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Sample records for abs 1b bis

  1. Antidiabetic Bis-Maltolato-OxoVanadium(IV): Conversion of inactive trans- to bioactive cis-BMOV for possible binding to target PTP-1B

    Science.gov (United States)

    Scior, Thomas; Mack, Hans-Georg; García, José Antonio Guevara; Koch, Wolfhard

    2008-01-01

    The postulated transition of Bis-Maltolato-OxoVanadium(IV) (BMOV) from its inactive trans- into its cis-aquo-BMOV isomeric form in solution was simulated by means of computational molecular modeling. The rotational barrier was calculated with DFT – B3LYP under a stepwise optimization protocol with STO-3G, 3-21G, 3-21G*, and 6-31G ab initio basis sets. Our computed results are consistent with reports on the putative molecular mechanism of BMOV triggering the insulin-like cellular response (insulin mimetic) as a potent inhibitor of the protein tyrosine phosphatase-1B (PTP-1B). Initially, trans-BMOV is present in its solid dosage form but in aqueous solution, and during oral administration, it is readily converted into a mixture of “open-type” and “closed-type” complexes of cis-aquo-BMOV under equilibrium conditions. However, in the same measure as the “closed-type” complex binds to the cytosolic PTP-1B, it disappears from solution, and the equilibrium shifts towards the “closed-type” species. In full accordance, the computed binding mode of cis-BMOV is energetically favored over sterically hindered trans-BMOV. In view of our earlier report on prodrug hypothesis of vanadium organic compounds the present results suggest that cis-BMOV is the bioactive species. PMID:19920909

  2. Synthesis, resolution, and applications of 2, 2'-bis(diphenylphosphino)-3,3'- binaphtho[2,1-b]furan.

    Science.gov (United States)

    Andersen, N G; Parvez, M; Keay, B A

    2000-09-07

    [structure: see text] A short five-step synthesis of (+/-)-2,2'-bis(diphenylphosphino)-3, 3'-binaphtho[2,1-b]furan (BINAPFu, 1) starting from 2-naphthoxyacetic acid is reported. The resolution of BINAPFu 1 was possible using our newly developed resolution procedure for phosphines wherein (1S)-camphorsulfonyl azide was used to prepare the bisphosphinimine of BINAPFu via the Staundinger reaction. BINAPFu consistently outperformed BINAP in an asymmetric Heck reaction between 2,3-dihydrofuran and phenyl triflate.

  3. Antidiabetic Bis-Maltolato-OxoVanadium(IV: Conversion of inactive trans- to bioactive cis-BMOV for possible binding to target PTP-1B

    Directory of Open Access Journals (Sweden)

    Thomas Scior

    2008-11-01

    Full Text Available Thomas Scior1, Hans-Georg Mack2, José Antonio Guevara García3, Wolfhard Koch41Departamento de Farmacia. Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Colonia San Manuel, Puebla, Mexico; 2Institut für Physikalische Chemie, Universität Tübingen, Tübingen, Germany; 3Laboratorio de Investigación en Bioinorgánica y Biorremediación (LIByB. Departamento de Ciencias Básicas, Ingeniería y Tecnología, Universidad Autónoma de Tlaxcala, Apizaco, Tlaxcala, Mexico; 4Facultad de Estudios Superiores Zaragoza (FESZ, Universidad Nacional Autónoma de México (UNAM, Colonia Ejército de Oriente, Delegación Iztapalapa, Mexico City, MexicoAbstract: The postulated transition of Bis-Maltolato-OxoVanadium(IV (BMOV from its inactive trans- into its cis-aquo-BMOV isomeric form in solution was simulated by means of computational molecular modeling. The rotational barrier was calculated with DFT – B3LYP under a stepwise optimization protocol with STO-3G, 3-21G, 3-21G*, and 6-31G ab initio basis sets. Our computed results are consistent with reports on the putative molecular mechanism of BMOV triggering the insulin-like cellular response (insulin mimetic as a potent inhibitor of the protein tyrosine phosphatase-1B (PTP-1B. Initially, trans-BMOV is present in its solid dosage form but in aqueous solution, and during oral administration, it is readily converted into a mixture of “open-type” and “closed-type” complexes of cis-aquo-BMOV under equilibrium conditions. However, in the same measure as the “closed-type” complex binds to the cytosolic PTP-1B, it disappears from solution, and the equilibrium shifts towards the “closed-type” species. In full accordance, the computed binding mode of cis-BMOV is energetically favored over sterically hindered trans-BMOV. In view of our earlier report on prodrug hypothesis of vanadium organic compounds the present results suggest that cis-BMOV is the bioactive species

  4. An ab-initio study of a1B3u→X1Ag transition in a neutral molecular N2 dimer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Presents the ab-initio calculations performed for differentsymmetry groups of neutral molecular N2 dimer, and the calculation of ground state and low-lying singlet excited states for each symmetry group and concludes from the results that there is an electric dipole transition between X1Ag and a1B3u (singlet-singlet) excited states belonging to D2h group symmetry, and discusses the vibrational energy levels and emission spectra calculates for this transition.

  5. Photoabsorption Assignments for the C̃(1)B2 ← X̃(1)A1 Vibronic Transitions of SO2, Using New Ab Initio Potential Energy and Transition Dipole Surfaces.

    Science.gov (United States)

    Kumar, Praveen; Jiang, Bin; Guo, Hua; Kłos, Jacek; Alexander, Millard H; Poirier, Bill

    2017-02-09

    The high resolution spectroscopy of the SO2 molecule is of great topical interest, in a wide variety of contexts ranging from origins of higher life, to astrophysics of the interstellar medium, to environmental chemistry. In particular, the C̃(1)B2 ← X̃(1)A1 UV photoabsorption spectrum has received considerable attention. This spectrum exhibits a highly regular progression of ∼20 or so strong peaks, spaced roughly 350 cm(-1) apart, which is comparable to the C̃(1)B2 bending vibrational frequency. Accordingly, they have for decades been largely attributed to the (1, v2('), 2) ← (0, 0, 0) bend progression. Using a highly accurate new ab initio potential energy surface (PES) for the C̃(1)B2 state, we compute vibrational energy levels and wave functions, and compare with a photoabsorption calculation obtained using the same PES and corresponding C̃(1)B2 ← X̃(1)A1 transition dipole surface (TDS). We find that the above putative assignment is incorrect, contradicting even general qualitative trends-thus necessitating a very different dynamical picture for this highly unusual molecule.

  6. Irradiation programme HFR phase 1b. Results of impact tests with the irradiated materials (2.4 dpa); Bestrahlungsprogramm HFR Phase 1b. Ergebnisse der Kerbschlagbiegeversuche mit den bis 2,4 dpa bestrahlten Werkstoffen

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, H.C.; Dafferner, B.; Ries, H.; Lautensack, S.; Romer, O.

    2004-04-01

    The irradiation project HFR phase 1b was planned and carried out in the frame of the European Long-term Fusion Materials Development Programme. It represents the continuation of the former High-Flux-Reactor irradiation programmes which are documented in detail in former FZK-reports. The problem of the irradiation induced embrittlement of possible martensitic alloy candidates is still not finally solved. After evaluation of sub-size Charpy tests with the 2.4 dpa irradiated specimens, the low activation 7-10%-Cr-W(Ge)VTa alloys showed outstandingly better characteristics compared to the modified commercial 10-11%-Cr-NiMoVNb steels. The emphasis of the phase 1b project is now on the investigation of low activating OPTIFER-alloys, which exhibit in contrast to the previously irradiated OPTIFER-steels a clearly reduced boron content in order to reduce the irradiation embrittlement. In the present report the results of instrumented impact tests within the phase 1b programme (irradiation dose 2.4 dpa, irradiation temperatures 250, 300, 350, 400, and 450 C) are analysed and assessed in comparison to the results of the MANITU- and HFR phase 1a- irradiation programmes. Herein, the OPTIFER-V steel, which is nearly identical to the industrial heat EUROFER97 (which became available after the irradiation), supplied the best results. (orig.)

  7. Ab initio MO study on equilibrium bond distance between Fe and pyridine in bis(pyridine)(porphinato) iron for various electronic states

    Science.gov (United States)

    Saito, Minoru; Kashiwagi, Hiroshi

    1985-04-01

    For bis(pyridine)(porphinato) iron [FeP(py)2], a correlation between the iron electronic state and the equilibrium Fe-Npy distance was investigated. Potential energy curves as a function of the Fe-Npy distance were calculated for low-spin, intermediate-spin, and high-spin states of the ferric and ferrous ions by the ab initio SCF MO method. The equilibrium Fe-Npy distances were obtained from the potential curves. The values obtained for the ferric low-spin and high-spin states were in good agreement with the experimental values for Fe(III)(OEP)(3-Clpy)2 within the differences, ±0.05 Å. The following significant features were found. The equilibrium distance is elongated by the occupation of the 3dz2 orbital and is shortened by the oxidation of the iron atom. The distance and the force constant for the symmetrical py-Fe-py stretching are strongly correlated with the overlap population between the 3dz2 orbital and pyridine-nitrogen orbitals.

  8. Crystal Structure, Vibrational Spectroscopy and ab Initio Density Functional Theory Calculations on the Ionic Liquid forming 1,1,3,3-Tetramethylguanidinium bis{(trifluoromethyl)sulfonyl}amide

    DEFF Research Database (Denmark)

    Berg, Rolf W.; Riisager, Anders; Nguyen van Buu, Olivier;

    2009-01-01

    The salt 1,1,3,3-tetramethylguanidinium bis{(trifluoromethyl)sulfonyl}amide, [((CH3)(2)N)(2)C=NH2](+)[N(SO2-CF3)(2)](-) or [tmgH][NTf2], easily forms an ionic liquid with high SO2 absorbing capacity. The crystal structure of the salt was determined at 120(2) K by X-ray diffraction. The structure...

  9. BIS 220 Tutorials /bis220dotcom

    OpenAIRE

    ramya85

    2015-01-01

    BIS 220 Entire Course   For more course tutorials visit www.bis220.com   BIS 220 Week 1 Individual Assignment Information Technology Acts Paper BIS 220 Week 1 DQ 1 BIS 220 Week 1 DQ 2 BIS 220 Week 2 LT Reflection Summary BIS 220 Week 2 Individual Assignment Information Systems Proposal BIS 220 Week 2 DQ 1 BIS 220 Week 2 DQ 2 BIS 220 Week 3 Individual Assignment Types of Electronic Commerce Activity BIS 220 Week 3 LT Reflection Summ...

  10. BIS 220 Tutorials / bis220dotcom

    OpenAIRE

    rajitha82

    2015-01-01

    BIS 220 Entire Course   For more course tutorials visit www.bis220.com   BIS 220 Week 1 Individual Assignment Information Technology Acts Paper BIS 220 Week 1 DQ 1 BIS 220 Week 1 DQ 2 BIS 220 Week 2 LT Reflection Summary BIS 220 Week 2 Individual Assignment Information Systems Proposal BIS 220 Week 2 DQ 1 BIS 220 Week 2 DQ 2 BIS 220 Week 3 Individual Assignment Types of Electronic Commerce Activity BIS 220 Week 3 LT Reflection Summ...

  11. Interferon Gamma-1b Injection

    Science.gov (United States)

    Interferon gamma-1b injection is used to reduce the frequency and severity of serious infections in people with ... with severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of medications called ...

  12. Interferon Beta-1b Injection

    Science.gov (United States)

    ... medications (Avonex, Plegridy, Rebif), any other medications, human albumin, mannitol, or any of the other ingredients in ... 1b powder at room temperature and away from excess heat and moisture (not in the bathroom). If ...

  13. BIS 220 Uop Material-bis220dotcom

    OpenAIRE

    greenappled

    2015-01-01

    BIS 220 Entire Course For more course tutorials visit www.bis220.com BIS 220 Week 1 Individual Assignment Information Technology Acts Paper BIS 220 Week 1 DQ 1 BIS 220 Week 1 DQ 2 BIS 220 Week 2 LT Reflection Summary BIS 220 Week 2 Individual Assignment Information Systems Proposal BIS 220 Week 2 DQ 1 BIS 220 Week 2 DQ 2 BIS 220 Week 3 Individual Assignment Types of Electronic Commerce Activity BIS 220 Week 3 LT Reflection Summary BIS 220 Week 3...

  14. The capsular polysaccharide Vi from Salmonella typhi is a B1b antigen.

    Science.gov (United States)

    Marshall, Jennifer L; Flores-Langarica, Adriana; Kingsley, Robert A; Hitchcock, Jessica R; Ross, Ewan A; López-Macías, Constantino; Lakey, Jeremy; Martin, Laura B; Toellner, Kai-Michael; MacLennan, Calman A; MacLennan, Ian C; Henderson, Ian R; Dougan, Gordon; Cunningham, Adam F

    2012-12-15

    Vaccination with purified capsular polysaccharide Vi Ag from Salmonella typhi can protect against typhoid fever, although the mechanism for its efficacy is not clearly established. In this study, we have characterized the B cell response to this vaccine in wild-type and T cell-deficient mice. We show that immunization with typhoid Vi polysaccharide vaccine rapidly induces proliferation in B1b peritoneal cells, but not in B1a cells or marginal zone B cells. This induction of B1b proliferation is concomitant with the detection of splenic Vi-specific Ab-secreting cells and protective Ab in Rag1-deficient B1b cell chimeras generated by adoptive transfer-induced specific Ab after Vi immunization. Furthermore, Ab derived from peritoneal B cells is sufficient to confer protection against Salmonella that express Vi Ag. Expression of Vi by Salmonella during infection did not inhibit the development of early Ab responses to non-Vi Ags. Despite this, the protection conferred by immunization of mice with porin proteins from Salmonella, which induce Ab-mediated protection, was reduced postinfection with Vi-expressing Salmonella, although protection was not totally abrogated. This work therefore suggests that, in mice, B1b cells contribute to the protection induced by Vi Ag, and targeting non-Vi Ags as subunit vaccines may offer an attractive strategy to augment current Vi-based vaccine strategies.

  15. ABS 497 Complete Class

    OpenAIRE

    admin

    2015-01-01

    ABS 497 Complete Class   To purchase this material click below link   http://www.assignmentcloud.com/ABS-497/ABS-497-Complete-Class-Guide   For more classes visit   www.assignmentcloud.com   ABS 497 Week 1 Assignment Community Change ABS 497 Week 1 DQ 1 Fabian's Story ABS 497 Week 1 DQ 2 Doug's Story ABS 497 Week 2 DQ 1 Parenting Styles ABS 497 Week 2 DQ 2 Ethnicity and Learning Theory ABS 497 Week 3 ...

  16. Main: 1B37 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B37 トウモロコシ Corn Zea mays L. Polyamine Oxidase Precursor Name=Pao; Zea Mays Molecul...FSNWPVGVNRYEYDQLRAPVGRVYFTGEHTSEHYNGYVHGAYLSGIDSAEILINCAQKKMCKYHVQGKYD corn_1B37.jpg ...

  17. Remembering AB

    Science.gov (United States)

    Belyayev, S. T.

    2013-06-01

    In 1947 I became a second-year student at Moscow State University's Physics and Engineering Department, where a part of the week's classes were taught at base organizations. Our group's base was the future Kurchatov Institute, at that time known as the mysterious "Laboratory N^circ 2," and later as LIPAN. REFID="9789814436571_0004FN001">. Besides group lectures and practical work at the experimental laboratories, we also had access to the general seminars which Igor Vasilyevich Kurchatov tried to hold, with Leonid Vasilyevich Groshev filling in when he was absent. At the seminar, theorists spoke as welcome co-presenters and commentators. In 1949 I felt ready to approach A. B. Migdal to ask if I could transfer to his theoretical sector. In response, he suggested a number of simple qualitative problems, which I then successfully solved. (Incidentally, AB used the very same "introductory problems" for screening many generations of students.) So I wound up among AB's students. From 1952 on (for 10 years) I also served as an employee of the Migdal Sector. My memoirs here are mainly inspired by these years of constant communication with AB. After my departure for Novosibirsk in 1962, although our meetings still took place, they became occasional....

  18. 18 CFR 1b.12 - Transcripts.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Transcripts. 1b.12 Section 1b.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.12 Transcripts. Transcripts, if any,...

  19. 18 CFR 1b.14 - Subpoenas.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Subpoenas. 1b.14 Section 1b.14 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.14 Subpoenas. (a) Service of a...

  20. 18 CFR 1b.19 - Submissions.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Submissions. 1b.19 Section 1b.19 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.19 Submissions. In the event...

  1. 18 CFR 1b.5 - Formal investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Formal investigations. 1b.5 Section 1b.5 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.5 Formal investigations....

  2. 18 CFR 1b.6 - Preliminary investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Preliminary investigations. 1b.6 Section 1b.6 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.6 Preliminary investigations....

  3. 18 CFR 1b.1 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.1 Definitions. For purposes of this part—...

  4. 18 CFR 1b.2 - Scope.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to...

  5. Unident AB

    OpenAIRE

    2004-01-01

    Abstract: Unident AB, a corporation based in Falkenberg/South West Sweden, deals with dental material. Its board consists of two young brothers who tried to launch a new dental product that their father intro-duced to them after having attended an international exhibition of dental products. Being only in their early twenties, the brothers originally man-aged the company beside their studies and other assignments. Within only a few years after starting out in the early 1990s, the company expe...

  6. 18 CFR 1b.21 - Enforcement hotline.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Enforcement hotline. 1b..., DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.21 Enforcement hotline. (a) The Hotline Staff may provide information to the public and give informal staff opinions. The opinions...

  7. Construction of HEK293 cells stably expressing wild-type organic anion transporting polypeptide 1B1 (OATP1B1*1a) and variant OATP1B1*1b and OATP1B1*15.

    Science.gov (United States)

    Chen, M; Qu, B X; Chen, X L; Hu, H H; Jiang, H D; Yu, L S; Zhou, Q; Zeng, S

    2016-06-01

    A transgenic cell line stably expressing the human organic anion transporting polypeptide (OATP1B1) was established. Human Embryonic Kidney 293 (HEK293) cell line stably expressing OATP1B1*1a sequence was amplified through PCR with the extracted total RNA as templates from human liver, then subcloned into the plasmid pMD19-T and verified by sequencing. OATP1B1*1b/OATP1B1*15 mutant sequences were obtained by site-directed mutation PCR with pMD19-T/ OATP1B1*1a as templates. The plasmids pcDNA3.1(+)/OATP1B1*1a, *1b and *15 were constructed and transfected into HEK293 cell line using Lipofectamine 2000 transfection reagent. Several stable transfected clones were obtained after selection with G418. Using rosuvastatin as a probe substrate of OATP1B1, the intracellular rosuvastatin accumulation in HEK293 and HEK-OATP1B1*1a, *1b and *15 monoclone cells were validated by a ultra-performance liquid chromatography-tandem mass spectrometry. OATP1B1 mRNA and protein expression were detected by RT-PCR and Western blot, respectively. The results from RT-PCR, rosuvastatin uptake and Western blot assay indicated that human OATP1B1 was highly expressed in transfected cells compared with controls. The HEK-293 cell lines stably expressing human OATP1B1-wild and variant (HEK-OATP1B1, *1b and *15) are potential models to study drug transport in vitro.

  8. Intramolecular Electron Transfer in Bis(tetraalkyl Hydrazine) and Bis(hydrazyl) Radical Cations.

    Science.gov (United States)

    Chang, Hao

    A series of multicyclic bis(hydrazine) and bis(diazenium) compounds connected by relatively rigid hydrocarbon frameworks were prepared for the study of intramolecular electron transfer. The thermodynamics of electron removal of these compounds was investigated by cyclic voltammetry. The difference between the first and second oxidation potentials for the 4 sigma-bonded species was found to be larger for the bis(hydrazyl) radical systems than for the bis(hydrazines) by ca. 0.2 V (4.6 kcal/mol). This indicates a greater degree of interaction between the two nitrogen moieties for the hydrazyl systems, which is consistent with a greater degree of electronic coupling (H _{rm AB}) in these systems. The ESR spectra of the 4 sigma -bonded bis(hydrazine) radical cations indicate localized radical cations, which corresponds to slow intramolecular electron transfer on the ESR timescale. Conversely, the ESR spectra of the corresponding bis(hydrazyl) radical cation systems show nitrogen hyperfine splittings of a(4N) of ca. 4.5 G. This indicates that intramolecular electron transfer between the two nitrogen moieties is fast on the ESR timescale; the rate of exchange, k_ {rm ex} was estimated to be well above 1.9 times 10^8 s^{-1}. The contrast in exchange rates is consistent with the large geometry change upon oxidation which is characteristic of hydrazines. The hydrazyls undergo a smaller geometry change upon oxidation, and thus are expected to exhibit smaller inner-sphere reorganization energies. The optical spectra of these radical species was investigated in hopes of observing absorption bands corresponding to intramolecular electron transfer, as predicted by Hush theory. A broad absorption band was observed in the near IR region for the saturated bis(hydrazyl) radical cation system at 1060 nm (9420 cm^{-1} ) in acetonitrile at room temperature, and was accompanied by a narrower band at 1430 nm (6993 cm^ {-1}). The width of this band was estimated to be 545 nm (6496 cm^{-1

  9. Bacterial Expression and Purification of an Active ω-Atracotoxin-Ar1b from Spider Atrax robustus

    Institute of Scientific and Technical Information of China (English)

    WANG Yu-qin; WANG Jue; LI Jian; LIU Qiang; HUANG Shi-di; WANG Dun

    2010-01-01

    The ω-atracotoxin-Ar1b toxin(ω-ACTX-Ar1b)is one of the arthropod-selective peptide neurotoxins from the venom of Australian funnel-web spider Atrax robustus.The gene of Ar1b was synthesized and cloned into pET-32a(+)vector to allow expression of Ar1b as a fusion protein with thioredoxin and the His-tag(rTrx-Ar1b)in E.coli BL21(DE3).The optimal condition for inducing the expression of rTrx-Ar1b was 1.0 mmol L-1 IPTG for 6 h at 28℃.The fusion protein rTrx-Ar1b was expressed in soluble form and was purified effectively by His Trap HP affinity column and rpHLPC and a final yield of purified rTrx-Ar1b was 95 mg from 1000 mL E.coli culture.The LD50 values for Mythimna separate and Tenebrio molitor were 111.66 and 11.04 μg g-1 determined by injection of the purified rTrx-Ar1b.The results indicated that the recombinant Ar1b protein was successfully expressed in E.coli and it was high toxicity against tested insects.

  10. 2000 Johnston Site 1B-P

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 1B-P was established at Johnston Atoll by Dr. James Maragos, U.S. Fish & Wildlife Service, on June 29, 2000. With a start point (meter 0) at...

  11. ABS 497 ASH Tutorial / Uoptutorial

    OpenAIRE

    Latifa Baka

    2015-01-01

    For more course tutorials visit www.uoptutorial.com   ABS 497 Week 1 Assignment Community Change ABS 497 Week 1 DQ 1 Fabian's Story ABS 497 Week 1 DQ 2 Doug's Story ABS 497 Week 2 DQ 1 Parenting Styles ABS 497 Week 2 DQ 2 Ethnicity and Learning Theory ABS 497 Week 3 DQ 1 Suicide ABS 497 Week 3 DQ 2 Development Theories ABS 497 Week 3 Assignment communication PowerPoint Presentation ABS 497 Week 4 DQ 1 Leadership Theories ABS 497 Week 4 ...

  12. ABS 497 ASH TUTORIAL / Uoptutorial

    OpenAIRE

    Remo

    2015-01-01

    For more course tutorials visit www.uoptutorial.com   ABS 497 Week 1 Assignment Community Change ABS 497 Week 1 DQ 1 Fabian's Story ABS 497 Week 1 DQ 2 Doug's Story ABS 497 Week 2 DQ 1 Parenting Styles ABS 497 Week 2 DQ 2 Ethnicity and Learning Theory ABS 497 Week 3 DQ 1 Suicide ABS 497 Week 3 DQ 2 Development Theories ABS 497 Week 3 Assignment communication PowerPoint Presentation ABS 497 Week 4 DQ 1 Leadership Theories ABS 497 Week 4...

  13. ABS 497 Courses/snaptutorial

    OpenAIRE

    charles

    2015-01-01

    For more classes visit www.snaptutorial.com   ABS 497 Week 1 Assignment Community Change ABS 497 Week 1 DQ 1 Fabian's Story ABS 497 Week 1 DQ 2 Doug's Story ABS 497 Week 2 DQ 1 Parenting Styles ABS 497 Week 2 DQ 2 Ethnicity and Learning Theory ABS 497 Week 3 DQ 1 Suicide ABS 497 Week 3 DQ 2 Development Theories ABS 497 Week 3 Assignment communication PowerPoint Presentation ABS 497 Week 4 DQ 1 Leadership Theories ABS 497 Week 4 DQ ...

  14. Unusual rearrangement in the photochemical addition of bis(alkylidene)disilacyclobutanes to C[sub 60

    Energy Technology Data Exchange (ETDEWEB)

    Kusukawa, Takahiro; Kabe, Yoshio; Erata, Tomoki; Nestler, B.; Ando, Wataru (Univ. of Tsukuba (Japan))

    1994-11-01

    The photochemical reaction of bis(alkylidene)-disilacyclobutanes 1a, b with C[sub 60] afforded the stable 1:1 adducts 3a,b, resulting from an unexpected rearrangement of the disilacyclobutane unit. The structures of 3a,b were determined by spectroscopic methods, including [sup 29]Si-[sup 1]H HMBC hetero nuclear shift correlation experiments. 18 refs., 2 figs.

  15. GIFTS SM EDU Level 1B algorithms

    Science.gov (United States)

    Tian, Jialin; Gazarik, Michael J.; Reisse, Robert A.; Johnson, David G.

    2007-10-01

    The Geosynchronous Imaging Fourier Transform Spectrometer (GIFTS) Sensor Module (SM) Engineering Demonstration Unit (EDU) is a high resolution spectral imager designed to measure infrared (IR) radiances using a Fourier transform spectrometer (FTS). The GIFTS instrument employs three focal plane arrays (FPAs), which gather measurements across the long-wave IR (LWIR), short/mid-wave IR (SMWIR), and visible spectral bands. The raw interferogram measurements are radiometrically and spectrally calibrated to produce radiance spectra, which are further processed to obtain atmospheric profiles via retrieval algorithms. This paper describes the GIFTS SM EDU Level 1B algorithms involved in the calibration. The GIFTS Level 1B calibration procedures can be subdivided into four blocks. In the first block, the measured raw interferograms are first corrected for the detector nonlinearity distortion, followed by the complex filtering and decimation procedure. In the second block, a phase correction algorithm is applied to the filtered and decimated complex interferograms. The resulting imaginary part of the spectrum contains only the noise component of the uncorrected spectrum. Additional random noise reduction can be accomplished by applying a spectral smoothing routine to the phase-corrected spectrum. The phase correction and spectral smoothing operations are performed on a set of interferogram scans for both ambient and hot blackbody references. To continue with the calibration, we compute the spectral responsivity based on the previous results, from which, the calibrated ambient blackbody (ABB), hot blackbody (HBB), and scene spectra can be obtained. We now can estimate the noise equivalent spectral radiance (NESR) from the calibrated ABB and HBB spectra. The correction schemes that compensate for the fore-optics offsets and off-axis effects are also implemented. In the third block, we developed an efficient method of generating pixel performance assessments. In addition, a

  16. GIFTS SM EDU Level 1B Algorithms

    Science.gov (United States)

    Tian, Jialin; Gazarik, Michael J.; Reisse, Robert A.; Johnson, David G.

    2007-01-01

    The Geosynchronous Imaging Fourier Transform Spectrometer (GIFTS) SensorModule (SM) Engineering Demonstration Unit (EDU) is a high resolution spectral imager designed to measure infrared (IR) radiances using a Fourier transform spectrometer (FTS). The GIFTS instrument employs three focal plane arrays (FPAs), which gather measurements across the long-wave IR (LWIR), short/mid-wave IR (SMWIR), and visible spectral bands. The raw interferogram measurements are radiometrically and spectrally calibrated to produce radiance spectra, which are further processed to obtain atmospheric profiles via retrieval algorithms. This paper describes the GIFTS SM EDU Level 1B algorithms involved in the calibration. The GIFTS Level 1B calibration procedures can be subdivided into four blocks. In the first block, the measured raw interferograms are first corrected for the detector nonlinearity distortion, followed by the complex filtering and decimation procedure. In the second block, a phase correction algorithm is applied to the filtered and decimated complex interferograms. The resulting imaginary part of the spectrum contains only the noise component of the uncorrected spectrum. Additional random noise reduction can be accomplished by applying a spectral smoothing routine to the phase-corrected spectrum. The phase correction and spectral smoothing operations are performed on a set of interferogram scans for both ambient and hot blackbody references. To continue with the calibration, we compute the spectral responsivity based on the previous results, from which, the calibrated ambient blackbody (ABB), hot blackbody (HBB), and scene spectra can be obtained. We now can estimate the noise equivalent spectral radiance (NESR) from the calibrated ABB and HBB spectra. The correction schemes that compensate for the fore-optics offsets and off-axis effects are also implemented. In the third block, we developed an efficient method of generating pixel performance assessments. In addition, a

  17. Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer’s Therapy?

    Science.gov (United States)

    Vieira, Marcelo N. N.; Lyra e Silva, Natalia M.; Ferreira, Sergio T.; De Felice, Fernanda G.

    2017-01-01

    Despite significant advances in current understanding of mechanisms of pathogenesis in Alzheimer’s disease (AD), attempts at drug development based on those discoveries have failed to translate into effective, disease-modifying therapies. AD is a complex and multifactorial disease comprising a range of aberrant cellular/molecular processes taking part in different cell types and brain regions. As a consequence, therapeutics for AD should be able to block or compensate multiple abnormal pathological events. Here, we examine recent evidence that inhibition of protein tyrosine phosphatase 1B (PTP1B) may represent a promising strategy to combat a variety of AD-related detrimental processes. Besides its well described role as a negative regulator of insulin and leptin signaling, PTB1B recently emerged as a modulator of various other processes in the central nervous system (CNS) that are also implicated in AD. These include signaling pathways germane to learning and memory, regulation of synapse dynamics, endoplasmic reticulum (ER) stress and microglia-mediated neuroinflammation. We propose that PTP1B inhibition may represent an attractive and yet unexplored therapeutic approach to correct aberrant signaling pathways linked to AD. PMID:28197094

  18. Distribution of fluorescence decay times for 1-anilinonaphthalene-8-sulfonate in human oxyhemoglobin A1b solution

    Science.gov (United States)

    Drazdou, A. S.; Sobchuk, A. N.; Syakhovich, V. E.; Bokut, O. S.; Kvasyuk, E. I.; Bushuk, B. A.; Bokut, S. B.

    2012-07-01

    We have studied complex formation between molecules of the fluorescent probe 1-anilinonaphthalene-8-sulfonate (1,8-ANS) and the major form (A1) and a minor form (Ab) of hemoglobin. The contribution of the longlived component f3 to the kinetic curves for fluorescence decay in HbA1b solutions is 0.021-0.036, which indicates a dramatic decrease (compared with HbA1) in the accessibility of the central cavity of HbA1b for binding 1,8-ANS. Disappearance of the long-lived component f3 in the fluorescence decay kinetics of 1,8-ANS in HbA1b solutions in the presence of inositol hexaphosphate (IHP) suggests that the regulatory region of HbA1b is completely inaccessible for interaction both with the negatively charged molecules of the probe and with natural regulators of the transport function for this form of the heme protein.

  19. Practical route to the left wing of CTX1B and total syntheses of CTX1B and 54-deoxyCTX1B.

    Science.gov (United States)

    Yamashita, Shuji; Takeuchi, Katsutoshi; Koyama, Takuya; Inoue, Masayuki; Hayashi, Yujiro; Hirama, Masahiro

    2015-02-02

    Ciguatoxins, the principal causative agents of ciguatera seafood poisoning, are extremely large polycyclic ethers. We report herein a reliable route for constructing the left wing of CTX1B, which possesses the acid/base/oxidant-sensitive bisallylic ether moiety, by a 6-exo radical cyclization/ring-closing metathesis strategy. This new route enabled us to achieve the second-generation total synthesis of CTX1B and the first synthesis of 54-deoxyCTX1B.

  20. From thiourea to bicyclic structures: an original route to imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines.

    Science.gov (United States)

    Landreau, Cyrille; Deniaud, David; Meslin, Jean Claude

    2003-06-13

    We report an example of an efficient regioselective synthesis of biheterocyclic compounds using thiourea as starting material. In fact, N,N'-bis(dimethylaminomethylene)thiourea (1), easily prepared by double condensation of N,N-dimethylformamide dimethyl acetal with thiourea, can be reacted with haloketones or acrylic dienophiles to give thiazolic (2) and thiazinic (3) diazadienes, respectively, themselves undergoing cyclization reactions to yield imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines without any regioisomeric ambiguity. This straightforward route represents an original and unambiguously regioselective pathway to these valuable heterocycles.

  1. Kinetics and Mechanism of Protein Tyrosine Phosphatase 1B (PTP1B) Inactivation by Acrolein

    Science.gov (United States)

    Seiner, Derrick R.; LaButti, Jason N.; Gates, Kent S.

    2010-01-01

    Human cells are exposed to the electrophilic α,β-unsaturated aldehyde acrolein from a variety of sources. Reaction of acrolein with functionally critical protein thiol residues can yield important biological consequences. Protein tyrosine phosphatases (PTPs) are an important class of cysteine-dependent enzymes whose reactivity with acrolein previously has not been well characterized. These enzymes catalyze the dephosphorylation of phosphotyrosine residues on proteins via a phosphocysteine intermediate. PTPs work in tandem with protein tyrosine kinases to regulate a number of critically important mammalian signal transduction pathways. We find that acrolein is a potent time-dependent inactivator of the enzyme PTP1B (kinact = 0.02 ± 0.005 s−1, KI = 2.3 ± 0.6 × 10−4 M). Enzyme activity does not return upon gel filtration of the inactivated enzyme and addition of the competitive phosphatase inhibitor vanadate slows inactivation of PTP1B by acrolein. Together these observations suggest that acrolein covalently modifies the active site of PTP1B. Mass spectrometric analysis reveals that acrolein modifies the catalytic cysteine residue at the active site of the enzyme. Aliphatic aldehydes such as glyoxal, acetaldehyde, and propanal are relatively weak inactivators of PTP1B under the conditions employed here. Similarly, unsaturated aldehydes such as crotonaldehyde and 3-methyl-2-butenal bearing substitution at the alkene terminus are poor inactivators of the enzyme. Overall, the data suggest that enzyme inactivation occurs via conjugate addition of the catalytic cysteine residue to the carbon-carbon double bond of acrolein. The results indicate that inactivation of PTPs should be considered as a possible contributor to the diverse biological activities of acrolein and structurally-related α,β-unsaturated aldehydes. PMID:17655273

  2. Main: 1B5Q [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5Q トウモロコシ Corn Zea mays L. Polyamine Oxidase Precursor Name=Pao; Zea Mays Molecul...EESRRIEQQSDEQTKAEIMQVLRKMFPGKDVPDATDILVPRWWSDRFYKGTFSNWPVGVNRYEYDQLRAPVGRVYFTGEHTSEHYNGYVHGAYLSGIDSAEILINCAQKKMCKYHVQGKYD corn_1B5Q.jpg ...

  3. 18 CFR 1b.11 - Limitation on participation.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Limitation on participation. 1b.11 Section 1b.11 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.11 Limitation...

  4. 18 CFR 1b.3 - Scope of investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope of investigations. 1b.3 Section 1b.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.3 Scope of investigations....

  5. 18 CFR 1b.8 - Requests for Commission investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Requests for Commission investigations. 1b.8 Section 1b.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.8 Requests for...

  6. 18 CFR 1b.7 - Procedure after investigation.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Procedure after investigation. 1b.7 Section 1b.7 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.7 Procedure after...

  7. 18 CFR 1b.18 - Right to submit statements.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Right to submit statements. 1b.18 Section 1b.18 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.18 Right to...

  8. 18 CFR 1b.9 - Confidentiality of investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Confidentiality of investigations. 1b.9 Section 1b.9 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Freedom of Information Act disclosure are set forth in 18 CFR part 3b and § 1b.20. A request...

  9. 18 CFR 1b.4 - Types of investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Types of investigations. 1b.4 Section 1b.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.4 Types of...

  10. 18 CFR 1b.10 - By whom conducted.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false By whom conducted. 1b.10 Section 1b.10 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.10 By whom conducted....

  11. GD1b-specific antibodies may bind to complex of GQ1b and GM1, causing ataxia.

    Science.gov (United States)

    Yuki, Nobuhiro; Fukami, Yuki; Yanaka, Chiaki; Koike, Saiko; Hirata, Koichi

    2014-08-01

    Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have been found in patients with acute ataxic neuropathy and Guillain-Barré syndrome, but the association of the GD1b-specific antibodies with specific neurological conditions has yet to be established. We tested sera from more than 10,000 patients with various neurological disorders, and found six sera, which contained IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b and GQ1b. All six patients who carried GD1b-specific antibodies presented with acute onset of ataxia and monophasic course of the illness, of whom five demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of upper respiratory tract infection. The six patients demonstrated areflexia, and four complained of distal numbness. All the six patients who had the GD1b-specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1. GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are associated with acute ataxia.

  12. Associations of the 5-hydroxytryptamine (Serotonin) Receptor 1B Gene (HTR1B) with Alcohol, Cocaine, and Heroin Abuse

    OpenAIRE

    Cao, Jian; LaRocque, Emily; Li, Dawei

    2013-01-01

    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To ...

  13. Analysis list: HNF1B [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available HNF1B Adipocyte,Digestive tract,Pluripotent stem cell + hg19 http://dbarchive.biosc...iencedbc.jp/kyushu-u/hg19/target/HNF1B.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HNF1B.5....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/HNF1B.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1...B.Adipocyte.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1...B.Digestive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/HNF1B.Pluripotent_st

  14. Inhibition of bromophenols against PTP1B and anti-hyperglycemic effect of Rhodomela confervoides extract in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    SHI DaYong; XU Feng; HE Juan; LI Jing; FAN Xiao; HAN LiJun

    2008-01-01

    Protein tyrosine phosphatase 1B (PTP1B) plays an important role as s negative regulator in insulin signaling pathways.PTP1B is an effective target for the treatment of type 2 diabetes mellitus.Four bromophenol derivatives from red algae Rhodomela confervoides,2,2',3,3'-tetrabromo-4,4',5,5"-tetra-hydroxydiphenyl methane (1),3-bormo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl) pyrocatechol (2),bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (3) and 2,2",3-tribromo-3",4,4",5-tetrahydroxy-6"-ethyloxy-methyldiphenylmethane (4) showed significant inhibitory activity against PTP1B (IC50 were 2.4,1.7,1.5 and 0.84 μmol/L,respectively) as potential therapeutical agents for the treatment of type 2 diabetes mellitus.The anti-hyperglycemic effects of the ethanol extracts from R.confervoides on streptozoto-cin-induced diabetes (STZ-diabetes) in male Wistar rats fed with high fat diet were investigated.The STZ-diabetic rats treated with medium-dose and high-dose alga extracts showed remarkable reductions in fasting blood glucose (FBG) as compared with the STZ-diabetic control.The results indicate that the in vivo anti-hyperglycemic activity of the R.confervoides extracts can be partially attributed to the in-hibitory actions against PTP1B of the bromophenol derivatives and that may be of clinical importance in improving the management of type 2 diabetes mellitus.

  15. Bis(1-adamantylammonium hexafluoridogermanate

    Directory of Open Access Journals (Sweden)

    Liying Cheng

    2008-01-01

    Full Text Available The title compound, (C10H18N2[GeF6], was obtained hydrothermally from an aqueous solution of GeO2, H3BO3, NiCl2, adamantylammonium chloride, butanol and hydrofluoric acid. The structure consists of discrete bis(1-adamantylammonium cations lying on crystallographic mirror planes and hexafluoridogermanate anions disordered about sites of 2/m point symmetry. In the latter, the Ge atom lies on the site of 2/m symmetry, one F atom lies on the mirror plane and two further F atoms are included in general positions with 50% site occupancy. The cations and anions lie in layers with N—H...F hydrogen bonds formed between them.

  16. Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells.

    Directory of Open Access Journals (Sweden)

    Timo H J Niedermeyer

    Full Text Available Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 and OATP1B3 transporters for uptake into human cells, and the high expression of these transporters in the liver accounts for their selective hepatic toxicity. Several human tumors have been shown to have high levels of expression of OATP1B3 but not OATP1B1, the main transporter in liver cells. We hypothesized that microcystin variants could be isolated that are transported preferentially by OATP1B3 relative to OATP1B1 to advance as anticancer agents with clinically tolerable hepatic toxicity. Microcystin variants have been isolated and tested for cytotoxicity in cancer cells stably transfected with OATP1B1 and OATP1B3 transporters. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. As microcystin structure has a significant impact on transporter selectivity, it is potentially possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs.

  17. Selectivity and potency of microcystin congeners against OATP1B1 and OATP1B3 expressing cancer cells.

    Science.gov (United States)

    Niedermeyer, Timo H J; Daily, Abigail; Swiatecka-Hagenbruch, Monika; Moscow, Jeffrey A

    2014-01-01

    Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 and OATP1B3 transporters for uptake into human cells, and the high expression of these transporters in the liver accounts for their selective hepatic toxicity. Several human tumors have been shown to have high levels of expression of OATP1B3 but not OATP1B1, the main transporter in liver cells. We hypothesized that microcystin variants could be isolated that are transported preferentially by OATP1B3 relative to OATP1B1 to advance as anticancer agents with clinically tolerable hepatic toxicity. Microcystin variants have been isolated and tested for cytotoxicity in cancer cells stably transfected with OATP1B1 and OATP1B3 transporters. Microcystin variants with cytotoxic OATP1B1/OATP1B3 IC50 ratios that ranged between 0.2 and 32 were found, representing a 150-fold range in transporter selectivity. As microcystin structure has a significant impact on transporter selectivity, it is potentially possible to develop analogs with even more pronounced OATP1B3 selectivity and thus enable their development as anticancer drugs.

  18. Ca(2+)-dependent anti-GQ1b antibody in GQ1b-seronegative Fisher syndrome and related disorders.

    Science.gov (United States)

    Uchibori, Ayumi; Gyohda, Atsuko; Chiba, Atsuro

    2016-09-15

    Although serum IgG anti-ganglioside GQ1b antibody is the most specific biomarker for Fisher syndrome and its related disorders (FS-RD), 10%-30% of the patients are still negative in conventional assays ("GQ1b-seronegative") and the relationship between GQ1b-seropositive and -seronegative patients has been unclear. Some molecules require Ca(2+) cations to interact with their ligands (Ca(2+)-dependency). Here we have investigated whether Ca(2+)-dependency is also present in anti-GQ1b antibodies in FS-RD, especially in the GQ1b-seronegative patients and show that IgG antibodies against GQ1b-related antigens (isolated GQ1b and GQ1b-containing complexes) are detected Ca(2+)-dependently in the majority of GQ1b-seronegative patients with FS-RD. The Ca(2+)-dependent antibodies might react specifically with GQ1b-Ca(2+) conformation. This is the first demonstration of disease-related Ca(2+)-dependent antibodies in neurological field. GQ1b-related pathology would be involved in FS-RD more extensively than previously revealed.

  19. The Formal Semantics of Core ABS and ABS-NET

    OpenAIRE

    Palmskog, Karl

    2013-01-01

    ABS is a language and framework for modelling distributed object-oriented systems, developed in the EU FP7 HATS project. Core ABS formalizes the key parts of ABS, including the syntax, type system, and an operational semantics in the style of rewriting logic. ABS-NET is a novel operational semantics for Core ABS programs, developed as a part of work on decentralized runtime adaptation of distributed objects. ABS-NET describes program execution on top of a network of nodes connected point-to-p...

  20. AMYLOID-β PEPTIDE BINDS TO MICROTUBULE-ASSOCIATED PROTEIN 1B (MAP1B)

    Science.gov (United States)

    Gevorkian, Goar; Gonzalez-Noriega, Alfonso; Acero, Gonzalo; Ordoñez, Jorge; Michalak, Colette; Munguia, Maria Elena; Govezensky, Tzipe; Cribbs, David H.; Manoutcharian, Karen

    2008-01-01

    Extracellular and intraneuronal formation of amyloid-beta aggregates have been demonstrated to be involved in the pathogenesis of Alzheimer’s disease. However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of targets have deleterious effects on cellular functions. In the present study we have shown for the first time that amyloid-beta 1-42 bound to a peptide comprising the microtubule binding domain of the heavy chain of microtubule-associated protein 1B by the screening of a human brain cDNA library expressed on M13 phage. This interaction may explain, in part, the loss of neuronal cytoskeletal integrity, impairment of microtubule-dependent transport and synaptic dysfunction observed previously in Alzheimer’s disease. PMID:18079022

  1. Curated human hyperbilirubinemia data and the respective OATP1B1 and 1B3 inhibition predictions.

    Science.gov (United States)

    Kotsampasakou, Eleni; Escher, Sylvia E; Ecker, Gerhard F

    2017-04-01

    Hyperbilirubinemia is a pathological condition, very often indicative of underlying liver condition that is characterized by excessive accumulation of conjugated or unconjugated bilirubin in sinusoidal blood. In literature there are several indications associating the inhibition of the basolateral hepatic transporters Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and 1B3) with hyperbilirubinemia. In this article, we present a curated human hyperbilirubinemia dataset and the respective OATP1B1 and 1B3 inhibition predictions obtained from an effort to generate a classification model for hyperbilirubinemia. These data originate from the research article "Linking organic anion transporting polypeptide 1b1 and 1b3 (oatp1b1 and oatp1b3) interaction profiles to hepatotoxicity- the hyperbilirubinemia use case" (E. Kotsampasakou, S.E. Escher, G.F. Ecker, 2017) [1]. We further provide the full list of descriptors used for generating the hyperbilirubinemia classification models as well as the calculated descriptors for each compound of the dataset that was used to build the classification model.

  2. Overexpression and enhanced specific activity of aldoketo reductases (AKR1B1 & AKR1B10) in human breast cancers.

    Science.gov (United States)

    Reddy, K Ashok; Kumar, P Uday; Srinivasulu, M; Triveni, B; Sharada, K; Ismail, Ayesha; Reddy, G Bhanuprakash

    2017-02-01

    The incidence of breast cancer in India is on the rise and is rapidly becoming the primary cancer in Indian women. The aldoketo reductase (AKR) family has more than 190 proteins including aldose reductase (AKR1B1) and aldose reductase like protein (AKR1B10). Apart from liver cancer, the status of AKR1B1 and AKR1B10 with respect to their expression and activity has not been reported in other human cancers. We studied the specific activity and expression of AKR1B1 and AKR1B10 in breast non tumor and tumor tissues and in the blood. Fresh post-surgical breast cancer and non-cancer tissues and blood were collected from the subjects who were admitted for surgical therapy. Malignant, benign and pre-surgical chemotherapy samples were evaluated by histopathology scoring. Expression of AKR1B1 and AKR1B10 was carried out by immunoblotting and immunohistochemistry (IHC) while specific activity was determined spectrophotometrically. The specific activity of AKR1B1 was significantly higher in red blood cells (RBC) in all three grades of primary surgical and post-chemotherapy samples. Specific activity of both AKR1B1 and AKR1B10 increased in tumor samples compared to their corresponding non tumor samples (primary surgical and post-chemotherapy). Immunoblotting and IHC data also indicated overexpression of AKR1B1 in all grades of tumors compared to their corresponding non tumor samples. There was no change in the specific activity of AKR1B1 in benign samples compared to all grades of tumor and non-tumors.

  3. MAN1B1 deficiency: an unexpected CDG-II.

    Directory of Open Access Journals (Sweden)

    Daisy Rymen

    Full Text Available Congenital disorders of glycosylation (CDG are a group of rare metabolic diseases, due to impaired protein and lipid glycosylation. In the present study, exome sequencing was used to identify MAN1B1 as the culprit gene in an unsolved CDG-II patient. Subsequently, 6 additional cases with MAN1B1-CDG were found. All individuals presented slight facial dysmorphism, psychomotor retardation and truncal obesity. Generally, MAN1B1 is believed to be an ER resident alpha-1,2-mannosidase acting as a key factor in glycoprotein quality control by targeting misfolded proteins for ER-associated degradation (ERAD. However, recent studies indicated a Golgi localization of the endogenous MAN1B1, suggesting a more complex role for MAN1B1 in quality control. We were able to confirm that MAN1B1 is indeed localized to the Golgi complex instead of the ER. Furthermore, we observed an altered Golgi morphology in all patients' cells, with marked dilatation and fragmentation. We hypothesize that part of the phenotype is associated to this Golgi disruption. In conclusion, we linked mutations in MAN1B1 to a Golgi glycosylation disorder. Additionally, our results support the recent findings on MAN1B1 localization. However, more work is needed to pinpoint the exact function of MAN1B1 in glycoprotein quality control, and to understand the pathophysiology of its deficiency.

  4. Theoretical study on S1(1B3u) state electronic structure and absorption spectrum of pyrazine

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Making use of a set of quantum chemistry methods, the harmonic potential surfaces of the ground state (S0(1Ag)) and the first (S1(1B3u)) excited state of pyrazine are investigated, and the electronic structures of the two states are characterized. In the present study, the conventional quantum mechanical method, taking account of the Born-Oppenheimer adiabatic approximation, is adopted to simulate the absorp-tion spectrum of S1(1B3u) state of pyrazine. The assignment of main vibronic transitions is made for S1(1B3u) state. It is found that the spectral profile is mainly described by the Franck-Condon progression of totally symmetric mode ν6a. For the five totally symmetric modes, the present calculations show that the frequency differences between the ground and the S1(1B3u) state are small. Therefore the displaced harmonic oscillator approximation along with Franck-Condon transition is used to simulate S1(1B3u) absorption spectra. The distortion effect due to the so-called quadratic coupling is demonstrated to be unimportant for the absorption spectrum, except the coupling mode ν10a. The calculated S1(1B3u) ab-sorption spectrum is in reasonable agreement with the experimental spectra.

  5. Theoretical study on S1(1B3u) state electronic structure and absorption spectrum of pyrazine

    Institute of Scientific and Technical Information of China (English)

    HE RongXing; ZHU ChaoYuan; CHIN Chih-Hao; LIN Sheng-Hsien

    2008-01-01

    Making use of a set of quantum chemistry methods, the harmonic potential surfaces of the ground state (S0(1Ag)) and the first (S1(1B3u)) excited state of pyrazine are investigated, and the electronic structures of the two states are characterized. In the present study, the conventional quantum mechanical method, taking account of the Born-Oppenheimer adiabatic approximation, is adopted to simulate the absorp-tion spectrum of S1(1B3u) state of pyrazine. The assignment of main vibronic transitions is made for S1(1B3u) state. It is found that the spectral profile is mainly described by the Franck-Condon progression of totally symmetric mode v6a. For the five totally symmetric modes, the present calculations show that the frequency differences between the ground and the S1(1B3u) state are small. Therefore the displaced harmonic oscillator approximation along with Franck-Condon transition is used to simulate S1(1B3u)absorption spectra. The distortion effect due to the so-called quadratic coupling is demonstrated to be unimportant for the absorption spectrum, except the coupling mode v10a. The calculated S1(1B3u) ab-sorption spectrum is in reasonable agreement with the experimental spectra.

  6. Aldo-Keto Reductases 1B in Endocrinology and Metabolism.

    Science.gov (United States)

    Pastel, Emilie; Pointud, Jean-Christophe; Volat, Fanny; Martinez, Antoine; Lefrançois-Martinez, Anne-Marie

    2012-01-01

    The aldose reductase (AR; human AKR1B1/mouse Akr1b3) has been the focus of many research because of its role in diabetic complications. The starting point of these alterations is the massive entry of glucose in polyol pathway where it is converted into sorbitol by this enzyme. However, the issue of AR function in non-diabetic condition remains unresolved. AR-like enzymes (AKR1B10, Akr1b7, and Akr1b8) are highly related isoforms often co-expressed with bona fide AR, making functional analysis of one or the other isoform a challenging task. AKR1B/Akr1b members share at least 65% protein identity and the general ability to reduce many redundant substrates such as aldehydes provided from lipid peroxidation, steroids and their by-products, and xenobiotics in vitro. Based on these properties, AKR1B/Akr1b are generally considered as detoxifying enzymes. Considering that divergences should be more informative than similarities to help understanding their physiological functions, we chose to review specific hallmarks of each human/mouse isoforms by focusing on tissue distribution and specific mechanisms of gene regulation. Indeed, although the AR shows ubiquitous expression, AR-like proteins exhibit tissue-specific patterns of expression. We focused on three organs where certain isoforms are enriched, the adrenal gland, enterohepatic, and adipose tissues and tried to connect recent enzymatic and regulation data with endocrine and metabolic functions of these organs. We presented recent mouse models showing unsuspected physiological functions in the regulation of glucido-lipidic metabolism and adipose tissue homeostasis. Beyond the widely accepted idea that AKR1B/Akr1b are detoxification enzymes, these recent reports provide growing evidences that they are able to modify or generate signal molecules. This conceptually shifts this class of enzymes from unenviable status of scavenger to upper class of messengers.

  7. The over-expression of two transcription factors, ABS5/bHLH30 and ABS7/MYB101, leads to upwardly curly leaves.

    Directory of Open Access Journals (Sweden)

    Rui An

    Full Text Available Proper leaf development is essential for plant growth and development, and leaf morphogenesis is under the control of intricate networks of genetic and environmental cues. We are interested in dissecting these regulatory circuits genetically and report here the isolation of two Arabidopsis dominant mutants, abnormal shoot5-1D (abs5-1D and abs7-1D identified through activation tagging screens. Both abs5-1D and abs7-1D display an intriguing upwardly curly leaf phenotype. Molecular cloning showed that the elevated expression of a bHLH transcription factor ABS5/T5L1/bHLH30 or a MYB transcription factor ABS7/MYB101 is the cause for the abnormal leaf phenotypes found in abs5-1D or abs7-1D, respectively. Protoplast transient expression assays confirmed that both ABS5/T5L1 and ABS7/MYB101 are targeted to the nucleus. Interestingly, the expression domains of auxin response reporter DR5::GUS were abnormal in leaves of abs5-1D and ABS5/T5L1 over-expression lines. Moreover, cotyledon venation analysis showed that more areoles and free-ending veins are formed in abs5-1D. We found that the epidermis-specific expressions of ABS5/T5L1 or ABS7/MYB101 driven by the Arabidopsis Meristem Layer 1 promoter (PAtML1 were sufficient to recapitulate the curly leaf phenotype of abs5-1D or abs7-1D. In addition, PAtML1::ABS5 lines exhibited similar changes in DR5::GUS expression patterns as those found in 35S-driven ABS5/T5L1 over-expression lines. Our work demonstrated that enhanced expressions of two transcription factors, ABS5/T5L1 and ABS7/MYB101, are able to alter leaf lamina development and reinforce the notion that leaf epidermis plays critical roles in regulating plant organ morphogenesis.

  8. Optimal humanization of 1B4, an anti-CD18 murine monoclonal antibody, is achieved by correct choice of human V-region framework sequences.

    Science.gov (United States)

    Singer, I I; Kawka, D W; DeMartino, J A; Daugherty, B L; Elliston, K O; Alves, K; Bush, B L; Cameron, P M; Cuca, G C; Davies, P

    1993-04-01

    The murine anti-CD18 mAb 1B4 has been humanized using CDR grafting. Three VH (Gal, Jon, and New) and two VL (Rei and Len) human frameworks, whose selection was based exclusively on their sequence identity with m1B4, were used to construct five human gamma 4/kappa recombinant antibodies: Gal/Rei, Gal/Len, Jon/Rei, and New/Rei, and a "hemichimeric" antibody pairing the VH of m1B4 with grafted Rei. Each of these h1B4 constructs completely inhibited the binding of m1B4 to activated human leukocytes with avidities (IC50) ranging from 1.5 to 8.0 nM, compared to 0.5 nM for m1B4. Replacement of three VH residues in the best VH framework, Gal, with the corresponding m1B4 "packing" (nonsolvent exposed) residues gave an h1B4 (mutant Gal/Rei) with the same avidity as m1B4. Avidity correlated with overall percent identity between the human and murine VH frameworks and, in particular, with conservation of "packing" residues. Rei and Len VL frameworks proved to be interchangeable. Further characterization showed that the Gal/Rei prototype was equipotent to m1B4 in blocking adhesion of polymorphonuclear leukocytes and monocytes to human vascular endothelium in vitro, and polymorphonuclear leukocyte extravasation into C5a-injected rabbit or monkey skin sites. Dual-label immunofluorescence microscopy of bone marrow cells with Gal/Rei h1B4 and m1B4 demonstrated that the fine specificity of the combining sites had not been altered by humanization. Reduced immunogenicity was demonstrated in rhesus monkeys that tolerated weekly treatment with h1B4 for 6 wk, whereas m1B4 induced profound anaphylaxis at 3 wk. Anti-1B4 titers in h1B4-treated rhesus were 50 to 66% lower and developed 1 wk later than in m1B4-treated monkeys. Crucially, the anti-h1B4 antibodies were anti-idiotypic while the anti-m1B4 antibodies were directed against constant and framework regions. We conclude that sequence identity searches are sufficient to identify suitable human frameworks for CDR-grafting of m1B4

  9. Syntheses, structures, magnetic properties, and density functional theory magneto-structural correlations of bis(μ-phenoxo) and bis(μ-phenoxo)-μ-acetate/bis(μ-phenoxo)-bis(μ-acetate) dinuclear Fe(III)Ni(II) compounds.

    Science.gov (United States)

    Hazra, Susanta; Bhattacharya, Sagarika; Singh, Mukesh Kumar; Carrella, Luca; Rentschler, Eva; Weyhermueller, Thomas; Rajaraman, Gopalan; Mohanta, Sasankasekhar

    2013-11-18

    The bis(μ-phenoxo) Fe(III)Ni(II) compound [Fe(III)(N3)2LNi(II)(H2O)(CH3CN)](ClO4) (1) and the bis(μ-phenoxo)-μ-acetate/bis(μ-phenoxo)-bis(μ-acetate) Fe(III)Ni(II) compound {[Fe(III)(OAc)LNi(II)(H2O)(μ-OAc)](0.6)·[Fe(III)LNi(II)(μ-OAc)2](0.4)}(ClO4)·1.1H2O (2) have been synthesized from the Robson type tetraiminodiphenol macrocyclic ligand H2L, which is the [2 + 2] condensation product of 4-methyl-2,6-diformylphenol and 2,2'-dimethyl-1,3-diaminopropane. Single-crystal X-ray structures of both compounds have been determined. The cationic part of the dinuclear compound 2 is a cocrystal of the two species [Fe(III)(OAc)LNi(II)(H2O)(μ-OAc)](+) (2A) and [Fe(III)LNi(II)(μ-OAc)2](+) (2B) with weights of 60% of the former and 40% of the latter. While 2A is a triply bridged bis(μ-phenoxo)-μ-acetate system, 2B is a quadruply bridged bis(μ-phenoxo)-bis(μ-acetate) system. Variable-temperature (2-300 K) magnetic studies reveal antiferromagnetic interaction in 1 and ferromagnetic interaction in 2 with J values of -3.14 and 7.36 cm(-1), respectively (H = -2JS1·S2). Broken-symmetry density functional calculations of exchange interaction have been performed on complexes 1 and 2 and also on previously published related compounds, providing good numerical estimates of J values in comparison to experiments. The electronic origin of the difference in magnetic behavior of 1 and 2 has been well understood from MO analyses and computed overlap integrals of BS empty orbitals. The role of acetate and thus its complementarity/countercomplementarity effect on the magnetic properties of diphenoxo-bridged Fe(III)Ni(II) compounds have been determined on computing J values of model compounds by replacing bridging acetate and nonbridging acetate ligand(s) by water ligands in the model compounds derived from 2A,B. The DFT calculations have also been extended to develop several magneto-structural correlations in these types of complexes, and the correlations focus on the role of Fe

  10. Oral-nasopharyngeal dendritic cells mediate T cell-independent IgA class switching on B-1 B cells.

    Directory of Open Access Journals (Sweden)

    Kosuke Kataoka

    Full Text Available Native cholera toxin (nCT as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs and nasal passages (NPs. Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs play a central role in the induction of B-1 B cell IgA class switch recombination (CSR for the enhancement of T cell-independent (TI mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ⁻/⁻ mice and wild-type mice given nasal trinitrophenyl (TNP-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA⁻ IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI.

  11. Oral-nasopharyngeal dendritic cells mediate T cell-independent IgA class switching on B-1 B cells.

    Science.gov (United States)

    Kataoka, Kosuke; Fujihashi, Keiko; Terao, Yutaka; Gilbert, Rebekah S; Sekine, Shinichi; Kobayashi, Ryoki; Fukuyama, Yoshiko; Kawabata, Shigetada; Fujihashi, Kohtaro

    2011-01-01

    Native cholera toxin (nCT) as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab) responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs) play a central role in the induction of B-1 B cell IgA class switch recombination (CSR) for the enhancement of T cell-independent (TI) mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ⁻/⁻ mice and wild-type mice given nasal trinitrophenyl (TNP)-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL) than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA⁻ IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI.

  12. Aldo-Keto Reductases 1B in Adrenal Cortex Physiology.

    Science.gov (United States)

    Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A Marie

    2016-01-01

    Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.

  13. 18 CFR 1b.20 - Request for confidential treatment.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Request for confidential treatment. 1b.20 Section 1b.20 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... disclosure requirements of the Freedom of Information Act (5 U.S.C. 552), is information referred to in 18...

  14. CYP1B1 and hormone-induced cancer.

    Science.gov (United States)

    Gajjar, Ketan; Martin-Hirsch, Pierre L; Martin, Francis L

    2012-11-01

    Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis.

  15. "AB neg AB"格式之再探

    Institute of Scientific and Technical Information of China (English)

    马凤霞

    2009-01-01

    "AB neg AB"格式松散,变化形式多样.正因如此,研究界关于这一格式的争论很多,还有很多悬而未决的问题.本文主要就以下两个问题作一些探索性研究:一、"A neg AB"格式的规范性问题;二、"AB negAB"格式中AB与各类词的相容性问题.

  16. Synthesis and protein tyrosine phosphatase 1B inhibition activities of two new synthetic bromophenols and their methoxy derivatives

    Science.gov (United States)

    Cui, Yongchao; Shi, Dayong; Hu, Zhiqiang

    2011-11-01

    3-bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol ( 1) is a natural bromophenol isolated from the red algae Rhodomela confervoides that exhibits significant inhibition against protein tyrosine phosphatase 1B (PTP1B). Based on its activity, we synthesized two new synthetic bromophenols and their methoxy derivatives from vanillin using the structure of natural bromophenol 1 as a scaffold. The structures of these bromophenols were elucidated from 1H NMR, 13C NMR, and high resolution electron ionization mass spectrometry as 2,3-dibromo-1-(2'-bromo-6'-(3″,4″-dimethoxybenzyl)-3',4'-dimethoxybenzyl)-4,5-dimethoxybenzene ( 2), 2,3-dibromo-1-(2'-bromo-6'-(2″-bromo-4″,5″-dimethoxybenzyl)-3',4'-dimethoxybenzyl)-4,5-dimethoxybenzene ( 3), 3,4-dibromo-5-(2'-bromo-6'-(2″-bromo-4″,5″-dihydroxybenzyl)-3',4'-dihydroxybenzyl)pyrocatechol ( 4) and 3,4-dibromo-5-(2'-bromo-6'-(3″,4″-dihydroxybenzyl)-3',4'-dihydroxybenzyl)pyrocatechol ( 5). PTP1B inhibition activities of these compounds were evaluated using a colorimetric assay, and compounds 3 and 4 demonstrated interesting activity against PTP1B.

  17. CYP1B1: a unique gene with unique characteristics.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Sharma, Reetika; Saluja, Daman; Dada, Tanuj

    2014-01-01

    CYP1B1, a recently described dioxin inducible oxidoreductase, is a member of the cytochrome P450 superfamily involved in the metabolism of estradiol, retinol, benzo[a]pyrene, tamoxifen, melatonin, sterols etc. It plays important roles in numerous physiological processes and is expressed at mRNA level in many tissues and anatomical compartments. CYP1B1 has been implicated in scores of disorders. Analyses of the recent studies suggest that CYP1B1 can serve as a universal/ideal cancer marker and a candidate gene for predictive diagnosis. There is plethora of literature available about certain aspects of CYP1B1 that have not been interpreted, discussed and philosophized upon. The present analysis examines CYP1B1 as a peculiar gene with certain distinctive characteristics like the uniqueness in its chromosomal location, gene structure and organization, involvement in developmentally important disorders, tissue specific, not only expression, but splicing, potential as a universal cancer marker due to its involvement in key aspects of cellular metabolism, use in diagnosis and predictive diagnosis of various diseases and the importance and function of CYP1B1 mRNA in addition to the regular translation. Also CYP1B1 is very difficult to express in heterologous expression systems, thereby, halting its functional studies. Here we review and analyze these exceptional and startling characteristics of CYP1B1 with inputs from our own experiences in order to get a better insight into its molecular biology in health and disease. This may help to further understand the etiopathomechanistic aspects of CYP1B1 mediated diseases paving way for better research strategies and improved clinical management.

  18. A cytotoxic study of eugenol and its ortho dimer (bis-eugenol)

    Energy Technology Data Exchange (ETDEWEB)

    Kashiwagi, Yasushi [Meikai Univ., Sakado, Saitama (Japan). School of Dentistry

    2000-07-01

    Eugenol is widely used not only as a dental material such as pulp capping material, provisional cement, root canal sealer, and impression paste, but also as a perfume ingredients. Eugenol has antioxidant, bactericidal, and sedative activities, inhibits and non-enzymatic peroxidation. It was previously reported that eugenol exhibited the cytotoxic activity toward pulp cells and gingial fibroblasts and also that the cytotoxic activity was predominantly performed by radicals derived from the oxidation of eugenol. This study was based on the hypothesis that the toxicity of eugenol may be greately reduced if the radicalization of eugenol was diminished by the dimerization of eugenol. Thus, bis-eugenol, the dimer of eugenol, was synthesized to characterize the effect of this eugenol-related compound. The cytotoxic activity of bis-eugenol against human gingival fibroblasts (HGF cell) or human submandibular gland cancer cells (HSG cell) was studied in the presence or absence of light irradiation (visible or ultraviolet light), and compared with that of eugenol. The cytotoxic activity of eugenol was significantly greater than that of bis-eugenol. The cytotoxic activity of irradiated eugenol, but not that of irradiated bis-eugenol, was significantly higher than that of the non-irradiated counterpart. Bis-eugenol at a relatively low concentration declined the phototoxic activity of irradiation on living cells. Also, the generation of reactive oxygen in HSG cells in the ab-sence or the presence of irradiated bis-eugenol or eugenol was evaluated by an ACAS laser cytometry, and the results indicated that eugenol, but not bis-eugenol, generated reactive oxygen in the cells. The DPPH-radical scavenging activity of bis-eugenol was larger than that of eugenol. Furthermore, eugenol had a positive apoptosis-inducing effect on HSG cells. The structure-activity relationships of eugenol-related compounds showed that the nature of the substituent at the ortho or para-position of eugenol

  19. Hepatic protein tyrosine phosphatase 1B (PTP1B) deficiency protects against obesity-induced endothelial dysfunction.

    Science.gov (United States)

    Agouni, Abdelali; Tual-Chalot, Simon; Chalopin, Matthieu; Duluc, Lucie; Mody, Nimesh; Martinez, M Carmen; Andriantsitohaina, Ramaroson; Delibegović, Mirela

    2014-12-15

    Growing evidence suggests that hepatic-insulin resistance is sufficient to promote progression to cardiovascular disease. We have shown previously that liver-specific protein-tyrosine-phosphatase 1B (PTP1B) deficiency improves hepatic-insulin sensitivity and whole-body glucose homeostasis. The aim of this study was to investigate the impact of liver-specific PTP1B-deficiency (L-PTP1B-/-) on cardiac and peripheral vascular function, with special emphasis on endothelial function in the context of high-fat diet (HFD)-induced obesity. L-PTP1B-/- mice exhibited an improved glucose and lipid homeostasis and increased insulin sensitivity, without changes in body weight. HFD-feeding increased systolic blood pressure (BP) in both L-PTP1B-/- and control littermates; however, this was significantly lower in L-PTP1B-/- mice. HFD-feeding increased diastolic BP in control mice only, whilst the L-PTP1B-/- mice were completely protected. The analysis of the function of the left ventricle (LV) revealed that HFD-feeding decreased LV fractional shortening in control animals, which was not observed in L-PTP1B-/- mice. Importantly, HFD feeding significantly impaired endothelium-dependent vasorelaxation in response to acetylcholine in aortas from control mice, whilst L-PTP1B-/- mice were fully protected. This was associated with alterations in eNOS phosphorylation. Selective inhibition of COX-2, using NS-398, decreased the contractile response in response to serotonin (5-HT) only in vessels from control mice. HFD-fed control mice released enhanced levels of prostaglandin E, a vasoconstrictor metabolite; whilst both chow- and HFD-fed L-PTP1B-/- mice released higher levels of prostacylin, a vasorelaxant metabolite. Our data indicate that hepatic-PTP1B inhibition protects against HFD-induced endothelial dysfunction, underscoring the potential of peripheral PTP1B inhibitors in reduction of obesity-associated cardiovascular risk in addition to its anti-diabetic effects.

  20. ABS 497 ASH Tutorial/Uoptutorial

    OpenAIRE

    Kathi

    2015-01-01

    ABS 497 Week 1 Assignment Community Change ABS 497 Week 1 DQ 1 Fabian's Story ABS 497 Week 1 DQ 2 Doug's Story ABS 497 Week 2 DQ 1 Parenting Styles ABS 497 Week 2 DQ 2 Ethnicity and Learning Theory ABS 497 Week 3 DQ 1 Suicide ABS 497 Week 3 DQ 2 Development Theories ABS 497 Week 3 Assignment communication PowerPoint Presentation ABS 497 Week 4 DQ 1 Leadership Theories ABS 497 Week 4 DQ 2 Problems of Adolescence ABS 497 Week 5 DQ Macro Social Systems...

  1. TES/Aura L1B Spectra Limb V002

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Limb granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.025 cm-1 resolution for an entire Global Survey &...

  2. TES/Aura L1B Spectra Nadir V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Nadir granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for an entire Global Survey &...

  3. TES/Aura L1B Spectra Nadir V004

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Nadir granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for an entire Global Survey &...

  4. Aldo-keto reductases 1B in adrenal cortex physiology

    Directory of Open Access Journals (Sweden)

    Emilie PASTEL

    2016-07-01

    Full Text Available Aldose reductase proteins are cytosolic monomeric enzymes, belonging to the aldo-keto reductase (AKR superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates such as aliphatic and aromatic aldehydes or ketones. The Aldose reductase subgroup (AKR1B is one of the most characterized because of its involvement in human diseases such as diabetic complications resulting from the ability of its human archetype AKR1B1 to reduce glucose into sorbitol. However the issue of AKR1B function in non pathologic condition remains poorly resolved. Adrenal steroidogenesis is strongly associated with high production of endogenous harmful lipid aldehyde by-products including isocaproaldehyde (4-methylpentanal derived from cholesterol side chain cleavage (the first step of steroid synthesis and 4-hydroxynonenal (4- HNE that can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase activity, suggesting that in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, previous studies have established that the adrenal gland is one of the major site for human and murine AKR1B expression suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms.This review presents the molecular mechanisms accounting for the adrenal specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.

  5. CIAE Signs Contract on B1/B2 Project

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    CIAE signed Contract on Design,Commissioning and Technology Service for B1/B2 Project of Birine Reactor with CZEC in December,2015.The B1/B2 project which was won over by CZEC is PhaseⅠand PhaseⅡof an Algeria project which aimed to upgrade and rebuild Algeria Birine Nuclear Research Center.According to the contract with total fund amounting to 110million Yuan,CIAE will provide

  6. CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma.

    Science.gov (United States)

    Faiq, Muneeb A; Dada, Rima; Qadri, Rizwana; Dada, Tanuj

    2015-01-01

    CYP1B1 is a dioxin-inducible enzyme belonging to the cytochrome P450 superfamily. It has been observed to be important in a variety of developmental processes including in utero development of ocular structures. Owing to its role in the developmental biology of eye, its dysfunction can lead to ocular developmental defects. This has been found to be true and CYP1B1 mutations have been observed in a majority of primary congenital glaucoma (PCG) patients from all over the globe. Primary congenital glaucoma is an irreversibly blinding childhood disorder (onset at birth or early infancy) typified by anomalous development of trabecular meshwork (TM). How CYP1B1 causes PCG is not known; however, some basic investigations have been reported. Understanding the CYP1B1 mediated etiopathomechanism of PCG is very important to identify targets for therapy and preventive management. In this perspective, we will make an effort to reconstruct the pathomechanism of PCG in the light of already reported information about the disease and the CYP1B1 gene. How to cite this article: Faiq MA, Dada R, Qadri R, Dada T. CYP1 B1-mediated Pathobiology of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015;9(3):77-80.

  7. PTP1B inhibitors from stems of Angelica keiskei (Ashitaba).

    Science.gov (United States)

    Li, Jin-Long; Gao, Li-Xin; Meng, Fan-Wang; Tang, Chun-Lan; Zhang, Ru-Jun; Li, Jing-Ya; Luo, Cheng; Li, Jia; Zhao, Wei-Min

    2015-01-01

    Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Among them, six chalcones, xanthoangelol K (1), xanthoangelol (4), xanthoangelol F (5), 4-hydroxyderricin (6), xanthoangelol D (7), xanthoangelol E (8), and a coumarin, methoxsalen (17), showed strong PTP1B inhibitory effect with IC50 values of 0.82, 1.97, 1.67, 2.47, 3.97, 1.43, and 2.53μg/mL, respectively. A kinetic study revealed that compound 1 inhibited PTP1B with characteristics typical of a competitive inhibitor. Molecular docking simulations elucidated that ring B of 1 may anchor in a pocket of PTP1B and the molecule is stabilized by hydrogen bonds with Arg47, Asp48, and π-π interaction with Phe182 of PTP1B.

  8. Association of transcription factor gene LMX1B with autism.

    Directory of Open Access Journals (Sweden)

    Ismail Thanseem

    Full Text Available Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217 showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008. Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049. Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

  9. Association of transcription factor gene LMX1B with autism.

    Science.gov (United States)

    Thanseem, Ismail; Nakamura, Kazuhiko; Anitha, Ayyappan; Suda, Shiro; Yamada, Kazuo; Iwayama, Yoshimi; Toyota, Tomoko; Tsujii, Masatsugu; Iwata, Yasuhide; Suzuki, Katsuaki; Matsuzaki, Hideo; Iwata, Keiko; Sugiyama, Toshiro; Yoshikawa, Takeo; Mori, Norio

    2011-01-01

    Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217) showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008). Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049). Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

  10. Evaluating autoimmunity markers (TPO Ab, Tg Ab and TM Ab in hypothyroid patients of Bushehr province

    Directory of Open Access Journals (Sweden)

    Iraj Nabipour

    2005-09-01

    Full Text Available Background: Chronic autoimmune thyroiditis (Hashimoto's Thyroiditis is the common cause of primary hypothyroidism in iodine sufficient countries. Iran is named an iodine sufficient country, in this century. Methods: A total of 88 hypothyroid patients, on suppressing dose of levothyroxine who were followed in a university endocrine disorder clinic were evaluated for serum thyroid autoimmunity markers: thyroid peroxidase antibody (TPO Ab, thyroglobulin antibody (Tg Ab and thyroid microsomal antibody (TM Ab using ELISA method. Results: The prevalence of TPO Ab, Tg Ab and TM Ab were 73.9%, 45.5% and 71.6%, respectively. Among the patients with high level of TPO Ab (> 75 u/ml, 45.3% had grade 1 or 2 of goiter (P< 0.05. Conclusion: Autoimmune thyroid disease (Hashimoto's thyroiditis is the most common cause of hypothyroidism in Bushehr province.

  11. Bis[μ-3,5-bis(pyridin-2-ylpyrazolato]bis[(hexafluorophosphatocopper(II

    Directory of Open Access Journals (Sweden)

    Satoshi Kawata

    2013-08-01

    Full Text Available The title dinuclear complex molecule, [Cu2(C13H9N42(PF62], lies about an inversion center. The CuII atom shows a square-pyramidal coordination geometry with the basal plane formed by four N atoms of the two bis-chelating 3,5-bis(pyridin-2-ylpyrazolate ions and with one F atom of the hexafluorophosphate ion in the apical position. Molecules are stacked in a column along the a axis through C—H...F hydrogen bonds. The columns are further linked by other C—H...F hydrogen bonds, forming a three-dimensional network.

  12. [1,2-Bis(diphenylphosphinoethane]{2-[bis(diphenylphosphinomethylamino]pyridinium}fluoridohydrazidatomolybdenum(IV bis(tetrafluoridoborate

    Directory of Open Access Journals (Sweden)

    Felix Tuczek

    2008-05-01

    Full Text Available In the crystal structure of the title compound, [MoF(N2H2(C31H29N2P2(C26H24P2](BF42, each Mo atom is surrounded by four P atoms of one 1,2-bis(diphenylphosphinoethane and one 2-[bis(diphenylphosphinomethylamino]pyridinium ligand. The remaining binding sites of the distorted octahedron are occupied by a hydrazidate (NNH22− and a fluoride ligand. Two F atoms of an anion are disordered over two positions; the site occupancy factors are ca 0.7 and 0.3.

  13. ABS 497 ASH Tutorial Course/Uoptutorial

    OpenAIRE

    thanu

    2015-01-01

    For More Course Tutorials Visit www.uoptutorial.com   ABS 497 Week 1 Assignment Community Change ABS 497 Week 1 DQ 1 Fabian's Story ABS 497 Week 1 DQ 2 Doug's Story ABS 497 Week 2 DQ 1 Parenting Styles ABS 497 Week 2 DQ 2 Ethnicity and Learning Theory ABS 497 Week 3 DQ 1 Suicide ABS 497 Week 3 DQ 2 Development Theories ABS 497 Week 3 Assignment communication PowerPoint Presentation ABS 497 Week 4 DQ 1 Leadership Theories ABS 497 Week 4 ...

  14. Synthesis and cytotoxic activities of novel 2-(1,5-bis(aryl penta-1,4-dien-2-yl benzo[d]thiazol derivatives

    Directory of Open Access Journals (Sweden)

    Betül Şahin

    2016-07-01

    Full Text Available Novel 2-(1,5-bis(arylpenta-1,4-dien-2-ylbenzo[d]thiazol (5a,b and 2-(((1S,2S,E-2-(benzo[d]thiazol-2-yl-1,5-di-arylpent-4-en-1-ylthioaniline (6a,b derivatives were obtained by addition of 2-aminobenzothiol to bis-benzylidinecyclobutanones (3a,b. The structures of the obtained compounds were characterized using the spectroscopic methods (NMR, IR, Elemental Analysis. Compounds 5a,b showed cytotoxic activities against C6 (Rat Brain tumor cells and HeLa (human uterus carcinoma in vitro. ©2016 ACG Publications. All rights reserved.

  15. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  16. LMX1B Mutations Cause Hereditary FSGS without Extrarenal Involvement

    Science.gov (United States)

    Boyer, Olivia; Woerner, Stéphanie; Yang, Fan; Oakeley, Edward J.; Linghu, Bolan; Gribouval, Olivier; Tête, Marie-Josèphe; Duca, José S.; Klickstein, Lloyd; Damask, Amy J.; Szustakowski, Joseph D.; Heibel, Françoise; Matignon, Marie; Baudouin, Véronique; Chantrel, François; Champigneulle, Jacqueline; Martin, Laurent; Nitschké, Patrick; Gubler, Marie-Claire; Johnson, Keith J.; Chibout, Salah-Dine

    2013-01-01

    LMX1B encodes a homeodomain-containing transcription factor that is essential during development. Mutations in LMX1B cause nail-patella syndrome, characterized by dysplasia of the patellae, nails, and elbows and FSGS with specific ultrastructural lesions of the glomerular basement membrane (GBM). By linkage analysis and exome sequencing, we unexpectedly identified an LMX1B mutation segregating with disease in a pedigree of five patients with autosomal dominant FSGS but without either extrarenal features or ultrastructural abnormalities of the GBM suggestive of nail-patella–like renal disease. Subsequently, we screened 73 additional unrelated families with FSGS and found mutations involving the same amino acid (R246) in 2 families. An LMX1B in silico homology model suggested that the mutated residue plays an important role in strengthening the interaction between the LMX1B homeodomain and DNA; both identified mutations would be expected to diminish such interactions. In summary, these results suggest that isolated FSGS could result from mutations in genes that are also involved in syndromic forms of FSGS. This highlights the need to include these genes in all diagnostic approaches to FSGS that involve next-generation sequencing. PMID:23687361

  17. Synthesis, characterization, and reactivity of furan- and thiophene-functionalized bis(n-heterocyclic carbene) complexes of iron(II)

    KAUST Repository

    Rieb, Julia

    2014-09-15

    The synthesis of iron(II) complexes bearing new heteroatom-functionalized methylene-bridged bis(N-heterocyclic carbene) ligands is reported. All complexes are characterized by single-crystal X-ray diffraction (SC-XRD), nuclear magnetic resonance (NMR) spectroscopy, and elemental analysis. Tetrakis(acetonitrile)-cis-[bis(o-imidazol-2-ylidenefuran)methane]iron(II) hexafluorophosphate (2a) and tetrakis(acetonitrile)-cis-[bis(o-imidazol-2-ylidenethiophene)methane]iron(II) hexafluorophosphate (2b) were obtained by aminolysis of [Fe{N(SiMe3)2}2(THF)] with furan- and thiophene-functionalized bis(imidazolium) salts 1a and 1b in acetonitrile. The SC-XRD structures of 2a and 2b show coordination of the bis(carbene) ligand in a bidentate fashion instead of a possible tetradentate coordination. The four other coordination sites of these distorted octahedral complexes are occupied by acetonitrile ligands. Crystallization of 2a in an acetone solution by the slow diffusion of Et2O led to the formation of cisdiacetonitriledi[ bis(o-imidazol-2-ylidenefuran)methane]iron(II) hexafluorophosphate (3a) with two bis(carbene) ligands coordinated in a bidentate manner and two cis-positioned acetonitrile molecules. Compounds 2a and 2b are the first reported iron(II) carbene complexes with four coordination sites occupied by solvent molecules, and it was demonstrated that those solvent ligands can undergo ligand-exchange reactions.

  18. Targeting of Ly9 (CD229) Disrupts Marginal Zone and B1 B Cell Homeostasis and Antibody Responses.

    Science.gov (United States)

    Cuenca, Marta; Romero, Xavier; Sintes, Jordi; Terhorst, Cox; Engel, Pablo

    2016-01-15

    Marginal zone (MZ) and B1 B cells have the capacity to respond to foreign Ags more rapidly than conventional B cells, providing early immune responses to blood-borne pathogens. Ly9 (CD229, SLAMF3), a member of the signaling lymphocytic activation molecule family receptors, has been implicated in the development and function of innate T lymphocytes. In this article, we provide evidence that in Ly9-deficient mice splenic transitional 1, MZ, and B1a B cells are markedly expanded, whereas development of B lymphocytes in bone marrow is unaltered. Consistent with an increased number of these B cell subsets, we detected elevated levels of IgG3 natural Abs and a striking increase of T-independent type II Abs after immunization with 2,4,6-trinitrophenyl-Ficoll in the serum of Ly9-deficient mice. The notion that Ly9 could be a negative regulator of innate-like B cell responses was supported by the observation that administering an mAb directed against Ly9 to wild-type mice selectively eliminated splenic MZ B cells and significantly reduced the numbers of B1 and transitional 1 B cells. In addition, Ly9 mAb dramatically diminished in vivo humoral responses and caused a selective downregulation of the CD19/CD21/CD81 complex on B cells and concomitantly an impaired B cell survival and activation in an Fc-independent manner. We conclude that altered signaling caused by the absence of Ly9 or induced by anti-Ly9 may negatively regulate development and function of innate-like B cells by modulating B cell activation thresholds. The results suggest that Ly9 could serve as a novel target for the treatment of B cell-related diseases.

  19. Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.

    Science.gov (United States)

    Cao, Jian; LaRocque, Emily; Li, Dawei

    2013-03-01

    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To clarify the roles of commonly reported single nucleotide polymorphisms (SNPs) of the HTR1B gene underlying alcohol and drug dependence (abuse), we performed a meta-analysis based on the available genotype data from individual candidate gene-based association studies. Evidence of association was found between the functional SNP -161A>T (rs130058) and alcohol, cocaine, and heroin dependence (e.g., P = 0.03 and odds ratio (OR) = 1.2 (1.02, 1.42) in the combined European, Asian, African, and Hispanic populations). SNP -261T>G (rs11568817) also showed evidence of association but with different directions in Europeans and non-Europeans (e.g., P = 0.0018 with OR = 1.42 (1.14, 1.76) and P = 0.01 with ORs = 0.5 (0.3, 0.85), respectively). This meta-analysis supports the associations of HTR1B -261T>G and -161A>T with alcohol and drug abuse and further investigations are warranted in larger samples.

  20. Origin of vestibular dysfunction in Usher syndrome type 1B.

    NARCIS (Netherlands)

    Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

    2001-01-01

    It is still debated to what extent the vestibular deficits in Usher patients are due to either central vestibulocerebellar or peripheral vestibular problems. Here, we determined the origin of the vestibular symptoms in Usher 1B patients by subjecting them to compensatory eye movement tests and by in

  1. PTP1B targets the endosomal sorting machinery

    DEFF Research Database (Denmark)

    Stuible, Matthew; Abella, Jasmine V; Feldhammer, Matthew;

    2010-01-01

    STAM2 specifically suppressed Akt activation, and a phosphorylation-deficient STAM2 mutant displayed prolonged localization on endosomes following EGF stimulation. These results reveal a novel link between the dephosphorylation and endocytic machinery and suggest that PTP1B can affect RTK signaling...

  2. Radiometric Cross-Calibration of the HJ-1B IRS in the Thermal Infrared Spectral Band

    Science.gov (United States)

    Sun, K.

    2012-12-01

    The natural calamities occur continually, environment pollution and destruction in a severe position on the earth presently, which restricts societal and economic development. The satellite remote sensing technology has an important effect on improving surveillance ability of environment pollution and natural calamities. The radiometric calibration is precondition of quantitative remote sensing; which accuracy decides quality of the retrieval parameters. Since the China Environment Satellite (HJ-1A/B) has been launched successfully on September 6th, 2008, it has made an important role in the economic development of China. The satellite has four infrared bands; and one of it is thermal infrared. With application fields of quantitative remote sensing in china, finding appropriate calibration method becomes more and more important. Many kinds of independent methods can be used to do the absolute radiometric calibration. In this paper, according to the characteristic of thermal infrared channel of HJ-1B thermal infrared multi-spectral camera, the thermal infrared spectral band of HJ-1B IRS was calibrated using cross-calibration methods based on MODIS data. Firstly, the corresponding bands of the two sensors were obtained. Secondly, the MONDTRAN was run to analyze the influences of different spectral response, satellite view zenith angle, atmosphere condition and temperature on the match factor. In the end, their band match factor was calculated in different temperature, considering the dissimilar band response of the match bands. Seven images of Lake Qinghai in different time were chosen as the calibration data. On the basis of radiance of MODIS and match factor, the IRS radiance was calculated. And then the calibration coefficients were obtained by linearly regressing the radiance and the DN value. We compared the result of this cross-calibration with that of the onboard blackbody calibration, which consistency was good.The maximum difference of brightness temperature

  3. Nascent bipolar outflows associated with the first hydrostatic core candidates Barnard 1b-N and 1b-S

    CERN Document Server

    Gerin, M; Fuente, A; Cernicharo, J; Commerçon, B; Marcelino, N

    2015-01-01

    In the theory of star formation, the first hydrostatic core (FHSC) phase is a critical step in which a condensed object emerges from a prestellar core. This step lasts about one thousand years, a very short time compared with the lifetime of prestellar cores, and therefore is hard to detect unambiguously. We present IRAM Plateau de Bure observations of the Barnard 1b dense molecular core, combining detections of H2CO and CH3OH spectral lines and dust continuum at 2.3" resolution (~ 500 AU). The two compact cores B1b-N and B1b-S are detected in the dust continuum at 2mm, with fluxes that agree with their spectral energy distribution. Molecular outflows associated with both cores are detected. They are inclined relative to the direction of the magnetic field, in agreement with predictions of collapse in turbulent and magnetized gas with a ratio of mass to magnetic flux somewhat higher than the critical value, \\mu ~ 2 - 7. The outflow associated with B1b-S presents sharp spatial structures, with ejection velocit...

  4. Cyclopolymerization-derived block-copolymers of 4,4-bis(octyloxymethyl)-1,6-heptadiyne with 4,4- dipropargyl malonodinitrile for use in photovoltaics

    DEFF Research Database (Denmark)

    Sudheendran, Mavila; Horecha, Marta; Kiriy, Anton;

    2013-01-01

    The synthesis of AB-type block copolymers of 4,4-bis(octyloxymethyl)-1,6-heptadiyne (M1) and dipropargyl malonodinitrile (M2) via metathesis-based cyclopolymerization using well-defined molybdenum- and ruthenium-based initiators is described. While backbiting reactions were observed in the case w...... and fluorescence spectroscopy and used for the construction of a photovoltaic device....

  5. abs417ashcoursesTutorial /uophelp

    OpenAIRE

    smith

    2015-01-01

    For more course tutorials visit www.uophelp.com     ABS 417 Week 1 DQ 1 ( The Power of Many )    ABS 417 Week 1 DQ 2 ( Social Change Model )    ABS 417 Week 2 DQ 1 ( Empowerment, Disempowerment and Social Change )   ABS 417 Week 2 DQ 2 ( Non-Profit vs. For-Profit Organizations )    ABS 417 Week 2 Assignment ( Reflection Paper )    ABS 417 Week 3 DQ 1 ( Social Problems )  &nb...

  6. Lithostratigraphy from downhole logs in Hole AND-1B, Antarctica

    Science.gov (United States)

    Williams, Trevor; Morin, Roger H.; Jarrard, Richard D.; Jackolski, Chris L.; Henrys, Stuart A.; Niessen, Frank; Magens, Diana; Kuhn, Gerhard; Monien, Donata; Powell, Ross D.

    2012-01-01

    The ANDRILL (Antarctic Drilling Project) McMurdo Ice Shelf (MIS) project drilled 1285 m of sediment in Hole AND–1B, representing the past 12 m.y. of glacial history. Downhole geophysical logs were acquired to a depth of 1018 mbsf (meters below seafloor), and are complementary to data acquired from the core. The natural gamma radiation (NGR) and magnetic susceptibility logs are particularly useful for understanding lithological and paleoenvironmental change at ANDRILL McMurdo Ice Shelf Hole AND–1B. NGR logs cover the entire interval from the seafloor to 1018 mbsf, and magnetic susceptibility and other logs covered the open hole intervals between 692 and 1018 and 237–342 mbsf. In the upper part of AND–1B, clear alternations between low and high NGR values distinguish between diatomite (lacking minerals containing naturally radioactive K, U, and Th) and diamictite (containing K-bearing clays, K-feldspar, mica, and heavy minerals). In the lower open hole logged section, NGR and magnetic susceptibility can also distinguish claystones (rich in K-bearing clay minerals, relatively low in magnetite) and diamictites (relatively high in magnetite). Sandstones can be distinguished by their high resistivity values in AND–1B. On the basis of these three downhole logs, diamictite, claystones, and sandstones can be predicted correctly for 74% of the 692–1018 mbsf interval. The logs were then used to predict facies for the 6% of this interval that was unrecovered by coring. Given the understanding of the physical property characteristics of different facies, it is also possible to identify subtle changes in lithology from the physical properties and help refine parts of the lithostratigraphy, for example, the varying terrigenous content of diatomites and the transitions from subice diamictite to open-water diatomite.

  7. Performance and Applications of L1B2 Ultrasonic Motors

    OpenAIRE

    Gal Peled; Roman Yasinov; Nir Karasikov

    2016-01-01

    Piezoelectric ultrasonic motors offer important advantages for motion applications where high speed is coupled with high precision. The advances made in the recent decades in the field of ultrasonic motor based motion solutions allow the construction of complete motion platforms in the fields of semiconductors, aerospace and electro-optics. Among the various motor designs, the L1B2 motor type has been successful in industrial applications, offering high precision, effective control and operat...

  8. Pharmacophore modeling for protein tyrosine phosphatase 1B inhibitors.

    Science.gov (United States)

    Bharatham, Kavitha; Bharatham, Nagakumar; Lee, Keun Woo

    2007-05-01

    A three dimensional chemical feature based pharmacophore model was developed for the inhibitors of protein tyrosine phosphatase 1B (PTP1B) using the CATALYST software, which would provide useful knowledge for performing virtual screening to identify new inhibitors targeted toward type II diabetes and obesity. A dataset of 27 inhibitors, with diverse structural properties, and activities ranging from 0.026 to 600 microM, was selected as a training set. Hypol, the most reliable quantitative four featured pharmacophore hypothesis, was generated from a training set composed of compounds with two H-bond acceptors, one hydrophobic aromatic and one ring aromatic features. It has a correlation coefficient, RMSD and cost difference (null cost-total cost) of 0.946, 0.840 and 65.731, respectively. The best hypothesis (Hypol) was validated using four different methods. Firstly, a cross validation was performed by randomizing the data using the Cat-Scramble technique. The results confirmed that the pharmacophore models generated from the training set were valid. Secondly, a test set of 281 molecules was scored, with a correlation of 0.882 obtained between the experimental and predicted activities. Hypol performed well in correctly discriminating the active and inactive molecules. Thirdly, the model was investigated by mapping on two PTP1B inhibitors identified by different pharmaceutical companies. The Hypol model correctly predicted these compounds as being highly active. Finally, docking simulations were performed on few compounds to substantiate the role of the pharmacophore features at the binding site of the protein by analyzing their binding conformations. These multiple validation approaches provided confidence in the utility of this pharmacophore model as a 3D query for virtual screening to retrieve new chemical entities showing potential as potent PTP1B inhibitors.

  9. Zinc ions modulate protein tyrosine phosphatase 1B activity.

    Science.gov (United States)

    Bellomo, Elisa; Massarotti, Alberto; Hogstrand, Christer; Maret, Wolfgang

    2014-07-01

    Protein tyrosine phosphatases (PTPs) are key enzymes in cellular regulation. The 107 human PTPs are regulated by redox signalling, phosphorylation, dimerisation, and proteolysis. Recent findings of very strong inhibition of some PTPs by zinc ions at concentrations relevant in a cellular environment suggest yet another mechanism of regulation. One of the most extensively investigated PTPs is PTP1B (PTPN1). It regulates the insulin and leptin signalling pathway and is implicated in cancer and obesity/diabetes. The development of novel assay conditions to investigate zinc inhibition of PTP1B provides estimates of about 5.6 nM affinity for inhibitory zinc(II) ions. Analysis of three PTP1B 3D structures (PDB id: 2CM2, 3I80 and 1A5Y) identified putative zinc binding sites and supports the kinetic studies in suggesting an inhibitory zinc only in the closed and cysteinyl-phosphate intermediate forms of the enzyme. These observations gain significance with regard to recent findings of regulatory roles of zinc ions released from the endoplasmic reticulum.

  10. Trisodium scandium bis(orthoborate

    Directory of Open Access Journals (Sweden)

    Kunpeng Wang

    2012-05-01

    Full Text Available Single crystals of trisodium scandium bis(orthoborate, Na3Sc(BO32, have been obtained by spontaneous crystallization from an Na2O–Sc2O3–B2O3 melt. The crystal structure features a three-dimensional framework composed of planar [BO3]3− groups and distorted ScO6 octahedra with Na atoms in the cavities. The Sc atom occupies a special position (Wyckoff position 2b, site symmetry -1 and of the two Na atoms, one occupies a special position (Wyckoff position 2c, site symmetry -1.

  11. A P387L variant in protein tyrosine phosphatase-1B (PTP-1B) is associated with type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro

    DEFF Research Database (Denmark)

    Echwald, Søren M; Riis, Helle Bach; Vestergaard, Henrik

    2002-01-01

    In the present study, we tested the hypothesis that variability in the protein tyrosine phosphatase-1B (PTP-1B) gene is associated with type 2 diabetes. Using single-strand conformational polymorphism analysis, we examined cDNA of PTP-1B from 56 insulin-resistant patients with type 2 diabetes...

  12. Novel bis-arylalkylamines as myeloperoxidase inhibitors

    DEFF Research Database (Denmark)

    Aldib, Iyas; Gelbcke, Michel; Soubhye, Jalal;

    2016-01-01

    Human myeloperoxidase (MPO) plays an important role in innate immunity but also aggravates tissue damage by oxidation of biomolecules at sites of inflammation. As a result from a recent high-throughput virtual screening approach for MPO inhibitors, bis-2,2'-[(dihydro-1,3(2H,4H) pyrimidinediyl)bis...

  13. Bis(1,3-dithiole) Compounds

    DEFF Research Database (Denmark)

    Andersen, Jan Rud; Engler, E. M.; Green, D. C.;

    1977-01-01

    There is described the preparation of bis-1,3-dithiole compounds (I) which are key synthetic precursors for the preparation of new polymeric metal bis(dithiolene) (i.e., II) and tetrathiafulvalene compounds (i.e., III): (Image Omitted)...

  14. Porphyrin amino acids-amide coupling, redox and photophysical properties of bis(porphyrin) amides.

    Science.gov (United States)

    Melomedov, Jascha; Wünsche von Leupoldt, Anica; Meister, Michael; Laquai, Frédéric; Heinze, Katja

    2013-07-14

    New trans-AB2C meso-substituted porphyrin amino acid esters with meso-substituents of tunable electron withdrawing power (B = mesityl, 4-C6H4F, 4-C6H4CF3, C6F5) were prepared as free amines 3a-3d, as N-acetylated derivatives Ac-3a-Ac-3d and corresponding zinc(II) complexes Zn-Ac-3a-Zn-Ac-3d. Several amide-linked bis(porphyrins) with a tunable electron density at each porphyrin site were obtained from the amino porphyrin precursors by condensation reactions (4a-4d) and mono- and bis(zinc(II)) complexes Zn(2)-4d and Zn(1)Zn(2)-4d were prepared. The electronic interaction between individual porphyrin units in bis(porphyrins) 4 is probed by electrochemical experiments (CV, EPR), electronic absorption spectroscopy, steady-state and time-resolved fluorescence spectroscopy in combination with DFT/PCM calculations on diamagnetic neutral bis(porphyrins) 4 and on respective charged mixed-valent radicals 4(+/-). The interaction via the -C6H4-NHCO-C6H4- bridge, the site of oxidation and reduction and the lowest excited singlet state S1, is tuned by the substituents on the individual porphyrins and the metalation state.

  15. Cytochrome P1B1 (CYP1B1) polymorphisms and ovarian cancer risk: a meta-analysis.

    Science.gov (United States)

    Gajjar, Ketan; Owens, Gemma; Sperrin, Matthew; Martin-Hirsch, Pierre L; Martin, Francis L

    2012-12-16

    CYP1B1 is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates and plays a key role in hormone-induced carcinogenesis. Risk factors for ovarian cancer are related to hormonal exposure and reproduction, and polymorphisms within genes involved in metabolism of oestrogen and certain xenobiotics may influence the risk of developing ovarian cancer. Current meta-analysis evaluated four CYP1B1 polymorphisms (Leu432Val, Arg48Gly, Ala119Ser and Asn453Ser) for their association with ovarian cancer risk. A search of the MEDLINE bibliographic database for the period up to April 2012 identified five relevant studies. With regards to Leu432Val polymorphism, all of the five studies were eligible (1199 cases and 2596 controls) for analysis, while for Arg48Gly (799 cases and 1169 controls), Ala119Ser (799 cases and 1172 controls) and Asn453Ser (361cases and 1577 controls) only two studies were eligible for analysis. Fixed-effect models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (95% CI) and chi-square based Q-test was used to test for heterogeneity. The pooled OR (95% CI) for CYP1B1_Leu432Val polymorphism were 1.1 (0.84-1.31) for heterozygous subjects and 0.82 (0.57-1.17) for homozygous Val subjects. In a recessive model, homozygous carriers of Leu432Val showed a weak trend towards reduced risk as compared to 'wild type' and heterozygous carriers (OR 0.8, 95% CI; 0.66-0.99); however, this association was of limited significance. Regarding Arg48Gly, the pooled OR (95% CI) were 1.06 (0.89-1.27) for heterozygous and 0.98 (1.72-1.33) for homozygous Gly subjects. With respect to Ala119Ser and Asn453Ser, the pooled OR were 1.06 (0.87-1.29) and 1.24 (0.94-1.63) for heterozygous and 1.1 (0.8-1.52) and 1.09 (0.5-2.34) for homozygous respectively. In conclusion, this meta-analysis suggests that CYP1B1 polymorphisms are not associated with ovarian cancer risk. Studies evaluating CYP1B1_Leu432Val polymorphism are required to

  16. Cytochrome P1B1 (CYP1B1) polymorphisms and cancer risk: a meta-analysis of 52 studies.

    Science.gov (United States)

    Li, Cuiping; Long, Bingshuang; Qin, Xianjing; Li, Weixiong; Zhou, Yang

    2015-01-02

    CYP1B1 plays a critical role in the oxidative metabolism of a variety of exogenous compounds, including carcinogenic compounds, which may be activated during metabolism. There are only a few studies that have examined the association between the two polymorphisms and cancer, and that these studies have been inconclusive. Hence, the aim of the present meta-analysis was to evaluate the relationship between polymorphisms in CYP1B1 G119T and A453G and cancer risk. We performed a detailed search using the PubMed and EMBASE libraries to obtain all relevant published reports on the relationship between the G119T and A453G polymorphisms in CYP1B1 and cancer risk. Combined odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by Stata version 11.2. We conducted stratified analyses based on cancer types, ethnicity, source of controls, and quality assessments. We also made assessments of heterogeneity tests, sensitivity analyses, and publication bias. There were a total of 25 articles with 15,376 cases and 18,382 controls concerning CYP1B1 G119T and 40 articles with 27,983 cases and 35,839 controls concerning A453G polymorphisms. Regarding G119T, the combined results indicate that the variant genotypes were significantly associated with a slightly increased cancer risk in comparison to the homozygote (TT versus GG: p=0.006, OR=1.231, 95% CI: 1.061-1.428), especially for breast cancer and prostate cancer. Moreover, significantly increased associations with cancer risk were demonstrated in Asians in all genetic models. The combined results indicated no association of A453G with cancer risk; however, an association was observed specifically for prostate cancer. This meta-analysis suggests that the CYP1B1 G119T polymorphism may confer to genetic susceptibility to cancer in Asians, especially to breast cancer and prostate cancer. The A453G polymorphism was found to modify the risk of prostate cancer.

  17. (Acetonitrile[bis(2-pyridylmethylamine]bis(perchloratocopper(II

    Directory of Open Access Journals (Sweden)

    Ray J. Butcher

    2008-01-01

    Full Text Available In the title compound, [Cu(ClO42(C12H13N3(C2H3N], the CuII atom is six-coordinate in a Jahn–Teller distorted octahedral geometry, with coordination by the tridentate chelating ligand, an acetonitrile molecule, and two axial perchlorate anions. The tridentate ligand bis(2-pyridylmethylamine chelates meridionally and equatorially while an acetonitrile molecule is coordinated at the fourth equatorial site. The two perchlorate anions are disordered with site occupancy factors of 0.72/0.28. The amine H is involved in intramolecular hydrogen bonding to the perchlorate O atoms and there are extensive but weak intermolecular C—H...O interactions.

  18. Relative photometry of HAT-P-1b occultations

    CERN Document Server

    Béky, Bence; Gilliland, Ronald L; Bakos, Gáspár Á; Winn, Joshua N; Noyes, Robert W; Sasselov, Dimitar D

    2013-01-01

    We present HST STIS observations of two occultations of the transiting exoplanet HAT-P-1b. By measuring the planet to star flux ratio near opposition, we constrain the geometric albedo of the planet, which is strongly linked to its atmospheric temperature gradient. An advantage of HAT-P-1 as a target is its binary companion ADS 16402 A, which provides an excellent photometric reference, simplifying the usual steps in removing instrumental artifacts from HST time-series photometry. We find that without this reference star, we would need to detrend the lightcurve with the time of the exposures as well as the first three powers of HST orbital phase, and this would introduce a strong bias in the results for the albedo. However, with this reference star, we only need to detrend the data with the time of the exposures to achieve the same per-point scatter, therefore we can avoid most of the bias associated with detrending. Our final result is a 2 sigma upper limit of 0.64 for the geometric albedo of HAT-P-1b betwee...

  19. Berberine inhibits PTP1B activity and mimics insulin action.

    Science.gov (United States)

    Chen, Chunhua; Zhang, Yuebo; Huang, Cheng

    2010-07-02

    Type 2 diabetes patients show defects in insulin signal transduction that include lack of insulin receptor, decrease in insulin stimulated receptor tyrosine kinase activity and receptor-mediated phosphorylation of insulin receptor substrates (IRSs). A small molecule that could target insulin signaling would be of significant advantage in the treatment of diabetes. Berberine (BBR) has recently been shown to lower blood glucose levels and to improve insulin resistance in db/db mice partly through the activation of AMP-activated protein kinase (AMPK) signaling and induction of phosphorylation of insulin receptor (IR). However, the underlying mechanism remains largely unknown. Here we report that BBR mimics insulin action by increasing glucose uptake ability by 3T3-L1 adipocytes and L6 myocytes in an insulin-independent manner, inhibiting phosphatase activity of protein tyrosine phosphatase 1B (PTP1B), and increasing phosphorylation of IR, IRS1 and Akt in 3T3-L1 adipocytes. In diabetic mice, BBR lowers hyperglycemia and improves impaired glucose tolerance, but does not increase insulin release and synthesis. The results suggest that BBR represents a different class of anti-hyperglycemic agents.

  20. The Response of Marine Biota to OAE 1b

    Science.gov (United States)

    Herrle, J. O.

    2006-12-01

    The latest Aptian to earliest Albian is characterized by the first appearance of a distinctly modern phytoplankton community accompanied by a cold episode during a generally extreme greenhouse climate. Massive burial of organic matter caused the formation of the black shale `Niveaus' Jacob, Kilian, Paquier and Leenhardt in the Vocontian Basin (SE France). This interval is reported as the Oceanic Anoxic Event 1b (OAE1b) following the definition of Leckie et al. (2002). Lasting about four million years, OAE1b facilitates analysis of rapid climate change in a greenhouse world, and crucial for understanding climate change. During latest Aptian angiosperms and diatoms became abundant in the terrestrial and marine environments (Gersonde & Haywood 1990; Heimhofer et al. 2005). Planktic foraminifera experienced their greatest turnover rates since their first appearance, accompanied by a decrease in test size and changes of the ultrastructures of their shells (Leckie et al. 2002). Calcareous nannoplankton show a major change characterized by the influx of the boreal cool water indicator Repagulum parvidentatum into the Tethyan Realm (Herrle & Mutterlose 2003). Moreover, ammonite faunas became more cosmopolitan at the expense of Tethyan taxa during this period. Both the influx of boreal nannoplankton taxa and the trend to more cosmopolitian ammonite assemblages in the Tethyan Realm was probably favored by a long-term sea level rise accompanied by a global cooling during the late Aptian to early Albian interval. Most dramatic changes of the marine carbonate system are reflected by the stepwise decrease of nannoconids and carbonate platform drowning accompanied by a positive carbon isotope excursion which is similar to the biocalcification crisis associated with the early Aptian OAE1a (Erba 1994, Weissert et al., 1998). The massive change in the global carbon cycle is probably linked to a major change in global marine productivity from a calcareous system (nannoconids

  1. Data of evolutionary structure change: 1B7QA-2G4QA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B7QA-2G4QA 1B7Q 2G4Q A A KVFERCELARTLKRLGMDGYRGISLALWMCLAKWESGYN...GRCELAAAMKRHGLDNYRGYSLGNWVCAAKFESNFNTQATNRNTD-GSTDYGILQINSRWWCNDGRTPGSRNLCNIPCSALLSSDITASVNCAKKIVSDGNGMNAWVAWRNRCKGTDVQA... A 2G4QA NRNTD-GSTDY 1B7Q A 1B7QA

  2. Interferon β-1b-neutralizing antibodies 5 years after clinically isolated syndrome

    DEFF Research Database (Denmark)

    Hartung, H-P; Freedman, M S; Polman, C H;

    2011-01-01

    To determine the frequency and consequences of neutralizing antibodies (NAbs) in patients with a first event suggestive of multiple sclerosis (MS) treated with interferon β-1b (IFNβ-1b).......To determine the frequency and consequences of neutralizing antibodies (NAbs) in patients with a first event suggestive of multiple sclerosis (MS) treated with interferon β-1b (IFNβ-1b)....

  3. Synthesis of mangiferin derivates and study their potent PTP1B inhibitory activity

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Protein tyrosine phosphatase 1B (PTP1B) has received considerable attention from the drug industry as a potential treatment fordiabetes mellitus. Mangiferin has been reported to possess significant antidiabetic activity. Based on the previous study, eight new mangiferin derivates were synthesized and evaluated for their PTP1B inhibitory activity. Some of them displayed good inhibitory activity on PTP1B.

  4. Synthesis and Crystal Structure of the Intermediate Bis-9-fluorenylmethylphenyl Silane

    Institute of Scientific and Technical Information of China (English)

    罗悔; 马怀柱; 苏庆德; 刘青山

    2003-01-01

    The title compound bis-9-fluorenylmethylphenyl silane (C33H26Si, Mr = 450.63) was synthesized and its structure has been synthesized and determined by X-ray analysis. The crystal is of triclinic, space group Pī with a = 9.478(1), b = 10.0956(1), c = 13.0243(2)(A°),α= 92.668(2),β= 90.809(2),γ= 99.348(2)°,λ= 0.71073(A°),μ(MoKα)= 0.115 mm-1, V = 1288.1(2)(A°)3, Z = 2, Dc = 1.219 g/cm3 and F(000) = 476. The structure was refined to R = 0.0437 and wR(F2) = 0.0963 for 3346 observed reflections with I>2σ(I). X-ray diffraction analysis reveals that the title compound is bis-9-fluorenylmethylphenyl silane.

  5. Monochromator development at 4W1B beamiline of BSRF

    Institute of Scientific and Technical Information of China (English)

    YaningXie; Y.Yan; T.D.Hu; T.Liu; D.C.Xian

    2001-01-01

    The 4W1B is a X-ary monochromator beamline for XAFS at BSRF.During the upgrading phase,we have redsigned the monochromator to improve the performnce of beamline.It is a goniometer based,fixed exit double crystal monochromator.A mechanical linkage is employed to adjust the distance between the surfaces of the two crystals as the Bragg angle is changed to keep the outgoing beam direction constant.The whole mechanism is driven by only one stepping motor.The testing result shows that over the scanning range of 5-30°,the shift of outgoing beam position is less then 70μm in the vertical direction.The basic principle,the mechanical realization,and the error analysis are discussed in detail.The performance and the testing results are also presented in this paper.2001 Elsevier Science B.V.All rights reserved.

  6. Monochromator development at 4W1B beamline of BSRF

    Science.gov (United States)

    Xie, Yaning; Yan, Y.; Hu, T. D.; Liu, T.; Xian, D. C.

    2001-07-01

    The 4W1B is a X-ray monochromator beamline for XAFS at BSRF. During the upgrading phase, we have redesigned the monochromator to improve the performance of the beamline. It is a goniometer based, fixed exit double crystal monochromator. A mechanical linkage is employed to adjust the distance between the surfaces of the two crystals as the Bragg angle is changed to keep the outgoing beam direction constant. The whole mechanism is driven by only one stepping motor. The testing result shows that over the scanning range of 5-30°, the shift of outgoing beam position is less then 70 μm in the vertical direction. The basic principle, the mechanical realization, and the error analysis are discussed in detail. The performance and the testing results are also presented in this paper.

  7. Performance and Applications of L1B2 Ultrasonic Motors

    Directory of Open Access Journals (Sweden)

    Gal Peled

    2016-06-01

    Full Text Available Piezoelectric ultrasonic motors offer important advantages for motion applications where high speed is coupled with high precision. The advances made in the recent decades in the field of ultrasonic motor based motion solutions allow the construction of complete motion platforms in the fields of semiconductors, aerospace and electro-optics. Among the various motor designs, the L1B2 motor type has been successful in industrial applications, offering high precision, effective control and operational robustness. This paper reviews the design of high precision motion solutions based on L1B2 ultrasonic motors—from the basic motor structure to the complete motion solution architecture, including motor drive and control, material considerations and performance envelope. The performance is demonstrated, via constructed motion stages, to exhibit fast move and settle, a repeatability window of tens of nanometers, lifetime into the tens of millions of operational cycles, and compatibility with clean room and aerospace environments. Example stages and modules for semiconductor, aerospace, electro-optical and biomedical applications are presented. The described semiconductor and aerospace solutions are powered by Nanomotion HR type motors, driven by a sine wave up to 80 V/mm rms, having a driving frequency of 39.6 kHz, providing a maximum force up to 4 N per driving element (at 5 W power consumption per element and a maximum linear velocity above 300 mm/s. The described electro-optical modules are powered by small Nanomotion Edge motors driven by voltages up to 11 V AC, providing stall forces up to 0.35 N (power consumption up to 0.75 W and maximum linear velocity above 200 mm/s.

  8. Synthesis, characterization, ab initio calculations, thermal behaviour and thermodynamics of some oxovanadium(IV) complexes involving O,O- and ,-donor moieties

    Indian Academy of Sciences (India)

    Mozaffar Asadi; Mohammad Hadi Ghatee; Susan Torabi; Khosro Mohammadi; Fatemeh Moosavi

    2010-07-01

    Some oxovanadium(IV) complexes, namely bis(1,1,1-trifluro-2,4-pentanedionato-,') oxovanadium (IV), [VO(tfac)2(H2O)], bis(1-phenyl-2,4-pentanedionato-,')oxovanadium(IV), [VO(phac)2(H2O)], bis(1,3-diphenyl-2,4-pentanedionato-,')oxovanadium(IV), [VO(dphac)2 (H2O)], of the type [VO(O4)] and bis(pyrolidineaniline)oxovanadium(IV), [VO(pyran)2(H2O)], bis(-hydroxypyrolidineaniline) oxovanadium(IV), [VO(-hydroxypyran)2(H2O)], bis(-methoxypyrolidineaniline)oxovanadium(IV), [VO(-MeOpyran)2 (H2O)], bis(-chloropyrolidineaniline)oxovanadium(IV), [VO(-chloropyran)2(H2O)], bis(-bromopyrolidineaniline)oxovanadium(IV), [VO(-bromopyran)2(H2O)], bis(-cyano pyrolidineaniline)oxovanadium(IV), [VO(-cyanopyran)2(H2O)], and bis(pyrolidinebenzylamine)oxovanadium(IV), [VO(pyrbz)2(H2O)], of the type [VO(N4)] were synthesized and characterized by IR, UV-Vis, mass spectrometry, elemental analysis, magnetic moment and thermogravimetry in order to evaluate their thermal stability and thermal decomposition pathways. The number of steps and, in particular, the starting temperature of decomposition of these complexes depends on the equatorial ligand. Also, formation constants of the complexes have been determined by UV-Vis absorption spectroscopy through titration of the ligands with the metal ions at constant ionic strength (0.1 M NaClO4) and at 25°C. According to the thermodynamic studies, as the steric character of the ligand increases, the complexation tendency to VO(IV) center decreases. Also, the ab initio calculations were carried out to determine the structural and the geometrical properties of the complexes.

  9. Protein tyrosine phosphatase 1B (PTP1B)-inhibiting constituents from the leaves of Syzygium polyanthum.

    Science.gov (United States)

    Saifudin, Azis; Tanaka, Ken; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2012-08-01

    A methanol extract of the leaves of Syzygium polyanthum (Wight) Walp. afforded four new acylbenzene derivatives (1-4) together with seven known compounds (5-11). The structures of 1-11 were elucidated by extensive spectroscopic methods and comparison with the literature data. The new compounds 1-3 and a known compound, campest-4-en-3-one (10), exhibited a significant protein tyrosine phosphatase 1B inhibitory activity with IC₅₀ values of 13.1 ± 0.1, 5.77 ± 0.15, 4.01 ± 0.26, and 10.4 ± 0.5 µM, respectively. The inhibitory potency of the new compounds 2 and 3 was comparable to that of a positive control RK-682 (IC₅₀, 5.51 ± 0.04 µM).

  10. Bis[1,3-bis(2-cyanophenyltriazenido]mercury(II

    Directory of Open Access Journals (Sweden)

    Mohammad Kazem Rofouei

    2009-10-01

    Full Text Available In the title compound, [Hg(C14H8N52], the central atom is four-coordinated by two bidentate 1,3-bis(2-cyanophenyltriazenide ligands in a distorted square-planar geometry. The asymmteric unit is composed of one ligand molecule and one HgII ion, which is disordered over two sites, one lying on an inversion center and the other on a general position with site-occupancy factors of 0.2378 (7 and 0.3811 (7, respectively. The monomeric molecules of the complex are linked into pairs through non-classical C—H...N hydrogen bonds. The resulting dimeric units are assembled by translation along the crystallographic c axis into chains linked through secondary π–π interactions [centroid–centroid distances = 3.685 (2 and 3.574 (2 Å], as well as C—H...π stacking interactions, resulting in a two-dimensional architecture.

  11. Syntheses of 3-substituted 2,3-dihydrobenzofuranes, 1,2-dihydronaphtho(2,1-b)furanes, and 2,3-dihydro-1H-indoles by tandem ring closure-S(RN)1 reactions.

    Science.gov (United States)

    Vaillard, Santiago E; Postigo, Al; Rossi, Roberto A

    2002-11-29

    3-Substituted 2,3-dihydrobenzofuranes (7a-c), 1,2-dihydronaphtho(2,1-b)furanes (10a-c), and N-substituted 2,3-dihydro-1H-indoles (8a-c, 9a,b) are obtained in very good yields by S(RN)1 photostimulated reactions in liquid ammonia from adequate haloaromatic compounds ortho-substituted with a suitable double bond (3a,b; 4a,b; 5a; 6a,b) and Me3Sn-, Ph2P-, and -CH2NO2 anions. The novelty of the work involves the versatile application of a 5-exo ring closure process during the propagation cycle of the S(RN)1 reaction; the alkyl radical intermediates formed react with the nucleophiles to afford the ring closure-substituted heterocycles. The factors governing the observed product distribution are discussed.

  12. Genetic variants in MTNR1B affecting insulin secretion.

    Science.gov (United States)

    Müssig, Karsten; Staiger, Harald; Machicao, Fausto; Häring, Hans-Ulrich; Fritsche, Andreas

    2010-09-01

    The incidence of type 2 diabetes mellitus has markedly increased worldwide over the past decades. Pancreatic beta-cell dysfunction as well as central and peripheral insulin resistance appears to be elementary features in the pathophysiology of type 2 diabetes mellitus. Major environmental conditions predisposing to the development of type 2 diabetes are excessive food intake and sedentary life-style on the background of a genetic predisposition. Recent genome-wide association studies identified several novel type 2 diabetes risk genes, with impaired pancreatic beta-cell function as the underlying mechanism of increased diabetes risk in the majority of genes. Many of the novel type 2 diabetes risk genes, including MTNR1B which encodes one of the two known human melatonin receptors, were unexpected at first glance. However, previous animal as well as human studies already pointed to a significant impact of the melatonin system on the regulation of glucose homeostasis, in addition to its well known role in modulation of sleep and circadian rhythms. This brief review aims to give an overview of how alterations in the melatonin system could contribute to an increased diabetes risk, paying special attention to the role of melatonin receptors in pancreatic beta-cell function.

  13. A Photometric Survey of Ori OB1b

    Science.gov (United States)

    Merritt, Allison T.; Sherry, W.

    2011-01-01

    Several mechanisms have been suggested to describe the formation of sub-stellar mass objects (SSMOs), specifically brown dwarfs. Each proposed mechanism predicts a unique spatial distribution of the brown dwarfs relative to the O and B stars of the association. We have 9 square degrees of optical (VRI) data and 7 square degrees of NIR (JHK) data of Orion OB1b. The purpose of the survey is to obtain the photometric data that will allow us to determine the spatial distribution of brown dwarfs in this region and constrain the various formation theories. We present an overview of the survey, with an emphasis on the NIR data, as well as color-magnitude diagrams. This research was supported by the NOAO/KPNO Research Experiences for Undergraduates (REU) Program which is funded by the National Science Foundation Research Experiences for Undergraduates Program and the Department of Defense ASSURE program through Scientific Program Order No. 13 (AST-0754223) of the Cooperative Agreement No. AST-0132798 between the Association of Universities for Research in Astronomy (AURA) and the NSF.

  14. Transit timing analysis of CoRoT-1b

    CERN Document Server

    Csizmadia, Sz; Barge, P; Agol, E; Aigrain, S; Alonso, R; Almenara, J M; Bonomo, A S; Borde, P; Bouchy, F; Cabrera, J; Deeg, H J; De la Reza, R; Deleuil, M; Dvorak, R; Erikson, A; Guenther, E W; Fridlund, M; Gondoin, P; Guillot, T; Hatzes, A; Jorda, L; Lammer, H; Lázaro, C; Leger, A; Llebaria, A; Magain, P; Moutou, C; Ollivier, M; Paetzold, M; Queloz, D; Rauer, H; Rouan, D; Schneider, J; Wuchterl, G; Gandolfi, D

    2009-01-01

    CoRoT, the pioneer space-based transit search, steadily provides thousands of high-precision light curves with continuous time sampling over periods of up to 5 months. The transits of a planet perturbed by an additional object are not strictly periodic. By studying the transit timing variations (TTVs), additional objects can be detected in the system. A transit timing analysis of CoRoT-1b is carried out to constrain the existence of additional planets in the system. We used data obtained by an improved version of the CoRoT data pipeline (version 2.0). Individual transits were fitted to determine the mid-transit times, and we analyzed the derived $O-C$ diagram. N-body integrations were used to place limits on secondary planets. No periodic timing variations with a period shorter than the observational window (55 days) are found. The presence of an Earth-mass Trojan is not likely. A planet of mass greater than $\\sim 1$ Earth mass can be ruled out by the present data if the object is in a 2:1 (exterior) mean mot...

  15. The secondary eclipse of CoRoT-1b

    CERN Document Server

    Alonso, R; Aigrain, S; Auvergne, M; Baglin, A; Barbieri, M; Barge, P; Bonomo, A S; Borde, P; Bouchy, F; Chaintreuil, S; De la Reza, R; Deeg, H J; Deleuil, M; Dvorak, R; Erikson, A; Fridlund, M; Fialho, F; Gondoin, P; Guillot, T; Hatzes, A; Jorda, L; Lammer, H; Léger, A; Llebaria, A; Magain, P; Mazeh, T; Moutou, C; Ollivier, M; Patzold, M; Pont, F; Queloz, D; Rauer, H; Rouan, D; Schneider, J; Wuchterl, G

    2009-01-01

    The transiting planet CoRoT-1b is thought to belong to the pM-class of planets, in which the thermal emission dominates in the optical wavelengths. We present a detection of its secondary eclipse in the CoRoT white channel data, whose response function goes from ~400 to ~1000 nm. We used two different filtering approaches, and several methods to evaluate the significance of a detection of the secondary eclipse. We detect a secondary eclipse centered within 20 min at the expected times for a circular orbit, with a depth of 0.016+/-0.006%. The center of the eclipse is translated in a 1-sigma upper limit to the planet's eccentricity of ecosomega<0.014. Under the assumption of a zero Bond Albedo and blackbody emission from the planet, it corresponds to a T_{CoRoT}=2330 +120-140 K. We provide the equilibrium temperatures of the planet as a function of the amount of reflected light. If the planet is in thermal equilibrium with the incident flux from the star, our results imply an inefficient transport mechanism ...

  16. Briefwechsel uber die Partikel "bis" (An Exchange of Letters about the Particle "bis").

    Science.gov (United States)

    Ludwig, Horst; Holschuh, Albrecht

    1990-01-01

    A discussion, in the form of an animated letter exchange, argues that, contrary to most current grammatical descriptions, the German particle "bis" should not be viewed as a preposition governing the accusative case. Rather, it is demonstrated that "bis" most often occurs as a proclitic adverb. (16 references) (JTC)

  17. Pregnancy and pregnancy outcome in hepatitis C type 1b.

    LENUS (Irish Health Repository)

    Jabeen, T

    2012-02-03

    A large cohort of rhesus-negative women in Ireland were inadvertently infected with hepatitis C virus following exposure to contaminated anti-D immunoglobulin in 1977-8. This major iatrogenic episode was discovered in 1994. We studied 36 women who had been infected after their first pregnancy, and compared them to an age- and parity-matched control group of rhesus-positive women. The presence of hepatitis C antibody was confirmed in all 36 by enzyme-linked immunosorbent assay and by recombinant immunoblot assay, while 26 (72%) of the cohort were HCV-RNA-positive (type 1b) on PCR testing. In the 20 years post-infection, all members of the study group had at least one pregnancy, and mean parity was 3.5. They had a total of 100 pregnancies and 85 of these went to term. There were four premature births, one being a twin pregnancy, and 11 spontaneous miscarriages. One miscarriage occurred in the pregnancy following HCV infection. There were two neonatal deaths due to severe congenital abnormalities in the PCR-positive women. Of the children born to HCV-RNA positive mothers, only one (2.3%) tested positive for the virus. Significant portal fibrosis on liver biopsy was confined to HCV-RNA-positive mothers apart from one single exception in the antibody-positive HCV-RNA-negative group. Comparison with the control group showed no increase in spontaneous miscarriage rate, and no significant difference in obstetric complications; birth weights were similar for the two groups.

  18. Protein tyrosine phosphatase 1B (PTP1B) inhibitors from Morinda citrifolia (Noni) and their insulin mimetic activity.

    Science.gov (United States)

    Nguyen, Phi-Hung; Yang, Jun-Li; Uddin, Mohammad N; Park, So-Lim; Lim, Seong-Il; Jung, Da-Woon; Williams, Darren R; Oh, Won-Keun

    2013-11-22

    As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of Morinda citrifolia showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (1 and 2) and three new neolignans (9, 10, and 14), as well as 10 known compounds (3-8, 11-13, and 15). The absolute configurations of compounds 9, 10, and 14 were determined by ECD spectra analysis. Compounds 3, 6, 7, and 15 showed inhibitory effects on PTP1B enzyme with IC50 values of 21.86 ± 0.48, 15.01 ± 0.20, 16.82 ± 0.42, and 4.12 ± 0.09 μM, respectively. Furthermore, compounds 3, 6, 7, and 15 showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds 3, 6, 7, and 15 as lead molecules for antidiabetic agents.

  19. The N-terminal region of organic anion transporting polypeptide 1B3 (OATP1B3) plays an essential role in regulating its plasma membrane trafficking.

    Science.gov (United States)

    Chun, Se-Eun; Thakkar, Nilay; Oh, Yunseok; Park, Ji Eun; Han, Songhee; Ryoo, Gongmi; Hahn, Hyunggu; Maeng, Sang Hyun; Lim, Young-Ran; Han, Byung Woo; Lee, Wooin

    2017-05-01

    Organic anion transporting polypeptide 1B3 (OATP1B3) is a major influx transporter mediating the hepatic uptake of various endogenous substrates as well as clinically important drugs such as statins and anticancer drugs. However, molecular mechanisms controlling the membrane trafficking of OATP1B3 have been largely unknown. Several reports recently indicated the presence of a distinct, cancer-type OATP1B3 variant lacking the N-terminal 28 amino acids compared to OATP1B3 expressed in non-malignant hepatocytes. Interestingly, the cancer-type OATP1B3 variant is located predominantly in the cytoplasm, implicating the involvement of the N-terminal region of OATP1B3 in its membrane trafficking. In the current study, we set out to experimentally validate the importance of the N-terminal region of OATP1B3 and to identify responsible sequence motif(s) in that region. A number of truncation or point mutants of OATP1B3 were transiently expressed in HEK293T, HCT-8 or MDCK II cells and their expression in cytoplasmic and surface membrane fractions were analyzed by immunoblotting. Our results indicated that the N-terminal sequence of OATP1B3, in particular, at the amino acid positions between 12 and 28, may be indispensable in its membrane trafficking. Moreover, our results using a fusion construct indicated that the first 50 amino acids of OATP1B3 are sufficient for its membrane localization. The importance of the N-terminal region in membranous localization was shared among the other OATP1B subfamily members, OATP1B1 and rat Oatp1b2. Our efforts to identify the responsible amino acid(s) or structure motif(s) in the N-terminal region did not pinpoint individual amino acids or motifs with putative secondary structures. Our current findings however demonstrate that the N-terminal region is important for the membrane localization of the OATP1B subfamily members and should facilitate future investigations of the mechanisms involved in the regulation and membrane trafficking of

  20. Nostocyclopeptide-M1: a potent, nontoxic inhibitor of the hepatocyte drug transporters OATP1B3 and OATP1B1.

    Science.gov (United States)

    Herfindal, Lars; Myhren, Lene; Kleppe, Rune; Krakstad, Camilla; Selheim, Frode; Jokela, Jouni; Sivonen, Kaarina; Døskeland, Stein O

    2011-04-01

    We have isolated a novel cyanobacterial cyclic peptide (nostocyclopeptide M1; Ncp-M1) that blocks the hepatotoxic action of microcystin (MC) and nodularin (Nod). We show here that Ncp-M1 is nontoxic to primary hepatocytes in long-term culture. Ncp-M1 does not affect any known intracellular targets or pathways involved in MC action, like protein phosphatases, CaM-KII, or ROS-dependent cell death effectors. In support of this conclusion Ncp-M1 had no protective effect when microinjected into cells. Rather, the antitoxin effect was solely due to blocked hepatocyte uptake of MC and Nod. The hepatic uptake of MC and Nod is mainly via the closely related organic anion transporters OATP1B1 and OATP1B3, which also mediate hepatic transport of endogenous metabolites and hormones as well as drugs. OATP1B3 is also expressed in some aggressive cancers, where it confers apoptosis resistance. We show that Ncp-M1 inhibits transport through OATP1B3 and OATP1B1 expressed in HEK293 cells. The Ncp-M1 molecule has several nonproteinogenic amino acids and an imino bond, which hamper its synthesis. Moreover, a cyclic all L-amino acid heptapeptide analogue of Ncp-M1 also inhibits the OATP1B1/1B3 transporters, and with higher OATP1B3 preference than Ncp-M1 itself. The nontoxic Ncp-M1 and its synthetic cyclic peptide analogues thus provide new tools to probe the role of OATB1B1/1B3 mediated drug and metabolite transport in liver and cancer cells. They can also serve as scaffolds to design new, exopeptidase resistant OATP1B3-specific modulators.

  1. Isolation of modulators of the liver-specific organic anion-transporting polypeptides (OATPs) 1B1 and 1B3 from Rollinia emarginata Schlecht (Annonaceae).

    Science.gov (United States)

    Roth, Megan; Araya, Juan J; Timmermann, Barbara N; Hagenbuch, Bruno

    2011-11-01

    Organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) are liver-specific transporters that mediate the uptake of a broad range of drugs into hepatocytes, including statins, antibiotics, and many anticancer drugs. Compounds that alter transport by one or both of these OATPs could potentially be used to target drugs to hepatocytes or improve the bioavailability of drugs that are cleared by the liver. In this study, we applied a bioassay-guided isolation approach to identify such compounds from the organic extract of Rollinia emarginata Schlecht (Annonaceae). Fractions of the plant extract were screened for effects on OATP1B1- and OATP1B3-mediated transport of the model substrates estradiol-17β-glucuronide and estrone-3-sulfate. We isolated three compounds, ursolic acid, oleanolic acid, and 8-trans-p-coumaroyloxy-α-terpineol, which inhibited estradiol-17β-glucuronide uptake by OATP1B1 but not OATP1B3. In addition, a rare compound, quercetin 3-O-α-l-arabinopyranosyl(1→2) α-L-rhamnopyranoside, was identified that had distinct effects on each OATP. OATP1B1 was strongly inhibited, as was OATP1B3-mediated transport of estradiol-17β-glucuronide. However, OATP1B3-mediated uptake of estrone-3-sulfate was stimulated 4- to 5-fold. Kinetic analysis of this stimulation revealed that the apparent affinity for estrone-3-sulfate was increased (decreased K(m)), whereas the maximal rate of transport (V(max)) was significantly reduced. These results demonstrate a mechanism through which the hepatic uptake of drug OATP substrates could be stimulated.

  2. Thermonuclear Reflect AB-Reactor

    CERN Document Server

    Bolonkin, Alexander

    2008-01-01

    The author offers a new kind of thermonuclear reflect reactor. The remarkable feature of this new reactor is a three net AB reflector, which confines the high temperature plasma. The plasma loses part of its energy when it contacts with the net but this loss can be compensated by an additional permanent plasma heating. When the plasma is rarefied (has a small density), the heat flow to the AB reflector is not large and the temperature in the triple reflector net is lower than 2000 - 3000 K. This offered AB-reactor has significantly less power then the currently contemplated power reactors with magnetic or inertial confinement (hundreds-thousands of kW, not millions of kW). But it is enough for many vehicles and ships and particularly valuable for tunnelers, subs and space apparatus, where air to burn chemical fuel is at a premium or simply not available. The author has made a number of innovations in this reactor, researched its theory, developed methods of computation, made a sample computation of typical pr...

  3. Data of evolutionary structure change: 1B5XA-1GHLA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5XA-1GHLA 1B5X 1GHL A A -KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGY...NTRATNYNAGDRSTDYGIFQINSRYWCNDGKTPGAVNACHLACSALLQDNIADAVACAKRVVRDPQGIRAWVAWRNRCQNRDVRQYVQGCGV GK...ID> A 1GHLA TNRNT-DGS

  4. Data of evolutionary structure change: 1DTGA-1B7ZA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DTGA-1B7ZA 1DTG 1B7Z A A ---KTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVAC...VAVVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFV...> 0 1DTG A 1DTGAA 1DTGA LFSSP-HGKDL 1DTGA HMKSVIPSDGPSV

  5. Data of evolutionary structure change: 1DTGA-1B0LA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DTGA-1B0LA 1DTG 1B0L A A ---KTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVAC...GYLAVAVVRRSDTSLTWNSVKGKKSCHTAVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPRSNLCALCIGDEQGENKCVPNSNERYYGYTGAFRCLAENAGD...ignment> 0 1DTG A 1DTGA...> 1 1DTG A 1DTGA 1DTG A 1DTGA

  6. Data of evolutionary structure change: 1B06A-2GDSB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B06A-2GDSB 1B06 2GDS A B VIQLKRYEFPQLPYKVDALEPYISKDIIDVHYNGHHKGYVNGANSLLDRL-EKLIKGD...NLQIMTVENH-FMNHIAELPVILIVDEFEHAYYLQYKNKRGDYLNAWWNVVNWDDAEKRLQKYLNK -----KHSLPDLPYDYGALEPHINAQIM...QLHHSKNHAAYVNNLNVTEEKYQEALAKGD-------VTAQIALQPALKFNGGGHINHSIFWTNLSP--NGGGEPKGELLE...264 2GDS B 2GD...el> 1 2GDS

  7. Data of evolutionary structure change: 1B9IA-2FNIA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B9IA-2FNIA 1B9I 2FNI A A KAPEFPAWPQYDDAERNGLVRALEQGQWWRMGGDEVNSF...ADTGVPLLQDAAHAHGARWQGKRVGELDSIATFSFQNGKLMTAGEGGAVVFPDGETEKYETAFLRHSCGRPRDD-RRYFHKIAGSNMRLNEFSASVLRAQLARLDEQIA...VRDERWTLLSRLLGAIDGVVPQGGDVRADRNSHYMAMFRIPGLTEERRNALVDRLVEAGLPAFAAFRAIYRTDAFWELGAPDESVDAIA...RR----CPNTDAISSDCVWLHHRVLLAGEPELHATAEIIADAVGRA-- MKEFAYSEPCLDKEDKKAVLEVLNSKQLTQ--GKRSL...------QLYQQLFNTAPLKSAEDFYHAEISLPCH-ANLNLESVQNIAHSVLKTFESFKI HHHHHHHHHHHH HHHHHHHHHHHH EEEEE HH

  8. An Lmx1b-miR135a2 regulatory circuit modulates Wnt1/Wnt signaling and determines the size of the midbrain dopaminergic progenitor pool.

    Directory of Open Access Journals (Sweden)

    Angela Anderegg

    Full Text Available MicroRNAs regulate gene expression in diverse physiological scenarios. Their role in the control of morphogen related signaling pathways has been less studied, particularly in the context of embryonic Central Nervous System (CNS development. Here, we uncover a role for microRNAs in limiting the spatiotemporal range of morphogen expression and function. Wnt1 is a key morphogen in the embryonic midbrain, and directs proliferation, survival, patterning and neurogenesis. We reveal an autoregulatory negative feedback loop between the transcription factor Lmx1b and a newly characterized microRNA, miR135a2, which modulates the extent of Wnt1/Wnt signaling and the size of the dopamine progenitor domain. Conditional gain of function studies reveal that Lmx1b promotes Wnt1/Wnt signaling, and thereby increases midbrain size and dopamine progenitor allocation. Conditional removal of Lmx1b has the opposite effect, in that expansion of the dopamine progenitor domain is severely compromised. Next, we provide evidence that microRNAs are involved in restricting dopamine progenitor allocation. Conditional loss of Dicer1 in embryonic stem cells (ESCs results in expanded Lmx1a/b+ progenitors. In contrast, forced elevation of miR135a2 during an early window in vivo phenocopies the Lmx1b conditional knockout. When En1::Cre, but not Shh::Cre or Nes::Cre, is used for recombination, the expansion of Lmx1a/b+ progenitors is selectively reduced. Bioinformatics and luciferase assay data suggests that miR135a2 targets Lmx1b and many genes in the Wnt signaling pathway, including Ccnd1, Gsk3b, and Tcf7l2. Consistent with this, we demonstrate that this mutant displays reductions in the size of the Lmx1b/Wnt1 domain and range of canonical Wnt signaling. We posit that microRNA modulation of the Lmx1b/Wnt axis in the early midbrain/isthmus could determine midbrain size and allocation of dopamine progenitors. Since canonical Wnt activity has recently been recognized as a key

  9. Genetic polymorphisms in CYP1A1, CYP1B1 and COMT genes in Greenlandic Inuit and Europeans

    Directory of Open Access Journals (Sweden)

    Mandana Ghisari

    2013-06-01

    Full Text Available Background. The Indigenous Arctic population is of Asian descent, and their genetic background is different from the Caucasian populations. Relatively little is known about the specific genetic polymorphisms in genes involved in the activation and detoxification mechanisms of environmental contaminants in Inuit and its relation to health risk. The Greenlandic Inuit are highly exposed to legacy persistent organic pollutants (POPs such as polychlorinated biphenyls (PCBs and organochlorine pesticides (OCPs, and an elucidation of gene–environment interactions in relation to health risks is needed. Objectives. The aim of this study was to determine and compare the genotype and allele frequencies of the cytochrome P450 CYP1A1 Ile462Val (rs1048943, CYP1B1 Leu432Val (rs1056836 and catechol-O-methyltransferase COMT Val158Met (rs4680 in Greenlandic Inuit (n=254 and Europeans (n=262 and explore the possible relation between the genotypes and serum levels of POPs. Results. The genotype and allele frequency distributions of the three genetic polymorphisms differed significantly between the Inuit and Europeans. For Inuit, the genotype distribution was more similar to those reported for Asian populations. We observed a significant difference in serum polychlorinated biphenyl (CB-153 and the pesticide 1,1-dichloro-2,2-bis(p-chlorophenyl-ethylene (p,p′-DDE levels between Inuit and Europeans, and for Inuit also associations between the POP levels and genotypes for CYP1A1, CYP1B1 and COMT. Conclusion. Our data provide new information on gene polymorphisms in Greenlandic Inuit that might support evaluation of susceptibility to environmental contaminants and warrant further studies.

  10. Four and a Half LIM Domains 1b (Fhl1b Is Essential for Regulating the Liver versus Pancreas Fate Decision and for β-Cell Regeneration.

    Directory of Open Access Journals (Sweden)

    Jin Xu

    2016-02-01

    Full Text Available The liver and pancreas originate from overlapping embryonic regions, and single-cell lineage tracing in zebrafish has shown that Bone morphogenetic protein 2b (Bmp2b signaling is essential for determining the fate of bipotential hepatopancreatic progenitors towards the liver or pancreas. Despite its pivotal role, the gene regulatory networks functioning downstream of Bmp2b signaling in this process are poorly understood. We have identified four and a half LIM domains 1b (fhl1b, which is primarily expressed in the prospective liver anlage, as a novel target of Bmp2b signaling. fhl1b depletion compromised liver specification and enhanced induction of pancreatic cells from endodermal progenitors. Conversely, overexpression of fhl1b favored liver specification and inhibited induction of pancreatic cells. By single-cell lineage tracing, we showed that fhl1b depletion led lateral endodermal cells, destined to become liver cells, to become pancreatic cells. Reversely, when fhl1b was overexpressed, medially located endodermal cells, fated to differentiate into pancreatic and intestinal cells, contributed to the liver by directly or indirectly modulating the discrete levels of pdx1 expression in endodermal progenitors. Moreover, loss of fhl1b increased the regenerative capacity of β-cells by increasing pdx1 and neurod expression in the hepatopancreatic ductal system. Altogether, these data reveal novel and critical functions of Fhl1b in the hepatic versus pancreatic fate decision and in β-cell regeneration.

  11. Long-term impact of interferon beta-1b in patients with CIS

    DEFF Research Database (Denmark)

    Edan, G; Kappos, L; Montalbán, X;

    2014-01-01

    OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). METHODS: In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μg...

  12. File list: Oth.ALL.10.HNF1B.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.10.HNF1B.AllCell hg19 TFs and others HNF1B All cell types SRX359840,SRX7020...21,SRX825396,SRX702024,SRX702022 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.10.HNF1B.AllCell.bed ...

  13. File list: Oth.ALL.05.HNF1B.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.05.HNF1B.AllCell hg19 TFs and others HNF1B All cell types SRX359840,SRX7020...21,SRX702022,SRX825396,SRX702024,SRX702023 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.ALL.05.HNF1B.AllCell.bed ...

  14. File list: Oth.PSC.20.HNF1B.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.PSC.20.HNF1B.AllCell hg19 TFs and others HNF1B Pluripotent stem cell SRX702021,...SRX702024,SRX702022 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.PSC.20.HNF1B.AllCell.bed ...

  15. Data of evolutionary structure change: 1CG8A-2DN1B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available equence>FSGFE-----ACNEQ ure> ----- HH> B 2DN1B FGDLSTPDAVMGNPK re>G HHHH HH...ence>VNLQA-FTPVT >HH - HHH> 2DN1 B 2DN1B HHFGKEFTPPV ...>HHHGGG HHH> ATOM 1931 CA HIS B 116 17.758 39.

  16. 18 CFR 1b.17 - Appearance and practice before the Commission.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Appearance and practice before the Commission. 1b.17 Section 1b.17 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.17...

  17. 18 CFR 1b.15 - Non-compliance with compulsory processes.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Non-compliance with compulsory processes. 1b.15 Section 1b.15 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.15 Non-compliance...

  18. A facile microwave assisted one-pot synthesis of novel 1-methylhexahydroquinazolin-5(6H-ones and bis-1-methylhexahydroquinazolin-5(6H-ones

    Directory of Open Access Journals (Sweden)

    Madhusudhan Saha

    2011-03-01

    Full Text Available Novel hexahydroquinazolin-5(6H-ones 3a-j have been synthesized in good yields by the reaction of enaminones 2a-b with primary amines and formaldehyde under the influence microwaves. Enaminones 2a-b have also been reacted with diamines and formaldehyde under similar conditions resulting in hitherto unreported bis- hexahydroquinazolin-5(6H-ones 4a-d and 5a-d. The structures of the molecules have been established with the help of spectral and analytical data.

  19. Interference of kallikrein 1b26 (klk1b26 translation by microRNA specifically expressed in female mouse submandibular glands: an additional mechanism for sexual dimorphism of klk1b26 protein in the glands

    Directory of Open Access Journals (Sweden)

    Kurihara Kinji

    2011-11-01

    Full Text Available Abstract Background Mouse kallikrein 1b26 (klk1b26 protein is more abundant in male submandibular glands (SMGs than in female ones. This sexual dimorphism has been thought to be due to increased mRNA synthesis stimulated by androgen. However, the klk1b26 protein level in female SMG is far less than that expected from the mRNA level, suggesting an additional mechanism for down-regulation of klk1b26 expression in female SMGs. Methods We examined the effects of small non-coding RNAs in mouse SMGs on in vitro translation of klk1b26 using a reticulocyte lysate system and reverse transcription (RT-PCR for klk1b26 mRNA. Statistical analyses were performed with a computer package (Microsoft Excel. Results The microRNA (miRNA preparation from female SMGs, but not male SMGs, interfered with the in vitro translation of the klk1b26 protein and inhibited the RT-PCR for klk1b26 mRNA with forward primers targeting its 5'-terminal region (between the 15th and 40th nucleotide from the 5'-terminal. The miRNA preparation from castrated mouse SMGs showed the inhibitory effect on the klk1b26 translation, but that from a 5α-dihydrotestosterone-treated female mouse SMGs did not. Synthetic miRNAs (miR-325 and miR-1497a, which have partial complementarity with klk1b26 mRNA at its 5'-terminal region (15th to 40th nucleotide position from the 5'-terminal, also interfered with the in vitro klk1b26 translation. When the female miRNA preparation was incubated with a 30-nucleotide-long single-strand oligoDNA (named [15th-44th]ssDNA, whose sequence corresponded to the 15th to 44th position from the 5'-terminal of klk1b26 mRNA prior to the addition into the in vitro translation system, the inhibitory effect of the miRNA preparation on klk1b26 translation disappeared, while [15th-44th]ssDNA itself had no effect on the translation. Preincubation of the miRNA preparation with another single-strand DNA ([169th-198th]ssDNA, whose sequence corresponded with 169th to 198th position

  20. Bis-naphthalimides self-assembly organogel formation and application in detection of p-phenylenediamine.

    Science.gov (United States)

    Cao, Xinhua; Zhao, Na; Gao, Aiping; Lv, Haiting; Jia, Yuling; Wu, Renmiao; Wu, Yongquan

    2017-01-01

    Two new gelators containing bis-naphthalimides group were designed and synthesized. The gelator 1b could form gels in DMF and mixed solvent of DMSO/H2O (10/1, v/v). The self-assembly processes of 1b in two kinds of solvents were detailedly investigated by UV-vis, fluorescence, infrared spectroscopy, field emission scanning electron microscope (FE-SEM), X-ray diffraction and contact angle experiments. The experiment results showed the hydrogen bonding was the main force for the gel formation. The gel 1b formed in mixed solvent of DMSO/H2O (10/1, v/v) possessed of the ability of distinguishing of o-phenylenediamine, m-phenylenediamine and p-phenylenediamine. At the same time, the gelator 1b could selectively and sensitively detect p-phenylenediamine in solution with the detection limit of 8.961×10(-8)ML(-1). The detection experiment was also confirmed by DFT theoretical calculations. This research would expand the supramolecular self-assembly materials application in sensor field and offer a new detection method for organic amines.

  1. A novel role for protein tyrosine phosphatase 1B as a positive regulator of neuroinflammation

    OpenAIRE

    Song, Gyun Jee; Jung, Myungsu; Kim, Jong-Heon; Park, Hana; RAHMAN, MD. HABIBUR; Zhang, Sheng; Zhang, Zhong-Yin; Park, Dong Ho; Kook, Hyun; Lee, In-Kyu; Suk, Kyoungho

    2016-01-01

    Background Protein tyrosine phosphatase 1B (PTP1B) is a member of the non-transmembrane phosphotyrosine phosphatase family. Recently, PTP1B has been proposed to be a novel target of anti-cancer and anti-diabetic drugs. However, the role of PTP1B in the central nervous system is not clearly understood. Therefore, in this study, we sought to define PTP1B’s role in brain inflammation. Methods PTP1B messenger RNA (mRNA) and protein expression levels were examined in mouse brain and microglial cel...

  2. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  3. [(Dimethylaminomethyl]dimethylazanium bis(trifluoromethanesulfonylamide

    Directory of Open Access Journals (Sweden)

    Michael Hummel

    2016-10-01

    Full Text Available The title molecular salt, C5H15N2+·C2F6NO4S2−, was obtained by a proton transfer reaction between bis(trifluoromethanesulfonylamine and bis(dimethylaminomethane. In the crystal, the ions are linked by N—H...O=S hydrogen bonds, and these units are linked by C—H...O hydrogen bonds, forming sheets parallel to the bc plane. The crystal was refined as a non-merohedral twin with a BASF factor of 0.316 (1.

  4. Expression of Catalytic Domain of Protein Tyrosine Phosphatase 1B and Preparation of Its Polyclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This study focuses on the expression of human protein tyrosine phosphatase 1B(PTP1B) catalytic domain (△PTP1B) and preparation of polyclonal antibody against △PTP1B. △PTP1B gene was PCR amplified with the cDNA of human PTP1B as the template, and cloned into the pT7 expression vector. The recombinant pT7-△PTP1B was expressed in E. coli Rosetta( DE3 ) host cells and purified. The antiserum was prepared by immunizing rabbit with purified recombinant △PTP1B. The polyclonal antibody against △PTP1B was purified by PVDF immobilized antigen affinity chromatography. △PTP1B was correctly cloned, expressed, and purified as confirmed by PCR, DNA sequence ratio) and 0. 1 ng, respectively. This study provides an important basis for further studying the biological function of PTP1B and its relationship with human diseases.

  5. ABS: Sequence alignment by scanning

    KAUST Repository

    Bonny, Mohamed Talal

    2011-08-01

    Sequence alignment is an essential tool in almost any computational biology research. It processes large database sequences and considered to be high consumers of computation time. Heuristic algorithms are used to get approximate but fast results. We introduce fast alignment algorithm, called Alignment By Scanning (ABS), to provide an approximate alignment of two DNA sequences. We compare our algorithm with the well-known alignment algorithms, the FASTA (which is heuristic) and the \\'Needleman-Wunsch\\' (which is optimal). The proposed algorithm achieves up to 76% enhancement in alignment score when it is compared with the FASTA Algorithm. The evaluations are conducted using different lengths of DNA sequences. © 2011 IEEE.

  6. AP calculus AB/BC

    CERN Document Server

    Schwartz, Stu

    2013-01-01

    All Access for the AP® Calculus AB & BC Exams Book + Web + Mobile Everything you need to prepare for the Advanced Placement® exam, in a study system built around you! There are many different ways to prepare for an Advanced Placement® exam. What's best for you depends on how much time you have to study and how comfortable you are with the subject matter. To score your highest, you need a system that can be customized to fit you: your schedule, your learning style, and your current level of knowledge. This book, and the free online tools that come with it, will help you personalize your AP® Cal

  7. CYP1B1 is polymorphic in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Matsushita, Akinori; Yamazaki, Hiroshi

    2011-09-01

    Cytochrome P450 (CYP) 1B1 is involved in the metabolic activation of various procarcinogens, and some CYP1B1 genetic variants alter CYP1B1-dependent procarcinogen metabolism. Cynomolgus and rhesus macaques are frequently used in toxicity tests due to their evolutionary closeness to humans. In this study, we attempted to identify CYP1B1 genetic variants in 13 cynomolgus and 4 rhesus macaques. A total of 17 genetic variants were identified, including 8 non-synonymous genetic variants, indicating that, similar to humans, CYP1B1 is polymorphic in macaques. These CYP1B1 genetic variants could be the basis for understanding potential inter-animal differences in macaque CYP1B1-dependent metabolism of promutagens.

  8. Screening of CYP1B1 and MYOC in Moroccan families with primary congenital glaucoma: Three novel mutations in CYP1B1

    OpenAIRE

    Hilal, Latifa; Boutayeb, Soraya; Serrou, Aziza; Refass-Buret, Loubna; Shisseh, Hafsa; Bencherifa, Fatiha; El Mzibri, Mohammed; Benazzouz, Bouchra; Berraho, Amina

    2010-01-01

    Purpose To investigate the contribution of cytochrome P4501B1 (CYP1B1) and myocillin (MYOC) mutations to primary congenital glaucoma (PCG) in Moroccan families. Methods This study included 90 unrelated families with PCG and 100 normal control individuals. Two previously reported CYP1B1 mutations (g.4339delG and p.G61E) were first screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The coding exons of CYP1B1 were sequenced in g.4339delG- and p.G61E-negati...

  9. CYP1B1 mRNA inducibility due to benzo(a)pyrene is modified by the CYP1B1 L432V gene polymorphism.

    Science.gov (United States)

    Helmig, Simone; Wenzel, Sibylle; Maxeiner, Hagen; Schneider, Joachim

    2014-07-01

    Benzo(a)pyrene (BaP), a primary component of tobacco smoke, is activated by cytochrome P450 1B1 (CYP1B1). Smokers homozygous for the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism have shown increased CYP1B1 expression, compared to smokers homozygous for the G-allele *3/*3. Since no difference has been shown in CYP1B1 expression between both genotypes in non-smokers, we assumed that the genetic impact is produced in combination with an exogenous induction (e.g. BaP). To confirm this theory and to quantify the effect, we induced human leucocytes with increasing BaP concentrations and determined CYP1B1 mRNA expression with real-time polymerase chain reaction (PCR). We incubated human leucocytes from 27 healthy donors with BaP concentrations ranging from 2.5 to 250 µM. We identified the CYP1B1 genotypes by melting curve analysis and assessed relative CYP1B1 mRNA expression using real-time PCR. Expression was related to β-2-microglobulin with the 2(-ΔΔCT) method. Inducibility of CYP1B1 mRNA by BaP was higher in leucocytes carrying the CYP1B1*1/*1 genotype than in leucocytes carrying the CYP1B1*3/*3 genotype (P = 0.012). We revealed significant differences, with BaP concentrations of 2.5 µM (P = 0.0094), 5 µM (P = 0.027), 10 µM (P = 0.0006), 25 µM (P = 0.0007) and 50 µM (P = 0.017). Homozygous carriers of the C-allele (*1/*1) at the CYP1B1 Leu432Val polymorphism show a higher response to environmental factors, such as carcinogenic BaP, than homozygous carriers of the G-allele *3/*3.

  10. Electronically asymmetric bis(porphyrin) sandwich complexes

    Energy Technology Data Exchange (ETDEWEB)

    Girolami, G.S.; Gorlin, P.A.; Suslick, K.S. [Univ. of Illinois, Urbana, IL (United States)

    1994-02-16

    Bis(porphyrin)metal(IV) complexes (M(porph){sub 2}) have been extensively studies in recent years due to their structural, chemical, and spectroscopic similarity to the {open_quotes}special pair{close_quotes} found in the reaction center of photosynthetic bacteria. Strong interactions arise in the bis(porphyrin) complexes due to the short inter-porphyrin separation (< 3 {angstrom}), which results in properties not seen in mono(porphyrin) analogs. For example, the bis(porphyrin) complexes are considerably easier to oxidize than analogous mono(porphyrin) species, and the M(porph){sub 2{sup n+}} cations (n = 1,2) exhibit near-IR absorptions not found in simple mono(porphyrin)cations. As part of the authors continuing effort to understand the factors that govern the electronic structures of bis(porphyrin) supermolecules, the authors now describe the synthesis of a series of zirconium sandwich complexes. Introduction of electron-withdrawing or -donating groups on the {beta}-pyrrole position considerably affects the electronic properties of these molecules without altering their steric parameters. Thus, peripheral substitution allows modification of the inter-porphyrin {pi} interactions while keeping the inter-porphyrin separation constant. Previous studies have changed the identity of the central metal, but the electronic structure and the interplanar distance could not be varied independently.

  11. Overexpression of SULT2B1b Promotes Angiogenesis in Human Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Wen Chen

    2016-03-01

    Full Text Available Background/Aims: Overexpression of cytosolic sulfotransferase 2B1b (SULT2B1b has been commonly found in colorectal and hepatocellular carcinoma, suggesting that SULT2B1b might act as a potential oncogenic protein. However, its clinical significance and biological role in gastric cancer progression remain largely unknown. Methods: Expressions of SULT2B1b in clinical gastric cancer (GC samples were examined using qRT-PCR and Western blot. Results: SULT2B1b was markedly overexpressed in human GC samples, and positively correlated with vessel density and associated with poor clinical features. We also demonstrated that overexpression of SULT2B1b resulted in increased tumor angiogenesis and tumor growth in mouse GC models. In addition, ablation of SULT2B1b in human GC cells lines BGC823 and MKN45 decreased the capability of the cells to recruit endothelial cells. Moreover, depletion of SULT2B1b in GC cells reduced VEGF-A expression by downregulating SP1 and AP2. Conclusion: Our results suggested that the SULT2B1b-mediated angiogenic pathway could serve as biomarkers for GC diagnosis and prognosis, and suppressing SULT2B1b-mediated angiogenic signaling might be a promising strategy for developing novel GC treatment.

  12. The Pafah1b complex interacts with the reelin receptor VLDLR.

    Directory of Open Access Journals (Sweden)

    Guangcheng Zhang

    Full Text Available Reelin is an extracellular protein that directs the organization of cortical structures of the brain through the activation of two receptors, the very low-density lipoprotein receptor (VLDLR and the apolipoprotein E receptor 2 (ApoER2, and the phosphorylation of Disabled-1 (Dab1. Lis1, the product of the Pafah1b1 gene, is a component of the brain platelet-activating factor acetylhydrolase 1b (Pafah1b complex, and binds to phosphorylated Dab1 in response to Reelin. Here we investigated the involvement of the whole Pafah1b complex in Reelin signaling and cortical layer formation and found that catalytic subunits of the Pafah1b complex, Pafah1b2 and Pafah1b3, specifically bind to the NPxYL sequence of VLDLR, but not to ApoER2. Compound Pafah1b1(+/-;Apoer2(-/- mutant mice exhibit a reeler-like phenotype in the forebrain consisting of the inversion of cortical layers and hippocampal disorganization, whereas double Pafah1b1(+/-;Vldlr(-/- mutants do not. These results suggest that a cross-talk between the Pafah1b complex and Reelin occurs downstream of the VLDLR receptor.

  13. [Preparation and identification of rabbit anti-AKR1B10 polyclonal antibody].

    Science.gov (United States)

    Hu, Jian; Wang, Qingmei; Huang, Li; Zeng, Yuanqing; Hu, Zheng; Luo, Dixian

    2016-11-01

    Objective To prepare rabbit anti-aldo-keto reductase family 1 member B10 (AKR1B10) polyclonal antibody and identify its specificity. Methods AKR1B10 cDNA was amplified by reverse transcription PCR (RT-PCR) and inserted into prokaryotic expression vector pET-15b to form recombinant plasmid pET-15b-AKR1B10. The recombinant plasmid pET-15b-AKR1B10 was transformed into E.coli DH5α. Isopropylthio-β-D-galactoside (IPTG) was used to induce the expression of the recombinant protein His-tagged AKR1B10 in E.coli DH5α. The expression products from different clones of E.coli DH5α were identified by SDS-PAGE. The positive bacteria were picked out and amplified. His-Tag-AKR1B10 protein was purified from the expression product of the positive clones by His-tagged purification column. The purified recombinant protein His-Tag-AKR1B10 was used to immunize New Zealand white rabbits. Antisera were acquired after two months. Anti-AKR1B10 polyclonal antibodies were purified by antigen purification column with AKR1B10 recombinant protein. Lastly, the purified polyclonal antibodies were identified by SDS-PAGE, ELISA, Western blotting. Results The recombinant plasmid pET-15b-AKR1B10 was constructed successfully, and the recombinant protein His-Tag-AKR1B10 with high purity was acquired. The purified polyclonal antibodies were able to specifically recognize AKR1B10 protein. Conclusion The rabbit anti-AKR1B10 polyclonal antibodies is prepared successfully with high specificity.

  14. Microwave Study of Recycled ABS Resins

    Institute of Scientific and Technical Information of China (English)

    A; M; Hasna

    2002-01-01

    This article provides a review of the research unde rt aken in order to determine the suitability of utilizing microwave technology in the production of Recycled ABS Acrylonitrile Butadiene Styrene resin for mouldin gs. The experimental investigation determined the suitability of the existing re cycled ABS material, the mould material used with respect to performance and lon gevity, potential commercial plant and equipment, end mould compression. Introduction Frequency Characterization of ABS The first ...

  15. abs497ashcoursesTutorial /uophelp

    OpenAIRE

    davids

    2015-01-01

    For more course tutorials visit www.uophelp.com       I.        ABS 497 Week 1 Assignment Community Change   II.        ABS 497 Week 1 DQ 1 Fabian's Story III.        ABS 497 Week 1 DQ 2 Doug's Story IV.        ABS 497 Week 2 DQ 1 Parenting Styles   V.      &nb...

  16. Herschel observations of B1-bS and B1-bN: two first hydrostatic core candidates in the Perseus star-forming cloud

    CERN Document Server

    Pezzuto, Stefano; Schisano, E; Strafella, F; Di Francesco, J; Sadavoy, S; André, P; Benedettini, M; Bernard, J P; di Giorgio, A M; Facchini, A; Hennemann, M; Hill, T; Könyves, V; Molinari, S; Motte, F; Nguyen-Luong, Q; Peretto, N; Pestalozzi, M; Polychroni, D; Rygl, K L J; Saraceno, P; Schneider, N; Spinoglio, L; Testi, L; Ward-Thompson, D; White, G J

    2012-01-01

    We report far-IR Herschel observations obtained between 70 $\\mu$m and 500 $\\mu$m of two star-forming dusty condensations, B1-bS and B1-bN, in the B1 region of the Perseus star-forming cloud. In the Western part of the Perseus cloud, B1-bS is the only source detected in all of the 6 PACS and SPIRE photometric bands without being visible in the Spitzer map at 24 $\\mu$m. B1-bN is clearly detected between 100 $\\mu$m and 250 $\\mu$m. We have fitted the spectral energy distributions of these sources to derive their physical properties, and find that a simple greybody model fails to reproduce the observed SEDs. At least a two-component model, consisting of a central source surrounded by a dusty envelope is required. The properties derived from the fit, however, suggest that the central source is not a Class 0 object. We then conclude that while B1-bS and B1-bN appear to be more evolved than a pre-stellar core, the best-fit models suggest that their central objects are younger than a Class 0 source. Hence, they may be...

  17. Src regulates membrane trafficking of the Kv3.1b channel.

    Science.gov (United States)

    Bae, Seong Han; Kim, Dong Hyun; Shin, Seok Kyo; Choi, Jin Sung; Park, Kang-Sik

    2014-01-03

    The Kv3.1 channel plays a crucial role in regulating the high-frequency firing properties of neurons. Here, we determined whether Src regulates the subcellular distributions of the Kv3.1b channel. Co-expression of active Src induced a dramatic redistribution of Kv3.1b to the endoplasmic reticulum. Furthermore, co-expression of the Kv3.1b channel with active Src induced a remarkable decrease in the pool of Kv3.1b at the cell surface. Moreover, the co-expression of active Src results in a significant decrease in the peak current densities of the Kv3.1b channel, and a substantial alteration in the voltage dependence of its steady-state inactivation. Taken together, these results indicate that Src kinase may play an important role in regulating membrane trafficking of Kv3.1b channels.

  18. Discovery of a novel competitive inhibitor of PTP1B by high-throughput screening

    Institute of Scientific and Technical Information of China (English)

    Lei SHI; Hai-ping YU; Yue-yang ZHOU; Jun-qin DU; Qiang SHEN; Jing-ya LI; Jia LI

    2008-01-01

    Aim: The aim of the present study was to discover novel protein tyrosine phos-phatase 1B (PTP1B) inhibitors. We expressed and purified the human PTP1B catalytic domain and set up a molecular level high-throughput screening (HTS) assay to screen a set of 48 000 pure compounds. Results: HTS was finished with an averaged Z' factor of 0.63, and LGH00081, a competitive inhibitor of PTP1B with novel structure and relatively good selectivity for receptor-type protein ty-rosine phosphatases, was identified. Conclusion: We established a molecular level assay which is useful for the screening of PTP1B inhibitors with therapeutic potential. The novel competitive PTP1B inhibitor LGH00081 offers a good start for structure modification and cellular functional activity study.

  19. Solvent-free Thia-Michael Addition Reactions Using 3-[Bis(alkylthio)methylene]pentane-2,4-diones as Efficient and Odorless Thiol Equivalents

    Institute of Scientific and Technical Information of China (English)

    LIN Chun; ZHAO Xiao-Liang; OUYANG Yan; YU Hai-Feng; DONG De-Wen

    2008-01-01

    3-[Bis(alkylthio)methylene]pentane-2,4-diones (1a and 1b) have been investigated as nonthiolic and odorless thiol equivalents for thia-Michael addition reactions under solvent-free conditions. Promoted by HCl (aq.), the cleavage of compounds 1 took place, and the in-situ generated thiols underwent facile conjugate addition to α,β-unsaturated carbonyl compounds 2 affording the corresponding β-keto sulfides 3 in high yields.

  20. Pierre Abélard

    OpenAIRE

    Adams, Jéremy du Quesnay; Asni, Raffaella; Bell, Nicolas; Biard, Joël; Bisson, Thomas N.; Colette, Marie-Noël; Fraioli, Deborah; Geldsetzer, Lutz; Hemion, Jean-Marc; Ilgner, Rainer M.; Iversen, Gunilla; Jolivet, Jean; Lejeune, François; Lobrichon, Guy; Luscombe, David

    2015-01-01

    Théologien, logicien, dialecticien, musicologue, Abélard reste un grand savant dont l’œuvre mérite d’être étudiée et enseignée. Neuf cents ans après sa mort, sa pensée, ses travaux, les polémiques savantes qu’il a nourries avec les grandes voix de son temps continuent de fasciner les chercheurs et les érudits. Le présent recueil marque sur plusieurs points une étape nouvelle dans la connaissance de cette haute et célèbre figure. Il ouvre sur des aspects historiographiques usuellement traités,...

  1. "AB了AB"与"AB了一AB"格式源流考察

    Institute of Scientific and Technical Information of China (English)

    贺卫国

    2008-01-01

    "AB了AB"格式与"AB了一AB"格式在中就出现了,其余少数明清白话小说中也可见到这种用法.在现当代的一些文学作品中,偶尔可以见到这两种格式.目前,"AB了AB"格式仍在使用,"AB了一AB"则基本上看不到了.

  2. ABS test equipment design%ABS 测试设备设计

    Institute of Scientific and Technical Information of China (English)

    王宇鹏

    2013-01-01

      This article simply introduces the structure and operating principle of ABS. and a new equipment for ABS signal testing is designed and put into use.%  简要介绍了 ABS 的组成及其工作原理,并结合自身情况,设计了测试 ABS 信号的设备,并投入使用。

  3. The structure of geminal imidazolium bis(trifluoromethylsulfonyl)amide ionic liquids: a theoretical study of the gas phase ionic complexes.

    Science.gov (United States)

    Bodo, E; Caminiti, R

    2010-12-02

    In this work we report molecular mechanics and ab initio calculations on the geminal di-imidazolium bis(trifluoromethylsulfonyl)amide ionic liquid in the gas phase. We report the likely energetically preferred geometries of the ionic complex and its main features in terms of charge distribution, electronic density, structure, and energetics. We find that the gas phase structure of the ionic complex is quite compact and that the alkyl chain connecting the two imidazolium charged rings is strongly bent in order to maximize their electrostatic interactions with the two anions.

  4. Ethanol and Mesolimbic Serotonin/Dopamine Interactions via 5HT-1B Receptors

    Science.gov (United States)

    2007-03-01

    Addiction, 101 (Suppl. 1): 23-30, 2006. 16. Kranzler HR, Hernandez -Avila CA, Gelenter J,: Polymorphism of the 5-HT1B receptor gene (HTR1B): strong within...Serotonin1B receptor stimulation enhances cocaine reinforcement, J. Neurosci., 18: 10078-10089, 1998. 25. Rojas -Corrales MO, Berrocoso E, Mico JA,: Role of...it has been reported that the effective receptor antagonist concentration of SB 216641 is similar to that of WAY 100635 ( Rojas -Corrales et al

  5. The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal

    DEFF Research Database (Denmark)

    Stewart, Morag H; Albert, Mareike; Sroczynska, Patrycja;

    2015-01-01

    Jarid1b/KDM5b is a histone demethylase that regulates self-renewal and differentiation in stem cells and cancer, however its function in hematopoiesis is unclear. Here, we find that Jarid1b is highly expressed in primitive hematopoietic compartments and is overexpressed in acute myeloid leukemias...... compromises hematopoietic stem cell (HSC) self-renewal capacity and suggest that Jarid1b is a positive regulator of HSC potential....

  6. Halogen-free bis(imidazolium)/bis(ammonium)-di[bis(salicylato)borate] ionic liquids as energy-efficient and environmentally friendly lubricant additives.

    Science.gov (United States)

    Gusain, Rashi; Gupta, Piyush; Saran, Sandeep; Khatri, Om P

    2014-09-10

    Bis(imidazolium)- and bis(ammonium)-di[bis(salicylato)borate] ionic liquids with variable alkyl chain and cyclic ring structures, were synthesized and then evaluated them as potential lubricant additives. The copper strip test results revealed noncorrosive properties of these ionic liquids. Introduction of halogen content in bis(imidazolium) ionic liquid by replacement of bis(salicylato)borate (BScB) anion with hexafluorophosphate (PF6(-)), severely corroded the copper strip. Thermogravimetric results showed that bis(imidazolium) ionic liquids exhibited higher thermal stability than bis(ammonium) ionic liquids owing to compact structure provided by imidazolium rings, higher intermolecular interactions, smaller free volume and low steric hindrance. The lubrication properties of these ionic liquids as additives to synthetic lubricant poly(ethylene) glycol (PEG 200) were evaluated for steel balls. Results showed that bis(ammonium)- and bis(imidazolium)-(BScB)2 ionic liquids as additives significantly reduced both friction coefficient and wear of PEG 200. The structure of cations, particularly the variation in substituted alkyl chain length monitored the degree of reduction in friction and wear. The excellent lubrication properties were attributed to the formation of adsorbed tribo-thin film and tribochemical product during the tribo-contact. Being halogen-, phosphorus-, and sulfur-free, these ionic liquids (a) protects contact surfaces from tribo-corrosive events, (b) reduces the friction and wear, and (c) keep environment green and clean.

  7. The mechanism of allosteric inhibition of protein tyrosine phosphatase 1B.

    Directory of Open Access Journals (Sweden)

    Shuai Li

    Full Text Available As the prototypical member of the PTP family, protein tyrosine phosphatase 1B (PTP1B is an attractive target for therapeutic interventions in type 2 diabetes. The extremely conserved catalytic site of PTP1B renders the design of selective PTP1B inhibitors intractable. Although discovered allosteric inhibitors containing a benzofuran sulfonamide scaffold offer fascinating opportunities to overcome selectivity issues, the allosteric inhibitory mechanism of PTP1B has remained elusive. Here, molecular dynamics (MD simulations, coupled with a dynamic weighted community analysis, were performed to unveil the potential allosteric signal propagation pathway from the allosteric site to the catalytic site in PTP1B. This result revealed that the allosteric inhibitor compound-3 induces a conformational rearrangement in helix α7, disrupting the triangular interaction among helix α7, helix α3, and loop11. Helix α7 then produces a force, pulling helix α3 outward, and promotes Ser190 to interact with Tyr176. As a result, the deviation of Tyr176 abrogates the hydrophobic interactions with Trp179 and leads to the downward movement of the WPD loop, which forms an H-bond between Asp181 and Glu115. The formation of this H-bond constrains the WPD loop to its open conformation and thus inactivates PTP1B. The discovery of this allosteric mechanism provides an overall view of the regulation of PTP1B, which is an important insight for the design of potent allosteric PTP1B inhibitors.

  8. Tobacco smoke induces CYP1B1 in the aerodigestive tract.

    Science.gov (United States)

    Port, Jeffrey L; Yamaguchi, Kentaro; Du, Baoheng; De Lorenzo, Mariana; Chang, Mindy; Heerdt, Paul M; Kopelovich, Levy; Marcus, Craig B; Altorki, Nasser K; Subbaramaiah, Kotha; Dannenberg, Andrew J

    2004-11-01

    Several members of the P450 family, including cytochrome P450 1B1 (CYP1B1), can convert tobacco smoke (TS) procarcinogens, including benzo[a]pyrene (B[a]P), to carcinogenic intermediates. In this study we investigated the effects of TS condensate and B[a]P on the expression of CYP1B1 in vitro and in vivo. CYP1B1 mRNA and protein were induced by both TS condensate and B[a]P in cell lines derived from the human aerodigestive tract. Treatment with TS condensate stimulated binding of the aryl hydrocarbon receptor (AhR) to an oligonucleotide containing a canonical xenobiotic response element (XRE) site and induced XRE-luciferase activity. These findings are consistent with prior evidence that polycyclic aromatic hydrocarbons, known ligands of the AhR, stimulate CYP1B1 transcription by an XRE-dependent mechanism. To determine whether these in vitro findings applied in vivo, both murine and human studies were carried out. Short-term exposure to TS induced CYP1B1 in the tongue, esophagus, lung and colon of experimental mice. In contrast, CYP1B1 was not induced by TS in the aorta of these mice. Levels of CYP1B1 mRNA were also elevated in the bronchial mucosa of human tobacco smokers versus never smokers (P CYP1B1 in TS-induced carcinogenesis in the aerodigestive tract.

  9. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes.

    Science.gov (United States)

    Schubert, Julian; Siekierska, Aleksandra; Langlois, Mélanie; May, Patrick; Huneau, Clément; Becker, Felicitas; Muhle, Hiltrud; Suls, Arvid; Lemke, Johannes R; de Kovel, Carolien G F; Thiele, Holger; Konrad, Kathryn; Kawalia, Amit; Toliat, Mohammad R; Sander, Thomas; Rüschendorf, Franz; Caliebe, Almuth; Nagel, Inga; Kohl, Bernard; Kecskés, Angela; Jacmin, Maxime; Hardies, Katia; Weckhuysen, Sarah; Riesch, Erik; Dorn, Thomas; Brilstra, Eva H; Baulac, Stephanie; Møller, Rikke S; Hjalgrim, Helle; Koeleman, Bobby P C; Jurkat-Rott, Karin; Lehman-Horn, Frank; Roach, Jared C; Glusman, Gustavo; Hood, Leroy; Galas, David J; Martin, Benoit; de Witte, Peter A M; Biskup, Saskia; De Jonghe, Peter; Helbig, Ingo; Balling, Rudi; Nürnberg, Peter; Crawford, Alexander D; Esguerra, Camila V; Weber, Yvonne G; Lerche, Holger

    2014-12-01

    Febrile seizures affect 2-4% of all children and have a strong genetic component. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.

  10. Yersinia pestis Requires Host Rab1b for Survival in Macrophages.

    Directory of Open Access Journals (Sweden)

    Michael G Connor

    2015-10-01

    Full Text Available Yersinia pestis is a facultative intracellular pathogen that causes the disease known as plague. During infection of macrophages Y. pestis actively evades the normal phagosomal maturation pathway to establish a replicative niche within the cell. However, the mechanisms used by Y. pestis to subvert killing by the macrophage are unknown. Host Rab GTPases are central mediators of vesicular trafficking and are commonly targeted by bacterial pathogens to alter phagosome maturation and killing by macrophages. Here we demonstrate for the first time that host Rab1b is required for Y. pestis to effectively evade killing by macrophages. We also show that Rab1b is specifically recruited to the Yersinia containing vacuole (YCV and that Y. pestis is unable to subvert YCV acidification when Rab1b expression is knocked down in macrophages. Furthermore, Rab1b knockdown also altered the frequency of association between the YCV with the lysosomal marker Lamp1, suggesting that Rab1b recruitment to the YCV directly inhibits phagosome maturation. Finally, we show that Rab1b knockdown also impacts the pH of the Legionella pneumophila containing vacuole, another pathogen that recruits Rab1b to its vacuole. Together these data identify a novel role for Rab1b in the subversion of phagosome maturation by intracellular pathogens and suggest that recruitment of Rab1b to the pathogen containing vacuole may be a conserved mechanism to control vacuole pH.

  11. Kv3.1b is a novel component of CNS nodes.

    Science.gov (United States)

    Devaux, Jérôme; Alcaraz, Gisèle; Grinspan, Judith; Bennett, Vann; Joho, Rolf; Crest, Marcel; Scherer, Steven S

    2003-06-01

    We herein demonstrate that Kv3.1b subunits are present at nodes of Ranvier in the CNS of both rats and mice. Kv3.1b colocalizes with voltage-gated Na+ channels in a subset of nodes in the spinal cord, particularly those of large myelinated axons. Kv3.1b is abundantly expressed in the gray matter of the spinal cord, but does not colocalize with Na+ channels in initial segments. In the PNS, few nodes are Kv3.1b-positive. During the development of the CNS, Kv3.1b clustering at nodes occurs later than that of Na+ channels, but precedes the juxtaparanodal clustering of Kv1.2. Moreover, in myelin-deficient rats, which have severe CNS dysmyelination, node-like clusters of Kv3.1b and Na+ channels are observed even in regions devoid of oligodendrocytes. Ankyrin G coimmunoprecipitates Kv3.1b in vivo, indicating that these two proteins may interact in the CNS at nodes. 4-Aminopyridine, a K+ channel blocker, broadened the compound action potential recorded from adult rat optic nerve and spinal cord, but not from the sciatic nerve. These effects were also observed in Kv3.1-deficient mice. In conclusion, Kv3.1b is the first K+ channel subunit to be identified in CNS nodes; but Kv3.1b does not account for the effects of 4-aminopyridine on central myelinated tracts.

  12. SUMOylation of the ING1b tumor suppressor regulates gene transcription

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Guérillon, Claire; Kim, Tae-Sun;

    2014-01-01

    The INhibitor of Growth (ING) proteins are encoded as multiple isoforms in five ING genes (ING1 -5) and act as type II tumor suppressors. They are growth inhibitory when overexpressed and are frequently mislocalized or downregulated in several forms of cancer. ING1 and ING2 are stoichiometric mem......1b E195A), we further demonstrate that ING1b SUMOylation regulates the binding of ING1b to the ISG15 and DGCR8 promoters, consequently regulating ISG15 and DGCR8 transcription. These results suggest a role for ING1b SUMOylation in the regulation of gene transcription....

  13. Plectin isoform 1b mediates mitochondrion-intermediate filament network linkage and controls organelle shape.

    Science.gov (United States)

    Winter, Lilli; Abrahamsberg, Christina; Wiche, Gerhard

    2008-06-16

    Plectin is a versatile intermediate filament (IF)-bound cytolinker protein with a variety of differentially spliced isoforms accounting for its multiple functions. One particular isoform, plectin 1b (P1b), remains associated with mitochondria after biochemical fractionation of fibroblasts and cells expressing exogenous P1b. Here, we determined that P1b is inserted into the outer mitochondrial membrane with the exon 1b-encoded N-terminal sequence serving as a mitochondrial targeting and anchoring signal. To study P1b-related mitochondrial functions, we generated mice that selectively lack this isoform but express all others. In primary fibroblasts and myoblasts derived from these mice, we observe a substantial elongation of mitochondrial networks, whereas other mitochondrial properties remain largely unaffected. Normal morphology of mitochondria could be restored by isoform-specific overexpression of P1b in P1b-deficient as well as plectin-null cells. We propose a model where P1b both forms a mitochondrial signaling platform and affects organelle shape and network formation by tethering mitochondria to IFs.

  14. Ultrasound Biomicroscopy Comparison of Ab Interno and Ab Externo Intraocular Lens Scleral Fixation.

    Science.gov (United States)

    Horiguchi, Lie; Garcia, Patricia Novita; Malavazzi, Gustavo Ricci; Allemann, Norma; Gomes, Rachel L R

    2016-01-01

    Purpose. To compare ab interno and ab externo scleral fixation of posterior chamber intraocular lenses (PCIOL) using ultrasound biomicroscopy (UBM). Methods. Randomized patients underwent ab externo or ab interno scleral fixation of a PCIOL. Ultrasound biomicroscopy was performed 3 to 6 months postoperatively, to determine PCIOL centration, IOL distance to the iris at 12, 3, 6, and 9 hours, and haptics placement in relation to the ciliary sulcus. Results. Fifteen patients were enrolled in the study. The ab externo technique was used in 7 eyes (46.6%) and the ab interno in 8 eyes (53.3%). In the ab externo technique, 14 haptics were located: 4 (28.57%) in the ciliary sulcus; 2 (14.28%) anterior to the sulcus; and 8 (57.14%) posterior to the sulcus, 6 in the ciliary body and 2 posterior to the ciliary body. In the ab interno group, 4 haptics (25.0%) were in the ciliary sulcus, 2 (12.50%) anterior to the sulcus, and 10 (75.0%) posterior to the sulcus, 4 in the ciliary body and 6 posterior to the ciliary body. Conclusions. Ab externo and ab interno scleral fixation techniques presented similar results in haptic placement. Ab externo technique presented higher vertical tilt when compared to the ab interno.

  15. Ultrasound Biomicroscopy Comparison of Ab Interno and Ab Externo Intraocular Lens Scleral Fixation

    Directory of Open Access Journals (Sweden)

    Lie Horiguchi

    2016-01-01

    Full Text Available Purpose. To compare ab interno and ab externo scleral fixation of posterior chamber intraocular lenses (PCIOL using ultrasound biomicroscopy (UBM. Methods. Randomized patients underwent ab externo or ab interno scleral fixation of a PCIOL. Ultrasound biomicroscopy was performed 3 to 6 months postoperatively, to determine PCIOL centration, IOL distance to the iris at 12, 3, 6, and 9 hours, and haptics placement in relation to the ciliary sulcus. Results. Fifteen patients were enrolled in the study. The ab externo technique was used in 7 eyes (46.6% and the ab interno in 8 eyes (53.3%. In the ab externo technique, 14 haptics were located: 4 (28.57% in the ciliary sulcus; 2 (14.28% anterior to the sulcus; and 8 (57.14% posterior to the sulcus, 6 in the ciliary body and 2 posterior to the ciliary body. In the ab interno group, 4 haptics (25.0% were in the ciliary sulcus, 2 (12.50% anterior to the sulcus, and 10 (75.0% posterior to the sulcus, 4 in the ciliary body and 6 posterior to the ciliary body. Conclusions. Ab externo and ab interno scleral fixation techniques presented similar results in haptic placement. Ab externo technique presented higher vertical tilt when compared to the ab interno.

  16. Ultrasound Biomicroscopy Comparison of Ab Interno and Ab Externo Intraocular Lens Scleral Fixation

    Science.gov (United States)

    Horiguchi, Lie; Garcia, Patricia Novita; Malavazzi, Gustavo Ricci; Allemann, Norma

    2016-01-01

    Purpose. To compare ab interno and ab externo scleral fixation of posterior chamber intraocular lenses (PCIOL) using ultrasound biomicroscopy (UBM). Methods. Randomized patients underwent ab externo or ab interno scleral fixation of a PCIOL. Ultrasound biomicroscopy was performed 3 to 6 months postoperatively, to determine PCIOL centration, IOL distance to the iris at 12, 3, 6, and 9 hours, and haptics placement in relation to the ciliary sulcus. Results. Fifteen patients were enrolled in the study. The ab externo technique was used in 7 eyes (46.6%) and the ab interno in 8 eyes (53.3%). In the ab externo technique, 14 haptics were located: 4 (28.57%) in the ciliary sulcus; 2 (14.28%) anterior to the sulcus; and 8 (57.14%) posterior to the sulcus, 6 in the ciliary body and 2 posterior to the ciliary body. In the ab interno group, 4 haptics (25.0%) were in the ciliary sulcus, 2 (12.50%) anterior to the sulcus, and 10 (75.0%) posterior to the sulcus, 4 in the ciliary body and 6 posterior to the ciliary body. Conclusions. Ab externo and ab interno scleral fixation techniques presented similar results in haptic placement. Ab externo technique presented higher vertical tilt when compared to the ab interno. PMID:27293878

  17. 78 FR 5210 - Open Government Initiative: Implementation of the iCERT Labor Certification Registry for the H-1B...

    Science.gov (United States)

    2013-01-24

    ... Certification Registry for the H-1B, H-1B1, E-3, H-2A, H-2B and Permanent Labor Certification Employment-Based... to the general public appropriately redacted copies of H-1B, H-1B1, E-3, H-2A, H-2B and permanent... a labor certification or, in the case of an H-1B, H-1B1, or E-3 visa, a labor condition...

  18. LMX1B is part of a transcriptional complex with PSPC1 and PSF.

    Directory of Open Access Journals (Sweden)

    Elisa J Hoekstra

    Full Text Available The LIM homeodomain transcription factor Lmx1b is essential for the development of the isthmic organizer and mesodiencephalic dopaminergic neurons. The uncoupling of Pitx3 and Th expression, in the Lmx1b null mutant, suggests that Lmx1b may act as a positional activator of the mdDA domain, eventually leading to properly differentiating mdDA neurons. In this study, we aimed to elucidate how Lmx1b functions mechanistically in this developmental process, by searching for molecular interactors of Lmx1b at the protein level. Initially, affinity-purification of LMX1B-HIS overexpressed protein in MN9D dopaminergic cells followed by mass-spectrometry analysis, resulted in the identification of PSPC1 protein as a possible binding partner of LMX1B. Subsequent immunoprecipitation experiments revealed an interaction between LMX1B and PSPC1 in a larger protein complex also containing PSF. This complex was observed in vitro and in vivo, and we hypothesize that, via PSF and PSPC1, LMX1B may be part of the previously identified Nurr1 transcriptional complex wherein interaction with the co-repressor PSF and the transcription factor Pitx3 is needed to drive expression of Nurr1 target genes in specifying the dopaminergic phenotype. Furthermore, we identified GRLF1, DHX9, MYO1C, HSP70 and TMPO as potential LMX1B interactors. DHX9 and GRLF1 are highly expressed in the developing mdDA neuronal field, and GRLF1 and MYO1C have both been linked to neurite outgrowth. The identification of these proteins suggests that Lmx1b may act directly in the transcriptional activation of Nurr1 target genes and be involved in other processes like neurite outgrowth as well.

  19. Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors.

    Science.gov (United States)

    De Vas, Matias G; Kopp, Janel L; Heliot, Claire; Sander, Maike; Cereghini, Silvia; Haumaitre, Cécile

    2015-03-01

    Heterozygous mutations in the human HNF1B gene are associated with maturity-onset diabetes of the young type 5 (MODY5) and pancreas hypoplasia. In mouse, Hnf1b heterozygous mutants do not exhibit any phenotype, whereas the homozygous deletion in the entire epiblast leads to pancreas agenesis associated with abnormal gut regionalization. Here, we examine the specific role of Hnf1b during pancreas development, using constitutive and inducible conditional inactivation approaches at key developmental stages. Hnf1b early deletion leads to a reduced pool of pancreatic multipotent progenitor cells (MPCs) due to decreased proliferation and increased apoptosis. Lack of Hnf1b either during the first or the secondary transitions is associated with cystic ducts. Ductal cells exhibit aberrant polarity and decreased expression of several cystic disease genes, some of which we identified as novel Hnf1b targets. Notably, we show that Glis3, a transcription factor involved in duct morphogenesis and endocrine cell development, is downstream Hnf1b. In addition, a loss and abnormal differentiation of acinar cells are observed. Strikingly, inactivation of Hnf1b at different time points results in the absence of Ngn3(+) endocrine precursors throughout embryogenesis. We further show that Hnf1b occupies novel Ngn3 putative regulatory sequences in vivo. Thus, Hnf1b plays a crucial role in the regulatory networks that control pancreatic MPC expansion, acinar cell identity, duct morphogenesis and generation of endocrine precursors. Our results uncover an unappreciated requirement of Hnf1b in endocrine cell specification and suggest a mechanistic explanation of diabetes onset in individuals with MODY5.

  20. Characteristics of stably expressed human dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor

    DEFF Research Database (Denmark)

    Pedersen, U B; Norby, B; Jensen, Anders A.

    1994-01-01

    Human dopamine D1a and D1b receptors were stably expressed in Baby Hamster Kidney (BHK) or Chinese Hamster Ovary (CHO) cells. [3H]SCH23390 saturation experiments indicated the presence of only a single binding site in the D1a expressing cell line with a Kd of 0.5 nM. In D1b expressing cell lines...... for these receptors. Besides SCH 23390, only NNC 112, fluphenazine and bulbocapnine were able to discriminate between the two states of the D1b receptor. In case of the D1a receptor, the Ki values obtained in binding experiments were very similar to Ki values obtained from inhibition of dopamine stimulated adenylyl...... cyclase. In the D1b expressing cell line, the Ki values obtained from inhibition of the dopamine stimulated adenylyl cyclase indicated a significantly better correlation with the state of the D1b receptor showing high affinity for antagonists. In agreement with observations from binding experiments...

  1. Synthesis, Characterization and Properties of Bis{oxo-bis[heteroaromatic carboxylatodibenzyltin(Ⅳ)]} and Crystal Structure of Bis{oxo-bis[2-furylcarboxylatodibenzyltin(Ⅳ)]}

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A series of bis{oxo-bis[heteroaromatic carboxylatodibenzyltin(Ⅳ)]} complexes {[(PhCH2)2Sn*(O2CR)]2O}2[where R=2-furyl, 2-(2-furyl)vinyl, 2-(5-tert-butyl)furyl, 2-thiophenyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-indolyl, 3-indolylmethyl, 3-indolylpropyl] was synthesized by the reactions of heteroaromatic carboxylic acids with dibenzyltin(Ⅳ) oxide. All the complexes were characterized by elemental analysis, IR, and NMR spectra. The complexes were tested against two human tumour cell lines: MCF-7 and WiDr. The results show that they have higher activities in vitro. The crystal structure of bis{oxo-bis[2-furylcarboxylatodibenzyltin(Ⅳ)]}(1) was determined by X-ray diffraction. The crystal belongs to monoclinic space group P21/n, a=1.6641(2) nm, b=1.25073(18) nm, c=1.7193(3) nm, β=101.951(2)°, Z=2, R1=0.0446, wR2=0.1100. Complex 1 is of a centrosymmetric dimer structure with a four-membered central endo-cyclic Sn2O2 unit in which the bridged oxygen atoms are tri-coordinated. Each bridged oxygen atom also connects with an exo-cyclic tin atom. The tin atoms are six-coordinated and have a coordination geometry of a distorted octahedron. The exo-cyclic tin atoms are five-coordinated and have a coordination geometry of a monocapped trigonal bipyramid with a very similarly distorted mode. Four carboxylate ligands are divided into two types. The two of the four carboxylate ligands are bidentate and bridged to each pair of exo- and endo-cyclic tin atoms by using both the oxygen atoms. The other two are monodentate and bridged to each pair of exo- and endo-cyclic tin atoms but each utilizes one O atom only.

  2. [N,N-Bis(diphenylphosphinoisopropylamine]dibromidonickel(II

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available The title compound, [NiBr2(C27H27NP2], was synthesized by the reaction of NiBr2(dme (dme is 1,2-dimethoxyethane with N,N-bis(diphenylphosphinoisopropylamine in methanol/tetrahydrofuran. The nickel(II center is coordinated by two P atoms of the chelating PNP ligand, Ph2PN(iPrPPh2, and two bromide ions in a distorted square-planar geometry.

  3. Data of evolutionary structure change: 1AIBB-2AY1B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AIBB-2AY1B 1AIB 2AY1 B B MFENITAAPADPILGLADLFRADERPGKINLGIGVYKDE...HHH HHHHHHHH EEEE EEEEEGG HHHHHHHHHHHHH 0 1AIB... B 1AIBB DFSFI--...e>ALA CA 413 THR CA 475 LEU CA 494 1AIB... B 1AIBB GSALINDKRARTA <

  4. Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor

    Institute of Scientific and Technical Information of China (English)

    Gui-xia LIU; Jin-zhi TAN; Chun-ying NIU; Jian-hua SHEN; Xiao-min LUO; Xu SHEN; Kai-xian CHEN; Hua-liang JIANG

    2006-01-01

    Aim: To investigate the dynamic properties of protein-tyrosine phosphatase (PTP)1B and reveal the structural factors responsible for the high inhibitory potency and selectivity of the inhibitor SNA for PTP1B. Methods: We performed molecular dynamics (MD) simulations using a long time-scale for both PTP1B and PTP1B complexed with the inhibitor SNA, the most potent and selective PTP1B inhibitor reported to date. The trajectories were analyzed by using principal component analysis. Results: Trajectory analyses showed that upon binding the ligand, the flexibility of the entire PTP1B molecule decreases. The most notable change is the movement of the WPD-loop. Our simulation results also indicated that electrostatic interactions contribute more to PTP1B-SNA complex conformation than the van der Waals interactions, and that Lys41, Arg47, and Asp48 play important roles in determining the conformation of the inhibitor SNA and in the potency and selectivity of the inhibitor. Of these, Arg47 contributed most. These results were in agreement with previous experimental results. Conclusion: The information presented here suggests that potent and selective PTP1B inhibitors can be designed by targeting the surface residues, for example the region containing Lys41,Arg47, and Asp48, instead of the second phosphate binding site (besides the active phosphate binding site).

  5. Tumor-specific expression of cytochrome P450 CYP1B1.

    Science.gov (United States)

    Murray, G I; Taylor, M C; McFadyen, M C; McKay, J A; Greenlee, W F; Burke, M D; Melvin, W T

    1997-07-15

    Cytochrome P450 CYP1B1 is a recently cloned dioxin-inducible form of the cytochrome P450 family of xenobiotic metabolizing enzymes. An antibody raised against a peptide specific for CYP1B1 was found to recognize CYP1B1 expressed in human lymphoblastoid cells but not to recognize other forms of cytochrome P450, particularly CYP1A1 and CYP1A2. Using this antibody, the cellular distribution and localization of CYP1B1 were investigated by immunohistochemistry in a range of malignant tumors and corresponding normal tissues. CYP1B1 was found to be expressed at a high frequency in a wide range of human cancers of different histogenetic types, including cancers of the breast, colon, lung, esophagus, skin, lymph node, brain, and testis. There was no detectable immunostaining for CYP1B1 in normal tissues. These results provide the basis for the development of novel methods of cancer diagnosis based on the identification of CYP1B1 in tumor cells and the development of anticancer drugs that are selectively activated in tumors by CYP1B1.

  6. The Phosphate Exporter xpr1b Is Required for Differentiation of Tissue-Resident Macrophages

    Directory of Open Access Journals (Sweden)

    Ana M. Meireles

    2014-09-01

    Full Text Available Phosphate concentration is tightly regulated at the cellular and organismal levels. The first metazoan phosphate exporter, XPR1, was recently identified, but its in vivo function remains unknown. In a genetic screen, we identified a mutation in a zebrafish ortholog of human XPR1, xpr1b. xpr1b mutants lack microglia, the specialized macrophages that reside in the brain, and also displayed an osteopetrotic phenotype characteristic of defects in osteoclast function. Transgenic expression studies indicated that xpr1b acts autonomously in developing macrophages. xpr1b mutants display no gross developmental defects that may arise from phosphate imbalance. We constructed a targeted mutation of xpr1a, a duplicate of xpr1b in the zebrafish genome, to determine whether Xpr1a and Xpr1b have redundant functions. Single mutants for xpr1a were viable, and double mutants for xpr1b;xpr1a were similar to xpr1b single mutants. Our genetic analysis reveals a specific role for the phosphate exporter Xpr1 in the differentiation of tissue macrophages.

  7. Myelin protein zero gene mutated in Charcot-Marie-Tooth type 1B patients

    Energy Technology Data Exchange (ETDEWEB)

    Su, Ying; Li, Lanying; Lepercq, J.; Lebo, R.V. (Univ. of California, San Francisco, CA (United States)); Brooks, D.G.; Ravetch, J.V. (Sloan-Kettering Institute, New York, NY (United States)); Trofatter, J.A. (Massachusetts General Hospital, Boston, MA (United States))

    1993-11-15

    The autosomal dominant of Charcot-Marie-Tooth disease (CMT), whose gene is type 1B (CMT1B), has slow nerve conduction with demyelinated Schwann cells. In this study the abundant peripheral myelin protein zero (MPZ) gene, MPZ, was mapped 130 kb centromeric to the Fc receptor immunoglobulin gene cluster in band 1q22, and a major MPZ point mutation was found to cosegregate with CMT1B in one large CMT1B family. The MPZ point mutation in 18 of 18 related CMT1B pedigree 1 patients converts a positively charged lysine in codon 96 to a negatively charged glutamate. The same MPZ locus cosegregates with the CMT1B disease gene in a second CMT1B family [total multipoint logarithm of odds (lod) = 11.4 at [theta] = 0.00] with a splice junction mutation. Both mutations occur in MPZ protein regions otherwise conserved identically in human, rat, and cow since these species diverged 100 million years ago. MPZ protein, expressed exclusively in myelinated peripheral nerve Schwann cells, constitutes >50% of myelin protein. These mutations are anticipated to disrupt homophilic MPZ binding and result in CMT1B peripheral nerve demyelination.

  8. PTP1B inhibition suggests a therapeutic strategy for Rett syndrome.

    Science.gov (United States)

    Krishnan, Navasona; Krishnan, Keerthi; Connors, Christopher R; Choy, Meng S; Page, Rebecca; Peti, Wolfgang; Van Aelst, Linda; Shea, Stephen D; Tonks, Nicholas K

    2015-08-01

    The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.

  9. Data of evolutionary structure change: 1B1GA-1CLMA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1GA-1CLMA 1B1G 1CLM A A KSPEELKGIFEKYAAK-EGDPNQLSKEELKLLLQTEFPS...-- LTEEQIAEFKEAFALFDKDGDGTITTKELGTVMRSL-----GQNPTEAELQDMINEVDADGNGTIDFPEFLSLMARKMKEQDSEEELIEAFK...SN CA 464 1CLM A 1CLMA...dbChain> 1CLMA LQDMINEVDADGN HHHHHH 2 1CLM A 1CLMA

  10. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    Science.gov (United States)

    Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

    2016-01-01

    RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

  11. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    Directory of Open Access Journals (Sweden)

    Márcia Faria

    2016-01-01

    Full Text Available RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs and 33 follicular thyroid adenomas (FTAs. RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01 and poorer clinical outcome (P = 0.01 suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions.

  12. Down-regulation of OATP1B proteins correlates with hyperbilirubinemia in advanced cholestasis

    NARCIS (Netherlands)

    Sticova, E.; Lodererova, A.; Steeg, E. van de; Frankova, S.; Kollar, M.; Lanska, V.; Kotalova, R.; Dedic, T.; Schinkel, A.H.; Jirsa, M.

    2015-01-01

    Aim: Organic anion-transporting polypeptides OATP1B1 and OATP1B3 are sinusoidal membrane transporters mediating liver uptake of a wide range of substrates including conjugated and unconjugated bilirubin, xenobiotics and drugs. Absence of OATP1Bs in the liver causes Rotor syndrome. Our aim was to cor

  13. Data of evolutionary structure change: 1DTGA-1B1XA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DTGA-1B1XA 1DTG 1B1X A A ---KTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVAC...VVRKSDADLTWNSLSGKKSCHTGVGRTAAWNIPMGLLFNQTGSCKFDKFFSQSCAPGADPQSSLCALCVGNNENENKCMPNSEERYYGYTGAFRCLAEKAGDVAFVKD...ndex>0 1DTG A 1DTGA A 1DTGA CQLCP-----GCGCS 2 1DTG A 1DTGA

  14. Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel

    NARCIS (Netherlands)

    A.J.M. de Graan (Anne-Joy); C.S. Lancaster (Cynthia); A. Obaidat (Amanda); B. Hagenbuch (Bruno); L. Elens (Laure); L.E. Friberg (Lena); P. de Bruijn (Peter); S. Hu (Shuiying); A.A. Gibson; G.H. Bruun (G.); T.J. Corydon (T.); T.S. Mikkelsen; A.L. Walker (Aisha); G. Du (Guoqing); W.J. Loos (Walter); R.H.N. van Schaik (Ron); S.D. Baker (Sharyn); A.H.J. Mathijssen (Ron); A. Sparreboom (Alex)

    2012-01-01

    textabstractPurpose: Docetaxel is extensively metabolized by CYP3A4 in the liver but mechanisms by which the drug is taken up into hepatocytes remain poorly understood. We hypothesized that (i) liver uptake of docetaxel is mediated by the polymorphic solute carriers OATP1B1 and OATP1B3 and (ii) inhe

  15. Data of evolutionary structure change: 1B38A-1WBSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B38A-1WBSA 1B38 1WBS A A -----------------MENFQKVEKIGEGTYGVVYKAR... ALA CA 254 ILE CA 274 1WBS A 1WBSA VKKLSRPFQSIIHA PRO CA 313 ASN CA 408 ILE CA 432 1WBS... A 1WBSA RELRLLKHMKHENV

  16. Data of evolutionary structure change: 1B99C-2AZ1D [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available GSDS--VESAN >E --HHHHH> ATOM 316...>D 2AZ1D HGSDHEDEGANE >E HHH...pdbID>1B99 C 1B99C EELLT-EVKPN ...> - > ATOM 3319 CA GLU C 141 17.330 5.755...DChain>2AZ1D DELVDWDRDAS re>GG EEGGHcture

  17. Data of evolutionary structure change: 1B9OA-1IOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B9OA-1IOTA 1B9O 1IOT A A KQFTKCELSQLLKDI--DGYGGIALPELICTMFHTSGYD...dbChain>A 1IOTA ALKRHGLDNYRG 5.116000175476074 15.197999954223633 tion> 0.9950000047683716 -0.796999990940094 tion> 2.0168049335479736 4.099109172821045 1IOT A 1IOTA <

  18. Data of evolutionary structure change: 1B4WD-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B4WD-2NOTA 1B4W 2NOT D A HLLQFRKMIKKMTG--KEPVVSYAFYGCYCGSGGRGKPK...line> 2NOT A 2NOTA...z>13.574999809265137 tion> -0.8450000286102295 -0....0000074505806 -0.44600000977516174 -0.09099999815225601 -0.8899999856948853 1 2NOT A 2NOTA

  19. Data of evolutionary structure change: 1B4WC-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B4WC-2NOTA 1B4W 2NOT C A HLLQFRKMIKKMTG--KEPVVSYAFYGCYCGSGGRGKPK...03 2NOT A 2NOTA...y> -17.684999465942383 tion> -0.7129999995231628 -0.03400000184774399 -0.04600000008940697 0.9980000257492065 ...el> 1 2NOT A 2NOTA

  20. Data of evolutionary structure change: 1B4WB-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B4WB-2NOTA 1B4W 2NOT B A HLLQFRKMIKKMTG--KEPVVSYAFYGCYCGSGGRGKPK... 2NOT A 2NOTA... 28.97100067138672 tion> 0.8460000157356262 0.4...550000190734863 0.531000018119812 -0.7149999737739563 -0.45399999618530273 ti...el> 1 2NOT A 2NOTA

  1. Data of evolutionary structure change: 1B4WA-2NOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B4WA-2NOTA 1B4W 2NOT A A HLLQFRKMIKKMTG--KEPVVSYAFYGCYCGSGGRGKPK... 2NOT A 2NOTA....69599914550781 tion> 0.7179999947547913 0.4429999...042915344 -0.19200000166893005 0.8669999837875366 0.46000000834465027 tion> 1 2NOT A 2NOTA

  2. New cis-regulatory elements in the Rht-D1b locus region of wheat

    Science.gov (United States)

    Fifteen gene-containing BACs with accumulated length of 1.82-Mb from the Rht-D1b locus region weresequenced and compared in detail with the orthologous regions of rice, sorghum, and maize. Our results show that Rht-D1b represents a conserved genomic region as implied by high gene sequence identity...

  3. Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics

    NARCIS (Netherlands)

    Groves, M R; Yao, Z J; Roller, P P; Burke, T R; Barford, D

    1998-01-01

    Protein tyrosine phosphatases regulate diverse cellular processes and represent important targets for therapeutic intervention in a number of diseases. The crystal structures of protein tyrosine phosphatase 1B (PTP1B) in complex with small molecule inhibitors based upon two classes of phosphotyrosin

  4. Data of evolutionary structure change: 1B7QA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B7QA-2G4NF 1B7Q 2G4N A F KVFERCELARTLKRLGMDGYRGISLALWMCLAKWESGYN... HHHH - GGGG -- EVID>EVID> 0 2G4N F 2G4NF VQNND...tation> 1.5742559432983398 3.2563140392303467 EVI...D> 1 2G4N F 2G4NF

  5. Data of evolutionary structure change: 1B5XA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5XA-2G4NF 1B5X 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYN...G HHHH -GGGG -- EVID>EVID> 0 2G4N F 2G4NF ELKDL...242798 2.054610013961792 4.014041900634766 ...EVID> 1 2G4N F 2G4NF

  6. Data of evolutionary structure change: 1B7OA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B7OA-2G4NF 1B7O 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESQYN... HHHH - GGGG -- EVID>EVID> 0 2G4N F 2G4NF IVQNN...on> 0.7017530202865601 1.3242100477218628 EVID> 1 2G4N F 2G4NF <

  7. Data of evolutionary structure change: 1B06A-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B06A-1UNFX 1B06 1UNF A X VIQLKRYEFPQLPYKVDALEPYISKDIIDVHYNGHHKGY...EEEEGGG EEEEEEE EEE EEE HHHH HHHHHHHHHH EEHHHHHHHHHHHHHH EVID> ...n> 1UNF X 1UNFX AVNP...127516031265259 5.276762008666992 EVID>...99 TRP CA 383 ASP CA 305 ASP CA 355 1UNF

  8. Data of evolutionary structure change: 1B5WA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5WA-2G4NF 1B5W 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYN...G HHHH -GGGG -- EVID>EVID> 0 2G4N F 2G4NF ELKDL...18 2.079693078994751 4.073005199432373 EVID>...EVID> 1 2G4N F 2G4NF

  9. Data of evolutionary structure change: 1B7NA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B7NA-2G4NF 1B7N 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWLSGYN... HHHH - GGGG -- EVID>EVID> 0 2G4N F 2G4NF IVQNN...n> 0.6914700269699097 1.3510249853134155 EVID> 1 2G4N F 2G4NF

  10. Data of evolutionary structure change: 1B06D-1UNFX [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available EVID>EVID> 2 1UNF X 1UNF...1B06D-1UNFX 1B06 1UNF D X VIQLKRYEFPQLPYKVDALEPYISKDIIDVHYNGHHKGY...HHHHHHHHHHHHH EEEEEEEEEEGGG EEEEEEE EEE EEE HHHH HHHHHHHHHH EEHHHHHHHHHHHHHH ... 1UNF X 1UNFX 3.1296169757843018 5.294285774230957

  11. A key role for PTP1B in dendritic cell maturation, migration, and T cell activation.

    Science.gov (United States)

    Martin-Granados, Cristina; Prescott, Alan R; Le Sommer, Samantha; Klaska, Izabela P; Yu, Tian; Muckersie, Elizabeth; Giuraniuc, Claudiu V; Grant, Louise; Delibegovic, Mirela; Forrester, John V

    2015-12-01

    Dendritic cells (DC) are the major antigen-presenting cells bridging innate and adaptive immunity, a function they perform by converting quiescent DC to active, mature DC with the capacity to activate naïve T cells. They do this by migrating from the tissues to the T cell area of the secondary lymphoid tissues. Here, we demonstrate that myeloid cell-specific genetic deletion of PTP1B (LysM PTP1B) leads to defects in lipopolysaccharide-driven bone marrow-derived DC (BMDC) activation associated with increased levels of phosphorylated Stat3. We show that myeloid cell-specific PTP1B deletion also causes decreased migratory capacity of epidermal DC, as well as reduced CCR7 expression and chemotaxis to CCL19 by BMDC. PTP1B deficiency in BMDC also impairs their migration in vivo. Further, immature LysM PTP1B BMDC display fewer podosomes, increased levels of phosphorylated Src at tyrosine 527, and loss of Src localization to podosome puncta. In co-culture with T cells, LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC. Finally, LysM PTP1B BMDC fail to present antigen to T cells as efficiently as control BMDC. These data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.

  12. Data of evolutionary structure change: 1B1ZA-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZA-2NTSA 1B1Z 2NTS A A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYTN--------------GPSKYETGYIKFIPKNKESFWFDFF-PEPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...ine> 2NTS A 2NTSA 2NTS A 2NTS.../line> PHE CA 274 2NTS A 2NTS

  13. Data of evolutionary structure change: 1B1ZC-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZC-2NTSA 1B1Z 2NTS C A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYTNG--------------PSKYETGYIKFIPKNKESFWFDFFP-EPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...e>THR CA 392 2NTS A 2NTS...CA 343 LYS CA 296 2NTS A 2NTS...208 PHE CA 276 THR CA 304 2NTS

  14. Data of evolutionary structure change: 1B1ZD-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZD-2NTSA 1B1Z 2NTS D A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYT--------------NGPSKYETGYIKFIPKNKESFWFDFFP-EPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...R CA 395 2NTS A 2NTS... LYS CA 294 2NTS A 2NTS...e>PHE CA 282 THR CA 304 2NTS

  15. Data of evolutionary structure change: 1B1ZB-2NTSA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B1ZB-2NTSA 1B1Z 2NTS B A DPDPSQLHRSSLVKNLQNIYFLYE-GDPVTHENVKSVDQ...ELDYKVRKYLTDNKQLYT--------------NGPSKYETGYIKFIPKNKESFWFDFF-PEPEFTQSKYLMIYKDNETLDSNTSQIEVYLTT-- ...4 2NTS A 2NTSA 2NTS A 2NTSAPHE CA 283 2NTS A 2NTS

  16. Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes

    DEFF Research Database (Denmark)

    Schubert, J.; Siekierska, A.; Langlois, M.

    2014-01-01

    Febrile seizures affect 2-4% of all children(1) and have a strong genetic component(2). Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)(3-5) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encodi...

  17. 18 CFR 2.1b - Availability in contested cases of information acquired by staff investigation.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Availability in contested cases of information acquired by staff investigation. 2.1b Section 2.1b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES GENERAL...

  18. 18 CFR 1b.13 - Powers of persons conducting formal investigations.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Powers of persons conducting formal investigations. 1b.13 Section 1b.13 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS §...

  19. Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolylpyrroles, Analogues of the Marine Alkaloid Nortopsentin

    Directory of Open Access Journals (Sweden)

    Gerhard Kelter

    2013-03-01

    Full Text Available 2,5-bis(3′-Indolylpyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.

  20. Synthesis and antiproliferative activity of 2,5-bis(3'-indolyl)pyrroles, analogues of the marine alkaloid nortopsentin.

    Science.gov (United States)

    Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert

    2013-03-01

    2,5-bis(3'-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes.

  1. Synthesis and Antiproliferative Activity of 2,5-bis(3′-Indolyl)pyrroles, Analogues of the Marine Alkaloid Nortopsentin

    Science.gov (United States)

    Carbone, Anna; Parrino, Barbara; Barraja, Paola; Spanò, Virginia; Cirrincione, Girolamo; Diana, Patrizia; Maier, Armin; Kelter, Gerhard; Fiebig, Heinz-Herbert

    2013-01-01

    2,5-bis(3′-Indolyl)pyrroles, analogues of the marine alkaloid nortopsentin, were conveniently prepared through a three step procedure in good overall yields. Derivatives 1a and 1b exhibited concentration-dependent antitumor activity towards a panel of 42 human tumor cell lines with mean IC50 values of 1.54 μM and 0.67 μM, respectively. Investigating human tumor xenografts in an ex-vivo clonogenic assay revealed selective antitumor activity, whereas sensitive tumor models were scattered among various tumor histotypes. PMID:23455514

  2. Cytochrome 450 1B1 (CYP1B1 polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC patients

    Directory of Open Access Journals (Sweden)

    Price Douglas K

    2010-09-01

    Full Text Available Abstract Background The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1 gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen. Methods CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition, 4326C>G (432LeuVal, and 4390A>G (453AsnSer polymorphisms and treatment response, progression-free-survival (PFS and overall-survival (OS was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test. Results Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014, shorter progression-free-survival (P = 0.032 and overall-survival (P Conclusions CYP1B1-4326C>G (432LeuVal polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

  3. [Structure and function of heavy metal transporter P(1B)-ATPase in plant: a review].

    Science.gov (United States)

    Zhang, Yuxiu; Zhang, Yuanya; Sun, Tao; Chai, Tuanyao

    2010-06-01

    The regulation of the heavy-metal accumulation in vivo for plant survival is very complex. The metal cation transporter plays key roles in the metabolic process. P(1B)-ATPases are the only subgroup of P-ATPases that contribute to heavy metal homeostasis presented in most organisms. Arabidopsis thaliana contains eight genes encoding P(1B)-ATPases. The current reports show that the functions of P(1B)-ATPases are involved in maintaining metal homeostasis, transporting and detoxification in plants. P(1B)-ATPases not only mediated metal ion mobilization and uptake in roots, but also contribute to the metal transport, storage and tolerance in shoots, especially in heavy metal hyperaccumulators. In this paper, we reviewed and discussed the evolution, classification, structure and function of P(1B)-ATPases in plants. HMAs-transgenic manipulation could be a feasible approach for phytoremediation and mineral nutrition fortification.

  4. Inhibition of protein tyrosine phosphatase 1B by lupeol and lupenone isolated from Sorbus commixta.

    Science.gov (United States)

    Na, Minkyun; Kim, Bo Yeon; Osada, Hiroyuki; Ahn, Jong Seog

    2009-08-01

    Protein tyrosine phosphatase 1B (PTP1B) appears to be an attractive target for the development of new drugs for type 2 diabetes and obesity. In our preliminary test, a MeOH extract of the stem barks of Sorbus commixta Hedl. (Rosaceae) showed strong PTP1B inhibitory activity. Bioassay-guided fractionation of the MeOH extract resulted in the isolation of two lupane-type triterpenes, lupenone (1) and lupeol (2). Compounds 1 and 2 inhibited PTP1B with IC(50) values of 13.7 +/- 2.1 and 5.6 +/- 0.9 microM, respectively. Kinetic studies revealed that both the compounds 1 and 2 are non-competitive inhibitors of PTP1B that decrease V(max) values with no effect on K(m) values.

  5. Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling

    DEFF Research Database (Denmark)

    Lund, I K; Hansen, J A; Andersen, H S

    2005-01-01

    Upon leptin binding, the leptin receptor is activated, leading to stimulation of the JAK/STAT signal transduction cascade. The transient character of the tyrosine phosphorylation of JAK2 and STAT3 suggests the involvement of protein tyrosine phosphatases (PTPs) as negative regulators...... of this signalling pathway. Specifically, recent evidence has suggested that PTP1B might be a key regulator of leptin signalling, based on the resistance to diet-induced obesity and increased leptin signalling observed in PTP1B-deficient mice. The present study was undertaken to investigate the mechanism by which...... PTP1B mediates the cessation of the leptin signal transduction. Leptin-induced activation of a STAT3 responsive reporter was dose-dependently inhibited by co-transfection with PTP1B. No inhibition was observed when a catalytically inactive mutant of PTP1B was used or when other PTPs were co...

  6. Water molecule network and active site flexibility of apo protein tyrosine phosphatase 1B

    DEFF Research Database (Denmark)

    Pedersen, A.K.; Peters, Günther H.J.; Møller, K.B.;

    2004-01-01

    Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator of insulin and leptin signalling and is therefore considered to be an important molecular target for the treatment of type 2 diabetes and obesity. Detailed structural information about the structure of PTP1B, including...... the conformation and flexibility of active-site residues as well as the water-molecule network, is a key issue in understanding ligand binding and enzyme kinetics and in structure-based drug design. A 1.95 Angstrom apo PTP1B structure has been obtained, showing four highly coordinated water molecules in the active...... of PTP1B and form a novel basis for structure-based inhibitor design....

  7. Palatal insufficiency as isolated sign of GQ1b antibody syndrome.

    Science.gov (United States)

    Verhelst, Helene; Maes, Michaela; Deblaere, Karel; Van Coster, Rudy

    2011-04-01

    Antiganglioside GQ1b antibodies mediate a continuum of disorders with overlapping features, fostering the concept of anti-GQ1b antibody syndrome. We present a patient whose palatal insufficiency was the only clinical sign of postinfectious GQ1b antibody syndrome. Cerebral magnetic resonance imaging confirmed involvement of the glossopharyngeal nerve and vagus nerve bilaterally, revealing gadolinium enhancement of both nerves bilaterally and thickening of the left nervus vagus. Magnetic resonance imaging may help in diagnosing postinfectious GQ1b antibody syndrome, especially at early stages and in monosymptomatic patients. Early diagnosis may lead to early therapy, resulting in a milder disease course by preventing further deterioration leading to the ataxia and ophthalmoplegia usually observed in patients with postinfectious GQ1b antibody syndrome.

  8. Inhibition of protein tyrosine phosphatase 1B by lignans from Myristica fragrans.

    Science.gov (United States)

    Yang, Senugmi; Na, Min Kyun; Jang, Jun Pil; Kim, Kyung Ah; Kim, Bo Yeon; Sung, Nak Ju; Oh, Won Keun; Ahn, Jong Seog

    2006-08-01

    Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as one of the drug targets for treating type 2 diabetes and obesity. Bioassay-guided fractionation of a MeOH extract of the semen of Myristica fragrans Houtt. (Myristicaceae) afforded PTP1B inhibitory compounds, meso-dihydroguaiaretic acid (1) and otobaphenol (2). Compounds 1 and 2 inhibited PTP1B with IC(50) values of 19.6 +/- 0.3 and 48.9 +/- 0.5 microM, respectively, in the manner of non-competitive inhibitors. Treatment with compound 1 on 32D cells overexpressing the insulin receptor (IR) resulted in a dose-dependent increase in the tyrosine phosphorylation of IR. These results indicate that compound 1 can act as an enhancing agent in intracellular insulin signaling, possibly through the inhibition of PTP1B activity.

  9. Cytochrome P450 CYP1B1 activity in renal cell carcinoma.

    Science.gov (United States)

    McFadyen, M C E; Melvin, W T; Murray, G I

    2004-08-31

    Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has a poor prognosis due to its late presentation and resistance to current anticancer drugs. One mechanism of drug resistance, which is potentially amenable to therapeutic intervention, is based on studies in our laboratory. CYP1B1 is a cytochrome P450 enzyme overexpressed in a variety of malignant tumours. Our studies are now elucidating a functional role for CYP1B1 in drug resistance. Cytochrome P450 reductase (P450R) is required for optimal metabolic activity of CYP1B1. Both CYP1B1 and P450R can catalyse the biotransformation of anticancer drugs at the site of the tumour. In this investigation, we determined the expression of CYP1B1 and P450R in samples of normal kidney and RCC (11 paired normal and tumour and a further 15 tumour samples). The O-deethylation of ethoxyresorufin to resorufin was used to measure CYP1B1 activity in RCC. Cytochrome P450 reductase activity was determined by following the reduction of cytochrome c at 550 nm. The key finding of this study was the presence of active CYP1B1 in 70% of RCC. Coincubation with the CYP1B1 inhibitor alpha-naphthoflavone (10 nM) inhibited this activity. No corresponding CYP1B1 activity was detected in any of the normal tissue examined (n=11). Measurable levels of active P450R were determined in all normal (n=11) and tumour samples (n=26). The presence of detectable CYP1B1, which is capable of metabolising anticancer drugs in tumour cells, highlights a novel target for therapeutic intervention.

  10. Identifying and structurally characterizing CD1b in Aotus nancymaae owl monkeys.

    Science.gov (United States)

    Castillo, Fabio; Guerrero, Carlos; Trujillo, Esperanza; Delgado, Gabriela; Martinez, Pilar; Salazar, Luz M; Barato, Paola; Patarroyo, Manuel E; Parra-López, Carlos

    2004-10-01

    This study reports the molecular characterization and tissue expression of the non-human Aotus nancymaae primate CD1b isoform in the search for an experimental animal model to be used in evaluating the role of non-peptide antigen-presentation molecules in the immune response to infectious agents. CD1b expression on the surface of A. nancymaae peripheral blood monocyte-derived dendritic cells, shown by flow cytometry, was made possible by using human CD1b isoform antibodies. Studying the expression of CD1b-encoded transcripts revealed this molecule's broad distribution in several tissues. The A. nancymaae CD1b transcript-encoded amino-acid sequence showed 95.5% identity with the human sequence. Such high sequence homology was reflected in the identical structural conservation of how pockets A', C' and F' and tunnel T' conforming the antigen's binding site are organized, the similar arrangement of those amino-acids interacting with the T-cell receptor (TCR) during antigen presentation, and the conservation of YQNI-motif sequence in the cytoplasmatic tail (responsible for the molecule's intracellular trafficking in humans). Comparing the structure of human CD1a and CD1b and mouse CD1d proteins with CD1b structure in A. nancymaae obtained by minimization revealed that changes in the latter molecule's alpha1 and alpha2 domains imposed a narrowing of the antigen-binding groove in A. nancymaae CD1b. The high structural similarity between A. nancymaae CD1b and that from humans presented in this study leads to A. nancymaae being proposed as a suitable experimental animal model for analyzing CD1b in vivo, mainly in bacterial and parasite infections such as tuberculosis and malaria, respectively.

  11. Hereditary and histologic characteristics of the CF1/b cac mouse cataract model.

    Science.gov (United States)

    Kondo, Tomohiro; Nagai, Hiroaki; Kawashima, Takamune; Taniguchi, Yusuke; Koyabu, Nozomu; Takeshita, Ai; Kusakabe, Ken-Takeshi; Okada, Toshiya

    2014-10-01

    A substrain of mice originating from the CF1 strain (an outbred colony) reared at Osaka Prefecture University (CF1/b cac mice) develops cataracts beginning at 14 d old. Affected mice were fully viable and fertile and had developed cataracts by 22 d of age. The incidence of cataracts did not differ between male and female mice. Histologically, 14-wk-old CF1/b cac mice showed vacuolated lens epithelial cells, swollen lens fibers, many pyknotic nuclei, and vacuolation of the lens cortex. To elucidate the mode of inheritance, we analyzed heterozygous mutants hybrids generated from CF1/b cac and wildtype BALB/c mice and the offspring of the backcrossed heterozygous mutants. None of the heterozygous mutants was affected, but the ratio of affected to unaffected mice was 1:3 among the offspring of the heterozygous mutants. The initial genomewide screen of 20 affected backcrossed offspring (CF1/b cac × [CF1/b cac × BALB/c]) indicated that the mutant gene resides on chromosome 16. For further mapping, we used affected progeny of CF1/b cac × (CF1/b cac × MSM/Ms) mice. We concluded that the cataracts in CF1/b cac mice are inherited through an autosomal recessive mutation and that the mutant gene is located on mouse chromosome 16 between D16Mit5 and D16Mit92 and between D16Mit92 and D16Mit201. The mapping of the mutant gene of the CF1/b cac mice to mouse chromosome 16 provides the positional information necessary to identify the candidate gene responsible for the CF1/b cac phenotype.

  12. Perioperative cerebral ischaemia in cardiac surgery and BIS.

    Science.gov (United States)

    Villacorta, J; Kerbaul, F; Collart, F; Guidon, C; Bonnet, M; Guillen, J C; Gouin, F

    2005-08-01

    A 46-year-old woman was monitored by bispectral index monitoring (BIS) during redo aortic and mitral valve replacement. On release of the aortic cross clamp there was a sudden, severe, unexplained, and sustained fall in the BIS value. Postoperatively, a CT scan was consistent with multiple ischaemic lesions. The lesions were presumed to be due to air embolism. This case suggests that a sudden unexplained and persistent fall in BIS may indicate cerebral ischaemia.

  13. Comparisons Between Tridentate Bis(benzazoles-pyridine and Bis(benzazolestriazine Ligands: a Theoretical Study

    Directory of Open Access Journals (Sweden)

    Mihaiela Andoni

    2015-12-01

    Full Text Available Twelve bis(benzazole structures with potential ligand character were investigated by means of computational chemistry. Global and local reactivity descriptors within DFT (Density Functional Theory theory (Fukui functions, chemical potential, hardness, electrophilicity index have been computed at B3LYP/6-31G(d,p level of theory. NICS(0 (Nucleus Independent Chemical Shift index computations were employed for the evaluation of the local aromatic character of each heterocyclic moiety. Best results have been reported for the bis(benzimidazole derivatives. Copper and zinc complexes of the investigated tridentate ligands have been proposed.

  14. AP calculus AB & BC crash course

    CERN Document Server

    Rosebush, J

    2012-01-01

    AP Calculus AB & BC Crash Course - Gets You a Higher Advanced Placement Score in Less Time Crash Course is perfect for the time-crunched student, the last-minute studier, or anyone who wants a refresher on the subject. AP Calculus AB & BC Crash Course gives you: Targeted, Focused Review - Study Only What You Need to Know Crash Course is based on an in-depth analysis of the AP Calculus AB & BC course description outline and actual AP test questions. It covers only the information tested on the exams, so you can make the most of your valuable study time. Written by experienced math teachers, our

  15. Applying experimental constraints to a one-dimensional model for BiS2 superconductivity

    Science.gov (United States)

    Griffith, M. A.; Foyevtsova, K.; Continentino, M. A.; Martins, G. B.

    2016-10-01

    Recent ARPES measurements [Sugimoto et al., Phys. Rev. B 92 (2015) 041113] have confirmed the one-dimensional character of the electronic structure of CeO0.5 F0.5 BiS2, a representative of BiS2-based superconductors. In addition, several members of this family present sizable increase in the superconducting transition temperature Tc under application of hydrostatic pressure. Motivated by these two results, we propose an effective one-dimensional three-orbital model, whose kinetic energy part, obtained through ab initio calculations, is supplemented by pair-scattering terms, which are treated at the mean-field level. We solve the gap equations self-consistently and then systematically probe which combination of pair-scattering terms gives results consistent with experiment, namely, a superconducting dome with a maximum Tc at the right chemical potential and a sizable increase in Tc when the magnitude of the hoppings is increased. For these constraints to be satisfied multi-gap superconductivity is required, in agreement with experiments, and one of the hoppings has a dominant influence over the increase of Tc with pressure.

  16. Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency

    DEFF Research Database (Denmark)

    Sim, J. C. H.; White, S. M.; Fitzpatrick, E.

    2014-01-01

    or nonsense mutations in all of them. Conclusions: This study broadens the spectrum of ARID1B associated phenotypes by describing a distinctive phenotype including plantar fat pads but lacking the hypertrichosis or fifth nail hypoplasia associated with Coffin-Siris syndrome. We present the first direct...

  17. Imidazo[2,1-b]benzothiazoles. II. Synthesis and antiinflammatory activity of some imidazo[2,1-b]benzothiazoles.

    Science.gov (United States)

    El-Shorbagi, A N; Sakai, S; el-Gendy, M A; Omar, N; Farag, H H

    1989-11-01

    3-[2-[p-(Un)substituted phenyl]imidazo [2,1-b]benzothiazol-3- yl]propionic acid derivatives (2a--e) were prepared via the interaction of the corresponding 2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazoles (1a--e) with acrylic acid in the presence of acetic anhydride and acetic acid. Esterification of 2a--e produced methyl esters (3a--e). Upon the interaction of 3a with m-chloroperbenzoic acid, the S-dioxide (4a) was obtained. Compound 5a was prepared from 4a by alkaline hydrolysis. Vilsmeier formylation for 1a--e produced novel [2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol-3- yl]formaldehyde derivatives (6a--e). Derivatives 6a--e reacted with ethyl bromoacetate to give ethyl 3-hydroxy-3-[2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol- 3-yl]propionate esters (7a--e). Compound dl-7a was resolved with l-(+)-tartaric acid. Compounds 2a--e showed weak or no activity in the carrageein-induced paw edema assay. Compound 4a significantly inhibited the leakage of pontamine-sky blue dye into the peritoneal cavity of mice, in the capillary permeability inhibition assay. Compound 5a inhibited the writhing by 62% in the acetic acid-induced writhing assay.

  18. Pathogenesis-Related Protein 1b1 (PR1b1) Is a Major Tomato Fruit Protein Responsive to Chilling Temperature and Upregulated in High Polyamine Transgenic Genotypes

    Science.gov (United States)

    Fatima, Tahira; Topuz, Muhamet; Bernadec, Anne; Sicher, Richard; Handa, Avtar K.; Mattoo, Autar K.

    2016-01-01

    Plants execute an array of mechanisms in response to stress which include upregulation of defense-related proteins and changes in specific metabolites. Polyamines – putrescine (Put), spermidine (Spd), and spermine (Spm) – are metabolites commonly found associated with abiotic stresses such as chilling stress. We have generated two transgenic tomato lines (556HO and 579HO) that express yeast S-adenosylmethionine decarboxylase and specifically accumulate Spd and Spm in fruits in comparison to fruits from control (556AZ) plants (Mehta et al., 2002). Tomato fruits undergo chilling injury at temperatures below 13°C. The high Spd and Spm tomato together with the control azygous line were utilized to address role(s) of polyamines in chilling-injury signaling. Exposure to chilling temperature (2°C) led to several-fold increase in the Put content in all the lines. Upon re-warming of the fruits at 20°C, the levels of Spd and Spm increased further in the fruit of the two transgenic lines, the higher levels remaining stable for 15 days after re-warming as compared to the fruit from the control line. Profiling their steady state proteins before and after re-warming highlighted a protein of ∼14 kD. Using proteomics approach, protein sequencing and immunoblotting, the ∼14-kD protein was identified as the pathogenesis related protein 1b1 (PR1b1). The PR1b1 protein accumulated transiently in the control fruit whose level was barely detectable at d 15 post-warming while in the fruit from both the 556HO and 579HO transgenic lines PR1b1 abundance increased and remained stable till d 15 post warming. PR1b1 gene transcripts were found low in the control fruit with a visible accumulation only on d 15 post warming; however, in both the transgenic lines it accumulated and increased soon after rewarming being several-fold higher on day 2 while in 556HO line this increase continued until d 6 than the control fruit. The chilling-induced increase in PR1b1 protein seems independent

  19. Schisandrin A and B induce organic anion transporting polypeptide 1B1 transporter activity.

    Science.gov (United States)

    Guo, Cheng-Xian; Deng, Sheng; Yin, Ji-Ye; Liu, Zhao-Qian; Zhang, Wei; Zhou, Hong-Hao

    2015-01-01

    Organic anion transporting polypeptide 1B1 (OATP1B1) is the most important transporter in the organic anion transporting polypeptide family. OATP1B1 plays an important role in the hepatic uptake of many endogenous compounds and xenobiotics, including many clinical drugs. At present, the combinational usage of Chinese traditional herbal medicines and conventional chemical pharmaceuticals may affect the activity of enzymes and transporters activity and cause absorption of their substrates and metabolic changes. In this study, we aimed to investigate the effect of schisandrin A, schisandrin B and tanshinone IIA, which were extracted from medicinal plants, on OATP1B1 activity. HepG2 cells are used as in vitro models for OATP1B1 activity studies. A combination of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assays, real-time RT-PCR, and transporter activity analysis were employed. We found that schisandrin A and B increased OATP1B1 mRNA levels by 1.81-fold (p Schisandrin A of 1 μM and 10 μM and schisandrin B of 10 μM significantly increased the uptake of [3H] estrone-3-sulfate (p schisandrin A and B induced OATP1B1 expression and increased its transporter activity in HepG2 cells.

  20. Ibuprofen Inhibits Colitis-Induced Overexpression of TumorRelated Rac1b

    Directory of Open Access Journals (Sweden)

    Paulo Matos

    2013-01-01

    Full Text Available The serrated pathway to colorectal tumor formation involves oncogenic mutations in the BRAF gene, which are sufficient for initiation of hyperplastic growth but not for tumor progression. A previous analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant BRAF and both events proved to cooperate in tumor cell survival. Here, we provide evidence for increased expression of Rac1b in patients with inflamed human colonic mucosa as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the nonsteroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumor cells through a cyclooxygenase inhibition–independent mechanism. Accordingly, the presence of ibuprofen led to a reduction of HT29 cell survival in vitro and inhibited Rac1b-dependent tumor growth of HT29 xenografts. Together, our results suggest that stromal cues, namely, inflammation, can trigger changes in Rac1b expression in the colon and identify ibuprofen as a highly specific and efficient inhibitor of Rac1b overexpression in colorectal tumors. Our data suggest that the use of ibuprofen may be beneficial in the treatment of patients with serrated colorectal tumors or with inflammatory colon syndromes.

  1. Essential roles for Pot1b in HSC self-renewal and survival.

    Science.gov (United States)

    Wang, Yang; Shen, Mei-Feng; Chang, Sandy

    2011-12-01

    Maintenance of mammalian telomeres requires both the enzyme telomerase and shelterin, which protect telomeres from inappropriately activating DNA damage response checkpoints. Dyskeratosis congenita is an inherited BM failure syndrome disorder because of defects in telomere maintenance. We have previously shown that deletion of the shelterin component Pot1b in the setting of telomerase haploinsufficiency results in rapid telomere shortening and fatal BM failure in mice, eliciting phenotypes that strongly resemble human syskeratosis congenita. However, it was unclear why BM failure occurred in the setting of Pot1b deletion. In this study, we show that Pot1b plays an essential role in HSC survival. Deletion of Pot1b results in increased apoptosis, leading to severe depletion of the HSC reserve. BM from Pot1b(Δ/Δ) mice cannot compete with BM from wild-type mice to provide multilineage reconstitution, indicating that there is an intrinsic requirement for Pot1b the maintenance of HSC function in vivo. Elimination of the p53-dependent apoptotic function increased HSC survival and significantly extended the lifespan of Pot1b-null mice deficient in telomerase function. Our results document for the first time the essential role of a component of the shelterin complex in the maintenance of HSC and progenitor cell survival.

  2. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy.

    Science.gov (United States)

    Wu, Nan; Shang, Siyuan; Su, Yanjie

    2015-09-01

    The vasopressin V1b receptor (AVPR1B) gene has been shown to be closely associated with bipolar disorder and depression. However, whether it relates to positive social outcomes, such as empathy and prosocial behavior, remains unknown. This study explored the possible role of the AVPR1B gene rs28373064 in empathy and prosociality. A total of 256 men, who were genetically unrelated, non-clinical ethnic Han Chinese college students, participated in the study. Prosociality was tested by measuring the prosocial tendencies of cognitive and emotional empathy using the Interpersonal Reactivity Index (IRI). The single nucleotide polymorphism (SNP), rs28373064, was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results suggest that the AVPR1B gene rs28373064 is linked to emotional empathy and prosociality. The mediation analysis indicated that the effect of the AVPR1B gene on prosociality might be mediated by emotional empathy. This study demonstrated the link between the AVPR1B gene and prosociality and provided evidence that emotional empathy might mediate the relation between the AVPR1B gene and prosociality.

  3. Expression and localization of aquaporin 1b during oocyte development in the Japanese eel (Anguilla japonica

    Directory of Open Access Journals (Sweden)

    Matsubara Hajime

    2011-05-01

    Full Text Available Abstract To elucidate the molecular mechanisms underling hydration during oocyte maturation, we characterized the structure of Japanese eel (Anguilla japonica novel-water selective aquaporin 1 (AQP1b that thought to be involved in oocyte hydration. The aqp1b cDNA encodes a 263 amino acid protein that includes the six potential transmembrane domains and two Asn-Pro-Ala motifs. Reverse transcription-polymerase chain reaction showed transcription of Japanese eel aqp1b in ovary and testis but not in the other tissues. In situ hybridization studies with the eel aqp1b cRNA probe revealed intense eel aqp1b signal in the oocytes at the perinucleolus stage and the signals became faint during the process of oocyte development. Light microscopic immunocytochemical analysis of ovary revealed that the Japanese eel AQP1b was expressed in the cytoplasm around the yolk globules which were located in the peripheral region of oocytes during the primary yolk globule stage; thereafter, the immunoreactivity was observed throughout the cytoplasm of oocyte as vitellogenesis progressed. The immunoreactivity became localized around the large membrane-limited yolk masses which were formed by the fusion of yolk globules during the oocyte maturation phase. These results together indicate that AQP1b, which is synthesized in the oocyte during the process of oocyte growth, is essential for mediating water uptake into eel oocytes.

  4. Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Damiano Paolicelli

    2009-07-01

    Full Text Available Damiano Paolicelli, Vita Direnzo, Maria TrojanoDepartment of Neurological and Psychiatric Sciences, University of Bari, Bari, ItalyAbstract: Multiple sclerosis (MS is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. Since the 1990s the results of several clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNβ-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNβ-1b reduces the frequency and severity of relapses and the development of new and active brain lesions as assessed by magnetic resonance imaging. Long-term data suggest a persistent efficacy of IFNβ-1b on disease activity and a positive effect in slowing disability worsening. Furthermore a reduction of relapse rate and a slight positive effect on the progression were demonstrated when IFNβ-1b was administered to still-active secondary progressive MS. IFNβ-1b therapy is well tolerated and relatively free of long-term side effects. In spite of the emergence of new agents for the treatment of MS, IFNβ-1b still remains a first-line therapy with a fundamental role in all stages of the disease.Keywords: interferon beta-1b, relapsing-remitting multiple sclerosis, clinically isolated syndromes, efficacy, safety, neutralizing antibodies

  5. Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

    Directory of Open Access Journals (Sweden)

    Nigel P S Crawford

    2007-11-01

    Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

  6. Drug-drug interactions between rosuvastatin and oral antidiabetic drugs occurring at the level of oatp1b1s

    NARCIS (Netherlands)

    Steeg, E. van de; Greupink, R.; Schreurs, M.; Nooijen, I.H.G.; Verhoeck, K.C.M.; Hanemaaijer, R.; Ripken, D.; Monshouwer, M.; Vlaming, M.L.H.; DeGroot, J.; Verwei, M.; Russel, F.G.M.; Huisman, M.T.; Wortelboer, H.M.

    2013-01-01

    Organic anion-transporting polypeptide 1B1 (OATP1B1) is an important hepatic uptake transporter, of which the polymorphic variant OATP1B1*15 (Asn130Asp and Val174Ala) has been associated with decreased transport activity. Rosuvastatin is an OATP1B1 substrate and often concomitantly prescribed with o

  7. Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B.

    Directory of Open Access Journals (Sweden)

    Kosuke Matsuo

    Full Text Available Protein-tyrosine phosphatase 1B (PTP1B is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation.To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO mice. In addition, we reconstituted KO cells with wild type, substrate-trapping (D/A and sumoylation-resistant (K/R PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR and insulin receptor substrate 1 (IRS1 tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells.These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B.

  8. Genetic variation of Cytochrome P450 1B1 (CYP1B1) and risk of breast cancer among Polish women.

    Science.gov (United States)

    Gaudet, Mia M; Chanock, Stephen; Lissowska, Jolanta; Berndt, Sonja I; Yang, Xiaohong Rose; Peplonska, Beata; Brinton, Louise A; Welch, Robert; Yeager, Meredith; Bardin-Mikolajczak, Alicja; Sherman, Mark E; Sutter, Thomas R; Garcia-Closas, Montserrat

    2006-08-01

    Four single nucleotide polymorphisms (SNPs) in CYP1B1 (Ex2 + 143 C > G, Ex2 + 356 G > T, Ex3 + 251 G > C, Ex3 + 315 A > G) cause amino acid changes (R48G, A119S, L432V and N453S, respectively) and are associated with increased formation of catechol estrogens; however, epidemiologic evidence only weakly supports an association between these variants and breast cancer risk. Because genetic variability conferring increased susceptibility could exist beyond these putative functional variants, we comprehensively examined the common genetic variability within CYP1B1. A total of eight haplotype-tagging (ht)SNPs (including Ex3 + 315 A > G), in addition to two putatively functional SNPs (Ex2 + 143 C > G and Ex3 + 251 G > C), were selected and genotyped in a large case-control study of Polish women (1995 cases and 2296 controls). Haplotypes were estimated using the expectation-maximization algorithm, and overall differences in the haplotype distribution between cases and controls were assessed using a global score test. We also evaluated levels of tumor CYP1B1 protein expression in a subset of 841 cases by immunohistochemistry, and their association with genetic variants. In the Polish population, we observed two linkage disequilibrium (LD)-defined blocks. Neither haplotypes (global P-value of 0.99 and 0.67 for each block of LD, respectively), nor individual SNPs (including three putatively functional SNPs) were associated with breast cancer risk. CYP1B1 was expressed in most tumor tissues (98%), and the level of expression was not related to the studied genetic variants. We found little evidence for modification of the estimated effect of haplotypes or individual SNPs by age, family history of breast cancer, or tumor hormone receptor status. The present study provides strong evidence against the existence of a substantial overall association between common genetic variation in CYP1B1 and breast cancer risk.

  9. New phenazine-containing ladder polymer of intrinsic microporosity from a spirobisindane-based AB-type monomer

    KAUST Repository

    Ghanem, Bader

    2016-08-15

    A new solution-processable ladder polymer (PSBI-AB) of intrinsic microporosity with dibenzodioxane linkages and bis(phenazine) units was designed and synthesized by self-polymerization of an AB-type monomer containing both catechol and aromatic dichloride groups. Such polymerization is an effective way to synthesize high molecular weight polymers and has a significant advantage over AA-BB polycondensation due to the lack of the requirement for strict control over stoichiometric balance. This protocol can be used to prepare a variety of phenazine-containing ladder type PIMs from their aromatic tetramethoxy precursors. The obtained polymer had high average molecular mass, excellent thermal stability, a high BET surface area of 705 m(2) g(-1) and good solubility in some organic solvents such as chloroform, m-cresol and dichlorobenzene. Gas permeation measurements showed comparable results to the previously reported analogous PIM-7 for films made under the same formation protocol.

  10. Association between CYP1B1 Gene Polymorphisms and Risk Factors and Susceptibility to Laryngeal Cancer

    OpenAIRE

    Yu, Peng-Ju; Chen, Wei-Guan; Feng, Quan-Lin; Chen, Wei; Jiang, Man-Jie; Li, Ze-Qing

    2015-01-01

    Background The aim of this study was to investigate the association between polymorphism of the cytochrome P450 1B1 (CYP1B1) gene, a metabolic enzyme gene, and the susceptibility to laryngeal cancer among the Chinese Han population. Material/Methods In a case-control study, we investigated polymorphisms in the CYP1B1 gene (rs10012, rs1056827, and rs1056836) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 300 Chinese Han patients with ...

  11. Otx2 Requires Lmx1b to Control the Development of Mesodiencephalic Dopaminergic Neurons

    Science.gov (United States)

    Sherf, Orna; Nashelsky Zolotov, Limor; Liser, Keren; Tilleman, Hadas; Jovanovic, Vukasin M.; Zega, Ksenija; Jukic, Marin M.; Brodski, Claude

    2015-01-01

    Studying the development of mesodiencephalic dopaminergic (mdDA) neurons provides an important basis for better understanding dopamine-associated brain functions and disorders and is critical for establishing cell replacement therapy for Parkinson’s disease. The transcription factors Otx2 and Lmx1b play a key role in the development of mdDA neurons. However, little is known about the genes downstream of Otx2 and Lmx1b in the pathways controlling the formation of mdDA neurons in vivo. Here we report on our investigation of Lmx1b as downstream target of Otx2 in the formation of mdDA neurons. Mouse mutants expressing Otx2 under the control of the En1 promoter (En1+/Otx2) showed increased Otx2 expression in the mid-hindbrain region, resulting in upregulation of Lmx1b and expansion of mdDA neurons there. In contrast, Lmx1b-/- mice showed decreased expression of Otx2 and impairments in several aspects of mdDA neuronal formation. To study the functional interaction between Otx2 and Lmx1b, we generated compound mutants in which Otx2 expression was restored in mice lacking Lmx1b (En1+/Otx2;Lmx1b-/-). In these animals Otx2 was not sufficient to rescue any of the aberrations in the formation of mdDA neurons caused by the loss of Lmx1b, but rescued the loss of ocular motor neurons. Gene expression studies in Lmx1b-/- embryos indicated that in these mutants Wnt1, En1 and Fgf8 expression are induced but subsequently lost in the mdDA precursor domain and the mid-hindbrain organizer in a specific, spatio-temporal manner. In summary, we demonstrate that Otx2 critically depends on Lmx1b for the formation of mdDA neurons, but not for the generation of ocular motor neurons. Moreover, our data suggest that Lmx1b precisely maintains the expression pattern of Wnt1, Fgf8 and En1, which are essential for mid-hindbrain organizer function and the formation of mdDA neurons. PMID:26444681

  12. Otx2 Requires Lmx1b to Control the Development of Mesodiencephalic Dopaminergic Neurons.

    Directory of Open Access Journals (Sweden)

    Orna Sherf

    Full Text Available Studying the development of mesodiencephalic dopaminergic (mdDA neurons provides an important basis for better understanding dopamine-associated brain functions and disorders and is critical for establishing cell replacement therapy for Parkinson's disease. The transcription factors Otx2 and Lmx1b play a key role in the development of mdDA neurons. However, little is known about the genes downstream of Otx2 and Lmx1b in the pathways controlling the formation of mdDA neurons in vivo. Here we report on our investigation of Lmx1b as downstream target of Otx2 in the formation of mdDA neurons. Mouse mutants expressing Otx2 under the control of the En1 promoter (En1+/Otx2 showed increased Otx2 expression in the mid-hindbrain region, resulting in upregulation of Lmx1b and expansion of mdDA neurons there. In contrast, Lmx1b-/- mice showed decreased expression of Otx2 and impairments in several aspects of mdDA neuronal formation. To study the functional interaction between Otx2 and Lmx1b, we generated compound mutants in which Otx2 expression was restored in mice lacking Lmx1b (En1+/Otx2;Lmx1b-/-. In these animals Otx2 was not sufficient to rescue any of the aberrations in the formation of mdDA neurons caused by the loss of Lmx1b, but rescued the loss of ocular motor neurons. Gene expression studies in Lmx1b-/- embryos indicated that in these mutants Wnt1, En1 and Fgf8 expression are induced but subsequently lost in the mdDA precursor domain and the mid-hindbrain organizer in a specific, spatio-temporal manner. In summary, we demonstrate that Otx2 critically depends on Lmx1b for the formation of mdDA neurons, but not for the generation of ocular motor neurons. Moreover, our data suggest that Lmx1b precisely maintains the expression pattern of Wnt1, Fgf8 and En1, which are essential for mid-hindbrain organizer function and the formation of mdDA neurons.

  13. CYP1B1 Mutations in Individuals With Primary Congenital Glaucoma and Residing in Denmark

    DEFF Research Database (Denmark)

    Grønskov, Karen; Redó-Riveiro, Alba; Sandfeld, Lisbeth;

    2016-01-01

    Primary congenital glaucoma (PCG OMIM 231300) can be caused by pathogenic sequence variations in cytochrome P450, subfamily 1, polypeptide 1 (CYP1B1). The purpose of this study was to investigate the contribution of sequence variations in CYP1B1 in a cohort of individuals with PCG residing...... mutations, 5 of which were novel. The frequency of CYP1B1 mutations in this cohort was comparable with other populations. We also detected an individual heterozygous for p.(Tyr81Asn) mutation, previously suggested to cause autosomal dominant primary open-angle glaucoma....

  14. Synthesis and Thermal Rearrangement of Tetramethyldisilane-bridged Bis(cyclopentadienyl) Diiron Complexes with Bis(phosphine)Substitution

    Institute of Scientific and Technical Information of China (English)

    孙秀丽; 王佰全; 等

    2003-01-01

    Photolysis of [Me2SiSiMe2)[C5H4Fe(CO2)]2with a series of bis(phosphine)ligands Ph2P(CH2)n PPh2(n=1-4) leads to the formation of the corresponding diiron complexes with intramolecular and intermolecular bis(phosphine) substitution.When these complexes were heated in refluxing xylene.only in the complexes with intermolecular bis(phosphine )substitution the thermal rearrangement reaction occurred.

  15. 40 CFR 721.5760 - Phenol, 4,4′-[methylene-bis (oxy-2,1-ethanediylthio)]bis-.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phenol, 4,4â²- bis-. 721.5760 Section... Substances § 721.5760 Phenol, 4,4′- bis-. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance phenol, 4,4′- bis- (PMN P-87-1760) is subject to reporting under...

  16. 21 CFR 73.3100 - 1,4-Bis[(2-hydroxyethyl)amino]-9,10-anthracenedione bis(2-propenoic)ester copolymers.

    Science.gov (United States)

    2010-04-01

    ...)ester copolymers. 73.3100 Section 73.3100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... § 73.3100 1,4-Bis -9,10-anthracenedione bis(2-propenoic)ester copolymers. (a) Identity. The color additives are 1,4-bis -9,10-anthracenedione bis(2-propenoic)ester (CAS Reg. No. 109561-07-1)...

  17. Reference: DREDR1ATRD29AB [PLACE

    Lifescience Database Archive (English)

    Full Text Available ization and expression of two Arabidopsis DREB2 genes encoding DRE-binding proteins...DREDR1ATRD29AB Nakashima K, Shinwari ZK, Sakuma Y, Seki M, Miura S, Shinozaki K, Yamaguchi-Shinozaki K Organ

  18. Synthesis and Structure of Bis-(o-vanillin)di-pyridine Nickel(Ⅱ)-pyridine Dihydrate

    Institute of Scientific and Technical Information of China (English)

    孙命; 王瑾玲; 段月琴; 缪方明; 翁林红; 冷雪冰

    2001-01-01

    The structure of the complex bis-(o-vanillin)di-pyridine nickel(Ⅱ)([ Ni X-ray analysis.The crystal data are as follows: Monoclinic,P21/n,a=12.273(1),b=17.4700.674mm-1,F(000)=1328,final R=0.0428,Rw=0.1228 for 4528 observable reflections with I≥2σ(Ⅰ).The Nickel(Ⅱ)atom in the complex has a slightly distorted octahedral coordination geometr y and is six-coordinated by four O atoms from two O-Vanillin ligands and two N atoms from two pyridines.In the crystal,the Ni(Ⅱ)-complex and water molecules are linked through a network of hydrogen bonds.

  19. The role of microtubule-associated protein 1B in axonal growth and neuronal migration in the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Maoguang Yang; Xiaoyu Yang; Minfei Wu; Peng Xia; Chunxin Wang; Peng Yan; Qi Gao; Jian Liu; Haitao Wang; Xingwei Duan

    2012-01-01

    In this review, we discuss the role of microtubule-associated protein 1B (MAP1B) and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during axonal development and regeneration. MAP1B and phosphorylated MAP1B in neurons and axons maintain a dynamic balance between cytoskeletal components, and regulate the stability and interaction of microtubules and actin to promote axonal growth, neural connectivity and regeneration in the central nervous system.

  20. Poly[bis[μ-1,4-bis(imidazol-1-ylmethylbenzene]dichloridocadmium(II

    Directory of Open Access Journals (Sweden)

    Xinliang Hu

    2008-07-01

    Full Text Available The title compound, [CdCl2(C14H14N42]n, has a slightly distorted octahedral coordination geometry, formed by four N atoms from 1,4-bis(imidazol-1-ylmethylbenzene ligands and two Cl atoms, giving a two-dimensional network. The Cd atom lies on a centre of inversion.

  1. Bis[N,N-bis(2-hydroxyethyldithiocarbamato-κ2S,S′]copper(II

    Directory of Open Access Journals (Sweden)

    Jun Fan

    2009-12-01

    Full Text Available In the title compound, [Cu(C5H10NO2S22], the CuII cation is chelated by two bis(2-hydroxyethyldithiocarbamate anions with a distorted square-planar coordination geometry. Intermolecular O—H...O hydrogen bonding is observed between the terminal hydroxy groups in the crystal structure.

  2. The new powder diffractometer D1B of the Institut Laue Langevin

    Science.gov (United States)

    Puente Orench, I.; Clergeau, J. F.; Martínez, S.; Olmos, M.; Fabelo, O.; Campo, J.

    2014-11-01

    D1B is a medium resolution high flux powder diffractometer located at the Institut Laue Langevin, ILL. D1B a suitable instrument for studying a large variety of polycrystalline materials. D1B runs since 1998 as a CRG (collaborating research group) instrument, being exploited by the CNRS (Centre National de la Recherche Scientifique, France) and CSIC (Consejo Superior de Investigaciones Cientificas, Spain). In 2008 the Spanish CRG started an updating program which included a new detector and a radial oscillating collimator (ROC). The detector, which has a sensitive height of 100mm, covers an angular range of 128°. Its 1280 gold wires provide a neutron detection point every 0.1°. The ROC is made of 198 gadolinium- based absorbing collimation blades, regular placed every 0.67°. Here the present characteristics of D1B are reviewed and the different experimental performances will be presented.

  3. Data of evolutionary structure change: 1B0FA-1O37A [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available -GYDPV >EEE - > ATOM 556 CA ARG ...ntryIDChain>1O37A KSIVHPSYNSN >EEEEE ...> 1B0FA LGRNR-GIASV > - ...KSSGTSYPDV > > ATOM 1849 CA THR ...tryIDChain> AHCYK----SGIQV >GGG ---- EEE>

  4. GLAS/ICESat L1B Global Waveform-based Range Corrections Data V033

    Data.gov (United States)

    National Aeronautics and Space Administration — The level 1B waveform parameterization data will contain waveform-based range corrections and surface characteristics at the full 40 per second resolution. Data...

  5. SAGE III Meteor-3M L1B Solar Event Transmission Data (Native) V004

    Data.gov (United States)

    National Aeronautics and Space Administration — Level 1B pixel group transmission profiles for a single solar event (Suggested Usage: Vertical transmission profiles for input into an inversion algorithm)

  6. SAGE III Meteor-3M L1B Solar Event Transmission Data (Native) V003

    Data.gov (United States)

    National Aeronautics and Space Administration — Level 1B pixel group transmission profiles for a single solar event (Suggested Usage: Vertical transmission profiles for input into an inversion algorithm)

  7. TES/Aura L1B Spectra Special Observation Low Resolution V004

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Low Resolution granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for a Special Observation &...

  8. TES/Aura L1B Spectra Special Observation Low Resolution V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Low Resolution granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for a Special Observation &...

  9. TES/Aura L1B Spectra Special Observation Low Resolution V005

    Data.gov (United States)

    National Aeronautics and Space Administration — The L1B Low Resolution granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.1 cm-1 resolution for a Special Observation &...

  10. Detection of the urban heat island in Beijing using HJ-1B satellite imagery

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Satellite images are used extensively in studying the urban heat island(UHI) phenomenon.We evaluated the suitability of thermal infrared(TIR) data from the HJ-1B satellite for detecting UHI using a case study in Beijing.Two modified algorithms for retrieving the land surface temperature(LST) from HJ-1B data were tested.The results were compared with LST images derived from a Landsat TM thermal band and the MODIS LST output.The spatial pattern of UHI generated using HJ-1B data matched well with that produced using TM and MODIS data.Of the two algorithms,the mono-window algorithm performed better but further tests are necessary.With more frequent coverage than TM and higher spatial resolution than MODIS,the HJ-1B TIR data present a unique opportunity to study thermal environments in cities in China and neighboring countries.

  11. Trafficking of α1B-adrenergic receptor mediated by inverse agonist in living cells

    Institute of Scientific and Technical Information of China (English)

    MingXU; Ying-huaGUAN; NingXU; Zhang-yiLIANG; Shu-yiWang; YaoSONG; Chi-deHAN; Xin-shengZHAO; You-yiZHANG

    2005-01-01

    AIM The project is aimed at understanding the action of inverse agonist at single molecule level and capturing the real time picture of molecular behavior of α1B-adrenergic receptor (AR) mediated by inverse agonist in living cells by single molecule detection (SMD). METHODS The location and distribution of α1B-AR was detected by laser confocal and whole cell 3H-prazosin binding assay. Dynamic imaging of BODIPY-FL-labeled prazosin (Praz), specific antagonist of (1-AR, was observed in α1B-AR stably expressed human embryonic kidney 293 (HEK293) living cells. The detection of real-time dynamic behaviors of AR was achieved by using fluorescence-labeled AR and its ligand combined with SMD techniques. RESULTS α1B-AR was predominantly distributed on the cell surface and 8.2% of the total receptors were located in cytosol.

  12. MISR Level 1B1 Local Mode Radiance Data V002

    Data.gov (United States)

    National Aeronautics and Space Administration — This is the Local Mode Level 1B1 Product containing the DNs radiometrically scaled to radiances with no geometric resampling (Suggested Usage: The MISR Instrument...

  13. TES/Aura L1B Spectra Special Observation High Resolution V004

    Data.gov (United States)

    National Aeronautics and Space Administration — A L1B High Resolution granule consists of radiometrically calibrated spectra & associated NESR, observed at 0.025 cm-1 resolution for a Special Observation &...

  14. Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Slobodan M Jankovic

    2010-03-01

    Full Text Available Slobodan M JankovicPharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, SerbiaAbstract: Multiple sclerosis (MS is chronic inflammatory and demyelinating disease with either a progressive (10%–15% or relapsing-remitting (85%–90% course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta-1b (IFN-β1b or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-β1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN-β1b reduces the risk of development of clinically defined MS from 45% (with placebo to 28% (with IFN-β1b. It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-β1b and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-β1b. In recommended doses IFN-β1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non

  15. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    OpenAIRE

    Trubicka Joanna; Grabowska-Kłujszo Ewa; Suchy Janina; Masojć Bartłomiej; Serrano-Fernandez Pablo; Kurzawski Grzegorz; Cybulski Cezary; Górski Bohdan; Huzarski Tomasz; Byrski Tomasz; Gronwald Jacek; Złowocka Elżbieta; Kładny Józef; Banaszkiewicz Zbigniew; Wiśniowski Rafał

    2010-01-01

    Abstract Background CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. Methods We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be ...

  16. Bidirectional regulation of emotional memory by 5-HT1B receptors involves hippocampal p11.

    Science.gov (United States)

    Eriksson, T M; Alvarsson, A; Stan, T L; Zhang, X; Hascup, K N; Hascup, E R; Kehr, J; Gerhardt, G A; Warner-Schmidt, J; Arango-Lievano, M; Kaplitt, M G; Ogren, S O; Greengard, P; Svenningsson, P

    2013-10-01

    Cognitive impairments are common in depression and involve dysfunctional serotonin neurotransmission. The 5-HT1B receptor (5-HT(1B)R) regulates serotonin transmission, via presynaptic receptors, but can also affect transmitter release at heterosynaptic sites. This study aimed at investigating the roles of the 5-HT(1B)R, and its adapter protein p11, in emotional memory and object recognition memory processes by the use of p11 knockout (p11KO) mice, a genetic model for aspects of depression-related states. 5-HT(1B)R agonist treatment induced an impairing effect on emotional memory in wild type (WT) mice. In comparison, p11KO mice displayed reduced long-term emotional memory performance. Unexpectedly, 5-HT(1B)R agonist stimulation enhanced memory in p11KO mice, and this atypical switch was reversed after hippocampal adeno-associated virus mediated gene transfer of p11. Notably, 5-HT(1B)R stimulation increased glutamatergic neurotransmission in the hippocampus in p11KO mice, but not in WT mice, as measured by both pre- and postsynaptic criteria. Magnetic resonance spectroscopy demonstrated global hippocampal reductions of inhibitory GABA, which may contribute to the memory enhancement and potentiation of pre- and post-synaptic measures of glutamate transmission by a 5-HT(1B)R agonist in p11KO mice. It is concluded that the level of hippocampal p11 determines the directionality of 5-HT(1B)R action on emotional memory processing and modulates hippocampal functionality. These results emphasize the importance of using relevant disease models when evaluating the role of serotonin neurotransmission in cognitive deficits related to psychiatric disorders.

  17. Integrative bioinformatics links HNF1B with clear cell carcinoma and tumor-associated thrombosis.

    Directory of Open Access Journals (Sweden)

    Justin Cuff

    Full Text Available Clear cell carcinoma (CCC is a histologically distinct carcinoma subtype that arises in several organ systems and is marked by cytoplasmic clearing, attributed to abundant intracellular glycogen. Previously, transcription factor hepatocyte nuclear factor 1-beta (HNF1B was identified as a biomarker of ovarian CCC. Here, we set out to explore more broadly the relation between HNF1B and carcinomas with clear cell histology. HNF1B expression, evaluated by immunohistochemistry, was significantly associated with clear cell histology across diverse gynecologic and renal carcinomas (P<0.001, as was hypomethylation of the HNF1B promoter (P<0.001. From microarray analysis, an empirically-derived HNF1B signature was significantly enriched for computationally-predicted targets (with HNF1 binding sites (P<0.03, as well as genes associated with glycogen metabolism, including glucose-6-phophatase, and strikingly the blood clotting cascade, including fibrinogen, prothrombin and factor XIII. Enrichment of the clotting cascade was also evident in microarray data from ovarian CCC versus other histotypes (P<0.01, and HNF1B-associated prothrombin expression was verified by immunohistochemistry (P = 0.015. Finally, among gynecologic carcinomas with cytoplasmic clearing, HNF1B immunostaining was linked to a 3.0-fold increased risk of clinically-significant venous thrombosis (P = 0.043, and with a 2.3-fold increased risk (P = 0.011 in a combined gynecologic and renal carcinoma cohort. Our results define HNF1B as a broad marker of clear cell phenotype, and support a mechanistic link to glycogen accumulation and thrombosis, possibly reflecting (for gynecologic CCC derivation from secretory endometrium. Our findings also implicate a novel mechanism of tumor-associated thrombosis (a major cause of cancer mortality, based on the direct production of clotting factors by cancer cells.

  18. Structural analysis of sulindac as an inhibitor of aldose reductase and AKR1B10.

    Science.gov (United States)

    Cousido-Siah, Alexandra; Ruiz, Francesc X; Crespo, Isidro; Porté, Sergio; Mitschler, André; Parés, Xavier; Podjarny, Alberto; Farrés, Jaume

    2015-06-05

    Aldose reductase (AR, AKR1B1) and AKR1B10 are enzymes implicated in important pathologies (diabetes and cancer) and therefore they have been proposed as suitable targets for drug development. Sulindac is the metabolic precursor of the potent non-steroidal anti-inflammatory drug (NSAID) sulindac sulfide, which suppresses prostaglandin production by inhibition of cyclooxygenases (COX). In addition, sulindac has been found to be one of the NSAIDs with higher antitumoral activity, presumably through COX inhibition. However, sulindac anticancer activity could be partially mediated through COX-independent mechanisms, including the participation of AR and AKR1B10. Previously, it had been shown that sulindac and sulindac sulfone were good AR inhibitors and the structure of the ternary complex with NADP(+) and sulindac was described (PDB ID 3U2C). In this work, we determined the three-dimensional structure of AKR1B10 with sulindac and established structure-activity relationships (SAR) of sulindac and their derivatives with AR and AKR1B10. The difference in the IC50 values for sulindac between AR (0.36 μM) and AKR1B10 (2.7 μM) might be explained by the different positioning and stacking interaction given by Phe122/Phe123, and by the presence of two buried and ordered water molecules in AKR1B10 but not in AR. Moreover, SAR analysis shows that the substitution of the sulfinyl group is structurally allowed in sulindac derivatives. Hence, sulindac and its derivatives emerge as lead compounds for the design of more potent and selective AR and AKR1B10 inhibitors.

  19. Aldo-keto Reductase Family 1 B10 as a Novel Target for Breast Cancer Treatment

    Science.gov (United States)

    2010-08-01

    cells via identifying the functional domain(s). Body 1) AKR1B10 silencing inhibits breast cancer cells BT-20 growth in culture and...Laboratory of Chemical Biology, Guangdong Province, Tsinghua University Graduate School at Shenzhen , Guangdong 518055 and 6School of Medicine, Tsinghua...breast cancer. Silencing of AKR1B10 in BT-20 human breast cancer cells inhibited cell growth in culture and tumorigenesis in female nude mice. Taken

  20. Role of CYP1B1 in PAH-DNA adduct formation and breast cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Russell, Marion L.; Muller, A.P.; Caleffi, M.; Eschiletti, J.; Graudenz, M.; Sohn, Michael D.

    2010-04-01

    This study investigated the hypothesis that increased exposure to polycyclic aromatic hydrocarbons (PAHs) increases breast cancer risk. PAHs are products of incomplete burning of organic matter and are present in cigarette smoke, ambient air, drinking water, and diet. PAHs require metabolic transformation to bind to DNA, causing DNA adducts, which can lead to mutations and are thought to be an important pre-cancer marker. In breast tissue, PAHs appear to be metabolized to their cancer-causing form primarily by the cytochrome P450 enzyme CYP1B1. Because the genotoxic impact of PAH depends on their metabolism, we hypothesized that high CYP1B1 enzyme levels result in increased formation of PAH-DNA adducts in breast tissue, leading to increased development of breast cancer. We have investigated molecular mechanisms of the relationship between PAH exposure, CYP1B1 expression and breast cancer risk in a clinic-based case-control study. We collected histologically normal breast tissue from 56 women (43 cases and 13 controls) undergoing breast surgery and analyzed these specimens for CYP1B1 genotype, PAH-DNA adducts and CYP1B1 gene expression. We did not detect any difference in aromatic DNA adduct levels of cases and controls, only between smokers and non-smokers. CYP1B1 transcript levels were slightly lower in controls than cases, but the difference was not statistically significant. We found no correlation between the levels of CYP1B1 expression and DNA adducts. If CYP1B1 has any role in breast cancer etiology it might be through its metabolism of estrogen rather than its metabolism of PAHs. However, due to the lack of statistical power these results should be interpreted with caution.

  1. Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish.

    Science.gov (United States)

    Yin, Wu; Hu, Bing

    2014-01-01

    Demyelinating diseases include multiple sclerosis, which is a neurodegenerative disease characterized by immune attacks on the central nervous system (CNS), resulting in myelin sheath damage and axonal loss. Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitory protein (Nogo) receptor-interacting protein-1 (LINGO-1) have been identified as a negative regulator of oligodendrocytes differentiation. Targeted LINGO-1 inhibition promotes neuron survival, axon regeneration, oligodendrocyte differentiation, and remyelination in diverse animal models. Although studies in rodent models have extended our understanding of LINGO-1, its roles in neural development and myelination in zebrafish (Danio rerio) are not yet clear. In this study, we cloned the zebrafish homolog of the human LINGO-1 and found that lingo1b regulated myelination and oligodendrocyte differentiation. The expression of lingo1b started 1 (mRNA) and 2 (protein) days post-fertilization (dpf) in the CNS. Morpholino oligonucleotide knockdown of lingo1b resulted in developmental abnormalities, including less dark pigment, small eyes, and a curly spinal cord. The lack of lingo1b enhanced myelination and oligodendrocyte differentiation during embryogenesis. Furthermore, immunohistochemistry and movement analysis showed that lingo1b was involved in the axon development of primary motor neurons. These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development.

  2. Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1

    DEFF Research Database (Denmark)

    Bassan, Merav; Liu, Hongguang; Madsen, Kenneth L

    2008-01-01

    with the PDZ domain protein PICK1, which plays a critical role in regulating the expression of glutamate receptors at excitatory synapses. A yeast two-hybrid screen of a neuronal library using the carboxyl tail of GLT1b yielded clones expressing PICK1. The GLT1b C-terminal peptide bound to PICK1 with high...... affinity (K(i) = 6.5 +/- 0.4 microM) in an in vitro fluorescence polarization assay. We also tested peptides based on other variants of GLT1 and other glutamate transporters. GLT1b co-immunoprecipitated with PICK1 from rat brain lysates and COS7 cell lysates derived from cells transfected with plasmids...... expressing PICK1 and GLT1b. In addition, expression of GLT1b in COS7 cells changed the distribution of PICK1, bringing it to the surface. GLT1b and PICK1 co-localized with each other and with synaptic markers in hippocampal neurons in culture. Phorbol ester, an activator of protein kinase C (PKC), a known...

  3. 4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B.

    Science.gov (United States)

    Zhi, Ying; Gao, Li-Xin; Jin, Yi; Tang, Chun-Lan; Li, Jing-Ya; Li, Jia; Long, Ya-Qiu

    2014-07-15

    Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.

  4. Association of PTP1B with Outcomes of Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy

    Science.gov (United States)

    Rivera Franco, Monica M.; Leon Rodriguez, Eucario; Martinez Benitez, Braulio; Villanueva Rodriguez, Luisa G.; de la Luz Sevilla Gonzalez, Maria; Armengol Alonso, Alejandra

    2016-01-01

    PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients’ responses were graded according to the Miller–Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded. PMID:27840578

  5. Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1.

    Directory of Open Access Journals (Sweden)

    Rita Fragoso

    Full Text Available Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL. mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1.

  6. Expression of the novel gene NM23-H1B in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    LI Wen; LIU Yan; JIN Zhi-Jun; FENG You-ji; XU Ling-ling

    2005-01-01

    Objective:To study the expression of the human novel gene NM23-H1B in ovarian cancer. Methods: Totally 24 samples from patients with epithelial ovarian tumor at different clinical stages and 4 from normal ovaries were examined for NM23-H1B mRNA expression by RT-PCR and Northern blot. Results: All samples expressed NM23-H1B mRNA through RT-PCR, while the level of expression in ovarian tumor was higher than that of normal ovary. The results of Northern blot showed that NM23-H1B was overexpressed in ovarian cancer while lowexpressed in normal ovary or low malignant potential (LMP). The level of expression at early stage cancer(stageⅠand Ⅱ) was higher than those in advanced cancer(stage Ⅲ and Ⅳ). In early stage carcinoma, the expression level was involved in the differentiation of tumor cell, and well-differentiated cancer expressed NM23-H1B mRNA in comparatively higher level. Conclusion: The novel gene NM23-N1B is closely correlated with the ovarian cancer.

  7. Identification of a hemerythrin-like domain in a P1B-type transport ATPase†

    Science.gov (United States)

    Traverso, Matthew E.; Subramanian, Poorna; Davydov, Roman; Hoffman, Brian M.; Stemmler, Timothy L.; Rosenzweig, Amy C.

    2010-01-01

    The P1B-type ATPases couple the energy of ATP hydrolysis to metal ion translocation across cell membranes. Important for prokaryotic metal resistance and essential metal distribution in eukaryotes, P1B-ATPases are divided into subclasses on the basis of their metal substrate specificities. Sequence analysis of putative P1B-5-ATPases, for which the substrate has not been identified, led to the discovery of a C-terminal soluble domain homologous to hemerythrin (Hr) proteins and domains. The Hr domain from the Acidothermus cellulolyticus P1B-5-ATPase was cloned, expressed, and purified (P1B-5-Hr). P1B-5-Hr binds two iron ions per monomer and adopts a predominantly helical fold. Optical absorption features of the iron-loaded and azide-treated protein are consistent with features observed for other Hr proteins. Autooxidation to the met form is very rapid, as reported for other prokaryotic Hr domains. The presence of a diiron center was confirmed by electron paramagnetic resonance (EPR) and X-ray absorption spectroscopic (XAS) data. The occurrence of a Hr-like domain in a P-type ATPase is unprecedented and suggests new regulatory mechanisms as well as an expanded function for Hr proteins in biology. PMID:20672819

  8. Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer.

    Science.gov (United States)

    McFadyen, M C; Cruickshank, M E; Miller, I D; McLeod, H L; Melvin, W T; Haites, N E; Parkin, D; Murray, G I

    2001-07-20

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P = 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary.

  9. Convenient Synthesis of Bis(oxazoline) Dicarboxylate Derivatives

    Institute of Scientific and Technical Information of China (English)

    Bin FU; Da Ming DU; Qing XIA

    2004-01-01

    The synthesis of bis(oxazoline) dicarboxylate derivatives was investigated.Diethyl-aminosulfur trifluoride(DAST)was used as a convenient cyclization reagent in the synthesis of bis(oxazoline)dicarboxylate derivatives,which can not be obtained by the general method using MsCl and Et3N as dehydrating cyclization reagent.

  10. Accelerated optical holographic recording using bis-DNO

    DEFF Research Database (Denmark)

    Rasmussen, Palle H.; Ramanujam, P.S.; Hvilsted, Søren

    1999-01-01

    The design, synthesis and optical holographic recording properties of bis-DNO are reported. Bis-DNO is composed of two identical azobenzene oligoornithine segments (DNO) connected via a dipeptide linker. The two segments were assembled in a parallel fashion at the two amino groups of the dipeptide...

  11. Synthesis, spectral and structural properties of bis-imidazoline selones

    Indian Academy of Sciences (India)

    Arruri Sathyanarayana; Katam Srinivas; Anindita Mandal; Saswati Gharami; Ganesan Prabusankar

    2014-09-01

    New biphenyl derivatives of bis-imidazoline selones were synthesized in good yield and characterized by multinuclear (1D and 2D) NMR and UV-vis studies. The solid state structures of bis-imidazoline selones were further confirmed by single crystal X ray diffraction technique.

  12. Bis-perfluoroalkylation of aromatic compounds with sodium perfluoroalkanesulfinates

    Institute of Scientific and Technical Information of China (English)

    LIU, Jin-Tao(刘金涛); LU, He-Jun(吕贺军)

    2000-01-01

    Bis-perfluoroalkylation of aromatic compounds such as dimethoxybenzenes (2,4,6), anisole (8), pyridine (10) and quinoline (13) was accomplished by reaction with excess sodium perfluoroalkanesulfinates, RFSO2Na (1), in the presence of Mn(OAc)3·2H2O under mild conditions. The reaction provides a facile method for the synthesis of bis-perfluoroalkylated aromatic compounds.

  13. INVESTIGATION OF SPECIFIC AB2 TYPE HYPERBRANCHED POLYESTERIFICATION REACTION WITH MONTE CARLO SIMULATION

    Institute of Scientific and Technical Information of China (English)

    Long Wang; Xiao-mei Yang; Xue-hao He

    2013-01-01

    The AB2 type bulk polymerization of 3,5-bis(trimethylsiloxy)benzoyl chloride is studied by the reactive 3d bond fluctuation lattice model (3d-BFLM).Through tuning the reactivity parameters,the experimental data are fitted well via an iterative dichotomy method.By using the optimized reactivity parameters,the number-average degree of polymerization and degree of branching obtained in simulation are very close to experimental data.Meanwhile,the information about the weight-average degree of polymerization and the polydispersity index is provided,and the internal structural properties of hyperbranched polyesters are investigated.Simulation results demonstrate that the 3d-BFLM can be used to study specific hyperbranched polymerizations semi-quantitatively which is helpful to deep understand the kinetics of reactions and make predictions for specific polymerization systems.

  14. Naringin attenuates the cytotoxicity of hepatotoxin microcystin-LR by the curious mechanisms to OATP1B1- and OATP1B3-expressing cells.

    Science.gov (United States)

    Takumi, Shota; Ikema, Satoshi; Hanyu, Tamami; Shima, Yusuke; Kurimoto, Takashi; Shiozaki, Kazuhiro; Sugiyama, Yasumasa; Park, Ho-Dong; Ando, Seiichi; Furukawa, Tatsuhiko; Komatsu, Masaharu

    2015-03-01

    Microcystin-LR, which is an inhibitor of serine/threonine protein phosphatase (PP)1 and PP2A, induces liver injury by its selective uptake system into the hepatocyte. It is also thought that microcystin-LR induces reactive oxygen species (ROS). We tried to establish the chemical prevention of microcystin-LR poisoning. We investigated the effect of grapefruit flavanone glycoside naringin on cytotoxicity of microcystin-LR using human hepatocyte uptake transporter OATP1B3-expressing HEK293-OATP1B3 cells. We found cytotoxicity of microcystin-LR was attenuated by naringin in a dose dependent manner. The inhibition magnitude of total cellular serine/threonine protein phosphatase activity induced by microcystin-LR was suppressed by naringin. In addition, uptake of microcystin-LR into HEK293-OATP1B3 cells was inhibited by naringin. Furthermore, microcystin-LR induced phosphorylation of p53 was inhibited by naringin. Regardless of the difference in the exposure pattern of pre-processing and post-processing of naringin, the toxicity of microcystin-LR was comparable. These results suggested that naringin is promising remedy as well as preventive medicine for liver damage with microcystin-LR. In addition, involvement of ROS production after exposure to the sublethal concentrations of microcystin-LR in the onset of cytotoxicity was negligible. Therefore, inhibition of microcystin-LR uptake and the pathway other than ROS production would be involved in the effect of naringin on the attenuation of microcystin-LR toxicity.

  15. Analysis of CYP1B1 in pediatric and adult glaucoma and other ocular phenotypes

    Science.gov (United States)

    Reis, Linda M.; Tyler, Rebecca C.; Weh, Eric; Hendee, Kathryn E.; Kariminejad, Ariana; Abdul-Rahman, Omar; Ben-Omran, Tawfeg; Manning, Melanie A.; McCarty, Catherine A.; Kitchner, Terrie E.; Costakos, Deborah

    2016-01-01

    Purpose The CYP1B1 gene encodes an enzyme that is a member of the cytochrome P450 superfamily. Mutations in CYP1B1 have been mainly reported in recessive pediatric ocular phenotypes, such as primary congenital glaucoma (PCG) and congenital glaucoma with anterior segment dysgenesis (CG with ASD), with some likely pathogenic variants also identified in families affected with adult-onset primary open angle glaucoma (POAG). Methods We examined CYP1B1 in 158 pediatric patients affected with PCG (eight), CG with ASD (22), CG with other developmental ocular disorders (11), juvenile glaucoma with or without additional ocular anomalies (26), and ASD or other developmental ocular conditions without glaucoma (91); in addition, a large cohort of adult patients with POAG (193) and POAG-negative controls (288) was examined. Results Recessive pathogenic variants in CYP1B1 were identified in two PCG pedigrees, three cases with CG and ASD, and two families with CG and other ocular defects, such as sclerocornea in one patient and microphthalmia in another individual; neither sclerocornea nor microphthalmia has been previously associated with CYP1B1. Most of the identified causative mutations are new occurrences of previously reported pathogenic alleles with two novel variants identified: a c.1325delC, p.(Pro442Glnfs*15) frameshift allele in a family with PCG and a c.157G>A, p.(Gly53Ser) variant identified in a proband with CG, Peters anomaly, and microphthalmia. Analysis of the family history in the CYP1B1-positive families revealed POAG in confirmed or presumed heterozygous relatives in one family with PCG and two families with ASD/CG; POAG was associated with the c.1064_1076del, p.(Arg355Hisfs*69) allele in two of these pedigrees. Screening of an unrelated POAG cohort identified the same c.1064_1076del heterozygous allele in one individual with sporadic POAG but not in age- and ethnicity-matched POAG-negative individuals. Overall, there was no significant enrichment for mutant

  16. A bis-calixarene from olefin metathesis

    Directory of Open Access Journals (Sweden)

    Shimelis T. Hailu

    2012-06-01

    Full Text Available A ring-closing olefin metathesis reaction of tetrakis(allyloxycalix[4]arene gave the bis calixarene, (15E,40E,60E-65,74-bis(prop-2-en-1-yloxy-13,18,38,43,58,63-hexaoxadodecacyclo[28.26.8.720,36.111,45.151,55.05,57.07,12.019,24.026,64.032,37.044,49.168,72]tetraheptaconta-1,3,5(57,7,9,11,15,19(24,20,22,26,28,30(64,32,34,36,40,44(49,45,47,51,53,55(65,60,68,70,72(74-heptacosaene, C74H68O8. It is a cage formed from two calix[4]arene units joined by butenyl groups at three of the O atoms on the narrow rim. The fourth O atom on each calixarene unit is joined with an allyl group. Each of the calix[4]arene units has a flattened cone conformation in which the allyloxy-substituted aryl group and the opposite aryl group are close together and almost parallel [dihedral angle between planes = 1.09 (11°], and the other two aryl groups are splayed outward [dihedral angle between planes = 79.53 (11°]. No guest molecule (e.g. solvent was observed within the cage. The alkene C atoms of one of the links between the calixarene moieties are disordered over two orientations with occupancies of 0.533 (9 and 0.467 (9.

  17. Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk: a meta-analysis.

    Science.gov (United States)

    Economopoulos, Konstantinos P; Sergentanis, Theodoros N

    2010-07-01

    Cytochrome P450 1B1 (CYP1B1) is a P450 enzyme implicated in the metabolism of exogenous and endogenous substrates. The metabolism of polycyclic aromatic hydrocarbons and other procarcinogens through CYP1B1 may well lead to their activation. Apart from the extensively studied Val432Leu polymorphism, three single nucleotide polymorphisms in CYP1B1 have been studied concerning their potential implication in terms of breast cancer risk: Arg48Gly, Ala119Ser and Asn453Ser. This meta-analysis aims to examine whether the three aforementioned polymorphisms are associated with breast cancer risk. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to December 2009. Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321 cases and 13,379 controls); 11 studies were eligible for Ala119Ser (10,715 cases and 11,678 controls); 12 cases were eligible regarding Asn453Ser (11,630 cases and 14,053 controls). Pooled odds ratios (OR) were appropriately derived form fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg equilibrium was performed. Concerning Arg48Gly, the pooled ORs (95% CI) were 0.933 (0.808-1.078) for heterozygous and 0.819 (0.610-1.100) for homozygous Gly subjects. Regarding Ala119Ser, the pooled ORs were 0.992 (0.896-1.097) for heterozygous and 0.935 (0.729-1.198) for homozygous Ser subjects. With respect to Asn453Ser, the pooled ORs were 0.961 (0.906-1.019) for heterozygous and 0.984 (0.846-1.144) for homozygous Ser subjects. In conclusion, this meta-analysis suggests that CYP1B1 Arg48Gly, Ala119Ser and Asn453Ser polymorphisms are not associated with breast cancer risk. Studies on Chinese populations are needed, to elucidate race-specific effects on East Asian populations, if any.

  18. Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes

    Directory of Open Access Journals (Sweden)

    Ziegler-Heitbrock Loems

    2009-10-01

    Full Text Available Abstract Background Cytochrome P450 monoxygenases play an important role in the defence against inhaled toxic compounds and in metabolizing a wide range of xenobiotics and environmental contaminants. In ambient aerosol the ultrafine particle fraction which penetrates deeply into the lungs is considered to be a major factor for adverse health effects. The cells mainly affected by inhaled particles are lung epithelial cells and cells of the monocyte/macrophage lineage. Results In this study we have analyzed the effect of a mixture of fine TiO2 and ultrafine carbon black Printex 90 particles (P90 on the expression of cytochrome P450 1B1 (CYP1B1 in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines. CYP1B1 expression is strongly down-regulated by P90 in monocytes with a maximum after P90 treatment for 3 h while fine and ultrafine TiO2 had no effect. CYP1B1 was down-regulated up to 130-fold and in addition CYP1A1 mRNA was decreased 13-fold. In vitro generated monocyte-derived macrophages (MDM, epithelial cell lines, and primary bronchial epithelial cells also showed reduced CYP1B1 mRNA levels. Benzo[a]pyrene (BaP is inducing CYB1B1 but ultrafine P90 can still down-regulate gene expression at 0.1 μM of BaP. The P90-induced reduction of CYP1B1 was also demonstrated at the protein level using Western blot analysis. Conclusion These data suggest that the P90-induced reduction of CYP gene expression may interfere with the activation and/or detoxification capabilities of inhaled toxic compounds.

  19. Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B

    Institute of Scientific and Technical Information of China (English)

    Yong WU; Jing-ping OU-YANG; Ke WU; Ya WANG; Yun-feng ZHOU; Chong-yuan WEN

    2005-01-01

    Aim: To examine the effects ofAstragalus polysaccharide (APS), a component of an aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction, and its potential role in the amelioration of insulin resistance.Methods: Ten-week-old fat-fed streptozotocin (STZ)-treated rats, an animal model of type Ⅱ diabetes mellitus (TIIDM), were treated with APS (400 mg/kg po) for 5 weeks. Insulin sensitivity was identified by the insulin-tolerance test. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle and liver were performed by immunoprecipitation or Western blotting. PTP1B activity was measured by an assay kit. Results: The diabetic rats responded to APS with a significant decrease in body weight, plasma glucose, and improved insulin sensitivity. The activity and expression of PTP1B were elevated in the skeletal muscle and liver of TIIDM rats. Thus the insulin signaling in target tissues was diminished. APS reduced both PTP1B protein level and activity in the muscle,but not in the liver of TIIDM rats. Insulin-induced tyrosine phosphorylation of the IR β-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle,but not in the liver of APS-treated TIIDM rats. There was no change in the activity or expression of PTP1B in APS-treated normal rats, and blood insulin levels did not change in TIIDM rats after treatment with APS. Conclusion: APS enables insulin-sensitizing and hypoglycemic activity at least in part by decreasing the elevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats.

  20. Myelin protein zero gene sequencing diagnoses Charcot-Marie-Tooth Type 1B disease

    Energy Technology Data Exchange (ETDEWEB)

    Su, Y.; Zhang, H.; Madrid, R. [Univ. of California, San Francisco, CA (United States)] [and others

    1994-09-01

    Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, affects about 1 in 2600 people in Norway and is found worldwide. CMT Type 1 (CMT1) has slow nerve conduction with demyelinated Schwann cells. Autosomal dominant CMT Type 1B (CMT1B) results from mutations in the myelin protein zero gene which directs the synthesis of more than half of all Schwann cell protein. This gene was mapped to the chromosome 1q22-1q23.1 borderline by fluorescence in situ hybridization. The first 7 of 7 reported CMT1B mutations are unique. Thus the most effective means to identify CMT1B mutations in at-risk family members and fetuses is to sequence the entire coding sequence in dominant or sporadic CMT patients without the CMT1A duplication. Of the 19 primers used in 16 pars to uniquely amplify the entire MPZ coding sequence, 6 primer pairs were used to amplify and sequence the 6 exons. The DyeDeoxy Terminator cycle sequencing method used with four different color fluorescent lables was superior to manual sequencing because it sequences more bases unambiguously from extracted genomic DNA samples within 24 hours. This protocol was used to test 28 CMT and Dejerine-Sottas patients without CMT1A gene duplication. Sequencing MPZ gene-specific amplified fragments identified 9 polymorphic sites within the 6 exons that encode the 248 amino acid MPZ protein. The large number of major CMT1B mutations identified by single strand sequencing are being verified by reverse strand sequencing and when possible, by restriction enzyme analysis. This protocol can be used to distringuish CMT1B patients from othre CMT phenotypes and to determine the CMT1B status of relatives both presymptomatically and prenatally.

  1. The CYP1B1 Leu432Val polymorphism and risk of urinary system cancers.

    Science.gov (United States)

    Liu, Yi; Lin, Chang-sheng; Zhang, Ai-min; Song, Hua; Fan, Chang-chun

    2014-05-01

    The cytochrome P450 1B1 (CYP1B1) gene plays a key role in the metabolism of various carcinogens. The CYP1B1 Leu432Val polymorphism leads to leucine to valine substitution at codon 432. A lot of studies have shown that the CYP1B1 Leu432Val polymorphism was associated with urinary system cancers, especially prostate cancer. However, the results were still inconclusive. In this meta-analysis, by searching online databases and references of related reviews, we identified 17 eligible studies to assess the relationship between CYP1B1 Leu432Val polymorphism and urinary system cancers, including 7,783 cancer cases and 7,238 controls. By pooling all eligible studies, we found that the CYP1B1 Leu432Val polymorphism was not associated with overall urinary system cancers. However, in subgroup analyses, we found that the variant 432Val allele significantly increased the risk of prostate cancer (Val vs. Leu, odds ratio (OR) = 1.064, 95% confidence interval (CI) 0.981-1.154; Pheterogeneity = 0.002), while no association was found for bladder cancer (Val vs. Leu, OR = 0.942, 95% CI 0.853-1.041; Pheterogeneity = 0.504). No evidence of publication bias was found (Begg's test, P = 0.053; Egger's test, P = 0.073). In conclusion, based on 17 eligible studies, we found that the CYP1B1 Leu432Val polymorphism was associated with an increased risk of prostate cancer, while no association of bladder cancer was observed.

  2. Upstream ORF affects MYCN translation depending on exon 1b alternative splicing

    Directory of Open Access Journals (Sweden)

    Tutrone Giovani

    2009-12-01

    Full Text Available Abstract Background The MYCN gene is transcribed into two major mRNAs: one full-length (MYCN and one exon 1b-spliced (MYCNΔ1b mRNA. But nothing is known about their respective ability to translate the MYCN protein. Methods Plasmids were prepared to enable translation from the upstream (uORF and major ORF of the two MYCN transcripts. Translation was studied after transfection in neuroblastoma SH-EP cell line. Impact of the upstream AUG on translation was evaluated after directed mutagenesis. Functional study with the two MYCN mRNAs was conducted by a cell viability assay. Existence of a new protein encoded by the MYCNΔ1b uORF was explored by designing a rabbit polyclonal antibody against a specific epitope of this protein. Results Both are translated, but higher levels of protein were seen with MYCNΔ1b mRNA. An upstream ORF was shown to have positive cis-regulatory activity on translation from MYCN but not from MYCNΔ1b mRNA. In transfected SH-EP neuroblastoma cells, high MYCN dosage obtained with MYCNΔ1b mRNA translation induces an antiapoptotic effect after serum deprivation that was not observed with low MYCN expression obtained with MYCN mRNA. Here, we showed that MYCNOT: MYCN Overlap Transcript, a new protein of unknown function is translated from the upstream AUG of MYCNΔ1b mRNA. Conclusions Existence of upstream ORF in MYCN transcripts leads to a new level of MYCN regulation. The resulting MYCN dosage has a weak but significant anti-apoptotic activity after intrinsic apoptosis induction.

  3. Seasonally Changing Cryptochrome 1b Expression in the Retinal Ganglion Cells of a Migrating Passerine Bird.

    Directory of Open Access Journals (Sweden)

    Christine Nießner

    Full Text Available Cryptochromes, blue-light absorbing proteins involved in the circadian clock, have been proposed to be the receptor molecules of the avian magnetic compass. In birds, several cryptochromes occur: Cryptochrome 2, Cryptochrome 4 and two splice products of Cryptochrome 1, Cry1a and Cry1b. With an antibody not distinguishing between the two splice products, Cryptochrome 1 had been detected in the retinal ganglion cells of garden warblers during migration. A recent study located Cry1a in the outer segments of UV/V-cones in the retina of domestic chickens and European robins, another migratory species. Here we report the presence of cryptochrome 1b (eCry1b in retinal ganglion cells and displaced ganglion cells of European Robins, Erithacus rubecula. Immuno-histochemistry at the light microscopic and electron microscopic level showed eCry1b in the cell plasma, free in the cytosol as well as bound to membranes. This is supported by immuno-blotting. However, this applies only to robins in the migratory state. After the end of the migratory phase, the amount of eCry1b was markedly reduced and hardly detectable. In robins, the amount of eCry1b in the retinal ganglion cells varies with season: it appears to be strongly expressed only during the migratory period when the birds show nocturnal migratory restlessness. Since the avian magnetic compass does not seem to be restricted to the migratory phase, this seasonal variation makes a role of eCry1b in magnetoreception rather unlikely. Rather, it could be involved in physiological processes controlling migratory restlessness and thus enabling birds to perform their nocturnal flights.

  4. Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies

    Directory of Open Access Journals (Sweden)

    Kalb Suzanne R

    2011-11-01

    Full Text Available Abstract Background Botulism is caused by botulinum neurotoxins (BoNTs, extremely toxic proteins which can induce respiratory failure leading to long-term intensive care or death. Treatment for botulism includes administration of antitoxins, which must be administered early in the course of the intoxication; therefore, rapid determination of human exposure to BoNT is an important public health goal. In previous work, our laboratory reported on Endopep-MS, a mass spectrometry-based activity method for detecting and differentiating BoNT/A, /B, /E, and /F in clinical samples. We also demonstrated that antibody-capture is effective for purification and concentration of BoNTs from complex matrices such as clinical samples. However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical. Results In this work, we evaluated 24 anti-BoNT/B monoclonal antibodies (mAbs for their ability to inhibit the in vitro activity of BoNT/B1, /B2, /B3, /B4, and /B5 and to extract those toxins. Among the mAbs, there were significant differences in ability to extract BoNT/B subtypes and inhibitory effect on BoNT catalytic activity. Some of the mAbs tested enhanced the in vitro light chain activity of BoNT/B, suggesting that BoNT/B may undergo conformational change upon binding some mAbs. Conclusions In addition to determining in vitro inhibition abilities of a panel of mAbs against BoNT/B1-/B5, this work has determined B12.2 and 2B18.2 to be the best mAbs for sample preparation before Endopep-MS. These mAb characterizations also have the potential to assist with mechanistic studies of BoNT/B protection and treatment, which is important for studying alternative therapeutics for botulism.

  5. TD-DFT Study on the Electronic Spectrum Properties of 2,7'-(Ethylene)-bis-8-hydroxyquinoline and Its Derivatives

    Institute of Scientific and Technical Information of China (English)

    LI Zhi-Feng; ZHU Yuan-Cheng; YUAN Kun; KANG Jing-Wan

    2008-01-01

    The structures of 2,7'-(ethylene)-bis-8-hydroxyquinoline and its derivatives were optimized at the ground states using ab initio HF and B3LYP methods. At the same time, the molecular structures of the first singlet excited state for 2,7'-(ethylene)-bis-8-hydroxyquinoline and its derivatives were optimized by CIS/6-31G(d). The absorption and emission spectra based on the above structures were obtained by the time-dependent density functional theory (TD-DFT) by the B3LYP method with the 6-31G(d) basis set. The calculated results of luminescence originate from the electronic transition from the hydroxphenol ring of 8-hydroxyquinoline A to the pyridine ring of 8-hydroxyquinoline B. Their luminescence wave bands can be tuned by different substituents on the ligand of 8-hydroxyquinoline.

  6. Prissättning av Nordic Cab AB:s multifunktionella barnvagn

    OpenAIRE

    Johansson, Daniel,; Severin, Erica

    2009-01-01

      Nordic Cab AB är ett företag som säljer multifunktionella barnvagnar. Dessa barnvagnar har utbytbara delar vilket gör att man kan omvandla dem till en jogging-, cykel-, skid-, hund- eller vandringsvagn. Syftet med denna uppsats är att prissätta Nordic Cab AB:s multifunktionella barnvagn. För att uppnå detta beskriver vi först hur olika faktorer påverkar Nordic Cab AB:s prissättning. Dessa faktorer är företagets mål, kostnader, efterfrågan och konkurrenter. Utifrån dessa faktorer och intervj...

  7. Bis(μ-bis{[4-(2-pyridylpyrimidin-2-yl]sulfanyl}methanedisilver(I bis(perchlorate

    Directory of Open Access Journals (Sweden)

    Hai-Bin Zhu

    2010-12-01

    Full Text Available In the macrocyclic centrosymmetric dinuclear complex, [Ag2(C19H14N6S22](ClO42, the AgI atom, bis{[4-(2-pyridylpyrimidin-2-yl]sulfanyl}methane (2-bppt ligand and perchlorate anion each lie on a twofold rotation axis. The 2-bppt ligand chelates two four-coordinated AgI atoms through its two bipyridine-like arms. The O atoms of the perchlorate anion are disordered each over two positions of equal occupancy. Adjacent complex molecules are linked by π–π interactions between the pyridine and pyrimidine rings [centroid–centroid distance = 3.663 (8 Å].

  8. Bis[N,N-bis(diphenylphosphanylpentylamine-κ2P,P′]platinum(II bis(hexafluoridophosphate dichloromethane disolvate

    Directory of Open Access Journals (Sweden)

    Ilana Engelbrecht

    2010-08-01

    Full Text Available The PtII atom in the title compound, [Pt(C29H31NP22](PF62·2CH2Cl2, is coordinated by four P atoms from two bis(diphenylphosphanylpentylamine ligands with an average Pt—P distance of 2.300 (1 Å. The coordination around the PtII atom shows a highly distorted square-planar geometry, as evidenced by the P—Pt—P bite angles of 70.45 (3 and 70.64 (3°. The asymmetric unit contains two hexafluoridophosphate ions, the metal complex and two dichloromethane solvent molecules. One of the chloride atoms of one of the dichloromethane molecules is disordered over two sites in a 0.515 (3:0.485 (3 ratio. C—H...F hydrogen bonds stabilize the crystal packing.

  9. Could the 5-HT1B receptor inverse agonism affect learning consolidation?

    Science.gov (United States)

    Meneses, A

    2001-03-01

    Diverse evidence indicates that, the 5-HT system might play a role in learning and memory, since it occurs in brain areas mediating such processes and 5-HT drugs modulate them. Hence in this work, in order to explore further 5-HT involvement on learning and memory 5-HT1B receptors' role is investigated. Evidence indicates that SB-224289 (a 5-HT1B receptor inverse agonist) post-training injection facilitated learning consolidation in an associative autoshaping learning task, this effect was partially reversed by GR 127935 (a 5-HT1B/1D receptor antagonist), but unaffected by MDL 100907 (a 5-HT2A receptor antagonist) or ketanserin (a 5-HT1D/2A/7 receptor antagonist) at low doses. Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). SB-224289 did not alter the 8-OH-DPAT (a 5-HT1A/7 receptor agonist) learning facilitatory effect. SB-224289 eliminated the deficit learning produced by the anticholinergic muscarinic scopolamine or the glutamatergic antagonist dizocilpine. Administration of both, GR 127935 (5mg/kg) plus ketanserin (0.01 mg/kg) did not modify learning consolidation; nevertheless, when ketanserin dose was increased (0.1-1.0mg/kg) and SB-224289 dose was maintained constant, a learning facilitation effect was observed. Notably, SB-224289 at 1.0mg/kg potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist mixed GR 127935, which facilitated learning consolidation and this effect was abolished by ketanserin at a higher dose. Collectively, the data confirm and extend the earlier findings with GR 127935 and the effects of non-selective 5-HT(1B) receptor agonists. Clearly 5-HT1B agonists induced a learning deficit which can be reversed with SB-224289. Perhaps more importantly, SB-224289 enhances learning consolidation when given alone and can reverse the deficits

  10. The radioresistance kinase TLK1B protects the cells by promoting repair of double strand breaks

    Directory of Open Access Journals (Sweden)

    De Benedetti Arrigo

    2005-09-01

    Full Text Available Abstract Background The mammalian protein kinase TLK1 is a homologue of Tousled, a gene involved in flower development in Arabidopsis thaliana. The function of TLK1 is not well known, although knockout of the gene in Drosophila or expression of a dominant negative mutant in mouse cells causes loss of nuclear divisions and missegregation of chromosomes probably, due to alterations in chromatin remodeling capacity. Overexpression of TLK1B, a spliced variant of the TLK1 mRNA, in a model mouse cell line increases it's resistance to ionizing radiation (IR or the radiomimetic drug doxorubicin, also likely due to changes in chromatin remodeling. TLK1B is translationally regulated by the availability of the translation factor eIF4E, and its synthesis is activated by IR. The reason for this mechanism of regulation is likely to provide a rapid means of promoting repair of DSBs. TLK1B specifically phosphorylates histone H3 and Asf1, likely resulting in changes in chromatin structure, particularly at double strand breaks (DSB sites. Results In this work, we provide several lines of evidence that TLK1B protects the cells from IR by facilitating the repair of DSBs. First, the pattern of phosphorylation and dephosphorylation of H2AX and H3 indicated that cells overexpressing TLK1B return to pre-IR steady state much more rapidly than controls. Second, the repair of episomes damaged with DSBs was much more rapid in cells overexpressing TLK1B. This was also true for repair of genomic damage. Lastly, we demonstrate with an in vitro repair system that the addition of recombinant TLK1B promotes repair of a linearized plasmid incubated with nuclear extract. In addition, TLK1B in this in vitro system promotes the assembly of chromatin as shown by the formation of more highly supercoiled topomers of the plasmid. Conclusion In this work, we provide evidence that TLK1B promotes the repair of DSBs, likely as a consequence of a change in chromatin remodeling capacity that

  11. Development of a monoclonal antibody against the left wing of ciguatoxin CTX1B: thiol strategy and detection using a sandwich ELISA.

    Science.gov (United States)

    Tsumuraya, Takeshi; Takeuchi, Katsutoshi; Yamashita, Shuji; Fujii, Ikuo; Hirama, Masahiro

    2012-09-01

    Ciguatera fish poisoning (CFP) is a form of food poisoning caused by the ingestion of a variety of reef fish that have accumulated trace amounts of ciguatoxins produced by dinoflagellates of the genus Gambierdiscus through the food chain. CFP affects more than 50,000 people each year. The extremely low level of the causative neurotoxins, ciguatoxins, in fish has hampered the preparation of antibodies for detecting the toxins. In this paper, we describe a thiol strategy for synthesizing a keyhole limpet hemocyanin (KLH)-conjugate (20) of the ABCDE-ring fragment of the Pacific ciguatoxins, CTX1B (1) and 54-deoxyCTX1B (4). We succeeded in producing a monoclonal antibody (3G8) against the left wings of these ciguatoxins by immunizing mice with the hapten-KLH conjugate (20) as the synthetic antigen. The most promising mAb, 3G8, does not cross-react with other related marine toxins. Sandwich enzyme-linked immunosorbent assay (ELISA) utilizing 3G8 and the previously prepared monoclonal antibody (8H4) enabled us to detect 1 specifically at less than 0.28 ng/mL.

  12. Anti-atherogenic peptide Ep1.B derived from apolipoprotein E induces tolerogenic plasmacytoid dendritic cells.

    Science.gov (United States)

    Bellemore, S M; Nikoopour, E; Au, B C Y; Krougly, O; Lee-Chan, E; Haeryfar, S M; Singh, B

    2014-09-01

    Tolerogenic dendritic cells (DCs) play a critical role in the induction of regulatory T cells (Tregs ), which in turn suppress effector T cell responses. We have previously shown the induction of DCs from human and mouse monocytic cell lines, mouse splenocytes and human peripheral blood monocytes by a novel apolipoprotein E (ApoE)-derived self-peptide termed Ep1.B. We also showed that this C-terminal region 239-252 peptide of ApoE has strong anti-atherogenic activity and reduces neointimal hyperplasia after vascular surgery in rats and wild-type as well as ApoE-deficient mice. In this study, we explored the phenotype of DC subset induced by Ep1.B from monocytic cell lines and from the bone marrow-derived cells. We found Ep1.B treatment induced cells that showed characteristics of plasmacytoid dendritic cells (pDC). We explored in-vitro and in-vivo effects of Ep1.B-induced DCs on antigen-specific T cell responses. Upon in-vivo injection of these cells with antigen, the subsequent ex-vivo antigen-specific proliferation of lymph node cells and splenocytes from recipient mice was greatly reduced. Our results suggest that Ep1.B-induced pDCs promote the generation of Treg cells, and these cells contribute to the induction of peripheral tolerance in adaptive immunity and potentially contribute its anti-atherogenic activity.

  13. Propagation of dysbindin-1B aggregates: exosome-mediated transmission of neurotoxic deposits.

    Science.gov (United States)

    Zhu, C-Y; Shen, Y; Xu, Q

    2015-04-16

    Given the detection of aggregated deposits in chronic mental diseases (CMD), the disturbance of proteostasis in those diseases is receiving increasing attention. The study of aggregated proteins can contribute to our understanding of the chronic and progressive condition of such diseases. Dysbindin, encoded by the schizophrenia susceptibility gene DTNBP1, has been reported to co-aggregate with DISC1. However, there has been no evidence to date on the aggregation tendency of dysbindin. Therefore, we investigated the isoform-specific aggregation of dysbindin. We found that dysbindin-1B aggregated into cell-invasive deposits in mice. Because of the efficient propagation of dysbindin-1B, we further studied the mechanism of propagation and identified it as exosome-mediated transmission of the aggregates. In addition, aggregates of dysbindin-1B were toxic. Through exosome-mediated propagation, the deposits of dysbindin-1B exerted toxic effects on recipient neurons a long distance away from the initial aggregation site in mice brain. The rapid long distance propagation of neurotoxic deposits of dysbindin-1B in affected neuronal circuitry indicates a possible mechanism for the progressive deterioration of neurons and cognitive function in CMD.

  14. Adherence to interferon β-1b treatment in patients with multiple sclerosis in Spain.

    Directory of Open Access Journals (Sweden)

    Oscar Fernández

    Full Text Available BACKGROUND: Adherence to interferon β-1b (INFβ-1b therapy is essential to maximize the beneficial effects of treatment in multiple sclerosis (MS. For that reason, the main objectives of this study are to assess adherence to INFβ-1b in patients suffering from MS in Spain, and to identify the factors responsible for adherence in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational, retrospective, cross-sectional study including 120 Spanish patients with MS under INFβ-1b treatment. Therapeutic adherence was assessed with Morisky-Green test and with the percentage of doses received. The proportion of adherent patients assessed by Morisky-Green test was 68.3%, being indicative of poor adherence. Nevertheless, the percentage of doses received, which was based on the number of injected medication, was 94.3%. The main reason for missing INFβ-1b injections was forgetting some of the administrations (64%. Therefore, interventions that diminish forgetfulness might have a positive effect in the proportion of adherent patients and in the percentage of doses received. In addition, age and comorbidities had a significant effect in the number of doses injected per month, and should be considered in the management of adherence in MS patients. CONCLUSION/SIGNIFICANCE: Among all the available methods for assessing adherence, the overall consumption of the intended dose has to be considered when addressing adherence.

  15. Vasopressin V1a and V1b receptors: from molecules to physiological systems.

    Science.gov (United States)

    Koshimizu, Taka-aki; Nakamura, Kazuaki; Egashira, Nobuaki; Hiroyama, Masami; Nonoguchi, Hiroshi; Tanoue, Akito

    2012-10-01

    The neurohypophysial hormone arginine vasopressin (AVP) is essential for a wide range of physiological functions, including water reabsorption, cardiovascular homeostasis, hormone secretion, and social behavior. These and other actions of AVP are mediated by at least three distinct receptor subtypes: V1a, V1b, and V2. Although the antidiuretic action of AVP and V2 receptor in renal distal tubules and collecting ducts is relatively well understood, recent years have seen an increasing understanding of the physiological roles of V1a and V1b receptors. The V1a receptor is originally found in the vascular smooth muscle and the V1b receptor in the anterior pituitary. Deletion of V1a or V1b receptor genes in mice revealed that the contributions of these receptors extend far beyond cardiovascular or hormone-secreting functions. Together with extensively developed pharmacological tools, genetically altered rodent models have advanced the understanding of a variety of AVP systems. Our report reviews the findings in this important field by covering a wide range of research, from the molecular physiology of V1a and V1b receptors to studies on whole animals, including gene knockout/knockdown studies.

  16. GENETIC VARIATION IN THE ALPHA1B - ADRENERGIC RECEPTOR AND VASCULAR RESPONSE

    Science.gov (United States)

    Adefurin, Abiodun; Ghimire, Laxmi V.; Kohli, Utkarsh; Muszkat, Mordechai; Sofowora, Gbenga G.; Li, Chun; Levinson, Rebecca T.; Paranjape, Sachin Y.; Stein, C. Michael; Kurnik, Daniel

    2016-01-01

    α1B- adrenergic receptors contribute to vasoconstriction in humans. We tested the hypothesis that variation in the ADRA1B gene contributes to interindividual variability and ethnic differences in adrenergic vasoconstriction. We measured dorsal hand vein responses to increasing doses of phenylephrine in 64 Caucasians and 41 African-Americans and genotyped 34 ADRA1B variants. We validated findings in another model of catecholamine-induced vasoconstriction, the increase in mean arterial pressure (ΔMAP) during a cold pressor test (CPT). One ADRA1B variant, rs10070745, present in 14 African-American heterozygotes but not in Caucasians, was associated with a lower phenylephrine ED50 (geometric mean [95% CI], 144 [69–299] ng/ml) compared to 27 African-American non-carriers (208 [130–334] ng/ml; P=0.015) and contributed to the ethnic differences in ED50. The same variant was also associated with a greater ΔMAP during CPT (P=0.008). In conclusion, ADRA1B rs10070745 was significantly associated with vasoconstrictor responses after adrenergic stimulation and contributed to the ethnic difference in phenylephrine sensitivity. PMID:27089938

  17. Near-uv and optical observations of the transiting hot Jupiter WASP-1b

    Science.gov (United States)

    Pearson, K. A.; Zellem, R.; Biddle, L. I.; Amaya, H.; Watson, Z.; Griffith, C.; Small, L.; Hume, J.

    2014-03-01

    We present simultaneous near-UV (U-band) and optical (B-band) photometric observations of the primary transit of the highly irradiated, hot-Jupiter WASP-1b on the Kuiper 61" telescope. We use our results to search for timing transit variations, which would indicate additional planets, and provide new constraints on WASP-1b's physical parameters. Assuming the opacity at these two photometric bands is dominated by Rayleigh scattering by molecular hydrogen, we can place strong upper limits on its radius. Such constraints can limit the degeneracy between an exoplanet's physical radius and atmospheric composition in radiative transfer retrievals. Additionally its host star is chromospherically active and WASP-1b orbits within in the co-rotation radius of the star making it likely that WASP-1b has a bowshock. Therefore, we will search for a planetary magnetic field as indicated by an early ingress in the near-UV light curve compared to the optical due to the bowshock itself. Such measurements would confirm the observational methodology of detecting magnetic fields around transiting exoplanets, place an upper limit on WASP-1b's magnetic field strength, and confirm previous theoretical estimations of hot Jupiter magnetic fields.

  18. Organic anion transporting polypeptide-1B1 haplotypes in Chinese patients

    Institute of Scientific and Technical Information of China (English)

    Lin-yong XU; Hong-hao ZHOU; Zhen-qiu SUN; Yi-jing HE; Wei ZHANG; Sheng Deng; Qing LI; Wei-xia ZHANG; Zhao-qian LIU; Dan WANG; Yuan-fei HUANG

    2007-01-01

    Aim: To detect 388G>A and 521T>C variant alleles in the organic anion transporting polypeptide- 1B 1 (OATP 1B 1, encoding gene SLCOIB1) gene. Methods:One hundred and eleven healthy volunteers were screened for OATPIB 1 alleles in our study. PCR-restriction fragment length polymorphism was used to identify the 388G>A polymorphism and a 1-step tetra-primer method was developed for the determination of 521T>C mutation. Results: The frequencies of the 388G>A and 521T>C variant alleles in the Chinese population were 73.4%and 14.0%,respectively. The frequencies of the SLCO1BI*lb and *15 haplotypes were 59.9% and 14.0%, respectively. Conclusion: The SLCO1B1*1b and SLCO1B1*15 variants are relatively common in the Chinese population. Their frequencies are similar to that in the Japanese, but significantly different from that in Caucasians and blacks.

  19. Planktic Foraminiferal Turnover and Stable Isotope Stratigraphy Across OAE1B in the Subtropical North Atlantic

    Science.gov (United States)

    Huber, B. T.; Price, N. A.; MacLeod, K. G.

    2003-12-01

    Stable isotope data generated from glassy (diagenetically unaltered) foraminifera from the subtropical North Atlantic (ODP Site 1049) reveal abrupt paleoceanographic and faunal changes that coincide with the Aptian/Albian boundary and the onset of Oceanic Anoxic Event (OAE) 1b. At least three planktic and one benthic species per sample, selected at closely spaced intervals from the Globigerinelloides algerianus Zone (mid-Aptian) through uppermost Ticinella bejaouaensis Zone (uppermost Aptian), reveal a consistently low (<1.1‰ ) vertical δ 18O gradient, suggesting that the thermocline was weakly developed throughout this time. Benthic δ 18O values show a slight positive increase from +0.5 ‰ during the mid-Aptian to +1.1% during the latest Aptian, then decrease to -0.2‰ during peak Corg deposition in OAE 1b (Hedbergella rischi Zone, lowermost Albian). Assuming that the δ 18O composition of Cretaceous seawater averaged -1.2‰ and polar ice sheets were absent or very small, we estimate that middle bathyal waters at this site ranged from 7-9° C during the mid-late Aptian and warmed to 12° C during OAE 1b peak Corg deposition. Mid-late Aptian upper surface waters ranged from 11-12° C, then warmed to 20° C during OAE 1b. The simultaneous change in planktic foraminifer assemblages and stable isotope values indicates that the onset of OAE 1b involved major changes in the North Atlantic climate and oceanography.

  20. Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients.

    Science.gov (United States)

    Rizzo, Roberta; Spaggiari, Federica; Indelli, Monica; Lelli, Giorgio; Baricordi, Olavio R; Rimessi, Paola; Ferlini, Alessandra

    2010-11-01

    Taxanes represent a group of anticancer drugs with a wide range of activity against breast cancer. Therapy side effects include haematologic toxicity (neutropenia, leucopenia), peripheral neuropathy and hypersensitivity, and demonstrate inter-individual variations. Since it is known that three genes are implicated in taxane turnover, namely ABCB1 in the transport, CYP2C8 in the metabolism and CYP1B1 in the activity, we explored the association among polymorphisms (single nucleotide polymorphisms, SNPs) in these three genes and the occurrence of taxane-induced toxicity. We studied 95 patients affected by breast cancer and under treatment with taxanes as adjuvant, metastatic or neo-adjuvant therapy. We genotyped them for SNPs in the CYP2C8 (alleles *1, *2, *3 and *4), CYP1B1 (alleles *1 and *3) and ABCB1 (1236 C>T; 2677 G>T/A; 3435 C>T) genes by real-time PCR assay. We observed a significant association between the CYP1B1*3 allele and a lower occurrence of hypersensitivity reactions to taxane treatment. We speculate that the highest production of 4-hydroxyestradiol (4-OHE2) metabolite by CYP1B1*3 allele could increase the formation of the 4-OHE2-taxane adduct and possibly inhibit taxane toxicity. We suggest that CYP1B1 might affect taxane hypersensitivity therefore representing, if confirmed in a large cohort of patients, an exploratory hypersensitivity predictive biomarker.

  1. CYP1B1 polymorphisms and k-ras mutations in patients with pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Crous-Bou, Marta; De Vivo, Immaculata; Porta, Miquel; Pumarega, José A; López, Tomàs; Alguacil, Joan; Morales, Eva; Malats, Núria; Rifà, Juli; Hunter, David J; Real, Francisco X

    2008-05-01

    The frequency of CYP1B1 polymorphisms in pancreatic cancer has never been reported. There is also no evidence on the relationship between CYP1B1 variants and mutations in ras genes (K-, H- or N-ras) in any human neoplasm. We analyzed the following CYP1B1 polymorphisms in 129 incident cases of pancreatic ductal adenocarcinoma (PDA): the m1 allele (Val to Leu at codon 432) and the m2 allele (Asn to Ser at codon 453). The calculated frequencies for the m1 Val and m2 Asn alleles were 0.45 and 0.68, respectively. CYP1B1 genotypes were out of Hardy-Weinberg equilibrium; this was largely due to K-ras mutated PDA cases. The Val/Val genotype was over five times more frequent in PDA cases with a K-ras mutation than in wild-type cases (OR = 5.25; P = 0.121). In PDA, polymorphisms in CYP1B1 might be related with K-ras activation pathways.

  2. MAP1B Regulates Axonal Development by Modulating Rho-GTPase Rac1 Activity

    Science.gov (United States)

    Montenegro-Venegas, Carolina; Tortosa, Elena; Rosso, Silvana; Peretti, Diego; Bollati, Flavia; Bisbal, Mariano; Jausoro, Ignacio; Avila, Jesus; Cáceres, Alfredo

    2010-01-01

    Cultured neurons obtained from MAP1B-deficient mice have a delay in axon outgrowth and a reduced rate of axonal elongation compared with neurons from wild-type mice. Here we show that MAP1B deficiency results in a significant decrease in Rac1 and cdc42 activity and a significant increase in Rho activity. We found that MAP1B interacted with Tiam1, a guanosine nucleotide exchange factor for Rac1. The decrease in Rac1/cdc42 activity was paralleled by decreases in the phosphorylation of the downstream effectors of these proteins, such as LIMK-1 and cofilin. The expression of a constitutively active form of Rac1, cdc42, or Tiam1 rescued the axon growth defect of MAP1B-deficient neurons. Taken together, these observations define a new and crucial function of MAP1B that we show to be required for efficient cross-talk between microtubules and the actin cytoskeleton during neuronal polarization. PMID:20719958

  3. Extreme differences in SLCO1B3 functional polymorphisms in Roma and Hungarian populations.

    Science.gov (United States)

    Nagy, Agnes; Szalai, Renata; Magyari, Lili; Bene, Judit; Toth, Kalman; Melegh, Bela

    2015-05-01

    Variants in SLCO1B3 transporter are linked to disposition and uptake of drugs and show high degree of heterogeneity between populations. A total of 467 Roma and 448 Hungarian subjects were genotyped for SLCO1B3 c.334T>G and c.1683-5676A>G variant alleles by PCR-RFLP assay and direct sequencing. We found significant differences in the frequencies of homozygous variant genotypes of SLCO1B3 334GG (41.54% vs. 8.04%, pRomas and Hungarians. A significantly increased prevalence was found in SLCO1B3 1683-5676G allele frequency in Hungarians compared to the Roma population (15.07% vs. 3.43%, p≤0.001). The frequency of SLCO1B3 334G allele was significantly increased in Roma population compared to Hungarians (70.56% vs. 52.23%, p=0.001). The LD values between the examined SNPs were 80 and 90 in Roma and in Hungarian samples, respectively. Our results highlight notable pharmacogenetic differences between Roma and Hungarian populations, which may have therapeutic implications.

  4. Lmx1b controls peptide phenotypes in serotonergic and dopaminergic neurons

    Institute of Scientific and Technical Information of China (English)

    Rui Yan; Tianwen Huang; Zhiqin Xie; Guannan Xia; Hui Qian; Xiaolin Zhao; Leping Cheng

    2013-01-01

    Serotonin (5-HT) neurons synthesize a variety of peptides.How these peptides are controlled during development remains unclear.It has been reported that the co-localization of peptides and 5-HT varies by species.In contrast to the situations in the rostral 5-HT neurons of human and rat brains,several peptides do not coexist with 5-HT in the rostral 5-HT neurons of mouse brain.In this study,we found that the peptide substance P and peptide genes,including those encoding peptides thyrotropin-releasing hormone,enkephalin,and calcitonin gene-related peptide,were expressed in the caudal 5-HT neurons of mouse brain; these findings are in line with observations in rat and monkey 5-HT neurons.We also revealed that these peptides/peptide genes partially overlapped with the transcription factor Lmx1b that specifies the 5-HT cell fate.Furthermore,we found that the peptide cholecystokinin was expressed in developing dopaminergic neurons and greatly overlapped with Lmx1b that specifies the dopaminergic cell fate.By examining the phenotype of Lmx1b deletion mice,we found that Lmx1b was required for the expression of above peptides expressed in 5-HT or dopaminergic neurons.Together,our results indicate that Lmx1b,a key transcription factor for the specification of 5-HT and dopaminergic transmitter phenotypes during embryogenesis,determines some peptide phenotypes in these neurons as well.

  5. Radio Continuum Sources Associated with AB Aur

    CERN Document Server

    Rodríguez, L F; Ho, P T P; Rodriguez, Luis F.; Zapata, Luis; Ho, Paul T. P.

    2006-01-01

    We present high angular resolution, high-sensitivity Very Large Array observations at 3.6 cm of the Herbig Ae star AB Aur. This star is of interest since its circumstellar disk exhibits characteristics that have been attributed to the presence of an undetected low mass companion or giant gas planet. Our image confirms the continuum emission known to exist in association with the star, and detects a faint protuberance that extends about $0\\rlap.{''}3$ to its SE. Previous theoretical considerations and observational results are consistent with the presence of a companion to AB Aur with the separation and position angle derived from our radio data. We also determine the proper motion of AB Aur by comparing our new observations with data taken about 17 years ago and find values consistent with those found by Hipparcos.

  6. Bis[N,N'-bis(diphenylmethylene)ethylenediamine-2N,N']copper(I) dichlorocuprate(I)

    NARCIS (Netherlands)

    Mirkhani, Valiollah; Harkema, Sybolt; Kia, Reza

    2004-01-01

    The 1:1 adduct of N,N'-bis(diphenylmethylene)ethylenediamine (bz2en) with copper(I) chloride, viz. [Cu(C28H24N2)2][CuCl2], has been synthesized. The structure contains cationic moieties of CuI ions (Cu on a twofold axis) coordinated to four N atoms of two bz2en molecules (in a distorted tetrahedron)

  7. Bis[1,3-bis(diphenylphosphanylpropane]copper(I tetrachloridogallate(III

    Directory of Open Access Journals (Sweden)

    Nian-Nian Wang

    2012-07-01

    Full Text Available In the title compound, [Cu(C27H26P22][GaCl4], the CuI atom in the complex cation is P,P′-chelated by two 1,3-bis(diphenylphosphanylpropane ligands in a distorted tetrahedral geometry, while the GaIII cation is coordinated by four chloride anions in a distorted tetrahedral geometry. In the crystal, weak C—H...π interactions occur between adjacent complex cations.

  8. Erythema ab igne (Unilateral due to "Chulla"

    Directory of Open Access Journals (Sweden)

    Sumit Kar

    2014-01-01

    Full Text Available Erythema ab igne (EAI is characterized by localized areas of reticulated erythema and hyperpigmentation due to chronic and repeated exposure to infrared radiation. Taking a good history plays an important role in coming to the diagnosis of the disease condition; and at the same time, the particular cultural practices of a place determine its occurrence in the local masses. Herein we report the case of a young lady in her early thirties who presented to us with a dusky hyperpigmentation over her right arm and leg. Her detailed history and cutaneous examination led to the diagnosis of erythema ab igne.

  9. Involvement of endocrine system in a patient affected by glycogen storage disease 1b: speculation on the role of autoimmunity.

    Science.gov (United States)

    Melis, Daniela; Della Casa, Roberto; Balivo, Francesca; Minopoli, Giorgia; Rossi, Alessandro; Salerno, Mariacarolina; Andria, Generoso; Parenti, Giancarlo

    2014-03-19

    Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases.

  10. CLINICAL INFECTION OF TWO CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) WITH ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 1B.

    Science.gov (United States)

    Fuery, Angela; Tan, Jie; Peng, RongSheng; Flanagan, Joseph P; Tocidlowski, Maryanne E; Howard, Lauren L; Ling, Paul D

    2016-03-01

    The ability of prior infection from one elephant endotheliotropic herpesvirus (EEHV) type to protect against clinical or lethal infection from others remains an important question. This report describes viremia and subsequent shedding of EEHV1B in two juvenile 4-yr-old Asian elephants within 3 wk or 2 mo following significant infections caused by the rarely seen EEHV4. High levels of EEHV1B shedding were detected in the first elephant prior to emergence of infection and viremia in the second animal. The EEHV1B virus associated with both infections was identical to the strain causing infection in two herd mates previously. High EEHV viremia correlated with leukopenia and thrombocytopenia, which was followed by leukocytosis and thrombocytosis when clinical signs started to resolve. The observations from these cases should be beneficial for helping other institutions monitor and treat elephants infected with EEHV1, the most common virus associated with lethal hemorrhagic disease.

  11. HATS-1b: THE FIRST TRANSITING PLANET DISCOVERED BY THE HATSouth SURVEY

    Energy Technology Data Exchange (ETDEWEB)

    Penev, K.; Bakos, G. A.; Hartman, J. D.; Csubry, Z. [Department of Astrophysical Sciences, Princeton University, NJ 08544 (United States); Bayliss, D.; Zhou, G.; Conroy, P. [Australian National University, Canberra (Australia); Jordan, A.; Suc, V.; Rabus, M.; Brahm, R.; Espinoza, N. [Departamento de Astronomia y Astrofisica, Pontificia Universidad Catolica de Chile, Av. Vicuna Mackenna 4860, 7820436 Macul, Santiago (Chile); Mohler, M.; Mancini, L.; Henning, T.; Nikolov, N.; Csak, B. [Max Planck Institute for Astronomy, Heidelberg (Germany); Beky, B.; Noyes, R. W. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA (United States); Buchhave, L., E-mail: kpenev@astro.princeton.edu [Niels Bohr Institute, Copenhagen University (Denmark); and others

    2013-01-01

    We report the discovery of HATS-1b, a transiting extrasolar planet orbiting the moderately bright V = 12.05 G dwarf star GSC 6652-00186, and the first planet discovered by HATSouth, a global network of autonomous wide-field telescopes. HATS-1b has a period of P Almost-Equal-To 3.4465 days, mass of M{sub p} Almost-Equal-To 1.86 M{sub J}, and radius of R{sub p} Almost-Equal-To 1.30 R{sub J}. The host star has a mass of 0.99 M{sub Sun} and radius of 1.04 R{sub Sun }. The discovery light curve of HATS-1b has near-continuous coverage over several multi-day timespans, demonstrating the power of using a global network of telescopes to discover transiting planets.

  12. mBin1b transgenic mice show enhanced resistance to epididymal infection by bacteria challenge.

    Science.gov (United States)

    Fei, Z; Hu, S; Xiao, L; Zhou, J; Diao, H; Yu, H; Fang, S; Wang, Y; Wan, Y; Wang, W; He, Y; Wang, C; Xu, G; Wang, Z; Zhang, Y; Fei, J

    2012-09-01

    The mBin1b is a beta-defensin gene identified in the mouse epididymis. In the current report, its expression pattern and antibacterial activities were characterized, and a transgenic (TG) mouse model was developed in which mBin1b was exclusively overexpressed by up to 50-fold over normal levels in the caput epididymis. The experimental animals are healthy with normal reproductive activity, but are more resistant to epididymal infection from Escherichia coli than normal animals. The expression of IL1α and IL1β in the epididymis was decreased in the TG mice, which suggests that mBin1b has a role in the regulation of inflammatory response in the epididymis.

  13. Distorted Wave Effects of the 1b3g Orbital in Ethylene

    Institute of Scientific and Technical Information of China (English)

    邓景康; 李桂琴; 黄建东; 王芳; 宁传刚; 卢杰; 何垚; 王晓东; 张亦安; 高虹; 王岩; 郑延友

    2002-01-01

    We study the unexpected distorted wave effects of the 1b3g orbital in ethylene using a high resolution binary (e, 2e) electron momentum spectrometer, at an impact energy of 800 eV plus the binding energy (8 - 22 eV) with symmetric non-coplanar kinematics. The experimental momentum profile of the 1bag orbital is obtained and compared with the data previously measured at an impact energy of 1200eV plus the binding energy. Also, the experimental momentum profles of the 1b3g orbital are compared with the theoretical momentum distributions calculated by using Hartree-Fock and density functional theory methods. The experimental momentum profiles of the 1b3g orbital of ethylene at different impact energies show that the cross section of the orbital below the momentum p~l a.u. is higher for lower impact energies.

  14. HATS-1b: The First Transiting Planet Discovered by the HATSouth Survey

    CERN Document Server

    Penev, K; Bayliss, D; Jordán, A; Mohler, M; Zhou, G; Suc, V; Rabus, M; Hartman, J D; Mancini, L; Béky, B; Csubry, Z; Buchhave, L; Henning, T; Nikolov, N; Csák, B; Brahm, R; Espinoza, N; Conroy, P; Noyes, R W; Sasselov, D D; Schmidt, B; Wright, D J; Tinney, C G; Addison, B C; Lázár, J; Papp, I; Sári, P

    2012-01-01

    We report the discovery of HATS-1b, a transiting extrasolar planet orbiting the moderately bright V=12.05 G dwarf star GSC 6652-00186, and the first planet discovered by HATSouth, a global network of autonomous wide-field telescopes. HATS-1b has a period P~3.4465 d, mass Mp~1.86MJ, and radius Rp~1.30RJ. The host star has a mass of 0.99Msun, and radius of 1.04Rsun. The discovery light curve of HATS-1b has near continuous coverage over several multi-day periods, demonstrating the power of using a global network of telescopes to discover transiting planets.

  15. Caring from Afar: Asian H1B Migrant Workers and Aging Parents.

    Science.gov (United States)

    Lee, Yeon-Shim; Chaudhuri, Anoshua; Yoo, Grace J

    2015-09-01

    With the growth in engineering/technology industries, the United States has seen an increase in the arrival of highly skilled temporary migrant workers on H1B visas from various Asian countries. Limited research exists on how these groups maintain family ties from afar including caring for aging parents. This study explores the experiences and challenges that Asian H1B workers face when providing care from a distance. A total of 21 Chinese/Taiwanese, Korean, and Indian H1B workers participated in in-depth qualitative interviews. Key findings indicate that despite distance, caring relationships still continue through regular communications, financial remittances, and return visits, at the same time creating emotional, psychological, and financial challenges for the workers. Findings highlight the need for further research in understanding how the decline of aging parent's health impacts the migrants' adjustment and health in the United States.

  16. sup 1 sup 1 B nutation NMR study of powdered borosilicates

    CERN Document Server

    Woo, A J; Han, D Y

    1998-01-01

    In this work, we applied the 1D sup 1 sup 1 B nutation NMR method for the analysis of the local structural environments in powdered borosilicates (SiO sub 2 -B sub 2 O sub 3). Spin dynamics during a rf irradiation for spin I=3/2 was analytically calculated with a density matrix formalism. Spectral simulation programs were written in MATLAB on a PC. Two borosilicates prepared by the sol-gel process at different stabilization temperature were used for the 1D sup 1 sup 1 B nutation NMR experiment. The sup 1 sup 1 B NMR parameters, quadrupole coupling constants (e sup 2 qQ/h) and asymmetry parameters (eta), for each borosilicate were extracted from the nonlinear least-squares fitting. The effects of heat treatments on the local structures of boron sites in borosilicates were discussed.

  17. Cytokines and adhesion molecules in multiple sclerosis patients treated with interferon-beta1b

    DEFF Research Database (Denmark)

    Jensen, Jakob; Krakauer, Martin; Sellebjerg, Finn

    2005-01-01

    of disease relapses and the development of irreversible symptoms and signs of disease. The mechanism of action of IFN-beta treatment is, however, not completely understood. Previous studies have suggested major effects on mononuclear cell cytokine production and T cell migration, but results have been......Multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS), is thought to be caused by a T cell-mediated attack on CNS myelin and axons. Recombinant interferon (IFN)-beta is an established treatment of multiple sclerosis, and is known to reduce the number...... initiated on de novo treatment with IFN-beta1b. We found only minor associations between the different changes induced by IFN-beta1b-treatment. Our findings are consistent with changes in T cell expression of CD49d/VLA-4 and induction of sVCAM-1 as important effects of treatment with IFN-beta1b in multiple...

  18. Similar frequency of paternal uniparental disomy involving chromosome 20q (patUPD20q) in Japanese and Caucasian patients affected by sporadic pseudohypoparathyroidism type Ib (sporPHP1B).

    Science.gov (United States)

    Takatani, Rieko; Minagawa, Masanori; Molinaro, Angelo; Reyes, Monica; Kinoshita, Kaori; Takatani, Tomozumi; Kazukawa, Itsuro; Nagatsuma, Misako; Kashimada, Kenichi; Sato, Kenichi; Matsushita, Kazuyuki; Nomura, Fumio; Shimojo, Naoki; Jüppner, Harald

    2015-10-01

    Pseudohypoparathyroidism type Ib (PHP1B) is caused by proximal tubular resistance to parathyroid hormone that occurs in most cases in the absence of Albright's Hereditary Osteodystrophy (AHO). Familial forms of PHP1B are caused by maternally inherited microdeletions within STX16, the gene encoding syntaxin 16, or within GNAS, a complex genetic locus on chromosome 20q13.3 encoding Gsα and several splice variants thereof. These deletions lead either to a loss-of-methylation affecting GNAS exon A/B alone or to epigenetic changes involving multiple differentially methylated regions (DMRs) within GNAS. Broad GNAS methylation abnormalities are also observed in most sporadic PHP1B (sporPHP1B) cases. However, with the exception of paternal uniparental disomy involving chromosome 20q (patUPD20q), the molecular mechanism leading to this disease variant remains unknown. We now investigated 23 Japanese sporPHP1B cases, who presented with hypocalcemia, hyperphosphatemia, elevated PTH levels, and occasionally with TSH elevations and mild AHO features. Age at diagnosis was 10.6 ± 1.45 years. Calcium, phosphate, and PTH were 6.3 ± 0.23 mg/dL, 7.7 ± 0.33 mg/dL, and 305 ± 34.5 pg/mL, respectively, i.e. laboratory findings that are indistinguishable from those previously observed for Caucasian sporPHP1B cases. All investigated patients showed broad GNAS methylation changes. Eleven individuals were homozygous for SNPs within exon NESP and a pentanucleotide repeat in exon A/B. Two of these patients furthermore revealed homozygosity for numerous microsatellite markers on chromosome 20q raising the possibility of patUPD20q, which was confirmed through the analysis of parental DNA. Based on this and our previous reports, paternal duplication of the chromosomal region comprising the GNAS locus appears to be a fairly common cause of sporPHP1B that is likely to occur with equal frequency in Caucasians and Asians.

  19. p53/E1b58kDa complex regulates adenovirus replication.

    Science.gov (United States)

    Ridgway, P J; Hall, A R; Myers, C J; Braithwaite, A W

    1997-10-27

    We have explored a role for the adenovirus (Ad5) E1b58kDa/p53 protein complex in adenovirus replication. This was done by using virus mutants containing different defects in the E1b58kDa gene and cell lines that express either a wild-type p53 protein or a mutant p53 protein. We find that infection of wild-type p53-containing cells with wild-type Ad5 causes a shutoff of p53 and alpha-actin protein synthesis by distinct mechanisms, but neither occurs in mutant p53 cells. Our data also indicate that the shutoff is dependent on formation of the p53/E1b complex and may also involve another virus protein, E4ORF6. Following from these observations we asked whether failure to form the complex resulted in impaired adenovirus replication. Our experiments showed that neither wild-type Ad5 nor the E1b mutant dl338 could replicate in cells expressing a mutant p53 protein, but that wild-type adenovirus replicated well in wild-type p53-expressing cells. Collectively, our data suggest that the interaction between p53 and the E1b58kDa protein is necessary for efficient adenovirus replication. This is the first time such a direct link between the complex and virus replication has been demonstrated. These data raise serious questions about the usefulness of E1b-defective viruses in tumor therapy.

  20. STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

    Science.gov (United States)

    Sinreih, Maša; Štupar, Saša; Čemažar, Luka; Verdenik, Ivan; Grazio-Frković, Snježana; Smrkolj, Špela; Rižner, Tea Lanišnik

    2017-02-20

    Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions, in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential STAR and AKR1B10 as

  1. A bis-calixarene from olefin metathesis

    Science.gov (United States)

    Hailu, Shimelis T.; Butcher, Ray J.; Hudrlik, Paul F.; Hudrlik, Anne M.

    2012-01-01

    A ring-closing olefin metathesis reaction of tetra­kis­(all­yl­oxy)calix[4]arene gave the bis­ calixarene, (15E,40E,60E)-65,74-bis­(prop-2-en-1-yl­oxy)-13,18,38,43,58,63-hexa­oxado­deca­cyclo­[28.26.8.720,36.111,45.151,55.05,57.07,12.019,24.026,64.032,37.044,49.168,72]tetra­hepta­conta-1,3,5(57),7,9,11,15,19(24),20,22,26,28,30(64),32,34,36,40,44(49),45,47,51,53,55(65),60,68,70,72(74)-hepta­cosa­ene, C74H68O8. It is a cage formed from two calix[4]arene units joined by butenyl groups at three of the O atoms on the narrow rim. The fourth O atom on each calixarene unit is joined with an allyl group. Each of the calix[4]arene units has a flattened cone conformation in which the all­yloxy-substituted aryl group and the opposite aryl group are close together and almost parallel [dihedral angle between planes = 1.09 (11)°], and the other two aryl groups are splayed outward [dihedral angle between planes = 79.53 (11)°]. No guest mol­ecule (e.g. solvent) was observed within the cage. The alkene C atoms of one of the links between the calixarene moieties are disordered over two orientations with occupancies of 0.533 (9) and 0.467 (9). PMID:22719604

  2. A bis-calixarene from olefin metathesis.

    Science.gov (United States)

    Hailu, Shimelis T; Butcher, Ray J; Hudrlik, Paul F; Hudrlik, Anne M

    2012-06-01

    A ring-closing olefin metathesis reaction of tetra-kis-(all-yl-oxy)calix[4]arene gave the bis- calixarene, (15E,40E,60E)-65,74-bis-(prop-2-en-1-yl-oxy)-13,18,38,43,58,63-hexa-oxado-deca-cyclo-[28.26.8.7(20,36).1(11,45).1(51,55).0(5,57).0(7,12).0(19,24).0(26,64).0(32,37).0(44,49).1(68,72)]tetra-hepta-conta-1,3,5(57),7,9,11,15,19(24),20,22,26,28,30(64),32,34,36,40,44(49),45,47,51,53,55(65),60,68,70,72(74)-hepta-cosa-ene, C(74)H(68)O(8). It is a cage formed from two calix[4]arene units joined by butenyl groups at three of the O atoms on the narrow rim. The fourth O atom on each calixarene unit is joined with an allyl group. Each of the calix[4]arene units has a flattened cone conformation in which the all-yloxy-substituted aryl group and the opposite aryl group are close together and almost parallel [dihedral angle between planes = 1.09 (11)°], and the other two aryl groups are splayed outward [dihedral angle between planes = 79.53 (11)°]. No guest mol-ecule (e.g. solvent) was observed within the cage. The alkene C atoms of one of the links between the calixarene moieties are disordered over two orientations with occupancies of 0.533 (9) and 0.467 (9).

  3. The capsular polysaccharide Vi from Salmonella Typhi is a B1b antigen

    OpenAIRE

    Marshall, Jennifer L.; Flores-Langarica, Adriana; Kingsley, Robert A.; Hitchcock, Jessica R; Ross, Ewan A.; Lopez-Macias, Constantino; Lakey, Jeremy; Martin, Laura B; Toellner, Kai-michael; MacLennan, Calman A.; MacLennan, Ian C; Henderson, Ian R.; Dougan, Gordon; Cunningham, Adam F.

    2012-01-01

    Vaccination with purified capsular polysaccharide Vi antigen from Salmonella Typhi can protect against typhoid fever, although the mechanism for its efficacy is not clearly established. Here, we have characterised the B cell response to this vaccine in wild-type and T cell-deficient mice. We show that immunization with Typhim Vi rapidly induces proliferation in B1b peritoneal cells, but not in B1a cells or marginal zone (MZ) B cells. This induction of B1b proliferation is concomitant with the...

  4. Transit observations at the observatory in Grossschwabhausen: XO-1b and TrES-1

    CERN Document Server

    Vanko, M; Mugrauer, M; Schmidt, T O B; Roell, T; Eisenbeiss, T; Hohle, M; Seifahrt, A; Koeltzsch, A; Broeg, Ch; Koppenhoefer, J; Neuhäuser, R

    2009-01-01

    We report on observations of transit events of the transiting planets XO-1b and TrES-1 with the AIU Jena telescope in Grossschwabhausen. Based on our IR photometry (in March 2007) and available transit timings (SuperWASP, XO and TLC-project-data) we improved the orbital period of XO-1b (P = 3.941497$\\pm$0.000006) and TrES-1 (P = 3.0300737$\\pm$0.000006), respectively. The new ephemeris for the both systems are presented.

  5. Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases

    Directory of Open Access Journals (Sweden)

    Tea eLanisnik Rizner

    2012-03-01

    Full Text Available Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas, 10% to 15% suffer from endometriosis, and 35% to 50% from infertility associated with endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG. They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B and 1C (AKR1C superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2alpha which stimulates cell proliferation. AKR1C3 converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor beta. AKR1B10 catalyzes the reduction of retinal to retinol, and in thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises a short introduction to uterine diseases, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes and their pathophysiologies are then discussed, followed by conclusions and

  6. Tetrahedral 1B4Sb nanoclusters in GaP:(B, Sb)

    Energy Technology Data Exchange (ETDEWEB)

    Elyukhin, V A, E-mail: elyukhin@cinvestav.m [Departamento de Ingenieria Electrica-SEES, CINVESTAV-IPN, Avenida IPN 2508, Col. San Pedro Zacatenco, C. P. 07360, Mexico, D. F. (Mexico)

    2009-05-01

    Self-assembling conditions of 1B4Sb tetrahedral nanoclusters in GaP doped with boron and Sb isoelectronic impurities are represented in the ultradilute and dilute limits of the boron and Sb contents, respectively. The fulfilled estimates demonstrated the preferential complete or almost complete allocation of boron atoms in 1B4Sb nanoclusters at temperatures of 500 {sup 0}C and 900 {sup 0}C, respectively. The significant decrease of the sum of the free energies of the constituent compounds is the main origin of self-assembling. The reduction of the strain energy is the additional cause of this phenomenon.

  7. Evidence for the Role of MAP1B in Axon Formation

    Science.gov (United States)

    Gonzalez-Billault, Christian; Avila, Jesus; Cáceres, Alfredo

    2001-01-01

    Cultured neurons obtained from a hypomorphous MAP1B mutant mouse line display a selective and significant inhibition of axon formation that reflects a delay in axon outgrowth and a reduced rate of elongation. This phenomenon is paralleled by decreased microtubule formation and dynamics, which is dramatic at the distal axonal segment, as well as in growth cones, where the more recently assembled microtubule polymer normally predominates. These neurons also have aberrant growth cone formation and increased actin-based protrusive activity. Taken together, this study provides direct evidence showing that by promoting microtubule dynamics and regulating cytoskeletal organization MAP1B has a crucial role in axon formation. PMID:11452005

  8. Macrosomia, obesity, and macrocephaly as first clinical presentation of PHP1b caused by STX16 deletion

    NARCIS (Netherlands)

    de Lange, Iris M; Verrijn Stuart, Annemarie A; van der Luijt, Rob B; Ploos van Amstel, Hans Kristian; van Haelst, Mieke M

    2016-01-01

    Pseudohypoparathyroidism (PHP) is a genetic disorder with resistance to parathyroid hormone (PTH) as most important feature. Main subtypes of the disease are pseudohypoparathyroidism 1b (PHP1b) and pseudohypoparathyroidism 1a (PHP1a). PHP1b is characterized by PTH resistance of the renal cortex due

  9. A functional polymorphism in the IL1B gene promoter, IL1B -31C>T, is not associated with cerebral malaria in Thailand

    OpenAIRE

    Tangpukdee Noppadon; Hananantachai Hathairad; Patarapotikul Jintana; Doi Akihiro; Naka Izumi; Ohashi Jun; Looareesuwan Sornchai; Tokunaga Katsushi

    2005-01-01

    Abstract Background IL-1β and IL-1RA levels are higher in the serum of cerebral malaria patients than in patients with mild malaria. Recently, the level of IL1B expression was reported to be influenced by a polymorphism in the promoter of IL1, IL1B -31C>T. Methods To examine whether polymorphisms in IL1B and IL1RA influence the susceptibility to cerebral malaria, IL1B -31C>T, IL1B 3953C>T, and IL1RA variable number of tandem repeat (VNTR) were analysed in 312 Thai patients with malaria (109 c...

  10. Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is Nlrp1b/Nalp1b-dependent.

    Directory of Open Access Journals (Sweden)

    Kathleen M Averette

    Full Text Available NOD-like receptors (NLRs are a group of cytoplasmic molecules that recognize microbial invasion or 'danger signals'. Activation of NLRs can induce rapid caspase-1 dependent cell death termed pyroptosis, or a caspase-1 independent cell death termed pyronecrosis. Bacillus anthracis lethal toxin (LT, is recognized by a subset of alleles of the NLR protein Nlrp1b, resulting in pyroptotic cell death of macrophages and dendritic cells. Here we show that LT induces lysosomal membrane permeabilization (LMP. The presentation of LMP requires expression of an LT-responsive allele of Nlrp1b, and is blocked by proteasome inhibitors and heat shock, both of which prevent LT-mediated pyroptosis. Further the lysosomal protease cathepsin B is released into the cell cytosol and cathepsin inhibitors block LT-mediated cell death. These data reveal a role for lysosomal membrane permeabilization in the cellular response to bacterial pathogens and demonstrate a shared requirement for cytosolic relocalization of cathepsins in pyroptosis and pyronecrosis.

  11. Deletion of SNURF / SNRPN U1B and U1B* upstream exons in a child with developmental delay and excessive weight

    Indian Academy of Sciences (India)

    COSTAS KOUFARIS; ANGELOS ALEXANDROU; IOANNIS PAPAEVRIPIDOU; IOANNA ALEXANDROU; VIOLETTA CHRISTOPHIDOU- ANASTASIADOU; CAROLINA SISMANI

    2016-09-01

    Prader–Willi syndrome is a rare syndrome characterized by hypotonia, developmental delay and excessive appetite. This syndrome is caused by the loss of function of paternally-expressed genes located in an imprinting centre in 15q11-q13. Here, we report the case of a patient who was referred to us with Prader–Willi syndrome-like symptoms including obesity and developmental delay. Examination of this patient revealed that he was a carrier of a paternally inherited deletion that affected the U1B and U1B* upstream exons of the SNURF–SNRNP gene within the 15q11-q13 imprinted region. Mutations localized within this genomic region have not been previously reported in Prader–Willi syndrome patients. It is possible that disruption of upstream exons of SNURF–SNRNP could contribute to Prader–Willi phenotype by disrupting brain-specific alternative transcripts, although, case reports from further patients with a comparable phenotype are required

  12. An elderly-onset limb girdle muscular dystrophy type 1B (LGMD1B) with pseudo-hypertrophy of paraspinal muscles.

    Science.gov (United States)

    Furuta, Mitsuru; Sumi-Akamaru, Hisae; Takahashi, Masanori P; Hayashi, Yukiko K; Nishino, Ichizo; Mochizuki, Hideki

    2016-09-01

    Mutations in LMNA, encoding A-type lamins, lead to diverse disorders, collectively called "laminopathies," which affect the striated muscle, cardiac muscle, adipose tissue, skin, peripheral nerve, and premature aging. We describe a patient with limb-girdle muscular dystrophy type 1B (LGMD1B) carrying a heterozygous p.Arg377His mutation in LMNA, in whom skeletal muscle symptom onset was at the age of 65 years. Her weakness started at the erector spinae muscles, which showed marked pseudo-hypertrophy even at the age of 72 years. Her first episode of syncope was at 44 years; however, aberrant cardiac conduction was not revealed until 60 years. The p.Arg377His mutation has been previously reported in several familial LMNA-associated myopathies, most of which showed muscle weakness before the 6th decade. This is the first report of pseudo-hypertrophy of paravertebral muscles in LMNA-associated myopathies. The pseudo-hypertrophy of paravertebral muscles and the elderly-onset of muscle weakness make this case unique and reportable.

  13. Ab interno trabeculectomy: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Vinod K

    2016-08-01

    Full Text Available Kateki Vinod, Steven J Gedde Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Ab interno trabeculectomy is one among several recently introduced minimally invasive glaucoma surgeries that avoid a conjunctival incision and full-thickness sclerostomy involved in traditional glaucoma surgery. Ablation of the trabecular meshwork and inner wall of Schlemm’s canal is performed in an arcuate fashion via a clear corneal incision, alone or in combination with phacoemulsification cataract surgery. Intraocular pressure reduction following ab interno trabeculectomy is limited by resistance in distal outflow pathways and generally stabilizes in the mid-to-high teens. Relief of medication burden has been demonstrated by some studies. A very low rate of complications, most commonly transient hyphema and intraocular pressure elevations in the immediate postoperative period, have been reported. However, available data are derived from small retrospective and prospective case series. Randomized, controlled trials are needed to better elucidate the potential merits of ab interno trabeculectomy in the combined setting versus phacoemulsification cataract surgery alone and to compare it with other minimally invasive glaucoma surgeries. Keywords: ab interno trabeculectomy, glaucoma, intraocular pressure, minimally invasive glaucoma surgery, surgical outcomes

  14. Entwicklung des schweizerischen Arbeitsmarkts 1992 bis 2008

    OpenAIRE

    Roland Aeppli

    2009-01-01

    Die kräftige Zunahme der Beschäftigung in den letzten drei Jahren war nicht breit abgestützt. Das Beschäftigungswachstum war massgeblich durch einen ausserordentlich starken Anstieg in einzelnen Branchen beeinflusst, die – mit Ausnahme «moderner» Dienstleistungen – zum staatlichen oder staatsnahen Sektor gehören. Dagegen nahm die Beschäftigung im sekundären Sektor und in den eher «traditionellen» (privaten) Dienstleistungsbranchen längerfristig gesehen ab. Vom Beschäftigungszuwachs profitiert...

  15. Vibrational spectra of bis(dmit) complexes of main group metals: IR, Raman and ab initio calculations

    OpenAIRE

    Ferreira,Glaucio B.; Nadia M. Comerlato; Wardell, James L.; Hollauer,Eduardo

    2004-01-01

    This work reports a theoretical-experimental investigation of the infrared/Raman vibrational spectra of several metal 1,3-dithole-2-thione-4,5-dithiolate (dmit) complexes; [NEt4]2[Zn(dmit)2], [NEt4][Sb(dmit)2] and [NEt4][Bi(dmit)2]. IR/Raman spectra of all the solids and the solution IR spectrum of [NEt4]2[Zn(dmit)2] were recorded from 4000 to 100 cm-1. Two regions were clearly identified: below 380 cm-1, the modes presented significant metal-ligand contributions, and above, the modes indicat...

  16. The Flammability of ABS/PET/APP Mixtures with Different Synergic Agents%不同协效剂对APP膨胀阻燃ABS/PET合金的影响

    Institute of Scientific and Technical Information of China (English)

    赵国栋; 潘治梁; 蔡绪福

    2011-01-01

    ABS/PET/APP mixtures with different synergic agents (SA) were prepared for investigating the effect of SA (2, 2' - bis ( 2 - oxazoline) (BOZ), thermoplastic phenolic resins (TPPF), manganese dioxide, montmorillonite (MMT), zinc borate, 4A Zeolite,zinc oxide (ZnO), and attapulgite on the flame retardancy of mixtures, and the thermal degradation and charring of ABS/PET/APP was analyzed. It was concluded that a novel intumescent flame retardant containing APP ( acid source and a blowing agent) and PET (carbon source) was obtained because APP mainly catalyzed PET to degrade into charring in ABS/PET/APP mixture on heating. The flammability of ABS/PET/APP mixtures with different SA was measured by the limited oxygen index (LOI) and UL-94 tests. Except for ABS/PET/APP/attapulgite mixture, ABS/PET/APP mixtures with other SA all passed the V-0 rating in UL-94 tests, the LOI of which was improved compare with ABS/PET/APP mixture. Thermo-oxidative degradation behaviors of mixtures were analyzed by thermal gravimetric analyzer (TGA), which showed an increasing char yield of ABS/PET/APP mixtures due to the addition of SA. And scanning electron microcopy (SEM) showed the denser carbon layer formation on the surface of ABS/PET/APP mixtures with SA ( except for attapulgite) after burning.%研究了8种协效剂(双噁唑啉、热塑性酚醛树脂、二氧化锰、蒙脱土、硼酸锌、4A分子筛、氧化锌和凹凸棒)对APP膨胀阻燃ABS/PET合金的影响,并探讨了ABS/PET/APP体系的降解成炭行为.研究表明,APP主要促进了PET分解成炭从而与其成为一种新型膨胀阻燃体系.通过氧指数(LOI)和UL-94标准测试燃烧性能,除凹凸棒外,其它7种协效剂均提高了ABS/PET/APP体系的氧指数,并使其通过V-0级测试;热失重分析(TGA)表明,ABS/PET/APP/协效剂体系具有更高的成炭率;通过扫描电子显微镜(SEM)对炭层表面进行观察,除凹凸棒体系外,其它7种协效剂体系的炭层表面均具有更好的致密性.

  17. o-Nitroaryl-bis(5-methylfur-2-ylmethanes as Versatile Synthons for the Synthesis of Nitrogen-Containing Heterocycles

    Directory of Open Access Journals (Sweden)

    Andrey V. Gutnov

    1997-04-01

    Full Text Available 2-Nitroaryldifurylmethanes 1a and 1b, readily available by condensation of 2-nitrobenzaldehyde and 6-nitroveratraldehyde with 2-methylfuran, were transformed into indole, cinnoline and benzothiazine-3,1 derivatives. The reduction of 2-nitroaryldifurylmethanes gave the corresponding anilines 2a,b or indole 3 depending on the reaction conditions. A plausible mechanism for the last reaction involving intramolecular heterocyclic addition between a nitroso-group and a furan ring is proposed. Diazotisation of the amine 2b gave a cinnoline derivative - a product of intramolecular oxidative furan ring opening. Treatment of isothiocyanates 7a,b with perchloric acid resulted in a new rearrangement with furan ring migration leading to the 4-Hbenzothiazine-3,1 derivatives.

  18. Johnston Atoll Site 1B-P 6/29/2000 8-9M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 8 and 9 meters along a permanent transect.

  19. Data of evolutionary structure change: 1AIBA-2AY1B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AIBA-2AY1B 1AIB 2AY1 A B MFENITAAPADPILGLADLFRADERPGKINLGIGVYKDE...HHHHHHH EEEE EEEEEGG HHHHHHHHHHHHH 0 1AIB... A 1AIBA DFSFI---IKQN...CA 475 LEU CA 494 1AIB A 1AIB... 1AIB A 1AIB

  20. Johnston Atoll Site 1B-P 6/29/2000 13-14M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 13 and 14 meters along a permanent transect.

  1. Johnston Atoll Site 1B-P 6/29/2000 10-11M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 10 and 11 meters along a permanent transect.

  2. RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity

    Science.gov (United States)

    Cellot, Sonia; Hope, Kristin J.; Chagraoui, Jalila; Sauvageau, Martin; Deneault, Éric; MacRae, Tara; Mayotte, Nadine; Wilhelm, Brian T.; Landry, Josette R.; Ting, Stephen B.; Krosl, Jana; Humphries, Keith; Thompson, Alexander; Sauvageau, Guy

    2017-01-01

    Histone methylation is a dynamic and reversible process proposed to directly impact on stem cell fate. The Jumonji (JmjC) domain–containing family of demethylases comprises 27 members that target mono-, di-, and trimethylated lysine residues of histone (or nonhistone) proteins. To evaluate their role in regulation of hematopoietic stem cell (HSC) behavior, we performed an in vivo RNAi-based functional screen and demonstrated that Jarid1b and Jhdm1f play opposing roles in regulation of HSC activity. Decrease in Jarid1b levels correlated with an in vitro expansion of HSCs with preserved long-term in vivo lymphomyeloid differentiation potential. Through RNA sequencing analysis, Jarid1b knockdown was associated with increased expression levels of several HSC regulators (Hoxa7, Hoxa9, Hoxa10, Hes1, Gata2) and reduced levels of differentiation-associated genes. shRNA against Jhdmlf, in contrast, impaired hematopoietic reconstitution of bone marrow cells. Together, our studies identified Jarid1b as a negative regulator of HSC activity and Jhdmlf as a positive regulator of HSC activity. PMID:23777767

  3. 76 FR 62455 - Announcement of Updated Funding Availability for H-1B Technical Skills Training Grants

    Science.gov (United States)

    2011-10-07

    .... SUMMARY: On May 3, 2011, the Employment and Training Administration (ETA) published a notice in the... to be awarded through a competitive process in SGA/DFA PY 10-13. Through this notice, ETA clarifies... available; however, because of additional H-1B fees collected, ETA is likely to award additional grants...

  4. The capsular polysaccharide Vi from Salmonella Typhi is a B1b antigen

    Science.gov (United States)

    Marshall, Jennifer L.; Flores-Langarica, Adriana; Kingsley, Robert A.; Hitchcock, Jessica R.; Ross, Ewan A.; Lopez-Macias, Constantino; Lakey, Jeremy; Martin, Laura B.; Toellner, Kai-Michael; MacLennan, Calman A.; MacLennan, Ian C; Henderson, Ian R.; Dougan, Gordon; Cunningham, Adam F.

    2012-01-01

    Vaccination with purified capsular polysaccharide Vi antigen from Salmonella Typhi can protect against typhoid fever, although the mechanism for its efficacy is not clearly established. Here, we have characterised the B cell response to this vaccine in wild-type and T cell-deficient mice. We show that immunization with Typhim Vi rapidly induces proliferation in B1b peritoneal cells, but not in B1a cells or marginal zone (MZ) B cells. This induction of B1b proliferation is concomitant with the detection of splenic Vi-specific antibody secreting cells and protective antibody and Rag1-deficient B1b cell chimeras generated by adoptive transfer induced specific antibody after Vi immunization. Furthermore, antibody derived from peritoneal B cells is sufficient to confer protection against Salmonella that express Vi antigen. Expression of Vi by Salmonella during infection did not inhibit the development of early antibody responses to non-Vi antigens. Despite this, the protection conferred by immunization of mice with porin proteins from Salmonella, which induce antibody-mediated protection, was reduced after infection with Vi-expressing Salmonella, although protection was not totally abrogated. This work therefore suggests that in mice, B1b cells contribute to the protection induced by Vi antigen and targeting non-Vi antigens as sub-unit vaccines may offer an attractive strategy to augment current Vi-based vaccine strategies. PMID:23162127

  5. A complex selection signature at the human AVPR1B gene

    Directory of Open Access Journals (Sweden)

    Cagliani Rachele

    2009-06-01

    Full Text Available Abstract Background The vasopressin receptor type 1b (AVPR1B is mainly expressed by pituitary corticotropes and it mediates the stimulatory effects of AVP on ACTH release; common AVPR1B haplotypes have been involved in mood and anxiety disorders in humans, while rodents lacking a functional receptor gene display behavioral defects and altered stress responses. Results Here we have analyzed the two exons of the gene and the data we present suggest that AVPR1B has been subjected to natural selection in humans. In particular, analysis of exon 2 strongly suggests the action of balancing selection in African populations and Europeans: the region displays high nucleotide diversity, an excess of intermediate-frequency alleles, a higher level of within-species diversity compared to interspecific divergence and a genealogy with common haplotypes separated by deep branches. This relatively unambiguous situation coexists with unusual features across exon 1, raising the possibility that a nonsynonymous variant (Gly191Arg in this region has been subjected to directional selection. Conclusion Although the underlying selective pressure(s remains to be identified, we consider this to be among the first documented examples of a gene involved in mood disorders and subjected to natural selection in humans; this observation might add support to the long-debated idea that depression/low mood might have played an adaptive role during human evolution.

  6. Effective cauda equina decompression in two siblings with Charcot-Marie-Tooth disease type 1B

    NARCIS (Netherlands)

    van Doormaal, Tristan P C; van Ruissen, Fred; Miller, Kai J; Hoogendijk, Jessica E

    2016-01-01

    Two siblings with Charcot-Marie-Tooth (CMT) 1B due to a c.517G>C (p.Gly173Arg) mutation in the MPZ gene both developed an acute cauda syndrome with unbearable back pain radiating to both legs, progressive muscle weakness of the legs, and saddle hypesthesia with fecal and urinary incontinence. MRI sh

  7. Gonadal mosaicism in ARID1B gene causes intellectual disability and dysmorphic features in three siblings.

    Science.gov (United States)

    Ben-Salem, Salma; Sobreira, Nara; Akawi, Nadia A; Al-Shamsi, Aisha M; John, Anne; Pramathan, Thachillath; Valle, David; Ali, Bassam R; Al-Gazali, Lihadh

    2016-01-01

    The gene encoding the AT-rich interaction domain-containing protein 1B (ARID1B) has recently been shown to be one of the most frequently mutated genes in patients with intellectual disability (ID). The phenotypic spectrums associated with variants in this gene vary widely ranging for mild to severe non-specific ID to Coffin-Siris syndrome. In this study, we evaluated three children from a consanguineous Emirati family affected with ID and dysmorphic features. Genomic DNA from all affected siblings was analyzed using CGH array and whole-exome sequencing (WES). Based on a recessive mode of inheritance, homozygous or compound heterozygous variants shared among all three affected children could not be identified. However, further analysis revealed a heterozygous variant (c.4318C>T; p.Q1440*) in the three affected children in an autosomal dominant ID causing gene, ARID1B. This variant was absent in peripheral blood samples obtained from both parents and unaffected siblings. Therefore, we propose that the most likely explanation for this situation is that one of the parents is a gonadal mosaic for the variant. To the best of our knowledge, this is the first report of a gonadal mosaicism inheritance of an ARID1B variant leading to familial ID recurrence.

  8. Johnston Atoll Site 1B-P 6/29/2000 29-30M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 29 and 30 meters along a permanent transect.

  9. Johnston Atoll Site 1B-P 6/29/2000 3-4M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 3 and 4 meters along a permanent transect.

  10. Johnston Atoll Site 1B-P 6/29/2000 0-1M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 0 and 1 meters along a permanent transect.

  11. Johnston Atoll Site 1B-P 6/29/2000 37-38M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 37 and 38 meters along a permanent transect.

  12. Johnston Atoll Site 1B-P 6/29/2000 14-15M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 14 and 15 meters along a permanent transect.

  13. Johnston Atoll Site 1B-P 6/29/2000 36-37M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 36 and 37 meters along a permanent transect.

  14. Johnston Atoll Site 1B-P 6/29/2000 1-2M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 1 and 2 meters along a permanent transect.

  15. Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia.

    Science.gov (United States)

    Khor, Chiea Chuen; Miyake, Masahiro; Chen, Li Jia; Shi, Yi; Barathi, Veluchamy A; Qiao, Fan; Nakata, Isao; Yamashiro, Kenji; Zhou, Xin; Tam, Pancy O S; Cheng, Ching-Yu; Tai, E Shyong; Vithana, Eranga N; Aung, Tin; Teo, Yik-Ying; Wong, Tien-Yin; Moriyama, Muka; Ohno-Matsui, Kyoko; Mochizuki, Manabu; Matsuda, Fumihiko; Yong, Rita Y Y; Yap, Eric P H; Yang, Zhenglin; Pang, Chi Pui; Saw, Seang-Mei; Yoshimura, Nagahisa

    2013-12-20

    Severe myopia (defined as spherical equivalent retinal pigmented epithelium. In an experimental mouse model for myopia, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for Zfhx1b and Sntb1. These new data advance our understanding of the molecular pathogenesis of severe myopia.

  16. Human CRISP-3 binds serum alpha(1)B-glycoprotein across species

    DEFF Research Database (Denmark)

    Udby, Lene; Johnsen, Anders H; Borregaard, Niels

    2010-01-01

    CRISP-3 was previously shown to be bound to alpha(1)B-glycoprotein (A1BG) in human serum/plasma. All mammalian sera are supposed to contain A1BG, although its presence in rodent sera is not well-documented. Since animal sera are often used to supplement buffers in experiments, in particular...

  17. The Ca2+-induced methyltransferase xPRMT1b controls neural fate in amphibian embryo.

    Science.gov (United States)

    Batut, Julie; Vandel, Laurence; Leclerc, Catherine; Daguzan, Christiane; Moreau, Marc; Néant, Isabelle

    2005-10-18

    We have previously shown that an increase in intracellular Ca2+ is both necessary and sufficient to commit ectoderm to a neural fate in Xenopus embryos. However, the relationship between this Ca2+ increase and the expression of early neural genes has yet to be defined. Using a subtractive cDNA library between untreated and caffeine-treated animal caps, i.e., control ectoderm and ectoderm induced toward a neural fate by a release of Ca2+, we have isolated the arginine N-methyltransferase, xPRMT1b, a Ca2+-induced target gene, which plays a pivotal role in this process. First, we show in embryo and in animal cap that xPRMT1b expression is Ca2+-regulated. Second, overexpression of xPRMT1b induces the expression of early neural genes such as Zic3. Finally, in the whole embryo, antisense approach with morpholino oligonucleotide against xPRMT1b impairs neural development and in animal caps blocks the expression of neural markers induced by a release of internal Ca2+. Our results implicate an instructive role of an enzyme, an arginine methyltransferase protein, in the embryonic choice of determination between epidermal and neural fate. The results presented provide insights by which a Ca2+ increase induces neural fate.

  18. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors.

    Science.gov (United States)

    Koshimizu, Taka-Aki; Kashiwazaki, Aki; Taniguchi, Junichi

    2016-05-03

    Reducing Na(+) in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na(+)-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na(+) sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na(+) increased cell surface [(3)H]AVP binding and decreased receptor internalization. Substitution of Na(+) by Cs(+) or NH4(+) inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na(+) over Cs(+). Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.

  19. Johnston Atoll Site 1B-P 6/29/2000 4-5M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 4 and 5 meters along a permanent transect.

  20. Data of evolutionary structure change: 1BU1B-1OOTA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BU1B-1OOTA 1BU1 1OOT B A -IIVVALYDYEAIHHEDLSFQKGDQMVVLEESGE---WW... 1OOT A 1OOTA -18.01099967956543 29.775999069213867 13.968000411987305 ...381469727 -0.722000002861023 -0.6259999871253967 tion> 1.83514404296875...1OOT A 1OOTA WTGRV--NGREG

  1. Crystal structure of bovine CD1b3 with endogenously bound ligands

    NARCIS (Netherlands)

    Girardi, E.; Wang, J.; Mac, T.T.; Versluis, C.; Bhowruth, V.; Besra, G.; Heck, A.J.R.; van Rhijn, I.; Zajonc, D.M.

    2010-01-01

    The CD1 family of Ag-presenting molecules is able to display lipids to T cells by binding them within a hydrophobic groove connected to the protein surface. In particular, the CD1b isotype is capable of binding ligands with greatly varying alkyl chain lengths through a complex network of interconnec

  2. CYP1B1 gene mutations causing primary congenital glaucoma in Tunisia.

    Science.gov (United States)

    Bouyacoub, Yosra; Ben Yahia, Salim; Abroug, Nesrine; Kahloun, Rim; Kefi, Rym; Khairallah, Moncef; Abdelhak, Sonia

    2014-07-01

    Primary congenital glaucoma (PCG) is responsible for a significant proportion of childhood blindness in Tunisia. Early prevention based on genetic diagnosis is therefore required. This study sought to determine the frequency of CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1) mutations in 18 PCG patients, recruited from Central and Southern of Tunisia. Genomic DNA was extracted and the coding regions of CYP1B1 were analysed by direct sequencing. A phylogenetic network of CYP1B1 haplotypes was drawn using the median-joining algorithm. Sequence analysis revealed a "tetra-allelic mutation" (two novel mutations, p.F231I and p.P437A in the homozygous state) in one patient. The healthy members of his family carried those variations on the same allele. Two previously described mutations p.G61E and c.535delG were also identified in the homozygous state in seven and two probands, respectively. Seven single-nucleotide polymorphisms were identified and used to generate haplotypes. Our results showed that the CYP1B1 mutations were present in 55% of Tunisian PCG patients' alleles. Haplotype analysis allowed us to define the proto-haplotype and to confirm historical migratory flows. Establishment of PCG genetic aetiology in Tunisia will improve genetic diagnosis and counselling.

  3. Data of evolutionary structure change: 1B0FA-1O3AA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available YDPV >EEE - > ATOM 556 CA ARG A ...ryIDChain>1O3AA KSIVHPSYNSN cture>EEEEE ucture...bChain> 1B0FA LGRNR-GIASV > - ...ence>TKSSGTSYPDV > > ATOM 1849 C...A AHCYK----SGIQV >GGG ---- EEEe>

  4. Data of evolutionary structure change: 1B1GA-1AK8A [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available entryIDChain>1B1GA KEGDP-NQLSK > - EEE...> A 1AK8A FDKDGDGTITT H ...A LFEEL---DKNGD >HHHHH--- ...entryIDChain>1AK8A LQDMINEVDADGN ...>HHHHH > ATOM 722 CA LEU A 48 3.325 7.917 -3.325 1.00 0

  5. Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor

    DEFF Research Database (Denmark)

    Bräuner-Osborne, H; Jensen, Anders A.; Krogsgaard-Larsen, P

    1999-01-01

    7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt) has previously been shown to be a selective non-competitive antagonist at the metabotropic glutamate (mGlu) receptor subtype 1. In this study we have tested the effect of CPCCOEt on mGlu1b, the calcium sensing receptor (...

  6. Data of evolutionary structure change: 1C4XA-2OG1B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1C4XA-2OG1B 1C4X 2OG1 A B ---TVEIIEKRFPSGT---LASHALVAGDPQSPAVVLLH...EEEEEEE HHHHHHHHHHHHH 0 1C4X... A 1C4XA FPSGT---LASHA ...645107269287 4.700198173522949 1 1C4X... A 1C4XA

  7. Functions of OATP1a/1b transporters in vivo: insights from mouse models

    NARCIS (Netherlands)

    Steeg, E. van de; Lusuf, D.; Schinkel, A.H.

    2011-01-01

    Organic anion-transporting polypeptides (OATPs) are a superfamily of uptake transporters that mediate the cellular uptake of a broad range of endogenous and exogenous compounds. Of these OATP transporters, members of the 1A and 1B subfamilies have broad substrate specificities. Because they are main

  8. Mirror Advanced Reactor Study (MARS). Final report. Volume 1-B. Commercial fusion electric plant

    Energy Technology Data Exchange (ETDEWEB)

    Donohue, M.L.; Price, M.E. (eds.)

    1984-07-01

    Volume 1-B contains the following chapters: (1) blanket and reflector; (2) central cell shield; (3) central cell structure; (4) heat transport and energy conversion; (5) tritium systems; (6) cryogenics; (7) maintenance; (8) safety; (9) radioactivity, activation, and waste disposal; (10) instrumentation and control; (11) balance of plant; (12) plant startup and operation; (13) plant availability; (14) plant construction; and (15) economic analysis.

  9. Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells.

    Directory of Open Access Journals (Sweden)

    César Mattei

    Full Text Available Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for ciguatera and neurotoxic shellfish poisoning (NSP respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of ciguatera. Pacific ciguatoxin-1B (P-CTX-1B activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and beta-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment for ciguatera.

  10. miR-200b mediates post-transcriptional repression of ZFHX1B

    DEFF Research Database (Denmark)

    Christoffersen, Nanna Rønbjerg; Silahtaroglu, Asli; Ørom, Ulf Lupo Andersson

    2007-01-01

    MicroRNAs have important functions during animal development and homeostasis through post-transcriptional regulation of their cognate mRNA targets. ZFHX1B is a transcriptional repressor involved in the TGFbeta signaling pathway and in processes of epithelial to mesenchymal transition via regulati...

  11. Johnston Atoll Site 1B-P 6/29/2000 15-16M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 15 and 16 meters along a permanent transect.

  12. Johnston Atoll Site 1B-P 6/29/2000 5-6M

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 1B-P (16 47.147N, 169 27.695W), between 5 and 6 meters along a permanent transect.

  13. Lmx-1b and Wnt-7a expression in axolotl limb during development and regeneration.

    Science.gov (United States)

    Shimokawa, Takashi; Yasutaka, Satoru; Kominami, Rieko; Shinohara, Harumichi

    2013-01-01

    Axolotls (Ambystoma mexicanum) have the ability to regenerate amputated limbs throughout their life span. During limb regeneration as well as development, undifferentiated cells in the blastema acquire positional information to reproduce the original pattern along three cardinal limb axes: anteroposterior, proximodistal and dorsoventral. In the present study, we attempted to understand the molecular mechanism involved in patterning of axolotl limb development and regeneration along the dorsoventral (DV) axis. We cloned axolotl Lmx-1b and Wnt-7a, and investigated the expression pattern of these genes in developing and regenerating limbs. In axolotl, unlike in amniotes, Wnt-7a was expressed in a diffuse manner throughout both developing limb bud and regenerating limb blastema. Lmx-1b expression was observed at the dorsal mesenchyme in the developing and regenerating limbs. On the basis of the expression patterns of Lmx-1b and Wnt-7a, it was difficult to identify the interaction between these two genes as reported in amniotes in previous studies. Possibly, with regard to Lmx-1b expression, a Wnt-7a-independent mechanism may exist in axolotl limb development and regeneration.

  14. Haploinsufficiency of the STX1B gene is associated with myoclonic astatic epilepsy

    NARCIS (Netherlands)

    Vlaskamp, Danique R.M.; Rump, Patrick; Callenbach, Petra M.C.; Vos, Yvonne J.; Sikkema-Raddatz, Birgit; van Ravenswaaij-Arts, Conny M.A.; Brouwer, Oebele F.

    2016-01-01

    We describe an 18-year-old male patient with myoclonic astatic epilepsy (MAE), moderate to severe intellectual disability, behavioural problems, several dysmorphisms and a 1.2-Mb de novo deletion on chromosome 16p11.2. This deletion results in haploinsufficiency of STX1B and other genes. Recently, v

  15. Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Akira; Yokoyama; Tetsuji; Yokoyama

    2010-01-01

    AIM:To evaluate the contribution of alcohol dehydrogenase-1B(ADH1B)and aldehyde dehydrogenase-2 (ALDH2)polymorphisms to the risk of esophageal cancer.METHODS:Nineteen articles were included by searching MEDLINE,EMBASE and the Chinese Biomedical Database,13 on ADH1B and 18 on ALDH2.We performed a meta-analysis of case-control studies including 13 studies on ADH1B(cases/controls:2390/7100)and 18 studies on ALDH2(2631/6030).RESULTS:The crude odds ratio[OR(95%confidence interval)]was 2.91(2.04-4.14)for ADH1B*1/...

  16. Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist.

    Science.gov (United States)

    Zhang, Minli; Zhou, Diansong; Wang, Yi; Maier, Donna L; Widzowski, Daniel V; Sobotka-Briner, Cynthia D; Brockel, Becky J; Potts, William M; Shenvi, Ashok B; Bernstein, Peter R; Pierson, M Edward

    2011-11-01

    The preclinical pharmacology and pharmacokinetic properties of (2R)-6-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)chromane-2-carboxamide (AZD3783), a potent 5-hydroxytryptamine 1B (5-HT(1B)) receptor antagonist, were characterized as part of translational pharmacokinetic/pharmacodynamic hypothesis testing in human clinical trials. The affinity of AZD3783 to the 5-HT(1B) receptor was measured in vitro by using membrane preparations containing recombinant human or guinea pig 5-HT(1B) receptors and in native guinea pig brain tissue. In vivo antagonist potency of AZD3783 for the 5HT(1B) receptor was investigated by measuring the blockade of 5-HT(1B) agonist-induced guinea pig hypothermia. The anxiolytic-like potency was assessed using the suppression of separation-induced vocalization in guinea pig pups. The affinity of AZD3783 for human and guinea pig 5-HT(1B) receptor (K(i), 12.5 and 11.1 nM, respectively) was similar to unbound plasma EC(50) values for guinea pig receptor occupancy (11 nM) and reduction of agonist-induced hypothermia (18 nM) in guinea pig. Active doses of AZD3783 in the hypothermia assay were similar to doses that reduced separation-induced vocalization in guinea pig pups. AZD3783 demonstrated favorable pharmacokinetic properties. The predicted pharmacokinetic parameters (total plasma clearance, 6.5 ml/min/kg; steady-state volume of distribution, 6.4 l/kg) were within 2-fold of the values observed in healthy male volunteers after a single 20-mg oral dose. This investigation presents a direct link between AZD3783 in vitro affinity and in vivo receptor occupancy to preclinical disease model efficacy. Together with predicted human pharmacokinetic properties, we have provided a model for the quantitative translational pharmacology of AZD3783 that increases confidence in the optimal human receptor occupancy required for antidepressant and anxiolytic effects in patients.

  17. Estimation of evapotranspiration over heterogeneous surfaces based on HJ1B satellite data in China

    Science.gov (United States)

    Xin, Xiaozhou; Jiao, Jingjun

    2014-05-01

    The HJ1B satellite of China is equipped with two CCD cameras with 30m resolution and one infrared multispectral camera with 300m resolution. And the revisit period of HJ1B satellite is 4 days. Compared to MODIS or TM, HJ1B data has the advantage of high spatial-temporal resolution. Methodology based on the one-source energy balance model was developed for net radiation (Rn), soil heat flux (G), sensible heat flux (H) and latent heat flux (LE) estimation from HI1B data. The core procedure is a scheme that was designed for correcting the spatial scale error over heterogeneous surfaces by taking advantage of the HJ1B data characteristics, i.e., high resolution CCD data (30m) along with thermal data (300m). First of all, a regression relationship between Ts and NDVI was built up at 300m resolution based on the data of Ts and NDVI of the selected "pure" pixels. And then the relationship function was applied at 30m resolution to derive Ts at high resolution, i.e., at the subpixel level. Furthermore, the 30m land class data was also used in the parameterization of surface energy balance and surface aerodynamic transfer, which is important since significant error may be resulted by using one land class type to represent the whole mixed pixel. By using high resolution NDVI and land class data, we are able to mitigate the spatial scale error of the mixed pixels at 300m resolution. At last, the 300m surface energy fluxes were obtained by aggregation of the 30m estimation. HJ1B data at Hai river basin in north China in 2010 were used to verify this method. The eddy-correlation system data were used as validation. The results of the method were compared with the results of a simple method that estimates the fluxes at 300m by aggregating all of the input parameters to 300m. It is shown that the method proposed in this study shows higher agreement with in-suit measurement, and the fluxes maps also show much more details of the spatial variation. By using this method, it can be

  18. Synthesis and Bioactivities of A Series of Bis-azoles

    Institute of Scientific and Technical Information of China (English)

    ZHOU Cheng-He; LIU Qiang; CHEN Jie; HU Xiang-Nan; CAI Meng-Shen; XIE Ru-Gang; Alfred Hassner

    2003-01-01

    @@ Imidazoles as pharmaceutical agents are widely used and investigated. A series of bis-azoles were prepared fromimidazole and its analogues and dibromides obtained according to similar procedures of literatures. [1 ~ 4

  19. On the Strain Rate Sensitivity of Abs and Abs Plus Fused Deposition Modeling Parts

    Science.gov (United States)

    Vairis, A.; Petousis, M.; Vidakis, N.; Savvakis, K.

    2016-09-01

    In this work the effect of strain rate on the tensile strength of fused deposition modeling parts built with Acrylonitrile-butadiene-styrene (ABS) and ABS plus material is presented. ASTM D638-02a specimens were built with ABS and ABS plus and they were tested on a Schenck Trebel Co. tensile test machine at three different test speeds, equal, lower, and higher to the test speed required by the ASTM D638-02a standard. The experimental tensile strength results were compared and evaluated. The fracture surfaces of selected specimens were examined with a scanning electron microscope, to determine failure mode of the filament strands. It was found that, as the test speed increases, specimens develop higher tensile strength and have higher elastic modulus. Specimens tested in the highest speed of the experiment had on average about 10% higher elastic modulus and developed on average about 11% higher tensile strength.

  20. Potent water extracts of Indonesian medicinal plants against PTP1B

    Institute of Scientific and Technical Information of China (English)

    Azis Saifudin; Tepy Usia; Subehan AbLallo; Hiroyuki Morita; Ken Tanaka; Yasuhiro Tezuka

    2016-01-01

    Objective: To examine the potent of water as a solvent agent in the preparation of traditional herbal medicine. Methods: Water extracts of 18 plants were prepared through reflux and examined (25 mg/mL) to evaluate their possibility for inhibiting protein tyrosine phosphatase 1B (PTP1B). The determination of IC50 values was performed for the samples possessing more than 80% inhibition. Meanwhile, those exhibiting IC50 values more than 7.0 mg/mL were further profiled for their chemical constituents through nuclear magnetic resonance (NMR) measurement. Results: About 44% (8) of the examined samples showed more than 80% inhibition against PTP1B. The water extracts of Elephantopus scaber, Helicteres isora aerial parts, Elaeocarpus grandiflorus (E. grandiflorus) fruits, Melaleuca leucadendron leaves, and Quercus infectoria gum had IC50 values ranging from 2.05 to 6.90 mg/mL. Meanwhile, Andropogon nardus and Centella asiatica were at the area of d 3.0–4.0 ppm. Further, the 13C NMR observation of samples possessing the most intensive signals in their proton NMR Cinnamomum burmannii and E. grandiflorus showed the peaks at the area of d 60–90 ppm as the supportive evidence for sugar group signals. Intriguingly, a disaccharide from E. grandiflorus could be an active inhibitor towards PTB1B. Conclusions: In contrast to the mainstream solvents currently used in modern herbal manufactures especially Jamu medicine in Indonesia, pure-water-extracted materials should be reconsidered and could be reemerged for future studies and for the manufacture of herbal medicines. In addition, the activity of Jamu components should be confirmed that their antidiabetes and antiobesity activities could be through the inhibition of PTP1B.

  1. Potent water extracts of Indonesian medicinal plants against PTP1B

    Institute of Scientific and Technical Information of China (English)

    Azis Saifudin; Tepy Usia; Subehan Ab Lallo; Hiroyuki Morita; Ken Tanaka; Yasuhiro Tezuka

    2016-01-01

    Objective:To examine the potent of water as a solvent agent in the preparation of traditional herbal medicine.Methods:Water extracts of 18 plants were prepared through reflux and examined(25μg/mL) to evaluate their possibility for inhibiting protein tyrosine phosphatase 1B(PTP1B).The determination of IC50 values was performed for the samples possessing more than 80%inhibition.Meanwhile,those exhibiting IC50 values more than 7.0 μg/mL were further profiled for their chemical constituents through nuclear magnetic resonance(NMR) measurement.Results:About 44%(8) of the examined samples showed more than 80%inhibition against PTP1 B.The water extracts of Elephantopus scaber,Helicteres isora aerial parts,Elaeocarpus grandiflorus(E.grandiflorus) fruits,Melaleuca leucadendron leaves,and Quercus infectoria gum had IC50 values ranging from 2.05 to 6.90 μg/mL.Meanwhile,Andropogon nardus and Centella asiatica were at the area of δ 3.0-4.0 ppm.Further,the13 C NMR observation of samples possessing the most intensive signals in their proton NMR Cinnamomum burmannii and E.grandiflorus showed the peaks at the area of δ 60-90 ppm as the supportive evidence for sugar group signals.Intriguingly,a disaccharide from E.grandiflorus could be an active inhibitor towards PTB1 B.Conclusions:In contrast to the mainstream solvents currently used in modern herbal manufactures especially Jamu medicine in Indonesia,pure-water-extracted materials should be reconsidered and could be reemerged for future studies and for the manufacture of herbal medicines.In addition,the activity of Jamu components should be confirmed that their antidiabetes and antiobesity activities could be through the inhibition of PTP1 B.

  2. A polymorphism in the CYP1B1 promoter is functionally associated with primary congenital glaucoma.

    Science.gov (United States)

    Chakrabarti, Subhabrata; Ghanekar, Yashoda; Kaur, Kiranpreet; Kaur, Inderjeet; Mandal, Anil K; Rao, Kollu N; Parikh, Rajul S; Thomas, Ravi; Majumder, Partha P

    2010-10-15

    Primary congenital glaucoma (PCG) is a childhood autosomal-recessive disorder caused by developmental defects in the trabecular meshwork and anterior chamber angle. These defects cause raised intraocular pressure (IOP) that damages the optic nerve and if left untreated, results in irreversible blindness. Mutations in CYP1B1 gene at the GLC3A locus (2p21) are associated with PCG. However, there has been very limited exploration of its promoter region. We resequenced the CYP1B1 promoter in a large cohort (n = 835) that included patients with PCG (n = 301), other primary glaucomas (primary open-angle glaucoma: n = 115 and primary angle closure glaucoma: n = 100) and unaffected controls (n = 319). We functionally characterized one associated variant by luciferase reporter assay using the trabecular meshwork (TM3) cell line. We found evidence of strong (P = 6.01 × 10(-4)) association of rs2567206 (T2805C) SNP in PCG and not in other primary glaucomas. Luciferase assay indicated a ∼90% reduction in CYP1B1 promoter activity in the risk-allele (C) compared to the other allele (T). The association of the risk allele was stronger in cases harboring homozygous CYP1B1 mutations (P = 3.42 × 10(-12)). The risk haplotype 'C-C-G' in the promoter had a strong non-random association to the previously characterized risk haplotype 'C-G-G-T-A' in the coding region. The independent effect of genotype at the promoter T2805C locus (P = 0.001), and the interaction effect of genotypes at the promoter and coding region mutations loci (P = 0.001) were significant for the presenting IOP of the worst affected eye. This is the first study that unequivocally shows the functional involvement of a CYP1B1 promoter variant in PCG.

  3. Spatial-Temporal Study of Rab1b Dynamics and Function at the ER-Golgi Interface.

    Science.gov (United States)

    Martinez, Hernán; García, Iris A; Sampieri, Luciana; Alvarez, Cecilia

    2016-01-01

    The GTPase Rab1b is involved in ER to Golgi transport, with multiple Rab1b effectors (located at ERES, VTCs and the Golgi complex) being required for its function. In this study, we performed live-cell dual-expression studies to analyze the dynamics of Rab1b and some effectors located at the ERES-Golgi interface. Rab1b occupied widely distributed mobile punctate and tubular structures, displaying a transient overlaps with its effectors and showing that these overlaps occurred at the same time in spatially distinct steps of ER to Golgi transport. In addition, we assessed Rab1b dynamics during cargo sorting by analyzing the concentration at ERES of a Golgi protein (SialT2-CFP) during Brefeldin A washout (BFA WO). Rab1b was associated to most of the ERES structures, but at different times during BFA WO, and recurrently SialT2-CFP was sorted in the ERES-Rab1b positive structures. Furthermore, we reveal for first time that Rab1b localization time at ERES depended on GBF1, a Rab1b effector that acts as the guanine nucleotide exchange factor of Arf1, and that Rab1b membrane association/dissociation dynamics at ERES was dependent on the GBF1 membrane association and activity, which strongly suggests that GBF1 activity modulates Rab1b membrane cycling dynamic.

  4. Spatial-Temporal Study of Rab1b Dynamics and Function at the ER-Golgi Interface

    Science.gov (United States)

    Martinez, Hernán; García, Iris A.; Sampieri, Luciana

    2016-01-01

    The GTPase Rab1b is involved in ER to Golgi transport, with multiple Rab1b effectors (located at ERES, VTCs and the Golgi complex) being required for its function. In this study, we performed live-cell dual-expression studies to analyze the dynamics of Rab1b and some effectors located at the ERES-Golgi interface. Rab1b occupied widely distributed mobile punctate and tubular structures, displaying a transient overlaps with its effectors and showing that these overlaps occurred at the same time in spatially distinct steps of ER to Golgi transport. In addition, we assessed Rab1b dynamics during cargo sorting by analyzing the concentration at ERES of a Golgi protein (SialT2-CFP) during Brefeldin A washout (BFA WO). Rab1b was associated to most of the ERES structures, but at different times during BFA WO, and recurrently SialT2-CFP was sorted in the ERES-Rab1b positive structures. Furthermore, we reveal for first time that Rab1b localization time at ERES depended on GBF1, a Rab1b effector that acts as the guanine nucleotide exchange factor of Arf1, and that Rab1b membrane association/dissociation dynamics at ERES was dependent on the GBF1 membrane association and activity, which strongly suggests that GBF1 activity modulates Rab1b membrane cycling dynamic. PMID:27500526

  5. 40 CFR 721.8100 - Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis (hy-droxy-ethyl) tal-lo-wa-mine oxide phos-phate. 721.8100... Substances § 721.8100 Potassium N,N-bis (hydroxy-ethyl) cocoamine oxide phosphate, and potassium N,N-bis...

  6. Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling.

    Science.gov (United States)

    Ozek, Ceren; Kanoski, Scott E; Zhang, Zhong-Yin; Grill, Harvey J; Bence, Kendra K

    2014-11-14

    Neuronal protein-tyrosine phosphatase 1B (PTP1B) deficiency in mice results in enhanced leptin signaling and protection from diet-induced obesity; however, whether additional signaling pathways in the brain contribute to the metabolic effects of PTP1B deficiency remains unclear. Here, we show that the tropomyosin receptor kinase B (TrkB) receptor is a direct PTP1B substrate and implicate PTP1B in the regulation of the central brain-derived neurotrophic factor (BDNF) signaling. PTP1B interacts with activated TrkB receptor in mouse brain and human SH-SY5Y neuroblastoma cells. PTP1B overexpression reduces TrkB phosphorylation and activation of downstream signaling pathways, whereas PTP1B inhibition augments TrkB signaling. Notably, brains of Ptpn1(-/-) mice exhibit enhanced TrkB phosphorylation, and Ptpn1(-/-) mice are hypersensitive to central BDNF-induced increase in core temperature. Taken together, our findings demonstrate that PTP1B is a novel physiological regulator of TrkB and that enhanced BDNF/TrkB signaling may contribute to the beneficial metabolic effects of PTP1B deficiency.

  7. Increased expression of 5-HT(1B) receptors by Herpes simplex virus gene transfer in septal neurons: New in vitro and in vivo models to study 5-HT(1B) receptor function.

    Science.gov (United States)

    Riegert, Céline; Rothmaier, Anna Katharina; Leemhuis, Jost; Sexton, Timothy J; Neumaier, John F; Cassel, Jean-Christophe; Jackisch, Rolf

    2008-07-01

    Serotonergic modulation of acetylcholine (ACh) release after neuron-specific increase of the expression of 5-HT(1B) receptors by gene transfer was studied in vitro and in vivo. The increased expression of the 5-HT(1B) receptor in vitro was induced by treating rat primary fetal septal cell cultures for 3 days with a viral vector inducing the expression of green fluorescent protein (GFP) vector alone, or, in addition, of 5-HT(1B) receptors (HA1B/GFP vector). The transfection resulted in a high number of GFP-positive cells, part of which being immunopositive for choline acetyltransferase. In HA1B/GFP-cultures (vs. GFP-cultures), electrically evoked ACh release was significantly more sensitive to the inhibitory action of the 5-HT(1B) agonist CP-93,129. Increased expression of the 5-HT(1B) receptor in vivo was induced by stereotaxic injections of the vectors into the rat septal region. Three days later, electrically evoked release of ACh in hippocampal slices of HA1B/GFP-treated rats was lower than in their GFP-treated counterparts, showing a higher inhibitory efficacy of endogenous 5-HT on cholinergic terminals after transfection. Moreover, CP-93,129 had a higher inhibitory potency. In conclusion, the HA1B/GFP vector reveals a useful tool to induce a targeted increase of 5-HT(1B) heteroreceptors on cholinergic neurons in selected CNS regions, which provides interesting perspectives for functional approaches at more integrated levels.

  8. The Roles of EMA in ABS/PMMA Alloy%EMA在ABS/PMMA合金中的作用

    Institute of Scientific and Technical Information of China (English)

    许家友; 林凯勉; 黄鹄斌; 梁以峰

    2012-01-01

    Effects of EMA on ABS/PMMA blends were studied by DSC,SEM and mechanical performance test. The experimental results showed that the EMA had compatibilizing and toughening effects on ABS/PMMA blends. Because the EMA contains vinyl group similarity to butadiene in ABS.and the same methyl-methacrylate group in PMMA, which could improve the interface compatibility between ABS and PMMA; At the same time,EMA dispersed as spherical in ABS/PMMA matrix and endured stress,the toughness of the ABS/PMMA blends could be obviously improved while increasing the content of EMA. The gloss of the surface of ABS/PMMA blends was affected by the compatibility of ABS/PMMA blends. When the content of EMA was 6 %,the gloss on surface of ABS/PMMA blends reached maximum.%通过DSC、SEM和力学性能测试研究了EMA在ABS/PMMA中的作用,结果表明:EMA对ABS/PMMA合金具有增容和增韧作甩.因为EMA含有与ABS中丁二烯结构相似的乙烯基,又含有与PMMA中相同的甲基丙烯酸甲酯,可以提高ABS/PMMA的界面相容性,但同时EMA在ABS/PMMA中呈球形分散,起应力集中物作用,能提高ABS/PMMA的韧性;EMA对ABS/PMMA增容程度影响着ABS/PMMA合金的表面光泽度,当EMA质量含量为6%时,ABS/PMMA合金的表面光泽度达到最大值.

  9. Co-existing Intermolecular Halogen Bonding and Hydrogen Bonding in the Compound Trans-5,10-bis(1-bromodifluoroacetyl-1-ethoxycarbonyl-methylidene)thianthrene

    Institute of Scientific and Technical Information of China (English)

    ZHU Shi-Fa祝诗发; ZHU Shi-Zheng朱士正; LIAO Yuan-Xi廖远熹; HUANG Chao-Feng黄超峰; LI Zhan-Ting黎占亭

    2004-01-01

    Trans-5,10-bis(1-bromodifluoroacetyl-1-ethoxycarbonyl-methylidene)thianthrene (1b) was prepared from the reaction of BrCF2COC(N2)CO2Et with thianthrene. X-ray single crystal diffraction analysis showed that the intermolecular halogen bonding and hydrogen bonding coexisted in this compound. The bromine atom acted as an electron acceptor in the halogen bond and an electron donor in the hydrogen bond. It is the first example that the bromine atom acted as such a dual role in the hydrogen and halogen bond.

  10. Solution pH-induced reversal of stereoselectivity. Deuteration of malonate methylenes in some bis(malonato) cobalt (III) complexes

    Energy Technology Data Exchange (ETDEWEB)

    Sakaguchi, U.; Morito, K.; Yoneda, H.

    1979-05-09

    Deuteration of some bis(malonate)cobalt(III) complexes takes place stereoselectively in heavy water. The malonate portion of the HNMR spectrum of K(Co(mal)/sub 2/(en)) in acidified D/sub 2/O (pD 3.23) was measured at intervals after dissolution. Initially, one set of an expected AB quartet was observed because of the two malonate protons; (H/sub N/) is adjacent to the NH/sub 2/ group in any conformation of the malonate--cobalt ring while the other (H/sub O/) is adjacent to the malonate oxygen. The low-field resonance pair was assigned to the H/sub N/ and the high-field pair to H/sub O/. As time passes, the singlet appears and grows in intensity. The singlet originates from the species CDHO produced by deuteration of only H/sub N/, because the chemical shift of this singlet is that of H/sub O/. The intensity of the singlet diminishes as the remaining H/sub O/ is deuterated. The whole spectral change with time can be expressed as CH/sub N/H/sub O/ ..-->.. CDH/sub O/ ..-->.. CDD. The rate of deuteration of H/sub N/ is much faster than that of H/sub O/. The novel feature of this process is the reversal of the stereoselectivity accompanying the pH change when the deuteration takes place in basic solution (pD 8.09). Natural logarithms of NMR intensities of the AB quartet and of the H/sub N/ or H/sub O/ singlet were plotted against time and from these plots pseudo first-order rate constants k/sub AB/ and k/sub HN/ or k/sub HO/ were obtained on the assumption that k/sub AB/ = k/sub HN/ + k/sub HO/.

  11. A review on bis-hydrazonoyl halides: Recent advances in their synthesis and their diverse synthetic applications leading to bis-heterocycles of biological interest

    Directory of Open Access Journals (Sweden)

    Ahmad Sami Shawali

    2016-11-01

    Full Text Available This review covers a summary of the literature data published on the chemistry of bis-hydrazonoyl halides over the last four decades. The biological activities of some of the bis-heterocyclic compounds obtained from these bis-hydrazonoyl halides are also reviewed and discussed.

  12. High diversity and no significant selection signal of human ADH1B gene in Tibet

    Directory of Open Access Journals (Sweden)

    Lu Yan

    2012-11-01

    Full Text Available Abstract Background ADH1B is one of the most studied human genes with many polymorphic sites. One of the single nucleotide polymorphism (SNP, rs1229984, coding for the Arg48His substitution, have been associated with many serious diseases including alcoholism and cancers of the digestive system. The derived allele, ADH1B*48His, reaches high frequency only in East Asia and Southwest Asia, and is highly associated with agriculture. Micro-evolutionary study has defined seven haplogroups for ADH1B based on seven SNPs encompassing the gene. Three of those haplogroups, H5, H6, and H7, contain the ADH1B*48His allele. H5 occurs in Southwest Asia and the other two are found in East Asia. H7 is derived from H6 by the derived allele of rs3811801. The H7 haplotype has been shown to have undergone significant positive selection in Han Chinese, Hmong, Koreans, Japanese, Khazak, Mongols, and so on. Methods In the present study, we tested whether Tibetans also showed evidence for selection by typing 23 SNPs in the region covering the ADH1B gene in 1,175 individuals from 12 Tibetan populations representing all districts of the Tibet Autonomous Region. Multiple statistics were estimated to examine the gene diversities and positive selection signals among the Tibetans and other populations in East Asia. Results The larger Tibetan populations (Qamdo, Lhasa, Nagqu, Nyingchi, Shannan, and Shigatse comprised mostly farmers, have around 12% of H7, and 2% of H6. The smaller populations, living on hunting or recently switched to farming, have lower H7 frequencies (Tingri 9%, Gongbo 8%, Monba and Sherpa 6%. Luoba (2% and Deng (0% have even lower frequencies. Long-range haplotype analyses revealed very weak signals of positive selection for H7 among Tibetans. Interestingly, the haplotype diversity of H7 is higher in Tibetans than in any other populations studied, indicating a longer diversification history for that haplogroup in Tibetans. Network analysis on the long

  13. Cytochrome P450 1B1 polymorphisms and risk of renal cell carcinoma in men.

    Science.gov (United States)

    Chang, Inik; Fukuhara, Shinichiro; Wong, Darryn K; Gill, Ankurpreet; Mitsui, Yozo; Majid, Shahana; Saini, Sharanjot; Yamamura, Soichiro; Chiyomaru, Takeshi; Hirata, Hiroshi; Ueno, Koji; Arora, Sumit; Shahryari, Varahram; Deng, Guoren; Tabatabai, Z Laura; Greene, Kirsten L; Shin, Dong Min; Enokida, Hideki; Shiina, Hiroaki; Nonomura, Norio; Dahiya, Rajvir; Tanaka, Yuichiro

    2014-10-01

    The cytochrome P450 1B1 (CYP1B1) enzyme activates xenobiotics to reactive forms as well as convert estradiol to 4-hydroxy-estradiol that has been shown to play a role in the carcinogenesis process of the kidney in male but not female animals. Prior reports show polymorphic variants of CYP1B1 to alter catalytic activity, and thus, we hypothesize that polymorphisms of the CYP1B1 gene are involved in the malignant transformation of the renal cell in men. The genetic distributions of five CYP1B1 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism in 480 normal healthy subjects and 403 sporadic renal cell carcinoma cases. All subjects were Caucasian men. The sites evaluated were codons 48 (C → G, Arg → Gly, rs10012), 119 (G → T, Ala → Ser, rs1056827), 432 (C → G, Leu → Val, rs1056836), 449 (C → T, Asp, rs1056837), and 453 (A → G, Asn → Ser, rs1800440). A trend was demonstrated for the 432 Val/Val (χ2, P = 0.06) and 449 T/T (χ2, P = 0.1) genotypes to play a protective role against renal cancer. Odds ratio (95 % confidence interval) for Val/Val compared to Leu/Leu at codon 432 was 0.65 (0.44-0.95) and T/T compared to C/C at codon 449 was 0.67 (0.45-0.99). Codons 432 and 449 were observed to be linked (D = 0.24), and haplotype involving 432 Val and 449 T was significantly reduced in cancer cases (P = 0.04). No association was found, however, when analyzing polymorphic sites with clinical stage of cancer. These results demonstrate polymorphisms of CYP1B1 to be associated with renal carcinogenesis and are of importance in understanding their role in the pathogenesis of renal cell carcinoma.

  14. Formation and Characterization of Mixed Crystals Based on Bis (Thiourea)Cadmium Chloride and Bis (Thiourea)Cadmium Iodide

    OpenAIRE

    2014-01-01

    Bis(thiourea)cadmium chloride(BTCC) and bis(thiourea)cadmium iodide (BTCI) are metal complexes of thiourea having better nonlinear optical properties than KH2PO4. An attempt has been made in the present study to form mixed crystals based on BTCC and BTCI (even though their crystal lattices mismatch) from aqueous solutions, the precursors mixed in proper proportions. A total of seven (including the end members) crystals were formed by the free evaporation method and characteriz...

  15. Structural studies of the formation of lipoplexes between siRNA and selected bis-imidazolium gemini surfactants.

    Science.gov (United States)

    Andrzejewska, W; Pietralik, Z; Skupin, M; Kozak, M

    2016-10-01

    Dicationic (gemini) surfactants are agents that can be used for the preparation of stable complexes of nucleic acids, particularly siRNA for therapeutic purposes. In this study, we demonstrated that bis-imidazolium gemini surfactants with variable lengths of dioxyalkyl linker groups (from dioxyethyl to dioxydodecyl) and dodecyl side chains are excellent for the complexation of siRNA. All of these compounds effectively complexed siRNA in a charge ratio range (p/n) of 1.5-10. The low resolution structure of siRNA oligomers was characterised by small angle scattering of synchrotron radiation (SR-SAXS) and ab initio modelling. The structures of the formed complexes were also analysed using SR-SAXS, circular dichroism studies and electrophoretic mobility tests. The most promising agents for complexation with siRNA were the surfactants that contained dioxyethyl and dioxyhexyl spacer groups.

  16. Discovering chemistry with an ab initio nanoreactor

    OpenAIRE

    Wang, Lee-Ping; Titov, Alexey; McGibbon, Robert; Liu, Fang; Pande, Vijay S.; Martínez, Todd J.

    2014-01-01

    Chemical understanding is driven by the experimental discovery of new compounds and reactivity, and is supported by theory and computation that provides detailed physical insight. While theoretical and computational studies have generally focused on specific processes or mechanistic hypotheses, recent methodological and computational advances harken the advent of their principal role in discovery. Here we report the development and application of the ab initio nanoreactor – a highly accelerat...

  17. Reciprocity Theorems for Ab Initio Force Calculations

    CERN Document Server

    Wei, C; Mele, E J; Rappe, A M; Lewis, Steven P.; Rappe, Andrew M.

    1996-01-01

    We present a method for calculating ab initio interatomic forces which scales quadratically with the size of the system and provides a physically transparent representation of the force in terms of the spatial variation of the electronic charge density. The method is based on a reciprocity theorem for evaluating an effective potential acting on a charged ion in the core of each atom. We illustrate the method with calculations for diatomic molecules.

  18. Ab interno trabeculectomy: patient selection and perspectives

    OpenAIRE

    Vinod K; Gedde SJ

    2016-01-01

    Kateki Vinod, Steven J Gedde Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Ab interno trabeculectomy is one among several recently introduced minimally invasive glaucoma surgeries that avoid a conjunctival incision and full-thickness sclerostomy involved in traditional glaucoma surgery. Ablation of the trabecular meshwork and inner wall of Schlemm’s canal is performed in an arcuate fashion via a clear corneal incision, alone o...

  19. Design and characteristic analysis of L1B4 ultrasonic motor considering contact mechanism.

    Science.gov (United States)

    Rho, Jong-Seok; Kim, Byung-Jai; Lee, Chang-Hwan; Joo, Hyun-Woo; Jung, Hyun-Kyo

    2005-11-01

    Up to the present time, the analysis and design of ultrasonic motors (USMs) have been performed using rough analytic methods or commercial analysis tools without considering the complex contact mechanisms. As a result, it was impossible to achieve an exact analysis and design of a USM. In order to address the problem, we proposed the analysis and design methodology of an L1B4 USM using a three-dimensional finite element method combined with an analytic method that considers complex contact mechanisms in linear operation. This methodology is applicable to many other kinds of USMs which use resonance modes and contact mechanisms. Also, we designed and prototyped the mechanical system and driving circuit of the L1B4 USM, and finally validated the proposed analysis and design methodology by comparing their outcomes with experimental data.

  20. Isolation of pathogenic Yersinia enterocolitica 1B/O:8 from Apodemus mice in Japan.

    Science.gov (United States)

    Oda, Shinya; Kabeya, Hidenori; Sato, Shingo; Shimonagane, Ai; Inoue, Kai; Hayashidani, Hideki; Takada, Nobuhiro; Fujita, Hiromi; Kawabata, Hiroki; Maruyama, Soichi

    2015-01-01

    Yersinia enterocolitica was isolated from 15.7% (88/560) of wild rodents captured in 15 prefectures in Japan. Prevalences by rodent species were 18.0% (70/388) in Japanese field mice (Apodemus speciosus), 20% (14/71) in small Japanese field mice (Apodemus argenteus), and 11% (4/38) in gray red-backed vole (Myodes rufocanus bedfordiae), suggesting that these rodent species are important reservoirs of Y. enterocolitica. Although most of the isolates were identified as biotype 1A, the pathogenic bioserotype 1B/O:8 was detected in one of the A. speciosus and in three of the A. argenteus captured in Aomori Prefecture. It is suggested that Apodemus mice may be an important reservoir of Y. enterocolitica, and that there are foci of the pathogenic bioserotype 1B/O:8 in Aomori Prefecture, because human sporadic cases by the serotype have been reported in this prefecture.

  1. Anti-HPA-1b Mediated Posttransfusion Purpura: A Case Report

    Directory of Open Access Journals (Sweden)

    O. P. Arewa

    2013-01-01

    Full Text Available Posttransfusion purpura (PTP is an uncommon, but potentially fatal, transfusion reaction characterized by profound thrombocytopenia and bleeding. PTP is caused by alloimmunization to human platelet specific antigens following blood component transfusion. Although there is evidence of a wide serological spectrum of culprit antibodies implicated, Anti-human-platelet-antigen- (HPA- 1a is the most common antibody in cases reported. We report a case of posttransfusion purpura in an African American. The patient was negative for HPA-1a antibodies, but anti-HPA-1b was identified with a platelet phenotype of HPA-1a/HPA-1a. Although less common, HPA-1b antibody may be an important consideration in posttransfusion purpura diagnosed in patients of African descent.

  2. Intrinsic fluorescence spectra characteristics of vitamin B1, B2, and B6

    Science.gov (United States)

    Yang, Hui; Xiao, Xue; Zhao, Xuesong; Hu, Lan; Lv, Caofang; Yin, Zhangkun

    2015-11-01

    This paper presents the intrinsic fluorescence characteristics of vitamin B1, B2 and B6 measured with 3D fluorescence Spectrophotometer. Three strong fluorescence areas of vitamin B2 locate at λex/λem=270/525nm, 370/525nm and 450/525nm, one fluorescence areas of vitamin B1 locates at λex/λem=370/460nm, two fluorescence areas of vitamin B6 locates at λex/λem=250/370nm and 325/370nm were found. The influence of pH of solution to the fluorescence profile was also discussed. Using the PARAFAC algorithm, 10 vitamin B1, B2 and B6 mixed solutions were successfully decomposed, and the emission profiles, excitation profiles, central wavelengths and the concentration of the three components were retrieved precisely through about 5 iteration times.

  3. Ab interno trabeculectomy: patient selection and perspectives

    Science.gov (United States)

    Vinod, Kateki; Gedde, Steven J

    2016-01-01

    Ab interno trabeculectomy is one among several recently introduced minimally invasive glaucoma surgeries that avoid a conjunctival incision and full-thickness sclerostomy involved in traditional glaucoma surgery. Ablation of the trabecular meshwork and inner wall of Schlemm’s canal is performed in an arcuate fashion via a clear corneal incision, alone or in combination with phacoemulsification cataract surgery. Intraocular pressure reduction following ab interno trabeculectomy is limited by resistance in distal outflow pathways and generally stabilizes in the mid-to-high teens. Relief of medication burden has been demonstrated by some studies. A very low rate of complications, most commonly transient hyphema and intraocular pressure elevations in the immediate postoperative period, have been reported. However, available data are derived from small retrospective and prospective case series. Randomized, controlled trials are needed to better elucidate the potential merits of ab interno trabeculectomy in the combined setting versus phacoemulsification cataract surgery alone and to compare it with other minimally invasive glaucoma surgeries. PMID:27574396

  4. Highly scalable Ab initio genomic motif identification

    KAUST Repository

    Marchand, Benoit

    2011-01-01

    We present results of scaling an ab initio motif family identification system, Dragon Motif Finder (DMF), to 65,536 processor cores of IBM Blue Gene/P. DMF seeks groups of mutually similar polynucleotide patterns within a set of genomic sequences and builds various motif families from them. Such information is of relevance to many problems in life sciences. Prior attempts to scale such ab initio motif-finding algorithms achieved limited success. We solve the scalability issues using a combination of mixed-mode MPI-OpenMP parallel programming, master-slave work assignment, multi-level workload distribution, multi-level MPI collectives, and serial optimizations. While the scalability of our algorithm was excellent (94% parallel efficiency on 65,536 cores relative to 256 cores on a modest-size problem), the final speedup with respect to the original serial code exceeded 250,000 when serial optimizations are included. This enabled us to carry out many large-scale ab initio motiffinding simulations in a few hours while the original serial code would have needed decades of execution time. Copyright 2011 ACM.

  5. Ab initio Bogoliubov coupled cluster theory

    Science.gov (United States)

    Signoracci, Angelo; Hagen, Gaute; Duguet, Thomas

    2014-09-01

    Coupled cluster (CC) theory has become a standard method in nuclear theory for realistic ab initio calculations of medium mass nuclei, but remains limited by its requirement of a Slater determinant reference state which reasonably approximates the nuclear system of interest. Extensions of the method, such as equation-of-motion CC, permit the calculation of nuclei with one or two nucleons added or removed from a doubly magic core, yet still only a few dozen nuclei are accessible with modern computational restrictions. In order to extend the applicability of ab initio methods to open-shell systems, the superfluid nature of nuclei must be taken into account. By utilizing Bogoliubov algebra and employing spontaneous symmetry breaking with respect to particle number conservation, superfluid systems can be treated by a single reference state. An ab initio theory to include correlations on top of a Bogoliubov reference state has been developed in the guise of standard CC theory. The formalism and first results of this Bogoliubov coupled cluster theory will be presented to demonstrate the applicability of the method.

  6. Kinetics and mechanism of protein tyrosine phosphatase 1B inactivation by acrolein.

    Science.gov (United States)

    Seiner, Derrick R; LaButti, Jason N; Gates, Kent S

    2007-09-01

    Human cells are exposed to the electrophilic alpha,beta-unsaturated aldehyde acrolein from a variety of sources. The reaction of acrolein with functionally critical protein thiol residues can yield important biological consequences. Protein tyrosine phosphatases (PTPs) are an important class of cysteine-dependent enzymes whose reactivity with acrolein previously has not been well-characterized. These enzymes catalyze the dephosphorylation of phosphotyrosine residues on proteins via a phosphocysteine intermediate. PTPs work in tandem with protein tyrosine kinases to regulate a number of critically important mammalian signal transduction pathways. We find that acrolein is a potent time-dependent inactivator of the enzyme PTP1B ( k inact = 0.02 +/- 0.005 s (-1) and K I = 2.3 +/- 0.6 x 10 (-4) M). The enzyme activity does not return upon gel filtration of the inactivated enzyme, and addition of the competitive phosphatase inhibitor vanadate slows inactivation of PTP1B by acrolein. Together, these observations suggest that acrolein covalently modifies the active site of PTP1B. Mass spectrometric analysis reveals that acrolein modifies the catalytic cysteine residue at the active site of the enzyme. Aliphatic aldehydes such as glyoxal, acetaldehyde, and propanal are relatively weak inactivators of PTP1B under the conditions employed here. Similarly, unsaturated aldehydes such as crotonaldehyde and 3-methyl-2-butenal bearing substitution at the alkene terminus are poor inactivators of the enzyme. Overall, the data suggest that enzyme inactivation occurs via conjugate addition of the catalytic cysteine residue to the carbon-carbon double bond of acrolein. The results indicate that inactivation of PTPs should be considered as a possible contributor to the diverse biological activities of acrolein and structurally related alpha,beta-unsaturated aldehydes.

  7. 5-HT1B receptor modulation of the serotonin transporter in vivo: Studies using KO mice

    OpenAIRE

    Montañez, Sylvia; Munn, Jaclyn L.; Owens, W. Anthony; Horton, Rebecca E.; Daws, Lynette C.

    2013-01-01

    The serotonin transporter (SERT) controls the strength and duration of serotonergic neurotransmission by the high-affinity uptake of ser otonin (5-HT) from extracellular fluid. SERT is a key target for many psychotherapeutic and abused drugs, therefore understanding how SERT activity and expression are regulated is of fundamental importance. A growing literature suggests that SERT activity is under regulatory control of the 5-HT1B autoreceptor. The present studies made use of mice with a cons...

  8. Potent water extracts of Indonesian medicinal plants against PTP1B

    Directory of Open Access Journals (Sweden)

    Azis Saifudin

    2016-01-01

    Conclusions: In contrast to the mainstream solvents currently used in modern herbal manufactures especially Jamu medicine in Indonesia, pure-water-extracted materials should be reconsidered and could be reemerged for future studies and for the manufacture of herbal medicines. In addition, the activity of Jamu components should be confirmed that their antidiabetes and antiobesity activities could be through the inhibition of PTP1B.

  9. Mixed adenosquamous histology is associated with poorer survival of cervical cancer stage 1b

    DEFF Research Database (Denmark)

    Lauszus, Finn; Tjessem, Ingvild; Al-Far, Hanine M

    2016-01-01

    Background: Evaluation of histopathological factors for women with radical hysterectomy a.m. Okabayashi for cervical cancer in stage 1bwith similar pre- and postoperative treatment Methods: Data on 141 women with cervical cancer stage 1b were revised. The local patient registry, data charts......, while survival was found to be 89 % (83-95 %) and 86 % (79-93 %), respectively. The women’s age at diagnosis showed no association with histology type or survival....

  10. Contribution of brain serotonin subtype 1B receptors in levodopa-induced motor complications.

    Science.gov (United States)

    Morin, Nicolas; Morissette, Marc; Grégoire, Laurent; Rajput, Alex; Rajput, Ali H; Di Paolo, Thérèse

    2015-12-01

    L-DOPA-induced dyskinesias (LID) are abnormal involuntary movements limiting the chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease. Serotonin receptors are implicated in the development of LID and modulation of basal ganglia 5-HT1B receptors is a potential therapeutic alternative in Parkinson's disease. In the present study, we used receptor-binding autoradiography of the 5-HT1B-selective radioligand [3H]GR125743 to investigate possible contributions of changes in ligand binding of this receptor in LID in post-mortem brain specimens from Parkinson's disease patients (n=14) and control subjects (n=11), and from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys treated with saline (n=5), L-DOPA (n=4) or L-DOPA+2-methyl-6-(phenylethynyl)pyridine (MPEP) (n=5), and control monkeys (n=4). MPEP is the prototypal metabotropic glutamate 5 (mGlu5) receptor antagonist and has been shown to reduce the development of LID in these monkeys in a chronic treatment of one month. [3H]GR125743 specific binding to striatal and pallidal 5-HT1B receptors respectively were only increased in L-DOPA-treated MPTP monkeys (dyskinetic monkeys) as compared to controls, saline and L-DOPA+MPEP MPTP monkeys; dyskinesias scores correlated positively with this binding. Parkinson's disease patients with motor complications (L-DOPA-induced dyskinesias and wearing-off) had higher [3H]GR125743 specific binding compared to those without motor complications and controls in the basal ganglia. Reduction of motor complications was associated with normal striatal 5-HT1B receptors, suggesting the potential of this receptor for the management of motor complications in Parkinson's disease.

  11. Antimicrobial Resistance of Shigella flexneri Serotype 1b Isolates in China.

    Directory of Open Access Journals (Sweden)

    Xianyan Cui

    Full Text Available Shigella flexneri serotype 1b is among the most prominent serotypes in developing countries, followed by serotype 2a. However, only limited data is available on the global phenotypic and genotypic characteristics of S. flexneri 1b. In the present study, 40 S. flexneri 1b isolates from different regions of China were confirmed by serotyping and biochemical characterization. Antimicrobial susceptibility testing showed that 85% of these isolates were multidrug-resistant strains and antibiotic susceptibility profiles varied between geographical locations. Strains from Yunnan were far more resistant than those from Xinjiang, while only one strain from Shanghai was resistant to ceftazidime and aztreonam. Fifteen cephalosporin resistant isolates were identified in this study. ESBL genes (blaSHV, blaTEM, blaOXA, and blaCTX-M and ampC genes (blaMOX, blaFOX, blaMIR(ACT-1, blaDHA, blaCIT and blaACC were subsequently detected among the 15 isolates. The results showed that these strains were positive only for blaTEM, blaOXA, blaCTX-M, intI1, and intI2. Furthermore, pulsed-field gel electrophoresis (PFGE analysis showed that the 40 isolates formed different profiles, and the PFGE patterns of Xinjiang isolates were distinct from Yunnan and Shanghai isolates by one obvious, large, missing band. In summary, similarities in resistance patterns were observed in strains with the same PFGE pattern. Overall, the results supported the need for more prudent selection and use of antibiotics in China. We suggest that antibiotic susceptibility testing should be performed at the start of an outbreak, and antibiotic use should be restricted to severe Shigella cases, based on resistance pattern variations observed in different regions. The data obtained in the current study might help to develop a strategy for the treatment of infections caused by S. flexneri 1b in China.

  12. CYP1B1 Asn453Ser polymorphism and colorectal cancer risk: a meta-analysis.

    Science.gov (United States)

    Mei, Qiang; Zhou, Daijun; Han, Jialong; Lu, Hai; Tang, Bo

    2012-09-01

    Studies investigating the association between cytochrome P450 1B1 (CYP1B1) Asn453Ser (453 A/G, rs1800440) polymorphism and colorectal cancer (CRC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline and Embase Databases. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP1B1 polymorphism and CRC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. The pooled ORs were performed for co-dominant model (GG vs AA, GA vs AA), dominant model (GG+GA vs AA), and recessive model (GG vs GA+AA). This meta-analysis included 7 case-control studies, which included 6375 CRC cases and 7003 controls. Overall, the variant genotypes (GG and GA) of the 453 A/G were not associated with CRC risk when compared with the wild-type AA homozygote (GG vs AA, OR=0.94, 95% CI=0.77-1.14; GA vs AA, OR=0.99, 95% CI=0.87-1.12). Similarly, no associations were found in the dominant and recessive models (dominant model, OR=0.98, 95% CI=0.87-1.09; recessive model, OR=0.94, 95% CI=0.77-1.14). When stratifying for country, study sample size, matched control and source of controls, no evidence of significant association was observed in any subgroup, except among those studies from "Canada". No publication bias was found in the present study. No association was found between the CYP1B1 Asn453Ser polymorphism and risk of CRC among Caucasians.

  13. B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-224 B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1) As of FY...10 Track to Budget 11 Cost and Funding 13 Low Rate Initial Production 19 Foreign Military Sales 20 Nuclear Costs 20 Unit Cost...Document CLIN - Contract Line Item Number CPD - Capability Production Document CY - Calendar Year DAB - Defense Acquisition Board DAE - Defense

  14. Polymorphisms in alcohol metabolism genes ADH1B and ALDH2, alcohol consumption and colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Marta Crous-Bou

    Full Text Available BACKGROUND: Colorectal cancer (CRC is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population. METHODOLOGY/PRINCIPAL FINDINGS: SNPs from ADH1B and ALDH2 genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC study (OR = 1.47; 95%CI = 1.18-1.81. Moreover, the SNPs rs1229984 in ADH1B gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025. A path analysis based on structural equation modeling showed a direct effect of ADH1B gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption. CONCLUSIONS/SIGNIFICANCE: Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants.

  15. Polymorphisms in Alcohol Metabolism Genes ADH1B and ALDH2, Alcohol Consumption and Colorectal Cancer

    Science.gov (United States)

    Crous-Bou, Marta; Rennert, Gad; Cuadras, Daniel; Salazar, Ramon; Cordero, David; Saltz Rennert, Hedy; Lejbkowicz, Flavio; Kopelovich, Levy; Monroe Lipkin, Steven; Bernard Gruber, Stephen; Moreno, Victor

    2013-01-01

    Background Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population. Methodology/Principal Findings SNPs from ADH1B and ALDH2 genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC) study (OR = 1.47; 95%CI = 1.18-1.81). Moreover, the SNPs rs1229984 in ADH1B gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025). A path analysis based on structural equation modeling showed a direct effect of ADH1B gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption. Conclusions/Significance Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants. PMID:24282520

  16. Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Yang Jae-Hyug

    2011-06-01

    Full Text Available Abstract Backgrounds Two SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM in previous studies. Since T2DM and gestational diabetes mellitus (GDM share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes. Methods A total of 1,918 subjects (928 GDM patients and 990 controls were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs, 95% confidence intervals (CIs, and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed. Results We found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses. Conclusion There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.

  17. Microtubule Associated Protein 1b (MAP1B Is a Marker of the Microtubular Cytoskeleton in Podocytes but Is Not Essential for the Function of the Kidney Filtration Barrier in Mice.

    Directory of Open Access Journals (Sweden)

    Markus Gödel

    Full Text Available Podocytes are essential for the function of the kidney glomerular filter. A highly differentiated cytoskeleton is requisite for their integrity. Although much knowledge has been gained on the organization of cortical actin networks in podocyte's foot processes, less is known about the molecular organization of the microtubular cytoskeleton in primary processes and the cell body. To gain an insight into the organization of the microtubular cytoskeleton of the podocyte, we systematically analyzed the expression of microtubule associated proteins (Maps, a family of microtubules interacting proteins with known functions as regulator, scaffold and guidance proteins. We identified microtubule associated protein 1b (MAP1B to be specifically enriched in podocytes in human and rodent kidney. Using immunogold labeling in electron microscopy, we were able to demonstrate an enrichment of MAP1B in primary processes. A similar association of MAP1B with the microtubule cytoskeleton was detected in cultured podocytes. Subcellular distribution of MAP1B HC and LC1 was analyzed using a double fluorescent reporter MAP1B fusion protein. Subsequently we analyzed mice constitutively depleted of MAP1B. Interestingly, MAP1B KO was not associated with any functional or structural alterations pointing towards a redundancy of MAP proteins in podocytes. In summary, we established MAP1B as a specific marker protein of the podocyte microtubular cytoskeleton.

  18. Clock gene modulates roles of OXTR and AVPR1b genes in prosociality.

    Directory of Open Access Journals (Sweden)

    Haipeng Ci

    Full Text Available BACKGROUND: The arginine vasopressin receptor (AVPR and oxytocin receptor (OXTR genes have been demonstrated to contribute to prosocial behavior. Recent research has focused on the manner by which these simple receptor genes influence prosociality, particularly with regard to the AVP system, which is modulated by the clock gene. The clock gene is responsible for regulating the human biological clock, affecting sleep, emotion and behavior. The current study examined in detail whether the influences of the OXTR and AVPR1b genes on prosociality are dependent on the clock gene. METHODOLOGY/PRINCIPAL FINDINGS: This study assessed interactions between the clock gene (rs1801260, rs6832769 and the OXTR (rs1042778, rs237887 and AVPR1b (rs28373064 genes in association with individual differences in prosociality in healthy male Chinese subjects (n = 436. The Prosocial Tendencies Measure (PTM-R was used to assess prosociality. Participants carrying both the GG/GA variant of AVPR1b rs28373064 and the AA variant of clock rs6832769 showed the highest scores on the Emotional PTM. Carriers of both the T allele of OXTR rs1042778 and the C allele of clock rs1801260 showed the lowest total PTM scores compared with the other groups. CONCLUSIONS: The observed interaction effects provide converging evidence that the clock gene and OXT/AVP systems are intertwined and contribute to human prosociality.

  19. Structure-based discovery of selective serotonin 5-HT(1B) receptor ligands.

    Science.gov (United States)

    Rodríguez, David; Brea, José; Loza, María Isabel; Carlsson, Jens

    2014-08-05

    The development of safe and effective drugs relies on the discovery of selective ligands. Serotonin (5-hydroxytryptamine [5-HT]) G protein-coupled receptors are therapeutic targets for CNS disorders but are also associated with adverse drug effects. The determination of crystal structures for the 5-HT1B and 5-HT2B receptors provided an opportunity to identify subtype selective ligands using structure-based methods. From docking screens of 1.3 million compounds, 22 molecules were predicted to be selective for the 5-HT1B receptor over the 5-HT2B subtype, a requirement for safe serotonergic drugs. Nine compounds were experimentally verified as 5-HT1B-selective ligands, with up to 300-fold higher affinities for this subtype. Three of the ligands were agonists of the G protein pathway. Analysis of state-of-the-art homology models of the two 5-HT receptors revealed that the crystal structures were critical for predicting selective ligands. Our results demonstrate that structure-based screening can guide the discovery of ligands with specific selectivity profiles.

  20. Synthesis of Al-5Ti-1B Refiner by Melt Reaction Method

    Directory of Open Access Journals (Sweden)

    LI He

    2017-02-01

    Full Text Available Al-5Ti-1B refiner was successfully prepared by melt reaction method. Through the thermodynamics calculation, the initial reaction temperature was determined. The influence of reaction temperature on microstructure and absorption rate of the alloy was investigated. The phase and microstructure of the alloy were observed by X-ray diffraction, scanning electron microscope and energy dispersive spectrometer. The Al-5Ti-1B refiner was extruded at high temperature to wire with the diameter of 9.5mm, and then the refinement experiment was carried out on pure aluminium. The results indicate that the refiner consists of TiB2, TiAl3 and α-Al, and the microstructure prepared at 850℃ is the optimum and the absorption rate of Ti and B matches the best. The TiAl3 and TiB2 phases distribute homogeneously in the matrix after extrusion. When adding 0.2%(mass fraction of Al-5Ti-1B refiner, the grain size of pure aluminium reduces from 3.99mm to 0.45mm.

  1. Perk Ablation Ameliorates Myelination in S63del-Charcot-Marie-Tooth 1B Neuropathy.

    Science.gov (United States)

    Musner, Nicolò; Sidoli, Mariapaola; Zambroni, Desireè; Del Carro, Ubaldo; Ungaro, Daniela; D'Antonio, Maurizio; Feltri, Maria L; Wrabetz, Lawrence

    2016-01-01

    In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER) and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del) accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot-Marie-Tooth disease type 1B (CMT1B)-S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF2alpha) in order to attenuate protein synthesis. We have shown that increasing phosphophorylated-eIF2alpha (P-eIF2alpha) is a potent therapeutic strategy, improving myelination and motor function in S63del mice. Here, we explore the converse experiment:Perkhaploinsufficiency reduces P-eIF2alpha in S63del nerves as expected, but surprisingly, ameliorates, rather than worsens S63del neuropathy. Motor performance and myelin abnormalities improved in S63del//Perk+/- compared with S63del mice. These data suggest that mechanisms other than protein translation might be involved in CMT1B/S63del neuropathy. In addition,Perkdeficiency in other cells may contribute to demyelination in a non-Schwann-cell autonomous manner.

  2. Forced expression of Hnf1b/Foxa3 promotes hepatic fate of embryonic stem cells.

    Science.gov (United States)

    Yahoo, Neda; Pournasr, Behshad; Rostamzadeh, Jalal; Hakhamaneshi, Mohammad Saeed; Ebadifar, Asghar; Fathi, Fardin; Baharvand, Hossein

    2016-05-20

    Embryonic stem (ES) cell-derived hepatocytes have the potential to be used for basic research, regenerative medicine, and drug discovery. Recent reports demonstrated that in addition to conventional differentiation inducers such as chemical compounds and cytokines, overexpression of lineage-specific transcription factors could induce ES cells to differentiate to a hepatic fate. Here, we hypothesized that lentivirus-mediated inducible expression of hepatic lineage transcription factors could enhance mouse ES cells to hepatocyte-like cells. We screened the effects of candidate transcription factors Hnf1b, Hnf1a, Hnf4a, Foxa1, Foxa3 and Hex, and determined that the combination of Hnf1b/Foxa3 promoted expression of several hepatic lineage-specific markers and proteins, in addition to glycogen storage, ICG uptake, and secretion of albumin and urea. The differentiated cells were engraftable and expressed albumin when transplanted into a carbon tetrachloride-injured mouse model. These results demonstrated the crucial role of Hnf1b and Foxa3 in hepatogenesis in vitro and provided a valuable tool for the efficient differentiation of HLCs from ES cells.

  3. A de novo microdeletion involving PAFAH1B (LIS1 related to lissencephaly phenotype

    Directory of Open Access Journals (Sweden)

    Keiko Shimojima

    2015-09-01

    Full Text Available Lissencephaly is a type of the congenital malformation of the brain. Due to the impairments of neuronal migration, patients show absence of brain convolution manifesting smooth brain surfaces. One of the human genes responsible for lissencephaly is the platelet-activating factor acetylhydrolase 1b gene (PAFAH1B; also known as LIS1 located on 17p13.3. Patients with heterozygous deletion of this chromosomal region exhibit lissencephaly. Recently, we encountered a male patient who showed typical lissencephaly. Using a microarray analysis, we identified a 1.3 Mb submicroscopic deletion in 17p13.3. This deletion included PAFAH1B. Both of the parents showed no deletion in this region. Therefore, this was determined to be derived from de novo origin. After obtaining the written informed consent, skin fibroblasts were provided from this patient and disease-specific induced pluripotent stem (iPS cells were generated and used for medical research (Shimojima K, Okumura A, Hayashi M, Kondo T, Inoue H, and Yamamoto T. CHCHD2 is down-regulated in neuronal cells differentiated from iPS cells derived from patients with lissencephaly. Genomics, in press.

  4. Galactic gamma ray excess and dark matter phenomenology in a U(1) B- L model

    Science.gov (United States)

    Biswas, Anirban; Choubey, Sandhya; Khan, Sarif

    2016-08-01

    In this work, we have considered a gauged U(1)B-L extension of the Standard Model (SM) with three right handed neutrinos for anomaly cancellation and two additional SM singlet complex scalars with nontrivial B-L charges. One of these is used to spontaneously break the U(1)B-L gauge symmetry, leading to Majorana masses for the neutrinos through the standard Type I seesaw mechanism, while the other becomes the dark matter (DM) candidate in the model. We test the viability of the model to simultaneously explain the DM relic density observed in the CMB data as well as the Galactic Centre (GC) γ-ray excess seen by Fermi-LAT. We show that for DM masses in the range 40-55 GeV and for a wide range of U(1)B-L gauge boson masses, one can satisfy both these constraints if the additional neutral Higgs scalar has a mass around the resonance region. In studying the dark matter phenomenology and GC excess, we have taken into account theoretical as well as experimental constraints coming from vacuum stability condition, Planck bound on DM relic density, LHC and LUX and present allowed areas in the model parameter space consistent with all relevant data, calculate the predicted gamma ray flux from the GC and discuss the related phenomenology.

  5. Association between the CYP1B1 polymorphisms and risk of cancer: a meta-analysis.

    Science.gov (United States)

    Liu, Jie-Ying; Yang, Yu; Liu, Zhi-Zhong; Xie, Jian-Jun; Du, Ya-Ping; Wang, Wei

    2015-04-01

    The previous, published data on the association between CYP1B1 polymorphisms and cancer risk remained controversial. To derive a more precise estimation of the association between the CYP1B1 polymorphisms and cancer risk, we performed a meta-analysis to investigate the association between cancer susceptibility and CYP1B1 Leu432Val, Asn453Ser, Arg48Gly, and Ala119Ser polymorphisms. For Asn453Ser and Arg48Gly polymorphisms, significantly decreased endometrial cancer was observed among Caucasians. For Ala119Ser polymorphism, we found that individuals with the minor variant genotypes had a high risk of prostate cancer. For Leu432Val polymorphism, we found that individuals with the minor variant genotypes had a higher risk of endometrial cancer and lung cancer and had a lower risk of ovarian cancer. In summary, this meta-analysis suggests that Leu432Val polymorphism is associated with ovarian cancer, lung cancer, and endometrial cancer risk; Asn453Ser and Arg48Gly polymorphisms are associated with endometrial cancer risk among Caucasians, Ala119Ser polymorphism is associated with prostate cancer risk, and Ala119Ser polymorphism is associated with breast cancer risk in Caucasians. In addition, our work also points out the importance of new studies for Ala119Ser polymorphism in endometrial cancer, because high heterogeneity was observed (I (2) > 75 %).

  6. Mutations of the CYP1B1 gene in congenital anterior staphylomas

    Directory of Open Access Journals (Sweden)

    Al Judaibi R

    2014-02-01

    Full Text Available Ramzi Al Judaibi,1 Khaled K Abu-Amero,2,3 Jose Morales,1 Sami Al Shahwan,1 Deepak P Edward1,4 1King Khaled Eye Specialist Hospital, 2Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, FL, USA; 4Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore MD, USA Purpose: Here, we present two patients with congenital anterior staphyloma, with mutations in the CYP1B1 gene. Methods: We reviewed the medical records, including the genetic analysis. Results: Two unrelated patients presented with congenital anterior staphylomas. Both patients showed mutations in the CYP1B1 gene. The first patient, the product of a consanguineous marriage, showed a homozygous misssense mutation g.3987G>A (p.G61E. The second patient had compound heterozygous misssense mutations [g.4160 G>T (p.A119S and g.8131 C>G (p.L432V]. Conclusion: CYP1B1 gene mutation may be associated with congenital anterior staphylomas. Keywords: mutation analysis, congenital glaucoma, consanguinity, congenital aphakia

  7. [Validation of HJ-1B thermal infrared channels onboard radiometric calibration based on spectral response differences].

    Science.gov (United States)

    Liu, Li; Fu, Qiao-yan; Shi, Ting-ting; Wang, Ai-chun; Zhang, Xue-wen

    2014-08-01

    Since HJ-1B was launched, 7 sets of blackbody data have been used to calculate onboard calibration coefficients, but the research work on the validation of coefficients is rare. According to the onboard calibration principle, calibration coefficients of HJ-1B thermal infrared channel on Sep 14th, 2009 were calculated with the half-width, moments and look-up table methods. MODIS was selected for the reference sensor, and algorithms of spectral match were improved between the HJ-1B thermal infrared channel and MODIS 31, 32 channels based on the spectral response divergence. The relationship of top of atmosphere (TOA) radiance between the remote sensors was calculated, based on which the surface leaving brightness temperature was calculated by Planck function to validate the brightness temperature calculated through the onboard calibration coefficients. The equivalent brightness temperature calculated by spectral response divergence method is 285.97 K, and the inversion brightness temperature calculated by half-width, moments and look-up table methods is 288.77, 274.52 and 285.97 K respectively. The difference between the inversion brightness temperature and the equivalent brightness temperature is 2.8, -11.46 and 0.02 K, respectively, which demonstrate that onboard calibration coefficients calculated by the look-up table method has better precision and feasibility.

  8. Hoxb1b controls oriented cell division, cell shape and microtubule dynamics in neural tube morphogenesis.

    Science.gov (United States)

    Zigman, Mihaela; Laumann-Lipp, Nico; Titus, Tom; Postlethwait, John; Moens, Cecilia B

    2014-02-01

    Hox genes are classically ascribed to function in patterning the anterior-posterior axis of bilaterian animals; however, their role in directing molecular mechanisms underlying morphogenesis at the cellular level remains largely unstudied. We unveil a non-classical role for the zebrafish hoxb1b gene, which shares ancestral functions with mammalian Hoxa1, in controlling progenitor cell shape and oriented cell division during zebrafish anterior hindbrain neural tube morphogenesis. This is likely distinct from its role in cell fate acquisition and segment boundary formation. We show that, without affecting major components of apico-basal or planar cell polarity, Hoxb1b regulates mitotic spindle rotation during the oriented neural keel symmetric mitoses that are required for normal neural tube lumen formation in the zebrafish. This function correlates with a non-cell-autonomous requirement for Hoxb1b in regulating microtubule plus-end dynamics in progenitor cells in interphase. We propose that Hox genes can influence global tissue morphogenesis by control of microtubule dynamics in individual cells in vivo.

  9. Construction and in vitro Study of an E1B-Defective Adenovirus

    Institute of Scientific and Technical Information of China (English)

    Xue Feng; Joshua Mallam Nock; Zhu Hua-bin; Dong Chang-yuan; Qi Yi-peng

    2004-01-01

    An E1B-defective adenovirus named r1/Ad was constructed by homologous recombination. The construction, selection and propagation of recombinant virus was done in the human embryonic kidney 293 cells (HEK293). The in vitro study demonstrated that the recombinant virus has the ability to replicate in and lyse some p53-deficient human tumor cells such as the human glioblastoma tumor cells (U251) and human bladder tumer cells (EJ) but not in the normal cells with functional p53 such as the human fibroblast cells (MRC-5). Also, based on the cytopathic effect (CPE), it was demonstrated that the U251 cells were more sensitive to the infection of r1/Ad than that of EJ cells under identical conditions. In this paper, it was found that r1/Ad could be very useful in studying the in vitro selective replication of E1B-defective adenovirus. This may help to determine the safety of using any E1B-defective adenoviruses in cancer gene therapy.

  10. Superoxide anion radicals induce IGF-1 resistance through concomitant activation of PTP1B and PTEN.

    Science.gov (United States)

    Singh, Karmveer; Maity, Pallab; Krug, Linda; Meyer, Patrick; Treiber, Nicolai; Lucas, Tanja; Basu, Abhijit; Kochanek, Stefan; Wlaschek, Meinhard; Geiger, Hartmut; Scharffetter-Kochanek, Karin

    2015-01-01

    The evolutionarily conserved IGF-1 signalling pathway is associated with longevity, metabolism, tissue homeostasis, and cancer progression. Its regulation relies on the delicate balance between activating kinases and suppressing phosphatases and is still not very well understood. We report here that IGF-1 signalling in vitro and in a murine ageing model in vivo is suppressed in response to accumulation of superoxide anions (O2∙-) in mitochondria, either by chemical inhibition of complex I or by genetic silencing of O2∙--dismutating mitochondrial Sod2. The O2∙--dependent suppression of IGF-1 signalling resulted in decreased proliferation of murine dermal fibroblasts, affected translation initiation factors and suppressed the expression of α1(I), α1(III), and α2(I) collagen, the hallmarks of skin ageing. Enhanced O2∙- led to activation of the phosphatases PTP1B and PTEN, which via dephosphorylation of the IGF-1 receptor and phosphatidylinositol 3,4,5-triphosphate dampened IGF-1 signalling. Genetic and pharmacologic inhibition of PTP1B and PTEN abrogated O2∙--induced IGF-1 resistance and rescued the ageing skin phenotype. We thus identify previously unreported signature events with O2∙-, PTP1B, and PTEN as promising targets for drug development to prevent IGF-1 resistance-related pathologies.

  11. U(1)B-L symmetry restoration and effective neutrino species

    Science.gov (United States)

    Ishida, Hiroyuki; Takahashi, Fuminobu

    2014-06-01

    The U(1)B-L symmetry could be restored during inflation, since the BICEP2 results suggest a GUT-scale inflation with the Hubble parameter, Hinf≃1014 GeV, close to the U(1)B-L breaking scale. We consider a scenario in which the B-L Higgs field dominates the Universe after inflation, and mainly decays into the U(1)B-L gauge bosons, whose subsequent decays reheat the Universe. Interestingly, if one of the right-handed neutrinos is extremely light and behaves as dark radiation or hot dark matter, its abundance is determined by the B-L charge assignment and the relativistic degree of freedom in plasma. We find that ΔNeff takes discrete values between 0.188 and 0.220 in the standard model plus three right-handed neutrinos, depending on whether the decay into heavier right-handed neutrinos is kinematically accessible or not. In the fiveness U(1)5 case, we find that ΔNeff takes discrete values between 0.313 and 0.423. The tension between BICEP2 and Planck can be partially relaxed by dark radiation.

  12. U(1)$_{B-L}$ Symmetry Restoration and Effective Neutrino Species

    CERN Document Server

    Ishida, Hiroyuki

    2014-01-01

    The U(1)$_{B-L}$ symmetry could be restored during inflation, since the BICEP2 results suggest a GUT-scale inflation with the Hubble parameter, $H_{\\rm inf} \\simeq 10^{14}$ GeV, close to the U(1)$_{B-L}$ breaking scale. If the ${B-L}$ Higgs field dominates the Universe after inflation, it can mainly decay into the U(1)$_{B-L}$ gauge bosons, whose subsequent decays reheat the Universe. Interestingly, if one (or more) of the right-handed neutrinos is extremely light and behaves as dark radiation or hot dark matter, its abundance is determined solely by the $B-L$ charge assignment and the relativistic degree of freedom in plasma. We find that $\\Delta N_{\\rm eff}$ takes discrete values between $0.188$ and $0.220$ in the standard model plus three right-handed neutrinos, depending on whether the decay into heavier right-handed neutrinos are kinematically accessible or not. In the fiveness U(1)$_{\\bf 5}$ case, we find that $\\Delta N_{\\rm eff}$ takes discrete values between $0.274$ and $0.386$. The tension between BI...

  13. Synthesis, properties and supramolecular structure of di(aqua)bis(ethylenediamine)nickel(II) bis(4-nitrobenzoate)

    Indian Academy of Sciences (India)

    Bikshandarkoil R Srinivasan; Gayatri K Rane

    2009-03-01

    The reaction of the sodium salt of 4-nitrobenzoic acid (4-nbaH) with [Ni(H2O)6]Cl2 or [Ni(en)3]Cl2.2H2O (en is ethylenediamine) results in the formation of the known octahedral compound [Ni(H2O)4(1-4-nba)2].2H2O (4-nba = 4-nitrobenzoate) 1 or the title compound di(aqua)bis(ethylenediamine) nickel(II) bis(4-nitrobenzoate) 2 respectively. Compounds 1 and 2 were characterized by elemental analysis, infrared spectra, DSC thermograms, weight loss studies and the structure of 2 was determined. Both 1 and 2 can be thermally decomposed to green NiO. The title compound [Ni(H2O)2(en)2](4-nba)2 2 crystallizes in the centrosymmetric monoclinic space group 21/ with the Ni(II) situated on an inversion center. The crystal structure of 2 consists of a hexacoordinated Ni(II) complex cation and an uncoordinated 4-nba anion. In the octahedral complex cation, the central metal is linked to two symmetry related bidentate en ligands and two water molecules. In the crystal structure, the cations and anions are linked by three varieties of hydrogen bonding interactions. A comparative study of seven nickel 4-nitrobenzoate compounds is described.

  14. Estructura molecular y cristalina del bis (bis(dietilamino glioximato níquel (II

    Directory of Open Access Journals (Sweden)

    Luis Alejandro Nuvan

    2009-07-01

    Full Text Available Ni(CioH2lN4022- monoclínico, grupo espacial P2i/a, a = 15.760 (2, b = 11.793 (3, c = 7.297 (1 A°, j3 = 99.10 (1°, V = 1339.0 (7 A°3, Z = 2 , De = 1.28 Mg M " \\ M = 765 M " ' . La estructura fue resuelta por el método del átomo pesado y afinada por mínimos cuadrados, utilizando la matriz completa, hasta obtener una concordancia R = 0.068 para todas las reflexiones observadas. El átomo de níquel está localizado en un centro de inversión y presenta una coordinación cuadrado planar. El complejo Bis (Bis (Dietilamino Glioximato Níquel (II es casi planar y el desplazamiento de los grupos etil con respecto al plano es producido por efectos estéricos. Las moléculas planares se apilan a lo largo de c, las normales a los planos forman con este eje un ángulo de 41.53 . Existen interacciones axiales entre el níquel y los grupos amino de las moléculas adyacentes de la columna.

  15. Stimulation of 5-HT(1B) receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior.

    Science.gov (United States)

    Pentkowski, Nathan S; Acosta, Jazmin I; Browning, Jenny R; Hamilton, Elizabeth C; Neisewander, Janet L

    2009-09-01

    Paradoxically, stimulation of 5-HT(1B) receptors (5-HT(1B)Rs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT(1B)R agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3-10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0-1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT(1B)Rs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT(1B)Rs may be a novel target for developing medications for cocaine dependence.

  16. Crystal structures of bis-[(9S,13S,14S)-3-meth-oxy-17-methyl-morphinanium] tetra-chlorido-cobaltate and tetra-chlorido-cuprate.

    Science.gov (United States)

    Gauchat, Eric; Nazarenko, Alexander Y

    2017-01-01

    (9S,13S,14S)-3-Meth-oxy-17-methyl-morphinan (dextromethorphan) forms two isostructural salts with (a) tetra-chlorido-cobaltate, namely bis-[(9S,13S,14S)-3-meth-oxy-17-methyl-morphinanium] tetra-chlorido-cobaltate, (C18H26NO)2[CoCl4], and (b) tetra-chlorido-cuprate, namely bis-[(9S,13S,14S)-3-meth-oxy-17-methyl-morphinanium] tetra-chlorido-cuprate, (C18H26NO)2[CuCl4]. The distorted tetra-hedral anions are located on twofold rotational axes. The dextromethorphan cation can be described as being composed of two ring systems, a tetra-hydro-naphthalene system A+B and a deca-hydro-isoquinolinium subunit C+D, that are nearly perpendicular to one another: the angle between mean planes of the A+B and C+D moieties is 78.8 (1)° for (a) and 79.0 (1)° for (b). Two symmetry-related cations of protonated dextromethorphan are connected to the tetra-chlorido-cobaltate (or tetra-chlorido-cuprate) anions via strong N-H⋯Cl hydrogen bonds, forming neutral ion associates. These associates are packed in the (001) plane with no strong attractive bonding between them. Both compounds are attractive crystalline forms for unambiguous identification of the dextromethorphan and, presumably, of its optical isomer, levomethorphan.

  17. Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental colitis via the expansion of myeloid-derived suppressor cells.

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    Full Text Available Protein tyrosine phosphatase 1B (PTP1B is a key molecule in modulating low-degree inflammatory conditions such as diabetes. The role of PTP1B in other chronic inflammations, however, remains unknown. Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS-induced murine experimental colitis via expanding CD11b(+Gr-1(+ myeloid-derived suppressor cells (MDSCs. Employing DSS-induced murine experimental colitis as inflammatory animal model, we found that, compared with wild-type littermates, PTP1B-null mice demonstrated greater resistance to DSS-induced colitis, as reflected by slower weight-loss, greater survival rates and decreased PMN and macrophage infiltration into the colon. The evidence collectively also demonstrated that the resistance of PTP1B-null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B-null mice exhibited a greater frequency of MDSCs in the bone marrow (BM, peripheral blood and spleen when compared with wild-type littermates. Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3 and Janus kinase 2 (JAK2. In conclusion, our study provides the first evidences that PTP1B deficiency ameliorates murine experimental colitis via expanding MDSCs.

  18. 76 FR 39254 - Airworthiness Directives; Schweizer Aircraft Corporation (Schweizer) Model 269A, A-1, B, C, C-1...

    Science.gov (United States)

    2011-07-06

    ... Corporation (Schweizer) Model 269A, A-1, B, C, C-1, and TH-55 Series Helicopters AGENCY: Federal Aviation... reviewed Schweizer Service Bulletins No. B-295 for Model 269A, A-1, B, and C helicopters, and No. C1B-032... continues to read as follows: Authority: 49 U.S.C. 106(g), 40113, 44701. Sec. 39.13 0 2. The FAA amends...

  19. Cytochrome P450 1B1 Contributes to the Development of Atherosclerosis and Hypertension in Apolipoprotein E-Deficient Mice.

    Science.gov (United States)

    Song, Chi Young; Ghafoor, Khuzema; Ghafoor, Hafiz U; Khan, Nayaab S; Thirunavukkarasu, Shyamala; Jennings, Brett L; Estes, Anne M; Zaidi, Sahar; Bridges, Dave; Tso, Patrick; Gonzalez, Frank J; Malik, Kafait U

    2016-01-01

    Cytochrome P450 (CYP) 1B1 contributes to vascular smooth muscle cell growth and hypertension in male mice. This study was conducted to determine the contribution of CYP1B1 to the development of atherosclerosis and hypertension and associated pathogenesis in 8-week-old male apolipoprotein E-deficient (ApoE(-/-)/Cyp1b1(+/+)), and ApoE- and CYP1B1-deficient (ApoE(-/-)/Cyp1b1(-/-)) mice fed a normal or atherogenic diet for 12 weeks. A separate group of ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet was injected every third day with the CYP1B1 inhibitor, 2,3',4,5'-tetramethoxystilbene (300 μg/kg), or its vehicle, dimethyl sulfoxide (30 μL, IP); systolic blood pressure was measured by the tail cuff method. After 12 weeks, mice were euthanized, blood collected for lipid analysis, and aortas harvested for measuring lesions and remodeling, and for infiltration of inflammatory cells by histological and immunohistochemical analysis, respectively, and for reactive oxygen species production. Blood pressure, areas of lipids and collagen deposition, elastin breaks, infiltration of macrophages and T lymphocytes, reactive oxygen species generation in the aorta, and plasma lipid levels were increased in ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet; these changes were minimized in mice given 2,3',4,5'-tetramethoxystilbene, and in ApoE(-/-)/Cyp1b1(-/-) mice on an atherogenic diet; absorption/production of lipids remained unaltered in these mice. These data suggest that aortic lesions, hypertension, and associated pathogenesis in ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet are most likely dependent on CYP1B1-generated oxidative stress and increased plasma lipid levels independent of blood pressure and absorption of lipids. CYP1B1 could serve as a novel target for developing drugs to treat atherosclerosis and hypertension caused by hypercholesterolemia.

  20. 1H-2,3-Dihydroperimidine Derivatives: A New Class of Potent Protein Tyrosine Phosphatase 1B Inhibitors

    Directory of Open Access Journals (Sweden)

    Wen-Long Wang

    2013-12-01

    Full Text Available A series of 1H-2,3-dihydroperimidine derivatives was designed, synthesized, and evaluated as a new class of inhibitors of protein tyrosine phosphatase 1B (PTP1B with IC50 values in the micromolar range. Compounds 46 and 49 showed submicromolar inhibitory activity against PTP1B, and good selectivity (3.48-fold and 2.10-fold respectively over T-cell protein tyrosine phosphatases (TCPTP. These results have provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

  1. A comparison of Verotoxin B-subunit (Stx1B) and CD77 antibody to define germinal centre populations.

    Science.gov (United States)

    Bailey, S; Mardell, C; Wheatland, L; Zola, H; Macardle, P J

    2005-01-01

    We have directly compared the use of a CD77 antibody with the binding subunit of Shiga-like toxin 1, Verotoxin 1, and (Stx1B) for delineation on human tonsil cells. We determined that the Stx1B produced a greater intensity of staining than the CD77 antibody, allowing three sub-populations of germinal centre cells to be seen. The populations express high, medium, and low levels of globotriaosylceramide as determined by the binding of the Stx1B reagent. The strong staining patterns of Stx1B suggest that it may be useful in defining germinal center B cell populations.

  2. Regulation of T Cell Receptor Signaling by DENND1B in TH2 Cells and Allergic Disease.

    Science.gov (United States)

    Yang, Chiao-Wen; Hojer, Caroline D; Zhou, Meijuan; Wu, Xiumin; Wuster, Arthur; Lee, Wyne P; Yaspan, Brian L; Chan, Andrew C

    2016-01-14

    The DENN domain is an evolutionary conserved protein module found in all eukaryotes and serves as an exchange factor for Rab-GTPases to regulate diverse cellular functions. Variants in DENND1B are associated with development of childhood asthma and other immune disorders. To understand how DENND1B may contribute to human disease, Dennd1b(-/-) mice were generated and exhibit hyper-allergic responses following antigen challenge. Dennd1b(-/-) TH2, but not other TH cells, exhibit delayed receptor-induced T cell receptor (TCR) downmodulation, enhanced TCR signaling, and increased production of effector cytokines. As DENND1B interacts with AP-2 and Rab35, TH2 cells deficient in AP-2 or Rab35 also exhibit enhanced TCR-mediated effector functions. Moreover, human TH2 cells carrying asthma-associated DENND1B variants express less DENND1B and phenocopy Dennd1b(-/-) TH2 cells. These results provide a molecular basis for how DENND1B, a previously unrecognized regulator of TCR downmodulation in TH2 cells, contributes to asthma pathogenesis and how DENN-domain-containing proteins may contribute to other human disorders.

  3. Association of Single Nucleotide Polymorphisms in CYP1B1 and COMT Genes with Breast Cancer Susceptibility in Indian Women

    OpenAIRE

    Sharawan Yadav; Naveen Kumar Singhal; Virendra Singh; Neeraj Rastogi; Pramod Kumar Srivastava; Mahendra Pratap Singh

    2009-01-01

    Cytochrome P450 1B1 (CYP1B1) and catechol-$O$-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of ...

  4. Analysen zur Funktion des E1B-55K-Proteins von Adenovirus Typ 5 im lytischen Replikationszyklus

    OpenAIRE

    Kindsmüller, Kathrin

    2007-01-01

    Das E1B-55K-Protein von Adenovirus Typ 5 ist ein multifunktionelles Phosphoprotein, das eine zentrale Rolle im produktiven Replikationszyklus von Ad5 einnimmt. Die lytischen Aktivitäten des E1B-Proteins werden zumindest teilweise im Komplex mit dem viralen Protein E4orf6 vermittelt. Soweit bekannt fördert der E1B-55K/E4orf6-Komplex (E1B/E4-Komplex) den nukleozytoplasmatischen Transport viraler mRNAs und fördert somit die Synthese viraler Kapsidproteine bzw. die Produktion von Nachkommenviren....

  5. Exogenous and Endogeneous Disialosyl Ganglioside GD1b Induces Apoptosis of MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sun-Hyung Ha

    2016-04-01

    Full Text Available Gangliosides have been known to play a role in the regulation of apoptosis in cancer cells. This study has employed disialyl-ganglioside GD1b to apoptosis in human breast cancer MCF-7 cells using exogenous treatment of the cells with GD1b and endogenous expression of GD1b in MCF-7 cells. First, apoptosis in MCF-7 cells was observed after treatment of GD1b. Treatment of MCF-7 cells with GD1b reduced cell growth rates in a dose and time dependent manner during GD1b treatment, as determined by XTT assay. Among the various gangliosides, GD1b specifically induced apoptosis of the MCF-7 cells. Flow cytometry and immunofluorescence assays showed that GD1b specifically induces apoptosis in the MCF-7 cells with Annexin V binding for apoptotic actions in early stage and propidium iodide (PI staining the nucleus of the MCF-7 cells. Treatment of MCF-7 cells with GD1b activated apoptotic molecules such as processed forms of caspase-8, -7 and PARP (Poly(ADP-ribose polymerase, without any change in the expression of mitochondria-mediated apoptosis molecules such as Bax and Bcl-2. Second, to investigate the effect of endogenously produced GD1b on the regulation of cell function, UDP-gal: β1,3-galactosyltransferase-2 (GD1b synthase, Gal-T2 gene has been transfected into the MCF-7 cells. Using the GD1b synthase-transfectants, apoptosis-related signal proteins linked to phenotype changes were examined. Similar to the exogenous GD1b treatment, the cell growth of the GD1b synthase gene-transfectants was significantly suppressed compared with the vector-transfectant cell lines and transfection activated the apoptotic molecules such as processed forms of caspase-8, -7 and PARP, but not the levels of expression of Bax and Bcl-2. GD1b-induced apoptosis was blocked by caspase inhibitor, Z-VAD. Therefore, taken together, it was concluded that GD1b could play an important role in the regulation of breast cancer apoptosis.

  6. Crystal Structure and Spectroscopic Studies of Bis (morpholine dithiocarbamate) Nickel (II) Complex, Ni (C4H8ONCS2) 2

    Institute of Scientific and Technical Information of China (English)

    PAN,Su(潘苏); PAN,Su; WANG,Ying(王瑛); WANG,Ying

    2001-01-01

    The title compound has been prepared and characterized by EA, IR and TG spectralstudies. The crystal structure of nickel (IⅡ) bis(morpholine dithiocarbamate) Ni(C4HsONC S2)2 is determied by X-ray diffraction methods. It crystal lizes in the monoclinic system, space groun P2n/n, with lat tice parameters a = 0.4288(1), b = 2.0526(4), c = 0.8333(2) nn, β = 97.43(3)°, and Z = 2. In the structure, central Ni atom coordination geometry is slightly distorted square-planar with the four S atoms from two morpholine dithiocarbamate ligands. The four Ni-S bond distancs are in the range of 0.2199(5)0.2201(2) nm. The IR spectral data are in agreement with the structural ones. The TG data indicate that it decomposed completely at the 766.89°C.

  7. A novel and facile synthesis of 3-(2-benzofuroyl- and 3,6-bis(2-benzofuroylcarbazole derivatives

    Directory of Open Access Journals (Sweden)

    Wentao Gao

    2011-11-01

    Full Text Available A facile synthesis of hitherto unreported 3-(2-benzofuroylcarbazoles 3a–k, 3,6-bis(2-benzofuroylcarbazoles 5a–k, and naphtho[2,1-b]furoylcarbazoles 3l and 5l is described. The synthesis mainly relies on the ultrasound-assisted Rap–Stoermer reaction of 3-chloroacetyl- (1 or 3,6-dichloroacetyl-9-ethyl-9H-carbazole (4 with various salicylaldehydes 2a–k as well as 2-hydroxy-1-naphthaldehyde (2l in CH3CN with the presence of PEG-400 as catalyst. The procedure offers easy access to benzofuroylcarbazoles in short reaction times and the products are obtained in moderate to good yields.

  8. Ion irradiation induced structural modifications of Fe{sub 81}Mo{sub 8}Cu{sub 1}B{sub 10} NANOPERM-type alloy

    Energy Technology Data Exchange (ETDEWEB)

    Miglierini, Marcel [Institute of Nuclear and Physical Engineering, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Bratislava (Slovakia); Department of Nuclear Reactors, Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University, Prague (Czech Republic); Hasiak, Mariusz [Department of Mechanics and Materials Science, Wroclaw University of Technology (Poland)

    2016-05-15

    Structural modifications and their impact upon magnetic properties are studied in amorphous NANOPERM-type {sup 57}Fe{sub 81}Mo{sub 10}Cu{sub 1}B{sub 10} metallic glass exposed to irradiation with 130 keV N{sup +} ions to the total fluencies of up to 2.5 x 10{sup 17} ions/cm{sup 2}. Using surface sensitive technique of Moessbauer spectrometry, traces of crystalline phases are found already in the as-quenched state after the sample production. On the air side of the ribbons, bcc-Fe dominates whereas on the opposite wheel side, also a presence of Fe{sub 3}O{sub 4} is unveiled. The amount of surface crystallization is higher on the wheel side of the ribbons. After ion irradiation, mostly the air side is affected because it was facing the incident ions. Gradual formation of iron nitrides is observed with increasing ion fluence. Though the radiation damage exhibits itself only at this side of the ribbons, its influence upon bulk magnetic properties is clearly identified by the help of magnetic measurements. Hysteresis loops exhibit changes in their shape as well as coercive field. Along with the formation of magnetic crystalline phases (bcc-Fe and nitrides), they are caused by structural rearrangement which takes place also inside the amorphous residual phase. Structural modifications are confirmed via evolution of hyperfine magnetic fields with ion fluence. Structural modification of the {sup 57}Fe{sub 81}Mo{sub 10}Cu{sub 1}B{sub 10} alloy caused by ion irradiation as demonstrated by microstructural (Moessbauer spectrometry (a,b)) and macroscopic (hysteresis loops (c,d)) measurements. As-quenched (a,c) and 2.5 x 10{sup 17} N{sup +}/cm{sup 2} irradiated (b,d) alloys are compared. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Bis{bis(azido-κNbis[bis(pyridin-2-yl-κNamine]cobalt(III} sulfate dihydrate

    Directory of Open Access Journals (Sweden)

    Fatima Setifi

    2016-04-01

    Full Text Available The search for new molecular materials with interesting magnetic properties, using the pseudohalide azide ion and di-2-pyridylamine (dpa, C10H9N3 as a chelating ligand, led to the synthesis and structure determination of the title compound, [Co(N32(dpa2]2SO4·2H2O. The crystal structure comprises discrete [Co(dpa2(N32]+ cations, sulfate anions, as well as H2O solvent molecules. The CoIII cations display a slightly distorted octahedral coordination sphere defined by two N atoms from azide anions and four N atoms from the pyridyl rings of two dpa ligands. In the crystal, extensive C—H...O, N—H...O, and O—H...O interactions result in supramolecular sheets that lie parallel to the ab plane. The sheets are further linked through O—H...N interactions between the water molecules of one sheet and azide anions of another sheet, forming a supramolecular framework.

  10. Hydroxysteroid sulfotransferase SULT2B1b promotes hepatocellular carcinoma cells proliferation in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Xiaoming Yang

    Full Text Available Hydroxysteroid sulfotransferase 2B1b (SULT2B1b is highly selective for the addition of sulfate groups to 3β-hydroxysteroids. Although previous reports have suggested that SULT2B1b is correlated with cell proliferation of hepatocytes, the relationship between SULT2B1b and the malignant phenotype of hepatocarcinoma cells was not clear. In the present study, we found that SULT2B1 was comparatively higher in the human hepatocarcinoma tumorous tissues than their adjacent tissues. Besides, SULT2B1b overexpression promoted the growth of the mouse hepatocarcinoma cell line Hepa1-6, while Lentivirus-mediated SULT2B1b interference inhibited growth as assessed by the CCK-8 assay. Likewise, inhibition of SULT2B1b expression induced cell-cycle arrest and apoptosis in Hepa1-6 cells by upregulating the expression of FAS, downregulating the expression of cyclinB1, BCL2 and MYC in vitro and in vivo at both the transcript and protein levels. Knock-down of SULT2B1b expression significantly suppressed tumor growth in nude mouse xenografts. Moreover, proliferation rates and SULT2B1b expression were highly correlated in the human hepatocarcinoma cell lines Huh-7, Hep3B, SMMC-7721 and BEL-7402 cells. Knock-down of SULT2B1b inhibited cell growth and cyclinB1 levels in human hepatocarcinoma cells and suppressed xenograft growth in vivo. In conclusion, SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC.

  11. Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

    Science.gov (United States)

    Painter, Jodie N; O'Mara, Tracy A; Batra, Jyotsna; Cheng, Timothy; Lose, Felicity A; Dennis, Joe; Michailidou, Kyriaki; Tyrer, Jonathan P; Ahmed, Shahana; Ferguson, Kaltin; Healey, Catherine S; Kaufmann, Susanne; Hillman, Kristine M; Walpole, Carina; Moya, Leire; Pollock, Pamela; Jones, Angela; Howarth, Kimberley; Martin, Lynn; Gorman, Maggie; Hodgson, Shirley; De Polanco, Ma Magdalena Echeverry; Sans, Monica; Carracedo, Angel; Castellvi-Bel, Sergi; Rojas-Martinez, Augusto; Santos, Erika; Teixeira, Manuel R; Carvajal-Carmona, Luis; Shu, Xiao-Ou; Long, Jirong; Zheng, Wei; Xiang, Yong-Bing; Montgomery, Grant W; Webb, Penelope M; Scott, Rodney J; McEvoy, Mark; Attia, John; Holliday, Elizabeth; Martin, Nicholas G; Nyholt, Dale R; Henders, Anjali K; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Renner, Stefan P; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Lambrechts, Diether; Coenegrachts, Lieve; Schrauwen, Stefanie; Amant, Frederic; Winterhoff, Boris; Dowdy, Sean C; Goode, Ellen L; Teoman, Attila; Salvesen, Helga B; Trovik, Jone; Njolstad, Tormund S; Werner, Henrica M J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Tzortzatos, Gerasimos; Mints, Miriam; Tham, Emma; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Jingmei; Hopper, John L; Southey, Melissa C; Ekici, Arif B; Ruebner, Matthias; Johnson, Nicola; Peto, Julian; Burwinkel, Barbara; Marme, Frederik; Brenner, Hermann; Dieffenbach, Aida K; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Depreeuw, Jeroen; Moisse, Matthieu; Chang-Claude, Jenny; Rudolph, Anja; Couch, Fergus J; Olson, Janet E; Giles, Graham G; Bruinsma, Fiona; Cunningham, Julie M; Fridley, Brooke L; Børresen-Dale, Anne-Lise; Kristensen, Vessela N; Cox, Angela; Swerdlow, Anthony J; Orr, Nicholas; Bolla, Manjeet K; Wang, Qin; Weber, Rachel Palmieri; Chen, Zhihua; Shah, Mitul; French, Juliet D; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Edwards, Stacey L; Thompson, Deborah J; Spurdle, Amanda B

    2015-03-01

    Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

  12. CYP1B1 polymorphisms and susceptibility to prostate cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hongtuan Zhang

    Full Text Available BACKGROUND: Studies investigating the association between single-nucleotide polymorphisms (SNPs of the cytochrome P450 1B1 (CYP1B1 and prostate cancer (PCa risk report conflicting results. To derive a more precise estimation of the relationship between CYP1B1 polymorphisms and PCa risk, a meta-analysis was performed. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive literature search was conducted to identify all eligible studies of CYP1B1 polymorphisms and PCa risk. A total of 14 independent studies, including 6380 cases and 5807 controls, were identified. We investigated by meta-analysis the effects of 5 polymorphisms in CYP1B1 L432V (12 studies, 5999 cases, 5438 controls, R48G (6 studies, 1647 cases, 1846 controls, N453S (4 studies, 1407 cases, 1499 controls, -13C/T (4 studies, 1116 cases, 1114 controls, and A119S (4 studies, 1057 cases, 1018 controls. There was no evidence that L432V had significant association with PCa in overall population. After subgroup analyses by ethnicity, we found that L432V was significantly associated with PCa risk in Asians (additive: OR = 2.38, 95%CI = 1.31-4.33, P = 0.004; recessive: OR = 2.11, 95%CI = 1.17-3.79, P = 0.01; dominant: OR = 1.52, 95%CI = 1.14-2.01, P = 0.004; allelic: OR = 1.52, 95%CI = 1.20-1.92, P = 0.0006. When stratified by source of controls, significantly elevated PCa risk was found in all genetic models in population based studies (additive: OR = 1.34, 95%CI = 1.14-1.57, P = 0.0003; recessive: OR = 1.25, 95%CI = 1.09-1.43, P = 0.002; dominant: OR = 1.25, 95%CI = 1.11-1.41, P = 0.0002; allelic: OR = 1.18, 95%CI = 1.09-1.28, P<0.0001. For N453S, there was a significant association between N453S polymorphism and PCa risk in both overall population (dominant: OR = 1.18, 95%CI = 1.00-1.38, P = 0.04 and mixed population (domiant: OR = 1.31, 95%CI = 1.06-1.63, P = 0.01; allelic: OR

  13. In vitro study of vitamins B1, B2 and B6 adsorption on zeolite

    Directory of Open Access Journals (Sweden)

    Basić Zorica

    2011-01-01

    Full Text Available Background/Aim. Zeolites are the hydratised alumosilicates of alcali and earthalcali cations, which have a long three-dimensional crystal structure. Preparations on the basis of zeolites are used for adsorption of organic and nonorganic toxic substances and they, also, find more and more use in veterinary and human medicine and pharmacy. The aim of this study was to evaluate the possibilities of zeolite to adsorb vitamins B1, B2 and B6 in acid and neutral solutions, as well as the characteristics of the process (saturability, reversibility and competitivness. Methods. The specific and sensitive HPLC method with fluorescent detector was used for determination of vitamins B1, B2 and B6. Analyte separation and detection were carried out by applying the reverse-phase method on column C18. An in vitro experiment was done by testing the influence of pH value (2 and 7, concentration of vitamin solution (1, 2 and 5 mg/L, the lenght of contact with zeolite (10-180 min and cation competitiveness on the exchange capacity, which is achieved by media and zeolite contact, as well as a possible vitamins desorption through changing pH value of the solution at 37°C. Jon competitiveness was examined by adding commercial feed mixture (grower with a defined content of the examined vitamines in zeolite solutions the pH = 2 and pH = 7. Results. Vitamins B1, B2 and B6 were stable in both pH=2 and pH = 7 solutions at 37°C, in the defined time intervals. In acid solution concentrations of vitamins significantly declined in the first 10 min, with no significant decline in further 30 min for all the three concentrations testch. In neutral solution, after the addition of 1% zeolite, decrease in vitamins concentrations was slightly lower than in acid solution, but also significant in the first 10 min of the contact with zeolite. It was found that zeolite, which adsorbed vitamins in acid solution, transferred in the neutral one released a significant quantity of adsorbed

  14. Massive Expansion of Marine Archaea During The Early Albian Oceanic Anoxic Event 1B

    Science.gov (United States)

    Kuypers, M. M.; Kuypers, M. M.; Blokker, P.; Erbacher, J.; Kinkel, H.; Pancost, R. D.; Pancost, R. D.; Schouten, S.; Sinninghe Damsté, J. S.

    2001-12-01

    Oceanic anoxic events (OAEs), periods of globally enhanced burial of organic matter (OM) in the marine realm, played an important role in the mid-Cretaceous `greenhouse climate' by effectively reducing atmospheric carbon dioxide concentrations. It is generally believed that these OAEs were caused either by decreased remineralisation or increased production of phytoplanktonic OM. Here we show that enhanced organic carbon (OC) burial during the early Albian OAE1b (~112 My) was caused by a different process. Combined biogeochemical and stable carbon isotopic analyses indicate that black shales from this period contain up to 80% of OC derived from archaea. Archaea-derived isoprenoidal tetraether membrane lipids and free and macromolecularly bound isoprenoid alkanes are abundantly present in these black shales. More specifically the presence of certain ether lipids (cyclic biphytane tetraethers) indicates representatives of the pelagic archaea. To the best of our knowledge this is the earliest fossil evidence for marine planktonic archaea, extending their geological record by more than 60 million years. The diversity of archaeal lipids recovered from the OAE1b black shales suggests that they derive from a multitude of archaeal species. However, the specific 13C enrichment of all such lipids indicates a common `heavy' (13C-rich) carbon source for the archaea and/or a common pathway of carbon-fixation with a reduced 13C fractionation effect compared to the Calvin cycle used by algae, cyanobacteria and higher plants. The large differences (up to 12%) in 13C/12C ratios between the algal biomarkers and the much more abundant archaeal molecular fossils suggest that the latter were not living heterotrophically on photoautotrophic biomass. It seems likely that the archaea present during OAE1b used a chemical energy source (possibly ammonium) for carbon fixation since photoautotrophy within the domain of the Archaea is restricted to only a few species from hypersaline

  15. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    Science.gov (United States)

    2010-01-01

    Background CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. Methods We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. Results The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Conclusion Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations. PMID:20701755

  16. Reduced inflammatory response in cigarette smoke exposed Mrp1/Mdr1a/1b deficient mice

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    Postma Dirkje S

    2007-07-01

    Full Text Available Abstract Background Tobacco smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD, though the mechanisms of its toxicity are still unclear. The ABC transporters multidrug resistance-associated protein 1 (MRP1 and P-glycoprotein (P-gp/MDR1 extrude a wide variety of toxic substances across cellular membranes and are highly expressed in bronchial epithelium. Their impaired function may contribute to COPD development by diminished detoxification of noxious compounds in cigarette smoke. Methods We examined whether triple knock-out (TKO mice lacking the genes for Mrp1 and Mdr1a/1b are more susceptible to develop COPD features than their wild-type (WT littermates. TKO and WT mice (six per group were exposed to 2 cigarettes twice daily by nose-only exposure or room air for 6 months. Inflammatory infiltrates were analyzed in lung sections, cytokines and chemokines in whole lung homogenates, emphysema by mean linear intercept. Multiple linear regression analysis with an interaction term was used to establish the statistical significances of differences. Results TKO mice had lower levels of interleukin (IL-7, KC (mouse IL-8, IL-12p70, IL-17, TNF-alpha, G-CSF, GM-CSF and MIP-1-alpha than WT mice independent of smoke exposure (P P P Conclusion Mrp1/Mdr1a/1b knock-out mice have a reduced inflammatory response to cigarette smoke. In addition, the expression levels of several cytokines and chemokines were also lower in lungs of Mrp1/Mdr1a/1b knock-out mice independent of smoke exposure. Further studies are required to determine whether dysfunction of MRP1 and/or P-gp contribute to the pathogenesis of COPD.

  17. Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein.

    Science.gov (United States)

    Matsushima, Soichiro; Maeda, Kazuya; Kondo, Chihiro; Hirano, Masaru; Sasaki, Makoto; Suzuki, Hiroshi; Sugiyama, Yuichi

    2005-09-01

    Until recently, it was generally believed that the transport of various organic anions across the bile canalicular membrane was mainly mediated by multidrug resistance-associated protein 2 (MRP2/ABCC2). However, a number of new reports have shown that some organic anions are also substrates of multidrug resistance 1 (MDR1/ABCB1) and/or breast cancer resistance protein (BCRP/ABCG2), implying MDR1 and BCRP could also be involved in the biliary excretion of organic anions in humans. In the present study, we constructed new double-transfected Madin-Darby canine kidney II (MDCKII) cells expressing organic anion-transporting polypeptide 1B1 (OATP1B1)/MDR1 and OATP1B1/BCRP, and we investigated the transcellular transport of four kinds of organic anions, estradiol-17beta-d-glucuronide (EG), estrone-3-sulfate (ES), pravastatin (PRA), and cerivastatin (CER), to identify which efflux transporters mediate the biliary excretion of compounds using double-transfected cells. We observed the vectorial transport of EG and ES in all the double transfectants. MRP2 showed the highest efflux clearance of EG among these efflux transporters, whereas BCRP-mediated clearance of ES was the highest in these double transfectants. In addition, two kinds of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, CER and PRA, were also substrates of all these efflux transporters. The rank order of the efflux clearance of PRA mediated by each transporter was the same as that of EG, whereas the contribution of MDR1 to the efflux of CER was relatively greater than for PRA. This experimental system is very useful for identifying which transporters are involved in the biliary excretion of organic anions that cannot easily penetrate the plasma membrane.

  18. Identification of protein tyrosine phosphatase 1B and casein as substrates for 124-v-Mos

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    Stabel Silvia

    2002-04-01

    Full Text Available Abstract Background The mos proto-oncogene encodes a cytoplasmic serine/threonine-specific protein kinase with crucial function during meiotic cell division in vertebrates. Based on oncogenic amino acid substitutions the viral derivative, 124-v-Mos, displays constitutive protein kinase activity and functions independent of unknown upstream effectors of mos protein kinase. We have utilized this property of 124-v-Mos and screened for novel mos substrates in immunocomplex kinase assays in vitro. Results We generated recombinant 124-v-Mos using the baculovirus expression system in Spodoptera frugiperda cells and demonstrated constitutive kinase activity by the ability of 124-v-Mos to auto-phosphorylate and to phosphorylate vimentin, a known substrate of c-Mos. Using this approach we analyzed a panel of acidic and basic substrates in immunocomplex protein kinase assays and identified novel in vitro substrates for 124-v-Mos, the protein tyrosine phosphatase 1B (PTP1B, alpha-casein and beta-casein. We controlled mos-specific phosphorylation of PTP1B and casein in comparative assays using a synthetic kinase-inactive 124-v-Mos mutant and further, tryptic digests of mos-phosphorylated beta-casein identified a phosphopeptide specifically targeted by wild-type 124-v-Mos. Two-dimensional phosphoamino acid analyses showed that 124-v-mos targets serine and threonine residues for phosphorylation in casein at a 1:1 ratio but auto-phosphorylation occurs predominantly on serine residues. Conclusion The mos substrates identified in this study represent a basis to approach the identification of the mos-consensus phosphorylation motif, important for the development of specific inhibitors of the Mos protein kinase.

  19. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Trubicka Joanna

    2010-08-01

    Full Text Available Abstract Background CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs, it represents an attractive candidate gene for studies into colorectal cancer susceptibility. Methods We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. Results The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Conclusion Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.

  20. Short-Term Dynamic and Local Epidemiological Trends in the South American HIV-1B Epidemic.

    Science.gov (United States)

    Junqueira, Dennis Maletich; de Medeiros, Rubia Marília; Gräf, Tiago; Almeida, Sabrina Esteves de Matos

    2016-01-01

    The human displacement and sexual behavior are the main factors driving the HIV-1 pandemic to the current profile. The intrinsic structure of the HIV transmission among different individuals has valuable importance for the understanding of the epidemic and for the public health response. The aim of this study was to characterize the HIV-1 subtype B (HIV-1B) epidemic in South America through the identification of transmission links and infer trends about geographical patterns and median time of transmission between individuals. Sequences of the protease and reverse transcriptase coding regions from 4,810 individuals were selected from GenBank. Maximum likelihood phylogenies were inferred and submitted to ClusterPicker to identify transmission links. Bayesian analyses were applied only for clusters including ≥5 dated samples in order to estimate the median maximum inter-transmission interval. This study analyzed sequences sampled from 12 South American countries, from individuals of different exposure categories, under different antiretroviral profiles, and from a wide period of time (1989-2013). Continentally, Brazil, Argentina and Venezuela were revealed important sites for the spread of HIV-1B among countries inside South America. Of note, from all the clusters identified about 70% of the HIV-1B infections are primarily occurring among individuals living in the same geographic region. In addition, these transmissions seem to occur early after the infection of an individual, taking in average 2.39 years (95% CI 1.48-3.30) to succeed. Homosexual/Bisexual individuals transmit the virus as quickly as almost half time of that estimated for the general population sampled here. Public health services can be broadly benefitted from this kind of information whether to focus on specific programs of response to the epidemic whether as guiding of prevention campaigns to specific risk groups.