/14). The comparison measurements between the two participants NSC 'IM' (pilot laboratory) and INRIM were started in December 2015 and finished in January 2016. Participants of comparisons were conducted at their national standards the measurements of the free fall acceleration in gravimetric point laboratory of absolute gravimetry of INRIM named INRiM.2. Absolute measurements of gravimetric acceleration were conducted by ballistic gravimeters. The agreement between the two participants is good. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2017-02-01

    Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P1, S1P2, and S1P3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to Gq. We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD. The S1P receptor subtypes and G proteins that regulate RhoA activation and downstream responses in the heart have not been determined. Using siRNA or pertussis toxin to inhibit different G proteins in NRVMs we established that S1P regulates RhoA activation through Gα13 but not Gα12, Gαq, or Gαi. Knockdown of the three major S1P receptors using siRNA demonstrated a requirement for S1P3 in RhoA activation and subsequent phosphorylation of PKD, and this was confirmed in studies using isolated hearts from S1P3 knockout (KO) mice. S1P treatment reduced infarct size induced by ischemia/reperfusion in Langendorff perfused wild-type (WT) hearts and this protection was abolished in the S1P3 KO mouse heart. CYM-51736, an S1P3-specific agonist, also decreased infarct size after ischemia/reperfusion to a degree similar to that achieved by S1P. The finding that S1P3 receptor- and Gα13-mediated RhoA activation is responsible for protection against ischemia/reperfusion suggests that selective targeting of S1P3 receptors could provide therapeutic benefits in ischemic heart disease.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26813587

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

    PubMed

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

    2014-05-01

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

  19. Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer

    PubMed Central

    Mochiki, E; Ogata, K; Ohno, T; Toyomasu, Y; Haga, N; Fukai, Y; Aihara, R; Ando, H; Uchida, N; Asao, T; Kuwano, H

    2012-01-01

    Background: A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. Methods: Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m−2 twice daily) on days 1–14 plus paclitaxel (60 mg m−2) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m−2 twice daily) on days 1–21 plus cisplatin (60 mg m−2) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7% P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin. Conclusion: S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials. PMID:22617130

  20. Sphingosine 1-phosphate receptor 1 (S1P(1)) upregulation and amelioration of experimental autoimmune encephalomyelitis by an S1P(1) antagonist.

    PubMed

    Cahalan, Stuart M; Gonzalez-Cabrera, Pedro J; Nguyen, Nhan; Guerrero, Miguel; Cisar, Elizabeth A George; Leaf, Nora B; Brown, Steven J; Roberts, Edward; Rosen, Hugh

    2013-02-01

    Sphingosine 1-phosphate receptor 1 (S1P(1)) is a G protein-coupled receptor that is critical for proper lymphocyte development and recirculation. Agonists to S1P(1) are currently in use clinically for the treatment of multiple sclerosis, and these drugs may act on both S1P(1) expressed on lymphocytes and S1P(1) expressed within the central nervous system. Agonists to S1P(1) and deficiency in S1P(1) both cause lymphocyte sequestration in the lymph nodes. In the present study, we show that S1P(1) antagonism induces lymphocyte sequestration in the lymph nodes similar to that observed with S1P(1) agonists while upregulating S1P(1) on lymphocytes and endothelial cells. Additionally, we show that S1P(1) antagonism reverses experimental autoimmune encephalomyelitis in mice without acting on S1P(1) expressed within the central nervous system, demonstrating that lymphocyte sequestration via S1P(1) antagonism is sufficient to alleviate autoimmune pathology.

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

    PubMed

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

    2016-08-01

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

  2. Possible Dust Models for C/2012 S1

    NASA Astrophysics Data System (ADS)

    Yanamandra-Fisher, P. A.

    2014-12-01

    Comet C/2012 S1 (ISON) provided a great opportunity to study a dynamically new Oort-cloud comet on its initial and only passage through the inner solar system. Contrary to expectations, the comet's activity fluctuated from high through a quiescent phase, and a major outburst days before its perihelion passage, ending in a dramatic race to complete disintegration on perihelion day, 28 November 2013. Amateur observations to professional ground-based, sub-orbital telescopes indicate the various changes of visible factors such as Afrho, a proxy for dust activity, and the measured production rates for water, consistent with the disintegration of the nucleus. Hines et al. (2013; ApJ Lett. 780) detected positive polarization in the inner coma and negative polarization in the outer coma, indicative of a jet, independently confirmed by Li et al. (2013, ApJ Lett., 779). Thermal emission observations of the comet pre-perihelion from NAOJ/Subaru/COMICS, a mid-infrared spectrometer, indicated a body with an equivalent brightness temperature of 265K (Ootsubo et al., 2013, ACM, Helsinki,FI); thermal observations acquired at the NASA/Infrared Telescope Facility (IRTF) with The Aerospace Corporation spectrometer (BASS, PI. R. Russell), before and after the November 12, 2013 outburst observed by the CIOC_ISON amateur network, indicates a brightness temperature of 330K and the presence, albeit weak, of the 11.3-micron crystalline silicate feature (Sitko et al., 2014, LPI abstract 1537). A Monte Carlo comet dust tail model, applied to extract the dust environment parameters of comet C/2012 S1 (ISON) from both Earth-based and Solar and Heliospheric Observatory (SOHO) calibrated observations, performed from about 6 AU (inbound), to right after perihelion passage, when just a small portion of the original comet nucleus survived in the form of a cloud of tiny particles, indicates that particles underwent disintegration and fragmentation (Moreno et al., 2014, ApJ Lett., 791). Ongoing work

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

    PubMed

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

    2016-08-26

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

  4. Outgassing and chemical evolution of C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Dello Russo, Neil; Vervack, Ronald J.; Kawakita, Hideyo; Cochran, Anita; McKay, Adam J.; Harris, Walter M.; Weaver, Harold A.; Lisse, Carey M.; DiSanti, Michael A.; Kobayashi, Hitomi; Biver, Nicolas; Bockelée-Morvan, Dominique; Crovisier, Jacques; Opitom, Cyrielle; Jehin, Emmanuel

    2015-11-01

    Volatile production rates, relative abundances, rotational temperatures, and spatial distributions in the coma were measured in C/2012 S1 (ISON) using long-slit high-dispersion (λ/Δλ ~ 25,000) infrared spectroscopy as part of a worldwide observing campaign. Spectra were obtained on UT 2013 October 26 and 28 with NIRSPEC at the W. M. Keck Observatory, and UT 2013 November 19 and 20 with CSHELL at the NASA IRTF. H2O was detected on all dates, with production rates increasing by about a factor of 40 between October 26 (Rh = 1.12 AU) and November 20 (Rh = 0.43 AU). Short-term variability of H2O was also seen as the production rate increased by nearly a factor of two during observations obtained over a period of about six hours on November 19. C2H6, CH3OH and CH4 abundances were slightly depleted relative to H2O in ISON compared to mean values for comets measured at infrared wavelengths. On the November dates, C2H2, HCN and OCS abundances relative to H2O appear to be close to the range of mean values, whereas H2CO and NH3 were significantly enhanced. We will compare derived chemical abundances in ISON to other comets measured with infrared spectroscopy.

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

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2017-02-08

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

  8. Sphingosine 1-phosphate (S1P) receptor agonists mediate pro-fibrotic responses in normal human lung fibroblasts via S1P2 and S1P3 receptors and Smad-independent signaling.

    PubMed

    Sobel, Katrin; Menyhart, Katalin; Killer, Nina; Renault, Bérengère; Bauer, Yasmina; Studer, Rolf; Steiner, Beat; Bolli, Martin H; Nayler, Oliver; Gatfield, John

    2013-05-24

    Synthetic sphingosine 1-phosphate receptor 1 modulators constitute a new class of drugs for the treatment of autoimmune diseases. Sphingosine 1-phosphate (S1P) signaling, however, is also involved in the development of fibrosis. Using normal human lung fibroblasts, we investigated the induction of fibrotic responses by the S1P receptor (S1PR) agonists S1P, FTY720-P, ponesimod, and SEW2871 and compared them with the responses induced by the known fibrotic mediator TGF-β1. In contrast to TGF-β1, S1PR agonists did not induce expression of the myofibroblast marker α-smooth muscle actin. However, TGF-β1, S1P, and FTY720-P caused robust stimulation of extracellular matrix (ECM) synthesis and increased pro-fibrotic marker gene expression including connective tissue growth factor. Ponesimod showed limited and SEW2871 showed no pro-fibrotic potential in these readouts. Analysis of pro-fibrotic signaling pathways showed that in contrast to TGF-β1, S1PR agonists did not activate Smad2/3 signaling but rather activated PI3K/Akt and ERK1/2 signaling to induce ECM synthesis. The strong induction of ECM synthesis by the nonselective agonists S1P and FTY720-P was due to the stimulation of S1P2 and S1P3 receptors, whereas the weaker induction of ECM synthesis at high concentrations of ponesimod was due to a low potency activation of S1P3 receptors. Finally, in normal human lung fibroblast-derived myofibroblasts that were generated by TGF-β1 pretreatment, S1P and FTY720-P were effective stimulators of ECM synthesis, whereas ponesimod was inactive, because of the down-regulation of S1P3R expression in myofibroblasts. These data demonstrate that S1PR agonists are pro-fibrotic via S1P2R and S1P3R stimulation using Smad-independent pathways.

  9. The turbomachine blading design using S2-S1 approach

    NASA Technical Reports Server (NTRS)

    Luu, T. S.; Bencherif, L.; Viney, B.; Duc, J. M. Nguyen

    1991-01-01

    The boundary conditions corresponding to the design problem when the blades being simulated by the bound vorticity distribution are presented. The 3D flow is analyzed by the two steps S2 - S1 approach. In the first step, the number of blades is supposed to be infinite, the vortex distribution is transformed into an axisymmetric one, so that the flow field can be analyzed in a meridional plane. The thickness distribution of the blade producing the flow channel striction is taken into account by the modification of metric tensor in the continuity equation. Using the meridional stream function to define the flow field, the mass conservation is satisfied automatically. The governing equation is deduced from the relation between the azimuthal component of the vorticity and the meridional velocity. The value of the azimuthal component of the vorticity is provided by the hub to shroud equilibrium condition. This step leads to the determination of the axisymmetric stream sheets as well as the approximate camber surface of the blade. In the second step, the finite number of blades is taken into account, the inverse problem corresponding to the blade to blade flow confined in each stream sheet is analyzed. The momentum equation implies that the free vortex of the absolute velocity must be tangential to the stream sheet. The governing equation for the blade to blade flow stream function is deduced from this condition. At the beginning, the upper and the lower surfaces of the blades are created from the camber surface obtained from the first step with the assigned thickness distribution. The bound vorticity distribution and the penetrating flux conservation applied on the presumed blade surface constitute the boundary conditions of the inverse problem. The detection of this flux leads to the rectification of the geometry of the blades.

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

    Comets are pristine bodies of the Solar System and their studies can give precious hints on the formation of the Solar System itself. New comets, coming form the Oort Colud at their first passage close to the Sun, are particularly important, because they are not differentiated by the 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 NH_3(1,1) emission at 23.7 GHz in comet C/2012 S1 ISON using a new dual-feed K-band receiver mounted on the Medicina 32-m antenna. We observed the comet once close to its perihelion, from 2013 Nov. 25 to Nov. 28, when its heliocentric distance changed from 0.25 au to 0.03 au. We integrated about 6 hrs per day, obtaining high-spectral-resolution (1 km/s) spectra with a typical rms noise of 10 mK. Such sensitivity allowed us to derive an upper limit of Q(NH_3) of about 2.5 ×10^{29} mol/s on November 26. This upper limit would correspond to a Q(H_2O) of about 2.5 ×10^{31} mol/s, assuming the typical Q(H_2O)/Q(NH_3) ratio of 100. These findings confirm that no significant Q(H_2O) enhancement happened near the perihelion, consistent with a definitive decrease of molecules production rate.

  11. WILL COMET ISON (C/2012 S1) SURVIVE PERIHELION?

    SciTech Connect

    Knight, Matthew M.; Walsh, Kevin J.

    2013-10-10

    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{sup –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{sup –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.

  12. A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

    PubMed

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-02-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells.

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

    PubMed

    Yang, Weiwei; Li, Qinghua; Pan, Zhifang

    2014-01-01

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

  14. Novel selective allosteric and bitopic ligands for the S1P(3) receptor.

    PubMed

    Jo, Euijung; Bhhatarai, Barun; Repetto, Emanuela; Guerrero, Miguel; Riley, Sean; Brown, Steven J; Kohno, Yasushi; Roberts, Edward; Schürer, Stephan C; Rosen, Hugh

    2012-12-21

    Sphingosine 1-phosphate (S1P) is a lysophospholipid signaling molecule that regulates important biological functions, including lymphocyte trafficking and vascular development, by activating G protein-coupled receptors for S1P, namely, S1P(1) through S1P(5). Here, we map the S1P(3) binding pocket with a novel allosteric agonist (CYM-5541), an orthosteric agonist (S1P), and a novel bitopic antagonist (SPM-242). With a combination of site-directed mutagenesis, ligand competition assay, and molecular modeling, we concluded that S1P and CYM-5541 occupy different chemical spaces in the ligand binding pocket of S1P(3). CYM-5541 allowed us to identify an allosteric site where Phe263 is a key gate-keeper residue for its affinity and efficacy. This ligand lacks a polar moiety, and the novel allosteric hydrophobic pocket permits S1P(3) selectivity of CYM-5541 within the highly similar S1P receptor family. However, a novel S1P(3)-selective antagonist, SPM-242, in the S1P(3) pocket occupies the ligand binding spaces of both S1P and CYM-5541, showing its bitopic mode of binding. Therefore, our coordinated approach with biochemical data and molecular modeling, based on our recently published S1P(1) crystal structure data in a highly conserved set of related receptors with a shared ligand, provides a strong basis for the successful optimization of orthosteric, allosteric, and bitopic modulators of S1P(3).

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

    PubMed

    Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji

    2015-10-01

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

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

    PubMed

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

    PubMed

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

    2017-02-27

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

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

    PubMed

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

    2016-05-10

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

  19. Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like head-group interactions

    PubMed Central

    Gonzalez-Cabrera, Pedro J.; Jo, Euijung; Sanna, M. Germana; Brown, Steven; Leaf, Nora; Marsolais, David; Schaeffer, Marie-Therese; Chapman, Jacqueline; Cameron, Michael; Guerrero, Miguel; Roberts, Edward; Rosen, Hugh

    2008-01-01

    Strong evidence exists for interactions of zwitterionic phosphate and amine groups in Sphingosine-1 phosphate (S1P) to conserved R and E residues present at the extracellular face of transmembrane-3 (TM3) of S1P receptors. The contribution of R120 and E121 for high affinity ligand-receptor interactions is essential, as single-point R120A or E121A S1P1 mutants neither bind S1P nor transduce S1P function. Because S1P receptors are therapeutically interesting, identifying potent selective agonists with different binding modes and in vivo efficacy is of pharmacological importance. Here we describe a modestly water-soluble highly-selective S1P1 agonist (CYM-5442) that does not require R120 or E121 residues for activating S1P1-dependent p42/p44 MAPK phosphorylation, which defines a new hydrophobic pocket in S1P1. CYM-5442 is a full agonist in vitro for S1P1 internalization, phosphorylation and ubiquitination. Importantly, CYM-5442 was a full agonist for induction and maintenance of S1P1-dependent lymphopenia, decreasing B-lymphocytes by 65% and T-lymphocytes by 85% of vehicle. Induction of CYM-5442 lymphopenia was dose and time-dependent, requiring serum concentrations in the 50 nM range. In vitro measures of S1P1 activation by CYM-5442 were non-competitively inhibited by a specific S1P1 antagonist (W146), competitive for S1P, FTY720-P and SEW2871. In addition, lymphopenia by CYM-5442 was reversed by W146 administration or upon pharmacokinetic agonist clearance. Pharmacokinetics in mice also indicated that CYM-5442 partitions significantly in central nervous tissue. These data show that CYM-5442 activates S1P1-dependent pathways in vitro and to levels of full efficacy in vivo through a hydrophobic pocket, separable from the orthosteric site of S1P binding that is headgroup dependent. PMID:18708635

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

    PubMed Central

    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

  1. Ligand-binding pocket shape differences between S1P1 and S1P3 determine efficiency of chemical probe identification by uHTS

    PubMed Central

    Schürer, Stephan C.; Brown, Steven J.; Cabrera, Pedro Gonzales; Schaeffer, Marie-Therese; Chapman, Jacqueline; Jo, Euijung; Chase, Peter; Spicer, Tim; Hodder, Peter; Rosen, Hugh

    2008-01-01

    We have studied the Sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function. Through systematic screening of the same libraries, we identified novel selective agonists chemotypes for each of the S1P1 and S1P3 receptors. uHTS for S1P1 was more effective than for S1P3, with many selective, low nanomolar hits of proven mechanism emerging for. Receptor structure modeling and ligand docking reveal differences between the receptor binding pockets, which are the basis for sub-type selectivity. Novel selective agonists interact primarily in the hydrophobic pocket of the receptor in the absence of head-group interactions. Chemistry-space and shape-based analysis of the screening libraries in combination with the binding models explain the observed differential hit rates and enhanced efficiency for lead discovery for S1P1 vs. S1P3 in this closely related receptor family. PMID:18590333

  2. Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, trafficking, and signaling of S1P1.

    PubMed

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

    2012-12-28

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

  3. Environmental Niche Modelling of Phlebotomine Sand Flies and Cutaneous Leishmaniasis Identifies Lutzomyia intermedia as the Main Vector Species in Southeastern Brazil

    PubMed Central

    Meneguzzi, Viviane Coutinho; dos Santos, Claudiney Biral; Leite, Gustavo Rocha; Fux, Blima; Falqueto, Aloísio

    2016-01-01

    Cutaneous leishmaniasis (CL) is caused by a protozoan of the genus Leishmania and is transmitted by sand flies. The state of Espírito Santo (ES), an endemic area in southeast Brazil, has shown a considerably high prevalence in recent decades. Environmental niche modelling (ENM) is a useful tool for predicting potential disease risk. In this study, ENM was applied to sand fly species and CL cases in ES to identify the principal vector and risk areas of the disease. Sand flies were collected in 466 rural localities between 1997 and 2013 using active and passive capture. Insects were identified to the species level, and the localities were georeferenced. Twenty-one bioclimatic variables were selected from WorldClim. Maxent was used to construct models projecting the potential distribution for five Lutzomyia species and CL cases. ENMTools was used to overlap the species and the CL case models. The Kruskal–Wallis test was performed, adopting a 5% significance level. Approximately 250,000 specimens were captured, belonging to 43 species. The area under the curve (AUC) was considered acceptable for all models. The slope was considered relevant to the construction of the models for all the species identified. The overlay test identified Lutzomyia intermedia as the main vector of CL in southeast Brazil. ENM tools enable an analysis of the association among environmental variables, vector distributions and CL cases, which can be used to support epidemiologic and entomological vigilance actions to control the expansion of CL in vulnerable areas. PMID:27783641

  4. Seasonal and Diel Vocalization Patterns of Antarctic Blue Whale (Balaenoptera musculus intermedia) in the Southern Indian Ocean: A Multi-Year and Multi-Site Study.

    PubMed

    Leroy, Emmanuelle C; Samaran, Flore; Bonnel, Julien; Royer, Jean-Yves

    2016-01-01

    Passive acoustic monitoring is an efficient way to provide insights on the ecology of large whales. This approach allows for long-term and species-specific monitoring over large areas. In this study, we examined six years (2010 to 2015) of continuous acoustic recordings at up to seven different locations in the Central and Southern Indian Basin to assess the peak periods of presence, seasonality and migration movements of Antarctic blue whales (Balaenoptera musculus intermedia). An automated method is used to detect the Antarctic blue whale stereotyped call, known as Z-call. Detection results are analyzed in terms of distribution, seasonal presence and diel pattern of emission at each site. Z-calls are detected year-round at each site, except for one located in the equatorial Indian Ocean, and display highly seasonal distribution. This seasonality is stable across years for every site, but varies between sites. Z-calls are mainly detected during autumn and spring at the subantarctic locations, suggesting that these sites are on the Antarctic blue whale migration routes, and mostly during winter at the subtropical sites. In addition to these seasonal trends, there is a significant diel pattern in Z-call emission, with more Z-calls in daytime than in nighttime. This diel pattern may be related to the blue whale feeding ecology.

  5. Graded hedgehog and fibroblast growth factor signaling independently regulate pituitary cell fates and help establish the pars distalis and pars intermedia of the zebrafish adenohypophysis.

    PubMed

    Guner, Burcu; Ozacar, A Tuba; Thomas, Jeanne E; Karlstrom, Rolf O

    2008-09-01

    The vertebrate adenohypophysis forms as a placode at the anterior margin of the neural plate, requiring both hedgehog (Hh) and fibroblast growth factor (Fgf) mediated cell-cell signaling for induction and survival of endocrine cell types. Using small molecule inhibitors to modulate signaling levels during zebrafish development we show that graded Hh and Fgf signaling independently help establish the two subdomains of the adenohypophysis, the anteriorly located pars distalis (PD) and the posterior pars intermedia (PI). High levels of Hh signaling are required for formation of the PD and differentiation of anterior endocrine cell types, whereas lower levels of Hh signaling are required for formation of the PI and differentiation of posterior endocrine cell types. In contrast, high Fgf signaling levels are required for formation of the PI and posterior endocrine cell differentiation, whereas anterior regions require lower levels of Fgf signaling. Based on live observations and marker analyses, we show that the PD forms first at the midline closest to the central nervous system source of Sonic hedgehog. In contrast the PI appears to form from more lateral/posterior cells close to a central nervous system source of Fgf3. Together our data show that graded Hh and Fgf signaling independently direct induction of the PD and PI and help establish endocrine cell fates along the anterior/posterior axis of the zebrafish adenohypophysis. These data suggest that there are distinct origins and signaling requirements for the PD and PI.

  6. Genotyping of human and porcine Yersinia enterocolitica, Yersinia intermedia, and Yersinia bercovieri strains from Switzerland by amplified fragment length polymorphism analysis.

    PubMed

    Boghenbor, Kathrin Kuehni; On, Stephen L W; Kokotovic, Branko; Baumgartner, Andreas; Wassenaar, Trudy M; Wittwer, Matthias; Bissig-Choisat, Beatrice; Frey, Joachim

    2006-06-01

    In this study, 231 strains of Yersinia enterocolitica, 25 strains of Y. intermedia, and 10 strains of Y. bercovieri from human and porcine sources (including reference strains) were analyzed using amplified fragment length polymorphism (AFLP), a whole-genome fingerprinting method for subtyping bacterial isolates. AFLP typing distinguished the different Yersinia species examined. Representatives of Y. enterocolitica biotypes 1A, 1B, 2, 3, and 4 belonged to biotype-related AFLP clusters and were clearly distinguished from each other. Y. enterocolitica biotypes 2, 3, and 4 appeared to be more closely related to each other (83% similarity) than to biotypes 1A (11%) and 1B (47%). Biotype 1A strains exhibited the greatest genetic heterogeneity of the biotypes studied. The biotype 1A genotypes were distributed among four major clusters, each containing strains from both human and porcine sources, confirming the zoonotic potential of this organism. The AFLP technique is a valuable genotypic method for identification and typing of Y. enterocolitica and other Yersinia spp.

  7. Chemoprotective properties of rooibos (Aspalathus linearis), honeybush (Cyclopia intermedia) herbal and green and black (Camellia sinensis) teas against cancer promotion induced by fumonisin B1 in rat liver.

    PubMed

    Marnewick, Jeanine L; van der Westhuizen, Francois H; Joubert, Elizabeth; Swanevelder, Sonja; Swart, Pieter; Gelderblom, Wentzel C A

    2009-01-01

    The chemoprotective properties of unfermented and fermented rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) herbal teas, and green and black teas (Camellia sinensis) were investigated against fumonisin B1 (FB1) promotion in rat liver utilizing diethylnitrosamine (DEN) as cancer initiator. The various teas differently affected the clinical chemical parameters associated with liver and kidney damage associated with FB1 suggesting specific FB1/iron/polyphenolic interactions. Green tea enhanced (P<0.05) the FB1-induced reduction of the oxygen radical absorbance capacity, while fermented herbal teas and unfermented honeybush significantly (P<0.05) decreased FB1-induced lipid peroxidation in the liver. The teas exhibited varying effects on FB1-induced changes in the activities of catalase, glutathione peroxidase (GPx) glutathione reductase (GR) as well as the glutathione (GSH) status. Unfermented rooibos and honeybush significantly (P<0.05) to marginally (P<0.1) reduced the total number of foci (>10microm), respectively, while all the teas reduced the relative amount of the larger foci. Fermentation seems to reduce the protective effect of the herbal teas. Differences in the major polyphenolic components and certain FB1/polyphenolic/tissue interactions may explain the varying effects of the different teas on the oxidative parameters, hepatotoxic effects and cancer promotion in rat liver.

  8. Inhibition of tumour promotion in mouse skin by extracts of rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia), unique South African herbal teas.

    PubMed

    Marnewick, Jeanine; Joubert, Elizabeth; Joseph, Shamiel; Swanevelder, Sonja; Swart, Pieter; Gelderblom, Wentzel

    2005-06-28

    The modulating effect of ethanol/acetone (E/A) soluble fractions, prepared from methanolic extracts of processed and unprocessed rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) as well as green (Camellia sinensis) teas was established in a two-stage mouse skin carcinogenesis assay. Topical application of the tea fractions prior to the tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), on ICR mouse skin initiated with 7,12-dimethylbenz[a]anthracene (DMBA) suppressed skin tumorigenesis significantly (P<0.001) with the green tea E/A fraction exhibiting a 100% inhibition, unprocessed honeybush 90%, processed honeybush 84.2%, processed rooibos 75% and unprocessed rooibos 60%. The green tea fraction, with the highest flavanol/proanthocyanidin content, also exhibited the highest protective activity (99%) against hepatic microsomal lipid peroxidation, and completely inhibited skin tumour formation. Differences in the flavanol/proanthocyanidin and flavonol/flavone composition and/or non polyphenolic constituents are likely to be important determinants in the inhibition of tumour promotion by the herbal tea E/A fractions in mouse skin.

  9. Differential accumulation of volatile terpene and terpene synthase mRNAs during lavender (Lavandula angustifolia and L. x intermedia) inflorescence development.

    PubMed

    Guitton, Yann; Nicolè, Florence; Moja, Sandrine; Valot, Nadine; Legrand, Sylvain; Jullien, Frédéric; Legendre, Laurent

    2010-02-01

    Despite the commercial importance of Lavandula angustifolia Mill. and L. x intermedia Emeric ex Loisel floral essential oils (EOs), no information is currently available on potential changes in individual volatile organic compound (VOC) content during inflorescence development. Calyces were found to be the main sites of VOC accumulation. The 20 most abundant VOCs could be separated into three sub-groups according to their patterns of change in concentration The three groups of VOCs sequentially dominated the global scent bouquet of inflorescences, the transition between the first and second groups occurring around the opening of the first flower of the inflorescence and the one between the second and third groups at the start of seed set. Changes in calyx VOC accumulation were linked to the developmental stage of individual flowers. Leaves accumulated a smaller number of VOCs which were a subset of those seen in preflowering inflorescences. Their nature and content remained constant during the growing season. Quantitative real time polymerase chain reaction assessments of the expression of two terpene synthase (TPS) genes, LaLIMS and LaLINS, revealed similar trends between their patterns of expression and those of their VOC products. Molecular and chemical analyses suggest that changes in TPS expression occur during lavender inflorescence development and lead to changes in EO composition. Both molecular data and terpene analysis support the findings that changes in biosynthesis of terpene occurred during inflorescence development.

  10. Seasonal and Diel Vocalization Patterns of Antarctic Blue Whale (Balaenoptera musculus intermedia) in the Southern Indian Ocean: A Multi-Year and Multi-Site Study

    PubMed Central

    Leroy, Emmanuelle C.; Samaran, Flore; Bonnel, Julien; Royer, Jean-Yves

    2016-01-01

    Passive acoustic monitoring is an efficient way to provide insights on the ecology of large whales. This approach allows for long-term and species-specific monitoring over large areas. In this study, we examined six years (2010 to 2015) of continuous acoustic recordings at up to seven different locations in the Central and Southern Indian Basin to assess the peak periods of presence, seasonality and migration movements of Antarctic blue whales (Balaenoptera musculus intermedia). An automated method is used to detect the Antarctic blue whale stereotyped call, known as Z-call. Detection results are analyzed in terms of distribution, seasonal presence and diel pattern of emission at each site. Z-calls are detected year-round at each site, except for one located in the equatorial Indian Ocean, and display highly seasonal distribution. This seasonality is stable across years for every site, but varies between sites. Z-calls are mainly detected during autumn and spring at the subantarctic locations, suggesting that these sites are on the Antarctic blue whale migration routes, and mostly during winter at the subtropical sites. In addition to these seasonal trends, there is a significant diel pattern in Z-call emission, with more Z-calls in daytime than in nighttime. This diel pattern may be related to the blue whale feeding ecology. PMID:27828976

  11. A Prokaryotic S1P Lyase Degrades Extracellular S1P In Vitro and In Vivo: Implication for Treating Hyperproliferative Disorders

    PubMed Central

    Huwiler, Andrea; Bourquin, Florence; Kotelevets, Nataliya; Pastukhov, Oleksandr; Capitani, Guido; Grütter, Markus G.; Zangemeister-Wittke, Uwe

    2011-01-01

    Sphingosine-1-phosphate (S1P) regulates a broad spectrum of fundamental cellular processes like proliferation, death, migration and cytokine production. Therefore, elevated levels of S1P may be causal to various pathologic conditions including cancer, fibrosis, inflammation, autoimmune diseases and aberrant angiogenesis. Here we report that S1P lyase from the prokaryote Symbiobacterium thermophilum (StSPL) degrades extracellular S1P in vitro and in blood. Moreover, we investigated its effect on cellular responses typical of fibrosis, cancer and aberrant angiogenesis using renal mesangial cells, endothelial cells, breast (MCF-7) and colon (HCT 116) carcinoma cells as disease models. In all cell types, wild-type StSPL, but not an inactive mutant, disrupted MAPK phosphorylation stimulated by exogenous S1P. Functionally, disruption of S1P receptor signaling by S1P depletion inhibited proliferation and expression of connective tissue growth factor in mesangial cells, proliferation, migration and VEGF expression in carcinoma cells, and proliferation and migration of endothelial cells. Upon intravenous injection of StSPL in mice, plasma S1P levels rapidly declined by 70% within 1 h and then recovered to normal 6 h after injection. Using the chicken chorioallantoic membrane model we further demonstrate that also under in vivo conditions StSPL, but not the inactive mutant, inhibited tumor cell-induced angiogenesis as an S1P-dependent process. Our data demonstrate that recombinant StSPL is active under extracellular conditions and holds promise as a new enzyme therapeutic for diseases associated with increased levels of S1P and S1P receptor signaling. PMID:21829623

  12. Genetic characterization of three qnrS1-harbouring multidrug-resistance plasmids and qnrS1-containing transposons circulating in Ho Chi Minh City, Vietnam

    PubMed Central

    Le, Vien; Nhu, Nguyen Thi Khanh; Cerdeno-Tarraga, Ana; Campbell, James I.; Tuyen, Ha Thanh; Nhu, Tran Do Hoang; Tam, Pham Thi Thanh; Schultsz, Constance; Thwaites, Guy; Thomson, Nicholas R.

    2015-01-01

    Plasmid-mediated quinolone resistance (PMQR) refers to a family of closely related genes that confer decreased susceptibility to fluoroquinolones. PMQR genes are generally associated with integrons and/or plasmids that carry additional antimicrobial resistance genes active against a range of antimicrobials. In Ho Chi Minh City (HCMC), Vietnam, we have previously shown a high frequency of PMQR genes within commensal Enterobacteriaceae. However, there are limited available sequence data detailing the genetic context in which the PMQR genes reside, and a lack of understanding of how these genes spread across the Enterobacteriaceae. Here, we aimed to determine the genetic background facilitating the spread and maintenance of qnrS1, the dominant PMQR gene circulating in HCMC. We sequenced three qnrS1-carrying plasmids in their entirety to understand the genetic context of these qnrS1-embedded plasmids and also the association of qnrS1-mediated quinolone resistance with other antimicrobial resistance phenotypes. Annotation of the three qnrS1-containing plasmids revealed a qnrS1-containing transposon with a closely related structure. We screened 112 qnrS1-positive commensal Enterobacteriaceae isolated in the community and in a hospital in HCMC to detect the common transposon structure. We found the same transposon structure to be present in 71.4 % (45/63) of qnrS1-positive hospital isolates and in 36.7 % (18/49) of qnrS1-positive isolates from the community. The resulting sequence analysis of the qnrS1 environment suggested that qnrS1 genes are widely distributed and are mobilized on elements with a common genetic background. Our data add additional insight into mechanisms that facilitate resistance to multiple antimicrobials in Gram-negative bacteria in Vietnam. PMID:26272054

  13. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.

    PubMed

    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.

  14. Moesin Controls Clathrin-Mediated S1PR1 Internalization in T Cells

    PubMed Central

    Nomachi, Akira; Yoshinaga, Masanori; Liu, Jaron; Kanchanawong, Pakorn; Tohyama, Kiyoshi; Thumkeo, Dean; Watanabe, Takeshi; Narumiya, Shuh; Hirata, Takako

    2013-01-01

    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. PMID:24358210

  15. 26 CFR 31.3121(s)-1 - Concurrent employment by related corporations with common paymaster.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with common paymaster. 31.3121(s)-1 Section 31.3121(s)-1 Internal Revenue INTERNAL REVENUE SERVICE... Revenue Code of 1954) General Provisions § 31.3121(s)-1 Concurrent employment by related corporations with... this section. Section 3121(s) and this section apply only to remuneration disbursed in the form...

  16. Therapeutic efficacy and safety of S-1-based combination therapy compare with S-1 monotherapy following gemcitabine failure in pancreatic cancer: a meta-analysis

    PubMed Central

    Lu, Sinan; Zhang, Yuan; Zhou, Xiaohu; Zhou, Dongkai; Yang, Qifan; Ju, Bingjie; Zhao, Xinyi; Hu, Zhenhua; Xie, Haiyang; Zhou, Lin; Zheng, Shusen; Wang, Weilin

    2016-01-01

    S-1 monotherapy is widely used following gemcitabine failure in pancreatic cancer, especially in East Asia. We performed a meta-analysis to determine whether S-1-based combination therapy had better efficacy and safety compared with S-1 monotherapy. We searched Pubmed, Web of Science, ClinicalTrials.gov, and Cochrane CENTRAL and subsequently included five trials with a total of 690 patients. The combined hazard ratio (HR) or risk ratio; the corresponding 95% confidence intervals of progression-free survival, overall survival, and overall response rate; and grade 3–4 adverse events were examined. Five randomized controlled trials were included. Meta-analysis demonstrated S-1-based combination therapy significantly increased progression-free survival (HR = 0.78, 95% confidence interval [CI]: 0.67–0.90, p = 0.0009) and overall response rate (HR = 1.74, 95% CI: 1.20–2.52, p = 0.003). Evidence was insufficient to confirm that S-1-based combined regimens improved overall survival (HR = 0.87, 95% CI: 0.75–1.00, p = 0.05). There was no significant difference in adverse events between the two treatment arms. In conclusion, S-1-based combination therapy improved progression-free survival and overall response rate compared to S-1 monotherapy with acceptable toxicity. PMID:27833144

  17. Therapeutic efficacy and safety of S-1-based combination therapy compare with S-1 monotherapy following gemcitabine failure in pancreatic cancer: a meta-analysis.

    PubMed

    Lu, Sinan; Zhang, Yuan; Zhou, Xiaohu; Zhou, Dongkai; Yang, Qifan; Ju, Bingjie; Zhao, Xinyi; Hu, Zhenhua; Xie, Haiyang; Zhou, Lin; Zheng, Shusen; Wang, Weilin

    2016-11-11

    S-1 monotherapy is widely used following gemcitabine failure in pancreatic cancer, especially in East Asia. We performed a meta-analysis to determine whether S-1-based combination therapy had better efficacy and safety compared with S-1 monotherapy. We searched Pubmed, Web of Science, ClinicalTrials.gov, and Cochrane CENTRAL and subsequently included five trials with a total of 690 patients. The combined hazard ratio (HR) or risk ratio; the corresponding 95% confidence intervals of progression-free survival, overall survival, and overall response rate; and grade 3-4 adverse events were examined. Five randomized controlled trials were included. Meta-analysis demonstrated S-1-based combination therapy significantly increased progression-free survival (HR = 0.78, 95% confidence interval [CI]: 0.67-0.90, p = 0.0009) and overall response rate (HR = 1.74, 95% CI: 1.20-2.52, p = 0.003). Evidence was insufficient to confirm that S-1-based combined regimens improved overall survival (HR = 0.87, 95% CI: 0.75-1.00, p = 0.05). There was no significant difference in adverse events between the two treatment arms. In conclusion, S-1-based combination therapy improved progression-free survival and overall response rate compared to S-1 monotherapy with acceptable toxicity.

  18. S1P3 confers differential S1P migration by autoreactive and non-autoreactive immature B cells and is required for normal B cell development

    PubMed Central

    Donovan, Erin E.; Pelanda, Roberta; Torres, Raul M.

    2010-01-01

    SUMMARY During B cell development, immature B cell fate is determined by whether the B cell antigen receptor is engaged in the bone marrow. Immature B cells that are non-autoreactive continue maturation and emigrate from the marrow whereas autoreactive immature B cells remain and are tolerized. However, the microenvironment where these events occur and the chemoattractants responsible for immature B cell trafficking within and out of the bone marrow remain largely undefined. Sphingosine 1-phosphate (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte egress and in this study we investigated whether S1P contributed to B cell development, egress and positioning within the bone marrow. Our findings show that immature B cells are chemotactic towards S1P but that this response is dependent on antigen receptor specificity: non-autoreactive, but not autoreactive, immature B cells migrate towards S1P and are shown to require S1P3 receptor for this response. Despite this response, S1P3 is shown not to facilitate immature B cell egress but is required for normal B cell development including the positioning of transitional B cells within bone marrow sinusoids. These data indicate that S1P3 signaling directs immature B cells to a bone marrow microenvironment important for both tolerance induction and maturation. PMID:20039302

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

    PubMed Central

    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). The conservation of both C/S1 bZIP interactions and SIRT remains poorly characterized in non-model species, leaving their evolutionary origin uncertain and limiting crop research. In this work, we explored recently published plant sequencing data to establish a detailed phylogeny of C and S1 bZIPs, investigating their intertwined role in plant evolution, and the origin of SIRT. Our analyses clarified C and S1 bZIP orthology relationships in angiosperms, and identified S1 sequences in gymnosperms. We experimentally showed that the gymnosperm orthologs are regulated by SIRT, tracing back the origin of this unique regulatory mechanism to the ancestor of seed plants. Additionally, we discovered an earlier S ortholog in the charophyte algae Klebsormidium flaccidum, together with a C ortholog. This suggests that C and S groups originated by duplication from a single algal proto-C/S ancestor. Based on our observations, we propose a model wherein the C/S1 bZIP dimer network evolved in seed plants from pre-existing C/S bZIP interactions. PMID:27457880

  20. S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells

    PubMed Central

    Wang, Dongmei; Zhao, Zhenwen; Caperell-Grant, Andrea; Yang, Gong; Mok, Samuel C.; Liu, Jinsong; Bigsby, Robert M.; Xu, Yan

    2009-01-01

    Epithelial ovarian cancer (EOC) arises from the epithelial layer covering the surface of ovaries and intra-peritoneal metastasis is commonly observed at diagnosis. Sphingosine-1-phosphate (S1P), a bioactive lipid signaling molecule, is potentially involved in EOC tumorigenesis. We have found that S1P is elevated in human EOC ascites. We show that physiologically relevant concentrations of S1P stimulate migration and invasion of EOC cells, but inhibit migration of human ovarian surface epithelial (HOSE) cells. In addition, S1P inhibits lysophosphatidic acid (LPA)-induced cell migration in HOSE, but not in EOC cells. We have provided the first line of evidence that the expression levels of S1P receptor subtypes are not the only determinants for how cells respond to S1P. Even though S1P1 is expressed and functional in HOSE cells, the inhibitory effect mediated by S1P2 is dominant in those cells. The cellular pre-existing stress fibers are also important determinants for the migratory response to S1P. Differential S1P-induced morphology changes are noted in EOC and HOSE cells. Pre-existing stress fibers in HOSE cells are further enhanced by S1P treatment, resulting in the negative migratory response to S1P. By contrast, EOC cells lost stress fibers and S1P treatment induces filopodium-like structures at cell edges, which correlates with increased cell motility. In addition, inhibition of the protein kinase C pathway is likely to be involved in the inhibitory effect of S1P on LPA-induced cell migration in HOSE cells. These findings are important for the development of new therapeutics targeting S1P and LPA in EOC. PMID:18645009

  1. Effects of exogenous GABA on gene expression of Caragana intermedia roots under NaCl stress: regulatory roles for H2O2 and ethylene production.

    PubMed

    Shi, Sheng-Qing; Shi, Zheng; Jiang, Ze-Ping; Qi, Li-Wang; Sun, Xiao-Mei; Li, Chun-Xiu; Liu, Jian-Feng; Xiao, Wen-Fa; Zhang, Shou-Gong

    2010-02-01

    gamma-aminobutyric acid (GABA) is a four-carbon non-protein amino acid presented in a wide range of organisms. In this study, a suppression subtractive hybridization (SSH) library was constructed using roots of a legume shrub, Caragana intermedia, with the combined treatment of 300 mm NaCl and 300 mm NaCl + 10 mm GABA. We obtained 224 GABA-regulated unique expressed sequence tags (ESTs) including signal transduction, transcriptional regulation, hormone biosynthesis, reactive oxygen species (ROS) and polyamine metabolism, etc. The key H(2)O(2)-generated genes, NADPH oxidase (CaGR60), peroxidase (CaGR61) and amine oxidase (CaGR62), were regulated at the mRNA level by 10 mm GABA, which clearly inhibited H(2)O(2) accumulation brought about by NaCl stress in roots and leaves with the observation of 3,3'-diaminobenzidine (DAB) staining. Similarly, 10 mm GABA also regulated the expression of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACO) genes (CaGR30 and CaGR31) and ethylene production in NaCl-treated roots. Surprisingly, these H(2)O(2)-generated genes were enhanced at the mRNA level by a lower concentration of GABA, at 0.25 mm, but not other alternative nitrogen sources, and endogenous GABA accumulated largely just by the application of GABA at either concentration. Our results further proved that GABA, as a signal molecule, participates in regulating the expression of genes in plants under salt stress.

  2. Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang β-Thalassemia Intermedia Patients.

    PubMed

    Lai, Yunli; Chen, Yun; Chen, Biyan; Zheng, Haiyang; Yi, Sheng; Li, Guojian; Wei, Hongwei; He, Sheng; Zheng, Chenguang

    2016-11-01

    Increased Hb F levels can ameliorate the symptoms of β-thalassemia (β-thal). Due to the genetic heterogenicity of β-thal, the relationship between genetic variants in modifier genes and Hb F level has been studied in different populations. The Chinese Zhuang has the second largest population in China and has 6.78% prevalence of β-thal. However, the effects of these single nucleotide polymorphism (SNP) variants on the Hb F levels of β-thal intermedia (β-TI) patients in this population have not been reported. To explore the association between modifier loci (β-globin gene cluster, HBS1L-MYB intergenic region and BCL11A) and Hb F levels in Chinese Zhuang β-TI patients, 96 unrelated β-TI patients (50 males and 46 females) with different Hb F levels were recruited and genotyped by mass spectrometry. A total of 13 SNPs were confirmed to be in a significant relationship with Hb F levels in this population. Of these, high-risk genotypes of six Hb F-associated SNPs, rs9376090, rs7776054, rs9399137, rs9389268, rs9402685 in the HBS1L-MYB intergenic region and rs189984760 in the BCL11A locus, showed association with high Hb F levels, especially for SNPs in linkage disequilibrium. One novel Hb F-associated SNP, rs189984760, was identified in our study. Our findings will be of valuable reference for correlation between modifier genes and Hb F in Chinese Zhuang populations and may lead to better understand the modifying mechanisms for β-thal.

  3. Phytosphingosine 1-phosphate: a high affinity ligand for the S1P(4)/Edg-6 receptor.

    PubMed

    Candelore, Mari Rios; Wright, Michael J; Tota, Laurie M; Milligan, James; Shei, Gan-ju; Bergstrom, James D; Mandala, Suzanne M

    2002-09-27

    It has been reported recently that the phosphorylated form of the immunomodulator FTY720 activates sphingosine 1-phosphate G protein-coupled receptors. Therefore, understanding the biology of this new class of receptors will be important in clarifying the immunological function of bioactive lysosphingolipid ligands. The S1P(4) receptor has generated interest due to its lymphoid tissue distribution. While the S1P(4) receptor binds the prototypical ligand, S1P, a survey of other lysosphingolipids demonstrated that 4D-hydroxysphinganine 1-phosphate, more commonly known as phytosphingosine 1-phosphate (PhS1P), binds to S1P(4) with higher affinity. Using radiolabeled S1P (S133P), the affinity of PhS1P for the S1P(4) receptor is 1.6nM, while that of S1P is nearly 50-fold lower (119+/-20nM). Radiolabeled PhS1P proved to be superior to S133P in routine binding assays due to improved signal-to-noise ratio. The present study demonstrates the utility of a novel radiolabeled probe, PhS133P, for in vitro studies of the S1P(4) receptor pharmacology.

  4. Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

    PubMed

    Tsuji, Takashi; Suzuki, Keisuke; Nakamura, Tsuyoshi; Goto, Taiji; Sekiguchi, Yukiko; Ikeda, Takuya; Fukuda, Takeshi; Takemoto, Toshiyasu; Mizuno, Yumiko; Kimura, Takako; Kawase, Yumi; Nara, Futoshi; Kagari, Takashi; Shimozato, Takaichi; Yahara, Chizuko; Inaba, Shinichi; Honda, Tomohiro; Izumi, Takashi; Tamura, Masakazu; Nishi, Takahide

    2014-08-01

    We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.

  5. S1P lyase in skeletal muscle regeneration and satellite cell activation: exposing the hidden lyase.

    PubMed

    Saba, Julie D; de la Garza-Rodea, Anabel S

    2013-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid whose actions are essential for many physiological processes including angiogenesis, lymphocyte trafficking and development. In addition, S1P serves as a muscle trophic factor that enables efficient muscle regeneration. This is due in part to S1P's ability to activate quiescent muscle stem cells called satellite cells (SCs) that are needed for muscle repair. However, the molecular mechanism by which S1P activates SCs has not been well understood. Further, strategies for harnessing S1P signaling to recruit SCs for therapeutic benefit have been lacking. S1P is irreversibly catabolized by S1P lyase (SPL), a highly conserved enzyme that catalyzes the cleavage of S1P at carbon bond C(2-3), resulting in formation of hexadecenal and ethanolamine-phosphate. SPL enhances apoptosis through substrate- and product-dependent events, thereby regulating cellular responses to chemotherapy, radiation and ischemia. SPL is undetectable in resting murine skeletal muscle. However, we recently found that SPL is dynamically upregulated in skeletal muscle after injury. SPL upregulation occurred in the context of a tightly orchestrated genetic program that resulted in a transient S1P signal in response to muscle injury. S1P activated quiescent SCs via a sphingosine-1-phosphate receptor 2 (S1P2)/signal transducer and activator of transcription 3 (STAT3)-dependent pathway, thereby facilitating skeletal muscle regeneration. Mdx mice, which serve as a model for muscular dystrophy (MD), exhibited skeletal muscle SPL upregulation and S1P deficiency. Pharmacological SPL inhibition raised skeletal muscle S1P levels, enhanced SC recruitment and improved mdx skeletal muscle regeneration. These findings reveal how S1P can activate SCs and indicate that SPL suppression may provide a therapeutic strategy for myopathies. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.

  6. Evidence of mutualism between two periodontal pathogens: co-operative haem acquisition by the HmuY haemophore of Porphyromonas gingivalis and the cysteine protease interpain A (InpA) of Prevotella intermedia.

    PubMed

    Byrne, D P; Potempa, J; Olczak, T; Smalley, J W

    2013-06-01

    Haem (iron protoporphyrin IX) is both an essential growth factor and a virulence regulator of the periodontal pathogens Porphyromonas gingivalis and Prevotella intermedia, which acquire it through the proteolytic degradation of haemoglobin and other haem-carrying plasma proteins. The haem-binding lipoprotein HmuY haemophore and the gingipain proteases of P. gingivalis form a unique synthrophic system responsible for capture of haem from haemoglobin and methaemalbumin. In this system, methaemoglobin is formed from oxyhaemoglobin by the activities of gingipain proteases and serves as a facile substrate from which HmuY can capture haem. This study examined the possibility of cooperation between HmuY and the cysteine protease interpain A (InpA) of Pr. intermedia in the haem acquisition process. Using UV-visible spectroscopy and polyacrylamide gel electrophoresis, HmuY was demonstrated to be resistant to proteolysis and so able to cooperate with InpA to extract haem from haemoglobin, which was proteolytically converted to methaemoglobin by the protease. Spectroscopic pH titrations showed that both the iron(II) and iron(III) protoporphyrin IX-HmuY complexes were stable over the pH range 4-10, demonstrating that the haemophore could function over a range of pH that may be encountered in the dental plaque biofilm. This is the first demonstration of a bacterial haemophore working in conjunction with a protease from another bacterial species to acquire haem from haemoglobin and may represent mutualism between P. gingivalis and Pr. intermedia co-inhabiting the periodontal pocket.

  7. Ribosome-messenger recognition: mRNA target sites for ribosomal protein S1.

    PubMed Central

    Boni, I V; Isaeva, D M; Musychenko, M L; Tzareva, N V

    1991-01-01

    Ribosomal protein S1 is known to play an important role in translational initiation, being directly involved in recognition and binding of mRNAs by 30S ribosomal particles. Using a specially developed procedure based on efficient crosslinking of S1 to mRNA induced by UV irradiation, we have identified S1 binding sites on several phage RNAs in preinitiation complexes. Targets for S1 on Q beta and fr RNAs are localized upstream from the coat protein gene and contain oligo(U)-sequences. In the case of Q beta RNA, this S1 binding site overlaps the S-site for Q beta replicase and the site for S1 binding within a binary complex. It is reasonable that similar U-rich sequences represent S1 binding sites on bacterial mRNAs. To test this idea we have used E. coli ssb mRNA prepared in vitro with the T7 promoter/RNA polymerase system. By the methods of toeprinting, enzymatic footprinting, and UV crosslinking we have shown that binding of the ssb mRNA to 30S ribosomes is S1-dependent. The oligo(U)-sequence preceding the SD domain was found to be the target for S1. We propose that S1 binding sites, represented by pyrimidine-rich sequences upstream from the SD region, serve as determinants involved in recognition of mRNA by the ribosome. Images PMID:2011495

  8. Discovery of a novel series of potent S1P1 agonists.

    PubMed

    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.

  9. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development

    PubMed Central

    Jung, Bongnam; Obinata, Hideru; Galvani, Sylvain; Mendelson, Karen; Ding, Bisen; Skoura, Athanasia; Kinzel, Bernd; Brinkmann, Volker; Rafii, Shahin; Evans, Todd; Hla, Timothy

    2012-01-01

    SUMMARY During angiogenesis, nascent vascular sprouts fuse to form vascular networks enabling efficient circulation. Mechanisms that stabilize the vascular plexus are not well understood. Sphingosine 1-phosphate (S1P) is a blood-borne lipid mediator implicated in the regulation of vascular and immune systems. Here we describe a mechanism by which the G protein-coupled S1P receptor-1 (S1P1) stabilizes the primary vascular network. A gradient of S1P1 expression from the mature regions of the vascular network to the growing vascular front was observed. In the absence of endothelial S1P1, adherens junctions are destabilized, barrier function is breached, and flow is perturbed resulting in abnormal vascular hypersprouting. Interestingly, S1P1 responds to S1P as well as laminar shear stress to transduce flow-mediated signaling in endothelial cells both in vitro and in vivo. These data demonstrate that blood flow and circulating S1P activate endothelial S1P1 to stabilize blood vessels in development and homeostasis. PMID:22975328

  10. Intersystem crossing rates of S1 state keto-amino cytosine at low excess energy.

    PubMed

    Lobsiger, Simon; Etinski, Mihajlo; Blaser, Susan; Frey, Hans-Martin; Marian, Christel; Leutwyler, Samuel

    2015-12-21

    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((1)ππ(∗)) 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 ⋅ 10(9) 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 ⋅ 10(9) s(-1) to the T1((3)ππ(∗)) triplet state. The surprisingly high rate of this El Sayed-forbidden transition is caused by a substantial admixture of (1)nOπ(∗) character into the S1((1)ππ(∗)) 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 ⋅ 10(10) s(-1), (2) the calculated S1⇝T1 ((1)ππ(∗)⇝(3)ππ(∗)) ISC rate is in good agreement with experiment, (3) being El-Sayed forbidden, the S1⇝T1 ISC is moderately fast (kISC = 3 ⋅ 10(9) 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.

  11. S1P₁ localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity.

    PubMed

    Montrose, David C; Scherl, Ellen J; Bosworth, Brian P; Zhou, Xi Kathy; Jung, Bongnam; Dannenberg, Andrew J; Hla, Timothy

    2013-03-01

    Signaling through sphingosine-1-phosphate receptor₁ (S1P₁) promotes blood vessel barrier function. Degradation of S1P₁ results in increased vascular permeability in the lung and may explain side effects associated with administration of FTY720, a functional antagonist of the S1P₁ receptor that is currently used to treat multiple sclerosis. Ulcerative colitis (UC) is characterized by an increased density of abnormal vessels. The expression or role of S1P₁ in blood vessels in the colon has not been investigated. In the present study, we show that S1P₁ is overexpressed in the colonic mucosa of UC patients. This increase in S1P₁ levels reflects increased vascular density in the inflamed mucosa. Genetic deletion of S1pr1 in mice increases colonic vascular permeability under basal conditions and increases bleeding in experimental colitis. In contrast, neither FTY720 nor AUY954, two S1P receptor-targeting agents, increases bleeding in experimental colitis. Taken together, our findings demonstrate that S1P₁ is critical to maintaining colonic vascular integrity and may play a role in UC pathogenesis.

  12. S1←S0 vibronic spectra and structure of cyclopropanecarboxaldehyde molecule in the S1 lowest excited singlet electronic state

    NASA Astrophysics Data System (ADS)

    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.

  13. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola / Prevotella intermedia Co-Infection Are Associated with Severe Periodontitis in a Thai Population.

    PubMed

    Torrungruang, Kitti; Jitpakdeebordin, Supawadee; Charatkulangkun, Orawan; Gleebbua, Yingampa

    2015-01-01

    Periodontitis is a polymicrobial infection of tooth-supporting tissues. This cross-sectional study aimed to examine the associations between five target species and severe periodontitis in a Thai population. Using the CDC/AAP case definition, individuals diagnosed with no/mild and severe periodontitis were included. Quantitative analyses of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), and Prevotella intermedia (Pi) in subgingival plaque were performed using real-time polymerase chain reaction. The association between target species and severe periodontitis was examined using logistic regression analysis. The study subjects comprised 479 individuals with no/mild periodontitis and 883 with severe periodontitis. Bacterial prevalence and quantity were higher in subjects with severe periodontitis than in those with no/mild disease. In the fully adjusted model, all species except Tf showed a dose-dependent relationship with periodontitis. The mere presence of Pg, even in low amount, was significantly associated with severe periodontitis, while the amount of Aa, Td, and Pi had to reach the critical thresholds to be significantly associated with disease. Compared to individuals with low levels of both Td and Pi, high colonization by either Td or Pi alone significantly increased the odds of having severe periodontitis by 2.5 (95%CI 1.7-3.5) folds. The odds ratio was further increased to 14.8 (95%CI 9.2-23.8) in individuals who were highly colonized by both species. Moreover, the presence of Pg and high colonization by Aa were independently associated with severe periodontitis with odds ratios of 5.6 (95%CI 3.4-9.1) and 2.2 (95%CI 1.5-3.3), respectively. Our findings suggest that the presence of Pg and high colonization by Aa, Td, and Pi play an important role in severe periodontitis in this study population. We also demonstrate for the first time that individuals co-infected with Td and Pi

  14. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola / Prevotella intermedia Co-Infection Are Associated with Severe Periodontitis in a Thai Population

    PubMed Central

    Torrungruang, Kitti; Jitpakdeebordin, Supawadee; Charatkulangkun, Orawan; Gleebbua, Yingampa

    2015-01-01

    Periodontitis is a polymicrobial infection of tooth-supporting tissues. This cross-sectional study aimed to examine the associations between five target species and severe periodontitis in a Thai population. Using the CDC/AAP case definition, individuals diagnosed with no/mild and severe periodontitis were included. Quantitative analyses of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), and Prevotella intermedia (Pi) in subgingival plaque were performed using real-time polymerase chain reaction. The association between target species and severe periodontitis was examined using logistic regression analysis. The study subjects comprised 479 individuals with no/mild periodontitis and 883 with severe periodontitis. Bacterial prevalence and quantity were higher in subjects with severe periodontitis than in those with no/mild disease. In the fully adjusted model, all species except Tf showed a dose-dependent relationship with periodontitis. The mere presence of Pg, even in low amount, was significantly associated with severe periodontitis, while the amount of Aa, Td, and Pi had to reach the critical thresholds to be significantly associated with disease. Compared to individuals with low levels of both Td and Pi, high colonization by either Td or Pi alone significantly increased the odds of having severe periodontitis by 2.5 (95%CI 1.7–3.5) folds. The odds ratio was further increased to 14.8 (95%CI 9.2–23.8) in individuals who were highly colonized by both species. Moreover, the presence of Pg and high colonization by Aa were independently associated with severe periodontitis with odds ratios of 5.6 (95%CI 3.4–9.1) and 2.2 (95%CI 1.5–3.3), respectively. Our findings suggest that the presence of Pg and high colonization by Aa, Td, and Pi play an important role in severe periodontitis in this study population. We also demonstrate for the first time that individuals co-infected with Td

  15. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    SciTech Connect

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui; Xiao, Gengfu

    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.

  16. Effects of α s1-casein (CSN1S1) and κ-casein (CSN3) genotypes on milk coagulation properties in Murciano-Granadina goats.

    PubMed

    Caravaca, Francisco; Ares, José Luis; Carrizosa, Juan; Urrutia, Baltasar; Baena, Francisca; Jordana, Jordi; Badaoui, Bouabid; Sànchez, Armand; Angiolillo, Antonella; Amills, Marcel; Serradilla, Juan Manuel

    2011-02-01

    The effects of the caprine α s1-casein (CSN1S1) polymorphisms on milk quality and cheese yield have been widely studied in French and Italian goat breeds. Much less is known about the consequences of κ-casein (CSN3) genotype on the technological and coagulation properties of goat milk. In the current study, we have performed an association analysis between polymorphisms at the goat CSN1S1 and CSN3 genes and milk coagulation (rennet coagulation time, curdling rate and curd firmness) and technological (time to cutting of curd and cheese yield) properties. In this analysis, we have included 193 records from 74 Murciano-Granadina goats (with genotypes constituted by different combinations of alleles B, E and F of the gene CSN1S1 and alleles A and B of the gene CSN3) distributed in three herds, which were collected bimonthly during a whole lactation. Data analysis, using a linear mixed model for repeated observations, revealed significant associations between CSN1S1 genotypes and the rate of the curdling process. In this way, milk from EE goats had a significantly higher curdling rate than milk from BB individuals (P<0·05). Contrary to previous experiments performed in French breeds, cheese yield was not significantly different in BB, EE and EF goats. Moreover, we have shown that CSN3 genotype has a significant effect on the rennet coagulation time (BB>AB, P<0·05) but not on cheese yield. No interaction between the CSN1S1 and CSN3 genotypes was observed.

  17. Pathophysiological Consequences of a Break in S1P1-Dependent Homeostasis of Vascular Permeability Revealed by S1P1 Competitive Antagonism

    PubMed Central

    Bigaud, Marc; Dincer, Zuhal; Bollbuck, Birgit; Dawson, Janet; Beckmann, Nicolau; Beerli, Christian; Fishli-Cavelti, Gina; Nahler, Michaela; Angst, Daniela; Janser, Philipp; Otto, Heike; Rosner, Elisabeth; Hersperger, Rene; Bruns, Christian; Quancard, Jean

    2016-01-01

    Rational Homeostasis of vascular barriers depends upon sphingosine 1-phosphate (S1P) signaling via the S1P1 receptor. Accordingly, S1P1 competitive antagonism is known to reduce vascular barrier integrity with still unclear pathophysiological consequences. This was explored in the present study using NIBR-0213, a potent and selective S1P1 competitive antagonist. Results NIBR-0213 was tolerated at the efficacious oral dose of 30 mg/kg BID in the rat adjuvant-induced arthritis (AiA) model, with no sign of labored breathing. However, it induced dose-dependent acute vascular pulmonary leakage and pleural effusion that fully resolved within 3–4 days, as evidenced by MRI monitoring. At the supra-maximal oral dose of 300 mg/kg QD, NIBR-0213 impaired lung function (with increased breathing rate and reduced tidal volume) within the first 24 hrs. Two weeks of NIBR-0213 oral dosing at 30, 100 and 300 mg/kg QD induced moderate pulmonary changes, characterized by alveolar wall thickening, macrophage accumulation, fibrosis, micro-hemorrhage, edema and necrosis. In addition to this picture of chronic inflammation, perivascular edema and myofiber degeneration observed in the heart were also indicative of vascular leakage and its consequences. Conclusions Overall, these observations suggest that, in the rat, the lung is the main target organ for the S1P1 competitive antagonism-induced acute vascular leakage, which appears first as transient and asymptomatic but could lead, upon chronic dosing, to lung remodeling with functional impairments. Hence, this not only raises the question of organ specificity in the homeostasis of vascular barriers, but also provides insight into the pre-clinical evaluation of a potential safety window for S1P1 competitive antagonists as drug candidates. PMID:28005953

  18. ( sup 125 I)Bolton-Hunter neuropeptide-Y-binding sites on folliculo-stellate cells of the pars intermedia of Xenopus laevis: A combined autoradiographic and immunocytochemical study

    SciTech Connect

    De Rijk, E.P.; Cruijsen, P.M.; Jenks, B.G.; Roubos, E.W. )

    1991-02-01

    It has previously been established that neuropeptide-Y (NPY) is a potent inhibitor of alpha MSH release from the pars intermedia of the amphibian Xenopus laevis. The location of binding sites for NPY in the pars intermedia of the pituitary has now been studied with light microscopic autoradiography, using a dispersed cell labeling method with the specific NPY receptor ligand ({sup 125}I)Bolton-Hunter NPY. The majority of radioactive labeling was associated with folliculo-stellate cells; the percentage of labeling as well as the mean number of grains were approximately 5 times higher for folliculo-stellate cells than for melanotropes. An excess of nonlabeled NPY drastically reduced radiolabeling of folliculo-stellate cells, but had no effect on the degree of labeling of melanotropes. These results show that folliculo-stellate cells of X. laevis possess specific binding sites for NPY and indicate that NPY exerts its inhibitory action on the release of alpha MSH in an indirect fashion, by acting on the folliculo-stellate cells.

  19. Localization of amylin-like immunoreactivity in melanocyte-stimulating hormone-containing cells of the pars intermedia but not those of the pars distalis in the axolotl (Ambystoma mexicanum) pituitary.

    PubMed

    Suzuki, Hirohumi; Yamamoto, Toshiharu

    2016-04-01

    Immunohistochemical techniques were employed to investigate the distribution of amylin-like immunoreactivity in the axolotl (Ambystoma mexicanum) pituitary. Amylin-immunoreactive cells were observed in the pars intermedia, and these cells were found to be immunoreactive for α-melanocyte-stimulating hormone (αMSH) as well. In contrast, αMSH-immunoreactive cells in the pars distalis were immuno-negaitive for amylin. These light microscopic findings were confirmed by immunoelectron microscopy. Amylin-immunoreactive signals were located on the haloes of presumable secretory granules in association with αMSH-immunoreactive signals in the amylin-positive cells. However, in the pars distalis, the αMSH-positive cells did not contain amylin-immunoreactive secretory granules. Western blot analysis of axolotl pituitary extracts revealed the labeling of a protein band at approximately 10.5-kDa by the anti-rat amylin serum, which was not labeled by the anti-αMSH antibody. These findings indicate that amylin secreted from MSH-producing cells in the pars intermedia may modulate MSH secretion in an autocrine fashion and may participate in MSH functions such as fatty homeostasis together with MSH.

  20. Lavandin (Lavandula × intermedia Emeric ex Loiseleur) essential oil from Spain: determination of aromatic profile by gas chromatography-mass spectrometry, antioxidant and lipoxygenase inhibitory bioactivities.

    PubMed

    Carrasco, Alejandro; Martinez-Gutierrez, Ramiro; Tomas, Virginia; Tudela, Jose

    2016-01-01

    Lavandin (Lavandula × intermedia Emeric ex Loiseleur) essential oils (EOs), from Abrial, Super and Grosso cultivars, cultivated and extracted in the South East of Spain, were analysed by using GC/MS to determine their composition, in both relative (peak area) and absolute (using standard curves) concentrations. Linalool (34-47%), linalyl acetate (17-34%), camphor (4-9%) and eucalyptol (3-7%) were determined as the main molecules. This characterisation was completed with the enantioselective gas chromatography, where ( - )-linalool, (+)-camphor and ( - )-linalyl acetate were determined as the main components. Antioxidant activity was evaluated positively by several methods: activity against free radicals, chelating and reducing power, probably due to linalool and linalyl acetate. Mild inhibitory activity on lipoxygenase was observed supporting potential anti-inflammatory activity, mainly due to linalool and camphor. These properties support the potential use of L. × intermedia essential oils as natural cosmetic and natural pharmaceutical ingredient to fight several skin diseases.

  1. Synthesis and evaluation of CS-2100, a potent, orally active and S1P(3)- sparing S1P(1) agonist.

    PubMed

    Nakamura, Tsuyoshi; Asano, Masayoshi; Sekiguchi, Yukiko; Mizuno, Yumiko; Tamaki, Kazuhiko; Nara, Futoshi; Kawase, Yumi; Yabe, Yoshiyuki; Nakai, Daisuke; Kamiyama, Emi; Urasaki-Kaneno, Yoko; Shimozato, Takaichi; Doi-Komuro, Hiromi; Kagari, Takashi; Tomisato, Wataru; Inoue, Ryotaku; Nagasaki, Miyuki; Yuita, Hiroshi; Oguchi-Oshima, Keiko; Kaneko, Reina; Nishi, Takahide

    2012-05-01

    Modulators of sphingosine phosphate receptor-1 (S1P(1)) have recently been focused as a suppressant of autoimmunity. We have discovered a 4-ethylthiophene-based S1P(1) agonist 1-({4-Ethyl-5-[5-(4-phenoxyphenyl)-1,2,4-oxadiazol-3-yl]-2-thienyl}methyl)azetidine-3-carboxylic acid (CS-2100, 8) showing potent S1P(1) agonist activity against S1P(3) and an excellent in vivo potency. We report herein the synthesis of CS-2100 (8) and pharmacological effects such as S1P(1) and S1P(3) agonist activity in vitro, peripheral blood lymphocyte lowering effects and the suppressive effects on adjuvant-induced arthritis and experimental autoimmune encephalomyelitis (EAE) in animal models. The pharmacokinetic data were also reported. CS-2100 (8) had >5000-fold greater agonist activity for human S1P(1) (EC(50); 4.0 nM) relative to S1P(3) (EC(50); >20,000 nM). Following administration of single oral doses of 0.1 and 1 mg/kg of CS-2100 (8) in rats, lymphocyte counts decreased significantly, with a nadir at 8 and/or 12 h post-dose and recovery to vehicle control levels by 24-48 h post-dose. CS-2100 (8) is efficacious in the adjuvant-induced arthritis model in rats (ID(50); 0.44 mg/kg). In the EAE model compared to the vehicle-treated group, significant decreases in the cumulative EAE scores were observed for 0.3 and 1 mg/kg CS-2100 (8) groups in mice. While CS-2100 (8) showed potent efficacy in various animal disease models, it was also revealed that the central 1,2,4-oxadiazole ring of CS-2100 (8) was decomposed by enterobacteria in intestine of rats and monkeys, implicating the latent concern about an external susceptibility in its metabolic process in the upcoming clinical studies.

  2. To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient.

    PubMed

    Liu, Jingjing; Hsu, Andrew; Lee, Jen-Fu; Cramer, Daniel E; Lee, Menq-Jer

    2011-01-26

    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 S1P(1), S1P(2) or S1P(3) receptors. Hence, S1P is important for stem cells circulation in blood system to accomplish its role in body surveillance and injury recovery.

  3. Mechanism of the S1 excited state internal conversion in vitamin B12.

    PubMed

    Lodowski, Piotr; Jaworska, Maria; Andruniów, Tadeusz; Garabato, Brady D; Kozlowski, Pawel M

    2014-09-21

    To explain the photostability of vitamin B12, internal conversion of the S1 state was investigated using TD-DFT. The active coordinates for radiationless deactivation were determined to be elongated axial bonds, overcoming a 5.0 kcal mol(-1) energy barrier between the relaxed ligand-to-metal charge transfer (S1), and the ground (S0) states.

  4. To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling.

    PubMed

    Chew, Wee Siong; Wang, Wei; Herr, Deron R

    2016-11-01

    Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and disease states, such as cardiovascular development, immune function, hypoxic responses, and cancer. The therapeutic potential of targeting this system took center stage when it was demonstrated that the immune modulator, fingolimod (FTY720/Gilenya), exerts it lymphopenic effect by acting on S1P receptors, primarily on S1P receptor 1 (S1P1). In 2010, fingolimod became the first oral medication approved for the treatment of multiple sclerosis (MS). Since then, second-generation S1P receptor modulators have been under development in an effort to provide improved safety and efficacy profiles for MS, and to broaden their use to other autoimmune indications. Beyond the development of S1P1-modulators, there has been considerable effort in targeting other components of the S1P signaling pathway for the treatment of other diseases, such as cardiovascular disease, sepsis, and cancer. This manuscript provides an overview of the clinical and preclinical development of drugs targeting S1P signaling.

  5. Genome sequence of Bacillus pumilus S-1, an efficient isoeugenol-utilizing producer for natural vanillin.

    PubMed

    Su, Fei; Hua, Dongliang; Zhang, Zhaobin; Wang, Xiaoyu; Tang, Hongzhi; Tao, Fei; Tai, Cui; Wu, Qiulin; Wu, Geng; Xu, Ping

    2011-11-01

    Bacillus pumilus S-1 is an efficient isoeugenol-utilizing producer of natural vanillin. The genome of B. pumilus S-1 contains the epoxide hydrolase and six candidate monooxygenases that make it possible to explore the mechanism involved in conversion of isoenguenol to vanillin in the B. pumilus strain.

  6. VIEW OF THE FROM SIDE OF WHARF S1 FROM WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF THE FROM SIDE OF WHARF S1 FROM WEST END OF QUARRY LOCK, FACING NORTHWEST - U.S. Naval Base, Pearl Harbor, Naval Submarine Base, Berthing Wharf S1, South Waterfront Road along north side of Quarry Loch, Pearl City, Honolulu County, HI

  7. Enhanced Raman scattering from cesium suboxides on silver particles and the structure of S-1 photocathodes

    NASA Technical Reports Server (NTRS)

    Bates, C. W., Jr.

    1984-01-01

    An explanation is given for the results of recent enhanced Raman scattering studies of photomultiplier tubes with S-1 photocathode surfaces which indicated the presence of Cs11O3 but not Cs2O. The reason for the discrepancy between the currently accepted model of the S-1 and this recent result is discussed.

  8. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury

    PubMed Central

    Liu, Huiying; Zhang, Zili; Li, Puyuan; Yuan, Xin; Zheng, Jing; Liu, Jinwen

    2016-01-01

    Background Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30–40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P. Methods By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. Results It was found that the down-regulation of TNF-α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. Discussions The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their

  9. Short communication: Carora cattle show high variability in alpha(s1)-casein.

    PubMed

    Caroli, A; Chessa, S; Chiatti, F; Rignanese, D; Meléndez, B; Rizzi, R; Ceriotti, G

    2008-01-01

    The objective of this study was to analyze the genetic variability of milk proteins of the Carora, a shorthorned Bos taurus cattle breed in Venezuela and in other Southern American countries that is primarily used for milk production. A total of 184 individual milk samples were collected from Carora cattle in 5 herds in Venezuela. The milk protein genes alpha(s1)-casein (CN) (CSN1S1), beta-CN (CSN2), kappa-CN (CSN3), and beta-lactoglobulin (LGB) were typed at the protein level by isoelectrofocusing. It was necessary to further analyze CSN1S1 at the DNA level by a PCR-based method to distinguish CSN1S1*G from B. Increased variation was found in particular at the CSN1S1 gene, where 4 variants were identified. The predominant variant was CSN1S1*B (frequency = 0.8). The second most common CSN1S1 variant was CSN1S1*G (0.101), followed by CSN1S1*C (0.082). Moreover, a new isoelectrofocusing pattern was identified, which may result from a novel CSN1S1 variant, named CSN1S1*I, migrating at an intermediate position between CSN1S1*B and CSN1S1*C. Six cows carried the variant at the heterozygous condition. For the other loci, predominance of CSN2*A2 (0.764), CSN3*B (0.609), and LGB*B (0.592) was observed. Haplotype frequencies (AF) at the CSN1S1-CSN2-CSN3 complex were also estimated by taking association into account. Only 7 haplotypes showed AF values >0.05, accounting for a cumulative frequency of 0.944. The predominant haplotype was B-A2-B (frequency = 0.418), followed by B-A2-A (0.213). The occurrence of the G variant is at a rather high frequency, which is of interest for selection within the Carora breed because of the negative association of this variant with the synthesis of the specific protein. From a cheese-making point of view, this variant is associated with improved milk-clotting parameters but is negatively associated with cheese ripening. Thus, milk protein typing should be routinely carried out in the breed, with particular emphasis on using a DNA test to

  10. Local Equivalence of Representations of {Diff^+(S^1)} Corresponding to Different Highest Weights

    NASA Astrophysics Data System (ADS)

    Weiner, Mihály

    2017-01-01

    Let c, h and {c,tilde{h}} be two admissible pairs of central charge and highest weight for {Diff^+(S^1)} . It is shown here that the positive energy irreducible projective unitary representations {U_{c,h}} and {U_{c,tilde{h}}} of the group {Diff^+(S^1)} are locally equivalent. This means that for any {ISubset S^1} open proper interval, there exists a unitary operator W I such that {W_I U_{c,h}(γ)W_I^* = U_{c,tilde{h}}(γ)} for all {γ in Diff^+(S^1)} which act identically on {I^c≡ S^1{setminus} I} (i.e., which can "displace" or "move" points only in I). This result extends and completes earlier ones that dealt with only certain regions of the "c, h-plane", and closes the gap in the full classification of superselection sectors of Virasoro nets.

  11. SUSY structures, representations and Peter-Weyl theorem for S 1 | 1

    NASA Astrophysics Data System (ADS)

    Carmeli, C.; Fioresi, R.; Kwok, S.

    2015-09-01

    The real compact supergroup S 1 | 1 is analysed from different perspectives and its representation theory is studied. We prove it is the only (up to isomorphism) supergroup, which is a real form of (C 1 | 1) × with reduced Lie group S1, and a link with SUSY structures on C 1 | 1 is established. We describe a large family of complex semisimple representations of S 1 | 1 and we show that any S 1 | 1-representation whose weights are all nonzero is a direct sum of members of our family. We also compute the matrix elements of the members of this family and we give a proof of the Peter-Weyl theorem for S 1 | 1.

  12. Estimates of epistatic and pleiotropic effects of casein alpha s1 (CSN1S1) and thyroglobulin (TG) genetic markers on beef heifer performance traits enhanced by selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for two years to equalize CSN1S1 and TG genetic marker frequencies to evaluate the epista...

  13. Phosphorylation of αS1-casein is regulated by different genes.

    PubMed

    Bijl, E; van Valenberg, H J F; Huppertz, T; van Hooijdonk, A C M; Bovenhuis, H

    2014-11-01

    Casein phosphorylation is a posttranslational modification catalyzed by kinase enzymes that attach phosphate groups to specific AA in the protein sequence. This modification is one of the key factors responsible for the stabilization of calcium phosphate nanoclusters in casein micelles and for the internal structure of the casein micelles. α(S1)-Casein (α(s1)-CN) is of special interest because it constitutes up to 40% of the total casein fraction in milk, and it has 2 common phosphorylation states, with 8 (α(S1)-CN-8P) and 9 (α(S1)-CN-9P) phosphorylated serine residues. Factors affecting this variation in the degree of phosphorylation are not currently known. The objective of this research was to determine the genetic background of α(S1)-CN-8P and α(S1)-CN-9P. The genetic and phenotypic correlation between α(S1)-CN-8P and α(S1)-CN-9P was low (0.18 and 0.19, respectively). This low genetic correlation suggests a different genetic background. These differences were further investigated by means of a genome-wide association study, which showed that both α(S1)-CN-8P and α(S1)-CN-9P were affected by a region on Bos taurus autosome (BTA) 6, but only α(S1)-CN-8P was affected by a region on BTA11 that contains the gene that encodes for β-lactoglobulin (β-LG), and only α(S1)-CN-9P was affected by a region on BTA14 that contains the diacylglycerol acyltransferase 1 (DGAT1) gene. Estimated effects of β-LG protein genotypes showed that only α(S1)-CN-8P was associated with the β-LG A/B polymorphism (g.1772G>A and g.3054C>T); the AA genotype of β-LG was associated with a lower concentration of α(S1)-CN-8P (-0.32% wt/wt) than the BB genotype (+0.41% wt/wt). Estimated effects of DGAT1 K232A genotypes showed that only α(S1)-CN-9P was associated with the DGAT1 gene polymorphism; DGAT1 AA genotype was associated with a higher α(S1)-CN-9P concentration (+0.53% wt/wt) than the DGAT1 KK genotype (-0.44% wt/wt). The results give insight in phosphorylation of α(S1

  14. One-stage surgery through posterior approach-for L5-S1 spondyloptosis

    PubMed Central

    Suslu, Hikmet Turan; Celikoglu, Erhan; Borekcı, Ali; Hıcdonmez, Tufan; Suslu, Hüsnü

    2011-01-01

    Grade 5 spondylolisthesis or spondyloptosis is a rare condition. Generally, the surgical management of spondyloptosis includes multi-staged procedures instead of one-staged procedures. One-stage treatment for spondyloptosis is very rare. A 15-year-old girl with L5-S1 spondyloptosis was admitted with severe low back pain. There was no history of trauma. The patient underwent L5 laminectomy, L5-S1 discectomy, resection of sacral dome, reduction, L3-L4-L5-S1 pedicular screw fixation, and interbody-posterolateral fusion through the posterior approach. The reduction was maintained with bilateral L5-S1 discectomy, resection of the sacral dome, and transpedicular instrumentation from L3 to S1. In this particular case, one-staged approach was adequate for the treatment of L5-S1 spondyloptosis. One-staged surgery using the posterior approach may be adequate for the treatment of L5-S1 spondyloptosis while avoiding the risks inherent in anterior approaches. PMID:23125496

  15. S1PR1 expression correlates with inflammatory responses to Newcastle disease virus infection.

    PubMed

    Li, Yaling; Xie, Peng; Sun, Minhua; Xiang, Bin; Kang, Yinfeng; Gao, Pei; Zhu, Wenxian; Ning, Zhangyong; Ren, Tao

    2016-01-01

    Newcastle disease virus (NDV) is the causative agent of Newcastle disease, which is characterized by inflammatory pathological changes in the organs of chickens. The inflammatory response to this disease has not been well characterized. Previous reports showed that the sphingosine-1-phosphate-1 receptor (S1PR1), a G protein-coupled receptor, is important to the activation of inflammatory responses. To understand better the viral pathogenesis and host inflammatory response, we analyzed S1PR1 expression during NDV infection. We observed a direct correlation between chicken embryo fibroblast (CEF) cellular inflammatory responses and S1PR1 expression. Virulent NDV-infected CEF cells also had elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-18). When S1PR1 was inhibited by using the specific antagonist W146, pro-inflammatory cytokine production declined. Overexpression of S1PR1 resulted in increased virus-induced IL-1β production. S1PR1 expression levels did not impact significantly NDV replication. These findings highlight the important role of S1PR1 in inflammatory responses in NDV infection.

  16. Identification of a pepducin acting as S1P3 receptor antagonist.

    PubMed

    Severino, Beatrice; Incisivo, Giuseppina Maria; Fiorino, Ferdinando; Bertolino, Antonio; Frecentese, Francesco; Barbato, Francesco; Manganelli, Serena; Maggioni, Giada; Capasso, Domenica; Caliendo, Giuseppe; Santagada, Vincenzo; Sorrentino, Raffaella; Roviezzo, Fiorentina; Perissutti, Elisa

    2013-11-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid with key functions in the immune, inflammatory, and cardiovascular systems. S1P exerts its action through the interaction with a family of five known G protein-coupled receptors, named S1P(1-5). Among them, S1P(3) has been implicated in the pathological processes of a number of diseases, including sepsis and cancer. KRX-725 (compound 1) is a pepducin that mimics the effects of S1P by triggering specifically S1P(3). Here, aiming to identify novel S1P(3) antagonists, we carried out an alanine scanning analysis to address the contribution of the side chains of each amino acid residue to the peptide function. Then, deleted peptides from both the C- and N-terminus were prepared in order to determine the minimal sequence for activity and to identify the structural requirements for agonistic and, possibly, antagonistic behaviors. The pharmacological results of the Ala-scan derived compounds (2-10) suggested a high tolerance of the pepducin 1 to amino acid substitutions. Importantly, the deleted peptide 16 has the ability to inhibit, in a dose-dependent manner, both pepducin 1-induced vasorelaxation and fibroblast proliferation. Finally, a computational analysis was performed on the prepared compounds, showing that the supposed antagonists 16 and 17 appeared to be aligned with each other but not with the others. These results suggested a correlation between specific conformations and activities.

  17. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    SciTech Connect

    Kasamatsu, Atsushi; Uzawa, Katsuhiro; Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki; Endo-Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Takiguchi, Yuichi; Tanzawa, Hideki

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  18. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2

    PubMed Central

    Santos-Cortez, Regie Lyn P.; Faridi, Rabia; Rehman, Atteeq U.; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J.; Isaacson, Rivka; Belyantseva, Inna A.; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A.; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-e-Huma; Smith, Joshua D.; Nickerson, Deborah A.; Bamshad, Michael J.; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B.; Leal, Suzanne M.

    2016-01-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2−/− mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2−/− mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  19. Components-dependent optical nonlinearity in a series of CdSexS1-x and CdSexS1-x/ZnS QDs

    NASA Astrophysics Data System (ADS)

    Zhao, Shunlong; Wu, Feng; Zhang, Siwen; Wang, Qian; Li, Songtao; Cheng, Xiaoman

    2016-08-01

    The different compositions of the ternary alloyed CdSexS1-x and CdSexS1-x/ZnS core/shell quantum dots(CSQDs) have been synthesized by the chemical routes. The nonlinear optical properties of these QDs were investigated using Z-scan technique under the excitation of the 1064 nm picosecond laser pulse. The Z-scan results reveal that the nonlinear refractive indices of these QDs can be tuned by changing the ratio of Se and S components. Nonlinear optical (NLO) properties have been shown to be enhanced in CSQDs as compared to their core semiconductor counterparts. These QDs exhibit the components-tuned nonlinear refraction indices, which lead to a wide application in the photonic field.

  20. Heart Disease Could Cost U.S. $1 Trillion Per Year by 2035: Report

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163587.html Heart Disease Could Cost U.S. $1 Trillion Per Year By ... estimates that nearly half of Americans will have heart disease in less than 20 years To use the ...

  1. Preparation of (S)-1-Halo-2-octanols Using Ionic Liquids and Biocatalysts.

    PubMed

    Oromí-Farrús, Mireia; Eras, Jordi; Sala, Núria; Torres, Mercè; Canela, Ramon

    2009-10-23

    Preparation of (S)-1-chloro-2-octanol and (S)-1-bromo-2-octanol was carried out by the enzymatic hydrolysis of halohydrin palmitates using biocatalysts. Halohydrin palmitates were prepared by various methods from palmitic acid and 1,2-octanediol. A tandem hydrolysis was carried out using lipases from Candida antarctica (Novozym 435), Rhizomucor miehei (Lipozyme IM), and "resting cells" from a Rhizopus oryzae strain that was not mycotoxigenic. The influence of the enzyme and the reaction medium on the selective hydrolysis of isomeric mixtures of halohydrin esters is described. Novozym 435 allowed preparation of (S)-1-chloro-2-octanol and (S)-1-bromo-2-octanol after 1-3 h of reaction at 40 degrees C in [BMIM][PF(6)].

  2. PMMA Cementoplasty in Symptomatic Metastatic Lesions of the S1 Vertebral Body

    SciTech Connect

    Dehdashti, Amir R.; Martin, Jean-Baptiste; Jean, Beatrix; Ruefenacht, Daniel A.

    2000-03-15

    We describe a lateral transiliac direct puncture approach to the S1 vertebral body for polymethylmethacrylate (PMMA) cementoplasty of painful metastatic lesions. This approach was performed using a 15-cm-long trocar needle with 3-mm outer diameter, introduced under general anesthesia and fluoroscopic control. A lateral projection was used to center the needle just in front of the spinal canal and subjacent to the superior plate of the S1 vertebral body. Needle progression was controlled using anteroposterior and lateral fluoroscopic projections alternately with a needle course parallel to an axial plane, avoiding conflict with the S1 foramen. After needle tip placement in the center of the S1 vertebral body, diluted PMMA with a setting time of 8 min was delivered. Ipsilateral lesions of the lateral sacral compartment were filled with the same needle by stepwise withdrawal and continuous PMMA injection.

  3. Second generation S1P pathway modulators: research strategies and clinical developments.

    PubMed

    Bigaud, Marc; Guerini, Danilo; Billich, Andreas; Bassilana, Frederic; Brinkmann, Volker

    2014-05-01

    Multiple Sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Until recently, major therapeutic treatments have relied on agents requiring injection delivery. In September 2010, fingolimod/FTY720 (Gilenya, Novartis) was approved as the first oral treatment for relapsing forms of MS. Fingolimod causes down-modulation of S1P1 receptors on lymphocytes which prevents the invasion of autoaggressive T cells into the CNS. In astrocytes, down-modulation of S1P1 by the drug reduces astrogliosis, a hallmark of MS, thereby allowing restoration of productive astrocyte communication with other neural cells and the blood brain barrier. Animal data further suggest that the drug directly supports the recovery of nerve conduction and remyelination. In human MS, such mechanisms may explain the significant decrease in the number of inflammatory markers on brain magnetic resonance imaging in recent clinical trials, and the reduction of brain atrophy by the drug. Fingolimod binds to 4 of the 5 known S1P receptor subtypes, and significant efforts were made over the past 5 years to develop next generation S1P receptor modulators and determine the minimal receptor selectivity needed for maximal therapeutic efficacy in MS patients. Other approaches considered were competitive antagonists of the S1P1 receptor, inhibitors of the S1P lyase to prevent S1P degradation, and anti-S1P antibodies. Below we discuss the current status of the field, and the functional properties of the most advanced compounds. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.

  4. Characterization of the L4-L5-S1 motion segment using the stepwise reduction method.

    PubMed

    Jaramillo, Héctor Enrique; Puttlitz, Christian M; McGilvray, Kirk; García, José J

    2016-05-03

    The two aims of this study were to generate data for a more accurate calibration of finite element models including the L5-S1 segment, and to find mechanical differences between the L4-L5 and L5-S1 segments. Then, the range of motion (ROM) and facet forces for the L4-S1 segment were measured using the stepwise reduction method. This consists of sequentially testing and reducing each segment in nine stages by cutting the ligaments, facet capsules, and removing the nucleus. Five L4-S1 human segments (median: 65 years, range: 53-84 years, SD=11.0 years) were loaded under a maximum pure moment of 8Nm. The ROM was measured using stereo-photogrammetry via tracking of three markers and the facet contact forces (CF) were measured using a Tekscan system. The ROM for the L4-L5 segment and all stages showed good agreement with published data. The major differences in ROM between the L4-L5 and L5-S1 segments were found for lateral bending and all stages, for which the L4-L5 ROM was about 1.5-3 times higher than that of the L5-S1 segment, consistent with L5-S1 facet CF about 1.3 to 4 times higher than those measured for the L4-L5 segment. For the other movements and few stages, the L4-L5 ROM was significantly lower that of the L5-S1 segment. ROM and CF provide important baseline data for more accurate calibration of FE models and to understand the role that their structures play in lower lumbar spine mechanics.

  5. Severe α-Thalassemia Intermedia Due to a Compound Heterozygosity for the Highly Unstable Hb Adana (HBA2: c.179G>A) and a Novel Codon 24 (HBA2: c.75T>A) Mutation

    PubMed Central

    Megawati, Dewi; Nainggolan, Ita M.; Swastika, Maria; Susanah, Susi; Mose, Johanes C.; Harahap, Alida R.

    2014-01-01

    HBA2 We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value. PMID:24351118

  6. Severe α-thalassemia intermedia due to a compound heterozygosity for the highly unstable Hb Adana (HBA2: c.179G>A) and a novel codon 24 (HBA2: c.75T>A) mutation.

    PubMed

    Megawati, Dewi; Nainggolan, Ita M; Swastika, Maria; Susanah, Susi; Mose, Johanes C; Harahap, Alida R; Setianingsih, Iswari

    2014-01-01

    We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.

  7. Isolation of new Stenotrophomonas bacteriophages and genomic characterization of temperate phage S1.

    PubMed

    García, Pilar; Monjardín, Cristina; Martín, Rebeca; Madera, Carmen; Soberón, Nora; Garcia, Eva; Meana, Alvaro; Suárez, Juan E

    2008-12-01

    Twenty-two phages that infect Stenotrophomonas species were isolated through sewage enrichment and prophage induction. Of them, S1, S3, and S4 were selected due to their wide host ranges compared to those of the other phages. S1 and S4 are temperate siphoviruses, while S3 is a virulent myovirus. The genomes of S3 and S4, about 33 and 200 kb, were resistant to restriction digestion. The lytic cycles lasted 30 min for S3 and about 75 min for S1 and S4. The burst size for S3 was 100 virions/cell, while S1 and S4 produced about 75 virus particles/cell. The frequency of bacteriophage-insensitive host mutants, calculated by dividing the number of surviving colonies by the bacterial titer of a parallel, uninfected culture, ranged between 10(-5) and 10(-6) for S3 and 10(-3) and 10(-4) for S1 and S4. The 40,287-bp genome of S1 contains 48 open reading frames (ORFs) and 12-bp 5' protruding cohesive ends. By using a combination of bioinformatics and experimental evidence, functions were ascribed to 21 ORFs. The morphogenetic and lysis modules are well-conserved, but no lysis-lysogeny switch or DNA replication gene clusters were recognized. Two major clusters of genes with respect to transcriptional orientation were observed. Interspersed among them were lysogenic conversion genes encoding phosphoadenosine phosphosulfate reductase and GspM, a protein involved in the general secretion system II. The attP site of S1 may be located within a gene that presents over 75% homology to a Stenotrophomonas chromosomal determinant.

  8. SIRT1 mediates Sphk1/S1P-induced proliferation and migration of endothelial cells.

    PubMed

    Gao, Zhan; Wang, Hua; Xiao, Feng-Jun; Shi, Xue-Feng; Zhang, Yi-Kun; Xu, Qin Qin; Zhang, Xiao-Yan; Ha, Xiao-Qin; Wang, Li-Sheng

    2016-05-01

    Angiogenesis is one of the most important components of embryonic organ formation and vessel growth after birth. Sphingosine kinase 1 (Sphk1) and S1P has been confirmed to participate in various cell signaling pathways and physiological processes including neovascularisation. However, the mechanisms that Sphk1/S1P regulates neovascularisation remain unclear. In this study, we elucidated that Sphk1/S1P upregulates sirtuin 1 (SIRT1), a NAD+ dependent deacetylases protease which exerts multiple cellular functions, to regulate the proliferation and migration of endothelial cells. By using CCK8 and Transwell assays, we demonstrated that Sphk1 and SIRT1 knockdown could significantly decrease proliferation and migration of HUVEC cells. Sphk1 inhibition results in SIRT1 downregulation which could be reversed by exogenous S1P in HUVEC cells. Treatment of HUVECs with S1P reverses the impaired proliferation and migration caused by SIRT1 knockdown. Furthermore, Sphk1 knockdown inhibits the phosphorylation of P38 MAPK, ERK and AKT. Treatment of HUVECs with PD98059, SB203580 and Wortmannin, which are the inhibitors of ERK, P38 MAPK and AKT respectively, resulted in decreased SIRT1 expression and reduced migration of HUVEC cells. Thus, we conclude that Sphk1/S1P induces SIRT1 upregulation through multiple pathways including P38 MAPK, ERK and AKT signals. This is the first report to disclose the existence and roles of Sphk1/S1P/SIRT1 axis in regulation of endothelial cell proliferation and migration, which may provide a theoretical basis for angiogenesis.

  9. The Effects of Spinopelvic Parameters and Paraspinal Muscle Degeneration on S1 Screw Loosening

    PubMed Central

    Kim, Jin-Bum; Lee, Young-Seok; Nam, Taek-Kyun; Park, Yong-Sook; Kim, Young-Baeg

    2015-01-01

    Objective To investigate risk factors for S1 screw loosening after lumbosacral fusion, including spinopelvic parameters and paraspinal muscles. Methods We studied with 156 patients with degenerative lumbar disease who underwent lumbosacral interbody fusion and pedicle screw fixation including the level of L5-S1 between 2005 and 2012. The patients were divided into loosening and non-loosening groups. Screw loosening was defined as a halo sign larger than 1 mm around a screw. We checked cross sectional area of paraspinal muscles, mean signal intensity of the muscles on T2 weight MRI as a degree of fatty degeneration, spinopelvic parameters, bone mineral density, number of fusion level, and the characteristic of S1 screw. Results Twenty seven patients showed S1 screw loosening, which is 24.4% of total. The mean duration for S1 screw loosening was 7.3±4.1 months after surgery. Statistically significant risk factors were increased age, poor BMD, 3 or more fusion levels (p<0.05). Among spinopelvic parameters, a high pelvic incidence (p<0.01), a greater difference between pelvic incidence and lumbar lordotic angle preoperatively (p<0.01) and postoperatively (p<0.05). Smaller cross-sectional area and high T2 signal intensity in both multifidus and erector spinae muscles were also significant muscular risk factors (p<0.05). Small converging angle (p<0.001) and short intraosseous length (p<0.05) of S1 screw were significant screw related risk factors (p<0.05). Conclusion In addition to well known risk factors, spinopelvic parameters and the degeneration of paraspinal muscles also showed significant effects on the S1 screw loosening. PMID:26587190

  10. Effects of S1P on skeletal muscle repair/regeneration during eccentric contraction.

    PubMed

    Sassoli, Chiara; Formigli, Lucia; Bini, Francesca; Tani, Alessia; Squecco, Roberta; Battistini, Chiara; Zecchi-Orlandini, Sandra; Francini, Fabio; Meacci, Elisabetta

    2011-11-01

    Skeletal muscle regeneration is severely compromised in the case of extended damage. The current challenge is to find factors capable of limiting muscle degeneration and/or potentiating the inherent regenerative program mediated by a specific type of myoblastic cells, the satellite cells. Recent studies from our groups and others have shown that the bioactive lipid, sphingosine 1-phosphate (S1P), promotes myoblast differentiation and exerts a trophic action on denervated skeletal muscle fibres. In the present study, we examined the effects of S1P on eccentric contraction (EC)-injured extensor digitorum longus muscle fibres and resident satellite cells. After EC, skeletal muscle showed evidence of structural and biochemical damage along with significant electrophysiological changes, i.e. reduced plasma membrane resistance and resting membrane potential and altered Na(+) and Ca(2+) current amplitude and kinetics. Treatment with exogenous S1P attenuated the EC-induced tissue damage, protecting skeletal muscle fibre from apoptosis, preserving satellite cell viability and affecting extracellular matrix remodelling, through the up-regulation of matrix metalloproteinase 9 (MMP-9) expression. S1P also promoted satellite cell renewal and differentiation in the damaged muscle. Notably, EC was associated with the activation of sphingosine kinase 1 (SphK1) and with increased endogenous S1P synthesis, further stressing the relevance of S1P in skeletal muscle protection and repair/regeneration. In line with this, the treatment with a selective SphK1 inhibitor during EC, caused an exacerbation of the muscle damage and attenuated MMP-9 expression. Together, these findings are in favour for a role of S1P in skeletal muscle healing and offer new clues for the identification of novel therapeutic approaches to counteract skeletal muscle damage and disease.

  11. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P{sub 2} on cell migration and invasiveness

    SciTech Connect

    Young, Nicholas; Van Brocklyn, James R. . E-mail: james.vanbrocklyn@osumc.edu

    2007-05-01

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

  12. Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial

    PubMed Central

    Zhou, Zun-Qiang; Guan, Jiao; Tong, Da-Nian; Zhou, Guang-Wen

    2016-01-01

    Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50–0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27–0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9<466 U/ml were more responsive to chemotherapeutic agents than those with CA19-9≥571 U/ml (88.9% vs 0%, P<0.001). We conclude that the combination of GEM plus S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733). PMID:27058753

  13. Arthrodesis to L5 versus S1 in long instrumentation and fusion for degenerative lumbar scoliosis.

    PubMed

    Cho, Kyu-Jung; Suk, Se-Il; Park, Seung-Rim; Kim, Jin-Hyok; Choi, Sung-Wook; Yoon, Young-Hyun; Won, Man-Hee

    2009-04-01

    There is a debate regarding the distal fusion level for degenerative lumbar scoliosis. Whether a healthy L5-S1 motion segment should be included or not in the fusion remains controversial. The purpose of this study was to determine the optimal indication for the fusion to the sacrum, and to compare the results of distal fusion to L5 versus the sacrum in the long instrumented fusion for degenerative lumbar scoliosis. A total of 45 patients who had undergone long instrumentation and fusion for degenerative lumbar scoliosis were evaluated with a minimum 2 year follow-up. Twenty-four patients (mean age 63.6) underwent fusion to L5 and 21 patients (mean age 65.6) underwent fusion to the sacrum. Supplemental interbody fusion was performed in 12 patients in the L5 group and eleven patients in the sacrum group. The number of levels fused was 6.08 segments (range 4-8) in the L5 group and 6.09 (range 4-9) in the sacrum group. Intraoperative blood loss (2,754 ml versus 2,938 ml) and operative time (220 min versus 229 min) were similar in both groups. The Cobb angle changed from 24.7 degrees before surgery to 6.8 degrees after surgery in the L5 group, and from 22.8 degrees to 7.7 degrees in the sacrum group without statistical difference. Correction of lumbar lordosis was statistically better in the sacrum group (P = 0.03). Less correction of lumbar lordosis in the L5 group seemed to be associated with subsequent advanced L5-S1 disc degeneration. The change of coronal and sagittal imbalance was not different in both groups. Subsequent advanced L5-S1 disc degeneration occurred in 58% of the patients in the L5 group. Symptomatic adjacent segment disease at L5-S1 developed in five patients. Interestingly, the development of adjacent segment disease was not related to the preoperative grade of disc degeneration, which proved minimal degeneration in the five patients. In the L5 group, there were nine patients of complications at L5-S1 segment, including adjacent segment disease at

  14. Improvement of intratumor microdistribution of PEGylated liposome via tumor priming by metronomic S-1 dosing

    PubMed Central

    Doi, Yusuke; Abu Lila, Amr S; Matsumoto, Haruna; Okada, Tomoko; Shimizu, Taro; Ishida, Tatsuhiro

    2016-01-01

    The efficient delivery of nanocarrier-based cancer therapeutics into tumor tissue is problematic. Structural abnormalities, tumor vasculature heterogeneity, and elevated intratumor pressure impose barriers against the preferential accumulation of nanocarrier-based cancer therapeutics within tumor tissues and, consequently, compromise their therapeutic efficacy. Recently, we have reported that metronomic S-1, orally available tegafur formulation, dosing synergistically augmented the therapeutic efficacy of oxaliplatin (l-OHP)-containing PEGylated liposome without increasing the toxicity in animal model. However, the exact mechanism behind such synergistic effect was not fully elucidated. In this study, therefore, we tried to shed the light on the contributions of metronomic S-1 dosing to the enhanced accumulation and/or spatial distribution of PEGylated liposome within tumor tissue. Tumor priming with metronomic S-1 treatment induced a potent apoptotic response against both angiogenic endothelial cells and tumor cells adjacent to tumor blood vessels, resulting in enhanced tumor blood flow via transient normalization of tumor vasculature, along with alleviation of intratumor pressure. Such a change in the tumor microenvironment imparted by S-1 treatment allows efficient delivery of PEGylated liposome to tumor tissue and permits their deep penetration/distribution into the tumor mass. Such a priming effect of S-1 dosing can be exploited as a promising strategy to enhance the therapeutic efficacy of nanocarrier-based cancer therapeutics suffering from inadequate/heterogeneous delivery to tumor tissues. PMID:27822036

  15. Ultrasound and electrical nerve stimulation-guided S1 nerve root block.

    PubMed

    Sato, Masaki; Mikawa, Yasuhito; Matuda, Akiko

    2013-10-01

    A selective lumbosacral nerve root block is generally is performed under X-ray fluoroscopy, which has the disadvantage of radiation exposure and the need for fluoroscopy equipment. In this study, we assessed the effectiveness of ultrasound and nerve stimulation-guided S1 nerve root block on 37 patients with S1 radicular syndrome. With the patient in a prone position, an ultrasound scan was performed by placing the probe parallel to the body axis. The needle was pointed slightly medial from the lateral side of the probe and advanced toward a hyperechoic area in the sacral foramina with ultrasound guidance. Contrast medium was then injected and its dispersion confirmed by fluoroscopy. The acquired contrast images were classified into intraneural, perineural, and paraneural patterns. The significance of differences in the effect of the block among the contrast image patterns was analyzed. After nerve block, decreased sensation at the S1 innervated region and pain relief was achieved in all patients. No significant difference was noted in the effect of the block between perineural and paraneural patterns. In conclusion, this technique provided reliable S1 nerve root block in patients with S1 radicular syndrome and minimized radiation exposure.

  16. Far-ultraviolet Observations of Comet C/2012 S1 (ISON) from FORTIS

    NASA Astrophysics Data System (ADS)

    McCandliss, Stephan R.; Feldman, Paul D.; Weaver, Harold; Fleming, Brian; Redwine, Keith; Li, Mary J.; Kutyrev, Alexander; Moseley, S. Harvey

    2016-09-01

    We have used the unique far-UV imaging capability offered by a sounding-rocket-borne instrument to acquire observations of C/2012 S1 (ISON) when its angular separation with respect to the Sun was 26.°3 on 2013 November 20.49. At the time of observation, the comet’s heliocentric distance and velocity relative to the Sun were r h = 0.43 au and {\\dot{r}}h = -62.7 km s-1. Images dominated by C i λ1657 and H i λ1216 were acquired over a 106 × 106 km2 region. The water production rate implied by the Lyα observations is constrained to be {Q}{{{H}}2{{O}}}≈ 8 × 1029 s-1 while the neutral carbon production rate was {Q}C ≈ 4 ×1028 s-1. The radial profile of C i was consistent with it being a dissociation product of a parent molecule with a lifetime τ ˜ 5 × 104 s, favoring a parent other than CO. We constrain the Q CO production rate to {5}-7.5+1.5 × 1028 s-1 with 1σ errors derived from photon statistics. The upper limit on the Q CO/{Q}{{{H}}2{{O}}} is ≲6%.

  17. Corneal Limbal Stem Cell Deficiency Associated with the Anticancer Drug S-1

    PubMed Central

    Kim, Kyeong Hwan; Kim, Wan Soo

    2015-01-01

    ABSTRACT Purpose An oral antineoplastic drug, S-1, is known to be more effective with less toxicity and fewer gastrointestinal side effects than the conventional intravenous 5-fluorouracil. We report a case of limbal stem cell deficiency that occurred in a patient receiving chemotherapy using S-1 alone for gastric cancer. Case Report A 65-year-old woman with symptoms of grittiness and epiphora in both eyes for several months was referred to the ophthalmology clinic. She had been receiving S-1 orally after total gastrectomy for advanced gastric cancer. Slit lamp examination revealed an irregular hazy corneal epithelium in both eyes that extended to the center of the cornea overlying the pupil and showed late staining with fluorescein dye. Palisades of Vogt at the superior limbus were absent in both eyes. Best-corrected distance vision was 20/50 in both eyes with all other structures of the anterior and posterior segment unremarkable including a patent lacrimal drainage system. There was no change in the corneal lesions of either eye despite 3 months of topical therapy. The lesions did resolve in 4 months after discontinuation of S-1 therapy owing to acute renal failure. Conclusions Early detection of this adverse reaction before significant visual loss through regular follow-up appears to be important in patients receiving S-1 therapy. PMID:25756340

  18. PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

    PubMed

    Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2013-11-01

    We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells.

  19. Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways.

    PubMed

    Yoon, Chang Min; Hong, Bok Sil; Moon, Hyung Geun; Lim, Seyoung; Suh, Pann-Ghill; Kim, Yoon-Keun; Chae, Chi-Bom; Gho, Yong Song

    2008-08-15

    The lymphatic system plays pivotal roles in mediating tissue fluid homeostasis and immunity, and excessive lymphatic vessel formation is implicated in many pathological conditions, which include inflammation and tumor metastasis. However, the molecular mechanisms that regulate lymphatic vessel formation remain poorly characterized. Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that is implicated in a variety of biologic processes such as inflammatory responses and angiogenesis. Here, we first report that S1P acts as a lymphangiogenic mediator. S1P induced migration, capillary-like tube formation, and intracellular Ca(2+) mobilization, but not proliferation, in human lymphatic endothelial cells (HLECs) in vitro. Moreover, a Matrigel plug assay demonstrated that S1P promoted the outgrowth of new lymphatic vessels in vivo. HLECs expressed S1P1 and S1P3, and both RNA interference-mediated down-regulation of S1P1 and an S1P1 antagonist significantly blocked S1P-mediated lymphangiogenesis. Furthermore, pertussis toxin, U73122, and BAPTA-AM efficiently blocked S1P-induced in vitro lymphangiogenesis and intracellular Ca(2+) mobilization of HLECs, indicating that S1P promotes lymphangiogenesis by stimulating S1P1/G(i)/phospholipase C/Ca(2+) signaling pathways. Our results suggest that S1P is the first lymphangiogenic bioactive lipid to be identified, and that S1P and its receptors might serve as new therapeutic targets against inflammatory diseases and lymphatic metastasis in tumors.

  20. [A Case of Local Recurrence of Bile Duct Cancer Completely Responding to Chemoradiotherapy with S-1].

    PubMed

    Yamamichi, Keigo; Sueyoshi, Hiroyuki; Tanaka, Yoshito; Sakaguchi, Tatsuma; Hishikawa, Hidehiko; Ueda, Aiko; Matsuura, Takashi; Ozaki, Takashi; Saito, Takuya

    2015-11-01

    An 80-year-old man with common bile duct cancer was treated by pancreaticoduodenectomy with D2 lymph node dissection in October 2005. The patient presented with frequent episodes of bloody-mucous rectal discharge in July 2009. An abdominal CT demonstrated local recurrence at the hepatoduodenal ligament. We treated him with concurrent chemoradiotherapy (CRT) with single-dose S-1 chemotherapy. After 6 months, we diagnosed a complete response (CR) by follow-up CT. The patient was treated with S-1 for 3 years after the diagnosis of a CR. He is alive without disease 6 years after the diagnosis of the recurrence. Concurrent CRT with S-1 chemotherapy may be the therapy of choice for recurrence of bile duct cancer.

  1. The 2(2S + 1)-formalism and its connection with other descriptions

    NASA Astrophysics Data System (ADS)

    Dvoeglazov, Valeriy V.

    2016-02-01

    In the framework of the Joos-Weinberg 2(2S + 1)-theory for massless particles, the dynamical invariants have been derived from the Lagrangian density which is considered to be a 4-vector. A la Majorana interpretation of the 6-component “spinors”, the field operators of S = 1 particles, as the left- and right-circularly polarized radiation, leads us to the conserved quantities which are analogous to those obtained by Lipkin and Sudbery. The scalar Lagrangian of the Joos-Weinberg theory is shown to be equivalent to the Lagrangian of a free massless field, introduced by Hayashi. As a consequence of a new “gauge” invariance this skew-symmetric field describes physical particles with the longitudinal components only. The interaction of the spinor field with the Weinberg’s 2(2S + 1)-component massless field is considered. New interpretation of the Weinberg field function is proposed.

  2. Molecular and immunological characterisation of the glycosylated orange allergen Cit s 1

    PubMed Central

    Pöltl, Gerald; Ahrazem, Oussama; Paschinger, Katharina; Ibañez, M. Dolores; Salcedo, Gabriel; Wilson, Iain B. H.

    2010-01-01

    The IgE of sera from patients with a history of allergy to oranges (Citrus sinensis) bind a number of proteins in orange extract, including Cit s 1, a germin-like protein. In the present study, we have analysed its immunological cross-reactivity and its molecular nature. Sera from many of the patients examined recognise a range of glycoproteins and neoglycoconjugates containing β1,2-xylose and core α1,3-fucose on their N-glycans. These reagents also inhibited the interaction of Cit s 1 with patients’ sera, thus underlining the critical role of glycosylation in the recognition of this protein by patients’ IgE and extending previous data showing that deglycosylated Cit s 1 does not possess IgE epitopes. In parallel, we examined the peptide sequence and glycan structure of Cit s 1 using mass spectrometric techniques. Indeed, we achieved complete sequence coverage of the mature protein as compared to the translation of an expressed sequence tag cDNA clone and demonstrated that the single N-glycosylation site of this protein carries oligosaccharides with xylose and fucose residues. Due to the presumed requirement for multivalency for in vivo allergenicity, our molecular data showing that Cit s 1 is monovalent as regards glycosylation and that the single N-glycan is the target of the IgE response to this protein, therefore, explain the immunological cross-reactive properties of Cit s 1 as well as its equivocal nature as a clinically-relevant allergen. PMID:17095532

  3. Doubled haploid versus S1 family recurrent selection for testcross performance in a maize population.

    PubMed

    Bordes, J; Charmet, G; de Vaulx, R Dumas; Pollacsek, M; Beckert, M; Gallais, A

    2006-04-01

    Theoretically, in a recurrent selection program, the use of doubled haploids (DH) can increase genetic advance per unit of time. To evaluate the efficiency expected from the use of DH for the improvement of grain yield in a maize (Zea mays L.) population, two recurrent selection programs for testcross performance were initiated using testcross progenies from DH lines and S1 families. In 4 years one selection cycle using DH and two selection cycles using S1 families were carried out with the same selection intensity for both methods. As expected, testcross genetic variance was twice as high among DH lines as among S1 families. The predicted genetic gain was 8.2% for the DH selection cycle, and 10.6% for the two S1 selection cycles, giving a per year advantage of 29% for the S1 family method over the DH method with a cycle of 4 years. With a 3-year cycle for the DH method, both methods were expected to be equivalent. Using a tester related to the one used for selection, the genetic gains obtained were equivalent for both methods: 6.6% for the DH cycle and 7.0% for the two S1 cycles. With a 3-year cycle for the DH method, the advantage would have been in favor of DH method. Furthermore, the DH method has the advantage of simultaneously producing lines that are directly usable as parents of a hybrid. Thus, if the genetic advance per unit of time is evaluated at the level of developed varieties even with the same or with a lower genetic advance in population improvement, the DH method appears to be the most efficient.

  4. 11-cis retinal torsion: A QTAIM and stress tensor analysis of the S1 excited state

    NASA Astrophysics Data System (ADS)

    Maza, Julio R.; Jenkins, Samantha; Kirk, Steven R.

    2016-05-01

    We investigate torsion about the C11-C12 bond mid-point for the S1 state of 11-cis retinal, using a QTAIM and stress tensor analysis. The QTAIM and stress tensor responses to a torsion ±α increase at a faster rate for the preferred direction of torsion though the CI seam. A QTAIM and stress tensor vector-based analysis provides an alternative way of characterising the asymmetry of the S1 potential energy surface. In the vicinity of the CI seam the ellipticity ε attained minimum values. The application of this analysis to molecular rotary motors is briefly discussed.

  5. Biochemical regulation of breast cancer cell expression of S1P2 (Edg-5) and S1P3 (Edg-3) G protein-coupled receptors for sphingosine 1-phosphate.

    PubMed

    Dolezalova, Hana; Shankar, Geetha; Huang, Mei-Chuan; Bikle, Daniel D; Goetzl, Edward J

    2003-03-01

    G protein-coupled receptors (GPCRs) for lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) transduce signals to many functions of normal cells. Most human cancer cells upregulate S1P and LPA GPCRs, in patterns distinctive for each type of tumor. The findings that 1-alpha, 25-dihydroxy-vitamin D(3) (VD3) and all-trans retinoic acid (RA) differentially alter expression of the predominant S1P(3) (Edg-3) R and S1P(2) (Edg-5) R in human breast cancer cells (BCCs) permitted analyses of their individual activities, despite a lack of selective pharmacological probes. S1P-evoked increases in [Ca(2+)](i) in S1P(3) R-predominant BCCs were suppressed by concentrations of VD3 and RA which decreased expression of S1P(3) Rs, despite RA-induced increases in S1P(2) Rs. S1P-elicited chemokinetic migration of S1P(3) R-predominant BCCs across a type IV collagen-coated micropore filter also was inhibited by concentrations of VD3 and RA which decreased expression of S1P(3) Rs. The RA-induced increase in expression of S1P(2) Rs did not prevent suppression by RA of S1P-elicited chemokinesis, which appears to be mediated by S1P(3) Rs, but instead exposed S1P(2) R-mediated inhibition of epidermal growth factor-stimulated chemotaxis of BCCs. In contrast, expression of the predominant LPA(2) Rs, LPA-evoked increase in [Ca(2+)](i) and LPA-stimulated chemokinetic migration were suppressed concomitantly by RA but not VD3. Thus two structurally-homologous S1P Rs of BCCs differ in coupling to [Ca(2+)](i) signaling and have opposite effects on protein growth factor-stimulated chemotaxis.

  6. Effect of Self-Regulated Learning and Motivation to Achieve against Teacher Professional Capability for Student S1 PGSD of Science Field Compared with Regular Student S1 PGSD at UPBJJ Serang

    ERIC Educational Resources Information Center

    Prayekti

    2015-01-01

    This study is to know effect of self-regulated learning and motivation to achieve against teacher professional capability for student S1 PGSD of science field compared with regular student S1 PGSD. The student uses grades of Classroom Action Research (CAR) and Stabilization of Professional Capability (SPC) on curriculum of S1 PGSD to see…

  7. Molecular basis of reovirus virulence: Role of the S1 gene

    PubMed Central

    Weiner, Howard L.; Drayna, Dennis; Averill, Damon R.; Fields, Bernard N.

    1977-01-01

    A genetic approach has been used to define the molecular basis for the different patterns of virulence and central nervous system cell tropism exhibited by reovirus types 1 and 3. Intracerebral inoculation of reovirus type 3 into newborn mice causes a necrotizing encephalitis (without ependymal damage) that is uniformly fatal. Animal inoculated with reovirus type 1 generally survive and may develop epedymal cell damage (without neuronal necrosis) and hydrocephalus. Using recombinant clones derived from crosses between reovirus types 1 and 3, we have been able to determine that the S1 genome segment is responsible for the differing cell tropism of reovirus serotypes and is the major determinant of neurovirulence. The type 1 S1 genome segment is responsible for ependymal damage with subsequent hydrocephalus; the type 3 S1 genome segment is responsible for neuronal necrosis and neurovirulence. We postulate that these differences are due to the specific interaction of the σ1 outer capsid polypeptide (the protein coded for by the S1 genome segment) with receptors on the surface of either ependymal cells or neuronal cells. Images PMID:271999

  8. SKI-1/S1P inhibitor PF-429242 impairs the onset of HCV infection.

    PubMed

    Blanchet, Matthieu; Sureau, Camille; Guévin, Carl; Seidah, Nabil G; Labonté, Patrick

    2015-03-01

    Worldwide, approximately 170 million individuals are afflicted with chronic hepatitis C virus (HCV) infection. To prevent the development of inherent diseases such as cirrhosis and hepatocellular carcinoma, tremendous efforts have been made, leading to the development of promising new treatments. However, their efficiency is still dependent on the viral genotype. Additionally, these treatments that target the virus directly can trigger the emergence of resistant variants. In a previous study, we have demonstrated that a long-term (72h) inhibition of SKI-1/S1P, a master lipogenic pathway regulator through activation of SREBP, resulted in impaired HCV genome replication and infectious virion secretion. In the present study, we sought to investigate the antiviral effect of the SKI-1/S1P small molecule inhibitor PF-429242 at the early steps of the HCV lifecycle. Our results indicate a very potent antiviral effect of the inhibitor early in the viral lifecycle and that the overall action of the compound relies on two different contributions. The first one is SREBP/SKI-1/S1P dependent and involves LDLR and NPC1L1 proteins, while the second one is SREBP independent. Overall, our study confirms that SKI-1/S1P is a relevant target to impair HCV infection and that PF-429242 could be a promising candidate in the field of HCV infection treatment.

  9. Universality of the Ising and the S=1 model on Archimedean lattices: a Monte Carlo determination.

    PubMed

    Malakis, A; Gulpinar, G; Karaaslan, Y; Papakonstantinou, T; Aslan, G

    2012-03-01

    The Ising models S=1/2 and S=1 are studied by efficient Monte Carlo schemes on the (3,4,6,4) and the (3,3,3,3,6) Archimedean lattices. The algorithms used, a hybrid Metropolis-Wolff algorithm and a parallel tempering protocol, are briefly described and compared with the simple Metropolis algorithm. Accurate Monte Carlo data are produced at the exact critical temperatures of the Ising model for these lattices. Their finite-size analysis provide, with high accuracy, all critical exponents which, as expected, are the same with the well-known 2D Ising model exact values. A detailed finite-size scaling analysis of our Monte Carlo data for the S=1 model on the same lattices provides very clear evidence that this model obeys, also very well, the 2D Ising model critical exponents. As a result, we find that recent Monte Carlo simulations and attempts to define effective dimensionality for the S=1 model on these lattices are misleading. Accurate estimates are obtained for the critical amplitudes of the logarithmic expansions of the specific heat for both models on the two Archimedean lattices.

  10. Crystallization and preliminary crystallographic study of the yeast Malassezia sympodialis allergen Mala s 1

    SciTech Connect

    Vilhelmsson, Monica; Hallberg, B. Martin; Rasool, Omid; Zargari, Arezou; Scheynius, Annika; Achour, Adnane

    2006-02-01

    Crystals of the M. sympodialis allergen Mala s 1 have been obtained using the hanging-drop vapour-diffusion method. A diffraction data set has been collected from native crystals to 1.35 Å resolution. The opportunistic yeast Malassezia sympodialis can act as an allergen and elicit specific IgE- and T-cell reactivity in patients with atopic eczema. The first identified major allergen from M. sympodialis, Mala s 1, is present on the cell surface of the yeast. Recombinant Mala s 1 was expressed in Escherichia coli, purified and refolded in a soluble form. Crystals of Mala s 1 were obtained in 25% PEG 8K, 0.2 M (NH{sub 4}){sub 2}SO{sub 4}. Crystals belong to space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 44.4, b = 163.7, c = 50.6 Å, and diffract to 1.35 Å resolution.

  11. Creation of a S1P Lyase bacterial surrogate for structure-based drug design.

    PubMed

    Argiriadi, Maria A; Banach, David; Radziejewska, Elzbieta; Marchie, Susan; DiMauro, Jennifer; Dinges, Jurgen; Dominguez, Eric; Hutchins, Charles; Judge, Russell A; Queeney, Kara; Wallace, Grier; Harris, Christopher M

    2016-05-01

    S1P Lyase (SPL) has been described as a drug target in the treatment of autoimmune diseases. It plays an important role in maintaining intracellular levels of S1P thereby affecting T cell egress from lymphoid tissues. Several groups have already published approaches to inhibit S1P Lyase with small molecules, which in turn increase endogenous S1P concentrations resulting in immunosuppression. The use of structural biology has previously aided SPL inhibitor design. Novel construct design is at times necessary to provide a reagent for protein crystallography. Here we present a chimeric bacterial protein scaffold used for protein X-ray structures in the presence of early small molecule inhibitors. Mutations were introduced to the bacterial SPL from Symbiobacterium thermophilum which mimic the human enzyme. As a result, two mutant StSPL crystal structures resolved to 2.8Å and 2.2Å resolutions were solved and provide initial structural hypotheses for an isoxazole chemical series, whose optimization is discussed in the accompanying paper.

  12. Conversion therapy for pancreatic cancer with peritoneal metastases using intravenous and intraperitoneal paclitaxel with S-1

    PubMed Central

    Kitayama, Hiromitsu; Tsuji, Yasushi; Kondo, Tomohiro; Sugiyama, Junko; Hirayama, Michiaki; Yamamoto, Kazuyuki; Kawarada, You; Oyamada, Yumiko; Hirano, Satoshi

    2016-01-01

    Combination chemotherapy consisting of systemic and intraperitoneal agents against peritoneal metastases from several types of cancer has shown promising results. We herein report a case in which combination therapy with intravenous and intraperitoneal paclitaxel with S-1 converted an unresectable pancreatic cancer with peritoneal metastases into a resectable one. The patient was a 65-year old woman with recurrent pancreatitis for 5 months. Endoscopic ultrasonography-guided fine-needle aspiration revealed minute epithelial masses composed of cells with irregular nuclei in the pancreatic body. The patient underwent abdominal surgery, but no excision was performed, as two peritoneal metastases in the bursa omentalis were detected. Combination therapy was initiated, consisting of intravenous and intraperitoneal paclitaxel with S-1 as a single-center clinical trial. The regimen consisted with 2-week administration of S-1 (80 mg per day) followed by 1 week of rest, intravenous paclitaxel 50 mg/m2, and intraperitoneal paclitaxel 20 mg/m2 by a peritoneal access device on days 1 and 8. Over the seven cycles of the chemotherapy, the primary lesion did not change in size, and peritoneal lavage cytology remained negative. After confirming the disappearance of the peritoneal lesions by exploratory laparoscopy, the patient underwent distal pancreatectomy combined with resection of the transverse mesocolon and stomach wall. Thus, the 2-way chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 was well-tolerated and was able to convert pancreatic cancer with peritoneal metastases to resectable disease. PMID:28105356

  13. Fundamental linewidth in solitary, ultranarrow output PbS(1-x)Se(x) diode lasers

    NASA Technical Reports Server (NTRS)

    Freed, C.; Bielinski, J. W.; Lo, W.

    1983-01-01

    The fundamental, quantum phase noise limited Lorentzian linewidth was directly measured from the beat-note spectra generated by heterodyning PbS(1-x)Se(x) diode lasers with a stable CO gas laser. The experimental results were matched by calculated theoretical line profiles. Linewidths as narrow as 22 kHz full width at half-maximum power were observed.

  14. Robustness of S1 statistic with Hodges-Lehmann for skewed distributions

    NASA Astrophysics Data System (ADS)

    Ahad, Nor Aishah; Yahaya, Sharipah Soaad Syed; Yin, Lee Ping

    2016-10-01

    Analysis of variance (ANOVA) is a common use parametric method to test the differences in means for more than two groups when the populations are normally distributed. ANOVA is highly inefficient under the influence of non- normal and heteroscedastic settings. When the assumptions are violated, researchers are looking for alternative such as Kruskal-Wallis under nonparametric or robust method. This study focused on flexible method, S1 statistic for comparing groups using median as the location estimator. S1 statistic was modified by substituting the median with Hodges-Lehmann and the default scale estimator with the variance of Hodges-Lehmann and MADn to produce two different test statistics for comparing groups. Bootstrap method was used for testing the hypotheses since the sampling distributions of these modified S1 statistics are unknown. The performance of the proposed statistic in terms of Type I error was measured and compared against the original S1 statistic, ANOVA and Kruskal-Wallis. The propose procedures show improvement compared to the original statistic especially under extremely skewed distribution.

  15. Bioremediation of wastewater from edible oil refinery factory using oleaginous microalga Desmodesmus sp. S1.

    PubMed

    Mar, Cho Cho; Fan, Yong; Li, Fu-Li; Hu, Guang-Rong

    2016-12-01

    Edible oil industry produced massive wastewater, which requires extensive treatment to remove pungent smell, high phosphate, carbon oxygen demand (COD), and metal ions prior to discharge. Traditional anaerobic and aerobic digestion could mainly reduce COD of the wastewater from oil refinery factories (WEORF). In this study, a robust oleaginous microalga Desmodesmus sp. S1 was adapted to grow in WEORF. The biomass and lipid content of Desmodesmus sp. S1 cultivated in the WEORF supplemented with sodium nitrate were 5.62 g·L(-1) and 14.49%, whereas those in the WEORF without adding nitrate were 2.98 g·L(-1) and 21.95%. More than 82% of the COD and 53% of total phosphorous were removed by Desmodesmus sp. S1. In addition, metal ions, including ferric, aluminum, manganese and zinc were also diminished significantly in the WEORF after microalgal growth, and pungent smell vanished as well. In comparison with the cells grown in BG-11 medium, the cilia-like bulges and wrinkles on the cell surface of Desmodesmus sp. S1 grown in WEORF became out of order, and more polyunsaturated fatty acids were detected due to stress derived from the wastewater. The study suggests that growing microalgae in WEORF can be applied for the dual roles of nutrient removal and biofuel feedstock production.

  16. High-Dispersion Spectroscopic Observations of Comet C/2012 S1 (ISON) with the Subaru Telescope

    NASA Astrophysics Data System (ADS)

    Shinnaka, Yoshiharu; Kawakita, Hideyo; Nagashima, Masayoshi; Hitomi, Kobayashi; Decock, Alice; Jehin, Emmanuel; Boice, Daniel C.

    2014-11-01

    Comet C/2012 S1 (ISON) was one of the Oort cloud comets and dynamically new. This comet was broken at its perihelion passage on UT 2013 November 28.1 (at Rh ~ 17 solar radius). We observed the comet C/2012 S1 (ISON) on UT 2013 November 15 with the High Dispersion Spectrograph (HDS) mounted on the Subaru Telescope atop Mauna Kea, Hawaii. Its heliocentric and geocentric distances were 0.601 and 0.898 AU, respectively. We selected the slit size of 0”.5 x 9”.0 on the sky to achieve the spectral resolution of R = 72,000 from 550 to 830 nm. The total exposure time of comet C/2012 S1 (ISON) was 1200 seconds. We detected many emission lines caused from radicals (e.g., CN, C2, NH2), ions (H2O+), atoms ([OI] and Na I) and also many unidentified lines in the spectra. We report the (1) the ortho-to-para abundance ratios (OPRs) of water and ammonia estimated from the high-dispersion spectra of H2O+ and NH2, (2) the green-to-red line ratio of forbidden oxygen emissions, (3) the isotopic ratios of C2 (the carbon isotopic ratio from Swan band) and CN (the carbon and nitrogen isotopic ratios from red band), (4) the sodium-to-continuum ratio of comet C/2012 S1 (ISON).

  17. Determination of the hyperfine coupling constant of the cesium 7S1/2 state

    NASA Astrophysics Data System (ADS)

    Yang, Guang; Wang, Jie; Yang, Baodong; Wang, Junmin

    2016-08-01

    We report the hyperfine splitting (HFS) measurement of the cesium (Cs) 7S1/2 state by optical-optical double-resonance spectroscopy with the Cs 6S1/2-6P3/2-7S1/2 (852 nm  +  1470 nm) ladder-type system. The HFS frequency calibration is performed by employing a phase-type waveguide electro-optic modulator together with a stable confocal Fabry-Perot cavity. From the measured HFS between the F″  =  3 and F″  =  4 manifolds of the Cs 7S1/2 state (HFS  =  2183.273  ±  0.062 MHz), we have determined the magnetic dipole hyperfine coupling constant (A  =  545.818  ±  0.016 MHz), which is in good agreement with the previous work but much more precise.

  18. Universality of the Ising and the S=1 model on Archimedean lattices: A Monte Carlo determination

    NASA Astrophysics Data System (ADS)

    Malakis, A.; Gulpinar, G.; Karaaslan, Y.; Papakonstantinou, T.; Aslan, G.

    2012-03-01

    The Ising models S=1/2 and S=1 are studied by efficient Monte Carlo schemes on the (3,4,6,4) and the (3,3,3,3,6) Archimedean lattices. The algorithms used, a hybrid Metropolis-Wolff algorithm and a parallel tempering protocol, are briefly described and compared with the simple Metropolis algorithm. Accurate Monte Carlo data are produced at the exact critical temperatures of the Ising model for these lattices. Their finite-size analysis provide, with high accuracy, all critical exponents which, as expected, are the same with the well-known 2D Ising model exact values. A detailed finite-size scaling analysis of our Monte Carlo data for the S=1 model on the same lattices provides very clear evidence that this model obeys, also very well, the 2D Ising model critical exponents. As a result, we find that recent Monte Carlo simulations and attempts to define effective dimensionality for the S=1 model on these lattices are misleading. Accurate estimates are obtained for the critical amplitudes of the logarithmic expansions of the specific heat for both models on the two Archimedean lattices.

  19. 75 FR 7027 - Airworthiness Directives; Turbomeca Arriel 2S1 Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-16

    ... applies to Turbomeca Arriel 2S1 turboshaft engines that have not incorporated Modification TU 109. These...) software to version 11.01, to implement modification TU 109. (2) Guidance on implementing TU 109 can be... twin-engine helicopter with one engine upgraded to modification TU 109 if the other engine is...

  20. Pan-STARRS 1 observations of the unusual active Centaur P/2011 S1(Gibbs)

    SciTech Connect

    Lin, H. W.; Ip, W. H.; Chen, W. P.; Chen, Y. T.; Lacerda, P.; Holman, M.; Protopapas, P.; Burgett, W. S.; Chambers, K. C.; Flewelling, H.; Huber, M. E.; Jedicke, R.; Kaiser, N.; Magnier, E. A.; Metcalfe, N.; Price, P. A.

    2014-05-01

    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 {sub P1} – r {sub P1} = 0.5 ± 0.02, r {sub P1} – i {sub P1} = 0.12 ± 0.02, and i {sub P1} – z {sub P1} = 0.46 ± 0.03. The comet remained active from 2010 to 2012, with a model-dependent mass-loss rate of ∼100 kg s{sup –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 ∼40 kg s{sup –1} to 150 kg s{sup –1}. Due to its rather circular orbit, we propose that P/2011 S1 (Gibbs) has 29P/Schwassmann-Wachmann 1-like outbursts that control the outgassing rate. The results indicate that it may have a similar surface composition to that of 29P/Schwassmann-Wachmann 1. Our numerical simulations show that the future orbital evolution of P/2011 S1 (Gibbs) is more similar to that of the main population of Centaurs than to that of 29P/Schwassmann-Wachmann 1. The results also demonstrate that P/2011 S1 (Gibbs) is dynamically unstable and can only remain near its current orbit for roughly a thousand years.

  1. The S1 Truss Prior to Installation on the International Space Station

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Being attached to the Canadarm2 on the International Space Station (ISS), the Remote Manipulator System arm built by the Canadian Space Agency, the Integrated Truss Assembly (S1) Truss is suspended over the Space Shuttle Orbiter Atlantis' cargo bay. Astronauts Sandra H. Magnus, STS-112 mission specialist, and Peggy A. Whitson, Expedition Five flight engineer, used the Canadarm2 from inside the Destiny laboratory on the ISS to lift the S1 truss out of the orbiter's cargo bay and move it into position prior to its installation on the ISS. The primary payloads of this mission, ISS Assembly Mission 9A, were the Integrated Truss Assembly S1 (S One), the starboard side thermal radiator truss, and the Crew Equipment Translation Aid (CETA) cart to the ISS. The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss was attached to the S0 (S Zero) truss, which was launched on April 8, 2002 aboard the STS-110, and flows 637 pounds of anhydrous ammonia through three heat-rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA cart was attached to the Mobil Transporter and will be used by assembly crews on later missions. Manufactured by the Boeing Company in Huntington Beach, California, the truss primary structure was transferred to the Marshall Space Flight Center in February 1999 for hardware installations and manufacturing acceptance testing. The launch of the STS-112 mission occurred on October 7, 2002, and its 11-day mission ended on October 18, 2002.

  2. Centennial-scale paleoceanography during sapropel S1 deposition in the NE Aegean (Mediterranean Sea)

    NASA Astrophysics Data System (ADS)

    Triantaphyllou, Maria; Gogou, Alexandra; Dimiza, Margarita; Kostopoulou, Sofia; Parinos, Constantine; Roussakis, Grigoris; Geraga, Maria; Skampa, Elisavet; Bouloubassi, Ioanna; Fleitmann, Dominik; Zervakis, Vassilis; Velaoras, Dimitris; Diamantopoulou, Antonia; Sampatakaki, Angeliki; Lykousis, Vassilis

    2016-04-01

    Combined micropaleontological and geochemical analyses in the high-sedimentation gravity core M-4G, provided new centennial scale paleoceanographic data for the sapropel S1 deposition in the NE Aegean Sea. Sapropel layer S1a (10.2-8.0 ka) is deposited in dysoxic to oxic bottom waters; sediments are characterized by the high abundance of benthic foraminifers Chilostomella mediterranensis and Globobulimina affinis that are able to tolerate surface sediment and/or pore water oxygen depletion and the presence of the oxic mesotrophic-eutrophic U. mediterranea. Adequate preservation of organic matter is proven by the high organic carbon and loliolide and isololiolide contents, whereas the biomarker record and the abundances of eutrophic planktonic foraminifera document enhanced productivity. Both alkenone-based SSTs and δO18 G. bulloides records indicate coolings at 8.2 ka (S1a) and at ~7.8 ka (S1 interruption). Sapropelic layer S1b (7.7-6.4 ka) is characterized by rather oxic conditions marked by the prominent increase of U. mediterranea. The highly fluctuating SSTs demonstrate repeated coolings and associated dense water formation; major event at 7.4 ka, followed by cold spells at 7.0, 6.8, 6.5 ka. Besides, the increase of algal biomarkers, labile organic matter-feeding foraminifera and eutrophic planktonic species pinpoints rise in in situ marine productivity, which is enhanced by more efficient vertical convection due to repeated cold events. The associated contributions of labile marine organic matter (OM) along with fresher terrestrial OM inputs after ~7.7 ka BP imply alternative/ additional than the north Aegean riverine borderland sources for the influx of organic matter at the south Limnos Basin, also related to the inflow of highly productive Marmara/Black Sea waters

  3. Index theorem for topological excitations on R3 × S1 and Chern-Simons theory

    NASA Astrophysics Data System (ADS)

    Poppitz, Erich; Ünsal, Mithat

    2009-03-01

    We derive an index theorem for the Dirac operator in the background of various topological excitations on an R3 × S1 geometry. The index theorem provides more refined data than the APS index for an instanton on R4 and reproduces it in decompactification limit. In the R3 limit, it reduces to the Callias index theorem. The index is expressed in terms of topological charge and the η-invariant associated with the boundary Dirac operator. Neither topological charge nor η-invariant is typically an integer, however, the non-integer parts cancel to give an integer-valued index. Our derivation is based on axial current non-conservation — an exact operator identity valid on any four-manifold — and on the existence of a center symmetric, or approximately center symmetric, boundary holonomy (Wilson line). We expect the index theorem to usefully apply to many physical systems of interest, such as low temperature (large S1, confined) phases of gauge theories, center stabilized Yang-Mills theories with vector-like or chiral matter (at S1 of any size), and supersymmetric gauge theories with supersymmetry-preserving boundary conditions (also at any S1). In QCD-like and chiral gauge theories, the index theorem should shed light into the nature of topological excitations responsible for chiral symmetry breaking and the generation of mass gap in the gauge sector. We also show that imposing chirally-twisted boundary condition in gauge theories with fermions induces a Chern-Simons term in the infrared. This suggests that some QCD-like gauge theories should possess components with a topological Chern-Simons phase in the small S1 regime.

  4. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme.

    PubMed

    Bien-Möller, Sandra; Lange, Sandra; Holm, Tobias; Böhm, Andreas; Paland, Heiko; Küpper, Johannes; Herzog, Susann; Weitmann, Kerstin; Havemann, Christoph; Vogelgesang, Silke; Marx, Sascha; Hoffmann, Wolfgang; Schroeder, Henry W S; Rauch, Bernhard H

    2016-03-15

    A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient´s survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P1, S1P2, S1P3 and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P1 and S1P2 with patient´s survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P1 and S1P2. The participation of S1P1 and S1P2 in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells.In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation.

  5. Investigating the molecular mechanisms through which FTY720-P causes persistent S1P1 receptor internalization

    PubMed Central

    Sykes, David A; Riddy, Darren M; Stamp, Craig; Bradley, Michelle E; McGuiness, Neil; Sattikar, Afrah; Guerini, Danilo; Rodrigues, Ines; Glaenzel, Albrecht; Dowling, Mark R; Mullershausen, Florian; Charlton, Steven J

    2014-01-01

    Background and Purpose The molecular mechanism underlying the clinical efficacy of FTY720-P is thought to involve persistent internalization and enhanced degradation of the S1P1 receptor subtype (S1P1R). We have investigated whether receptor binding kinetics and β-arrestin recruitment could play a role in the persistent internalization of the S1P1R by FTY720-P. Experimental Approach [3H]-FTY720-P and [33P]-S1P were used to label CHO-S1P1/3Rs for binding studies. Ligand efficacy was assessed through [35S]-GTPγS binding and β-arrestin recruitment. Metabolic stability was evaluated using a bioassay measuring intracellular Ca2+ release. CHO-S1P1/3R numbers were determined, following FTY720-P treatment using flow cytometry. Key Results The kinetic off-rate of [3H]-FTY720-P from the S1P1R was sixfold slower than from the S1P3R, and comparable to [33P]-S1P dissociation from S1P1/3Rs. S1P and FTY720-P stimulated [35S]-GTPγS incorporation to similar degrees, but FTY720-P was over 30-fold less potent at S1P3Rs. FTY720-P stimulated a higher level of β-arrestin recruitment at S1P1Rs, 132% of the total recruited by S1P. In contrast, FTY720-P was a weak partial agonist at S1P3R, stimulating just 29% of the total β-arrestin recruited by S1P. Internalization experiments confirmed that cell surface expression of the S1P1R but not the S1P3R was reduced following a pulse exposure to FTY720-P, which is metabolically stable unlike S1P. Conclusions and Implications FTY720-P and S1P activation of the S1P1R results in receptor internalization as a consequence of an efficient recruitment of β-arrestin. The combination of slow off-rate, efficacious β-arrestin recruitment and metabolic stability all contribute to FTY720-P's ability to promote prolonged S1P1R internalization and may be critical factors in its efficacy in the clinic. PMID:24641481

  6. 40 CFR Table S-1 to Subpart S of... - Basic Parameters for the Calculation of Emission Factors for Lime Production

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Basic Parameters for the Calculation of Emission Factors for Lime Production S Table S-1 to Subpart S of Part 98 Protection of Environment... Manufacturing Pt. 98, Subpt. S, Table S-1 Table S-1 to Subpart S of Part 98—Basic Parameters for the...

  7. The Character of the Long-Lived State Formed from S_1 of Phenylacetylene

    NASA Astrophysics Data System (ADS)

    Johnson, Philip M.; Sears, Trevor J.

    2013-06-01

    Compared to other small aromatic molecules, phenylacetylene (PA) and benzonitrile exhibit strikingly anomalous photophysics on excitation to the S_1 state. Firstly, products are formed on S_1 excitation of a beam-cooled sample that seem to live indefinitely (as defined by the flight time through the apparatus), while action spectra of their formation mirror the rotationally-resolved absorption spectrum of the monomer. Secondly, the long lived products appear immediately during the nsec. laser pulse rather than build up during the lifetime of the singlet level, as is seen in benzene, for example. The question has therefore arisen: is the long lived product of the S_1 excitation the triplet state, as is assumed in all previous work on other molecules, or is it an isomer of some sort? New pump-probe ionization mass spectroscopy experiments have been performed to study the distribution of fragments and metastable ions produced by PA cation derived from the neutral S_1 state, and from the long-lived species. These combined with other experimental results showing weak long-lived components in both the S_1 fluorescence and pump-probe photoelectron spectra that we interpret as recurrence behavior, definitively show the long-lived state is a triplet state of PA, not an isomer. PA with a singlet-triplet gap of 10000 cm^{-1} is acting like intermediate case molecules with much smaller singlet-triplet gaps such as pyrazine and pyrimidine. Calculations point to the existence of four triplet states of PA at or below the energy of S_1 providing a very large density of vibronic states in which to distribute the energy from singlet-triplet crossing. PA T_1 is calculated to be non-planar, in contrast to what is found in benzene, possibly helping to explain the different photophysics. Acknowledgments: We gratefully acknowledge G. V. Lopez for his contributions to some of the experimental masurements. Work at Brookhaven National Laboratory was carried out under Contract No. DE-AC02

  8. [Side effects analyses in consideration of renal function for S-1-administered patients].

    PubMed

    Iwai, Mina; Kimura, Michio; Yoshimura, Tomoaki; Yasuda, Tadashi

    2011-06-01

    Although many analyses of S-1 side effects are reported, there are no reports where the analyses of side effects were performed in consideration of renal function, which is an important index of medication dose. Therefore, we investigated side effects in consideration of renal function. The subjects were 163 patients administered S-1 at the Department of Surgery of Ogaki Municipal Hospital, between October 2008 and December 2009. The frequency and severity of side effects were high and serious in the groupwhose creatinine clearance was low. A significant difference was observed among 3 groups with regard to thrombocytopenia and dehydration. In conclusion, we think that pharmacists must take renal function into consideration when administering medication, to keepclose medicinal guidance, and to actively observe progress.

  9. Raman spectrum of bacteriochlorophyll a in the S1 state

    NASA Astrophysics Data System (ADS)

    Nishizawa, Ei-ichi; Hashimoto, Hideki; Koyama, Yasushi

    1991-07-01

    The S 1 Raman spectrum of bacteriochlorophyll a is reported for the first time. A one-color experiment using the 351 nm picosecond pulses (duration 50 ps and repetition 1 kHz) for tetrahydrofuran solution detected a transient species, which showed distinct Raman lines at 1567, 1409 and 1320 cm -1 and weak profiles around 1169, 1092, 1051 and 794 cm -1. The other one-color experiment using the 355 nm nanosecond pulses (duration 12 ns and repetition 10 Hz) detected the T 1 species reported previously showing Raman lines at 1578 and 1330 cm -1. Thus, the newly identified transient species, which was pumped and probed within 50 ps, is assigned to S 1.

  10. Physical Contact between the +20 km s-1 Cloud and the Galactic Circumnuclear Disk

    NASA Astrophysics Data System (ADS)

    Takekawa, Shunya; Oka, Tomoharu; Tanaka, Kunihiko

    2017-01-01

    We report the discovery of physical contact between the Galactic circumnuclear disk (CND) and an adjacent giant molecular cloud. The central 10 pc of our Galaxy has been imaged in molecular lines at millimeter wavelength using the Nobeyama Radio Observatory 45 m radio telescope. In the position-velocity maps of several high-density probe lines, we have found an emission ``bridge'' connecting the +20 km s-1 cloud (M-0.13-0.08) and the negative longitude extension of the CND. The collision between the +20 km s-1 cloud and the CND may be responsible for the formation of the bridge. This event can promote mass accretion onto the CND and/or into the inner cavity.

  11. Structural deformation of the S =1 kagome-lattice compound KV3Ge2O9

    NASA Astrophysics Data System (ADS)

    Takagi, Eigo; Aoyama, Takuya; Hara, Shigeo; Sato, Hirohiko; Kimura, Tsuyoshi; Wakabayashi, Yusuke

    2017-03-01

    The dielectric and structural properties of the S =1 kagome antiferromagnet KV3Ge2O9 are examined. The low-temperature structure below 50 K is orthorhombic with a typical correlation length of 8 nm. While the high-temperature hexagonal phase can be considered C -centered orthorhombic, the C -centered symmetry is broken below 50 K. The low-temperature symmetry does not support the simplex solid state, which is the theoretically expected ground state for the S =1 kagome lattice. Above 60 K, incommensurate lattice modulation is observed. The lock-in transition suggests that the origin of the orthorhombic deformation is the development of a short-range magnetic ordering.

  12. Mapping of Epitopes Occurring in Bovine α(s1)-Casein Variants by Peptide Microarray Immunoassay.

    PubMed

    Lisson, Maria; Erhardt, Georg

    2016-01-01

    Immunoglobulin E epitope mapping of milk proteins reveals important information about their immunologic properties. Genetic variants of αS1-casein, one of the major allergens in bovine milk, are until now not considered when discussing the allergenic potential. Here we describe the complete procedure to assess the allergenicity of αS1-casein variants B and C, which are frequent in most breeds, starting from milk with identification and purification of casein variants by isoelectric focusing (IEF) and anion-exchange chromatography, followed by in vitro gastrointestinal digestion of the casein variants, identification of the resulting peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), in silico analysis of the variant-specific peptides as allergenic epitopes, and determination of their IgE-binding properties by microarray immunoassay with cow's milk allergic human sera.

  13. Superconformal index on R P2×S1 and mirror symmetry

    NASA Astrophysics Data System (ADS)

    Tanaka, Akinori; Mori, Hironori; Morita, Takeshi

    2015-05-01

    We study N =2 supersymmetric gauge theories on RP 2×S1 and compute the superconformal index by using the localization technique. We consider not only the round real projective plane RP 2 but also the squashed real projective plane RPb 2 which turns back to RP 2 by taking a squashing parameter b as 1. In addition, we find that the result is independent of the squashing parameter b . We apply our new superconformal index to check the simplest case of 3D mirror symmetry, i.e., the equivalence between the N =2 supersymmetric quantum electrodynamics (SQED) and the X Y Z model on RP 2×S1. We prove it by using a mathematical formula called the q -binomial theorem. We also comment on the N =4 version of mirror symmetry, mirror symmetry via generalized indices, and possibilities of generalizations from mathematical viewpoints.

  14. Ising Model Spin S = 1 ON Directed BARABÁSI-ALBERT Networks

    NASA Astrophysics Data System (ADS)

    Lima, F. W. S.

    On directed Barabási-Albert networks with two and seven neighbours selected by each added site, the Ising model with spin S = 1/2 was seen not to show a spontaneous magnetisation. Instead, the decay time for flipping of the magnetisation followed an Arrhenius law for Metropolis and Glauber algorithms, but for Wolff cluster flipping the magnetisation decayed exponentially with time. On these networks the Ising model spin S = 1 is now studied through Monte Carlo simulations. However, in this model, the order-disorder phase transition is well defined in this system. We have obtained a first-order phase transition for values of connectivity m = 2 and m = 7 of the directed Barabási-Albert network.

  15. Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice.

    PubMed

    Rieck, Michael; Kremser, Christiane; Jobin, Katarzyna; Mettke, Elisabeth; Kurts, Christian; Gräler, Markus; Willecke, Klaus; Kolanus, Waldemar

    2017-02-15

    Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine. We, therefore, investigated whether Cers2 is involved in the regulation of S1P gradients and S1P-dependent egress into the circulation. By analyzing Cers2-deficient mice, we demonstrate that Cers2 limits the levels of S1P in thymus and blood to maintain functional S1P gradients that mediate thymocyte emigration into the circulation. This function is specific for Cers2, as we also show that Cers4 is not involved in the regulation of thymic egress. Our study identified Cers2 as an important regulator of S1P-dependent thymic egress, and thus contributes to the understanding of how S1P gradients are maintained in vivo.

  16. Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival.

    PubMed

    Jaillard, C; Harrison, S; Stankoff, B; Aigrot, M S; Calver, A R; Duddy, G; Walsh, F S; Pangalos, M N; Arimura, N; Kaibuchi, K; Zalc, B; Lubetzki, C

    2005-02-09

    Endothelial differentiation gene (Edg) proteins are G-protein-coupled receptors activated by lysophospholipid mediators: sphingosine-1-phosphate (S1P) or lysophosphatidic acid. We show that in the CNS, expression of Edg8/S1P5, a high-affinity S1P receptor, is restricted to oligodendrocytes and expressed throughout development from the immature stages to the mature myelin-forming cell. S1P activation of Edg8/S1P5 on O4-positive pre-oligodendrocytes induced process retraction via a Rho kinase/collapsin response-mediated protein signaling pathway, whereas no retraction was elicited by S1P on these cells derived from Edg8/S1P5-deficient mice. Edg8/S1P5-mediated process retraction was restricted to immature cells and was no longer observed at later developmental stages. In contrast, S1P activation promoted the survival of mature oligodendrocytes but not of pre-oligodendrocytes. The S1P-induced survival of mature oligodendrocytes was mediated through a pertussis toxin-sensitive, Akt-dependent pathway. Our data demonstrate that Edg8/S1P5 activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival and that these effects depend on the developmental stage of the cell.

  17. Complete Measurement of S(1D2) Photofragment Alignment from Abel-Invertible Ion Images

    NASA Astrophysics Data System (ADS)

    Rakitzis, T. Peter; Samartzis, Peter C.; Kitsopoulos, Theofanis N.

    2001-09-01

    A novel method to measure directly the photofragment alignment from Abel-invertible two-dimensional ion images, as a function of photofragment recoil velocity, is demonstrated for S(1D2) atoms from the photodissociation of carbonyl sulfide at 223 nm. The results are analyzed in terms of coherent and incoherent contributions from two dissociative states, showing that the phase differences of the asymptotic wave functions of the fast and slow recoil-velocity channel are approximately π/2 and 0, respectively.

  18. Room for an S=+1 pentaquark in K+-nucleus phenomenology

    NASA Astrophysics Data System (ADS)

    Gal, A.; Friedman, E.

    2006-01-01

    Evidence for excitation of exotic S=+1 pentaquark degrees of freedom is presented by studying optical-potential fits to K+-nucleus total, reaction and elastic-differential cross section data at plab~500-700 MeV/c. Estimates of the underlying two-nucleon absorption K+nN→Θ+N reaction cross section are made and are used for discussing the anticipated cross section of the strangeness exchange reaction K+N→πΘ+.

  19. Regarding the Charmed-Strange Member of the 23S1 Meson State

    PubMed Central

    Feng, Xue-Chao; Chen, Jing

    2013-01-01

    By employing the mass relations derived from the mass matrix and Regge trajectory, we investigate the masses of charmed and charmed-strange members of the 23S1 meson. The masses are compared with the values predicted by other theoretical approaches and experimental data. The results may be useful for the discovery of the unobserved meson and the determination of the quantum number of the newly discovered states. PMID:24250272

  20. Electroluminescence spectra of rare-earth-doped ZnS 1-XSe X thin films

    NASA Astrophysics Data System (ADS)

    Miura, Noboru; Ogawa, Kiyoshi; Kobayashi, Shuko; Matsumoto, Hironaga; Nakano, Ryotaro

    1994-04-01

    Electroluminescence has been measured for ZnS 1- XSe X thin films doped with rare-earth ions. As X increases the band-gap energy of the host decreases. The emission levels of trivalent rare-earth ions are not observed when the band-gap energy is narrower than the excitation levels. This is because of the energy transfer between the host and the emission center.

  1. Application of the S=1 underscreened Anderson lattice model to Kondo uranium and neptunium compounds

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher; da Rosa Simões, Acirete S.; Iglesias, J. R.; Lacroix, C.; Perkins, N. B.; Coqblin, B.

    2011-01-01

    Magnetic properties of uranium and neptunium compounds showing the coexistence of the Kondo screening effect and ferromagnetic order are investigated within the Anderson lattice Hamiltonian with a two-fold degenerate f level in each site, corresponding to 5f2 electronic configuration with S=1 spins. A derivation of the Schrieffer-Wolff transformation is presented and the resulting Hamiltonian has an effective f-band term, in addition to the regular exchange Kondo interaction between the S=1 f spins and the s=1/2 spins of the conduction electrons. The resulting effective Kondo lattice model can describe both the Kondo regime and a weak delocalization of the 5f electrons. Within this model we compute the Kondo and Curie temperatures as a function of model parameters, namely the Kondo exchange interaction constant JK, the magnetic intersite exchange interaction JH, and the effective f bandwidth. We deduce, therefore, a phase diagram of the model which yields the coexistence of the Kondo effect and ferromagnetic ordering and also accounts for the pressure dependence of the Curie temperature of uranium compounds such as UTe.

  2. Synchronous Basin-Wide Formation and Redox-Controled Preservation of Mediterranean s1 Sapropel

    NASA Astrophysics Data System (ADS)

    De Lange, G. J.; Slomp, C. P.; Corselli, C.; Erba, E.; Thomson, J.; Reitz, A.

    2012-12-01

    Deposition of distinct organic-rich units (sapropels) in eastern Mediterraneran sediments is precession-related and associated with humid climate conditions. The last of such 'humid periods' occurred from 11 - 5 kyr 14C ago, simultaneous with a sustained circum-Mediterranean wet period. The end of this period coincides with a high manganeseoxide peak in all 30 studied cores and concurs with an abrupt re-ventilation event at 5.7 kyr. We demonstrate that the most recent sapropel (S1) formed synchronously between 9.8 and 5.7 14C ky BP at all water depths greater than a few hundred metres. As a consequence of increased fresh water (monsoon) input, surface waters had a reduced salinity and concomitantly the deep (> 1.8 km) eastern Mediterranean Sea was devoid of oxygen during 4,000 years of S1 formation (De Lange ea., 2008). This has resulted in a differential basin-wide preservation of S1 determined by water depth, as a result of different ventilation/climate-related redox conditions above and below 1.8 km. Climate-induced stratification of the ocean may thus contribute to enhanced preservation of organic matter, ie formation of sapropels (and potentially black shales)

  3. S-1 monotherapy in a patient with cholangiolocellular carcinoma: A case report

    PubMed Central

    Yamaguchi, Takashi; Seki, Toshihito; Inokuchi, Ryosuke; Kawamura, Rinako; Murata, Miki; Matsuzaki, Koichi; Nakashima, Osamu; Kumabe, Tsutomu; Okazaki, Kazuichi

    2016-01-01

    A 71-year-old man with alcoholic cirrhosis was found to have multiple hypervascular lesions in the liver on enhanced computed tomography. An ultrasound-guided biopsy of the lesion was performed. Immunohistochemical analysis for hepatocyte paraffin 1 expression was negative; cytokeratin (CK) 7, CK19, epithelial cell adhesion molecule and epithelial membrane antigens were positive; mucicarmine staining was negative. The tumor was thus histologically diagnosed as cholangiolocellular carcinoma (CoCC). The tumor was inoperable due to the associated advanced liver disease. In addition, the patient preferred systemic chemotherapy using only orally administered agents. Thus, S-1 monotherapy was recommended. S-1 was initially administered orally at a dose of 80 mg/day. Although the levels of tumor marker (prothrombin induced by vitamin K absence/antagonist-II and carbohydrate antigen 19-9) levels were marginally elevated, their values did not change over the entire course. The patient achieved a partial response according to the Response Evaluation Criteria In Solid Tumors (RECIST) and modified RECIST 1 year after chemotherapy initiation. In conclusion, S-1 monotherapy exhibited promising efficacy against unresectable CoCC. PMID:28105354

  4. Alternative nonallelic deletion is constitutive of ruminant alpha(s1)-casein.

    PubMed

    Ferranti, P; Lilla, S; Chianese, L; Addeo, F

    1999-07-01

    Multiple forms of alpha(s1)-casein were identified in the four major ruminant species by structural characterization of the protein fraction. While alpha(s1)-casein phenotypes were constituted by a mixture of at least seven molecular forms in ovine and caprine species, there were only two forms in bovine and water buffalo species. In ovine and caprine forms the main component corresponded to the 199-residue-long form, and the deleted proteins differed from the complete one by the absence of peptides 141-148, 110-117, or Gln78, or a combination of such deletions. The deleted segments corresponded to the sequence regions encoded by exons 13 and 16, and by the first triplet of exon 11 (CAG), suggesting that the occurrence of the short protein forms is due to alternative skipping, as previously demonstrated for some caprine and ovine phenotypes. The alternative deletion of Gln78 in alpha(s1)-casein, the only form common to the milk of all the species examined and located in a sequence region joining the polar phosphorylation cluster and the hydrophobic C-terminal domain of the protein, may play a functional role in the stabilization of the milk micelle structure.

  5. On the Absence of EUV Emission from Comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Bryans, Paul; Pesnell, W. Dean

    2016-05-01

    When the sungrazing comet C/2012 S1 (ISON) made its perihelion passage within two solar radii of the Sun’s surface, it was expected to be a bright emitter at extreme ultraviolet (EUV) wavelengths. However, despite solar EUV telescopes repointing to track the orbit of the comet, no emission was detected. This “null result” is interesting in its own right, offering the possibility of placing limits on the size and composition of the nucleus. We explain the lack of detection by considering the properties of the comet and the solar atmosphere that determine the intensity of EUV emission from sungrazing comets. By comparing these properties with those of sungrazing comet C/2011 W3 (Lovejoy), which did emit in the EUV, we conclude that the primary factor resulting in non-detectable EUV emission from C/2012 S1 (ISON) was an insufficiently large nucleus. We conclude that the radius of C/2012 S1 (ISON) was at least a factor of four less than that of C/2011 W3 (Lovejoy). This is consistent with white-light observations in the days before perihelion that suggested the comet was dramatically reducing in size on approach.

  6. Short Time-Scale Sensory Coding in S1 during Discrimination of Whisker Vibrotactile Sequences

    PubMed Central

    Miyashita, Toshio; Lee, Daniel J.; Smith, Katherine A.; Feldman, Daniel E.

    2016-01-01

    Rodent whisker input consists of dense microvibration sequences that are often temporally integrated for perceptual discrimination. Whether primary somatosensory cortex (S1) participates in temporal integration is unknown. We trained rats to discriminate whisker impulse sequences that varied in single-impulse kinematics (5–20-ms time scale) and mean speed (150-ms time scale). Rats appeared to use the integrated feature, mean speed, to guide discrimination in this task, consistent with similar prior studies. Despite this, 52% of S1 units, including 73% of units in L4 and L2/3, encoded sequences at fast time scales (≤20 ms, mostly 5–10 ms), accurately reflecting single impulse kinematics. 17% of units, mostly in L5, showed weaker impulse responses and a slow firing rate increase during sequences. However, these units did not effectively integrate whisker impulses, but instead combined weak impulse responses with a distinct, slow signal correlated to behavioral choice. A neural decoder could identify sequences from fast unit spike trains and behavioral choice from slow units. Thus, S1 encoded fast time scale whisker input without substantial temporal integration across whisker impulses. PMID:27574970

  7. Identification of New {CIS} Vibrational Levels in the S1 State of C2H2

    NASA Astrophysics Data System (ADS)

    Baraban, J. H.; Changala, P. B.; Shaver, R. G.; Field, R. W.; Stanton, J. F.; Merer, A. J.

    2012-06-01

    Although the S_1 (tilde{A} ^1A_u) state of the trans conformer of acetylene has been known for many years, the corresponding S_1 (tilde{A} ^1A_2) state of the cis conformer was only discovered recently. Transitions to it from the ground state are electronically forbidden, but its vibrational levels acquire intensity by tunneling through the isomerization barrier and interacting with levels of the trans conformer. We have recently identified two new vibrational levels (32 and 41 61) of the {cis} conformer of S1 C2H2, bringing the total number of levels observed to six out of an expected ten up to the energies studied in this work. The appearance of these levels in IR-UV double resonance LIF spectra will be discussed, along with their vibrational assignments. Experimentally determined vibrational parameters and {ab initio} anharmonic force fields for both the {trans} and {cis} conformers will be presented as part of the evidence supporting these assignments. These results shed new light on the vibrational level structure of both conformers in this isomerizing system. A. J. Merer, A. H. Steeves, J. H. Baraban, H. A. Bechtel, and R. W. Field. J. Chem. Phys., 134(24):244310, 2011.

  8. Hyperconjugation in the S1 State of Substituted Toluene Probed by Infrared Spectroscopy

    NASA Astrophysics Data System (ADS)

    Chiba, Takashi; Okuyama, Katsuhiko; Fujii, Asuka

    2016-06-01

    Internal rotation of the methyl group in substituted toluenes is one of prototypes of large amplitude motions in polyatomic molecules. The internal rotation of o-fluorotoluene is strongly hindered in the S0 state, but that of m-fluorotoluene is almost free. For the S1 state, however, the substantial changes of the internal rotation potentials have been reported; while the potential barrier in the o-isomer drastically decreases and the methyl group becomes almost a free rotor, the barrier in the m-isomer largely increases. These surprising barrier changes have been attributed to the methyl conformation-dependent stabilization in the S1 state by the π*-σ* hyperconjugation. In the present study, to test this interpretation, we observed infrared spectra of o- and m-fluorotoluenes in the S0 and S1 states. Both the isomers showed decrease of the methyl CH stretch frequencies upon the electronic excitation. We concluded that this frequency decrease is the evidence of the π*-σ* hyperconjugation. K,Okuyama.;N,Mikami.;M,Ito. J.Phys.Chem. 1985, 89, 5617 H,Nakai.;M,Kawai. Chem.Phys.Lett 1999, 307, 272

  9. Correlation of charge, hydrophobicity, and structure with antimicrobial activity of S1 and MIRIAM peptides.

    PubMed

    Leptihn, Sebastian; Har, Jia Yi; Wohland, Thorsten; Ding, Jeak Ling

    2010-11-02

    Antimicrobial peptides are key elements of the innate immune system. Many of them interact with membranes of bacteria leading to perturbation of the lipid bilayer and eventually to inactivation of the pathogen. The emergence of multidrug-resistant bacteria has necessitated innovations of new and more powerful classes of antimicrobials. Here we present the in-depth study of an antimicrobial peptide, MIRIAM, derived from Sushi1 (S1), a well-characterized peptide from the horseshoe crab. MIRIAM interacts strongly with negatively charged lipids, forming an α-helical structure. MIRIAM was found to neutralize LPS and kill Gram-negative bacteria with high efficiency, while not releasing LPS. The promising therapeutic potential of MIRIAM is shown by hemolytic assays, which demonstrate that eukaryotic membranes are unaffected at bactericidal concentrations. Nanoparticle-conjugated MIRIAM used in single-molecule fluorescence and electron microscopy experiments showed that MIRIAM targets bacterial membranes to kill bacteria similarly to parental S1. Furthermore, fragments derived from MIRIAM and S1 provided insights on their molecular mechanisms of action, in particular, the relationships of functional motifs comprised by charge, hydrophobicity, and structure within each peptide. We conclude that the combination of charge, hydrophobicity, and length of the peptide is important. A close interaction of amino acids in a single molecule in a carefully balanced ensemble of sequence position and secondary structure is crucial.

  10. Cloning and characterization of a gene from Rhizobium melilotii 2011 coding for ribosomal protein S1.

    PubMed Central

    Schnier, J; Thamm, S; Lurz, R; Hussain, A; Faist, G; Dobrinski, B

    1988-01-01

    A 7 kb chromosomal DNA fragment from R. melilotii was cloned, which complemented temperature-sensitivity of an E. coli amber mutant in rpsA, the gene for ribosomal protein S1 (ES1). From complementation and maxicell analysis a 58 kd protein was identified as the homolog of protein S1 (RS1). DNA sequence analysis of the R. melilotii rpsA gene identified a protein of 568 amino acids, which showed 47% identical amino acid homology to protein S1 from E. coli. The RS1 protein lacked the two Cys residues which had been reported to play an important role for the function of ES1. Two repeats containing Shine-Dalgarno sequences were identified upstream of the structural gene. Binding studies with RNA polymerase from E. coli and Pseudomonas putida located one RNA-polymerase binding site close to the RS1 gene and another one several hundred basepairs upstream. One possible promoter was also identified by DNA sequence comparison with the corresponding E. coli promoter. Images PMID:3368316

  11. Analysing the New Saturnian Rings, R/2004 S1 and R/2004 S2

    NASA Astrophysics Data System (ADS)

    Winter, S. M. Giuliatti; Sfair, R.; Mourão, D. C.; Bastos, T. A.

    2005-12-01

    The Cassini-Huygens arrival into the Saturnian system brought a large amount of data about the satellites and rings. Two diffuse rings were found in the region between the A ring and Prometheus. R/2004 S1 is coorbital to Atlas and R/2004 S2 is close to Prometheus. In this work we analysed the closest approach between Prometheus and both rings. As a result we found that the satellite removes particles from R/2004 S2 ring. Long-term numerical simulations showed that some particles can cross the F ring region . The well known region of the F ring, where small satellites are present and particles are being taking from the ring, gains a new insight with the presence of particles from R/2004 S2 ring. The computation of the Lyapunov Characteristic Exponent reveled that the R/2004 S2 ring lies in a chaotic region while R/2004 S1 ring and Atlas are in a stable region. Atlas is responsible for the formation of three regimes in the R/2004 S1 ring, as expected for a satellite embedded in a ring.

  12. Sphingosine 1-phosphate protects primary human keratinocytes from apoptosis via nitric oxide formation through the receptor subtype S1P₃.

    PubMed

    Schmitz, Elisabeth I; Potteck, Henrik; Schüppel, Melanie; Manggau, Marianti; Wahydin, Elly; Kleuser, Burkhard

    2012-12-01

    Although the lipid mediator sphingosine 1-phosphate (S1P) has been identified to induce cell growth arrest of human keratinocytes, the sphingolipid effectively protects these epidermal cells from apoptosis. The molecular mechanism of the anti-apoptotic action induced by S1P is less characterized. Apart from S1P, endogenously produced nitric oxide (NO•) has been recognized as a potent modulator of apoptosis in keratinocytes. Therefore, it was of great interest to elucidate whether S1P protects human keratinocytes via a NO•-dependent signalling pathway. Indeed, S1P induced an activation of endothelial nitric oxide synthase (eNOS) in human keratinocytes leading to an enhanced formation of NO•. Most interestingly, the cell protective effect of S1P was almost completely abolished in the presence of the eNOS inhibitor L-NAME as well as in eNOS-deficient keratinocytes indicating that the sphingolipid metabolite S1P protects human keratinocytes from apoptosis via eNOS activation and subsequent production of protective amounts of NO•. It is well established that most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Therefore, the involvement of S1P-receptor subtypes in S1P-mediated eNOS activation has been examined. Indeed, this study clearly shows that the S1P(3) is the exclusive receptor subtype in human keratinocytes which mediates eNOS activation and NO• formation in response to S1P. In congruence, when the S1P(3) receptor subtype is abrogated, S1P almost completely lost its ability to protect human keratinocytes from apoptosis.

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

    PubMed Central

    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. PMID:28367448

  14. Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts

    PubMed Central

    Kudo, Masahisa; Yamamoto, Yoshiyuki; Koga, Yoshikatsu; Hamaguchi, Tetsuya; Akimoto, Tetsuo; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-01-01

    Combination therapy with S-1 and cisplatin (CDDP) is the standard chemotherapy for advanced gastric cancer in Japan; however, its administration requires hospitalization for hydration to prevent nephrotoxicity from CDDP. By contrast, NC-6004 appears to reduce the renal toxicity of CDDP and may be used on an outpatient basis. Thus, the effects of combined treatment with S-1 and NC-6004 were compared with those of S-1 and CDDP in a human gastric cancer model. In vitro cytotoxic effects were investigated in 44As3Luc, MKN45 and MKN74 human gastric cancer cell lines. The effects of NC-6004 and 5-fluorouracil (5-FU) were compared with the effects of CDDP and 5-FU using the combination index method. The in vivo antitumor effects of S-1/NC-6004 and S-1/CDDP were evaluated in mice bearing 44As3Luc xenografts. Both combinations exhibited synergistic activity in MKN45 and MKN74 cells and additive effects in 44As3Luc cells. Moreover, the in vivo antitumor effects did not differ between the S-1/NC-6004 and S-1/CDDP treatment groups. However, a significantly lower body weight loss was observed in S-1/NC-6004-treated mice compared with the S-1/CDDP-treated mice. Our data warrant a clinical evaluation of S-1/NC-6004 combination therapy. PMID:28101359

  15. Assay to measure the secretion of sphingosine-1-phosphate from cells induced by S1P lyase inhibitors.

    PubMed

    Loetscher, Erika; Schneider, Karolina; Beerli, Christian; Billich, Andreas

    2013-04-12

    Inhibitors of the sphingosine-1-phosphate (S1P) degrading enzyme S1P lyase (SPL) may be useful in the therapy of inflammatory diseases by preventing lymphocyte recruitment to diseased tissues. Here we describe a cellular assay for such inhibitors, which takes advantage of the observation that a fraction of the intracellular S1P accumulated in the presence of SPL inhibitors is secreted into the medium of cultured cells. The secreted S1P is then quantified using an S1P-sensitive reporter cell line. In the routine assay protocol, human HEK293T cells are treated with SPL inhibitors in the presence of phosphatase inhibitors and sphingosine; while the phosphatase inhibitors are included to prevent the degradation of S1P secreted from the cells, sphingosine is added as source for intracellular S1P that is prone to SPL degradation. The secreted S1P in the supernatant of the cell cultures is then quantified by measuring calcium flux induced in CHO-K1 cells expressing the human S1P3 receptor. Using this method SPL inhibitors were shown to induce a concentration-dependent increase of extracellular S1P under the conditions used; thus, the assay allows for the ranking of SPL inhibitors according to their potency on living cells.

  16. MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells.

    PubMed

    Kalhori, Veronica; Törnquist, Kid

    2015-03-15

    The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion.

  17. Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts.

    PubMed

    Kudo, Masahisa; Yamamoto, Yoshiyuki; Koga, Yoshikatsu; Hamaguchi, Tetsuya; Akimoto, Tetsuo; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-12-01

    Combination therapy with S-1 and cisplatin (CDDP) is the standard chemotherapy for advanced gastric cancer in Japan; however, its administration requires hospitalization for hydration to prevent nephrotoxicity from CDDP. By contrast, NC-6004 appears to reduce the renal toxicity of CDDP and may be used on an outpatient basis. Thus, the effects of combined treatment with S-1 and NC-6004 were compared with those of S-1 and CDDP in a human gastric cancer model. In vitro cytotoxic effects were investigated in 44As3Luc, MKN45 and MKN74 human gastric cancer cell lines. The effects of NC-6004 and 5-fluorouracil (5-FU) were compared with the effects of CDDP and 5-FU using the combination index method. The in vivo antitumor effects of S-1/NC-6004 and S-1/CDDP were evaluated in mice bearing 44As3Luc xenografts. Both combinations exhibited synergistic activity in MKN45 and MKN74 cells and additive effects in 44As3Luc cells. Moreover, the in vivo antitumor effects did not differ between the S-1/NC-6004 and S-1/CDDP treatment groups. However, a significantly lower body weight loss was observed in S-1/NC-6004-treated mice compared with the S-1/CDDP-treated mice. Our data warrant a clinical evaluation of S-1/NC-6004 combination therapy.

  18. Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction

    PubMed Central

    Sanna, M. Germana; Vincent, Kevin P.; Repetto, Emanuela; Nguyen, Nhan; Brown, Steven J.; Abgaryan, Lusine; Riley, Sean W.; Leaf, Nora B.; Cahalan, Stuart M.; Kiosses, William B.; Kohno, Yasushi; Brown, Joan Heller; McCulloch, Andrew D.

    2016-01-01

    The molecular pharmacology of the G protein–coupled receptors for sphingosine 1-phosphate (S1P) provides important insight into established and new therapeutic targets. A new, potent bitopic S1P3 antagonist, SPM-354, with in vivo activity, has been used, together with S1P3-knockin and S1P3-knockout mice to define the spatial and functional properties of S1P3 in regulating cardiac conduction. We show that S1P3 is a key direct regulator of cardiac rhythm both in vivo and in isolated perfused hearts. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in vivo and S1P in isolated hearts induced a spectrum of cardiac effects, ranging from sinus bradycardia to complete heart block, as measured by a surface electrocardiogram in anesthetized mice and in volume-conducted Langendorff preparations. The agonist effects on complete heart block are absent in S1P3-knockout mice and are reversed in wild-type mice with SPM-354, as characterized and described here. Homologous knockin of S1P3-mCherry is fully functional pharmacologically and is strongly expressed by immunohistochemistry confocal microscopy in Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4 (HCN4)-positive atrioventricular node and His-Purkinje fibers, with relative less expression in the HCN4-positive sinoatrial node. In Langendorff studies, at constant pressure, SPM-354 restored sinus rhythm in S1P-induced complete heart block and fully reversed S1P-mediated bradycardia. S1P3 distribution and function in the mouse ventricular cardiac conduction system suggest a direct mechanism for heart block risk that should be further studied in humans. A richer understanding of receptor and ligand usage in the pacemaker cells of the cardiac system is likely to be useful in understanding ventricular conduction in health, disease, and pharmacology. PMID:26494861

  19. Scaling and root planning, and locally delivered minocycline reduces the load of Prevotella intermedia in an interdependent pattern, correlating with symptomatic improvements of chronic periodontitis: a short-term randomized clinical trial

    PubMed Central

    Deng, Shuli; Wang, Ying; Sun, Wei; Chen, Hui; Wu, Gang

    2015-01-01

    Background To evaluate the respective or combinatory efficacy of locally delivered 2% minocycline (MO), and scaling and root planning (SRP) by assessing both clinical parameters and the loads of four main periodontal pathogens in treating chronic periodontitis (CP). Methods Seventy adults with CP were randomly assigned to the three treatment groups: 1) SRP alone; 2) MO alone; and 3) combinatory use of SRP and MO (SRP + MO). Before and 7 days after the treatments, we evaluated both clinical parameters (pocket depth [PD] and sulcus bleeding index [SBI]) and the gene load of four main periodontal pathogens (Aggregatibacter actinomycetemcomitans [Aa], Fusobacterium nucleatum [Fn], Porphyromonas gingivalis [Pg], and Prevotella intermedia [Pi]). Results The bacterial prevalence per patient was: Aa, 31.25%; Fn, 100%; Pg, 95.31%; and Pi, 98.44%. Seven days after treatment, the three treatments significantly reduced both PD and SBI, but not detection frequencies of the four pathogens. For PD, the reduction efficacy of SRP + MO was significantly higher than that of either MO or SRP. Only Pg responded significantly to SRP. Pg and Fn were significantly reduced in the presence of MO. Only SRP + MO showed a significant reduction effect on the gene load of Pi. The reduction of PD significantly correlated with the gene load of Pi (r=0.26; P=0.042) but not of the other bacteria. Conclusion SRP and MO reduced the load of Pi in an interdependent pattern, which correlated with symptomatic improvements of CP. PMID:26676022

  20. The glucose/xylose facilitator Gxf1 from Candida intermedia expressed in a xylose-fermenting industrial strain of Saccharomyces cerevisiae increases xylose uptake in SSCF of wheat straw.

    PubMed

    Fonseca, César; Olofsson, Kim; Ferreira, Carla; Runquist, David; Fonseca, Luís L; Hahn-Hägerdal, Bärbel; Lidén, Gunnar

    2011-05-06

    Ethanolic fermentation of lignocellulose raw materials requires industrial xylose-fermenting strains capable of complete and efficient D-xylose consumption. A central question in xylose fermentation by Saccharomyces cerevisiae engineered for xylose fermentation is to improve the xylose uptake. In the current study, the glucose/xylose facilitator Gxf1 from Candida intermedia, was expressed in three different xylose-fermenting S. cerevisiae strains of industrial origin. The in vivo effect on aerobic xylose growth and the initial xylose uptake rate were assessed. The expression of Gxf1 resulted in enhanced aerobic xylose growth only for the TMB3400 based strain. It displayed more than a 2-fold higher affinity for D-xylose than the parental strain and approximately 2-fold higher initial specific growth rate at 4 g/L D-xylose. Enhanced xylose consumption was furthermore observed when the GXF1-strain was assessed in simultaneous saccharification and co-fermentation (SSCF) of pretreated wheat straw. However, the ethanol yield remained unchanged due to increased by-product formation. Metabolic flux analysis suggested that the expression of the Gxf1 transporter had shifted the control of xylose catabolism from transport to the NAD(+) dependent oxidation of xylitol to xylulose.

  1. Unusual Water Production Activity of Comet C/2012 S1 (ISON): Outbursts and Continuous Fragmentation

    NASA Astrophysics Data System (ADS)

    Combi, M. R.; Fougere, N.; Mäkinen, J. T. T.; Bertaux, J.-L.; Quémerais, E.; Ferron, S.

    2014-06-01

    The Solar Wind ANisotropies (SWAN) all-sky hydrogen Lyα camera on the SOlar and Heliospheric Observer (SOHO) satellite observed the hydrogen coma of comet C/2012 S1 (ISON) for most of the last month of its activity from 2013 October 24 to November 24, ending just 4 days before perihelion and its final disruption. The water production rate of the comet was determined from these observations. SOHO has been operating in a halo orbit around the Earth-Sun L1 Lagrange point since its launch in late 1995. Most water vapor produced by comets is ultimately photodissociated into two H atoms and one O atom producing a huge hydrogen coma that is routinely observed in the daily SWAN images in comets of sufficient brightness. Water production rates were calculated from 22 images over most of the last month of the pre-perihelion apparition. The water production rate increased very slowly on average from October 24.9 until November 12.9, staying between 1.8 and 3.4 × 1028 s-1, after which it increased dramatically, reaching 1.6 to 2 × 1030 s-1 from November 21.6 to 23.6. It was not detected after perihelion on December 3.7 when it should have been visible. We examine the active surface area necessary to explain the water production rate and its variation and are able to place constraints on the physical size of the original nucleus necessary to account for the large amount of activity from November 12.9 and until just before perihelion.

  2. Synchronous basin-wide Mediterranean Sapropel S1 formation; Preservation versus Productivity

    NASA Astrophysics Data System (ADS)

    De Lange, Gert J.; Slomp, Caroline; Corselli, Cesare; Erba, Elisabetta; Thomson, John; Reitz, Anja

    2013-04-01

    The timing of deposition of all distinct organic-rich units (sapropels) in eastern Mediterraneran sediments is precession-related and is associated with humid climate conditions. The last of such 'humid periods' occurred from 11 - 5 kyr 14C ago, simultaneous with a sustained circum-Mediterranean wet period including a vegetated Sahara. The end of this period coincides with a high manganese-oxide peak in all 30 studied cores and concurs with an abrupt re-ventilation event at 5.7 kyr for the deep-water. We demonstrate that the most recent sapropel (S1) formed synchronously between 9.8 and 5.7 14C ky BP at all water depths greater than a few hundred metres. As a consequence of increased fresh water (monsoon) input, surface waters had a reduced salinity and concomitantly the deep (> 1.8 km) eastern Mediterranean Sea was devoid of oxygen during 4,000 years of S1 formation (De Lange ea., 2008). This has resulted in a differential basin-wide preservation of S1 determined by water depth, as a result of different ventilation/climate-related redox conditions above and below 1.8 km. Climate-induced stratification of the ocean may thus contribute to enhanced preservation of organic matter, i.e. formation of sapropels (and potentially black shales). Reference De Lange G.J., Thomson J., Reitz A., Slomp C.P., Principato M.S., Erba E., and Corselli C. (2008) Synchronous basin-wide formation and redox-controlled preservation of a Mediterranean sapropel. Nature Geo 1, 606-610.

  3. Experimental design and environmental parameters affect Rhodospirillum rubrum S1H response to space flight.

    PubMed

    Mastroleo, Felice; Van Houdt, Rob; Leroy, Baptiste; Benotmane, M Abderrafi; Janssen, Ann; Mergeay, Max; Vanhavere, Filip; Hendrickx, Larissa; Wattiez, Ruddy; Leys, Natalie

    2009-12-01

    In view of long-haul space exploration missions, the European Space Agency initiated the Micro-Ecological Life Support System Alternative (MELiSSA) project targeting the total recycling of organic waste produced by the astronauts into oxygen, water and food using a loop of bacterial and higher plant bioreactors. In that purpose, the alpha-proteobacterium, Rhodospirillum rubrum S1H, was sent twice to the International Space Station and was analyzed post-flight using a newly developed R. rubrum whole genome oligonucleotide microarray and high throughput gel-free proteomics with Isotope-Coded Protein Label technology. Moreover, in an effort to identify a specific response of R. rubrum S1H to space flight, simulation of microgravity and space-ionizing radiation were performed on Earth under identical culture set-up and growth conditions as encountered during the actual space journeys. Transcriptomic and proteomic data were integrated and permitted to put forward the importance of medium composition and culture set-up on the response of the bacterium to space flight-related environmental conditions. In addition, we showed for the first time that a low dose of ionizing radiation (2 mGy) can induce a significant response at the transcriptomic level, although no change in cell viability and only a few significant differentially expressed proteins were observed. From the MELiSSA perspective, we could argue the effect of microgravity to be minimized, whereas R. rubrum S1H could be more sensitive to ionizing radiation during long-term space exploration mission.

  4. Source and development of large manganese enrichments above eastern Mediterranean sapropel S1

    NASA Astrophysics Data System (ADS)

    Reitz, Anja; Thomson, John; de Lange, Gert J.; Hensen, Christian

    2006-09-01

    The residual dark unit of the most recent eastern Mediterranean sapropel (S1) is usually overlain by sediments with enhanced concentrations of MnOx in two separated layers. The variability and magnitude of the Mn enrichment at different locations and water depths indicate that Mn must have been added preferentially to sediments at intermediate (1-2 km) water depths. We propose a two-stage mechanism for the Mn enrichment that involves decreasing oxygenation with increasing water depth. This mechanism involves the loss of reduced Mn2+ from the deepest sediments (>2 km water depth) into overlying anoxic waters and a variable gain of MnOx in sediments in contact with oxygenated waters at shallower depth. In the S1 unit that receives the extra MnOx input, an upper higher Mn-enriched zone (>3 wt %) is maintained continuously at the top of the accumulating S1 unit because the pore waters are anoxic at shallow sediment depth while bottom waters are oxic to some degree. In a reactive-transport model, the Mn enrichment in the upper zone could not be supported by normal sediment diagenesis. Thus the MnOx in the upper Mn horizon must have formed mainly in the water column. The MnOx in the upper Mn-enriched zone adsorbed Mo and Li from seawater in a similar manner as other Mn-enriched oxic sediments, nodules, and crusts, with a Mn:Mo ratio of ˜600:1, a Mn:Li ratio of ˜750:1, and a δ98/95MoMOMO of -2.5 ‰.

  5. Numerical modeling of the oceanic S1 tide for Earth rotation studies

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Einspigel, David

    2015-04-01

    Diurnal S1 oceanic oscillations induced by atmospheric pressure loading elicit small but measurable perturbations of universal time, polar motion, and the prograde annual component of nutation. In a priori models of Earth rotation variations, these signals are as-yet unconsidered'partly due to the fact that the underlying globally-gridded S1 harmonics can only be inferred from purely hydrodynamic ocean models which lack the reliable elevation constraints from satellite altimetry. Such free-running forward integrations of the shallow water equations usually overestimate tidal energies and therefore also OAM (oceanic angular momentum), unless the model formulation allows for significant dissipation in the deep ocean. For practical purposes, abyssal energy flux and hence the accuracy of tidal elevations can be controlled by a tunable but inordinately high viscosity value or by evoking additional quadratic wave drag when surface heights change rapidly. A third and physically plausible modeling route is to parametrize the sub-grid scale conversion of barotropic currents into small internal tides by aid of a linear drag term. In the present paper, we study the impact of these different dissipation schemes on the fidelity of surface elevations in a simple barotropic time-stepping model forced by selected gravitational equilibrium tides as well as diurnal air pressure variations. After determining the optimal drag formulation through validation runs with the well-known principal gravitational K1 tide, the OAM values for each of the hydrodynamic S1 solutions are documented and discussed in the specific context of their contribution to the prograde annual signal in Earth's nutation.

  6. Odin observations of ammonia in the Sgr A +50 km s-1 cloud and circumnuclear disk

    NASA Astrophysics Data System (ADS)

    Sandqvist, Aa.; Hjalmarson, Å.; Frisk, U.; Lundin, S.; Nordh, L.; Olberg, M.; Olofsson, G.

    2017-03-01

    Context. The Odin satellite is now into its sixteenth year of operation, much surpassing its design life of two years. One of the sources which Odin has observed in great detail is the Sgr A complex in the centre of the Milky Way. Aims: To study the presence of NH3 in the Galactic centre and spiral arms. Methods: Recently, Odin has made complementary observations of the 572 GHz NH3 line towards the Sgr A +50 km s-1 cloud and circumnuclear disk (CND). Results: Significant NH3 emission has been observed in both the +50 km s-1 cloud and the CND. Clear NH3 absorption has also been detected in many of the spiral arm features along the line of sight from the Sun to the core of our Galaxy. Conclusions: The very large velocity width (80 km s-1) of the NH3 emission associated with the shock region in the southwestern part of the CND may suggest a formation/desorption scenario similar to that of gas-phase H2O in shocks/outflows. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), the Centre National d'Études Spatiales (CNES), France, and the European Space Agency (ESA). The former Space division of the Swedish Space Corporation, today OHB Sweden, is the prime contractor, also responsible for Odin operations.The reduced spectra are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/599/A135

  7. Cloning and characterization of monofunctional catalase from photosynthetic bacterium Rhodospirillum rubrum S1.

    PubMed

    Lee, Dong-Heon; Oh, Duck-Chul; Oh, You-Sung; Malinverni, Juliana C; Kukor, Jerome J; Kahng, Hyung-Yeel

    2007-09-01

    In this study, an approx. 2.5-kb gene fragment including the catalase gene from Rhodospirillum rubrum S1 was cloned and characterized. The determination of the complete nucleotide sequence revealed that the cloned DNA fragment was organized into three open reading frames, designated as ORF1, catalase, and ORF3 in that order. The catalase gene consisted of 1,455 nucleotides and 484 amino acids, including the initiation and stop codons, and was located 326 bp upstream in the opposite direction of ORF1. The catalase was overproduced in Escherichia coli UM255, a catalase-deficient mutant, and then purified for the biochemical characterization of the enzyme. The purified catalase had an estimated molecular mass of 189 kDa, consisting of four identical subunits of 61 kDa. The enzyme exhibited activity over a broad pH range from pH 5.0 to pH 11.0 and temperature range from 20 degrees C to 60 degrees C. The catalase activity was inhibited by 3-amino-1,2,4-triazole, cyanide, azide, and hydroxylamine. The enzyme's K(m) value and V(max) of the catalase for H2O2 were 21.8 mM and 39,960 U/mg, respectively. Spectrophotometric analysis revealed that the ratio of A406 to A280 for the catalase was 0.97, indicating the presence of a ferric component. The absorption spectrum of catalase-4 exhibited a Soret band at 406 nm, which is typical of a heme-containing catalase. Treatment of the enzyme with dithionite did not alter the spectral shape and revealed no peroxidase activity. The combined results of the gene sequence and biochemical characterization proved that the catalase cloned from strain S1in this study was a typical monofunctional catalase, which differed from the other types of catalases found in strain S1.

  8. Toxicogenomic Response of Rhodospirillum rubrum S1H to the Micropollutant Triclosan▿

    PubMed Central

    Pycke, Benny F. G.; Vanermen, Guido; Monsieurs, Pieter; De Wever, Heleen; Mergeay, Max; Verstraete, Willy; Leys, Natalie

    2010-01-01

    In the framework of the Micro-Ecological Life Support System Alternative (MELiSSA) project, a pilot study was performed to identify the effects of triclosan on the MELiSSA carbon-mineralizing microorganism Rhodospirillum rubrum S1H. Triclosan is a biocide that is commonly found in human excrement and is considered an emerging pollutant in wastewater and the environment. Chronic exposure to MELiSSA-relevant concentrations (≥25 μg liter−1) of triclosan resulted in a significant extension of the lag phase of this organism but hardly affected the growth rate. Analytical determinations gave no indication of triclosan biodegradation during the growth experiment, and flow cytometric viability analyses revealed that triclosan is bacteriostatic and only slightly toxic to R. rubrum S1H. Using microarray analyses, the genetic mechanisms supporting the reversibility of triclosan-induced inhibition were scrutinized. An extremely triclosan-responsive cluster of four small adjacent genes was identified, for which there was up to 34-fold induction with 25 μg liter−1 triclosan. These four genes, for which the designation muf (micropollutant-upregulated factor) is proposed, appear to be unique to R. rubrum and are shown here for the first time to be involved in the response to stress. Moreover, numerous other systems that are associated with the proton motive force were shown to be responsive to triclosan, but they were never as highly upregulated as the muf genes. In response to triclosan, R. rubrum S1H induced transcription of the phage shock protein operon (pspABC), numerous efflux systems, cell envelope consolidation mechanisms, the oxidative stress response, beta-oxidation, and carbonic anhydrase, while there was downregulation of bacterial conjugation and carboxysome synthesis genes. The muf genes and three efflux-related genes showed the most potential to be low-dose biomarkers. PMID:20363786

  9. Properties of digital 1/3-octave filters implemented according to ANSI S1.11

    NASA Astrophysics Data System (ADS)

    Geras, Antonina; Starecki, Tomasz

    The paper presents results of investigation into properties of digital filters implemented in compliance with ANSI S1.11 Standard: Octave-Band and Fractional-Octave Band Analog and Digital Filters. The discussed solutions are digital one-third-octave IIR filters with Direct Form I topology. Performed simulations showed that the filters exhibit strong problems with stability, especially in the case of low center frequency filters. Another problem clearly visible in all investigated structures was poor attenuation at the frequencies above the passband. Although the filters were implemented according to the ANSI standard, none of them met all of the requirements of the standard.

  10. Observation of an Exotic S = +1 Baryon in Exclusive Photoproduction from the Deuteron

    SciTech Connect

    Stepan Stepanyan; Kenneth Hicks; Daniel Carman; Evgueni Pasyuk; Reinhard Schumacher; Elton Smith; David Tedeschi; Luminita Todor

    2003-12-19

    In an exclusive measurement of the reaction {gamma}d {yields} K{sup +} K{sup -} p n, a narrow peak that can be attributed to an exotic baryon with strangeness S = +1 is seen in the K{sup +}n invariant mass spectrum. The peak is at 1542 {+-} 5 MeV/c{sup 2} with a measured width of 21 MeV/c{sup 2} FWHM, equivalent to the experimental invariant mass resolution. The statistical significance of the peak is 5.3 {+-} 0.5 {sigma} for a Gaussian peak shape on top of a smooth background.

  11. Mechanisms for spin supersolidity in S=(1/2) spin-dimer antiferromagnets

    SciTech Connect

    Picon, J.-D.; Albuquerque, A. F.; Schmidt, K. P.; Laflorencie, N.; Troyer, M.; Mila, F.

    2008-11-01

    Using perturbative expansions and the contractor renormalization (CORE) algorithm, we obtain effective hard-core bosonic Hamiltonians describing the low-energy physics of S=1/2 spin-dimer antiferromagnets known to display supersolid phases under an applied magnetic field. The resulting effective models are investigated by means of mean-field analysis and quantum Monte Carlo simulations. A 'leapfrog mechanism,' through means of which extra singlets delocalize in a checkerboard-solid environment via correlated hoppings, is unveiled that accounts for the supersolid behavior.

  12. Strangeness S =-1 hyperon-nucleon scattering in covariant chiral effective field theory

    NASA Astrophysics Data System (ADS)

    Li, Kai-Wen; Ren, Xiu-Lei; Geng, Li-Sheng; Long, Bingwei

    2016-07-01

    Motivated by the successes of covariant baryon chiral perturbation theory in one-baryon systems and in heavy-light systems, we study relevance of relativistic effects in hyperon-nucleon interactions with strangeness S =-1 . In this exploratory work, we follow the covariant framework developed by Epelbaum and Gegelia to calculate the Y N scattering amplitude at leading order. By fitting the five low-energy constants to the experimental data, we find that the cutoff dependence is mitigated, compared with the heavy-baryon approach. Nevertheless, the description of the experimental data remains quantitatively similar at leading order.

  13. SU(2s+1) symmetry and nonlinear dynamics of high spin magnets

    SciTech Connect

    Kovalevsky, M.Y. Glushchenko, A.V.

    2014-10-15

    The article is devoted to the description of dynamics of magnets with arbitrary spin on the basis of the Hamiltonian formalism. The relationship of quantum states and magnetic degrees of freedom has been considered. Subalgebras of Poisson bracket of magnetic values for spin s=1/2; 1; 3/2 have been established. We have obtained non-linear dynamic equations for the normal and degenerate non-equilibrium states of high-spin magnets with the SO(3), SU(4), SU(2)×SU(2), SU(3), SO(4), SO(5) symmetries of exchange interaction. The connection between models of magnetic exchange energy and the Casimir invariants has been discussed.

  14. φ meson production frompbar p collisions atsqrt s = 1.8 TeV

    NASA Astrophysics Data System (ADS)

    Alexopoulos, T.; Allen, C.; Anderson, E. W.; Balamurali, V.; Banerjee, S.; Beery, P. D.; Bhat, P.; Bishop, J. M.; Biswas, N. N.; Bujak, A.; Carmony, D. D.; Carter, T.; Cole, P.; Choi, Y.; Debonte, R.; Decarlo, V.; Erwin, A. R.; Findeisen, C.; Goshaw, A. T.; Gutay, L. J.; Hirsch, A. S.; Hojvat, C.; Jennings, J. R.; Kenney, V. P.; Lindsey, C. S.; Loomis, C.; Losecco, J. M.; McMahon, T.; McManus, A. P.; Morgan, N.; Nelson, K.; Oh, S. H.; Porile, N. T.; Rimai, A.; Reeves, D.; Robertson, W. J.; Scharenberg, R. P.; Stringfellow, B. C.; Stampke, S. R.; Thompson, M.; Turkot, F.; Walker, W. D.; Wang, C. H.; Warchol, J.; Wesson, D. K.; Zhan, Y.

    1995-09-01

    Fermilab experiment E735 located at the CO intersection region of thesqrt s = 1.8 TeVpbar p collider analysed over 900 Φ→ K + K - events. Measured were the transverse momentum spectrum, the correlation between the average transverse momentum < pt> and the charged particle multiphcity N c , as well as the probability of Φ production per charged track, N Φ / N c , versus N c . We have also made an estinate of the total inclusive cross section for Φ mesons,σ (pbar p to φ X) = 7.3 ± 2.2 mb.

  15. Amplification of S-1 Spheromak current by an inductive current transformer

    SciTech Connect

    Jardin, S.C.; Janos, A.; Yamada, M.

    1985-11-01

    We attempt to predict the consequences of adding an inductive current transformer (OH Transformer) to the present S-1 Spheromak experiment. Axisymmetric modeling with only classical dissipation shows an increase of toroidal current and a shrinking and hollowing of the current channel, conserving toroidal flux. These unstable profiles will undergo helical reconnection, conserving helicity K = ..integral.. A-vector x B-vector d tau while increasing the toroidal flux and decreasing the poloidal flux so that the plasma relaxes toward the Taylor state. This flux rearrangement is modeled by a new current viscosity term in the mean-field Ohm's law which conserves helicity and dissipates energy.

  16. QCD Results from the CDF Experiment at squareroot s = 1.96 TeV

    SciTech Connect

    Michele Gallinaro

    2003-05-19

    First QCD results obtained from the CDF experiment using Run II data are reported. The Run II physics program at the Tevatron started in the spring of 2001, with protons and anti-protons colliding at an energy of {radical}s = 1.96 TeV. The size of the data sample already compares to that of Run I. Results presented here include the measurement of the inclusive jet cross section, a search for new particles decaying to dijets, and a study of diffractive dijet events.

  17. Exciton mobility edge in CdS 1-xSe x solid solutions

    NASA Astrophysics Data System (ADS)

    Permogorov, S.; Reznitsky, A.; Verbin, S.; Lysenko, V.

    1983-07-01

    Low temperature emission spectra of localized excitons in CdS 1-xSe x solid solutions under the monochromatic excitation with tunable laser have been studied. It has been found that the luminescence of localized excitons has a high degree of linear polarization with respect to the polarization direction of exciting light. This polarization reflects the "hidden" anisotropy of macroscopically isotropic localized exciton system and strongly depends on the frequency of exciting light. Study of this dependence has permitted for the first time a determination of position of the "mobility edge" for exciton migration in disordered semiconductor solid solution.

  18. Redox-Controled Preservation of Mediterranean Sapropel S1 deposits during Formation and Interruption

    NASA Astrophysics Data System (ADS)

    De Lange, Gert J.; Filippidi, Amalia; Goudeau, Marie-Louise; Hennekam, Rick

    2016-04-01

    Organic-rich units (sapropels) occur in Mediterraneran sediments in a repetitive, climate-controled way. Their deposition is thought to be precession-related and to be associated with humid climate conditions. The last humid period from 11 - 5 kyr 14C ago, occurred simultaneous with a sustained circum-Mediterranean wet period and vegetated Sahara. Within that period, the most recent sapropel (S1) formed synchronously between 9.8 and 5.7 14C ky BP at all water depths greater than a few hundred metres. As a consequence of increased fresh water (monsoon) input, surface waters had a reduced salinity and concomitantly the deep (> 1.8 km) eastern Mediterranean Sea was devoid of oxygen during 4,000 years of S1 formation. This has resulted in a differential basin-wide preservation of S1sediments determined by water depth, as a result of different ventilation/climate-related redox conditions above and below 1.8 km. The end of this period is marked by a basin-wide high sedimentary manganese-oxide peak that represents an abrupt re-ventilation of the deep-water at 5.7 kyr. The sustaining oxic conditions thereafter have resulted in a downward progressing oxidation-front that is not only characterized by the degradation of most organic matter over its active pathway, but also by the built-up of manganese oxide. The latter has resulted in a secondary diagenetic Mn-peak below the first, upper, ventilation Mn-peak. Apart from the major re-ventilation event at the end of sapropel S1 formation, also other, short-term ventilation events appear to have occurred during its formation, notably during the 8.2 ka event. This potentially basin-wide event is particularly noticeable at relatively shallow near-coastal sites of high sedimentation rates. It marks a brief episode of not only re-oxygenated deep water thus reduced preservation, but also decreased primary productivity thus nutrient supply. This 8.2 cal ka BP interruption event is thought to be related to enhanced deep water formation

  19. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor

    SciTech Connect

    Maize, Kimberly M.; Kurbanov, Elbek K.; Johnson, Rodney L.; Amin, Elizabeth Ambrose; Finzel, Barry C.

    2016-07-05

    The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1'* which might afford new opportunities to design selective inhibitors that target this subsite.

  20. Phospholipid transfer protein deficiency decreases the content of S1P in HDL via the loss of its transfer capability.

    PubMed

    Yu, Yang; Guo, Shoudong; Feng, Yumei; Feng, Lei; Cui, Yingjie; Song, Guohua; Luo, Tian; Zhang, Ke; Wang, Yiwei; Jiang, Xian-Cheng; Qin, Shucun

    2014-02-01

    Sphingosine-1-phosphate (S1P) is an amphiphilic signaling molecule, which is enriched in functional high density lipoprotein (HDL) and shows arterial protection. The distribution of S1P is changed with increased plasma phospholipid transfer protein (PLTP) activity and impaired HDL function in patients with coronary heart diseases. Therefore, we hypothesized that PLTP might transfer S1P among cells or lipoproteins. We found that plasma S1P contents were decreased by 60.1 % in PLTP knockout mice (PLTP-/-, N = 5) compared with their wild type littermates (WT, N = 5) (151.70 ± 38.59 vs. 379.32 ± 59.90 nmol/l, P<0.01). S1P content in HDL fraction (HDL-S1P) from PLTP-/- was decreased by 64.7 % compared with WT (49.36 ± 1.49 vs. 139.76 ± 2.94 nmol/l, P<0.01). The results of the S1P transfer assay indicated that PLTP could facilitate S1P transport from erythrocytes to HDL at 37 °C in D-Hanks buffer. Plasma content of apolipoprotein M, a specific adaptor of S1P, was not changed in PLTP-/- compared with WT. Therefore, we concluded that PLTP was a key factor to maintain plasma HDL-S1P, and PLTP deficiency could decrease the S1P content in plasma lipoproteins, which involves its capability of transferring S1P from erythrocyte to HDL.

  1. ClpS1 Is a Conserved Substrate Selector for the Chloroplast Clp Protease System in Arabidopsis[C][W

    PubMed Central

    Nishimura, Kenji; Asakura, Yukari; Friso, Giulia; Kim, Jitae; Oh, Soo-hyun; Rutschow, Heidi; Ponnala, Lalit; van Wijk, Klaas J.

    2013-01-01

    Whereas the plastid caseinolytic peptidase (Clp) P protease system is essential for plant development, substrates and substrate selection mechanisms are unknown. Bacterial ClpS is involved in N-degron substrate selection and delivery to the ClpAP protease. Through phylogenetic analysis, we show that all angiosperms contain ClpS1 and some species also contain ClpS1-like protein(s). In silico analysis suggests that ClpS1 is the functional homolog of bacterial ClpS. We show that Arabidopsis thaliana ClpS1 interacts with plastid ClpC1,2 chaperones. The Arabidopsis ClpS1 null mutant (clps1) lacks a visible phenotype, and no genetic interactions with ClpC/D chaperone or ClpPR core mutants were observed. However, clps1, but not clpc1-1, has increased sensitivity to the translational elongation inhibitor chloramphenicol suggesting a link between translational capacity and ClpS1. Moreover, ClpS1 was upregulated in clpc1-1, and quantitative proteomics of clps1, clpc1, and clps1 clpc1 showed specific molecular phenotypes attributed to loss of ClpC1 or ClpS1. In particular, clps1 showed alteration of the tetrapyrrole pathway. Affinity purification identified eight candidate ClpS1 substrates, including plastid DNA repair proteins and Glu tRNA reductase, which is a control point for tetrapyrrole synthesis. ClpS1 interaction with five substrates strictly depended on two conserved ClpS1 residues involved in N-degron recognition. ClpS1 function, substrates, and substrate recognition mechanisms are discussed. PMID:23898032

  2. Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.

    PubMed

    Loh, Kenneth C; Leong, Weng-In; Carlson, Morgan E; Oskouian, Babak; Kumar, Ashok; Fyrst, Henrik; Zhang, Meng; Proia, Richard L; Hoffman, Eric P; Saba, Julie D

    2012-01-01

    Sphingosine-1-phosphate (S1P) activates a widely expressed family of G protein-coupled receptors, serves as a muscle trophic factor and activates muscle stem cells called satellite cells (SCs) through unknown mechanisms. Here we show that muscle injury induces dynamic changes in S1P signaling and metabolism in vivo. These changes include early and profound induction of the gene encoding the S1P biosynthetic enzyme SphK1, followed by induction of the catabolic enzyme sphingosine phosphate lyase (SPL) 3 days later. These changes correlate with a transient increase in circulating S1P levels after muscle injury. We show a specific requirement for SphK1 to support efficient muscle regeneration and SC proliferation and differentiation. Mdx mice, which serve as a model for muscular dystrophy (MD), were found to be S1P-deficient and exhibited muscle SPL upregulation, suggesting that S1P catabolism is enhanced in dystrophic muscle. Pharmacological SPL inhibition increased muscle S1P levels, improved mdx muscle regeneration and enhanced SC proliferation via S1P receptor 2 (S1PR2)-dependent inhibition of Rac1, thereby activating Signal Transducer and Activator of Transcription 3 (STAT3), a central player in inflammatory signaling. STAT3 activation resulted in p21 and p27 downregulation in a S1PR2-dependent fashion in myoblasts. Our findings suggest that S1P promotes SC progression through the cell cycle by repression of cell cycle inhibitors via S1PR2/STAT3-dependent signaling and that SPL inhibition may provide a therapeutic strategy for MD.

  3. The effect of low levels of lead (Pb) in the blood on levels of sphingosine-1-phosphate (S1P) and expression of S1P receptor 1 in the brain of the rat in the perinatal period.

    PubMed

    Łukomska, A; Baranowska-Bosiacka, I; Budkowska, M; Pilutin, A; Tarnowski, M; Dec, K; Dołęgowska, B; Metryka, E; Chlubek, D; Gutowska, I

    2017-01-01

    Sphingolipids are the main components of the lipid membrane. They also perform structural functions and participate in many signal transmission processes. One of the bioactive sphingolipids is sphingosine-1-phosphate (S1P), a ligand for five G protein-coupled receptors (S1PRs1-5), which can also act as an intracellular second messenger. S1P is responsible for the stimulation of progenitor cells in the brain, but it can also induce apoptosis of mature neurons. This study is aimed at assessing the effect of pre- and neonatal exposure to permissible Pb concentrations on S1P levels and S1PR1 (EDG1) expression in the prefrontal cortex, cerebellum, and hippocampus of rats. The concentrations of S1P were determined by RP-HPLC, S1PR1 expression was determined by RT PCR and Western Blot, and receptor immunolocalization was determined by immunohistochemistry method. Our results showed that even low blood Pb concentrations, i.e. within the acceptable limit of 10 μg/dL caused changes in the concentration of S1P in the cerebellum, prefrontal cortex, and hippocampus. Our data also showed a significant decrease in the level of S1PR1 in all studied part of brain, without significant changes in S1PR1 gene expression. Pre- and neonatal exposure to Pb also resulted in a decrease in the expression of S1PR1 in glial cells in all regions of the Cornu Ammonis (CA1-CA4) and Dentate Gyrus in the hippocampus, as well as in all layers of the cerebellum and prefrontal cortex, compared to the unexposed control group.

  4. Sphingosine-1-phosphate (S1P): A Potential Biomarker and Therapeutic Target for Endothelial Dysfunction and Sepsis?

    PubMed

    Winkler, Martin S; Nierhaus, Axel; Poppe, Annika; Greiwe, Gillis; Gräler, Markus; Daum, Guenter

    2016-12-02

    Sepsis is an acute life-threatening multiple organ failure caused by a dysregulated host response to infection. Endothelial dysfunction, particularly barrier disruption leading to increased vascular permeability, edema and insufficient tissue oxygenation is critical to sepsis pathogenesis. Sphingosine-1-phosphate (S1P) is a signaling lipid that regulates important pathophysiological processes including vascular endothelial cell permeability, inflammation and coagulation. It is present at high concentrations in blood and lymph and at very low concentrations in tissues due to the activity of the S1P-degrading enzyme S1P-lyase in tissue cells. Recently, four preclinical observational studies determined S1P levels in serum or plasma of sepsis patients, and all found reduced S1P levels associated with the disease. Based on these findings, this review summarizes S1P-regulated processes pertaining to endothelial functions, discusses the possible use of S1P as a marker and possibilities how to manipulate S1P levels and S1P receptor activation to restore endothelial integrity, dampen the inflammatory host response, and improve organ function in sepsis.

  5. Dynamics of vibrational relaxation in the S 1 state of carotenoids having 11 conjugated CC bonds

    NASA Astrophysics Data System (ADS)

    Hörvin Billsten, Helena; Zigmantas, Donatas; Sundström, Villy; Polívka, Tomáš

    2002-04-01

    Transient absorption spectra and kinetics in the 470-650 nm region were recorded for lycopene, β-carotene and zeaxanthin, all carotenoids with 11 conjugated double bonds, in two solvents with different polarity. Analysis of the red wing of the carotenoid S 1-S n transition revealed presence of a pronounced shoulder at early delay times. The kinetics recorded at this low-energy shoulder of the S 1-S n transition yields an additional decay component of 500-800 fs in addition to the main S 1 decay. This dynamics is ascribed to a vibrational relaxation in the S 1 state of the carotenoids.

  6. T-bet–dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow

    PubMed Central

    Jenne, Craig N.; Enders, Anselm; Rivera, Richard; Watson, Susan R.; Bankovich, Alexander J.; Pereira, Joao P.; Xu, Ying; Roots, Carla M.; Beilke, Joshua N.; Banerjee, Arnob; Reiner, Steven L.; Miller, Sara A.; Weinmann, Amy S.; Goodnow, Chris C.

    2009-01-01

    During a screen for ethylnitrosourea-induced mutations in mice affecting blood natural killer (NK) cells, we identified a strain, designated Duane, in which NK cells were reduced in blood and spleen but increased in lymph nodes (LNs) and bone marrow (BM). The accumulation of NK cells in LNs reflected a decreased ability to exit into lymph. This strain carries a point mutation within Tbx21 (T-bet), which generates a defective protein. Duane NK cells have a 30-fold deficiency in sphingosine-1-phosphate receptor 5 (S1P5) transcript levels, and S1P5-deficient mice exhibit an egress defect similar to Duane. Chromatin immunoprecipitation confirms binding of T-bet to the S1pr5 locus. S1P-deficient mice exhibit a more severe NK cell egress block, and the FTY720-sensitive S1P1 also plays a role in NK cell egress from LNs. S1P5 is not inhibited by CD69, a property that may facilitate trafficking of activated NK cells to effector sites. Finally, the accumulation of NK cells within BM of S1P-deficient mice was associated with reduced numbers in BM sinusoids, suggesting a role for S1P in BM egress. In summary, these findings identify S1P5 as a T-bet–induced gene that is required for NK cell egress from LNs and BM. PMID:19808259

  7. Protein crystallography beamline BL2S1 at the Aichi synchrotron

    SciTech Connect

    Watanabe, Nobuhisa; Nagae, Takayuki; Yamada, Yusuke; Tomita, Ayana; Matsugaki, Naohiro; Tabuchi, Masao

    2017-01-01

    The protein crystallography beamline BL2S1, constructed at one of the 5 T superconducting bending-magnet ports of the Aichi synchrotron, is available to users associated with academic and industrial organizations. The beamline is mainly intended for use in X-ray diffraction measurements of single-crystals of macromolecules such as proteins and nucleic acids. Diffraction measurements for crystals of other materials are also possible, such as inorganic and organic compounds. BL2S1 covers the energy range 7–17 keV (1.8–0.7 Å) with an asymmetric-cut curved single-crystal monochromator [Ge(111) or Ge(220)], and a platinum-coated Si mirror is used for vertical focusing and as a higher-order cutoff filter. The beamline is equipped with a single-axis goniometer, a CCD detector, and an open-flow cryogenic sample cooler. Lastly, high-pressure protein crystallography with a diamond anvil cell can also be performed using this beamline.

  8. S1 gene-based phylogeny of infectious bronchitis virus: An attempt to harmonize virus classification.

    PubMed

    Valastro, Viviana; Holmes, Edward C; Britton, Paul; Fusaro, Alice; Jackwood, Mark W; Cattoli, Giovanni; Monne, Isabella

    2016-04-01

    Infectious bronchitis virus (IBV) is the causative agent of a highly contagious disease that results in severe economic losses to the global poultry industry. The virus exists in a wide variety of genetically distinct viral types, and both phylogenetic analysis and measures of pairwise similarity among nucleotide or amino acid sequences have been used to classify IBV strains. However, there is currently no consensus on the method by which IBV sequences should be compared, and heterogeneous genetic group designations that are inconsistent with phylogenetic history have been adopted, leading to the confusing coexistence of multiple genotyping schemes. Herein, we propose a simple and repeatable phylogeny-based classification system combined with an unambiguous and rationale lineage nomenclature for the assignment of IBV strains. By using complete nucleotide sequences of the S1 gene we determined the phylogenetic structure of IBV, which in turn allowed us to define 6 genotypes that together comprise 32 distinct viral lineages and a number of inter-lineage recombinants. Because of extensive rate variation among IBVs, we suggest that the inference of phylogenetic relationships alone represents a more appropriate criterion for sequence classification than pairwise sequence comparisons. The adoption of an internationally accepted viral nomenclature is crucial for future studies of IBV epidemiology and evolution, and the classification scheme presented here can be updated and revised novel S1 sequences should become available.

  9. Quantum vs Classical Magnetization Plateaus of S=1/2 Frustrated Heisenberg Chains

    NASA Astrophysics Data System (ADS)

    Hida, Kazuo; Affleck, Ian

    2005-06-01

    The competition between quantum and classical magnetization plateaus of S=1/2 frustrated Heisenberg chains with modified exchange couplings is investigated. The conventional S=1/2 frustrated Heisenberg chain is known to exhibit a 3-fold degenerate \\uparrow\\downarrow\\uparrow-type classical plateau at 1/3 of the saturation magnetization accompanied by the spontaneous Z3 translational symmetry breakdown. The stability of this plateau phase against period 3 exchange modulation which favors the \\bullet\\hskip -1pt-\\hskip -1pt\\bullet \\uparrow-type quantum plateau state (\\bullet\\hskip -1pt-\\hskip -1pt\\bullet = singlet dimer) is studied by bosonization, renormalization group and numerical diagonalization methods. The ground state phase diagram and the spin configuration in each phase are numerically determined. The translationally invariant Valence Bond Solid-type model with 4-spin and third neighbor interactions, which has the exact \\bullet\\hskip -1pt-\\hskip -1pt\\bullet \\uparrow-type quantum plateau state, is also presented. The phase transition to the classical \\uparrow\\downarrow\\uparrow-type ground state is also observed by varying the strength of 4-spin and third neighbor interactions. The relation between these two types of models with quantum plateau states is discussed.

  10. Synthesis, characterization and chemical stability of silicon dichalcogenides, Si(SexS1-x)2

    NASA Astrophysics Data System (ADS)

    Chen, Chen; Zhang, Xiaotian; Krishna, Lakshmi; Kendrick, Chito; Shang, Shun-Li; Toberer, Eric; Liu, Zi-Kui; Tamboli, Adele; Redwing, Joan M.

    2016-10-01

    Silicon dichalcogenides have an intriguing crystal structure consisting of long tetrahedral chains held together by van der Waals forces but the electronic and optical properties have been less explored. In the present work, bulk SiSe2, SiS2, and Si(SexS1-x)2 were synthesized by the congruent melt growth method and characterized by Raman spectroscopy, X-ray Diffraction and UV/visible/IR transmission measurements supported by first-principles calculations. First-principles calculations reveal a nearly linear decrease of band gap energy in Si(SexS1-x)2 with increasing Se content, i.e., from SiS2 to SiSe2 which corresponds with a blue-shift in the transmission spectra from bulk SiSe2 to Si(Se0.6S0.4)2, and to SiS2. Air stability tests demonstrate the formation of toxic H2Se/H2S gas from sample oxidation at room temperature upon exposure to ambient air, and great care should be paid when handling these materials.

  11. Benthic foraminiferal stable isotope record of organic carbon fluxes during deposition of Mediterranean sapropel S1

    NASA Astrophysics Data System (ADS)

    Theodor, Marc; Schmiedl, Gerhard; Mackensen, Andreas

    2016-04-01

    We integrated Late Glacial to Holocene stable isotope records for different epi- and endobenthic foraminifera from the Mediterranean Sea in order to document the sequence of environmental changes across formation of the most recent sapropel S1. The stable carbon isotope record of epibenthic taxa corroborates results from model experiments indicating a Late Glacial onset of deep-water stagnation with short-term reventilation events during cold intervals of the Heinrich event 1, the Younger Dryas, and the 8.2 event. The stable carbon isotope difference between epi- and shallow endobenthic foraminifera exhibits marked temporal fluctuations linked to microhabitat shifts and changes in organic matter fluxes. We generated a transfer function for organic carbon fluxes based on a correlation between the stable carbon isotope signature of modern benthic foraminifera and observed organic carbon flux rates from different Mediterranean basins. Application of this transfer function to the down-core data reveals generally elevated organic matter fluxes during the Last Glacial Maximum and the Younger Dryas, while values drop significantly during the Bølling-Allerød interstadial and with onset of the Holocene. Our results support a scenario where average organic matter fluxes in the eastern Mediterranean Sea were not significantly enhanced during formation of sapropel S1. Instead, our data corroborate earlier results from benthic foraminiferal faunal successions and model experiments suggesting that sufficient amounts of organic matter are buried under oligotrophic conditions in an intermittently hypoxic water column.

  12. Isomerization, Perturbations, Calculations and the S_{1} State of C_{2}H_{2}

    NASA Astrophysics Data System (ADS)

    Baraban, J. H.; Changala, P. B.; Berk, J. R. P.; Field, R. W.; Stanton, J. F.; Merer, A. J.

    2013-06-01

    Preliminary analysis of the energy region of the cis-trans isomerization transition state on the S_{1} surface of C_{2}H_{2} has revealed novel patterns and surprising perturbations, including unusually large (and high-order) anharmonicities, as well as K-staggerings of several vibrational levels. These effects complicate the analysis considerably, and require new models and calculations to account for and predict features of the observed spectra. The ˜{A}-˜{X} spectrum of acetylene has been studied both experimentally and theoretically for almost a century, and this cycle of unexpected phenomena eliciting innovative responses is found throughout its history. Especially in the last ten years, progress in understanding the S_{1} state rovibrational level structure and cis-trans isomerization has been accelerated by combining the information available from both ab initio computation and spectroscopic observations. The resulting dialogue has then frequently suggested fruitful avenues for further experiments and calculations. Current challenges and recent results in understanding the cis-trans isomerization transition state region will be discussed in this context.

  13. Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing.

    PubMed

    Manes, Nathan P; Angermann, Bastian R; Koppenol-Raab, Marijke; An, Eunkyung; Sjoelund, Virginie H; Sun, Jing; Ishii, Masaru; Germain, Ronald N; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra

    2015-10-01

    Osteoclasts are monocyte-derived multinuclear cells that directly attach to and resorb bone. Sphingosine-1-phosphate (S1P)(1) regulates bone resorption by functioning as both a chemoattractant and chemorepellent of osteoclast precursors through two G-protein coupled receptors that antagonize each other in an S1P-concentration-dependent manner. To quantitatively explore the behavior of this chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule-based pathway modeling using the Simmune toolset. RAW264.7 cells (a mouse monocyte/macrophage cell line) were used as model osteoclast precursors, RNA-seq was used to identify expressed target proteins, and selected reaction monitoring (SRM) mass spectrometry using internal peptide standards was used to perform absolute abundance measurements of pathway proteins. The resulting transcript and protein abundance values were strongly correlated. Measured protein abundance values, used as simulation input parameters, led to in silico pathway behavior matching in vitro measurements. Moreover, once model parameters were established, even simulated responses toward stimuli that were not used for parameterization were consistent with experimental findings. These findings demonstrate the feasibility and value of combining targeted mass spectrometry with pathway modeling for advancing biological insight.

  14. Protein crystallography beamline BL2S1 at the Aichi synchrotron

    PubMed Central

    Watanabe, Nobuhisa; Nagae, Takayuki; Yamada, Yusuke; Tomita, Ayana; Matsugaki, Naohiro; Tabuchi, Masao

    2017-01-01

    The protein crystallography beamline BL2S1, constructed at one of the 5 T superconducting bending-magnet ports of the Aichi synchrotron, is available to users associated with academic and industrial organizations. The beamline is mainly intended for use in X-ray diffraction measurements of single-crystals of macromolecules such as proteins and nucleic acids. Diffraction measurements for crystals of other materials are also possible, such as inorganic and organic compounds. BL2S1 covers the energy range 7–17 keV (1.8–0.7 Å) with an asymmetric-cut curved single-crystal monochromator [Ge(111) or Ge(220)], and a platinum-coated Si mirror is used for vertical focusing and as a higher-order cutoff filter. The beamline is equipped with a single-axis goniometer, a CCD detector, and an open-flow cryogenic sample cooler. High-pressure protein crystallography with a diamond anvil cell can also be performed using this beamline. PMID:28009576

  15. [Combination Chemotherapy Using Oxaliplatin plus S-1 for Well-Advanced Gastric Cancer].

    PubMed

    Saito, Hiroyuki; Suematsu, Yuki; Yamagishi, Shunsuke; Takahashi, Miyuki; Nakayama, Mao; Fukabori, Michiko; Morita, Akihiko; Wakabayashi, Kazuhiko; Itoh, Yutaka

    2016-11-01

    We studied the clinical efficacy of pre-operative combination chemotherapy using S-1 plus oxaliplatin for advanced gastric cancer. Four patients hadclinical Stage IV disease, 1 patient had clinical Stage III C disease, 2 patients had clinical Stage III B disease, and 1 patient had clinical Stage III A disease. The patients received 2-8 courses of oxaliplatin(130mg/m2)on day 1, andS -1 on days 1-14 every 3 weeks. The response rate was 56%(5 PR, 1 PD, and2 SD), andthe disease control rate was 88%. Toxicities were Grade 2 anemia, Grade 1 peripheral neuropathy, Grade 1 fatigue, and anorexia. Five of the 8 patients underwent R0 surgery after SOX chemotherapy, and no severe complications occurred. Histological responses were Grade 3 for 2 cases, Grade 2 for 2 cases, andGrad e 1a for 1 case. The SOX regimen showeda high objective tumor response, andis one of the promising regimens in the neoadjuvant setting for well-advanced gastric cancer.

  16. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    SciTech Connect

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J. )

    1989-11-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from (3H-nicotinamide)NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from (32P-adenylate)NAD (0.2 mol/mol of protein). Label from (3H-nicotinamide)NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with (3H-nicotinamide)NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

  17. The chiral S = -1 meson-baryon interaction with new constraints on the NLO contributions

    NASA Astrophysics Data System (ADS)

    Ramos, A.; Feijoo, A.; Magas, V. K.

    2016-10-01

    We present a study of the S = - 1 meson-baryon interaction, employing a chiral SU(3) Lagrangian up to next-to-leading order (NLO) and implementing unitarization in coupled channels. The parameters of the model have been fitted to a large set of experimental scattering data in different two-body channels, to threshold branching ratios, and to the precise SIDDHARTA value of the energy shift and width of kaonic hidrogen. In contrast to other groups, we have taken into consideration the K- p →K+Ξ- ,K0Ξ0 reaction data, since we found in a previous work to be especially sensitive to the NLO parameters of the chiral Lagrangian. In the present work we also include the Born terms, which usually have very little effect, and find them to be non-negligible in the K- p → KΞ channels, correspondingly causing significant modifications to the NLO parameters. We furthermore show that the importance of the Born terms becomes more visible in the isospin projected amplitudes of the K- p → KΞ reactions. The measurement of processes that filter single isospin components, like the KL0 p →K+Ξ0 reaction that could be measured at the proposed secondary KL0 beam at Jlab, would put valuable constraints on the chiral models describing the meson-baryon interaction in the S = - 1 sector.

  18. Optical Parameters of Spray-Deposited CdS1- y Te y Thin Films

    NASA Astrophysics Data System (ADS)

    Ikhmayies, Shadia J.

    2017-02-01

    CdS x Te1- x and CdS1- y Te y solid solutions are usually formed in the interfacial region in CdS/CdTe solar cells during the deposition of the CdTe layer and/or the processing steps of the device. In this work, indium-doped CdS1- y Te y thin films were prepared by first producing CdS:In thin films by the spray pyrolysis technique on glass substrates, then annealing the films in nitrogen atmosphere in the presence of elemental tellurium. The films were characterized by scanning electron microscopy, energy dispersive x-ray spectroscopy, and transmittance measurements. The transmittance was used to deduce the reflectance from which the optical parameters were computed. The extinction coefficient, refractive index, the real and imaginary parts of the dielectric constant, optical conductivity, and energy loss were computed, and their dependence on the composition was investigated. In addition, the dispersion of the refractive index was analyzed by the single oscillator model, and dispersion parameters were investigated.

  19. Complete genome sequence of Rhodospirillum rubrum type strain (S1T)

    SciTech Connect

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

    2011-01-01

    Rhodospirillum rubrum (Esmarch 1887) Molisch 1907 is the type species of the genus Rho- dospirillum, which is the type genus of the family Rhodospirillaceae in the class Alphaproteo- bacteria. The species is of special interest because it is an anoxygenic phototroph that pro- duces 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 S1T 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 partic- ular for physiological and genetic studies. Next to R. centenum strain SW, the genome se- quence of strain S1T 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 chro- mosome 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.

  20. Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer.

    PubMed

    Suzuki, Shuji; Shimazaki, Jiro; Morishita, Keiichi; Koike, Nobusada; Harada, Nobuhiko; Hayashi, Tsuneo; Suzuki, Mamoru

    2016-10-01

    The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m(2)) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1-14. The drug regimen was repeated every 4 weeks. SOX+bev treatment was associated with a response rate of 45.2%, a disease control rate of 71%, and a median progression-free survival (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients who received first-line chemotherapy benefited from treatment in terms of prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase level and skin rash. In conclusion, SOX+bev therapy was found to be feasible and safe for patients with advanced and recurrent colorectal cancer.

  1. Electronic and vibrational structures in the S0 and S1 states of coronene

    NASA Astrophysics Data System (ADS)

    Kunishige, Sachi; Kanaoka, Ayumi; Katori, Toshiharu; Kawabata, Megumi; Baba, Masaaki; Yamanaka, Takaya; Higashibayashi, Shuhei; Sakurai, Hidehiro

    2017-01-01

    We observed the fluorescence excitation spectra and dispersed fluorescence spectra of jet-cooled coronene-h12 and coronene-d12. We analyzed the vibronic structures, assuming a planar and sixfold symmetric molecular structure (D6 h). The S1 state was identified to be 2u1B. The S12u1B ←S01g1A transition is symmetry forbidden, so the 000 band is missing in the fluorescence excitation spectrum. We found a number of vibronic bands that were assigned to the e2 g fundamental bands and their combination bands with totally symmetric a1 g vibrations. This spectral feature is similar to that of benzene although several strong e2 g bands are seen in coronene. The band shape (rotational envelope) was significantly different in each e2 g mode. It was shown that degenerate rotational levels were shifted and split by the Coriolis interaction. We calculated the Coriolis parameter using the molecular structure in the S1 state and the normal coordinate of each e2 g vibrational mode, which were obtained by theoretical calculations. The calculated band shapes well reproduced the observed ones, suggesting that the isolated coronene molecule has D6 h symmetry.

  2. Experimental signatures of spin liquid physics on the S=1/2 kagom'e lattice

    NASA Astrophysics Data System (ADS)

    Lee, Young

    2012-02-01

    I will describe our recent experimental progress on the quest to study novel ground states in frustrated magnets. New states of matter may be produced if quantum effects and frustration conspire to prevent the ground state from achieving classical order. Materials based on the kagom'e lattice appear to be ideal hosts for the possibility of a quantum spin liquid ground state in two-dimensions. I will discuss our work which includes single crystal growth, bulk characterization, and neutron scattering measurements of the S=1/2 kagom'e lattice material ZnCu3(OH)6Cl2 (also known as herbertsmithite). Recent susceptibility measurements on single crystals yield valuable information on the additional terms in the spin Hamiltonian beyond nearest neighbor Heisenberg exchange, and anomalous x-ray diffraction yields detailed information on the presence of a small amount of atomic impurities. Most interestingly, inelastic neutron scattering measurements of the spin correlations in a single crystal sample reveal a continuum of spinon excitations in this two-dimensional insulating magnet. We will discuss our results in relation to recent theories for spin liquid physics on the S=1/2 kagom'e lattice.

  3. Synthesis, characterization and thermoluminescence studies of (ZnS)1-x (MnTe)x nanophosphors.

    PubMed

    Pateria, Deepti; Baghel, R N; Bisen, D P; Jha, Piyush; Chandra, V K; Chandra, B P

    2017-05-01

    The present paper reports the thermoluminescence (TL) of (ZnS)1-x (MnTe)x nanophosphors that were prepared by a wet chemical synthesis method. The structure investigated by X-ray diffraction patterns confirms the formation of a sphalerite phase whose space group was found to be F 4¯3m. From XRD, TEM and SEM analyses the average sizes of the particles were found to be 12 nm, 11 nm and 15 nm, respectively. Initially the TL intensity increased with increasing values of x because the number of luminescence centres increased; however, for higher values of x the TL intensity decreased because of the concentration quenching. Thus the TL, mechanoluminescence and photoluminescence intensities are optimum for a particular value of x, that is for x = 0.05. Thermoluminescence of the (ZnS)1-x (MnTe)x nanophosphor has not been reported previously. There were two peaks seen in the thermoluminescence glow curves in which the first peak lay at 105-100 °C and the second peak lay at 183.5-178.5 °C. The activation energies for the first and second peaks were found to be 0.45 eV and 0.75 eV, respectively.

  4. S1 nuclease definition of highly repeated DNA sequences in the Guinea pig, Cavia porcellus.

    PubMed Central

    Hubbell, H R; Robberson, D L; Hsu, T C

    1979-01-01

    Native DNA of the Guinea pig, Cavia porcellus, purified from liver or tissue culture cells, was heat denatured and reassociated to a Cot value of 0.01 (equivalent Cot value of 7.2 x 10(-2)). The reassociated DNA was isolated by digestion with the single-strand DNA specific enzyme S1 nuclease. Spectrophotometric and radioactivity assays demonstrated that 24% of the total DNA was resistant to S1 nuclease treatment. Zero-time reassociation indicated that approximately 3% of the DNA was inverted repeat sequences. Thus, highly repeated sequences comprised 21% of the total genome. CsCl buoyant density ultracentrifugation indicated that this fraction was composed of both main band and satellite sequences. Although actinomycin D - CsCl density gradients failed to give significant separation of the repetitive sequences, distamycin A - CsCl gradients were able to fractionate the DNA into several overlapping bands. The heterogeneity of the repetitive DNA was further demonstrated by the first derivative plots calculated from their thermal denaturation profiles. This analysis revealed six major thermalytes which indicate that there may be at least six discrete components in the repetitive DNA. Images PMID:523322

  5. Yielding of tantalum at strain rates up to 109 s-1

    NASA Astrophysics Data System (ADS)

    Crowhurst, Jonathan C.; Armstrong, Michael R.; Gates, Sean D.; Zaug, Joseph M.; Radousky, Harry B.; Teslich, Nick E.

    2016-08-01

    We have used a 45 μJ laser pulse to accelerate the free surface of fine-grained tantalum films up to peak velocities of ˜1.2 km s-1. The films had thicknesses of ˜1-2 μm and in-plane grain widths of ˜75-150 nm. Using ultrafast interferometry, we have measured the time history of the velocity of the surface at different spatial positions across the accelerated region. The initial part of the histories (assumed to correspond to the "elastic precursor" observed previously) exhibited measured strain rates of ˜0.6 to ˜3.2 × 109 s-1 and stresses of ˜4 to ˜22 GPa. Importantly, we find that elastic amplitudes exhibit little variation with strain rate for a constant peak surface velocity, even though, via covariation of the strain rate with peak surface velocity, they vary with strain rate. Furthermore, by comparison with data obtained at lower strain rates, we find that amplitudes are much better predicted by peak velocities rather than by either strain rate or sample thickness.

  6. Epidermal surface antigen (MS17S1) is highly conserved between mouse and human

    SciTech Connect

    Cho, Y.J.; Chema, D.; Cho, M.

    1995-05-20

    A mouse monoclonal antibody ECS-1 raised to human keratinocytes detects a 35-kDa epidermal surface antigen (ESA) and causes keratinocyte dissociation in vitro. ECS-1 stains skin of 16-day mouse embryo and 8- to 9-week human fetus. Mouse Esa cDNA encodes a 379-amino-acid protein that is 99.2% identical to the human, differing at only 3 amino acids. The gene (M17S1) was mapped to mouse chromosome 11, highlighting the conserved linkage synteny existing between human chromosome 17 and mouse chromosome 11. Although the nude locus has been mapped to the same region of chromosome 11, no abnormalities in protein, mRNA, or cDNA or genomic sequences were detected in nude mice. However, both nude and control mice were found to have a second Esa mRNA transcript that conserves amino acid sequence and molecular weight. The mouse and human 5{prime} and 3{prime} untranslated sequences are conserved. Similar RNA folding patterns of the 5{prime} untranslated region are predicted despite a 91-bp insertion in the mouse. These data suggest that both the function and the regulation of ESA protein are of importance and that Esa (M17S1) is not the nude locus gene. 42 refs., 7 figs., 3 tabs.

  7. Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing*

    PubMed Central

    Manes, Nathan P.; Angermann, Bastian R.; Koppenol-Raab, Marijke; An, Eunkyung; Sjoelund, Virginie H.; Sun, Jing; Ishii, Masaru; Germain, Ronald N.; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra

    2015-01-01

    Osteoclasts are monocyte-derived multinuclear cells that directly attach to and resorb bone. Sphingosine-1-phosphate (S1P)1 regulates bone resorption by functioning as both a chemoattractant and chemorepellent of osteoclast precursors through two G-protein coupled receptors that antagonize each other in an S1P-concentration-dependent manner. To quantitatively explore the behavior of this chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule-based pathway modeling using the Simmune toolset. RAW264.7 cells (a mouse monocyte/macrophage cell line) were used as model osteoclast precursors, RNA-seq was used to identify expressed target proteins, and selected reaction monitoring (SRM) mass spectrometry using internal peptide standards was used to perform absolute abundance measurements of pathway proteins. The resulting transcript and protein abundance values were strongly correlated. Measured protein abundance values, used as simulation input parameters, led to in silico pathway behavior matching in vitro measurements. Moreover, once model parameters were established, even simulated responses toward stimuli that were not used for parameterization were consistent with experimental findings. These findings demonstrate the feasibility and value of combining targeted mass spectrometry with pathway modeling for advancing biological insight. PMID:26199343

  8. Low-energy spin dynamics of the s = 1/2 kagome system herbertsmithite.

    PubMed

    Nilsen, G J; de Vries, M A; Stewart, J R; Harrison, A; Rønnow, H M

    2013-03-13

    The low-energy (ε = ħω < 1 meV), low-temperature (T = 0.05 K) spin dynamics of the s = 1/2 kagome candidate herbertsmithite are probed in the presence of magnetic fields up to 2.5 T. The zero-field spectra reveal a very weak continuum of scattering at T = 10 K and a broad inelastic peak centred at ε(max) = 0.2 meV at lower temperatures, T < 1 K. The broad peak is found to be strongly damped, with a liquid-like structure factor implying correlations at length scales up to r = 6 Å. The field dependence of the peak appears to follow the Zeeman splitting of s = 1/2 excitations, consistent with the weakly split 'doublets' observed in low-temperature specific heat. A possible explanation of these observations is a short-range correlated state involving defect spins between the kagome planes and moments in the kagome layers.

  9. Dynamics of S 1 acetone studied with single rotorvibronic level resolution

    NASA Astrophysics Data System (ADS)

    Bitto, H.

    1994-08-01

    The spectroscopy and dynamics of selected vibronic bands of the S 1(nπ *) ← S 0 transition of acetone and acetone- d6 were studied with single rotational-torsional-vibronic (rotorvibronic) level resolution in a jet up to an S 1 excess energy of 1300 cm -1. Using clean coherent excitation with Fourier transform-limited nanosecond laser pulses quantum beats were observed in the time-resolved fluorescence and were attributed to coherently excited siglet-triplet eigenstates as identified by their magnetic properties. In the 8 123 0- and the 8 1 23 0+I(2,1) state of acetone, and the 7 1I(1,0) state of aceton- d6, lifetimes increase with the rotational quantum number of the excited state N due to a breakdown of K selection rules for the spin-orbit interaction in this very asymmetric rotor. In the 8 123 0- state, the rotorvibronic levels of the methyl torsion tunnelling component with G symmetry exhibit the longest lifetimes among the tunnelling components. Vibrational coupling of G torsional levels in the triplet manifold favoured by symmetry is proposed to selectively increase the density of coupling triplet states and, hence, the lifetime of the eigenstates.

  10. Transcatheter arterial chemoembolisation (TACE) plus S-1 for the treatment of BCLC stage B hepatocellular carcinoma refractory to TACE

    PubMed Central

    Huang, Wu-Kui; Yang, Shu-Fa; You, Li-na; Liu, Mo; Liu, Deng-Yao; Gu, Peng

    2017-01-01

    Aim of the study To assess the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus S-1 for the treatment of Barcelona Clinic Liver Cancer (BCLC) Stage B HCC refractory to TACE. Material and methods 26 patients meeting the eligibility criteria were enrolled. TACE was given on day 1, and S-1 on days 2–15. Tumor assessment was performed one month later according to mRECIST. The primary endpoints were TTP and OS. Results Twenty-six patients received 176 TACE interventions in all. Fifteen patients of TACE plus S-1 received a total of 55 cycles of treatment of S-1, with a median of 4 cycles (range, 2–6). The total dose of S-1 was 6165 mg per day, while average was 120 mg (range, 100–125 mg) for 15 patients of TACE plus S-1. Median TTP and OS of TACE plus S-1 were 6 months (95% CI: 4.7–7.3) and 18 months (95% CI: 15.3–24.7), respectively, while TACE monotherapy was 4 months (95% CI: 2.4–5.6) and 13 months (95% CI: 9.8–16.2), respectively, and significant differences were detected. Though there were higher DCRs in patients of TACE plus S-1, no significant differences were detected. A total of 612 adverse events occurred during the course of the treatment, 367 in TACE plus S-1 and 245 in TACE mono-therapy. There were significant differences to anorexia and nausea, but they were tolerable. Conclusions TACE plus S-1 in the present analysis was tolerable and associated with an interesting TTP and OS. TACE plus S-1 may be used as a new treatment method to BCLC Stage B HCC refractory to TACE. PMID:28239285

  11. Far-UV observations of comet C/2012 S1 (ISON) with FORTIS

    NASA Astrophysics Data System (ADS)

    McCandliss, Stephan R.; Feldman, Paul D.; Weaver, Harold A.; Fleming, Brian; Redwine, Keith; Li, Mary J.; Kutyrev, Alexander; Moseley, Samuel H.

    2015-01-01

    Far-UV imagery and objective grating spectroscopy of comet C/2012 S1 (ISON) were acquired from NASA sounding rocket 36.296 UG, launched on 20 November 2013 at 04:40 MST (20.48 Nov 2013 UT), 8.32 days pre-perihelion, from the White Sands Missile Range, NM. The comet was 0.1° below ground horizon, 0.44 AU from the Sun, 0.86 AU from the Earth, and at a solar elongation of 26.3°. The payload reached an apogee of 279 km and the total time pointed at the comet was 353 s. At the time of launch ISON was undergoing a factor of 5 increase in water production rate, going from 3.5e29 to 19.6e29 molecules s-1between 19.6 and 21.6 Nov (Combi et al. 2014), marking what is thought to be a final fragmentation event (Sekanina & Kracht 2014). Our instrument, a wide-field multi-object spectro-telescope called FORTIS (Far-UV Off Rowland-circle Telescope for Imaging and Spectroscopy), observed Lyα emissions in an objective grating mode through an open microshutter array, developed at the Goddard Space Flight Center, over a (1/2°)2 field-of-view. After accounting for slit losses and deadtime corrections we find a preliminary lower limit to the Lyα surface brightness of ~ 400 kilorayleighs, yielding a hydrogen production rate of QH ~ 5e29 atoms s-1, in reasonable agreement with the Combi result. We also acquired a broadband image of the comet in the 1280 to 1900 Å bandpass. This image shows a drop in count rate proportional to altitude caused by increased absorption of cometary emissions by terrestrial O2 located in the lower thermosphere. O2 absorption acts as a selective time dependent filter that attenuates cometary emissions from different atomic and molecular species at different rates during descent. Preliminary analysis suggests that the dominant species in a (1e5 km)2 nuclear region is neutral carbon. The radial profile in comparison to a Haser model suggests that the C parent molecule had a lifetime (at 1 AU) ~ 105 s; much shorter than the expected lifetime of CO. We

  12. The excitonic photoluminescence mechanism and lasing action in band-gap-tunable CdS1-xSex nanostructures

    NASA Astrophysics Data System (ADS)

    Dai, Jun; Zhou, Pengxia; Lu, Junfeng; Zheng, Hongge; Guo, Jiyuan; Wang, Fang; Gu, Ning; Xu, Chunxiang

    2015-12-01

    Bandgap tunable semiconductor materials have wide application in integrated-optoelectronic and communication devices. The CdS1-xSex ternary semiconductor materials covering green-red bands have been reported previously, but their basic band-gap and optical properties crucial to the performance of the CdS1-xSex-based optoelectronic devices have not been deeply understood. In this paper, we theoretically simulated and discussed the feasibility of bandgap-tunable CdS1-xSex nanomaterials for designing wavelength tunable microlasers. Then we fabricated the CdS1-xSex nanobelts with their band gap ranging from 2.4 to 1.74 eV by adjusting the composition ratio x in the vapor-phase-transport growth process. The temperature-dependent photoluminescence and exciton-related optical constants of the CdS1-xSex nanobelts were carefully demonstrated. Finally, the wavelength-tunable Fabry-Perot lasing in CdS1-xSex nanobelts was obtained, and the Fabry-Perot lasing mechanism was numerically simulated by the FDTD method. The systematic results on the mechanism of the tunable band gap, exciton properties and lasing of the CdS1-xSex nanostructure help us deeply understand the intrinsic optical properties of this material, and will build a strong foundation for future application of green-red wavelength-tunable CdS1-xSex microlasers.

  13. Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P).

    PubMed

    Zhang, Lin; Urtz, Nicole; Gaertner, Florian; Legate, Kyle R; Petzold, Tobias; Lorenz, Michael; Mazharian, Alexandra; Watson, Steve P; Massberg, Steffen

    2013-08-01

    Human megakaryocytes (MKs) release trillions of platelets each day into the circulation to maintain normal homeostatic platelet levels. We have previously shown that extracellular sphingosine 1-phosphate (S1P) plays a key role in thrombopoiesis via its receptor S1pr1. In addition to its role as an extracellular mediator, S1P can also function as a second messenger in the intracellular compartment. Although signaling via intracellular S1P is involved in various cellular processes, a role in thrombopoiesis has not been examined. Sphingosine kinases are the key enzymes that produce intracellular S1P. Here we report that sphingosine kinase 2 (Sphk2) is the major messenger RNA species present in MKs. Sphk2 predominantly localizes to the nucleus and is the major source of intracellular S1P in MKs. Loss of Sphk2 significantly reduced intracellular S1P in MKs and downregulated the expression and activity of Src family kinases (SFKs). Loss of Sphk2 and inhibition of SFK activity resulted in defective intravascular proplatelet shedding, the final stage of thrombopoiesis. Correspondingly, mice lacking Sphk2 in the hematopoietic system display thrombocytopenia. Together, our data suggest that Sphk2 provides the source of intracellular S1P that controls thrombopoiesis, which is associated with SFK expression and activity in MKs.

  14. 75 FR 27411 - Airworthiness Directives; Turbomeca Arriel 1B, 1D, 1D1, and 1S1 Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-17

    ... (that incorporate Turbomeca Modification (mod) TU 148), Arriel 1D, 1D1, and 1S1 turboshaft engines that do not incorporate mod TU 347. That AD also requires initial and repetitive replacements of 2nd stage... incorporate mod TU 148), 1D, 1D1, and 1S1 turboshaft engines that do not incorporate mod TU 347. We...

  15. Complete Genome Sequence of a Marine Bacterium, Pseudomonas pseudoalcaligenes Strain S1, with High Mercury Resistance and Bioaccumulation Capacity

    PubMed Central

    Liu, Bing; Bian, Chao; Huang, Huiwei; Yin, Zhiwei

    2016-01-01

    Pseudomonas pseudoalcaligenes S1, a marine bacterium, exhibited strong resistance to a high concentration of Hg2+ and remarkable Hg2+ bioaccumulation capacity. Here, we report the 6.9-Mb genome sequence of P. pseudoalcaligenes S1, which may help clarify its phylogenetic status and provide further understanding of the mechanisms of mercury bioremediation in a marine environment. PMID:27198018

  16. The Occurrence of Type S1A Serine Proteases in Sponge and Jellyfish

    NASA Technical Reports Server (NTRS)

    Rojas, Ana; Doolittle, Russell F.

    2003-01-01

    Although serine proteases are found in all kinds of cellular organisms and many viruses, the classic "chymotrypsin family" (Group S1A by th e 1998 Barrett nomenclature) has an unusual phylogenetic distribution , being especially common in animals, entirely absent from plants and protists, and rare among fungi. The distribution in Bacteria is larg ely restricted to the genus Streptomyces, although a few isolated occ urrences in other bacteria have been reported. The family may be enti rely absent from Archaea. Although more than a thousand sequences have been reported for enzymes of this type from animals, none of them ha ve been from early diverging phyla like Porifera or Cnidaria, We now report the existence of Group SlA serine proteases in a sponge (phylu m Porifera) and a jellyfish (phylum Cnidaria), making it safe to conc lude that all animal groups possess these enzymes.

  17. Optical and Phonon Characterization of Ternary CdSe x S1- x Alloy Quantum Dots

    NASA Astrophysics Data System (ADS)

    Thi, L. A.; Cong, N. D.; Dang, N. T.; Nghia, N. X.; Quang, V. X.

    2016-05-01

    Ternary CdSe x S1- x alloy quantum dots (QDs) were synthesized using a wet chemical method. Their morphology, particle size, structural, optical, and vibrational properties were investigated using transmission electron microscopy, x-ray diffraction, UV-Vis, fluorescence and Raman spectroscopy, respectively. The optical and vibrational properties of the QDs can be controlled by adjusting the Se/S molar ratio. The absorption and emission peaks shift to a longer wavelength range when increasing the Se content. The presence of two CdSe-like and CdS-like longitudinal optical phonon modes was observed. The dependencies of the optical and phonon modes on the Se content are discussed in detail.

  18. Mott lobes of the S =1 Bose-Hubbard model with three-body interactions

    NASA Astrophysics Data System (ADS)

    Hincapie-F, A. F.; Franco, R.; Silva-Valencia, J.

    2016-09-01

    Using the density-matrix renormalization-group method, we studied the ground state of the one-dimensional S =1 Bose-Hubbard model with local three-body interactions, which can be a superfluid or a Mott insulator state. We drew the phase diagram of this model for both ferromagnetic and antiferromagnetic interaction. Regardless of the sign of the spin-dependent coupling, we obtained that the Mott lobes area decreases as the spin-dependent strength increases, which means that the even-odd asymmetry of the two-body antiferromagnetic chain is absent for local three-body interactions. For antiferromagnetic coupling, we found that the density drives first-order superfluid-Mott insulator transitions for even and odd lobes. Ferromagnetic Mott insulator and superfluid states were obtained with a ferromagnetic coupling, and a tendency to a "long-range" order was observed.

  19. O/S-1/ interactions - The product channels. [collisional electron quenching and chemical reaction pathway frequencies

    NASA Technical Reports Server (NTRS)

    Slanger, T. G.; Black, G.

    1978-01-01

    The first measurements are reported of the reaction pathways for the interaction between oxygen atoms in the 4.19 eV S-1 state, and four molecules, N2O, CO2, H2O, and NO. Distinction is made between three possible paths - quenching to O(D-1), quenching to O(P-3), and chemical reaction. With N2O, the most reasonable interpretation of the data indicates that there no reaction, in sharp contrast with the interaction between O(D-1) and N2O, which proceeds entirely by reaction. Similarly, there is no reaction with CO2. With H2O, the reactive pathway is the dominant one, although electronic quenching is not negligible. With NO, O(D-1) is the preferred product.

  20. The Case for a Hubble Constant of 30 km s-1 Mpc-1.

    PubMed

    Bartlett, J G; Blanchard, A; Silk, J; Turner, M S

    1995-02-17

    Although recent determinations of the distance to the Virgo cluster based on Cepheid variable stars represent an important step in pinning down the Hubble constant, after 65 years a definitive determination of the Hubble constant still eludes cosmologists. At present, most of the observational determinations place the Hubble constant between 40 and 90 kilometers per second per megaparsec (km s(-1) Mpc(-1)). The case is made here for a Hubble constant that is even smaller than the lower bound of the accepted range on the basis of the great advantages, all theoretical in nature, of a Hubble constant of around 30 kilometers per second per megaparsec. Such a value for the Hubble cures all of the ills of the current theoretical orthodoxy, that is, a spatially flat universe composed predominantly of cold dark matter.

  1. Ferrimagnetic states in S = 1/2 frustrated Heisenberg chains with period 3 exchange modulation

    NASA Astrophysics Data System (ADS)

    Hida, K.

    2007-04-01

    The ground state properties of the S = 1/2 frustrated Heisenberg chain with period 3 exchange modulation are investigated using the numerical diagonalization and density matrix renormalization group (DMRG) method. It is known that this model has a magnetization plateau at one third of the saturation magnetization Ms. On the other hand, the ground state is ferrimagnetic even in the absence of frustration if one of the nearest neighbour bond is ferromagnetic and the others are antiferromagnetic. In the present work, we show that this ferrimagnetic state continues to the region in which all bonds are antiferromagnetic if the frustration is strong. This state further continues to the above-mentioned 1/3 plateau state. In between, we also find the noncollinear ferrimagnetic phase in which the spontaneous magnetization is finite but less than Ms/3. The intuitive interpretation for the phase diagram is given and the physical properties of these phases are discussed.

  2. Therapeutic Strategies and Pharmacological Tools Influencing S1P Signaling and Metabolism.

    PubMed

    Vogt, Dominik; Stark, Holger

    2017-01-01

    During the last two decades the study of the sphingolipid anabolic, catabolic, and signaling pathways has attracted enormous interest. Especially the introduction of fingolimod into market as first p.o. therapeutic for the treatment of multiple sclerosis has boosted this effect. Although the complex regulation of sphingosine-1-phosphate (S1P) and other catabolic and anabolic sphingosine-related compounds is not fully understood, the influence on different (patho)physiological states from inflammation to cytotoxicity as well as the availability of versatile pharmacological tools that represent new approaches to study these states are described. Here, we have summarized various aspects concerning the many faces of sphingolipid function modulation by different pharmacological tools up to clinical candidates. Due to the immense heterogeneity of physiological or pharmacological actions and complex cross regulations, it is difficult to predict their role in upcoming therapeutic approaches. Currently, inflammatory, immunological, and/or antitumor aspects are discussed.

  3. Technical evaluation report for the demonstration of radio frequency soil decontamination at Site S-1

    SciTech Connect

    Lyon, C.R.; Blanchard, C.F.; Whitt, L.H.

    1995-04-01

    The Air Force`s Armstrong Laboratory at Tyndall Air Force Base, Florida, has supported the research and development of Radio Frequency Soil Decontamination. Radio frequency soil decontamination is essentially a heat-assisted soil vapor extraction process. Site S-1 at Kelly Air Force Base, San Antonio, Texas, was selected for the demonstration of two patented techniques. The site is a former sump that collected spills and surface run-off from a waste petroleum, oils, and lubricants and solvent storage and transfer area. In 1993, a technique developed by the IIT Research Institute using an array of electrodes placed in the soil was demonstrated. In 1994, a technique developed by KAI Technologies, Inc. using a single applicator placed in a vertical borehole was demonstrated. Approximately 120 tons of soil were heated during each demonstration to a temperature of about 150 degrees Celsius.

  4. Lower Extremity Radicular Pain Caused by Entrapped Sigmoid Colon Between L5 and S1 Vertebrae

    PubMed Central

    Ko, Sanghyung; Park, Noh Kyoung; Cho, Kyoung Jin; Baek, Jung Hyun; Lim, Jeong-Wook; Choi, Dongjin

    2015-01-01

    Intestinal entrapment between two vertebral bodies is very rare. In all previous cases, it occurred by major trauma. However, the bowel entrapment between two vertebral bodies without trauma has never been reported, not to mention as the cause of lower extremity radicular pain. We describe the case of an 82-year-old female patient with right lower extremity radicular pain without recent trauma history. The patient was diagnosed sigmoid colon entrapment between the L5 and S1 vertebrae by lumbar spinal computerized tomography and magnetic resonance imaging, and showed improvement in radicular pain after manual reduction of interpositioned colon during surgery. Intestinal entrapment between two vertebrae without trauma is caused by degenerative and vacuum changes of the intervertebral disc combined with the anterior longitudinal ligament injury. PMID:26619145

  5. Semiclassical on-the-fly computation of the S(0)-->S(1) absorption spectrum of formaldehyde.

    PubMed

    Tatchen, Jörg; Pollak, Eli

    2009-01-28

    The anharmonic S(0)-->S(1) vibronic absorption spectrum of the formaldehyde molecule is computed on the fly using semiclassical dynamics. This first example of an on-the-fly semiclassical computation of a vibronic spectrum was achieved using a unit prefactor modified frozen Gaussian semiclassical propagator for the excited state. A sample of 6000 trajectories sufficed for obtaining a converged spectrum, which is in reasonable agreement with experiment. Similar agreement is not obtained when using a harmonic approximation for the spectrum, demonstrating the need for a full anharmonic computation. This first example provides a resolution of approximately 100 cm(-1). Potential ways of improving the methodology and obtaining higher resolution and accuracy are discussed.

  6. Picosecond transient gratings in CdS1- xSex mixed crystals

    NASA Astrophysics Data System (ADS)

    Dörnfeld, C.; Noll, G.; Schwab, H.; Hvam, J. M.; Weber, Ch.; Renner, R.; Göbel, E. O.; Reznitsky, A.; Lyssenko, V.; Pendjur, S. A.; Talensky, O. N.; Klingshirn, C.

    1990-04-01

    We performed transient grating experiments to study various relaxation processes of localized excitons in CdS1 xSex mixed crystals. At low temperatures we observe a strong nonlinear response, spectrally in the localized states. We measured the phase relaxation time of localized excitons with a correlation technique. At low excitation levels we found long phase relaxation times of 75 ps. In a three beam configuration of a transient grating experiment we investigated the recombination as well as the diffusion of excitons within the localized states. We observed a reduced mobility compared to the mobility of free excitons in the pure compounds and found diffusion coefficients D < 2 cm2/ s.

  7. Linear and nonlinear optical studies of CdS1- x Se x quantum dots

    NASA Astrophysics Data System (ADS)

    Uhrig, A.; Banyai, L.; Gaponenko, S.; Wörner, A.; Neuroth, N.; Klingshirn, C.

    1991-03-01

    In this contribution we present and discuss our measurements on CdS1- x Se x quantum dots in a glass matrix. In linear absorption measurements we find the typical blue shift of the transitions with decreasing crystallite radius due to quantization. The luminescence shows a significant Stokes shift with respect to absorption, which is interpreted in terms of strong exciton-phonon coupling and allows to deduce the Huang-Rhys factor S. Under high excitation we find an additional emission band on the high energy side, which can be attributed to the recombination of an excited two electron-hole pair state to a one electron-hole pair state in agreement with theory. Pump and probe beam experiments give a bleaching but no hole burning. Finally we discuss some open questions especially concerning the high energy structures in the absorption spectrum.

  8. Supersymmetry and CP violation in {delta}S=1 {tau} decays

    SciTech Connect

    Delepine, D.; Faisel, G.; Khalil, S.; Lopez Castro, G.

    2006-09-01

    We compute the supersymmetry (SUSY) effective Hamiltonian that describes the {delta}S=1 semileptonic decays of tau leptons. We provide analytical expressions for supersymmetric contribution to {tau}{yields}us{nu}{sub {tau}} transition in mass insertion approximation. We show that SUSY contributions may enhance the CP asymmetry of {tau}{yields}K{pi}{nu}{sub {tau}} decays by several orders of magnitude with respect to the standard model expectations. However, the resulting asymmetry is still well below the current experimental limits obtained by CLEO Collaborations. We emphasize that measuring CP rate asymmetry in this decay larger than 10{sup -6} would be a clear evidence of physics beyond the supersymmetric extensions of the standard model.

  9. Tarlov cyst as a rare cause of S1 radiculopathy: A case report.

    PubMed

    Nadler, S F; Bartoli, L M; Stitik, T P; Chen, B

    2001-05-01

    A 37-year-old female physician presented with a chief complaint of left posterior thigh pain, which began insidiously approximately 4 months before her initial examination. Initially, she had been evaluated by her physician, and magnetic resonance imaging (MRI) was ordered. The MRI scan was reported to be within normal limits, with the exception of minimal disc bulging at L4-5. She had received physical therapy with little benefit and was referred for physiatric assessment. Review of the patient's original MRI scan showed the presence of perineurial (Tarlov) cysts within the sacral canal at the level of S2, with compression of the adjacent nerve root. Subsequent electrodiagnostic testing showed axonal degeneration consistent with an S1 radiculopathy. Tarlov cysts can be a rare cause of lumbosacral radiculopathy and should be considered in the differential diagnosis of radicular leg pain.

  10. Classifying magnetic and superfluid equilibrium states in magnets with the spin s = 1

    NASA Astrophysics Data System (ADS)

    Kovalevskii, M. Yu.

    2016-03-01

    Based on the method of quasiaverages, we classify magnetic and superfluid equilibrium states in magnets with the spin s = 1. Under certain simplifications, assumptions about the residual symmetry of degenerate states and the transformation properties of order parameter operators under transformations generated by additive integrals of motions lead to linear algebraic equations for a classification of the equilibrium means of the order parameters. We consider different cases of the magnetic SO(3) or SU(3) symmetry breaking and obtain solutions for the vector and tensor order parameters for particular forms of the parameters of the residual symmetry generators. We study the equilibriums of magnets with simultaneously broken phase and magnetic symmetries. We find solutions of the classification equations for superfluid equilibrium states and establish relations between the parameters of the residual symmetry generator that allow the thermodynamic coexistence of nonzero equilibrium means of the order parameters.

  11. Critical Keller-Segel meets Burgers on {{{S}}^{1}} : large-time smooth solutions

    NASA Astrophysics Data System (ADS)

    Burczak, Jan; Granero-Belinchón, Rafael

    2016-12-01

    We show that solutions to the parabolic-elliptic Keller-Segel system on {{{S}}1} with critical fractional diffusion (- Δ ){{}\\frac{1{2}}} remain smooth for any initial data and any positive time. This disproves, at least in the periodic setting, the large-data-blowup conjecture by Bournaveas and Calvez [15]. As a tool, we show smoothness of solutions to a modified critical Burgers equation via a generalization of the ingenious method of moduli of continuity by Kiselev, Nazarov and Shterenberg [35] over a setting where the considered equation has no scaling. This auxiliary result may be interesting by itself. Finally, we study the asymptotic behavior of global solutions corresponding to small initial data, improving the existing results.

  12. IMAGING COMET ISON C/2012 S1 IN THE INNER CORONA AT PERIHELION

    SciTech Connect

    Druckmüller, Miloslav; Habbal, Shadia Rifai; Aniol, Peter; Ding, Adalbert; Morgan, Huw

    2014-04-01

    Much anticipation and speculation were building around comet ISON, or C/2012 S1, discovered on 2012 September 21 by the International Scientific Optical Network telescope in Russia, and bound for the Sun on 2013 November 28, with a closest heliocentric approach distance of 2.7 R {sub ☉}. Here we present the first white light image of the comet's trail through the inner corona. The image was taken with a wide field Lyot-type coronagraph from the Mees Observatory on Haleakala at 19:12 UT, past its perihelion passage at 18:45 UT. The perfect match between the comet's trail captured in the inner corona and the trail that had persisted across the field of view of 2-6 R {sub ☉} of the Solar and Heliospheric Observatory Large Angle and Spectrometric Coronagraph Experiment/C2 coronagraph at 19:12 UT demonstrates that the comet survived its perihelion passage.

  13. Early changes in shoot transcriptome of rice in response to Rhodotorula mucilaginosa JGTA-S1

    PubMed Central

    Saha, Chinmay; Seal, Anindita

    2015-01-01

    Yeasts of Rhodotorula genus have been reported to show endophytic colonization in different plants. Some of the Rhodotorula species are found to e