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Sample records for r-3 derivatives exhibited

  1. Synthesis of carbasugars from aldonolactones, part III - A study on the allylic substitution of (1R,5R,8R)- and (1R,5R,8S)-8-hydroxy-2-oxabicyclo[3.3.0]oct-6-en-3-one derivatives - Preparation of (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H-adenine

    DEFF Research Database (Denmark)

    Johansen, Steen Karsk; Lundt, Inge

    2001-01-01

    The palladium-catalyzed substitution of acylated (1R,5R,8R)- and (1R,SR,8S)-8-hydroxy-2-oxabicyclo[3.3.0] ones has been studied using a number of C- and N-nucleophiles, In all cases, the exo derivatives (8R) were found to be more reactive than the corresponding endo derivatives (8S). The reaction...... with these nucleophiles. Additionally, Mitsunobu substitution of (1R,5R,8R)-8-hydroxy-2-oxabicyclo[3.3.0]oct-B-en-3-one (3) with 6-chloropurine, followed by reduction of the lactone moiety and treatment with Liquid ammonia, gave the carbocyclic nucleoside (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H...

  2. Fate of thymic lymphocytes. [/sup 125/IudR and /sup 3/HTdR tracer studies in mice

    Energy Technology Data Exchange (ETDEWEB)

    Laissue, J A; Chanana, A D; Cronkite, E P; Joel, D D

    1976-01-01

    Data are summarized from a number of studies on the fate of thymic lymphocytes. Results are reported from studies in mice in which /sup 125/IudR and /sup 3/HTdR were used as tracers to study the production, maturation, migration, and life span of thymic lymphocytes. It is pointed out that thymus-derived cells constitute the majority of recirculating lymphocytes and that peripheral, differentiated thymus-derived lymphocytes exhibit a number of immunological functions. 114 references.

  3. Primary amino acid derivatives: substitution of the 4'-N'-benzylamide site in (R)-N'-benzyl 2-amino-3-methylbutanamide, (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide, and (R)-N'-benzyl 2-amino-3-methoxypropionamide provides potent anticonvulsants with pain-attenuating properties.

    Science.gov (United States)

    King, Amber M; Salomé, Christophe; Salomé-Grosjean, Elise; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Stables, James P; Kohn, Harold

    2011-10-13

    Recently, we reported that select N'-benzyl 2-substituted 2-amino acetamides (primary amino acid derivatives (PAADs)) exhibited pronounced activities in established whole animal anticonvulsant (i.e., maximal electroshock seizure (MES)) and neuropathic pain (i.e., formalin) models. The anticonvulsant activities of C(2)-hydrocarbon N'-benzyl 2-amino acetamides (MES ED(50) = 13-21 mg/kg) exceeded those of phenobarbital (ED(50) = 22 mg/kg). Two additional studies defining the structure-activity relationship of PAADs are presented in this issue of the journal. In this study, we demonstrated that the anticonvulsant activities of (R)-N'-benzyl 2-amino-3-methylbutanamide and (R)-N'-benzyl 2-amino-3,3-dimethylbutanamide were sensitive to substituents at the 4'-N'-benzylamide site; electron-withdrawing groups retained activity, electron-donating groups led to a loss of activity, and incorporating either a 3-fluorobenzyloxy or 3-fluorophenoxymethyl group using a rationally designed multiple ligand approach improved activity. Additionally, we showed that substituents at the 4'-N'-benzylamide site of (R)-N'-benzyl 2-amino-3-methoxypropionamide also improved anticonvulsant activity, with the 3-fluorophenoxymethyl group providing the largest (∼4-fold) increase in activity (ED(50) = 8.9 mg/kg), a value that surpassed phenytoin (ED(50) = 9.5 mg/kg). Collectively, the pharmacological findings provided new information that C(2)-hydrocarbon PAADs represent a novel class of anticonvulsants.

  4. Electrical and mechanical anharmonicities from NIR-VCD spectra of compounds exhibiting axial and planar chirality: the cases of (S)-2,3-pentadiene and methyl-d(3) (R)- and (S)-[2.2]paracyclophane-4-carboxylate.

    Science.gov (United States)

    Abbate, Sergio; Longhi, Giovanna; Gangemi, Fabrizio; Gangemi, Roberto; Superchi, Stefano; Caporusso, Anna Maria; Ruzziconi, Renzo

    2011-10-01

    The IR and Near infrared (NIR) vibrational circular dichroism (VCD) spectra of molecules endowed with noncentral chirality have been investigated. Data for fundamental, first, and second overtone regions of (S)-2,3-pentadiene, exhibiting axial chirality, and methyl-d(3) (R)- and (S)-[2.2]paracyclophane-4-carboxylate, exhibiting planar chirality have been measured and analyzed. The analysis of NIR and IR VCD spectra was based on the local-mode model and the use of density functional theory (DFT), providing mechanical and electrical anharmonic terms for all CH-bonds. The comparison of experimental and calculated spectra is satisfactory and allows one to monitor fine details in the asymmetric charge distribution in the molecules: these details consist in the harmonic frequencies, in the principal anharmonicity constants, in both the atomic polar and axial tensors and in their first and second derivatives with respect to the CH-stretching coordinates. Copyright © 2011 Wiley-Liss, Inc.

  5. Synthesis and nootropic activity of some 2,3-dihydro-1H-isoindol-1-one derivatives structurally related with piracetam.

    Science.gov (United States)

    Reyes, Adelfo; Huerta, Leticia; Alfaro, Marisol; Navarrete, Andrés

    2010-11-01

    Three 2,3-dihydro-1H-isoindol-1-ones structurally related with piracetam (=2-oxopyrrolidine-1-acetamide) have been synthesized and tested for their nootropic effects in the passive avoidance test in mice. Compounds (RS)-2, (R,R)-3, and (R,S)-3 were obtained in good yields in only two steps starting from methyl DL-phthaloylalanine. Compound (RS)-2 exhibited nootropic activity at lower doses than piracetam, used as reference drug, but it showed lower efficacy. Whereas diastereoisomers (R,R)-3 and (R,S)-3 were as potent as piracetam to revert amnesia induced by scopolamine, (R,S)-3 showed lower efficacy than (R,R)-3. Only (R,R)-3 showed myorelaxant effect at doses of 10 and 30 mg/kg; other compounds did not exhibit any anticonvulsant, sedative, myorelaxant, or impaired motor-coordination effect in mice. These synthesized 2,3-dihydro-1H-isoindol-1-one derivatives constitute a new kind of nootropic compounds.

  6. Classical r-matrices for the generalised Chern–Simons formulation of 3d gravity

    Science.gov (United States)

    Osei, Prince K.; Schroers, Bernd J.

    2018-04-01

    We study the conditions for classical r-matrices to be compatible with the generalised Chern–Simons action for 3d gravity. Compatibility means solving the classical Yang–Baxter equations with a prescribed symmetric part for each of the real Lie algebras and bilinear pairings arising in the generalised Chern–Simons action. We give a new construction of r-matrices via a generalised complexification and derive a non-linear set of matrix equations determining the most general compatible r-matrix. We exhibit new families of solutions and show that they contain some known r-matrices for special parameter values.

  7. NEW DERIVATIVES OF 2-R1-N-(5-R-1,3,4-THIADIAZOL-2-YL-BENZOLSULFONAMIDES: SYNTHESIS, PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITY PREDICTION

    Directory of Open Access Journals (Sweden)

    Sych I.V.

    2015-12-01

    Full Text Available Introduction: The analysis of modern literature, including overseas one, showed that a lot of the scientific researches is devoted to finding and creating biologically active compounds on base 1,3,4-thiadiazole. Derivatives of 1,3,4-thiadiazole are the large group of heterocyclic compounds with high rates of antimicrobial, antituberculosis, antidiabetic, antineoplastic and anticonvulsant activity. Material and methods: The purpose of this study was the expansion of sulfone derivatives substituted nitrogen-containing heterocyclic systems through the synthesis of 2-R1-N (5-R-1,3,4-thiadiazol-2-ilbenzolsulfonamides and prediction their pharmacological activity for future planning pharmacological screening. Synthesis of semi-products 2-amino-5-R-1,3,4-thiadiazoles was carried out by cyclization thiosemicarbazide and substituted derivatives of carboxylic acids in the presence of concentrated sulfuric acid. The synthesis of target compounds 2-R1-N(5-R-1,3,4-thiadiazol-2-ylbenzolsulfon-amides was carried out by N-acylation of 2-amino-5R-1,3,4-thiadiazole substituted benzolsul-fochlorides in the presence of anhydrous pyridine. The reaction proceeds by the classic SN2-mechanism. The resulting compounds are white crystalline substances, soluble in alcohol, chloroform and acetone, difficult to dissolve in water. Yields of obtained compounds was satisfactory (76-84%. The purity of the obtained compounds was determined by TLC. The structure of the obtained compounds was proved by elemental analysis, IR methods and 1H NMR spectroscopy. NMR 1H spectra were recorded at Bruker WM spectrometer (200 MHz; solvent DMSO-d6; chemical shifts were in ppm, internal standard (TMS (tetramethylsilane was used. The prognosis of biological activity for obtained compounds were carried out using the program PASS (Prediction of Activity Spectra for Substances in order to plan the further pharmacological screening. The program PASS predicts more than 500 kinds of biological

  8. Experimental and computational thermochemical studies of 9-R-xanthene derivatives (R=OH, COOH, CONH2)

    International Nuclear Information System (INIS)

    Freitas, Vera L.S.; Gomes, José R.B.; Ribeiro da Silva, Maria D.M.C.

    2012-01-01

    Highlights: ► Energetics of 9-R-xanthene derivatives (R=OH, COOH, CONH 2 ). ► Δ f H m o (cr) of three xanthenes derivatives was measured by static bomb calorimetry. ► Δ cr g H m o of xanthenes derivatives was derived Knudsen effusion technique. ► Molecular orbital calculations for xanthene derivatives were done by G3(MP2)//B3LYP. - Abstract: In the present work, the standard (p° = 0.1 MPa) molar enthalpies of formation of xanthydrol, 9-xanthenecarboxylic acid and 9-xanthenecarboxamide, in the gaseous state, at T = 298.15 K, were determined by experimental and computational studies. The experimental techniques used were the static-bomb combustion calorimetry, which enabled the determination of the standard molar enthalpy of formation, in the crystalline state, and the vacuum drop microcalorimetric and the Knudsen effusion techniques used to derive the enthalpy of sublimation. For comparison purposes, we performed standard ab initio molecular orbital calculations, using the G3(MP2)//B3LYP composite procedure, of the enthalpies of several homodesmotic reactions, allowing to extract the standard molar enthalpies of formation, in the gaseous state, of the three xanthene derivatives considered in this work. The calculated results are in good agreement with the experimental data.

  9. Water-soluble derivatives of 25-OCH3-PPD and their anti-proliferative activities.

    Science.gov (United States)

    Zhou, Wu-Xi; Sun, Yuan-Yuan; Yuan, Wei-Hui; Zhao, Yu-Qing

    2017-05-01

    (20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH 3 -PPD, AD-1) is a dammarane-type sapogenin showing anti-tumor potential. In the search for new anti-tumor agents with higher potency than our previously identified compound 25-OCH 3 -PPD, 11 novel sulfamic acid and diacid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 25-OCH 3 -PPD, compounds 1, 4, and 5 exhibited higher cytotoxic activity on almost all cell lines, together with lower toxicity in the normal cell. In particular, compound 1 exhibited the best anti-tumor activity in the in vitro assays. The water solubility of 25-OCH 3 -PPD and its derivatives was tested and the results showed that the solubility of 25-OCH 3 -PPD sulfamic acid and diacid derivatives were better than that of 25-OCH 3 -PPD in water, which may provide valuable data for the research and development of new anti-tumor agents. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Synthesis of New Chiral Amines with a Cyclic 1,2-Diacetal Skeleton Derived from (2R, 3R-(+-Tartaric Acid

    Directory of Open Access Journals (Sweden)

    Ana Maria Faísca Phillips

    2006-03-01

    Full Text Available The syntheses of new chiral cyclic 1,2-diacetals from (2R, 3R-( -tartaric acidare described. C2-symmetrical diamines were prepared via direct amidation of the tartrate orfrom the corresponding bismesylate via reaction with sodium azide. For C1-symmetricalcompounds, the Appel reaction was used to form the key intermediate, amonochlorocarbinol, from the diol. Some of the new chiral compounds, produced in good tohigh yields, may be potentially useful as asymmetric organocatalysts or as nitrogen andsulfur chelating ligands for asymmetric metal catalyzed reactions. Thus, a bis-N-methyl-methanamine derivative, used in substoichiometric amounts, was found to catalyze theenantioselective addition of cyclohexanone to (E-β-nitrostyrene with highdiastereoselectivity (syn / anti = 92:8, albeit giving moderate optical purity (syn: 30 %.

  11. Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides as potent and long acting muscarinic antagonists.

    Science.gov (United States)

    Prat, Maria; Buil, María Antonia; Fernández, Maria Dolors; Tort, Laia; Monleón, Juan Manuel; Casals, Gaspar; Ferrer, Manuel; Castro, Jordi; Gavaldà, Amadeu; Miralpeix, Montserrat; Ramos, Israel; Vilella, Dolors; Huerta, Josep Maria; Espinosa, Sònia; Hernández, Begoña; Segarra, Victor; Córdoba, Mònica

    2015-04-15

    Novel quaternary ammonium derivatives of (3R)-quinuclidinyl amides have been identified as potent M3 muscarinic antagonists with a long duration of action in an in vivo model of bronchoconstriction. The synthesis, structure-activity relationships and biological evaluation of this series of compounds are reported. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Chiral gels derived from secondary ammonium salts of (1R,3S-(+-camphoric acid

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    Tapas Kumar Adalder

    2010-09-01

    Full Text Available In order to have access to chiral gels, a series of salts derived from (1R,3S-(+-camphoric acid and various secondary amines were prepared based on supramolecular synthon rationale. Out of seven salts prepared, two showed moderate gelation abilities. The gels were characterized by differential scanning calorimetry, table top rheology, scanning electron microscopy, single crystal and powder X-ray diffraction. Structure property correlation based on X-ray diffraction techniques remain inconclusive indicating that some of the integrated part associated with the gelation phenomena requires a better understanding.

  13. An efficient conversion of (3R,3'R,6'R)-lutein to (3R,3'S,6'R)-lutein (3'-epilutein) and (3R,3'R)-zeaxanthin.

    Science.gov (United States)

    Khachik, Frederick

    2003-01-01

    Two dietary carotenoids, (3R,3'R,6'R)-lutein (1) and (3R,3'R)-zeaxanthin (2), and their metabolite (3R,3'S,6'R)-lutein (3'-epilutein) (3) accumulate in human serum, milk, and ocular tissues. There is increasing evidence that compounds 1 and 2 play an important role in the prevention of age-related macular degeneration. Therefore, the availability of these carotenoids for metabolic studies and clinical trials is essential. Compound 1 is isolated from extracts of marigold flowers (Tagete erecta) and is commercially available, whereas 2 is only accessible by a lengthy total synthesis, and a viable method for synthesis of 3 has not yet been developed. This report describes an efficient conversion of technical grade 1 to 2 via 3. Acid-catalyzed epimerization of 1 yields an equimolar mixture of diastereomers 1 and 3. The mixture was separated by enzyme-mediated acylation with lipase AK from Pseudomonas fluorescens that preferentially esterified 3 and after alkaline hydrolysis yielded this carotenoid in 90% diastereomeric excess (de). Compound 3 was also separated from 1 in 56-88% de by solvent extraction and low-temperature crystallization, Soxhlet extraction, or supercritical fluid extraction. Base-catalyzed isomerization of 3 gave 2 in excellent yield, providing a convenient alternative to the total synthesis of this important dietary carotenoid.

  14. Synthesis of new chiral amines with a cyclic 1,2-diacetal skeleton derived from (2R, 3R)-(+)-tartaric acid.

    Science.gov (United States)

    Barros, M Teresa; Phillips, Ana Maria Faísca

    2006-03-17

    The syntheses of new chiral cyclic 1,2-diacetals from (2R, 3R)-( )-tartaric acid are described. C(2)-symmetrical diamines were prepared via direct amidation of the tartrate or from the corresponding bismesylate via reaction with sodium azide. For C1-symmetrical compounds, the Appel reaction was used to form the key intermediate, a monochlorocarbinol, from the diol. Some of the new chiral compounds, produced in good to high yields, may be potentially useful as asymmetric organocatalysts or as nitrogen and sulfur chelating ligands for asymmetric metal catalyzed reactions. Thus, a bis-N-methyl-methanamine derivative, used in substoichiometric amounts, was found to catalyze the enantioselective addition of cyclohexanone to (E)-beta-nitrostyrene with high diastereoselectivity (syn / anti = 92:8), albeit giving moderate optical purity (syn: 30 %).

  15. Partial synthesis of (3R,6'R)-alpha-cryptoxanthin and (3R)-beta-cryptoxanthin from (3R,3'R,6'R)-lutein.

    Science.gov (United States)

    Khachik, Frederick; Chang, An-Ni; Gana, Audry; Mazzola, Eugene

    2007-02-01

    (3R,3'R,6'R)-Lutein (1), (3R,3'R)-zeaxanthin (2), (3R,6'R)-alpha-cryptoxanthin (3), and (3R)-beta-cryptoxanthin (4) are among dietary hydroxycarotenoids that have been identified in human serum, milk, and ocular tissues. While 1 containing 6% of 2 is commercially available, industrial production of optically active 3 and 4 has not yet been accomplished. Several processes have been developed that transform 1 into 3, 4, and minor quantities of (3R,5'RS,6'R)-3',4'-didehydro-5',6'-dihydro-beta,beta-caroten-3-ol (5) (a regioisomer of 3). In one process, lutein (1) was cleanly deoxygenated to 3 in the presence of trifluoroacetic acid (TFA) and Me3N.BH3 in CH2Cl2 at ambient temperature in nearly 90% yield. Reaction of lutein (1) with a Lewis acid (AlCl3, ZnBr2, ZnI2) and a hydride donor (Me3N.BH3, Na[BH3(OCOCF3)], NaCNBH3) in solvents such as CH2Cl2, THF, and TBME produced similar results. In a two-step process, high-temperature acid-catalyzed dehydration of 1 (propanol/water/acid, 90 degrees C) gave a mixture of anhydroluteins 6, 7, and 8 in 86% yield. In the second step, these dehydration products underwent ionic hydrogenation with TFA/Me3N.BH3 in CH2Cl2 to afford a mixture of 3 and 4 in nearly 80% yield that contained only 1% of 5.

  16. Resolution of 1-n-butyl-3-methyl-3-phospholene 1-oxide with TADDOL derivatives and calcium salts of O,O'-Dibenzoyl-(2R,3R)- or O,O'-di-p-toluoyl-(2R,3R)-tartaric acid.

    Science.gov (United States)

    Bagi, Péter; Fekete, András; Kállay, Mihály; Hessz, Dóra; Kubinyi, Miklós; Holczbauer, Tamás; Czugler, Mátyás; Fogassy, Elemér; Keglevich, György

    2014-03-01

    The resolution methods applying (-)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane ("TADDOL"), (-)-(2R,3R)-α,α,α',α'-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol ("spiro-TADDOL"), as well as the acidic and neutral Ca(2+) salts of (-)-O,O'-dibenzoyl- and (-)-O,O'-di-p-toluoyl-(2R,3R)-tartaric acid were extended for the preparation of 1-n-butyl-3-methyl-3-phospholene 1-oxide in optically active form. In one case, the intermediate diastereomeric complex could be identified by single-crystal X-ray analysis. The absolute P-configuration of the enantiomers of the phospholene oxide was also determined by comparing the experimentally obtained and calculated CD spectra. © 2014 Wiley Periodicals, Inc.

  17. Synthesis, Characterization and Biological Activities of Novel (E)-3-(1-(Alkyloxyamino)ethylidene)-1-alkylpyrrolidine-2,4-dione Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zhao Yong; Shi, Qing Ming; Han, Bao Feng; Wang, Xian Feng; Qiang, Sheng; Yang, Chun Long [Nanjing Agricultural University, Nanjing (China)

    2010-09-15

    Twenty novel tetramic acid derivatives (E)-3-(1-(alkyloxyamino)ethylidene)-1-alkylpyrrolidine-2,4-diones were synthesized by the reaction of 3-(1-hydroxyethylidene)pyrrolidine-2,4-diones with O-alkyl hydroxylamines. The title compounds were confirmed by IR, {sup 1}H NMR, MS and elemental analysis. The structure of compound 6r was further verified by X-ray diffraction crystallography. The bioassays showed that most of the title compounds exhibited noticeable herbicidal and fungicidal activities.

  18. Spearmint R2R3-MYB transcription factor MsMYB negatively regulates monoterpene production and suppresses the expression of geranyl diphosphate synthase large subunit (MsGPPS.LSU).

    Science.gov (United States)

    Reddy, Vaishnavi Amarr; Wang, Qian; Dhar, Niha; Kumar, Nadimuthu; Venkatesh, Prasanna Nori; Rajan, Chakravarthy; Panicker, Deepa; Sridhar, Vishweshwaran; Mao, Hui-Zhu; Sarojam, Rajani

    2017-09-01

    Many aromatic plants, such as spearmint, produce valuable essential oils in specialized structures called peltate glandular trichomes (PGTs). Understanding the regulatory mechanisms behind the production of these important secondary metabolites will help design new approaches to engineer them. Here, we identified a PGT-specific R2R3-MYB gene, MsMYB, from comparative RNA-Seq data of spearmint and functionally characterized it. Analysis of MsMYB-RNAi transgenic lines showed increased levels of monoterpenes, and MsMYB-overexpressing lines exhibited decreased levels of monoterpenes. These results suggest that MsMYB is a novel negative regulator of monoterpene biosynthesis. Ectopic expression of MsMYB, in sweet basil and tobacco, perturbed sesquiterpene- and diterpene-derived metabolite production. In addition, we found that MsMYB binds to cis-elements of MsGPPS.LSU and suppresses its expression. Phylogenetic analysis placed MsMYB in subgroup 7 of R2R3-MYBs whose members govern phenylpropanoid pathway and are regulated by miR858. Analysis of transgenic lines showed that MsMYB is more specific to terpene biosynthesis as it did not affect metabolites derived from phenylpropanoid pathway. Further, our results indicate that MsMYB is probably not regulated by miR858, like other members of subgroup 7. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  19. Sub-populations within the major European and African derived haplogroups R1b3 and E3a are differentiated by previously phylogenetically undefined Y-SNPs.

    Science.gov (United States)

    Sims, Lynn M; Garvey, Dennis; Ballantyne, Jack

    2007-01-01

    Single nucleotide polymorphisms on the Y chromosome (Y-SNPs) have been widely used in the study of human migration patterns and evolution. Potential forensic applications of Y-SNPs include their use in predicting the ethnogeographic origin of the donor of a crime scene sample, or exclusion of suspects of sexual assaults (the evidence of which often comprises male/female mixtures and may involve multiple perpetrators), paternity testing, and identification of non- and half-siblings. In this study, we used a population of 118 African- and 125 European-Americans to evaluate 12 previously phylogenetically undefined Y-SNPs for their ability to further differentiate individuals who belong to the major African (E3a)- and European (R1b3, I)-derived haplogroups. Ten of these markers define seven new sub-clades (equivalent to E3a7a, E3a8, E3a8a, E3a8a1, R1b3h, R1b3i, and R1b3i1 using the Y Chromosome Consortium nomenclature) within haplogroups E and R. Interestingly, during the course of this study we evaluated M222, a sub-R1b3 marker rarely used, and found that this sub-haplogroup in effect defines the Y-STR Irish Modal Haplotype (IMH). The new bi-allelic markers described here are expected to find application in human evolutionary studies and forensic genetics. (c) 2006 Wiley-Liss, Inc.

  20. Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.

    Science.gov (United States)

    Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2014-01-01

    From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation.

  1. Amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole

    International Nuclear Information System (INIS)

    Saidov, D.K.; Rakhmonov, R.O.; Khodzhiboev, Yu.; Kukaniev, M.A.; Bandaev, S.

    2015-01-01

    Present article is devoted to amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole. The reaction of new modifications of derivatives of imidazo-[2.1-B]-1.3.4-thiadiazoles-2-bromine-6-p-bromophenyl and 2-alkyl alkylene sulfonyl-6-phenyl imidazo--[2.1-B]-1.3.4-thiadiazole on Mannich with secondary and heterocyclic amines was studied.

  2. 17 CFR 240.15c3-3a - Exhibit A-formula for determination reserve requirement of brokers and dealers under § 240.15c3-3.

    Science.gov (United States)

    2010-04-01

    ... related to security futures products on deposit with: (1) A registered clearing agency or derivatives... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exhibit A-formula for... Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND...

  3. Pharmacological aspects of application of 1,2,4-triazole-3-thiol furan derivatives

    Directory of Open Access Journals (Sweden)

    O. A. Bihdan

    2016-12-01

    Full Text Available Introduction. Nowadays 1,2,4-triazole-3-thiol furan derivatives have established themselves as a separate class of promising bioactive compounds. Presented substance is practically non-toxic and exhibits various kinds of pharmacological activity. New original drug «Tryfuzol» in two dosage forms (1% injectable solution and 1% solution for oral administration triumphantly entered the practice of the national veterinary. The most attractive in pharmacological aspects are water-soluble compounds 5-(furan-2-yl-4R-1,2,4-triazole-3-thiols. Other classes of 1,2,4-triazole-3-thiol furan derivatives are also in considerable scientific interest. However, despite the presence of a sufficiently large number of publications, the issue of pharmacological tests systematization of the 1,2,4-triazole-3-thiol furan derivatives is still open. In this way the aim of our work was the systematization of the available sources of domestic authors. Materials and methods. Our work presents the results of systematic analysis of the available domestic literature related to the study of pharmacological properties of 1,2,4-triazole-3-thiol furan derivatives. Research results. It is known that 1,2,4-triazole-3-thiol furan derivatives have wide range of properties and biological activities. Thioacetate salts of corresponding acids show the highest results. The authors investigated the properties of water-soluble compounds of 1,2,4-triazole-3-thiol furan derivatives. Another group of compounds was investigated on hypoglycemic activity. It was established that the most active were piperidine 2-(5-(furan-2-yl-4-(3-methylphenyl-1,2,4-triazol-3-ylthio acetate and piperidine 2-(5-(furan-2-yl-4-phenyl-1,2,4-triazol-3-ylthio acetate. Conclusion. The scientific potential of the domestic pharmaceutical industry has no doubts for today. The literature analysis of Russian authors proves the obvious prospect of further research of biologically active compounds among 1,2,4-triazole-3-thiol

  4. Structure activity relationships of quinoxalin-2-one derivatives as platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors, derived from molecular modeling.

    Science.gov (United States)

    Mori, Yoshikazu; Hirokawa, Takatsugu; Aoki, Katsuyuki; Satomi, Hisanori; Takeda, Shuichi; Aburada, Masaki; Miyamoto, Ken-ichi

    2008-05-01

    We previously reported a quinoxalin-2-one compound (Compound 1) that had inhibitory activity equivalent to existing platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors. Lead optimization of Compound 1 to increase its activity and selectivity, using structural information regarding PDGFbeta R-ligand interactions, is urgently needed. Here we present models of the PDGFbeta R kinase domain complexed with quinoxalin-2-one derivatives. The models were constructed using comparative modeling, molecular dynamics (MD) and ligand docking. In particular, conformations derived from MD, and ligand binding site information presented by alpha-spheres in the pre-docking processing, allowed us to identify optimal protein structures for docking of target ligands. By carrying out molecular modeling and MD of PDGFbeta R in its inactive state, we obtained two structural models having good Compound 1 binding potentials. In order to distinguish the optimal candidate, we evaluated the structural activity relationships (SAR) between the ligand-binding free energies and inhibitory activity values (IC50 values) for available quinoxalin-2-one derivatives. Consequently, a final model with a high SAR was identified. This model included a molecular interaction between the hydrophobic pocket behind the ATP binding site and the substitution region of the quinoxalin-2-one derivatives. These findings should prove useful in lead optimization of quinoxalin-2-one derivatives as PDGFb R inhibitors.

  5. Anomalous magnetoresistance in antiferromagnetic polycrystalline materials R2Ni3Si5 (R=rare earth)

    International Nuclear Information System (INIS)

    Mazumdar, C.; Nigam, A.K.; Nagarajan, R.; Gupta, L.C.; Chandra, G.; Padalia, B.D.; Godart, C.; Vijayaraghaven, R.

    1997-01-01

    Magnetoresistance (MR) studies on polycrystalline R 2 Ni 3 Si 5 , (R=Y, rare earth) which order antiferromagnetically at low temperatures, are reported here. MR of the Nd, Sm, and Tb members of the series exhibit positive giant magnetoresistance, largest among polycrystalline materials (85%, 75%, and 58% for Tb 2 Ni 3 Si 5 , Sm 2 Ni 3 Si 5 , and Nd 2 Ni 3 Si 5 , respectively, at 4.4 K in a field of 45 kG). These materials have, to the best of our knowledge, the largest positive GMR reported ever for any bulk polycrystalline compounds. The magnitude of MR does not correlate with the rare earth magnetic moments. We believe that the structure of these materials, which can be considered as a naturally occurring multilayer of wavy planes of rare earth atoms separated by Ni endash Si network, plays a role. The isothermal MR of other members of this series (R=Pr,Dy,Ho) exhibits a maximum and a minimum, below their respective T N close-quote s. We interpret these in terms of a metamagnetic transition and short-range ferromagnetic correlations. The short-range ferromagnetic correlations seem to be dominant in the temperature region just above T N . copyright 1997 American Institute of Physics

  6. Colorectal cancer cell-derived exosomes containing miR-10b regulate fibroblast cells via the PI3K/Akt pathway.

    Science.gov (United States)

    Dai, Guangyao; Yao, Xiaoguang; Zhang, Yubin; Gu, Jianbin; Geng, Yunfeng; Xue, Fei; Zhang, Jingcheng

    2018-04-01

    Cancer-associated fibroblasts (CAFs) contribute to the proliferation of colorectal cancer(CRC) cells. However, the mechanism by which CAFs develop in the tumor microenvironment remains unknown. Exosomes may be involved in activating CAFs. Using a miRNA expression profiling array, we determined the miRNA expression profile of secretory exosomes in CRC cells and then identified potential miRNAs with significant differential expression compared to normal cells via enrichment analysis. Predicted targets of candidate miRNAs were then assessed via bioinformatics analysis. Realtime qPCR, western blot, and cell cycle analyses were performed to evaluate the role of candidate exosomal miRNAs. Luciferase reporter assays were applied to confirm whether candidate exosomal miRNAs control target pathway expression. A CRC xenograft mouse model was constructed to evaluate tumor growth in vivo. Exosomes from CRC cells contained significantly higher levels of miR-10b than did exosomes from normal colorectal epithelial cells. Moreover, exosomes containing miR-10b were transferred to fibroblasts. Bioinformatics analysis identified PIK3CA, as a potential target of miR-10b. Luciferase reporter assays confirmed that miR-10b directly inhibited PIK3CA expression. Co-culturing fibroblasts with exosomes containing miR-10b significantly suppressed PIK3CA expression and decreased PI3K/Akt/mTOR pathway activity. Finally, exosomes containing miR-10b reduced fibroblast proliferation but promoted expression of TGF-β and SM α-actin, suggesting that exosomal miR-10b may activate fibroblasts to become CAFs that express myofibroblast markers. These activated fibroblasts were able to promote CRC growth in vitro and in vivo. CRC-derived exosomes actively promote disease progression by modulating surrounding stromal cells, which subsequently acquire features of CAFs. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  7. Synthesis of (3R)-acetoin and 2,3-butanediol isomers by metabolically engineered Lactococcus lactis

    DEFF Research Database (Denmark)

    Kandasamy, Vijayalakshmi; Liu, Jianming; Dantoft, Shruti Harnal

    2016-01-01

    -BDO) and (2R,3R)-butanediol (R-BDO). Efficient production of (3R)-acetoin was accomplished using a strain where the competing lactate, acetate and ethanol forming pathways had been blocked. By introducing different alcohol dehydrogenases into this strain, either EcBDH from Enterobacter cloacae or SadB from......The potential that lies in harnessing the chemical synthesis capabilities inherent in living organisms is immense. Here we demonstrate how the biosynthetic machinery of Lactococcus lactis, can be diverted to make (3R)-acetoin and the derived 2,3-butanediol isomers meso-(2,3)-butanediol (m...... Achromobacter xylosooxidans, it was possible to achieve high-yield production of m-BDO or R-BDO respectively. To achieve biosustainable production of these chemicals from dairy waste, we transformed the above strains with the lactose plasmid pLP712. This enabled efficient production of (3R)-acetoin, m-BDO and R...

  8. 5S rRNA-derived and tRNA-derived SINEs in fruit bats.

    Science.gov (United States)

    Gogolevsky, Konstantin P; Vassetzky, Nikita S; Kramerov, Dmitri A

    2009-05-01

    Most short retroposons (SINEs) descend from cellular tRNA of 7SL RNA. Here, four new SINEs were found in megabats (Megachiroptera) but neither in microbats nor in other mammals. Two of them, MEG-RS and MEG-RL, descend from another cellular RNA, 5S rRNA; one (MEG-T2) is a tRNA-derived SINE; and MEG-TR is a hybrid tRNA/5S rRNA SINE. Insertion locus analysis suggests that these SINEs were active in the recent fruit bat evolution. Analysis of MEG-RS and MEG-RL in comparison with other few 5S rRNA-derived SINEs demonstrates that the internal RNA polymerase III promoter is their most invariant region, while the secondary structure is more variable. The mechanisms underlying the modular structure of these and other SINEs as well as their variation are discussed. The scenario of evolution of MEG SINEs is proposed.

  9. Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load.

    Science.gov (United States)

    Karlsson, Ulf; Antonsson, Liselotte; Ljungberg, Bengt; Medstrand, Patrik; Esbjörnsson, Joakim; Jansson, Marianne; Gisslen, Magnus

    2012-09-10

    To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS). HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4 T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1 or BLT1). All isolates from both plasma and CSF utilized CCR5 and/or CXCR4. However, the ability to use both CCR3 and CCR5 (R3R5) was more pronounced in CSF isolates and correlated with high CSF viral load and low CD4 T-cell count. Notably, four out of five CSF isolates of subtype C origin exhibited CXCR6 use, which coincided with high CSF viral load despite preserved CD4 T-cell counts. The use of other alternative coreceptors was less pronounced. Dual-tropic R3R5 HIV-1 isolates in CSF coincide with high CSF viral load and low CD4 T-cell counts. Frequent CXCR6 use by CSF-derived subtype C isolates indicates that subtype-specific differences in coreceptor use may exist that will not be acknowledged when assessing plasma virus isolates. The findings may also bare relevance for HIV-1 replication within the CNS, and consequently, for the neuropathogenesis of AIDS.

  10. Substituted N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamides: potent anticonvulsants that affect frequency (use) dependence and slow inactivation of sodium channels.

    Science.gov (United States)

    Lee, Hyosung; Park, Ki Duk; Torregrosa, Robert; Yang, Xiao-Fang; Dustrude, Erik T; Wang, Yuying; Wilson, Sarah M; Barbosa, Cindy; Xiao, Yucheng; Cummins, Theodore R; Khanna, Rajesh; Kohn, Harold

    2014-07-24

    We prepared 13 derivatives of N-(biphenyl-4'-yl)methyl (R)-2-acetamido-3-methoxypropionamide that differed in type and placement of a R-substituent in the terminal aryl unit. We demonstrated that the R-substituent impacted the compound's whole animal and cellular pharmacological activities. In rodents, select compounds exhibited excellent anticonvulsant activities and protective indices (PI=TD50/ED50) that compared favorably with clinical antiseizure drugs. Compounds with a polar, aprotic R-substituent potently promoted Na+ channel slow inactivation and displayed frequency (use) inhibition of Na+ currents at low micromolar concentrations. The possible advantage of affecting these two pathways to decrease neurological hyperexcitability is discussed.

  11. Inhibition of adenocarcinoma TA3 ascites tumor growth by rifamycin derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, A M; Tenforde, T S; Calvin, M; Bissell, M J; Tischler, A N; Bennett, E L

    1978-01-01

    A growth inhibitory effect on adenocarcinoma TA3 ascites tumors in LAF/sub 1//J mice resulted from the repeated IP administration of subtoxic doses of 3 rifamycin derivatives: rifampicin (Rif)/sup 1/, dimethylbenzyldesmethylrifampicin (DMB), and rifazone-8/sub 2/ (R-8/sub 2/). A high-viscosity methylcellulose vehicle was found to be essential for obtaining a uniform drug suspension and a significant antitumor effect by the least water soluble derivatives, DMB and and R-8/sub 2/. The more hydrophilic derivative, Rif, was found to have a comparable growth inhibitory effect on TA3 cells when prepared in 0.9% NaCl solution with or without added methylcellulose. Oral or SC drug injections did not have an antitumor effect. The results of this study point to the importance of vehicle and route of administration in chemotherapy trials with these compounds.

  12. Serotonergic and dopaminergic activities of rigidified (R)-aporphine derivatives.

    Science.gov (United States)

    Linnanen, T; Brisander, M; Mohell, N; Johansson, A M

    2001-02-12

    Novel rigidified (R)-aporphine derivatives were synthesized from (R)-1,11-carbonylaporphine by ring expansion reactions. The structures of the novel analogues were assigned by NMR spectroscopy and X-ray crystallography. The compounds showed moderate affinities and selectivities at serotonin S-HT1A and 5-HT7 and dopamine D2A receptors.

  13. Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r.

    Science.gov (United States)

    Björn, Camilla; Mahlapuu, Margit; Mattsby-Baltzer, Inger; Håkansson, Joakim

    2016-07-01

    Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing ≥99% of microorganisms in vitro, was in the range of 3-50μg/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-α) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400μg/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. R3-R4 deletion in the PRNP gene is associated with Creutzfeldt-Jakob disease (CJD)

    Energy Technology Data Exchange (ETDEWEB)

    Cervenakova, L.; Brown, P.; Nagle, J. [and others

    1994-09-01

    There are conflicting reports on the association of deletions in the PRNP gene on chromosome 20 with CJD, a rapidly progressive fatal spongiform encephalopathy. We accumulated data suggesting that a deletion of R3-R4 type (parts of the third and fourth repeats are deleted from the area of four repeating 24 bp sequences in the 5{prime} region of the gene) is causing CJD. Screening of 129 unaffected control individuals demonstrated presence of a deletion of R2 type in four (1.55% of the studied chromosomes), but none of them had the R3-R4 type. Of 181 screened patients with spongiform encephalopathies, two had a deletion of R3-R4 type with no other mutations in the coding sequence. Both patients had a classical rapidly progressive dementing disease and diffuse spongiform degeneration, and both cases were apparently sporadic. The same R3-R4 type of deletion was detected in three additional neuropathologically confirmed spongiform encephalopathy patients, of which two had other known pathogenic mutations in the PRNP gene: at codon 178 on the methionine allele exhibiting the phenotype of fatal familial insomnia, and codon 200 causing CJD with severe dementia; the third was a patient with iatrogenic CJD who developed the disease after treatment with growth hormone extracted from cadaveric human pituitary glands. In all cases the deletion coincided with a variant sequence at position 129 coding for methionine.

  15. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

    Science.gov (United States)

    Glendinning, John I; Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F; Vasselli, Joseph R; Sclafani, Anthony

    2015-09-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. Copyright © 2015 the American Physiological Society.

  16. Experimental and computational thermochemistry of 1,4-benzodioxan and its 2-R derivatives

    International Nuclear Information System (INIS)

    Matos, M. Agostinha R.; Sousa, Clara C.S.; Morais, Victor M.F.

    2008-01-01

    The standard molar energies of combustion, at T = 298.15 K, of crystalline 1,4-benzodioxan-2-carboxylic acid and 1,4-benzodioxan-2-hydroxymethyl were measured by static bomb calorimetry in an oxygen atmosphere. The standard molar enthalpies of sublimation, at T = 298.15 K, were obtained by Calvet microcalorimetry. These values were used to derive the standard molar enthalpies of formation of the compounds in the gas phase at T = 298.15 K: 1,4-benzodioxan-2-carboxylic acid -(547.7 ± 3.0) kJ . mol -1 and 1,4-benzodioxan-2-hydroxymethyl -(374.2 ± 2.3) kJ . mol -1 . In addition, density functional theory calculations using the B3LYP hybrid exchange-correlation energy functional with extended basis sets, 6-311G** and cc-pVTZ, have been performed for the compounds studied. We have also tested two more accurate computational procedures involving multiple levels of electron structure theory in order to get reliable estimates of the thermochemical parameters of the compounds studied. The agreement between experiment and theory gives confidence to estimate the enthalpies of formation of other 2-R derivatives of 1,4-benzodioxan (R = -CH 2 COOH, -OH, -COCH 3 , -CHO, -CH 3 , -CN, and -NO 2 )

  17. Electronic and conformational properties of 2,3-benzodiazepine derivates

    International Nuclear Information System (INIS)

    Pelaggi, M.; Girlanda, R.; Chimirri, A.; Gitto, R.

    1996-01-01

    The molecular geometric and electronic structures of 2,3-benzodiazepine derivates have been studied by means of the MNDO-PM3 method. A number of electronic properties have been computed and examined in order to find indication of the role of the electronic characteristics of the different molecules and their pharmacological properties. Theoretical data indicate that both electronic and structural properties appear responsible for the varying degree of anticonvulsant activity exhibited by compounds 1-4

  18. Electronic and conformational properties of 2,3-benzodiazepine derivates

    Energy Technology Data Exchange (ETDEWEB)

    Pelaggi, M.; Girlanda, R. [Messina Univ. (Italy). Dip. di Fisica della Materia e Fisica dell`Ambiente; Chimirri, A.; Gitto, R. [Messina Univ. (Italy). Dip. Farmaco-Chimico

    1996-04-01

    The molecular geometric and electronic structures of 2,3-benzodiazepine derivates have been studied by means of the MNDO-PM3 method. A number of electronic properties have been computed and examined in order to find indication of the role of the electronic characteristics of the different molecules and their pharmacological properties. Theoretical data indicate that both electronic and structural properties appear responsible for the varying degree of anticonvulsant activity exhibited by compounds 1-4.

  19. Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

    OpenAIRE

    Mishra, Om P.; Simmons, Nicholas; Tyagi, Sonia; Pietrofesa, Ralph; Shuvaev, Vladimir V.; Valiulin, Roman A.; Heretsch, Philipp; Nicolaou, K. C.; Christofidou-Solomidou, Melpo

    2013-01-01

    Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC50 = 292.17 ± 27.71 μM and 331.94 ± 21.21 μM, respectively) which compared well with...

  20. A New Type of Synthesis of 1,2,3-Thiadiazole and 1,2,3-Diazaphosphole Derivatives Via-Hurd-Mori Cyclization

    Directory of Open Access Journals (Sweden)

    Mona A. Hosny

    2012-01-01

    Full Text Available We present a short and efficient synthesis of the title compounds starting with cheap and readily available camphor and derivatives of acetophenone. The optimized sequence allows the large-scale preparation of this new type of synthesis in a few steps. New 1,2,3-thiadiazole and 1,2,3-diazaphosphole derivatives 11-20, were prepared from the ketones 1-5 via the corresponding semicarbazones 6-10. The Hurd-Mori and Lalezari methods were used, respectively, for the preparation of these 1,2,3-thiadiazole and 1,2,3-diazaphospholene derivatives. These derivatives exhibit anticancer effect due to their high potential biological activity.

  1. Identification and Characterization of an Antifungal Protein, AfAFPR9, Produced by Marine-Derived Aspergillus fumigatus R9.

    Science.gov (United States)

    Rao, Qi; Guo, Wenbin; Chen, Xinhua

    2015-05-01

    A fungal strain, R9, was isolated from the South Atlantic sediment sample and identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 μg/disc, respectively. Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion and denaturant tolerance. The iodoacetamide assay showed that the disulfide bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity against C. gloeosporioides, T. viride, and A. longipes. These results reveal the antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus fumigatus and indicated its potential application in controlling plant pathogenic fungi.

  2. A simple derivation of r* for curved exponential families

    DEFF Research Database (Denmark)

    Jensen, Jens Ledet

    1997-01-01

    For curved exponential families we consider modified likelihood ratio statistics of the form rL = r + log (u/r)/r, where r is the signed root of the likelihood ratio statistic. We are testing a one-dimensional hypothesis, but in order to specify approximate ancillary statistics we consider the test...... as one in a series of tests. By requiring asymptotic independence and asymptotic normality of the test statistics in a large deviation region there is a particular choice of the statistic u which suggests itself. The derivation of this result is quite simple, only involving a standard saddlepoint...... approximation followed by a transformation. We give explicit formulas for the statistic u, and include a discussion of the case where some coordinates of the underlying variable are lattice....

  3. Synthesis and Biological Activity of 3-[Phenyl(1,3-thiazol-2-yl-amino]propanoic Acids and Their Derivatives

    Directory of Open Access Journals (Sweden)

    Vytautas Mickevičius

    2013-12-01

    Full Text Available New N,N-disubstituted β-amino acids and their derivatives with thiazole, aromatic, and heterocyclic substituents were synthesized from N-phenyl-N-thiocarbamoyl-β-alanine by the Hantzsch method; derivatives with hydrazone fragments were also obtained. Some of the synthesized compounds exhibited discrete antimicrobial activity, and 3-[(4-oxo-4,5-dihydro-1,3-thiazol-2-yl(phenylamino]propanoic acid was found to promote rapeseed growth and to increase seed yield and oil content.

  4. Research on the Solid State Fermentation of Jerusalem Artichoke Pomace for Producing R,R-2,3-Butanediol by Paenibacillus polymyxa ZJ-9.

    Science.gov (United States)

    Cao, Can; Zhang, Li; Gao, Jian; Xu, Hong; Xue, Feng; Huang, Weiwei; Li, Yan

    2017-06-01

    R,R-2,3-butanediol (R,R-2,3-BD) was produced by Paenibacillus polymyxa ZJ-9, which was capable of utilizing inulin without previous hydrolysis. The Jerusalem artichoke pomace (JAP) derived from the conversion of Jerusalem artichoke powder into inulin extract, which was usually used for biorefinery by submerged fermentation (SMF), was utilized in solid state fermentation (SSF) to produce R,R-2,3-BD. In this study, the fermentation parameters of SSF were optimized and determined in flasks. A novel bioreactor was designed and assembled for the laboratory scale-up of SSF, with a maximum yield of R,R-2,3-BD (67.90 g/kg (JAP)). This result is a 36.3% improvement compared with the flasks. Based on the same bath of Jerusalem artichoke powder, the total output of R,R-2,3-BD increased by 38.8% for the SSF of JAP combined with the SMF of inulin extraction. Overall, the utilization of JAP for R,R-2,3-BD production was beneficial to the comprehensive utilization of Jerusalem artichoke tuber.

  5. Structure, magnetism, and transport of single-crystalline R NiSi3 (R = Y, Gd-Tm, Lu)

    Science.gov (United States)

    Arantes, Fabiana R.; Aristizábal-Giraldo, Deisy; Masunaga, Sueli H.; Costa, Fanny N.; Ferreira, Fabio F.; Takabatake, Toshiro; Mendonça-Ferreira, Leticie; Ribeiro, Raquel A.; Avila, Marcos A.

    2018-04-01

    We report on the physical properties of the intermetallic series R NiSi3 (R =Y , Gd-Tm, Lu). High quality single crystals with platelike morphology were grown using the Sn flux method. X-ray powder diffraction data show that this series crystallizes in the orthorhombic space group Cmmm, and Laue patterns indicate that the b axis remains perpendicular to the plane of the plates. Magnetization measurements show anisotropic antiferromagnetic ground states for R = Gd-Tm with Néel temperatures ranging from TN=2.6 K (TmNiSi3) up to 32.2 K (TbNiSi3), as well as metamagnetic transitions that in some cases appear together with hysteresis (TbNiSi3,DyNiSi3, and HoNiSi3). The easy axis changes from a axis to b axis on going from R = Gd-Ho to R = Er-Tm. All transitions from antiferromagnetic to paramagnetic states are clearly marked by sharp peaks in specific heat as well as in the derivative of resistivity measurements, which show metallic temperature dependence for all compounds and residual values in the range of 1 μ Ω cm . DyNiSi3 has two close phase transitions, while HoNiSi3 presents distinct critical temperatures for applied fields in the a or c directions (10.4 and 6.3 K, respectively), pointing to possible component-specific ordering of the local magnetic moments.

  6. Total synthesis of (3S, 5R, 3'S, 5'R)-capsorubin

    International Nuclear Information System (INIS)

    Frederico, Daniel; Constantino, Mauricio G.; Donate, Paulo M.

    2009-01-01

    The total synthesis of enantiomerically enriched (3S, 5R, 3'S, 5'R)-capsorubin (1) by aldol condensation of (1R, 4S)-1-(4-hydroxy-1,2,2-trimethyl-cyclopentyl)ethanone (2a) and crocetindial (3) is described. An alternative, short eight-step synthesis of the optically active compound 2a (ee 89%) is also reported. (author)

  7. Configurational Reassignment and Improved Preparation of the Competitive IL-6 Receptor Antagonist 20R,21R-Epoxyresibufogenin-3-formate

    Science.gov (United States)

    Boos, Terrence L.; Cheng, Kejun; Greiner, Elisabeth; Deschamps, Jeffrey R.; Jacobson, Arthur E.; Rice, Kenner C.

    2012-01-01

    20R,21R-Epoxyresibufogenin-3-formate (1) and 20S,21S-epoxyresibufogenin-3-formate (2) were synthesized from commercial resibufogenin (3) using known procedures. The major product (1) was dextrorotatory, as was the major product from the reported synthesis of epoxyresibufogenin-3-formate; however, the literature (+)-compound was assigned the 20S,21S-configuration based on NMR data. We have now unequivocally determined, using single-crystal X-ray structure analyses of the major and minor products of the synthesis and of their derivatives, that the major product from the synthesis was (+)-20R,21R-epoxyresibufogenin-3-formate (1). Our minor synthetic product was determined to have the (-)-20S,21S-configuration (2). The (+)-20R,21R-compound 1 has been found to have high affinity for the IL-6 receptor and to act as an IL-6 antagonist. A greatly improved synthesis of 1 was achieved through oxidation of preformed resibufogenin-3-formate. This has enabled us to prepare, from the very expensive commercial resibufogenin, considerably larger quantities of 1, the only known non-peptide small molecule IL-6 antagonist. PMID:22360661

  8. Synthesis and antimalarial activity evaluation of 3-(3-(7-chloroquinolin-4-ylaminopropyl-1,3-thiazinan-4-one derivatives

    Directory of Open Access Journals (Sweden)

    Mukesh Kumar Kumawat

    2016-09-01

    Full Text Available Some novel derivatives of 3-(3-(7-chloroquinolin-4-ylaminopropyl-1,3-thiazinan-4-one were synthesized and characterized by their physical and spectral data. All the synthesized compounds were subsequently screened for in vitro antimalarial activity against chloroquine sensitive strain of Plasmodium falciparum (RKL-2 employing chloroquine as the reference drug. Most of the synthesized compounds exhibited mild to moderate susceptibilities towards the parasite in comparison to the standard. It was found that antimalarial activity of 3-(3-(7-chloroquinolin-4-ylaminopropyl-2-(4-bromophenyl-1,3-thiazinan-4-one was marginally superior than all the compounds evaluated.

  9. RNi{sub 8}Si{sub 3} (R=Gd,Tb): Novel ternary ordered derivatives of the BaCd{sub 11} type

    Energy Technology Data Exchange (ETDEWEB)

    Pani, M., E-mail: marcella@chimica.unige.it [Department of Chemistry, University of Genova, Via Dodecaneso 31, 16146 Genova (Italy); Institute SPIN-CNR, Corso Perrone 24, 16152 Genova (Italy); Morozkin, A.V. [Department of Chemistry, Moscow State University, Leninskie Gory, House 1, Building 3, Moscow, GSP-2 119992 (Russian Federation); Yapaskurt, V.O. [Department of Petrology, Geological Faculty, Moscow State University, Leninskie Gory, Moscow 119992 (Russian Federation); Provino, A.; Manfrinetti, P. [Department of Chemistry, University of Genova, Via Dodecaneso 31, 16146 Genova (Italy); Institute SPIN-CNR, Corso Perrone 24, 16152 Genova (Italy); Nirmala, R. [Indian Institute of Technology Madras, Chennai 600036 (India); Malik, S.K. [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Natal 59082-970 (Brazil)

    2016-01-15

    BaCd{sub 11} structure. The large R–R interatomic distances mediated via Ni–Si network lead to a weak magnetism in both compounds. - Highlights: • Novel RNi{sub 8}Si{sub 3} (R=Gd, Tb) compounds have been synthesized and characterized. • GdNi{sub 8}Si{sub 3} and TbNi{sub 8}Si{sub 3} are isostructural compounds, belonging to a new monoclinic structure type. • The monoclinic GdNi{sub 8}Si{sub 3} type is an ordered derivative of the tetragonal BaCd{sub 11} type. • The large R–R interatomic distances mediated via Ni–Si network lead to a weak magnetism. • Both compounds GdNi{sub 8}Si{sub 3} and TbNi{sub 8}Si{sub 3} show antiferromagnetic-like order around 3 K.

  10. miR-758-5p regulates cholesterol uptake via targeting the CD36 3'UTR.

    Science.gov (United States)

    Li, Bi-Rong; Xia, Lin-Qin; Liu, Jing; Liao, Lin-Ling; Zhang, Yang; Deng, Min; Zhong, Hui-Juan; Feng, Ting-Ting; He, Ping-Ping; Ouyang, Xin-Ping

    2017-12-09

    miR-758-3p plays an important role via regulting ABCA1-mediated cholesterol efflux in atherosclerosis. However, the mechanism of miR-758-5p in cholesterol metabolism is still unclear. Here, we revealed that miR-758-5p decreased total cholesterol accumulation in THP-1 macrophage derived foam cells through markedly reducing cholesterol uptake, and no effect on the cholesterol efflux. Interestingly, computational analysis suggests that CD36 may be a target gene of miR-758-5p. Our study further demonstrated that miR-758-5p decreased CD36 expression at both protein and mRNA levels via targeting the CD36 3'UTR in THP-1 macrophage derived foam cells. The present present study concluded that miR-758-5p decreases lipid accumulation of foam cell via regulating CD36-mediated the cholesterol uptake. Therefore, targeting miR-758-5p may offer a promising strategy to treat atherosclerotic vascular disease. Copyright © 2017. Published by Elsevier Inc.

  11. Synthesis and fluorosolvatochromism of 3-arylnaphtho[1,2-b]quinolizinium derivatives

    Directory of Open Access Journals (Sweden)

    Phil M. Pithan

    2016-05-01

    Full Text Available Cationic biaryl derivatives were synthesized by Suzuki–Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids. The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained by a charge shift (CS in the excited state and subsequent solvent relaxation. Furthermore, the polarity of protic polar and aprotic polar solvents affects the emission energy to different extent, which indicates a major influence of hydrogen bonding on the stabilization of the ground and excited states.

  12. Production of (R)-3-hydroxybutyric acid by fermentation and bioconversion processes with Azohydromonas lata.

    Science.gov (United States)

    Ugwu, Charles U; Tokiwa, Yutaka; Ichiba, Toshio

    2011-06-01

    Feasibility of producing (R)-3-hydroxybutyric acid ((R)-3-HB) using wild type Azohydromonas lata and its mutants (derived by UV mutation) was investigated. A. lata mutant (M5) produced 780 m g/l in the culture broth when sucrose was used as the carbon source. M5 was further studied in terms of its specificity with various bioconversion substrates for production of (R)-3-HB. (R)-3-HB concentration produced in the culture broth by M5 mutant was 2.7-fold higher than that of the wild type strain when sucrose (3% w/v) and (R,S)-1,3-butanediol (3% v/v) were used as carbon source and bioconversion substrate, respectively. Bioconversion of resting cells (M5) with glucose (1% v/w), ethylacetoacetate (2% v/v), and (R,S)-1,3-butanediol (3% v/v), resulted in (R)-3-HB concentrations of 6.5 g/l, 7.3g/l and 8.7 g/l, respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for activity toward monoamine transporters.

    Science.gov (United States)

    Kharkar, Prashant S; Batman, Angela M; Zhen, Juan; Beardsley, Patrick M; Reith, Maarten E A; Dutta, Aloke K

    2009-07-01

    A novel series of optically active molecules based on a 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol template were developed. Depending on stereochemistry, the compounds exhibit various degrees of affinity for three dopamine, serotonin, and norepinephrine transporters. These molecules have the potential for treating several neurological disorders such as drug abuse, depression, and attention deficit hyperactivity disorder.Herein we describe the synthesis and biological evaluation of a series of asymmetric 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol-based dihydroxy compounds in which the hydroxy groups are located on both the piperidine ring and the N-phenylethyl side chain. In vitro uptake inhibition data of these molecules indicate high affinity for the dopamine transporter (DAT) in addition to moderate to high affinity for the norepinephrine transporter (NET). Interestingly, compounds 9 b and 9 d exhibit affinities for all three monoamine transporters, with highest potency at DAT and NET, and moderate potency at the serotonin transporter (SERT) (K(i): 2.29, 78.4, and 155 nM for 9 b and 1.55, 14.1, and 259 nM for 9 d, respectively). Selected compounds 9 a, 9 d, and 9 d' were tested for their locomotor activity effects in mice and for their ability to occasion the cocaine-discriminative stimulus in rats. These test compounds generally exhibit a much longer duration of action than cocaine for elevating locomotor activity, and completely generalize the cocaine-discriminative stimulus in a dose-dependent manner.

  14. Magnetic properties of the tetragonal RCuGa{sub 3} (R=Pr, Nd and Gd) single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Nagalakshmi, R., E-mail: nagaphys@yahoo.com [Department of Physics, National Institute of Technology, Tiruchirappalli 6200015 (India); Kulkarni, Ruta; Dhar, S.K.; Thamizhavel, A. [DCMPMS, Tata Institute of Fundamental Research, Mumbai 400005 (India); Krishnakumar, V. [Department of Physics, Periyar University, Salem 636011 (India); Reiffers, Marian; Čurlík, Ivan [Institute of Experimental Physics, Watsonova 47, SK-040 01 Kosice (Slovakia); Department of Physics, University of Presov, 17 Novembra 1, SK-080 01 (Slovakia); Hagemann, Hans; Lovy, Dominique [Department of Physical Chemistry, University of Geneva, Geneva (Switzerland); Nallamuthu, S. [Department of Physics, National Institute of Technology, Tiruchirappalli 6200015 (India)

    2015-07-15

    Single crystals of tetragonal RCuGa{sub 3} (R=La, Pr, Nd and Gd), with BaNiSn{sub 3} type structure (space group I4 mm), have been grown by high temperature solution growth technique using Ga as flux. Their magnetic properties were determined by heat capacity and the measurement of magnetization and electrical resistivity along [100] and [001] directions. Except LaCuGa{sub 3}, the compounds order magnetically. PrCuGa{sub 3} undergoes a ferromagnetic transition with Curie temperature of 4.6 K. NdCuGa{sub 3} shows a bulk magnetic transition at 3.3 K. The data on GdCuGa{sub 3} indicate combined characteristics of spin glass and antiferromagnetic behavior at low temperatures. From the Schottky heat capacity data the crystal electric field level energy spectra have been determined. Further we have performed temperature dependent measurements of electron spin resonance (ESR) on GdCuGa{sub 3} between 11 K and room temperature. The ESR data indicate an enhancement of magnetic fluctuations associated with spin reorientation and both homogeneous and inhomogeneous thermal broadening of the linewidth. - Highlights: • RCuGa{sub 3} (R=La, Pr, Nd and Gd) single crystals were grown by flux technique. • The compounds exhibit long range magnetic ordering. • Crystal electric field levels have been derived from Schottky heat capacity. • Electron spin resonance (ESR) studies of GdCuGa{sub 3} are also discussed.

  15. Differential cytotoxic effects of 7-dehydrocholesterol-derived oxysterols on cultured retina-derived cells: Dependence on sterol structure, cell type, and density.

    Science.gov (United States)

    Pfeffer, Bruce A; Xu, Libin; Porter, Ned A; Rao, Sriganesh Ramachandra; Fliesler, Steven J

    2016-04-01

    Tissue accumulation of 7-dehydrocholesterol (7DHC) is a hallmark of Smith-Lemli-Opitz Syndrome (SLOS), a human inborn error of the cholesterol (CHOL) synthesis pathway. Retinal 7DHC-derived oxysterol formation occurs in the AY9944-induced rat model of SLOS, which exhibits a retinal degeneration characterized by selective loss of photoreceptors and associated functional deficits, Müller cell hypertrophy, and engorgement of the retinal pigment epithelium (RPE) with phagocytic inclusions. We evaluated the relative effects of four 7DHC-derived oxysterols on three retina-derived cell types in culture, with respect to changes in cellular morphology and viability. 661W (photoreceptor-derived) cells, rMC-1 (Müller glia-derived) cells, and normal diploid monkey RPE (mRPE) cells were incubated for 24 h with dose ranges of either 7-ketocholesterol (7kCHOL), 5,9-endoperoxy-cholest-7-en-3β,6α-diol (EPCD), 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), or 4β-hydroxy-7-dehydrocholesterol (4HDHC); CHOL served as a negative control (same dose range), along with appropriate vehicle controls, while staurosporine (Stsp) was used as a positive cytotoxic control. For 661W cells, the rank order of oxysterol potency was: EPCD > 7kCHOL > DHCEO > 4HDHC ≈ CHOL. EC50 values were higher for confluent vs. subconfluent cultures. 661W cells exhibited much higher sensitivity to EPCD and 7kCHOL than either rMC-1 or mRPE cells, with the latter being the most robust when challenged, either at confluence or in sub-confluent cultures. When tested on rMC-1 and mRPE cells, EPCD was again an order of magnitude more potent than 7kCHOL in compromising cellular viability. Hence, 7DHC-derived oxysterols elicit differential cytotoxicity that is dose-, cell type-, and cell density-dependent. These results are consistent with the observed progressive, photoreceptor-specific retinal degeneration in the rat SLOS model, and support the hypothesis that 7DHC-derived oxysterols are causally linked to that

  16. 3D-QSAR Investigation of Synthetic Antioxidant Chromone Derivatives by Molecular Field Analysis

    Directory of Open Access Journals (Sweden)

    Jiraporn Ungwitayatorn

    2008-02-01

    Full Text Available A series of 7-hydroxy, 8-hydroxy and 7,8-dihydroxy synthetic chromone derivatives was evaluated for their DPPH free radical scavenging activities. A training set of 30 synthetic chromone derivatives was subject to three-dimensional quantitative structure-activity relationship (3D-QSAR studies using molecular field analysis (MFA. The substitutional requirements for favorable antioxidant activity were investigated and a predictive model that could be used for the design of novel antioxidants was derived. Regression analysis was carried out using genetic partial least squares (G/PLS method. A highly predictive and statistically significant model was generated. The predictive ability of the developed model was assessed using a test set of 5 compounds (r2pred = 0.924. The analyzed MFA model demonstrated a good fit, having r2 value of 0.868 and crossvalidated coefficient r2cv value of 0.771.

  17. Energy transfer in LaF3: R3+, Pr3+ (where R = Nd, Dy)

    International Nuclear Information System (INIS)

    Reddy, B.R.; Venkateswarlu, P.

    1982-01-01

    Fluorescence is observed for 1 D 2 levels of Pr 3+ on exciting the higher lying level 3 P 0 in doubly doped systems LaF 3 : R 3+ , Pr 3+ (R = Nd or Dy) but not in LaF 3 :Pr 3+ . From the recorded excitation spectra, and the measured decay times, it has been found that the drain mechanism of population to 1 D 2 levels is caused in doubly doped systems by ion-pair relaxation between Pr 3+ ( 3 P 0 -- 1 D 2 ) and Nd 3+ (Z-X) or Dy 3+ (Z-Y) ions

  18. Resveratrol, Acetyl-Resveratrol, and Polydatin Exhibit Antigrowth Activity against 3D Cell Aggregates of the SKOV-3 and OVCAR-8 Ovarian Cancer Cell Lines

    OpenAIRE

    Hogg, Simon J.; Chitcholtan, Kenny; Hassan, Wafaa; Sykes, Peter H.; Garrill, Ashley

    2015-01-01

    Resveratrol has aroused significant scientific interest as it has been claimed that it exhibits a spectrum of health benefits. These include effects as an anti-inflammatory and an antitumour compound. The purpose of this study was to investigate and compare any potential antigrowth effects of resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, on 3D cell aggregates of the EGFR/Her-2 positive and negative ovarian cancer cell lines SKOV-3 and OVCAR-8, respectively. Results...

  19. The impact of R1and R3a genes on tuber resistance to late blight of the potato breeding clones

    Directory of Open Access Journals (Sweden)

    Zoteyeva Nadezhda

    2016-04-01

    Full Text Available Potato breeding clones were evaluated for resistance to late blight (agent Phytophthora infestans using tuber inoculation tests and for presence of the resistance alleles of R1 and R3a genes in polymerase chain reaction tests. Among clones tested those expressing high, moderate and low resistance were identified. The data were analysed for the impact of R1 and R3a genes on tuber resistance to late blight in tested plant material. In previous evaluations performed on smaller amount of clones the tuber resistance levels significantly depended on presence/absence of the resistance allele of R3a gene and did not depend on presence of R1 gene allele. In the current study the statistical analyses did not prove the significant difference in resistance levels depending on presence of the resistance alleles, neither of R1 gene, nor of R3a gene. Tuber resistant clones bearing R3a gene resistance alleles still noticeably prevailed over the clones bearing the alleles of R1 gene as well as over the clones bearing the no resistance alleles of both genes. In several cases the resistance of clones with detected resistance allele of R1 gene was higher compared to those derived from the same crosses and showing amplification of the allele of R3a gene or those with no resistance alleles. Clones accumulating the resistance alleles of both (R1 and R3a genes expressed high tuber resistance accompanied by necrotic reaction.

  20. A 3'-untranslated region (3'UTR) induces organ adhesion by regulating miR-199a* functions.

    Science.gov (United States)

    Lee, Daniel Y; Shatseva, Tatiana; Jeyapalan, Zina; Du, William W; Deng, Zhaoqun; Yang, Burton B

    2009-01-01

    Mature microRNAs (miRNAs) are single-stranded RNAs of 18-24 nucleotides that repress post-transcriptional gene expression. However, it is unknown whether the functions of mature miRNAs can be regulated. Here we report that expression of versican 3'UTR induces organ adhesion in transgenic mice by modulating miR-199a* activities. The study was initiated by the hypothesis that the non-coding 3'UTR plays a role in the regulation of miRNA function. Transgenic mice expressing a construct harboring the 3'UTR of versican exhibits the adhesion of organs. Computational analysis indicated that a large number of microRNAs could bind to this fragment potentially including miR-199a*. Expression of versican and fibronectin, two targets of miR-199a*, are up-regulated in transgenic mice, suggesting that the 3'UTR binds and modulates miR-199a* activities, freeing mRNAs of versican and fibronectin from being repressed by miR-199a*. Confirmation of the binding was performed by PCR using mature miR-199a* as a primer and the targeting was performed by luciferase assays. Enhanced adhesion by expression of the 3'UTR was confirmed by in vitro assays. Our results demonstrated that upon arrival in cytoplasm, miRNA activities can be modulated locally by the 3'UTR. Our assay may be developed as sophisticated approaches for studying the mutual regulation of miRNAs and mRNAs in vitro and in vivo. We anticipate that expression of the 3'UTR may be an approach in the development of gene therapy.

  1. Identifying small RNAs derived from maternal- and somatic-type rRNAs in zebrafish development.

    Science.gov (United States)

    Locati, Mauro D; Pagano, Johanna F B; Abdullah, Farah; Ensink, Wim A; van Olst, Marina; van Leeuwen, Selina; Nehrdich, Ulrike; Spaink, Herman P; Rauwerda, Han; Jonker, Martijs J; Dekker, Rob J; Breit, Timo M

    2018-02-09

    rRNAs are non-coding RNAs present in all prokaryotes and eukaryotes. In eukaryotes there are four rRNAs: 18S, 5.8S, 28S, originating from a common precursor (45S), and 5S. We have recently discovered the existence of two distinct developmental types of rRNA: a maternal-type, present in eggs and a somatic-type, expressed in adult tissues. Lately, next-generation sequencing has allowed the discovery of new small-RNAs deriving from longer non-coding RNAs, including small-RNAs from rRNAs (srRNAs). Here, we systemically investigated srRNAs of maternal- or somatic-type 18S, 5.8S, 28S, with small-RNAseq from many zebrafish developmental stages. We identified new srRNAs for each rRNA. For 5.8S, we found srRNA consisting of the 5' or 3' halves, with only the latter having different sequence for the maternal- and somatic-types. For 18S, we discovered 21 nt srRNA from the 5' end of the 18S rRNA with a striking resemblance to microRNAs; as it is likely processed from a stem-loop precursor and present in human and mouse Argonaute-complexed small-RNA. For 28S, an abundant 80 nt srRNA from the 3' end of the 28S rRNA was found. The expression levels during embryogenesis of these srRNA indicate they are not generated from rRNA degradation and might have a role in the zebrafish development.

  2. Synthesis and fungicidal activity of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline.

    Science.gov (United States)

    Lei, Peng; Zhang, Xuebo; Xu, Yan; Xu, Gaofei; Liu, Xili; Yang, Xinling; Zhang, Xiaohe; Ling, Yun

    2016-01-01

    Take-all of wheat, caused by the soil-borne fungus Gaeumannomyces graminis var. tritici, is one of the most important and widespread root diseases. Given that take-all is still hard to control, it is necessary to develop new effective agrochemicals. Pyrazole derivatives have been often reported for their favorable bioactivities. In order to discover compounds with high fungicidal activity and simple structures, 1,2,3,4-tetrahydroquinoline, a biologically active group of natural products, was introduced to pyrazole structure. A series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were synthesized, and their fungicidal activities were evaluated. The bioassay results demonstrated that the title compounds displayed obvious fungicidal activities at a concentration of 50 μg/mL, especially against V. mali, S. sclerotiorum and G. graminis var. tritici. The inhibition rates of compounds 10d, 10e, 10h, 10i and 10j against G. graminis var. tritici were all above 90 %. Even at a lower concentration of 16.7 μg/mL, compounds 10d and 10e exhibited satisfied activities of 100 % and 94.0 %, respectively. It is comparable to that of the positive control pyraclostrobin with 100 % inhibition rate. A series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were synthesized and their structures were confirmed by (1)H NMR, (13)C NMR, IR spectrum and HRMS or elemental analysis. The crystal structure of compound 10g was confirmed by X-ray diffraction. Bioassay results indicated that all title compounds exhibited obvious fungicidal activities. In particular, compounds 10d and 10e showed comparable activities against G. graminis var. tritici with the commercial fungicide pyraclostrobin at the concentration of 16.7 μg/mL.Graphical abstractA series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were designed and synthesized. Bioassay results indicated that all these compounds exhibited obvious fungicidal activities.

  3. Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free Radical-Scavenging Activity.

    Science.gov (United States)

    Li, Qing; Sun, Xueqi; Gu, Guodong; Guo, Zhanyong

    2018-03-28

    Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating "click reaction" with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC 50 radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains.

  4. A R2R3-MYB transcription factor regulates the flavonol biosynthetic pathway in a traditional Chinese medicinal plant, Epimedium sagittatum

    Directory of Open Access Journals (Sweden)

    Wenjun Huang

    2016-07-01

    Full Text Available Flavonols as plant secondary metabolites with vital roles in plant development and defense against UV light, have been demonstrated to be the main bioactive components in the genus Epimedium plants, several species of which are used as materials for Herba Epimedii, an important traditional Chinese medicine. The flavonol biosynthetic pathway genes had been already isolated from E. sagittatum, but a R2R3-MYB transcription factor regulating the flavonol synthesis has not been functionally characterized so far in Epimedium plants. In this study, we isolated and characterized the R2R3-MYB transcription factor EsMYBF1 involved in regulation of the flavonol biosynthetic pathway from E. sagittatum. Sequence analysis indicated that EsMYBF1 belongs to the subgroup 7 of R2R3-MYB family which contains the flavonol-specific MYB regulators identified to date. Transient reporter assay showed that EsMYBF1 strongly activated the promoters of EsF3H (flavanone 3-hydroxylase and EsFLS (flavonol synthase, but not the promoters of EsDFRs (dihydroflavonol 4-reductase and EsANS (anthocyanidin synthase in transiently transformed Nicotiana benthamiana leaves. Both yeast two-hybrid assay and transient reporter assay validated EsMYBF1 to be independent of EsTT8, or AtTT8 bHLH regulators of the flavonoid pathway as cofactors. Ectopic expression of EsMYBF1 in transgenic tobacco resulted in the increased flavonol content and the decreased anthocyanin content in flowers. Correspondingly, the structural genes involved in flavonol synthesis were upregulated in the EsMYBF1 overexpression lines, including NtCHS (chalcone synthase, NtCHI (chalcone isomerase, NtF3H and NtFLS, whereas the late biosynthetic genes of the anthocyanin pathway (NtDFR and NtANS were remarkably downregulated, compared to the controls. These results suggest that EsMYBF1 is a flavonol-specific R2R3-MYB regulator, and involved in regulation of the biosynthesis of the flavonol-derived bioactive components in E

  5. Quinoline-3-carboxamide Derivatives as Potential Cholesteryl Ester Transfer Protein Inhibitors

    Directory of Open Access Journals (Sweden)

    Jing-Kang Shen

    2012-05-01

    Full Text Available A series of novel quinoline-3-carboxamide derivatives 1017 and 2327 were designed and synthesized as cholesteryl ester transfer protein (CETP inhibitors. All of them exhibited activity against CETP. Particularly, compounds 24 and 26 displayed the best activity against CETP with the same inhibitory rate of 80.1%.

  6. The moduli space of two U(1) instantons on noncommutative $R^4$ and $R^3\\times S^1$

    OpenAIRE

    Lee, Kimyeong; Tong, David; Yi, Sangheon

    2000-01-01

    We employ the ADHM method to derive the moduli space of two instantons in U(1) gauge theory on a noncommutative space. We show by an explicit hyperK\\"ahler quotient construction that the relative metric of the moduli space of two instantons on $R^4$ is the Eguchi-Hanson metric and find a unique threshold bound state. For two instantons on $R^3\\times S^1$, otherwise known as calorons, we give the asymptotic metric and conjecture a completion. We further discuss the relationship of caloron modu...

  7. Enterovirus 71 antagonizes the antiviral activity of host STAT3 and IL-6R with partial dependence on virus-induced miR-124.

    Science.gov (United States)

    Chang, Zhangmei; Wang, Yan; Bian, Liang; Liu, Qingqing; Long, Jian-Er

    2017-12-01

    Enterovirus 71 (EV71) has caused major outbreaks of hand, foot and mouth disease. EV71 infections increase the production of many host cytokines and pro-inflammatory factors, including interleukin (IL)-6, IL-10 and COX-2. Some of these molecules could stimulate the signal transducer and activator of transcription 3 (STAT3), which plays a key role in regulating host immune responses and several viral diseases. However, the role of STAT3 in EV71 infection remains unknown. This study found that the phosphorylation levels of STAT3 (p Y705 -STAT3) are closely related to EV71 infection. Further experiments revealed that STAT3 exerts an anti-EV71 activity. However, the antiviral activity of STAT3 is partially antagonized by EV71-induced miR-124, which directly targets STAT3 mRNA. Similarly, IL-6R, the α-subunit of the IL-6 receptor complex, exhibits anti-EV71 activity and is directly targeted by the virus-induced miR-124. These results indicate that EV71 can evade host IL-6R- and STAT3-mediated antiviral activities by EV71-induced miR-124. This suggests that controlling miR-124 and the downstream targets, IL-6R and STAT3, might benefit the antiviral treatment of EV71 infection.

  8. Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free Radical-Scavenging Activity

    Directory of Open Access Journals (Sweden)

    Qing Li

    2018-03-01

    Full Text Available Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating “click reaction” with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC50 < 0.01 mg mL−1 was more efficient than that of derivatives with triazole and Vitamin C. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH and hydroxyl radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains.

  9. A 3'-untranslated region (3'UTR induces organ adhesion by regulating miR-199a* functions.

    Directory of Open Access Journals (Sweden)

    Daniel Y Lee

    Full Text Available Mature microRNAs (miRNAs are single-stranded RNAs of 18-24 nucleotides that repress post-transcriptional gene expression. However, it is unknown whether the functions of mature miRNAs can be regulated. Here we report that expression of versican 3'UTR induces organ adhesion in transgenic mice by modulating miR-199a* activities. The study was initiated by the hypothesis that the non-coding 3'UTR plays a role in the regulation of miRNA function. Transgenic mice expressing a construct harboring the 3'UTR of versican exhibits the adhesion of organs. Computational analysis indicated that a large number of microRNAs could bind to this fragment potentially including miR-199a*. Expression of versican and fibronectin, two targets of miR-199a*, are up-regulated in transgenic mice, suggesting that the 3'UTR binds and modulates miR-199a* activities, freeing mRNAs of versican and fibronectin from being repressed by miR-199a*. Confirmation of the binding was performed by PCR using mature miR-199a* as a primer and the targeting was performed by luciferase assays. Enhanced adhesion by expression of the 3'UTR was confirmed by in vitro assays. Our results demonstrated that upon arrival in cytoplasm, miRNA activities can be modulated locally by the 3'UTR. Our assay may be developed as sophisticated approaches for studying the mutual regulation of miRNAs and mRNAs in vitro and in vivo. We anticipate that expression of the 3'UTR may be an approach in the development of gene therapy.

  10. Directed Evolution of Carbonyl Reductase from Rhodosporidium toruloides and Its Application in Stereoselective Synthesis of tert-Butyl (3R,5S)-6-Chloro-3,5-dihydroxyhexanoate.

    Science.gov (United States)

    Liu, Zhi-Qiang; Wu, Lin; Zhang, Xiao-Jian; Xue, Ya-Ping; Zheng, Yu-Guo

    2017-05-10

    tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is a key intermediate of atorvastatin and rosuvastatin synthesis. Carbonyl reductase RtSCR9 from Rhodosporidium toruloides exhibited excellent activity toward tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH). For the activity of RtSCR9 to be improved, random mutagenesis and site-saturation mutagenesis were performed. Three positive mutants were obtained (mut-Gln95Asp, mut-Ile144Lys, and mut-Phe156Gln). These mutants exhibited 1.94-, 3.03-, and 1.61-fold and 1.93-, 3.15-, and 1.97-fold improvement in the specific activity and k cat /K m , respectively. Asymmetric reduction of (S)-CHOH by mut-Ile144Lys coupled with glucose dehydrogenase was conducted. The yield and enantiomeric excess of (3R,5S)-CDHH reached 98 and 99%, respectively, after 8 h bioconversion in a single batch reaction with 1 M (S)-CHOH, and the space-time yield reached 542.83 mmol L -1 h -1 g -1 wet cell weight. This study presents a new carbonyl reductase for efficient synthesis of (3R,5S)-CDHH.

  11. Two Major Bile Acids in the Hornbills, (24R,25S)-3α,7α,24-Trihydroxy-5β-cholestan-27-oyl Taurine and Its 12α-Hydroxy Derivative.

    Science.gov (United States)

    Satoh, Rika; Ogata, Hiroaki; Saito, Tetsuya; Zhou, Biao; Omura, Kaoru; Kurabuchi, Satoshi; Mitamura, Kuniko; Ikegawa, Shigeo; Hagey, Lee R; Hofmann, Alan F; Iida, Takashi

    2016-06-01

    Two major bile acids were isolated from the gallbladder bile of two hornbill species from the Bucerotidae family of the avian order Bucerotiformes Buceros bicornis (great hornbill) and Penelopides panini (Visayan tarictic hornbill). Their structures were determined to be 3α,7α,24-dihydroxy-5β-cholestan-27-oic acid and its 12α-hydroxy derivative, 3α,7α,12α,24-tetrahydroxy-5β-cholestan-27-oic acid (varanic acid, VA), both present in bile as their corresponding taurine amidates. The four diastereomers of varanic acid were synthesized and their assigned structures were confirmed by X-ray crystallographic analysis. VA and its 12-deoxy derivative were found to have a (24R,25S)-configuration. 13 additional hornbill species were also analyzed by HPLC and showed similar bile acid patterns to B. bicornis and P. panini. The previous stereochemical assignment for (24R,25S)-VA isolated from the bile of varanid lizards and the Gila monster should now be revised to the (24S,25S)-configuration.

  12. Antitumor Efficacy of the Dual PI3K/mTOR Inhibitor PF-04691502 in a Human Xenograft Tumor Model Derived from Colorectal Cancer Stem Cells Harboring a PIK3CA Mutation.

    Directory of Open Access Journals (Sweden)

    Douglas D Fang

    Full Text Available PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide mutations can help predict the antitumor activity of phosphatidylinositol-3-kinase (PI3K/mammalian target of rapamycin (mTOR pathway inhibitors in both preclinical and clinical settings. In light of the recent discovery of tumor-initiating cancer stem cells (CSCs in various tumor types, we developed an in vitro CSC model from xenograft tumors established in mice from a colorectal cancer patient tumor in which the CD133+/EpCAM+ population represented tumor-initiating cells. CD133+/EpCAM+ CSCs were enriched under stem cell culture conditions and formed 3-dimensional tumor spheroids. Tumor spheroid cells exhibited CSC properties, including the capability for differentiation and self-renewal, higher tumorigenic potential and chemo-resistance. Genetic analysis using an OncoCarta™ panel revealed a PIK3CA (H1047R mutation in these cells. Using a dual PI3K/mTOR inhibitor, PF-04691502, we then showed that blockage of the PI3K/mTOR pathway inhibited the in vitro proliferation of CSCs and in vivo xenograft tumor growth with manageable toxicity. Tumor growth inhibition in mice was accompanied by a significant reduction of phosphorylated Akt (pAKT (S473, a well-established surrogate biomarker of PI3K/mTOR signaling pathway inhibition. Collectively, our data suggest that PF-04691502 exhibits potent anticancer activity in colorectal cancer by targeting both PIK3CA (H1047R mutant CSCs and their derivatives. These results may assist in the clinical development of PF-04691502 for the treatment of a subpopulation of colorectal cancer patients with poor outcomes.

  13. Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems

    Directory of Open Access Journals (Sweden)

    Mingzhu Lin

    2017-03-01

    Full Text Available Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In this study, three new Er monoester derivatives were obtained from the reflux reaction with Er: organic acids (furoic acid, salicylic acid and 2-naphthoic acid, 1-Ethylethyl-3-(3-dimethyllaminopropyl carbodiimide hydrochloride (EDCI and 4-dimethylaminopyridine (DMAP in dichloromethane. Their chemical structures were defined by IR and NMR. The present study was also undertaken to investigate the antidepressant-like effects of Er and its derivatives in male adult mice models of depression, and their probable involvement of GABAergic and glutamatergic systems by the forced swim test (FST. The results indicated that Er and its derivatives display antidepressant effects. Moreover, one derivative of Er, ergosteryl 2-naphthoate (ErN, exhibited stronger antidepressant activity in vivo compared to Er. Acute administration of ErN (5 mg/kg, i.p. and a combination of ErN (0.5 mg/kg, i.p., reboxetine (2.5 mg/kg, i.p., and tianeptine (15 mg/kg, i.p. reduced the immobility time in the FST. Pretreatment with bicuculline (a competitive γ-aminobutyric acid (GABA antagonist, 4 mg/kg, i.p. and N-methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg/kg, i.p. effectively reversed the antidepressant-like effect of ErN (5 mg/kg, i.p.. However, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p. and haloperidol (a non-selective D2 receptor antagonist, 0.2 mg/kg, i.p. did not eliminate the reduced immobility time. Altogether, these results indicated that ErN produced antidepressant-like activity, which might be mediated by GABAergic and glutamatergic systems.

  14. Analysis of SNPs of MC4R , GNB3 and FTO gene polymorphism in ...

    African Journals Online (AJOL)

    Regarding GNB3 rs5443 polymorphism, the likelihood of obesity was linked to ... On the other hand, the SNP of MC4R A822G did not exhibit any significant association with obesity ..... In parallel, fried food consumption and particularly satu-.

  15. Aminosilanes derived from 1H-benzimidazole-2(3H)-thione

    International Nuclear Information System (INIS)

    Palomo-Molina, Juliana; García-Báez, Efrén V.; Contreras, Rosalinda; Pineda-Urbina, Kayim; Ramos-Organillo, Angel

    2015-01-01

    In two trimethylsilyl-substituted 1H-benzimidazole-2(3H)-thiones, noncovalent C—H⋯π interactions between the centroid of the benzmidazole system and the SiMe 3 groups form helicoidal arrangements in one, and dimerization results in the formation of R s 2 (8) rings via N—H⋯S interactions, along with parallel π–π interactions between imidazole and benzene rings, in the second compound. Two new molecular structures, namely 1,3-bis(trimethylsilyl)-1H-benzimidazole-2(3H)-thione, C 13 H 22 N 2 SSi 2 , (2), and 1-trimethylsilyl-1H-benzimidazole-2(3H)-thione, C 10 H 14 N 2 SSi, (3), are reported. Both systems were derived from 1H-benzimidazole-2(3H)-thione. Noncovalent C—H⋯π interactions between the centroid of the benzmidazole system and the SiMe 3 groups form helicoidal arrangements in (2). Dimerization of (3) results in the formation of R 2 2 (8) rings via N—H⋯S interactions, along with parallel π–π interactions between imidazole and benzene rings

  16. Stereocomplementary Construction of Optically Active Bicyclo[4.3.0]nonenone Derivatives.

    Science.gov (United States)

    Mukai, Chisato; Kim, Jin Sung; Sonobe, Hiroshi; Hanaoka, Miyoji

    1999-09-03

    Treatment of (5S,6S)-5,6-bis(tert-butyldimethylsiloxy)-8-(substituted)oct-1-en-7-yne derivatives, prepared from diethyl L-tartrate, with Co(2)(CO)(8) afforded the corresponding cobalt-complexed enynes, which were subsequently exposed to the typical Pauson-Khand conditions to furnish highly stereoselectively or exclusively (2S,3S,6S)-2,3-bis(tert-butyldimethylsiloxy)-9-(substituted)bicyclo[4.3.0]non-1(9)-en-8-ones. On the other hand, (3S,4S)-1-(substituted)oct-7-en-1-yne-3,4-diol congeners produced, on exposure to the Pauson-Khand conditions, (2S,3S,6R)-2,3-dihydroxy-9-(substituted)bicyclo[4.3.0]-non-1(9)-en-8-one derivatives in a highly stereoselective manner. The newly developed procedure has been shown to be useful for construction of the 2,3-bis(oxygenated)-7-(substituted)bicyclo[4.3.0]non-6-en-8-one framework in a stereocomplementary as well as stereoselective fashion.

  17. Phase diagram of new lactic acid derivatives exhibiting ferro- and antiferroelectric phases

    Czech Academy of Sciences Publication Activity Database

    Kašpar, Miroslav; Novotná, Vladimíra; Hamplová, Věra; Pociecha, D.; Glogarová, Milada

    2008-01-01

    Roč. 35, č. 8 (2008), 975-985 ISSN 0267-8292 R&D Projects: GA AV ČR IAA100100710 Grant - others:ERDF(XE) WKP 1/1.4.3./1/2004/72/72/165/2005/U Institutional research plan: CEZ:AV0Z10100520 Keywords : ferroelectricity * antiferroelectricity * liquid crystals * polymorphism Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.132, year: 2008

  18. Radical Ions of 3-Styryl-quinoxalin-2-one Derivatives Studied by Pulse Radiolysis in Organic Solvents.

    Science.gov (United States)

    Skotnicki, Konrad; De la Fuente, Julio R; Cañete, Álvaro; Berrios, Eduardo; Bobrowski, Krzysztof

    2018-04-12

    The absorption-spectral and kinetic behaviors of radical ions and neutral hydrogenated radicals of seven 3-styryl-quinoxalin-2(1 H)-one (3-SQ) derivatives, one without substituents in the styryl moiety, four others with electron-donating (R = -CH 3 , -OCH 3 , and -N(CH 3 ) 2 ) or electron-withdrawing (R = -OCF 3 ) substituents in the para position in their benzene ring, and remaining two with double methoxy substituents (-OCH 3 ), however, at different positions (meta/para and ortho/meta) have been studied by UV-vis spectrophotometric pulse radiolysis in neat acetonitrile saturated with argon (Ar) and oxygen (O 2 ) and in 2-propanol saturated with Ar, at room temperature. In acetonitrile solutions, the radical anions (4R-SQ •- ) are characterized by two absorption maxima located at λ max = 470-490 nm and λ max = 510-540 nm, with the respective molar absorption coefficients ε 470-490 = 8500-13 100 M -1 cm -1 and ε 510-540 = 6100-10 300 M -1 cm -1 , depending on the substituent (R). All 4R-SQ •- decay in acetonitrile via first-order kinetics, with the rate constants in the range (1.2-1.5) × 10 6 s -1 . In 2-propanol solutions, they decay predominantly through protonation by the solvent, forming neutral hydrogenated radicals (4R-SQH • ), which are characterized by weak absorption bands with λ max = 480-490 nm. Being oxygen-insensitive, the radical cations (4R-SQ •+ ) are characterized by a strong absorption with λ max = 450-630 nm, depending on the substituent (R). They are formed in a charge-transfer reaction between a radical cation derived from acetonitrile (ACN •+ ) and substituted 3-styryl-quinoxalin-2-one derivatives (4R-SQ) with a pseudo-first-order rate constant k = (2.7-4.7) × 10 5 s -1 measured in solutions containing 0.1 mM 4R-3-SQ. The Hammett equation plot gave a very small negative slope (ρ = -0.08), indicating a very weak influence of the substituents in the benzene ring on the rate of charge-transfer reaction. The decay of 4R

  19. Identification of novel β-lactams and pyrrolidinone derivatives as selective Histamine-3 receptor (H3R) modulators as possible anti-obesity agents.

    Science.gov (United States)

    Ghoshal, Anirban; Kumar, Ajeet; Yugandhar, Doddapaneni; Sona, Chandan; Kuriakose, Sunu; Nagesh, Kommu; Rashid, Mamunur; Singh, Sandeep K; Wahajuddin, Muhammad; Yadav, Prem N; Srivastava, Ajay K

    2018-05-25

    Four series of structurally related β-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) were synthesized by utilizing post-Ugi modifications in one-pot, and their activity towards human histamine-3 receptor (H3R) was evaluated. Out of 94 compounds, screened against histamine-3 receptor (H3R), 21 compounds showed high H3R selective agonist property with EC 50 values ranging from 187 nM to 0.1 nM, whereas none of the compound was found to have the affinity towards other receptors of histamine family such as histamine H1, H2, and H4 receptor. All active compounds have no assay interference activity as determined by in-silico analysis and receptor independent luciferase assay and cell cytotoxicity assay. Given the important role of H3R in hypophagia, we also evaluated the in vivo effect of the representative compound 6k on the cumulative food intake in diet induce obese C57BL6/J mice. Interestingly, we observed that single dose administration (20 mg/kg, intraperitoneal injection) of 6k significantly suppressed cumulative food intake, while no significant effect was observed at 10 mg/kg. These results suggest that β-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) could be useful for the development of anti-obesity candidate drugs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Synthesis, Docking, In Vitro and In Vivo Antimalarial Activity of Hybrid 4-aminoquinoline-1,3,5-triazine Derivatives Against Wild and Mutant Malaria Parasites.

    Science.gov (United States)

    Bhat, Hans Raj; Singh, Udaya Pratap; Gahtori, Prashant; Ghosh, Surajit Kumar; Gogoi, Kabita; Prakash, Anil; Singh, Ramendra K

    2015-09-01

    A new series of hybrid 4-aminoquinoline-1,3,5-triazine derivatives was synthesized by a four-step reaction. Target compounds were screened for in vitro antimalarial activity against chloroquine-sensitive (3D-7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Compounds exhibited, by and large, good antimalarial activity against the resistant strain, while two of them, that is 8g and 8a, displayed higher activity against both the strains of P. falciparum. Additionally, docking study was performed on both wild (1J3I.pdb) and quadruple mutant (N51I, C59R, S108 N, I164L, 3QG2.pdb) type pf-DHFR-TS to highlight the structural features of hybrid molecules. © 2014 John Wiley & Sons A/S.

  1. The vapor pressure and vaporization enthalpy of R-(+)-menthofuran, a hepatotoxin metabolically derived from the abortifacient terpene, (R)-(+)-pulegone by correlation gas chromatography

    International Nuclear Information System (INIS)

    Gobble, Chase; Chickos, James S.

    2016-01-01

    Highlights: • The vaporization enthalpy and vapor pressure of R-(+) menthofuran is evaluated. • The normal boiling temperature is predicted and compared to experimental and predicted values. • A vapor pressure equation as a function of temperature for menthofuran is evaluated. - Abstract: The vapor pressure as a function of temperature and its vaporization enthalpy at T = 298.15 K of R-(+)-menthofuran, a substance metabolically derived from R-(+)-pulegone that is both a flavoring agent at low concentrations and a hepatotoxin at larger ones, is evaluated by correlation-gas chromatography. A vapor pressure p/Pa = (36 ± 12) has been evaluated at T = 298.15 K, and a normal boiling temperature of T_b/K = 482.4 K is predicted. A boiling temperature of T_b/K = 374.3 compares with the literature value of T_b/K = 371.2 at reduced pressure, p/kPa = 2.93. The vaporization enthalpy of (56.5 ± 3.0) kJ·mol"−"1 compares to an estimated value of (57.8 ± 2.9) kJ·mol"−"1.

  2. Spectroscopic studies on the interactions of 5-ethyl-6-phenyl-3,8-bis((3-aminoalkyl)propanamido)phenanthridin-5-ium derivatives with G-quadruplex DNA

    Science.gov (United States)

    Yalçın, Ergin; Duyar, Halil; Ihmels, Heiko; Seferoğlu, Zeynel

    2018-05-01

    An improved microwave-induced synthesis of five ethidium derivatives (Ethidium derivatives, 2a-d) is presented. As the derivatives 2a-d have been proposed previously to be telomerase inhibitors, the binding interactions of these ethidium derivatives with G-quadruplex DNA were evaluated by means of photometric and fluorimetric titration, thermal DNA denaturation, CD and 1H NMR spectroscopy. In particular, the compound bearing 3,8-bis(pyrrolidin-1-yl)propanamido substituent 2a exhibits high selectivity for G-quadruplex DNA relative to duplex DNA.

  3. Synthesis, physical-chemical properties of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acid esters

    Directory of Open Access Journals (Sweden)

    V. M. Odyntsova

    2017-04-01

    Full Text Available The nitrogen-containing heterocyclic systems from the class of 1,2,4-triazole derivatives, which exhibit wide range of actions, occupy special place among the variety of heterocyclic compounds. Derived biologically active substances are actively introduced into practice as new original and effective drugs. We were interested in esters of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids, which exhibit high biological activity and can be intermediates for the synthesis of amides, hydrazides, ylidenderivatives of corresponding acids. The aim of this work is the synthesis of new esters of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids and the establishment of their physical-chemical properties. Materials and methods. Melting point was determined by open capillary method on the device OptiMelt MPA100. The elemental composition of the synthesized compounds was determined on the universal analyzer ElementarVario ЕL cube (CHNS (standard – sulfanilamide. 1H NMR spectra were recorded on spectrometer Varian Mercury VX-200 (1H, 200 MHz in the solvent dimethyl sulfoxide-d6 (tetramethylsilane internal standard and decoded using a program ADVASP(tm Analyzer program (Umatek International Inc.. Chromato-mass-spectral studies were performed on hazarding chromatograph Agilent 1260 Infinity HPLC equipped with mass spectrometer Agilent 6120 (ionization electro-spray (ESI. The results and discussion. Synthesis of 11 new compounds, namely esters of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids was carried out by two methods. According to the A method the alkylation of previously synthesized 3-(adamantan-1-yl-1H-1,2,4-triazole-5-thiol was performed with the use of corresponding methyl ester of 2-chloroacetic acid and the presence of equivalent amount of sodium hydroxide. The B method involves the etherification of 2-((5-(adamantan-1-yl-4-R-4H-1,2,4-triazole-3-ylthioacetic acid with the use of methyl, ethyl, i

  4. Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics.

    Directory of Open Access Journals (Sweden)

    Kara G Lassen

    2009-04-01

    Full Text Available Elite suppressors (ES are a rare subset of HIV-1-infected individuals who are able to maintain HIV-1 viral loads below the limit of detection by ultra-sensitive clinical assays in the absence of antiretroviral therapy. Mechanism(s responsible for this elite control are poorly understood but likely involve both host and viral factors. This study assesses ES plasma-derived envelope glycoprotein (env fitness as a function of entry efficiency as a possible contributor to viral suppression. Fitness of virus entry was first evaluated using a novel inducible cell line with controlled surface expression levels of CD4 (receptor and CCR5 (co-receptor. In the context of physiologic CCR5 and CD4 surface densities, ES envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. ES envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, ES env clones were less efficient at mediating entry than chronic progressor envs. Interestingly, acute infection envs exhibited an intermediate phenotypic pattern not distinctly different from ES or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in ES individuals.

  5. Dancing together and separate again: gymnosperms exhibit frequent changes of fundamental 5S and 35S rRNA gene (rDNA) organisation.

    Science.gov (United States)

    Garcia, S; Kovařík, A

    2013-07-01

    In higher eukaryotes, the 5S rRNA genes occur in tandem units and are arranged either separately (S-type arrangement) or linked to other repeated genes, in most cases to rDNA locus encoding 18S-5.8S-26S genes (L-type arrangement). Here we used Southern blot hybridisation, PCR and sequencing approaches to analyse genomic organisation of rRNA genes in all large gymnosperm groups, including Coniferales, Ginkgoales, Gnetales and Cycadales. The data are provided for 27 species (21 genera). The 5S units linked to the 35S rDNA units occur in some but not all Gnetales, Coniferales and in Ginkgo (∼30% of the species analysed), while the remaining exhibit separate organisation. The linked 5S rRNA genes may occur as single-copy insertions or as short tandems embedded in the 26S-18S rDNA intergenic spacer (IGS). The 5S transcript may be encoded by the same (Ginkgo, Ephedra) or opposite (Podocarpus) DNA strand as the 18S-5.8S-26S genes. In addition, pseudogenised 5S copies were also found in some IGS types. Both L- and S-type units have been largely homogenised across the genomes. Phylogenetic relationships based on the comparison of 5S coding sequences suggest that the 5S genes independently inserted IGS at least three times in the course of gymnosperm evolution. Frequent transpositions and rearrangements of basic units indicate relatively relaxed selection pressures imposed on genomic organisation of 5S genes in plants.

  6. Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21 and miR-146a

    Directory of Open Access Journals (Sweden)

    Qian Cheng

    2017-01-01

    Full Text Available Exosomes derived from cancer cells can affect various functions of mesenchymal stem cells (MSCs via conveying microRNAs (miRs. miR-21 and miR-146a have been demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL-6 secreted from transformed MSCs in turn favors the survival of multiple myeloma (MM cells. However, the effects of MM exosomes on MSC functions remain largely unclear. In this study, we investigated the effects of OPM2 (a MM cell line exosomes (OPM2-exo on regulating the proliferation, cancer-associated fibroblast (CAF transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo induced CAF transformation of MSCs, which was evidenced by increased fibroblast-activated protein (FAP, α-smooth muscle actin (α-SMA, and stromal-derived factor 1 (SDF-1 expressions and IL-6 secretion. Inhibition of miR-21 or miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could promote the proliferation, CAF transformation, and IL-6 secretion of MSCs partially through regulating miR21 and miR146a.

  7. Synthesis and Preliminary Cytotoxicity Studies of 1-[1-(4,5-Dihydrooxazol- 2-yl)-1H-indazol-3-yl]-3-phenylurea and 3-phenylthiourea Derivatives.

    Science.gov (United States)

    Kornicka, Anita; Saczewski, Franciszek; Bednarski, Patrick J; Korcz, Martyna; Szumlas, Piotr; Romejko, Ewa; Sakowicz, Aneta; Sitek, Lukasz; Wojciechowska, Monika

    2017-01-01

    N-substituted 3-amino-1H-indazoles represent an interesting class of biologically active compounds. Among them, derivatives containing phenylurea moiety are of particular interest. Such compounds have been found to possess inhibitory activity against cancer cell growth. Additionally, various oxazoline-containing compounds have also been designed as potential anticancer agents. The aim of this work was to obtain a new class of N-substituted 3-amino-1H-indazole derivatives with cytotoxic activity towards cancer cells. Two series of 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-phenylurea and 3- phenylthiourea derivatives 7-17 and 18-22, respectively, were prepared and screened for their potential in vitro cytotoxic activities against lung carcinoma LCLC-103H cell line using a crystal violet microtiter plate assay. All the urea derivatives, except the compound 8, were inactive at a concentration of 20 μM attainable in cancer cells, while the thiourea derivatives showed a pronounced cancer cell growth inhibitory effects. The most potent 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-ptolylthiourea (19) exhibited cytotoxicity on the lung cancer LCLC-103H and cervical cancer SISO cell lines at a concentration of 10 µM. Moreover, compound 19 displayed cytostatic activity against pancreas cancer DAN-G cell line. The 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-phenylthiourea derivatives described herein may serve as a useful scaffold for the search for novel anticancer agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Properties of a non-bioactive fluorescent derivative of differentiation-inducing factor-3, an anti-tumor agent found in Dictyostelium discoideum

    Directory of Open Access Journals (Sweden)

    Yuzuru Kubohara

    2014-03-01

    Full Text Available Differentiation-inducing factor-3 (DIF-3, found in the cellular slime mold Dictyostelium discoideum, and its derivatives, such as butoxy-DIF-3 (Bu-DIF-3, are potent anti-tumor agents. To investigate the activity of DIF-like molecules in tumor cells, we recently synthesized a green fluorescent DIF-3 derivative, BODIPY-DIF-3G, and analyzed its bioactivity and cellular localization. In this study, we synthesized a red (orange fluorescent DIF-3 derivative, BODIPY-DIF-3R, and compared the cellular localization and bioactivities of the two BODIPY-DIF-3s in HeLa human cervical cancer cells. Both fluorescent compounds penetrated the extracellular membrane within 0.5 h and localized mainly to the mitochondria. In formalin-fixed cells, the two BODIPY-DIF-3s also localized to the mitochondria, indicating that the BODIPY-DIF-3s were incorporated into mitochondria independently of the mitochondrial membrane potential. After treatment for 3 days, BODIPY-DIF-3G, but not BODIPY-DIF-3R, induced mitochondrial swelling and suppressed cell proliferation. Interestingly, the swollen mitochondria were stainable with BODIPY-DIF-3G but not with BODIPY-DIF-3R. When added to isolated mitochondria in vitro, BODIPY-DIF-3G increased dose-dependently the rate of O2 consumption, but BODIPY-DIF-3R did not. These results suggest that the bioactive BODIPY-DIF-3G suppresses cell proliferation, at least in part, by altering mitochondrial activity, whereas the non-bioactive BODIPY-DIF-3R localizes to the mitochondria but does not affect mitochondrial activity or cell proliferation.

  9. Aminosilanes derived from 1H-benzimidazole-2(3H)-thione

    Energy Technology Data Exchange (ETDEWEB)

    Palomo-Molina, Juliana [Facultad de Ciencias Químicas, Universidad de Colima, Carretera Coquimatlán-Colima, Coquimatlán Colima 28400 (Mexico); García-Báez, Efrén V. [Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Avenida Acueducto s/n, Barrio La Laguna Ticomán, México DF 07340 (Mexico); Contreras, Rosalinda [Departamento de Química, Centro de Investigación y de Estudios Avanzados del IPN, Apartado Postal 14-740, México DF 07000 (Mexico); Barrio La Laguna Ticomán, México DF 07340 (Mexico); Pineda-Urbina, Kayim; Ramos-Organillo, Angel, E-mail: aaramos@ucol.mx [Facultad de Ciencias Químicas, Universidad de Colima, Carretera Coquimatlán-Colima, Coquimatlán Colima 28400 (Mexico)

    2015-08-12

    In two trimethylsilyl-substituted 1H-benzimidazole-2(3H)-thiones, noncovalent C—H⋯π interactions between the centroid of the benzmidazole system and the SiMe{sub 3} groups form helicoidal arrangements in one, and dimerization results in the formation of R{sub s} {sup 2}(8) rings via N—H⋯S interactions, along with parallel π–π interactions between imidazole and benzene rings, in the second compound. Two new molecular structures, namely 1,3-bis(trimethylsilyl)-1H-benzimidazole-2(3H)-thione, C{sub 13}H{sub 22}N{sub 2}SSi{sub 2}, (2), and 1-trimethylsilyl-1H-benzimidazole-2(3H)-thione, C{sub 10}H{sub 14}N{sub 2}SSi, (3), are reported. Both systems were derived from 1H-benzimidazole-2(3H)-thione. Noncovalent C—H⋯π interactions between the centroid of the benzmidazole system and the SiMe{sub 3} groups form helicoidal arrangements in (2). Dimerization of (3) results in the formation of R{sub 2}{sup 2}(8) rings via N—H⋯S interactions, along with parallel π–π interactions between imidazole and benzene rings.

  10. Selectivity criterion for pyrazolo[3,4-b]pyrid[az]ine derivatives as GSK-3 inhibitors: CoMFA and molecular docking studies.

    Science.gov (United States)

    Patel, Dhilon S; Bharatam, Prasad V

    2008-05-01

    In the development of drugs targeted for GSK-3, its selective inhibition is an important requirement owing to the possibility of side effects arising from other kinases for the treatment of diabetes mellitus. A three-dimensional quantitative structure-activity relationship study (3D-QSAR) has been carried out on a set of pyrazolo[3,4-b]pyrid[az]ine derivatives, which includes non-selective and selective GSK-3 inhibitors. The CoMFA models were derived from a training set of 59 molecules. A test set containing 14 molecules (not used in model generation) was used to validate the CoMFA models. The best CoMFA model generated by applying leave-one-out (LOO) cross-validation study gave cross-validation r(cv)(2) and conventional r(conv)(2) values of 0.60 and 0.97, respectively, and r(pred)(2) value of 0.55, which provide the predictive ability of model. The developed models well explain (i) the observed variance in the activity and (ii) structural difference between the selective and non-selective GSK-3 inhibitors. Validation based on the molecular docking has also been carried out to explain the structural differences between the selective and non-selective molecules in the given series of molecules.

  11. MnO{sub 2} nanorods/3D-rGO composite as high performance anode materials for Li-ion batteries

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hongdong; Hu, Zhongli; Su, Yongyao; Ruan, Haibo; Hu, Rong [Research Institute for New Materials Technology, Chongqing University of Arts and Sciences, Chongqing 402160 (China); Zhang, Lei, E-mail: leizhang0215@126.com [College of Life Science, Chongqing Normal University, Chongqing 401331 (China)

    2017-01-15

    Highlights: • MnO{sub 2} nanorods/3D-rGO composite has been synthesized by a simple in situ hydrothermal methord. • MnO{sub 2} nanorods/3D-rGO composite exhibits high reversible capacity, outstanding rate capacity and excellent cyclic stability. • Building metal oxides/3D-rGO composite is an effective way for improving the electrochemical performance of Li-ion batteries. - Abstract: MnO{sub 2} nanorods/three-dimensional reduced graphene oxide (3D-rGO) composite has been synthesized by a simple in situ hydrothermal methord. The X-ray diffraction (XRD) pattern of the as-prepared composite reveals tetragonal structure of α-MnO{sub 2.} Raman spectroscopic and X-ray photoelectron spectroscopy (XPS) of the samples confirm the coexistence of MnO{sub 2} and graphene. The Brunauer-Emmett-Teller (BET) analysis shows the large surface area of the composite. The electron microscopy images of the as-synthesized products reveals the MnO{sub 2} nanorods are homogeneously grown on 3D-rGO matrix. Electrochemical characterization exhibits the MnO{sub 2} nanorods/3D-rGO composite with large reversible capacity (595 mA h g{sup −1} over 60 cycles at 100 mA g{sup −1}), high coulombic efficiency (above 99%), excellent rate capability and good cyclic stability. The superior electrochemical performance can be attributed to the turf-like nanostructure of composite, high capacity of MnO{sub 2} and superior electrical conductivity of 3D-rGO. It suggests that MnO{sub 2} nanorods/3D-rGO composite will be a promising anode material for Li-ion batteries.

  12. A 3′-Untranslated Region (3′UTR) Induces Organ Adhesion by Regulating miR-199a* Functions

    Science.gov (United States)

    Lee, Daniel Y.; Shatseva, Tatiana; Jeyapalan, Zina; Du, William W.; Deng, Zhaoqun; Yang, Burton B.

    2009-01-01

    Mature microRNAs (miRNAs) are single-stranded RNAs of 18–24 nucleotides that repress post-transcriptional gene expression. However, it is unknown whether the functions of mature miRNAs can be regulated. Here we report that expression of versican 3′UTR induces organ adhesion in transgenic mice by modulating miR-199a* activities. The study was initiated by the hypothesis that the non-coding 3′UTR plays a role in the regulation of miRNA function. Transgenic mice expressing a construct harboring the 3′UTR of versican exhibits the adhesion of organs. Computational analysis indicated that a large number of microRNAs could bind to this fragment potentially including miR-199a*. Expression of versican and fibronectin, two targets of miR-199a*, are up-regulated in transgenic mice, suggesting that the 3′UTR binds and modulates miR-199a* activities, freeing mRNAs of versican and fibronectin from being repressed by miR-199a*. Confirmation of the binding was performed by PCR using mature miR-199a* as a primer and the targeting was performed by luciferase assays. Enhanced adhesion by expression of the 3′UTR was confirmed by in vitro assays. Our results demonstrated that upon arrival in cytoplasm, miRNA activities can be modulated locally by the 3′UTR. Our assay may be developed as sophisticated approaches for studying the mutual regulation of miRNAs and mRNAs in vitro and in vivo. We anticipate that expression of the 3′UTR may be an approach in the development of gene therapy. PMID:19223980

  13. Chiral auxiliary-mediated enantioenrichment of (+-)-ibuprofen, under Steglich conditions, with secondary alcohols derived from (R)-carvone

    Energy Technology Data Exchange (ETDEWEB)

    Amongero, Marcela; Visnovezky, Damian; Kaufman, Teodoro S., E-mail: kaufman@iquir-conicet.gov.a [Instituto de Quimica Rosario (IQUIR, CONICET-UNR) (Argentina); Universidad Nacional de Rosario (Argentina)

    2010-07-01

    The synthesis of a series of chiral secondary alcohols derived from (R)-carvone, and the stereochemical outcome of their reaction with (+-)-ibuprofen, is reported. The racemic drug was transformed into the corresponding diastereomeric esters mediated by DCC/DMAP, affording up to 5.7:1 diastereomeric ratios of the esters derived from either (S)- or (R)-ibuprofen, depending on the type of chiral auxiliary employed. (author)

  14. Chiral auxiliary-mediated enantioenrichment of (+-)-ibuprofen, under Steglich conditions, with secondary alcohols derived from (R)-carvone

    International Nuclear Information System (INIS)

    Amongero, Marcela; Visnovezky, Damian; Kaufman, Teodoro S.

    2010-01-01

    The synthesis of a series of chiral secondary alcohols derived from (R)-carvone, and the stereochemical outcome of their reaction with (±)-ibuprofen, is reported. The racemic drug was transformed into the corresponding diastereomeric esters mediated by DCC/DMAP, affording up to 5.7:1 diastereomeric ratios of the esters derived from either (S)- or (R)-ibuprofen, depending on the type of chiral auxiliary employed. (author)

  15. Synthesis of 24S and 24R-hydroxy-[24-3H] vitamin D3 and their metabolism in rachitic rats

    International Nuclear Information System (INIS)

    Tanaka, Y.; DeLuca, H.F.; Akaiwa, A.; Morisaki, M.; Ikekawa, N.

    1976-01-01

    An epimeric mixture of 24-hydroxy-[24- 3 H] vitamin D 3 was synthesized by the reduction of 24-ketovitamin D 3 by sodium borotritide. The epimeric mixture was converted to the trimethylsilylether derivatives and subjected to high-pressure liquid chromatography using silica gel columns to separate the 24-hydroxy-[24- 3 H] vitamin D 3 isomers. The 24R-hydroxy-[24- 3 H]vitamin D 3 induced calcification in rachitic rats while the 24S-hydroxy-[24- 3 H]vitamin D 3 had little or no such activity. As both isomers of 24-hydroxy-vitamin D 3 are metabolized to 24,25-dihydroxyvitamin D 3 , it appears that the 24-hydroxyvitamin D 3 -25-hydroxylase does not discriminate between the isomers. Only the R-isomer of 24-hydroxyvitamin D 3 is metabolized to 1,24-dihydroxyvitamin D 3 , although only trace amounts of this compound were found 2 days after the administration of 24-hydroxyvitamin D 3 . The striking difference in the metabolism of the isomers is the high selectivity of the 1-hydroxylase for the R-isomer. It is suggested that the high specificity of biological activity for the R-isomer of 24-hydroxyvitamin D 3 is because of the specificity of the 1-hydroxylation of 24,25-dihydroxyvitamin D 3 for the R configuration

  16. Design, Synthesis and Evaluation of 3-(2-Aminoheterocycle-4-benzyloxyphenylbenzamide Derivatives as BACE-1 Inhibitors

    Directory of Open Access Journals (Sweden)

    Lushan Yu

    2013-03-01

    Full Text Available Three series of 3-(2-aminoheterocycle-4-benzyloxyphenylbenzamide derivatives, 2-aminooxazoles, 2-aminothiazoles, and 2-amino-6H-1,3,4-thiadizines were designed, synthesized and evaluated as β-secretase (BACE-1 inhibitors. Preliminary structure-activity relationships revealed that the existence of a 2-amino-6H-1,3,4-thiadizine moiety and α-naphthyl group were favorable for BACE-1 inhibition. Among the synthesized compounds, 5e exhibited the most potent BACE-1 inhibitory activity, with an IC50 value of 9.9 μΜ and it exhibited high brain uptake potential in Madin-Darby anine kidney cell lines (MDCK and a Madin-Darby canine kidney-multidrug resistance 1 (MDCK-MDR1 model.

  17. Design, synthesis and evaluation of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives as BACE-1 inhibitors.

    Science.gov (United States)

    Shangguan, Shihao; Wang, Fei; Liao, Yong; Yu, Haiping; Li, Jia; Huang, Wenhai; Hu, Haihong; Yu, Lushan; Hu, Yongzhou; Sheng, Rong

    2013-03-20

    Three series of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives, 2-aminooxazoles, 2-aminothiazoles, and 2-amino-6H-1,3,4-thiadizines were designed, synthesized and evaluated as β-secretase (BACE-1) inhibitors. Preliminary structure-activity relationships revealed that the existence of a 2-amino-6H-1,3,4-thiadizine moiety and α-naphthyl group were favorable for BACE-1 inhibition. Among the synthesized compounds, 5e exhibited the most potent BACE-1 inhibitory activity, with an IC50 value of 9.9 μΜ and it exhibited high brain uptake potential in Madin-Darby anine kidney cell lines (MDCK) and a Madin-Darby canine kidney-multidrug resistance 1 (MDCK-MDR1) model.

  18. Adipose tissue-derived microvascular fragments from aged donors exhibit an impaired vascularisation capacity

    Directory of Open Access Journals (Sweden)

    MW Laschke

    2014-10-01

    Full Text Available Adipose tissue-derived microvascular fragments are promising vascularisation units for applications in the field of tissue engineering. Elderly patients are the major future target population of such applications due to an increasing human life expectancy. Therefore, we herein investigated the effect of aging on the fragments’ vascularisation capacity. Microvascular fragments were isolated from epididymal fat pads of adult (8 months and aged (16 months C57BL/6 donor mice. These fragments were seeded onto porous polyurethane scaffolds, which were implanted into dorsal skinfold chambers to study their vascularisation using intravital fluorescence microscopy, histology and immunohistochemistry. Scaffolds seeded with fragments from aged donors exhibited a significantly lower functional microvessel density and intravascular blood flow velocity. This was associated with an impaired vessel maturation, as indicated by vessel wall irregularities, constantly elevated diameters and a lower fraction of CD31/α-smooth muscle actin double positive microvessels in the implants’ border and centre zones. Additional in vitro analyses revealed that microvascular fragments from adult and aged donors do not differ in their stem cell content as well as in their release of angiogenic growth factors, survival and proliferative activity under hypoxic conditions. However, fragments from aged donors exhibit a significantly lower number of matrix metalloproteinase -9-positive perivascular cells. Taken together, these findings demonstrate that aging is a crucial determinant for the vascularisation capacity of isolated microvascular fragments.

  19. Magnetic moment and magnetocrystalline anisotropy of 3d-ion subsystem in R2T14B

    International Nuclear Information System (INIS)

    Bartashevich, M.I.; Kudrevatykh, N.V.; Andreev, A.V.; Rejmer, V.A.

    1990-01-01

    The effect of substituting cobalt for iron on the magnetic moment, magneto-crystalline anisotropy and thermal expansion of R 2 (Fe 1-x Co x ) 14 B single crystals (R=Y, Gd, 0≤x≤0.3) is investigated. The uniaxial magnetic anisotropy constant K 1 for the 3d-subsystem passes through a maximum at T=4.2 K with increasing Co concentration. For T c the temperature dependence of K 1 does not possess a positive slope. The magnetic moment of the 3d-subsystem at 4.2 K does not exhibit the maximum at intermediate concentrations observed for most R(Fe, Co)-intermetallics. An explanation is presented of the changes in the magnetic properties. It is shown that the variation of the interatomic distances on thermal expansion should not affect the magnitude of the anisotropy constant of the 3d- and R-subsystems

  20. [Secondary metabolites from a deep-sea-derived actinomycete Micrococcus sp. R21].

    Science.gov (United States)

    Peng, Kun; Su, Rui-qiang; Zhang, Gai-yun; Cheng, Xuan-xuan; Yang, Quan; Liu, Yong-hong; Yang, Xian-wen

    2015-06-01

    To investigate cytotoxic secondary metabolites of Micrococcus sp. R21, an actinomycete isolated from a deep-sea sediment (-6 310 m; 142 degrees 19. 9' E, 10 degrees 54. 6' N) of the Western Pacific Ocean, column chromatography was introduced over silica gel, ODS, and Sephadex LH-20. As a result, eight compounds were obtained. By mainly detailed analysis of the NMR data, their structures were elucidated as cyclo(4-hydroxy-L-Pro-L-leu) (1), cyclo(L-Pro-L-Gly) (2), cyclo( L-Pro-L-Ala) (3), cyclo( D-Pro-L-Leu) (4), N-β-acetyltryptamine (5), 2-hydroxybenzoic acid (6), and phenylacetic acid (7). Compound 1 exhibited weak cytotoxic activity against RAW264. 7 cells with IC50 value of 9.1 μmol x L(-1).

  1. Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity.

    Science.gov (United States)

    Jayakumar, Sundarraj; Patwardhan, Raghavendra S; Pal, Debojyoti; Singh, Babita; Sharma, Deepak; Kutala, Vijay Kumar; Sandur, Santosh Kumar

    2017-12-01

    Mitocurcumin is a derivative of curcumin, which has been shown to selectively enter mitochondria. Here we describe the anti-tumor efficacy of mitocurcumin in lung cancer cells and its mechanism of action. Mitocurcumin, showed 25-50 fold higher efficacy in killing lung cancer cells as compared to curcumin as demonstrated by clonogenic assay, flow cytometry and high throughput screening assay. Treatment of lung cancer cells with mitocurcumin significantly decreased the frequency of cancer stem cells. Mitocurcumin increased the mitochondrial reactive oxygen species (ROS), decreased the mitochondrial glutathione levels and induced strand breaks in the mitochondrial DNA. As a result, we observed increased BAX to BCL-2 ratio, cytochrome C release into the cytosol, loss of mitochondrial membrane potential and increased caspase-3 activity suggesting that mitocurcumin activates the intrinsic apoptotic pathway. Docking studies using mitocurcumin revealed that it binds to the active site of the mitochondrial thioredoxin reductase (TrxR2) with high affinity. In corroboration with the above finding, mitocurcumin decreased TrxR activity in cell free as well as the cellular system. The anti-cancer activity of mitocurcumin measured in terms of apoptotic cell death and the decrease in cancer stem cell frequency was accentuated by TrxR2 overexpression. This was due to modulation of TrxR2 activity to NADPH oxidase like activity by mitocurcumin, resulting in higher ROS accumulation and cell death. Thus, our findings reveal mitocurcumin as a potent anticancer agent with better efficacy than curcumin. This study also demonstrates the role of TrxR2 and mitochondrial DNA damage in mitocurcumin mediated killing of cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Extraction of Features from High-resolution 3D LiDaR Point-cloud Data

    Science.gov (United States)

    Keller, P.; Kreylos, O.; Hamann, B.; Kellogg, L. H.; Cowgill, E. S.; Yikilmaz, M. B.; Hering-Bertram, M.; Hagen, H.

    2008-12-01

    Airborne and tripod-based LiDaR scans are capable of producing new insight into geologic features by providing high-quality 3D measurements of the landscape. High-resolution LiDaR is a promising method for studying slip on faults, erosion, and other landscape-altering processes. LiDaR scans can produce up to several billion individual point returns associated with the reflection of a laser from natural and engineered surfaces; these point clouds are typically used to derive a high-resolution digital elevation model (DEM). Currently, there exist only few methods that can support the analysis of the data at full resolution and in the natural 3D perspective in which it was collected by working directly with the points. We are developing new algorithms for extracting features from LiDaR scans, and present method for determining the local curvature of a LiDaR data set, working directly with the individual point returns of a scan. Computing the curvature enables us to rapidly and automatically identify key features such as ridge-lines, stream beds, and edges of terraces. We fit polynomial surface patches via a moving least squares (MLS) approach to local point neighborhoods, determining curvature values for each point. The size of the local point neighborhood is defined by a user. Since both terrestrial and airborne LiDaR scans suffer from high noise, we apply additional pre- and post-processing smoothing steps to eliminate unwanted features. LiDaR data also captures objects like buildings and trees complicating greatly the task of extracting reliable curvature values. Hence, we use a stochastic approach to determine whether a point can be reliably used to estimate curvature or not. Additionally, we have developed a graph-based approach to establish connectivities among points that correspond to regions of high curvature. The result is an explicit description of ridge-lines, for example. We have applied our method to the raw point cloud data collected as part of the Geo

  3. Dancing together and separate again: gymnosperms exhibit frequent changes of fundamental 5S and 35S rRNA gene (rDNA) organisation

    Czech Academy of Sciences Publication Activity Database

    Garcia, S.; Kovařík, Aleš

    2013-01-01

    Roč. 111, č. 1 (2013), s. 23-33 ISSN 0018-067X R&D Projects: GA ČR(CZ) GA13-10057S; GA ČR GBP501/12/G090 Institutional support: RVO:68081707 Keywords : rRNA gene organisation * intergenic spacer * Ginkgo Subject RIV: BO - Biophysics Impact factor: 3.804, year: 2013

  4. Fluorine-ion conductivity of different technological forms of solid electrolytes R{sub 1–y}M{sub y}F{sub 3–y} (LaF{sub 3} Type ) (M = Ca, Sr, Ba; R Are Rare Earth Elements)

    Energy Technology Data Exchange (ETDEWEB)

    Sorokin, N. I., E-mail: nsorokin1@yandex.ru; Sobolev, B. P. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

    2016-05-15

    We have investigated the conductivity of some representatives of different technological forms of fluoride-conducting solid electrolytes R{sub 1–y}M{sub y}F{sub 3–y} (M = Ca, Sr, Ba; R are rare earth elements) with an LaF{sub 3} structure: single crystals, cold- and hot-pressing ceramics based on a charge prepared in different ways (mechanochemical synthesis, solid-phase synthesis, and fragmentation of single crystals), polycrystalline alloys, etc. It is shown (by impedance spectroscopy), that different technological forms of identical chemical composition (R, M, y) exhibit different electrical characteristics. The maximum conductivity is observed for the single-crystal form of R{sub 1–y}M{sub y}F{sub 3–y} tysonite phases, which provides (in contrast to other technological forms) the formation of true volume ion-conducting characteristics.

  5. Hsa-miR-1587 G-quadruplex formation and dimerization induced by NH4+, molecular crowding environment and jatrorrhizine derivatives.

    Science.gov (United States)

    Tan, Wei; Yi, Long; Zhu, Zhentao; Zhang, Lulu; Zhou, Jiang; Yuan, Gu

    2018-03-01

    A guanine-rich human mature microRNA, miR-1587, was discovered to form stable intramolecular G-quadruplexes in the presence of K + , Na + and low concentration of NH 4 + (25mM) by electrospray ionization mass spectrometry (ESI-MS) combined with circular dichroism (CD) spectroscopy. Furthermore, under high concentration of NH 4 + (100mM) or molecular crowding environments, miR-1587 formed a dimeric G-quadruplex through 3'-to-3' stacking of two monomeric G-quadruplex subunits with one ammonium ion sandwiched between the interfaces. Specifically, two synthesized jatrorrhizine derivatives with terminal amine groups could also induce the dimerization of miR-1587 G-quadruplex and formed 1:1 and 2:1 complexes with the dimeric G-quadruplex. In contrast, jatrorrhizine could bind with the dimeric miR-1587 G-quadruplex, but could not induce dimerization of miR-1587 G-quadruplex. These results provide a new strategy to regulate the functions of miR-1587 through induction of G-quadruplex formation and dimerization. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Understanding Am3+/Cm3+ separation with H4TPAEN and its hydrophilic derivatives: a quantum chemical study.

    Science.gov (United States)

    Huang, Pin-Wen; Wang, Cong-Zhi; Wu, Qun-Yan; Lan, Jian-Hui; Song, Gang; Chai, Zhi-Fang; Shi, Wei-Qun

    2018-05-10

    Am3+/Cm3+ separation is an extremely hard but important task in nuclear waste treatment. In this study, Am and Cm complexes formed with a back-extraction agent N,N,N',N'-tetrakis[(6-carboxypyridin-2-yl)methyl]ethylene-diamine (H4TPAEN) and its two derivatives with hydrophilic substituents (methoxy and morpholine groups) were investigated using the density functional theory (DFT). The optimized geometrical structures indicated that the Am3+ cation matched better with the cavities of the three studied ligands than Cm3+, and the Am3+ cations were located deeper in the cavities of the ligands. The bond order and quantum theory of atoms in molecules (QTAIM) analyses suggested that ionic interactions dominated An-N and An-O (An = Cm and Am) bonds. However, weak and different extents of partial covalency could also be found in the Am-N and Cm-N bonds. The O donor atoms in the carboxylate groups preferably coordinated with Cm3+ rather than Am3+, whereas the N atoms preferred Am3+. Therefore, the Am3+/Cm3+ selectivity of H4TPAEN and its two hydrophilic derivatives may be ascribed to the competition between the An-N and An-O interactions and the few dissimilarities in their geometrical structures. Based on our calculations, the methoxy and morpholine groups in the two derivatives can serve as electron-donating groups and enhance the strength of the An-NPY bonds (NPY denotes the nitrogen atom of pyridine ring). When compared with the Am-complex, the Cm-complex exhibited significant strength effect, resulting in the relatively lower Am3+/Cm3+ separation ability of the H4TPAEN's hydrophilic derivatives.

  7. Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076.

    Science.gov (United States)

    Huertas Méndez, Nataly De Jesús; Vargas Casanova, Yerly; Gómez Chimbi, Anyelith Katherine; Hernández, Edith; Leal Castro, Aura Lucia; Melo Diaz, Javier Mauricio; Rivera Monroy, Zuly Jenny; García Castañeda, Javier Eduardo

    2017-03-12

    Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B-containing non-natural amino acids and the RWQWR motif were synthesized, purified, and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism. The antibacterial activity of peptides against Escherichia coli ATCC 11775, Stenotrophomonas maltophilia ATCC 13636, and Salmonella enteritidis ATCC 13076 was evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The synthetic bovine lactoferricin exhibited antibacterial activity against E. coli ATCC 11775 and S. enteritidis ATCC 13076. The dimeric peptide (RRWQWR)₂K-Ahx exhibited the highest antibacterial activity against the tested bacterial strain. The monomeric, cyclic, tetrameric, and palindromic peptides containing the RWQWR motif exhibited high and specific activity against E. coli ATCC 11775. The results suggest that short peptides derived from lactoferricin B could be considered as potential candidates for the development of antibacterial agents against infections caused by E. coli .

  8. Synthesis and biological evaluation of new pyrazolo[3,4-d]pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    Asma Agrebi

    2014-05-01

    Full Text Available Several new pyrazolopyrimidine compounds were achieved from aminocyanopyarazole 1. The starting material 1 was initially coupled with orthoester at refluxed with various primary amines, ammonia, hydrazines and hydroxylamine to furnish a series of pyrazolo[3,4-d]pyrimidines. The reaction of imidate 2a-b with hydrazide derivatives led to the formation of pyrazolo[3,4-d][1,2,4]triazolo[4,3-c]pyrimidines. Some of the synthesized compounds 3a and 4c were evaluated for their anti-inflammatory, antipyretic and nociceptive activities. We start by studing the toxicity of these two molecules by measuring the corresponding DL50. The DL50 of 3a and 4c are estimated to 1333.2mg / kg and 1593.5mg / kg respectively. Pharmacological evaluation showed that compounds 3a and 4c at doses (5.5-22.2 mg / Kg, i.p exhibited anti-inflammatory activities compared to Ibuprofen (150 mg / Kg, i.p, used as a refer ence drug. Further, our study showed that the injection of derived pyrazolopyrimidines on hyperthermic animal leads to a decrease in temperature after 1 hours of treatment compared to paracetamol used as reference. In addition, the injection of derived pyrazolopyrimidines at different doses contains a potent nociceptive activity. This effect is dose-dependent compared to aspirin.

  9. Brain-derived neurotrophic factor promotes VEGF-C-dependent lymphangiogenesis by suppressing miR-624-3p in human chondrosarcoma cells.

    Science.gov (United States)

    Lin, Chih-Yang; Wang, Shih-Wei; Chen, Yen-Ling; Chou, Wen-Yi; Lin, Ting-Yi; Chen, Wei-Cheng; Yang, Chen-Yu; Liu, Shih-Chia; Hsieh, Chia-Chu; Fong, Yi-Chin; Wang, Po-Chuan; Tang, Chih-Hsin

    2017-08-03

    Chondrosarcoma is the second most common primary malignancy of bone, and one of the most difficult bone tumors to diagnose and treat. It is well known that increased levels of vascular endothelial growth factor-C (VEGF-C) promote active tumor lymphangiogenesis and lymphatic tumor spread to regional lymph nodes. Brain-derived neurotrophic factor (BDNF) is known to promote metastasis in human chondrosarcoma cells. Knowing more about the mechanism of BDNF in VEGF-C expression and lymphangiogenesis in human chondrosarcoma would improve our understanding as how to prevent chondrosarcoma angiogenesis and metastasis, which currently lacks effective adjuvant treatment. Here, we found that BDNF expression was at least 2.5-fold higher in the highly migratory JJ012(S10) cell line as compared with the primordial cell line (JJ012). In addition, VEGF-C expression and secretion was markedly increased in JJ012(S10) cells. Conditioned medium from JJ012(S10) cells significantly promoted migration and tube formation of human lymphatic endothelial cells (LECs), whereas knockdown of BDNF attenuated LEC migration and tube formation by suppressing VEGF-C production in JJ012(S10) cells. Mechanistic investigations indicated that BDNF facilitated VEGF-C-dependent lymphangiogenesis through the MEK/ERK/mTOR signaling pathway. We also showed that microRNA (miR)-624-3p expression was negatively regulated by BDNF via the MEK/ERK/mTOR cascade. Importantly, BDNF knockdown profoundly inhibited tumor-associated lymphangiogenesis in vivo. Further analyses identified that BDNF promoted tumor lymphangiogenesis by downregulating miR-624-3p in human chondrosarcoma tissues. In conclusion, this study is the first to reveal the mechanism underlying BDNF-induced lymphangiogenesis. We suggest that BDNF may serve as a promising therapeutic target for the restriction of VEGF-C-mediated tumor lymphangiogenesis and lymphatic metastasis.

  10. (1R,2R,3R,4R,5S-2,3-Bis[(2S′-2-acetoxy-2-phenylacetoxy]-4-azido-1-[(2,4-dinitrophenylhydrazonomethyl]bicyclo[3.1.0]hexane

    Directory of Open Access Journals (Sweden)

    Robert McDonald

    2008-02-01

    Full Text Available In the title compound, C38H29N7O12, the five-membered ring adopts an envelope conformation in which the `flap' is cis to the cyclopropane group. This conformation is similar to those of other bicyclo[3.1.0]hexane analogues for which crystal structures have been reported. The absolute configuration of the stereogenic centers on the cyclopentane ring, as determined by comparison with the known configurations of the stereogenic centers in the (2S-2-acetoxy-2-phenylacetoxy groups, is 1(R, 2(R, 3(R, 4(R and 5(S. An intramolecular N—H...O hydrogen bond is present.

  11. Cysteine-based 3-substituted 1,5-benzoxathiepin derivatives: Two new classes of anti-proliferative agents

    Directory of Open Access Journals (Sweden)

    Nawal Mahfoudh

    2018-03-01

    Full Text Available Two distinct series of the 3-amino-1,5-benzoxathiepin scaffold, derived from L-cysteine, were synthesized and evaluated for their anti-proliferative activity in the breast cancer MDA-MB-231 and MCF-7 cells, and in the ovarian carcinoma SKOV-3 cell line. (3R-Amino-3,4-dihydro-2H-1,5-benzoxathiepin [(R-10] was diversified into two forms: (a by incorporating different amino acids at its position 3, through an amide bond; and (b by construction of the purine ring to give 6-chloro-9-[2-(3,4-dihydro-2H-1,5-benzoxathiepin-(3R-yl]-9H-purine [(R-28]. Nevertheless, when the introduction of iodine was tried at position 2 of the purine ring of (R-28, 2-{[2-(6-chloro-2-iodo-9H-purin-9-ylprop-2-en-1-yl]thio}phenol (34 was obtained. Compound 34 shows activity against cancer cells. Interestingly, 34 inhibits mammosphere formation at the micromolar range, demonstrating activity against cancer stem cells. Although further studies of its targets and mechanism of action are needed, these findings support the therapeutic potential of this compound in cancer.

  12. Synthesis and antiproliferative activity of novel limonene derivatives with a substituted thiourea moiety

    International Nuclear Information System (INIS)

    Figueiredo, Isis M.; Santos, Luciane V. dos; Costa, Willian F. da; Silva, Cleuza C. da; Sarragiotto, Maria H.; Carvalho, Joao E. de; Sacoman, Juliana L.; Kohn, Luciana K.

    2006-01-01

    A series of R-(+)-limonene derivatives bearing a substituted thiourea moiety (3-13) and five S-methyl analogs (14-18) were synthesized and evaluated for their in vitro antiproliferative activity against human cancer cell lines. Compounds bearing aromatic substituents (3-6) exhibit cytostatic activity in the full panel of cell lines tested, with GI 50 values in the range of 2.5 to 24 μmol L -1 . Compounds 3, 10, 12 and 16 were the most active with GI 5 )0 values in the range of 0.41 to 3.0 μmol L -1 , against different cell lines. (author)

  13. Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads

    Directory of Open Access Journals (Sweden)

    Yi Bi

    2017-04-01

    Full Text Available Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300 and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606 in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC value of 2–16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL and kanamycin (KAN (FICI < 0.5. Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity.

  14. Enhanced fullerene–Au(111 coupling in (2√3 × 2√3R30° superstructures with intermolecular interactions

    Directory of Open Access Journals (Sweden)

    Michael Paßens

    2015-06-01

    Full Text Available Disordered and uniform (2√3 × 2√3R30° superstructures of fullerenes on the Au(111 surface have been studied using scanning tunneling microscopy and spectroscopy. It is shown that the deposition and growth process of a fullerene monolayer on the Au(111 surface determine the resulting superstructure. The supply of thermal energy is of importance for the activation of a Au vacancy forming process and thus, one criterion for the selection of the respective superstructure. However, here it is depicted that a vacancy–adatom pair can be formed even at room temperature. This latter process results in C60 molecules that appear slightly more bright in scanning tunnelling microscopy images and are identified in disordered (2√3 x 2√3R30° superstructures based on a detailed structure analysis. In addition, these slightly more bright C60 molecules form uniform (2√3 x 2√3R30° superstructures, which exhibit intermolecular interactions, likely mediated by Au adatoms. Thus, vacancy–adatom pairs forming at room temperature directly affect the resulting C60 superstructure. Differential conductivity spectra reveal a lifting of the degeneracy of the LUMO and LUMO+1 orbitals in the uniform (2√3 x 2√3R30° superstructure and in addition, hybrid fullerene–Au(111 surface states suggest partly covalent interactions.

  15. Magnetic order of Y{sub 3}NiSi{sub 3}-type R{sub 3}NiSi{sub 3} (R=Gd–DY) compounds

    Energy Technology Data Exchange (ETDEWEB)

    Morozkin, A.V., E-mail: morozkin@tech.chem.msu.ru [Department of Chemistry, Moscow State University, Leninskie Gory, House 1, Building 3, GSP-2, Moscow 119992 (Russian Federation); Yapaskurt, V.O. [Department of Petrology, Faculty of Geology, Moscow State University, Leninskie Gory, Moscow 119992 (Russian Federation); Nirmala, R. [Indian Institute of Technology Madras, Chennai 600036 (India); Malik, S.K.; Quezado, S. [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Natal 59082-970 (Brazil); Yao, Jinlei; Mozharivskyj, Y. [Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1 (Canada); Nigam, A.K. [Tata Institute of Fundamental Research, Mumbai 400005 (India); Isnard, O. [Université Grenoble Alpes, Inst NEEL, BP166, F-38042 Grenoble (France); CNRS, Institut NEEL, 25 rue des martyrs, F-38042 Grenoble (France)

    2016-01-15

    Magnetic measurements and neutron powder diffraction investigations on the Y{sub 3}NiSi{sub 3}-type R{sub 3}NiSi{sub 3} compounds (R=Gd, Tb, Dy) reveal their complex antiferromagnetic ordering. Magnetic measurements on Gd{sub 3}NiSi{sub 3}, Tb{sub 3}NiSi{sub 3} and Dy{sub 3}NiSi{sub 3} indicate antiferromagnetic-like transition at temperatures 260 K, 202 K and 140 K, respectively. Also, the Tb{sub 3}NiSi{sub 3} and Dy{sub 3}NiSi{sub 3} compounds show spin-reorientation transition at 132 K and 99 K, respectively. Below the spin-reorientation transition, the isothermal magnetization curves indicate the metamagnetic-like behavior of Tb{sub 3}NiSi{sub 3} and Dy{sub 3}NiSi{sub 3}. The magnetocaloric effect of Dy{sub 3}NiSi{sub 3} is calculated in terms of isothermal magnetic entropy change and it reaches a maximum value of −1.2 J/kg K and −1.1 J/kg K for a field change of 50 kOe near 146 K and 92 K, respectively. The neutron diffraction studies of Tb{sub 3}NiSi{sub 3} suggest the magnetic ordering of the Tb2 4j sublattice and no magnetic ordering of the Tb1 2a sublattice. Tb{sub 3}NiSi{sub 3} transforms from the high temperature paramagnetic state to the commensurate high-temperature a- and c-axis antiferromagnet of I′2/m magnetic space group below 250 K. Below 150 K, the high-temperature antiferromagnet transforms into the low-temperature a-, b- and c-axis antiferromagnet of I′i magnetic space group. At 1.5 K, the terbium magnetic moment in Tb2 sublattice and its a-, b- and c-axis components reach the values of M{sub Tb2}=8.2(1) μ{sub B}, M{sub aTb2}=5.9(1) μ{sub B}, M{sub bTb2}=4.3(2) μ{sub B} and M{sub cTb2}=3.7(2) μ{sub B}, respectively. - Highlights: • Gd{sub 3}NiSi{sub 3}, Tb{sub 3}NiSi{sub 3} and Dy{sub 3}NiSi{sub 3} have Neel points of 260. 202 and 140 K. • Tb{sub 3}NiSi{sub 3} and Dy{sub 3}NiSi{sub 3} show spin-reorientation transition at 132 and 99 K. • Tb{sub 3}NiSi{sub 3} exhibits the commensurate magnetic ordering of Tb2 4j sublattice

  16. N-Heterocyclic Carbene Coinage Metal Complexes of the Germanium-Rich Metalloid Clusters [Ge9R3]− and [Ge9RI2]2− with R = Si(iPr3 and RI = Si(TMS3

    Directory of Open Access Journals (Sweden)

    Felix S. Geitner

    2017-07-01

    Full Text Available We report on the synthesis of novel coinage metal NHC (N-heterocyclic carbene compounds of the germanium-rich metalloid clusters [Ge9R3]− and [Ge9RI2]2− with R = Si(iPr3 and RI = Si(TMS3. NHCDippCu{η3Ge9R3} with R = Si(iPr3 (1 represents a less bulky silyl group-substituted derivative of the known analogous compounds with R = Si(iBu3 or Si(TMS3. The coordination of the [NHCDippCu]+ moiety to the cluster unit occurs via one triangular face of the tri-capped trigonal prismatic [Ge9] cluster. Furthermore, a series of novel Zintl cluster coinage metal NHC compounds of the type (NHCM2{η3Ge9RI2} (RI = Si(TMS3 M = Cu, Ag and Au; NHC = NHCDipp or NHCMes is presented. These novel compounds represent a new class of neutral dinuclear Zintl cluster coinage metal NHC compounds, which are obtained either by the stepwise reaction of a suspension of K12Ge17 with Si(TMS3Cl and the coinage metal carbene complexes NHCMCl (M = Cu, Ag, Au, or via a homogenous reaction using the preformed bis-silylated cluster K2[Ge9(Si(TMS32] and the corresponding NHCMCl (M = Cu, Ag, Au complex. The molecular structures of NHCDippCu{η3Ge9(Si(iPr33} (1 and (NHCDippCu2{η3-Ge9(Si(TMS32} (2 were determined by single crystal X-ray diffraction methods. In 2, the coordination of the [NHCDippCu]+ moieties to the cluster unit takes place via both open triangular faces of the [Ge9] entity. Furthermore, all compounds were characterized by means of NMR spectroscopy (1H, 13C, 29Si and ESI-MS.

  17. The monoclonal S9.6 antibody exhibits highly variable binding affinities towards different R-loop sequences.

    Directory of Open Access Journals (Sweden)

    Fabian König

    Full Text Available The monoclonal antibody S9.6 is a widely-used tool to purify, analyse and quantify R-loop structures in cells. A previous study using the surface plasmon resonance technology and a single-chain variable fragment (scFv of S9.6 showed high affinity (0.6 nM for DNA-RNA and also a high affinity (2.7 nM for RNA-RNA hybrids. We used the microscale thermophoresis method allowing surface independent interaction studies and electromobility shift assays to evaluate additional RNA-DNA hybrid sequences and to quantify the binding affinities of the S9.6 antibody with respect to distinct sequences and their GC-content. Our results confirm high affinity binding to previously analysed sequences, but reveals that binding affinities are highly sequence specific. Our study presents R-loop sequences that independent of GC-content and in different sequence variations exhibit either no binding, binding affinities in the micromolar range and as well high affinity binding in the nanomolar range. Our study questions the usefulness of the S9.6 antibody in the quantitative analysis of R-loop sequences in vivo.

  18. Diagnostic of tumours of epithelial origin with the monoclonal antibody IOR EGF/R3 murino

    International Nuclear Information System (INIS)

    Ramos, M.

    1997-01-01

    Despite of the advantages on anti tumoral therapy, the cancer of epithelial origin constitutes one of the first causes of death worldwide. That kind of tumors have a 10-30-fold overexpression of the epidermal growth factor receptor (EGFr). Monoclonal antibody ior egf/r3 is a lgG2a, which recognizes the epidermal growth factor receptor. The aim of the present work was the evaluate the diagnostic efficacy of the 99m Tc-labelled ior egf/r3 for the detection of epithelial derived tumors, its metastasis and its recurrences

  19. Selective Hydrogenation of Biomass-derived Furfural over Supported Ni3Sn2 Alloy: Role of Supports

    Directory of Open Access Journals (Sweden)

    Rodiansono Rodiansono

    2016-03-01

    Full Text Available A highly active and selective hydrogenation of biomass-derived furfural into furfuryl alcohol was achieved using supported single phase Ni3Sn2 alloy catalysts. Various supports such as active carbon (AC, g-Al2O3, Al(OH3, ZnO, TiO2, ZrO2, MgO, Li-TN, and SiO2 have been employed in order to understand the role of the support on the formation of Ni3Sn2 alloy phase and its catalytic performance. Supported Ni3Sn2 alloy catalysts were synthesised via a simple hydrothermal treatment of the mixture of aqueous solution of nickel chloride hexahydrate and ethanol solution of tin(II chloride dihydrate in presence of ethylene glycol at 423 K for 24 h followed by H2 treatment at 673 K for 1.5 h, then characterised by using ICP-AES, XRD, H2- and N2-adsorption. XRD profiles of samples showed that the Ni3Sn2 alloy phases are readily formed during hydrothermal processes and become clearly observed at 2θ = 43-44o after H2 treatment. The presence of Ni3Sn2 alloy species that dispersed on the supports is believed to play a key role in highly active and selective hydrogenation of biomass-derived furfural towards furfuryl alcohol. Ni3Sn2 on TiO2 and ZnO supports exhibited much lower reaction temperature to achieved >99% yield of furfuryl alcohol product compared with other supports. The effects of loading amount of Ni-Sn, reaction conditions (temperature and time profile on the activity and selectivity towards the desired product are systematically discussed. Copyright © 2016 BCREC GROUP. All rights reserved Received: 10th November 2015; Revised: 31st December 2015; Accepted: 5th January 2016 How to Cite: Rodiansono, R., Astuti, M.D., Khairi, S., Shimazu, S. (2016. Selective Hydrogenation of Biomass-derived Furfural over Supported Ni3Sn2 Alloy: Role of Supports. Bulletin of Chemical Reaction Engineering & Catalysis, 11 (1: 1-9. (doi:10.9767/bcrec.11.1.393.1-9 Permalink/DOI: http://dx.doi.org/10.9767/bcrec.11.1.393.1-9

  20. Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance

    Science.gov (United States)

    Hsu, Alan Yi-Hui; Wu, Shang-Rung; Tsai, Jih-Jin; Chen, Po-Lin; Chen, Ya-Ping; Chen, Tsai-Yun; Lo, Yu-Chih; Ho, Tzu-Chuan; Lee, Meed; Chen, Min-Ting; Chiu, Yen-Chi; Perng, Guey Chuen

    2015-01-01

    The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a “sunny-side up egg” appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development. PMID:26657027

  1. miR-34a expands myeloid-derived suppressor cells via apoptosis inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Anfei, E-mail: huang_anfei@163.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Zhang, Haitao, E-mail: zhanghtjp@126.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215021, Jiangsu Province (China); Chen, Si, E-mail: chensisdyxb@126.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Xia, Fei, E-mail: xiafei87@gmail.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Yang, Yi, E-mail: 602744364@qq.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Dong, Fulu, E-mail: adiok0903@126.com [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Sun, Di, E-mail: dongfl@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Xiong, Sidong, E-mail: sdxiong@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China); Zhang, Jinping, E-mail: j_pzhang@suda.edu.cn [Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, Jiangsu Province (China)

    2014-08-15

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population and show significant expansion under pathological conditions. microRNA plays important roles in many biological processes, whether microRNAs have a function in the expansion of MDSCs is still not very clear. In this study, miR-34a overexpression can induce the expansion of MDSCs in bone marrow chimera and transgenic mice model. The experimental results suggest that miR-34a inhibited the apoptosis of MDSCs but did not affect the proliferation of MDSCs. The distinct mRNA microarray profiles of MDSCs of wild type and miR-34a over-expressing MDSCs combined with the target prediction of miR-34a suggest that miR-34a may target genes such as p2rx7, Tia1, and plekhf1 to inhibit the apoptosis of MDSCs. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis of MDSCs. - Highlights: • Over-expression of miR-34a increases the number of MDSCs. • miR-34a inhibits the apoptosis of MDSCs, but does not affects their proliferation. • miR-34a may inhibit the apoptosis of MDSCs via targeting the p2rx7, Tia1 and plekhf1.

  2. Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076

    Directory of Open Access Journals (Sweden)

    Nataly De Jesús Huertas Méndez

    2017-03-01

    Full Text Available Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B–containing non-natural amino acids and the RWQWR motif were synthesized, purified, and characterized using RP-HPLC, MALDI-TOF mass spectrometry, and circular dichroism. The antibacterial activity of peptides against Escherichia coli ATCC 11775, Stenotrophomonas maltophilia ATCC 13636, and Salmonella enteritidis ATCC 13076 was evaluated. The minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC were determined. The synthetic bovine lactoferricin exhibited antibacterial activity against E. coli ATCC 11775 and S. enteritidis ATCC 13076. The dimeric peptide (RRWQWR2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strain. The monomeric, cyclic, tetrameric, and palindromic peptides containing the RWQWR motif exhibited high and specific activity against E. coli ATCC 11775. The results suggest that short peptides derived from lactoferricin B could be considered as potential candidates for the development of antibacterial agents against infections caused by E. coli.

  3. STAT3-regulated exosomal miR-21 promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells.

    Science.gov (United States)

    Liu, Yi; Luo, Fei; Wang, Bairu; Li, Huiqiao; Xu, Yuan; Liu, Xinlu; Shi, Le; Lu, Xiaolin; Xu, Wenchao; Lu, Lu; Qin, Yu; Xiang, Quanyong; Liu, Qizhan

    2016-01-01

    Although microRNA (miRNA) enclosed in exosomes can mediate intercellular communication, the roles of exosomal miRNA and angiogenesis in lung cancer remain unclear. We investigated functions of STAT3-regulated exosomal miR-21 derived from cigarette smoke extract (CSE)-transformed human bronchial epithelial (HBE) cells in the angiogenesis of CSE-induced carcinogenesis. miR-21 levels in serum were higher in smokers than those in non-smokers. The medium from transformed HBE cells promoted miR-21 levels in normal HBE cells and angiogenesis of human umbilical vein endothelial cells (HUVEC). Transformed cells transferred miR-21 into normal HBE cells via exosomes. Knockdown of STAT3 reduced miR-21 levels in exosomes derived from transformed HBE cells, which blocked the angiogenesis. Exosomes derived from transformed HBE cells elevated levels of vascular endothelial growth factor (VEGF) in HBE cells and thereby promoted angiogenesis in HUVEC cells. Inhibition of exosomal miR-21, however, decreased VEGF levels in recipient cells, which blocked exosome-induced angiogenesis. Thus, miR-21 in exosomes leads to STAT3 activation, which increases VEGF levels in recipient cells, a process involved in angiogenesis and malignant transformation of HBE cells. These results, demonstrating the function of exosomal miR-21 from transformed HBE cells, provide a new perspective for intervention strategies to prevent carcinogenesis of lung cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. 3D-QSAR and molecular docking studies on derivatives of MK-0457, GSK1070916 and SNS-314 as inhibitors against Aurora B kinase.

    Science.gov (United States)

    Zhang, Baidong; Li, Yan; Zhang, Huixiao; Ai, Chunzhi

    2010-11-02

    Development of anticancer drugs targeting Aurora B, an important member of the serine/threonine kinases family, has been extensively focused on in recent years. In this work, by applying an integrated computational method, including comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), homology modeling and molecular docking, we investigated the structural determinants of Aurora B inhibitors based on three different series of derivatives of 108 molecules. The resultant optimum 3D-QSAR models exhibited (q(2) = 0.605, r(2) (pred) = 0.826), (q(2) = 0.52, r(2) (pred) = 0.798) and (q(2) = 0.582, r(2) (pred) = 0.971) for MK-0457, GSK1070916 and SNS-314 classes, respectively, and the 3D contour maps generated from these models were analyzed individually. The contour map analysis for the MK-0457 model revealed the relative importance of steric and electrostatic effects for Aurora B inhibition, whereas, the electronegative groups with hydrogen bond donating capacity showed a great impact on the inhibitory activity for the derivatives of GSK1070916. Additionally, the predictive model of the SNS-314 class revealed the great importance of hydrophobic favorable contour, since hydrophobic favorable substituents added to this region bind to a deep and narrow hydrophobic pocket composed of residues that are hydrophobic in nature and thus enhanced the inhibitory activity. Moreover, based on the docking study, a further comparison of the binding modes was accomplished to identify a set of critical residues that play a key role in stabilizing the drug-target interactions. Overall, the high level of consistency between the 3D contour maps and the topographical features of binding sites led to our identification of several key structural requirements for more potency inhibitors. Taken together, the results will serve as a basis for future drug development of inhibitors against Aurora B kinase for various tumors.

  5. Synthesis and biological characterization of (3R,4R)-4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol and its stereoisomers for monoamine transporters

    Science.gov (United States)

    Kharkar, Prashant S.; Batman, Angela M.; Zhen, Juan; Beardsley, Patrick M.; Reith, Maarten E. A.

    2012-01-01

    In this report we describe synthesis and biological evaluation of a series of asymmetric 4-(2-(benzhydryloxy)ethyl)-1-((R)-2-hydroxy-2-phenylethyl)-piperidin-3-ol based dihydroxy compounds where the hydroxy groups are located both on the piperidine ring and also on the N-phenylethyl side chain exo-cyclically. In vitro uptake inhibition data indicates high affinity of these molecules for the dopamine transporter (DAT) in addition to their moderate to high affinity for the norepinephrine transporter (NET). Interestingly, compounds 9b and 9d exhibited affinities for all three monoamine transporters with highest potency at DAT and NET and moderate potency at the serotonin transporter (SERT) (Ki 2.29, 78.4 and 155 nM for 9b and 1.55, 14.1 and 259 nM for 9d, respectively). Selected compounds, 9a, 9d and 9d’ were tested for their locomotor activity effects in mice, and for their ability to occasion the cocaine discriminative stimulus in rats. These test compounds generally exhibited a much longer duration of action than cocaine for elevating locomotor activity, and dose-dependently completely generalized the cocaine discriminative stimulus. PMID:19449323

  6. N9-Substituted N(6)-[(3-methylbut-2-en-1-yl)amino]purine derivatives and their biological activity in selected cytokinin bioassays

    Czech Academy of Sciences Publication Activity Database

    Mik, V.; Szüčová, Lucie; Spíchal, Lukáš; Plíhal, O.; Nisler, Jaroslav; Zahajská, L.; Doležal, Karel; Strnad, Miroslav

    2011-01-01

    Roč. 19, č. 23 (2011), s. 7244-7251 ISSN 0968-0896 R&D Projects: GA MŠk ED0007/01/01; GA ČR GA522/09/1576 Keywords : N6-[(3-Methylbut-2-en-1-yl)amino]purine * Isopentenyladenine derivatives * N9-Substituted derivatives * Cytokinins * Cytokinin receptors Subject RIV: EF - Botanics Impact factor: 2.921, year: 2011

  7. Dielectric properties of thin C r2O3 films grown on elemental and oxide metallic substrates

    Science.gov (United States)

    Mahmood, Ather; Street, Michael; Echtenkamp, Will; Kwan, Chun Pui; Bird, Jonathan P.; Binek, Christian

    2018-04-01

    In an attempt to optimize leakage characteristics of α-C r2O3 thin films, its dielectric properties were investigated at local and macroscopic scale. The films were grown on Pd(111), Pt(111), and V2O3 (0001), supported on A l2O3 substrate. The local conductivity was measured by conductive atomic force microscopy mapping of C r2O3 surfaces, which revealed the nature of defects that formed conducting paths with the bottom Pd or Pt layer. A strong correlation was found between these electrical defects and the grain boundaries revealed in the corresponding topographic scans. In comparison, the C r2O3 film on V2O3 exhibited no leakage paths at similar tip bias value. Electrical resistance measurements through e-beam patterned top electrodes confirmed the resistivity mismatch between the films grown on different electrodes. The x-ray analysis attributes this difference to the twin free C r2O3 growth on V2O3 seeding.

  8. Self-assembly of nano/micro-structured Fe3O4 microspheres among 3D rGO/CNTs hierarchical networks with superior lithium storage performances

    International Nuclear Information System (INIS)

    Liu, Jinlong; Feng, Haibo; Wang, Xipeng; Qian, Dong; Jiang, Jianbo; Li, Junhua; Peng, Sanjun; Deng, Miao; Liu, Youcai

    2014-01-01

    Nano/micro-structured Fe 3 O 4 microspheres among three-dimensional (3D) reduced graphene oxide (rGO)/carbon nanotubes (CNTs) hierarchical networks (the ternary composite is denoted as rGCFs) have been synthesized using a facile, self-assembled and one-pot hydrothermal approach. The rGCFs composite exhibits superior lithium storage performances: initial discharge and charge capacities of 1452 and 1036 mAh g −1 , respectively, remarkable rate capability at current densities from 100 mA g −1 to 10 A g −1 and outstanding cycling performance up to 200 cycles. The highly enhanced electrochemical performances of rGCFs depend heavily on the robust 3D rGO/CNTs hierarchical networks, the stable nano/microstructures of active Fe 3 O 4 microspheres and the positive synergistic effects of building components. The systematic structure characterizations and electrochemical investigations provide insightful understanding towards the relationship between structure/morphology and lithium storage performances, which may pave the way for the rational design of composite materials with desirable goals. (papers)

  9. Steviamine, a new class of indolizidine alkaloid [(1R,2S,3R,5R,8aR-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol hydrobromide

    Directory of Open Access Journals (Sweden)

    Amber L. Thompson

    2009-11-01

    Full Text Available X-ray crystallographic analysis of the title hydrobromide salt, C10H20N+·Br−, of (1R,2S,3R,5R,8aR-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol defines the absolute and relative stereochemistry at the five chiral centres in steviamine, a new class of polyhydroxylated indolizidine alkaloid isolated from Stevia rebaudiana (Asteraceae leaves. In the crystal structure, molecules are linked by intermolecular O—H...Br and N—H...Br hydrogen bonds, forming double chains around the twofold screw axes along the b-axis direction. Intramolecular O—H...O interactions occur.

  10. Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster.

    Science.gov (United States)

    Mondal, Tanmoy; Lavanya, A V S; Mallick, Akash; Dadmala, Tulshiram L; Kumbhare, Ravindra M; Bhadra, Utpal; Bhadra, Manika Pal

    2017-06-01

    Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibit miR-2, miR-13 and miR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species (ROS) level to trigger apoptotic cell death.

  11. Dielectric and piezoelectric properties of sol-gel derived Ca doped PbTiO3

    International Nuclear Information System (INIS)

    Chauhan, Arun Kumar Singh; Gupta, Vinay; Sreenivas, K.

    2006-01-01

    Synthesis of Ca doped PbTiO 3 powder by a chemically derived sol-gel process is described. Crystallization characteristics of different compositions Pb 1-x Ca x TiO 3 (PCT) with varying calcium (Ca) content in the range x = 0-0.45 has been investigated by DTA/TGA, X-ray diffraction and scanning electron microscopy. The crystallization temperature is found to decrease with increasing calcium content. X-ray diffraction reveals a tetragonal structure for PCT compositions with x ≤ 0.35, and a cubic structure for x = 0.45. Dielectric properties on sintered ceramics prepared with fine sol-gel derived powders have been measured. The dielectric constant is found to increase with increasing Ca content, and the dielectric loss decreases continuously. Sol-gel derived Pb 1-x Ca x TiO 3 ceramics with x = 0.45 after poling exhibit infinite electromechanical anisotropy (k t /k p ) with a high d 33 = 80 pC/N, ε' = 298 and low dielectric loss (tan δ = 0.0041)

  12. A new class of nitrosoureas. 4. Synthesis and antitumor activity of disaccharide derivatives of 3,3-disubstituted 1-(2-chloroethyl)-1-nitrosoureas.

    Science.gov (United States)

    Tsujihara, K; Ozeki, M; Morikawa, T; Kawamori, M; Akaike, Y; Arai, Y

    1982-04-01

    A series of 33 N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of N-substituted glycosylamines has been prepared and tested for antitumor activities. The compounds were obtained by reaction of glycosylamines with isocyanate, followed by nitrosation with N2O4. Structure-activity relationships of these trisubstituted nitrosoureas were investigated by varying the N-substituents and disaccharide groups and by comparing them with the corresponding disubstituted analogues. A large number of the nitrosoureas bearing a maltosyl group exhibited strong antitumor activities against leukemia L1210 and Ehrlich ascites carcinoma, and 60-day survivors against leukemia L1210 were found at the optimal dose for these derivatives. In contrast, the lactosyl and the melibiosyl derivatives were almost inactive. The most interesting compound in this series, the 3-isobutyl-3-maltosyl derivative (37), was tested against leukemia L1210 by single and multiple treatment. Its therapeutic ratio (96.3) obtained by multiple treatment is 3 times larger than that (31.5) obtained by single treatment, suggesting a possible clinical utility of 37 by multiple treatment. The favorable effect of a maltosyl moiety in this class of compounds is discussed.

  13. Effect of 1,24R-dihydroxyvitamin D3 on the growth of human keratinocytes.

    LENUS (Irish Health Repository)

    Matsumoto, K

    1990-02-01

    The effect of 1,24R-dihydroxyvitamin D3 (1,24R(OH)2D3), a synthetic analogue of a biologically active form of vitamin D3 (1,25-dihydroxyvitamin D3, 1,25(OH)2D3), on the growth of human keratinocytes cultured in serum-free medium was investigated. The growth of cultured normal human keratinocytes was inhibited by 65% by 10(-8)M 1,24R(OH)2D3 and by 90% by 10(-7)M 1,24(OH)2D3. It inhibited cell growth almost completely at 10(-6)M. The DNA synthesis of keratinocytes was also inhibited with 1,24R(OH)2D3 by 27% at 10(-8)M, 59% at 10(-7)M, and 92% at 10(-6)M. The inhibition of cell growth and DNA synthesis were more remarkable by 1,24R(OH)2D3 than by 1,25(OH)2D3. 1,24R(OH)2D3 also inhibited the growth of keratinocytes derived from patients with psoriasis vulgaris; the growth inhibitory effect was again more remarkable with 1,24R(OH)2D3 than with 1,25(OH)2D3. The viability and protein synthesis of keratinocytes were not affected by 1,24R(OH)2D3, suggesting that the growth inhibitory effect is due to its biological activity, not to cytotoxicity. The binding of [3H]-labeled 1,25(OH)2D3 to its receptor in the cytosolic fraction of cultured keratinocytes was competitively substituted by unlabeled 1,24R(OH)2D3 as well as 1,25(OH)2D3, suggesting that 1,24R(OH)2D3 binds to the 1,25(OH)2D3 receptor. It was found that the affinity of 1,24R(OH)2D3 for the receptor was slightly higher than that of 1,25(OH)2D3. These results demonstrate that 1,24R(OH)2D3 functions as a potent growth inhibitor in vitro in human keratinocytes from both normal and psoriatic epidermis, and it possesses a higher affinity for the 1,25(OH)2D3 receptor in cultured human keratinocytes. The difference in affinity of 1,24R(OH)2D3 for the 1,25(OH)2D3 receptor correlates with its greater inhibition of keratinocyte growth than 1,25(OH)2D3. 1,24R(OH)2D3 may be useful in the treatment of psoriasis.

  14. Dental pulp-derived stromal cells exhibit a higher osteogenic potency than bone marrow-derived stromal cells in vitro and in a porcine critical-size bone defect model

    Directory of Open Access Journals (Sweden)

    Jensen Jonas

    2016-01-01

    Full Text Available Introduction: The osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSCs was compared with that of dental pulp-derived stromal cells (DPSCs in vitro and in a pig calvaria critical-size bone defect model. Methods: BMSCs and DPSCs were extracted from the tibia bone marrow and the molar teeth of each pig, respectively. BMSCs and DPSCs were cultured in monolayer and on a three-dimensional (3D polycaprolactone (PCL – hyaluronic acid – tricalcium phosphate (HT-PCL scaffold. Population doubling (PD, alkaline phosphatase (ALP activity, and calcium deposition were measured in monolayer. In the 3D culture ALP activity, DNA content, and calcium deposition were evaluated. Six non-penetrating critical-size defects were made in each calvarium of 14 pigs. Three paired sub-studies were conducted: (1 empty defects vs. HT-PCL scaffolds; (2 PCL scaffolds vs. HT-PCL scaffolds; and (3 autologous BMSCs on HT-PCL scaffolds vs. autologous DPSCs on HT-PCL scaffolds. The observation time was five weeks. Bone volume fractions (BV/TV were assessed with micro-computed tomography (μCT and histomorphometry. Results and discussion: The results from the in vitro study revealed a higher ALP activity and calcium deposition of the DPSC cultures compared with BMSC cultures. Significantly more bone was present in the HT-PCL group than in both the pure PCL scaffold group and the empty defect group in vivo. DPSCs generated more bone than BMSCs when seeded on HT-PCL. In conclusion, DPSCs exhibited a higher osteogenic potential compared with BMSCs both in vitro and in vivo, making it a potential cell source for future bone tissue engineering.

  15. Taste information derived from T1R-expressing taste cells in mice.

    Science.gov (United States)

    Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-03-01

    The taste system of animals is used to detect valuable nutrients and harmful compounds in foods. In humans and mice, sweet, bitter, salty, sour and umami tastes are considered the five basic taste qualities. Sweet and umami tastes are mediated by G-protein-coupled receptors, belonging to the T1R (taste receptor type 1) family. This family consists of three members (T1R1, T1R2 and T1R3). They function as sweet or umami taste receptors by forming heterodimeric complexes, T1R1+T1R3 (umami) or T1R2+T1R3 (sweet). Receptors for each of the basic tastes are thought to be expressed exclusively in taste bud cells. Sweet (T1R2+T1R3-expressing) taste cells were thought to be segregated from umami (T1R1+T1R3-expressing) taste cells in taste buds. However, recent studies have revealed that a significant portion of taste cells in mice expressed all T1R subunits and responded to both sweet and umami compounds. This suggests that sweet and umami taste cells may not be segregated. Mice are able to discriminate between sweet and umami tastes, and both tastes contribute to behavioural preferences for sweet or umami compounds. There is growing evidence that T1R3 is also involved in behavioural avoidance of calcium tastes in mice, which implies that there may be a further population of T1R-expressing taste cells that mediate aversion to calcium taste. Therefore the simple view of detection and segregation of sweet and umami tastes by T1R-expressing taste cells, in mice, is now open to re-examination. © 2016 Authors; published by Portland Press Limited.

  16. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study.

    Science.gov (United States)

    Wu, Jing; Lu, Chanyi; Diao, Ni; Zhang, Shu; Wang, Sen; Wang, Feifei; Gao, Yan; Chen, Jiazhen; Shao, Lingyun; Lu, Jingning; Zhang, Xuelian; Weng, Xinhua; Wang, Honghai; Zhang, Wenhong; Huang, Yuxian

    2012-01-01

    To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  17. 3D Adaptive Virtual Exhibit for the University of Denver Digital Collections

    Directory of Open Access Journals (Sweden)

    Shea-Tinn Yeh

    2015-07-01

    Full Text Available While the gaming industry has taken the world by storm with its three-dimensional (3D user interfaces, current digital collection exhibits presented by museums, historical societies, and libraries are still limited to a two-dimensional (2D interface display. Why can’t digital collections take advantage of this 3D interface advancement? The prototype discussed in this paper presents to the visitor a 3D virtual exhibit containing a set of digital objects from the University of Denver Libraries’ digital image collections, giving visitors an immersive experience when viewing the collections. In particular, the interface is adaptive to the visitor’s browsing behaviors and alters the selection and display of the objects throughout the exhibit to encourage serendipitous discovery. Social media features were also integrated to allow visitors to share items of interest and to create a sense of virtual community.

  18. Chemistry of the oxophosphinidene ligand. 2. Reactivity of the anionic complexes [MCp{P(O)R*}(CO)(2)](-) (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3)) toward electrophiles based on elements different from carbon.

    Science.gov (United States)

    Alonso, María; Alvarez, M Angeles; García, M Esther; Ruiz, Miguel A; Hamidov, Hayrullo; Jeffery, John C

    2010-12-20

    The anionic oxophosphinidene complexes (H-DBU)[MCp{P(O)R*}(CO)(2)] (M = Mo, W; R* = 2,4,6-C(6)H(2)(t)Bu(3); Cp = η(5)-C(5)H(5), DBU = 1,8-diazabicyclo [5.4.0] undec-7-ene) displayed multisite reactivity when faced with different electrophilic reagents. The reactions with the group 14 organochloride compounds ER(4-x)Cl(x) (E = Si, Ge, Sn, Pb) led to either phosphide-like, oxophosphinidene-bridged derivatives [MCp{P(OE')R*}(CO)(2)] (E' = SiMe(3), SiPh(3), GePh(3), GeMe(2)Cl) or to terminal oxophosphinidene complexes [MCp{P(O)R*}(CO)(2)(E')] (E' = SnPh(3), SnPh(2)Cl, PbPh(3); Mo-Pb = 2.8845(4) Å for the MoPb compound). A particular situation was found in the reaction with SnMe(3)Cl, this giving a product existing in both tautomeric forms, with the phosphide-like complex [MCp{P(OSnMe(3))R*}(CO)(2)] prevailing at room temperature and the tautomer [MCp{P(O)R*}(CO)(2)(SnMe(3))] being the unique species present below 203 K in dichloromethane solution. The title anions also showed a multisite behavior when reacting with transition-metal based electrophiles. Thus, the reactions with the complexes [M'Cp(2)Cl(2)] (M' = Ti, Zr) gave phosphide-like derivatives [MCp{P(OM')R*}(CO)(2)] (M = Mo, M' = TiCp(2)Cl, ZrCp(2)Cl; M = W, M' = ZrCp(2)Cl), displaying a bridging κ(1),κ(1)-P,O- oxophosphinidene ligand connecting MCp(CO)(2) and M'Cp(2)Cl metal fragments (W-P = 2.233(1) Å, O-Zr = 2.016(4) Å for the WZr compound]. In contrast, the reactions with the complex [AuCl{P(p-tol)(3)}] gave the metal-metal bonded derivatives trans-[MCp{P(O)R*}(CO)(2){AuP(p-tol)(3)}] (M = Mo, W; Mo-Au = 2.7071(7) Å). From all the above results it was concluded that the terminal oxophosphinidene complexes are preferentially formed under conditions of orbital control, while charge-controlled reactions tend to give derivatives with the electrophilic fragment bound to the oxygen atom of the oxophosphinidene ligand (phosphide-like, oxophosphinidene-bridged derivatives).

  19. Synthesis of 1-isopropyl-3-acyl-5-methyl-benzimidazolone Derivatives and Their Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Shaopeng Wei

    2013-03-01

    Full Text Available A series of N-acylated analogues of 1-isopropyl-3-acyl-5-methyl-benzimidazolone were synthesized. Bioassay results indicated that analogues 5-07 and 5-19 exhibited the most potency against Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Analogues 5-02, 5-07, 5-12, 5-15, 5-19, 5-20 and 5-25 could effectively inhibit the spore germination of Botrytis cinerea. The relationship between structure and their antimicrobial activity (SAR has also been discussed according to aliphatic acids and aromatic acids derivatives, respectively. This implied that the N-acylated derivatives of 5-methyl-benzimidazolone might be potential antimicrobial agents.

  20. miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9.

    Science.gov (United States)

    Su, Mei-Tsz; Tsai, Pei-Yin; Tsai, Hui-Ling; Chen, Yi-Chi; Kuo, Pao-Lin

    2017-03-01

    Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an important regulator for embryo implantation and placental development, and is clinically associated with several obstetric disorders related to insufficient or inappropriate trophoblast invasion, such as recurrent abortion, preeclampsia, and intrauterine fetal growth restriction. This study was performed to identify the microRNAs targeting EG-VEGF, and evaluate the regulatory effect on trophoblast biology. miR-346 and miR-582-3p were initially identified via bioinformatic tools, and their specific binding sites on the EG-VEGF 3'UTR were further confirmed using dual luciferase and a co-transfection assays. miR-346 and miR-582-3p were demonstrated not only to suppress EG-VEGF expression, but also inhibit trophoblast invasion and migration in the JAR and HTR-8/SVneo cell lines. We further evaluated the effect of microRNAs in HTR-8/SVneo cells coexpressing EG-VEGF and miR-346 or miR-582-3p on matrix metalloproteinase (MMP 2 and MMP 9) and the tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2) using RT-PCR, western blotting and gelatin zymography. TIMP 1 and TIMP 2 were not affected by the two microRNAs, whereas the expressions and activities of MMP 2 and MMP 9 were significantly downregulated, which in turn inhibited the invasion ability of trophoblasts. In conclusion, miR-346 and miR-582-3p regulate EG-VEGF-induced trophoblast invasion through repressing MMP 2 and MMP 9, and may become novel diagnostic biomarkers or therapeutic targets for EG-VEGF-related obstetric disorders. © 2016 BioFactors, 43(2):210-219, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  1. Analytical computation of thermodynamic performance parameters of actual vapour compression refrigeration system with R22, R32, R134a, R152a, R290 and R1270

    Directory of Open Access Journals (Sweden)

    Vali Shaik Sharmas

    2018-01-01

    Full Text Available The present work focuses on analytical computation of thermodynamic performance of actual vapour compression refrigeration system by using six pure refrigerants. The refrigerants are namely R22, R32, R134a, R152a, R290 and R1270 respectively. A MATLAB code is developed to compute the thermodynamic performance parameters of actual vapour compression system such as refrigeration effect, compressor work, COP, power per ton of refrigeration, compressor discharge temperature and volumetric refrigeration capacity at condensing and evaporating temperatures of 54.4oC and 7.2oC respectively. Analytical results exhibited that COP of both R32 and R134a are 15.95% and 11.71% higher among the six investigated refrigerants. However R32 and R134a cannot be replaced directly into R22 system. This is due to their higher compressor discharge temperature and poor volumetric capacity respectively. The discharge temperature of both R1270 and R290 are lower than R22 by 20-26oC. Volumetric refrigeration capacity of R1270 (3197 kJ/m3 is very close to that of volumetric capacity of R22 (3251 kJ/m3. Both R1270 and R290 shows good miscibility with R22 mineral oil. Overall R1270 would be a suitable ecofriendly refrigerant to replace R22 from the stand point of ODP, GWP, volumetric capacity, discharge temperature and miscibility with mineral oil although its COP is lower.

  2. Verification of failure avoidance concepts in R6 Rev3

    International Nuclear Information System (INIS)

    Milne, I.; Knee, N.

    1988-09-01

    The first part of this Report outlines how recent developments in fracture mechanics have led to a more accurate interpretation of the two-criteria approach to defect assessment. The implementation of these developments into Revision 3 of the Central Electricity Generating Board code of practice for the assessment of the defect tolerance of structures (R6) is described. One of the key elements of the revised version is the recommendation that the failure assessment line should be derived from the actual tensile stress/strain properties of the material. The second part of the Report addresses the validation of the method, which is a crucial step on the way to obtaining acceptance of R6 by, in particular, the regulatory bodies. The range of structures used to validate the procedure is illustrated by two examples. The use of conservative data and assumptions is fundamental to the R6 philosophy, which means that the procedure should not be used as a predictive tool. In the second example the importance of making these conservative assumptions is clearly illustrated. (author)

  3. Crystal structure of (1S,3R,8R,9R-2,2-dichloro-3,7,7-trimethyl-10-methylenetricyclo[6.4.0.01,3]dodecan-9-ol

    Directory of Open Access Journals (Sweden)

    Ahmed Benzalim

    2016-08-01

    Full Text Available The title compound, C16H24Cl2O, was synthesized by treating (1S,3R,8S,9R,10S-2,2-dichloro-3,7,7,10-tetramethyl-9,10-epoxytricyclo[6.4.0.01,3]dodecane with a concentrated solution of hydrobromic acid. It is built up from three fused rings: a cycloheptane ring, a cyclohexyl ring bearing alkene and hydroxy substituents, and a cyclopropane ring bearing two chlorine atoms. The asymmetric unit contains two molecules linked by an O—H...O hydrogen bond. In the crystal, further O—H...O hydrogen bonds build up an R44(8 cyclic tetramer. One of the molecules presents disorder that affects the seven-membered ring. In both molecules, the six-membered rings display a chair conformation, whereas the seven-membered rings display conformations intermediate between boat and twist-boat for the non-disordered molecule and either a chair or boat and twist-boat for the disordered molecule owing to the disorder. The absolute configuration for both molecules is 1S,3R,8R,9R and was deduced from the chemical pathway and further confirmed by the X-ray structural analysis.

  4. N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors.

    Science.gov (United States)

    Fang, Ming; Chai, Yiqiu; Chen, Guanjv; Wang, Huidong; Huang, Bo

    The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32-35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR.

  5. Design, Synthesis and Antitumor Activity of Novel 4-Methyl-(3'S,4'S-cis-khellactone Derivatives

    Directory of Open Access Journals (Sweden)

    Taigang Liang

    2013-04-01

    Full Text Available An asymmetric synthesis of a series of novel 4-methyl-(3'S,4'S-cis-khellactone derivatives 3a–o is reported for the first time. Their structures were confirmed by 1H-NMR, 13C-NMR and MS. Their cytotoxic activity was evaluated by the MTT assay against three selected human cancer cell lines: HEPG-2 (human liver carcinoma, SGC-7901 (human gastric carcinoma, LS174T (human colon carcinoma. Some compounds showed high inhibitory activity against these human cancer cell lines. Among them, compound 3a exhibited strong cytotoxicity, with IC50 values ranging from 8.51 to 29.65 μM. The results showed that 4-methyl-cis-khellactone derivatives with S,S configuration could be a potential antitumor agents.

  6. New lanthanide(III) complexes of chiral nonadendate macrocyclic amine derived from (1R,2R)-1,2-diaminocyclohexane and 2,6-diformyl-4-methylphenol

    Energy Technology Data Exchange (ETDEWEB)

    Paluch, Marta [Department of Chemistry, University of Wroclaw, 14 F. Joliot-Curie, 50-383 Wroclaw (Poland); Lisowski, Jerzy [Department of Chemistry, University of Wroclaw, 14 F. Joliot-Curie, 50-383 Wroclaw (Poland)], E-mail: jurekl@wchuwr.chem.uni.wroc.pl

    2008-02-28

    The series of complexes [LnH{sub 4}L(NO{sub 3}){sub 2}](NO{sub 3}){sub 2}.nH{sub 2}O (Ln = La, Ce, Pr, Nd, Gd, Tb, Ho, Er, Tm) of the positively charged protonated form of a chiral macrocyclic amine H{sub 4}L{sup +}, derived from the 3 + 3 condensation product of (1R,2R)-1,2-diaminocyclohexane and 2,6-diformyl-4-methylphenol, have been synthesized. The series of complexes Na{sub x}[LnL](X){sub y}(OH){sub x-y}.n(solv) (X = NO{sup 3-} or Cl{sup -}, and Ln = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) of the deprotonated anionic form of the ligand, L{sup 3-}, have also been synthesised. The complexes have been characterised by elemental analyses, {sup 1}H NMR and ESI MS spectra. The X-ray crystal structures of the [LaH{sub 4}L(NO{sub 3}){sub 2}](NO{sub 3}){sub 2}.5CH{sub 3}OH and [GdH{sub 4}L(NO{sub 3}){sub 2}](NO{sub 3}){sub 2}.5CH{sub 3}OH complexes have been determined. The two complexes are isostructural, and the protonated macrocycle acts as pentadentate ligand. The Ln(III) ion is bound to three phenolate oxygen atoms and two amine nitrogen atoms of the macrocyclic ligand and its coordination sphere is completed by the two axial bidendate nitrate anions.

  7. Biosynthesis of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate by carbonyl reductase from Rhodosporidium toruloides in mono and biphasic media.

    Science.gov (United States)

    Liu, Zhi-Qiang; Wu, Lin; Zheng, Ling; Wang, Wen-Zhong; Zhang, Xiao-Jian; Jin, Li-Qun; Zheng, Yu-Guo

    2018-02-01

    tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is the key intermediate for synthesis of atorvastatin and rosuvastatin. Carbonyl reductase exhibits excellent activity toward tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH) to synthesize (3R,5S)-CDHH. In this study, a whole cell biosynthesis reaction system to produce (3R,5S)-CDHH was constructed in organic solvents. A solution of 10% (v/v) Tween-80 was introduced to the reaction system as a co-solvent, which greatly enhanced biotransformation process, giving 98.9% yield, >99% ee and 1.8-fold higher space time yield in 5 h bioconversion of 1 M (S)-CHOH, compared with 98.7% yield and >99% ee in 9 h bioconversion of a purely aqueous reaction system. Moreover, a water-octanol biphasic reaction system was built and 20% of octanol was added as reservoir of substrate resulting in 98% yield, >99% ee and 4.08 mmol L -1  h -1  g -1 (wet cell weight) space time yield. This study paved a way for the whole cell biosynthesis of (3R,5S)-CDHH in mono and biphasic media. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. A 3D QSAR study of betulinic acid derivatives as anti-tumor agents using topomer CoMFA: model building studies and experimental verification.

    Science.gov (United States)

    Ding, Weimin; Sun, Miao; Luo, Shaman; Xu, Tao; Cao, Yibo; Yan, Xiufeng; Wang, Yang

    2013-08-22

    Betulinic acid (BA) is a natural product that exerts its cytotoxicity against various malignant carcinomas without side effects by triggering the mitochondrial pathway to apoptosis. Betulin (BE), the 28-hydroxyl analog of BA, is present in large amounts (up to 30% dry weight) in the outer bark of birch trees, and shares the same pentacyclic triterpenoid core as BA, yet exhibits no significant cytotoxicity. Topomer CoMFA studies were performed on 37 BA and BE derivatives and their in vitro anti-cancer activity results (reported as IC₅₀ values) against HT29 human colon cancer cells in the present study. All derivatives share a common pentacyclic triterpenoid core and the molecules were split into three pieces by cutting at the C-3 and C-28 sites with a consideration toward structural diversity. The analysis gave a leave-one-out cross-validation q² value of 0.722 and a non-cross-validation r² value of 0.974, which suggested that the model has good predictive ability (q² > 0.2). The contour maps illustrated that bulky and electron-donating groups would be favorable for activity at the C-28 site, and a moderately bulky and electron-withdrawing group near the C-3 site would improve this activity. BE derivatives were designed and synthesized according to the modeling result, whereby bulky electronegative groups (maleyl, phthalyl, and hexahydrophthalyl groups) were directly introduced at the C-28 position of BE. The in vitro cytotoxicity values of the given analogs against HT29 cells were consistent with the predicted values, proving that the present topomer CoMFA model is successful and that it could potentially guide the synthesis of new betulinic acid derivatives with high anti-cancer activity. The IC₅₀ values of these three new compounds were also assayed in five other tumor cell lines. 28-O-hexahydrophthalyl BE exhibited the greatest anti-cancer activities and its IC₅₀ values were lower than those of BA in all cell lines, excluding DU145 cells.

  9. Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics.

    Science.gov (United States)

    Yang, Yanping; Wang, Xuedan; Yang, Hui; Fu, Hualong; Zhang, Jinming; Zhang, Xiaojun; Dai, Jiapei; Zhang, Zhiyong; Lin, Chunping; Guo, Yuzhi; Cui, Mengchao

    2016-11-07

    This study describes an effective strategy to improve pharmacokinetics of Aβ imaging agents, offering a novel class of (R)- and (S)- 18 F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aβ aggregates with K i values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[ 18 F]28 possessed high binding potency (K i = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain 2min /brain 60min = 27.8) that is superior to well-established [ 18 F]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[ 18 F]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[ 18 F]28 clearly labeled Aβ plaques both in vitro and ex vivo. These results might qualify (S)-[ 18 F]28 to detect Aβ plaques with high signal-to-noise ratio.

  10. Evaluation of the gait performance of above-knee amputees while walking with 3R20 and 3R15 knee joints

    Directory of Open Access Journals (Sweden)

    AliReza Taheri

    2012-01-01

    Full Text Available Background: The performance of the subjects with above-knee amputation is noticeably poorer than normal subjects. Various types of components have been designed to compensate their performance. Among various prosthetic components, the knee joint has great influence on the function. Two types of knee joints (3R15, 3R20 have been used broadly for above-knee prostheses. However, there is not enough research to highlight the influence of these joints on the gait performance of the subjects. Therefore, an aim of this research was to investigate the performance of the above-knee amputees while walking with 3R15 and 3R20 knee joints. Materials and Methods: 7 above-knee amputees were recruited in this research study. They were asked to walk with a comfortable speed to investigate the gait function of the subjects with 3 cameras 3D motion analysis system (Kinematrix system. The difference between the performances of the subjects with these joints was compared by use of paired t-test. Results: The results of this study showed that, the performances of the subjects with 3R20 were better than that with 3R15. The walking speed of the subjects with 3R20 was 66.7 m/min compared to 30.4 m/min (P-value = 0.045. Moreover; the symmetry of walking with 3R20 was more than that with 3R15, based on the spatio- temporal gait parameters values (P-value <0.05. Conclusion: The difference between the performances of the subjects with 3R20 and 3R15 knee joints was related to the walking speed, which improved while walking with 3R20 joint.

  11. Data-Driven Analysis of Virtual 3D Exploration of a Large Sculpture Collection in Real-World Museum Exhibitions

    KAUST Repository

    Agus, Marco

    2018-01-29

    We analyze use of an interactive system for the exploration of highly detailed three-dimensional (3D) models of a collection of protostoric Mediterranean sculptures. In this system, when the object of interest is selected, its detailed 3D model and associated information are presented at high resolution on a large display controlled by a touch-enabled horizontal surface at a suitable distance. The user interface combines an object-Aware interactive camera controller with an interactive point-ofinterest selector and is implemented within a scalable implementation based on multiresolution structures shared between the rendering and user interaction subsystems. The system was installed in several temporary and permanent exhibitions and was extensively used by tens of thousands of visitors. We provide a data-driven analysis of usage experience based on logs gathered during a 27-month period at four exhibitions in archeological museums for a total of more than 75K exploration sessions. We focus on discerning the main visitor behaviors during 3D exploration by employing tools for deriving interest measures on surfaces and tools for clustering and knowledge discovery from high-dimensional data. The results highlight the main trends in visitor behavior during the interactive sessions. These results provide useful insights for the design of 3D exploration user interfaces in future digital installations.© 2017 ACM 1556-4673/2017/12-ART2 $15.00.

  12. Data-Driven Analysis of Virtual 3D Exploration of a Large Sculpture Collection in Real-World Museum Exhibitions

    KAUST Repository

    Agus, Marco; Marton, Fabio; Bettio, Fabio; Hadwiger, Markus; Gobbetti, Enrico

    2018-01-01

    We analyze use of an interactive system for the exploration of highly detailed three-dimensional (3D) models of a collection of protostoric Mediterranean sculptures. In this system, when the object of interest is selected, its detailed 3D model and associated information are presented at high resolution on a large display controlled by a touch-enabled horizontal surface at a suitable distance. The user interface combines an object-Aware interactive camera controller with an interactive point-ofinterest selector and is implemented within a scalable implementation based on multiresolution structures shared between the rendering and user interaction subsystems. The system was installed in several temporary and permanent exhibitions and was extensively used by tens of thousands of visitors. We provide a data-driven analysis of usage experience based on logs gathered during a 27-month period at four exhibitions in archeological museums for a total of more than 75K exploration sessions. We focus on discerning the main visitor behaviors during 3D exploration by employing tools for deriving interest measures on surfaces and tools for clustering and knowledge discovery from high-dimensional data. The results highlight the main trends in visitor behavior during the interactive sessions. These results provide useful insights for the design of 3D exploration user interfaces in future digital installations.© 2017 ACM 1556-4673/2017/12-ART2 $15.00.

  13. Dielectric and piezoelectric properties of sol-gel derived Ca doped PbTiO{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Chauhan, Arun Kumar Singh [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India); Gupta, Vinay [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India)]. E-mail: drvin_gupta@rediffmail.com; Sreenivas, K. [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India)

    2006-06-15

    Synthesis of Ca doped PbTiO{sub 3} powder by a chemically derived sol-gel process is described. Crystallization characteristics of different compositions Pb{sub 1-x}Ca {sub x}TiO{sub 3} (PCT) with varying calcium (Ca) content in the range x = 0-0.45 has been investigated by DTA/TGA, X-ray diffraction and scanning electron microscopy. The crystallization temperature is found to decrease with increasing calcium content. X-ray diffraction reveals a tetragonal structure for PCT compositions with x {<=} 0.35, and a cubic structure for x = 0.45. Dielectric properties on sintered ceramics prepared with fine sol-gel derived powders have been measured. The dielectric constant is found to increase with increasing Ca content, and the dielectric loss decreases continuously. Sol-gel derived Pb{sub 1-x}Ca {sub x}TiO{sub 3} ceramics with x = 0.45 after poling exhibit infinite electromechanical anisotropy (k {sub t}/k {sub p}) with a high d {sub 33} = 80 pC/N, {epsilon}' = 298 and low dielectric loss (tan {delta} = 0.0041)

  14. Synthesis, physical-chemical properties, antimicrobial and antifungal activity of some 2-(2-((5-(adamantane-1-yl-4-R-1,2,4-triazole-3-ylthioacetyl-N-R1–hydrazine-carbothioamides

    Directory of Open Access Journals (Sweden)

    V. M. Odyntsova

    2017-12-01

    Full Text Available Special attention of pharmaceutical scientists is attracted to the creation of new potential substances. They select natural heterocyclic molecules that exhibit various types of pharmacological activity as basic structures. Adamantane derivatives, as well as a number of other framework compounds, in the vast majority are biologically active substances. This fact causes interest to the given classes of organic compounds as potential sources for the development of new drugs. Due to the high pharmacological action of 1,2,4-triazole derivatives, the combination of adamantane and 1,2,4-triazole in one molecule can lead to the formation of high-level pharmacological substances. The aim of this work is the synthesis of some 2- (2 - ((5- (adamantane-1-yl -4-R-1,2,4-triasole-3-yl thio acetyl -N-R1-hydrazine-carbothioamides, study of their physical and chemical properties, antimicrobial and antifungal activity. Materials and methods. The chemical names of the compounds are given in accordance with the requirements of the IUPAC nomenclature (1979 and the recommendations of the IUPAC (1993. Study of the physical and chemical properties of 2-(2-((5-(adamantane-1-yl-4-R-1,2,4-triazole-3-ylthioacetyl-N-R1-hydrazine-carbothioamides have been carried out on the certified and licensed equipment in the ZSMU physical-chemical laboratories. The melting temperature was determined by an open capillary method on the Opti Melt MPA 100. The elemental composition of the synthesized compounds was determined on the universal analyzer Elementar Vario L cube (CHNS (standard – sulfanilamide. 1H NMR spectra were recorded on a spectrometer Varian Mercury VX-200 (1H, 200 MHz in dimethylsulfoxide-d6solvent (tetramethylsilane - internal standard and are decoded using ADVASP(tmAnalyzer program (Umatek International Inc.. Chromatographic mass spectral studies were performed on a gas-liquid chromatograph Agilent 1260 Infinity HPLC equipped with an Agilent 6120 mass spectrometer

  15. The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building.

    Science.gov (United States)

    Dupradeau, François-Yves; Pigache, Adrien; Zaffran, Thomas; Savineau, Corentin; Lelong, Rodolphe; Grivel, Nicolas; Lelong, Dimitri; Rosanski, Wilfried; Cieplak, Piotr

    2010-07-28

    Deriving atomic charges and building a force field library for a new molecule are key steps when developing a force field required for conducting structural and energy-based analysis using molecular mechanics. Derivation of popular RESP charges for a set of residues is a complex and error prone procedure because it depends on numerous input parameters. To overcome these problems, the R.E.D. Tools (RESP and ESP charge Derive, ) have been developed to perform charge derivation in an automatic and straightforward way. The R.E.D. program handles chemical elements up to bromine in the periodic table. It interfaces different quantum mechanical programs employed for geometry optimization and computing molecular electrostatic potential(s), and performs charge fitting using the RESP program. By defining tight optimization criteria and by controlling the molecular orientation of each optimized geometry, charge values are reproduced at any computer platform with an accuracy of 0.0001 e. The charges can be fitted using multiple conformations, making them suitable for molecular dynamics simulations. R.E.D. allows also for defining charge constraints during multiple molecule charge fitting, which are used to derive charges for molecular fragments. Finally, R.E.D. incorporates charges into a force field library, readily usable in molecular dynamics computer packages. For complex cases, such as a set of homologous molecules belonging to a common family, an entire force field topology database is generated. Currently, the atomic charges and force field libraries have been developed for more than fifty model systems and stored in the RESP ESP charge DDataBase. Selected results related to non-polarizable charge models are presented and discussed.

  16. Functional Characterization of a Novel R2R3-MYB Transcription Factor Modulating the Flavonoid Biosynthetic Pathway from Epimedium sagittatum

    Directory of Open Access Journals (Sweden)

    Wenjun Huang

    2017-07-01

    potential role of EsMYB9 in modulating the biosynthesis and accumulation of sucrose-induced anthocyanin and flavonol-derived BCs is also discussed. These findings suggest that EsMYB9 is a novel R2R3-MYB TF, which regulates the flavonoid biosynthetic pathway in Epimedium, but distinctly different with the anthocyanin or flavonol-specific MYB regulators identified previously in Epimedium plants.

  17. Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

    Directory of Open Access Journals (Sweden)

    Giordano Lesma

    2014-06-01

    Full Text Available An efficient Ugi three-component reaction of a preformed chiral ketimine derived from isatin with various isonitrile and acid components has been developed. The reactions proceeded smoothly and in a stereocontrolled manner with regard to the new center of the Ugi products due to the stereoinduction of the amine chiral residue. A wide variety of novel chiral 3,3-disubstituted 3-aminooxindoles were obtained, a selection of which were subjected to post-Ugi transformations, paving the way to application as peptidomimetics.

  18. Poly-(R)-3-hydroxybutyrates (PHB) are Atherogenic Components of Lipoprotein Lp(a).

    Science.gov (United States)

    Reusch, Rosetta N

    2015-12-01

    The hypothesis is that poly-(R)-3-hydroxybutyrates (PHB), linear polymers of the ketone body, R-3-hydroxybutyrate (R-3HB), are atherogenic components of lipoprotein Lp(a). PHB are universal constituents of biological cells and are thus components of all foods. Medium chain-length PHB (PHB (PHB are highly insoluble in water, but soluble in lipids in which they exhibit a high intrinsic viscosity. They have a higher density than other cellular lipids and they are very adhesive, i.e. they engage in multiple noncovalent interactions with other molecules and salts via hydrogen, hydrophobic and coordinate bonds, thus producing insoluble deposits. Following digestive processes, PHB enter the circulation in chylomicrons and very low density lipoproteins (VLDL). The majority of the PHB (>70%) are absorbed by albumin, which transports them to the liver for disposal. When the amount of PHB in the diet exceed the capacity of albumin to safely remove them from the circulation, the excess PHB remain in the lipid core of LDL particles that become constituents of lipoprotein Lp(a), and contribute to the formation of arterial deposits. In summary, the presence of PHB – water-insoluble, dense, viscous, adhesive polymers – in the lipid cores of the LDL moieties of Lp(a) particles supports the hypothesis that PHB are atherogenic components of Lp(a).

  19. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    International Nuclear Information System (INIS)

    López, Jacqueline; Poitevin, Adela; Mendoza-Martínez, Veverly; Pérez-Plasencia, Carlos; García-Carrancá, Alejandro

    2012-01-01

    Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 10 3 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 10 5 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, Si

  20. Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

    Science.gov (United States)

    Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

    2012-11-01

    A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  1. R[ionuclide transport after the Chernobyl reactor accident and derivation of r[ioecological parameters

    International Nuclear Information System (INIS)

    Bonka, H.

    1998-01-01

    Since due to the nuclear reactor accident in Chernobyl r[ionuclides arrived in the vicinity of Aachen, the enhancement of the local dose rate, the deposition of the different r[ionuclides on ground and vegetation and the transport of the r[ionuclides into the environment were measured. Partly the measurements were continued until today. Very informative time sequences of the specific activity in grass, food, cow's milk, beef, in the different plants, trees, ploughed soil and undisturbed soil, mushrooms, game, in humans etc. resulted. During different private and official journeys in the old Laender of the Federal Republic of Germany surface covering measurements of the 134 Cs and 137 Cs activity deposited on grass land at different places were carried out. These data were implemented into a map on ground contamination in 1986 in Germany, published in 1991 by the Institute for Water, Soil and Air Hygiene of the Federal Public Health Department in Berlin. Transfer factors soil-grass were measured in the whole Federal Republic of Germany analyzing grass samples which were partly taken at the same time. A large amount of r[ioecological parameters could be derived from the different time sequences. These are in particular: The deposition velocity for iodine and particle bound r[ioanuclides on grass and in forests, the rainout coefficient in dependence of the precipitation intensity, the retention factors on grass, the biological half-life time on grass, the transfer factor soil-grass in dependence of time, the transfer factor food-milk during the pasture period and during stable stay, the transfer factor food-beef, the transfer factors in eatable mushrooms, the translocation factor of cesium in cereals etc. A multi-compartment model was developed to calculate the specific Cs activity in cow's milk and beef. The specific activity in milk can be calculated sufficiently exact using a simple single compartment model. The correlation of the specific Cs activity in spruce

  2. Luminescence investigation of R{sup 3+}-doped alkaline earth tungstates prepared by a soft chemistry method

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Helliomar P. [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Kai, Jiang [Pontifícia Universidade Católica do Rio de Janeiro, Departamento de Química, Rio de Janeiro, RJ, Brazil (Brazil); Silva, Ivan G.N.; Rodrigues, Lucas C.V. [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Felinto, Maria C.F.C. [Centro de Química e Meio Ambiente, Instituto de Pesquisas Energéticas e Nucleares, São Paulo, SP (Brazil); Hölsä, Jorma [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Department of Chemistry, University of Turku,FI-20014 Turku (Finland); Turku University Centre for Materials and Surfaces (MatSurf), Turku (Finland); Malta, Oscar L. [Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife, PE (Brazil); Brito, Hermi F., E-mail: hefbrito@iq.usp.br [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil)

    2016-02-15

    Highly luminescent rare earth (R{sup 3+}) doped alkaline-earth tungstates MWO{sub 4}:R{sup 3+} (M{sup 2+}: Ca, Sr and Ba, R{sup 3+}: Eu, Tb, Gd) were prepared with a room temperature coprecipitation method. The phosphors were characterized by X-ray powder diffraction (XPD), thermal analysis (TG), infrared absorption spectroscopy (FTIR) and UV excited photoluminescence. The as-prepared MWO{sub 4}:R{sup 3+} particles belong to the tetragonal scheelite phase, and are well crystallized and are of the average size of 16–48 nm. The excitation and emission spectra of the materials were recorded at 300 and 77 K temperatures. The luminescent materials exhibit intense red (Eu{sup 3+}) and green (Tb{sup 3+}) colors under UV excitation. The excitation spectra of the Eu{sup 3+} doped materials show broad bands arising from the ligand-to-metal charge transfer transitions (O{sup 2−}→W{sup VI} and O{sup 2−}→Eu{sup 3+}) as well as narrow bands from 4f–4f intraconfigurational transitions of Eu{sup 3+}. 4f–4f emission data of the Eu{sup 3+} and Tb{sup 3+} in the MWO{sub 4} host matrices as well as the values of emission quantum efficiencies of the {sup 5}D{sub 0} level and the 4f–4f experimental intensity parameters of Eu{sup 3+} ion are presented and discussed. - Highlights: • Highly red Europium and green Terbium doped tungstate under UV excitation. • Efficient energy transfer process from tungstate to R{sup 3+} ion. • Promising candidates for a red (Eu{sup 3+}) and green (Tb{sup 3+}) emitting phosphors. • Ligand Metal charge transfer to R{sup 3+} ion. • Charge compensation with Na{sup +}.

  3. Effect of aromatization of the ring on intramolecular H-bond in 3-hydroxy-4-formylo derivatives of fulvene

    Science.gov (United States)

    Oziminski, Wojciech P.; Krygowski, Tadeusz M.

    2011-06-01

    DFT optimization of H-bonded 3-hydroxy-4-formylo derivatives of fulvene aromatized by amino substitution at C6 or by complexation with Li atom was performed using the B3LYP functional together with 6-311+G(d,p) basis set. Several aromaticity indicators (HOMA, NICS, pEDA and Shannon aromaticity) confirm an increase of aromaticity in the sequence: fulvene, 6-aminofulvene, Li-complex with fulvene and in the case of H-bonded 3-hydroxy-4-formylo derivatives, exhibited in the same sequence an increase of H-bond strength estimated by direct comparison of energy for H-bonded and open conformations, as well as by using AIM based electron densities at bond critical point.

  4. Synthesis and physical-chemical properties of 6-(5-(1Н-tetrazole-1-ylmethyl-4-R-1,2,4-triazole-3-ylthiopyridin-3-amines and 6-((5-(1Н-tetrazole-1-ylmethil-4-R-1,2,4-triazole-3-ylthiopyridin-3-yl-(alk,ar,heterylmethanimines

    Directory of Open Access Journals (Sweden)

    Yu. S. Hulina

    2017-02-01

    compounds, which have not been described previously, were obtained during the synthetic studies. The computer prediction was performed using PASS online service, it was found that the synthesized 6-(5-(1Н-tetrazole-1-ylmethyl-4-R-1,2,4-triazole-3-ylthiopyridin-3-amines and 6-((5-(1Н-tetrazole-1-ylmethil-4-R-1,2,4-triazole-3-ylthiopyridin-3-yl-(alk,ar,heterylmethanimines are low-toxic compounds and exhibit a wide range of biological actions, which corresponds to literature data. Conclusions. The results of our work have confirmed the structure of the synthesized compounds, which indicates the possibility of their further use in biological studies.

  5. 3D-QSAR and Molecular Docking Studies on Derivatives of MK-0457, GSK1070916 and SNS-314 as Inhibitors against Aurora B Kinase

    Directory of Open Access Journals (Sweden)

    Chunzhi Ai

    2010-11-01

    Full Text Available Development of anticancer drugs targeting Aurora B, an important member of the serine/threonine kinases family, has been extensively focused on in recent years. In this work, by applying an integrated computational method, including comparative molecular field analysis (CoMFA, comparative molecular similarity indices analysis (CoMSIA, homology modeling and molecular docking, we investigated the structural determinants of Aurora B inhibitors based on three different series of derivatives of 108 molecules. The resultant optimum 3D-QSAR models exhibited (q2 = 0.605, r2pred = 0.826, (q2 = 0.52, r2pred = 0.798 and (q2 = 0.582, r2pred = 0.971 for MK-0457, GSK1070916 and SNS-314 classes, respectively, and the 3D contour maps generated from these models were analyzed individually. The contour map analysis for the MK-0457 model revealed the relative importance of steric and electrostatic effects for Aurora B inhibition, whereas, the electronegative groups with hydrogen bond donating capacity showed a great impact on the inhibitory activity for the derivatives of GSK1070916. Additionally, the predictive model of the SNS-314 class revealed the great importance of hydrophobic favorable contour, since hydrophobic favorable substituents added to this region bind to a deep and narrow hydrophobic pocket composed of residues that are hydrophobic in nature and thus enhanced the inhibitory activity. Moreover, based on the docking study, a further comparison of the binding modes was accomplished to identify a set of critical residues that play a key role in stabilizing the drug-target interactions. Overall, the high level of consistency between the 3D contour maps and the topographical features of binding sites led to our identification of several key structural requirements for more potency inhibitors. Taken together, the results will serve as a basis for future drug development of inhibitors against Aurora B kinase for various tumors.

  6. Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System

    Directory of Open Access Journals (Sweden)

    Raul Vizcardo

    2018-03-01

    Full Text Available Summary: Induced pluripotent stem cell (iPSC-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs. iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies. : A barrier for clinical application of iPSC-derived CD8 T cells using OP9/DLL1 is their abnormal biology. Vizcardo et al. show that a 3D thymic culture system enables the generation of a homogeneous antigen-specific T cell subset, named iTEs, which closely mimics naive T cells and exhibits potent anti-tumor activity. Keywords: thymopoiesis, T cell differentiation, iPSC differentiation, adoptive cell transfer, naïve T cell, recent rhymic emigrants, fetal thymus organ culture, immunotherapy, 3D culture, tumor antigen specific T cell

  7. Derivation of Z-R equation using Mie approach for a 77 GHz radar

    Science.gov (United States)

    Bertoldo, Silvano; Lucianaz, Claudio; Allegretti, Marco; Perona, Giovanni

    2017-04-01

    The ETSI (European Telecommunications Standards Institute) defines the frequency band around 77 GHz as dedicated to automatic cruise control long-range radars. This work aims to demonstrate that, with specific assumption and the right theoretical background it is also possible to use a 77 GHz as a mini weather radar and/or a microwave rain gauge. To study the behavior of a 77 GHz meteorological radar, since the raindrop size are comparable to the wavelength, it is necessary to use the general Mie scattering theory. According to the Mie formulation, the radar reflectivity factor Z is defined as a function of the wavelength on the opposite of Rayleigh approximation in which is frequency independent. Different operative frequencies commonly used in radar meteorology are considered with both the Rayleigh and Mie scattering theory formulation. Comparing them it is shown that with the increasing of the radar working frequency the use of Rayleigh approximation lead to an always larger underestimation of rain. At 77 GHz such underestimation is up to 20 dB which can be avoided with the full Mie theory. The crucial derivation of the most suited relation between the radar reflectivity factor Z and rainfall rate R (Z-R equation) is necessary to achieve the best Quantitative Precipitation Estimation (QPE) possible. Making the use of Mie scattering formulation from the classical electromagnetic theory and considering different radar working frequencies, the backscattering efficiency and the radar reflectivity factor have been derived from a wide range of rain rate using specific numerical routines. Knowing the rain rate and the corresponding reflectivity factor it was possible to derive the coefficients of the Z-R equation for each frequency with the least square method and to obtain the best coefficients for each frequency. The coefficients are then compared with the ones coming from the scientific literature. The coefficients of a 77 GHz weather radar are then obtained. A

  8. Extraction and characterization of mixed phase KNO2-KNO3 nanocrystals derived from flat-leaf green spinach

    International Nuclear Information System (INIS)

    Hazarika, S; Mohanta, D

    2013-01-01

    Naturally available green spinach, which is a rich source of potassium, was used as the key ingredient to extract mixed-phase ferroelectric crystals of nitrite and nitrate derivatives (KNO 2 + KNO 3 ). The KNO 3 phase was found to be dominant for higher pH values, as revealed by the x-ray diffraction patterns. The characteristic optical absorption spectra exhibited intra-band π-π* electronic transitions, whereas Fourier transform infrared spectra exhibited characteristic N-O stretching vibrations. Differential scanning calorimetry revealed a broad endothermic peak at ∼121.8 °C, highlighting a transition from phase II to I via phase III of KNO 3 . Obtaining nanoscale ferroelectrics via the adoption of green synthesis is economically viable for large-scale production and possible application in ferroelectric elements/devices.

  9. TOTAL HYDROGENATION OF BIOMASS-DERIVED FURFURAL OVER RANEY NICKEL-CLAY NANOCOMPOSITE CATALYSTS

    Directory of Open Access Journals (Sweden)

    Rodiansono Rodiansono

    2013-08-01

    Full Text Available Inexpensive Raney Ni-clay composite (R-Ni/clay catalysts exhibited excellent activity and reusability in the total hydrogenation of biomass-derived furfural into tetrahydrofurfuryl alcohol under mild conditions. For the Raney Ni-bentonite (R-Ni/BNT catalysts, the complete reaction was achieved at 393 K, 180 min giving almost 99% yield of tetrahydrofurfuryl alcohol. The R-Ni/BNT catalyst was found to be reusable without any significant loss of activity and selectivity for at least six consecutive runs.

  10. The structures of T6, T3R3 and R6 bovine insulin: combining X-ray diffraction and absorption spectroscopy

    DEFF Research Database (Denmark)

    Frankær, Christian Grundahl; Knudsen, Marianne Vad; Noren, Katarina

    2012-01-01

    The crystal structures of three conformations, T6, T3R3 and R6, of bovine insulin were solved at 1.40, 1.30 and 1.80 Å resolution, respectively. All conformations crystallized in space group R3. In contrast to the T6 and T3R3 structures, different conformations of the N-terminal B-chain residue Phe......B1 were observed in the R6 insulin structure, resulting in an eightfold doubling of the unit-cell volume upon cooling. The zinc coordination in each conformation was studied by X-ray absorption spectroscopy (XAS), including both EXAFS and XANES. Zinc adopts a tetrahedral coordination in all R3 sites...... molecules, as well as in other high-resolution insulin structures. As the radiation dose for XRD experiments is two orders of magnitude higher compared with that of XAS experiments, the single crystals were exposed to a higher degree of radiation damage that affected the zinc coordination in the T3 sites...

  11. Synthesis and antibacterial activity of some new 3-hydroxy-2-naphthoic acid hydrazide derivatives for dyeing polyester fabrics

    Directory of Open Access Journals (Sweden)

    Abd El-Galil M. Khalil

    2016-03-01

    Full Text Available Dibenzobarallene was used as a key intermediate for the synthesis of 2-(3-hydroxy-2-naphthoyl-3,4,4a,5,10,10a-hexahydro-1H-5,10-benzenobenzo[g]phthalazine-1,4-dione (2. The previous compound was coupled with the appropriate diazonium chloride to give the corresponding 4-arylazo-2-naphthol derivatives 3a–l. Also, nitration, nitrosation and bromination of compound 2 afforded the corresponding nitro, nitroso and bromo derivatives 4–6, respectively. The synthesized compounds were established and evaluated as antibacterial agents. The results showed clearly that compounds 2, 3a, 3c, 3d, 3g, 3i, 4, 5 and 6 exhibited interesting high activities compared with reference drugs. Also, these compounds were applied to polyester as disperse dyes in which their color measurement and fastness properties were evaluated.

  12. Histamine H3 receptor ligands in the group of (homo)piperazine derivatives.

    Science.gov (United States)

    Szczepanska, Katarzyna; Kuder, Kamil; Kiec-Kononowicz, Katarzyna

    2017-11-23

    Since its' discovery in 1983, followed by gene cloning in 1999, the histamine H3 receptor served as an outstanding target for drug discovery. The wide spectrum of possible therapeutic implications make H3R's one of the most researched areas in the vast GPCR ligands field - started from imidazole containing ligands, through various successful imidazole replacements, with recent introduction of Wakix® to pharmaceutical market. One of such replacements is piperazine moiety, a significant versatile scaffold in rational drug design for most of the GPCR ligands. Therefore, herein we review ligands built on piperazine, as well as its seven membered analogue azepine, that target H3R's and their potential therapeutical applications, in order to elucidate the current state of the art in this vast field. Due to a high level of structural divergence among compounds described herein, we decided to divide them into groups, where the key division element was the position of nitrogen basicity decreasing moieties in (homo)piperazine ring. Paying attention to a number of published structures and their overall high biological activity, one can realize that the (homo)piperazine scaffold bids a versatile template also for histamine H3 receptor ligands. With two possible substitution sites and therefore a number of possible structural combinations, piperazine derivatives stand as one of the largest group of high importance among H3R ligands. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Crystal structure of (1R,3S,8R,11R-11-acetyl-3,7,7-trimethyl-10-oxatricyclo[6.4.0.01,3]dodecan-9-one

    Directory of Open Access Journals (Sweden)

    Abdoullah Bismoussa

    2015-12-01

    Full Text Available The title compound, C16H24O3, is built up from three fused rings, a six-membered, a seven-membered and a three-membered ring. The absolute configuration of the title compound was determined as (1R,3S,8R,11R based on the synthetic pathway. The six-membered ring has an half-chair conformation whereas the seven-membered ring displays a boat conformation. In the cyrstal, C—H...O hydrogen bonds build up a two-dimensional network parallel to (0 0 1. The crystal studied was an inversion twin with a minor twin component of 34%.

  14. Induced pluripotent stem cells derived from rabbits exhibit some characteristics of naïve pluripotency

    Directory of Open Access Journals (Sweden)

    Pierre Osteil

    2013-05-01

    Not much is known about the molecular and functional features of pluripotent stem cells (PSCs in rabbits. To address this, we derived and characterized 2 types of rabbit PSCs from the same breed of New Zealand White rabbits: 4 lines of embryonic stem cells (rbESCs, and 3 lines of induced PSCs (rbiPSCs that were obtained by reprogramming adult skin fibroblasts. All cell lines required fibroblast growth factor 2 for their growth and proliferation. All rbESC lines showed molecular and functional properties typically associated with primed pluripotency. The cell cycle of rbESCs had a prolonged G1 phase and a DNA damage checkpoint before entry into the S phase, which are the 2 features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naïve pluripotency, including resistance to single-cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naïve pluripotency-specific genes, as defined in rodents. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass (ICM than rbESCs. Furthermore, rbiPSCs were capable of colonizing the ICM after aggregation with morulas. Therefore, we propose that rbiPSCs self-renew in an intermediate state between naïve and primed pluripotency, which represents a key step toward the generation of bona fide naïve PSC lines in rabbits.

  15. Induced pluripotent stem cells derived from rabbits exhibit some characteristics of naïve pluripotency

    Science.gov (United States)

    Osteil, Pierre; Tapponnier, Yann; Markossian, Suzy; Godet, Murielle; Schmaltz-Panneau, Barbara; Jouneau, Luc; Cabau, Cédric; Joly, Thierry; Blachère, Thierry; Gócza, Elen; Bernat, Agnieszka; Yerle, Martine; Acloque, Hervé; Hidot, Sullivan; Bosze, Zsuzsanna; Duranthon, Véronique; Savatier, Pierre; Afanassieff, Marielle

    2013-01-01

    Summary Not much is known about the molecular and functional features of pluripotent stem cells (PSCs) in rabbits. To address this, we derived and characterized 2 types of rabbit PSCs from the same breed of New Zealand White rabbits: 4 lines of embryonic stem cells (rbESCs), and 3 lines of induced PSCs (rbiPSCs) that were obtained by reprogramming adult skin fibroblasts. All cell lines required fibroblast growth factor 2 for their growth and proliferation. All rbESC lines showed molecular and functional properties typically associated with primed pluripotency. The cell cycle of rbESCs had a prolonged G1 phase and a DNA damage checkpoint before entry into the S phase, which are the 2 features typically associated with the somatic cell cycle. In contrast, the rbiPSC lines exhibited some characteristics of naïve pluripotency, including resistance to single-cell dissociation by trypsin, robust activity of the distal enhancer of the mouse Oct4 gene, and expression of naïve pluripotency-specific genes, as defined in rodents. According to gene expression profiles, rbiPSCs were closer to the rabbit inner cell mass (ICM) than rbESCs. Furthermore, rbiPSCs were capable of colonizing the ICM after aggregation with morulas. Therefore, we propose that rbiPSCs self-renew in an intermediate state between naïve and primed pluripotency, which represents a key step toward the generation of bona fide naïve PSC lines in rabbits. PMID:23789112

  16. Clustering of galaxies with f(R) gravity

    Science.gov (United States)

    Capozziello, Salvatore; Faizal, Mir; Hameeda, Mir; Pourhassan, Behnam; Salzano, Vincenzo; Upadhyay, Sudhaker

    2018-02-01

    Based on thermodynamics, we discuss the galactic clustering of expanding Universe by assuming the gravitational interaction through the modified Newton's potential given by f(R) gravity. We compute the corrected N-particle partition function analytically. The corrected partition function leads to more exact equations of state of the system. By assuming that the system follows quasi-equilibrium, we derive the exact distribution function that exhibits the f(R) correction. Moreover, we evaluate the critical temperature and discuss the stability of the system. We observe the effects of correction of f(R) gravity on the power-law behaviour of particle-particle correlation function also. In order to check the feasibility of an f(R) gravity approach to the clustering of galaxies, we compare our results with an observational galaxy cluster catalogue.

  17. Synthesis and biological evaluation of 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives as potential c-met inhibitors.

    Science.gov (United States)

    Zhao, Sijia; Zhang, Yu; Zhou, Hongyang; Xi, Shuancheng; Zou, Bin; Bao, Guanglong; Wang, Limei; Wang, Jiao; Zeng, Tianfang; Gong, Ping; Zhai, Xin

    2016-09-14

    Six series of novel 4-(2-fluorophenoxy)-3,3'-bipyridine derivatives conjugated with aza-aryl formamide/amine scaffords were designed and synthesized through a structure-based molecular hybridization approach. The target compounds were evaluated for c-Met kinase inhibitory activities and cytotoxicity against four cancer cell lines (HT-29, A549, MKN-45 and MDA-MB-231) in vitro. Most compounds exhibited moderate to excellent potency, and the most promising candidate 26c (c-Met kinase IC50 = 8.2 nM) showed a 4.7-fold increase in cytotoxicity against c-Met-addicted MKN-45 cell line in vitro (IC50 = 3 nM), superior to that of Foretinib (IC50 = 23 nM). The preliminary structure-activity relationship indicated that a 1H-benzo [e] [1,3,4]thiadiazine-3-carboxamide-4,4-dioxide moiety as linker contributed to the antitumor potency. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Theoretical studies of the tautomerism in 3-(2-R-Phenylhydrazono)-naphthalene- 1,2,4-triones: synthesis of copper(II) complexes and studies of antibacterial and antitumor activities

    International Nuclear Information System (INIS)

    Francisco, Acacio I.; Vargas, Maria D.; Fragoso, Thais P.; Carneiro, J. Walkimar de M.; Silva, Fernando de C. da; Ferreira, Vitor F.; Pessoa, Claudia; Costa-Lotufo, Leticia V.; Marinho Filho, Jose D.B.; Moraes, Manoel O. de; Mangrich, Antonio S.

    2010-01-01

    DFT calculations using the B3LYP and PBE1PBE functionals with the standard 6-31G(d) and 6-311+G(2d,p) basis sets were carried out for the 3-(2-phenylhydrazone)-naphthalene-1,2,4-trione system in solution (dmso) and in the gas phase, and showed the keto-hydrazone forms (rotamers Ia and Ib) to be more stable than the enol-azo forms (rotamers IIa and IIb, by about 14 kcal mol-1) and III (by approximately 6 kcal mol-1), independently of the nature of the substituent in the phenylene ring. These results were confirmed by spectroscopic data on the derivatives HL1-HL13, obtained from 2-hydroxy-1,4-naphthoquinone and arylamines (R = 4-OMe, 4-N 2 -C 6 H 5 , 4-Cl, 4-I, 3-I, 2-I, 4-COOH, 3-COOH, 4-CN, 3-CN, 4-NO 2 , 3-NO 2 , 2-NO 2 ). The in vitro antitumor (against SF-295, HCT-8, MDAMB-435 and HL-60 cancer cell lines) and antibacterial activities (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa) of compounds HL1-HL13 and of their respective copper(II) complexes, [Cu(L1-13) 2 ], were tested. In general, these compounds exhibited low antibacterial activity, except for HL5 (R 3-I), more active than the control; however, the corresponding complex was inactive. In contrast, increased cytotoxicity was observed upon complexation. Complex [Cu(L13) 2 ] (R = 3-NO 2 ) presented moderate cytotoxicity against human leukemia (HL-60). (author)

  19. Characterization of oil-palm trunk residue degradation enzymes derived from the isolated fungus, Penicillium rolfsii c3-2(1) IBRL.

    Science.gov (United States)

    Lee, Kok Chang; Arai, Takamitsu; Ibrahim, Darah; Deng, Lan; Murata, Yoshinori; Mori, Yutaka; Kosugi, Akihiko

    2016-01-01

    This study characterizes crude enzymes derived from Penicillium rolfsii c3-2(1) IBRL, a mesophilic fungus isolated from the local soil of Malaysia. Prior to enzyme activity evaluation, P. rolfsii c3-2(1) IBRL was inoculated into a broth medium containing oil-palm trunk residues for the preparation of crude enzymes. Oil-palm trunk residues were optimally hydrolysed at pH5.0 and 50°C. P. rolfsii c3-2(1) IBRL-derived crude enzymes displayed higher thermal stability compared with the commercial enzymes, Celluclast 1.5 L and Acellerase 1500. Moreover, the hydrolysing activities of the P. rolfsii c3-2(1) IBRL-derived crude enzymes (xylan, arabinan, and laminarin) were superior compared to that of Celluclast 1.5 L and Acellerase 1500, and exhibit 2- to 3-fold and 3- to 4-fold higher oil-palm trunk residues-hydrolysing specific activity, respectively. This higher hydrolysis efficiency may be attributed to the weak 'lignin-binding' ability of the P. rolfsii c3-2(1) IBRL-derived enzymes compared to the commercial enzymes.

  20. miR-375 induces human decidua basalis-derived stromal cells to become insulin-producing cells.

    Science.gov (United States)

    Shaer, Anahita; Azarpira, Negar; Vahdati, Akbar; Karimi, Mohammad Hosein; Shariati, Mehrdad

    2014-09-01

    This paper focuses on the development of renewable sources of isletreplacement tissue for the treatment of type I diabetes mellitus. Placental tissue-derived mesenchymal stem cells (MSCs) are a promising source for regenerative medicine due to their plasticity and easy availability. They have the potential to differentiate into insulin-producing cells. miR-375 is a micro RNA that is expressed in the pancreas and involved in islet development. Human placental decidua basalis MSCs (PDB-MSCs) were cultured from full-term human placenta. The immunophenotype of the isolated cells was checked for CD90, CD105, CD44, CD133 and CD34 markers. The MSCs (P3) were chemically transfected with hsa-miR-375. Total RNA was extracted 4 and 6 days after transfection. The expressions of insulin, NGN3, GLUT2, PAX4, PAX6, KIR6.2, NKX6.1, PDX1, and glucagon genes were evaluated using real-time qPCR. On day 6, we tested the potency of the clusters in response to the high glucose challenge and assessed the presence of insulin and NGN3 proteins via immunocytochemistry. Flow cytometry analysis confirmed that more than 90% of the cells were positive for CD90, CD105 and CD44 and negative for CD133 and CD34. Morphological changes were followed from day 2. Cell clusters formed during day 6. Insulin-producing clusters showed a deep red color with DTZ. The expression of pancreatic-specific transcription factors increased remarkably during the four days after transfection and significantly increased on day 7. The clusters were positive for insulin and NGN3 proteins, and C-peptide and insulin secretion increased in response to changes in the glucose concentration (2.8 mM and 16.7 mM). In conclusion, the MSCs could be programmed into functional insulin-producing cells by transfection of miR-375.

  1. Study of the scientific reasoning methods: Identifying the salient reasoning characteristics exhibited by engineers and scientists in an R&D environment

    Science.gov (United States)

    Kuhn, William F.

    At the core of what it means to be a scientist or engineer is the ability to think rationally using scientific reasoning methods. Yet, typically if asked, scientist and engineers are hard press for a reply what that means. Some may argue that the meaning of scientific reasoning methods is a topic for the philosophers and psychologist, but this study believes and will prove that the answers lie with the scientists and engineers, for who really know the workings of the scientific reasoning thought process than they. This study will provide evidence to the aims: (a) determine the fundamental characteristics of cognitive reasoning methods exhibited by engineer/scientists working in R&D projects, (b) sample the engineer/scientist community to determine their views as to the importance, frequency, and ranking of each of characteristics towards benefiting their R&D projects, (c) make concluding remarks regarding any identified competency gaps in the exhibited or expected cognitive reasoning methods of engineer/scientists working on R&D projects. To drive these aims are the following three research questions. The first, what are the salient characteristics of cognitive reasoning methods exhibited by engineer/scientists in an R&D environment? The second, what do engineer/scientists consider to be the frequency and importance of the salient cognitive reasoning methods characteristics? And the third, to what extent, if at all, do patent holders and technical fellows differ with regard to their perceptions of the importance and frequency of the salient cognitive reasoning characteristics of engineer/scientists? The methodology and empirical approach utilized and described: (a) literature search, (b) Delphi technique composed of seven highly distinguish engineer/scientists, (c) survey instrument directed to distinguish Technical Fellowship, (d) data collection analysis. The results provide by Delphi Team answered the first research question. The collaborative effort validated

  2. Global well-posedness for Schrödinger equation with derivative in H(R)

    Science.gov (United States)

    Miao, Changxing; Wu, Yifei; Xu, Guixiang

    In this paper, we consider the Cauchy problem of the cubic nonlinear Schrödinger equation with derivative in H(R). This equation was known to be the local well-posedness for s⩾1/2 > (Takaoka, 1999 [27]), ill-posedness for s (Biagioni and Linares, 2001 [1], etc.) and global well-posedness for s>1/2 > (I-team, 2002 [10]). In this paper, we show that it is global well-posedness in the endpoint space H(R), which remained open previously. The main approach is the third generation I-method combined with a new resonant decomposition technique. The resonant decomposition is applied to control the singularity coming from the resonant interaction.

  3. MiR-29c regulates the expression of miR-34c and miR-449a by targeting DNA methyltransferase 3a and 3b in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Niu, Man; Gao, Dan; Wen, Qiuyuan; Wei, Pingpin; Pan, Suming; Shuai, Cijun; Ma, Huiling; Xiang, Juanjuan; Li, Zheng; Fan, Songqing; Li, Guiyuan; Peng, Shuping

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is prevalent in South East Asia and Southern China particularly, despite the reported 5-year survival ratio is relative higher than other deadly cancers such as liver, renal, pancreas cancer, the lethality is characterized by high metastatic potential in the early stage and high recurrence rate after radiation treatment. MicroRNA-29c was found to be down-regulated in the serum as well as in the tissue of nasopharyngeal carcinoma tissue. In this study, we found accidentally that the transfection of pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a but doesn’t affect that of miR-222 using real-time quantitative PCR in nasopharyngeal carcinoma cell lines. To explore the molecular mechanism of the regulatory role, the cells are treated with 5-Aza-2-deoxycytidine (5-Aza-CdR) treatment and the level of miR-34c and miR-449a but not miR-222 accumulated by the treatment. DNA methyltransferase 3a, 3b were down-regulated by the 5-Aza-CdR treatment with western blot and real-time quantitative PCR. We found that pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a. We further found DNA methyltransferase 3a and 3b are the target gene of miR-29c. Restoration of miR-29c in NPC cells down-regulated DNA methyltransferase 3a, 3b, but not DNA methyltransferase T1. The regulation of miR-29c/DNMTs/miR-34c/449a is an important molecular axis of NPC development and targeting DNMTs or restoring of miR-29c might be a promising therapy strategy for the prevention of NPC

  4. N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors

    Science.gov (United States)

    Fang, Ming; Chai, Yiqiu; Chen, Guanjv; Wang, Huidong; Huang, Bo

    2016-01-01

    The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32–35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR. PMID:27668428

  5. Association of miR-548c-5p, miR-7-5p, miR-210-3p, miR-128-3p with recurrence in systemically untreated breast cancer

    DEFF Research Database (Denmark)

    Block, Ines; Burton, Mark; Sørensen, Kristina Pilekær

    2018-01-01

    . To validate their prognostic potential, we analyzed microRNA expression in an independent cohort (n = 110) using a pairmatched study design minimizing dependence of classical markers. The expression of hsa-miR-548c-5p was significantly associated with abridged disease-free survival (hazard ratio [HR]:1.96, p...... = 0.027). Contradicting published results, high hsa-miR516-3p expression was associated with favorable outcome (HR:0.29, p = 0.0068). The association is probably time-dependent indicating later relapse. Additionally, re-analysis of previously published expression data of two matching cohorts (n = 100......, n = 255) supports an association of hsa-miR-128-3p with shortened diseasefree survival (HR:2.48, p = 0.0033) and an upregulation of miR-7-5p (p = 0.0038; p = 0.039) and miR-210-3p (p = 0.031) in primary tumors of patients who experienced metastases. Further analysis may verify the prognostic...

  6. Reactions of R(2)P-P(SiMe(3))Li with [(R'(3)P)(2)PtCl(2)]. A general and efficient entry to phosphanylphosphinidene complexes of platinum. Syntheses and structures of [(eta(2)-P=(i)Pr(2))Pt(p-Tol(3)P)(2)], [(eta(2)-P=(t)Bu(2))Pt(p-Tol(3)P)(2)], [{eta(2)-P=(N(i)Pr(2))(2)}Pt(p-Tol(3)P)(2)] and [{(Et(2)PhP)(2)Pt}(2)P(2)].

    Science.gov (United States)

    Domańska-Babul, Wioleta; Chojnacki, Jaroslaw; Matern, Eberhard; Pikies, Jerzy

    2009-01-07

    The reactions of lithium derivatives of diphosphanes R(2)P-P(SiMe(3))Li (R = (t)Bu, (i)Pr, Et(2)N and (i)Pr(2)N) with [(R'(3)P)(2)PtCl(2)] (R'(3)P = Et(3)P, Et(2)PhP, EtPh(2)P and p-Tol(3)P) proceed in a facile manner to afford side-on bonded phosphanylphosphinidene complexes of platinum [(eta(2)-P=R(2))Pt(PR'(3))(2)]. The related reactions of Ph(2)P-P(SiMe(3))Li with [(R'(3)P)(2)PtCl(2)] did not yield [(eta(2)-P=PPh(2))Pt(PR'(3))(2)] and resulted mainly in the formation of [{(R'(3)P)(2)Pt}(2)P(2)], Ph(2)P-PLi-PPh(2), (Me(3)Si)(2)PLi and (Me(3)Si)(3)P. Crystallographic data are reported for the compounds [(eta(2)-P=R(2))Pt(p-Tol(3)P)(2)] (R = (t)Bu, (i)Pr, ((i)Pr(2)N)(2)P) and for [{(Et(2)PhP)(2)Pt}(2)P(2)].

  7. miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia.

    Science.gov (United States)

    Li, Qinghua; Pan, Zhifang; Wang, Xuejian; Gao, Zhiqin; Ren, Chune; Yang, Weiwei

    2014-10-10

    Preeclampsia (PE) is the leading cause of maternal and perinatal mortality and morbidity. Understanding the molecular mechanisms underlying placentation facilitates the development of better intervention of this disease. MicroRNAs are strongly implicated in the pathogenesis of this syndrome. In current study, we found that miR-125b-1-3p was elevated in placentas derived from preeclampsia patients. Transfection of miR-125b-1-3p mimics significantly inhibited the invasiveness of human trophoblast cells, whereas miR-125b-1-3p inhibitor enhanced trophoblast cell invasion. Luciferase assays identified that S1PR1 was a novel direct target of miR-125b-1-3p in the placenta. Overexpression of S1PR1 could reverse the inhibitory effect of miR-125b-1-3p on the invasion of trophoblast cells. These findings suggested that abnormal expression of miR-125b-1-3p might contribute to the pathogenesis of preeclampsia. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Increased circulating miR-21 levels are associated with kidney fibrosis.

    Directory of Open Access Journals (Sweden)

    François Glowacki

    Full Text Available MicroRNAs (miRNAs are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA. Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001. By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03, and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006. Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.

  9. Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study.

    Science.gov (United States)

    Mirzaa, Ghayda M; Conti, Valerio; Timms, Andrew E; Smyser, Christopher D; Ahmed, Sarah; Carter, Melissa; Barnett, Sarah; Hufnagel, Robert B; Goldstein, Amy; Narumi-Kishimoto, Yoko; Olds, Carissa; Collins, Sarah; Johnston, Kathreen; Deleuze, Jean-François; Nitschké, Patrick; Friend, Kathryn; Harris, Catharine; Goetsch, Allison; Martin, Beth; Boyle, Evan August; Parrini, Elena; Mei, Davide; Tattini, Lorenzo; Slavotinek, Anne; Blair, Ed; Barnett, Christopher; Shendure, Jay; Chelly, Jamel; Dobyns, William B; Guerrini, Renzo

    2015-12-01

    megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome. 19 patients had the same mutation (Gly373Arg), and one had a nearby missense mutation (Lys376Glu). Mutations were constitutional in 12 patients and mosaic in eight patients. In patients with mosaic mutations, we noted substantial variation in alternate (mutant) allele levels, ranging from ten (3%) of 377 reads to 39 (37%) of 106 reads, equivalent to 5-73% of cells analysed. Levels of mosaicism varied from undetectable to 37 (17%) of 216 reads in blood-derived DNA compared with 2030 (29%) of 6889 reads to 275 (43%) of 634 reads in saliva-derived DNA. Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from BPP with a normal head size to the MPPH syndrome. The phenotypic variability and low-level mosaicism, which challenge conventional molecular methods, have important implications for genetic testing and counselling. US National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

    Science.gov (United States)

    Zhang, Junfeng; Zhang, Zongqi; Zhang, David Y; Zhu, Jianbing; Zhang, Tiantian; Wang, Changqian

    2013-01-01

    Endothelial progenitor cells (EPCs) are capable of proliferating and differentiating into mature endothelial cells, and they have been considered as potential candidates for coronary heart disease therapy. However, the transition of EPCs to mesenchymal cells is not fully understood. This study aimed to explore the role of microRNA 126 (miR-126) in the endothelial-to-mesenchymal transition (EndMT) induced by transforming growth factor beta 1 (TGFβ1). EndMT of rat bone marrow-derived EPCs was induced by TGFβ1 (5 ng/mL) for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The luciferase reporter assay showed that the PI3K regulatory subunit p85 beta (PIK3R2) was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a lentiviral vector (lenti-miR-126) was found to downregulate the mRNA expression of mesenchymal cell markers (α-SMA, sm22-a, and myocardin) and to maintain the mRNA expression of progenitor cell markers (CD34, CD133). In the cellular process of EndMT, there was an increase in the protein expression of PIK3R2 and the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt expression decreased, a change that was reversed markedly by overexpression of miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed morphological changes of the EPCs treated with TGFβ1, thereby giving the evidence that PIK3R2 is the target gene of miR-126 during EndMT process. These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT and that this process involves regulation of the PI3K/Akt signalling pathway. miR-126 has the potential to be used as a biomarker for the early diagnosis of intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool for treating cardiovascular diseases mediated by the EndMT process.

  11. A manganese sulfite with extended metal-oxygen-metal bonds exhibiting hydrogen uptake

    International Nuclear Information System (INIS)

    Rao, K. Prabhakara; Govindaraj, A.; Rao, C.N.R.

    2007-01-01

    A manganese sulfite of the formula Mn 5 (OH) 4 (SO 3 ) 3 .2H 2 O, I{a=7.5759(7) A, b=8.4749(8) A, c=10.852(1) A, β=100.732(2) o , Z=2, space group=P2 1 /m (no. 11), R 1 =0.0399 and wR 2 =0.1121 [for R indexes I>2σ(I)]}, comprising Mn 3 O 14 units and extended Mn-O-Mn bonds along the three dimensions has been synthesized under hydrothermal conditions. It has narrow channels along the b-axis and exhibits hydrogen storage of 2.1 wt% at 300 K and 134 bar. - Graphical abstract: A three-dimensional manganese sulfite with one-dimensional channels showing selective hydrogen absorption has been synthesized and characterized

  12. Nye integrerede ledelsesinformationssystemer SAP/R3

    DEFF Research Database (Denmark)

    Nielsen, Steen

    1998-01-01

    Artiklen beskriver og analyserer hovedindholdet i SAP/R3's controlling modul, speciel med sigte på hvilke forudsætninger systemet bygger på, dels med reference til den danske lønsomheds- og kapacitetsmodel.......Artiklen beskriver og analyserer hovedindholdet i SAP/R3's controlling modul, speciel med sigte på hvilke forudsætninger systemet bygger på, dels med reference til den danske lønsomheds- og kapacitetsmodel....

  13. New effective coupled F((4)R, φ) modified gravity from f((5)R) gravity in five dimensions

    International Nuclear Information System (INIS)

    Madriz Aguilar, Jose Edgar

    2015-01-01

    Using some ideas of the Wesson induced matter theory, we obtain a new kind of F( (4) R, φ) modified gravity theory as an effective four-dimensional (4D) theory derived from f( (5) R) gravity in five dimensions (5D). This new theory exhibits a different matter coupling than the one in BBHL theory. We show that the field equations of the Wesson induced matter theory and of some brane-world scenarios can be obtained as maximally symmetric solutions of the same f( (5) R) theory. We found criteria for the Dolgov-Kawasaki instabilities for both the f( (5) R) and the F( (4) R, φ) theories. We demonstrate that under certain conditions imposed on the 5D geometry it is possible to interpret the F( (4) R, φ) theory as a modified gravity theory with dynamical coefficients, making this new theory a viable candidate to address the present accelerating cosmic expansion issue. Matter sources in the F( (4) R, φ) case appear induced by the 5D geometry without the necessity of the introduction of matter sources in 5D. (orig.)

  14. Crystallization and preliminary X-ray study of a (2R,3R)-2,3-butanediol dehydrogenase from Bacillus coagulans 2-6.

    Science.gov (United States)

    Miao, Xiangzhi; Huang, Xianhui; Zhang, Guofang; Zhao, Xiufang; Zhu, Xianming; Dong, Hui

    2013-10-01

    (2R,3R)-2,3-Butanediol dehydrogenase (R,R-BDH) from Bacillus coagulans 2-6 is a zinc-dependent medium-chain alcohol dehydrogenase. Recombinant R,R-BDH with a His6 tag at the C-terminus was expressed in Escherichia coli BL21 (DE3) cells and purified by Ni2+-chelating affinity and size-exclusion chromatography. Crystals were grown by the hanging-drop vapour-diffusion method at 289 K. The crystallization condition consisted of 8%(v/v) Tacsimate pH 4.6, 18%(w/v) polyethylene glycol 3350. The crystal diffracted to 2.8 Å resolution in the orthorhombic space group P2₁2₁2₁, with unit-cell parameters a=88.35, b=128.73, c=131.03 Å.

  15. Cobalt Ion Promoted Redox Cascade: A Route to Spiro Oxazine-Oxazepine Derivatives and a Dinuclear Cobalt(III) Complex of an N-(1,4-Naphthoquinone)-o-aminophenol Derivative.

    Science.gov (United States)

    Mondal, Sandip; Bera, Sachinath; Maity, Suvendu; Ghosh, Prasanta

    2017-11-06

    The study discloses that the redox activity of N-(1,4-naphthoquinone)-o-aminophenol derivatives (L R H 2 ) containing a (phenol)-NH-(1,4-naphthoquinone) fragment is notably different from that of a (phenol)-NH-(phenol) precursor. The former is a platform for a redox cascade. L R H 2 is redox noninnocent and exists in Cat-N-(1,4-naphthoquinone)(2-) (L R 2- ) and SQ-N-(1,4-naphthoquinone) (L R •- ) states in the complexes. Reactions of L R H 2 with cobalt(II) salts in MeOH in air promote a cascade affording spiro oxazine-oxazepine derivatives ( OX L R ) in good yields, when R = H, Me, t Bu. Spiro oxazine-oxazepine derivatives are bioactive, and such a molecule has so far not been isolated by a schematic route. In this context this cascade is significant. Dimerization of L R H 2 → OX L R in MeOH is a (6H + + 6e) oxidation reaction and is composed of formations of four covalent bonds and 6-exo-trig and 7-endo-trig cyclization based on C-O coupling reactions, where MeOH is the source of a proton and the ester function. It was established that the active cascade precursor is [(L Me •- )Co III Cl 2 ] (A). Notably, formation of a spiro derivative was not detected in CH 3 CN and the reaction ends up furnishing A. The route of the reaction is tunable by R, when R = NO 2 , it is a (2e + 4H + ) oxidation reaction affording a dinuclear L R 2- complex of cobalt(III) of the type [(L NO2 2- ) 2 Co III 2 (OMe) 2 (H 2 O) 2 ] (1) in good yields. No cascade occurs with zinc(II) ion even in MeOH and produces a L Me •- complex of type [(L Me •- )Zn II Cl 2 ] (2). The intermediate A and 2 exhibit strong EPR signals at g = 2.008 and 1.999, confrming the existence of L Me •- coordinated to low-spin cobalt(III) and zinc(II) ions. The intermediates of L R H 2 → OX L R conversion were analyzed by ESI mass spectrometry. The molecular geometries of OX L R and 1 were confirmed by X-ray crystallography, and the spectral features were elucidated by TD DFT calculations.

  16. A cold active (2R,3R)-(-)-di-O-benzoyl-tartrate hydrolyzing esterase from Rhodotorula mucilaginosa.

    Science.gov (United States)

    Zimmer, Christian; Platz, Tanja; Cadez, Neza; Giffhorn, Friedrich; Kohring, Gert-Wieland

    2006-11-01

    In a screening procedure a pink-colored yeast was isolated from enrichment cultures with (2R,3R)-(-)-di-O-benzoyl-tartrate (benzoyl-tartrate) as the sole carbon source. The organism saar1 was identified by morphological, physiological, and 18S ribosomal DNA/internal transcribed spacer analysis as Rhodotorula mucilaginosa, a basidiomycetous yeast. During growth the yeast hydrolyzed the dibenzoyl ester stoichiometrically to the monoester using the separated benzoate as the growth substrate, before the monoester was further cleaved into benzoate and tartrate, which were both metabolized. The corresponding benzoyl esterase was purified from the culture supernatant and characterized as a monomeric glycosylated 86-kDa protein with an optimum pH of 7.5 and an optimum temperature of 45 degrees C. At 0 degrees C the esterase still exhibited 20% of the corresponding activity at 30 degrees C, which correlates it to psychrophilic enzymes. The esterase could hydrolyze short chain p-nitrophenyl-alkyl esters and several benzoyl esters like benzoyl-methyl ester, ethylene-glycol-dibenzoyl ester, phenyl-benzoyl ester, cocaine, and 1,5-anhydro-D: -fructose-tribenzoyl ester. However feruloyl-ethyl ester was not hydrolyzed. The activity characteristics let the enzyme appear as a promising tool for synthesis of benzoylated compounds for pharmaceutical, cosmetic, or fine chemical applications, even at low temperatures.

  17. A Wheat R2R3-type MYB Transcription Factor TaODORANT1 Positively Regulates Drought and Salt Stress Responses in Transgenic Tobacco Plants

    Directory of Open Access Journals (Sweden)

    Qiuhui Wei

    2017-08-01

    Full Text Available MYB transcription factors play important roles in plant responses to biotic and abiotic stress. In this study, TaODORANT1, a R2R3-MYB gene, was cloned from wheat (Triticum aestivum L.. TaODORANT1 was localized in the nucleus and functioned as a transcriptional activator. TaODORANT1 was up-regulated in wheat under PEG6000, NaCl, ABA, and H2O2 treatments. TaODORANT1-overexpressing transgenic tobacco plants exhibited higher relative water content and lower water loss rate under drought stress, as well as lower Na+ accumulation in leaves under salt stress. The transgenic plants showed higher CAT activity but lower ion leakage, H2O2 and malondialdehyde contents under drought and salt stresses. Besides, the transgenic plants also exhibited higher SOD activity under drought stress. Our results also revealed that TaODORANT1 overexpression up-regulated the expression of several ROS- and stress-related genes in response to both drought and salt stresses, thus enhancing transgenic tobacco plants tolerance. Our studies demonstrate that TaODORANT1 positively regulates plant tolerance to drought and salt stresses.

  18. Visible-light driven photocatalytic degradation of methylene-violet by rGO/Fe{sub 3}O{sub 4}/ZnO ternary nanohybrid structures

    Energy Technology Data Exchange (ETDEWEB)

    Thangavel, Srinivas [Nanomaterials Research Lab ( NmRL ), Department of Nanoscience and Technology, Karunya University, Coimbatore 641 114, Tamil Nadu (India); Center of Excellence in Advanced Materials and Green Technologies, Department of Chemical Engineering and Material Science, Amrita Vishwa Vidyapeetham, Coimbatore 641 112, Tamil Nadu (India); Thangavel, Sakthivel [Nanomaterials Research Lab ( NmRL ), Department of Nanoscience and Technology, Karunya University, Coimbatore 641 114, Tamil Nadu (India); Department of Mechanical Engineering, Jeju National University, Jeju 690-756 (Korea, Republic of); Raghavan, Nivea [Nanomaterials Research Lab ( NmRL ), Department of Nanoscience and Technology, Karunya University, Coimbatore 641 114, Tamil Nadu (India); Krishnamoorthy, Karthikeyan [Department of Mechanical Engineering, Jeju National University, Jeju 690-756 (Korea, Republic of); Venugopal, Gunasekaran, E-mail: gunasekaran@karunya.edu [Nanomaterials Research Lab ( NmRL ), Department of Nanoscience and Technology, Karunya University, Coimbatore 641 114, Tamil Nadu (India); Solid State Electronics Lab, Research Institute of Electrical Communication, Tohoku University, Katahira, Sendai 980-8577 (Japan)

    2016-04-25

    A novel ternary nanohybrid structure was constructed with reduced graphene-oxide/iron-oxide/zinc-oxide (rGO/Fe{sub 3}O{sub 4}/ZnO) via a facile hydrothermal method. The structural, morphological and optical properties were explored using X-ray diffraction, scanning electron microscope (SEM) with energy dispersive spectra and photoluminescence (PL) studies. The functional groups of ternary nanohybrid were characterized by Fourier transform-infrared spectroscopy. SEM images confirm the presence of two-dimensional GO sheets, one dimensional Fe{sub 3}O{sub 4} and ZnO nanorods. The PL spectra showed the quenching effect which has been observed from the reduction of electron–hole recombination in hybrid. Degradation efficiency of this system was evaluated and compared with pure ZnO and Fe{sub 3}O{sub 4}/ZnO. Under visible light condition, the ternary nanohybrid has shown an excellent photocatalytic degradation of methylene-violet dye. The degradation efficiency of rGO/Fe{sub 3}O{sub 4}/ZnO was systematically analyzed by absorption spectra and total organic carbon removal techniques. Our experimental results will show the potential way for the development of futuristic rGO based nanohybrids as an effective photocatalytic materials for waste-water treatment and environmental remedial applications. - Graphical abstract: A new ternary nanohybrid has been constructed with 1D Fe{sub 3}O{sub 4}–ZnO and 2D rGO sheets to utilize as visible-light photocatalyst. Highly active photocatalyst has been prepared by a feasible hydrothermal approach. For the first time, rGO/Fe{sub 3}O{sub 4}/ZnO ternary nanohybrid exhibits a superior photocatalytic activity towards the degradation of methylene-violet (dye) and the same can be used for environmental remediation applications. - Highlights: • Ternary nanohybrid constructed with 1D ZnO, Fe{sub 3}O{sub 4} and 2D rGO. • Aggregation free rGO/Fe{sub 3}O{sub 4}/ZnO nanohybrid exhibits superior photocatalytic activity. • rGO boost up

  19. The installations maintenance control using SAP R/3; O controle de manutencao de instalacoes utilizando o SAP R/3

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Robison Tirre; Pereira, Paulo Manoel Borges; Jorge, Kemal Vieira [Transportadora Brasileira Gasoduto Bolivia Brasil S.A., Rio de Janeiro, RJ (Brazil)

    2004-07-01

    TBG (Transportadora Brasileira Gasoduto Bolivia Brasil S.A.) began their operations in 1999 and since the beginning the SAP R/3 PM module (Plant Maintenance) is used for the control of the maintenance activities and to manager the Master Maintenance and Inspection Plans. On these five years, a series of reports and SAP functionalities were developed or configured to adapt the system R/3 to the needs of TBG maintenance. Now, the whole management and control of the surface facilities maintenance (compression station, city gate, measurement station, etc) is accomplished by SAP R/3 system. (author)

  20. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Geiger, Adolf, E-mail: ageiger@dreirosen-pharma.com; Walker, Audrey, E-mail: awalker@dreirosen-pharma.com; Nissen, Erwin, E-mail: enissen@dreirosen-pharma.com

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. - Highlights: • Fibrocytes have shown potent wound healing properties in vitro and in vivo. • Their clinical use is precluded by low numbers and antigen-presenting function. • We isolated exosomes with no immunogenicity potential from human fibrocytes. • Their cargo included microRNAs and proteins that are known healing promoters. • They accelerated wound closure in diabetic mice in a dose-dependent manner.

  1. Characterization of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next generation sequencing study

    Science.gov (United States)

    Mirzaa, Ghayda; Conti, Valerio; Timms, Andrew E.; Smyser, Christopher D.; Ahmed, Sarah; Carter, Melissa; Barnett, Sarah; Hufnagel, Robert B.; Goldstein, Amy; Narumi-Kishimoto, Yoko; Olds, Carissa; Collins, Sarah; Johnston, Kathreen; Deleuze, Jean-François; Nitschké, Patrick; Friend, Kathryn; Harris, Catharine; Goetsch, Allison; Martin, Beth; Boyle, Evan August; Parrini, Elena; Mei, Davide; Tattini, Lorenzo; Slavotinek, Anne; Blair, Ed; Barnett, Christopher; Shendure, Jay; Chelly, Jamel; Dobyns, William B.; Guerrini, Renzo

    2015-01-01

    variation in alternate (mutant) allele levels ranging from 2·5% (10/377) to 36·7% (39/106) of reads, equivalent to 5–73·4% of cells analyzed. Levels of mosaicism varied from undetectable to 17·1% (37/216) of reads in blood-derived compared to 29·4% (2030/6889) to 43·3% (275/634) in saliva-derived DNA. Interpretation Constitutional and mosaic mutations in the PIK3R2 gene are associated with a spectrum of developmental brain disorders ranging from BPP with a normal head size to the megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. The phenotypic variability and low-level mosaicism challenging conventional molecular methods have important implications for genetic testing and counseling. PMID:26520804

  2. Fine tuning the HOMO energy levels of polythieno[3,4-b]thiophene derivatives by incorporation of thiophene-3,4-dicarboxylate moiety for photovoltaic applications

    DEFF Research Database (Denmark)

    Hu, Xiao-Lian; Zuo, Li-Jian; Nan, Ya-Xiong

    2012-01-01

    To lower the HOMO (highest occupied molecular orbital) energy level of polythieno[3,4-b]thiophene (∼−4.5eV), a series of ester-functionalized polythieno[3,4-b]thiophene derivatives (P1–P3) were designed and synthesized by Stille cross coupling reaction. The resulting copolymers exhibited broad...... voltage (Voc) of 0.54V, a short circuit current density (Isc) of 3.3mA/cm2, a fill factor (FF) of 0.57, and a power conversion efficiency (PCE) of 1.02%. A high Voc up to 0.71V was achieved in the solar cell based on a P3:PCBM blend....

  3. Graphene derivatives/Fe_3O_4/polymer nanocomposite films: Optical and electrical properties

    International Nuclear Information System (INIS)

    Hatel, Rhizlane; Goumri, Meryem; Ratier, Bernard; Baitoul, Mimouna

    2017-01-01

    This paper reports a simple solution casting method for the preparation of nanocomposite films in which graphene oxide (GO)/Fe_3O_4 nanocomposites are incorporated into poly (vinyl alcohol) (PVA) matrix. The films obtained with different weight percent of GO/Fe_3O_4 (0.5, 0.7 and 1 wt%) are subjected an in situ chemical and thermal reduction in order to explore the evolution and interactions between these components under different treatments and get an insight into on how this can affects the optical and electrical properties of these nanocomposites. Characterization was carried out using, UV–Vis absorption, Photoluminescence, electrical conductivity measurements, Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. Strong covalent functionalization occurs between the polymer and graphene derivatives (GD)/Fe_3O_4 hybrids. The experimental results obtained for our nanocomposites films exhibit significant enhancement in properties highlighted the efficiency of the in situ thermal reduction. The high absorption with strong photoluminescence and electrical conductivity achieved might promote these nanocomposites for opto-electronic devices in near future. - Highlights: • Novel inorganic-organic hybrid flexible films were successfully prepared. • Good interfacial interaction between the graphene/Fe_3O_4 and the hydroxyl-rich PVA. • Optical and electrical properties of Graphene Derivatives/Fe_3O_4/PVA were investigated. • Thermally reduced GO/Fe_3O_4/PVA films show high absorption and strong photoluminescence.

  4. Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.

    Science.gov (United States)

    Allende, Maria L; Cook, Emily K; Larman, Bridget C; Nugent, Adrienne; Brady, Jacqueline M; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J; Proia, Richard L

    2018-03-01

    Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB -corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB -corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB -corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses.

  5. Synthesis, Antiviral Bioactivity of Novel 4-Thioquinazoline Derivatives Containing Chalcone Moiety

    Directory of Open Access Journals (Sweden)

    Zhihua Wan

    2015-06-01

    Full Text Available A series of novel 4-thioquinazoline derivatives containing chalcone moiety were designed, synthesized and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds exhibited moderate to good anti-TMV activity. In particular, compounds M2 and M6 possessed appreciable protection activities against TMV in vivo, with 50% effective concentration (EC50 values of 138.1 and 154.8 μg/mL, respectively, which were superior to that of Ribavirin (436.0 μg/mL. The results indicated that chalcone derivatives containing 4-thioquinazoline moiety could effectively control TMV. Meanwhile, the structure-activity relationship (SAR of the target compounds, studied using the three-dimensional quantitative structure-activity relationship (3D-QSAR method of comparative molecular field analysis (CoMFA based on the protection activities against TMV, demonstrated that the CoMFA model exhibited good predictive ability with the cross-validated q2 and non-cross-validated r2 values of 0.674 and 0.993, respectively. Meanwhile, the microscale thermophoresis (MST experimental showed that the compound M6 may interaction with the tobacco mosaic virus coat protein (TMV CP.

  6. Syntheses of 24R,25-dihydroxy-[6,19,19-3H]vitamin D3 and 24R,25-dihydroxy-[6,19,19-2H]vitamin D3

    International Nuclear Information System (INIS)

    Yamada, S.; Shimizu, M.; Fukushima, K.; Niimura, K.; Maeda, Y.

    1989-01-01

    24R,25-Dihydroxy-[6,19,19-3H]vitamin D3 with a specific activity of 54 Ci/mmol and 24R,25-dihydroxy-[6,19,19-2H]vitamin D3 with 2.6 deuterium atoms/mol were synthesized in four steps starting from 24R,25-Dihydroxyvitamin D3 via its sulfur dioxide adduct

  7. NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.

    Science.gov (United States)

    Olszewski, Rafal T; Janczura, Karolina J; Bzdega, Tomasz; Der, Elise K; Venzor, Faustino; O'Rourke, Brennen; Hark, Timothy J; Craddock, Kirsten E; Balasubramanian, Shankar; Moussa, Charbel; Neale, Joseph H

    2017-09-01

    Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1.5 h) and long- (24 h) term novel object recognition tests were used to assess memory. Treatment with ZJ43 or 2-PMPA prior to acquisition trials increased long-term memory in mGluR2, but not mGluR3, ko mice. Nine month-old triple transgenic Alzheimer's disease model mice exhibited impaired short-term novel object recognition memory that was rescued by treatment with a NAAG peptidase inhibitor. NAAG peptidase inhibitors and the group II mGluR agonist, LY354740, reversed the short-term memory deficit induced by acute ethanol administration in wild type mice. 2-PMPA also moderated the effect of ethanol on short-term memory in mGluR2 ko mice but failed to do so in mGluR3 ko mice. LY354740 and ZJ43 blocked ethanol-induced motor activation. Both GCPII inhibitors and LY354740 also significantly moderated the loss of motor coordination induced by 2.1 g/kg ethanol treatment. These data support the conclusion that inhibitors of glutamate carboxypeptidase II are efficacious in object recognition models of normal memory and memory deficits via an mGluR3 mediated process, actions that could have widespread clinical applications.

  8. 3D-QSAR studies on CCR2B receptor antagonists: Insight into the structural requirements of (R-3-aminopyrrolidine series of molecules based on CoMFA/CoMSIA models

    Directory of Open Access Journals (Sweden)

    Swetha Gade

    2012-01-01

    Full Text Available Objective: Monocyte chemo attractant protein-1 (MCP-1 is a member of the CC-chemokine family and it selectively recruits leukocytes from the circulation to the site of inflammation through binding with the chemotactic cytokine receptor 2B (CCR2B. The recruitment and activation of selected populations of leukocytes is a key feature in a variety of inflammatory conditions. Thus MCP-1 receptor antagonist represents an attractive target for drug discovery. To understand the structural requirements that will lead to enhanced inhibitory potencies, we have carried out 3D-QSAR (quantitative structure-activity relationship studies on (R-3-aminopyrrolidine series of molecules as CCR2B receptor antagonists. Materials and Methods: Comparative molecular field analysis (CoMFA and comparative molecular similarity indices analysis (CoMSIA were performed on a series of (R-3-aminopyrrolidine derivatives as antagonists of CCR2B receptor with Sybyl 6.7v. Results: We have derived statistically significant model from 37 molecules and validated it against an external test set of 13 compounds. The CoMFA model yielded a leave one out r 2 (r 2 loo of 0.847, non-cross-validated r 2 (r 2 ncv of 0.977, F value of 267.930, and bootstrapped r 2 (r 2 bs of 0.988. We have derived the standard error of prediction value of 0.367, standard error of estimate 0.141, and a reliable external predictivity, with a predictive r 2 (r 2 pred of 0.673. While the CoMSIA model yielded an r 2 loo of 0.719, r 2 ncv of 0.964,F value of 135.666, r 2 bs of 0.975, standard error of prediction of 0.512, standard error of estimate of 0.180, and an external predictivity with an r 2 pred of 0.611. These validation tests not only revealed the robustness of the models but also demonstrated that for our models r 2 pred, based on the mean activity of test set compounds can accurately estimate external predictivity. Conclusion: The QSAR model gave satisfactory statistical results in terms of q 2 and r 2

  9. Genome-wide identification, functional prediction, and evolutionary analysis of the R2R3-MYB superfamily in Brassica napus.

    Science.gov (United States)

    Hajiebrahimi, Ali; Owji, Hajar; Hemmati, Shiva

    2017-10-01

    R2R3-MYB transcription factors (TFs) have been shown to play important roles in plants, including in development and in various stress conditions. Phylogenetic analysis showed the presence of 249 R2R3-MYB TFs in Brassica napus, called BnaR2R3-MYB TFs, clustered into 38 clades. BnaR2R3-MYB TFs were distributed on 19 chromosomes of B. napus. Sixteen gene clusters were identified. BnaR2R3-MYB TFs were characterized by motif prediction, gene structure analysis, and gene ontology. Evolutionary analysis revealed that BnaR2R3-MYB TFs are mainly formed as a result of whole-genome duplication. Orthologs and paralogs of BnaR2R3-MYB TFs were identified in B. napus, B. rapa, B. oleracea, and Arabidopsis thaliana using synteny-based methods. Purifying selection was pervasive within R2R3-MYB TFs. K n /K s values lower than 0.3 indicated that BnaR2R3-MYB TFs are being functionally converged. The role of gene conversion in the formation of BnaR2R3-MYB TFs was significant. Cis-regulatory elements in the upstream regions of BnaR2R3-MYB genes, miRNA targeting BnaR2R3MYB TFs, and post translational modifications were identified. Digital expression data revealed that BnaR2R3-MYB genes were highly expressed in the roots and under high salinity treatment after 24 h. BnaMYB21, BnaMYB141, and BnaMYB148 have been suggested for improving salt-tolerant B. napus. BnaR2R3-MYB genes were mostly up regulated on the 14th day post inoculation with Leptosphaeria biglobosa and L. maculan. BnaMYB150 is a candidate for increased tolerance to Leptospheria in B. napus.

  10. Expressions of the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase genes are stimulated by recombinant platelet-derived growth factor isomers

    International Nuclear Information System (INIS)

    Roth, M.; Emmons, L.R.; Perruchoud, A.; Block, L.H.

    1991-01-01

    The plausible role that platelet-derived growth factor (PDGF) has in the localized pathophysiological changes that occur in the arterial wall during development of atherosclerotic lesions led the authors to investigate the influence of recombinant (r)PDGF isomers -AA, -AB, and -BB on the expression of low density lipoprotein receptor (LDL-R) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG0CoA) reductase [(S)-mevalonate:NAD + oxidoreductase (CoA-acylating), EC 1.1.1.88] genes. In addition, they clarified the role of protein kinase C (PKC) in expression of the two genes in human skin fibroblasts and vascular smooth muscle cells. The various rPDGF isoforms are distinct in their ability to activate transcription of both genes: (i) both rPDGF-AA and -BB stimulate transcription of the LDL-R gene; in contrast, rPDGF-BB but not -AA, activates transcription of the HMG-CoA reductase gene; (ii) all recombinant isoforms of PDGF activate transcription of the c-fos gene; (iii) while rPDGF-dependent transcription of the lDL-R gene occurs independently of PKC, transcription of the HMG-CoA reductase gene appears to involve the action of that enzyme

  11. Readily Available Chiral Benzimidazoles-Derived Guanidines as Organocatalysts in the Asymmetric α-Amination of 1,3-Dicarbonyl Compounds.

    Science.gov (United States)

    Benavent, Llorenç; Puccetti, Francesco; Baeza, Alejandro; Gómez-Martínez, Melania

    2017-08-11

    The synthesis and the evaluation as organocatalysts of new chiral guanidines derived from benzimidazoles in the enantioselective α-amination of 1,3-dicarbonyl compounds using di- t -butylazodicarboxylate as aminating agent is herein disclosed. The catalysts are readily synthesized through the reaction of 2-chlorobezimidazole and a chiral amine in moderate-to-good yields. Among all of them, those derived from ( R )-1-phenylethan-1-amine ( 1 ) and ( S )-1-(2-naphthyl)ethan-1-amine ( 3 ) turned out to be the most efficient for such asymmetric transformation, rendering good-to-high yields and moderate-to-good enantioselectivities for the amination products.

  12. Novel chalcone-based fluorescent human histamine H3 receptor ligands as pharmacological tools

    Directory of Open Access Journals (Sweden)

    Holger eStark

    2012-03-01

    Full Text Available Novel fluorescent chalcone-based ligands at human histamine H3 receptors (hH3R have been designed, synthesized and characterized. Compounds described are non-imidazole analogues of ciproxifan with a tetralone motif. Tetralones as chemical precursors and related fluorescent chalcones exhibit affinities at hH3R in the same concentration range like that of the reference antagonist ciproxifan (hH3R pKi value of 7.2. Fluorescence characterization of our novel ligands shows emission maxima about 570 nm for yellow fluorescent chalcones and ≥600 nm for the red fluorescent derivatives. Interferences to cellular autofluorescence could be excluded. All synthesized chalcone compounds could be taken to visualize hH3R proteins in stably transfected HEK-293 cells using confocal laser scanning fluorescence microscopy. These novel fluorescent ligands possess high potential to be used as pharmacological tools for hH3R visualization in different tissues.

  13. Exhibition | CERN Micro Club | 1-30 September

    CERN Multimedia

    2014-01-01

    The CERN Micro Club (CMC) is organising an exhibition looking back on the origins of the personal computer, also known as the micro-computer, to mark the 60th anniversary of CERN and the club’s own 30th anniversary.   CERN, Building 567, R-021 and R-029 01.09.2014 - 30.09.2014 from 4.00 to 6.00 p.m. The exhibition will be held in the club’s premises (Building 567, rooms R-0121 and R-029) and will be open Mondays to Thursdays from 1 to 30 September 2014. Come and admire, touch and use makes and models that disappeared from the market many years ago, such as Atari, Commodore, Olivetti, DEC, IBM and Apple II and III, all in good working order and installed with applications and games from the period. Club members will be on hand to tell you about these early computers, which had memories of just of a few kilobytes, whereas those of modern computers can reach several gigabytes or even terabytes.

  14. Three New Resveratrol Derivatives from the Mangrove Endophytic Fungus Alternaria sp.

    Directory of Open Access Journals (Sweden)

    Jinhua Wang

    2014-05-01

    Full Text Available Three new resveratrol derivatives, namely, resveratrodehydes A–C (1–3, were isolated from the mangrove endophytic fungus Alternaria sp. R6. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. All compounds showed broad-spectrum inhibitory activities against three human cancer cell lines including human breast MDA-MB-435, human liver HepG2, and human colon HCT-116 by MTT assay (IC50 < 50 μM. Among them, compounds 1 and 2 both exhibited marked cytotoxic activities against MDA-MB-435 and HCT-116 cell lines (IC50 < 10 μM. Additionally, compounds 1 and 3 showed moderate antioxidant activity by DPPH radical scavenging assay.

  15. Synthesis and Cytotoxic Effect of Some Novel 1,2-Dihydropyridin-3-carbonitrile and Nicotinonitrile Derivatives

    Directory of Open Access Journals (Sweden)

    Eman M. Flefel

    2015-12-01

    Full Text Available 1-(2,4-Dichlorophenyl-3-(4-fluorophenylpropen-1-one (1 was prepared and reacted with an active methylene compound (ethyl cyanoacetate in the presence of ammonium acetate to give the corresponding cyanopyridone 2. Compound 2 reacted with hydrazine hydrate, malononitrile, ethyl bromoacetate and phosphorous oxychloride to afford compounds 4 and 7–11, respectively. The 2-chloropyridine derivative 11 reacted with different primary amines, namely benzyl amine, piperonyl amine, 1-phenylethyl amine, and/or the secondary amines 2-methyl-pipridine and morpholine to give the corresponding derivatives 12–15. Hydrazinolysis of chloropyridine derivative 11 with hydrazine hydrate afforded the corresponding hydrazino derivative 17. Condensation of compound 17 with ethyl acetoacetate, acetylacetone, isatin and different aldehydes gave the corresponding derivatives 18–21. Some of newly synthesized compounds were screened for cytotoxic activity against three tumor cell lines. The results indicated that compounds 8 and 16 showed the best results, exhibiting the highest inhibitory effects towards the three tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic towards normal cells (IC50 values > 100 μg/mL.

  16. T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference.

    Science.gov (United States)

    Brasser, Susan M; Norman, Meghan B; Lemon, Christian H

    2010-05-01

    Elevated alcohol consumption is associated with enhanced preference for sweet substances across species and may be mediated by oral alcohol-induced activation of neurobiological substrates for sweet taste. Here, we directly examined the contribution of the T1r3 receptor protein, important for sweet taste detection in mammals, to ethanol intake and preference and the neural processing of ethanol taste by measuring behavioral and central neurophysiological responses to oral alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain. T1r3 knockout and wild-type mice were tested in behavioral preference assays for long-term voluntary intake of a broad concentration range of ethanol, sucrose, and quinine. For neurophysiological experiments, separate groups of mice of each genotype were anesthetized, and taste responses to ethanol and stimuli of different taste qualities were electrophysiologically recorded from gustatory neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were behaviorally indifferent to alcohol (i.e., ∼50% preference values) at concentrations typically preferred by wild-type mice (5-15%). Central neural taste responses to ethanol in T1r3-deficient mice were significantly lower compared with C57BL/6J controls, a strain for which oral ethanol stimulation produced a concentration-dependent activation of sweet-responsive NTS gustatory neurons. An attenuated difference in ethanol preference between knockouts and controls at concentrations >15% indicated that other sensory and/or postingestive effects of ethanol compete with sweet taste input at high concentrations. As expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural taste responses to sweeteners but did not differ from wild-type mice in responses to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3 receptor in the sensory detection and transduction of ethanol taste.

  17. Theoretical studies of the tautomerism in 3-(2-R-Phenylhydrazono)-naphthalene- 1,2,4-triones: synthesis of copper(II) complexes and studies of antibacterial and antitumor activities

    Energy Technology Data Exchange (ETDEWEB)

    Francisco, Acacio I.; Vargas, Maria D.; Fragoso, Thais P.; Carneiro, J. Walkimar de M.; Silva, Fernando de C. da; Ferreira, Vitor F., E-mail: mdvargas@vm.uff.b [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Inst. de Quimica; Casellato, Annelise [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Quimica; Barbosa, Jussara P. [Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil); Pessoa, Claudia; Costa-Lotufo, Leticia V.; Marinho Filho, Jose D.B.; Moraes, Manoel O. de [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Fisiologia e Farmacologia; Mangrich, Antonio S. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Quimica

    2010-07-01

    DFT calculations using the B3LYP and PBE1PBE functionals with the standard 6-31G(d) and 6-311+G(2d,p) basis sets were carried out for the 3-(2-phenylhydrazone)-naphthalene-1,2,4-trione system in solution (dmso) and in the gas phase, and showed the keto-hydrazone forms (rotamers Ia and Ib) to be more stable than the enol-azo forms (rotamers IIa and IIb, by about 14 kcal mol-1) and III (by approximately 6 kcal mol-1), independently of the nature of the substituent in the phenylene ring. These results were confirmed by spectroscopic data on the derivatives HL1-HL13, obtained from 2-hydroxy-1,4-naphthoquinone and arylamines (R = 4-OMe, 4-N{sub 2}-C{sub 6}H{sub 5}, 4-Cl, 4-I, 3-I, 2-I, 4-COOH, 3-COOH, 4-CN, 3-CN, 4-NO{sub 2}, 3-NO{sub 2}, 2-NO{sub 2}). The in vitro antitumor (against SF-295, HCT-8, MDAMB-435 and HL-60 cancer cell lines) and antibacterial activities (Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa) of compounds HL1-HL13 and of their respective copper(II) complexes, [Cu(L1-13){sub 2}], were tested. In general, these compounds exhibited low antibacterial activity, except for HL5 (R 3-I), more active than the control; however, the corresponding complex was inactive. In contrast, increased cytotoxicity was observed upon complexation. Complex [Cu(L13){sub 2}] (R = 3-NO{sub 2}) presented moderate cytotoxicity against human leukemia (HL-60). (author)

  18. (1R,6R,13R,18R-(Z,Z-1,18-Bis[(4R-2,2-dimethyl-1,3-dioxolan-4-yl]-3,16-dimethylene-8,20-diazadispiro[5.6.5.6]tetracosa-7,19-diene

    Directory of Open Access Journals (Sweden)

    Stéphanie M. Guéret

    2010-07-01

    Full Text Available The crystal structure of the title compound, C34H54N2O4, has been solved in order to prove the relative and absolute chirality of the newly-formed stereocentres which were established using an asymmetric Diels–Alder reaction at an earlier stage in the synthesis. This unprecedented stable dialdimine contains a 14-membered ring and was obtained as the minor diastereoisomer in the Diels–Alder reaction. The absolute stereochemistry of the stereocentres of the acetal functionality was known to be R based on the use of a chiral (R-trisubstituted dienophile derived from enantiopure (S-glyceraldehyde. The assignment of the configuration in the dienophile and the title di-aldimine differs from (S-glyceraldehyde due to a change in the priority order of the substituents. The crystal structure establishes the presence of six stereocentres all attributed to be R. The 14-membered ring contains two aldimine bonds [C—N = 1.258 (2 and 1.259 (2 Å]. It adopts a similar conformation to that proposed for trans–trans-cyclotetradeca-1,8-dienes.

  19. Hematopoietic stem cell-derived exosomes promote hematopoietic differentiation of mouse embryonic stem cells in vitro via inhibiting the miR126/Notch1 pathway.

    Science.gov (United States)

    Liao, Feng-Ling; Tan, Lin; Liu, Hua; Wang, Jin-Ju; Ma, Xiao-Tang; Zhao, Bin; Chen, Yanfang; Bihl, Ji; Yang, Yi; Chen, Ri-Ling

    2018-04-01

    Cell-derived exosomes (EXs) can modulate target cell differentiation via microRNAs (miRs) that they carried. Previous studies have shown that miR126 is highly expressed in hematopoietic stem cells (HSCs) and plays a role in hematopoiesis via modulating the Notch pathway that participates in progenitors' cell fate decisions. In this study we investigated whether HSC-derived EXs (HSC-EXs) could affect the differentiation of mouse embryonic stem cells (ESCs) into HSCs. We prepared HSC-EXs con , HSC-EXs sc and HSC-EXs miR126 from control HSCs and the HSCs transfected with scramble control or miR126 mimics, respectively. HSC-EXs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis. We incubated the collected EXs with mouse ESCs over a 10-d differentiation induction period, during which HSC-EXs and a Notch pathway activator (Jagged1, 100 ng/mL) were added to the cultures every 3 d. After the 10-d differentiation period, the expression levels of miR126, SSEA1, CD117, Sca1, Notch1 and Hes1 in ESCs were assessed. The generated HSCs were validated by flow cytometry using antibodies against HSC markers (CD117, CD34 and Sca1). Our results revealed that: (1) transfection with miR126 mimics significantly increased miR126 levels in HSC-EXs miR126 . (2) HSC-EX co-culture promoted mouse ESCs differentiation into HSCs with the most prominent effect found in the HSC-EXs miR126 co-culture. (3) HSC differentiation was verified by reduced SSEA1 expression and increased CD117 and Sca1 expression. (4) All the effects caused by HSC-EXs were accompanied by significant reduction of Notch1 and Hes1 expression, thus inhibition of the Notch1/Hes1 pathway, whereas activation of Notch by Jagged1 abolished the effects of HSC-EXs miR126 . In conclusion, HSC-EXs promote hematopoietic differentiation of mouse ESCs in vitro by inhibiting the miR126/Notch1 pathway.

  20. 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

    Science.gov (United States)

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-01-19

    Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent.

  1. Asymmetric Benzylic Allylic Alkylation Reaction of 3-Furfural Derivatives by Dearomatizative Dienamine Activation.

    Science.gov (United States)

    He, Xiao-Long; Zhao, Hui-Ru; Duan, Chuan-Qi; Han, Xu; Du, Wei; Chen, Ying-Chun

    2018-04-20

    The dearomatizative dienamine-type ortho-quinodimethane species are smoothly generated between 2-alkyl-3-furfurals and chiral secondary amine catalysts, which undergo asymmetric benzylic allylic alkylation reactions with 2-nitroallylic acetates efficiently. A spectrum of densely functionalized 3-furfural derivatives are delivered in moderate to high yields with good to excellent diastereo- and enantioselectivity (up to 98 % yield, >19:1 d.r., >99 % ee). The latent transformations allow the facile production of some enantioenriched architectures, such as 1,1,2,2-tetraarylethanes and triarylmethanes, which are not easily available from other protocols. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Genome-wide identification and characterization of R2R3MYB family in Rosaceae.

    Science.gov (United States)

    González, Máximo; Carrasco, Basilio; Salazar, Erika

    2016-09-01

    Transcription factors R2R3MYB family have been associated with the control of secondary metabolites, development of structures, cold tolerance and response to biotic and abiotic stress, among others. In recent years, genomes of Rosaceae botanical family are available. Although this information has been used to study the karyotype evolution of these species from an ancestral genome, there are no studies that treat the evolution and diversity of gene families present in these species or in the botanical family. Here we present the first comparative study of the R2R3MYB subfamily of transcription factors in three species of Rosaceae family (Malus domestica, Prunus persica and Fragaria vesca). We described 186, 98 and 86 non-redundant gene models for apple, peach and strawberry, respectively. In this research, we analyzed the intron-exon structure and genomic distribution of R2R3MYB families mentioned above. The phylogenetic comparisons revealed putative functions of some R2R3MYB transcription factors. This analysis found 44 functional subgroups, seven of which were unique for Rosaceae. In addition, our results showed a highly collinearity among some genes revealing the existence of conserved gene models between the three species studied. Although some gene models in these species have been validated under several approaches, more research in the Rosaceae family is necessary to determine gene expression patterns in specific tissues and development stages to facilitate understanding of the regulatory and biochemical mechanism in this botanical family.

  3. Natural superhydrophilicity and photocatalytic properties of sol–gel derived ZnTiO3-ilmenite/r-TiO2 films

    Czech Academy of Sciences Publication Activity Database

    Krylova, G.; Spanhel, L.; Brioude, A.; Soraya, A.G.; Mrázek, Jan

    2010-01-01

    Roč. 12, č. 45 (2010), s. 15101-15110 ISSN 1463-9076 R&D Projects: GA MŠk OC08023 Institutional research plan: CEZ:AV0Z20670512 Keywords : nanomaterial * photocatalyze * optical properties Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 3.454, year: 2010

  4. R3D3 : The Rolling Receptionist Robot with Double Dutch Dialogue

    NARCIS (Netherlands)

    Linssen, Jeroen; Theune, Mariet

    We discuss the design of R3D3, a rolling receptionist robot with the ability to conduct 'double Dutch dialogues': dialogues (in Dutch) that involve, besides a human user, both a robot and a virtual human. R3D3 is intended to assist people when they visit shops, museums, or other establishments by

  5. R3D3: The Rolling Receptionist Robot with Double Dutch Dialogue

    NARCIS (Netherlands)

    Linssen, Jeroen; Theune, Mariet

    We discuss the design of R3D3, a rolling receptionist robot with the ability to conduct 'double Dutch dialogues': dialogues (in Dutch) that involve, besides a human user, both a robot and a virtual human. R3D3 is intended to assist people when they visit shops, museums, or other establishments by

  6. miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages

    Directory of Open Access Journals (Sweden)

    Fei Huang

    2017-10-01

    Full Text Available The Notch pathway plays critical roles in the differentiation and polarized activation of macrophages; however, the downstream molecular mechanisms underlying Notch activity in macrophages remain elusive. Our previous study has identified a group of microRNAs that mediate Notch signaling to regulate macrophage activation and tumor-associated macrophages (TAMs. In this study, we demonstrated that miR-148a-3p functions as a novel downstream molecule of Notch signaling to promote the differentiation of monocytes into macrophages in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF. Meanwhile, miR-148a-3p promoted M1 and inhibited M2 polarization of macrophages upon Notch activation. Macrophages overexpressing miR-148a-3p exhibited enhanced ability to engulf and kill bacteria, which was mediated by excessive production of reactive oxygen species (ROS. Further studies using reporter assay and Western blotting identified Pten as a direct target gene of miR-148a-3p in macrophages. Macrophages overexpressing miR-148a-3p increased their ROS production through the PTEN/AKT pathway, likely to defend against bacterial invasion. Moreover, miR-148a-3p also enhanced M1 macrophage polarization and pro-inflammatory responses through PTEN/AKT-mediated upregulation of NF-κB signaling. In summary, our data establish a novel molecular mechanism by which Notch signaling promotes monocyte differentiation and M1 macrophage activation through miR-148a-3p, and suggest that miR-148a-3p-modified monocytes or macrophages are potential new tools for the treatment of inflammation-related diseases.

  7. A library synthesis of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as anti-tumor agents.

    Science.gov (United States)

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-09-06

    As a result of a hit-to-lead program using a technique of solution-phase parallel synthesis, a highly potent (2,4-dimethoxyphenyl)-[6-(3-fluorophenyl)-4-hydroxy-3-methylbenzofuran-2-yl]methanone (15b) was synthesized as an optimized derivative of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which was discovered as a screening hit from small-molecule libraries and exhibited selective cytotoxicity against a tumorigenic cell line.

  8. Effect of the structure of compounds in the series (RO)3PO-R3PO-R3ASO-R3NO on the extraction of, and nature of complex formation with, HClO4, HReO4, and HTcO4

    International Nuclear Information System (INIS)

    Rozen, A.M.; Skotnikov, A.S.

    1982-01-01

    Basicity increases considerably in the series of extractants (RO) 3 PO-R 3 AsO-R 3 NO. The effect of this factor was first studied in the extractions of nitric acid and uranyl nitrate which are characterized by a solvate mechanism of complex formation (the extractant enters into the inner sphere of the complex). In this series, a very large increase in extractive ability was observed and for HNO 3 the mechanism of addition changed, going from complexation with H-bonding ((RO) 3 PO-R 3 PO) to complexation with proton transfer of the type (R 3 XOH) + NO -3 . Correspondingly, a new mechanism (ion exchange) of extraction of metals arose, for example, in the form (R 3 XOH) + UO 2 (NO 3 ) -3 . The previously incomprehensible similarity of the distribution coefficients for extractions with amines and amine oxides (the most basic organic oxides, R 3 AsO and R 3 NO being similar to amines in the mechanism of complex formation) became clear. It was of interest to study the effect of the increase in basicity in this same series of compounds on the extraction equilibria of strong acids. These are characterized by a hydrate-solvation mechanism of extraction (the organic ligand is found in the inner sphere of the complex joined to a proton of the acid or to the metal through water. The qualitative side of such processes has been, to a considerable degree, explained but a quantitative investigation presents considerable difficulty because of the multiplicity of complexes being formed. Thus, in order to solve the problem proposed, it was necessary to develop a mathematical analysis of the processes taking place in the hydratosolvate mechanism and also to obtain the experimental data needed for such as analysis

  9. microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

    Directory of Open Access Journals (Sweden)

    Junfeng Zhang

    Full Text Available AIMS: Endothelial progenitor cells (EPCs are capable of proliferating and differentiating into mature endothelial cells, and they have been considered as potential candidates for coronary heart disease therapy. However, the transition of EPCs to mesenchymal cells is not fully understood. This study aimed to explore the role of microRNA 126 (miR-126 in the endothelial-to-mesenchymal transition (EndMT induced by transforming growth factor beta 1 (TGFβ1. METHODS AND RESULTS: EndMT of rat bone marrow-derived EPCs was induced by TGFβ1 (5 ng/mL for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The luciferase reporter assay showed that the PI3K regulatory subunit p85 beta (PIK3R2 was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a lentiviral vector (lenti-miR-126 was found to downregulate the mRNA expression of mesenchymal cell markers (α-SMA, sm22-a, and myocardin and to maintain the mRNA expression of progenitor cell markers (CD34, CD133. In the cellular process of EndMT, there was an increase in the protein expression of PIK3R2 and the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt expression decreased, a change that was reversed markedly by overexpression of miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed morphological changes of the EPCs treated with TGFβ1, thereby giving the evidence that PIK3R2 is the target gene of miR-126 during EndMT process. CONCLUSIONS: These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT and that this process involves regulation of the PI3K/Akt signalling pathway. miR-126 has the potential to be used as a biomarker for the early diagnosis of intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool for treating cardiovascular diseases mediated by the EndMT process.

  10. Production of (R)-3-hydroxybutyric acid by Arxula adeninivorans.

    Science.gov (United States)

    Biernacki, Mateusz; Riechen, Jan; Hähnel, Urs; Roick, Thomas; Baronian, Kim; Bode, Rüdiger; Kunze, Gotthard

    2017-12-01

    (R)-3-hydroxybutyric acid can be used in industrial and health applications. The synthesis pathway comprises two enzymes, β-ketothiolase and acetoacetyl-CoA reductase which convert cytoplasmic acetyl-CoA to (R)-3-hydroxybutyric acid [(R)-3-HB] which is released into the culture medium. In the present study we used the non-conventional yeast, Arxula adeninivorans, for the synthesis enantiopure (R)-3-HB. To establish optimal production, we investigated three different endogenous yeast thiolases (Akat1p, Akat2p, Akat4p) and three bacterial thiolases (atoBp, thlp, phaAp) in combination with an enantiospecific reductase (phaBp) from Cupriavidus necator H16 and endogenous yeast reductases (Atpk2p, Afox2p). We found that Arxula is able to release (R)-3-HB used an existing secretion system negating the need to engineer membrane transport. Overexpression of thl and phaB genes in organisms cultured in a shaking flask resulted in 4.84 g L -1 (R)-3-HB, at a rate of 0.023 g L -1  h -1 over 214 h. Fed-batch culturing with glucose as a carbon source did not improve the yield, but a similar level was reached with a shorter incubation period [3.78 g L -1 of (R)-3-HB at 89 h] and the rate of production was doubled to 0.043 g L -1  h -1 which is higher than any levels in yeast reported to date. The secreted (R)-3-HB was 99.9% pure. This is the first evidence of enantiopure (R)-3-HB synthesis using yeast as a production host and glucose as a carbon source.

  11. Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

    Directory of Open Access Journals (Sweden)

    Cheng Qian

    2018-01-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs have been described to have important roles in primary immune thrombocytopenia (ITP. To gain additional understanding, we have now further evaluated the involvement of miRNAs in ITP. Methods: Microarray experiments were performed to examine the expression profiles of miRNAs and mRNAs in samples from subjects with newly diagnosed ITP (G1, chronic ITP (G2, and normal controls. The systematic Pipeline of Outlier MicroRNA Analysis framework was applied to identify key miRNAs expressed in the G1 and G2 samples. Quantitative PCR and receiver operator characteristic curves were used to confirm the performance of key miRNAs. Results: Compared with normal controls, 14 miRNAs (12 over-expressed and 2 under-expressed and 7 over-expressed miRNAs were identified as key in G1 and G2 samples, respectively. miR-106b-5p, miR-200c-3p, and miR-92a-3p exhibited significantly different expression profiles among the groups. In particular, miR-106b-5p and miR-200c-3p were expressed at higher levels in patients with ITP compared to the normal controls. Furthermore, these two miRNAs expressions were even higher in patients with chronic ITP. Conclusion: MiR-106b-5p and miR-200c-3p may represent valuable biomarkers of ITP, although further studies are needed to confirm and assess the value of these potential biomarkers at various stages of ITP.

  12. Members of an R2R3-MYB transcription factor family in Petunia are developmentally and environmentally regulated to control complex floral and vegetative pigmentation patterning.

    Science.gov (United States)

    Albert, Nick W; Lewis, David H; Zhang, Huaibi; Schwinn, Kathy E; Jameson, Paula E; Davies, Kevin M

    2011-03-01

    We present an investigation of anthocyanin regulation over the entire petunia plant, determining the mechanisms governing complex floral pigmentation patterning and environmentally induced vegetative anthocyanin synthesis. DEEP PURPLE (DPL) and PURPLE HAZE (PHZ) encode members of the R2R3-MYB transcription factor family that regulate anthocyanin synthesis in petunia, and control anthocyanin production in vegetative tissues and contribute to floral pigmentation. In addition to these two MYB factors, the basic helix-loop-helix (bHLH) factor ANTHOCYANIN1 (AN1) and WD-repeat protein AN11, are also essential for vegetative pigmentation. The induction of anthocyanins in vegetative tissues by high light was tightly correlated to the induction of transcripts for PHZ and AN1. Interestingly, transcripts for PhMYB27, a putative R2R3-MYB active repressor, were highly expressed during non-inductive shade conditions and repressed during high light. The competitive inhibitor PhMYBx (R3-MYB) was expressed under high light, which may provide feedback repression. In floral tissues DPL regulates vein-associated anthocyanin pigmentation in the flower tube, while PHZ determines light-induced anthocyanin accumulation on exposed petal surfaces (bud-blush). A model is presented suggesting how complex floral and vegetative pigmentation patterns are derived in petunia in terms of MYB, bHLH and WDR co-regulators. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  13. New derivatives of 3,4-dihydroisoquinoline-3-carboxylic acid with free-radical scavenging, D-amino acid oxidase, acetylcholinesterase and butyrylcholinesterase inhibitory activity.

    Science.gov (United States)

    Solecka, Jolanta; Guśpiel, Adam; Postek, Magdalena; Ziemska, Joanna; Kawęcki, Robert; Lęczycka, Katarzyna; Osior, Agnieszka; Pietrzak, Bartłomiej; Pypowski, Krzysztof; Wyrzykowska, Agata

    2014-09-30

    A series of 3,4-dihydroisoquinoline-3-carboxylic acid derivatives were synthesised and tested for their free-radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS·+), superoxide anion radical (O2·-) and nitric oxide radical (·NO) assays. We also studied d-amino acid oxidase (DAAO), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Almost each of newly synthesised compounds exhibited radical scavenging capabilities. Moreover, several compounds showed moderate inhibitory activities against DAAO, AChE and BuChE. Compounds with significant free-radical scavenging activity may be potential candidates for therapeutics used in oxidative-stress-related diseases.

  14. Noggin and Wnt3a enable BMP4-dependent differentiation of telencephalic stem cells into GluR-agonist responsive neurons

    DEFF Research Database (Denmark)

    Andersson, Therese; Duckworth, Joshua K; Fritz, Nicolas

    2011-01-01

    levels, that in turn exerted a concentration-dependent inhibition of BMP4-mediated mesenchymal differentiation of NSCs. Instead, BMP4 exposure of NSCs induced neuronal differentiation in mesenchyme-preventing conditions, whereas treatment with recombinant noggin alone did not. Wnt signaling is known...... to be essential for the development of neurons derived from the dorsal telencephalon, and co-stimulation of NSCs with BMP4+Wnt3a resulted in a synergistic effect yielding significantly increased number of mature neurons compared to stimulation with each factor alone. Thus whereas only a subset of BMP4-induced...... neurons derived from telencephalic NSCs, responded to glutamate receptor (GluR) agonists, over 80% of BMP4+Wnt3a-induced neurons responded appropriately to GluR-agonists. Our results increase the understanding of the role for BMP4 in differentiation of telencephalic multipotent progenitors, and reveal...

  15. Reversal of the sign of giant magnetoresistance upon boron filling in RPd{sub 3} compounds (R=Tb,Er)

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Abhishek [S. N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata-700098 (India); Mazumdar, Chandan; Ranganathan, R, E-mail: abhishek.phy@gmail.co, E-mail: chandan.mazumar@saha.ac.i, E-mail: r.ranganathan@saha.ac.i [Experimental Condensed Matter Physics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata-700064 (India)

    2010-01-01

    We report the study of magnetic and transport properties of binary intermetallic compounds RPd{sub 3} (R: Tb and Er) and boron-filled perovskite compounds RPd{sub 3}B. Our results suggest that the magnetic and transport behavior of boron-filled compositions is substantially different compared to that of undoped compounds. For example, TbPd{sub 3} and ErPd{sub 3} exhibit negative magnetoresistance, while boron-filled TbPd{sub 3}B and ErPd{sub 3}B shows positive magnetoresistance. In addition, our results also suggest that there exists a strong correlation between magnetic and electrical-transport behavior of these systems.

  16. A Dynamic Supramolecular System Exhibiting Substrate Selectivity in the Catalytic Epoxidation of Olefins

    DEFF Research Database (Denmark)

    Jonsson, Stefan; Odille, Fabrice G. J.; Norrby, Per-Ola

    2005-01-01

    A dynamic supramolecular system involving hydrogen bonding between a Mn(III) salen catalyst and a Zn(II) porphyrin receptor exhibits selectivity for pyridine appended cis-beta-substituted styrene derivatives over phenyl appended derivatives in a catalytic epoxidation reaction.......A dynamic supramolecular system involving hydrogen bonding between a Mn(III) salen catalyst and a Zn(II) porphyrin receptor exhibits selectivity for pyridine appended cis-beta-substituted styrene derivatives over phenyl appended derivatives in a catalytic epoxidation reaction....

  17. Selective expression of the type 3 isoform of ryanodine receptor Ca2+ release channel (RyR3) in a subset of slow fibers in diaphragm and cephalic muscles of adult rabbits

    International Nuclear Information System (INIS)

    Conti, Antonio; Reggiani, Carlo; Sorrentino, Vincenzo

    2005-01-01

    The expression pattern of the RyR3 isoform of Ca 2+ release channels was analysed by Western blot in neonatal and adult rabbit skeletal muscles. The results obtained show that the expression of the RyR3 isoform is developmentally regulated. In fact, RyR3 expression was detected in all muscles analysed at 2 and 15 days after birth while, in adult animals, it was restricted to a subset of muscles that includes diaphragm, masseter, pterygoideus, digastricus, and tongue. Interestingly, all of these muscles share a common embryonic origin being derived from the somitomeres or from the cephalic region of the embryo. Immunofluorescence analysis of rabbit skeletal muscle cross-sections showed that RyR3 staining was detected in all fibers of neonatal muscles. In contrast, in those adult muscles expressing RyR3 only a fraction of fibers was labelled. Staining of these muscles with antibodies against fast and slow myosins revealed a close correlation between expression of RyR3 and fibers expressing slow myosin isoform

  18. miR-21-3p is a positive regulator of L1CAM in several human carcinomas.

    Science.gov (United States)

    Doberstein, Kai; Bretz, Niko P; Schirmer, Uwe; Fiegl, Heidi; Blaheta, Roman; Breunig, Christian; Müller-Holzner, Elisabeth; Reimer, Dan; Zeimet, Alain G; Altevogt, Peter

    2014-11-28

    Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, β-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Investigating the Role of the Post-transcriptional Gene Regulator MiR-24-3p in the Proliferation, Migration and Apoptosis of Human Arterial Smooth Muscle Cells in Arteriosclerosis Obliterans

    Directory of Open Access Journals (Sweden)

    Xiao-feng Zhu

    2015-07-01

    Full Text Available Aims: To explore the expression of miR-24-3p in human arteries with arteriosclerosis obliterans (ASO as well as the role of miR-24-3p in the pathogenesis of ASO. Methods: We used quantitative real-time PCR (qRT-PCR and in situ hybridization to monitor miR-24-3p expression in human arteries. To investigate the effect of miR-24-3p on human arterial smooth muscle cells (HASMCs, we applied cell counting and EdU assays to monitor proliferation and transwell and wound healing assays to investigate migration and flow cytometry to investigate apoptosis. Furthermore, we applied 3'-untranslated region (3'-UTR luciferase assays to investigate the role of miR-24-3p in targeting platelet-derived growth factor receptor B (PDGFRB and c-Myc. Results: MiR-24-3p was mainly located in the media of arteries and was downregulated in ASO arteries compared with normal arteries. Platelet-derived growth factor BB (PDGF-BB treatment reduced the expression of miR-24-3p in primary cultured HASMCs. MiR-24-3p mimic oligos inhibited the proliferation and migration, and promotes apoptosis of HASMCs. Our 3'-UTR luciferase assays confirmed that PDGFRB and c-Myc were targets of miR-24-3p. Conclusion: The results suggest that miR-24-3p regulates the proliferation and migration of HASMCs by targeting PDGFRB and c-Myc. The PDGF/miR-24-3p/PDGFRB and PDGF/miR-24-3p/c-Myc pathways may play critical roles in the pathogenesis of ASO. These findings highlight the potential for new therapeutic targets for ASO.

  20. HuR binding to AU-rich elements present in the 3' untranslated region of Classical swine fever virus

    Directory of Open Access Journals (Sweden)

    Huang Chin-Cheng

    2011-07-01

    Full Text Available Abstract Background Classical swine fever virus (CSFV is the member of the genus Pestivirus under the family Flaviviridae. The 5' untranslated region (UTR of CSFV contains the IRES, which is a highly structured element that recruits the translation machinery. The 3' UTR is usually the recognition site of the viral replicase to initiate minus-strand RNA synthesis. Adenosine-uridine rich elements (ARE are instability determinants present in the 3' UTR of short-lived mRNAs. However, the presence of AREs in the 3' UTR of CSFV conserved in all known strains has never been reported. This study inspects a possible role of the ARE in the 3' UTR of CSFV. Results Using RNA pull-down and LC/MS/MS assays, this study identified at least 32 possible host factors derived from the cytoplasmic extracts of PK-15 cells that bind to the CSFV 3' UTR, one of which is HuR. HuR is known to bind the AREs and protect the mRNA from degradation. Using recombinant GST-HuR, this study demonstrates that HuR binds to the ARE present in the 3' UTR of CSFV in vitro and that the binding ability is conserved in strains irrespective of virulence. Conclusions This study identified one of the CSFV 3' UTR binding proteins HuR is specifically binding to in the ARE region.

  1. miR-21 modulates tumor outgrowth induced by human adipose tissue-derived mesenchymal stem cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Keun Koo; Lee, Ae Lim; Kim, Jee Young [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Lee, Sun Young [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Bae, Yong Chan [Department of Plastic Surgery, School of Medicine, Pusan National University, Pusan 602-739 (Korea, Republic of); Jung, Jin Sup, E-mail: jsjung@pusan.ac.kr [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Institute, Pusan National University, Pusan 602-739 (Korea, Republic of)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer miR-21 modulates hADSC-induced increase of tumor growth. Black-Right-Pointing-Pointer The action is mostly mediated by the modulation of TGF-{beta} signaling. Black-Right-Pointing-Pointer Inhibition of miR-21 enhances the blood flow recovery in hindlimb ischemia. -- Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical situations, due principally to their potential use in regenerative medicine and tissue engineering applications. However, the therapeutic application of MSCs remains limited, unless the favorable effects of MSCs on tumor growth in vivo, and the long-term safety of the clinical applications of MSCs, can be more thoroughly understood. In this study, we determined whether microRNAs can modulate MSC-induced tumor outgrowth in BALB/c nude mice. Overexpression of miR-21 in human adipose-derived stem cells (hADSCs) inhibited hADSC-induced tumor growth, and inhibition of miR-21 increased it. Downregulation of transforming growth factor beta receptor II (TGFBR2), but not of signal transducer and activator of transcription 3, in hADSCs showed effects similar to those of miR-21 overexpression. Downregulation of TGFBR2 and overexpression of miR21 decreased tumor vascularity. Inhibition of miR-21 and the addition of TGF-{beta} increased the levels of vascular endothelial growth factor and interleukin-6 in hADSCs. Transplantation of miR-21 inhibitor-transfected hADSCs increased blood flow recovery in a hind limb ischemia model of nude mice, compared with transplantation of control oligo-transfected cells. These findings indicate that MSCs might favor tumor growth in vivo. Thus, it is necessary to study the long-term safety of this technique before MSCs can be used as therapeutic tools in regenerative medicine and tissue engineering.

  2. Synthesis and antifungal activity of nicotinamide derivatives as succinate dehydrogenase inhibitors.

    Science.gov (United States)

    Ye, Yong-Hao; Ma, Liang; Dai, Zhi-Cheng; Xiao, Yu; Zhang, Ying-Ying; Li, Dong-Dong; Wang, Jian-Xin; Zhu, Hai-Liang

    2014-05-07

    Thirty-eight nicotinamide derivatives were designed and synthesized as potential succinate dehydrogenase inhibitors (SDHI) and precisely characterized by (1)H NMR, ESI-MS, and elemental analysis. The compounds were evaluated against two phytopathogenic fungi, Rhizoctonia solani and Sclerotinia sclerotiorum, by mycelia growth inhibition assay in vitro. Most of the compounds displayed moderate activity, in which, 3a-17 exhibited the most potent antifungal activity against R. solani and S. sclerotiorum with IC50 values of 15.8 and 20.3 μM, respectively, comparable to those of the commonly used fungicides boscalid and carbendazim. The structure-activity relationship (SAR) of nicotinamide derivatives demonstrated that the meta-position of aniline was a key position contributing to the antifungal activity. Inhibition activities against two fungal SDHs were tested and achieved the same tendency with the data acquired from in vitro antifungal assay. Significantly, 3a-17 was demonstrated to successfully suppress disease development in S. sclerotiorum infected cole in vivo. In the molecular docking simulation, sulfur and chlorine of 3a-17 were bound with PHE291 and PRO150 of the SDH homology model, respectively, which could explain the probable mechanism of action between the inhibitory and target protein.

  3. On the relation between the modular double of Uq(sl(2,R)) and the quantum Teichmueller theory

    International Nuclear Information System (INIS)

    Nidaiev, Iurii; Teschner, Joerg

    2013-02-01

    We exhibit direct relations between the modular double of U q (sl(2,R)) and the quantum Teichmueller theory. Explicit representations for the fusion- and braiding operations of the quantum Teichmueller theory are immediate consequences. Our results include a simplified derivation of the Clebsch-Gordan decomposition for the principal series of representation of the modular double of U q (sl(2,R)).

  4. Synthesis, photochemical synthesis and antitumor evaluation of novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones.

    Science.gov (United States)

    DoganKoruznjak, Jasna; Slade, Neda; Zamola, Branimir; Pavelić, Kresimir; Karminski-Zamola, Grace

    2002-05-01

    The novel derivatives of thieno[3',2':4,5]thieno[2,3-c]quinolones 6a, 6b, 7, 10a and 10b were synthesized in multistep synthesis starting from thiophene-3-carboxaldehyde and malonic acid reacting in aldol condensation or from 3-bromothiophenes or methyl 4-bromothiophene-2-carboxylate reacting in Heck reaction. They resulted in corresponding substituted thienylacrylic acids 3a-c, which were cyclized into thieno[2,3-c]thiophene-2-carbonyl chlorides 4a-c and converted into thieno[2,3-c]thiophene-2-carboxamides 5a-d. Prepared carboxamides were photochemically dehydrohalogenated into corresponding substituted thieno[3',2':4,5]thieno[2,3-c]quinolones 6a-d. Compound 7 was prepared from 6d by alkylation with N-[3-(dimethylamino)propyl]chloride hydrochloride in the presence of NaH. Compounds 10a and 10b were prepared from 6c in the multistep synthesis over acid 8 and acid chloride 9. Compounds 6a, 6b, 7, 10a and 10b were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), and human fibroblast cell lines (WI-38). The compound 6b, which bears the 3-dimethylaminopropyl substituent on quinolone nitrogen and methoxycarbonyl substituent on position 9, exhibited marked antitumor activity. On the contrary, compound 7, which also bears the 3-dimethylaminopropyl substituent on the quinolone nitrogen but anilido substituent on position 9, exhibited less antitumor activity than the others.

  5. miR-342-3p suppresses hepatocellular carcinoma proliferation through inhibition of IGF-1R-mediated Warburg effect.

    Science.gov (United States)

    Liu, Wenpeng; Kang, Lei; Han, Juqiang; Wang, Yadong; Shen, Chuan; Yan, Zhifeng; Tai, Yanhong; Zhao, Caiyan

    2018-01-01

    Insulin-like growth factor-1 receptor (IGF-1R) is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC). Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-342-3p and IGF-1R. The effect of miR-342-3p on glycolysis was determined by glucose uptake, ATP concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. In vivo, subcutaneous tumor formation assay and PET were performed in nude mice. In this study, we demonstrate that by directly targeting the 3'-UTR (3'-untranslated regions) of IGF-1R, microRNA-342-3p (miR-342-3p) suppresses IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway both in vitro and in vivo. Through suppression of IGF-1R, miR-342-3p dampens glycolysis by decreasing glucose uptake, lactate generation, ATP production, and extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in hepatoma cells. Importantly, glycolysis regulated by miR-342-3p is critical for its regulating HCC growth both in vitro and in vivo. Our findings provide clues regarding the role of miR-342-3p as a tumor suppressor in liver cancer mainly through the inhibition of IGF-1R. Targeting IGF-1R by miR-342-3p could be a potential therapeutic strategy in liver cancer.

  6. A practical deca-gram scale ring expansion of (R)-(-)-carvone to (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1.

    Science.gov (United States)

    Alves, Leandro de C; Desiderá, André L; de Oliveira, Kleber T; Newton, Sean; Ley, Steven V; Brocksom, Timothy J

    2015-07-28

    A route to enantiopure (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1, an intermediate for terpenoids, has been developed and includes a highly chemo- and regioselective Tiffeneau-Demjanov reaction. Starting from readily available (R)-(-)-carvone, this robust sequence is available on a deca-gram scale and uses flow chemistry for the initial epoxidation reaction. The stereochemistry of the addition of two nucleophiles to the carbonyl group of (R)-(-)-carvone has been determined by X-ray diffraction studies and chemical correlation.

  7. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    Science.gov (United States)

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  8. p53 Represses the Oncogenic Sno-MiR-28 Derived from a SnoRNA.

    Directory of Open Access Journals (Sweden)

    Feng Yu

    Full Text Available p53 is a master tumour repressor that participates in vast regulatory networks, including feedback loops involving microRNAs (miRNAs that regulate p53 and that themselves are direct p53 transcriptional targets. We show here that a group of polycistronic miRNA-like non-coding RNAs derived from small nucleolar RNAs (sno-miRNAs are transcriptionally repressed by p53 through their host gene, SNHG1. The most abundant of these, sno-miR-28, directly targets the p53-stabilizing gene, TAF9B. Collectively, p53, SNHG1, sno-miR-28 and TAF9B form a regulatory loop which affects p53 stability and downstream p53-regulated pathways. In addition, SNHG1, SNORD28 and sno-miR-28 are all significantly upregulated in breast tumours and the overexpression of sno-miR-28 promotes breast epithelial cell proliferation. This research has broadened our knowledge of the crosstalk between small non-coding RNA pathways and roles of sno-miRNAs in p53 regulation.

  9. Washout of tritium from 3R-3(3H)-L-aspartate in the aspartase reaction

    International Nuclear Information System (INIS)

    Katz, B.M.; Cook, P.F.

    1987-01-01

    Bacterial aspartase catalyzes the reversible conversion of L-aspartate to fumarate and ammonia. Recent studies that made use of deuterium and 15 N isotope effects suggested a carbanion intermediate mechanism in which C-N bond cleavage is rate determining. This could result in removal of a proton from the 3R position of aspartate at a rate of faster than the elimination of ammonia. 3R-3( 3 H)-Aspartate was prepared enzymatically using aspartase from fumarate, ammonia and 3 H 2 O and aspartate isolated via chromatography on Dowex 50W x 8 at pH 1, eluting with 2N pyridine. The rate of 3 H washout from this aspartate was then measured as a function of aspartate concentration and compared to the rate of production of fumarate. Tritium does washout of aspartate at a rate faster than fumarate is formed but the proton is apparently not rapidly equilibrated with solvent. The tritium washout experiments were supplemented using 3R-3( 2 H)-aspartate prepared as above with 2 H 2 O replacing 3 H 2 O and monitoring the appearance of 3R-3( 1 H)-aspartate via 1 H-NMR. Results confirm the tritium washout results. Data are discussed in terms of the carbanion mechanism

  10. Synthesis and evaluation of 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivatives as potential anticonvulsants.

    Science.gov (United States)

    Madaiah, Malavalli; Prashanth, Maralekere K; Revanasiddappa, Hosakere D; Veeresh, Bantal

    2013-03-01

    New 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivatives 8-37 were synthesized and their pharmacological activities were determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. All the compounds were evaluated for their possible anticonvulsant activity by maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) test. Compounds 11, 18, 31, and 32 showed significant and protective effect on seizure, when compared with the standard drug valproate. The same compounds were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the reference drug. From this study, it is quite apparent that there are at least three parameters for the activity of anticonvulsant drugs, that is, a lipophilic domain, a hydrophobic center, and a two-electron donor. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Synthesis, physical and chemical properties, antihypoxic activity of some 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-4-R1-4H-1,2,4-t

    Directory of Open Access Journals (Sweden)

    V. M. Odyntsova

    2018-03-01

    compounds, among the investigated ones were weaker then comparison drug action, but they did not reduce the life expectancy of the investigated groups in comparison with control. The effect of the remaining compounds on the lifetime of the investigated group was at the level of control group that received the physiological solution. Conclusions. A series of new compounds of derivatives among 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazol-3-ylthiomethyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-(5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl-4-R1-4H-1,2,4-triazole-3-thiols have been synthesized, the structure of which has been confirmed with the help of modern physical and chemical methods of analysis. The most active compounds among the studied ones were 3a and 2a, their antihypoxic activity exceeds control on 37.86 % and 36.30 % and Mexidol is on 7.35 % and 5.79 % respectively.

  12. Characterization of Catalase from Psychrotolerant Psychrobacter piscatorii T-3 Exhibiting High Catalase Activity

    OpenAIRE

    Kimoto, Hideyuki; Yoshimune, Kazuaki; Matsuyma, Hidetoshi; Yumoto, Isao

    2012-01-01

    A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii), that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H2O2 as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein−1) that was higher than that of Micrococcus luteus used for industrial catalase production. Catalase was approximately 10% of the total proteins in the cell extract of the strain. The catalase (PktA) was purif...

  13. Synthesis, physical-chemical properties of 2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioacetohydrazides

    Directory of Open Access Journals (Sweden)

    O. A. Suhak

    2017-04-01

    Full Text Available Aim. Analysis of the scientific literature over the past decade has shown that large synthetic possibilities towards creating new and effective drug substances have heterocyclic compounds, in particular the derivatives of 1,2,4-triazole. 1,2,4-Triazole is a structural fragment of many synthetic drugs. The special interest cause ylidene hydrazides of 2-(5-R-1,2,4-triazole-3-ylthioacetic acids as potential biologically active compounds, among which highly effective medicines can be found. With the aim of finding new biologically active compounds the derivatives of 2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioaceticohydrazides have been synthesized, their physical-chemical properties have been studied with the use of modern methods, namely elemental analysis, IR,1H-NMR spectroscopy, and their individuality by HPLC-MS. Materials and methods. N'-R1-еden-2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioaceticohydrazides were received by adding aromatic (2-BrC6H4, 2,3-(OCH32C6H3, 3,5-(OCH32C6H3, 4-N(CH32C6H4, 3,4-F2C6H3, 2-NO2C6H4,4-NO2C6H4, 4-OHC6H4, 2-OHC6H4, 4-FC6H4, 2-CI-6-FC6H3 or heterocyclic (2-SC4H3, 5-NO2-2-C4H2O aldehyde to an equivalent amount of the appropriate 2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioaceticohydrazide in the acetic acid medium. The study of physical-chemical properties of obtained compounds was carried out according to the methods outlined in SPU. Chromato-mass-spectral studies were performed on hazarding chromatograph Agilent 1260 Infinity HPLC equipped with mass spectrometer Agilent 6120 with ionization in electro-spray (ESI. Conclusion. This suggests the possibility for further study of biological action of the synthesized compounds. As a result of studies the N'-R1-eden-2-((4-R-5-(thiophene-2-ylmethyl-4H-1,2,4-triazole-3-ylthioaceticohydrazides have been synthesized and their physical-chemical properties have been studied.

  14. Crystal structure of ({(1R,2R-N,N′-bis[(quinolin-2-ylmethyl]cyclohexane-1,2-diamine}chloridoiron(III-μ-oxido-[trichloridoferrate(III] chloroform monosolvate

    Directory of Open Access Journals (Sweden)

    Hannah Swift

    2017-07-01

    Full Text Available The first FeIII atom in the solvated title compound, [Fe2Cl4O(C26H28N4]·CHCl3, adopts a distorted six-coordinate octahedral geometry. It is coordinated by one chloride ligand, four N atoms from the (1R,2R-N,N′-bis[(quinolin-2-ylmethyl]cyclohexane-1,2-diamine ligand, and a bridging oxido ligand attached to the second FeIII atom, which is also bonded to three chloride ions. A very weak intramolecular N—H...Cl hydrogen bond occurs. In the crystal, the coordination complexes stack in columns, and a grouping of six such columns create channels, which are populated by disordered chloroform solvent molecules. Although the Fe—Cl bond lengths for the two metal atoms are comparable to the mean Fe—Cl bond lengths as derived from the Cambridge Structural Database, the Fe—O bond lengths are notably shorter. The solvent chloroform molecule exhibits `flip' disorder of the C—H moiety in a 0.544 (3:0.456 (3 ratio. The only directional interaction noted is a weak C—H...Cl hydrogen bond.

  15. Synthesis and crystal structures of 5'-phenylspiro[indoline-3, 2'-pyrrolidin]-2-one derivatives

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    Perumal Subbu

    2011-07-01

    Full Text Available Abstract Background The spiro- indole-pyrrolidine ring system is a frequently encountered structural motif in many biologically important and pharmacologically relevant alkaloids. The derivatives of spirooxindole ring systems are used as antimicrobial, antitumour agents and as inhibitors of the human NKI receptor besides being found in a number of alkaloids like horsifiline, spirotryprostatin and (+ elacomine. The recently discovered small-molecule MDM2 inhibitor MI-219 and its analogues are in advanced preclinical development as cancer therapeutics. Results In the crystal structures of the two organic compounds, 4'-Nitro-3',5'-diphenylspiro[indoline-3,2'-pyrrolidin]-2-one and 3'-(4-Methoxyphenyl- 4'-nitro -5'-phenylspiro[indoline-3,2'-pyrrolidin]-2-one, N-H···O hydrogen bonds make the R22 (8 ring motif. Further, the structures are stabilized by intermolecular hydrogen bonds. Conclusion The crystal structures of 4'-Nitro-3',5'-diphenylspiro[indoline-3,2'-pyrrolidin]-2-one and 3'-(4-Methoxyphenyl- 4'-nitro -5'-phenylspiro[indoline-3,2'-pyrrolidin]-2-one have been investigated in detail. In both the compounds, the R22(8 motif is present. Due to the substitution of methoxyphenyl instead of phenyl ring, the entire configuration is inverted with respect to the 2-oxyindole ring.

  16. miR-371, miR-138, miR-544, miR-145, and miR-214 could modulate Th1/Th2 balance in asthma through the combinatorial regulation of Runx3.

    Science.gov (United States)

    Qiu, Yu-Ying; Zhang, Ying-Wei; Qian, Xiu-Fen; Bian, Tao

    2017-01-01

    Asthma is tightly related to the imbalance of Th1/Th2 cells, and Runx3 plays a pivotal role in the differentiation of T helper cells. The present study aimed to investigate dysregulated microRNAs that may target Runx3 in CD4 + T cells from asthmatic patients and reveal Runx3 function in Th1/Th2 balance regulation. We detected the levels of Th1- and Th2-related cytokines by ELISA and analyzed the differentiation marker gene of T helper cells by qRT-PCR. Results indicated that an imbalance of Th1/Th2 cells was present in our asthmatic subject. Runx3 expression was reduced in the CD4 + T cells from asthmatic patients. Overexpression of Runx3 could restore the Th1/Th2 balance. After performing microRNA microarray assay, we found a series of microRNAs that were considerably altered in the CD4 + T cells from asthmatic patients. Among these upregulated microRNAs, eight microRNAs that may target Runx3 were selected by bioinformatics prediction. Five microRNAs, namely miR-371, miR-138, miR-544, miR-145, and miR-214, were confirmed by qRT-PCR and selected as candidate microRNAs. Luciferase reporter assay showed that these five microRNAs could directly target the 3'-UTR of Runx3. However, only simultaneous inhibition of these five microRNAs could alter the expression of Runx3. Most importantly, only simultaneous inhibition could improve the Th1/Th2 balance. Thus, we suggest that miR-371, miR-138, miR-544, miR-145, and miR-214 can modulate the Th1/Th2 balance in asthma by regulating Runx3 in a combinatorial manner.

  17. Pharmacokinetics and metabolism of (R,R)-methoxyfenoterol in rat.

    Science.gov (United States)

    Siluk, D; Mager, D E; Kim, H S; Wang, Y; Furimsky, A M; Ta, A; Iyer, L V; Green, C E; Wainer, I W

    2010-03-01

    (R,R)-fenoterol (Fen), a beta(2)-adrenoceptor agonist, is under clinical investigation in the treatment of congestive heart disease. The pharmacokinetics and metabolism of the 4-methoxyphenyl derivative of (R,R)-Fen, (R,R)-MFen, have been determined following intravenous and oral administration to the rat and compared with corresponding results obtained with (R,R)-Fen. Results from the study suggest that (R,R)-MFen can offer pharmacokinetic and metabolic advantages in comparison to an earlier (R,R)-Fen. The oral administration revealed that the net exposure of (R,R)-MFen was about three-fold higher than that of (R,R)-Fen (7.2 versus 2.3 min x nmol ml(-1)), while intravenous administration proved that the clearance was significantly reduced, 48 versus 146 ml min(-1) kg(-1), the T(1/2) was significantly longer, 152.9 versus 108.9 min, and the area under the curve (AUC) was significantly increased, 300 versus 119 min x nmol ml(-1). (R,R)-MFen was primarily cleared by glucuronidation associated with significant presystemic glucuronidation of the compound. After intravenous and oral administration of (R,R)-MFen, (R,R)-Fen and (R,R)-Fen-G were detected in the urine samples indicating that (R,R)-MFen was O-demethylated and subsequently conjugated to (R,R)-Fen-G. The total (R,R)-Fen and (R,R)-Fen-G as a percentage of the dose after intravenous administration was 3.6%, while after oral administration was 0.3%, indicating that only a small fraction of the drug escaped presystemic glucuronidation and was available for O-demethylation. The glucuronidation pattern was confirmed by the results from in vitro studies where incubation of (R,R)-MFen with rat hepatocytes produced (R,R)-MFen-G, (R,R)-Fen and (R,R)-Fen-G, while incubation with rat intestinal microsomes only resulted in the formation of (R,R)-MFen-G.

  18. Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives

    Directory of Open Access Journals (Sweden)

    Asunción Burguete

    2008-12-01

    Full Text Available A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E-3-(3,4,5-trimethoxy-phenyl-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.

  19. miR-342-3p suppresses hepatocellular carcinoma proliferation through inhibition of IGF-1R-mediated Warburg effect

    Directory of Open Access Journals (Sweden)

    Liu W

    2018-03-01

    Full Text Available Wenpeng Liu,1,* Lei Kang,2,* Juqiang Han,3 Yadong Wang,1 Chuan Shen,1 Zhifeng Yan,4 Yanhong Tai,5 Caiyan Zhao1 1Department of Infectious Diseases, Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China; 2Department of Nuclear Medicine, Peking University First Hospital, Beijing, China; 3Institute of Liver Disease, Beijing Military General Hospital, Beijing, China; 4Department of Gynecology and Obstetrics, PLA General Hospital, Beijing, China; 5Department of Pathology, Hospital of PLA, Beijing, China *These authors contributed equally to this work Background: Insulin-like growth factor-1 receptor (IGF-1R is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC. Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Materials and methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-342-3p and IGF-1R. The effect of miR-342-3p on glycolysis was determined by glucose uptake, ATP concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. In vivo, subcutaneous tumor formation assay and PET were performed in nude mice. Results: In this study, we demonstrate that by directly targeting the 3’-UTR (3’-untranslated regions of IGF-1R, microRNA-342-3p (miR-342-3p suppresses IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway both in vitro and in vivo. Through suppression of IGF-1R, miR-342-3p dampens glycolysis by decreasing glucose uptake, lactate generation

  20. Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R

    International Nuclear Information System (INIS)

    Atsmon, Jacob; Brill-Almon, Einat; Nadri-Shay, Carmit; Chertkoff, Raul; Alon, Sari; Shaikevich, Dimitri; Volokhov, Inna; Haim, Kirsten Y.; Bartfeld, Daniel; Shulman, Avidor; Ruderfer, Ilya; Ben-Moshe, Tehila; Shilovitzky, Orit; Soreq, Hermona; Shaaltiel, Yoseph

    2015-01-01

    PRX-105 is a plant-derived recombinant version of the human ‘read-through’ acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50 nmol/kg PRX-105, 2 min before being exposed to 1.33 × LD 50 and 1.5 × LD 50 of toxin and 10 min after exposure to 1.5 × LD 50 survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200 mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t ½ ) in mice was 994 (± 173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t ½ in humans was substantially longer than in mice (average 26.7 h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation. - Highlights: • PRX-105 is a PEGylated plant-derived recombinant human acetylcholinesterase-R. • PRX-105 is a promising bio-scavenger for organophosphorous toxins at lethal doses. • PRX-105 was shown to protect animals both prophylactically and post-poisoning. • First-in-human study exhibited its safety

  1. Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R

    Energy Technology Data Exchange (ETDEWEB)

    Atsmon, Jacob [Clinical Research Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University (Israel); Brill-Almon, Einat; Nadri-Shay, Carmit; Chertkoff, Raul; Alon, Sari [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Shaikevich, Dimitri; Volokhov, Inna; Haim, Kirsten Y. [Clinical Research Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University (Israel); Bartfeld, Daniel [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Shulman, Avidor, E-mail: avidors@protalix.com [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Ruderfer, Ilya; Ben-Moshe, Tehila; Shilovitzky, Orit [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Soreq, Hermona [Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem (Israel); Shaaltiel, Yoseph [Protalix Biotherapeutics, Science Park, Carmiel (Israel)

    2015-09-15

    PRX-105 is a plant-derived recombinant version of the human ‘read-through’ acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50 nmol/kg PRX-105, 2 min before being exposed to 1.33 × LD{sub 50} and 1.5 × LD{sub 50} of toxin and 10 min after exposure to 1.5 × LD{sub 50} survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200 mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t{sub ½}) in mice was 994 (± 173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t{sub ½} in humans was substantially longer than in mice (average 26.7 h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation. - Highlights: • PRX-105 is a PEGylated plant-derived recombinant human acetylcholinesterase-R. • PRX-105 is a promising bio-scavenger for organophosphorous toxins at lethal doses. • PRX-105 was shown to protect animals both prophylactically and post-poisoning. • First-in-human study

  2. Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

    Science.gov (United States)

    Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

    2017-08-02

    The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS

  3. (R,S-3-Carboxy-2-(isoquinolinium-2-ylpropanoate monohydrate

    Directory of Open Access Journals (Sweden)

    Vladimir Stilinović

    2010-06-01

    Full Text Available The title compound, C13H11NO4·H2O, is a monohydrate of a betaine exhibiting a positively charged N-substituted isoquinoline group and a deprotonated carboxyl group. In the crystal, molecules are connected via short O—H...O hydrogen bonds between protonated and deprotonated carboxyl groups into chains of either R or S enantiomers along [001]. These chains are additionally connected by hydrogen bonding between water molecules and the deprotonated carboxy groups of neighbouring molecules.

  4. Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine.

    Science.gov (United States)

    Shirayama, Yukihiko; Hashimoto, Kenji

    2018-01-01

    (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine's antidepressant actions. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  5. Synthesis and physical-chemical properties of 3-alkylthio-5-(quinoline-2-yl, 2-hydroxyquinoline-4-yl-4-R-2,4-dihydro-3H-1,2,4-triazoles

    Directory of Open Access Journals (Sweden)

    T. M. Kaplaushenko

    2016-06-01

    Full Text Available The major social and economic problem of pharmaceutical industry is the search for biologically active substances, which may become the basis of new drugs, competitive with expensive imported drugs. Analysis of literature shows that in recent decades the attention is paid to researches of heterocyclic systems as potential biologically active agents of both domestic and foreign scientists. Particular interest in this regard cause 3-thio derivatives of 1,2,4-triazoles. Despite high number of publications relating to synthesis and biological properties of 1,2,4-triazole derivatives, the structure and physical-chemical properties of these compounds are studied insufficiently. In this regard, the study of synthetic, physical-chemical and biological properties of 3-alkylthio-5-(quinoline-2-yl, 2-hydroxyquinoline-4-yl-4-R1-2,4-dihydro-3H-1,2,4-triazoles in our point of view is a new, theoretically and practically significant direction. Purpose - targeted synthesis of new low-toxic and highly effective compounds with potential pharmacological activity in a series of 3-alkylthio-5-(quinoline-2-yl, 2-hydroxyquinoline-4-yl-4-R-2,4-dihydro-3H-1,2,4-triazoles and the study of physical and chemical properties of the synthesized compounds. Materials and methods. As starting compounds 5-(quinoline-2-il- 2-hydroxyquinoline-4-yl-4-R1-3-thio-1,2,4-triazoles have been used. Through further cooperation with halogen alkanes (ethyl bromide, propyl bromide, amyl bromide, octyl bromide, nonyl bromide, decyl bromide, cyclohexyl chloride, benzyl chloride 3-alkylthio-5-(quinoline-2-yl, 2-hydroxyquinoline-4-yl-4-R1-2,4-dyhidro-3H-1,2,4-triazoles have been obtained. Results. 15 New compounds have been received as a result of synthetic transformations, the structure of synthesized compounds has been confirmed by modern complex of physical and chemical methods of analysis (IR-spectrophotometry, 1H NMR-spectroscopy, elemental analysis, and their individuality has been proved by

  6. Chemical Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with Substituted Amino Moiety

    Science.gov (United States)

    Shang, Ruofeng; Wang, Shengyu; Xu, Ximing; Yi, Yunpeng; Guo, Wenzhu; YuLiu; Liang, Jianping

    2013-01-01

    Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC) of 23S rRNA. PMID:24376551

  7. Chemical synthesis and biological activities of novel pleuromutilin derivatives with substituted amino moiety.

    Directory of Open Access Journals (Sweden)

    Ruofeng Shang

    Full Text Available Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC of 23S rRNA.

  8. Polystyrene-template-assisted synthesis of Li3VO4/C/rGO ternary composite with honeycomb-like structure for durable high-rate lithium ion battery anode materials

    International Nuclear Information System (INIS)

    Yang, Yang; Li, Jiaqi; Huang, Jingxin; Huang, Jianxing; Zeng, Jing; Zhao, Jinbao

    2017-01-01

    Highlights: •Li 3 VO 4 /C/rGO ternary composite with honeycomb-like structure is prepared by taking advantage of spray drying method and polystyrene (PS) soft template. •Li 3 VO 4 /C/rGO composite electrode possesses rapid Li + ions intercalation kinetics and good structure integrity. •Li 3 VO 4 /C/rGO composite exhibits outstanding high-rate performance and long cycle-life (the high reversible capacity of 312 mAh g −1 can be maintained after 1000 cycles at 10C). -- Abstract: Li 3 VO 4 /C/rGO (HC-LVO/C/G) ternary composite with honeycomb-like structure is successfully prepared through a simple spray drying method with polystyrene (PS) microspheres as soft template. In this characteristic structure, carbon-coated Li 3 VO 4 nanoparticles are well wrapped by rGO sheets and uniformly distributed within the honeycomb-like micrometer-sized clusters. The double coating layers of amorphous carbon and rGO can avoid the direct exposure of Li 3 VO 4 nanoparticles to the electrolyte and enhance the electronic conductivity. Meanwhile, the honeycomb-like structure can shorten the diffusion paths of Li + ions and favors the relaxation of the strain/stress during cycling. The resultant HC-LVO/C/G composite exhibits significantly improved high-rate performance and long cycle-life (the high reversible capacity of 312 mAh g −1 can be maintained after 1000 cycles at 10 C) compared with the contrastive Li 3 VO 4 /C composite synthesized by a typical solid-state reaction method.

  9. Flow condensation heat transfer coefficients of R22, R134a, R407C, and R410A inside plain and microfin tubes

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Dongsoo; Cho, Youngmok; Park, Kiho [Inha Univ., Incheon (Korea). Dept. of Mechanical Engineering

    2004-01-01

    Flow condensation heat transfer coefficients (HTCs) of R22, R134a, R407C, and R410A inside horizontal plain and microfin tubes of 9.52 mm outside diameter and 1 m length were measured at the condensation temperature of 40{sup o}C with mass fluxes of 100, 200, and 300 kg m{sup -2} s{sup -1} and a heat flux of 7.7-7.9 kW m{sup -2}. For a plain tube, HTCs of R134a and R410A were similar to those of R22 while HTCs of R407C are 11-15% lower than those of R22. For a microfin tube, HTCs of R134a were similar to those of R22 while HTCs of R407C and R410A were 23-53% and 10-21% lower than those of R22. For a plain tube, our correlation agreed well with the present data for all refrigerants exhibiting a mean deviation of 11.6%. Finally, HTCs of a microfin tube were 2-3 times higher than those of a plain tube and the heat transfer enhancement factor decreased as the mass flux increased for all refrigerants tested. (Author)

  10. Selective 3,4-Dihydroxyphenylalanine Analysis in Human Urine as Ethoxycarbonyltert- butyldimethylsilyl Derivatives by Gas Chromatography-Mass Spectrometry

    International Nuclear Information System (INIS)

    Paik, Man Jeong; Nguyen, Duc Toan; Cho, In Seon; Kim, Kyoung Rae; Cho, Ki Hong; Choi, Sang Dun; Lee, Gwang; Yoon, Jae Hwan; Shim, Woo Young

    2011-01-01

    A new analytical method for measurement of 3,4-dihydroxyphenylalanine (DOPA) in human urine was developed. DOPA from an aqueous solution was converted into an ethoxycarbonyl (EOC) derivative. A tertbutyldimethylsilyl (TBDMS) reaction under anhydrous conditions was then attempted for analysis by gas chromatography-mass spectrometry in selected ion monitoring mode. A new mass spectral data on DOPA as a tri-EOC/mono-TBDMS derivative was built. This method showed good linearity (r ≥ 0.999), precision (% relative standard deviation = 3.1-9.2), and accuracy (% relative error = .7.2-8.8), with a detection limit of 0.05 ng/mL. This selective and accurate method of DOPA analysis will be useful for biochemical monitoring of various neurological disorders including Parkinson's disease in biological fluids

  11. Microbial carbonylation and hydroxylation of 20(R)-panaxadiol by Aspergillus niger.

    Science.gov (United States)

    Yan, Bin; Chen, Zhihua; Zhai, Xuguang; Yin, Guibo; Ai, Yafei; Chen, Guangtong

    2018-04-01

    20(R)-panaxadiol (PD) was metabolised by the fungus Aspergillus niger AS 3.3926 to its C-3 carbonylated metabolite and five other hydroxylated metabolites (1-6). Their structures were elucidated as 3-oxo-20(R)-panaxadiol (1), 3-oxo-7β-hydroxyl- 20(R)-panaxadiol (2), 3-oxo-7β,23α-dihydroxyl-20(R)-panaxadiol (3), 3,12-dioxo- 7β,23β-dihydroxyl-20(R)-panaxadiol (4), 3-oxo-1α,7β-dihydroxyl-20(R)-panaxadiol (5) and 3-oxo-7β,15β-dihydroxyl-20(R)-panaxadiol (6) by spectroscopic analysis. Among them, compounds 2-6 were new compounds. Pharmacological studies revealed that compound 6 exhibited significant anti-hepatic fibrosis activity.

  12. Why bacteria derived R-M nucleic enzymatic peptides are likely ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-06-17

    Jun 17, 2008 ... (3) Human genome contains several palindromes recognizable by R-M peptides, making ..... mutation and likely has affected genome evolution. .... Microbicide to prevent sexual transmission of HIV among high risk.

  13. A Novel TetR Family Transcriptional Regulator, CalR3, Negatively Controls Calcimycin Biosynthesis in Streptomyces chartreusis NRRL 3882

    Directory of Open Access Journals (Sweden)

    Lixia Gou

    2017-11-01

    Full Text Available Calcimycin is a unique ionophoric antibiotic that is widely used in biochemical and pharmaceutical applications, but the genetic basis underlying the regulatory mechanisms of calcimycin biosynthesis are unclear. Here, we identified the calR3 gene, which encodes a novel TetR family transcriptional regulator and exerts a negative effect on calcimycin biosynthesis. Disruption of calR3 in Streptomyces chartreusis NRRL 3882 led to significantly increased calcimycin and its intermediate cezomycin. Gene expression analysis showed that the transcription of calR3 and its adjacent calT gene were dramatically enhanced (30- and 171-fold, respectively in GLX26 (ΔcalR3 mutants compared with the wild-type strains. Two CalR3-binding sites within the bidirectional calR3-calT promoter region were identified using a DNase I footprinting assay, indicating that CalR3 directly repressed the transcription of its own gene and the calT gene. In vitro electrophoretic mobility shift assays suggested that both calcimycin and cezomycin can act as CalR3 ligands to induce CalR3 to dissociate from its binding sites. These findings indicate negative feedback for the regulation of CalR3 in calcimycin biosynthesis and suggest that calcimycin production can be improved by manipulating its biosynthetic machinery.

  14. Ultraviolet radiation-induced mutability of uvrD3 strains of Escherichia coli B/r and K-12: a problem in analyzing mutagenesis data

    International Nuclear Information System (INIS)

    Smith, K.C.

    1976-01-01

    The involvement of the uvrD gene product in UV-induced mutagenesis in Escherichia coli was studied by comparing wild-type and uvrA or uvrB strains with their uvrD derivatives in B/r and K-12(W3110) backgrounds. Mutations per survivor (reversions to prototrophy) were compared as a function of surviving fraction and of UV fluence. While recognizing that both methods are not without problems, arguments are presented for favoring the former rather than the latter method of presenting the data when survival is less than 100%. When UV-induced mutation frequencies were plotted as a function of surviving fraction, the uvrD derivatives were less mutable than the corresponding parent strains. The B/r strains exhibited higher mutation frequencies than did the K-12(W3110) strains. A uvrB mutation increased the mutation frequency of its parental K-12 strain, but a uvrA mutation only increased the mutation frequency of its parental B/r strain at UV survivals greater than approximately 80%. Both the uvrA and uvrB mutations increased the mutation frequencies of the uvrD strains in the B/r and K-12 backgrounds, respectively. Rather different conclusions would be drawn if mutagenesis were considered as a function of UV fluence rather than of survival, a situation that calls for further work and discussion. Ideally mutation efficiencies should be compared as a function of the number of repair events per survivor, a number that is currently unobtainable. (author)

  15. Effect of tempe waste on excreation of purine derivatives and microbial–N supply in lactating Etawah crossbred goats

    Directory of Open Access Journals (Sweden)

    D.A Astuti

    2002-10-01

    Full Text Available The aim of this study was to evaluate excretion of purine derivatives and microbial–N supply in lactating Etawah crossbred goats fed with fermented soybean waste. Sixteen first lactating goats were randomly allotted into four dietary treatment groups that received 50% king grass plus R1: 50% concentrate, R2: 25% concentrate and 25% fresh tempe waste, R3: 25% concentrate and 25% fermented tempe waste, and R4: 25% concentrate and 25% gelatinizing of liquid tempe waste. Fermented tempe waste was made by fermentation of tempe waste (seed content of soybean using Aspergillus niger, while for the gellatinizing of liquid tempe waste was made by gelatinized with maize flour. Protein balance studies were conducted during two week trial and at the end of the research. Urinary protein and purine derivatives were collected for analysis. Microbial–N supply was calculated from purine derivatives excretion. Results showed that nitrogen consumptions were significantly different between R4 and three other treatments and apparent digestible nitrogen in R3 were higher than that of R4 (P<0.05. The nitrogen retention in R1 and R3 were higher than that of R2 and R4. Urinary purine derivatives in this study showed that allantoin, xanthine and hypoxanthine in R3 were higher than that of R4, while R1 and R2 were the same and the highest uric acid excretion and total purine derivatives were observed in R3. Microbial–N supply were significantly different between all treatments where R3 was the highest. This research concluded that fermented soybean waste had the highest total purine derivatives excretion and microbial–N supply to the lactating Etawah crossbred goats.

  16. Tyms double (2R) and triple repeat (3R) confers risk for human oral squamous cell carcinoma.

    Science.gov (United States)

    Bezerra, Alexandre Medeiros; Sant'Ana, Thalita Araújo; Gomes, Adriana Vieira; de Lacerda Vidal, Aurora Karla; Muniz, Maria Tereza Cartaxo

    2014-12-01

    The oral cancer is responsible for approximately 3 % of cases of cancer in Brazil. Epidemiological studies have associated low folate intake with an increased risk of epithelial cancers, including oral cancer. Folic acid has a key role in DNA synthesis, repair, methylation and this is the basis of explanations for a putative role for folic acid in cancer prevention. The role of folic acid in carcinogenesis may be modulated by polymorphism C677T in MTHFR and tandem repeats 2R/3R in the promoter site of TYMS gene that are related to decreased enzymatic activity and quantity and availability of the enzyme, respectively. These events cause a decrease in the synthesis, repair and DNA methylation, which can lead to a disruption in the expression of tumor suppressor genes as TP53. The objective of this study was investigate the distribution of polymorphisms C677T and tandem repeats 2R/3R associated with the development of oral squamous cell carcinoma (OSCC). 53 paraffin-embedded samples from patients who underwent surgery but are no longer at the institution and 43 samples collected by method of oral exfoliation by cytobrush were selected. 132 healthy subjects were selected by specialists at the dental clinics of the Faculdade de Odontologia de Pernambuco-FOP. The MTHFR genotyping was performed by PCR-RFLP, and the TYMS genotyping was performed by conventional PCR. Fisher's Exact test at significant level of 5 %. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to measure the strength of association between genotype frequency and OSCC development. The results were statistically significant for the tandem repeats of the TYMS gene (p = 0.015). The TYMS 2R3R genotype was significantly associated with the development of OSCC (OR = 3.582; 95 % CI 1.240-10.348; p = 0.0262) and also the genotype 3R3R (OR = 3.553; 95 % CI 1.293-9.760; p = 0.0345). When analyzed together, the TYMS 2R3R + 3R3R genotypes also showed association (OR = 3.518; 95 % CI 11.188-10.348; p

  17. Effects of Pseudomonas putida WCS358r and its genetically modified phenazine producing derivative on the Fusarium population in a field experiment, as determined by 18S rDNA analysis

    NARCIS (Netherlands)

    Leeflang, P.; Smit, E.; Glandorf, D.C.M.; Van Hannen, E.J.; Wernars, K.

    2002-01-01

    We measured effects of Pseudomonas putida WCS358r and its genetically modified phenazine producing derivative on the Fusarium population in the soil of a wheat field in the Netherlands. We used 18S rDNA analysis to study the Fusarium population through a strategy based on screening clone libraries

  18. MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells

    International Nuclear Information System (INIS)

    Wang, Zhigang; Zhang, Xiaoping; Yang, Zhili; Du, Hangxiang; Wu, Zhenqian; Gong, Jianfeng; Yan, Jun; Zheng, Qi

    2012-01-01

    Highlights: ► MiR-145 targets a putative binding site in the 3′UTR of PAK4. ► MiR-145 played an important role in inhibiting cell growth by directly targeting PAK4. ► MiR-145 may function as tumor suppressors. -- Abstract: MicroRNAs (miRNAs) are regulators of numerous cellular events; accumulating evidence indicates that miRNAs play a key role in a wide range of biological functions, such as cellular proliferation, differentiation, and apoptosis in cancer. Down-regulated expression of miR-145 has been reported in colon cancer tissues and cell lines. The molecular mechanisms underlying miR-145 and the regulation of colon carcinogenesis remain unclear. In this study, we investigated the levels of miR-145 in human colon cancer cells using qRT-PCR and found markedly decreased levels compared to normal epithelial cells. We identified PAK4 as a novel target of miR-145 using informatics screening. Additionally, we demonstrated that miR-145 targets a putative binding site in the 3′UTR of PAK4 and that its abundance is inversely associated with miR-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. Furthermore, restoration of miR-145 by mimics in SW620 cells significantly attenuated cell growth in vitro, in accordance with the inhibitory effects induced by siRNA mediated knockdown of PAK4. Taken together, these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.

  19. 46 CFR Exhibit No. 3 to Subpart E... - Petition for Leave To Intervene

    Science.gov (United States)

    2010-10-01

    ... PROVISIONS RULES OF PRACTICE AND PROCEDURE Proceedings; Pleadings; Motions; Replies Pt. 502, Subpt. E, Exh. 3...., as in Exhibit No. 1 to this subpart, and nature and principal place of business]. II. [Here set out...

  20. Growth hormone secretagogue receptor (GHS-R1a) knockout mice exhibit improved spatial memory and deficits in contextual memory.

    Science.gov (United States)

    Albarran-Zeckler, Rosie G; Brantley, Alicia Faruzzi; Smith, Roy G

    2012-06-15

    Although the hormone ghrelin is best known for its stimulatory effect on appetite and regulation of growth hormone release, it is also reported to have beneficial effects on learning and memory formation in mice. Nevertheless, controversy exists about whether endogenous ghrelin acts on its receptors in extra-hypothalamic areas of the brain. The ghrelin receptor (GHS-R1a) is co-expressed in neurons that express dopamine receptor type-1 (DRD1a) and type-2 (DRD2), and we have shown that a subset of GHS-R1a, which are not occupied by the agonist (apo-GHSR1a), heterodimerize with these two receptors to regulate dopamine signaling in vitro and in vivo. To determine the consequences of ghsr ablation on brain function, congenic ghsr -/- mice on the C57BL6/J background were subjected to a battery of behavioral tests. We show that the ghsr -/- mice exhibit normal balance, movement, coordination, and pain sensation, outperform ghsr +/+ mice in the Morris water maze, but show deficits in contextual fear conditioning. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Functional Characterization of MC1R-TUBB3 Intergenic Splice Variants of the Human Melanocortin 1 Receptor.

    Directory of Open Access Journals (Sweden)

    Cecilia Herraiz

    Full Text Available The melanocortin 1 receptor gene (MC1R expressed in melanocytes is a major determinant of skin pigmentation. It encodes a Gs protein-coupled receptor activated by α-melanocyte stimulating hormone (αMSH. Human MC1R has an inefficient poly(A site allowing intergenic splicing with its downstream neighbour Tubulin-β-III (TUBB3. Intergenic splicing produces two MC1R isoforms, designated Iso1 and Iso2, bearing the complete seven transmembrane helices from MC1R fused to TUBB3-derived C-terminal extensions, in-frame for Iso1 and out-of-frame for Iso2. It has been reported that exposure to ultraviolet radiation (UVR might promote an isoform switch from canonical MC1R (MC1R-001 to the MC1R-TUBB3 chimeras, which might lead to novel phenotypes required for tanning. We expressed the Flag epitope-tagged intergenic isoforms in heterologous HEK293T cells and human melanoma cells, for functional characterization. Iso1 was expressed with the expected size. Iso2 yielded a doublet of Mr significantly lower than predicted, and impaired intracellular stability. Although Iso1- and Iso2 bound radiolabelled agonist with the same affinity as MC1R-001, their plasma membrane expression was strongly reduced. Decreased surface expression mostly resulted from aberrant forward trafficking, rather than high rates of endocytosis. Functional coupling of both isoforms to cAMP was lower than wild-type, but ERK activation upon binding of αMSH was unimpaired, suggesting imbalanced signaling from the splice variants. Heterodimerization of differentially labelled MC1R-001 with the splicing isoforms analyzed by co-immunoprecipitation was efficient and caused decreased surface expression of binding sites. Thus, UVR-induced MC1R isoforms might contribute to fine-tune the tanning response by modulating MC1R-001 availability and functional parameters.

  2. Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex-different manner.

    Science.gov (United States)

    Liu, Peng; Xing, Bo; Chu, Zheng; Liu, Fei; Lei, Gang; Zhu, Li; Gao, Ya; Chen, Teng; Dang, Yong-Hui

    2017-07-01

    Pain is a complex and subjective experience. Previous studies have shown that mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a role of the D3 receptor in modulation of nociception. Given that there are sex differences in pain perception, there may be differences in responses to nociceptive stimuli between male and female D3RKO mice. In the current study, we examined the role of the D3 receptor in modulating nociception in male and female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was performed at different temperatures including 52°C, 55°C, and 58°C. The von Frey hair test was applied to evaluate mechanical pain. And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice generally exhibited longer latencies at each of the three temperatures. Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the temperature was 55°C, while for the female mice, there was a statistical difference between genotypes when the test condition was 52°C. In the von Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the formalin test, the male D3RKO mice displayed a similar nociceptive behavior as their sex-matched WT littermates, whereas significantly depressed late-phase formalin-induced nociceptive behaviors were observed in the female mutants. These findings indicated that the D3 receptor affects nociceptive behaviors in a sex-specific manner and that its absence induces more analgesic behavior in the female knockout mice. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. The Hamburg/ESO R-process Enhanced Star survey (HERES). XI. The highly r-process-enhanced star CS 29497-004

    Science.gov (United States)

    Hill, V.; Christlieb, N.; Beers, T. C.; Barklem, P. S.; Kratz, K.-L.; Nordström, B.; Pfeiffer, B.; Farouqi, K.

    2017-11-01

    We report an abundance analysis for the highly r-process-enhanced (r-II) star CS 29497-004, a very metal-poor giant with solar system Teff = 5013 K and [Fe/H] = -2.85, whose nature was initially discovered in the course of the HERES project. Our analysis is based on high signal-to-noise ratio, high-resolution (R 75 000) VLT/UVES spectra and MARCS model atmospheres under the assumption of local thermodynamic equilibrium, and obtains abundance measurements for a total of 46 elements, 31 of which are neutron-capture elements. As is the case for the other 25 r-II stars currently known, the heavy-element abundance pattern of CS 29497-004 well-matches a scaled solar system second peak r-process-element abundance pattern. We confirm our previous detection of Th, and demonstrate that this star does not exhibit an "actinide boost". Uranium is also detected (log ɛ(U) = -2.20 ± 0.30), albeit with a large measurement error that hampers its use as a precision cosmo-chronometer. Combining the various elemental chronometer pairs that are available for this star, we derive a mean age of 12.2 ± 3.7 Gyr using the theoretical production ratios from published waiting-point approximation models. We further explore the high-entropy wind model (Farouqi et al. 2010, ApJ, 712, 1359) production ratios arising from different neutron richness of the ejecta (Ye), and derive an age of 13.7 ± 4.4 Gyr for a best-fitting Ye = 0.447. The U/Th nuclei-chronometer is confirmed to be the most resilient to theoretical production ratios and yields an age of 16.5 ± 6.6 Gyr. Lead (Pb) is also tentatively detected in CS 29497-004, at a level compatible with a scaled solar r-process, or with the theoretical expectations for a pure r-process in this star. Based on observations collected at the European Southern Observatory, Paranal, Chile (Proposal Number 170.D-0010).Table B.1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http

  4. Crystal structure of 2-[(3aS,6R-3,3,6-trimethyl-3,3a,4,5,6,7-hexahydro-2H-indazol-2-yl]thiazol-4(5H-one

    Directory of Open Access Journals (Sweden)

    Abdellah N'ait Ousidi

    2016-03-01

    Full Text Available The title compound, C13H19N3OS, is a new thiazolidin-4-one derivative prepared and isolated as the pure (3aS,6R-diastereisomer from (R-thiosemicarbazone pulegone. It crystallized with two independent molecules (A and B in the asymmetric unit. The compound is composed of a hexhydroindazole ring system (viz. a five-membered dihydropyrazole ring fused to a cyclohexyl ring with a thiazole-4-one ring system attached to one of the pyrazole N atoms (at position 2. The overall geometry of the two molecules differs slightly, with the mean planes of the pyrazole and thiazole rings being inclined to one another by 10.4 (1° in molecule A and 0.9 (1° in molecule B. In the crystal, the A and B molecules are linked via C—H...O hydrogen bonds, forming slabs parallel to the ab plane. There are C—H...π interactions present within the layers, and between the layers, so forming a three-dimensional structure.

  5. Two-Dimensional Raman Correlation Spectroscopy Study of Poly[(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] Copolymers.

    Science.gov (United States)

    Noda, Isao; Roy, Anjan; Carriere, James; Sobieski, Brian J; Chase, D Bruce; Rabolt, John F

    2017-07-01

    Two-dimensional correlation analysis was applied to the time-dependent evolution of Raman spectra during the isothermal crystallization of bioplastic, poly[(R)-3-hydroxybutyrate- co-(R)-3-hydroxyhexanoate] or PHBHx copolymer. Simultaneous Raman measurement of both carbonyl stretching and low-frequency crystalline lattice mode regions made it possible to carry out the highly informative hetero-mode correlation analysis. The crystallization process of PHBHx involves: (1) the early nucleation stage; (2) the primary growth of well-ordered crystals of PHBHx; and (3) the secondary crystal growth phase. The latter stage probably occurs in the inter-lamellar region, with an accompanying reduction of the amorphous component, which occurs most dominantly during the primary crystal growth. The development of a fully formed lamellar structure comprising the 2 1 helices occurs after the primary growth of crystals. In the later stage, secondary inter lamellar space crystallization occurs after the full formation of packed helices comprising the lamellae.

  6. miR-409-3p sensitizes colon cancer cells to oxaliplatin by inhibiting Beclin-1-mediated autophagy.

    Science.gov (United States)

    Tan, Shifan; Shi, Huijuan; Ba, Mingchen; Lin, Shengqv; Tang, Hongsheng; Zeng, Xiaoqi; Zhang, Xiangliang

    2016-04-01

    The chemoresistance of colon cancer cells limits the efficacy of chemotherapy. miR-409-3p has been shown to be downregulated in various types of cancer. In the present study, we examined the role of miR-409-3p in colon cancer as well as the effects of miR‑409-3p on the sensitivity of colon cancer cells to oxaliplatin. The expression of miR-409 was significantly downregulated in the human colon cancer cell lines compared with the normal colon epithelial cells. Importantly, the miR-409-3p expression levels were lower in human colon cancer patient samples than in normal colon tissues. Moreover, we observed a negative correlation between the miR‑409-3p levels and resistance to oxaliplatin: the oxaliplatin-resistant colon cancer cells exhibited significantly downregulated miR‑409-3p levels, but higher autophagic activity than the oxaliplatin-sensitive cells. Using bioinformatics analysis, we predicted that miR‑409-3p miRNA binds to the key autophagy gene encoding Beclin-1. Our findings indicated that the overexpression of miR‑409-3p inhibited Beclin-1 expression and autophagic activity by binding to the 3'-untranslated region of Beclin-1 mRNA. In addition, the overexpression of miR‑409-3p enhanced the chemosensitivity of the oxaliplatin-sensitive and oxaliplatin-resistant colon cancer cells. The restoration of Beclin-1 abrogated these effects of miR‑409-3p. In a xenograft model using nude mice, we examined the effects of miR‑409-3p on tumor growth during chemotherapy. miR‑409-3p overexpression sensitized the tumor to chemotherapy, while inhibiting chemotherapy-induced autophagy in a manner dependent on Beclin-1. The findings of our study suggest that miR-409-3p is capable of enhancing the chemosensitivity of colon cancer cells by inhibiting Beclin-1-mediated autophagy.

  7. A single-repeat R3-MYB transcription factor MYBC1 negatively regulates freezing tolerance in Arabidopsis

    International Nuclear Information System (INIS)

    Zhai, Hong; Bai, Xi; Zhu, Yanming; Li, Yong; Cai, Hua; Ji, Wei; Ji, Zuojun; Liu, Xiaofei; Liu, Xin; Li, Jing

    2010-01-01

    We had previously identified the MYBC1 gene, which encodes a single-repeat R3-MYB protein, as a putative osmotic responding gene; however, no R3-MYB transcription factor has been reported to regulate osmotic stress tolerance. Thus, we sought to elucidate the function of MYBC1 in response to osmotic stresses. Real-time RT-PCR analysis indicated that MYBC1 expression responded to cold, dehydration, salinity and exogenous ABA at the transcript level. mybc1 mutants exhibited an increased tolerance to freezing stress, whereas 35S::MYBC1 transgenic plants exhibited decreased cold tolerance. Transcript levels of some cold-responsive genes, including CBF/DREB genes, KIN1, ADC1, ADC2 and ZAT12, though, were not altered in the mybc1 mutants or the 35S::MYBC1 transgenic plants in response to cold stress, as compared to the wild type. Microarray analysis results that are publically available were investigated and found transcript level of MYBC1 was not altered by overexpression of CBF1, CBF2, and CBF3, suggesting that MYBC1 is not down regulated by these CBF family members. Together, these results suggested that MYBC1is capable of negatively regulating the freezing tolerance of Arabidopsis in the CBF-independent pathway. In transgenic Arabidopsis carrying an MYBC1 promoter driven β-glucuronidase (GUS) construct, GUS activity was observed in all tissues and was relatively stronger in the vascular tissues. Fused MYBC1 and GFP protein revealed that MYBC1 was localized exclusively in the nuclear compartment.

  8. New effective coupled F({sup (4)}R, φ) modified gravity from f({sup (5)}R) gravity in five dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Madriz Aguilar, Jose Edgar [Centro Universitario de Ciencias Exactas e ingenierias (CUCEI), Universidad de Guadalajara (UdG), Departamento de Matematicas, Guadalajara, Jalisco (Mexico)

    2015-12-15

    Using some ideas of the Wesson induced matter theory, we obtain a new kind of F({sup (4)}R, φ) modified gravity theory as an effective four-dimensional (4D) theory derived from f({sup (5)}R) gravity in five dimensions (5D). This new theory exhibits a different matter coupling than the one in BBHL theory. We show that the field equations of the Wesson induced matter theory and of some brane-world scenarios can be obtained as maximally symmetric solutions of the same f({sup (5)}R) theory. We found criteria for the Dolgov-Kawasaki instabilities for both the f({sup (5)}R) and the F({sup (4)}R, φ) theories. We demonstrate that under certain conditions imposed on the 5D geometry it is possible to interpret the F({sup (4)}R, φ) theory as a modified gravity theory with dynamical coefficients, making this new theory a viable candidate to address the present accelerating cosmic expansion issue. Matter sources in the F({sup (4)}R, φ) case appear induced by the 5D geometry without the necessity of the introduction of matter sources in 5D. (orig.)

  9. Autocrine Effects of Tumor-Derived Complement

    Directory of Open Access Journals (Sweden)

    Min Soon Cho

    2014-03-01

    Full Text Available We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

  10. Bone marrow cellularity in normal and polycythemic mice estimated by DNA incorporation of /sup 3/H-TdR

    Energy Technology Data Exchange (ETDEWEB)

    Blackwell, L.H.; Ledney, G.D.

    1982-07-01

    Nucleated bone marrow cell numbers in normal and polycythemic mice were determined using /sup 3/H-thymidine (/sup 3/H-TdR). The cellularities were estimated by extrapolating the exponential disappearance of labeled cells after a single injection of /sup 3/H-TdR to the time of injection. Dermestid beetles (Anthrenus piceus) were used to prepare tissue-free skeletons labeled with /sup 3/H-TdR. The correlation between tritium activity in bone marrow DNA and tritium derived from the combusted skeleton was determined. The total skeletal cellularity determined by isotope dilution analysis in both normal and polycythemic mice was 2.6 x 10(8) cells/mouse or 17.6 x 10(9) cells/kg body weight. Although the red cell component of the marrow was reduced in the polycythemic mouse, the total numbers of nucleated cells in both types of animals were similar. The differential distribution of cells in the polycythemic animal showed a twofold increase in granulocytic cells, which may explain the identical nucleated cell count in normal and in polycythemic mice.

  11. Establishment of a Novel Permissive Cell Line for the Propagation of Hepatitis C Virus by Expression of MicroRNA miR122

    Science.gov (United States)

    Kambara, Hiroto; Fukuhara, Takasuke; Shiokawa, Mai; Ono, Chikako; Ohara, Yuri; Kamitani, Wataru

    2012-01-01

    The robust cell culture systems for hepatitis C virus (HCV) are limited to those using cell culture-adapted clones (HCV in cell culture [HCVcc]) and cells derived from the human hepatoma cell line Huh7. However, accumulating data suggest that host factors, including innate immunity and gene polymorphisms, contribute to the variation in host response to HCV infection. Therefore, the existing in vitro systems for HCV propagation are not sufficient to elucidate the life cycle of HCV. A liver-specific microRNA, miR122, has been shown to participate in the efficient replication of HCV. In this study, we examined the possibility of establishing a new permissive cell line for HCV propagation by the expression of miR122. A high level of miR122 was expressed by a lentiviral vector placed into human liver cell lines at a level comparable to the endogenous level in Huh7 cells. Among the cell lines that we examined, Hep3B cells stably expressing miR122 (Hep3B/miR122) exhibited a significant enhancement of HCVcc propagation. Surprisingly, the levels of production of infectious particles in Hep3B/miR122 cells upon infection with HCVcc were comparable to those in Huh7 cells. Furthermore, a line of “cured” cells, established by elimination of HCV RNA from the Hep3B/miR122 replicon cells, exhibited an enhanced expression of miR122 and a continuous increase of infectious titers of HCVcc in every passage. The establishment of the new permissive cell line for HCVcc will have significant implications not only for basic HCV research but also for the development of new therapeutics. PMID:22114337

  12. Novel Eicosapentaenoic Acid-derived F3-isoprostanes as Biomarkers of Lipid Peroxidation*

    Science.gov (United States)

    Song, Wen-Liang; Paschos, Georgios; Fries, Susanne; Reilly, Muredach P.; Yu, Ying; Rokach, Joshua; Chang, Chih-Tsung; Patel, Pranav; Lawson, John A.; FitzGerald, Garret A.

    2009-01-01

    Isoprostanes (iPs) are prostaglandin (PG) isomers generated by free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs). Urinary F2-iPs, PGF2α isomers derived from arachidonic acid (AA) are used as indices of lipid peroxidation in vivo. We now report the characterization of two major F3-iPs, 5-epi-8,12-iso-iPF3α-VI and 8,12-iso-iPF3α-VI, derived from the ω-3 fatty acid, eicosapentaenoic acid (EPA). Although the potential therapeutic benefits of EPA receive much attention, a shift toward a diet rich in ω-3 PUFAs may also predispose to enhanced lipid peroxidation. Urinary 5-epi-8,12-iso-iPF3α-VI and 8,12-iso-iPF3α-VI are highly correlated and unaltered by cyclooxygenase inhibition in humans. Fish oil dose-dependently elevates urinary F3-iPs in mice and a shift in dietary ω-3/ω-6 PUFAs is reflected by an increasing slope [m] of the line relating urinary 8, 12-iso-iPF3α-VI and 8,12-iso-iPF2α-VI. Administration of bacterial lipopolysaccharide evokes a reversible increase in both urinary 8,12-iso-iPF3α-VI and 8,12-iso-iPF2α-VI in humans on an ad lib diet. However, while excretion of the iPs is highly correlated (R2 median = 0.8), [m] varies by an order of magnitude, reflecting marked inter-individual variability in the relative peroxidation of ω-3 versus ω-6 substrates. Clustered analysis of F2- and F3-iPs refines assessment of the oxidant stress response to an inflammatory stimulus in vivo by integrating variability in dietary intake of ω-3/ω-6 PUFAs. PMID:19520854

  13. Digoxin derivatives with selectivity for the α2β3 isoform of Na,K-ATPase potently reduce intraocular pressure.

    Science.gov (United States)

    Katz, Adriana; Tal, Daniel M; Heller, Dan; Habeck, Michael; Ben Zeev, Efrat; Rabah, Bilal; Bar Kana, Yaniv; Marcovich, Arie L; Karlish, Steven J D

    2015-11-03

    The ciliary epithelium in the eye consists of pigmented epithelial cells that express the α1β1 isoform of Na,K-ATPase and nonpigmented epithelial cells that express mainly the α2β3 isoform. In principle, a Na,K-ATPase inhibitor with selectivity for α2β3 that penetrates the cornea could effectively reduce intraocular pressure, with minimal systemic or local toxicity. We have recently synthesized perhydro-1,4-oxazepine derivatives of digoxin by NaIO4 oxidation of the third digitoxose and reductive amination with various R-NH2 substituents and identified derivatives with significant selectivity for human α2β1 over α1β1 (up to 7.5-fold). When applied topically, the most α2-selective derivatives effectively prevented or reversed pharmacologically raised intraocular pressure in rabbits. A recent structure of Na,K-ATPase, with bound digoxin, shows the third digitoxose approaching one residue in the β1 subunit, Gln84, suggesting a role for β in digoxin binding. Gln84 in β1 is replaced by Val88 in β3. Assuming that alkyl substituents might interact with β3Val88, we synthesized perhydro-1,4-oxazepine derivatives of digoxin with diverse alkyl substituents. The methylcyclopropyl and cyclobutyl derivatives are strongly selective for α2β3 over α1β1 (22-33-fold respectively), as determined either with purified human isoform proteins or intact bovine nonpigmented epithelium cells. When applied topically on rabbit eyes, these derivatives potently reduce both pharmacologically raised and basal intraocular pressure. The cyclobutyl derivative is more efficient than Latanoprost, the most widely used glaucoma drug. Thus, the conclusion is that α2β3-selective digoxin derivatives effectively penetrate the cornea and inhibit the Na,K-ATPase, hence reducing aqueous humor production. The new digoxin derivatives may have potential for glaucoma drug therapy.

  14. Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

    Directory of Open Access Journals (Sweden)

    Qin X

    2017-05-01

    Full Text Available Xiaobing Qin,1,2,* Shaorong Yu,1,3,* Leilei Zhou,1,4 Meiqi Shi,3 Yong Hu,1 Xiaoyue Xu,1 Bo Shen,1 Siwen Liu,1 Dali Yan,1 Jifeng Feng1,3 1Research Center for Clinical Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 2Department of Oncology, Xuzhou First People’s Hospital, Xuzhou, 3Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 4Department of Oncology, Affiliated Huai’an Hospital of Nanjing Medical University, Huai’an, Jiangsu, China *These authors have contributed equally to this work Abstract: Exosomes derived from lung cancer cells confer cisplatin (DDP resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP was established. Microarray was used to analyze microRNA (miRNA expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p

  15. QSAR Studies on Andrographolide Derivatives as α-Glucosidase Inhibitors

    Directory of Open Access Journals (Sweden)

    Shaohui Cai

    2010-03-01

    Full Text Available Andrographolide derivatives were shown to inhibit α-glucosidase. To investigate the relationship between activities and structures of andrographolide derivatives, a training set was chosen from 25 andrographolide derivatives by the principal component analysis (PCA method, and a quantitative structure-activity relationship (QSAR was established by 2D and 3D QSAR methods. The cross-validation r2 (0.731 and standard error (0.225 illustrated that the 2D-QSAR model was able to identify the important molecular fragments and the cross-validation r2 (0.794 and standard error (0.127 demonstrated that the 3D-QSAR model was capable of exploring the spatial distribution of important fragments. The obtained results suggested that proposed combination of 2D and 3D QSAR models could be useful in predicting the α-glucosidase inhibiting activity of andrographolide derivatives.

  16. MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhigang [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China); Zhang, Xiaoping [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine (China); Yang, Zhili; Du, Hangxiang; Wu, Zhenqian; Gong, Jianfeng; Yan, Jun [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China); Zheng, Qi, E-mail: zhengqi1957@yahoo.com.cn [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer MiR-145 targets a putative binding site in the 3 Prime UTR of PAK4. Black-Right-Pointing-Pointer MiR-145 played an important role in inhibiting cell growth by directly targeting PAK4. Black-Right-Pointing-Pointer MiR-145 may function as tumor suppressors. -- Abstract: MicroRNAs (miRNAs) are regulators of numerous cellular events; accumulating evidence indicates that miRNAs play a key role in a wide range of biological functions, such as cellular proliferation, differentiation, and apoptosis in cancer. Down-regulated expression of miR-145 has been reported in colon cancer tissues and cell lines. The molecular mechanisms underlying miR-145 and the regulation of colon carcinogenesis remain unclear. In this study, we investigated the levels of miR-145 in human colon cancer cells using qRT-PCR and found markedly decreased levels compared to normal epithelial cells. We identified PAK4 as a novel target of miR-145 using informatics screening. Additionally, we demonstrated that miR-145 targets a putative binding site in the 3 Prime UTR of PAK4 and that its abundance is inversely associated with miR-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. Furthermore, restoration of miR-145 by mimics in SW620 cells significantly attenuated cell growth in vitro, in accordance with the inhibitory effects induced by siRNA mediated knockdown of PAK4. Taken together, these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.

  17. Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based liposome

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2016-10-01

    Full Text Available Yun-Chun Zhao,1 Li Zhang,2 Shi-Sen Feng,3 Lu Hong,3 Hai-Li Zheng,3 Li-Li Chen,4 Xiao-Ling Zheng,1 Yi-Qing Ye,1 Meng-Dan Zhao,1 Wen-Xi Wang,3 Cai-Hong Zheng1 1Pharmacy Department, Women’s Hospital, 2Pharmacy Department, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Pharmaceutic Preparation, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 4Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Abstract: A novel cationic cholesterol derivative-based small interfering RNA (siRNA interference strategy was suggested to inhibit Notch1 activation in SKOV3 cells for the gene therapy of ovarian cancer. The cationic cholesterol derivative, N-(cholesterylhemisuccinoyl-amino-3-propyl-N, N-dimethylamine (DMAPA-chems liposome, was incubated with siRNA at different nitrogen-to-phosphate ratios to form stabilized, near-spherical siRNA/DMAPA-chems nanoparticles with sizes of 100–200 nm and zeta potentials of 40–50 mV. The siRNA/DMAPA-chems nanoparticles protected siRNA from nuclease degradation in 25% fetal bovine serum. The nanoparticles exhibited high cell uptake and Notch1 gene knockdown efficiency in SKOV3 cells at an nitrogen-to-phosphate ratio of 100 and an siRNA concentration of 50 nM. They also inhibited the growth and promoted the apoptosis of SKOV3 cells. These results may provide the potential for using cationic cholesterol derivatives as efficient nonviral siRNA carriers for the suppression of Notch1 activation in ovarian cancer cells. Keywords: siRNA, cationic cholesterol derivative, Notch1, ovarian cancer cells

  18. High performance Li2MnO3/rGO composite cathode for lithium ion batteries

    Science.gov (United States)

    Zhao, Wei; Xiong, Lilong; Xu, Youlong; Li, Houli; Ren, Zaihuang

    2017-05-01

    The novel composite Li2MnO3 (LMO)/reduced graphene oxide (rGO) has been synthesized successfully. Based on the scanning electron microscopy and transmission electron microscopy, LMO is found to distribute separately on the rGO sheets by forming a laminated structure, which is in favor of good electrical contact between the cathode active materials and the rGO matrix, and also facilitates the separation of LMO secondary particles with reduced size. Cyclic voltammetry and electrochemical impedance spectroscopy tests show that the charge transfer resistance decreases from 81.2 Ω for LMO to 29.6 Ω for LMO/rGO composite. The Li-ion diffusion coefficient of LMO/rGO composite is almost triple that of LMO. As a result, the LMO/rGO composite delivers an initial discharge capacity of 284.9 mAh g-1 with a capacity retention of 86.6% after 45 cycles at 0.1 C between 2.0 and 4.6 V. Cycle performance is even better at a higher current density 0.2 C while the retention ratio is up to 97.1% after 45 cycles. The rate capability is also significantly enhanced, and the LMO/rGO composite could exhibit a large discharge capacity of 123.7 mAh g-1 which is more than three times larger than that of LMO (40.8 mAh g-1) at a high rate of 8 C.

  19. In vitro and in vivo cytotoxic activity of human lactoferricin derived antitumor peptide R-DIM-P-LF11-334 on human malignant melanoma.

    Science.gov (United States)

    Riedl, Sabrina; Rinner, Beate; Schaider, Helmut; Liegl-Atzwanger, Bernadette; Meditz, Katharina; Preishuber-Pflügl, Julia; Grissenberger, Sarah; Lohner, Karl; Zweytick, Dagmar

    2017-09-22

    Di-peptides derived from the human host defense peptide lactoferricin were previously described to specifically interact with the negatively charged lipid phosphatidylserine exposed by cancer cells. In this study one further derivative, namely R-DIM-P-LF11-334 is shown to exhibit even increased cancer toxicity in vitro and in vivo while non-neoplastic cells are not harmed. In liposomal model systems composed of phosphatidylserine mimicking cancerous and phosphatidylcholine mimicking non-cancerous membranes the specific interaction with the cancer marker PS was confirmed by specific induction of membrane perturbation and permeabilization in presence of the peptide. In vitro studies with cell lines of human malignant melanoma, such as A375, or primary cells of human melanoma metastases to the brain, as MUG Mel1, and non-neoplastic human dermal fibroblasts NHDF revealed high cytotoxic effect of R-DIM-P-LF11-334 on melanoma cells of A375 and MUG Mel1, whereas only minor effect on the dermal fibroblasts NHDF was observed, yielding an about 20-fold killing-specificity for A375 and MUG-Mel1. The LC 50 values for melanoma A375 and MUG Mel1 were about 10 μM. Analysis of secondary structure of the peptide revealed an increase in the proportion of β-sheets exclusively in presence of the cancer mimic. Stability studies further indicated a potential adequate stability in blood or under stringent conditions. Importantly the cytotoxic effect on cancer cells was also proven in vivo in mouse xenografts of human melanoma, where peptide treatment induced strong tumor regression and in average a tumor area reduction of 85% compared to tumors of control mice without peptide treatment.

  20. Gender-dependent expression of leading and passenger strand of miR-21 and miR-16 in human colorectal cancer and adjacent colonic tissues.

    Science.gov (United States)

    Hasáková, K; Bezakova, J; Vician, M; Reis, R; Zeman, M; Herichova, I

    2017-12-30

    miRNAs are small regulatory RNA molecules involved in posttranscriptional gene silencing. Their biosynthesis results in the formation of duplex consisting of a leading and a passenger strand of mature miRNA. The leading strand exhibits the main activity but recent findings indicate a certain role of the passenger strand as well. Deregulated levels of miRNA were found in many types of cancers including colorectal cancer. miR-21 and miR-16 were indicated as possible markers of colorectal cancer, however, small attention to gender differences in their expression was paid so far. Therefore, the aim of our study was to investigate the expression of miR-21-5p, miR-21-3p, miR-16-5p and miR-16-3p in human colorectal cancer tissue and compare it to the adjacent tissues taken during surgery in men and women separately. Our results showed an up-regulation of all measured miRNAs in tumor tissue compared to adjacent tissues. As expected, tumors and adjacent tissues exhibited a significantly higher expression of leading miRNAs compared to passenger strand of miR-21 and miR-16. The expression of leading and passenger strand of miR-21 and miR-16 positively correlated exhibiting the highest correlation coefficient in the distal tissue. The expression pattern showed gender-dependent differences, with higher levels of miRNA in men than in women. Our findings indicate a gender-related expression pattern of miRNA, which should be considered as an important factor in generating new prognostic or diagnostic biomarkers.

  1. The presentation of energy topics at exhibitions

    International Nuclear Information System (INIS)

    Moergeli, H.P.

    1984-01-01

    The author examines the problems confronting an electricity supply company when trying to communicate its energy policy to the general public at exhibitions and fairs. The company has to convey a message of reliable power supplies, increasing demand, the advantages of nuclear energy, the safe storage of radioactive waste and the need for new generating plants. The author describes some of the displays being used to attract the public to the Bern Power Stations stand at the Bern Exhibition 1984. (R.S.)

  2. C3a Enhances the Formation of Intestinal Organoids through C3aR1

    Directory of Open Access Journals (Sweden)

    Naoya Matsumoto

    2017-09-01

    Full Text Available C3a is important in the regulation of the immune response as well as in the development of organ inflammation and injury. Furthermore, C3a contributes to liver regeneration but its role in intestinal stem cell function has not been studied. We hypothesized that C3a is important for intestinal repair and regeneration. Intestinal organoid formation, a measure of stem cell capacity, was significantly limited in C3-deficient and C3a receptor (C3aR 1-deficient mice while C3a promoted the growth of organoids from normal mice by supporting Wnt-signaling but not from C3aR1-deficient mice. Similarly, the presence of C3a in media enhanced the expression of the intestinal stem cell marker leucine-rich repeat G-protein-coupled receptor 5 (Lgr5 and of the cell proliferation marker Ki67 in organoids formed from C3-deficient but not from C3aR1-deficient mice. Using Lgr5.egfp mice we showed significant expression of C3 in Lgr5+ intestinal stem cells whereas C3aR1 was expressed on the surface of various intestinal cells. C3 and C3aR1 expression was induced in intestinal crypts in response to ischemia/reperfusion injury. Finally, C3aR1-deficient mice displayed ischemia/reperfusion injury comparable to control mice. These data suggest that C3a through interaction with C3aR1 enhances stem cell expansion and organoid formation and as such may have a role in intestinal regeneration.

  3. Studies on Synthesis of Some Novel Heterocyclic Azlactone Derivatives and Imidazolinone Derivatives and their Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Rakesh N. Mistry

    2005-01-01

    Full Text Available p - Methyl benzoic acid on reaction with phosphorus pentachloride gives p - methyl benzoyl chloride derivative which on condensation with glycine gives p - methyl benzoyl glycine derivative. Now, this p - methyl benzoyl glycine derivative on condensation with various substituted aldehydes gives corresponding substituted 4 - [aryl methylidine] - 2 - [p - methyl phenyl] - oxazole - 5 - one derivatives [1(a-j]. Further, these derivatives [1(a-j] on condensation with 4 , 4’ - diamino diphenyl sulphone gives corresponding substituted imidazolinone - dibenzsulphone derivatives [2(a-j], on condensation with 4 , 4’ - diamino diphenyl methane gives corresponding substituted imidazolinone - dibenzmethane derivatives [3(a-j], on condensation with 4,4’- diamino benzanilide gives corresponding substituted imidazolinone - benzanilide derivatives [4(a-j] and on condensation with 2 - amino pyridine gives corresponding substituted imidazolinone - pyridine derivatives [5(a-j] respectively. Structure elucidation of synthesised compounds has been made on the basis of elemental analysis, I.R. spectral studies and 1H N.M.R. spectral studies. The antimicrobial activity of the synthesised compounds has been studied against the cultures “Staphylococcus aureus”, “Escherichia coli” and “Candela albicans”.

  4. Synthesis, structure and luminescence properties of zinc (II) complexes with terpyridine derivatives as ligands

    International Nuclear Information System (INIS)

    Chen Xuegang; Zhou Quanguo; Cheng Yanxiang; Geng Yanhou; Ma Dongge; Xie Zhiyuan; Wang Lixiang

    2007-01-01

    Five zinc (II) complexes (1-5) with 4'-phenyl-2,2':6',2''-terpyridine (ptpy) derivatives as ligands have been synthesized and fully characterized. The para-position of phenyl in ptpy is substituted by the group (R), i.e. tert-butyl (t-Bu), hexyloxy (OHex), carbazole-9-yl (Cz), naphthalen-1-yl-phenyl-amine-N-yl (NPA) and diphenyl amine-N-yl (DPA), with different electron-donating ability. With increasing donor ability of the R, the emission color of the complexes in film was modulated from violet (392 nm) to reddish orange (604 nm). The photoexcited luminescence exhibits significant solvatochromism because the emission of the complexes involves the intra-ligand charge transfer (ILCT) excited state. The electrochemical investigations show that the complexes with stronger electro-donating substituent have lower oxidation potential and then higher HOMO level. The electroluminescence (EL) properties of these zinc (II) complexes were studied with the device structure of ITO/PEDOT/Zn (II) complex: PBD:PMMA/BCP/AlQ/LiF/Al. Complexes 3, 4 and 5 exhibit EL wavelength at 552, 600 and 609 nm with maximum current efficiency of 5.28, 2.83 and 2.00 cd/A, respectively

  5. Chloroform-Methanol Residue of Coxiella burnetii Markedly Potentiated the Specific Immunoprotection Elicited by a Recombinant Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B of Rickettsia rickettsii in C3H/HeN Mice.

    Directory of Open Access Journals (Sweden)

    Wenping Gong

    Full Text Available The obligate intracellular bacteria, Rickettsia rickettsii and Coxiella burnetii, are the potential agents of bio-warfare/bio-terrorism. Here C3H/HeN mice were immunized with a recombinant protein fragment rOmp-4 derived from outer membrane protein B, a major protective antigen of R. rickettsii, combined with chloroform-methanol residue (CMR extracted from phase I C. burnetii organisms, a safer Q fever vaccine. These immunized mice had significantly higher levels of IgG1 and IgG2a to rOmpB-4 and interferon-γ (IFN-γ and tumor necrosis factor-α (TNF-α, two crucial cytokines in resisting intracellular bacterial infection, as well as significantly lower rickettsial loads and slighter pathological lesions in organs after challenge with R. rickettsii, compared with mice immunized with rOmpB-4 or CMR alone. Additionally, after challenge with C. burnetii, the coxiella loads in the organs of these mice were significantly lower than those of mice immunized with rOmpB-4 alone. Our results prove that CMR could markedly potentiate enhance the rOmpB-4-specific immunoprotection by promoting specific and non-specific immunoresponses and the immunization with the protective antigen of R. rickettsii combined with CMR of C. burnetii could confer effective protection against infection of R. rickettsii or C. burnetii.

  6. THE STUDY OF HYPOGLYCEMIC ACTIVITY OF 3-BENZYL-8-METHYLXANTHINE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    I. М. Bilay

    2015-04-01

    Full Text Available Diabetes mellitus is a chronic endocrine disease. It etiology is the impact of both endogenous (genetic and exogenous factors that cause absolute or relative shortage of insulin or not effective use of it, which in turn leads to disruption of all kinds of substances exchange. The study of this problem is actual due to the high prevalence of diabetes, chronic disease, the tendency to increase the number of patients, their high morbidity and mortality. Diabetes is characterized by high blood glucose levels, which eventually leads to various complications associated with many human systems damage. Hormones (insulin and its analogues and synthetic drugs (sulfonylureas, biguanides etc. are used For the treatment of diabetes, but their high toxicity, cumulativeness, various side effects (autoimmunization, cutaneous allergic reactions, disturbance of the micro flora of the digestive tract, and the formation of insulin resistance restrict the use of these drugs in clinical practice. On this aspect the attention of researchers is attracted to xanthine derivatives, which are known as substances with wide range of biological activities including hypoglycemic. Based on the above, the search and development of new drugs among new 3-R-substituted xanthine, which would have hypoglycemic effect and would be deprived of most side effects is an acute problem of modern medical and pharmaceutical sciences. The aim of this study was to investigate the hypoglycemic activity of newly synthesized derivatives of 3-benzyl-8-methylxanthine and establish certain patterns "structure-activity" relationship. Materials and methods As objects of study for hypoglycemic activity we used derivatives of 3-benzyl-8-methylxanthine synthesized at the Department of Biochemistry and LaboratoryDiagnostics ofZaporizhzhyaStateMedicalUniversity. Hypoglycemic action of xanthine derivatives evaluated by intraperitoneal glucose tolerance test, which was reproduced by injection to animals

  7. Neuroprotective properties of cannabigerol in Huntington's disease: studies in R6/2 mice and 3-nitropropionate-lesioned mice.

    Science.gov (United States)

    Valdeolivas, Sara; Navarrete, Carmen; Cantarero, Irene; Bellido, María L; Muñoz, Eduardo; Sagredo, Onintza

    2015-01-01

    Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and peroxisome proliferator-activated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBG-treated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.

  8. Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptor.

    Science.gov (United States)

    Jozwiak, Krzysztof; Targowska-Duda, Katarzyna M; Kaczor, Agnieszka A; Kozak, Joanna; Ligeza, Agnieszka; Szacon, Elzbieta; Wrobel, Tomasz M; Budzynska, Barbara; Biala, Grazyna; Fornal, Emilia; Poso, Antti; Wainer, Irving W; Matosiuk, Dariusz

    2014-12-15

    9 N-alkylated derivatives of dextromethorphan are synthesized and studied as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptors (nAChRs). In vitro activity towards α3β4 nicotinic acetylcholine receptor is determined using a patch-clamp technique and is in the micromolar range. Homology modeling, molecular docking and molecular dynamics of ligand-receptor complexes in POPC membrane are used to find the mode of interactions of N-alkylated dextromethorphan derivatives with α3β4 nAChR. The compounds, similarly as dextromethorphan, interact with the middle portion of α3β4 nAChR ion channel. Finally, behavioral tests confirmed potential application of the studied compounds for the treatment of addiction. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. 6-Hydroxyflavone and derivatives exhibit potent anti-inflammatory activity among mono-, di- and polyhydroxylated flavones in kidney mesangial cells.

    Directory of Open Access Journals (Sweden)

    Xing Wang

    Full Text Available Inflammatory responses by kidney mesangial cells play a critical role in the glomerulonephritis. The anti-inflammatory potential of nineteen mono-, di- and polyhydroxylated flavones including fisetin, quercetin, morin, tricetin, gossypetin, apigenin and myricetin were investigated on rat mesangial cells with lipopolysaccharide (LPS as the inflammatory stimuli. 6-Hydroxyflavone and 4',6-dihydroxyflavone exhibited high activity with IC50 in the range of 2.0 μM, a much better inhibition potential in comparison to the well-studied polyhydroxylated flavones. Interestingly, the anti-inflammatory activity was not due to direct quenching of NO radicals. Investigation on derivatives with methylation, acetylation or sulfation of 6-hydroxyl group revealed that 6-methoxyflavone was the most potent with an IC50 of 192 nM. Mechanistic study indicated that the anti-inflammatory activity of 6-methoxyflavone arose via the inhibition of LPS-induced downstream inducible NO synthase in mesangial cells. The identification of 6-hydroxyflavone and 6-methoxyflavone with potent anti-inflammatory activity in kidney mesangial cells provides a new flavone scaffold and direction to develop naturally derived products for potential nephritis prevention and treatment.

  10. Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

    Science.gov (United States)

    Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

    2009-06-01

    In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

  11. The Psychometric Assessment of Children with Learning Disabilities: An Index Derived from a Principal Components Analysis of the WISC-R.

    Science.gov (United States)

    Lawson, J. S.; Inglis, James

    1984-01-01

    A learning disability index (LDI) for the assessment of intellectual deficits on the Wechsler Intelligence Scale for Children-Revised (WISC-R) is described. The Factor II score coefficients derived from an unrotated principal components analysis of the WISC-R normative data, in combination with the individual's scaled scores, are used for this…

  12. Group 13 β-ketoiminate compounds: gallium hydride derivatives as molecular precursors to thin films of Ga2O3.

    Science.gov (United States)

    Pugh, David; Marchand, Peter; Parkin, Ivan P; Carmalt, Claire J

    2012-06-04

    Bis(β-ketoimine) ligands, [R{N(H)C(Me)-CHC(Me)═O}(2)] (L(1)H(2), R = (CH(2))(2); L(2)H(2), R = (CH(2))(3)), linked by ethylene (L(1)) and propylene (L(2)) bridges have been used to form aluminum, gallium, and indium chloride complexes [Al(L(1))Cl] (3), [Ga(L(n))Cl] (4, n = 1; 6, n = 2) and [In(L(n))Cl] (5, n = 1; 7, n = 2). Ligand L(1) has also been used to form a gallium hydride derivative [Ga(L(1))H] (8), but indium analogues could not be made. β-ketoimine ligands, [Me(2)N(CH(2))(3)N(H)C(R')-CHC(R')═O] (L(3)H, R' = Me; L(4)H, R' = Ph), with a donor-functionalized Lewis base have also been synthesized and used to form gallium and indium alkyl complexes, [Ga(L(3))Me(2)] (9) and [In(L(3))Me(2)] (10), which were isolated as oils. The related gallium hydride complexes, [Ga(L(n))H(2)] (11, n = 3; 12, n = 4), were also prepared, but again no indium hydride species could be made. The complexes were characterized mainly by NMR spectroscopy, mass spectrometry, and single crystal X-ray diffraction. The β-ketoiminate gallium hydride compounds (8 and 11) have been used as single-source precursors for the deposition of Ga(2)O(3) by aerosol-assisted (AA)CVD with toluene as the solvent. The quality of the films varied according to the precursor used, with the complex [Ga(L(1))H] (8) giving by far the best quality films. Although the films were amorphous as deposited, they could be annealed at 1000 °C to form crystalline Ga(2)O(3). The films were analyzed by powder XRD, SEM, and EDX.

  13. R-Stable Embedded DIRKN Method of Orders 4(3) for Solving ...

    African Journals Online (AJOL)

    The motivation for this work comes from the fact that not much work seems to have been done on the embedded implicit RKN methods compared to the explicit case. In the present consideration, we derive coefficients of the method with minimized truncation error coefficients and show that it is R-stable.

  14. Crystal structure of 2-amino-4-methyl-pyridin-1-ium (2R,3R)-3-carb-oxy-2,3-di-hydroxy-propano-ate monohydrate.

    Science.gov (United States)

    Jovita, J V; Sathya, S; Usha, G; Vasanthi, R; Ramanand, A

    2014-09-01

    The title mol-ecular salt, C6H9N2 (+)·C4H5O6 (-)·H2O, crystallized with two 2-amino-4-methyl-pyridin-1-ium cations, two l-(+)-tartaric acid monoanions [systematic name: (2R,3R)-3-carb-oxy-2,3-di-hydroxy-propano-ate] and two water mol-ecules in the asymmetric unit. In the crystal, the cations, anions and water mol-ecules are linked via a number of O-H⋯O and N-H⋯O hydrogen bonds, and a C-H⋯O hydrogen bond, forming a three-dimensional structure.

  15. Gorenstein derived functions

    DEFF Research Database (Denmark)

    Holm, Henrik Granau

    2004-01-01

    Over any associative ring R it is standard to derive HomR(􀀀;􀀀) using projective resolutions in the rst variable, or injective resolutions in the second variable, and doing this, one obtains Extn R(􀀀;􀀀) in both cases. We examine the situation where projective...... and injective modules are replaced by Gorenstein projective and Gorenstein injective ones, respectively. Furthermore, we derive the tensor product 􀀀 R 􀀀 using Gorenstein at modules....

  16. A R2R3-MYB transcription factor from Epimedium sagittatum regulates the flavonoid biosynthetic pathway.

    Directory of Open Access Journals (Sweden)

    Wenjun Huang

    Full Text Available Herba epimedii (Epimedium, a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Many R2R3-MYB transcription factors (TFs have been identified to regulate the flavonoid and anthocyanin biosynthetic pathways. However, little is known about the R2R3-MYB TFs involved in regulation of the flavonoid pathway in Epimedium. Here, we reported the isolation and functional characterization of the first R2R3-MYB TF (EsMYBA1 from Epimedium sagittatum (Sieb. Et Zucc. Maxim. Conserved domains and phylogenetic analysis showed that EsMYBA1 belonged to the subgroup 6 clade (anthocyanin-related MYB clade of R2R3-MYB family, which includes Arabidopsis AtPAP1, apple MdMYB10 and legume MtLAP1. EsMYBA1 was preferentially expressed in leaves, especially in red leaves that contain higher content of anthocyanin. Alternative splicing of EsMYBA1 resulted in three transcripts and two of them encoded a MYB-related protein. Yeast two-hybrid and transient luciferase expression assay showed that EsMYBA1 can interact with several bHLH regulators of the flavonoid pathway and activate the promoters of dihydroflavonol 4-reductase (DFR and anthocyanidin synthase (ANS. In both transgenic tobacco and Arabidopsis, overexpression of EsMYBA1 induced strong anthocyanin accumulation in reproductive and/or vegetative tissues via up-regulation of the main flavonoid-related genes. Furthermore, transient expression of EsMYBA1 in E. sagittatum leaves by Agrobacterium infiltration also induced anthocyanin accumulation in the wounded area. This first functional characterization of R2R3-MYB TFs in Epimedium species will promote further studies of the flavonoid biosynthesis and regulation in medicinal plants.

  17. A R2R3-MYB transcription factor from Epimedium sagittatum regulates the flavonoid biosynthetic pathway.

    Science.gov (United States)

    Huang, Wenjun; Sun, Wei; Lv, Haiyan; Luo, Ming; Zeng, Shaohua; Pattanaik, Sitakanta; Yuan, Ling; Wang, Ying

    2013-01-01

    Herba epimedii (Epimedium), a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Many R2R3-MYB transcription factors (TFs) have been identified to regulate the flavonoid and anthocyanin biosynthetic pathways. However, little is known about the R2R3-MYB TFs involved in regulation of the flavonoid pathway in Epimedium. Here, we reported the isolation and functional characterization of the first R2R3-MYB TF (EsMYBA1) from Epimedium sagittatum (Sieb. Et Zucc.) Maxim. Conserved domains and phylogenetic analysis showed that EsMYBA1 belonged to the subgroup 6 clade (anthocyanin-related MYB clade) of R2R3-MYB family, which includes Arabidopsis AtPAP1, apple MdMYB10 and legume MtLAP1. EsMYBA1 was preferentially expressed in leaves, especially in red leaves that contain higher content of anthocyanin. Alternative splicing of EsMYBA1 resulted in three transcripts and two of them encoded a MYB-related protein. Yeast two-hybrid and transient luciferase expression assay showed that EsMYBA1 can interact with several bHLH regulators of the flavonoid pathway and activate the promoters of dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS). In both transgenic tobacco and Arabidopsis, overexpression of EsMYBA1 induced strong anthocyanin accumulation in reproductive and/or vegetative tissues via up-regulation of the main flavonoid-related genes. Furthermore, transient expression of EsMYBA1 in E. sagittatum leaves by Agrobacterium infiltration also induced anthocyanin accumulation in the wounded area. This first functional characterization of R2R3-MYB TFs in Epimedium species will promote further studies of the flavonoid biosynthesis and regulation in medicinal plants.

  18. Synthesis and Anti-Inflammatory Activity of New Alkyl-Substituted Phthalimide 1H-1,2,3-Triazole Derivatives

    Directory of Open Access Journals (Sweden)

    Shalom Pôrto de Oliveira Assis

    2012-01-01

    Full Text Available Four new 1,2,3-triazole phthalimide derivatives with a potent anti-inflammatory activity have been synthesized in the good yields by the 1,3-dipolar cycloaddition reaction from N-(azido-alkylphthalimides and terminal alkynes. The anti-inflammatory activity was determined by injecting carrageenan through the plantar tissue of the right hind paw of Swiss white mice to produce inflammation. All the compounds 3a–c and 5a–c exhibited an important anti-inflammatory activity; the best activity was found for the compounds 3b and 5c, which showed to be able to decrease by 69% and 56.2% carrageenan-induced edema in mice. These compounds may also offer a future promise as a new anti-inflammatory agent.

  19. On the relation between the modular double of U{sub q}(sl(2,R)) and the quantum Teichmueller theory

    Energy Technology Data Exchange (ETDEWEB)

    Nidaiev, Iurii; Teschner, Joerg

    2013-02-15

    We exhibit direct relations between the modular double of U{sub q}(sl(2,R)) and the quantum Teichmueller theory. Explicit representations for the fusion- and braiding operations of the quantum Teichmueller theory are immediate consequences. Our results include a simplified derivation of the Clebsch-Gordan decomposition for the principal series of representation of the modular double of U{sub q}(sl(2,R)).

  20. Preparation of rT3 in human serum ria kit

    International Nuclear Information System (INIS)

    Zhang Peixuan; Han Shiquan; Zhang Liling

    1991-02-01

    A method for the measurement of rT 3 in serum by radioimmunoassay is presented. The double antibody plus polyethylene glycol was used as separating reagent. The method is simple, precise and sensitive. Serum rT 3 values of normal (n = 61) were 47.7 ± 11.34 x 10 -8 g/L (X-bar ± SD). Patients with hyperthyroidism (n = 8) serum rT 3 values were 272.2 ± 91.1 x 10 -8 g/L (X-bar ± SD) and patients with hypothyroidism (n = 2) serum rT 3 values were 11.4 ± 8.3 x 10 -8 g/L (X-bar ± SD). It appears to be a useful diagnostic procedure for thyroid diseases

  1. Synthesis, physical and chemical properties of 2-((4-R-3-(morfolinomethylen-4H-1,2,4-triazole-5-ylthioacetic acid salts

    Directory of Open Access Journals (Sweden)

    R. О. Shcherbyna

    2017-04-01

    Full Text Available Today’s medicine and pharmacy undoubtedly need new and effective drugs. The 1,2,4-triazole derivatives occupy a special place among the wide variety of active organic compounds. This interest is caused primarily by high biological activity of these derivatives, low toxicity and high accessibility in terms of synthesis. Thus, drugs from 1,2,4-triazoles are known and are used extensively in medicine. It is important that a sufficiently large number of scientists-synthetics are paying attention on the heterocyclic system. Although a huge amount of information in the scientific literature is devoted to the 1,2,4-triazole derivatives, the 2-((4-R-3-(morfolinometylen-4H-1,2,4-triazole-5-ylthioacetic acid salts are virtually unexplored. The purpose of the work. Synthesis and establishing of the physical and chemical parameters of new 2-((4-R-3-(morfolinometylen-4H-1,2,4-triazole-5-ylthioacetic acid salts. Materials and methods. The study of physical and chemical properties of the obtained compounds was conducted by the methods that are listed in the State Pharmacopoeia of Ukraine 2.0. The melting point was defined on the device which determines the melting point MPA100. The elemental composition of the compounds was found on the analyzer Elementar Vario ЕL cube (CHNS . 1H NMR specters of obtained compounds were recorded by using a spectrometer Varian Mercury VX-200 (1H, 200 MHz and decrypted by a computer program SpinWorks 3.1.8. Chromatography-mass spectral studies were conducted on the gas-liquid chromatograph Agilent 1260 Infinity HPLC equipped with a mass spectrometer Agilent 6120 (ionization in electrospray (ESI. Results and discussion. As the source (starting compounds 2-((4-R-3-(morfolinometylen-4H-1,2,4-triazole-5-ylthioacetic acids (where, R = H, CH3, C2H5, C6H5, NH2 were taken. Further, by the action of ammonia hydroxide, sodium and potassium hidrogen carbonates, piperidine, morpholine, methylamine, monoethanolamine and tributylamine in

  2. Diazadienes in chemistry of lanthanides: latest view on old ligands. Synthesis, structure and properties of complexes {[(R)CNC6H3Pr2i]2}Lu(THF)2(μ-Cl)2Li(THF2 (R=CH3, CH2)

    International Nuclear Information System (INIS)

    Makhrova, T.V.; Fukin, G.K.; Cherkasov, A.V.; Trifonov, A.A.

    2008-01-01

    Reaction of dianion derivative [DADLi 2 ] (DAD -1,4-bis(2,6-diisopropylphenyl)-2,3-dimethyl-1,4-diaza-1,3-butadiene) prepared in situ by the reduction of corresponding DAD by the excess of metal lithium in THF with anhydrous LuCl 3 (1:1) results in the formation of the metal cyclic complex {[(R)CNC 6 H 3 Pr 2 i ] 2 }Lu(THF) 2 (μ-Cl) 2 Li(THF) 2 (1) containing the fragment N-C(Me)=C(Me)-N. DAD Treatment by two equivalents BuLi in the mixture ether-hexane (20 Deg C) results in the activation of the C-H bond of methyl substitutes at imine carbon. By the reaction of dilithium derivative [DAD - 2 H Li 2 ] formed in situ with LuCl 3 in THF the complex {[(CH 2 )CNC 6 H 3 Pr 2 i ] 2 }Lu(THF) 2 (μ-Cl) 2 Li(THF) 2 (2) with diamide ligand N-C(=CH 2 )-C(=CH 2 )-N was prepared. Structures of 1 and 2 complexes have been established by X-ray structure analysis [ru

  3. On Chromatic no. of 3K1-free graphs and R(3, k)

    OpenAIRE

    Dhurandhar, Medha S.

    2012-01-01

    Here we prove that if G has independence no. 2 and clique size omega with omega less than or equal to 11, then (1) chromatic no. is less than or equal to (omega2+12omega-13)/8, if omega is odd, and (2) chromatic no. is less than or equal to (omega2+10omega)/8, if omega is even. We further conjecture that the results are true in general for all omega. We also conjecture that (A) if omega is odd and R(3, omega) is even, then R(3, omega) = (omega2+8omega-9)/4, (B) if omega and R(3, omega) are bo...

  4. A New Acetylenic Compound and Other Bioactive Metabolites from a Shark Gill-derived Penicillium Strain

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2017-01-01

    Full Text Available Nine chiral compounds (1−9 were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium polonicum AP2T1. These compounds include a new acetylenic aromatic ether (1 , (--WA , four alkaloids ( a urantiomide C ( 2 , fructigenine A (3, cyclopenin (4 and cyclopenol (5 and four oxygenated compounds ((R-penipratynolene (6, (3S,4S-3,4-dihydro-3,4,8-trihydroxyl-naphthalenone (7, verrucosidin (8 and norverrucosidin (9. Their structures were elucidated by MS, NMR , optical rotation and circular dichroism (CD . In antimicrobial tests , compounds 1–4, 6 and 8–9 showed weak antibacterial activity against Staphylococcus aureus, Bacillus subtilis, and/or Escherichia coli.Compounds 3, 8 and 9 also exhibited moderate toxicity against Artemia salina larva , and showed cytotoxicity against human colon cancer cell line HCT116.

  5. Phloroglucinol derivatives and flavones from Helichrysum paronychioides

    Directory of Open Access Journals (Sweden)

    J. Mutanyatta-Comar

    2006-06-01

    Full Text Available Investigation of Helichrysum paronychioides afforded a total of nine compounds: 4 phloroglucinol derivatives, 2 of which are novel natural products, and 5 flavone derivatives. Structures were established by various spectroscopic techniques (NMR, MS, UV, IR, CD and by comparison with literature data for the known compounds. The four phloroglucinols, trans-(2R,3R-5,7-dihydroxy-2,3-dimethyl-4-chromanone (1, 2-butanoyl-4-prenyl-1-methoxy phloroglucinol (2, 2-(2-methylpropanoyl-4-prenylphloroglucinol (3 and 2-(2-methyl- butanoyl-4-prenylphloroglucinol (4 were screened for antioxidant activity against Cu-induced LDL oxidation. Compound 4 was found to be the most active inhibiting LDL oxidation at all concentrations (0.5-10 μM while the other three showed moderate to no activity.

  6. Parallel effects of the inversion In(3R)Payne on body size across the North American and Australian clines in Drosophila melanogaster.

    Science.gov (United States)

    Kapun, M; Schmidt, C; Durmaz, E; Schmidt, P S; Flatt, T

    2016-05-01

    Chromosomal inversions are thought to play a major role in climatic adaptation. In D. melanogaster, the cosmopolitan inversion In(3R)Payne exhibits latitudinal clines on multiple continents. As many fitness traits show similar clines, it is tempting to hypothesize that In(3R)P underlies observed clinal patterns for some of these traits. In support of this idea, previous work in Australian populations has demonstrated that In(3R)P affects body size but not development time or cold resistance. However, similar data from other clines of this inversion are largely lacking; finding parallel effects of In(3R)P across multiple clines would considerably strengthen the case for clinal selection. Here, we have analysed the phenotypic effects of In(3R)P in populations originating from the endpoints of the latitudinal cline along the North American east coast. We measured development time, egg-to-adult survival, several size-related traits (femur and tibia length, wing area and shape), chill coma recovery, oxidative stress resistance and triglyceride content in homokaryon lines carrying In(3R)P or the standard arrangement. Our central finding is that the effects of In(3R)P along the North American cline match those observed in Australia: standard arrangement lines were larger than inverted lines, but the inversion did not influence development time or cold resistance. Similarly, In(3R)P did not affect egg-to-adult survival, oxidative stress resistance and lipid content. In(3R)P thus seems to specifically affect size traits in populations from both continents. This parallelism strongly suggests an adaptive pattern, whereby the inversion has captured alleles associated with growth regulation and clinal selection acts on size across both continents. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  7. Photoinduced electron-transfer from imidazole derivative to nano-semiconductors.

    Science.gov (United States)

    Karunakaran, C; Jayabharathi, J; Jayamoorthy, K; Devi, K Brindha

    2012-04-01

    Bioactive imidazole derivative absorbs in the UV region at 305 nm. The interaction of imidazole derivative with nanoparticulate WO3, Fe2O3, Fe3O4, CuO, ZrO2 and Al2O3 has been studied by UV-visible absorption, FT-IR and fluorescence spectroscopies. The imidazole derivative adsorbs strongly on the surfaces of nanosemiconductor, the apparent binding constants for the association between nanomaterials and imidazole derivative have been determined from the fluorescence quenching. In the case of nanocrystalline insulator, fluorescence quenching through electron transfer from the excited state of the imidazole derivative to alumina is not possible. However, a possible mechanism for the quenching of fluorescence by the insulator is energy transfer, that is, energy transferred from the organic molecule to the alumina lattice. Based on Forster's non-radiation energy transfer theory, the distance between the imidazole derivative and nanoparticles (r0∼2.00 nm) as well as the critical energy transfer distance (R0∼1.70 nm) has been calculated. The interaction between the imidazole derivative and nanosurfaces occurs through static quenching mechanism. The free energy change (ΔGet) for electron transfer process has been calculated by applying Rehm-Weller equation. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysis.

    Science.gov (United States)

    Souza, Beatriz C C; De Oliveira, Tiago B; Aquino, Thiago M; de Lima, Maria C A; Pitta, Ivan R; Galdino, Suely L; Lima, Edeltrudes O; Gonçalves-Silva, Teresinha; Militão, Gardênia C G; Scotti, Luciana; Scotti, Marcus T; Mendonça, Francisco J B

    2012-06-01

    A series of 2-[(arylidene)amino]-cycloalkyl[b]thiophene-3-carbonitriles (2a-x) was synthesized by incorporation of substituted aromatic aldehydes in Gewald adducts (1a-c). The title compounds were screened for their antifungal activity against Candida krusei and Criptococcus neoformans and for their antiproliferative activity against a panel of 3 human cancer cell lines (HT29, NCI H-292 and HEP). For antiproliferative activity, the partial least squares (PLS) methodology was applied. Some of the prepared compounds exhibited promising antifungal and proliferative properties. The most active compounds for antifungal activity were cyclohexyl[b]thiophene derivatives, and for antiproliferative activity cycloheptyl[b]thiophene derivatives, especially 2-[(1H-indol-2-yl-methylidene)amino]- 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbonitrile (2r), which inhibited more than 97 % growth of the three cell lines. The PLS discriminant analysis (PLS-DA) applied generated good exploratory and predictive results and showed that the descriptors having shape characteristics were strongly correlated with the biological data.

  9. Synthesis and biological evaluation of new C-12(α/β)-(N-) sulfamoyl-phenylamino-14-deoxy-andrographolide derivatives as potent anti-cancer agents.

    Science.gov (United States)

    Kandanur, Sai Giridhar Sarma; Nanduri, Srinivas; Golakoti, Nageswara Rao

    2017-07-01

    Andrographolide, the major diterpenoidal constituent of Andrographis paniculata (Acanthaceae) and its derivatives have been reported to possess plethora of biological properties including potent anti-cancer activity. In this work, synthesis and in-vitro anti-cancer evaluation of new C-12-substituted aryl amino 14-deoxy-andrographolide derivatives (III a-f) are reported. The substitutions include various sulfonamide moieties -SO 2 -NH-R 1 . The new derivatives (III a-e) exhibited improved cytotoxicity (GI 50 , TGI and LC 50 ) compared to andrographolide (I) and the corresponding 3,14,19-O-triacetyl andrographolide (II) when evaluated against 60 NCI cell line panel. Compounds III c and III e are found to be non-toxic to normal human dermal fibroblasts (NHDF) cells compared to reference drug THZ-1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Synthesis and antimicrobial activity of some novel fused heterocyclic 1,2,4-triazolo [3,4-b][1,3,4] thiadiazine derivatives

    Science.gov (United States)

    Sahu, Jagdish K.; Ganguly, Swastika; Kaushik, Atul

    2014-01-01

    In the present investigation, the synthesis and antimicrobial evaluation of 1,2,4-triazolo [3,4-b][1,3,4] thiadiazine including different pharmacophores are aimed at. In this study, a series of 6-aryl-3- (3,4 -dialkoxyphenyl)-7H -[1,2,4]triazolo [3,4-b][1,3,4] thiadiazine (7a-7k) was synthesized by condensing 4-amino-5-(3,4-dialkoxyphenyl)-4H-[1,2,4]- triazole-3-thiol (6) with various aromatic carboxylic acids in the presence of phenacyl bromides through one-pot reaction. Eleven fused heterocyclic derivatives were successfully synthesized. The structures of these newly synthesized compounds were characterized by IR, 1H NMR and mass spectroscopic studies. All the synthesized compounds were screened for their antimicrobial evaluation. Some of the compounds exhibited promising antimicrobial activity. From the present study it may be concluded that synthesized compounds are fruitful in terms of their structural novelty and marked biological activities. These compounds could be further modified to develop potential and safer antifungal agents. PMID:24959418

  11. Rational design and enantioselective synthesis of (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid - a novel inhibitor at human glutamate transporter subtypes 1, 2, and 3

    DEFF Research Database (Denmark)

    Bunch, Lennart; Nielsen, Birgitte; Jensen, Anders A.

    2006-01-01

    The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglut......The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S...

  12. Synthesis of (3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetra-hydro-9-[4-3H] carbazolepropanoic acid

    International Nuclear Information System (INIS)

    Pleiss, Ulrich; Radtke, Martin; Schmitt, Peter

    1990-01-01

    (3R)-3-(4-Fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-[4- 3 H]carbazolepropanoic acid ( [ 3 H]BAY u 3405) (5) was synthesized by catalytic reduction of (3R)-3-(4-fluorophenylsulfonamido)-4-oxo-1,2,3,4-tetrahydro-9-carbazolepropanoic acid (4) with tritium. The precursor (4) was prepared by esterification and following oxidation of BAY u 3405 with 2,3-dichloro-5,6-dicyano-p-benzoquinone. 3 H NMR analysis of the final product showed the formation of [4α- 3 H]BAY us 3405 and [4β- 3 H]BAY u 3405 in a ratio of 1:1. (author)

  13. A Multifunctional and Possible Skin UV Protectant, (3R-5-Hydroxymellein, Produced by an Endolichenic Fungus Isolated from Parmotrema austrosinense

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    2016-12-01

    Full Text Available Lichens are considered a great bio-resource because they produce large numbers of secondary metabolites with many biological activities; however, they have not been cultivated under artificial conditions to date. As a result, lichen substances from natural sources are limited and have not been widely utilized in commercial applications. Accordingly, interest in lichen-associated fungi, especially endogenic fungi, has increased. Ultraviolet (UV radiation in sunlight is harmful to human health, resulting in demand for effective UV filtering agents for use in sunscreen. In this study, we purified (3R-5-hydroxymellein, which has UVA absorption activity, from the secondary metabolites of an endolichenic fungus (ELF000039. The antioxidant properties were then assessed by in vitro tests. The antioxidant activity of (3R-5-hydroxymellein was high when compared to the recognized antioxidants ascorbic acid (ASA and butyl hydroxyl anisole (BHA. Moreover, the compound exhibited no cytotoxicity toward mouse melanoma cell lines, B16F1 and B16F10, or the normal cell line, HaCaT. Furthermore, (3R-5-hydroxymellein recovered the damage caused by UVB irradiation and inhibited melanin synthesis. Taken together, these results suggest that (3R-5-hydroxymellein could have an interesting and vital profile to go further development as a multifunctional skin UV protectant.

  14. Characterization of Catalase from Psychrotolerant Psychrobacter piscatorii T-3 Exhibiting High Catalase Activity

    Science.gov (United States)

    Kimoto, Hideyuki; Yoshimune, Kazuaki; Matsuyma, Hidetoshi; Yumoto, Isao

    2012-01-01

    A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii), that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H2O2 as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein−1) that was higher than that of Micrococcus luteus used for industrial catalase production. Catalase was approximately 10% of the total proteins in the cell extract of the strain. The catalase (PktA) was purified homogeneously by only two purification steps, anion exchange and hydrophobic chromatographies. The purified catalase exhibited higher catalytic efficiency and higher sensitivity of activity at high temperatures than M. luteus catalase. The deduced amino acid sequence showed the highest homology with catalase of Psycrobacter cryohalolentis, a psychrotolelant bacterium obtained from Siberian permafrost. These findings suggest that the characteristics of the PktA molecule reflected the taxonomic relationship of the isolate as well as the environmental conditions (low temperatures and high concentrations of H2O2) under which the bacterium survives. Strain T-3 efficiently produces a catalase (PktA) at a higher rate than Exiguobacterium oxidotolerans, which produces a very strong activity of catalase (EktA) at a moderate rate, in order to adapt to high concentration of H2O2. PMID:22408420

  15. Synthesis and Antifungal Activity of Novel Sulfone Derivatives Containing 1,3,4-Oxadiazole Moieties

    Directory of Open Access Journals (Sweden)

    Maoguo Tong

    2011-11-01

    Full Text Available A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC50 values of 5.21 μg/mL, 8.25 µg/mL, 8.03 µg/mL, and 21.00 µg/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals.

  16. Higher-derivative superparticle in AdS3 space

    Science.gov (United States)

    Kozyrev, Nikolay; Krivonos, Sergey; Lechtenfeld, Olaf

    2016-03-01

    Employing the coset approach we construct component actions for a superparticle moving in AdS3 with N =(2 ,0 ), D =3 supersymmetry partially broken to N =2 , d =1 . These actions may contain higher time-derivative terms, which are chosen to possess the same (super)symmetries as the free superparticle. In terms of the nonlinear-realization superfields, the component actions always take a simpler form when written in terms of covariant Cartan forms. We also consider in detail the reduction to the nonrelativistic case and construct the corresponding action of a Newton-Hooke superparticle and its higher-derivative generalizations. The structure of these higher time-derivative generalizations is completely fixed by invariance under the supersymmetric Newton-Hooke algebra extended by two central charges.

  17. Magnetic properties of CaCu{sub 5}-type RNi{sub 3}TSi (R=Gd and Tb, T=Mn, Fe, Co and Cu) compounds

    Energy Technology Data Exchange (ETDEWEB)

    Morozkin, A.V., E-mail: morozkin@tech.chem.msu.ru [Department of Chemistry, Moscow State University, Leninskie Gory, House 1, Building 3, GSP-2, Moscow 119992 (Russian Federation); Knotko, A.V. [Department of Chemistry, Moscow State University, Leninskie Gory, House 1, Building 3, GSP-2, Moscow 119992 (Russian Federation); Yapaskurt, V.O. [Department of Petrology, Geological Faculty, Moscow State University, Leninskie Gory, Moscow 119992 (Russian Federation); Yao, Jinlei [Research Center for Solid State Physics and Materials, School of Mathematics and Physics, Suzhou University of Science and Technology, Suzhou 215009 (China); Yuan, Fang; Mozharivskyj, Y. [Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1 (Canada); Nirmala, R. [Indian Institute of Technology Madras, Chennai 600036 (India); Quezado, S.; Malik, S.K. [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Natal 59082-970 (Brazil)

    2015-12-15

    Magnetic properties and magnetocaloric effect of CaCu{sub 5}-type RNi{sub 3}TSi (R=Gd and Tb, T=Mn, Fe, Co and Cu) compounds have been investigated. Magnetic measurements of RNi{sub 3}TSi display the increasing of Curie temperature and the decreasing of magnetocaloric effect and saturated magnetic moment in the row of ‘RNi{sub 3}CuSi–RNi{sub 3}NiSi–RNi{sub 3}CoSi–RNi{sub 3}MnSi–RNi{sub 3}FeSi’. In contrast to GdNi{sub 3}{Mn, Fe, Co}Si, TbNi{sub 3}{Mn, Fe, Co}Si exhibit significant magnetic hysteresis. The coercive field increases from TbNi{sub 4}Si (~0.5 kOe) to TbNi{sub 3}CoSi (4 kOe), TbNi{sub 3}MnSi (13 kOe) and TbNi{sub 3}FeSi (16 kOe) in field of 50 kOe at 5 K, whereas TbNi{sub 3}CuSi exhibits a negligible coercive field. - Graphical abstract: Magnetic measurements of RNi{sub 3}TSi show the increasing of Curie temperature and the decreasing of magnetocaloric effect and saturated magnetic moment in the row of 'RNi{sub 3}CuSi–RNi{sub 3}NiSi–RNi{sub 3}CoSi–RNi{sub 3}MnSi–RNi{sub 3}FeSi'. In contrast to GdNi{sub 3}{Mn, Fe, Co}Si, TbNi{sub 3}{Mn, Fe, Co}Si exhibit significant magnetic hysteresis. The coercive field increases from TbNi{sub 4}Si (~0.5 kOe) to TbNi{sub 3}CoSi (4 kOe), TbNi{sub 3}MnSi (13 kOe) and TbNi{sub 3}FeSi (16 kOe) in field of 50 kOe at 5 K, whereas TbNi{sub 3}CuSi exhibits a negligible coercive field. - Highlights: • CaCu{sub 5}-type RNi{sub 3}TSi show ferromagnetic ordering (R=Gd, Tb, T=Mn–Co, Cu). • Curie point increases in ‘RNi{sub 3}CuSi–RNi{sub 3}NiSi–RNi{sub 3}CoSi–RNi{sub 3}MnSi–RNi{sub 3}FeSi’ row. • MCE decreases in ‘RNi{sub 3}CuSi–RNi{sub 3}NiSi–RNi{sub 3}CoSi–RNi{sub 3}MnSi–RNi{sub 3}FeSi’ row. • TbNi{sub 3}{Mn, Fe, Co}Si exhibit significant magnetic hysteresis. • The coercive field of TbNi{sub 3}MnSi and TbNi{sub 3}FeSi reach 13 kOe and 16 kOe at 5 K.

  18. Identification of novel 3,5-diarylpyrazoline derivatives containing salicylamide moiety as potential anti-melanoma agents.

    Science.gov (United States)

    Li, Qing-Shan; Lv, Xian-Hai; Zhang, Yan-Bin; Dong, Jing-Jun; Zhou, Wen-Ping; Yang, Yang; Zhu, Hai-Liang

    2012-11-01

    There is an accumulating body of experimental evidences validating oncogenic BRAF(V600E) as a therapeutic target and offering opportunities for anti-melanoma drug development. Encouraged by the positive results of pyrazole derivatives as BRAF(V600E) inhibitors, we sought to design diverse novel potential BRAF(V600E) inhibitors as antitumor agents based on pyrazole skeleton. In silico and in vitro screening of our designed pyrazole derivatives has identified Hit 1 as BRAF(V600E) inhibitor. Based on its structure and through further structure modification, compound 25, which exhibited the most potent inhibitory activity with an IC(50) value of 0.16 μM for BRAF(V600E) and GI(50) value of 0.24 μM for mutant BRAF-dependent melanoma cells, was obtained. The 3D-QSAR models and the molecular docking simulation were introduced to analyze the structure-activity relationship. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. High-resolution structural and functional assessments of cerebral microvasculature using 3D Gas ΔR2*-mMRA.

    Science.gov (United States)

    Huang, Chien-Hsiang; Chen, Chiao-Chi V; Siow, Tiing-Yee; Hsu, Sheng-Hsiou S; Hsu, Yi-Hua; Jaw, Fu-Shan; Chang, Chen

    2013-01-01

    The ability to evaluate the cerebral microvascular structure and function is crucial for investigating pathological processes in brain disorders. Previous angiographic methods based on blood oxygen level-dependent (BOLD) contrast offer appropriate visualization of the cerebral vasculature, but these methods remain to be optimized in order to extract more comprehensive information. This study aimed to integrate the advantages of BOLD MRI in both structural and functional vascular assessments. The BOLD contrast was manipulated by a carbogen challenge, and signal changes in gradient-echo images were computed to generate ΔR2* maps. Simultaneously, a functional index representing the regional cerebral blood volume was derived by normalizing the ΔR2* values of a given region to those of vein-filled voxels of the sinus. This method is named 3D gas ΔR2*-mMRA (microscopic MRA). The advantages of using 3D gas ΔR2*-mMRA to observe the microvasculature include the ability to distinguish air-tissue interfaces, a high vessel-to-tissue contrast, and not being affected by damage to the blood-brain barrier. A stroke model was used to demonstrate the ability of 3D gas ΔR2*-mMRA to provide information about poststroke revascularization at 3 days after reperfusion. However, this technique has some limitations that cannot be overcome and hence should be considered when it is applied, such as magnifying vessel sizes and predominantly revealing venous vessels.

  20. Event Reconstruction and Analysis in the R3BRoot Framework

    International Nuclear Information System (INIS)

    Kresan, Dmytro; Al-Turany, Mohammad; Bertini, Denis; Karabowicz, Radoslaw; Manafov, Anar; Rybalchenko, Alexey; Uhlig, Florian

    2014-01-01

    The R 3 B experiment (Reaction studies with Relativistic Radioactive Beams) will be built within the future FAIR / GSI (Facility for Antiproton and Ion Research) in Darmstadt, Germany. The international collaboration R 3 B has a scientific program devoted to the physics of stable and radioactive beams at energies between 150 MeV and 1.5 GeV per nucleon. In preparation for the experiment, the R3BRoot software framework is under development, it deliver detector simulation, reconstruction and data analysis. The basic functionalities of the framework are handled by the FairRoot framework which is used also by the other FAIR experiments (CBM, PANDA, ASYEOS, etc) while the R 3 B detector specifics and reconstruction code are implemented inside R3BRoot. In this contribution first results of data analysis from the detector prototype test in November 2012 will be reported, moreover, comparison of the tracker performance versus experimental data, will be presented

  1. Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability.

    Science.gov (United States)

    Zago, Michela; Sheridan, Jared A; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H; Hamid, Qutayba; Baglole, Carolyn J

    2017-01-01

    Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients.

  2. Calculations of the magnetic properties of R2M14B intermetallic compounds (R=rare earth, M=Fe, Co)

    International Nuclear Information System (INIS)

    Ito, Masaaki; Yano, Masao; Dempsey, Nora M.; Givord, Dominique

    2016-01-01

    The hard magnetic properties of “R–M–B” (R=rare earth, M=mainly Fe) magnets derive from the specific intrinsic magnetic properties encountered in Fe-rich R 2 M 14 B compounds. Exchange interactions are dominated by the 3d elements, Fe and Co, and may be modeled at the macroscopic scale with good accuracy. Based on classical formulae that relate the anisotropy coefficients to the crystalline electric field parameters and exchange interactions, a simple numerical approach is used to derive the temperature dependence of anisotropy in various R 2 Fe 14 B compounds (R=Pr, Nd, Dy). Remarkably, a unique set of crystal field parameters give fair agreement with the experimentally measured properties of all compounds. This implies reciprocally that the properties of compounds that incorporate a mixture of different rare-earth elements may be predicted accurately. This is of special interest for material optimization that often involves the partial replacement of Nd with another R element and also the substitution of Co for Fe. - Highlights: • Anisotropy constants derived from CEF parameters of R 2 M 14 B compounds (M=Fe, Co). • Anisotropy constants of all R 2 Fe 14 B compounds using unique set of CEF parameters. • Moment non-collinearity in magnetization processes under B app along hard axis.

  3. CeNi{sub 3}-type rare earth compounds: crystal structure of R{sub 3}Co{sub 7}Al{sub 2} (R=Y, Gd–Tm) and magnetic properties of {Gd–Er}{sub 3}Co{sub 7}Al{sub 2}, {Tb, Dy}{sub 3}Ni{sub 8}Si and Dy{sub 3}Co{sub 7.68}Si{sub 1.32}

    Energy Technology Data Exchange (ETDEWEB)

    Morozkin, A.V., E-mail: morozkin@tech.chem.msu.ru [Department of Chemistry, Moscow State University, Leninskie Gory, House 1, Building 3, GSP-1, Moscow 119991 (Russian Federation); Yapaskurt, V.O. [Department of Petrology, Geological Faculty Moscow State University, Leninskie Gory, Moscow 119991 (Russian Federation); Nirmala, R. [Indian Institute of Technology Madras, Chennai 600 036 (India); Quezado, S.; Malik, S.K. [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Natal 59082-970 (Brazil)

    2017-03-15

    The crystal structure of new CeNi{sub 3}-type {Y, Gd–Tm}{sub 3}Co{sub 7}Al{sub 2} (P63/mmc. N 194, hP24) compounds has been established using powder X-ray diffraction studies. The magnetism of Tb{sub 3}Ni{sub 8}Si and Dy{sub 3}Ni{sub 8}Si is dominated by rare earth sublattice and the magnetic properties of R{sub 3}Co{sub 7}Al{sub 2} (R =Gd–Er) and Dy{sub 3}Co{sub 7.68}Si{sub 1.32} are determined by both rare earth and cobalt sublattices. Magnetization data indicate ferromagnetic ordering of {Tb, Dy}{sub 3}Ni{sub 8}Si at 32 K and 21 K, respectively. Gd{sub 3}Co{sub 7}Al{sub 2} and Tb{sub 3}Co{sub 7}Al{sub 2} exhibit ferromagnetic ordering at 309 K and 209 K, respectively, whereas Dy{sub 3}Co{sub 7}Al{sub 2}, Ho{sub 3}Co{sub 7}Al{sub 2}, Er{sub 3}Co{sub 7}Al{sub 2} and Dy{sub 3}Co{sub 7.68}Si{sub 1.32} show a field dependent ferromagnetic-like ordering at 166 K, 124 K, 84 K and 226 K, respectively followed by a low temperature transition at 34 K for Dy{sub 3}Co{sub 7}Al{sub 2}, 18 K for Ho{sub 3}Co{sub 7}Al{sub 2}, 56 K for Er{sub 3}Co{sub 7}Al{sub 2}, 155 K and 42 K for Dy{sub 3}Co{sub 7.68}Si{sub 1.32}. Among these compounds, Dy{sub 3}Ni{sub 8}Si shows largest magnetocaloric effect (isothermal magnetic entropy change) of −11.6 J/kg·K at 18 K in field change of 50 kOe, whereas Tb{sub 3}Co{sub 7}Al{sub 2}, Dy{sub 3}Co{sub 7}Al{sub 2} and Dy{sub 3}Co{sub 7.68}Si{sub 1.32} exhibit best permanent magnet properties in the temperature range of 2–5 K with remanent magnetization of 11.95 μ{sub B}/fu, 12.86 μ{sub B}/fu and 14.4 μ{sub B}/fu, respectively and coercive field of 3.0 kOe, 1.9 kOe and 4.4 kOe, respectively. - Highlights: • {Y, Gd–Tm}{sub 3}Co{sub 7}Al{sub 2} compounds crystallize in the CeNi{sub 3}-type structure. • {Gd-Er}{sub 3}Co{sub 7}Al{sub 2} show ferrimagnetic ordering at 309 K, 209 K, 166 K, 124 K and 84 K. • Dy{sub 3}Co{sub 7.68}Si{sub 1.32} exhibits magnetic transitions at 226 K, 155 K and 42 K. • {Tb-Er}{sub 3}Co{sub 7}Al{sub 2

  4. LAND/R3B DAQ developments

    Energy Technology Data Exchange (ETDEWEB)

    Toernqvist, Hans; Aumann, Thomas; Loeher, Bastian [Technische Universitaet Darmstadt, Darmstadt (Germany); Simon, Haik [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Darmstadt (Germany); Johansson, Haakan [Chalmers Institute of Technology, Goeteborg (Sweden); Collaboration: R3B-Collaboration

    2015-07-01

    Existing experimental setups aim to exploit most of the improved capabilities and specifications of the upcoming FAIR facility at GSI. Their DAQ designs will require some re-evaluation and upgrades. This presentation summarizes the R3B experimental campaigns in 2014, where the R3B DAQ was subject to testing of several new features that will aid researchers in using larger and more complicated experimental setups in the future. It also acted as part of a small testing ground for the NUSTAR DAQ infrastructure. In order to allow to extract correlations between several experimental sites, new suggested triggering and timestamping implementations were tested over significant distances. Also, with growing experimental complexity comes a greater risk of problems that may be difficult to characterize and solve. To this end, essential remote monitoring and debugging tools have been used successfully.

  5. NSAI activity study of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

    Science.gov (United States)

    Darias, V; Abdallah, S S; Tello, M L; Delgado, L D; Vega, S

    1994-12-01

    A series of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives endowed with anti-inflammatory and related pharmacological properties were submitted to a more extensive study to know their exact pharmacological profile and their possible side effects. The studied compounds possess a remarkable analgesic activity, devoid of central effects. They also show an interesting anti-inflammatory profile evidenced by their effectiveness in different experimental models of inflammation. In addition, these compounds exhibit none or very little activity on CNS, scarce toxicity and low gastrointestinal aggressivity.

  6. The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture.

    Science.gov (United States)

    Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Broich, Karl; Papazoglou, Anna; Weiergräber, Marco

    2014-05-01

    Voltage-gated Ca(2+) channels (VGCCs) are key elements in mediating thalamocortical rhythmicity. Low-voltage activated (LVA) CaV 3 T-type Ca(2+) channels have been related to thalamic rebound burst firing and to generation of non-rapid eye movement (NREM) sleep. High-voltage activated (HVA) CaV 1 L-type Ca(2+) channels, on the opposite, favor the tonic mode of action associated with higher levels of vigilance. However, the role of the HVA Non-L-type CaV2.3 Ca(2+) channels, which are predominantly expressed in the reticular thalamic nucleus (RTN), still remains unclear. Recently, CaV2.3(-/-) mice were reported to exhibit altered spike-wave discharge (SWD)/absence seizure susceptibility supported by the observation that CaV2.3 mediated Ca(2+) influx into RTN neurons can trigger small-conductance Ca(2+)-activated K(+)-channel type 2 (SK2) currents capable of maintaining thalamic burst activity. Based on these studies we investigated the role of CaV2.3 R-type Ca(2+) channels in rodent sleep. The role of CaV2.3 Ca(2+) channels was analyzed in CaV2.3(-/-) mice and controls in both spontaneous and artificial urethane-induced sleep, using implantable video-EEG radiotelemetry. Data were analyzed for alterations in sleep architecture using sleep staging software and time-frequency analysis. CaV2.3 deficient mice exhibited reduced wake duration and increased slow-wave sleep (SWS). Whereas mean sleep stage durations remained unchanged, the total number of SWS epochs was increased in CaV2.3(-/-) mice. Additional changes were observed for sleep stage transitions and EEG amplitudes. Furthermore, urethane-induced SWS mimicked spontaneous sleep results obtained from CaV2.3 deficient mice. Quantitative Real-time PCR did not reveal changes in thalamic CaV3 T-type Ca(2+) channel expression. The detailed mechanisms of SWS increase in CaV2.3(-/-) mice remain to be determined. Low-voltage activated CaV2.3 R-type Ca(2+) channels in the thalamocortical loop and extra

  7. Pharmacokinetics and Metabolism of (R,R)-Methoxyfenoterol in Rat

    OpenAIRE

    Siluk, Danuta; Mager, Donald E.; Kim, Hee Seung; Wang, Yan; Furimsky, Anna M.; Ta, Amy; Iyer, Lalitha V.; Green, Carol E.; Wainer, Irving W.

    2010-01-01

    (R,R)-Fenoterol (Fen), a β2-adrenoceptor agonist, is under clinical investigation in the treatment of congestive heart disease. The pharmacokinetics and metabolism of the 4-methoxyphenyl derivative of (R,R)-Fen, (R,R)-MFen, have been determined following intravenous and oral administration to the rat and compared with corresponding results obtained with (R,R)-Fen. Results of the study suggest that (R,R)-MFen can offer pharmacokinetic and metabolic advantages in comparison to an earlier (R,R)-...

  8. Graphene derivatives/Fe{sub 3}O{sub 4}/polymer nanocomposite films: Optical and electrical properties

    Energy Technology Data Exchange (ETDEWEB)

    Hatel, Rhizlane [University Sidi Mohammed Ben Abdellah, Faculty of Sciences Dhar El Mahraz, Laboratory of Solid State Physics, Group of Polymers and Nanomaterials, PO Box 1796, Atlas, Fez 30000 (Morocco); Goumri, Meryem [University Sidi Mohammed Ben Abdellah, Faculty of Sciences Dhar El Mahraz, Laboratory of Solid State Physics, Group of Polymers and Nanomaterials, PO Box 1796, Atlas, Fez 30000 (Morocco); XLIM UMR 7252- University of Limoges/CNRS, 123 Avenue Albert Thomas, 87060 Limoges Cedex (France); Ratier, Bernard [XLIM UMR 7252- University of Limoges/CNRS, 123 Avenue Albert Thomas, 87060 Limoges Cedex (France); Baitoul, Mimouna, E-mail: baitoul@yahoo.fr [University Sidi Mohammed Ben Abdellah, Faculty of Sciences Dhar El Mahraz, Laboratory of Solid State Physics, Group of Polymers and Nanomaterials, PO Box 1796, Atlas, Fez 30000 (Morocco)

    2017-06-01

    This paper reports a simple solution casting method for the preparation of nanocomposite films in which graphene oxide (GO)/Fe{sub 3}O{sub 4} nanocomposites are incorporated into poly (vinyl alcohol) (PVA) matrix. The films obtained with different weight percent of GO/Fe{sub 3}O{sub 4} (0.5, 0.7 and 1 wt%) are subjected an in situ chemical and thermal reduction in order to explore the evolution and interactions between these components under different treatments and get an insight into on how this can affects the optical and electrical properties of these nanocomposites. Characterization was carried out using, UV–Vis absorption, Photoluminescence, electrical conductivity measurements, Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. Strong covalent functionalization occurs between the polymer and graphene derivatives (GD)/Fe{sub 3}O{sub 4} hybrids. The experimental results obtained for our nanocomposites films exhibit significant enhancement in properties highlighted the efficiency of the in situ thermal reduction. The high absorption with strong photoluminescence and electrical conductivity achieved might promote these nanocomposites for opto-electronic devices in near future. - Highlights: • Novel inorganic-organic hybrid flexible films were successfully prepared. • Good interfacial interaction between the graphene/Fe{sub 3}O{sub 4} and the hydroxyl-rich PVA. • Optical and electrical properties of Graphene Derivatives/Fe{sub 3}O{sub 4}/PVA were investigated. • Thermally reduced GO/Fe{sub 3}O{sub 4}/PVA films show high absorption and strong photoluminescence.

  9. Quantitative multi-parameter mapping of R1, PD*, MT and R2* at 3T: a multi-center validation

    Directory of Open Access Journals (Sweden)

    Nikolaus eWeiskopf

    2013-06-01

    Full Text Available Multi-center studies using magnetic resonance imaging facilitate studying small effect sizes, global population variance and rare diseases. The reliability and sensitivity of these multi-center studies crucially depend on the comparability of the data generated at different sites and time points. The level of inter-site comparability is still controversial for conventional anatomical T1-weighted MRI data. Quantitative multi-parameter mapping (MPM was designed to provide MR parameter measures that are comparable across sites and time points, i.e., 1mm high-resolution maps of the longitudinal relaxation rate (R1=1/T1, effective proton density (PD*, magnetization transfer saturation (MT and effective transverse relaxation rate (R2*=1/T2*. MPM was validated at 3T for use in multi-center studies by scanning five volunteers at three different sites. We determined the inter-site bias, inter-site and intra-site coefficient of variation (CoV for typical morphometric measures (i.e., gray matter probability maps used in voxel-based morphometry and the four quantitative parameters. The inter-site bias and CoV were smaller than 3.1% and 8%, respectively, except for the inter-site CoV of R2* (< 20%. The gray matter probability maps based on the MT parameter maps had a 14% higher inter-site reproducibility than maps based on conventional T1-weighted images. The low inter-site bias and variance in the parameters and derived gray matter probability maps confirm the high comparability of the quantitative maps across sites and time points. The reliability, short acquisition time, high resolution and the detailed insights into the brain microstructure provided by MPM makes it an efficient tool for multi-center imaging studies.

  10. Phase relations in the pseudobinary systems RAO3-R2Ti2O7 (R: rare earth element and Y, A: Fe, Ga, Al, Cr and Mn) and syntheses of new compounds R(A1-xTix)O3+x/2 (2/3≤x≤3/4) at elevated temperatures in air

    Science.gov (United States)

    Brown, Francisco; Jacobo-Herrera, Ivan; Alvarez-Montaño, Victor; Kimizuka, Noboru; Kurashina, Keiji; Michiue, Yuichi; Matsuo, Yoji; Mori, Shigeo; Ikeda, Naoshi; Medrano, Felipe

    2017-07-01

    Phase relations in the pseudo-binary systems RFeO3-R2Ti2O7 (R: Lu, Ho and Dy), RGaO3-R2Ti2O7 (R: Lu and Er), LuAlO3-Lu2Ti2O7 and RAO3-R2Ti2O7 (R: Lu and Yb. A: Cr and Mn) at elevated temperatures in air were determined by means of a classic quenching method. There exist Lu(Fe1-xTix)O3+x/2, R(Ga1-xTix)O3+x/2 (R: Lu and Er) and Lu(Al1-xTix)O3+x/2 (2/3≤ x≤3/4) having the Yb(Fe1-xTix)O3+x/2-type of crystal structure (x=0.72, space group: R3m, a(Å)=17.9773 and c(Å)=16.978 as a hexagonal setting) in these pseudo binary systems. Eighteen compounds R(A1-xTix)O3+x/2 (R: Lu-Sm and Y, A: Fe, Ga and Al) were newly synthesized and their lattice constants as a hexagonal setting were measured by means of the X-ray powder diffraction method. The R occupies the octahedral site and both A and Ti does the trigonalbipyramidal one in these compounds. Relation between lattice constants for the rhombic R(A1-xTix)O3+x/2 and the monoclinic In(A1-xTix)O3+x/2 are as follows, ah≈5 x bm, ch≈3 x cm x sin β and am=31/2 x bm, where ah and ch are the lattice constants as a hexagonal setting for R(A1-xTix)O3+x/2 and am, bm, cm and β are those of the monoclinic In(A1-xTix)O3+x/2. Crystal structural relationships among α-InGaO3 (hexagonal, high pressure form, space group: P63/mmc), InGaO3 (rhombic, hypothetical), (RAO3)n(BO)m and RAO3(ZnO)m (R: Lu-Ho, Y and In, A: Fe, Ga, and Al, B: divalent cation element, m, n: natural number), the orthorhombic-and monoclinic In(A1-xTix)O3+x/2 (A: Fe, Ga, Al, Cr and Mn) and the hexagonal-and rhombic R(A1-xTix)O3+x/2 (R: Lu-Sm and Y, A: Fe, Ga and Al) are schematically presented. We concluded that the crystal structures of both the α-InGaO3 (high pressure form, hexagonal, space group: P63/mmc) and the hypothetical InGaO3 (rhombic) are the key structures for constructing the crystal structures of these compounds having the cations with CN=5.

  11. Effects of fullerol on the osteogenic differentiation of adipose-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Yan-ting TANG

    2016-09-01

    Full Text Available Objective  To investigate the effect of fullerol on the osteogenic differentiation of rat adipose-derived mesenchymal stem cells (rADSCs based on hanging drop culture. Methods  rADSC spheres were formed by hanging drop culture for 3 days, then the spheres were dissociated to single cell by trypsin (called rADSC sphere-derived cells. The rADSC sphere-derived cells were cultured in 2-D adherent cell cultures for 24 hours, then the ordinary culture medium was replaced by osteogenic induction medium (osteogenic medium, OM. OM without fullerol served as control group (CM; OM with 1.0μmol/L fullerol was used as the experimental group (OM+Ful1.0μmol/L. Two groups were induced to differentiation for 14d and 21d, using two methods of alizarin red staining and quantitative real-time PCR (qPCR to detecte the ability of rADSC sphere-derived cells differentiating into osteoblasts. Results  rADSCs could form a uniform size microspheres structure through hanging drop culture for 3 days; rADSC sphere-derived cells were obtained by dissipation of trypsin. Compared with OM group, OM+Ful1.0μmol/L can make rADSC sphere-derived cells form more mineralized calcium nodules, and enhance the expression of the relevant osteogenic gene Runx2, OCN and ColI. Conclusion  Fullerol can significantly enhance the osteogenic differentiation of rADSCs based on hanging drop culture, and it is helpful to improve the efficiency of osteogenic induction of rADSCs. DOI: 10.11855/j.issn.0577-7402.2016.08.03

  12. Simple synthesis of graphene nanocomposites MgO-rGO and Fe2O3-rGO for multifunctional applications

    Science.gov (United States)

    Abdel-Aal, Seham K.; Ionov, Andrey; Mozhchil, R. N.; Naqvi, Alim H.

    2018-05-01

    Hummer's method was used to prepare graphene oxide (GO) by chemical exfoliation of graphite. Simple precipitation method was used for the preparation of hybrid nanocomposites MgO-rGO and Fe2O3-rGO. A 0.3 Molar of corresponding metal nitrate solution and GO solution are used for the preparation process. XRD, FT-IR, and XPS were used to characterize the prepared nanocomposites. The reduction of GO into reduced rGO in the formed nanocomposites was confirmed. Morphological characterization showed the formation of needle-shaped nanocrystals of MgO successfully grown on graphene nanosheet with average crystallite size 8.4 nm. Hematite nanocomposite Fe2O3-rGO forms rod-shaped crystals with average crystallite size 27.5 nm. The saturation magnetization observed for Fe2O3-rGO is less than reported value for the pure Fe2O3 nanoparticles. Thermal properties of as-prepared hybrid nanocomposites MgO-rGO and Fe2O3-rGO showed thermal stability of the prepared nanocomposite over long range of temperature.

  13. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's 50th anniversary celebrations. Fifty candles for CERN, an international laboratory renowned for fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting exhibitions of plastic arts and performances entitled: Accelerated Particles. Several works will be exhibited and performed in two 'salons'. Salon des matières: An exhibition of plastic arts From Tues 12 October to Wed 3 November 2004 Tuesdays to Fridays: 16:00 to 19:00 Saturdays: 14:00 to 18:00 Exhibition open late on performance nights, entrance free Salon des particules: Musical and visual performances Tues 12 and Mon 25 October from 20:00 to 23:00 Preview evening for both events: Tues 12 October from 18:...

  14. R3D Align web server for global nucleotide to nucleotide alignments of RNA 3D structures.

    Science.gov (United States)

    Rahrig, Ryan R; Petrov, Anton I; Leontis, Neocles B; Zirbel, Craig L

    2013-07-01

    The R3D Align web server provides online access to 'RNA 3D Align' (R3D Align), a method for producing accurate nucleotide-level structural alignments of RNA 3D structures. The web server provides a streamlined and intuitive interface, input data validation and output that is more extensive and easier to read and interpret than related servers. The R3D Align web server offers a unique Gallery of Featured Alignments, providing immediate access to pre-computed alignments of large RNA 3D structures, including all ribosomal RNAs, as well as guidance on effective use of the server and interpretation of the output. By accessing the non-redundant lists of RNA 3D structures provided by the Bowling Green State University RNA group, R3D Align connects users to structure files in the same equivalence class and the best-modeled representative structure from each group. The R3D Align web server is freely accessible at http://rna.bgsu.edu/r3dalign/.

  15. Design, synthesis and antifungal activities of novel strobilurin derivatives containing pyrimidine moieties

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiang; Geo, Yongxin; Liu, Huijun; Guo, Baoyuan; Wang, Huili [Research Center for Eco-Environmental Sciences/Chinese Academy of Sciences, Beijing (China)

    2012-04-15

    Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel β-methoxy acrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, {sup 1}H nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbicular, Botrytis cinerea Pers and Protoporphyria caps ici Leon ian at the concentration of 50 μg/mL. Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial stilbenetriol fungicide azoxystrobin.

  16. FIB/FESEM experimental and analytical assessment of R-curve behavior of WC–Co cemented carbides

    Energy Technology Data Exchange (ETDEWEB)

    Tarragó, J.M., E-mail: jose.maria.tarrago@upc.edu [CIEFMA, Departament de Ciència dels Materials i Enginyeria Metallúrgica, ETSEIB, Universitat Politècnica de Catalunya, 08028 Barcelona (Spain); CRnE, Centre de Recerca en Nanoenginyeria, Universitat Politècnica de Catalunya, 08028 Barcelona (Spain); Jiménez-Piqué, E. [CIEFMA, Departament de Ciència dels Materials i Enginyeria Metallúrgica, ETSEIB, Universitat Politècnica de Catalunya, 08028 Barcelona (Spain); CRnE, Centre de Recerca en Nanoenginyeria, Universitat Politècnica de Catalunya, 08028 Barcelona (Spain); Schneider, L. [Sandvik Hyperion, Coventry CV4 0XG (United Kingdom); Casellas, D. [Fundació CTM Centre Tecnològic, 08243 Manresa (Spain); Torres, Y. [Departamento de Ingeniería y Ciencia de los Materiales y del Transporte, ETSI, Universidad de Sevilla, 41092 Sevilla (Spain); Llanes, L. [CIEFMA, Departament de Ciència dels Materials i Enginyeria Metallúrgica, ETSEIB, Universitat Politècnica de Catalunya, 08028 Barcelona (Spain); CRnE, Centre de Recerca en Nanoenginyeria, Universitat Politècnica de Catalunya, 08028 Barcelona (Spain)

    2015-10-01

    Exceptional fracture toughness levels exhibited by WC–Co cemented carbides (hardmetals) are due mainly to toughening derived from plastic stretching of crack-bridging ductile enclaves. This takes place due to the development of a multiligament zone at the wake of cracks growing in a stable manner. As a result, hardmetals exhibit crack growth resistance (R-curve) behavior. In this work, the toughening mechanics and mechanisms of these materials are investigated by combining experimental and analytical approaches. Focused Ion Beam technique (FIB) and Field-Emission Scanning Electron Microscopy (FESEM) are implemented to obtain serial sectioning and imaging of crack–microstructure interaction in cracks arrested after stable extension under monotonic loading. The micrographs obtained provide experimental proof of the developing multiligament zone, including failure micromechanisms within individual bridging ligaments. Analytical assessment of the multiligament zone is then conducted on the basis of experimental information attained from FIB/FESEM images, and a model for the description of R-curve behavior of hardmetals is proposed. It was found that, due to the large stresses supported by the highly constrained and strongly bonded bridging ligaments, WC–Co cemented carbides exhibit quite steep but short R-curve behavior. Relevant strength and reliability attributes exhibited by hardmetals may then be rationalized on the basis of such toughening scenario.

  17. The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: the influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents.

    Science.gov (United States)

    Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L; Gündisch, Daniela

    2013-12-01

    3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for α4β2(∗) were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for α4β2(∗) possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Rhythmic expression of miR-27b-3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver.

    Science.gov (United States)

    Zhang, Wenxiang; Wang, Peng; Chen, Siyu; Zhang, Zhao; Liang, Tingming; Liu, Chang

    2016-06-01

    Circadian clocks orchestrate daily oscillations in mammalian behaviors, physiology, and gene expression. MicroRNAs (miRNAs) play a crucial role in fine-tuning of the circadian system. However, little is known about the direct regulation of the clock genes by specific miRNAs. In this study, we found that miR-27b-3p exhibits rhythmic expression in the metabolic tissues of the mice subjected to constant darkness. MiR-27b-3p's expression is induced in livers of unfed and ob/ob mice. In addition, the oscillation phases of miR-27b-3p can be reversed by restricted feeding, suggesting a role of peripheral clock in regulating its rhythmicity. Bioinformatics analysis indicated that aryl hydrocarbon receptor nuclear translocator-like (also known as Bmal1) may be a direct target of miR-27b-3p. Luciferase reporter assay showed that miR-27b-3p suppressed Bmal1 3' UTR activity in a dose-dependent manner, and mutagenesis of their binding site abolished this suppression. Furthermore, overexpression of miR-27b-3p dose-dependently reduced the protein expression levels of BMAL1 and impaired the endogenous BMAL1 and gluconeogenic protein rhythmicity. Collectively, our results suggest that miR-27b-3p plays an important role in the posttranscriptional regulation of BMAL1 protein in the liver. MiR-27b-3p may serve as a novel node to integrate the circadian clock and energy metabolism.-Zhang, W., Wang, P., Chen, S., Zhang, Z., Liang, T., Liu, C. Rhythmic expression of miR-27b-3p targets the clock gene Bmal1 at the posttranscriptional level in the mouse liver. © FASEB.

  19. [Central muscle relaxant activities of 2-methyl-3-aminopropiophenone derivatives].

    Science.gov (United States)

    Kontani, H; Mano, A; Koshiura, R; Yamazaki, M; Shimada, Y; Oshita, M; Morikawa, K; Kato, H; Ito, Y

    1987-02-01

    In this experiment, we synthetized new 2-methyl-3-aminopropiophenone (MP) derivatives, whose structure is known to have central muscle relaxant activities, and quinolizidine and indan . tetralin derivatives derived from MP by cyclization, and we investigated the central muscle relaxant activity. Among the quinolizidine derivatives, there was a very strong central depressant agent, trans (3H, 9aH)-3-(p-chloro) benzoyl-quinolizidine (HSR-740), and among the indan . tetralin derivatives, there was an excitant agents, trans (1H, 2H)-5-methoxy-3, 3-dimethyl-2-piperidinomethyl indan-1-ol (HSR-719). From the results, these derivatives were not considered to be adequate for central muscle relaxant. Among the MP derivatives, (4'-chloro-2'-methoxy-3-piperidino) propiophenone HCl (HSR-733) and (4'-ethyl-2-methyl-3-pyrrolidino) propiophenone HCl (HSR-770) strongly inhibited the cooperative movement in the rotating rod method using mice, and it exerted almost the same depressant activity on the cross extensor reflex using alpha-chloralose anesthetized rats. However, the inhibitory effects of HSR-733 on the anemic decerebrate rigidity and the rigidity induced by intracollicular decerebration in rats were weaker than those of HSR-770 and eperisone. In spinal cats, at a low dose (5 mg/kg, i.v.), HSR-733 depressed monosynaptic and dorsal root reflex potentials as compared with polysynaptic reflex potentials, and inhibitory effects of HSR-733 on these three reflex potentials were more potent than those of eperisone and HSR-770. Although HSR-770 acts on the spinal cord and supraspinal level on which eperisone has been reported to act, HSR-733 may mainly act on the spinal cord. These results indicate that the MP derivative with a 2-methyl group may be suitable as a central muscle relaxant. HSR-770, which has equipotent muscle relaxant activity to eperisone, exerted strong inhibitory effects on oxotremorine-induced tremor and weak inhibitory effects on spontaneous motor activity in the

  20. Determination of LongR3-IGF-I, R3-IGF-I, Des1-3 IGF-I and their metabolites in human plasma samples by means of LC-MS.

    Science.gov (United States)

    Thomas, Andreas; Walpurgis, Katja; Delahaut, Philippe; Fichant, Eric; Schänzer, Wilhelm; Thevis, Mario

    2017-08-01

    According to the regulations of the World Anti-Doping Agency (WADA), growth promoting peptides such as the insulin-like growth factor-I (IGF-I) and its synthetic analogues belong to the class of prohibited compounds. While several assays to quantify endogenous IGF-I have been established, the potential misuse of synthetic analogues such as LongR 3 -IGF-I, R 3 -IGF-I and Des1-3-IGF-I remains a challenge and superior pharmacokinetic properties have been described for these analogues. Within the present study, it was demonstrated that the target peptides can be successfully detected in plasma samples by means of magnetic beads-based immunoaffinity purification and subsequent nanoscale liquid chromatographic separation with high resolution mass spectrometric detection. Noteworthy, the usage of a specific antibody for LongR 3 -IGF-I enables the determination in low ng/mL levels despite the presence of an enormous excess of endogenous human IGF-I. In addition, different metabolism studies (in-vitro and in-vivo) were performed using sophisticated strategies such as incubation with skin tissue microsomes, degradation in biological fluids (for all analogues), and administration to rats (for LongR 3 -IGF-I). Herewith, several C-and N-terminally truncated metabolites were identified and their relevancy was additionally confirmed by in-vivo experiments with rodents. Especially for LongR 3 -IGF-I, a metabolite ((Des1-11)-LongR 3 -IGF-I) was identified that prolonged the detectability in-vivo by a factor of approximately 2. The method was validated for qualitative interpretation considering the parameters specificity, identification capability, recovery (26-60%), limit of detection (0.5ng/mL), imprecision (IGF-I was used as internal standard to control all sample preparation steps. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Metabolism of Lutein and Zeaxanthin in Rhesus Monkeys: Identification of (3R,6′R)- and (3R,6′S)-3′-Dehydro-lutein as Common Metabolites and Comparison to Humans

    Science.gov (United States)

    Albert, Gesa I.; Hoeller, Ulrich; Schierle, Joseph; Neuringer, Martha; Johnson, Elizabeth J.; Schalch, Wolfgang

    2012-01-01

    Lutein and zeaxanthin are xanthophylls that can be found highly concentrated in the macula of the retina. They are thought to protect the macula through their role as blue-light filters and because of their antioxidant and singlet oxygen quenching properties. Examination of metabolites unique to lutein and zeaxanthin such as 3′-dehydro-lutein, and of their stereochemistry may provide insight to the mechanism by which they are formed and by which they exert protection. To evaluate the formation of such metabolites, eleven monkeys were raised on a xanthophyll-free diet, and supplemented with pure lutein or pure zeaxanthin (2.2 mg/kg body weight/d). The period of supplementation ranged between 12 to 92 weeks. At study start and throughout the study, serum samples were taken and analyzed for xanthophylls using different HPLC systems. Xanthophyll metabolites were identified using UV/VIS and HR-MS detection. Lutein and zeaxanthin metabolites were found in detectable amounts with 3′-dehydro-lutein being a common metabolite of both. Using chiral-phase HPLC, two diastereomers, (3R,6′R)-3′-dehydro-lutein and (3R,6′S)-3′-dehydro-lutein, were identified and shown to be present in nearly equimolar amounts. A pathway for their formation from either lutein or zeaxanthin is proposed. These finding were comparable to results obtained with human plasma. PMID:18582588

  2. On the dimensional reduction of a gravitational theory containing higher-derivative terms

    International Nuclear Information System (INIS)

    Pollock, M.D.

    1990-02-01

    From the higher-dimensional gravitational theory L-circumflex=R-circumflex-2Λ-circumflex-α-circumflex 1 R-circumflex 2 =α-circumflex 2 R-circumflex AB R-circumflex AB -α-circumflex 3 R-circumflex ABCD R-circumflex ABCD , we derive the effective four-dimensional Lagrangian L. (author). 12 refs

  3. Pharmacological properties of homomeric and heteromeric GluR1o and GluR3o receptors

    DEFF Research Database (Denmark)

    Nielsen, B S; Banke, T G; Schousboe, A

    1998-01-01

    Homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits GluR1o and GluR3o were expressed in Spodoptera frugiperda (Sf9) insect cells. Membranes containing the recombinant receptors showed a doublet of bands of the expected size (99-109 kDa) after...

  4. The C-Terminal Segment of Yeast BMH Proteins Exhibits Different Structure Compared to Other 14-3-3 Protein Isoforms

    Czech Academy of Sciences Publication Activity Database

    Veisová, Dana; Řežábková, L.; Štěpánek, M.; Novotná, P.; Herman, P.; Večeř, J.; Obšil, T.; Obšilová, Veronika

    2010-01-01

    Roč. 49, č. 18 (2010), s. 3853-3861 ISSN 0006-2960 R&D Projects: GA AV ČR(CZ) IAA501110801; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : yeast BMH proteins * sedimentation equilibrium and velocity measurements * dynamic light scattering Subject RIV: BO - Biophysics Impact factor: 3.226, year: 2010

  5. 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate promotes megakaryocytic differentiation of myeloid leukaemia cells and primary human CD34⁺ haematopoietic stem cells.

    Science.gov (United States)

    Limb, Jin-Kyung; Song, Doona; Jeon, Mijeong; Han, So-Yeop; Han, Gyoonhee; Jhon, Gil-Ja; Bae, Yun Soo; Kim, Jaesang

    2015-04-01

    In this study we showed that 2-(trimethylammonium)ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient differentiation of megakaryocytes. Specifically, (R)-TEMOSPho induces cell cycle arrest, cell size increase and polyploidization from K562 and HEL cells, which are used extensively to model megakaryocytic differentiation. In addition, megakaryocyte-specific cell surface markers showed a dramatic increase in expression in response to (R)-TEMOSPho treatment. Importantly, we demonstrated that such megakaryocytic differentiation can also be induced from primary human CD34(+) haematopoietic stem cells. Activation of the PI3K-AKT pathway and, to a lesser extent, the MEK-ERK pathway appears to be required for this process, as blocking with specific inhibitors interferes with the differentiation of K562 cells. A subset of (R)-TEMOSPho-treated K562 cells undergoes spontaneous apoptosis and produces platelets that are apparently functional, as they bind to fibrinogen, express P-selectin and aggregate in response to SFLLRN and AYPGFK, the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken together, these results indicate that (R)-TEMOSPho will be useful for dissecting the molecular mechanisms of megakaryocytic differentiation, and that this class of compounds represents potential therapeutic reagents for thrombocytopenia. Copyright © 2012 John Wiley & Sons, Ltd.

  6. R3 Index for Four-Dimensional N =2 Field Theories

    Science.gov (United States)

    Alexandrov, Sergei; Moore, Gregory W.; Neitzke, Andrew; Pioline, Boris

    2015-03-01

    In theories with N =2 supersymmetry on R3 ,1, supersymmetric bound states can decay across walls of marginal stability in the space of Coulomb branch parameters, leading to discontinuities in the BPS indices Ω (γ ,u ) . We consider a supersymmetric index I which receives contributions from 1 /2 -BPS states, generalizing the familiar Witten index Tr (-1 )Fe-β H . We expect I to be smooth away from loci where massless particles appear, thanks to contributions from the continuum of multiparticle states. Taking inspiration from a similar phenomenon in the hypermultiplet moduli space of N =2 string vacua, we conjecture a formula expressing I in terms of the BPS indices Ω (γ ,u ), which is continuous across the walls and exhibits the expected contributions from single particle states at large β . This gives a universal prediction for the contributions of multiparticle states to the index I . This index is naturally a function on the moduli space after reduction on a circle, closely related to the canonical hyperkähler metric and hyperholomorphic connection on this space.

  7. R^{3} index for four-dimensional (N)=2 field theories.

    Science.gov (United States)

    Alexandrov, Sergei; Moore, Gregory W; Neitzke, Andrew; Pioline, Boris

    2015-03-27

    In theories with N=2 supersymmetry on R^{3,1}, supersymmetric bound states can decay across walls of marginal stability in the space of Coulomb branch parameters, leading to discontinuities in the BPS indices Ω(γ,u). We consider a supersymmetric index I which receives contributions from 1/2-BPS states, generalizing the familiar Witten index Tr(-1)^{F}e^{-βH}. We expect I to be smooth away from loci where massless particles appear, thanks to contributions from the continuum of multiparticle states. Taking inspiration from a similar phenomenon in the hypermultiplet moduli space of N=2 string vacua, we conjecture a formula expressing I in terms of the BPS indices Ω(γ,u), which is continuous across the walls and exhibits the expected contributions from single particle states at large β. This gives a universal prediction for the contributions of multiparticle states to the index I. This index is naturally a function on the moduli space after reduction on a circle, closely related to the canonical hyperkähler metric and hyperholomorphic connection on this space.

  8. Genome-Wide Identification of R2R3-MYB Genes and Expression Analyses During Abiotic Stress in Gossypium raimondii

    Science.gov (United States)

    He, Qiuling; Jones, Don C.; Li, Wei; Xie, Fuliang; Ma, Jun; Sun, Runrun; Wang, Qinglian; Zhu, Shuijin; Zhang, Baohong

    2016-01-01

    The R2R3-MYB is one of the largest families of transcription factors, which have been implicated in multiple biological processes. There is great diversity in the number of R2R3-MYB genes in different plants. However, there is no report on genome-wide characterization of this gene family in cotton. In the present study, a total of 205 putative R2R3-MYB genes were identified in cotton D genome (Gossypium raimondii), that are much larger than that found in other cash crops with fully sequenced genomes. These GrMYBs were classified into 13 groups with the R2R3-MYB genes from Arabidopsis and rice. The amino acid motifs and phylogenetic tree were predicted and analyzed. The sequences of GrMYBs were distributed across 13 chromosomes at various densities. The results showed that the expansion of the G. Raimondii R2R3-MYB family was mainly attributable to whole genome duplication and segmental duplication. Moreover, the expression pattern of 52 selected GrMYBs and 46 GaMYBs were tested in roots and leaves under different abiotic stress conditions. The results revealed that the MYB genes in cotton were differentially expressed under salt and drought stress treatment. Our results will be useful for determining the precise role of the MYB genes during stress responses with crop improvement. PMID:27009386

  9. Studies on Synthesis of Pyrimidine Derivatives and their Pharmacological Evaluation

    Directory of Open Access Journals (Sweden)

    T. A. Naik

    2007-01-01

    Full Text Available 1,3,4-Oxadiazoles were associated with broad spectrum of biological activities including antituberculosis, anticonvulsant, anti-inflammatory, insecticidal, antifungal, analgesic and antitumor properties. Morpholine derivatives find their wide spectrum of antimicrobial activity and exhibit anthelmintic, bactericidal and insecticidal activity. Pyrimidine derivatives are also reported to possess antibacterial, antimicrobial, antifungal, anticancer and anticonvulsant activities. Encouraged by this observations we decided to synthesised novel pyrimidine derivatives.

  10. Gain-of-function R225W mutation in human AMPKgamma(3 causing increased glycogen and decreased triglyceride in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Sheila R Costford

    Full Text Available BACKGROUND: AMP-activated protein kinase (AMPK is a heterotrimeric enzyme that is evolutionarily conserved from yeast to mammals and functions to maintain cellular and whole body energy homeostasis. Studies in experimental animals demonstrate that activation of AMPK in skeletal muscle protects against insulin resistance, type 2 diabetes and obesity. The regulatory gamma(3 subunit of AMPK is expressed exclusively in skeletal muscle; however, its importance in controlling overall AMPK activity is unknown. While evidence is emerging that gamma subunit mutations interfere specifically with AMP activation, there remains some controversy regarding the impact of gamma subunit mutations. Here we report the first gain-of-function mutation in the muscle-specific regulatory gamma(3 subunit in humans. METHODS AND FINDINGS: We sequenced the exons and splice junctions of the AMPK gamma(3 gene (PRKAG3 in 761 obese and 759 lean individuals, identifying 87 sequence variants including a novel R225W mutation in subjects from two unrelated families. The gamma(3 R225W mutation is homologous in location to the gamma(2R302Q mutation in patients with Wolf-Parkinson-White syndrome and to the gamma(3R225Q mutation originally linked to an increase in muscle glycogen content in purebred Hampshire Rendement Napole (RN- pigs. We demonstrate in differentiated muscle satellite cells obtained from the vastus lateralis of R225W carriers that the mutation is associated with an approximate doubling of both basal and AMP-activated AMPK activities. Moreover, subjects bearing the R225W mutation exhibit a approximately 90% increase of skeletal muscle glycogen content and a approximately 30% decrease in intramuscular triglyceride (IMTG. CONCLUSIONS: We have identified for the first time a mutation in the skeletal muscle-specific regulatory gamma(3 subunit of AMPK in humans. The gamma(3R225W mutation has significant functional effects as demonstrated by increases in basal and AMP

  11. The in-beam tracking detectors for R3B

    Energy Technology Data Exchange (ETDEWEB)

    Paschalis, Stefanos; Johansen, Jacob; Scheit, Heiko [Institut fuer Kernphysik, Technische Universitaet, D 64289 Darmstadt (Germany); Heil, Michael [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, D-64291 Darmstadt (Germany); Aumann, Thomas [Institut fuer Kernphysik, Technische Universitaet, D 64289 Darmstadt (Germany); GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, D-64291 Darmstadt (Germany); Krivshich, Anatoly [PNPI St. Petersburg, 188300 Gatchina (Russian Federation); Collaboration: R3B-Collaboration

    2015-07-01

    The R3B experiment is part of the NUSTAR pillar at FAIR. One of the great strengths of the R3B experiment is the kinematically complete measurement of reactions with exotic ions with energies of up to 1 AGeV. Key components of the R3B experiment are the neutron detector NeuLAND, the γ and charge-particle calorimeter CALIFA, the Si Tracker and the in-beam tracking detectors. A cornerstone instrument of the setup is the new dipole magnet (GLAD) which bends and momentum analyses the high-rigidity beams. A precise tracking of the charged particles through the magnetic field is crucial to resolve the masses of heavy ions and measure the momentum of the fragments with high resolution. In this contribution we present the technical design details of the in-beam tracking detectors that will be used in the R3B experiment together with recent results obtained from in-beam prototype testing. In particular, we discuss Si detectors, detectors based on plastic-scintillator fibers and paddles, straw-tube gas detectors and the overall performance of the system.

  12. (±-Pestalachloride D, an Antibacterial Racemate of Chlorinated Benzophenone Derivative from a Soft Coral-Derived Fungus Pestalotiopsis sp.

    Directory of Open Access Journals (Sweden)

    Dong-Sheng Deng

    2013-03-01

    Full Text Available A new antibacterial chlorinated benzophenone derivative, (±-pestalachloride D (1, along with a related analog, (±-pestalachloride C (2, was recently isolated from the marine-derived fungus Pestalotiopsis sp. isolated from a soft coral Sarcophyton sp. collected from Yongxing Island in the South China Sea. Both chiral HPLC analysis and single-crystal X-ray data indicated that 1 is a racemic mixture. Interestingly, 1 did not exhibit any effect in the zebrafish embryo teratogenicity assay, while 2 led to abnormal growth. The potential impact on zebrafish embryo growth is discussed based on their crystal structures. The main difference of crystal structures between 1 and 2 is that the six-member non-aromatic ring (O4, C10, C9, C8, C2′, and C3′ in 1 exhibits a distorted chair conformation, while 2 shows a distorted boat conformation. Moreover, compounds 1 and 2 both exhibited moderate antibacterial activity.

  13. miR-223 is upregulated in monocytes from patients with tuberculosis and regulates function of monocyte-derived macrophages.

    Science.gov (United States)

    Liu, Yanhua; Wang, Ruo; Jiang, Jing; Yang, Bingfen; Cao, Zhihong; Cheng, Xiaoxing

    2015-10-01

    Tuberculosis (TB) is a serious infectious disease that most commonly affects the lungs. Macrophages are among the first line defenders against establishment of Mycobacterium tuberculosis infection in the lungs. In this study, we found that activation and cytokine production in monocyte-derived macrophages (MDM) from patients with active TB was impaired. miR-223 expression was significantly elevated in monocytes and MDM from patients with TB compared with healthy controls. To determine the functional role of miR-223 in macrophages, stable miR-223-expressing and miR-223 antisense-expressing U937 cells were established. Compared with empty vector controls, expression of IL-1β, IL-6, TNF-α and IL-12p40 genes was significantly higher in miR-223 antisense-expressing U937 cells, but lower in miR-223-expressing U937 cells. miR-223 can negatively regulate activation of NF-κB by inhibition of p65 phosphorylation and nuclear translocation. It is concluded that miR-223 can regulate macrophage function by inhibition of cytokine production and NF-κB activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. -5p and -3p strands of miR-145 and miR-140 during mesenchymal stem cell chondrogenic differentiation.

    Science.gov (United States)

    Kenyon, Jonathan D; Sergeeva, Olga; Somoza, Rodrigo A; Li, Ming; Caplan, Arnold I; Khalil, Ahmad M; Lee, Zhenghong

    2018-04-20

    The chondrogenic differentiation of mesenchymal stem cells (MSCs) is mediated by transcription factors and small non-coding RNAs such as micro-RNAs (miRNAs). Each miRNA is initially transcribed as a long transcript, which matures to produce -5p and -3p strands. It is widely believed that the mature and functional miRNA from any given pre-miRNA, usually the -5p strand, is functional, while the opposing -3p strand is degraded. However, recent cartilage literature started to show functional -3p stands for a few miRNAs. This study aimed at examining both -5p and -3p strands of two key miRNAs miR-140 and miR-145 that are known to be involved in the chondrogenic differentiation of MSCs. The level (copy number) of both -5p and -3p strands of miR-145 and miR-140 along the timeline of MSC chondrogenic differentiation was determined by PCR. The gene expression profiles of several genes related to MSC chondrogenesis were compared with these miRNA profiles along the same timeline. While miR-145-3p is declining in step with miR-145-5p in pellet cultures during the process, the -3p strand is only 1% - 2% of the total miR-145 products. In contrast, the mature -3p and -5p products of miR-140 are found to increase with near equal molar expression throughout chondrogenic differentiation. Numerous genes are expressed by cartilage progenitor cells during development. One such target gene, Sox9 is a regulatory target of the dominant miR-145-5p, consistent with the data. Further experimental validations are warranted to confirm that ACAN, FOXO1 and RUNX3 as direct targets of miR-145-5p in the context of MSC chondrogenesis. Similarly, TRSP1 and ACAN are worth further validation as direct targets of miR-145-3p. For miR-140, SOX4 shall be further validated as a direct target of miR-140-5p while KLF4, PTHLH, and WNT5A can be validated as direct targets of miR-140-3p.

  15. High-grade histologic features of DCIS are associated with R5 rather than R3 calcifications in breast screening mammography.

    LENUS (Irish Health Repository)

    Hayes, Brian D

    2013-01-01

    Mammographic calcification is an important radiologic feature of early breast carcinoma whose index of suspicion for malignancy may be reported by a five-tier R-category system. This study aims to describe the histologic diagnoses underlying screen-detected mammographic calcifications using both digital and screen-film mammography, and to correlate these findings with radiologic R-categories. Patients attending the Merrion Breast Screening Unit in Dublin between 2000 and 2011 were identified, who underwent needle-core biopsy for assessment of mammographic calcifications without associated mass or architectural distortion. Radiologic R-category was correlated with biopsy and excision histology reports. A total of 776 cases of calcification were identified, involving 769 individual patients. The radiologic R-categories were as follows: R3 513 (66.1%), R4 192 (24.7%), R5 71 (9.1%). The positive predictive values for malignancy were R3 32.6%, R4 69.8%, R5 95.8%. Several histologic features of DCIS were associated with R5 rather than R3 radiology: high nuclear grade, solid or cribriform architecture, necrosis, periductal inflammation or fibrosis, and associated microinvasive or invasive carcinoma. Mammographic lesions and histologic whole and invasive tumors increased in size from R3 to R5. Radiologic size of calcifications correlated with whole (but not invasive) tumor size, although it tended to underestimate it by several millimeters. Digital-detected calcifications were more likely than screen-film detected to be categorized as R3 and less likely R4 or R5, and there was no significant difference in positive predictive value between the two imaging techniques in any R-category. In conclusion, histologic features of DCIS, in particular those associated with high grade, are associated with R5 radiology. There is no significant difference in positive predictive value for malignancy in any R-category between digital and screen-film mammography.

  16. SYNTHESIS AND PHYSICAL-CHEMICAL PROPERTIES OF WATER-SOLUBLE 3-BENZYLXANTHINE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    K. V. Аleksandrova

    2015-04-01

    Full Text Available Introduction Nowadays, research of novel biological active compounds with low toxicity, are carried out among different classes of organic compounds of natural and synthetic genesis. One of the main ways of these studies is search of water-soluble compounds – convenient objects for pharmacological researches. In recent years researchers paid attention to xanthine derivatives, because of their high variativity of possible chemical modification and ability to form different salts with wide spectrum of biological action. Thus, among water-soluble xanthine derivatives were found compounds with pronounced antioxidant, diuretic and analeptic properties. Primary methods of obtaining water-soluble xanthine derivatives are direct interaction of bases with xanthine molecule or insertion basic or acidic residues in positions 7 or 8 of xanthine bicycle. According from the above, search of biologically active compounds among water-soluble substituted xanthines is prospective and actual. The aim of the study was development of synthetic ways of obtaining novel water-soluble derivatives of 3-benzyl-8-methylxanthine and studying their physical and chemical properties. Material and methods Melting points of obtained compounds were determined by capillary method on PTP (M device. ІR-spectra of synthesized compounds were recorded on the Bruker Alpha device (company «Bruker» – Germany on 4000-400 sm-1 with using console ATR (direct insertion of compound. 1Н NMR-spectra were recorded on the Varian Mercury VX-200 device (company «Varian» – USA solvent – (DMSO-d6, internal standart – ТМС. Elemental analysis was made on Elementar Vario L cube device. Chromatoraphic studies were made on the plates Sorbfil-AFV-UV (company «Sobrpolimer» –Russia. Systhems for chromatography: «acetone-propanol-2» in ratio 2:3, «propanol-2-benzene» in ratio 10:1 and exersized in UV-light in wave 200-300 nm. Results and discussion We developed methodic of synthesis

  17. (R,S)-3-Carb?oxy-2-(isoquinolinium-2-yl)propanoate monohydrate

    OpenAIRE

    Stilinovi?, Vladimir; Frkanec, Leo; Kaitner, Branko

    2010-01-01

    The title compound, C13H11NO4·H2O, is a monohydrate of a betaine exhibiting a positively charged N-substituted isoquinoline group and a deprotonated carboxyl group. In the crystal, molecules are connected via short O—H...O hydrogen bonds between protonated and deprotonated carboxyl groups into chains of either R or S enantiomers along [001]. These chains are additionally connected by hydrogen bonding between water molecules and the deprotonated carboxy groups of neighbourin...

  18. Neutron scattering study on R2PdSi3 (R=Ho,Er,Tm) compounds

    International Nuclear Information System (INIS)

    Tang, Fei

    2010-01-01

    Previous studies on the family of inter-metallic rare-earth compounds R 2 PdSi 3 revealed multifaceted magnetic properties, for instance, spin-glass like behavior. Experimental observations include: Signs of a crystallographic superstructure, complicated magnetic structures both in zero field and in applied magnetic fields as well as a generic phase in applied fields for compounds in the series with the heavy rare-earths R=Gd, Tb, Dy, Ho, Er and Tm. This thesis expands the studies on the magnetic properties of R 2 PdSi 3 employing mainly neutron scattering on single crystals with the focus on the compounds with R=Ho, Er and Tm. A detailed analysis of the crystallographic superstructure using modulation wave approach and group theory is presented. The resulting structure implies the existence of two different rare-earth sites with reduced symmetry and an arrangement of the different sites according to sequences as determined by the superstructure. It is shown that the reduced symmetry of the rare-earth sites is explicitly observed in the energy spectra of inelastic neutron scattering. The results on the magnetic structures and excitations are shown and discussed in the framework of the superstructure model. Specifically the generic phase in applied fields is interpreted as a direct consequence of the crystallographic superstructure. It is rather unusual that a crystallographic superstructure is playing such a decisive, and through the field dependence also tunable role in determining the magnetic properties as observed in R 2 PdSi 3 . The mediating interactions between the crystallographic part and the magnetic part of the system are discussed. (orig.)

  19. Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291.

    Science.gov (United States)

    Zhang, Peng; Li, Xiao-Ming; Mao, Xin-Xin; Mándi, Attila; Kurtán, Tibor; Wang, Bin-Gui

    2016-01-01

    A new indolyl-6,10b-dihydro-5a H -[1]benzofuro[2,3- b ]indole derivative, varioloid A ( 1 ), was isolated from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291. Its structure was elucidated on the basis of extensive analysis of 1D and 2D NMR data and the absolute configuration was determined by time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. A similar compound, whose planar structure was previously described but the relative and absolute configurations and 13 C NMR data were not reported, was also identified and was tentatively named as varioloid B ( 2 ). Both compounds 1 and 2 exhibited cytotoxicity against A549, HCT116, and HepG2 cell lines, with IC 50 values ranging from 2.6 to 8.2 µg/mL.

  20. Novel series of 1,2,4-trioxane derivatives as antimalarial agents.

    Science.gov (United States)

    Rudrapal, Mithun; Chetia, Dipak; Singh, Vineeta

    2017-12-01

    Among three series of 1,2,4-trioxane derivatives, five compounds showed good in vitro antimalarial activity, three compounds of which exhibited better activity against P. falciparum resistant (RKL9) strain than the sensitive (3D7) one. Two best compounds were one from aryl series and the other from heteroaryl series with IC 50 values of 1.24 µM and 1.24 µM and 1.06 µM and 1.17 µM, against sensitive and resistant strains, respectively. Further, trioxane derivatives exhibited good binding affinity for the P. falciparum cysteine protease falcipain 2 receptor (PDB id: 3BPF) with well defined drug-like and pharmacokinetic properties based on Lipinski's rule of five with additional physicochemical and ADMET parameters. In view of having antimalarial potential, 1,2,4-trioxane derivative(s) reported herein may be useful as novel antimalarial lead(s) in the discovery and development of future antimalarial drug candidates as P. falciparum falcipain 2 inhibitors against resistant malaria.

  1. DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC.

    Science.gov (United States)

    Liu, Yan-Ping; Zhu, Hui-Fang; Liu, Ding-Li; Hu, Zhi-Yan; Li, Sheng-Nan; Kan, He-Ping; Wang, Xiao-Yan; Li, Zu-Guo

    2016-11-22

    Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.

  2. Theoretical study of GC+/GC base pair derivatives

    International Nuclear Information System (INIS)

    Meng Fancui; Wang Huanjie; Xu Weiren; Liu Chengbu

    2005-01-01

    The geometries of R (R=CH 3 , CH 3 O, F, NO 2 ) substituted GC base pair derivatives and their cations have been optimized at B3LYP/6-31G* level and the substituent effects on the neutral and cationic geometric structures and energies have been discussed. The inner reorganization energies of various base pair derivatives and the native GC base pair have been calculated to discuss the substituent effects on the reorganization energy. NBO (natural bond orbital) analysis has been carried out on both the neutral and the cationic systems to investigate the differences of the charge distributions and the electronic structures. The outcomes indicate that 8-CH 3 O-G:C has the greatest reorganization energy and 8-NO 2 -G:C has the least, while the other substituted base pairs have a reorganization energy close to that of G:C. The one charge is mostly localized on guanine part after ionization and as high as 0.95e. The bond distances of N1-N3'andN2-O2' in the cationic base pair derivatives shortened and that of O6-N4' elongated as compared with the corresponding bond distances of the neutral GC base pair derivatives

  3. Electronic, elastic and optical properties of divalent (R+2X) and trivalent (R+3X) rare earth monochalcogenides

    Science.gov (United States)

    Kumar, V.; Chandra, S.; Singh, J. K.

    2017-08-01

    Based on plasma oscillations theory of solids, simple relations have been proposed for the calculation of bond length, specific gravity, homopolar energy gap, heteropolar energy gap, average energy gap, crystal ionicity, bulk modulus, electronic polarizability and dielectric constant of rare earth divalent R+2X and trivalent R+3X monochalcogenides. The specific gravity of nine R+2X, twenty R+3X, and bulk modulus of twenty R+3X monochalcogenides have been calculated for the first time. The calculated values of all parameters are compared with the available experimental and the reported values. A fairly good agreement has been obtained between them. The average percentage deviation of two parameters: bulk modulus and electronic polarizability for which experimental data are known, have also been calculated and found to be better than the earlier correlations.

  4. A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines.

    Science.gov (United States)

    Solarte, Víctor A; Rosas, Jaiver E; Rivera, Zuly J; Arango-Rodríguez, Martha L; García, Javier E; Vernot, Jean-Paul

    2015-01-01

    Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20-25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC.

  5. Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma

    International Nuclear Information System (INIS)

    Zhai, Qingna; Zhou, Liang; Zhao, Chunjuan; Wan, Jun; Yu, Zhendong; Guo, Xin; Qin, Jie; Chen, Jing; Lu, Ruijing

    2012-01-01

    Highlights: ► Previous method was the second-generation sequencing technology. ► miR-508-3p and miR-509-3p were significantly down-regulated in RCC tissues. ► They can inhibit cell proliferation and migration and promote cell apoptosis. ► The expression of miR-508-3p was significantly decreased in RCC patients plasma. ► miR-508-3p may be a novel diagnostic marker of RCC. -- Abstract: MicroRNAs (miRNAs) have emerged as powerful regulators of multiple processes linked to human cancer, including cell apoptosis, proliferation and migration, suggesting that the regulation of miRNA function could play a critical role in cancer progression. Recent studies have found that human serum/plasma contains stably expressed miRNAs. If they prove indicative of disease states, miRNAs measured from peripheral blood samples may be a source for routine clinical detection of cancer. Our studies showed that both miR-508-3p and miR-509-3p were down-regulated in renal cancer tissues. The level of miR-508-3p but not miR-509-3p in renal cell carcinoma (RCC) patient plasma demonstrated significant differences from that in control plasma. In addition, the overexpression of miR-508-3p and miR-509-3p suppressed the proliferation of RCC cells (786-0), induced cell apoptosis and inhibited cell migration in vitro. Our data demonstrated that miR-508-3p and miR-509-3p played an important role as tumor suppressor genes during tumor formation and that they may serve as novel diagnostic markers for RCC.

  6. 1,3-Oxazin-6-one Derivatives and Bohemamine-Type Pyrrolizidine Alkaloids from a Marine-Derived Streptomyces spinoverrucosus.

    Science.gov (United States)

    Fu, Peng; La, Scott; MacMillan, John B

    2016-03-25

    Two new 1,3-oxazin-6-one derivatives (1 and 2) and six new bohemamine-type pyrrolizidine alkaloids (3-8) were isolated from the marine-derived Streptomyces spinoverrucosus strain SNB-048. Their structures including the absolute configurations were fully elucidated on the basis of spectroscopic analysis, ECD spectra, quantum chemical calculations, and chemical methods. Compounds 1 and 2 possess a γ-lactam moiety and a 1,3-oxazin-6-one system.

  7. Three-dimensional tetranuclear Cd(II) coordination network based on a 1,3-alternate calix[4]arene derivative

    International Nuclear Information System (INIS)

    Lee, Eun Ji; Ju, Hui Yeong; Park, Ki Min; Moon, ASuk Hee; Kang, Young Jin

    2015-01-01

    Polynuclear coordination polymers can exhibit more intriguing network topologies and better functionalities than those of common complexes because they have metal-cluster nodes for the construction of multidimensional frameworks and the potential applications induced by collaborative activities between metal ions. New tetranuclear Cd(II) coordination polymer 1 based on 1,3-alternate calix arene derivative (H_4 CTA) with four carboxyl pendant arms has been synthesized by the solvo thermal reaction at 110 .deg. C for 2 days. Compound 1 shows a 3-D framework consisting of tetranuclear Cd(II) cluster core as a metal-cluster node and 1,3-alternate H_4CTA as a multidentate linker. The coordination polymer 1 displays intense blue emission, implying that this tetranuclear Cd(II) coordination polymer could be a suitable material in the area of luminescence research

  8. Altered regulation of miR-34a and miR-483-3p in alcoholic hepatitis and DDC fed mice.

    Science.gov (United States)

    Liu, Hui; French, Barbara A; Li, Jun; Tillman, Brittany; French, Samuel W

    2015-12-01

    MicroRNAs are small noncoding RNAs that negatively regulate gene expression by binding to the untranslated regions of their target mRNAs. Deregulation of miRNAs is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of miR-34a and miR-483-3p by RNA sequencing (RNA-Seq) analyses. Real-time PCR further shows a 3- and 6-fold upregulation (respectively) of miR-34a in the AH livers and in the livers of DDC re-fed mice, while miR-483-3p was significantly downregulated in AH and DDC re-fed mice livers. This indicates that miR-34a and miR-483-3p may be crucial for liver MDB formation. P53 mRNA was found to be significantly downregulated both in the AH livers and in the livers of DDC re-fed mice, indicating that the upregulation of miR-34a is permitted by the decrease of p53 in AH since miR-34a is a main target of p53. Overexpression of miR-34a leads to an increase of p53 targets such as p27, which inhibits the cell cycle leading to cell cycle arrest. Importantly, BRCA1 is a target gene of miR-483-3p by RNA-Seq analyses and the downregulation of miR-483-3p may be the mechanism for liver MDB formation since the BRCA1 signal was markedly upregulated in AH livers. These results constitute a demonstration of the altered regulation of miR-34a and miR-483-3p in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by miR-34a and miR-483-3p in AH. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. [Over-expression of miR-151a-3p inhibits proliferation and migration of PC-3 prostate cancer cells].

    Science.gov (United States)

    Zhang, Yi; Hao, Tongtong; Zhang, Han; Wei, Pengtao; Li, Xiaohui

    2018-03-01

    Objective To observe the effect of microRNA-151a-3p (miR-151a-3p) up-regulation on the proliferation and migration of prostate cancer cells and explore the possible molecular mechanism. Methods The expression of miR-151a-3p in PC-3M, C4-2B, 22RV1, DU-145, PC-3, LNCap human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time fluorescence quantitative PCR. PC-3 cells with the lowest expression of miR-151a-3p were used for subsequent experiments. Bioinformatics and dual-luciferase reporter assay were performed to predict and test potential target genes of miR-151a-3p. The miR-151a-3p mimics or negative control microRNAs (miR-NCs) were transfected into PC-3 cells. Real-time fluorescence quantitative PCR was used to detect the expression of miR-151a-3p and potential target gene mRNA. The protein expressions of target genes and downstream signaling pathway proteins were analyzed by Western blotting. The proliferation of PC-3 cells was examined by MTT assay, and the migration of PC-3 cells was detected by Transwell TM assay. Results The expression level of miR-151a-3p in the prostate cancer cells was significantly lower than that in RWPE-1 normal human prostate epithelial cells. PC-3 cells had the lowest expression level of miR-151a-3p. The bioinformatics and dual-luciferase reporter assay showed that NEK2 was the potential target gene for miR-151a-3p. After transfection with miR-151a-3p mimics, the expression of miR-151a-3p in PC-3 cells significantly increased and the expression of NEK2 mRNA significantly decreased. The protein expressions of PI3K-AKT-mTOR signaling pathway were also reduced. Up-regulation of miR-151a-3p significantly inhibited the proliferation and migration of PC-3 cells. Conclusion The expression of miR-151a-3p is reduced in prostate cancer cells. Up-regulation of miR-151a-3p can inhibit the proliferation and migration of P-3 in prostate cancer by decreasing the expression of NEK2 and PI3K

  10. Centrally acting serotonergic and dopaminergic agents. 1. Synthesis and structure-activity relationships of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives.

    Science.gov (United States)

    Lin, C H; Haadsma-Svensson, S R; Lahti, R A; McCall, R B; Piercey, M F; Schreur, P J; Von Voigtlander, P F; Smith, M W; Chidester, C G

    1993-04-16

    The synthesis and structure-activity relationships (SAR) of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives (3) are described. These compounds are conformationally restricted, angular tricyclic analogs of 2-aminotetralin. The synthesis was achieved in several steps from the corresponding 2-tetralones. The enantiomers of the cis analogs were obtained from either fractional recrystallizations of the diastereomeric salts of di-p-toluoyl-L-(or D)-tartaric acid or an asymmetric synthesis using chiral (R)-alpha-methylbenzylamine. All analogs were evaluated in the in vitro 5-HT1A and D2 binding assays and selected analogs were investigated further in biochemical and behavioral tests. Analogs with 9-methoxy substitution (R1 in 3) showed mixed 5-HT1A agonist and dopamine antagonist activities whereas the corresponding 9-hydroxy analogs displayed selective 5-HT1A agonist activity. The cis analogs were found to be more potent than the corresponding trans analogs and in the cis series, the (3aR)-(-)-enantiomers displayed higher potency. Nitrogen substitution (R2 in 3) with either an n-propyl or an allyl group produced similar activities whereas replacement with a bulky alpha-methylbenzyl group resulted in loss of activity. Analogs without aromatic substitution (R1 = H in 3) still showed good 5-HT1A agonist activity, although less potent than the 9-methoxy series. In this case, the trans analogs possessed equal or higher in vitro 5-HT1A affinity than the corresponding cis analogs. Analogs with either 6-methoxy or 6-hydroxy substitution (R1 in 3) were found to display dopamine antagonist properties. However, only N-allyl analogs showed this activity. In the 6-methoxy-N-allyl series, the cis analog was found to be more potent than the trans analog. Again, between the pair of cis enantiomers, the (3aR)-(-)-enantiomer showed higher potency. Incorporation of an additional methyl group into 9-methoxy cis analogs at C-2 resulted in retention of potent 5-HT1A agonist activity.

  11. The coordination office at SIREME 2008 exhibition

    International Nuclear Information System (INIS)

    Grotz, Claudia; Cassin, Fabrice; Evrard, Aurelien; Froeding, Veronique; Galaup, Serge; Kaelble, Laure; Persem, Melanie; Regnier, Yannick; )

    2008-01-01

    The French-German office for Renewable energies (OFAEnR) organised several presentations at the occasion of the SIREME International exhibition of renewable energies and energy management. This document brings together these presentations (slides) dealing with: 1 - The new German Renewable Energy Sources Act (EEG) and its impact on wind energy (Claudia Grotz); 2 - Consequences of the July 10, 2006 wind energy tariff bylaw cancelling (Fabrice Cassin); 3 - Wind energy trajectory in France and Germany: a political perspective (Aurelien Evrard); 4 - The wind energy development areas (Veronique Froeding); 5 - A commitment at the heart of our business: renewable energy sources (Serge Galaup); 6 - The wind energy coordination office (Laure Kaelble); 7 - New challenges of the German wind energy market (Melanie Persem); 8 - An industry - a qualification standard (Yannick Regnier)

  12. An R2R3-MYB transcription factor, OjMYB1, functions in anthocyanin biosynthesis in Oenanthe javanica.

    Science.gov (United States)

    Feng, Kai; Xu, Zhi-Sheng; Que, Feng; Liu, Jie-Xia; Wang, Feng; Xiong, Ai-Sheng

    2018-02-01

    This study showed that an R2R3-MYB transcription factor, OjMYB1, is involved in anthocyanin biosynthesis and accumulation in Oenanthe javanica. Anthocyanins can be used as safe natural food colorants, obtained from many plants. R2R3-MYB transcription factors (TFs) play important roles in anthocyanins biosynthesis during plant development. Oenanthe javanica is a popular vegetable with high nutritional values and numerous medical functions. O. javanica has purple petioles that are mainly due to anthocyanins accumulation. In the present study, the gene encoding an R2R3-MYB TF, OjMYB1, was isolated from purple O. javanica. Sequencing results showed that OjMYB1 contained a 912-bp open reading frame encoding 303 amino acids. Sequence alignments revealed that OjMYB1 contained bHLH-interaction motif ([DE]Lx2[RK]x3Lx6Lx3R) and ANDV motif ([A/G]NDV). Phylogenetic analysis indicated that the OjMYB1 classified into the anthocyanins biosynthesis clade. Subcellular localization assay showed that OjMYB1 was a nuclear protein in vivo. The heterologous expression of OjMYB1 in Arabidopsis could enhance the anthocyanins content and up-regulate the expression levels of the structural genes-related anthocyanins biosynthesis. Yeast two-hybrid assay indicated that OjMYB1 could interact with AtTT8 and AtEGL3 proteins. Enzymatic analysis revealed that overexpression of OjMYB1 gene up-regulated the enzyme activity of 3-O-glycosyltransferase encoded by AtUGT78D2 in transgenic Arabidopsis. Our results provided a comprehensive understanding of the structure and function of OjMYB1 TF in O. javanica.

  13. Implantación del sistema ERP SAP R/3

    OpenAIRE

    Muñoz Fernandez, Jorge Juan

    2012-01-01

    El objetivo del presente trabajo ha sido realizar un estudio de investigación y desarrollo sobre la implantación del sistema Enterprise Resource Planning (ERP) SAP R/3 de una empresa. L'objectiu d'aquest treball final de carrera ha estat realitzar un estudi d'investigació i desenvolupament sobre la implantació del sistema Enterprise Resource Planning (ERP) SAP R/3 d'una empresa.

  14. The TLX-miR-219 cascade regulates neural stem cell proliferation in neurodevelopment and schizophrenia iPSC model.

    Science.gov (United States)

    Murai, Kiyohito; Sun, Guoqiang; Ye, Peng; Tian, E; Yang, Su; Cui, Qi; Sun, Guihua; Trinh, Daniel; Sun, Olivia; Hong, Teresa; Wen, Zhexing; Kalkum, Markus; Riggs, Arthur D; Song, Hongjun; Ming, Guo-li; Shi, Yanhong

    2016-03-11

    Dysregulated expression of miR-219, a brain-specific microRNA, has been observed in neurodevelopmental disorders, such as schizophrenia (SCZ). However, its role in normal mammalian neural stem cells (NSCs) and in SCZ pathogenesis remains unknown. We show here that the nuclear receptor TLX, an essential regulator of NSC proliferation and self-renewal, inhibits miR-219 processing. miR-219 suppresses mouse NSC proliferation downstream of TLX. Moreover, we demonstrate upregulation of miR-219 and downregulation of TLX expression in NSCs derived from SCZ patient iPSCs and DISC1-mutant isogenic iPSCs. SCZ NSCs exhibit reduced cell proliferation. Overexpression of TLX or inhibition of miR-219 action rescues the proliferative defect in SCZ NSCs. Therefore, this study uncovers an important role for TLX and miR-219 in both normal neurodevelopment and in SCZ patient iPSC-derived NSCs. Moreover, this study reveals an unexpected role for TLX in regulating microRNA processing, independent of its well-characterized role in transcriptional regulation.

  15. Neuroprotective Efficacy of an Aminopropyl Carbazole Derivative P7C3-A20 in Ischemic Stroke.

    Science.gov (United States)

    Wang, Shu-Na; Xu, Tian-Ying; Wang, Xia; Guan, Yun-Feng; Zhang, Sai-Long; Wang, Pei; Miao, Chao-Yu

    2016-09-01

    NAMPT is a novel therapeutic target of ischemic stroke. The aim of this study was to investigate the effect of a potential NAMPT activator, P7C3-A20, an aminopropyl carbazole derivative, on ischemic stroke. In vitro study, neuron protection effect of P7C3-A20 was investigated by co-incubation with primary neurons subjected to oxygen-glucose deprivation (OGD) or oxygen-glucose deprivation/reperfusion (OGD/R) injury. In vivo experiment, P7C3-A20 was administrated in middle cerebral artery occlusion (MCAO) rats and infarct volume was examined. Lastly, the brain tissue nicotinamide adenine dinucleotide (NAD) levels were detected in P7C3-A20 treated normal or MCAO mice. Cell viability, morphology, and Tuj-1 staining confirmed the neuroprotective effect of P7C3-A20 in OGD or OGD/R model. P7C3-A20 administration significantly reduced cerebral infarction in MCAO rats. Moreover, brain NAD levels were elevated both in normal and MCAO mice after P7C3-A20 treatment. P7C3-A20 has neuroprotective effect in cerebral ischemia. The study contributes to the development of NAMPT activators against ischemic stroke and expands the horizon of the neuroprotective effect of aminopropyl carbazole chemicals. © 2016 John Wiley & Sons Ltd.

  16. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Yerly Vargas Casanova

    2017-09-01

    Full Text Available Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922 and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

  17. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines.

    Science.gov (United States)

    Vargas Casanova, Yerly; Rodríguez Guerra, Jorge Antonio; Umaña Pérez, Yadi Adriana; Leal Castro, Aura Lucía; Almanzar Reina, Giovanni; García Castañeda, Javier Eduardo; Rivera Monroy, Zuly Jenny

    2017-09-29

    Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)₂K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

  18. Stability and Antioxidant Activity of Semi-synthetic Derivatives of 4-Nerolidylcatechol

    Directory of Open Access Journals (Sweden)

    Emerson Silva Lima

    2012-12-01

    Full Text Available 4-nerolidylcatechol (4-NC is an unstable natural product that exhibits important antioxidant, anti-inflammatory and other properties. It is readily obtainable on a multi-gram scale through straightforward solvent extraction of the roots of cultivated Piper peltatum or P. umbellatum, followed by column chromatography on the resulting extract. Semi-synthetic derivatives of 4-NC with one or two substituent groups (methyl, acetyl, benzyl, benzoyl on the O atoms have been introduced that have increased stability compared to 4-NC and significant in vitro inhibitory activity against the human malaria parasite Plasmodium falciparum. Antioxidant and anti-inflammatory properties may be important for the antiplasmodial mode of action of 4-NC derivatives. Thus, we decided to investigate the antioxidant properties, cytotoxicity and stability of 4-NC derivatives as a means to explore the potential utility of these compounds. 4-NC showed high antioxidant activity in the DPPH and ABTS assays and in 3T3-L1 cells (mouse embryonic fibroblast, however 4-NC was more cytotoxic (IC50 = 31.4 µM and more unstable than its derivatives and lost more than 80% of its antioxidant activity upon storage in solution at −20 °C for 30 days. DMSO solutions of mono-O-substituted derivatives of 4-NC exhibited antioxidant activity and radical scavenging activity in the DPPH and ABTS assays that was comparable to that of BHA and BHT. In the cell-based antioxidant model, most DMSO solutions of derivatives of 4-NC were less active on day 1 than 4-NC, quercetin and BHA and more active antioxidants than BHT. After storage for 30 days at −20 °C, DMSO solutions of most of the derivatives of 4-NC were more stable and exhibited more antioxidant activity than 4-NC, quercetin and BHA and exhibited comparable antioxidant activity to BHT. These findings point to the potential of derivatives of 4-NC as antioxidant compounds.

  19. Phenotypic characterization of miR-92a-/- mice reveals an important function of miR-92a in skeletal development.

    Directory of Open Access Journals (Sweden)

    Daniela Penzkofer

    Full Text Available MicroRNAs (miRNAs, miRs emerged as key regulators of gene expression. Germline hemizygous deletion of the gene that encodes the miR-17∼92 miRNA cluster was associated with microcephaly, short stature and digital abnormalities in humans. Mice deficient for the miR-17∼92 cluster phenocopy several features such as growth and skeletal development defects and exhibit impaired B cell development. However, the individual contribution of miR-17∼92 cluster members to this phenotype is unknown. Here we show that germline deletion of miR-92a in mice is not affecting heart development and does not reduce circulating or bone marrow-derived hematopoietic cells, but induces skeletal defects. MiR-92a-/- mice are born at a reduced Mendelian ratio, but surviving mice are viable and fertile. However, body weight of miR-92a-/- mice was reduced during embryonic and postnatal development and adulthood. A significantly reduced body and skull length was observed in miR-92a-/- mice compared to wild type littermates. µCT analysis revealed that the length of the 5th mesophalanx to 5th metacarpal bone of the forelimbs was significantly reduced, but bones of the hindlimbs were not altered. Bone density was not affected. These findings demonstrate that deletion of miR-92a is sufficient to induce a developmental skeletal defect.

  20. Total Synthesis of (R, R, R)-gamma-Tocopherol through Cu-Catalyzed Asymmetric 1,2-Addition

    NARCIS (Netherlands)

    Wu, Zhongtao; Harutyunyan, Syuzanna R.; Minnaard, Adriaan J.

    2014-01-01

    Based on the asymmetric copper-catalyzed 1,2-addition of Grignard reagents to ketones, (R,R,R)--tocopherol has been synthesized in 36% yield over 12 steps (longest linear sequence). The chiral center in the chroman ring was constructed with 73% ee by the 1,2-addition of a phytol-derived Grignard

  1. High Performance Analytics with the R3-Cache

    Science.gov (United States)

    Eavis, Todd; Sayeed, Ruhan

    Contemporary data warehouses now represent some of the world’s largest databases. As these systems grow in size and complexity, however, it becomes increasingly difficult for brute force query processing approaches to meet the performance demands of end users. Certainly, improved indexing and more selective view materialization are helpful in this regard. Nevertheless, with warehouses moving into the multi-terabyte range, it is clear that the minimization of external memory accesses must be a primary performance objective. In this paper, we describe the R 3-cache, a natively multi-dimensional caching framework designed specifically to support sophisticated warehouse/OLAP environments. R 3-cache is based upon an in-memory version of the R-tree that has been extended to support buffer pages rather than disk blocks. A key strength of the R 3-cache is that it is able to utilize multi-dimensional fragments of previous query results so as to significantly minimize the frequency and scale of disk accesses. Moreover, the new caching model directly accommodates the standard relational storage model and provides mechanisms for pro-active updates that exploit the existence of query “hot spots”. The current prototype has been evaluated as a component of the Sidera DBMS, a “shared nothing” parallel OLAP server designed for multi-terabyte analytics. Experimental results demonstrate significant performance improvements relative to simpler alternatives.

  2. Degenerate r-Stirling Numbers and r-Bell Polynomials

    Science.gov (United States)

    Kim, T.; Yao, Y.; Kim, D. S.; Jang, G.-W.

    2018-01-01

    The purpose of this paper is to exploit umbral calculus in order to derive some properties, recurrence relations, and identities related to the degenerate r-Stirling numbers of the second kind and the degenerate r-Bell polynomials. Especially, we will express the degenerate r-Bell polynomials as linear combinations of many well-known families of special polynomials.

  3. 4-cyano-3-hydroxybutanoyl hydrazines, derivatives and process for the preparation thereof

    Energy Technology Data Exchange (ETDEWEB)

    Hollingsworth, Rawle I. (Haslett, MI); Wang, Guijun (East Lansing, MI)

    2000-01-01

    Novel 4-cyano-3-hydroxybutanoyl hydrazides (10), particularly R-chiral intermediates are described. The intermediates are useful in preparing (R)-3-hydroxy-4-trimethylaminobutyric acid (L-carnitine) and R-4-amino-3-hydroxybutyric acid (GABOB) and chiral chemical intermediates which are medically useful.

  4. Deep R-band counts of z ≈ 3 Lyman-break galaxy candidates with the LBT

    Science.gov (United States)

    Boutsia, K.; Grazian, A.; Giallongo, E.; Castellano, M.; Pentericci, L.; Fontana, A.; Fiore, F.; Gallozzi, S.; Cusano, F.; Paris, D.; Speziali, R.; Testa, V.

    2014-03-01

    Aims: We present a deep multiwavelength imaging survey (UGR) in 3 different fields, Q0933, Q1623, and COSMOS, for a total area of ~1500 arcmin2. The data were obtained with the Large Binocular Camera on the Large Binocular Telescope. Methods: To select our Lyman-break galaxy (LBG) candidates, we adopted the well established and widely used color-selection criterion (U - G vs. G - R). One of the main advantages of our survey is that it has a wider dynamic color range for U-dropout selection than in previous studies. This allows us to fully exploit the depth of our R-band images, obtaining a robust sample with few interlopers. In addition, for 2 of our fields we have spectroscopic redshift information that is needed to better estimate the completeness of our sample and interloper fraction. Results: Our limiting magnitudes reach 27.0(AB) in the R band (5σ) and 28.6(AB) in the U band (1σ). This dataset was used to derive LBG candidates at z ≈ 3. We obtained a catalog with a total of 12 264 sources down to the 50% completeness magnitude limit in the R band for each field. We find a surface density of ~3 LBG candidates arcmin-2 down to R = 25.5, where completeness is ≥95% for all 3 fields. This number is higher than the original studies, but consistent with more recent samples. Observations were carried out using the Large Binocular Telescope at Mt. Graham, AZ. The LBT is an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are The University of Arizona on behalf of the Arizona university system; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Astrophysical Institute Potsdam, and Heidelberg University; The Ohio State University; and The Research Corporation, on behalf of The University of Notre Dame, University of Minnesota, and University of Virginia.Full Tables A.1-A.3 are only available at the CDS via anonymous ftp to http

  5. Magnetic nanosized rare earth iron garnets R_3Fe_5O_1_2: Sol–gel fabrication, characterization and reinspection

    International Nuclear Information System (INIS)

    Opuchovic, Olga; Kareiva, Aivaras; Mazeika, Kestutis; Baltrunas, Dalis

    2017-01-01

    The magnetic nanosized rare earth iron garnets (R_3Fe_5O_1_2, where R=Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) were prepared by an aqueous sol–gel method. Herein we present, that all these garnets can be obtained by this effective synthesis method simply by changing the temperature of the final annealing. It was also demonstrated, that a different annealing temperature leads to a different particle size distribution of the final product. The SEM analysis results revealed that the smallest particles were formed in the range of 75–130 nm. The phase purity and structure of the rare earth iron garnets were estimated using XRD analysis and Mössbauer spectroscopy. Magnetic properties were determined by magnetization measurements. The relation between the particle size, composition and magnetic properties of the sol-gel derived garnets were also discussed in this study. - Highlights: • First time series of R_3Fe_5O_1_2 (R=from Sm to Lu) are prepared by sol–gel process. • Different sintering temperature leads to the different particle size distribution. • Correlation between microstructure, composition and magnetic properties is shown.

  6. 22nd September 2010 - Korean Minister of Education, Science and Technology J.-H. Lee signing the guest book and exchanging gifts with CERN Director-General R. Heuer and Head of International Relations F. Pauss; visiting ALICE exhibition with Collaboration Spokesperson J. Schukraft; accompanied throughout by Adviser R. Voss.

    CERN Multimedia

    Teams : M. Brice ; JC Gadmer

    2010-01-01

    22nd September 2010 - Korean Minister of Education, Science and Technology J.-H. Lee signing the guest book and exchanging gifts with CERN Director-General R. Heuer and Head of International Relations F. Pauss; visiting ALICE exhibition with Collaboration Spokesperson J. Schukraft; accompanied throughout by Adviser R. Voss.

  7. Creation of Cardiac Tissue Exhibiting Mechanical Integration of Spheroids Using 3D Bioprinting.

    Science.gov (United States)

    Ong, Chin Siang; Fukunishi, Takuma; Nashed, Andrew; Blazeski, Adriana; Zhang, Huaitao; Hardy, Samantha; DiSilvestre, Deborah; Vricella, Luca; Conte, John; Tung, Leslie; Tomaselli, Gordon; Hibino, Narutoshi

    2017-07-02

    This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted and mixed at desired cell ratios. They are co-cultured in individual wells in ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These spheroids are then picked up by a nozzle using vacuum suction and assembled on a needle array using a 3D bioprinter. The spheroids are then allowed to fuse on the needle array. Three days after 3D bioprinting, the spheroids are removed as an intact patch, which is already spontaneously beating. 3D bioprinted cardiac patches exhibit mechanical integration of component spheroids and are highly promising in cardiac tissue regeneration and as 3D models of heart disease.

  8. Complexing of vanadium(3) with chromotropic acid derivatives

    International Nuclear Information System (INIS)

    Babenko, N.L.; Busev, A.I.; Sukhorukova, N.V.; Frolova, O.S.

    1976-01-01

    A spectrophotometric study has been made of the complex formation of vanadium (3) with arsenazo(1), arsenazo(3) and some monosubstituted derivatives of chromotropic acid and sulphanylamides. In acid medium vanadium (3) reacts with each of these reagents to produce a 1:1 complex. Optimum conditions of the complex formation was found. The effect of H + on the complex formation of vanadium (3) with chromotropic acid derivatives was established. It was found by the graphical method that the formation of the complex is accompanied by the elimination of one proton. Patterns were found of the influence of the nature of substituents in the organic compound on the ionization constants of acid groups and stability of complexes. Molar extinction coefficients, equilibrium constants of the formation reactions and instability constants for the complexes were calculated. The structure of complexes was suggested. Similar behaviour of all the reagents was established in the complex formation with vanadium (3)

  9. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's fiftieth anniversary celebrations. The fiftieth anniversary of a world famous organization like CERN, an international laboratory specializing in fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting two "salons" consisting of an exhibition of plastic arts and evenings of music and visual arts performances with the collective title of "Accelerated Particles". Several works will be exhibited and performed. Salon des matières: An exhibition of plastic arts Until Wednesday 3 November 2004. Tuesdays to Fridays: 4.00 p.m. to 7.00 p.m. Saturdays: 2.00 p.m. to 6.00 p.m. Doors open late on the evening of the performances. Salon des ...

  10. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI Attenuates Elastase-Induced Emphysema in Mice

    Directory of Open Access Journals (Sweden)

    Bruno Tadeu Martins-Olivera

    2016-01-01

    Full Text Available Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD. However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group or saline (SAL group and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups. At day 28, the following analyses were performed: (I lung mechanics, (II exhaled nitric oxide (ENO, (III bronchoalveolar lavage fluid (BALF, and (IV lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

  11. The First Pentacyclic Triterpenoid Gypsogenin Derivative Exhibiting Anti-ABL1 Kinase and Anti-chronic Myelogenous Leukemia Activities.

    Science.gov (United States)

    Ciftci, Halil Ibrahim; Ozturk, Safiye Emirdag; Ali, Taha F S; Radwan, Mohamed O; Tateishi, Hiroshi; Koga, Ryoko; Ocak, Zeynep; Can, Mustafa; Otsuka, Masami; Fujita, Mikako

    2018-04-01

    The discovery of the chimeric tyrosine kinase breakpoint cluster region kinase-Abelson kinase (BCR-ABL)-targeted drug imatinib conceptually changed the treatment of chronic myelogenous leukemia (CML). However, some CML patients show drug resistance to imatinib. To address this issue, some artificial heterocyclic compounds have been identified as BCR-ABL inhibitors. Here we examined whether plant-derived pentacyclic triterpenoid gypsogenin and/or their derivatives show inhibitory activity against BCR-ABL. Among the three derivatives, benzyl 3-hydroxy-23-oxoolean-12-en-28-oate (1c) was found to be the most effective anticancer agent on the CML cell line K562, with an IC 50 value of 9.3 µM. In contrast, the IC 50 against normal peripheral blood mononuclear cells was 276.0 µM, showing better selectivity than imatinib. Compound 1c had in vitro inhibitory activity against Abelson kinase 1 (ABL1) (IC 50 =8.7 µM), the kinase component of BCR-ABL. In addition, compound 1c showed a different inhibitory profile against eight kinases compared with imatinib. The interaction between ATP binding site of ABL and 1c was examined by molecular docking study, and the binding mode was different from imatinib and newer generation inhibitors. Furthermore, 1c suppressed signaling downstream of BCR-ABL. This study suggests the possibility that plant extracts may be a source for CML treatment and offer a strategy to overcome drug resistance to known BCR-ABL inhibitors.

  12. A note on derivations in semiprime rings

    Directory of Open Access Journals (Sweden)

    Joso Vukman

    2005-01-01

    Full Text Available We prove in this note the following result. Let n>1 be an integer and let R be an n!-torsion-free semiprime ring with identity element. Suppose that there exists an additive mapping D:R→R such that D(xn=∑j=1nxn−jD(xxj−1 is fulfilled for all x∈R. In this case, D is a derivation. This research is motivated by the work of Bridges and Bergen (1984. Throughout, R will represent an associative ring with center Z(R. Given an integer n>1, a ring R is said to be n-torsion-free if for x∈R, nx=0 implies that x=0. Recall that a ring R is prime if for a,b∈R, aRb=(0 implies that either a=0 or b=0, and is semiprime in case aRa=(0 implies that a=0. An additive mapping D:R→R is called a derivation if D(xy=D(xy+xD(y holds for all pairs x,y∈R and is called a Jordan derivation in case D(x2=D(xx+xD(x is fulfilled for all x∈R. Every derivation is a Jordan derivation. The converse is in general not true. A classical result of Herstein (1957 asserts that any Jordan derivation on a prime ring with characteristic different from two is a derivation. A brief proof of Herstein's result can be found in 1988 by Brešar and Vukman. Cusack (1975 generalized Herstein's result to 2-torsion-free semiprime rings (see also Brešar (1988 for an alternative proof. For some other results concerning derivations on prime and semiprime rings, we refer to Brešar (1989, Vukman (2005, Vukman and Kosi-Ulbl (2005.

  13. Industrial Exhibition “11th Germany at CERN“

    CERN Multimedia

    FP Department

    2010-01-01

    Administration Building (Bldg. 60/61) Tuesday 25 January: 11a.m. - 5.30 p.m. Wednesday 26 January: 9 a.m. - 5 p.m. The Federal Ministry of Education and Research (BMBF), together with CERN, will hold the Industrial Exhibition “11th Germany at CERN”. Some 30 German companies will present their latest products/technologies related to the field of particle physics and their services to the scientists and buyers of CERN, establish contacts and find out about future purchasing opportunities. On 25 January, Dr. B. Vierkorn-Rudolph of the Federal Ministry of Education and Research and CERN Director-General, Prof. R. D. Heuer, will open the exhibition, followed by a tour of the stands. The main subjects are: electrical engineering, electronics, informatics, mechanical engineering, vacuum & low temperature technologies, instrumentation and safety. CERN staff wishing to obtain information concerning the programme, the exhibitors and their profiles or to get in contact with exhibitors are r...

  14. Structure-activity relationship of daptomycin analogues with substitution at (2S, 3R) 3-methyl glutamic acid position.

    Science.gov (United States)

    Lin, Du'an; Lam, Hiu Yung; Han, Wenbo; Cotroneo, Nicole; Pandya, Bhaumik A; Li, Xuechen

    2017-02-01

    Daptomycin is a highly effective lipopeptide antibiotic against Gram-positive pathogens. The presence of (2S, 3R) 3-methyl glutamic acid (mGlu) in daptomycin has been found to be important to the antibacterial activity. However the role of (2S, 3R) mGlu is yet to be revealed. Herein, we reported the syntheses of three daptomycin analogues with (2S, 3R) mGlu substituted by (2S, 3R) methyl glutamine (mGln), dimethyl glutamic acid and (2S, 3R) ethyl glutamic acid (eGlu), respectively, and their antibacterial activities. The detailed synthesis of dimethyl glutamic acid was also reported. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Dual-Use Space Technology Transfer Conference and Exhibition. Volume 1

    Science.gov (United States)

    Krishen, Kumar (Compiler)

    1994-01-01

    This document contains papers presented at the Dual-Use Space Technology Transfer Conference and Exhibition held at the Johnson Space Center February 1-3, 1994. Possible technology transfers covered during the conference were in the areas of information access; innovative microwave and optical applications; materials and structures; marketing and barriers; intelligent systems; human factors and habitation; communications and data systems; business process and technology transfer; software engineering; biotechnology and advanced bioinstrumentation; communications signal processing and analysis; new ways of doing business; medical care; applications derived from control center data systems; human performance evaluation; technology transfer methods; mathematics, modeling, and simulation; propulsion; software analysis and decision tools systems/processes in human support technology; networks, control centers, and distributed systems; power; rapid development perception and vision technologies; integrated vehicle health management; automation technologies; advanced avionics; ans robotics technologies. More than 77 papers, 20 presentations, and 20 exhibits covering various disciplines were presented b experts from NASA, universities, and industry.

  16. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma.

    Science.gov (United States)

    Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshifumi

    2017-05-16

    Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

  17. Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2016-09-01

    Full Text Available A new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative, varioloid A (1, was isolated from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291. Its structure was elucidated on the basis of extensive analysis of 1D and 2D NMR data and the absolute configuration was determined by time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD calculations. A similar compound, whose planar structure was previously described but the relative and absolute configurations and 13C NMR data were not reported, was also identified and was tentatively named as varioloid B (2. Both compounds 1 and 2 exhibited cytotoxicity against A549, HCT116, and HepG2 cell lines, with IC50 values ranging from 2.6 to 8.2 µg/mL.

  18. R3B time projection chamber

    Directory of Open Access Journals (Sweden)

    Legou P.

    2012-07-01

    Full Text Available Within the international FAIR project, the R3B collaboration (Reaction studies with Radioactive Relativistic beams will be in charge of the physics program with secondary beams of energy between 200 and 1500MeV per nucleon. Central to the R3B set-up will be a large-aperture superconducting magnet under construction at CEA-Saclay. An international collaboration has been formed to work on the design of a large time-projection chamber (TPC to be installed behind this magnet to cover the full phase-space of the charged fragments produced in the target. Within this collaboration, tests of detector prototypes were performed with the heavy-ions beams at GSI Darmstadt. These prototypes were equipped with a gaseous Micromegas detector. Two amplification technologies were tested, either conventional or resistive Micromegas and two construction concepts, bulk-Micromegas or micro-meshes screwed on the PCB. We will present the results of the last beam and the 1m TPC station which will be dedicated to make tests using the real drift distance and compare the performances of micromegas and GEM.

  19. Electron density distribution and crystal structure of 27R-AlON, Al9O3N7

    International Nuclear Information System (INIS)

    Asaka, Toru; Banno, Hiroki; Funahashi, Shiro; Hirosaki, Naoto; Fukuda, Koichiro

    2013-01-01

    The crystal structure of Al 9 O 3 N 7 was characterized by laboratory X-ray powder diffraction (CuKα 1 ). The title compound is trigonal with space group R3-bar m (centrosymmetric). The hexagonal unit-cell dimensions (Z=3) are a=0.30656(2) nm, c=7.2008(3) nm and V=0.58605(5) nm 3 . The initial structural model was derived by the powder charge-flipping method and subsequently refined by the Rietveld method. The final structural model showed the positional disordering of two of the five types of Al sites. The maximum-entropy method-based pattern fitting method was used to confirm the validity of the split-atom model, in which conventional structure bias caused by assuming intensity partitioning was minimized. The disordered crystal structure was successfully described by overlapping five types of domains with ordered atom arrangements. The distribution of atomic positions in one of the five types of domains can be achieved in the space group R3 ¯ m. The atom arrangements in the four other domains are noncentrosymmetric with the space group R3m. Two of the four types of domains are related by a pseudo-symmetry inversion, and the two remaining domains also have each other the inversion pseudo-symmetry. The very similar domain structure has been also reported for 21R-AlON (Al 7 O 3 N 5 ) in our previous study. - Graphical abstract: A bird’s eye view of electron densities up to 50% (0.074 nm −3 ) of the maximum on the plane parallel to (110) with the corresponding atomic arrangements of Al 9 O 3 N 7 . Highlights: • Crystal structure of Al 9 O 3 N 7 is determined by laboratory X-ray powder diffraction. • The atom arrangements are represented by the split-atom model. • The maximum-entropy method-based pattern fitting method is used to confirm the validity of the model. • The disordered structure is described by overlapping five types of domains with ordered atom arrangements

  20. (R,S)-3-Carb-oxy-2-(isoquinolinium-2-yl)propanoate monohydrate.

    Science.gov (United States)

    Stilinović, Vladimir; Frkanec, Leo; Kaitner, Branko

    2010-05-22

    The title compound, C(13)H(11)NO(4)·H(2)O, is a monohydrate of a betaine exhibiting a positively charged N-substituted isoquino-line group and a deprotonated carboxyl group. In the crystal, mol-ecules are connected via short O-H⋯O hydrogen bonds between protonated and deprotonated carboxyl groups into chains of either R or S enanti-omers along [001]. These chains are additionally connected by hydrogen bonding between water mol-ecules and the deprotonated carb-oxy groups of neighbouring mol-ecules.

  1. Determining Optimal New Generation Satellite Derived Metrics for Accurate C3 and C4 Grass Species Aboveground Biomass Estimation in South Africa

    Directory of Open Access Journals (Sweden)

    Cletah Shoko

    2018-04-01

    Full Text Available While satellite data has proved to be a powerful tool in estimating C3 and C4 grass species Aboveground Biomass (AGB, finding an appropriate sensor that can accurately characterize the inherent variations remains a challenge. This limitation has hampered the remote sensing community from continuously and precisely monitoring their productivity. This study assessed the potential of a Sentinel 2 MultiSpectral Instrument, Landsat 8 Operational Land Imager, and WorldView-2 sensors, with improved earth imaging characteristics, in estimating C3 and C4 grasses AGB in the Cathedral Peak, South Africa. Overall, all sensors have shown considerable potential in estimating species AGB; with the use of different combinations of the derived spectral bands and vegetation indices producing better accuracies. However, WorldView-2 derived variables yielded better predictive accuracies (R2 ranging between 0.71 and 0.83; RMSEs between 6.92% and 9.84%, followed by Sentinel 2, with R2 between 0.60 and 0.79; and an RMSE 7.66% and 14.66%. Comparatively, Landsat 8 yielded weaker estimates, with R2 ranging between 0.52 and 0.71 and high RMSEs ranging between 9.07% and 19.88%. In addition, spectral bands located within the red edge (e.g., centered at 0.705 and 0.745 µm for Sentinel 2, SWIR, and NIR, as well as the derived indices, were found to be very important in predicting C3 and C4 AGB from the three sensors. The competence of these bands, especially of the free-available Landsat 8 and Sentinel 2 dataset, was also confirmed from the fusion of the datasets. Most importantly, the three sensors managed to capture and show the spatial variations in AGB for the target C3 and C4 grassland area. This work therefore provides a new horizon and a fundamental step towards C3 and C4 grass productivity monitoring for carbon accounting, forage mapping, and modelling the influence of environmental changes on their productivity.

  2. Melanogenesis-inhibitory and cytotoxic activities of diarylheptanoids from Acer nikoense bark and their derivatives.

    Science.gov (United States)

    Akihisa, Toshihiro; Takeda, Ayano; Akazawa, Hiroyuki; Kikuchi, Takashi; Yokokawa, Satoru; Ukiya, Motohiko; Fukatsu, Makoto; Watanabe, Kensuke

    2012-08-01

    Nine cyclic diarylheptanoids, 1-9, including two new compounds, i.e., 9-oxoacerogenin A (8) and 9-O-β-D-glucopyranosylacerogenin K (9), along with three acyclic diarylheptanoids, 10-12, and four phenolic compounds, 13-16, were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K (17) and D-glucose. Two of the cyclic diarylheptanoids, acerogenin A (1) and (R)-acerogenin B (5), were converted to their ether and ester derivatives, 18-24 and 27-33, respectively, and to the dehydrated derivatives, 25, 26, 34, and 35. Upon evaluation of compounds 1-16 and 18-35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α-melanocyte-stimulating hormone (α-MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2-4, 6, 9, and 12, and two phenolic glycosides, 15 and 16, exhibited inhibitory activities with 24-61% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (88-106% of cell viability at 100 μM). In addition, when compounds 1-16 and 18-35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11, ten ether and ester derivatives, 18-22 and 27-31, and two dehydrated derivatives, 34 and 35, exhibited potent cytotoxicities against HL60 human leukemia cell line (IC(50) 8.1-19.3 μM), and five compounds, 10, 11, 20, 29, and 30, against CRL1579 human melanoma cell line (IC(50) 10.1-18.4 μM). Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  3. Identification and characterization of epoxide hydrolase activity of polycyclic aromatic hydrocarbon-degrading bacteria for biocatalytic resolution of racemic styrene oxide and styrene oxide derivatives.

    Science.gov (United States)

    Woo, Jung-Hee; Kwon, Tae-Hyung; Kim, Jun-Tae; Kim, Choong-Gon; Lee, Eun Yeol

    2013-04-01

    A novel epoxide hydrolase (EHase) from polycyclic aromatic hydrocarbon (PAH)-degrading bacteria was identified and characterized. EHase activity was identified in four strains of PAH-degrading bacteria isolated from commercial gasoline and oil-contaminated sediment based on their growth on styrene oxide and its derivatives, such as 2,3- and 4-chlorostyrene oxides, as a sole carbon source. Gordonia sp. H37 exhibited high enantioselective hydrolysis activity for 4-chlorostyrene oxide with an enantiomeric ratio of 27. Gordonia sp. H37 preferentially hydrolyzed the (R)-enantiomer of styrene oxide derivatives resulting in the preparation of a (S)-enantiomer with enantiomeric excess greater than 99.9 %. The enantioselective EHase activity was identified and characterized in various PAH-degrading bacteria, and whole cell Gordonia sp. H37 was employed as a biocatalyst for preparing enantiopure (S)-styrene oxide derivatives.

  4. A concise route to branched erythrono-gamma-lactones. Synthesis of the leaf-closing substance potassium (+/-)-(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate

    DEFF Research Database (Denmark)

    Pedersen, Daniel Sejer; Robinson, Tony V; Taylor, Dennis K

    2009-01-01

    -94% yield), including the natural plant lactone (+/-)-2-C-d-methylerythrono-1,4-lactone 1. The latter compound was treated with aqueous potassium hydroxide to afford potassium (+/-)-(2R,3R)-2,3,4-trihydroxy-2-methylbutanoate 2, which is a leaf-closing substance of Leucaena leucocephalam....

  5. Synthesis of New 3-(2-Chloroquinolin-3-yl)-5-Phenylisoxazole Derivatives via Click-Chemistry Approach

    International Nuclear Information System (INIS)

    Fernández-Galleguillos, Carlos; Saavedra, Luis A.; Gutierrez, Margarita

    2014-01-01

    Herein, we report the synthesis of new substituted 3-(2-chloroquinolin-3-yl)-5-phenylisoxazole (3a-j) by click chemistry in good to moderate yields. This approach is based on the regioselective copper(I)-catalyzed cycloaddition between different nitrile oxides derived from 2-chloroquinoline- 3-carbaldehyde (2a-j) and phenylacetylene. Finally these derivatives were screened for their antibacterial evaluation in vitro against three Gram-negative clinical bacteria: Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii using standard methods. (author)

  6. Synthesis of New 3-(2-Chloroquinolin-3-yl)-5-Phenylisoxazole Derivatives via Click-Chemistry Approach

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Galleguillos, Carlos; Saavedra, Luis A.; Gutierrez, Margarita [Laboratorio de Sintesis Organica, Instituto de Quimica de Recursos Naturales, Universidad de Talca (Chile)

    2014-02-15

    Herein, we report the synthesis of new substituted 3-(2-chloroquinolin-3-yl)-5-phenylisoxazole (3a-j) by click chemistry in good to moderate yields. This approach is based on the regioselective copper(I)-catalyzed cycloaddition between different nitrile oxides derived from 2-chloroquinoline- 3-carbaldehyde (2a-j) and phenylacetylene. Finally these derivatives were screened for their antibacterial evaluation in vitro against three Gram-negative clinical bacteria: Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii using standard methods. (author)

  7. Homochiral coordination polymers with helixes and metal clusters based on lactate derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhong-Xuan, E-mail: xuzhongxuan4201@163.com [Department of Chemistry, Zunyi Normal College, Zunyi, Guizhou 563002 (China); Ma, Yu-Lu [School of Chemical Science and Technology, Yunnan University, Kunming 650091 (China); Lv, Guo-ling [Department of Chemistry, Zunyi Normal College, Zunyi, Guizhou 563002 (China)

    2017-05-15

    Utilizing the lactic acid derivatives (R)-4-(1-carboxyethoxy)benzoic acid (denoted: (R)-H{sub 2}CBA) and (S)-4-(1-carboxyethoxy)benzoic acid (denoted: (S)-H{sub 2}CBA)as chiral linkers to self-assemble with 4, 4′-bipyridine (denoted: BIP) and Cd(II) ions, a couple of three-dimensional homochiral coordination polymers, namely [Cd{sub 3}((R)-CBA){sub 3} (BIP){sub 2}(H{sub 2}O)]·xGuest (1-D) and [Cd{sub 3}((S)-CBA){sub 3}(BIP){sub 2}(H{sub 2}O)]·xGuest (1-L), have been synthesized under solvothermal reaction condition. Single crystal X-ray diffraction analysis reveals the two complexes contain single helical chains based on enantiopure ligands and cadmium clusters. Moreover, some physical characteristics such as PXRD, thermal stability, solid-state circular dichroism (CD) and luminescent were also investigated. - Graphical abstract: Utilizing enantiomeric lactic acid derivatives (R)-H{sub 2}CBA and (S)-H{sub 2}CBA to assemble with Cd{sup 2+} ions and ancillary BIP ligands, a couple of 3D homochiral coordination polymers with metal clusters and helical chains have been prepared by hydrothermal reaction. - Highlights: • Chiral lactic acid derivative. • Enantiomeric coordination polymer. • Helical chain. • Trinuclear cadmium cluster.

  8. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    Science.gov (United States)

    Murovets, Vladimir O; Bachmanov, Alexander A; Zolotarev, Vasiliy A

    2015-01-01

    The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+) inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-). Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  9. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    Directory of Open Access Journals (Sweden)

    Vladimir O Murovets

    Full Text Available The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+ inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-. Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  10. Synthesis of (R)-(+)-3H-etomidate

    International Nuclear Information System (INIS)

    Janssen, C.G.M.; Thijssen, J.B.A.; Verluyten, W.L.M.; Heykants, J.J.P.

    1987-01-01

    Etomidate, (R)-(+)-ethyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate, is a short-acting hypnotic. A new synthesis, featuring optical resolution on a non-radioactive precursor and introduction of the tritium label by reductive dehalogenation, is described. The title compound was obtained at a specific activity of 3.77 Ci/mmol and a 99.9% HPLC purity. (author)

  11. Signaling via class IA Phosphoinositide 3-kinases (PI3K in human, breast-derived cell lines.

    Directory of Open Access Journals (Sweden)

    Veronique Juvin

    Full Text Available We have addressed the differential roles of class I Phosphoinositide 3-kinases (PI3K in human breast-derived MCF10a (and iso-genetic derivatives and MDA-MB 231 and 468 cells. Class I PI3Ks are heterodimers of p110 catalytic (α, β, δ and γ and p50-101 regulatory subunits and make the signaling lipid, phosphatidylinositol (3,4,5-trisphosphate (PtdIns(3,4,5P3 that can activate effectors, eg protein kinase B (PKB, and responses, eg migration. The PtdIns(3,4,5P3-3-phosphatase and tumour-suppressor, PTEN inhibits this pathway. p110α, but not other p110s, has a number of onco-mutant variants that are commonly found in cancers. mRNA-seq data shows that MCF10a cells express p110β>>α>δ with undetectable p110γ. Despite this, EGF-stimulated phosphorylation of PKB depended upon p110α-, but not β- or δ- activity. EGF-stimulated chemokinesis, but not chemotaxis, was also dependent upon p110α, but not β- or δ- activity. In the presence of single, endogenous alleles of onco-mutant p110α (H1047R or E545K, basal, but not EGF-stimulated, phosphorylation of PKB was increased and the effect of EGF was fully reversed by p110α inhibitors. Cells expressing either onco-mutant displayed higher basal motility and EGF-stimulated chemokinesis.This latter effect was, however, only partially-sensitive to PI3K inhibitors. In PTEN(-/- cells, basal and EGF-stimulated phosphorylation of PKB was substantially increased, but the p110-dependency was variable between cell types. In MDA-MB 468s phosphorylation of PKB was significantly dependent on p110β, but not α- or δ- activity; in PTEN(-/- MCF10a it remained, like the parental cells, p110α-dependent. Surprisingly, loss of PTEN suppressed basal motility and EGF-stimulated chemokinesis. These results indicate that; p110α is required for EGF signaling to PKB and chemokinesis, but not chemotaxis; onco-mutant alleles of p110α augment signaling in the absence of EGF and may increase motility, in part, via acutely

  12. Anthocyanin biosynthesis in pears is regulated by a R2R3-MYB transcription factor PyMYB10.

    Science.gov (United States)

    Feng, Shouqian; Wang, Yanling; Yang, Song; Xu, Yuting; Chen, Xuesen

    2010-06-01

    Skin color is an important factor in pear breeding programs. The degree of red coloration is determined by the content and composition of anthocyanins. In plants, many MYB transcriptional factors are involved in regulating anthocyanin biosynthesis. In this study, a R2R3-MYB transcription factor gene, PyMYB10, was isolated from Asian pear (Pyrus pyrifolia) cv. 'Aoguan'. Sequence analysis suggested that the PyMYB10 gene was an ortholog of MdMYB10 gene, which regulates anthocyanin biosynthesis in red fleshed apple (Malus x domestica) cv. 'Red Field'. PyMYB10 was identified at the genomic level and had three exons, with its upstream sequence containing core sequences of cis-acting regulatory elements involved in light responsiveness. Fruit bagging showed that light could induce expression of PyMYB10 and anthocyanin biosynthesis. Quantitative real-time PCR revealed that PyMYB10 was predominantly expressed in pear skins, buds, and young leaves, and the level of transcription in buds was higher than in skin and young leaves. In ripening fruits, the transcription of PyMYB10 in the skin was positively correlated with genes in the anthocyanin pathway and with anthocyanin biosynthesis. In addition, the transcription of PyMYB10 and genes of anthocyanin biosynthesis were more abundant in red-skinned pear cultivars compared to blushed cultivars. Transgenic Arabidopsis plants overexpressing PyMYB10 exhibited ectopic pigmentation in immature seeds. The study suggested that PyMYB10 plays a role in regulating anthocyanin biosynthesis and the overexpression of PyMYB10 was sufficient to induce anthocyanin accumulation.

  13. The mibefradil derivative NNC55-0396, a specific T-type calcium channel antagonist, exhibits less CYP3A4 inhibition than mibefradil.

    Science.gov (United States)

    Bui, Peter H; Quesada, Arnulfo; Handforth, Adrian; Hankinson, Oliver

    2008-07-01

    A novel mibefradil derivative, NNC55-0396, designed to be hydrolysis-resistant, was shown to be a selective T-type Ca(2+) channel inhibitor without L-type Ca(2+) channel efficacy. However, its effects on cytochromes P450 (P450s) have not previously been examined. We investigated the inhibitory effects of NNC55-0396 toward seven major recombinant human P450s--CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C8, CYPC19, and CYP2E1--and compared its effects with those of mibefradil and its hydrolyzed metabolite, Ro40-5966. Our results show that CYP3A4 and CYP2D6 are the two P450s most affected by mibefradil, Ro40-5966, and NNC55-0396. Mibefradil (IC(50) = 33 +/- 3 nM, K(i) = 23 +/- 0.5 nM) and Ro40-5966 (IC(50) = 30 +/- 7.8 nM, K(i) = 21 +/- 2.8 nM) have a 9- to 10-fold greater inhibitory activity toward recombinant CYP3A4 benzyloxy-4-trifluoromethylcoumarin-O-debenzylation activity than NNC55-0396 (IC(50) = 300 +/- 30 nM, K(i) = 210 +/- 6 nM). More dramatically, mibefradil (IC(50) = 566 +/- 71 nM, K(i) = 202 +/- 39 nM) shows 19-fold higher inhibition of CYP3A-associated testosterone 6beta-hydroxylase activity in human liver microsomes compared with NNC55-0396 (IC(50) = 11 +/- 1.1 microM, K(i) = 3.9 +/- 0.4 microM). Loss of testosterone 6beta-hydroxylase activity by recombinant CYP3A4 was shown to be time- and concentration-dependent with both compounds. However, NNC55-0396 (K(I) = 3.87 microM, K(inact) = 0.061/min) is a much less potent mechanism-based inhibitor than mibefradil (K(I) = 83 nM, K(inact) = 0.048/min). In contrast, NNC55-0396 (IC(50) = 29 +/- 1.2 nM, K(i) = 2.8 +/- 0.3 nM) and Ro40-5966 (IC(50) = 46 +/- 11 nM, K(i) = 4.5 +/- 0.02 nM) have a 3- to 4-fold greater inhibitory activity toward recombinant CYP2D6 than mibefradil (IC(50) = 129 +/- 21 nM, K(i) = 12.7 +/- 0.9 nM). Our results suggest that NNC55-0396 could be a more favorable T-type Ca(2+) antagonist than its parent compound, mibefradil, which was withdrawn from the market because of strong inhibition of CYP3A4.

  14. Anatomy of an Asteroid Breakup: The Case of P/2013 R3

    Science.gov (United States)

    Jewitt, David; Agarwal, Jessica; Li, Jing; Weaver, Harold; Mutchler, Max; Larson, Stephen

    2017-05-01

    We present an analysis of new and published data on P/2013 R3, the first asteroid detected while disintegrating. Thirteen discrete components are measured in the interval between UT 2013 October 01 and 2014 February 13. We determine a mean, pair-wise velocity dispersion among these components of Δv = 0.33 ± 0.03 m s-1 and find that their separation times are staggered over an interval of ˜5 months. Dust enveloping the system has, in the first observations, a cross-section of ˜30 km2 but fades monotonically at a rate consistent with the action of radiation pressure sweeping. The individual components exhibit comet-like morphologies and also fade except where secondary fragmentation is accompanied by the release of additional dust. We find only upper limits to the radii of any embedded solid nuclei, typically ˜100-200 m (geometric albedo 0.05 assumed). Combined, the components of P/2013 R3 would form a single spherical body with a radius of ≲ 400 m, which is our best estimate of the size of the precursor object. The observations are consistent with rotational disruption of a weak (cohesive strength of ˜50 to 100 N m-2) parent body, ˜400 m in radius. Estimated radiation (YORP) spin-up times of this parent are ≲ 1 {Myr}, shorter than the collisional lifetime. If present, water ice sublimating at as little as 10-3 kg s-1 could generate a torque on the parent body rivaling the YORP torque. Under conservative assumptions about the frequency of similar disruptions, the inferred asteroid debris production rate is ≳103 kg s-1, which is at least 4% of the rate needed to maintain the Zodiacal Cloud.

  15. Conformational studies on pertrimethylsilyl derivatives of 2-acetamido-2-deoxyaldohexopyranoses by 220- and 300-MHz P.M.R. spectroscopy

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Streefkerk, D.G.; Bie, M.J.A. de

    1974-01-01

    The complete interpretation of high-resolution p.m.r. spectra and the accurate chemical shifts and coupling constants, obtained after computer simulation of the spectra, of the trimethylsilyl (TMS) derivatives of six 2-acetamido-2-deoxy-D-aldo-hexopyranoses are given. All pyranoid rings occur in the

  16. PENINGKATAN KEMANDIRIAN BELAJAR DAN KEMAMPUAN KOMUNIKASI MATEMATIKA MELALUI PEMBELAJARAN SQ3R

    Directory of Open Access Journals (Sweden)

    Fitrianto Eko Subekti

    2016-08-01

    Full Text Available The aim for this research are : 1 increasing the learning independency students, 2 increasing the ability of communication of learning SQ3R Mathematic. SQ3R Learning consist of surveying question, read, recite and review. The subject of this research is student who take Diskrit Mathematic course. This procedure of the research are : (1 Preparing (2 Do (3 Observation and (4 Reflection. Based of the result of this research shows that there is increasing student in how to comunicate of learning mathematic with SQ3R. Especially in The second meeting there is high increasing in their ability and we can say that the ability of student comunication in learning mathematic is quite good. Abstrak: Tujuan dari penelitian ini adalah: 1 meningkatkan kemandirian belajar siswa, 2 meningkatkan kemampuan komunikasi pembelajaran SQ3R Matematika. SQ3R Belajar terdiri dari survei pertanyaan, membaca, melafalkan dan meninjau. Subyek penelitian ini adalah mahasiswa yang mengambil kursus Matematika diskrit di Prodi Pendidikan Matematika Universitas Muhammadiyah Purwokerto. Prosedur ini dari penelitian ini adalah: (1 Mempersiapkan (2 Melaksanakan (3 Observasi, dan (4 Refleksi. Berdasarkan hasil penelitian ini menunjukkan bahwa ada peningkatan mahasiswa dalam cara berkomunikasi belajar matematika dengan SQ3R. Terutama di pertemuan kedua ada peningkatan tinggi dalam kemampuan mereka dan dapat disimpulkan kemampuan komunikasi siswa dalam belajar matematika cukup baik. Kata Kunci: belajar mandiri, kemampuan komunikasi, SQ3R

  17. MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation.

    Directory of Open Access Journals (Sweden)

    James R Howe

    Full Text Available Neurogenesis is a highly-regulated process occurring in the dentate gyrus that has been linked to learning, memory, and antidepressant efficacy. MicroRNAs (miRNAs have been previously shown to play an important role in the regulation of neuronal development and neurogenesis in the dentate gyrus via modulation of gene expression. However, this mode of regulation is both incompletely described in the literature thus far and highly multifactorial. In this study, we designed sensors and detected relative levels of expression of 10 different miRNAs and found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is expressed most highly in the mature neuron. We also designed a viral "sponge" to knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down, neurons sprout multiple primary dendrites that branch off of the soma in a disorganized manner, cellular proliferation is upregulated, and neoplasms form spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma cell lines slows their proliferation in vitro. Further, low miR-338-3p expression is associated with increased mortality and disease progression in patients with glioblastoma. These data identify miR-338-3p as a clinically relevant tumor suppressor in glioblastoma.

  18. In Quest of the Alanine R3 Radical: Multivariate EPR Spectral Analyses of X-Irradiated Alanine in the Solid State.

    Science.gov (United States)

    Jåstad, Eirik O; Torheim, Turid; Villeneuve, Kathleen M; Kvaal, Knut; Hole, Eli O; Sagstuen, Einar; Malinen, Eirik; Futsaether, Cecilia M

    2017-09-28

    The amino acid l-α-alanine is the most commonly used material for solid-state electron paramagnetic resonance (EPR) dosimetry, due to the formation of highly stable radicals upon irradiation, with yields proportional to the radiation dose. Two major alanine radical components designated R1 and R2 have previously been uniquely characterized from EPR and electron-nuclear double resonance (ENDOR) studies as well as from quantum chemical calculations. There is also convincing experimental evidence of a third minor radical component R3, and a tentative radical structure has been suggested, even though no well-defined spectral signature has been observed experimentally. In the present study, temperature dependent EPR spectra of X-ray irradiated polycrystalline alanine were analyzed using five multivariate methods in further attempts to understand the composite nature of the alanine dosimeter EPR spectrum. Principal component analysis (PCA), maximum likelihood common factor analysis (MLCFA), independent component analysis (ICA), self-modeling mixture analysis (SMA), and multivariate curve resolution (MCR) were used to extract pure radical spectra and their fractional contributions from the experimental EPR spectra. All methods yielded spectral estimates resembling the established R1 spectrum. Furthermore, SMA and MCR consistently predicted both the established R2 spectrum and the shape of the R3 spectrum. The predicted shape of the R3 spectrum corresponded well with the proposed tentative spectrum derived from spectrum simulations. Thus, results from two independent multivariate data analysis techniques strongly support the previous evidence that three radicals are indeed present in irradiated alanine samples.

  19. Hierarchical Cr_2O_3@OPC composites with octahedral shape for rechargeable nonaqueous lithium-oxygen batteries

    International Nuclear Information System (INIS)

    Gan, Yongqing; Lai, Yanqing; Zhang, Zhian; Chen, Wei; Du, Ke; Li, Jie

    2016-01-01

    The development of catalyst materials is the most significant issue that hinders the practical applications of Li-O_2 batteries. Herein we show the design and synthesis of the hierarchical chromic oxide-octahedral porous carbon (Cr_2O_3@OPC) composites catalyst with octahedral shape that derived from Cr-based metal-organic frameworks (MIL-101(Cr)) precursor. When applied as cathode catalysts in rechargeable Li-O_2 batteries, the electrode with Cr_2O_3@OPC composites catalyst exhibits a low charge and discharge over-potential, high discharge capacity and excellent cycling stability. What's more, the electrode with Cr_2O_3@OPC composite shows a discharge capacity up to ∼4800 mAh g_(_c_a_t_a_l_y_s_t _+ _c_a_r_b_o_n_)"−"1 at a current density of 0.1 mA cm"−"2, and exhibits a very stable discharge voltage plateau of 2.7 V and a charge voltage plateau of ∼3.9 V. With the addition of Cr_2O_3@OPC composite, the Li-O_2 batteries can obtain good cycle performance over 50 cycles at a fixed capacity of 800 mAh g_(_c_a_t_a_l_y_s_t _+ _c_a_r_b_o_n_)"−"1. These results indicating that the Cr_2O_3@OPC composite derived from MIL-101(Cr) would be a promising catalyst for Li-O_2 batteries. - Highlights: • The Cr_2O_3@C composites were prepared by the pyrolysis of Cr-MIL-101. • The Cr_2O_3@C composites possess octahedral shape consisted of Cr_2O_3@C nanoparticle. • The Cr_2O_3@C composites have mesoporous structure with large specific area. • The Cr_2O_3@C composites have an excellent intrinsic electrocatalytic activity. • The Cr_2O_3@C electrode exhibits great cycling performance.

  20. Three-dimensional tetranuclear Cd(II) coordination network based on a 1,3-alternate calix[4]arene derivative

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ji; Ju, Hui Yeong; Park, Ki Min [Dept. of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju (Korea, Republic of); Moon, ASuk Hee [Dept. of Food and Nutrition, Kyungnam College of Inform ation and Technology, Busan (Korea, Republic of); Kang, Young Jin [Div. of cience Education, Kangwon National University, Chuncheon (Korea, Republic of)

    2015-08-15

    Polynuclear coordination polymers can exhibit more intriguing network topologies and better functionalities than those of common complexes because they have metal-cluster nodes for the construction of multidimensional frameworks and the potential applications induced by collaborative activities between metal ions. New tetranuclear Cd(II) coordination polymer 1 based on 1,3-alternate calix arene derivative (H{sub 4} CTA) with four carboxyl pendant arms has been synthesized by the solvo thermal reaction at 110 .deg. C for 2 days. Compound 1 shows a 3-D framework consisting of tetranuclear Cd(II) cluster core as a metal-cluster node and 1,3-alternate H{sub 4}CTA as a multidentate linker. The coordination polymer 1 displays intense blue emission, implying that this tetranuclear Cd(II) coordination polymer could be a suitable material in the area of luminescence research.

  1. Combretastatin A-4 based thiophene derivatives as antitumor agent: Development of structure activity correlation model using 3D-QSAR, pharmacophore and docking studies

    Directory of Open Access Journals (Sweden)

    Vijay K. Patel

    2017-12-01

    Full Text Available The structure and ligand based synergistic approach is being applied to design ligands more correctly. The present report discloses the combination of structure and ligand based tactics i.e., molecular docking, energetic based pharmacophore, pharmacophore and atom based 3D-QSAR modeling for the analysis of thiophene derivatives as anticancer agent. The main purpose of using structure and ligand based synergistic approach is to ascertain a correlation between structure and its biological activity. Thiophene derivatives have been found to possess cytotoxic activity in several cancer cell lines and its mechanism of action basically involves the binding to the colchicine site on β-tubulin. The structure based approach (molecular docking was performed on a series of thiophene derivatives. All the structures were docked to colchicine binding site of β tubulin for examining the binding affinity of compounds for antitumor activity. The pharmacophore and atom based 3D-QSAR modeling was accomplished on a series of thiophene (32 compounds analogues. Five-point common pharmacophore hypotheses (AAAAR.38 were selected for alignment of all compounds. The atom based 3D-QSAR models were developed by selection of 23 compounds as training set and 9 compounds as test set, demonstrated good partial least squares statistical results. The generated common pharmacophore hypothesis and 3D-QSAR models were validated further externally by measuring the activity of database compounds and assessing it with actual activity. The common pharmacophore hypothesis AAAAR.38 resulted in a 3D-QSAR model with excellent PLSs data for factor two characterized by the best predication coefficient Q2 (cross validated r2 (0.7213, regression R2 (0.8311, SD (0.3672, F (49.2, P (1.89E-08, RMSE (0.3864, Stability (0.8702, Pearson-r (0.8722. The results of these molecular modeling studies i.e., molecular docking, energetic based pharmacophore, pharmacophore and atom based 3D-QSAR modeling

  2. The Eucalyptus grandis R2R3-MYB transcription factor family: evidence for woody growth-related evolution and function.

    Science.gov (United States)

    Soler, Marçal; Camargo, Eduardo Leal Oliveira; Carocha, Victor; Cassan-Wang, Hua; San Clemente, Hélène; Savelli, Bruno; Hefer, Charles A; Paiva, Jorge A Pinto; Myburg, Alexander A; Grima-Pettenati, Jacqueline

    2015-06-01

    The R2R3-MYB family, one of the largest transcription factor families in higher plants, controls a wide variety of plant-specific processes including, notably, phenylpropanoid metabolism and secondary cell wall formation. We performed a genome-wide analysis of this superfamily in Eucalyptus, one of the most planted hardwood trees world-wide. A total of 141 predicted R2R3-MYB sequences identified in the Eucalyptus grandis genome sequence were subjected to comparative phylogenetic analyses with Arabidopsis thaliana, Oryza sativa, Populus trichocarpa and Vitis vinifera. We analysed features such as gene structure, conserved motifs and genome location. Transcript abundance patterns were assessed by RNAseq and validated by high-throughput quantitative PCR. We found some R2R3-MYB subgroups with expanded membership in E. grandis, V. vinifera and P. trichocarpa, and others preferentially found in woody species, suggesting diversification of specific functions in woody plants. By contrast, subgroups containing key genes regulating lignin biosynthesis and secondary cell wall formation are more conserved across all of the species analysed. In Eucalyptus, R2R3-MYB tandem gene duplications seem to disproportionately affect woody-preferential and woody-expanded subgroups. Interestingly, some of the genes belonging to woody-preferential subgroups show higher expression in the cambial region, suggesting a putative role in the regulation of secondary growth. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

  3. Fluoroethoxy-1,4-diphenethylpiperidine and piperazine derivatives: Potent and selective inhibitors of [3H]dopamine uptake at the vesicular monoamine transporter-2.

    Science.gov (United States)

    Hankosky, Emily R; Joolakanti, Shyam R; Nickell, Justin R; Janganati, Venumadhav; Dwoskin, Linda P; Crooks, Peter A

    2017-12-15

    A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [ 3 H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [ 3 H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [ 3 H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [ 3 H]DA uptake at VMAT2, Ki changes in the nanomolar range (K i  = 0.014-0.073 µM). Compound 15d exhibited the highest affinity (K i  = 0.014 µM) at VMAT2, and had 160-, 5-, and 60-fold greater selectivity for VMAT2 vs. DAT, SERT and hERG, respectively. Compound 15b exhibited the greatest selectivity (>60-fold) for VMAT2 relative to all the other targets evaluated, and 15b had high affinity for VMAT2 (K i  = 0.073 µM). Compound 15b was considered the lead compound from this analog series due to its high affinity and selectivity for VMAT2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Calculations of the magnetic properties of R{sub 2}M{sub 14}B intermetallic compounds (R=rare earth, M=Fe, Co)

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Masaaki, E-mail: masaaki.ito@neel.cnrs.fr [CNRS, Institut Néel, 25 rue des Martyrs, BP166, 38042 Grenoble (France); University Grenoble Alpes, Institut Néel, 38042 Grenoble (France); Advanced Material Engineering Division, Toyota Motor Corporation, Susono 410-1193 (Japan); Yano, Masao [Advanced Material Engineering Division, Toyota Motor Corporation, Susono 410-1193 (Japan); Dempsey, Nora M. [CNRS, Institut Néel, 25 rue des Martyrs, BP166, 38042 Grenoble (France); University Grenoble Alpes, Institut Néel, 38042 Grenoble (France); Givord, Dominique [CNRS, Institut Néel, 25 rue des Martyrs, BP166, 38042 Grenoble (France); University Grenoble Alpes, Institut Néel, 38042 Grenoble (France); Instituto de Fisica, Universidade Federal do Rio de Janeiro, Rio de Janeiro (Brazil)

    2016-02-15

    The hard magnetic properties of “R–M–B” (R=rare earth, M=mainly Fe) magnets derive from the specific intrinsic magnetic properties encountered in Fe-rich R{sub 2}M{sub 14}B compounds. Exchange interactions are dominated by the 3d elements, Fe and Co, and may be modeled at the macroscopic scale with good accuracy. Based on classical formulae that relate the anisotropy coefficients to the crystalline electric field parameters and exchange interactions, a simple numerical approach is used to derive the temperature dependence of anisotropy in various R{sub 2}Fe{sub 14}B compounds (R=Pr, Nd, Dy). Remarkably, a unique set of crystal field parameters give fair agreement with the experimentally measured properties of all compounds. This implies reciprocally that the properties of compounds that incorporate a mixture of different rare-earth elements may be predicted accurately. This is of special interest for material optimization that often involves the partial replacement of Nd with another R element and also the substitution of Co for Fe. - Highlights: • Anisotropy constants derived from CEF parameters of R{sub 2}M{sub 14}B compounds (M=Fe, Co). • Anisotropy constants of all R{sub 2}Fe{sub 14}B compounds using unique set of CEF parameters. • Moment non-collinearity in magnetization processes under B{sub app} along hard axis.

  5. Synthesis and Electroluminescence Properties of 3-(Trifluoromethylphenyl-Substituted 9,10-Diarylanthracene Derivatives for Blue Organic Light-Emitting Diodes

    Directory of Open Access Journals (Sweden)

    Sang Woo Kwak

    2017-10-01

    Full Text Available Diaryl-substituted anthracene derivatives containing 3-(trifluoromethylphenyl groups, 9,10-diphenyl-2-(3-(trifluoromethylphenylanthracene (1, 9,10-di([1,1′-biphenyl]-4-yl-2-(3-(trifluoromethylphenylanthracene (2, and 9,10-di(naphthalen-2-yl-2-(3-(trifluoromethylphenylanthracene (3 were synthesized and characterized. The compounds 1–3 possessed high thermal stability and proper frontier-energy levels, which make them suitable as host materials for blue organic light-emitting diodes. The electroluminescent (EL emission maximum of the three N,N-diphenylamino phenyl vinyl biphenyl (DPAVBi-doped (8 wt % devices for compounds 1–3 was exhibited at 488 nm (for 1 and 512 nm (for 2 and 3. Among them, the 1-based device displayed the highest device performances in terms of brightness (Lmax = 2153.5 cd·m−2, current efficiency (2.1 cd·A−1, and external quantum efficiency (0.8%, compared to the 2- and 3-based devices.

  6. Mammalian ChlR1 has a role in heterochromatin organization

    International Nuclear Information System (INIS)

    Inoue, Akira; Hyle, Judith; Lechner, Mark S.; Lahti, Jill M.

    2011-01-01

    The ChlR1 DNA helicase, encoded by DDX11 gene, which is responsible for Warsaw breakage syndrome (WABS), has a role in sister-chromatid cohesion. In this study, we show that human ChlR1 deficient cells exhibit abnormal heterochromatin organization. While constitutive heterochromatin is discretely localized at perinuclear and perinucleolar regions in control HeLa cells, ChlR1-depleted cells showed dispersed localization of constitutive heterochromatin accompanied by disrupted centromere clustering. Cells isolated from Ddx11 -/- embryos also exhibited diffuse localization of centromeres and heterochromatin foci. Similar abnormalities were found in HeLa cells depleted of combinations of HP1α and HP1β. Immunofluorescence and chromatin immunoprecipitation showed a decreased level of HP1α at pericentric regions in ChlR1-depleted cells. Trimethyl-histone H3 at lysine 9 (H3K9-me3) was also modestly decreased at pericentric sequences. The abnormality in pericentric heterochromatin was further supported by decreased DNA methylation within major satellite repeats of Ddx11 -/- embryos. Furthermore, micrococcal nuclease (MNase) assay revealed a decreased chromatin density at the telomeres. These data suggest that in addition to a role in sister-chromatid cohesion, ChlR1 is also involved in the proper formation of heterochromatin, which in turn contributes to global nuclear organization and pleiotropic effects. -- Highlights: → New role for ChlR1 (DDX11), a cohesinopathy gene, in heterochromatin organization. → Loss of ChlR1 altered heterochromatin localization and centromere clustering. → Reduced ChlR1 levels also reduced HP1α and H3K9-me3 binding to pericentric DNA. → Decreased DNA methylation was found in pericentric repeats of Ddx11 -/- embryos. → These findings will aid in understanding the pathogenesis of Warsaw breakage syndrome.

  7. Luminescence and magnetic properties of novel nanoparticle-sheathed 3D Micro-Architectures of Fe0.5R0.5(MoO4)1.5:Ln3+ (R = Gd3+, La3+), (Ln = Eu, Tb, Dy) for bifunctional application

    Science.gov (United States)

    Krishnan, Rajagopalan; Thirumalai, Jagannathan; Kathiravan, Arunkumar

    2015-01-01

    For the first time, we report the successful synthesis of novel nanoparticle-sheathed bipyramid-like and almond-like Fe0.5R0.5(MoO4)1.5:Ln3+ (R = Gd3+, La3+), (Ln = Eu, Tb, Dy) 3D hierarchical microstructures through a simple disodium ethylenediaminetetraacetic acid (Na2EDTA) facilitated hydrothermal method. Interestingly, time-dependent experiments confirm that the assembly-disassembly process is responsible for the formation of self-aggregated 3D architectures via Ostwald ripening phenomena. The resultant products are characterized by x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM), photoluminescence (PL), and magnetic measurements. The growth and formation mechanisms of the self-assembled 3D micro structures are discussed in detail. To confirm the presence of all the elements in the microstructure, the energy loss induced by the K, L shell electron ionization is observed in order to map the Fe, Gd, Mo, O, and Eu components. The photo luminescence properties of Fe0.5R0.5(MoO4)1.5 doped with Eu3+, Tb3+, Dy3+ are investigated. The room temperature and low temperature magnetic properties suggest that the interaction between the local-fields introduced by the magnetic Fe3+ ions and the R3+ (La, Gd) ions in the dodecahedral sites determine the magnetism in Fe0.5R0.5(MoO4)1.5:Eu3+. This work provides a new approach to synthesizing the novel Fe0.5R0.5(MoO4)1.5:Ln3+ for bi-functional magnetic and luminescence applications.

  8. MiR-155 modulates the progression of neuropathic pain through targeting SGK3.

    Science.gov (United States)

    Liu, Shaoxing; Zhu, Bo; Sun, Yan; Xie, Xianfeng

    2015-01-01

    This study aimed to illustrate the potential effects of miR-155 in neuropathic pain and its potential mechanism. Spragure-Dawley (SD) rats were used for neuropathic pain model of bilateral chronic constriction injury (bCCI) construction. Effects of miR-155 expression on pain threshold of mechanical stimuli (MWT), paw withdrawal threshold latency (PMTL) and cold threshold were analyzed. Target for miR-155 was analyzed using bioinformatics methods. Moreover, effects of miR-155 target gene expression on pain thresholds were also assessed. Compared with the controls and sham group, miR-155 was overexpressed in neuropathic pain rats (P<0.05), but miR-155 slicing could significantly decreased the pain thresholds (P<0.05). Serum and glucocorticoid regulated protein kinase 3 (SGK3) was predicted as the target gene for miR-155, and miR-155 expression was negatively correlated to SGK3 expression. Furthermore, SGK3 overexpression could significantly decreased the pain thresholds which was the same as miR-155 (P<0.05). Moreover, miR-155 slicing and SGK3 overexpression could significantly decrease the painthreshold. The data presented in this study suggested that miR-155 slicing could excellently alleviate neuropathic pain in rats through targeting SGK3 expression. miR-155 may be a potential therapeutic target for neuropathic pain treatment.

  9. Synthesis and properties of 1,3-dioxo-1H-inden-2(3H)-ylidene fragment and (3-(dicyanomethylene)-5,5-dimethylcyclohex-1-enyl)vinyl fragment containing derivatives of azobenzene for holographic recording materials

    Science.gov (United States)

    Zarins, Elmars; Kokars, Valdis; Ozols, Andris; Augustovs, Peteris

    2011-06-01

    New glassy 1,3-dioxo-1H-inden-2(3H)-ylidene fragment und (3-(dicyanomethylene)-5,5-dimethylcyclohex-1-enyl)vinyl fragment containing push-pull type derivatives of azobenzene able to create thin layers have been synthesized. Thin films of synthesized glasses for holographic recording were prepared using spin coating technique from saturated chloroform solution. Holographic grating recording in films of 6a-b, 7 and 12 has been experimentally studied at 633 and 532 nm in both transmission and reflection modes with p-p recording beam polarizations. The film 12 was found to be the most efficient at both wavelengths in transmission mode exhibiting the maximum self-diffraction efficiency of 9.9% at 633 nm, and 15.3% at 532 nm. The film of 6a was the most efficient in reflection mode with the maximum selfdiffraction efficiency of about 3%.

  10. Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenylmethyl-4R-4H-1,2,4-triazole-3-ylthioacetic acids and its salts

    Directory of Open Access Journals (Sweden)

    A. M. Rud

    2018-02-01

    Full Text Available Today’s a creation of new domestic medicines is very important problem for pharmacy and medicine. Therefore, it is relevant to synthesize new domestic biologically active compounds. It is known that a large number of new 3-thio and 4-amino derivatives on the basis of 1,2,4-triazole have recently been synthesized, among which compounds with high pharmacological activity have been found. Based on the experience of previous studies and with the aim of creating new original drugs, our goal was to synthesize 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids series and to obtain salts on its basis, which have high indicators of pharmacological activity based on the literature data. The goal of the work is a targeted synthesis of potential low-toxic and highly effective compounds with a wide spectrum of pharmacological activity among 5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-thione derivatives, confirmation of their individuality and structure, as well as the study of physical-chemical properties, for the further pharmacological screening. Materials and methods. 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids were prepared by heating 5- (hydroxy(phenylmethyl-4-R-4H-1,2,4-triazol-3-thiones with chloroacetic acid. Subsequently, the synthesized thioacetic acids were subject for modification. Salts of 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids were obtained by reacting thioacetic acids with equivalents of sodium or potassium hydroxides. To obtain Iron(II, Copper(II or Zinc(II salts, half-molar amounts of the appropriate sulfates were added to the obtained solutions. Salts of 2-((5-(hydroxy(phenylmethyl-4-R-4H-1,2,4-triazole-3-ylthioacetic acids with organic bases were obtained by the reaction of acids with piperidine or morpholine in ethanol medium. Results. During the synthetic studies, 13 previously undescribed new compounds were obtained. The individuality of 2-((5-(hydroxy

  11. Synthesis of (benzimidazol-2-yl)aniline derivatives as glycogen phosphorylase inhibitors.

    Science.gov (United States)

    Galal, Shadia A; Khattab, Muhammad; Andreadaki, Fotini; Chrysina, Evangelia D; Praly, Jean-Pierre; Ragab, Fatma A F; El Diwani, Hoda I

    2016-11-01

    A series of (benzimidazol-2-yl)-aniline (1) derivatives has been synthesized and evaluated as glycogen phosphorylase (GP) inhibitors. Kinetics studies revealed that compounds displaying a lateral heterocyclic residue with several heteroatoms (series 3 and 5) exhibited modest inhibitory properties with IC 50 values in the 400-600μM range. Arylsulfonyl derivatives 7 (Ar: phenyl) and 9 (Ar: o-nitrophenyl) of 1 exhibited the highest activity (series 2) among the studied compounds (IC 50 324μM and 357μM, respectively) with stronger effect than the p-tolyl analogue 8. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Role of Caspase-3 Cleaved IP3R1 on Ca2+ Homeostasis and Developmental Competence of Mouse Oocytes and Eggs

    Science.gov (United States)

    Zhang, Nan; Fissore, Rafael. A.

    2014-01-01

    Apoptosis in most cell types is accompanied by altered Ca2+ homeostasis. During apoptosis, caspase-3 mediated cleavage of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) generates a 95-kDa C-terminal fragment (C-IP3R1), which represents the channel domain of the receptor. Aged mouse eggs display abnormal Ca2+ homeostasis and express C-IP3R1, although whether or not C-IP3R1 expression contributes to Ca2+ misregulation or a decrease in developmental competency is unknown. We sought to answer these questions by injecting in mouse oocytes and eggs cRNAs encoding CIP3R1. We found that: 1) expression of C-IP3R1 in eggs lowered the Ca2+ content of the endoplasmic reticulum (ER), although, as C-IP3R1 is quickly degraded at this stage, its expression did not impair pre-implantation embryo development; 2) expression of CIP3R1 in eggs enhanced fragmentation associated with aging; 3) endogenous IP3R1 is required for aging associated apoptosis, as its down-regulation prevented fragmentation, and expression of C-IP3R1 in eggs with downregulated IP3R1 partly restored fragmentation; 4) C-IP3R1 expression in GV oocytes resulted in persistent levels of protein, which abolished the increase in the ER releasable Ca2+ pool that occurs during maturation, undermined the Ca2+ oscillatory ability of matured eggs and their activation potential. Collectively, this study supports a role for IP3R1 and C-IP3R1 in regulating Ca2+ homeostasis and the ER Ca2+ content during oocyte maturation. Nevertheless, the role of C-IP3R1 on Ca2+ homeostasis in aged eggs seems minor, as in MII eggs the majority of endogenous IP3R1 remains intact and C-IP3R1 undergoes rapid turnover. PMID:24692207

  13. A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Víctor A. Solarte

    2015-01-01

    Full Text Available Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20–254, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90% in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC.

  14. Highly selective room temperature NO2 gas sensor based on rGO-ZnO composite

    Science.gov (United States)

    Jyoti, Kanaujiya, Neha; Varma, G. D.

    2018-05-01

    Blending metal oxide nanoparticles with graphene or its derivatives can greatly enhance gas sensing characteristics. In the present work, ZnO nanoparticles have been synthesized via reflux method. Thin films of reduced graphene oxide (rGO) and composite of rGO-ZnO have been fabricated by drop casting method for gas sensing application. The samples have been characterized by X-ray diffraction (XRD) and Field-emission scanning electron microscope (FESEM) for the structural and morphological studies respectively. Sensing measurements have been carried out for the composite film of rGO-ZnO for different concentrations of NO2 ranging from 4 to 100 ppm. Effect of increasing temperature on the sensing performance has also been studied and the rGO-ZnO composite sensor shows maximum percentage response at room temperature. The limit of detection (LOD) for rGO-ZnO composite sensor is 4ppm and it exhibits a high response of 48.4% for 40 ppm NO2 at room temperature. To check the selectivity of the composite sensor, sensor film has been exposed to 40 ppm different gases like CO, NH3, H2S and Cl2 at room temperature and the sensor respond negligibly to these gases. The present work suggests that rGO-ZnO composite material can be a better candidate for fabrication of highly selective room temperature NO2 gas sensor.

  15. A Stabilized Demethoxyviridin Derivative Inhibits PI3 kinase

    Science.gov (United States)

    Yuan, Hushan; Pupo, Monica T.; Blois, Joe; Smith, Adam; Weissleder, Ralph; Clardy, Jon; Josephson, Lee

    2009-01-01

    The viridins like demethoxyviridin (Dmv) and wortmannin (Wm) are nanomolar inhibitors of the PI3 kinases, a family of enzymes that play key roles in a host of regulatory processes. Central to the use of these compounds to investigate the role of PI3 kinase in biological systems, or as scaffolds for drug development, are the interrelated issues of stability, chemical reactivity, and bioactivity as inhibitors of PI3 kinase. We found that Dmv was an even more potent inhibitor of PI3 kinase than Wm. However, Dmv was notably less stable than Wm in PBS, with a half-life of 26 min vs Wm’s half-life of 3470 min. Dmv, like Wm, disappeared in culture media with a half-life of less than 1 min. To overcome Dmv’s instability, it was esterified at the C1 position, and then reacted with glycine at the C20 position. The resulting Dmv derivative, termed SA-DmvC20-Gly had a half-life of 218 min in PBS and 64 min in culture media. SA-DmvC20-Gly underwent an exchange reaction at the C20 position with N-acetyl lysine in a manner similar to a WmC20 derivative, WmC20-Proline. SA-DmvC20-Gly inhibited PI3 kinase with an IC50 of 44 nM, compared to Wm’s IC50 of 12 nM. These results indicate that the stability of Dmv can be manipulated by reactions at the C1 and C20 positions, while substantially maintaining its ability to inhibit PI3 kinase. Our results indicate it may be possible to obtain stabilized Dmv derivatives for use as PI3 kinase inhibitors in biological systems. PMID:19523825

  16. Decreased Expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T Cells and Peripheral Blood from Tuberculosis Patients

    Science.gov (United States)

    Schattling, Stefanie; Kohns, Malte; Sander-Jülch, Claudia; Walzl, Gerhard; Hesseling, Anneke; Mayatepek, Ertan; Fleischer, Bernhard; Marx, Florian M.; Jacobsen, Marc

    2013-01-01

    The vast majority of Mycobacterium tuberculosis (M. tuberculosis) infected individuals are protected from developing tuberculosis and T cells are centrally involved in this process. MicroRNAs (miRNA) regulate T-cell functions and are biomarker candidates of disease susceptibility and treatment efficacy in M. tuberculosis infection. We determined the expression profile of 29 selected miRNAs in CD4+ T cells from tuberculosis patients and contacts with latent M. tuberculosis infection (LTBI). These analyses showed lower expression of miR-21, miR-26a, miR-29a, and miR-142-3p in CD4+ T cells from tuberculosis patients. Whole blood miRNA candidate analyses verified decreased expression of miR-26a, miR-29a, and miR-142-3p in children with tuberculosis as compared to healthy children with LTBI. Despite marked variances between individual donor samples, trends of increased miRNA candidate expression during treatment and recovery were observed. Functional in vitro analysis identified increased miR-21 and decreased miR-26a expression after re-stimulation of T cells. In vitro polarized Interleukin-17 positive T-cell clones showed activation-dependent miR-29a up-regulation. In order to characterize the role of miR-29a (a described suppressor of Interferon-γ in tuberculosis), we analyzed M. tuberculosis specific Interferon-γ expressing T cells in children with tuberculosis and healthy contacts but detected no correlation between miR-29a and Interferon-γ expression. Suppression of miR-29a in primary human T cells by antagomirs indicated no effect on Interferon-γ expression after in vitro activation. Finally, classification of miRNA targets revealed only a moderate overlap between the candidates. This may reflect differential roles of miR-21, miR-26a, miR-29a, and miR-142-3p in T-cell immunity against M. tuberculosis infection and disease. PMID:23613882

  17. 3-(2-Benzofuranyl)quinuclidin-2-ene derivatives: novel muscarinic antagonists.

    Science.gov (United States)

    Nordvall, G; Sundquist, S; Johansson, G; Glas, G; Nilvebrant, L; Hacksell, U

    1996-08-16

    A series of 26 derivatives of the novel muscarinic antagonist 3-(2-benzofuranyl)quinuclidin-2-ene (1) has been synthesized and evaluated for muscarinic and antimuscarinic properties. The affinity of the compounds was determined by competition experiments in homogenates of cerebral cortex, heart, parotid gland, and urinary bladder from guinea pigs using (-)-[3H]-3-quinuclidinyl benzilate as the radioligand, and the antimuscarinic-potency was determined in a functional assay on isolated guinea pig urinary bladder using carbachol as the agonist. The 5-fluorobenzofuranyl derivative was slightly more potent than 1. The 7-bromo-substituted 8 displayed a 14-fold tissue selectivity ratio for muscarinic receptors in the cortex versus the parotid gland. Comparative molecular field analysis and quantitative structure-activity relationship models were developed for this series of substituted benzofuranyl derivatives.

  18. New Linear and Star-Shaped Thermogelling Poly([R]-3-hydroxybutyrate) Copolymers.

    Science.gov (United States)

    Barouti, Ghislaine; Liow, Sing Shy; Dou, Qingqing; Ye, Hongye; Orione, Clément; Guillaume, Sophie M; Loh, Xian Jun

    2016-07-18

    The synthesis of multi-arm poly([R]-3-hydroxybutyrate) (PHB)-based triblock copolymers (poly([R]-3-hydroxybutyrate)-b-poly(N-isopropylacrylamide)-b-[[poly(methyl ether methacrylate)-g-poly(ethylene glycol)]-co-[poly(methacrylate)-g-poly(propylene glycol)

  19. QSAR of adenosine receptor antagonists. Part 3: Exploring physicochemical requirements for selective binding of 1,2,4-triazolo[5,1-i]purine derivatives with human adenosine A3 receptor subtype.

    Science.gov (United States)

    Roy, Kunal; Leonard, J Thomas; Sengupta, Chandana

    2004-07-16

    Considering potential of selective adenosine A3 receptor antagonists in the development of prospective therapeutic agents, an attempt has been made to explore selectivity requirements of 1,2,4-triazolo[5,1-i]purine derivatives for binding with cloned human adenosine A3 receptor subtype. In this study, partition coefficient (logP) values of the molecules (calculated by Crippen's fragmentation method) and Wang-Ford charges of the common atoms of the triazolopurine nucleus (calculated from molecular electrostatic potential surface of energy minimized geometry using AM1 technique) were used as independent variables along with suitable dummy parameters. The best equation describing A3 binding affinity [n=29, Q2=0.796, Ra2=0.853, R2=0.874, R=0.935, s=0.342, F=41.5 (df 4,24), SDEP=0.396] showed parabolic relation with logP (optimum value being 4.134). Further, it was found that an aromatic substituent conjugated with the triazole nucleus should be present at R2 position for A3 binding affinity. Again, high negative charges on N2 and N4 are conducive to the binding affinity. While exploring selectivity requirements of the compounds for binding with A3 receptor over that with A2A receptor, the selectivity relation [n=23, Q2=0.909, Ra2=0.918, R2=0.933, R=0.966, s=0.401, F=62.4 (df 4,18), SDEP=0.412] showed that an aromatic R2 substituent conjugated with the triazole nucleus contributes significantly to the selectivity. Again, presence of a 4-substituted-phenyl ring (except 4-OH-phenyl and 4-CH3-phenyl) at R2 position also increases selectivity. Further, charge difference between N2 and N11 (negative charge on the former should be higher and that on the latter should be less) contributes significantly to the selectivity. In addition, negative charge on N7 is conducive while presence of substituents like propyl, butyl, pentyl or phenyl at R1 position is detrimental for the A3 selectivity.

  20. 1,2- and 1,3-dihydroxylated and hydroxynitrogenated monoterpenes as chiral ligands in the asymmetric reformatsky reaction

    International Nuclear Information System (INIS)

    Ribeiro, Carlos Magno R.; Morita, Cristina M.; Maia, Monica P.

    2008-01-01

    This study describes the use of three (-)-α-pinene derivatives, one diol-1,2 [(-)- (1R, 2R, 3S, 5R)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol 4] and two pyridine-hydroxy derivatives [(+)-(1R,2S,3R,5S)-2,6,6- trimethyl-3-(2-pyridinylmethyl)bicyclo[3.1.1]heptane-3-ol 7 and (-)-(1R,2S,3R,5S)-2,6,6-trimethyl-3-[2-(2-pyridinyl) ethyl]bicyclo[3.1.1]heptane-3-ol 8]; one diol-1,3 [(-)-(1S,2R,5S)-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanol 5] derived from (+)-isopulegol 2 and one diol-1,3 [(+)-(1R,2R,5R)-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanol 6] derived from (+)-neoisopulegol 3, as ligands in the asymmetric Reformatsky reaction. The best enantiomeric excess of β-hydroxy ester obtained in the Reformatsky asymmetric reaction was 18% using ligand 6, and the chemical yield of the reactions was 65% on average. (author)

  1. A Most Incredible Asteroid: The Break-Up of P/2013 R3

    Science.gov (United States)

    Jewitt, David; Agarwal, Jessica; Li, Jing; Weaver, Harold A.; Mutchler, Maximilian J.; Larson, Stephen M.

    2017-10-01

    We present a comprehensive study of the actively disintegrating asteroid P/2013 R3. Using the Hubble and Keck telescopes, we identified thirteen discrete components separating with a mean, pair-wise velocity dispersion of v = 0.33+/-0.03 m/s. Their separation times are staggered over an interval of 5 months. Combined, the components of P/2013 R3 would form a single spherical body with radius 400 m, which is our best estimate of the size of the precursor object. Dust enveloping the system has, in the first observations, a cross-section 30 sq. km but fades monotonically at a rate consistent with the action of radiation pressure sweeping. The individual components exhibit comet-like morphologies and also fade except where secondary fragmentation is accompanied by the release of additional dust. Upper limits to the radii of any embedded solid nuclei are typically 100 to 200 m (geometric albedo 0.05 assumed). The observations are consistent with rotational disruption of a weak (cohesive strength 50 to 100 Pa) parent body, 400 m in radius. Estimated radiation (YORP) spin-up times of this parent are less than 1 Myr, shorter than the collisional lifetime. If present, water ice sublimating at as little as 1 g/s could generate a torque on the parent body rivaling the YORP torque. Under conservative assumptions about the frequency of similar disruptions, the inferred asteroid debris production rate is 1000 kg/s, which is at least 4 percent of the rate needed to maintain the Zodiacal Cloud.The work has been recently published: D. Jewitt, J. Agarwal, J. Li, H. Weaver, M. Mutchler, S. Larson (2017). The Astronomical Journal, 153:223(17pp)

  2. Magnetic properties of the high-Tsub(c) superconductors RBa2Cu3Osub(9-delta) (R=Gd, Dy, Er)

    International Nuclear Information System (INIS)

    Groot, P.A.J. de; Rainford, B.D.; McK-Paul, D.; Balakrishnan, G.; Lanchester, P.C.; Weller, M.T.; Grasmeder, J.

    1987-01-01

    Magnetic properties of RBa 2 Cu 3 Osub(9-delta) with R = Y, Gd, Dy, Er have been measured for 4.2 K < T < 300 K and magnetic fields up to 7 T. They exhibit a superconductive transition around 91 K, above which temperature the magnetisation can be described by a Curie-Weiss law. The magnetic and superconductive properties develop independently below the phase transition. Magnetic hysteresis is prominent at low temperatures (T < or approx. 25 K) and varies for different samples. Estimates for critical densities are given. (author)

  3. Derivation of the MMPI-2-RF Henry-Heilbronner Index-r (HHI-r) scale.

    Science.gov (United States)

    Henry, George K; Heilbronner, Robert L; Algina, James; Kaya, Yasemin

    2013-01-01

    The 15-item Henry-Heilbronner Index (HHI) was published in 2006 as an MMPI-2 embedded measure of psychological response validity. When the MMPI-2 was revised in 2008 only 11 of the 15 original HHI items were retained on the MMPI-2-RF, prohibiting use of the HHI as an embedded validity indicator on the MMPI-2-RF. Using the original HHI sample an 11-item version of the HHI, the HHI-r, was evaluated for use as an embedded measure of psychological response validity for the MMPI-2-RF. The 11-item HHI-r was very similar to the HHI in classification accuracy. An HHI-r cutoff score of ≥7 was associated with a classification accuracy rate of 84.0%, good sensitivity (68.9%), and high specificity (93.2%) in identifying symptom exaggeration in personal injury and disability litigants versus non-litigating head-injured patients. These preliminary results suggest the HHI-r functions in a manner similar to the original HHI as a measure of psychological response validity, and may be used by psychologists and neuropsychologists as an MMPI-2-RF embedded validity indicator.

  4. miR-494 up-regulates the PI3K/Akt pathway via targetting PTEN and attenuates hepatic ischemia/reperfusion injury in a rat model.

    Science.gov (United States)

    Su, Song; Luo, De; Liu, Xiangdong; Liu, Jiang; Peng, Fangyi; Fang, Cheng; Li, Bo

    2017-10-31

    A rat HIRI model was constructed and treated with an intraperitoneal injection of agomir- miR-494 or agomir-NC (negative control) for 7 days after the surgery. The pathophysiological changes in sham-operated rats, HIRI, HIRI + agomir- miR-494 , and HIRI + agomir-NC were compared. The effect of miR-494 was also assessed in an H 2 O 2 -induced apoptosis model. Hepatic AML12 cells were transfected with mimics NC or miR-494 mimics, followed by 6-h H 2 O 2 treatment. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Further, the miR-494 target gene was identified by luciferase reporter assay, and verified both in vitro and in vivo experiments. The activity of AKT pathway was further analyzed in vivo by Western blot. HIRI + agomir- miR-494 rats exhibited significantly higher miR-494 expression, lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and glutamate dehydrogenase (GLDH) level, lower hepatic MDA, TOA, and OSI, alleviated hepatic necrosis, reduced hepatocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI + agomir-NC rats ( P <0.05 or 0.01). After H 2 O 2 treatment, AML-12 cells transfected with miR-494 mimics had significantly higher proliferation and lower apoptosis rate compared with mimics NC group ( P <0.01). PTEN was identified as an miR-494 target gene. PTEN expression was significantly down-regulated in AML12 cells transfected with miR-494 mimics, and was up-regulated by treatment of miR-494 inhibitor ( P <0.01). Moreover, HIRI + agomir- miR-494 rats exhibited significantly lower PTEN expression, and higher p-AKT, p-mTOR, and p-p70S6K levels compared with HIRI + agomir-NC rats. Therefore, miR-494 protected rats against hepatic ischemia/reperfusion (I/R) injury through down-regulating its downstream target gene PTEN , leading to the activation of PI3K/AKT signaling pathway. © 2017 The Author(s).

  5. 3D-QSAR CoMFA of a series of DABO derivatives as HIV-1 reverse transcriptase non-nucleoside inhibitors.

    Science.gov (United States)

    de Brito, Monique Araújo; Rodrigues, Carlos Rangel; Cirino, José Jair Vianna; de Alencastro, Ricardo Bicca; Castro, Helena Carla; Albuquerque, Magaly Girão

    2008-08-01

    A series of 74 dihydroalkoxybenzyloxopyrimidines (DABOs), a class of highly potent non-nucleoside reverse transcriptase inhibitors (NNRTIs), was retrieved from the literature and studied by comparative molecular field analysis (CoMFA) in order to derive three-dimensional quantitative structure-activity relationship (3D-QSAR) models. The CoMFA study has been performed with a training set of 59 compounds, testing three alignments and four charge schemes (DFT, HF, AM1, and PM3) and using defaults probe atom (Csp (3), +1 charge), cutoffs (30 kcal.mol (-1) for both steric and electrostatic fields), and grid distance (2.0 A). The best model ( N = 59), derived from Alignment 1 and PM3 charges, shows q (2) = 0.691, SE cv = 0.475, optimum number of components = 6, r (2) = 0.930, SEE = 0.226, and F-value = 115.544. The steric and electrostatic contributions for the best model were 43.2% and 56.8%, respectively. The external predictive ability (r (2) pred = 0.918) of the resultant best model was evaluated using a test set of 15 compounds. In order to design more potent DABO analogues as anti-HIV/AIDS agents, attention should be taken in order to select a substituent for the 4-oxopyrimidine ring, since, as revealed by the best CoMFA model, there are a steric restriction at the C2-position, a electron-rich group restriction at the C6-position ( para-substituent of the 6-benzyl group), and a steric allowed region at the C5-position.

  6. 3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model.

    Science.gov (United States)

    Ul-Haq, Zaheer; Ashraf, Sajda; Al-Majid, Abdullah Mohammed; Barakat, Assem

    2016-04-30

    Urease enzyme (EC 3.5.1.5) has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship) advance studies were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q²) value of 0.597 and correlation coefficients (r²) of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q² and r² of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r²pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity.

  7. 3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model

    Directory of Open Access Journals (Sweden)

    Zaheer Ul-Haq

    2016-04-01

    Full Text Available Urease enzyme (EC 3.5.1.5 has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship advance studies were performed by Comparative Molecular Field Analysis (CoMFA and Comparative Molecular Similarity Indices Analysis (CoMSIA methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q2 value of 0.597 and correlation coefficients (r2 of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q2 and r2 of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r2pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity.

  8. MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA

    International Nuclear Information System (INIS)

    Lang, Qingbo; Ling, Changquan

    2012-01-01

    Highlights: ► PIK3CA is a novel target of miR-124 in HepG2 cells. ► MiR-124 suppresses cell proliferation by downregulating PIK3CA expression. ► MiR-124 regulates the PI3K/Akt pathway in HepG2 cells. ► MiR-124 overexpression inhibits the tumorigenesis in nude mice. -- Abstract: MicroRNAs (miRNAs) have crucial roles in the development and progression of human cancers, including hepatocellular carcinoma (HCC). Recent studies have shown that microRNA-124 (miR-124) was downregulated in HCC; however, the underlying mechanisms by which miR-124 suppresses tumorigenesis in HCC are largely unknown. In this study, we report that phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) is a novel target of miR-124 in HepG2 cells. Overexpression of miR-124 resulted in decreased expression of PIK3CA at both mRNA and protein levels. We found that miR-124 overexpression markedly suppressed cell proliferation by inducing G1-phase cell-cycle arrest in vitro. Consistent with the restoring miR-124 expression, PIK3CA knockdown suppressed cell proliferation, whereas overexpression of PIK3CA abolished the suppressive effect of miR-124. Mechanistic studies showed that miR-124-mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. The expressions of Akt and mTOR, key components of the PI3K/Akt pathway, were all downregulated. Moreover, we found overexpressed miR-124 effectively repressed tumor growth in xenograft animal experiments. Taken together, our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA.

  9. MiR-124 suppresses cell proliferation in hepatocellular carcinoma by targeting PIK3CA

    Energy Technology Data Exchange (ETDEWEB)

    Lang, Qingbo [Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Ling, Changquan, E-mail: lingchangquan@hotmail.com [Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2012-09-21

    Highlights: Black-Right-Pointing-Pointer PIK3CA is a novel target of miR-124 in HepG2 cells. Black-Right-Pointing-Pointer MiR-124 suppresses cell proliferation by downregulating PIK3CA expression. Black-Right-Pointing-Pointer MiR-124 regulates the PI3K/Akt pathway in HepG2 cells. Black-Right-Pointing-Pointer MiR-124 overexpression inhibits the tumorigenesis in nude mice. -- Abstract: MicroRNAs (miRNAs) have crucial roles in the development and progression of human cancers, including hepatocellular carcinoma (HCC). Recent studies have shown that microRNA-124 (miR-124) was downregulated in HCC; however, the underlying mechanisms by which miR-124 suppresses tumorigenesis in HCC are largely unknown. In this study, we report that phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) is a novel target of miR-124 in HepG2 cells. Overexpression of miR-124 resulted in decreased expression of PIK3CA at both mRNA and protein levels. We found that miR-124 overexpression markedly suppressed cell proliferation by inducing G1-phase cell-cycle arrest in vitro. Consistent with the restoring miR-124 expression, PIK3CA knockdown suppressed cell proliferation, whereas overexpression of PIK3CA abolished the suppressive effect of miR-124. Mechanistic studies showed that miR-124-mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. The expressions of Akt and mTOR, key components of the PI3K/Akt pathway, were all downregulated. Moreover, we found overexpressed miR-124 effectively repressed tumor growth in xenograft animal experiments. Taken together, our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA.

  10. 17 CFR 240.3b-12 - Definition of OTC derivatives dealer.

    Science.gov (United States)

    2010-04-01

    ... to options, forwards, futures, swap agreements, or collars involving currencies, interest or other... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of OTC derivatives... Securities Exchange Act of 1934 Definitions § 240.3b-12 Definition of OTC derivatives dealer. The term OTC...

  11. Towards Coleoptera-specific high-throughput screening systems for compounds with ecdysone activity: development of EcR reporter assays using weevil (Anthonomus grandis)-derived cell lines and in silico analysis of ligand binding to A. grandis EcR ligand-binding pocket.

    Science.gov (United States)

    Soin, Thomas; Iga, Masatoshi; Swevers, Luc; Rougé, Pierre; Janssen, Colin R; Smagghe, Guy

    2009-08-01

    Molting in insects is regulated by ecdysteroids and juvenile hormones. Several synthetic non-steroidal ecdysone agonists are on the market as insecticides. These ecdysone agonists are dibenzoylhydrazine (DBH) analogue compounds that manifest their toxicity via interaction with the ecdysone receptor (EcR). Of the four commercial available ecdysone agonists, three (tebufenozide, methoxyfenozide and chromafenozide) are highly lepidopteran specific, one (halofenozide) is used to control coleopteran and lepidopteran insects in turf and ornamentals. However, compared to the very high binding affinity of these DBH analogues to lepidopteran EcRs, halofenozide has a low binding affinity for coleopteran EcRs. For the discovery of ecdysone agonists that target non-lepidopteran insect groups, efficient screening systems that are based on the activation of the EcR are needed. We report here the development and evaluation of two coleopteran-specific reporter-based screening systems to discover and evaluate ecdysone agonists. The screening systems are based on the cell lines BRL-AG-3A and BRL-AG-3C that are derived from the weevil Anthonomus grandis, which can be efficiently transduced with an EcR reporter cassette for evaluation of induction of reporter activity by ecdysone agonists. We also cloned the almost full length coding sequence of EcR expressed in the cell line BRL-AG-3C and used it to make an initial in silico 3D-model of its ligand-binding pocket docked with ponasterone A and tebufenozide.

  12. A pair of novel Cd(II) enantiomers based on lactate derivatives: Synthesis, crystal structures and properties

    International Nuclear Information System (INIS)

    Xu, Zhong-Xuan; Ao, Ke-Hou; Zhang, Jian

    2016-01-01

    A pair of novel 3D homochiral metal−organic frameworks (HMOFs), namely [Cd 2.5 ((R)-CIA) 6 (1,4-DIB)(H 2 O) 2 ]·((CH 3 ) 2 NH 2 )·H 2 O (1-D), [Cd 2.5 ((S)-CIA) 6 (1,4-DIB)(H 2 O) 2 ]·((CH 3 ) 2 NH 2 )·H 2 O (1-L), have been synthesized using lactic acid derivative ligands ((R)-H 3 CIA and (S)-H 3 CIA) and 1,4-DIB. Crystallographic analyses indicate that the complexes 1-D and 1-L are packed by cage substructures. Some physical characteristics, such as solid-state circular dichroism (CD), thermal stabilities and photoluminescent properties are also investigated. Our results highlight the effective method to apply lactic acid derivative ligands to form interesting HMOFs. - Graphical abstract: Using lactic acid derivative ligands ((R)-H 3 CIA and (S)-H 3 CIA) and 1,4-DIB to assemble with Cd 2+ ions, a pair of novel 3D homochiral metal-organic frameworks (HMOFs) with cage substructures have been synthesized. Display Omitted - Highlights: • Lactic acid derivative ligands • Cage substructure • Enantiomers

  13. The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis.

    Science.gov (United States)

    Ren, Lin-Lin; Yan, Ting-Ting; Shen, Chao-Qin; Tang, Jia-Yin; Kong, Xuan; Wang, Ying-Chao; Chen, Jinxian; Liu, Qiang; He, Jie; Zhong, Ming; Chen, Hao-Yan; Hong, Jie; Fang, Jing-Yuan

    2018-06-07

    The abnormal expression of microRNAs (miRNAs) in colorectal cancer (CRC) progression has been widely investigated. It was reported that the same hairpin RNA structure could generate mature products from each strand, termed 5p and 3p, which binds different target mRNAs. Here, we explored the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in CRC cells and tissues. We found that miR-514b-3p was significantly down-regulated in CRC samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. Follow-up functional experiments illustrated that miR-514b-3p and miR-514b-5p had distinct effects through interacting with different target genes: MiR-514b-3p reduced CRC cell migration, invasion and drug resistance through increasing epithelial marker and decreasing mesenchymal marker expressions, conversely, miR-514b-5p exerted its pro-metastatic properties in CRC by promoting EMT progression. MiR-514b-3p overexpressing CRC cells developed tumors more slowly in mice compared with control cells, however, miR-514b-5p accelerated tumor metastasis. Overall, our data indicated that though miR-514b-3p and miR-514b-5p were transcribed from the same RNA hairpin, each microRNA has distinct effect on CRC metastasis.

  14. Laser-diode-excited blue upconversion in Tm3+/Yb3+ -codoped TeO2-Ga2O3-R2O (R=Li, Na, K) glasses.

    Science.gov (United States)

    Zhao, Chun; Zhang, Qinyuan; Yang, Gangfeng; Jiang, Zhonghong

    2008-01-01

    This paper reports on intense blue upconversion in Tm(3+)/Yb(3+) codoped TeO(2)-Ga(2)O(3)-R(2)O(R=Li, Na, K) glasses upon excitation with commercial available laser diode (LD). Effects of alkali ions on the Raman spectra, thermal stability and spectroscopic properties of the tellurite-gallium glasses have also been investigated. Energy transfer and the involved upconversion mechanisms have been discussed. Intense blue upconversion emission centered at 476 nm along with a weak red emission at 650 nm has been observed upon excitation of 977 nm LD, assigned to the transitions of 1G4-->3H6, and 1G4-->3H4 and/or 3F(2,3)-->3H6 of Tm(3+), respectively. The blue upconversion intensity has a cubelike dependence on incident pump laser power, indicating a three-photon process. However, a quadratic dependence of the 476 nm upconversion intensity on the incident pump laser power has been observed when samples under excitation of 808 nm LD due to a two-photon absorption process. Enhanced upconversion luminescence have been observed with replacing K(+) for Na(+) and Li(+).

  15. 17 CFR 240.3b-13 - Definition of eligible OTC derivative instrument.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of eligible OTC derivative instrument. 240.3b-13 Section 240.3b-13 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Under the Securities Exchange Act of 1934 Definitions § 240.3b-13 Definition of eligible OTC derivative...

  16. Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice.

    Science.gov (United States)

    Barker, Jacqueline M; Lench, Daniel H; Chandler, L Judson

    2016-01-01

    Alcohol use disorders are associated with deficits in adaptive behavior. While some behavioral impairments that are associated with alcohol use disorders may predate exposure to drugs of abuse, others may result directly from exposure to drugs of abuse, including alcohol. Identifying a causal role for how alcohol exposure leads to these impairments will enable further investigation of the neurobiological mechanisms by which it acts to dysregulate adaptive behavior. In the present study, we examined the effects of chronic intermittent ethanol exposure (CIE) on the use of reward-paired cues to guide consummatory behaviors in a mouse model, and further, how manipulations of mGluR2/3 signaling-known to be dysregulated after chronic alcohol exposure-may alter the expression of this behavior. Adult male C57B/6J mice were trained to self-administer 10 % ethanol and exposed to CIE via vapor inhalation. After CIE exposure, mice were trained in a Pavlovian task wherein a cue (tone) was paired with the delivery of a 10 % sucrose unconditioned stimulus. The use of the reward-paired cue to guide licking behavior was determined across training. The effect of systemic mGluR2/3 manipulation on discrimination between cue-on and cue-off intervals was assessed by administration of the mGluR2/3 agonist LY379268 or the antagonist LY341495 prior to a testing session. Exposure to CIE resulted in reductions in discrimination between cue-on and cue-off intervals, with CIE-exposed mice exhibiting significantly lower consummatory behavior during reward-paired cues than air controls. In addition, systemic administration of an mGluR2/3 agonist restored the use of reward-paired cues in CIE-exposed animals without impacting behavior in air controls. Conversely, administration of an mGluR2/3 antagonist mimicked the effects of CIE on cue-guided licking behavior, indicating that mGluR2/3 signaling can bidirectionally regulate the ability to use reward-paired cues to guide behavior. Together

  17. A consistent and unified picture for critical phenomena of f(R) AdS black holes

    International Nuclear Information System (INIS)

    Mo, Jie-Xiong; Li, Gu-Qiang; Wu, Yu-Cheng

    2016-01-01

    A consistent and unified picture for critical phenomena of charged AdS black holes in f ( R ) gravity is drawn in this paper. Firstly, we investigate the phase transition in canonical ensemble. We derive the explicit solutions corresponding to the divergence of C Q . The two solutions merge into one when the condition Q c =√(−1/3 R 0 ) is satisfied. The curve of specific heat for Q < Q c has two divergent points and can be divided into three regions. Both the large radius region and the small radius region are thermodynamically stable with positive specific heat while the medium radius region is unstable with negative specific heat. However, when Q > Q c , the specific heat is always positive, implying the black holes are locally stable and no phase transition will take place. Secondly, both the T − r + curve and T − S curve f ( R ) AdS black holes are investigated and they exhibit Van der Vaals like behavior as the P − v curve in the former research. Critical physical quantities are obtained and they are consistent with those derived from the specific heat analysis. We carry out numerical check of Maxwell equal area law for the cases Q =0.2 Q c , 0.4 Q c , 0.6 Q c , 0.8 Q c . The relative errors are amazingly small and can be negligible. So the Maxwell equal area law holds for T − S curve of f ( R ) black holes. Thirdly, we establish geometrothermodynamics for f ( R ) AdS black hole to examine the phase structure. It is shown that the Legendre invariant scalar curvature R would diverge exactly where the specific heat diverges. To summarize, the above three perspectives are consistent with each other, thus providing a unified picture which deepens the understanding of critical phenomena of f ( R ) AdS black holes.

  18. The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice.

    Directory of Open Access Journals (Sweden)

    Neri Mercatelli

    Full Text Available BACKGROUND: MiR-221 and miR-222 are two highly homologous microRNAs whose upregulation has been recently described in several types of human tumors, for some of which their oncogenic role was explained by the discovery of their target p27, a key cell cycle regulator. We previously showed this regulatory relationship in prostate carcinoma cell lines in vitro, underlying the role of miR-221/222 as inducers of proliferation and tumorigenicity. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a number of in vivo approaches confirming our previous data. The ectopic overexpression of miR-221 is able, per se, to confer a high growth advantage to LNCaP-derived tumors in SCID mice. Consistently, the anti-miR-221/222 antagomir treatment of established subcutaneous tumors derived from the highly aggressive PC3 cell line, naturally expressing high levels of miR-221/222, reduces tumor growth by increasing intratumoral p27 amount; this effect is long lasting, as it is detectable as long as 25 days after the treatment. Furthermore, we provide evidence in favour of a clinical relevance of the role of miR-221/222 in prostate carcinoma, by showing their general upregulation in patient-derived primary cell lines, where we find a significant inverse correlation with p27 expression. CONCLUSIONS/SIGNIFICANCE: These findings suggest that modulating miR-221/222 levels may have a therapeutic potential in prostate carcinoma.

  19. Detector production for the R3B Si-tracker

    Energy Technology Data Exchange (ETDEWEB)

    Borri, M., E-mail: marcello.borri@liverpool.ac.uk [University of Liverpool, Department of Physics, Oxford Street, Liverpool L69 7ZE (United Kingdom); Lemmon, R. [STFC Daresbury Laboratory, Daresbury, Warrington WA4 4 CE (United Kingdom); Thornhill, J.; Bate, R.; Chartier, M. [University of Liverpool, Department of Physics, Oxford Street, Liverpool L69 7ZE (United Kingdom); Clague, N. [STFC Daresbury Laboratory, Daresbury, Warrington WA4 4 CE (United Kingdom); Herzberg, R.-D. [University of Liverpool, Department of Physics, Oxford Street, Liverpool L69 7ZE (United Kingdom); Labiche, M. [STFC Daresbury Laboratory, Daresbury, Warrington WA4 4 CE (United Kingdom); Lindsay, S.; Nolan, P.; Pearce, F.; Powell, W.; Wells, D. [University of Liverpool, Department of Physics, Oxford Street, Liverpool L69 7ZE (United Kingdom)

    2016-11-11

    R3B is a fixed target experiment which will study reactions with relativistic radioactive beams at FAIR. Its Si-tracker will surround the target volume and it will detect light charged-particles like protons. The detector technology in use consists of double-sided silicon strip sensors wire bonded to the custom made R3B-ASIC. The tracker allows for a maximum of two outer layers and one inner layer. This paper reports on the production of detectors necessary to build the minimum tracking configuration: one inner layer and one outer layer.

  20. The β-1,3-glucanosyltransferase Gas1 regulates Sir2-mediated rDNA stability in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ha, Cheol Woong; Kim, Kwantae; Chang, Yeon Ji; Kim, Bongkeun; Huh, Won-Ki

    2014-07-01

    In Saccharomyces cerevisiae, the stability of highly repetitive rDNA array is maintained through transcriptional silencing. Recently, a β-1,3-glucanosyltransferase Gas1 has been shown to play a significant role in the regulation of transcriptional silencing in S. cerevisiae. Here, we show that the gas1Δ mutation increases rDNA silencing in a Sir2-dependent manner. Remarkably, the gas1Δ mutation induces nuclear localization of Msn2/4 and stimulates the expression of PNC1, a gene encoding a nicotinamidase that functions as a Sir2 activator. The lack of enzymatic activity of Gas1 or treatment with a cell wall-damaging agent, Congo red, exhibits effects similar to those of the gas1Δ mutation. Furthermore, the loss of Gas1 or Congo red treatment lowers the cAMP-dependent protein kinase (PKA) activity in a cell wall integrity MAP kinase Slt2-dependent manner. Collectively, our results suggest that the dysfunction of Gas1 plays a positive role in the maintenance of rDNA integrity by decreasing PKA activity and inducing the accumulation of Msn2/4 in the nucleus. It seems that nuclear-localized Msn2/4 stimulate the expression of Pnc1, thereby enhancing the association of Sir2 with rDNA and promoting rDNA stability. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Evaluating the potential for near-shore bathymetry on the Majuro Atoll, Republic of the Marshall Islands, using Landsat 8 and WorldView-3 imagery

    Science.gov (United States)

    Poppenga, Sandra K.; Palaseanu-Lovejoy, Monica; Gesch, Dean B.; Danielson, Jeffrey J.; Tyler, Dean J.

    2018-04-16

    Satellite-derived near-shore bathymetry (SDB) is becoming an increasingly important method for assessing vulnerability to climate change and natural hazards in low-lying atolls of the northern tropical Pacific Ocean. Satellite imagery has become a cost-effective means for mapping near-shore bathymetry because ships cannot collect soundings safely while operating close to the shore. Also, green laser light detection and ranging (lidar) acquisitions are expensive in remote locations. Previous research has demonstrated that spectral band ratio-based techniques, commonly called the natural logarithm approach, may lead to more precise measurements and modeling of bathymetry because of the phenomenon that different substrates at the same depth have approximately equal ratio values. The goal of this research was to apply the band ratio technique to Landsat 8 at-sensor radiance imagery and WorldView-3 atmospherically corrected imagery in the coastal waters surrounding the Majuro Atoll, Republic of the Marshall Islands, to derive near-shore bathymetry that could be incorporated into a seamless topobathymetric digital elevation model of Majuro. Attenuation of light within the water column was characterized by measuring at-sensor radiance and reflectance at different depths and calculating an attenuation coefficient. Bathymetric lidar data, collected by the U.S. Naval Oceanographic Office in 2006, were used to calibrate the SDB results. The bathymetric lidar yielded a strong linear relation with water depths. The Landsat 8-derived SDB estimates derived from the blue/green band ratio exhibited a water attenuation extinction depth of 6 meters with a coefficient of determination R2=0.9324. Estimates derived from the coastal/red band ratio had an R2=0.9597. At the same extinction depth, SDB estimates derived from WorldView-3 imagery exhibited an R2=0.9574. Because highly dynamic coastal shorelines can be affected by erosion, wetland loss, hurricanes, sea-level rise, urban

  2. Constraint propagation equations of the 3+1 decomposition of f(R) gravity

    International Nuclear Information System (INIS)

    Paschalidis, Vasileios; Shapiro, Stuart L; Halataei, Seyyed M H; Sawicki, Ignacy

    2011-01-01

    Theories of gravity other than general relativity (GR) can explain the observed cosmic acceleration without a cosmological constant. One such class of theories of gravity is f(R). Metric f(R) theories have been proven to be equivalent to Brans-Dicke (BD) scalar-tensor gravity without a kinetic term (ω = 0). Using this equivalence and a 3+1 decomposition of the theory, it has been shown that metric f(R) gravity admits a well-posed initial value problem. However, it has not been proven that the 3+1 evolution equations of metric f(R) gravity preserve the (Hamiltonian and momentum) constraints. In this paper, we show that this is indeed the case. In addition, we show that the mathematical form of the constraint propagation equations in BD-equilavent f(R) gravity and in f(R) gravity in both the Jordan and Einstein frames is exactly the same as in the standard ADM 3+1 decomposition of GR. Finally, we point out that current numerical relativity codes can incorporate the 3+1 evolution equations of metric f(R) gravity by modifying the stress-energy tensor and adding an additional scalar field evolution equation. We hope that this work will serve as a starting point for relativists to develop fully dynamical codes for valid f(R) models.

  3. Elevation of circulating miR-210-3p in high-altitude hypoxic environment

    Directory of Open Access Journals (Sweden)

    Yan eYan

    2016-03-01

    Full Text Available Background: The induction of miR-210-3p, a master hypoxamir, is a consistent feature of the hypoxic response in both normal and malignant cells. However, whether miR-210-3p acts as a circulating factor in response to a hypoxic environment remains unknown. The current study aimed to examine the effect of a high-altitude hypoxic environment on circulating miR-210-3p.Methods: We examined and compared the levels of miR-210-3p using TaqMan-based qRT-PCR in both peripheral blood cells and plasma from 84 ethnic Chinese Tibetans residing at 3560 m, 46 newly arrived migrant Han Chinese (Tibet Han and 82 Han Chinese residing at 8.9 m (Nanjing Han. Furthermore, we analyzed the correlations of miR-210-3p with hematological indices. Results: The relative concentrations of miR-210-3p to internal reference U6 in blood cells were significantly higher in the Tibet Han group (1.01±0.11, P<0.001 and in the Tibetan group (1.17±0.09, P<0.001 than in the Nanjing Han group (0.51±0.04. The absolute concentrations of plasma miR-210-3p were also markedly elevated in the Tibet Han group (503.54±42.95 fmol/L, P=0.004 and in the Tibetan group (557.78±39.84 fmol/L, P<0.001 compared to the Nanjing Han group (358.39±16.16 fmol/L. However, in both blood cells and plasma, miR-210-3p levels were not significantly different between the Tibet Han group and the Tibetan group (P=0.280, P=0.620, respectively. Plasma miR-210-3p concentrations were positively correlated with miR-210-3p levels in blood cells (r=0.192, P=0.005. Furthermore, miR-210-3p levels in both blood cells and plasma showed strong positive correlations with red blood cell counts and hemoglobin and hematocrit values. Conclusion: These data demonstrated, for the first time, that miR-210-3p might act as a circulating factor in response to hypoxic environments and could be associated with human adaptation to life at high altitudes.

  4. Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors

    Czech Academy of Sciences Publication Activity Database

    Mikyšková, Romana; Indrová, Marie; Polláková, Veronika; Bieblová, Jana; Šímová, Jana; Reiniš, Milan

    2012-01-01

    Roč. 35, č. 5 (2012), s. 374-384 ISSN 1524-9557 R&D Projects: GA ČR(CZ) GPP301/11/P220; GA ČR GA301/09/1024; GA ČR GA301/07/1410 EU Projects: European Commission(XE) 18933 - CLINIGENE Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : myeloid-derived suppressor cells * cyclophosphamide * all-trans-retinoic acid * IL-12 * HPV16 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.463, year: 2012

  5. Volumetric properties of binary mixtures of {difluoromethane (R32) + trans-1,3,3,3-tetrafluoropropene (R1234ze(E))} at temperatures from 283.15 K to 363.15 K and pressures up to 100 MPa

    International Nuclear Information System (INIS)

    Jia, Tao; Bi, Shengshan; Hu, Xiaozhen; Meng, Xianyang; Wu, Jiangtao

    2016-01-01

    Highlights: • Densities of R32+R1234ze(E) mixtures were measured with a vibrating-tube densimeter. • Densities of mixtures were conducted from (283 to 363) K, at pressures up to 100 MPa. • Excess molar volumes were correlated with the Redlich–Kister equation. - Abstract: Values of experimental density of difluoromethane (R32) and five compositions of {R32 + trans-1,3,3,3-tetrafluoropropene (R1234ze(E))} binary mixtures are reported over the temperature range from 283 K to 363 K and at pressures up to 100 MPa with a vibrating-tube densimeter. The excess molar volumes were calculated from experimental results and fitted to the Redlich–Kister equation. The maximum standard deviation and average standard deviations of the experimental and calculated values of excess molar volume from Redlich–Kister equation are 0.07789 cm"3·mol"−"1 and 0.01645 cm"3·mol"−"1, respectively.

  6. The Onion (Allium cepa L.) R2R3-MYB Gene MYB1 Regulates Anthocyanin Biosynthesis

    Science.gov (United States)

    Schwinn, Kathy E.; Ngo, Hanh; Kenel, Fernand; Brummell, David A.; Albert, Nick W.; McCallum, John A.; Pither-Joyce, Meeghan; Crowhurst, Ross N.; Eady, Colin; Davies, Kevin M.

    2016-01-01

    Bulb color is an important consumer trait for onion (Allium cepa L., Allioideae, Asparagales). The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red), flavonols (pale yellow), and chalcones (bright yellow). Flavonoid regulation is poorly characterized in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs) that commonly activate anthocyanin (SG6, MYB1) or flavonol (SG7, MYB29) production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5). MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressed and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic (Allium sativum L.) plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum majus of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species. PMID:28018399

  7. The onion (Allium cepa L. R2R3-MYB gene MYB1 regulates anthocyanin biosynthesis

    Directory of Open Access Journals (Sweden)

    Kathy Schwinn

    2016-12-01

    Full Text Available Bulb colour is an important consumer trait for onion (Allium cepa L., Allioideae, Asparagales. The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red, flavonols (pale yellow and chalcones (bright yellow. Flavonoid regulation is poorly characterised in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs that commonly activate anthocyanin (SG6, MYB1 or flavonol (SG7, MYB29 production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5. MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressd and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic (A. sativum L. plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum majus of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species.

  8. The Onion (Allium cepa L.) R2R3-MYB Gene MYB1 Regulates Anthocyanin Biosynthesis.

    Science.gov (United States)

    Schwinn, Kathy E; Ngo, Hanh; Kenel, Fernand; Brummell, David A; Albert, Nick W; McCallum, John A; Pither-Joyce, Meeghan; Crowhurst, Ross N; Eady, Colin; Davies, Kevin M

    2016-01-01

    Bulb color is an important consumer trait for onion ( Allium cepa L., Allioideae, Asparagales). The bulbs accumulate a range of flavonoid compounds, including anthocyanins (red), flavonols (pale yellow), and chalcones (bright yellow). Flavonoid regulation is poorly characterized in onion and in other plants belonging to the Asparagales, despite being a major plant order containing many important crop and ornamental species. R2R3-MYB transcription factors associated with the regulation of distinct branches of the flavonoid pathway were isolated from onion. These belonged to sub-groups (SGs) that commonly activate anthocyanin (SG6, MYB1) or flavonol (SG7, MYB29) production, or repress phenylpropanoid/flavonoid synthesis (SG4, MYB4, MYB5). MYB1 was demonstrated to be a positive regulator of anthocyanin biosynthesis by the induction of anthocyanin production in onion tissue when transiently overexpressed and by reduction of pigmentation when transiently repressed via RNAi. Furthermore, ectopic red pigmentation was observed in garlic ( Allium sativum L.) plants stably transformed with a construct for co-overexpression of MYB1 and a bHLH partner. MYB1 also was able to complement the acyanic petal phenotype of a defined R2R3-MYB anthocyanin mutant in Antirrhinum maju s of the asterid clade of eudicots. The availability of sequence information for flavonoid-related MYBs from onion enabled phylogenetic groupings to be determined across monocotyledonous and dicotyledonous species, including the identification of characteristic amino acid motifs. This analysis suggests that divergent evolution of the R2R3-MYB family has occurred between Poaceae/Orchidaceae and Allioideae species. The DNA sequences identified will be valuable for future analysis of classical flavonoid genetic loci in Allium crops and will assist the breeding of these important crop species.

  9. (1S,3S,8R,9S,10R-9,10-Epoxy-3,7,7,10-tetramethyltricyclo[6.4.0.01,3]dodecane

    Directory of Open Access Journals (Sweden)

    Abdoullah Bimoussa

    2014-04-01

    Full Text Available The title compound, C16H26O, was synthesized by treating (1S,3S,8R-3,7,7,10-tetramethyltricyclo[6.4.0.01,3]dodec-9-ene with metachloroperbenzoic acid. The molecule is built up from two fused six- and seven-membered rings. The six-membered ring has a half-chair conformation, whereas the seven-membered ring displays a boat conformation. In the crystal, there are no significant intermolecular interactions present.

  10. Individual GaN nanowires exhibit strong piezoelectricity in 3D.

    Science.gov (United States)

    Minary-Jolandan, Majid; Bernal, Rodrigo A; Kuljanishvili, Irma; Parpoil, Victor; Espinosa, Horacio D

    2012-02-08

    Semiconductor GaN NWs are promising components in next generation nano- and optoelectronic systems. In addition to their direct band gap, they exhibit piezoelectricity, which renders them particularly attractive in energy harvesting applications for self-powered devices. Nanowires are often considered as one-dimensional nanostructures; however, the electromechanical coupling leads to a third rank tensor that for wurtzite crystals (GaN NWs) possesses three independent coefficients, d(33), d(13), and d(15). Therefore, the full piezoelectric characterization of individual GaN NWs requires application of electric fields in different directions and measurements of associated displacements on the order of several picometers. In this Letter, we present an experimental approach based on scanning probe microscopy to directly quantify the three-dimensional piezoelectric response of individual GaN NWs. Experimental results reveal that GaN NWs exhibit strong piezoelectricity in three dimensions, with up to six times the effect in bulk. Based on finite element modeling, this finding has major implication on the design of energy harvesting systems exhibiting unprecedented levels of power density production. The presented method is applicable to other piezoelectric NW materials as well as wires manufactured along different crystallographic orientations. © 2011 American Chemical Society

  11. The oxanorbornene approach to 3-hydroxy, 3,4-dihydroxy and 3,4,5-trihydroxy derivatives of 2-aminocyclohexanecarboxylic acid

    Directory of Open Access Journals (Sweden)

    Howard Judith AK

    2006-05-01

    Full Text Available Abstract The nitro oxanorbornene adduct derived from the Diels-Alder reaction of ethyl (E-3-nitroacrylate and furan provides a versatile template for the stereoselective synthesis of hydroxylated derivatives of 2-aminocyclohexanecarboxylic acid (ACHC.

  12. Synthesis and physical-chemical properties of 2-((4-R-3-(morpholinomethylen-4H-1,2,4-triazole-5ylthioacetic acid

    Directory of Open Access Journals (Sweden)

    R. О. Shcherbyna

    2014-12-01

    Full Text Available The creation and improvement of the original domestic medicines is anactual problem of medical and pharmaceutical industries. Chemistry of heterocyclicsystems attracts scientists all over the world, as it is associated with a number of properties of this class of compounds which allow to use them for various purposes. It is known that the morpholine salts of 2-((4-R-5-R1-4H-1,2,4-triazoles-3-ylthioacetic acids exhibit low toxicity and pronounced pharmacological effect. The additional morpholine moiety in the 1,2,4-triazole’s nucleusshould lead to compounds with high biological activity. The aim of researchis the synthesis of 2-((4-R-3-(morpholinomethylen-4H-1,2,4-triazole-5-ylthioaceticacidsand determination of its physical-chemical properties. Materials and methods.The determinationof physical-chemical propertiesof the obtained compounds has been carried out according to the methods listed in the State Pharmacopoeia of Ukraine. The determinationof melting temperature has been performed for the synthesized compounds (device OptiMelt Stanford Research Systems MPA100. The structure of the compoundshas been confirmed by 1H NMR spectroscopy (Mercury 400, chromatography-mass spectrometry (Agilent 1260 Infinity device with mass detector Agilent 6120 LC / MS and elemental analysis (ElementarVario L cube. Results.14 new synthesized compounds, namely isopropyl 2-morpholinoacetate, 2-morpholinoacetohydrazide, N-R-2-(2-morpholinoacetylhydrazinecarbothioamides, 2-(2-morpholinoacetyl-hydrazinecarbothioamide, 3-(morpholinomethyl-4-R-4H-1,2,4-triazole-5-thiolesand2-((4-R-3-(morpholinomethylen-4H-1,2,4-triazole-5-ylthioaceticacid(where, R=H, CH3, C2H5,C6H5 have been studied.The fragmentation of 2-((4-ethyl-3-(morpholinomethyl-4H-1,2,4-triazol-5-ylthioacetic acid has been carried out usingmethod of LC/MS and fragment ions have been identified. The structure of the synthesized compounds in all cases has been confirmed by modern instrumental methods of analysis

  13. Analysis of the grape MYB R2R3 subfamily reveals expanded wine quality-related clades and conserved gene structure organization across Vitis and Arabidopsis genomes

    Science.gov (United States)

    Matus, José Tomás; Aquea, Felipe; Arce-Johnson, Patricio

    2008-01-01

    Background The MYB superfamily constitutes the most abundant group of transcription factors described in plants. Members control processes such as epidermal cell differentiation, stomatal aperture, flavonoid synthesis, cold and drought tolerance and pathogen resistance. No genome-wide characterization of this family has been conducted in a woody species such as grapevine. In addition, previous analysis of the recently released grape genome sequence suggested expansion events of several gene families involved in wine quality. Results We describe and classify 108 members of the grape R2R3 MYB gene subfamily in terms of their genomic gene structures and similarity to their putative Arabidopsis thaliana orthologues. Seven gene models were derived and analyzed in terms of gene expression and their DNA binding domain structures. Despite low overall sequence homology in the C-terminus of all proteins, even in those with similar functions across Arabidopsis and Vitis, highly conserved motif sequences and exon lengths were found. The grape epidermal cell fate clade is expanded when compared with the Arabidopsis and rice MYB subfamilies. Two anthocyanin MYBA related clusters were identified in chromosomes 2 and 14, one of which includes the previously described grape colour locus. Tannin related loci were also detected with eight candidate homologues in chromosomes 4, 9 and 11. Conclusion This genome wide transcription factor analysis in Vitis suggests that clade-specific grape R2R3 MYB genes are expanded while other MYB genes could be well conserved compared to Arabidopsis. MYB gene abundance, homology and orientation within particular loci also suggests that expanded MYB clades conferring quality attributes of grapes and wines, such as colour and astringency, could possess redundant, overlapping and cooperative functions. PMID:18647406

  14. The Odorant ( R)-Citronellal Attenuates Caffeine Bitterness by Inhibiting the Bitter Receptors TAS2R43 and TAS2R46.

    Science.gov (United States)

    Suess, Barbara; Brockhoff, Anne; Meyerhof, Wolfgang; Hofmann, Thomas

    2018-03-14

    Sensory studies showed the volatile fraction of lemon grass and its main constituent, the odor-active citronellal, to significantly decrease the perceived bitterness of a black tea infusion as well as caffeine solutions. Seven citronellal-related derivatives were synthesized and shown to inhibit the perceived bitterness of caffeine in a structure-dependent manner. The aldehyde function at carbon 1, the ( R)-configuration of the methyl-branched carbon 3, and a hydrophobic carbon chain were found to favor the bitter inhibitory activity of citronellal; for example, even low concentrations of 25 ppm were observed to reduce bitterness perception of caffeine solution (6 mmol/L) by 32%, whereas ( R)-citronellic acid (100 pm) showed a reduction of only 21% and ( R)-citronellol (100 pm) was completely inactive. Cell-based functional experiments, conducted with the human bitter taste receptors TAS2R7, TAS2R10, TAS2R14, TAS2R43, and TAS2R46 reported to be sensitive to caffeine, revealed ( R)-citronellal to completely block caffeine-induced calcium signals in TAS2R43-expressing cells, and, to a lesser extent, in TAS2R46-expressing cells. Stimulation of TAS2R43-expressing cells with structurally different bitter agonists identified ( R)-citronellal as a general allosteric inhibitor of TAS2R43. Further structure/activity studies indicated 3-methyl-branched aliphatic aldehydes with a carbon chain of ≥4 C atoms as best TAS2R43 antagonists. Whereas odor-taste interactions have been mainly interpreted in the literature to be caused by a central neuronal integration of odors and tastes, rather than by peripheral events at the level of reception, the findings of this study open up a new dimension regarding the interaction of the two chemical senses.

  15. Anthracycline antibiotics derivate mitoxantrone-Destructive sorption and photocatalytic degradation

    Czech Academy of Sciences Publication Activity Database

    Štenglová Netíková, I. R.; Petruželka, L.; Šťastný, Martin; Štengl, Václav

    2018-01-01

    Roč. 13, č. 3 (2018), č. článku e0193116. E-ISSN 1932-6203 R&D Projects: GA TA ČR(CZ) TG02010049 Institutional support: RVO:61388980 Keywords : Anthracycline antibiotics derivate * nanostructured titanium(IV) oxide Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 2.806, year: 2016

  16. Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors.

    Science.gov (United States)

    Cui, Jing; Peng, Xia; Gao, Dingding; Dai, Yang; Ai, Jing; Li, Yingxia

    2017-08-15

    Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy because of its critical role in promoting cancer formation and progression. In a continuing effort to improve the cellular activity of hit compound 7r bearing an indazole scaffold, which was previously discovered by our group, several compounds harnessing fluorine substituents were designed, synthesized and biological evaluated. Besides, the region extended out to the ATP binding pocket toward solvent was also explored. Among them, compound 2a containing 2,6-difluoro-3-methoxyphenyl residue exhibited the most potent activities (FGFR1: less than 4.1nM, FGFR2: 2.0±0.8nM). More importantly, compound 2a showed an improved antiproliferative effect against KG1 cell lines and SNU16 cell lines with IC 50 values of 25.3±4.6nM and 77.4±6.2nM respectively. Copyright © 2017. Published by Elsevier Ltd.

  17. T cell expression of IL-18R and DR3 is essential for non-cognate stimulation of Th1 cells and optimal clearance of intracellular bacteria.

    Science.gov (United States)

    Pham, Oanh H; O'Donnell, Hope; Al-Shamkhani, Aymen; Kerrinnes, Tobias; Tsolis, Renée M; McSorley, Stephen J

    2017-08-01

    Th1 cells can be activated by TCR-independent stimuli, but the importance of this pathway in vivo and the precise mechanisms involved require further investigation. Here, we used a simple model of non-cognate Th1 cell stimulation in Salmonella-infected mice to examine these issues. CD4 Th1 cell expression of both IL-18R and DR3 was required for optimal IFN-γ induction in response to non-cognate stimulation, while IL-15R expression was dispensable. Interestingly, effector Th1 cells generated by immunization rather than live infection had lower non-cognate activity despite comparable IL-18R and DR3 expression. Mice lacking T cell intrinsic expression of MyD88, an important adapter molecule in non-cognate T cell stimulation, exhibited higher bacterial burdens upon infection with Salmonella, Chlamydia or Brucella, suggesting that non-cognate Th1 stimulation is a critical element of efficient bacterial clearance. Thus, IL-18R and DR3 are critical players in non-cognate stimulation of Th1 cells and this response plays an important role in protection against intracellular bacteria.

  18. Production of R,R-2,3-butanediol of ultra-high optical purity from Paenibacillus polymyxa ZJ-9 using homologous recombination.

    Science.gov (United States)

    Zhang, Li; Cao, Can; Jiang, Ruifan; Xu, Hong; Xue, Feng; Huang, Weiwei; Ni, Hao; Gao, Jian

    2018-08-01

    The present study describes the use of metabolic engineering to achieve the production of R,R-2,3-butanediol (R,R-2,3-BD) of ultra-high optical purity (>99.99%). To this end, the diacetyl reductase (DAR) gene (dud A) of Paenibacillus polymyxa ZJ-9 was knocked out via homologous recombination between the genome and the previously constructed targeting vector pRN5101-L'C in a process based on homologous single-crossover. PCR verification confirmed the successful isolation of the dud A gene disruption mutant P. polymyxa ZJ-9-△dud A. Moreover, fermentation results indicated that the optical purity of R,R-2,3-BD increased from about 98% to over 99.99%, with a titer of 21.62 g/L in Erlenmeyer flasks. The latter was further increased to 25.88 g/L by fed-batch fermentation in a 5-L bioreactor. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Puupehanol, a Sesquiterpene-Dihydroquinone Derivative from the Marine Sponge Hyrtios sp

    Science.gov (United States)

    Puupehanol (1), a new sesquiterpene-dihydroquinone derivative, was isolated from the marine sponge Hyrtios sp., along with the known compounds puupehenone (2) and chloropuupehenone (3). The structure of 1 was established as (20R,21R)-21-hydroxy-20,21-dihydropuupehenone by interpretation of spectros...

  20. 6-Bromocholesterol derivatives

    International Nuclear Information System (INIS)

    Flanagan, R.J.

    1984-01-01

    Novel 6-bromo derivatives of cholesterol have the formula 3-(R-O-),6-BR,17-((H3C-)2-HC-H2C-H2C-H2C-HC(-CH3)-)-ESTR-5-ENE Such compounds are prepared from the known 6-iodocholesterol by treatment with cuprous bromide. These compounds, labelled with radioisotopes of Br-82 or Br-77, are localized in the adrenal, mammary and ovary tissue of female mammals and in the adrenal or prostate tissue of males when administered to such individuals. This provides a method for imaging adrenal, ovary or prostate tissue which is superior to use of the prior art 6-iodo-cholesterol