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Sample records for a1 b1 c1

  1. Structural Reassignment and Absolute Stereochemistry of Madurastatin C1 (MBJ-0034) and the Related Aziridine Siderophores: Madurastatins A1, B1, and MBJ-0035.

    PubMed

    Tyler, Andrew R; Mosaei, Hamed; Morton, Stephanie; Waddell, Paul G; Wills, Corinne; McFarlane, William; Gray, Joe; Goodfellow, Michael; Errington, Jeff; Allenby, Nick; Zenkin, Nikolay; Hall, Michael J

    2017-04-11

    The madurastatins are pentapeptide siderophores originally described as containing an unusual salicylate-capped N-terminal aziridine ring. Isolation of madurastatin C1 (1) (also designated MBJ-0034), from Actinomadura sp. DEM31376 (itself isolated from a deep sea sediment), prompted structural reevaluation of the madurastatin siderophores, in line with the recent work of Thorson and Shaaban. NMR spectroscopy in combination with partial synthesis allowed confirmation of the structure of madurastatin C1 (1) as containing an N-terminal 2-(2-hydroxyphenyl)oxazoline in place of the originally postulated aziridine, while absolute stereochemistry was determined via Harada's advanced Marfey's method. Therefore, this work further supports Thorson and Shaaban's proposed structural revision of the madurastatin class of siderophores (madurastatins A1 (2), B1 (3), C1 (1), and MBJ-0036 (4)) as N-terminal 2-(2-hydroxyphenyl)oxazolines.

  2. Nine New Triterpene Glycosides, Magnumosides A1–A4, B1, B2, C1, C2 and C4, from the Vietnamese Sea Cucumber Neothyonidium (=Massinium) magnum: Structures and Activities against Tumor Cells Independently and in Synergy with Radioactive Irradiation

    PubMed Central

    Silchenko, Alexandra S.; Kalinovsky, Anatoly I.; Avilov, Sergey A.; Kalinin, Vladimir I.; Andrijaschenko, Pelageya V.; Dmitrenok, Pavel S.; Chingizova, Ekaterina A.; Ermakova, Svetlana P.; Dautova, Tatyana N.

    2017-01-01

    Nine new sulfated triterpene glycosides, magnumosides A1 (1), A2 (2), A3 (3), A4 (4), B1 (5), B2 (6), C1 (7), C2 (8) and C4 (9) as well as a known colochiroside B2 (10) have been isolated from the tropical Indo-West Pacific sea cucumber Neothynidium (=Massinium) magnum (Phyllophoridae, Dendrochirotida) collected in the Vietnamese shallow waters. The structures of new glycosides were elucidated by 2D NMR spectroscopy and mass-spectrometry. All the isolated new glycosides were characterized by the non-holostane type lanostane aglycones having 18(16)-lactone and 7(8)-double bond and differed from each other by the side chains and carbohydrate moieties structures. Magnumoside A1 (1) has unprecedented 20(24)-epoxy-group in the aglycone side chain. Magnumosides of the group A (1–4) contained disaccharide monosulfated carbohydrate moieties, of the group B (5, 6)—tetrasaccharide monosulfated carbohydrate moieties and, finally, of the group C (7–9)—tetrasaccharide disulfated carbohydrate moieties. The cytotoxic activities of the compounds 1–9 against mouse spleen lymphocytes, the ascites form of mouse Ehrlich carcinoma cells, human colorectal carcinoma DLD-1 cells as well as their hemolytic effects have been studied. Interestingly, the erythrocytes were more sensitive to the glycosides action than spleenocytes and cancer cells tested. The compounds 3 and 7 significantly inhibited the colony formation and decreased the size of colonies of DLD-1 cancer cells at non-cytotoxic concentrations. Moreover, the synergism of effects of radioactive irradiation and compounds 3 and 7–9 at subtoxic doses on proliferation of DLD-1 cells was demonstrated. PMID:28813020

  3. Crystal structures of human sulfotransferases SULT1B1 and SULT1C1 complexed with the cofactor product adenosine-3'- 5'-diphosphate (PAP)

    SciTech Connect

    Dombrovski, Luidmila; Dong, Aiping; Bochkarev, Alexey; Plotnikov, Alexander N.

    2008-09-17

    Cytosolic sulfotransferases (SULTs), often referred as Phase II enzymes of chemical defense, are a superfamily of enzymes that catalyze the transfer of a sulfonate group from 3{prime}-phosphoadenosine 5{prime}-phosphosulfate (PAPS) to an acceptor group of substrates. This reaction modulates the activities of a large array of small endogenous and foreign chemicals including drugs, toxic compounds, steroid hormones, and neurotransmitters. In some cases, however, SULTs activate certain food and environmental compounds to mutagenenic and carcinogenic metabolites. Twelve human SULTs have been identified, which are partitioned into three families: SULT1, SULT2 and SULT4. The SULT1 family is further divided in four subfamilies, A, B, C, and E, and comprises eight members (1A1, 1A2, 1A3, 1B1, 1C1, 1C2, 1C3, and 1E1). Despite sequence and structural similarity among the SULTs, the family and subfamily members appear to have different biological function. SULT1 family shows substrate-binding specificity for simple phenols, estradiol, and thyroid hormones, as well as environmental xenobiotics and drugs. Human SULT1B1 is expressed in liver, colon, small intestine, and blood leukocytes, and shows substrate-binding specificity to thyroid hormones and benzylic alcohols. Human SULT1C1 is expressed in the adult stomach, kidney, and thyroid, as well as in fetal kidney and liver. SULT1C1 catalyzes the sulfonation of p-nitrophenol and N-hydroxy-2-acetylaminofluorene in vitro. However, the in vivo function of the enzyme remains unknown. We intend to solve the structures for all of the SULTs for which structural information is not yet available, and compare the structural and functional features of the entire SULT superfamily. Here we report the structures of two members of SULT1 family, SULT1B1 and SULT1C1, both in complex with the product of the PAPS cofactor, adenosine-3{prime}-5{prime}-diphosphate (PAP).

  4. Soluble CD100 functions on human monocytes and immature dendritic cells require plexin C1 and plexin B1, respectively.

    PubMed

    Chabbert-de Ponnat, Isabelle; Marie-Cardine, Anne; Pasterkamp, R Jeroen; Schiavon, Valérie; Tamagnone, Luca; Thomasset, Nicole; Bensussan, Armand; Boumsell, Laurence

    2005-04-01

    CD100 represents the first semaphorin described in the immune system. It is expressed as a 300-kDa homodimer at the surface of most hematopoietic cells, but is also found in a soluble form following a proteolytic cleavage upon cell activation. We herein established that soluble CD100 (sCD100) impaired the migration of human monocytes and immature dendritic cells (DCs), but not of mature DCs. Performing competition assays, we identified plexin C1 (VESPR/CD232) as being involved in sCD100-mediated effects on human monocytes. Interestingly, we observed a complete down-regulation of plexin C1 expression during the in vitro differentiation process of monocytes to immature DCs, while concomitantly the surface expression of plexin B1 was induced. The latter receptor then binds sCD100 on immature DCs, mediating its inhibitory effect on cell migration. Finally, we showed that sCD100 modulated the cytokine production from monocytes and immature DCs. Together these results suggest that sCD100 plays a critical role in the regulation of antigen-presenting cell migration and functions via a tightly regulated process of receptor expression.

  5. TgrC1 mediates cell-cell adhesion by interacting with TgrB1 via mutual IPT/TIG domains during development of Dictyostelium discoideum.

    PubMed

    Chen, Gong; Wang, Jun; Xu, Xiaoqun; Wu, Xiangfu; Piao, Ruihan; Siu, Chi-Hung

    2013-06-01

    Cell-cell adhesion plays crucial roles in cell differentiation and morphogenesis during development of Dictyostelium discoideum. The heterophilic adhesion protein TgrC1 (Tgr is transmembrane, IPT, IG, E-set, repeat protein) is expressed during cell aggregation, and disruption of the tgrC1 gene results in the arrest of development at the loose aggregate stage. We have used far-Western blotting coupled with MS to identify TgrB1 as the heterophilic binding partner of TgrC1. Co-immunoprecipitation and pull-down studies showed that TgrB1 and TgrC1 are capable of binding with each other in solution. TgrB1 and TgrC1 are encoded by a pair of adjacent genes which share a common promoter. Both TgrB1 and TgrC1 are type I transmembrane proteins, which contain three extracellular IPT/TIG (immunoglobulin, plexin, transcription factor-like/transcription factor immunoglobulin) domains. Antibodies raised against TgrB1 inhibit cell reassociation at the post-aggregation stage of development and block fruiting body formation. Ectopic expression of TgrB1 and TgrC1 driven by the actin15 promoter leads to heterotypic cell aggregation of vegetative cells. Using recombinant proteins that cover different portions of TgrB1 and TgrC1 in binding assays, we have mapped the cell-binding regions in these two proteins to Lys(537)-Ala(783) in TgrB1 and Ile(336)-Val(360) in TgrC1, corresponding to their respective TIG3 and TIG2 domain.

  6. Dispersed fluorescence spectroscopy of the CBr2A1B1-X1A1 transition.

    PubMed

    Hsu, Hui-Ju; Chang, Wei-Zhong; Chang, Bor-Chen

    2005-06-21

    Dispersed fluorescence spectra following the excitation of the CBr2A1B1-X1A1 2 and 2 bands at visible wavelengths were acquired in a discharge supersonic free jet expansion using an intensified charge-coupled device (ICCD) detector. The dispersed fluorescence spectra show signal-to-noise ratios of up to 60 and extend out to a maximum red shift frequency of 6000 cm(-1). Complete and detailed vibrational structure of the ground singlet state (X1A1) was observed. Vibrational parameters including fundamental frequencies, anharmonicities, and coupling constants were determined for the CBr2 X1A1 state. Additional vibrational structure starting at approximately 3650 cm(-1) was observed and this indicates the singlet-triplet energy gap to be >10 kcal mol(-1).

  7. 75 FR 36581 - Airworthiness Directives; Eurocopter France Model EC 155B, EC155B1, SA-360C, SA-365C, SA-365C1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... Model EC 155B, EC155B1, SA-360C, SA-365C, SA-365C1, SA-365C2, SA-365N, SA-365N1, AS- 365N2, AS 365 N3... additional crack has been found in the MGB planet gear carrier of a Eurocopter Model EC 155 helicopter. That.... Applicability Model EC 155B, EC155B1, SA-360C, SA-365C, SA-365C1, SA-365C2, SA-365N, SA-365N1, AS-365N2, AS...

  8. Constitutive Expression of the Maize Genes B1 and C1 in Transgenic Hi II Maize Results in Differential Tissue Pigmentation and Generates Resistance to Helicoverpa zea

    USDA-ARS?s Scientific Manuscript database

    Anthocyanin biosynthesis in maize protects tissues from biotic and abiotic stresses. Constitutive expression of the maize B1 and C1 genes, which induces anthocyanin biosynthesis, resulted in transgenic plants with varied phenotypes. Some colored leaves were substantially resistant to thrips damage...

  9. Modulating the Strength and Threshold of NOTCH Oncogenic Signals by mir-181a-1/b-1

    PubMed Central

    Wang, Song; Schaffert, Steven; Gong, Xue; Yue, Sibiao; Luong, Richard; Min, Hyeyoung; Yashiro-Ohtani, Yumi; Davis, Mark; Pear, Warren; Chen, Chang-Zheng

    2012-01-01

    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. PMID:22916024

  10. Axial resonances a$$_{1}$$(1260), b$$_{1}$$(1235) and their decays from the lattice

    DOE PAGES

    Lang, C. B.; Leskovec, Luka; Mohler, Daniel; ...

    2014-04-28

    The light axial-vector resonancesmore » $$a_1(1260)$$ and $$b_1(1235)$$ are explored in Nf=2 lattice QCD by simulating the corresponding scattering channels $$\\rho\\pi$$ and $$\\omega\\pi$$. Interpolating fields $$\\bar{q} q$$ and $$\\rho\\pi$$ or $$\\omega\\pi$$ are used to extract the s-wave phase shifts for the first time. The $$\\rho$$ and $$\\omega$$ are treated as stable and we argue that this is justified in the considered energy range and for our parameters $$m_\\pi\\simeq 266~$$MeV and $$L\\simeq 2~$$fm. We neglect other channels that would be open when using physical masses in continuum. Assuming a resonance interpretation a Breit-Wigner fit to the phase shift gives the $$a_1(1260)$$ resonance mass $$m_{a1}^{res}=1.435(53)(^{+0}_{-109})$$ GeV compared to $$m_{a1}^{exp}=1.230(40)$$ GeV. The $$a_1$$ width $$\\Gamma_{a1}(s)=g^2 p/s$$ is parametrized in terms of the coupling and we obtain $$g_{a_1\\rho\\pi}=1.71(39)$$ GeV compared to $$g_{a_1\\rho\\pi}^{exp}=1.35(30)$$ GeV derived from $$\\Gamma_{a1}^{exp}=425(175)$$ MeV. In the $$b_1$$ channel, we find energy levels related to $$\\pi(0)\\omega(0)$$ and $$b_1(1235)$$, and the lowest level is found at $$E_1 \\gtrsim m_\\omega+m_\\pi$$ but is within uncertainty also compatible with an attractive interaction. Lastly, assuming the coupling $$g_{b_1\\omega\\pi}$$ extracted from the experimental width we estimate $$m_{b_1}^{res}=1.414(36)(^{+0}_{-83})$$.« less

  11. Axial resonances a$_{1}$(1260), b$_{1}$(1235) and their decays from the lattice

    SciTech Connect

    Lang, C. B.; Leskovec, Luka; Mohler, Daniel; Prelovsek, Sasa

    2014-04-28

    The light axial-vector resonances $a_1(1260)$ and $b_1(1235)$ are explored in Nf=2 lattice QCD by simulating the corresponding scattering channels $\\rho\\pi$ and $\\omega\\pi$. Interpolating fields $\\bar{q} q$ and $\\rho\\pi$ or $\\omega\\pi$ are used to extract the s-wave phase shifts for the first time. The $\\rho$ and $\\omega$ are treated as stable and we argue that this is justified in the considered energy range and for our parameters $m_\\pi\\simeq 266~$MeV and $L\\simeq 2~$fm. We neglect other channels that would be open when using physical masses in continuum. Assuming a resonance interpretation a Breit-Wigner fit to the phase shift gives the $a_1(1260)$ resonance mass $m_{a1}^{res}=1.435(53)(^{+0}_{-109})$ GeV compared to $m_{a1}^{exp}=1.230(40)$ GeV. The $a_1$ width $\\Gamma_{a1}(s)=g^2 p/s$ is parametrized in terms of the coupling and we obtain $g_{a_1\\rho\\pi}=1.71(39)$ GeV compared to $g_{a_1\\rho\\pi}^{exp}=1.35(30)$ GeV derived from $\\Gamma_{a1}^{exp}=425(175)$ MeV. In the $b_1$ channel, we find energy levels related to $\\pi(0)\\omega(0)$ and $b_1(1235)$, and the lowest level is found at $E_1 \\gtrsim m_\\omega+m_\\pi$ but is within uncertainty also compatible with an attractive interaction. Lastly, assuming the coupling $g_{b_1\\omega\\pi}$ extracted from the experimental width we estimate $m_{b_1}^{res}=1.414(36)(^{+0}_{-83})$.

  12. Inhalational botulism in rhesus macaques exposed to botulinum neurotoxin complex serotypes A1 and B1.

    PubMed

    Sanford, Daniel C; Barnewall, Roy E; Vassar, Michelle L; Niemuth, Nancy; Metcalfe, Karen; House, Robert V; Henderson, Ian; Shearer, Jeffry D

    2010-09-01

    A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD(50)) and to estimate 50% lethal exposure concentrations relative to time (LCt(50)) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD(50) and LCt(50) for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication.

  13. Excitation of the \\tilde{a}\\,^3B_1 and \\tilde{A}\\,^1B_1 states of H2O by low-energy electron impact

    NASA Astrophysics Data System (ADS)

    Hargreaves, L.; Ralphs, K.; Serna, G.; Khakoo, M. A.; Winstead, C.; McKoy, V.

    2012-10-01

    We report measured and calculated differential cross-sections for inelastic scattering of low-energy electrons by water leading to excitation of the dissociative (1b1 → 4a1) 1, 3B1 states. The measurements were taken using conventional energy-loss spectroscopy at incident energies of 9, 10, 12, 15, and 20 eV for scattering angles from 10° to 130°. The calculations were carried out using the Schwinger multichannel method, with a Born-dipole correction applied in the singlet excitation channel. Integral excitation cross sections for the \\tilde{a}\\,^3B_1 and \\tilde{A}\\,^1B_1 states are also derived from the differential cross section results.

  14. Classical ferroelectriclike behavior of highly ordered Pb (S c1 /2N b1 /2)O3 studied by dielectric and Brillouin scattering spectroscopy

    NASA Astrophysics Data System (ADS)

    Sivasubramanian, V.; Subramanian, V.; Kojima, S.

    2016-02-01

    The ferroelectric phase transition behavior in the highly ordered Pb (S c1 /2N b1 /2) O3 has been investigated by the dielectric and Brillouin spectroscopy. The dielectric permittivity ɛr exhibits a sharp maximum without any frequency dispersion at its Curie temperature Tc. In the temperature range far above Tc, it was noted that the dielectric permittivity exhibits a noticeable deviation from the Curie-Weiss law below the characteristic intermediate temperature T*=500 K , which is common to most of the Pb-based oxide perovskite relaxors. Upon cooling, the frequency of the longitudinal acoustic phonon mode exhibits a remarkable softening towards Tc. The relaxation time of the order parameter calculated using the Landau-Khalatnikov approach was determined to be more than one order of magnitude lower than that of the disordered Pb (S c1 /2N b1 /2)O3 and is very close to that observed in the paraelectric phase of the classical ferroelectric, BaTi O3 . The observed dielectric and relaxation features are qualitatively discussed in terms of the difference in the strength of the random electric fields.

  15. Synthesis of fagopyritols A1 and B1 from D-chiro-inositol.

    PubMed

    Cid, M Belén; Alfonso, Francisco; Martín-Lomas, Manuel

    2004-09-13

    Fagopyritol A1 (3-O-alpha-d-galactopyranosyl-d-chiro-inositol) and fagopyritol B1 (2-O-alpha-d-galactopyranosyl-d-chiro-inositol) have been synthesized by glycosylation of the diequatorial diol 1,4,5,6-tetra-O-benzoyl-d-chiro-inositol, readily obtained from d-chiro-inositol, with 2,3,4,6-tetra-O-benzyl-d-galactopyranosyl trichloroacetimidate.

  16. B^1Π → A^1Σ^+ Electronic Transfer in NaK

    NASA Astrophysics Data System (ADS)

    Ross, Amanda J.; Harker, Heather; Giraud, Maxime; Wyllie, Ella

    2017-06-01

    We investigate collisionally-induced A^1Σ^+ → X^1 Σ^+} fluorescence in NaK, observed following ro-vibrationally selective excitation of the B^1Π state. NaK molecules are formed in a heatpipe oven, and excited with a single-mode dye laser operating around 17000 {cm^{-1}}. Direct B^1Π→ X^1 Σ^+ fluorescence is dominated by Δ J =0 or ±1 transitions, with rotational satellites whose intensities vary according to collisional partner (rare gas or K atoms). The B→X emission also shows even weaker {Δ v ±1} vibrational relaxation bands, with a more even spread of rotational population. Some 5000 {cm^{-1}} to lower wavenumber, we observe apparently non-selective A^1Σ^+ → X^1 Σ^+ emission, with an oscillating bound-free c^3Σ^+ → a^3 Σ^+ contribution to the baseline that becomes increasingly important as higher vibrational levels of B^1Π are populated by the laser. Earlier work defining analytical functions describing the A^1Σ^+ and b^3Π states of NaK, and the spin-orbit functions coupling them allowed us to assign this dense and irregular A→X spectrum, and to see how upper state level populations change as a function of B state excitation and heatpipe conditions (He, Ar or N_2 as buffer gas). Our spectra reveal a propensity to conserve vibrational quantum number, at least from low v in the B state. This is in contradiction with A-X emission in Na_2 observed following laser excitation of the (corresponding) B^1Π_u state. The non-Boltzmann populations in the A^1 Σ_u^+ state of Na_2 were explained by near-resonant transfer from B^1Π_u to 2^1Σ_g^+ (with no counterpart in heteronuclear NaK), followed by spontaneous emission to the A^1Σ_u^+ state. Harker et al., Phys. Rev. A 92 (1), 012506 (2015), Astill et al., Chem. Phys. Lett. 125 33 (1986) Camacho et al., J. Phys B. 39 2665 (2006) Hussein et al., J. Mol Spectrosc. 114 105 (1985)

  17. Study of infrared emission spectroscopy for the B1Δg-A1Πu and B'1Σg+-A1Πu systems of C2

    NASA Astrophysics Data System (ADS)

    Chen, Wang; Kawaguchi, Kentarou; Bernath, Peter F.; Tang, Jian

    2016-02-01

    Thirteen bands for the B1Δg-A1Πu system and eleven bands for the B'1Σg+-A1Πu system of C2 were identified in the Fourier transform infrared emission spectra of hydrocarbon discharges. The B'1Σg+ v = 4 and the B1Δg v = 6, 7, and 8 vibrational levels involved in nine bands were studied for the first time. A direct global analysis with Dunham parameters was carried out satisfactorily for the B1Δg-A1Πu system except for a small perturbation in the B1Δg v = 6 level. The calculated rovibrational term energies up to B1Δg v = 12 showed that the level crossing between the B1Δg and d3Πg states is responsible for many of the prominent perturbations in the Swan system observed previously. Nineteen forbidden transitions of the B1Δg-a3Πu transition were identified and the off-diagonal spin-orbit interaction constant AdB between d3Πg and B1Δg was derived as 8.3(1) cm-1. For the B'1Σg+-A1Πu system, only individual band analyses for each vibrational level in the B'1Σg+ state could be done satisfactorily and Dunham parameters obtained from these effective parameters showed that the anharmonic vibrational constant ωexe is anomalously small (nearly zero). Inspection of the RKR (Rydberg-Klein-Rees) potential curves for the B'1Σg+ and X1Σg+ states revealed that an avoided crossing or nearly avoided crossing may occur around 30 000 cm-1, which is responsible for the anomalous molecular constants in these two states.

  18. Study of infrared emission spectroscopy for the B(1)Δg-A(1)Πu and B'(1)Σg(+)-A(1)Πu systems of C2.

    PubMed

    Chen, Wang; Kawaguchi, Kentarou; Bernath, Peter F; Tang, Jian

    2016-02-14

    Thirteen bands for the B(1)Δg-A(1)Πu system and eleven bands for the B'(1)Σg(+)-A(1)Πu system of C2 were identified in the Fourier transform infrared emission spectra of hydrocarbon discharges. The B'(1)Σg(+)v = 4 and the B(1)Δg v = 6, 7, and 8 vibrational levels involved in nine bands were studied for the first time. A direct global analysis with Dunham parameters was carried out satisfactorily for the B(1)Δg-A(1)Πu system except for a small perturbation in the B(1)Δg v = 6 level. The calculated rovibrational term energies up to B(1)Δg v = 12 showed that the level crossing between the B(1)Δg and d(3)Πg states is responsible for many of the prominent perturbations in the Swan system observed previously. Nineteen forbidden transitions of the B(1)Δg-a(3)Πu transition were identified and the off-diagonal spin-orbit interaction constant AdB between d(3)Πg and B(1)Δg was derived as 8.3(1) cm(-1). For the B'(1)Σg(+)-A(1)Πu system, only individual band analyses for each vibrational level in the B'(1)Σg(+) state could be done satisfactorily and Dunham parameters obtained from these effective parameters showed that the anharmonic vibrational constant ωexe is anomalously small (nearly zero). Inspection of the RKR (Rydberg-Klein-Rees) potential curves for the B'(1)Σg(+) and X(1)Σg(+) states revealed that an avoided crossing or nearly avoided crossing may occur around 30,000 cm(-1), which is responsible for the anomalous molecular constants in these two states.

  19. Aflatoxin B1 detoxification by CYP321A1 in Helicoverpa zea.

    PubMed

    Niu, Guodong; Wen, Zhimou; Rupasinghe, Sanjeewa G; Zeng, Ren Sen; Berenbaum, May R; Schuler, Mary A

    2008-09-01

    The polyphagous corn earworm Helicoverpa zea frequently encounters aflatoxins, mycotoxins produced by the pathogens Aspergillus flavus and A. parasiticus, which infect many of this herbivore's host plants. While aflatoxin B1 metabolism by midgut enzymes isolated from fifth instars feeding on control diets was not detected, this compound was metabolized by midgut enzymes isolated from larvae consuming diets supplemented with xanthotoxin, coumarin, or indole-3-carbinol, phytochemicals that are likely to co-occur with aflatoxin in infected host plants. Of the two metabolites generated, the main derivative identified in midguts induced with these chemicals and in reactions containing heterologously expressed CYP321A1 was aflatoxin P1 (AFP1), an O-demethylated product of AFB1. RT-PCR gel blots indicated that the magnitude of CYP321A1 transcript induction by these chemicals is associated with the magnitude of increase in the metabolic activities of induced midgut enzymes (coumarin>xanthotoxin>indole 3-carbinol). These results indicate that induction of P450s, such as CYP321A1, plays an important role in reducing AFB1 toxicity to H. zea. Docking of AFB1 in the molecular models of CYP321A1 and CYP6B8 highlights differences in their proximal catalytic site volumes that allow only CYP321A1 to generate the AFP1 metabolite. Copyright 2008 Wiley-Liss, Inc.

  20. Mitochondrial haplogroup M9a1a1c1b is associated with hypoxic adaptation in the Tibetans.

    PubMed

    Li, Qian; Lin, Keqin; Sun, Hao; Liu, Shuyuan; Huang, Kai; Huang, Xiaoqin; Chu, Jiayou; Yang, Zhaoqing

    2016-12-01

    While hypoxic environment at high altitude remains a major challenge for travelers from low-altitude areas, Tibetans have adapted to the high-altitude environment. Mitochondria are the energy conversion and supplement centers in eukaryotic cells. In recent years, studies have found that the diversity of the mitochondrial genome may have a role in the adaptation to hypoxia in Tibetans. In this study, mitochondrial haplogroup classification and variant genotyping were performed in Tibetan and Han Chinese populations living at different altitudes. The frequencies of mitochondrial haplogroups B and M7 in the high-altitude population were significantly lower compared with those in the low-altitude population (P=0.003 and 0.029, respectively), whereas the frequencies of haplogroups G and M9a1a1c1b in the high-altitude group were significantly higher compared with those in the low-altitude group (P=0.01 and 0.002, respectively). The frequencies of T3394C and G7697A, which are the definition sites of haplogroup M9a1a1c1b, were significantly higher in the high-altitude group compared with that in the low-altitude group (P=0.012 and 0.02, respectively). Our results suggest that mitochondrial haplogroups B and M7 are associated with inadaptability to hypoxic environments, whereas haplogroups G and M9a1a1c1b may be associated with hypoxic adaptation. In particular, the T3394C and G7697A variants on haplogroup M9a1a1c1b may be the primary cause of adaptation to hypoxia.

  1. Projected dynamics of abiotic risks in boreal forest ecosystems (SRES A1B, B1)

    NASA Astrophysics Data System (ADS)

    Panferov, O.; Ahrends, B.; Doering, C.; Sogachev, A.

    2009-04-01

    The ongoing climate change causes an increasing frequency of weather extremes (Leckebusch et al., 2008), which can result in wide area damage events (drought, windthrows/breaks) within boreal forest ecosystem. The damage effects, however, depend not only on the strength of a driving force itself (e.g. wind speed) but also on combinations of effecting agents and forest structure. Thus, the present study investigates the projected future developments of abiotic risks in different boreal forests during the 21st Century under conditions of SRES scenarios A1B and B1. Climate scenario data of coupled ECHAM5-MPIOM were downscaled by the regional climate model (CLM) to the spatial resolution of 0.2° x 0.2°, using daily time- steps. With these input data the small-scale modelling with coupled process based sub-models (Jansen et al., 2008) was carried out e.g. for Solling region, (Germany) calculating the water and energy balance of forest ecosystems with modified BROOK 90 (Ahrends et al., 2009) and wind loading on trees with 3D ABL model SCADIS (Panferov and Sogachev, 2008). Norway spruce and Scots pine of various ages were chosen as typical tree species for boreal forest ecosystems and cambisols, podzolic cambisols and stagnosols as typical soil types. The risks of drought and windthrow/breaks for a certain forest stand result from daily combinations of soil water characteristics, static and gust wind loads and soil texture. Damaged stands show higher vulnerability and thus - positive feedback to climate forcing (Vygodskaya et al., 2008). Therefore differences of microclimatological conditions in the remaining stand after changes in forest structure (Radler et al, 2008) were taken into account. Modell output was aggregated to 30-years periods and compared to "present conditions" of 1981-2010. The results show an increment of drought risks towards 2100 caused by changes in precipitation pattern and increase of mean air temperature, whereas the A1B scenario is

  2. Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1.

    PubMed

    Gale, Daniel P; Molyneux, Karen; Wimbury, David; Higgins, Patricia; Levine, Adam P; Caplin, Ben; Ferlin, Anna; Yin, Peiran; Nelson, Christopher P; Stanescu, Horia; Samani, Nilesh J; Kleta, Robert; Yu, Xueqing; Barratt, Jonathan

    2017-02-16

    IgA nephropathy (IgAN), an important cause of kidney failure, is characterized by glomerular IgA deposition and is associated with changes in O-glycosylation of the IgA1 molecule. Here, we sought to identify genetic factors contributing to levels of galactose-deficient IgA1 (Gd-IgA1) in white and Chinese populations. Gd-IgA1 levels were elevated in IgAN patients compared with ethnically matched healthy subjects and correlated with evidence of disease progression. White patients with IgAN exhibited significantly higher Gd-IgA1 levels than did Chinese patients. Among individuals without IgAN, Gd-IgA1 levels did not correlate with kidney function. Gd-IgA1 level heritability (h(2)), estimated by comparing midparental and offspring Gd-IgA1 levels, was 0.39. Genome-wide association analysis by linear regression identified alleles at a single locus spanning the C1GALT1 gene that strongly associated with Gd-IgA1 level (β=0.26; P=2.35×10(-9)). This association was replicated in a genome-wide association study of separate cohorts comprising 308 patients with membranous GN from the UK (P<1.00×10(-6)) and 622 controls with normal kidney function from the UK (P<1.00×10(-10)), and in a candidate gene study of 704 Chinese patients with IgAN (P<1.00×10(-5)). The same extended haplotype associated with elevated Gd-IgA1 levels in all cohorts studied. C1GALT1 encodes a galactosyltransferase enzyme that is important in O-galactosylation of glycoproteins. These findings demonstrate that common variation at C1GALT1 influences Gd-IgA1 level in the population, which independently associates with risk of progressive IgAN, and that the pathogenic importance of changes in IgA1 O-glycosylation may vary between white and Chinese patients with IgAN.

  3. Study of Infrared Emission Spectroscopy for the B1Δg-A1Πu and B'1Σg+-A1Πu Systems of C2

    NASA Astrophysics Data System (ADS)

    Tang, Jian; Chen, Wang; Kawaguchi, Kentarou; Bernath, Peter F.

    2016-06-01

    Recently, we carried out the perturbation analysis of C_2 spectra and identified forbidden singlet-triplet intersystem transitions, which aroused further interest in other C_2 spectra for the many low-lying electronic states of this fundamental molecule. In 1988, the B1Δg-A1Πu and B'1Σg+-A1Πu band systems were discovered by Douay et al., who observed eight bands of the B1Δg-A1Πu system with v up to 5 for the B1Δg state and six bands of the B'1Σg+-A1Πu system with v up to 3 for the B'1Σg+ state in the Fourier transform infrared emission spectra of hydrocarbon discharges. In the work presented here, we identified twenty-four bands of the two systems, among which the B'1Σg+ v = 4 and the B1Δg v = 6, 7 and 8 vibrational levels involved in nine bands were studied for the first time. A direct global analysis with Dunham parameters was carried out satisfactorily for the B1Δg-A1Πu system except for a small perturbation in the B1Δg v = 6 level. The calculated rovibrational term energies up to B1Δg v = 12 showed that the level crossing between the B1Δg and d3Πg states is responsible for many of the prominent perturbations in the Swan system observed previously. Nineteen lines of the B1Δg-a3Πu forbidden transitions were identified and the off-diagonal spin-orbit interaction constant AdB between d3Πg and B1Δg was derived as 8.3(1) wn. For the B'1Σg+-A1Πu system, only individual band analyses for each vibrational level in the B'1Σg+ state could be done satisfactorily and Dunham parameters obtained from these effective parameters showed that the anharmonic vibrational constant ω_e x_e is anomalously small (nearly zero). Inspection of the RKR potential curves for the B'1Σg+ and X1Σg+ states revealed that an avoided crossing may occur around 30000 wn, which is responsible for the anomalous molecular constants in these two states. W. Chen, K. Kawaguchi, P. F. Bernath, and J. Tang, J. Chem. Phys., 141, 064317 (2015) M. Douay, R. Nietmann and P. F. Bernath

  4. Expression Profile of CYP1A1 and CYP1B1 Enzymes in Colon and Bladder Tumors

    PubMed Central

    Androutsopoulos, Vasilis P.; Spyrou, Ioannis; Ploumidis, Achilles; Papalampros, Alexandros Eystathios; Kyriakakis, Michalis; Delakas, Demetrios; Spandidos, Demetrios A.; Tsatsakis, Aristidis M.

    2013-01-01

    Background The cytochrome P450 CYP1A1 and CYP1B1 enzymes are involved in carcinogenesis via activation of pro-carcinogenic compounds to carcinogenic metabolites. CYP1A1 and CYP1B1 have shown elevated levels in human tumors as determined by qRT-PCR and immunohistochemical studies. However studies that have examined CYP1 expression by enzyme activity assays are limited. Results In the current study the expression of CYP1A1 and CYP1B1 was investigated in a panel of human tumors of bladder and colorectal origin by qRT-PCR and enzyme activity assays. The results demonstrated that 35% (7/20) of bladder tumors and 35% (7/20) of colon tumors overexpressed active CYP1 enzymes. CYP1B1 mRNA was overexpressed in 65% and 60% of bladder and colon tumors respectively, whereas CYP1A1 was overexpressed in 65% and 80% of bladder and colon tumors. Mean mRNA levels of CYP1B1 and CYP1A1 along with mean CYP1 activity were higher in bladder and colon tumors compared to normal tissues (p<0.05). Statistical analysis revealed CYP1 expression levels to be independent of TNM status. Moreover, incubation of tumor microsomal protein in 4 bladder and 3 colon samples with a CYP1B1 specific antibody revealed a large reduction (72.5 ± 5.5 % for bladder and 71.8 ± 7.2% for colon) in catalytic activity, indicating that the activity was mainly attributed to CYP1B1 expression. Conclusions The study reveals active CYP1 overexpression in human tumors and uncovers the potential use of CYP1 enzymes and mainly CYP1B1 as targets for cancer therapy. PMID:24358191

  5. Theoretical calculations of the 2B 1- 2A 1 subband of NO 2

    NASA Astrophysics Data System (ADS)

    Zhao, X. Z.; Lu, T. X.; Cui, Z. F.

    1989-06-01

    The vibronic levels of the 2B 1( K' = 0) state of NO 2 and the fluorescence intensity distribution from these levels is calculated in this Letter using the Rennet-Teller theory. The vibronic quantum number of the upper level of the 454.5 nm subband is found to be ν' 2 = 17, and the band origin and the fluorescence distribution agree with experimental data.

  6. Dynamics of combined forest damage risks for 21st century (SRES A1B, B1)

    NASA Astrophysics Data System (ADS)

    Panferov, Oleg; Merklein, Johannes; Sogachev, Andrey; Junghans, Udo; Ahrends, Bernd

    2010-05-01

    The ongoing climate change can result in increasing frequency of weather extremes (Leckebusch et al., 2008) which in turn can produce wide area forest damage (windthrows, droughts, insect attacks) within forest ecosystems in Europe. The probability and extent of damage, depend not only on a strength of a driving force itself but especially on combinations of effecting agents and their interactions with forest ecosystem structure and soil properties. The combined effect of several factors which are not the extremes themselves can lead to the biotic and/or abiotic damage so that the combination becomes an extreme event. As soon as a damage event occurs, the forest structure is changed. The changes in forest structure in their turn strengthen or inhibits the influence of different climatic factors thus increase or decrease the probability of the next damage event creating positive or negative feedbacks. To assess the roles of separate meteorological factors and their combinations in forest damage under present and future climatic conditions the coupled model was created in University of Goettingen, as a part of a Decision Support System (Jansen et al, 2008, Panferov et al., 2009). The model combines the 3D ABL Model SCADIS (Panferov and Sogachev, 2008) with modified soil hydrology model BROOK 90 (Federer, 2003, Ahrends et al. 2009) and the model of climate dependent biotic damage. The projected future developments of forest damage events in 21st Century were carried out under conditions of SRES scenarios A1B and B1; the present conditions were evaluated using the measured data of German Weather Service. Climate scenario data of coupled ECHAM5-MPIOM were downscaled by the regional climate model Climate Local Model (CLM) to the spatial resolution of 0.2° x 0.2° and temporal resolution of 24 hours. Using these data as input the small-scale coupled process based modeling was then carried out for example region of Solling, Germany calculating the water and energy balance

  7. Spectroscopy of the X^1Σ^+, A^1Π and B^1Σ^+ Electronic States of MgS

    NASA Astrophysics Data System (ADS)

    Caron, Nicholas; Tokaryk, Dennis W.; Adam, Allan G.; Linton, Colan

    2016-06-01

    The spectra of some astrophysical sources contain signatures from molecules containing magnesium or sulphur atoms. Therefore, we have extended previous studies of the diatomic molecule MgS, which is a possible candidate for astrophysical detection. Microwave spectra of X^1Σ^+ , the ground electronic state, were reported in 1989 and 1997, and the B^1Σ^+-X^1Σ^+ electronic absorption spectrum in the blue was last studied in 1970. We have investigated the B^1Σ^+-X^1Σ^+ 0-0 spectrum of MgS at high resolution under jet-cooled conditions in a laser-ablation molecular source, and have obtained laser-induced fluorescence spectra from four isotopologues. Dispersed fluorescence from this source identified the low-lying A^1Π state near 4520 wn. We also created MgS in a Broida oven, with the help of a stream of activated nitrogen, and took rotationally resolved dispersed fluorescence spectra of the B^1Σ^+-A^1Π transition with a grating spectrometer by laser excitation of individual rotational levels of the B^1Σ^+ state via the B^1Σ^+-X^1Σ^+ transition. These spectra provide a first observation and analysis of the A^1Π state. S. Takano, S. Yamamoto and S. Saito, Chem. Phys. Lett. 159, 563-566 (1989) K. A. Walker and M. C. L. Gerry, J. Mol. Spectrosc 182, 178-183 (1997) M. Marcano and R. F. Barrow, Trans. Faraday Soc. 66, 2936-2938 (1970)

  8. 76 FR 49300 - Corporate Reorganizations; Distributions Under Sections 368(a)(1)(D) and 354(b)(1)(B); Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 RIN 1545-BF83 Corporate Reorganizations; Distributions Under Sections 368(a)(1)(D) and 354(b)(1)(B); Correction AGENCY: Internal Revenue Service (IRS), Treasury....

  9. Investigation of the Herzberg (C1Σ+→A1Π) band system in 12C17O

    NASA Astrophysics Data System (ADS)

    Hakalla, Rafał

    2015-10-01

    The C→A (0,1), (0,2) and (0,3) rovibronic bands of the less-abundant 12C17O isotopologue are studied in high resolution using a high-accuracy dispersive optical spectroscopy in the region of 22,800-26,100 cm-1. Calibration with respect to simultaneously recorded thorium atomic lines, obtained from several overlapped orders of the spectrum in the visible range, as well as a stainless steel hollow-cathode molecular lamp with two anodes, yields an absolute accuracy of wavenumbers measurements of about 0.0025 cm-1 for the CO spectra. All 261 spectra lines of the Herzberg band system in 12C17O, up to Jmax=34, were precisely measured and rotationally analyzed. As a result, the merged rotational constants and rotational equilibrium constants for the C1Σ+ Rydberg state, as well as the band origins, the isotope shifts, the RKR turning points, Franck-Condon factors, relative intensities, and r-centroids of the C→A system in the 12C17O isotopologue were obtained. An experimental RKR potential energy curve and vibrational levels of the C1Σ+ state in 12C17O together with highly excited k3Π, c3Π, E1Π, B1Σ+ and D‧1Σ+ states lying in the region between the first dissociation limit and the ionization potential of CO were plotted. A detailed investigation of possible perturbations that should occur in the C1Σ+(υ=0) Rydberg state of less-abundant 12C17O isotopologue in the close vicinity of the k3Π(υ=1, 2) and c3Π(υ=0) states in the region 92,000 cm-1 was performed. In the A1Π, υ=3 state of 12C17O, extensive, multi-state rotational perturbations were found and analyzed. Also, a global isotopic analysis of the C1Σ+ Rydberg state was carried out in the 12C16O, 12C17O, 13C16O, 12C18O, 13C17O, and 13C18O as well as in 14C16O and 14C18O isotopologues. This analysis enabled us to determine, amongst others, the vibrational equilibrium constants in 12C17O for the C1Σ+ state, to improve these constants in the 12C16O, 13C16O, 12C18O, 13C17O, and 13C18O isotopologues and

  10. Analysis of B→a1(1260)(b1(1235))K* decays in the perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Zhang, Zhi-Qing; Fu, Jian-Hua

    2015-03-01

    Within the framework of the perturbative quantum chromodynamics (PQCD) approach, we study the charmless two-body decays B→a1(1260)K*, b1(1235)K*. Using the decay constants and the light-cone distribution amplitudes for these mesons derived from the QCD sum rule method, we find the following results. (a) Our predictions for the branching ratios are consistent with the QCD factorization (QCDF) results within errors, but much larger than the naive factorization approach calculation values. (b) We predict that the anomalous polarizations occurring in the decays B→φK*, rHK* also happen in B→a1K* decays, while they do not happen in B→b1K* decays. Here the contributions from the annihilation diagrams play an important role in explaining the larger transverse polarizations in the B→a1K* decays, while they are not sensitive to the polarizations for the B→b1K* decays. (c) Our predictions for the direct CP-asymmetries agree well with the QCDF results within errors. The decays B¯0 → b+1K*-, B- → b01K*- have larger direct CP-asymmetries, which could be measured by the present LHCb experiment and the forthcoming Super-B experiment. Supported by National Natural Science Foundation of China (11147004, 11347030), Program of Youthful Key Teachers in University of Henan Province (001166), and by Foundation of Henan Educational Committee (14HASTIT037)

  11. Vitamin A-dependent transcriptional activation of the nuclear factor of activated T cells c1 (NFATc1) is critical for the development and survival of B1 cells.

    PubMed

    Maruya, Mikako; Suzuki, Keiichiro; Fujimoto, Hanae; Miyajima, Michio; Kanagawa, Osami; Wakayama, Teruhiko; Fagarasan, Sidonia

    2011-01-11

    B1 cells represent a distinct subset of B cells that produce most of the natural serum IgM and much of the gut IgA and function as an important component of early immune responses to pathogens. The development of B1 cells depends on the nuclear factor of activated T cells c1 (NFATc1), a transcription factor abundantly expressed by B1 cells but not by conventional B2 cells. However, the factors that regulate the expression of NFATc1 in B1 cells remain unknown. Here we show that a vitamin A-deficient diet results in reduction of NFATc1 expression in B1 cells and almost complete loss of the B1 cell compartment. As a consequence, vitamin A-deficient mice have reduced serum IgM and are unable to mount T cell-independent antibody responses against bacterial antigens. We demonstrate that injection of all-trans retinoic acid induces the expression of NFATc1, particularly from the constitutive P2 promoter, and leads to the increase of the B1 cells. Thus, the retinoic acid-dependent pathway is critical for regulating NFATc1 expression and for maintenance of the natural memory B cell compartment.

  12. On the 1A1 - 3B1 separation in CH2 and SiH2

    NASA Astrophysics Data System (ADS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

    1987-07-01

    The 1A1 - 3B1 separation in CH2 and SiH2 has been computed using extended basis sets and CASSCF/SOCI wave functions. Using theoretical estimates for the effects of zero-point vibration yields T(0) values of 8.9 and -20.9 kcal/mol respectively, in excellent agreement with the experimental values of 9.02 and -21.0 kcal/mol. A corollary to the small zero-point vibrational contribution to the separation is that the symmetric stretching fundamental in CH2(3B1) must be near 3100/cm, much less than a recently suggested value of around 3400/cm. An accurate Te value for SiH2 establishes the ionization potential of the 1A1 state as 9.15 eV, the higher of two recent experimental values.

  13. Polymorphisms of POR, SULT2A1 and HSD11B1 in children with premature adrenarche.

    PubMed

    Utriainen, Pauliina; Laakso, Saila; Jääskeläinen, Jarmo; Voutilainen, Raimo

    2012-09-01

    Premature adrenarche (PA) refers to an earlier than normal increase in adrenocortical androgen production. The pathogenesis of PA remains largely unknown. We hypothesized that common polymorphisms at P450 oxidoreductase (POR), steroid sulfotransferase (SULT2A1), or 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) genes could contribute to the polygenic pathogenesis of PA. We performed a case-control study on the polymorphisms rs1057868 at POR, rs182420 at SULT2A1, and rs12086634 at HSD11B1. The study cohort comprised 73 prepubertal children with PA (defined by clinical signs) and 97 age- and gender-matched healthy controls from a Finnish Caucasian population. Genotype distributions and clinical and metabolic phenotypes were determined. The genotype distributions of the polymorphisms were similar between the study groups. No variant was associated with alterations in serum adrenal steroid concentrations. The minor C variant at SULT2A1 was associated with higher serum sex hormone binding globulin (SHBG) concentrations (T/T, n=64 vs T/C&C/C, n=33; mean 94 vs 116 nmol/L; P=.001) and a trend for lower dehydroepiandrosterone sulfate/dehydroepiandrosterone ratios in the controls (P=.06), and with higher plasma total cholesterol concentrations in the PA subjects (T/T, n=42 vs T/C&C/C, n=31; 4.0 vs 4.6 mmol/L; P<.001). The minor G variant at HSD11B1 was associated with lower plasma triglyceride concentration in the controls (T/T, n=65 vs T/G&G/G, n=32; 0.61 vs 0.49 mmol/L; P=.013). Common polymorphisms at POR, SULT2A1 or HSD11B1 were not associated with PA in a Finnish Caucasian population. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Polymorphic variation of CYP1A1 and CYP1B1 genes in a Haryana population.

    PubMed

    Giri, Shiv Kumar; Yadav, Anita; Kumar, Anil; Dev, Kapil; Gulati, Sachin; Gupta, Ranjan; Aggarwal, Neeraj; Gautam, Sanjeev Kumar

    2013-12-01

    Cytochrome P450 (CYP) 1A1 and CYP1B1 are important phase I xenobiotic metabolizing enzymes involved in the metabolism of numbers of toxins, endogenous hormones, and pharmaceutical drugs. Polymorphisms in these phase I genes can alter enzyme activity and are known to be associated with cancer susceptibility related to environmental toxins and hormone exposure. Their genotypes may also display ethnicity-dependent population frequencies. The present study was aimed to determine the frequencies of commonly known functional polymorphisms of CYP1A1 and CYP1B1 genes in a Haryana state population of North India. The allelic frequency of CYP1A1 polymorphism m1 (MspI) was 29.65% and m2 (Ile(462)Val) was 24.85%. The frequency of CYP1B1 polymorphism m1 (Val(432)Leu) was 45.85% and m2 (Asn(453)Ser) was 16.2%. We observed inter- and intra-ethnic variation in the frequency distribution of these polymorphisms. Analysis of polymorphisms in these genes might help in predicting the risk of cancer. Our results emphasize the need for more such studies in high-risk populations.

  15. mir-181a-1/b-1 Modulates Tolerance through Opposing Activities in Selection and Peripheral T Cell Function.

    PubMed

    Schaffert, Steven A; Loh, Christina; Wang, Song; Arnold, Christopher P; Axtell, Robert C; Newell, Evan W; Nolan, Garry; Ansel, K Mark; Davis, Mark M; Steinman, Lawrence; Chen, Chang-Zheng

    2015-08-15

    Understanding the consequences of tuning TCR signaling on selection, peripheral T cell function, and tolerance in the context of native TCR repertoires may provide insight into the physiological control of tolerance. In this study, we show that genetic ablation of a natural tuner of TCR signaling, mir-181a-1/b-1, in double-positive thymocytes dampened TCR and Erk signaling and increased the threshold of positive selection. Whereas mir-181a-1/b-1 deletion in mice resulted in an increase in the intrinsic reactivity of naive T cells to self-antigens, it did not cause spontaneous autoimmunity. Loss of mir-181a-1/b-1 dampened the induction of experimental autoimmune encephalomyelitis and reduced basal TCR signaling in peripheral T cells and their migration from lymph nodes to pathogenic sites. Taken together, these results demonstrate that tolerance can be modulated by microRNA gene products through the control of opposing activities in T cell selection and peripheral T cell function. Copyright © 2015 by The American Association of Immunologists, Inc.

  16. Protein expression of CYP1A1, CYP1B1, ALDH1A1, and ALDH2 in young patients with oral squamous cell carcinoma.

    PubMed

    Kaminagakura, E; Caris, A; Coutinho-Camillo, C; Soares, F A; Takahama-Júnior, A; Kowalski, L P

    2016-06-01

    The purpose of this study was to evaluate the expression of the enzymes involved in the biotransformation of tobacco and alcohol. A study group of 41 young patients (≤40 years old) with oral squamous cell carcinoma (OSCC) was compared to 59 control subjects (≥50 years old) with tumours of similar clinical stages and topographies. The immunohistochemical expression of CYP1A1, CYP1B1, ALDH1A1, and ALDH2 was evaluated using the tissue microarray technique. There was a predominance of males, smokers, and alcohol drinkers in both groups. Most tumours were located in the tongue (43.9% vs. 50.8%), were well-differentiated (63.4% vs. 56.6%), and were in clinical stages III or IV (80.5% vs. 78.0%). No difference was observed in the expression of CYP1A1, ALDH1A1, or ALDH2 between the two groups. CYP1A1 and ALDH2 protein expression had no influence on the prognosis. The immunoexpression of CYP1B1 was significantly higher in the control group than in the young group (P<0.001). The 5-year relapse-free survival was better in patients with CYP1B1 overexpression vs. protein underexpression (64% vs. 25%; P<0.05), regardless of age. ALDH1A1 expression improved relapse-free survival in young patients. These results suggest a lower risk of recurrence with increased metabolism of carcinogens by CYP1B1. Further studies involving other genes and proteins are necessary to complement the results of this research.

  17. Hypervelocity Impact (HVI). Volume 8; Tile Small Targets A-1, Ag-1, B-1, and Bg-1

    NASA Technical Reports Server (NTRS)

    Gorman, Michael R.; Ziola, Steven M.

    2007-01-01

    During 2003 and 2004, the Johnson Space Center's White Sands Testing Facility in Las Cruces, New Mexico conducted hypervelocity impact tests on the space shuttle wing leading edge. Hypervelocity impact tests were conducted to determine if Micro-Meteoroid/Orbital Debris impacts could be reliably detected and located using simple passive ultrasonic methods. The objective of Targets A-1, Ag-1, B-1, and Bg-1 was to study hypervelocity impacts on the reinforced Shuttle Heat Shield Tiles of the Wing. Impact damage was detected using lightweight, low power instrumentation capable of being used in flight.

  18. CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

    PubMed Central

    Ye, Yi; Cheng, Xiao; Luo, Hai-Bo; Liu, Li; Li, Ying-Bi

    2008-01-01

    Purpose The aim of the study was to evaluate the association of CYP1A1 and CYP1B1 polymorphisms with uterine leiomyoma in Chinese women. Methods We investigated 100 women with clinically diagnosed uterine leiomyoma and 110 healthy normal subjects from Chinese women. The genetic distribution of two CYP1A1 polymorphisms at MspI, Ile462Val and four CYP1B1 polymorphisms at Arg48Gly, Ala119Ser, Leu432Val, Asp449Asp were analyzed by polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing method. Results All the SNPs showed polymorphisms in Chinese women. The genotype A/G and the allele G on Ile462Val was significantly different between uterine leiomyoma patients and controls (P < 0.05). Conclusion These results suggest that the genotype of CYP1A1 Ile462Val was associated with the increased risk of uterine leiomyomas in Chinese women. PMID:18763031

  19. Ethnic differences in the prevalence of polymorphisms in CYP7A1, CYP7B1 AND CYP27A1 enzymes involved in cholesterol metabolism.

    PubMed

    Dias, Vera; Ribeiro, V

    2011-07-01

    It is well known that drug disposition and response are greatly determined by the activities of drug metabolizing enzymes, which are polymorphic. Some of these polymorphisms are clinically relevant and presented an ethnic-dependent pattern of distribution. The characterization of the genetic distribution of different populations allows the selection of therapeutic options in accordance with the genetic background, with the objective to avoid adverse reactions and inefficacy of the treatment. In this work, we studied selected genetic polymorphisms in drug metabolizing enzymes in three different ethnic groups - Portugal, Mozambique and Colombia. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping methods were developed for drug metabolizing enzymes, namely, cholesterol 7α-hydroxylase (CYP7A1) (-203A>C, -346C>T, -496C>T, N233S, G347S), sterol 27-hydroxylase (CYP27A1) (R164W, A169V, D273N, V400A) and oxysterol 7α-hydroxylase (CYP7B1) (-116C>G, R324H, 1774C>T) to characterize the allelic distribution of these polymorphisms among three different ethnic/geographic origins. A total of 12 CYP7A1, CYP27A1 and CYP7B1 genetic variants were genotyped in a sample of 92 Portuguese, 151 Mozambican and 91 Colombian subjects. The variants N233S in CYP7A1 and 1774C>T in CYP7B1 were not detected in any population studied. The promoter polymorphisms in CYP7A1 (-203A>C, -346C>T, -496C>T) had high frequency in the three ethnic groups. G347S (CYP7A1), R164W, A169V and V400A (CYP27A1) were present in a low frequency but with a similar distribution in the three ethnic groups. Significant differences were observed for D273N (CYP27A1), -346C>T (CYP7A1), -116C>G and R324H (CYP7B1)Our results demonstrate a high variability of drug metabolizing enzymes between the different populations analyzed, indicating that at least some of these polymorphisms are ethnic specific.

  20. Aryl hydrocarbon hydroxylase represents CYP1B1, and not CYP1A1, in human freshly isolated white cells: trimodal distribution of Japanese population according to induction of CYP1B1 mRNA by environmental dioxins.

    PubMed

    Toide, Kenji; Yamazaki, Hiroshi; Nagashima, Rikako; Itoh, Keisuke; Iwano, Shunsuke; Takahashi, Yoshiki; Watanabe, Shaw; Kamataki, Tetsuya

    2003-03-01

    The expression level of mRNAs for cytochrome P450 (CYP) 1A1 and 1B1 in freshly prepared white cells from 72 subjects exposed to dioxins at waste incinerators was investigated. The amounts of CYP1B1 mRNA ranged from 0.16 to 671 molecules/10(7) molecules of 18S rRNA, whereas the amounts of CYP1A1 mRNA were <6 molecules/10 ng total RNA, indicating that CYP1A1 was not induced to a detectable level by environmentally exposed dioxins. The inducibility of CYP1B1 mRNA in leukocytes, defined as the ratio of CYP1B1 mRNA to the plasma concentration of dioxins, varied among the subjects. It was found that the subjects showed trimodal distribution according to inducibility: 39 (54.2%), 25 (34.7%), and 8 (11.1%) of 72 subjects were judged as poor, intermediate, and high responders to environmental dioxins, respectively. The amounts of CYP1B1 mRNA in leukocytes of the intermediate and high responders were highly correlated with the plasma concentrations of dioxins (P < 0.05 and <0.01). These results suggest that CYP1B1 with polymorphic inducibility by dioxins is involved in aromatic hydrocarbon hydroxylase activities in human lymphocytes.

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

    PubMed Central

    Ghisari, Mandana; Long, Manhai; Bonefeld-Jørgensen, Eva C.

    2013-01-01

    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. PMID:23785672

  2. DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease

    PubMed Central

    Suntharalingham, Jenifer P.; Buonocore, Federica; Duncan, Andrew J.; Achermann, John C.

    2016-01-01

    DAX-1 (NR0B1) and SF-1 (NR5A1) are two nuclear receptor transcription factors that play a key role in human adrenal and reproductive development. Loss of DAX-1 function is classically associated with X-linked adrenal hypoplasia congenita. This condition typically affects boys and presents as primary adrenal insufficiency in early infancy or childhood, hypogonadotropic hypogonadism at puberty and impaired spermatogenesis. Late onset forms of this condition and variant phenotypes are increasingly recognized. In contrast, disruption of SF-1 only rarely causes adrenal insufficiency, usually in combination with testicular dysgenesis. Variants in SF-1/NR5A1 more commonly cause a spectrum of reproductive phenotypes ranging from 46,XY DSD (partial testicular dysgenesis or reduced androgen production) and hypospadias to male factor infertility or primary ovarian insufficiency. Making a specific diagnosis of DAX-1 or SF-1 associated conditions is important for long-term monitoring of endocrine and reproductive function, appropriate genetic counselling for family members, and for providing appropriate informed support for young people. PMID:26303087

  3. Association of vdr, cyp27b1, cyp24a1 and mthfr gene polymorphisms with oral lichen planus risk.

    PubMed

    Kujundzic, Bojan; Zeljic, Katarina; Supic, Gordana; Magic, Marko; Stanimirovic, Dragan; Ilic, Vesna; Jovanovic, Barbara; Magic, Zvonko

    2016-05-01

    The current study investigated the association between VDR EcoRV (rs4516035), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236), CYP27B1 (rs4646536), CYP24A1 (rs2296241), and MTHFR (rs1801133) gene polymorphisms and risk of oral lichen planus (OLP) occurrence. The study group consisted of 65 oral lichen planus patients and 100 healthy blood donors in the control group. Single nucleotide polymorphisms were genotyped by real time PCR or PCR-restriction fragment length polymorphism (RFLP) method. Heterozygous as well as mutated genotype of vitamin D receptor (VDR) FokI (rs2228570) polymorphism was associated with increased oral lichen planus risk in comparison with wild type genotype (odds ratio (OR) = 3.877, p = 0.017, OR = 38.153, p = 0.001, respectively). A significantly decreased OLP risk was observed for heterozygous genotype of rs2296241 polymorphism in CYP24A1 gene compared with the wild type form (OR = 0.314, p = 0.012). VDR gene polymorphisms ApaI and TaqI were in linkage disequilibrium (D' = 0.71, r(2) = 0.22). Identified haplotype AT was associated with decreased OLP risk (OR = 0.592, p = 0.047). Our results highlight the possible important role of VDR FokI (rs2228570) and CYP24A1 rs2296241 gene polymorphisms for oral lichen planus susceptibility. Identification of new molecular biomarkers could potentially contribute to determination of individuals with OLP predisposition.

  4. Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function.

    PubMed

    El-Khairi, Ranna; Martinez-Aguayo, Alejandro; Ferraz-de-Souza, Bruno; Lin, Lin; Achermann, John C

    2011-01-01

    The nuclear receptor transcription factors DAX-1 (NR0B1) and SF-1 (NR5A1) regulate many aspects of adrenal and reproductive development and function. Disruption of the genes encoding these factors can be associated with pediatric adrenal disease. DAX-1 mutations are classically associated with X-linked adrenal hypoplasia congenita, hypogonadotropic hypogonadism and impaired spermatogenesis. However, other phenotypes are also being reported, such as isolated mineralocorticoid insufficiency, premature sexual development, primary adrenal insufficiency in a 46, XX patient and late-onset X-linked adrenal hypoplasia congenita and/or hypogonadotropic hypogonadism. SF-1 mutations have also been associated with primary adrenal insufficiency, together with 46, XY disorders of sex development. However it is emerging that SF-1 changes are a relatively rare cause of primary adrenal failure in humans, and most individuals with SF-1 mutations have a spectrum of 46, XY disorders of sex development phenotypes. These conditions range from 46, XY females with streak gonads and müllerian structures, through children with ambiguous genitalia and inguinal testes, to severe penoscrotal hypospadias with undescended testes. Therefore, the human gonad appears to be more sensitive than the adrenal gland to loss of SF-1 function. This review will focus on the expanding range of phenotypes associated with DAX-1 and SF-1 mutations. Copyright © 2011 S. Karger AG, Basel.

  5. Exact quantum scattering calculations of transport properties: CH2(X̃3B1, ã1A1)-helium.

    PubMed

    Dagdigian, Paul J; Alexander, Millard H

    2013-04-28

    Transport properties for collisions of methylene, in both its ground X̃(3)B1 and low-lying ã(1)A1 electronic states, with helium have been computed using recently computed high-quality ab initio potential energy surfaces (PESs). Because of the difference in the orbital occupancy of the two electronic states, the anisotropies of the PESs are quite different. The CH2(ã)-He PES is very anisotropic because of the strong interaction of the electrons on the helium atom with the unoccupied CH2 orbital perpendicular to the molecular plane, while the anisotropy of the CH2(X̃)-He PES is significantly less since this orbital is singly occupied in this case. To investigate the importance of the anisotropy on the transport properties, calculations were performed with the full potential and with the spherical average of the potential for both electronic states. Significant differences (over 20% for the ã state at the highest temperatures considered) in the computed transport properties were found.

  6. Identification of Tazarotenic Acid as the First Xenobiotic Substrate of Human Retinoic Acid Hydroxylase CYP26A1 and CYP26B1.

    PubMed

    Foti, Robert S; Isoherranen, Nina; Zelter, Alex; Dickmann, Leslie J; Buttrick, Brian R; Diaz, Philippe; Douguet, Dominique

    2016-05-01

    Cytochrome P450 (CYP) 26A1 and 26B1 are heme-containing enzymes responsible for metabolizing all-trans retinoic acid (at-RA). No crystal structures have been solved, and therefore homology models that provide structural information are extremely valuable for the development of inhibitors of cytochrome P450 family 26 (CYP26). The objectives of this study were to use homology models of CYP26A1 and CYP26B1 to characterize substrate binding characteristics, to compare structural aspects of their active sites, and to support the role of CYP26 in the metabolism of xenobiotics. Each model was verified by dockingat-RA in the active site and comparing the results to known metabolic profiles ofat-RA. The models were then used to predict the metabolic sites of tazarotenic acid with results verified by in vitro metabolite identification experiments. The CYP26A1 and CYP26B1 homology models predicted that the benzothiopyranyl moiety of tazarotenic acid would be oriented toward the heme of each enzyme and suggested that tazarotenic acid would be a substrate of CYP26A1 and CYP26B1. Metabolite identification experiments indicated that CYP26A1 and CYP26B1 oxidatively metabolized tazarotenic acid on the predicted moiety, with in vitro rates of metabolite formation by CYP26A1 and CYP26B1 being the highest across a panel of enzymes. Molecular analysis of the active sites estimated the active-site volumes of CYP26A1 and CYP26B1 to be 918 Å(3)and 977 Å(3), respectively. Overall, the homology models presented herein describe the enzyme characteristics leading to the metabolism of tazarotenic acid by CYP26A1 and CYP26B1 and support a potential role for the CYP26 enzymes in the metabolism of xenobiotics.

  7. Trends of abiotic damage in forest ecosystems in Germany at regional scale under SRES A1B, B1

    NASA Astrophysics Data System (ADS)

    Panferov, O.; Doering, C.; Sogachev, A.; Merklein, J.; Ahrends, B.

    2009-09-01

    Current climate projections indicate that the ongoing climate change may cause an increase of frequency of weather extremes (Leckebusch et al., 2008), which can result in wide area abiotic and consequent biotic damage events (e.g. drought and following insect attacks) within forest ecosystems. The type and degree of damage depends not only on the strength of a primary driving force itself (e.g. wind speed) but also on complex interactions between combinations of effecting agents with above- and belowground forest structure characteristics. The present study investigates the projected trends of abiotic risks factors and their combinations on coniferous and deciduous forests during the 21st Century under conditions of SRES scenarios A1B and B1. The downscaling of ECHAM5-MPIOM by the regional climate model (CLM) to the spatial resolution of 0.2° x 0.2° with daily time-steps is used for the analysis of future climate extremes and their combinations. With these input data the small-scale modeling with coupled process based sub-models (Jansen et al., 2008) was carried out for Solling region, (Central Germany) calculating the water and energy balance of spruce and beech forest ecosystems on cambisols and podzols with BROOK90 (Federer et al. 2003) and wind loading on trees with 3D ABL model SCADIS (Panferov and Sogachev, 2008). The risks of drought or wind damage for a certain forest stand result from combinations of soil water characteristics, static and gust wind loads, which in turn depend on current above- and belowground tree structure and on soil texture. The actual soil water content and forest structure depends on climate-soil-vegetation interactions in previous years. Therefore, differences of microclimatological conditions in the remaining stand after changes in forest structure are taken into account. Model outputs are aggregated to 30-years periods and compared to "present” conditions of 1971-2000. The results demonstrate an increment of abiotic risks

  8. Comparison of the Function and Expression of CYP26A1 and CYP26B1, the two Retinoic Acid Hydroxylases

    PubMed Central

    Topletz, Ariel R.; Thatcher, Jayne E.; Zelter, Alex; Lutz, Justin D.; Tay, Suzanne; Nelson, Wendel L.; Isoherranen, Nina

    2011-01-01

    All-trans-retinoic acid (atRA) is an important signaling molecule in all chordates. The cytochrome P450 enzymes CYP26 are believed to partially regulate cellular concentrations of atRA via oxidative metabolism and hence affect retinoid homeostasis and signaling. CYP26A1 and CYP26B1 are atRA hydroxylases that catalyze formation of similar metabolites in cell systems. However, they have only 40% sequence similarity suggesting differences between the two enzymes. The aim of this study was to determine whether CYP26A1 and CYP26B1 have similar catalytic activity, form different metabolites from atRA and are expressed in different tissues in adults. The mRNA expression of CYP26A1 and CYP26B1 correlated between human tissues except for human cerebellum in which CYP26B1 was the predominant CYP26 and liver in which CYP26A1 dominated. Quantification of CYP26A1 and CYP26B1 protein in human tissues was in agreement with the mRNA expression and showed correlation between the two isoforms. Qualitatively, recombinant CYP26A1 and CYP26B1 formed the same primary and sequential metabolites from atRA. Quantitatively, CYP26B1 had a lower Km (19nM) and Vmax (0.8pmol/min/pmol) than CYP26A1 (Km=50nM and Vmax=10pmol/min/pmol) for formation of 4-OH-RA. The major atRA metabolites 4-OH-RA, 18-OH-RA and 4-oxo-RA were all substrates of CYP26A1 and CYP26B1, and CYP26A1 had a 2–10 fold higher catalytic activity towards all substrates tested. This study shows that CYP26A1 and CYP26B1 are qualitatively similar RA hydroxylases with overlapping expression profiles. CYP26A1 has higher catalytic activity than CYP26B1 and seems to be responsible for metabolism of atRA in tissues that function as a barrier for atRA exposure. PMID:22020119

  9. Metformin suppresses CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating aryl hydrocarbon receptor expression

    SciTech Connect

    Do, Minh Truong; Kim, Hyung Gyun; Tran, Thi Thu Phuong; Khanal, Tilak; Choi, Jae Ho; Chung, Young Chul; Jeong, Tae Cheon; Jeong, Hye Gwang

    2014-10-01

    Induction of cytochrome P450 (CYP) 1A1 and CYP1B1 by environmental xenobiotic chemicals or endogenous ligands through the activation of the aryl hydrocarbon receptor (AhR) has been implicated in a variety of cellular processes related to cancer, such as transformation and tumorigenesis. Here, we investigated the effects of the anti-diabetes drug metformin on expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and inducible conditions. Our results indicated that metformin down-regulated the expression of CYP1A1 and CYP1B1 in breast cancer cells under constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced conditions. Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression, and the metformin-mediated CYP1A1 and CYP1B1 reduction is irrelevant to estrogen receptor α (ERα) signaling. Furthermore, we found that metformin markedly down-regulated Sp1 protein levels in breast cancer cells. The use of genetic and pharmacological tools revealed that metformin-mediated down-regulation of AhR expression was mediated through the reduction of Sp1 protein. Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing tryptophan-2,3-dioxygenase (TDO) expression in MCF-7 cells. Finally, metformin inhibits TDO expression through a down-regulation of Sp1 and glucocorticoid receptor (GR) protein levels. Our findings demonstrate that metformin reduces CYP1A1 and CYP1B1 expression in breast cancer cells by down-regulating AhR signaling. Metformin would be able to act as a potential chemopreventive agent against CYP1A1 and CYP1B1-mediated carcinogenesis and development of cancer. - Graphical abstract: Schematic of the CYP1A1 and CYP1B1 gene regulation by metformin. - Highlights: • Metformin inhibits CYP1A1 and CYP1B1 expression. • Metformin down-regulates the AhR signaling. • Metformin reduces Sp1 protein expression. • Metformin suppresses TDO expression.

  10. CYP1A1 and CYP1B1 genotypes, haplotypes, and TCDD-induced gene expression in subjects from Seveso, Italy.

    PubMed

    Landi, Maria Teresa; Bergen, Andrew W; Baccarelli, Andrea; Patterson, Donald G; Grassman, Jean; Ter-Minassian, Monica; Mocarelli, Paolo; Caporaso, Neil; Masten, Scott A; Pesatori, Angela C; Pittman, Gary S; Bell, Douglas A

    2005-02-14

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is highly toxic in experimental animals, and is known to induce cytochrome P450 (CYP) gene expression. We investigated the effect of CYP1A1 and CYP1B1 variant genotypes and haplotypes on CYP1A1 and CYP1B1 mRNA expression and ethoxyresorufin-O-deethylase (EROD) activity in lymphocytes from 121 subjects from the Seveso population, Italy, accidentally exposed to TCDD in 1976. The 3'UTR 3801T>C and I462V variants of CYP1A1 were present in 16% and 6% of the subjects, respectively. The frequency of CYP1B1 variants was 85.2% for L432V, 49.6% for R48G and A119S, and 28.7% for N453S. There was complete linkage disequilibrium (LD) among the CYP1B1 variant loci (D'=-1) and high LD among the CYP1A1 loci (D'=0.86). Gene expression measured by RT-PCR did not vary by CYP1B1 genotype in uncultured lymphocytes. However, when lymphocytes were treated in vitro with 10 nM TCDD, CYP1B1 and CYP1A1 mRNA expression was strongly induced and modified by CYP variant alleles. Specifically, the CYP1B1*3 haplotype (L432V) was associated with increased CYP1B1 mRNA expression (P=0.03), following an additive model; the CYP1A1 I462V polymorphism was positively, although not significantly, associated with CYP1A1 expression. The CYP1B1*3 variant may have affected CYP1B1 expression in subjects highly and acutely exposed to dioxin at the time of the accident. Although based on small number of subjects, a slight increase in eczema (P=0.05, n=8) and urticaria (P=0.02, n=2) was observed 20 years after the accident in subjects carrying the CYP1B1*3 allele. Genetic variation in cytochrome P450 induction may identify subjects with variable responsiveness to TCDD and potentially increased risk of disease.

  11. The Involvement of Two P450 Enzymes, CYP83B1 and CYP83A1, in Auxin Homeostasis and Glucosinolate Biosynthesis1

    PubMed Central

    Bak, Søren; Feyereisen, René

    2001-01-01

    The first committed step in the biosynthesis of indole glucosinolates is the conversion of indole-3-acetaldoxime into an indole-3-S-alkyl-thiohydroximate. The initial step in this conversion is catalyzed by CYP83B1 in Arabidopsis (S. Bak, F.E. Tax, K.A. Feldmann, D.A. Galbraith, R. Feyereisen [2001] Plant Cell 13: 101–111). The knockout mutant of the CYP83B1 gene (rnt1-1) shows a strong auxin excess phenotype and are allelic to sur-2. CYP83A1 is the closest relative to CYP83B1 and shares 63% amino acid sequence identity. Although expression of CYP83A1 under control of its endogenous promoter in the rnt1-1 background does not prevent the auxin excess and indole glucosinolate deficit phenotype caused by the lack of the CYP83B1 gene, ectopic overexpression of CYP83A1 using a 35S promoter rescues the rnt1-1 phenotype. CYP83A1 and CYP83B1 heterologously expressed in yeast (Saccharomyces cerevisiae) cells show marked differences in their substrate specificity. Both enzymes convert indole-3-acetaldoxime to a thiohydroximate adduct in the presence of NADPH and a nucleophilic thiol donor. However, indole-3-acetaldoxime has a 50-fold higher affinity toward CYP83B1 than toward CYP83A1. Both enzymes also metabolize the phenylalanine- and tyrosine-derived aldoximes. Enzyme kinetic comparisons of CYP83A1 and CYP83B1 show that indole-3-acetaldoxime is the physiological substrate for CYP83B1 but not for CYP83A1. Instead, CYP83A1 catalyzes the initial conversion of aldoximes to thiohydroximates in the synthesis of glucosinolates not derived from tryptophan. The two closely related CYP83 subfamily members therefore are not redundant. The presence of putative auxin responsive cis-acting elements in the CYP83B1 promoter but not in the CYP83A1 promoter supports the suggestion that CYP83B1 has evolved to selectively metabolize a tryptophan-derived aldoxime intermediate shared with the pathway of auxin biosynthesis in Arabidopsis. PMID:11553739

  12. Postprandial response and tissue distribution of the bile acid synthesis-related genes, cyp7a1, cyp8b1 and shp, in rainbow trout Oncorhynchus mykiss.

    PubMed

    Murashita, Koji; Yoshiura, Yasutoshi; Chisada, Shin-ichi; Furuita, Hirofumi; Sugita, Tsuyoshi; Matsunari, Hiroyuki; Yamamoto, Takeshi

    2013-10-01

    In mammals, cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) are rate-limiting enzymes in bile acid synthesis. In addition, a small heterodimer partner (SHP) is also known to inhibit bile acid synthesis via the suppression of CYP7A1 and CYP8B1 expression. However, little information is currently available regarding primary structure of the genes involved in bile acid synthesis in fish. We therefore cloned cyp7a1, cyp8b1 and shp genes from rainbow trout and obtained cDNAs encoding two isoforms each of Cyp7a1 (-1 and -2), Cyp8b1 (-1 and -2) and Shp (-1 and -2). Both cyp7a1-1 and -2 encoded proteins of 512 amino acids. Trout cyp7a1-1 was expressed not only primarily in the kidney, pyloric caecum and mid-gut, but also weakly in the liver, eye, gill and ovary. cyp7a1-2 was highly expressed in the liver, pyloric caecum and mid-gut. cyp8b1-1 and -2, which encoded proteins of 512 and 509 amino acids, respectively, were principally expressed in the liver. Both shp-1 and -2, which encoded proteins of 288 and 290 amino acids, respectively, were strongly expressed in the liver, but shp-2 was also highly expressed in the gallbladder and digestive tract. The temporal changes in the expression of cyp7a1-1/-2, cyp8b1-1/-2 and shp-1/-2 in the liver were assessed after consumption of a single meal. Expression of cyp7a1-1/-2 and cyp8b1-1/-2 increased within 3h post feeding (hpf) when the stomach was still approximately 84% full and the gallbladder was almost completely empty. Although the expression of shp-1 did not change after feeding, the expression pattern of shp-2 was inversely related to the expression patterns of cyp7a1-1/-2 and cyp8b1-1/-2. Specifically, shp-2 expression decreased until 3 hpf before returning to initial levels at 24 hpf. These findings suggest that Cyp7a1s/8b1s and Shp-2 function antagonistically in bile acid synthesis in rainbow trout.

  13. Haemocoel injection of PirA1B1 to Galleria mellonella larvae leads to disruption of the haemocyte immune functions

    PubMed Central

    Wu, Gongqing; Yi, Yunhong

    2016-01-01

    The bacterium Photorhabdus luminescens produces a number of insecticidal proteins to kill its larval prey. In this study, we cloned the gene coding for a binary toxin PirA1B1 and purified the recombinant protein using affinity chromatography combined with desalination technology. Furthermore, the cytotoxicity of the recombinant protein against the haemocytes of Galleria mellonella larvae was investigated. We found that the protein had haemocoel insecticidal activity against G. mellonella with an LD50 of 131.5 ng/larva. Intrahaemocoelic injection of PirA1B1 into G. mellonella resulted in significant decreases in haemocyte number and phagocytic ability. In in vitro experiments, PirA1B1 inhibited the spreading behaviour of the haemocytes of G. mellonella larvae and even caused haemocyte degeneration. Fluorescence microscope analysis and visualization of haemocyte F-actin stained with phalloidin-FITC showed that the PirA1B1 toxin disrupted the organization of the haemocyte cytoskeleton. Our results demonstrated that the PirA1B1 toxin disarmed the insect cellular immune system. PMID:27734915

  14. Haemocoel injection of PirA1B1 to Galleria mellonella larvae leads to disruption of the haemocyte immune functions.

    PubMed

    Wu, Gongqing; Yi, Yunhong

    2016-10-13

    The bacterium Photorhabdus luminescens produces a number of insecticidal proteins to kill its larval prey. In this study, we cloned the gene coding for a binary toxin PirA1B1 and purified the recombinant protein using affinity chromatography combined with desalination technology. Furthermore, the cytotoxicity of the recombinant protein against the haemocytes of Galleria mellonella larvae was investigated. We found that the protein had haemocoel insecticidal activity against G. mellonella with an LD50 of 131.5 ng/larva. Intrahaemocoelic injection of PirA1B1 into G. mellonella resulted in significant decreases in haemocyte number and phagocytic ability. In in vitro experiments, PirA1B1 inhibited the spreading behaviour of the haemocytes of G. mellonella larvae and even caused haemocyte degeneration. Fluorescence microscope analysis and visualization of haemocyte F-actin stained with phalloidin-FITC showed that the PirA1B1 toxin disrupted the organization of the haemocyte cytoskeleton. Our results demonstrated that the PirA1B1 toxin disarmed the insect cellular immune system.

  15. Interactions between genetic polymorphism of cytochrome P450-1B1, sulfotransferase 1A1, catechol-o-methyltransferase and tobacco exposure in breast cancer risk.

    PubMed

    Saintot, Monique; Malaveille, Christian; Hautefeuille, Agnès; Gerber, Mariette

    2003-11-20

    Genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and estrogens might play a role in breast carcinogenesis related to environmental exposures. In a case-only study on 282 women with breast cancer, we studied the interaction effects (ORi) between smoking habits and the gene polymorphisms of Cytochrome P450 1B1 (Val432Leu CYP1B1), Phenol-sulfotransferase 1A1 (Arg213His SULT1A1) and Catechol-O-methyltransferase (Val158Met COMT). The smokers carrying the Val CYP1B1 allele associated with a high hydroxylation activity had a higher risk of breast cancer than never smokers with the Leu/Leu genotype (ORi=2.32, 95%CI: 1.00-5.38). Also, the smokers carrying the His SULT1A1 allele associated with a low sulfation activity had a 2-fold excess risk compared to never smokers carrying Arg/Arg SULT1A1 common genotype (ORi= 2.55, 95%CI: 1.21-5.36). The His SULT1A1 allele increased the risk only in premenopausal patients. The Met COMT allele with a lower methylation activity than Val COMT did not modify the risk among smokers. The excess risk due to joint effect could result from a higher exposure to activated tobacco-compounds for women homo/heterozygous for the Val CYP1B1 allele. Also, a lower sulfation of the tobacco carcinogens among women with His SULT1A1 could increase exposure to genotoxic compounds. Alternatively, the Val CYP1B1 or His SULT1A1 allele with modified ability to metabolize estrogens could increase the level of genotoxic catechol estrogen (i.e., 4-hydroxy-estradiol) among smokers. Our study showed that gene polymorphisms of CYP1B1 and SULT1A1 induce an individual susceptibility to breast cancer among current smokers.

  16. Differential hepatocellular zonation pattern of cholesterol 7alpha-hydroxylase (Cyp7a1) and sterol 12alpha-hydroxylase (Cyp8b1) in the mouse.

    PubMed

    Wang, Jin; Olin, Maria; Rozell, Björn; Björkhem, Ingemar; Einarsson, Curt; Eggertsen, Gösta; Gåfvels, Mats

    2007-03-01

    The synthesis of primary bile acids is confined to the hepatocytes. This study aimed to evaluate the expression pattern within the liver architecture of the rate-limiting enzyme of the neutral pathway, cholesterol 7alpha-hydroxylase (Cyp7a1), and sterol 12alpha-hydroxylase (Cyp8b1), the enzyme necessary for the synthesis of cholic acid. Specific Cyp8b1 and Cyp7a1 peptide antiserums were used for immunohistochemical staining of livers from wild type and Cyp8b1 null mice, the latter instead expressing beta-galactosidase (beta-Gal) as a replacement reporter gene. Cyp8b1 was mainly expressed in the hepatocytes in a zonal pattern surrounding the central vein while the areas surrounding the portal zones showed much lower levels. The zonation was maintained in cholic acid-depleted mice using beta-Gal as a reporter protein. Cyp7a1 expression in wild type mice also showed a zonal distribution pattern, although less distinct, with a maximal expression within a 1-2 cell thick layer of hepatocytes surrounding the central vein. In Cyp8b1 null mice, a more intense staining was obtained, in accordance with the higher expression level of Cyp7a1, although the overall expression pattern was maintained. Our results in mice indicate possible differences in the regulation of the cellular zonation of Cyp7a1 and Cyp8b1. Also, cholic acid affects the set-point of Cyp7a1 expression but not its zonal distribution.

  17. Molecular Cloning, Tissue Distribution, and Functional Characterization of Marmoset Cytochrome P450 1A1, 1A2, and 1B1.

    PubMed

    Uehara, Shotaro; Uno, Yasuhiro; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi

    2016-01-01

    The common marmoset (Callithrix jacchus), a New World monkey, has potential to be an animal model for drug metabolism studies. In this study, we identified and characterized cytochrome P450 (P450) 1A1 and 1B1 in addition to the known P450 1A2 in marmosets. Marmoset P450 1A1 and 1B1 cDNA contained open reading frames encoding 512 and 543 amino acids, respectively, with high sequence identities (90%-93%) to other primate P450 1A1s and 1B1s. A phylogenetic tree based on amino acid sequences showed close evolutionary relationships among marmoset, macaque, and human P450 1A and 1B enzymes. By mRNA quantification and immunoblot analyses in five marmoset tissues, P450 1A1 was mainly expressed in lungs and small intestines, and P450 1A2 was expressed predominantly in livers. In contrast, P450 1B1 was expressed in all tissues tested. Marmoset P450 1A1, 1A2, and 1B1 heterologously expressed in Escherichia coli catalyzed 7-ethoxyresorufin O-deethylation, 7-ethoxycoumarin O-deethylation, and phenacetin O-deethylation, similar to those of humans and cynomolgus monkeys. Notably, marmoset P450 1A1 and 1A2 more efficiently catalyzed 7-ethoxyresorufin O-deethylation than those of the human homologs, but were comparable to those of the cynomolgus monkey homologs. Additionally, marmoset P450 1B1 preferentially catalyzed estradiol 4-hydroxylation; however, rat P450 1B1 more favorably catalyzed estradiol 2-hydroxylation, indicating that the estradiol hydroxylation specificity of marmoset P450 1B1 was similar to those of human and cynomolgus monkey P450 1B1. These results indicated that marmoset P450 1A and 1B enzymes had functional characteristics similar to those of humans and cynomolgus monkeys, suggesting that P450 1A and 1B-dependent metabolism was similar among marmosets, cynomolgus monkeys, and humans. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  18. CYP1A1 and CYP1B1 polymorphisms and their association with estradiol and estrogen metabolites in women who are premenopausal and perimenopausal.

    PubMed

    Sowers, MaryFran R; Wilson, Angela L; Kardia, Sharon R; Chu, Jian; McConnell, Daniel S

    2006-09-01

    The purpose of this study was to relate measured concentrations of estradiol (E2) and the urinary estrogen metabolites 2-hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1) to single nucleotide polymorphisms (SNPs) from CYP1A1 and CYP1B1, the primary genes involved in estrogen catabolism. We investigated the association of 4 CYP1A1 SNPs (CYP1A1 rs4646903, CYP1A1 rs1531163, CYP1A1 rs2606345, and CYP1A1 rs1048943) and 2 CYP1B1 SNPs (CYP1B1 rs162555 and CYP1B1 rs1056836) to circulating serum E2 concentrations and the urinary estrogen metabolites 2-OHE1 and 16alpha-OHE1. The associations were evaluated in 1,340 participants of 4 racial/ethnic groups from the Study of Women's Health Across the Nation (SWAN) who were premenopausal and perimenopausal. There was substantial variation in the allele frequencies of the SNPs for African American and Caucasian women. There was, however, remarkable comparability between Chinese and Japanese women; their CYP1A1 and CYP1B1 allele frequencies differed by only < or =11%. There was significant variation in E2 concentrations by genotype within racial/ethnic group for CYP1A1 rs2606345. In particular, Japanese women with the CC genotype had lower E2 concentrations than did Japanese women with the AC genotype. Chinese women with the CC genotype had higher 2-OHE1 concentrations than did Chinese women with the AC genotype. Further, African American women with the CC genotype had higher 16alpha-OHE1 concentrations than did those with other genotypes. CYP1A1 rs2606345 may play an important role in estrogen metabolism in women who are premenopausal and perimenopausal.

  19. Effects of statin treatments and polymorphisms in UGT1A1 and SLCO1B1 on serum bilirubin levels in Chinese patients with hypercholesterolaemia.

    PubMed

    Hu, Miao; Tomlinson, Brian

    2012-08-01

    In vitro and animal studies showed that statins could increase bilirubin levels by activation of haem oxygenase-1, whereas the effect of statins on serum bilirubin levels in humans remains controversial. The organic anion transporting polypeptide 1B1 (OATP1B1, gene SLCO1B1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) play an important role in the disposition of bilirubin. This study investigated 1) whether common polymorphisms in UGT1A1 and SLCO1B1 influence bilirubin levels; 2) whether statin treatments affect bilirubin levels; and 3) whether the polymorphisms examined influence the drug effect. Associations between common polymorphisms in UGT1A1 and SLCO1B1 and the serum bilirubin levels on no lipid-lowering treatment were analyzed in 379 Chinese patients with hypercholesterolaemia. Effects of simvastatin 40 mg daily and rosuvastatin 10 mg daily on the bilirubin levels were compared in 236 subjects with good compliance to both statins. The UGT1A1 polymorphisms associated with reduced enzyme activity were significantly associated with increased baseline bilirubin levels. The bilirubin levels were increased from a geometric mean (95% CI) of 10.9 (10.3-11.4) μmol/L at baseline to 11.6 (11.1-12.0) μmol/L with rosuvastatin and 12.5 (11.9-13.0) μmol/L with simvastatin and the increase was greater with simvastatin (P < 0.001). There was no relationship between polymorphisms in UGT1A1 or SLCO1B1 and changes in bilirubin levels with the two statins. This study showed that the polymorphisms in UGT1A1, but not SLCO1B1, were associated with serum bilirubin levels in Chinese patients. Statins increased bilirubin levels and this effect was independent of the polymorphisms in UGT1A1 and SLCO1B1. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Molecular characterization of cyp11a1 and cyp11b1 and their gene expression profile in pejerrey (Odontesthes bonariensis) during early gonadal development.

    PubMed

    Blasco, Martín; Fernandino, Juan I; Guilgur, Leonardo G; Strüssmann, Carlos A; Somoza, Gustavo M; Vizziano-Cantonnet, Denise

    2010-05-01

    Sex steroids are known to be involved in gonadal differentiation in fish, but whether androgens are early mediators of testis differentiation remains unclear. We studied the sex-related developmental variations in the gene expression of two key enzymes involved in steroids and androgen synthesis (cyp11a1 and cyp11b1) in trunks and isolated gonads of pejerrey (Odontesthes bonariensis) larvae during and after the sex determination period. Also, and in order to have a better characterization of this process we studied the expression of Sertoli (dmrt1, amh, sox9) and Leydig (nr5a1 or sf-1) cell markers as well as a gene with higher expression in females (cyp19a1a). No clear differences were observed in the expression of cyp11a1 and cyp11b1 during the temperature-sensitive window in the trunk of pejerrey larvae. Nevertheless, a clear increase of cyp11b1 was observed in isolated gonads taken from fish reared at the male producing temperature. In these gonads we also confirmed the trends of genes with higher expression in males (dmrt1, amh) and females (cyp19a1a) as previously described in larval trunks of pejerrey. Our results showed that the expression of cyp11b1 was positively associated with the morphological differentiation of the testis. Nevertheless the involvement of 11-oxygenated androgens during the temperature-sensitive window could not be clearly established. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Non-Franck-Condon electron-impact dissociative-excitation cross sections of molecular hydrogen producing H(1s)+H(2l) through X 1Σ+g(v=0)-->\\{B 1Σ+u, B' 1Σ+u, C 1Πu\\}

    NASA Astrophysics Data System (ADS)

    Borges, Itamar, Jr.; Jalbert, Ginette; Bielschowsky, Carlos Eduardo

    1998-02-01

    Dissociation cross sections of H2 for high-energy electron impact (100-1000 eV) producing H(1s), H(2s), and H(2p) for excitation from the ground vibrational state (v=0) to the continuum of the B1Σ+u, B' 1Σ+u, and C 1Πu states were computed in the first Born approximation. Configuration-interaction electronic wave functions were used and vibrational degrees of freedom taken in account. The dissociative excitation cross sections as a function of the continuum energy for each final state were presented, and the accuracy of the wave function, including the importance of relaxation effects and the validity of the Franck-Condon approximation, is analyzed in comparison to available previous theoretical results. The computed dissociation cross sections were compared to experimental results making use of the separation of the various breakup channels proposed by Ajello, Shemansky, and James [Astrophys. J. 371, 422 (1991)]. The obtained cross sections to produce H(2p)+H(1s) fragments via dissociative excitation to the B and C states have agreed well with the decomposed experimental results within the error bars. The dissociation cross sections to produce H(2s)+H(1s) through the B' state were in most cases somewhat larger than the reported experimental error bars. In the most favorable case our theoretical B' dissociation cross section was 3.1% within the reported error bar at 300 eV electron impact energy. A possible experimental reason for this discrepancy was raised.

  2. Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk

    PubMed Central

    Bethke, Lara; Webb, Emily; Sellick, Gabrielle; Rudd, Matthew; Penegar, Stephen; Withey, Laura; Qureshi, Mobshra; Houlston, Richard

    2007-01-01

    Background Cytochrome P450 (CYP) enzymes have the potential to affect colorectal cancer (CRC) risk by determining the genotoxic impact of exogenous carcinogens and levels of sex hormones. Methods To investigate if common variants of CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1 and CYP19A1 influence CRC risk we genotyped 2,575 CRC cases and 2,707 controls for 20 single nucleotide polymorphisms (SNPs) that have not previously been shown to have functional consequence within these genes. Results There was a suggestion of increased risk, albeit insignificant after correction for multiple testing, of CRC for individuals homozygous for CYP1B1 rs162558 and heterozygous for CYP1A2 rs2069522 (odds ratio [OR] = 1.36, 95% confidence interval [CI]: 1.03–1.80 and OR = 1.34, 95% CI: 1.00–1.79 respectively). Conclusion This study provides some support for polymorphic variation in CYP1A2 and CYP1B1 playing a role in CRC susceptibility. PMID:17615053

  3. Functional evaluation of novel single nucleotide polymorphisms and haplotypes in the promoter regions of CYP1B1 and CYP1A1 genes.

    PubMed

    Han, Weiguo; Pentecost, Brian T; Spivack, Simon D

    2003-07-01

    Interindividual variation in the expression of the carcinogen- and estrogen-metabolizing enzymes cytochrome P4501B1 and 1A1 (CYP1B1 and CYP1A1) has been detected in human lung. To search for polymorphisms with functional consequences for CYP1B1 and CYP1A1 gene expression, we examined 1.5 kb of the promoter region of each gene. Genomic DNA from 21 Caucasian individuals was amplified by polymerase chain reaction (PCR) for direct cycle sequencing. Eight single nucleotide polymorphisms (SNPs) for CYP1B1 and 13 SNPs for CYP1A1 were found. The majority of polymorphisms occurred as multiSNP combinations for individual subjects. The wild-type sequences were cloned into a luciferase reporter construct. The most frequent polymorphisms were then recreated by iterative site-directed mutagenesis, replicating single polymorphisms and multiSNP combinations. These wild-type and variant constructs were functionally evaluated in transient transfection experiments employing exposures to either the index polycyclic aromatic hydrocarbon (PAH) inducer benzo[a]pyrene (B[a]P), a composite mixture of cigarette smoke extract (CSE), or the repressor chemopreventive agent trans-3,4,5-trihydroxystilbene (reseveratrol). Results indicated that all wild-type and variant constructs responded in qualitatively concordant fashion to the inducers and to the repressor. The CYP1B1 haplotypes and the majority of CYP1A1 haplotypes were shown to have no functional consequence, as compared to those of the wild-type promoter sequences. Two constructs of composite polymorphisms of CYP1A1 appeared to result in a statistically significant increase in basal promoter activity (1.38- and 1.50-fold, respectively), but the degree of functional impact was judged unlikely to be biologically important in vivo. We conclude that the observed promoter region polymorphisms in these genes are common, but are of unclear functional consequence.

  4. Isolation and purification of enniatins A, A(1), B, B(1), produced by Fusarium tricinctum in solid culture, and cytotoxicity effects on Caco-2 cells.

    PubMed

    Meca, G; Ruiz, M J; Soriano, J M; Ritieni, A; Moretti, A; Font, G; Mañes, J

    2010-09-01

    Enniatins (ENs) are antibiotic compounds of hexadepsipeptidic structure produced by several strains of Fusarium spp. The ENs A, A(1), B, B(1) were purified from extracts of Fusarium tricinctum grown on a solid medium of corn, by a low pressure liquid chromatography (LPLC) on reverse phase of Amberlite XAD-7 followed by semipreparative LC. The purity and the structure of the isolated compounds were confirmed by LC-MS/MS. The technique of the purification of the fungal extract enabled complete separation of the ENs A, A(1), B, B(1) with a mean purity of 97% for all the compounds. The cytoxicity of the ENs was tested in the cell lines of human origin (epithelial colorectal adenocarcinoma cells, Caco-2) by MTT assays. Only EN A(1) and B(1) evoked toxicity at the tested concentrations. The inhibitory concentration (IC(50)) for EN A(1) on Caco-2 cells was 12.3 microM, whereas the IC(50) produced by the EN B(1) was 19.5 microM. This study indicates that ENs, fungal metabolites that are commonly found in corn and in general in product composed by corn, may have a toxic potential for human health. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. Carnosol, a Constituent of Zyflamend, Inhibits Aryl Hydrocarbon Receptor-Mediated Activation of CYP1A1 and CYP1B1 Transcription and Mutagenesis

    PubMed Central

    Mohebati, Arash; Guttenplan, Joseph B.; Kochhar, Amit; Zhao, Zhong-Lin; Kosinska, Wieslawa; Subbaramaiah, Kotha; Dannenberg, Andrew J.

    2012-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated member of the basic-helix-loop-helix family of transcription factors, plays a significant role in polycyclic aromatic hydrocarbon (PAH) induced carcinogenesis. In the upper aerodigestive tract of humans, tobacco smoke, a source of PAHs, activates the AhR leading to increased expression of CYP1A1 and CYP1B1, which encode proteins that convert PAHs to genotoxic metabolites. Inhibitors of Hsp90 ATPase cause a rapid decrease in levels of AhR, an Hsp90 client protein, and thereby block PAH-mediated induction of CYP1A1 and CYP1B1. The main objective of this study was to determine whether Zyflamend, a polyherbal preparation, suppressed PAH-mediated induction of CYP1A1 and CYP1B1 and inhibited DNA adduct formation and mutagenesis. We also investigated whether carnosol, one of multiple phenolic antioxidants in Zyflamend, had similar inhibitory effects. Treatment of cell lines derived from oral leukoplakia (MSK-Leuk1) and skin (HaCaT) with benzo[a]pyrene (B[a]P), a prototypic PAH, induced CYP1A1 and CYP1B1 transcription, resulting in enhanced levels of message and protein. Both Zyflamend and carnosol suppressed these effects of B[a]P. Notably, both Zyflamend and carnosol inhibited Hsp90 ATPase activity and caused a rapid reduction in AhR levels. The formation of B[a]P induced DNA adducts and mutagenesis were also inhibited by Zyflamend and carnosol. Collectively, these results show that Zyflamend and carnosol inhibit Hsp90 ATPase leading to reduced levels of AhR, suppression of B[a]P-mediated induction of CYP1A1 and CYP1B1 and inhibition of mutagenesis. Carnosol-mediated inhibition of Hsp90 ATPase activity can help explain the chemopreventive activity of herbs such as Rosemary, which contain this phenolic antioxidant. PMID:22374940

  6. Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss.

    PubMed

    Saijo, Y; Sata, F; Yamada, H; Suzuki, K; Sasaki, S; Kondo, T; Gong, Y Y; Kato, E H; Shimada, S; Morikawa, M; Minakami, H; Kishi, R

    2004-10-01

    The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.

  7. CYP1A1 and CYP1B1 genetic polymorphisms, smoking and breast cancer risk in a Finnish Caucasian population.

    PubMed

    Sillanpää, Pia; Heikinheimo, Liisa; Kataja, Vesa; Eskelinen, Matti; Kosma, Veli-Matti; Uusitupa, Matti; Vainio, Harri; Metsola, Katja; Hirvonen, Ari

    2007-09-01

    We investigated the associations between two CYP1A1 polymorphisms (Ile462Val and Thr461Asn) and one CYP1B1 polymorphism (Leu432Val) and breast cancer risk. The study population consisted of 483 breast cancer patients and 482 healthy population controls, all of homogenous Finnish origin. No statistically significant overall associations were found between the CYP1A1 and CYP1B1 genotypes and breast cancer risk. However, a significant increase in the breast cancer risk was seen for women who had smoked 1-9 cigarettes/day and carried the CYP1B1 432Val allele; the OR was 2.6 (95% CI 1.07-6.46) for women carrying the Leu/Val genotype and 5.1 (95% CI 1.30-19.89, P for trend 0.005) for women with the Val/Val genotype compared to similarly smoking women homozygous for the 432Leu allele. Furthermore, when CYP1B1 genotypes were combined with the previously analyzed N-acetyl transferase (NAT2) genotypes, a significant increase in breast cancer risk was found among women who had at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype (OR 1.52; 95% CI 1.03-2.24) compared to women carrying a combination of CYP1B1 Leu/Leu and NAT2 rapid acetylator genotypes. This risk was seen to be confined to ever smokers; the OR was 2.46 (95% CI 1.11-5.45) for ever smokers carrying at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype compared to ever smokers with the CYP1B1 Leu/Leu and NAT2 rapid acetylator genotype combination. Our results suggest that the CYP1B1 polymorphism may be an important modifier of breast cancer risk in Finnish Caucasian women who have been exposed to tobacco smoke and/or carry the NAT2 slow acetylator genotype.

  8. Soy isoflavones, CYP1A1, CYP1B1, and COMT polymorphisms, and breast cancer: a case-control study in southwestern China.

    PubMed

    Wang, Qiong; Li, Hui; Tao, Ping; Wang, Yuan-Ping; Yuan, Ping; Yang, Chun-Xia; Li, Jia-Yuan; Yang, Fei; Lee, Hui; Huang, Yuan

    2011-08-01

    CYP1A1, CYP1B1, and COMT are key enzymes involved in estrogen metabolism. Soy isoflavones, phytoestrogens found in soy foods, may modify the activity of these enzymes. A case-control study was conducted to assess the associations between soy isoflavone intake and the CYP1A1 Ile462Val, CYP1B1 Val432Leu, and COMT Val158Met polymorphisms and breast cancer, as well as their combined effects on breast cancer. A total of 400 newly diagnosed breast cancer cases and 400 healthy controls were recruited. Participants' daily intake of soy isoflavones (DISI [mg/day]) was calculated and transformed to energy-adjusted DISI by the residual method. Gene sequencing was used to analyze CYP1A1, CYP1B1, and COMT polymorphisms. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated by conditional logistic regression. A strong protective dose-dependent effect of energy-adjusted DISI on breast cancer was found in both pre- and postmenopausal women (P(trend) < 0.05). Among all women and in the postmenopausal subgroup, COMT Met/Met and CYP1B1 Leu/Leu susceptible genotype carriers had higher risk of breast cancer (aORs > 1, OR 95% CIs exclude 1). In premenopausal women, only carrying CYP1B1 Leu/Leu was associated with breast cancer risk (aOR = 2.05, 95% CI: 1.11-3.79). Carrying CYP1A1 Val/Val was related to breast cancer risk only among all women. A stratified analysis was performed at two levels of energy-adjusted DISI, with wildtype homozygous genotypes and low energy-adjusted DISI as the reference. In the high energy-adjusted DISI subgroup, carrying the CYP1B1 Leu/Leu genotype did not affect breast cancer risk in either all women or in the menopausal subgroups, compared with the reference. Overall, in Han Chinese women, carrying CYP1A1 Val/Val and COMT Met/Met appears to be associated with breast cancer risk, especially in postmenopausal women. CYP1B1 susceptible genotypes (Val/Leu or Leu/Leu) also contribute to increased breast cancer risk

  9. Fully relativistic rovibrational energies and spectroscopic constants of the lowest X:(1)0(+)g, A':(1)2( u ), A:(1)1 ( u ), B':(1)0(-)u and B:(1)0(+)u states of molecular chlorine.

    PubMed

    Machado, Daniel F S; Silva, Valter H C; Esteves, Cristiano S; Gargano, Ricardo; Macedo, Luiz G M; Mundim, Kleber C; de Oliveira, Heibbe C B

    2012-09-01

    The main goal of this paper is to present the rovibrational energies and spectroscopic constants of the Cl(2) molecular system in the relativistic states [Formula: see text], A':(1)2( u ), A:(1)1( u ), [Formula: see text] and [Formula: see text]. More precisely, we have evaluated the Cl(2) ω ( e ), ω ( e ) x ( e ), ω ( e ) y ( e ), α ( e ), γ ( e ) and B ( e ) rovibrational spectroscopic constants using two different procedures. The first was obtained by combining the rovibrational energies, calculated through solving Schrödinger's nuclear equation and the diatomic rovibrational energy equation. The second was obtained by using the Dunham method. The calculated properties are in good agreement with available experimental data.

  10. Gender, but not CYP7A1 or SLCO1B1 polymorphism, affects the fasting plasma concentrations of bile acids in human beings.

    PubMed

    Xiang, Xiaoqiang; Backman, Janne T; Neuvonen, Pertti J; Niemi, Mikko

    2012-03-01

    Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production in human beings, and organic anion-transporting polypeptide 1B1 (OATP1B1) may influence bile acid hepatic uptake and cholesterol and bile acid synthesis rate. Our purpose was to investigate the effects of gender and CYP7A1 and SLCO1B1 polymorphisms on the fasting plasma concentrations of bile acids, bile acid synthesis marker and total cholesterol in a Finnish population. Fasting plasma concentrations of 16 endogenous bile acids, their synthesis marker (7α-hydroxy-4-cholesten-3-one) and total cholesterol were measured in 243 samples from 143 healthy volunteers. The volunteers were genotyped for 6 haplotype-tagging single-nucleotide polymorphisms (SNPs) of CYP7A1 and two functionally relevant SNPs in SLCO1B1. The mean plasma concentrations of chenodeoxycholic acid, glycochenodeoxycholic acid, ursodeoxycholic acid and glycoursodeoxycholic acid were 61-111% higher in men than in women (P ≤ 0.001). Accordingly, the mean concentration of total bile acids was 51% higher in men than in women (P = 0.001). The CYP7A1 rs8192879 and rs1023652 SNPs were associated with deoxycholic acid and hyodeoxycholic acid concentrations, respectively, but the associations were not significant after correction for multiple testing. None of the six CYP7A1 SNPs was associated with the plasma concentrations of cholesterol or 7α-hydroxy-4-cholesten-3-one. SLCO1B1 genotype was associated with total plasma cholesterol concentration only, but the association was not significant after correction for multiple testing. In general, the gender contributes substantially more to variation in fasting plasma bile acid concentrations than CYP7A1 or SLCO1B1 polymorphism do. Common genetic variability in CYP7A1 is unlikely to play a significant role in cholesterol metabolism and bile acid homeostasis under normal physiological conditions. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011

  11. Fitness Assays Reveal Incomplete Functional Redundancy of the HoxA1 and HoxB1 Paralogs of Mice

    PubMed Central

    Ruff, James S.; Saffarini, Raed B.; Ramoz, Leda L.; Morrison, Linda C.; Baker, Shambralyn; Laverty, Sean M.; Tvrdik, Petr; Potts, Wayne K.

    2015-01-01

    Gene targeting techniques have led to the phenotypic characterization of numerous genes; however, many genes show minimal to no phenotypic consequences when disrupted, despite many having highly conserved sequences. The standard explanation for these findings is functional redundancy. A competing hypothesis is that these genes have important ecological functions in natural environments that are not needed under laboratory settings. Here we discriminate between these hypotheses by competing mice (Mus musculus) whose Hoxb1 gene has been replaced by Hoxa1, its highly conserved paralog, against matched wild-type controls in seminatural enclosures. This Hoxb1A1 swap was reported as a genetic manipulation resulting in no discernible embryonic or physiological phenotype under standard laboratory tests. We observed a transient decline in first litter size for Hoxb1A1 homozygous mice in breeding cages, but their fitness was consistently and more dramatically reduced when competing against controls within seminatural populations. Specifically, males homozygous for the Hoxb1A1 swap acquired 10.6% fewer territories and the frequency of the Hoxb1A1 allele decreased from 0.500 in population founders to 0.419 in their offspring. The decrease in Hoxb1A1 frequency corresponded with a deficiency of both Hoxb1A1 homozygous and heterozygous offspring. These data suggest that Hoxb1 and Hoxa1 are more phenotypically divergent than previously reported and support that sub- and/or neofunctionalization has occurred in these paralogous genes leading to a divergence of gene function and incomplete redundancy. Furthermore, this study highlights the importance of obtaining fitness measures of mutants in ecologically relevant conditions to better understand gene function and evolution. PMID:26447130

  12. Evidence for the 2B1-2A1 electronic transition in chlorine dioxide from resonance Raman depolarization ratios

    NASA Astrophysics Data System (ADS)

    Reid, Philip J.; Esposito, Anthony P.; Foster, Catherine E.; Beckman, Robert A.

    1997-11-01

    The resonance Raman depolarization ratios of chlorine dioxide (OClO) dissolved in cyclohexane are measured and analyzed to establish the existence of a 2A1 excited state that is nearly degenerate with the optically stronger, 2A2 excited state. The depolarization ratio of the symmetric stretch fundamental transition is measured at several excitation wavelengths spanning the lowest-energy electronic transition centered at ˜360 nm. The depolarization ratio of this transition reaches a maximum value of 0.25±0.04 directly on resonance suggesting that scattered intensity is not derived from a single excited state. The depolarization ratios are modeled utilizing the time-dependent formalism for Raman scattering. This analysis demonstrates that the observed Raman depolarization ratios are derived from contributions of two excited states of 2A1 and 2A2 symmetry to the observed scattering. The results presented here support the emerging picture of OClO excited-state reaction dynamics in which photoexcitation to the 2A2 excited state is followed by internal conversion from this state to the 2A1 surface. Both the role of the 2A1 state in the photochemistry of OClO and the importance of this state in modeling resonance Raman intensities are discussed.

  13. A dispersed fluorescence and ab initio investigation of the X2B1 and A2A1 electronic states of the PH2 molecule.

    PubMed

    Jakubek, Z J; Bunker, P R; Zachwieja, M; Nakhate, S G; Simard, B; Yurchenko, S N; Thiel, W; Jensen, Per

    2006-03-07

    In this work, the X2B1 and A2A1 electronic states of the phosphino (PH2) free radical have been studied by dispersed fluorescence and ab initio methods. PH2 molecules were produced in a molecular free-jet apparatus by laser vaporizing a silicon rod in the presence of phosphine (PH3) gas diluted in helium. The laser-induced fluorescence, from the excited A2A1 electronic state down to the ground electronic state, was dispersed and analyzed. Ten (upsilon1upsilon2upsilon3) vibrationally excited levels of the ground electronic state, with upsilon1 < or = 2, upsilon2 < or = 6, and upsilon3 = 0, have been observed. Ab initio potential-energy surfaces for the X2B1 and A2A1 electronic states have been calculated at 210 points. These two states correlate with a 2Pi(u) state at linearity and they interact by the Renner-Teller coupling and spin-orbit coupling. Using the ab initio potential-energy surfaces with our RENNER computer program system, the vibronic structure and relative intensities of the A2A1 --> X2B1 emission band system have been calculated in order to corroborate the experimental assignments.

  14. Phenotype of the Cyp1a1/1a2/1b1(−/−) Triple-Knockout Mouse*

    PubMed Central

    Dragin, Nadine; Shi, Zhanquan; Madan, Rajat; Karp, Christopher L.; Sartor, Maureen A.; Chen, Chi; Gonzalez, Frank J.; Nebert, Daniel W.

    2009-01-01

    Crossing the Cyp1a1/1a2(−/−) double-knockout mouse with the Cyp1b1(−/−) single-knockout mouse, we generated the Cyp1a1/1a2/1b1(−/−) triple-knockout mouse. In this triple-knockout mouse, statistically significant phenotypes (with incomplete penetrance) included slower weight gain and greater risk of embryolethality before gestational day 11, hydrocephalus, hermaphroditism, and cystic ovaries. Oral benzo[a]pyrene (BaP) daily for 18 days in the Cyp1a1/1a2(−/−) produced the same degree of marked immunosuppression as seen in the Cyp1a1(−/−) mouse; we believe this reflects the absence of intestinal CYP1A1. Oral BaP-treated Cyp1a1/1a2/1b1(−/−) mice showed the same “rescued” response as that seen in the Cyp1a1/1b1(−/−) mouse; we believe this reflects the absence of CYP1B1 in immune tissues. Urinary metabolite profiles were dramatically different between untreated triple-knockout and wild-type; principal components analysis showed that the shifts in urinary metabolite patterns in oral BaP-treated triple-knockout and wild-type mice were also strikingly different. Liver microarray cDNA differential expression (comparing triple-knockout with wild-type) revealed at least 89 genes up- and 62 genes down-regulated (P-value ≤0.00086). Gene Ontology “classes of genes” most perturbed in the untreated triple-knockout (compared with wild-type) include lipid, steroid, and cholesterol biosynthesis and metabolism; nucleosome and chromatin assembly; carboxylic and organic acid metabolism; metal-ion binding; and ion homeostasis. In the triple-knockout compared with the wild-type mice, response to zymosan-induced peritonitis was strikingly exaggerated, which may well reflect down-regulation of Socs2 expression. If a single common molecular pathway is responsible for all of these phenotypes, we suggest that functional effects of the loss of all three Cyp1 genes could be explained by perturbations in CYP1-mediated eicosanoid production, catabolism and

  15. Rotational analysis of the Ångström system (B1Σ+-A1Π) in the rare 13C17O isotopologue

    NASA Astrophysics Data System (ADS)

    Hakalla, Rafał; Zachwieja, Mirosław

    2012-02-01

    Although yet unobserved in the very rare 13C17O isotopologue, the Ångström system (B1Σ+-A1Π) was obtained under high resolution as an emission spectrum using a conventional spectroscopic technique. The emission from the discharge was observed with a plane grating spectrograph and recorded by a photomultiplier tube. In total, 192 transition wave numbers belonging to two bands (0-1 and 0-2) were precisely measured and rotationally analyzed. This method allowed us to determine the merged rotational constants B0 = 1.8131941(58) cm-1 and D0 = 5.5620(46) × 10-6 cm-1 and the individual molecular constant B1 = 1.471059(47) cm-1, D1 = 5.315(64) × 10-6 cm-1, B2 = 1.451762(13) cm-1, D2 = 7.812(16) × 10-6 cm-1 for the as yet unanalyzed 13C17O molecule B1Σ+ and A1Π states, respectively. The band origins σ of the Ångström system in the 13C17O molecule were also calculated. Numerous rotational perturbations observed in the A1Π state in 13C17O molecule have been identified and analyzed in detail. The suspected candidates responsible for these irregularities were indicated by means of a graph of the rovibronic levels of the neighboring states based on the estimated term value in the 13C17O molecule. The values of these perturbations have also been defined for both the e- and f-parity of the A1Π(v = 1 and 2) state. Simultaneously, the B1Σ+ state was observed to be quite regular up to the observed Jmax level.

  16. About the origin of European spelt ( Triticum spelta L.): allelic differentiation of the HMW Glutenin B1-1 and A1-2 subunit genes.

    PubMed

    Blatter, R H E; Jacomet, S; Schlumbaum, A

    2004-01-01

    To investigate the origin of European spelt ( Triticum spelta L., genome AABBDD) and its relation to bread wheat ( Triticum aestivum L., AABBDD), we analysed an approximately 1-kb sequence, including a part of the promoter and the coding region, of the high-molecular-weight (HMW) glutenin B1-1 and A1-2 subunit genes in 58 accessions of hexa- and tetraploid wheat from different geographical regions. Six Glu-B1-1 and five Glu-A1-2 alleles were identified based on 21 and 19 informative sites, respectively, which suggests a polyphyletic origin of the A- and B-genomes of hexaploid wheat. In both genes, a group of alleles clustered in a distinct, so-called beta subclade. High frequencies of alleles from the Glu-B1-1 and Glu-A1-2 beta subclades differentiated European spelt from Asian spelt and bread wheat. This indicates different origins of European and Asian spelt, and that European spelt does not derive from the hulled progenitors of bread wheat. The conjoint differentiation of alleles of the A- and B-genome in European spelt suggests the introgression of a tetraploid wheat into free-threshing hexaploid wheat as the origin of European spelt.

  17. Extended analysis of the Ångström band system (B1Σ+ - A1Π) in the rare 12C17O isotopologue

    NASA Astrophysics Data System (ADS)

    Hakalla, R.; Szajna, W.; Zachwieja, M.

    2012-11-01

    The Ångström band system (B1Σ+ - A1Π), so far unobserved in the rare 12C17O isotopologue, was obtained under high resolution as an emission spectrum using high accuracy dispersive optical spectroscopy. In total, 200 transition wave numbers belonging to the 0-1 and 0-2 bands were precisely measured and rotationally analysed. The obtained result was the merged rotational constants B0 = 1.898 8823(41) cm-1 and D0 = 6.4283(26) × 10-6 cm-1 for the B1Σ+ Rydberg state as well as the individual rotational constants B1 = 1.540 88(12) cm-1, D1 = 6.950(87) × 10-6 cm-1, B2 = 1.519 292(69) cm-1, D2 = 8.22(16) × 10-6 cm-1 for the A1Π state in the 12C17O isotopologue. The \\sigma _{0 - v^{\\prime \\prime }} band origins were also calculated. Numerous rotational perturbations observed in the A1Π state in this molecule have been identified. The observed perturbations were confronted with those predicted from theoretical calculations.

  18. Transposon insertions in the promoter of the Zea mays a1 gene differentially affect transcription by the Myb factors P and C1.

    PubMed Central

    Pooma, Wilailak; Gersos, Christos; Grotewold, Erich

    2002-01-01

    The understanding of control of gene regulation in higher eukaryotes relies heavily on results derived from non-in vivo studies, but rarely can the significance of these approximations be established in vivo. Here, we investigated the effect of Mutator and Spm insertions on the expression of the flavonoid biosynthetic gene a1, independently regulated by the transcription factors C1 and P. The a1-mum2 and a1-m2 alleles carry Mu1 and Spm insertions, respectively, in a cis-element (ARE) of unknown function located between the P- and C1-binding sites. We show that the insertions of Mu1 and Spm similarly influence the expression of a1 controlled by C1 or P. The P-controlled a1 expression in a1-m2 is Spm dependent, and the mutant phenotype of a1-mum2 is suppressed in the pericarp in the absence of the autonomous MuDR element. Footprints within the ARE affect the regulation of a1 by C1 and P differently, providing evidence that these factors control a1 expression using distinct cis-acting regulatory elements. Together, our findings contribute significantly to one of the best-described plant regulatory systems, while stressing the need to complement with in vivo experiments current approaches used for the study of control of gene expression. PMID:12072474

  19. Association of genetic variants of xenobiotic and estrogen metabolism pathway (CYP1A1 and CYP1B1) with gallbladder cancer susceptibility.

    PubMed

    Sharma, Kiran Lata; Agarwal, Akash; Misra, Sanjeev; Kumar, Ashok; Kumar, Vijay; Mittal, Balraj

    2014-06-01

    Gallbladder carcinoma is a highly aggressive cancer with female predominance. Interindividual differences in the effectiveness of the activation/detoxification of environmental carcinogens and endogenous estrogens may play a crucial role in cancer susceptibility. The present study included 410 patients with carcinoma of the gallbladder (GBC) and 230 healthy subjects. This study examined association of CYP1A1-MspI, CYP1A1-Ile462Val, and CYP1B1-Val432Leu with GBC susceptibility. CYP1A1-MspI [CC] and CYP1A1-Ile462Val [iso/val] genotypes were found to be significantly associated with GBC (p=0.006 and p=0.03, respectively), as compared to healthy controls, while CYP1B1-Val432Leu was not associated with GBC. The CYP1A1 haplotype [C-val] showed a significant association with GBC (p=0.006). On stratification based on gender, the CYP1A1-MspI [CC] genotype showed an increased risk of GBC in females (p=0.018). In case-only analysis, tobacco users with CYP1A1-MspI [CT] genotypes were at a higher risk of GBC (p=0.008). Subdividing the GBC patients on the basis of gallstone status, the CYP1A1 haplotype [C-val] imparted a higher risk in patients without stones when compared to controls (p=0.001). The results remained significant even after applying Bonferroni correction. Multivariate analysis revealed an increased risk of CYP1A1 iso/val and val/val genotypes in GBC patients having BMI >25 (p=0.021). The CYP1A1 polymorphisms may confer increased risk of GBC, probably due to impaired xenobiotic or hormone metabolism through a gallstone-independent pathway.

  20. CYP1A1 and CYP1B1 polymorphisms as modifying factors in patients with pneumoconiosis and occupationally related tumours: A pilot study.

    PubMed

    Schneider, Joachim; Bernges, Ulrike

    2009-01-01

    CYP1A1 and CYP1B1 are involved in the metabolism of carcinogens. The effect of CYP1A1 and CYP1B1 polymorphisms as genetic modifiers of risk was investigated in individuals with asbestos, silica dust or ionizing radiation-induced occupational tumours compared to exposed non-cancer subjects suffering from pneumoconiosis, particularly in relation to tobacco smoking. CYP1A1 T6235C, CYP1A1 A4889G and CYP1B1 codon 432 polymorphisms were determined by real-time PCR analysis in patients with asbestos-related lung cancer (n=39), patients with diffuse malignant mesotheliomas (n=19), lung cancer in silicosis patients (n=7), uranium miners with lung cancer (UMLC) (n=40), patients with asbestosis (n=181), and silicosis patients (n=204). The results were compared to those from a healthy unexposed control group (n=50) not exposed to carcinogenic (or fibrogenic) agents in the workplace. An additional healthy control group (n=134) comprised smokers and ex-smokers. Allele frequencies were within the range described for Caucasians. Multivariate analysis revealed that patients with occupational diseases with the susceptible CYP1A1 T6235C genotype had a calculated risk ranging from OR=0.5 (95% CI 0.18-1.36) for UMLC to OR=1.23 (95% CI 0.39-4.05) for uranium miners with silicosis. The risk for patients with the susceptible CYP1A1 A4889G allele was calculated as being between OR=0.39 (95% CI 0.10-1.54) for mesothelioma patients and OR=1.54 (95% CI 0.49-4.89) for UMLC. CYP1B1 Val432Leu polymorphisms were associated with a risk of OR=0.56 (95% CI 0.2-1.55) for UMLC and OR=1.52 (95% CI 0.68-3.39) for asbestos-exposed lung cancer patients. By analyzing the interaction between tobacco smoking, type of exposure to carcinogens and the genotypes, it was determined that smoking and the presence of the susceptible genotypes did not have a combined effect. In this pilot study, the analyzed polymorphism had no consistent modifying effect on pneumoconiosis or occupationally related tumours.

  1. Toxic effect of high concentration of sonochemically synthesized polyvinylpyrrolidone-coated silver nanoparticles on Citrobacter sp. A1 and Enterococcus sp. C1.

    PubMed

    Lau, Chew Ping; Abdul-Wahab, Mohd Firdaus; Jaafar, Jafariah; Chan, Giek Far; Abdul Rashid, Noor Aini

    2017-08-01

    Currently, silver nanoparticles (AgNPs) have gained importance in various industrial applications. However, their impact upon release into the environment on microorganisms remains unclear. The aim of this study was to analyze the effect of polyvinylpyrrolidone-capped AgNPs synthesized in this laboratory on two bacterial strains isolated from the environment, Gram-negative Citrobacter sp. A1 and Gram-positive Enterococcus sp. C1. Polyvinylpyrrolidone-capped AgNPs were synthesized by ultrasound-assisted chemical reduction. Characterization of the AgNPs involved UV-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and energy dispersive X-ray spectroscopy. Citrobacter sp. A1 and Enterococcus sp. C1 were exposed to varying concentrations of AgNPs, and cell viability was determined. Scanning electron microscopy was performed to evaluate the morphological alteration of both species upon exposure to AgNPs at 1000 mg/L. The synthesized AgNPs were spherical in shape, with an average particle size of 15 nm. The AgNPs had different but prominent effects on either Citrobacter sp. A1 or Enterococcus sp. C1. At an AgNP concentration of 1000 mg/L, Citrobacter sp. A1 retained viability for 6 hours, while Enterococcus sp. C1 retained viability only for 3 hours. Citrobacter sp. A1 appeared to be more resistant to AgNPs than Enterococcus sp. C1. The cell wall of both strains was found to be morphologically altered at that concentration. Minute and spherical AgNPs significantly affected the viability of the two bacterial strains selected from the environment. Enterococcus sp. C1 was more vulnerable to AgNPs, probably due to its cell wall architecture and the absence of silver resistance-related genes. Copyright © 2015. Published by Elsevier B.V.

  2. Heat shock protein 90 inhibitors suppress aryl hydrocarbon receptor-mediated activation of CYP1A1 and CYP1B1 transcription and DNA adduct formation.

    PubMed

    Hughes, Duncan; Guttenplan, Joseph B; Marcus, Craig B; Subbaramaiah, Kotha; Dannenberg, Andrew J

    2008-11-01

    The aryl hydrocarbon receptor (AhR), a client protein of heat shock protein 90 (HSP90), plays a significant role in polycyclic aromatic hydrocarbon (PAH)-induced carcinogenesis. Tobacco smoke, a source of PAHs, activates the AhR, leading to enhanced transcription of CYP1A1 and CYP1B1, which encode proteins that convert PAHs to genotoxic metabolites. The main objectives of this study were to determine whether HSP90 inhibitors suppress PAH-mediated induction of CYP1A1 and CYP1B1 or block benzo(a)pyrene [B(a)P]-induced formation of DNA adducts. Treatment of cell lines derived from oral leukoplakia (MSK-Leuk1) or esophageal squamous cell carcinoma (KYSE450) with a saline extract of tobacco smoke, B(a)P, or dioxin induced CYP1A1 and CYP1B1 transcription, resulting in enhanced levels of message and protein. Inhibitors of HSP90 [17-allylamino-17-demethoxygeldanamycin (17-AAG); celastrol] suppressed these inductive effects of PAHs. Treatment with 17-AAG and celastrol also caused a rapid and marked decrease in amounts of AhR protein without modulating levels of HSP90. The formation of B(a)P-induced DNA adducts in MSK-Leuk1 cells was inhibited by 17-AAG, celastrol, and alpha-naphthoflavone, a known AhR antagonist. The reduction in B(a)P-induced DNA adducts was due, at least in part, to reduced metabolic activation of B(a)P. Collectively, these results suggest that 17-AAG and celastrol, inhibitors of HSP90, suppress the activation of AhR-dependent gene expression, leading, in turn, to reduced formation of B(a)P-induced DNA adducts. Inhibitors of HSP90 may have a role in chemoprevention in addition to cancer therapy.

  3. Competitive inhibition of carcinogen-activating CYP1A1 and CYP1B1 enzymes by a standardized complex mixture of PAH extracted from coal tar

    SciTech Connect

    Mahadevan, B.; Marston, C.P.; Luch, A.; Dashwood, W.M.; Brooks, E.; Pereira, C.; Doehmer, J.; Baird, W.M.

    2007-03-15

    A complex mixture of polycyclic aromatic hydrocarbons (PAH) extracted from coal tar, the Standard Reference Material (SRM) 1597, was recently shown to decrease the levels of DNA binding of the 2 strong carcinogens benzo(a)pyrene (BP) and dibenzo(a,l)pyrene (DBP) in the human mammary carcinoma-derived cell line MCF-7. The present study was designed to further elucidate the biochemical mechanisms involved in this inhibition process. We examined the effects of SRM 1597 on the metabolic activation of BP and DBP toward DNA-binding derivatives in Chinese hamster cells expressing either human cytochrome P450 (CYP) 1A1 or CYP1B1. The data obtained from biochemical experiments revealed that SRM 1597 competitively inhibited the activity of both human enzymes as analyzed by 7-ethoxyresorufin O-deethylation assays. While the Michaelis-Menten constant (K-M) was {lt} 0.4 {mu}M in the absence of SRM 1597, this value increased up to 1.12 (CYP1A1) or 4.45 {mu}M (CYP1B1) in the presence of 0.1 {mu} g/ml SRM 1597. Hence the inhibitory effects of the complex mixture on human CYP1B1 were much stronger when compared to human CYP1A1 Taken together, the decreases in PAH-DNA adduct formation on co-treatment with SRM 1597 revealed inhibitory effects on the CYP enzymes that convert carcinogenic PAH into DNA-binding metabolites. The implications for the tumorigenicity of complex environmental PAR mixtures are discussed.

  4. A General Approach for Calculating Strongly Anharmonic Vibronic Spectra with a High Density of States: The X2B1 <- X1A1 Photoelectron Spectrum of Difluoromethane.

    PubMed

    Petrenko, Taras; Rauhut, Guntram

    2017-09-22

    Due to a low lying fragmentation channel the X2B1 <- X1A1 photoelectron spectrum of difluoromethane is dominated by strong anharmonicity effects. We have used a time-independent eigenstate-free Raman wave function approach (RWF) to calculate the entire spectrum. Vibronic transitions with the most significant Franck-Condon factors were determined by employing our recently developed residual-based algorithm for the calculation of eigenpairs (RACE). An analysis of the factors controlling the accuracy of the predicted bandshape is provided. The calculated spectrum is in very close agreement with experimental results.

  5. Triclosan activates aryl hydrocarbon receptor (AhR)-dependent apoptosis and affects Cyp1a1 and Cyp1b1 expression in mouse neocortical neurons.

    PubMed

    Szychowski, Konrad A; Wnuk, Agnieszka; Kajta, Małgorzata; Wójtowicz, Anna K

    2016-11-01

    Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitizing products, such as soaps, toothpastes, and hair products. A number of studies have revealed the presence of TCS in human tissues, such as fat, liver and brain, in addition to blood and breast milk. The aim of the present study was to investigate the impact of TCS on AhR and Cyp1a1/Cyp1b1 signaling in mouse neocortical neurons in primary cultures. In addition to the use of selective ligands and siRNAs, expression levels of mRNA and proteins as well as caspase-3 activity, reactive oxygen species (ROS) formation, and lactate dehydrogenase (LDH) release have been measured. We also studied the involvement of the AhR in TCS-induced LDH release and caspase-3 activation as well as the effect of TCS on ROS generation. Cultures of neocortical neurons were prepared from Swiss mouse embryos on day 15/16 of gestation. The cells were cultured in phenol red-free Neurobasal medium with B27 and glutamine, and the neurons were exposed to 1 and 10µM TCS. Our experiments showed that the expression of AhR and Cyp1a1 mRNA decreased in cells exposed to 10µM TCS for 3 or 6h. In the case of Cyp1b1, mRNA expression remained unchanged compared with the control group following 3h of exposure to TCS, but after 6h, the mRNA expression of Cyp1b1 was decreased. Our results confirmed that the AhR is involved in the TCS mechanism of action, and our data demonstrated that after the cells were transfected with AhR siRNA, the cytotoxic and pro-apoptotic properties of TCS were decreased. The decrease in Cyp1a1 mRNA and protein expression levels accompanied by a decrease in its activity. The stimulation of Cyp1a1 activity produced by the application of an AhR agonist (βNF) was attenuated by TCS, whereas the addition of AhR antagonist (αNF) reversed the inhibitory effects of TCS. In our experiments, TCS diminished Cyp1b1 mRNA and enhanced its protein expression. In case of Cyp1a1 we observed

  6. Association of CYP1A1, CYP1B1 and CYP17 gene polymorphisms and organochlorine pesticides with benign prostatic hyperplasia.

    PubMed

    Kumar, Vivek; Banerjee, Basu Dev; Datta, Sudip Kumar; Yadav, Chandra Shekhar; Singh, Satyender; Ahmed, Rafat Sultana; Gupta, Sanjay

    2014-08-01

    It is well established that steroidal hormones (testosterone and estrogen) increase benign prostatic hyperplasia (BPH) risk. Cytochrome P450 (CYP) enzymes especially CYP1A1, CYP1B1 and CYP17 metabolize these hormones. Apart from that, several endocrine disrupting organochlorine pesticides (OCPs) are reported to mimic the activity of these steroidal hormones. Therefore, functional polymorphisms in these genes and exposure to such pesticides may increase BPH risk further. Our study included 100 newly diagnosed BPH subjects and 100 age-matched healthy male controls. CYP1A1, CYP1B1 and CYP17 polymorphisms were studied using PCR-RFLP and allele-specific PCR method. OCP levels in blood were analyzed by gas chromatography (GC). Levels of p,p'-DDE and endosulfan α were found to be significantly higher amongst BPH subjects as compared to controls (p-values=0.001 and 0.03 respectively) and CYP17 polymorphism was observed to be significantly associated with BPH subjects as compared to controls (p-values=0.03), indicating that these factors may be important risk factors for BPH. However, further studies are required before unequivocal conclusion.

  7. Copy number variation affecting the Photoperiod-B1 and Vernalization-A1 genes is associated with altered flowering time in wheat (Triticum aestivum).

    PubMed

    Díaz, Aurora; Zikhali, Meluleki; Turner, Adrian S; Isaac, Peter; Laurie, David A

    2012-01-01

    The timing of flowering during the year is an important adaptive character affecting reproductive success in plants and is critical to crop yield. Flowering time has been extensively manipulated in crops such as wheat (Triticum aestivum L.) during domestication, and this enables them to grow productively in a wide range of environments. Several major genes controlling flowering time have been identified in wheat with mutant alleles having sequence changes such as insertions, deletions or point mutations. We investigated genetic variants in commercial varieties of wheat that regulate flowering by altering photoperiod response (Ppd-B1 alleles) or vernalization requirement (Vrn-A1 alleles) and for which no candidate mutation was found within the gene sequence. Genetic and genomic approaches showed that in both cases alleles conferring altered flowering time had an increased copy number of the gene and altered gene expression. Alleles with an increased copy number of Ppd-B1 confer an early flowering day neutral phenotype and have arisen independently at least twice. Plants with an increased copy number of Vrn-A1 have an increased requirement for vernalization so that longer periods of cold are required to potentiate flowering. The results suggest that copy number variation (CNV) plays a significant role in wheat adaptation.

  8. Copy Number Variation Affecting the Photoperiod-B1 and Vernalization-A1 Genes Is Associated with Altered Flowering Time in Wheat (Triticum aestivum)

    PubMed Central

    Isaac, Peter; Laurie, David A.

    2012-01-01

    The timing of flowering during the year is an important adaptive character affecting reproductive success in plants and is critical to crop yield. Flowering time has been extensively manipulated in crops such as wheat (Triticum aestivum L.) during domestication, and this enables them to grow productively in a wide range of environments. Several major genes controlling flowering time have been identified in wheat with mutant alleles having sequence changes such as insertions, deletions or point mutations. We investigated genetic variants in commercial varieties of wheat that regulate flowering by altering photoperiod response (Ppd-B1 alleles) or vernalization requirement (Vrn-A1 alleles) and for which no candidate mutation was found within the gene sequence. Genetic and genomic approaches showed that in both cases alleles conferring altered flowering time had an increased copy number of the gene and altered gene expression. Alleles with an increased copy number of Ppd-B1 confer an early flowering day neutral phenotype and have arisen independently at least twice. Plants with an increased copy number of Vrn-A1 have an increased requirement for vernalization so that longer periods of cold are required to potentiate flowering. The results suggest that copy number variation (CNV) plays a significant role in wheat adaptation. PMID:22457747

  9. A widespread sequence-specific mRNA decay pathway mediated by hnRNPs A1 and A2/B1

    PubMed Central

    Geissler, Rene; Simkin, Alfred; Floss, Doreen; Patel, Ravi; Fogarty, Elizabeth A.; Scheller, Jürgen; Grimson, Andrew

    2016-01-01

    3′-untranslated regions (UTRs) specify post-transcriptional fates of mammalian messenger RNAs (mRNAs), yet knowledge of the underlying sequences and mechanisms is largely incomplete. Here, we identify two related novel 3′ UTR motifs in mammals that specify transcript degradation. These motifs are interchangeable and active only within 3′ UTRs, where they are often preferentially conserved; furthermore, they are found in hundreds of transcripts, many encoding regulatory proteins. We found that degradation occurs via mRNA deadenylation, mediated by the CCR4–NOT complex. We purified trans factors that recognize the motifs and identified heterogeneous nuclear ribonucleoproteins (hnRNPs) A1 and A2/B1, which are required for transcript degradation, acting in a previously unknown manner. We used RNA sequencing (RNA-seq) to confirm hnRNP A1 and A2/B1 motif-dependent roles genome-wide, profiling cells depleted of these factors singly and in combination. Interestingly, the motifs are most active within the distal portion of 3′ UTRs, suggesting that their role in gene regulation can be modulated by alternative processing, resulting in shorter 3′ UTRs. PMID:27151978

  10. CYP1B1, CYP1A1, MPO, and GSTP1 polymorphisms and lung cancer risk in never-smoking Korean women.

    PubMed

    Yoon, Kyong-Ah; Kim, Jin Hee; Gil, Hyea-Jin; Hwang, Hyukkee; Hwangbo, Bin; Lee, Jin Soo

    2008-04-01

    Polymorphisms in metabolic genes encoding phase I and phase II enzymes are thought to modulate the risk of lung cancer via changes in enzymatic activity. Recently, the effect of these metabolic enzymes and their interaction with environmental factors has been studied in both smokers and also never-smokers, since never-smokers are a good model in which to study genetic susceptibility at low-dose carcinogen exposure. Here, we investigated the association of CYP1A1 Ile462Val, CYP1B1 Leu432Val, GSTP1 Ile105Val, MPO G-463A polymorphisms and lung cancer risk in never-smoking Korean women. In this case-control study of 213 lung cancer patients and 213 age-matched healthy controls, we found that carrying one variant allele of the CYP1A1 Ile462Val polymorphism was associated with a significantly decreased risk of lung adenocarcinoma (adjusted odds ratio (OR)=0.63; 95% confidence interval (CI), 0.41-0.99). Furthermore, the combination of risk genotypes of CYP1B1 Leu432Val with CYP1A1 Ile462Val was associated with the risk of lung adenocarcinoma (adjusted OR=2.16; 95% CI, 1.02-4.57) as well as overall lung cancer (adjusted OR=2.23; 95% CI 1.01-4.89). The polymorphisms of GSTP1 Ile105Val and MPO G-463A showed no significant association with lung cancer. Theses results suggest that the CYP1A1 Ile462Val polymorphism is associated with a reduced risk of lung adenocarcinoma in never-smoking Korean women, whereas specific combinations of variant genotypes for metabolic enzymes increase lung cancer risk considerably.

  11. Dopamine D2-Receptor Antagonists Down-Regulate CYP1A1/2 and CYP1B1 in the Rat Liver

    PubMed Central

    Harkitis, P.; Lang, M. A.; Marselos, M.; Fotopoulos, A.; Albucharali, G.; Konstandi, M.

    2015-01-01

    Dopaminergic systems regulate the release of several hormones including growth hormone (GH), thyroid hormones, insulin, glucocorticoids and prolactin (PRL) that play significant roles in the regulation of various Cytochrome P450 (CYP) enzymes. The present study investigated the role of dopamine D2-receptor-linked pathways in the regulation of CYP1A1, CYP1A2 and CYP1B1 that belong to a battery of genes controlled by the Aryl Hydrocarbon Receptor (AhR) and play a crucial role in the metabolism and toxicity of numerous environmental toxicants. Inhibition of dopamine D2-receptors with sulpiride (SULP) significantly repressed the constitutive and benzo[a]pyrene (B[a]P)-induced CYP1A1, CYP1A2 and CYP1B expression in the rat liver. The expression of AhR, heat shock protein 90 (HSP90) and AhR nuclear translocator (ARNT) was suppressed by SULP in B[a]P-treated livers, whereas the AhRR expression was increased by the drug suggesting that the SULP-mediated repression of the CYP1 inducibility is due to inactivation of the AhR regulatory system. At signal transduction level, the D2-mediated down-regulation of constitutive CYP1A1/2 and CYP1B1 expression appears to be mediated by activation of the insulin/PI3K/AKT pathway. PRL-linked pathways exerting a negative control on various CYPs, and inactivation of the glucocorticoid-linked pathways that positively control the AhR-regulated CYP1 genes, may also participate in the SULP-mediated repression of both, the constitutive and induced CYP1 expression. The present findings indicate that drugs acting as D2-dopamine receptor antagonists can modify several hormone systems that regulate the expression of CYP1A1, CYP1A2 and CYP1B1, and may affect the toxicity and carcinogenicity outcome of numerous toxicants and pre-carcinogenic substances. Therefore, these drugs could be considered as a part of the strategy to reduce the risk of exposure to environmental pollutants and pre-carcinogens. PMID:26466350

  12. Ångström (B1Σ+ →A1Π) 0-1 and 1-1 bands in isotopic CO molecules: further investigations

    NASA Astrophysics Data System (ADS)

    Kȩpa, R.; Ostrowska-Kopeć, M.; Piotrowska, I.; Zachwieja, M.; Hakalla, R.; Szajna, W.; Kolek, P.

    2014-02-01

    In the emission spectrum of six 12C16O, 13C16O, 12C18O, 14C16O, 13C18O and 14C18O isotopologues of the carbon monoxide molecule, new recordings and analyses or new reanalyses of the selected and strongest bands belonging to the Ångström (B1Σ+ - A1Π) system were carried out. Under high resolution, emission spectra of the 0-1 and 1-1 bands were recorded and reanalysed, representing both the 0 - v″ and 1 - v″ progressions of this system. Unobserved so far, new spectral lines were identified, and for the 12C16O, 13C16O, 12C18O, 14C16O and 14C18O molecules new parameters of the rovibronic structure B0, B1, D0 and D1 of the v = 0 and v = 1 levels of the B1Σ+ state and band origins ν0 of the 0-1 and 1-1 bands of the B - A transition were determined. A detailed analysis included the predissociation regions of the spectra observed in all analysed bands and isotopologues. The values of rotational quantum numbers and rovibronic terms of the highest nonpredissociated Jh as well as the first, already predissociated Jf levels were determined. On that basis, a new and more precise value of dissociation energy of the CO molecule was determined: {D}_e=(90\\,679.1+/- 6.0) cm-1. Also, atomic states of the dissociation products of this molecule, which correspond to this energy, were identified as C(3P0) + O(3P2) i.e. as both triplet ground atomic sublevels.

  13. Ab Initio Multiple Spawning Method for Intersystem Crossing Dynamics: Spin-Forbidden Transitions between (3)B1 and (1)A1 States of GeH2.

    PubMed

    Fedorov, Dmitry A; Pruitt, Spencer R; Keipert, Kristopher; Gordon, Mark S; Varganov, Sergey A

    2016-05-12

    Dynamics at intersystem crossings are fundamental to many processes in chemistry, physics, and biology. The ab initio multiple spawning (AIMS) method was originally developed to describe internal conversion dynamics at conical intersections where derivative coupling is responsible for nonadiabatic transitions between electronic states with the same spin multiplicity. Here, the applicability of the AIMS method is extended to intersystem crossing dynamics in which transitions between electronic states with different spin multiplicities are mediated by relativistic spin-orbit coupling. In the direct AIMS dynamics, the nuclear wave function is expanded in the basis of frozen multidimensional Gaussians propagating on the coupled electronic potential energy surfaces calculated on the fly. The AIMS method for intersystem crossing is used to describe the nonadiabatic transitions between the (3)B1 and (1)A1 states of GeH2. The potential energies and gradients were obtained at the CASSCF(6,6)/6-31G(d) level of theory. The spin-orbit coupling matrix elements were calculated with the configuration interaction method using the two-electron Breit-Pauli Hamiltonian. The excited (3)B1 state lifetime and intersystem crossing rate constants were estimated by fitting the AIMS state population with the first-order kinetics equation for a reversible unimolecular reaction. The obtained rate constants are compared with the values predicted by the statistical nonadiabatic transition state theory with transition probabilities calculated using the Landau-Zener and weak coupling formulas.

  14. Cambrian origin of the CYP27C1-mediated vitamin A1-to-A2 switch, a key mechanism of vertebrate sensory plasticity

    USGS Publications Warehouse

    Morshedian, Ala; Toomery, Matthew B.; Pollock, Gabriel E.; Frederiksen, Rikard; Enright, Jennifer; McCormick, Stephen; Cornwall, M. Carter; Fain, Gordon L.; Corbo, Joseph C.

    2017-01-01

    The spectral composition of ambient light varies across both space and time. Many species of jawed vertebrates adapt to this variation by tuning the sensitivity of their photoreceptors via the expression of CYP27C1, an enzyme that converts vitamin A1 into vitamin A2, thereby shifting the ratio of vitamin A1-based rhodopsin to red-shifted vitamin A2-based porphyropsin in the eye. Here, we show that the sea lamprey (Petromyzon marinus), a jawless vertebrate that diverged from jawed vertebrates during the Cambrian period (approx. 500 Ma), dynamically shifts its photoreceptor spectral sensitivity via vitamin A1-to-A2 chromophore exchange as it transitions between photically divergent aquatic habitats. We further show that this shift correlates with high-level expression of the lamprey orthologue of CYP27C1, specifically in the retinal pigment epithelium as in jawed vertebrates. Our results suggest that the CYP27C1-mediated vitamin A1-to-A2 switch is an evolutionarily ancient mechanism of sensory plasticity that appeared not long after the origin of vertebrates.

  15. Cambrian origin of the CYP27C1-mediated vitamin A1-to-A2 switch, a key mechanism of vertebrate sensory plasticity.

    PubMed

    Morshedian, Ala; Toomey, Matthew B; Pollock, Gabriel E; Frederiksen, Rikard; Enright, Jennifer M; McCormick, Stephen D; Cornwall, M Carter; Fain, Gordon L; Corbo, Joseph C

    2017-07-01

    The spectral composition of ambient light varies across both space and time. Many species of jawed vertebrates adapt to this variation by tuning the sensitivity of their photoreceptors via the expression of CYP27C1, an enzyme that converts vitamin A1 into vitamin A2, thereby shifting the ratio of vitamin A1-based rhodopsin to red-shifted vitamin A2-based porphyropsin in the eye. Here, we show that the sea lamprey (Petromyzon marinus), a jawless vertebrate that diverged from jawed vertebrates during the Cambrian period (approx. 500 Ma), dynamically shifts its photoreceptor spectral sensitivity via vitamin A1-to-A2 chromophore exchange as it transitions between photically divergent aquatic habitats. We further show that this shift correlates with high-level expression of the lamprey orthologue of CYP27C1, specifically in the retinal pigment epithelium as in jawed vertebrates. Our results suggest that the CYP27C1-mediated vitamin A1-to-A2 switch is an evolutionarily ancient mechanism of sensory plasticity that appeared not long after the origin of vertebrates.

  16. Polymorphisms in CYP1B1, CYP3A5, GSTT1, and SULT1A1 Are Associated with Early Age Acute Leukemia.

    PubMed

    Lopes, Bruno Almeida; Emerenciano, Mariana; Gonçalves, Bruno Alves Aguiar; Vieira, Tállita Meciany; Rossini, Ana; Pombo-de-Oliveira, Maria S

    2015-01-01

    Based on observational studies, early age leukemia (EAL) was associated with maternal hormone exposure during pregnancy. We studied the association between genetic polymorphisms of estrogen metabolism and EAL. Using data from the Brazilian Collaborative Study Group of Infant Acute Leukemia (2000-2012), 350 cases and 404 age-matched controls and 134 mothers of cases and controls were genotyped to explore polymorphisms in genes of the estrogen metabolism pathway: CYP1B1 (c.1294C>G, rs1056836), CYP3A4 (c.-392A>G, rs2740574), CYP3A5 (c.219-237G>A, rs776746), GSTM1/GSTT1 deletions, and SULT1A1 (c.638G>A, rs9282861; and c.667A>G, rs1801030). Logistic regression was used to calculate the odds ratios (OR) with 95% confidence intervals (CIs), and unconditional logistic regression was used to estimate adjusted odds ratios (aORs) by ethnicity. Because of multiple testing, p values < 0.01 were significant after Bonferroni correction. SULT1A1 (c.638G>A) was associated to infant acute lymphoblastic leukemia and acute myeloid leukemia (AML) risk in males (additive model: aOR = 0.52; 95% CI: 0.29-0.95, p = 0.03; dominant model: aOR = 2.18; 95% CI: 1.17-4.05, p = 0.01, respectively). CYP1B1 polymorphism was associated with a decreased risk of AML either for non-white or female children (additive model: OR = 0.24; 95% CI: 0.08-0.76, p < 0.01; additive model: aOR = 0.27; 95% CI: 0.08-0.89, p = 0.03, respectively). Since polymorphisms of Cytochrome P450 genes presented gender-specific risk associations, we also investigated their expression. CYP1B1 was not expressed in 57.1% of EAL cases, and its expression varied by genotype, gender, and leukemia subtype. Maternal-fetal GSTT1 null genotype was associated with risk of EAL. This study shows that polymorphisms in genes of estrogen metabolism confer genetic susceptibility to EAL, mainly in males, and maternal susceptibility genes modify the risk for developing EAL in newborns.

  17. Polymorphisms in CYP1B1, CYP3A5, GSTT1, and SULT1A1 Are Associated with Early Age Acute Leukemia

    PubMed Central

    Lopes, Bruno Almeida; Emerenciano, Mariana; Gonçalves, Bruno Alves Aguiar; Vieira, Tállita Meciany; Rossini, Ana; Pombo-de-Oliveira, Maria S.

    2015-01-01

    Based on observational studies, early age leukemia (EAL) was associated with maternal hormone exposure during pregnancy. We studied the association between genetic polymorphisms of estrogen metabolism and EAL. Using data from the Brazilian Collaborative Study Group of Infant Acute Leukemia (2000–2012), 350 cases and 404 age-matched controls and 134 mothers of cases and controls were genotyped to explore polymorphisms in genes of the estrogen metabolism pathway: CYP1B1 (c.1294C>G, rs1056836), CYP3A4 (c.-392A>G, rs2740574), CYP3A5 (c.219-237G>A, rs776746), GSTM1/GSTT1 deletions, and SULT1A1 (c.638G>A, rs9282861; and c.667A>G, rs1801030). Logistic regression was used to calculate the odds ratios (OR) with 95% confidence intervals (CIs), and unconditional logistic regression was used to estimate adjusted odds ratios (aORs) by ethnicity. Because of multiple testing, p values < 0.01 were significant after Bonferroni correction. SULT1A1 (c.638G>A) was associated to infant acute lymphoblastic leukemia and acute myeloid leukemia (AML) risk in males (additive model: aOR = 0.52; 95% CI: 0.29–0.95, p = 0.03; dominant model: aOR = 2.18; 95% CI: 1.17–4.05, p = 0.01, respectively). CYP1B1 polymorphism was associated with a decreased risk of AML either for non-white or female children (additive model: OR = 0.24; 95% CI: 0.08–0.76, p < 0.01; additive model: aOR = 0.27; 95% CI: 0.08–0.89, p = 0.03, respectively). Since polymorphisms of Cytochrome P450 genes presented gender-specific risk associations, we also investigated their expression. CYP1B1 was not expressed in 57.1% of EAL cases, and its expression varied by genotype, gender, and leukemia subtype. Maternal-fetal GSTT1 null genotype was associated with risk of EAL. This study shows that polymorphisms in genes of estrogen metabolism confer genetic susceptibility to EAL, mainly in males, and maternal susceptibility genes modify the risk for developing EAL in newborns. PMID:25992585

  18. Association of CYP1A1 and CYP1B1 polymorphisms with bone mineral density variations in postmenopausal Mexican-Mestizo women.

    PubMed

    Chávez, Bertha; Vilchis, Felipe; Rojano-Mejía, David; Coral Vázquez, Ramón Mauricio; Aguirre-García, María Del Carmen; Canto, Patricia

    2017-08-01

    Herein, we investigated potential associations between polymorphisms of genes related to estrogen metabolism and bone mineral density (BMD) in postmenopausal women. This was a cross-sectional study, in which two hundred and ninety postmenopausal Mexican-Mestizo women were studied. The BMD of the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured. The distribution of the genetic polymorphisms, including rs1799814 and rs1048943 at CYP1A1 as well as rs1056836 at CYP1B1, were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-stranded conformational polymorphism (SSCP), and DNA sequencing. Deviations from Hardy-Weinberg equilibrium (HWE) were tested, and linkage disequilibrium (LD) was calculated by direct correlation (r(2)). Moreover, haplotype analysis was performed. All polymorphisms were in HWE. The genotype and allele distributions of the three single nucleotide polymorphisms (SNPs) studied showed no significant differences. However, statistical significance was reached when constructing haplotypes. The CG haplotype in CYP1A1 was associated with variations in LS and FN BMD after adjustment for covariates (p = 0.021 and 0.045, respectively), but the association with TH BMD was not significant. These results suggested that the CG haplotype in CYP1A1 may play an important role in the mechanism of osteoporosis and may be useful as a genetic marker.

  19. Skatole (3-Methylindole) Is a Partial Aryl Hydrocarbon Receptor Agonist and Induces CYP1A1/2 and CYP1B1 Expression in Primary Human Hepatocytes

    PubMed Central

    Balaguer, Patrick; Ekstrand, Bo; Daujat-Chavanieu, Martine; Gerbal-Chaloin, Sabine

    2016-01-01

    Skatole (3-methylindole) is a product of bacterial fermentation of tryptophan in the intestine. A significant amount of skatole can also be inhaled during cigarette smoking. Skatole is a pulmonary toxin that induces the expression of aryl hydrocarbon receptor (AhR) regulated genes, such as cytochrome P450 1A1 (CYP1A1), in human bronchial cells. The liver has a high metabolic capacity for skatole and is the first organ encountered by the absorbed skatole; however, the effect of skatole in the liver is unknown. Therefore, we investigated the impact of skatole on hepatic AhR activity and AhR-regulated gene expression. Using reporter gene assays, we showed that skatole activates AhR and that this is accompanied by an increase of CYP1A1, CYP1A2 and CYP1B1 expression in HepG2-C3 and primary human hepatocytes. Specific AhR antagonists and siRNA-mediated AhR silencing demonstrated that skatole-induced CYP1A1 expression is dependent on AhR activation. The effect of skatole was reduced by blocking intrinsic cytochrome P450 activity and indole-3-carbinole, a known skatole metabolite, was a more potent inducer than skatole. Finally, skatole could reduce TCDD-induced CYP1A1 expression, suggesting that skatole is a partial AhR agonist. In conclusion, our findings suggest that skatole and its metabolites affect liver homeostasis by modulating the AhR pathway. PMID:27138278

  20. Role of spinal 5-HT5A, and 5-HT1A/1B/1D, receptors in neuropathic pain induced by spinal nerve ligation in rats.

    PubMed

    Avila-Rojas, Sabino Hazael; Velázquez-Lagunas, Isabel; Salinas-Abarca, Ana Belen; Barragán-Iglesias, Paulino; Pineda-Farias, Jorge Baruch; Granados-Soto, Vinicio

    2015-10-05

    Serotonin (5-HT) participates in pain modulation by interacting with different 5-HT receptors. The role of 5-HT5A receptor in neuropathic pain has not previously studied. The purpose of this study was to investigate: A) the role of 5-HT5A receptors in rats subjected to spinal nerve injury; B) the expression of 5-HT5A receptors in dorsal spinal cord and dorsal root ganglia (DRG). Neuropathic pain was induced by L5/L6 spinal nerve ligation. Tactile allodynia in neuropathic rats was assessed with von Frey filaments. Western blot methodology was used to determine 5-HT5A receptor protein expression. Intrathecal administration (on day 14th) of 5-HT (10-100 nmol) or 5-carboxamidotryptamine (5-CT, 0.03-0.3 nmol) reversed nerve injury-induced tactile allodynia. Intrathecal non-selective (methiothepin, 0.1-0.8 nmol) and selective (SB-699551, 1-10 nmol) 5-HT5A receptor antagonists reduced, by ~60% and ~25%, respectively, the antiallodynic effect of 5-HT (100 nmol) or 5-CT (0.3 nmol). Moreover, both selective 5-HT1A and 5-HT1B/1D receptor antagonists, WAY-100635 (0.3-1 nmol) and GR-127935 (0.3-1 nmol), respectively, partially diminished the antiallodynic effect of 5-HT or 5-CT by about 30%. Injection of antagonists, by themselves, did not affect allodynia. 5-HT5A receptors were expressed in the ipsilateral dorsal lumbar spinal cord and DRG and L5/L6 spinal nerve ligation did not modify 5-HT5A receptor protein expression in those sites. Results suggest that 5-HT5A receptors reduce pain processing in the spinal cord and that 5-HT and 5-CT reduce neuropathic pain through activation of 5-HT5A and 5-HT1A/1B/1D receptors. These receptors could be an important part of the descending pain inhibitory system.

  1. Elements of the maize A1 promoter required for transactivation by the anthocyanin B/C1 or phlobaphene P regulatory genes.

    PubMed Central

    Tuerck, J A; Fromm, M E

    1994-01-01

    The extensive genetic and molecular characterization of the flavonoid pathway's structural and regulatory genes has provided some of the most detailed knowledge of gene interactions in plants. In maize flavonoid biosynthesis, the A1 gene is independently regulated in the anthocyanin and phlobaphene pathways. Anthocyanin production requires the expression of the C1 or PI and R or B regulatory genes, whereas phlobaphene production requires only the P regulatory gene. By deletion analysis of the A1 promoter, we show that the sequences between -123 and -88 are critical for activation by anthocyanin and phlobaphene regulatory genes. Linker-scanner mutations indicated that the -123 to -100 region is more important for transactivation by the P protein. The -98 to -88 region is more important for B/C1 transactivation and shows a strong homology with the region of the Bz1 anthocyanin structural gene promoter shown to be activated by B/C1 and not by P. We identified a 14-bp consensus sequence that is also present in the promoters of three other genes in the anthocyanin pathway, and we propose a model for how the flavonoid regulatory proteins interact with the promoters of the structural genes. PMID:7827497

  2. Electrophoretic protein analysis for the identification of doubled haploid 1A-1R, 1B-1R wheat-rye double translocation lines and for the assessment of their genetic stability.

    PubMed

    Vahl, U; Müller, G; Böhme, T

    1993-06-01

    Eighteen available doubled haploid wheat lines with a cytologically proven 1A-1R, 1B-1R double translocation, which where derived via anther culture from four crosses of the 1A-1R wheat-rye translocation cv "Amigo" with several 1B-1R wheat-rye translocation forms, were subjected to electrophoretic seed protein analysis. Besides, the five parents used in the crosses and some other wheat cultivars and doubled haploid lines (19 with a 1B-1R single translocation, 10 with a 1A-1R translocation and 7 without any 1R translocation) were also included in the investigation. It was found that the gliadin patterns visualized after SDS polyacrylamide gel electrophoresis of alcohol-soluble seed protein extracts can differentiate not only 1B-1R and 1A-1R translocation forms from wheats without any 1R-translocation chromosome, but also 1B-1R and 1A-1R wheats from each other. Moreover, 1A-1R, 1B-1R double translocation lines can be distinguished as well due to characteristic differences revealed between 1A-1R and 1B-1R translocation forms. Thus, all of tested dh1- and dh2-grains of the double translocation lines showed the expected doublet: the 1A-1R translocation ("Amigo")-typical rye band and the 1B-1R translocation ("Kawkas")-typical rye band. Consequently, gliadin patterns estimated after SDS electrophoresis may be used as markers for the fast detection of the desired 1A-1R, 1B-1R double translocation forms among 1A-1R single translocation lines, 1B-1R single translocation lines and lines without any 1R-translocation in the progenies of appropriate crosses. Furthermore, by means of gliadin tests on the dh2-generation the excellent stability of the double translocation 1A-1R, 1B-1R during more than one propagation phase has been proven. Estimations of high-molecular weight (HMW) glutenin subunits coded by 1A and 1B chromosomes are compatible with the double translocation constitution. A few deviating results can be explained by crossing-over events. Seed protein analysis

  3. Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1.

    PubMed

    Chaouch, Leila; Kalai1, Miniar; Darragi, Imen; Boudrigua, Imen; Chaouachi, Dorra; Ammar, Slim Ben; Mellouli, F; Bjaoui, M; Abbes, Salem

    2016-03-01

    Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians. Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P < 0.05 (compare 2, version 1.02). The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P = 0.0027, RR = 18.27 (20.0061-915.28)). Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.

  4. Allele frequencies in the VRN-A1, VRN-B1 and VRN-D1 vernalization response and PPD-B1 and PPD-D1 photoperiod sensitivity genes, and their effects on heading in a diverse set of wheat cultivars (Triticum aestivum L.).

    PubMed

    Kiss, Tibor; Balla, Krisztina; Veisz, Ottó; Láng, László; Bedő, Zoltán; Griffiths, Simon; Isaac, Peter; Karsai, Ildikó

    2014-01-01

    Heading of cereals is determined by complex genetic and environmental factors in which genes responsible for vernalization and photoperiod sensitivity play a decisive role. Our aim was to use diagnostic molecular markers to determine the main allele types in VRN-A1, VRN-B1, VRN-D1, PPD-B1 and PPD-D1 in a worldwide wheat collection of 683 genotypes and to investigate the effect of these alleles on heading in the field. The dominant VRN-A1, VRN-B1 and VRN-D1 alleles were present at a low frequency. The PPD-D1a photoperiod-insensitive allele was carried by 57 % of the cultivars and was most frequent in Asian and European cultivars. The PPD-B1 photoperiod-insensitive allele was carried by 22 % of the genotypes from Asia, America and Europe. Nine versions of the PPD-B1-insensitive allele were identified based on gene copy number and intercopy structure. The allele compositions in PPD-D1, PPD-B1 and VRN-D1 significantly influenced heading and together explained 37.5 % of the phenotypic variance. The role of gene model increased to 39.1 % when PPD-B1 intercopy structure was taken into account instead of overall PPD-B1 type (sensitive vs. insensitive). As a single component, PPD-D1 had the most important role (28.0 % of the phenotypic variance), followed by PPD-B1 (12.3 % for PPD-B1_overall, and 15.1 % for PPD-B1_intercopy) and VRN-D1 (2.2 %). Significant gene interactions were identified between the marker alleles within PPD-B1 and between VRN-D1 and the two PPD1 genes. The earliest heading genotypes were those with the photoperiod-insensitive allele in PPD-D1 and PPD-B1, and with the spring allele for VRN-D1 and the winter alleles for VRN-A1 and VRN-B1. This combination could only be detected in genotypes from Southern Europe and Asia. Late-heading genotypes had the sensitivity alleles for both PPD1 genes, regardless of the allelic composition of the VRN1 genes. There was a 10-day difference in heading between the earliest and latest groups under field conditions.

  5. Differential Induction of CYP1A1 and CYP1B1 by Benzo[a]pyrene in Oral Squamous Cell Carcinoma Cell Lines and by Tobacco Smoking in Oral Mucosa

    PubMed Central

    Chi, Angela C.; Appleton, Kathryn; Henriod, Joel B.; Krayer, Joe W.; Marlow, Nicole M.; Bandyopadhyay, Dipankar; Sigmon, Ryan C.; Kurtz, David T.

    2009-01-01

    Polyaromatic hydrocarbons, including benzo[a]pyrene (BP), are major tobacco carcinogens. Their carcinogenic effects require metabolic activation by cytochrome p450 (CYP) enzymes. Relative CYP isoform expression is related to tissue-specific tobacco-related squamous cell carcinoma (SCC) susceptibility. There have been conflicting reports regarding relative CYP1A1 and CYP1B1 oral expression, and information regarding CYP1B1 expression in oral tissues is limited. OBJECTIVE To quantify BP- and tobacco-induced CYP1A1 and CYP1B1 expression in oral SCC cells and oral mucosa. STUDY DESIGN Real-time qPCR was performed to measure 1) BP-induced CYP1A1 and CYP1B1 mRNA expression in seven oral/other head and neck SCC cell lines 2) CYP1A1 and CYP1B1 mRNA expression in gingiva from 22 smokers and 24 nonsmokers. RESULTS SCC lines exhibited either similar induction of both isoforms or preferential CYP1A1 induction (CYP1A1-to-CYP1B1 ratios 0.8-4.3). In contrast, gingival tissues from smokers exhibited preferential CYP1B1 induction. Marked interindividual variation in CYP1A1 and CYP1B1 expression was observed among smokers. CONCLUSIONS In vitro conditions may not account for factors that modulate expression in vivo. Interindividual variation in inducible CYP1A1 and CYP1B1 expression may account in part for variation in tobacco-related oral SCC risk. PMID:19576839

  6. Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells

    PubMed Central

    Fahrmayr, C; König, J; Auge, D; Mieth, M; Fromm, MF

    2012-01-01

    BACKGROUND AND PURPOSE The coordinate activity of hepatic uptake transporters [e.g. organic anion transporting polypeptide 1B1 (OATP1B1)], drug-metabolizing enzymes [e.g. UDP-glucuronosyltransferase 1A1 (UGT1A1)] and efflux pumps (e.g. MRP2) is a crucial determinant of drug disposition. However, limited data are available on transport of drugs (e.g. ezetimibe, etoposide) and their glucuronidated metabolites by human MRP2 in intact cell systems. EXPERIMENTAL APPROACH Using monolayers of newly established triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells as well as MDCK control cells, single- (OATP1B1) and double-transfected (OATP1B1-UGT1A1, OATP1B1-MRP2) MDCK cells, we therefore studied intracellular concentrations and transcellular transport after administration of ezetimibe or etoposide to the basal compartment. KEY RESULTS Intracellular accumulation of ezetimibe was significantly lower in MDCK-OATP1B1-UGT1A1-MRP2 triple-transfected cells compared with all other cell lines. Considerably higher amounts of ezetimibe glucuronide were found in the apical compartment of MDCK-OATP1B1-UGT1A1-MRP2 monolayers compared with all other cell lines. Using HEK cells, etoposide was identified as a substrate of OATP1B1. Intracellular concentrations of etoposide equivalents (i.e. parent compound plus metabolites) were affected only to a minor extent by the absence or presence of OATP1B1/UGT1A1/MRP2. In contrast, apical accumulation of etoposide equivalents was significantly higher in monolayers of both cell lines expressing MRP2 (MDCK-OATP1B1-MRP2, MDCK-OATP1B1-UGT1A1-MRP2) compared with the single-transfected (OATP1B1) and the control cell line. CONCLUSIONS AND IMPLICATIONS Ezetimibe glucuronide is a substrate of human MRP2. Moreover, etoposide and possibly also its glucuronide are substrates of MRP2. These data demonstrate the functional interplay between transporter-mediated uptake, phase II metabolism and export by hepatic proteins involved in drug disposition. PMID:21923755

  7. Franck-Condon factors perturbed by damped harmonic oscillators: Solvent enhanced X 1Ag ↔ A1B1u absorption and fluorescence spectra of perylene

    NASA Astrophysics Data System (ADS)

    Wang, Chen-Wen; Yang, Ling; Zhu, Chaoyuan; Yu, Jian-Guo; Lin, Sheng-Hsien

    2014-08-01

    Damped harmonic oscillators are utilized to calculate Franck-Condon factors within displaced harmonic oscillator approximation. This is practically done by scaling unperturbed Hessian matrix that represents local modes of force constants for molecule in gaseous phase, and then by diagonalizing perturbed Hessian matrix it results in direct modification of Huang-Rhys factors which represent normal modes of solute molecule perturbed by solvent environment. Scaling parameters are empirically introduced for simulating absorption and fluorescence spectra of an isolated solute molecule in solution. The present method is especially useful for simulating vibronic spectra of polycyclic aromatic hydrocarbon molecules in which hydrogen atom vibrations in solution can be scaled equally, namely the same scaling factor being applied to all hydrogen atoms in polycyclic aromatic hydrocarbons. The present method is demonstrated in simulating solvent enhanced X 1Ag ↔ A1B1u absorption and fluorescence spectra of perylene (medium-sized polycyclic aromatic hydrocarbon) in benzene solution. It is found that one of six active normal modes v10 is actually responsible to the solvent enhancement of spectra observed in experiment. Simulations from all functionals (TD) B3LYP, (TD) B3LYP35, (TD) B3LYP50, and (TD) B3LYP100 draw the same conclusion. Hence, the present method is able to adequately reproduce experimental absorption and fluorescence spectra in both gas and solution phases.

  8. Argon ion laser-induced BaS B1Σ +- A1Σ +, A' 1Π, a3Π, and X1Σ + fluorescence spectra: Analysis of A ˜ A', A ˜ a, and A' ˜ a perturbations

    NASA Astrophysics Data System (ADS)

    Cummins, P. G.; Field, Robert W.; Renhorn, Ingemar

    1981-12-01

    The 333.6-, 351.1-, and 363.8-nm lines of a cw argon ion laser are found to coincide with the BaS B1Σ +- X1Σ + (12, 0) R(17), (6, 0) P(35), and (3, 0) R(125) transitions, respectively. Fluorescence transitions from the laser-prepared upper levels terminating in X1Σ +v = 0-28, A1Σ +v = 1-3, A' 1Π v = 1-13, and a3Π 1v = 3-12 are assigned. These results are combined with a previous analysis of the extensively perturbed BaS A1Σ +- X1Σ + system [R. F. Barrow, W. G. Burton, and P. A. Jones, Trans. Farad. Soc.67, 902-906 (1971)]. Every observed perturbation of the BaS A1Σ + state is electronically and vibrationally assigned. The levels a3Π 0v = 10-13, a3Π 1v = 12-14, a3Π 2v = 15, and A' 1Π v = 10-13 are sampled via their perturbations of A1Σ +v = 0-2. Although the mutual interactions of the a3Π, A' 1Π, and A1Σ + states approach Hund's case ( c) limit, a complete deperturbation is performed from a case ( a) starting point. Of the five lowest energy electronic states of BaS, only b3Σ + remains uncharacterized. Principal deperturbed molecular constants are (in cm -1, 1σ uncertainties in parentheses):

  9. 75 FR 910 - Airworthiness Directives; General Electric Company CF34-1A, -3A, -3A1, -3A2, -3B, and -3B1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ... -3B1 turbofan engines. That AD currently requires a onetime visual and tactile inspection of certain..., removing from service fan disks with electrical arc-out indications, performing tactile and enhanced visual...-A0233, Revision 04, dated October 27, 2008, do the following: Tactile and Enhanced Visual...

  10. Cytochrome P450 1A1 and 1B1 in human blood lymphocytes are not suitable as biomarkers of exposure to dioxin-like compounds: polymorphisms and interindividual variation in expression and inducibility.

    PubMed

    van Duursen, Majorie B M; Sanderson, J Thomas; van den Berg, Martin

    2005-05-01

    Cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) are phase I enzymes, the expression of which can be affected by many environmental compounds, including dioxins and dioxin-like compounds. Because CYP1A1 and CYP1B1 expression can easily be determined in peripheral blood lymphocytes, it is often suggested as biomarker of exposure to these compounds. In this study we investigated the interindividual differences in constitutive and induced CYP1A1-catalyzed ethoxyresorufin-O-deethylase (EROD) activity and CYP1A1 and CYP1B1 gene expression in human blood lymphocytes in a group of ten non-smoking females. Freshly isolated lymphocytes were cultured in medium containing the mitogen PHA and were exposed to the most potent dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or the less potent dioxin-like polychlorinated biphenyl 126 (PCB126). In addition, we determined the occurrence of the CYP1A1 MspI and CYP1B1 Leu432Val polymorphisms. All individuals showed a concentration-dependent increase of EROD activity by TCDD, which was significantly correlated with an increase in CYP1A1, but not CYP1B1 expression. The maximum induced EROD activity by TCDD was very different among the individuals, but the EC50 values were about the same. PCB126 also caused a concentration-dependent increase of EROD activity, but was a factor 100-1000 less potent than TCDD among the individuals. The allele frequencies for CYP1A1 MspI and CYP1B1 Leu432Val reflected a normal Caucasian population and in this study the polymorphisms had no apparent effect on the expression and activity of these enzymes. Our study shows a large interindividual variability in constitutive and induced EROD activity, and CYP1A1 and CYP1B1 expression in human lymphocytes. In addition, dioxin concentrations at which effects were observed in our in vitro study are about 10-fold higher than the human blood levels found in vivo, indicating that EROD activity and CYP1A1 and CYP1B1 expression in human lymphocytes might not be

  11. Evaluation of CYP1A1 and CYP2B1/2 m-RNA induction in rat liver slices using the NanoString technology: a novel tool for drug discovery lead optimization.

    PubMed

    Palamanda, Jairam R; Kumari, Pramila; Murgolo, Nicholas; Benbow, Larry; Lin, Xinjie; Nomeir, Amin A

    2009-08-01

    Cytochrome P450 (CYP) induction in rodents and humans is considered a liability for new chemical entities (NCEs) in drug discovery. In particular, CYP1A1 and CYP2B1/2 have been associated with the induction of liver tumors in oncogenicity studies during safety evaluation studies of potential drugs. In our laboratory, real time PCR (Taqman) has been used to quantify the induction of rat hepatic CYP1A1 and CYP2B1/2 in precision -cut rat liver slices. A novel technology that does not require m-RNA isolation or RT-PCR, (developed by NanoString Technologies) has been investigated to quantify CYP1A1 and CYP2B1/2 induction in rat liver slices. Seventeen commercially available compounds were evaluated using both Taqman and NanoString technologies. Precision-cut rat liver slices were incubated with individual compounds for 24 hr at 37 degrees C in a humidified CO(2) incubator and CYP1A1 and CYP2B1/2 m-RNA were quantified. The results from the NanoString technology were similar to those of the Taqman(R) with a high degree of correlation for both CYP isoforms (r(2)>0.85). Therefore, NanoString provides an additional new technology to evaluate the induction of CYP1A1 and 2B1/2, as well as potentially other enzymes or transporters in rat liver slices.

  12. CYP1A1 and CYP1B1 gene expression and DNA adduct formation in normal human mammary epithelial cells exposed to benzo[a]pyrene in the absence or presence of chlorophyllin.

    PubMed

    John, Kaarthik; Divi, Rao L; Keshava, Channa; Orozco, Christine C; Schockley, Marie E; Richardson, Diana L; Poirier, Miriam C; Nath, Joginder; Weston, Ainsley

    2010-06-28

    Benzo[a]pyrene (BP) is a potent pro-carcinogen and ubiquitous environmental pollutant. Here, we examined the induction and modulation of CYP1A1 and CYP1B1 and 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG) adduct formation in DNA from 20 primary normal human mammary epithelial cell (NHMEC) strains exposed to BP (4muM) in the absence or presence of chlorophyllin (5muM). Real-time polymerase chain reaction (RT-PCR) analysis revealed strong induction of both CYP1A1 and CYP1B1 by BP, with high levels of inter-individual variability. Variable BPdG formation was found in all strains by r7, t8-dihydroxy-t-9, 10 epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA chemiluminescence assay (CIA). Chlorophyllin mitigated BP-induced CYP1A1 and CYP1B1 gene expression in all 20 strains when administered with BP. Chlorophyllin, administered prior to BP-exposure, mitigated CYP1A1 expression in 18/20 NHMEC strains (p<0.005) and CYP1B1 expression in 17/20 NHMEC strains (p<0.005). Maximum percent reductions of CYP1A1 and CYP1B1 gene expression and BPdG adduct formation were observed when cells were pre-dosed with chlorophyllin followed by administration of the carcinogen with chlorophyllin (p<0.005 for CYP1A1 and CYP1B1 expression and p<0.0005 for BPdG adducts). Therefore, chlorophyllin is likely to be a good chemoprotective agent for a large proportion of the human population.

  13. Enzymatic characterization of in vitro-expressed Baikal seal cytochrome P450 (CYP) 1A1, 1A2, and 1B1: implication of low metabolic potential of CYP1A2 uniquely evolved in aquatic mammals.

    PubMed

    Iwata, Hisato; Yamaguchi, Keisuke; Takeshita, Yoko; Kubota, Akira; Hirakawa, Shusaku; Isobe, Tomohiko; Hirano, Masashi; Kim, Eun-Young

    2015-05-01

    This study aimed to elucidate the catalytic function of cytochrome P450 (CYP) 1 enzymes in aquatic mammals. Alkoxyresorufin O-dealkylation (AROD) activities including methoxy- (MROD), ethoxy- (EROD), pentoxy- (PROD), and benzyloxyresorufin O-dealkylation (BROD), and 2- and 4-hydroxylation activities of 17β-estradiol (E2) were measured by using yeast-expressed Baikal seal (Pusa sibirica) CYP1A1, 1A2, and 1B1 proteins. Heterologous protein expression of the Baikal seal CYP1s (bsCYP1s) in yeast microsomes was confirmed by reduced CO-difference spectra and immunoblotting. Heterologously expressed human CYP1 enzyme (hCYP1) activities were simultaneously measured and compared with those of bsCYP1 isozymes. Recombinant bsCYP1A1 protein showed the highest Vmax of EROD, followed by MROD, PROD, and BROD, similar to that of hCYP1A1. Vmax/Km ratios of all AROD activities catalyzed by bsCYP1A1 were lower than those catalyzed by hCYP1A1, suggesting less potential for AROD by bsCYP1A1. Enzymatic assays for bsCYP1A2 showed no or minimal AROD activities, while hCYP1A2 displayed MROD and EROD activities. bsCYP1B1 showed an AROD profile (EROD>BROD>MROD>PROD) similar to that of hCYP1B1; however, Vmax/Km ratios of all AROD activities by bsCYP1B1 were higher. Yeast microsomes containing bsCYP1A1 and 1B1 and hCYP1A1, 1A2, and 1B1 metabolized E2 to 2-OHE2 and 4-OHE2, whereas bsCYP1A2 showed no such activity. Comparison of 4- and 2-hydroxylations of E2 by CYP1As suggests that bsCYP1A1, hCYP1A1, and 1A2 preferentially catalyze 2- rather than 4-hydroxylation. As for CYP1B1, the Vmax/Km ratios suggest that both Baikal seal and human CYPs catalyze 4- rather than 2-hydroxylation. Interspecies comparison showed that bsCYP1B1 has higher metabolic potencies for both E2 hydroxylations than does hCYP1B1, whereas the activity of bsCYP1A1 was lower than that of hCYP1A1. Messenger RNA expression levels of bsCYP1s in the liver of Baikal seals indicated that bsCYP1A1 and 1A2 enzymes contributed to 16

  14. Structure-function analysis of CYP27B1 and CYP27A1. Studies on mutants from patients with vitamin D-dependent rickets type I (VDDR-I) and cerebrotendinous xanthomatosis (CTX).

    PubMed

    Sawada, N; Sakaki, T; Kitanaka, S; Kato, S; Inouye, K

    2001-12-01

    We have determined eight types of missense mutants of CYP27B1 from Japanese vitamin D-dependent rickets type I (VDDR-I) patients [Kitanaka, S., Takeyama, K., Murayama, A., Sato, T., Okumura, K., Nogami, M., Hasegawa, Y., Niimi, H., Yanagisawa, J., Tanaka, T. & Kato, S. (1998) New England J. Med., 338, 653-661 and Kitanaka, S., Murayama, A., Sakaki, T., Inouye, K., Seino, Y., Fukumoto, S., Shima, M., Yukizane, S., Takayanagi, M., Niimi, H., Takeyama, K. & Kato, S. (1999) J. Clin. Endocrine Metab., 84, 4111-4117]. None of the CYP27B1 mutants showed 1alpha-hydroxylase activity towards 25-hydroxyvitamin D3. Thus, it was assumed that the mutated amino-acid residues play important roles in the 1alpha-hydroxylase activity, such as substrate binding, activation of molecular oxygen, interaction with adrenodoxin, and folding of the cytochrome P450 structure. To examine our hypothesis, we generated various mutants of CYP27B1 and studied their enzymatic properties. In addition, the corresponding mutations were introduced to CYP27A1, which belongs to the same family as CYP27B1. As CYP27A1 showed much higher expression level than CYP27B1 in Escherichia coli, further analysis including heme-binding and substrate-binding was performed with CYP27A1 in place of CYP27B1. Western blot analysis, spectral analysis including reduced CO-difference spectra and substrate-induced difference spectra, and enzymatic analysis of the mutant CYP27A1 gave information on the structure-function relationships of both CYP27A1 and CYP27B1. Although the sequence alignment suggested that Arg107, Gly125, and Pro497 of CYP27B1 might be involved in substrate binding, the experimental data strongly suggested that mutations of these amino-acid residues destroyed the tertiary structure of the substrate-heme pocket. It was also suggested that Arg389 and Arg453 of CYP27B1 were involved in heme-propionate binding, and Asp164 stabilized the four-helix bundle consisting of D, E, I and J helices, possibly by forming

  15. Maternal separation is associated with strain-specific responses to stress and epigenetic alterations to Nr3c1, Avp, and Nr4a1 in mouse

    PubMed Central

    Kember, R L; Dempster, E L; Lee, T H A; Schalkwyk, L C; Mill, J; Fernandes, C

    2012-01-01

    Stressful events early in life have been widely linked to behavioral phenotypes and have been implicated in the development of psychiatric disorders. Using a maternal separation paradigm, we investigated phenotypic and epigenetic changes following early life stress in two inbred strains of mice, C57BL/6J and DBA/2J. We found an increase in the corticosterone response to stress in male, C57BL/6J mice that had undergone maternal separation compared to controls. In addition, early life stress induced a number of mild but significant behavioral changes, many of which were sex and strain dependent. Following maternal separation anxiety was decreased in males but increased in DBA/2J females, DBA/2J males displayed reduced exploration of a novel object, and baseline activity was altered in males of both strains. Finally, we examined DNA methylation levels in the hippocampus across promoter regions of Nr3c1, Avp, and Nr4a1, and found altered levels at several CpG sites in maternally separated male mice compared to controls. This study contributes to a growing body of recent literature suggesting that epigenetic changes may mediate the impact of early life stress on behavior. In particular, we establish that the phenotypic and epigenetic responses to an adverse environment differ as a function of genetic background. PMID:22950049

  16. Active Site Mutations as a Suitable Tool Contributing to Explain a Mechanism of Aristolochic Acid I Nitroreduction by Cytochromes P450 1A1, 1A2 and 1B1

    PubMed Central

    Milichovský, Jan; Bárta, František; Schmeiser, Heinz H.; Arlt, Volker M.; Frei, Eva; Stiborová, Marie; Martínek, Václav

    2016-01-01

    Aristolochic acid I (AAI) is a plant drug found in Aristolochia species that causes aristolochic acid nephropathy, Balkan endemic nephropathy and their associated urothelial malignancies. AAI is activated via nitroreduction producing genotoxic N-hydroxyaristolactam, which forms DNA adducts. The major enzymes responsible for the reductive bioactivation of AAI are NAD(P)H:quinone oxidoreductase and cytochromes P450 (CYP) 1A1 and 1A2. Using site-directed mutagenesis we investigated the possible mechanisms of CYP1A1/1A2/1B1-catalyzed AAI nitroreduction. Molecular modelling predicted that the hydroxyl groups of serine122/threonine124 (Ser122/Thr124) amino acids in the CYP1A1/1A2-AAI binary complexes located near to the nitro group of AAI, are mechanistically important as they provide the proton required for the stepwise reduction reaction. In contrast, the closely related CYP1B1 with no hydroxyl group containing residues in its active site is ineffective in catalyzing AAI nitroreduction. In order to construct an experimental model, mutant forms of CYP1A1 and 1A2 were prepared, where Ser122 and Thr124 were replaced by Ala (CYP1A1-S122A) and Val (CYP1A2-T124V), respectively. Similarly, a CYP1B1 mutant was prepared in which Ala133 was replaced by Ser (CYP1B1-A133S). Site-directed mutagenesis was performed using a quickchange approach. Wild and mutated forms of these enzymes were heterologously expressed in Escherichia coli and isolated enzymes characterized using UV-vis spectroscopy to verify correct protein folding. Their catalytic activity was confirmed with CYP1A1, 1A2 and 1B1 marker substrates. Using 32P-postlabelling we determined the efficiency of wild-type and mutant forms of CYP1A1, 1A2, and 1B1 reconstituted with NADPH:CYP oxidoreductase to bioactivate AAI to reactive intermediates forming covalent DNA adducts. The S122A and T124V mutations in CYP1A1 and 1A2, respectively, abolished the efficiency of CYP1A1 and 1A2 enzymes to generate AAI-DNA adducts. In contrast

  17. Active Site Mutations as a Suitable Tool Contributing to Explain a Mechanism of Aristolochic Acid I Nitroreduction by Cytochromes P450 1A1, 1A2 and 1B1.

    PubMed

    Milichovský, Jan; Bárta, František; Schmeiser, Heinz H; Arlt, Volker M; Frei, Eva; Stiborová, Marie; Martínek, Václav

    2016-02-05

    Aristolochic acid I (AAI) is a plant drug found in Aristolochia species that causes aristolochic acid nephropathy, Balkan endemic nephropathy and their associated urothelial malignancies. AAI is activated via nitroreduction producing genotoxic N-hydroxyaristolactam, which forms DNA adducts. The major enzymes responsible for the reductive bioactivation of AAI are quinone oxidoreductase and cytochromes P450 (CYP) 1A1 and 1A2. Using site-directed mutagenesis we investigated the possible mechanisms of CYP1A1/1A2/1B1-catalyzed AAI nitroreduction. Molecular modelling predicted that the hydroxyl groups of serine122/threonine124 (Ser122/Thr124) amino acids in the CYP1A1/1A2-AAI binary complexes located near to the nitro group of AAI, are mechanistically important as they provide the proton required for the stepwise reduction reaction. In contrast, the closely related CYP1B1 with no hydroxyl group containing residues in its active site is ineffective in catalyzing AAI nitroreduction. In order to construct an experimental model, mutant forms of CYP1A1 and 1A2 were prepared, where Ser122 and Thr124 were replaced by Ala (CYP1A1-S122A) and Val (CYP1A2-T124V), respectively. Similarly, a CYP1B1 mutant was prepared in which Ala133 was replaced by Ser (CYP1B1-A133S). Site-directed mutagenesis was performed using a quickchange approach. Wild and mutated forms of these enzymes were heterologously expressed in Escherichia coli and isolated enzymes characterized using UV-vis spectroscopy to verify correct protein folding. Their catalytic activity was confirmed with CYP1A1, 1A2 and 1B1 marker substrates. Using (32)P-postlabelling we determined the efficiency of wild-type and mutant forms of CYP1A1, 1A2, and 1B1 reconstituted with NADPH:CYP oxidoreductase to bioactivate AAI to reactive intermediates forming covalent DNA adducts. The S122A and T124V mutations in CYP1A1 and 1A2, respectively, abolished the efficiency of CYP1A1 and 1A2 enzymes to generate AAI-DNA adducts. In contrast, the

  18. Pyranoflavones: A Group of Small-molecule Probes for Exploring the Active Site Cavities of Cytochrome P450 Enzymes 1A1, 1A2, and 1B1

    PubMed Central

    Liu, Jiawang; Taylor, Shannon F.; Dupart, Patrick S.; Arnold, Corey L.; Sridhar, Jayalakshmi; Jiang, Quan; Wang, Yuji; Skripnikova, Elena V.; Zhao, Ming; Foroozesh, Maryam

    2013-01-01

    Selective inhibition of P450 enzymes is the key to block the conversion of environmental procarcinogens to their carcinogenic metabolites in both animals and humans. To discover highly potent and selective inhibitors of P450s 1A1, 1A2, and 1B1, as well as to investigate active site cavities of these enzymes, 14 novel flavone derivatives were prepared as chemical probes. Fluorimetric enzyme inhibition assays were used to determine the inhibitory activities of these probes towards P450s 1A1, 1A2, 1B1, 2A6, and 2B1. A highly selective P450 1B1 inhibitor, 5-hydroxy-4′-propargyloxyflavone (5H4′FPE) was discovered. Some tested compounds also showed selectivity between P450s 1A1 and 1A2. Alpha-naphthoflavone-like and 5-hydroxyflavone derivatives preferentially inhibited P450 1A2, while beta-naphthoflavone-like flavone derivatives showed selective inhibition of P450 1A1. On the basis of structural analysis, the active site cavity models of P450 enzymes 1A1 and 1A2 were generated, demonstrating a planar long strip cavity and a planar triangular cavity, respectively. PMID:23600958

  19. CYP1A1 (Ile462Val), CYP1B1 (Ala119Ser and Val432Leu), GSTM1 (null), and GSTT1 (null) polymorphisms and bladder cancer risk in a Turkish population.

    PubMed

    Berber, Ufuk; Yilmaz, Ismail; Yilmaz, Omer; Haholu, Aptullah; Kucukodaci, Zafer; Ates, Ferhat; Demirel, Dilaver

    2013-01-01

    We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

  20. Design synthesis and evaluation of the inhibitory selectivity of novel trans-resveratrol analogues on human recombinant CYP1A1 CYP1A2 and CYP1B1

    USDA-ARS?s Scientific Manuscript database

    A series of trans-stilbene derivatives containing 4’-thiomethyl substituent were synthesized and evaluated for inhibitory activities on human recombinant cytochrome P450(s): CYP1A1, CYP1A2, and CYP1B1. CYP1A2-related metabolism of stilbene derivatives was estimated by using NADPH oxidation assay. A...

  1. Human natural killer cell microRNA: differential expression of MIR181A1B1 and MIR181A2B2 genes encoding identical mature microRNAs.

    PubMed

    Presnell, S R; Al-Attar, A; Cichocki, F; Miller, J S; Lutz, C T

    2015-01-01

    Natural killer (NK) and T lymphocytes share many properties, yet only NK cells respond rapidly to infection and cancer without pre-activation. We found that few microRNAs (miRNAs) differed significantly between human NK and T cells. Among those miRNAs, miR-181a and miR-181b levels rose during NK cell differentiation. Prior studies indicate that miR-181a and miR-181b are critical for human NK cell development and are co-transcribed from genes on chromosome 1 (MIR181A1B1) and on chromosome 9 (MIR181A2B2). We mapped human MIR181A1B1 and MIR181A2B2 transcription start sites to 78.3 kb and 34.0 kb upstream of the mature miRNAs, generating predominantly unspliced transcripts of 80-127 kb and ~60 kb, respectively. Unlike mouse thymocytes, human T cells expressed both MIR181A1B1 and MIR181A2B2. We tested the hypothesis that NK cells differentially transcribe the two genes during development and in response to immune regulatory cytokines. During NK-cell differentiation, MIR181A2B2 expression rose markedly and exceeded that of MIR181A1B1. TGF-β treatment increased NK-cell MIR181A2B2 transcription, whereas IL-2, IL-15 and IL-12/IL-18 treatments upregulated MIR181A1B1. The MIR181A2B2 promoter was strongly transactivated by SMAD3 and SMAD4 transcription factors, suggesting that TGF-β signaling upregulates MIR181A2B2 expression, at least in part, through SMAD-dependent promoter activation.

  2. Estrogen Receptor α Increases Basal and Cigarette Smoke Extract-Induced Expression of CYP1A1 and CYP1B1, but not GSTP1, in Normal Human Bronchial Epithelial Cells

    PubMed Central

    Han, W; Pentecost, BT; Pietropaolo, RL; Fasco, MJ; Spivack, SD

    2005-01-01

    Gender-specific estrogen receptor α (ERα) expression may plausibly influence lung carcinogenesis in females. Initial genome-wide microarray studies confirmed that carcinogen metabolism genes (CYP1A1, CYP1B1) were those most responsive to cigarette smoke extract (CSE) in normal bronchial epithelial (NHBE) cells. These two genes encoding phase I bioactivating enzymes and the GSTP1 gene encoding a phase II deactivating enzyme were then tested for induction by ERα. NHBE cells (native ERα−) were transfected with wild-type ERα-adenoviral constructs, and then exposed to CSE, 17β-estradiol (E2), and/or the ERα inhibitor, ICI 182,780. The expression levels of CYP1A1, CYP1B1 and GSTP1 were then determined by RNA-specific quantitative RT-PCR and immunoassay. ERα increased the basal expression of CYP1B1 4.04-fold (p<0.01) at the mRNA level and 6.5-fold at the protein level. ERα also increased the CSE-induced mRNA expression of CYP1B1 2.26-fold (p<0.01), but not the protein expression. ERα did not alter the CYP1A1 mRNA levels, but did increase protein expression 2.0-fold (p<0.01) on CSE exposure, and 6.2-fold (p<0.01) upon E2 exposure. These effects could be inhibited by ICI 182,780. ERα did not alter the expression of GSTP1. ChIP assay confirmed ERα binding to CYP1B1 promoter near the transcription start site. These results suggest that ERα regulates the CYP1B1 expression at a transcriptional level, and CYP1A1 expression at a translational level. These data raise the possibility that inter-gender differences in expression of ERα that are known to exist in human lung may contribute to inter-individual expression differences in CYP1A1 and CYP1B1, and to differences in carcinogen metabolism and mutation. PMID:16010691

  3. Determination of O2(a1 delta g) and O2(b1 sigma+ g) yields in the reaction O + ClO --> Cl + O2: implications for photochemistry in the atmosphere of Venus

    NASA Technical Reports Server (NTRS)

    Leu, M. T.; Yung, Y. L.

    1987-01-01

    A discharge flow apparatus with chemiluminescence detector has been used to study the reaction O + ClO --> Cl + O2, where O2 = O2(a1 delta g) or O2(b1 sigma+ g). The measured quantum yields for producing O2(a1 delta g) and O2(b1 sigma+ g) in the above reaction are less than 2.5 x 10(-2) and equal to (4.4 +/- 1.1) x 10(-4), respectively. The observed O2(a1 delta g) airglow of Venus cannot be explained in the context of standard photochemistry using our experimental results and those reported in recent literature. The possibility of an alternative source of O atoms derived from SO2 photolysis in the mesosphere of Venus is suggested.

  4. Determination of O2(a1 delta g) and O2(b1 sigma+ g) yields in the reaction O + ClO --> Cl + O2: implications for photochemistry in the atmosphere of Venus

    NASA Technical Reports Server (NTRS)

    Leu, M. T.; Yung, Y. L.

    1987-01-01

    A discharge flow apparatus with chemiluminescence detector has been used to study the reaction O + ClO --> Cl + O2, where O2 = O2(a1 delta g) or O2(b1 sigma+ g). The measured quantum yields for producing O2(a1 delta g) and O2(b1 sigma+ g) in the above reaction are less than 2.5 x 10(-2) and equal to (4.4 +/- 1.1) x 10(-4), respectively. The observed O2(a1 delta g) airglow of Venus cannot be explained in the context of standard photochemistry using our experimental results and those reported in recent literature. The possibility of an alternative source of O atoms derived from SO2 photolysis in the mesosphere of Venus is suggested.

  5. Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labor.

    PubMed

    Alzamil, Hana A; Pawade, Joya; Fortier, Michel A; Bernal, A López

    2014-01-01

    Human labor is a complex series of cellular and molecular events that occur at the materno-fetal and uterine levels. Many hypotheses have been proposed for the initiation of human labor, one hypothesis suggests that maturation of the fetus releases a signal in the amniotic fluid that will be transmitted to myometrium via the fetal membranes and initiate uterine contractions. There is strong evidence that prostaglandins (PGs) play a central role in initiation and progression of human labor. In this study we intended to investigate the expression of prostaglandin F synthase and the prostaglandin transporter in the human fetal membranes and to explore the relationship between cytokines and PGs in the mechanism of human labor. We used fetal membranes obtained before labor at term and after spontaneous labor at term or preterm to identify the changes in prostaglandin F synthase (AKR1B1) and human prostaglandin transporter (SLCO2A1) proteins in relation to parturition. Using fetal membranes explants we tested the effect of cytokines (interleukin-1 and tumor necrosis factor alpha) on PG production and the concomitant changes in cyclooxygenase-2 (PTGS2), AKR1B1 and SLCO2A1 expression. Expression of PTGS2 and AKR1B1 was upregulated in the fetal membranes in association with term labor while SLCO2A1 was downregulated with advancing gestation and during term labor. Before labor, IL-1 increased the expression of PTGS2, however during labor TNF upregulated PTGS2 and AKR1B1 proteins. The prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labor. The amnion is more responsive than choriodecidua to stimulation with pro-inflammatory cytokines. The mechanisms of term and preterm labor are different.

  6. Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labor

    PubMed Central

    Alzamil, Hana A.; Pawade, Joya; Fortier, Michel A.; Bernal, A. López

    2014-01-01

    Background: Human labor is a complex series of cellular and molecular events that occur at the materno-fetal and uterine levels. Many hypotheses have been proposed for the initiation of human labor, one hypothesis suggests that maturation of the fetus releases a signal in the amniotic fluid that will be transmitted to myometrium via the fetal membranes and initiate uterine contractions. There is strong evidence that prostaglandins (PGs) play a central role in initiation and progression of human labor. Objectives: In this study we intended to investigate the expression of prostaglandin F synthase and the prostaglandin transporter in the human fetal membranes and to explore the relationship between cytokines and PGs in the mechanism of human labor. Methods: We used fetal membranes obtained before labor at term and after spontaneous labor at term or preterm to identify the changes in prostaglandin F synthase (AKR1B1) and human prostaglandin transporter (SLCO2A1) proteins in relation to parturition. Using fetal membranes explants we tested the effect of cytokines (interleukin-1 and tumor necrosis factor alpha) on PG production and the concomitant changes in cyclooxygenase-2 (PTGS2), AKR1B1 and SLCO2A1 expression. Results: Expression of PTGS2 and AKR1B1 was upregulated in the fetal membranes in association with term labor while SLCO2A1 was downregulated with advancing gestation and during term labor. Before labor, IL-1 increased the expression of PTGS2, however during labor TNF upregulated PTGS2 and AKR1B1 proteins. Conclusions: The prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labor. The amnion is more responsive than choriodecidua to stimulation with pro-inflammatory cytokines. The mechanisms of term and preterm labor are different. PMID:25126080

  7. CYP1A1 and CYP1B1 expressions in medulloblastoma cells are AhR-independent and have no direct link with resveratrol-induced differentiation and apoptosis.

    PubMed

    Wu, Mo-Li; Li, Hong; Wu, Da-Chang; Wang, Xiao-Wei; Chen, Xiao-Yan; Kong, Qing-You; Ma, Jing-Xin; Gao, Ying; Liu, Jia

    Resveratrol induces apoptosis and regulates CYP1A1 and CYP1B1 expression in human medulloblastoma cells. To elucidate the potential correlation of their expressions with the anti-medulloblastoma effects of resveratrol, human medulloblastoma cells, UW228-3, were treated with CYP1A1 selective inhibitor (alpha-naphthoflavone, alpha-NF), selective CYP1A1/1A2 inducer (beta-naphthoflavone, beta-NF) and their combination with resveratrol, respectively. The influences of those treatments on the expressions of CYP1A1, 1A2 and 1B1 as well as the cell growth, differentiation and death were analyzed. It was found that neither alpha-NF nor beta-NF had any effect on cell growth. alpha-NF inhibited resveratrol-induced CYP1A1 expression without interfering cell differentiation and apoptosis. beta-NF could up-regulate resveratrol-induced CYP1A1 expression but not enhance the anti-cancer effects of resveratrol. CYP1A2 was undetectable in the cells irrespective to the treatments. Aryl hydrocarbon receptor (AhR) was absent in UW228-3 cells under normal culture and treated with resveratrol but induced by both alpha- and beta-NF. Immunohistochemical examination performed on 11 pairs of human medulloblastoma and noncancerous cerebellar tissues revealed that AhR was undetectable in either of them, whereas CYP1A1 was expressed in cerebellum but down-regulated or diminished in their malignant counterparts. Our data suggest for the first time that CYP1A1 and 1B1 expressions in human medulloblastoma cells are AhR-independent and have no direct links with resveratrol-induced differentiation and apoptosis. Appearance of CYP1A1 expression may reflect a more maturated status and a better prognosis of medulloblastomas.

  8. Chlorophyllin significantly reduces benzo[a]pyrene [BP]-DNA adduct formation and alters Cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells (NHMECs)

    PubMed Central

    Keshava, Channa; Divi, Rao L.; Einem, Tracey L.; Richardson, Diana L.; Leonard, Sarah L.; Keshava, Nagalakshmi; Poirier, Miriam C.; Weston, Ainsley

    2008-01-01

    We hypothesized that chlorophyllin (CHLN) would reduce BP-DNA adduct levels. Using NHMECs exposed to 4 μM BP for 24 hr in the presence or absence of 5 μM CHLN, we measured BP-DNA adducts by chemiluminescence immunoassay (CIA). The protocol included the following experimental groups: BP alone, BP given simultaneously with CHLN (BP+CHLN) for 24 hr, CHLN given for 24 hr followed by BP for 24 hr (preCHLN, postBP), and CHLN given for 48 hr with BP added for the last 24 hr (preCHLN, postBP+CHLN). Incubation with CHLN decreased BPdG levels in all groups, with 87 % inhibition in the preCHLN, postBP+CHLN group. To examine metabolic mechanisms, we monitored expression by Affymetrix microarray (U133A), and found BP-induced up-regulation of CYP1A1 and CYP1B1 expression, as well as up-regulation of groups of interferon-inducible, inflammation and signal transduction genes. Incubation of cells with CHLN and BP in any combination decreased expression of many of these genes. Using real time PCR (RT-PCR) the maximal inhibition of BP-induced gene expression, >85% for CYP1A1 and >70% for CYP1B1, was observed in the preCHLN, postBP+CHLN group. To explore the relationship between transcription and enzyme activity, the ethoxyresorufin-O-deethylase (EROD) assay was used to measure the combined CYP1A1 and CYP1B1 activities. BP exposure caused the EROD levels to double, compared to the unexposed controls. The CHLN-exposed groups all showed EROD levels similar to the unexposed controls. Therefore, the addition of CHLN to BP-exposed cells reduced BPdG formation and CYP1A1 and CYP1B1 expression, but EROD activity was not significantly reduced. PMID:19152381

  9. Hypervelocity Impact (HVI). Volume 2; WLE Small-Scale Fiberglass Panel Flat Multi-Layer Targets A-1, A-2, and B-1

    NASA Technical Reports Server (NTRS)

    Gorman, Michael R.; Ziola, Steven M.

    2007-01-01

    During 2003 and 2004, the Johnson Space Center's White Sands Testing Facility in Las Cruces, New Mexico conducted hypervelocity impact tests on the space shuttle wing leading edge. Hypervelocity impact tests were conducted to determine if Micro-Meteoroid/Orbital Debris impacts could be reliably detected and located using simple passive ultrasonic methods. The objective of Targets A-1, A-2, and B-2 was to study hypervelocity impacts through multi-layered panels simulating Whipple shields on spacecraft. Impact damage was detected using lightweight, low power instrumentation capable of being used in flight.

  10. Differences in 4-hydroxyestradiol levels in leukocytes are related to CYP1A1(∗)2C, CYP1B1(∗)3 and COMT Val158Met allelic variants.

    PubMed

    Martínez-Ramírez, O C; Pérez-Morales, R; Petrosyan, P; Castro-Hernández, C; Gonsebatt, M E; Rubio, J

    2015-10-01

    Exposure to estrogen and its metabolites, including catechol estrogens (CEs) and catechol estrogen quinones (CE-Qs) is closely related to breast cancer. Polymorphisms of the genes involved in the catechol estrogens metabolism pathway (CEMP) have been shown to affect the production of CEs and CE-Qs. In this study, we measured the induction of CYP1A1, CYP1B1, COMT, and GSTP1 by 17β-estradiol (17β-E2) in leukocytes with CYP1A1(∗)2C, CYP1B1(∗)3, COMT Val158Met and GSTP1 Ile105Val polymorphisms by semi quantitative RT-PCR and compared the values to those of leukocytes with wild type alleles; we also compared the differences in formation of 4- hydroxyestradiol (4-OHE2) and DNA-adducts. The data show that in the leukocytes with mutant alleles treatment with 17β-E2 up-regulates CYP1A1 and CYP1B1 and down-regulates COMT mRNA levels, resulting in major increments in 4-OHE2 levels compared to leukocytes with wild-type alleles. Therefore, we propose induction levels of gene expression and intracellular 4-OHE2 concentrations associated with allelic variants in response to exposure of 17β-E2 as a noninvasive biomarker that can help determine the risk of developing non-hereditary breast cancer in women.

  11. Determination of O2(a1Delta g) and O2(b1Sigma + g) yields in the reaction O + ClO yields Cl + O2 - Implications for photochemistry in the atmosphere of Venus

    NASA Technical Reports Server (NTRS)

    Leu, Ming-Taun; Yung, Yuk L.

    1987-01-01

    A discharge flow apparatus with a chemiluminescence detector was used to investigate the reaction O + ClO yields Cl + O2(asterisk), where O2(asterisk) = O2(a1Delta g) or O2(b1Sigma + g). It is found that the observed O2(a1Delta g) airglow of Venus cannot be explained in the framework of standard photochemistry using the experimental results obtained here and those reported in the recent literature. The possibility of an alternative source of O atoms derived from SO2 photolysis in the Venus mesosphere is suggested.

  12. Determination of O2(a1Delta g) and O2(b1Sigma + g) yields in the reaction O + ClO yields Cl + O2 - Implications for photochemistry in the atmosphere of Venus

    NASA Technical Reports Server (NTRS)

    Leu, Ming-Taun; Yung, Yuk L.

    1987-01-01

    A discharge flow apparatus with a chemiluminescence detector was used to investigate the reaction O + ClO yields Cl + O2(asterisk), where O2(asterisk) = O2(a1Delta g) or O2(b1Sigma + g). It is found that the observed O2(a1Delta g) airglow of Venus cannot be explained in the framework of standard photochemistry using the experimental results obtained here and those reported in the recent literature. The possibility of an alternative source of O atoms derived from SO2 photolysis in the Venus mesosphere is suggested.

  13. Analyses of non-synonymous obesity risk alleles in SH2B1 (rs7498665) and APOB48R (rs180743) in obese children and adolescents undergoing a 1-year lifestyle intervention.

    PubMed

    Volckmar, A-L; Pütter, C; Song, J-Y; Graniger, J; Knoll, N; Wolters, B; Hebebrand, J; Scherag, A; Reinehr, T; Hinney, A

    2013-06-01

    Association of obesity risk alleles of single nucleotide polymorphisms (SNPs) near or in the SH2B adaptor protein 1 gene (SH2B1) and increased body mass index (BMI) has been often described. A gene in close proximity, apolipoprotein B48 receptor gene (APOB48R), is tagged by the same SNP(s).We analyzed 454 overweight and obese children and adolescents (10.8±2.6 years, BMI-SDS 2.4±0.5; 55% girls) who completed a 1-year lifestyle intervention ('Obeldicks' program). Carriers of obesity risk alleles of non-synonymous SNPs in SH2B1 (rs7498665, Thr484Ala) or APOB48R (rs180743, Pro419Ala), as genotyped by TaqMan, were analysed for changes in anthropometrics (body-mass index (BMI), and standardized BMI (BMI-SDS)), blood pressure (systolic and diastolic) and plasma parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides, glucose, insulin, and HOMA).We observed no evidence for an association of the obesity risk alleles to alterations in any of the analyzed phenotypes. Both mean BMI and BMI-SDS improved during the intervention independent of genotype. The mean systolic blood pressure was lowered and concentrations of HDL-cholesterol increased significantly.The obesity risk alleles of non-synonymous SNPs at SH2B1 and APOB48R have no strong effect on weight loss-related phenotypes in overweight children after a 1-year lifestyle intervention.

  14. Utility of Oatp1a/1b-knockout and OATP1B1/3-humanized mice in the study of OATP-mediated pharmacokinetics and tissue distribution: case studies with pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein.

    PubMed

    Higgins, J William; Bao, Jing Q; Ke, Alice B; Manro, Jason R; Fallon, John K; Smith, Philip C; Zamek-Gliszczynski, Maciej J

    2014-01-01

    Although organic anion transporting polypeptide (OATP)-mediated hepatic uptake is generally conserved between rodents and humans at a gross pharmacokinetic level, the presence of three major hepatic OATPs with broad overlap in substrate and inhibitor affinity, and absence of rodent-human orthologs preclude clinical translation of single-gene knockout/knockin findings. At present, changes in pharmacokinetics and tissue distribution of pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein were studied in oatp1a/1b-knockout mice lacking the three major hepatic oatp isoforms, and in knockout mice with liver-specific knockin of human OATP1B1 or OATP1B3. Relative to wild-type controls, oatp1a/1b-knockout mice exhibited 1.6- to 19-fold increased intravenous and 2.1- to 115-fold increased oral drug exposure, due to 33%-75% decreased clearance, 14%-60% decreased volume of distribution, and ≤74-fold increased oral bioavailability, with the magnitude of change depending on the contribution of oatp1a/1b to pharmacokinetics. Hepatic drug distribution was 4.2- to 196-fold lower in oatp1a/1b-knockout mice; distributional attenuation was less notable in kidney, brain, cardiac, and skeletal muscle. Knockin of OATP1B1 or OATP1B3 partially restored control clearance, volume, and bioavailability values (24%-142% increase, ≤47% increase, and ≤77% decrease vs. knockout, respectively), such that knockin pharmacokinetic profiles were positioned between knockout and wild-type mice. Consistent with liver-specific humanization, only hepatic drug distribution was partially restored (1.3- to 6.5-fold increase vs. knockout). Exposure and liver distribution changes in OATP1B1-humanized versus knockout mice predicted the clinical impact of OATP1B1 on oral exposure and contribution to human hepatic uptake of statins within 1.7-fold, but only after correcting for human/humanized mouse liver relative protein expression factor (OATP1B1 = 2.2, OATP1B3 = 0.30).

  15. Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes

    PubMed Central

    2013-01-01

    Background Primary distal renal tubular acidosis (dRTA) caused by mutations in the genes that codify for the H + −ATPase pump subunits is a heterogeneous disease with a poor phenotype-genotype correlation. Up to now, large cohorts of dRTA Tunisian patients have not been analyzed, and molecular defects may differ from those described in other ethnicities. We aim to identify molecular defects present in the ATP6V1B1, ATP6V0A4 and SLC4A1 genes in a Tunisian cohort, according to the following algorithm: first, ATP6V1B1 gene analysis in dRTA patients with sensorineural hearing loss (SNHL) or unknown hearing status. Afterwards, ATP6V0A4 gene study in dRTA patients with normal hearing, and in those without any structural mutation in the ATP6V1B1 gene despite presenting SNHL. Finally, analysis of the SLC4A1 gene in those patients with a negative result for the previous studies. Methods 25 children (19 boys) with dRTA from 20 families of Tunisian origin were studied. DNAs were extracted by the standard phenol/chloroform method. Molecular analysis was performed by PCR amplification and direct sequencing. Results In the index cases, ATP6V1B1 gene screening resulted in a mutation detection rate of 81.25%, which increased up to 95% after ATP6V0A4 gene analysis. Three ATP6V1B1 mutations were observed: one frameshift mutation (c.1155dupC; p.Ile386fs), in exon 12; a G to C single nucleotide substitution, on the acceptor splicing site (c.175-1G > C; p.?) in intron 2, and one novel missense mutation (c.1102G > A; p.Glu368Lys), in exon 11. We also report four mutations in the ATP6V0A4 gene: one single nucleotide deletion in exon 13 (c.1221delG; p.Met408Cysfs*10); the nonsense c.16C > T; p.Arg6*, in exon 3; and the missense changes c.1739 T > C; p.Met580Thr, in exon 17 and c.2035G > T; p.Asp679Tyr, in exon 19. Conclusion Molecular diagnosis of ATP6V1B1 and ATP6V0A4 genes was performed in a large Tunisian cohort with dRTA. We identified three different ATP6V1

  16. Relative effect potency estimates of dioxin-like activity for dioxins, furans, and dioxin-like PCBs in adults based on cytochrome P450 1A1 and 1B1 gene expression in blood.

    PubMed

    Wimmerová, Soňa; van den Berg, Martin; Chovancová, Jana; Patayová, Henrieta; Jusko, Todd A; van Duursen, Majorie B M; Palkovičová Murínová, Ľubica; Canton, Rocio F; van Ede, Karin I; Trnovec, Tomáš

    2016-11-01

    In the risk assessment of PCDDs, PCDFs, and dioxin-like (DL) PCBs, regulatory authorities support the use of the toxic equivalency factor (TEF)-scheme derived from a heterogeneous data set of the relative effect potency (REPs) estimates. We sought to determine REPs for dioxin-like compounds (DLCs) using expression of cytochrome P450 (CYP) 1A1 and 1B1 mRNA in human peripheral blood mononuclear cells representing two different pathways. We used a sex and age adjusted regression-based approach comparing the strength of association between each DLC and the cytochrome P450 (CYP) 1A1 and 1B1 mRNA expression in 320 adults residing in an organochlorine-polluted area of eastern Slovakia. We calculated REPs based on CYP1A1 expression for 4 PCDDs, 8 PCDFs, and 1 PCB congener, and based on CYP1B1 expression for 5 PCDFs and 11 PCB congeners. REPs from CYP1A1 correlated with REPs previously derived from thyroid volume (ρ=0.85; p<0.001) and serum FT4 (ρ=0.77; p=0.009). The 13 log REPs from CYP1A1 correlated with log WHO-TEFs (r=0.63; p=0.015) and 11 log PCB REPs with PCB consensus toxicity factors (CTFs) for compounds with WHO-TEFs (r=0.80; p=0.003). The complete set of derived 56 log REPs correlated with the log CTFs (r=0.77; p=0.001) and log WHO-TEFs (r=0.81; p<0.001). REPs calculated from thyroid and cytochrome P450 endpoints realistically reflect human exposure scenarios because they are based on human chronic and low-dose exposures. While the CYP 1A1 seems more suitable for toxicity evaluation of PCDD/Fs, the CYP 1B1 is more apt for PCDFs and PCBs and reflects different pathways. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Structure-Function Relationships of Inhibition of Human Cytochromes P450 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 Flavonoid Derivatives

    PubMed Central

    Shimada, Tsutomu; Tanaka, Katsuhiro; Takenaka, Shigeo; Murayama, Norie; Martin, Martha V.; Foroozesh, Maryam K.; Yamazaki, Hiroshi; Guengerich, F. Peter; Komori, Masayuki

    2010-01-01

    Structure-function relationships for inhibition of human cytochrome P450s (P450s) 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives were studied. Thirty-two of the 33 flavonoids tested produced Reverse Type I binding spectra with P450 1B1, and the potencies of binding were correlated with the abilities to inhibit 7-ethoxyresorufin O-deethylation activity. The presence of a hydroxyl group in flavones, e.g. 3-, 5-, and 7-monohydroxy- and 5,7-dihydroxyflavone, decreased the 50% inhibition concentration (IC50) of P450 1B1 from 0.6 µM to 0.09, 0.21, 0.25, and 0.27 µM, respectively, and 3,5,7-trihydroxyflavone (galangin) was the most potent, with an IC50 of 0.003 µM. The introduction of a 4’-methoxy- or 3’,4’-dimethoxy group into 5,7-dihydroxyflavone yielded other active inhibitors of P450 1B1 with IC50 values of 0.014 and 0.019 µM, respectively. The above hydroxyl- and/or methoxy-groups in flavone molecules also increased the inhibition activity with P450 1A1 but not always towards P450 1A2, where 3-, 5-, or 7-hydroxyflavone, and 4’-methoxy-5,7-dihydroxyflavone were less inhibitory than flavone itself. P450 2C9 was more inhibited by 7-hydroxy-,5,7-dihydroxy-, and 3,5,7-trihydroxyflavones than by flavone but was weakly inhibited by 3-and 5-hydroxyflavone. Flavone and several other flavonoids produced Type I binding spectra with P450 3A4, but such binding was not always related to the inhibitiory activities towards P450 3A4. These results indicate that there are different mechanisms of inhibition for P450s 1A1, 1A2, 1B1, 2C9, and 3A4 by various flavonoid derivatives and that the number and position of hydroxyl and/or methoxy groups highly influence the inhibitory actions of flavonoids towards these enzymes. Molecular docking studies suggest that there are different mechanisms involved in the interaction of various flavonoids with the active site of P450s, thus causing differences in inhibition of these P450 catalytic activities by flavonoids. PMID

  18. Structure-function relationships of inhibition of human cytochromes P450 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives.

    PubMed

    Shimada, Tsutomu; Tanaka, Katsuhiro; Takenaka, Shigeo; Murayama, Norie; Martin, Martha V; Foroozesh, Maryam K; Yamazaki, Hiroshi; Guengerich, F Peter; Komori, Masayuki

    2010-12-20

    Structure-function relationships for the inhibition of human cytochrome P450s (P450s) 1A1, 1A2, 1B1, 2C9, and 3A4 by 33 flavonoid derivatives were studied. Thirty-two of the 33 flavonoids tested produced reverse type I binding spectra with P450 1B1, and the potencies of binding were correlated with the abilities to inhibit 7-ethoxyresorufin O-deethylation activity. The presence of a hydroxyl group in flavones, for example, 3-, 5-, and 7-monohydroxy- and 5,7-dihydroxyflavone, decreased the 50% inhibition concentration (IC50) of P450 1B1 from 0.6 μM to 0.09, 0.21, 0.25, and 0.27 μM, respectively, and 3,5,7-trihydroxyflavone (galangin) was the most potent, with an IC50 of 0.003 μM. The introduction of a 4'-methoxy- or 3',4'-dimethoxy group into 5,7-dihydroxyflavone yielded other active inhibitors of P450 1B1 with IC50 values of 0.014 and 0.019 μM, respectively. The above hydroxyl and/or methoxy groups in flavone molecules also increased the inhibition activity with P450 1A1 but not always toward P450 1A2, where 3-, 5-, or 7-hydroxyflavone and 4'-methoxy-5,7-dihydroxyflavone were less inhibitory than flavone itself. P450 2C9 was more inhibited by 7-hydroxy-, 5,7-dihydroxy-, and 3,5,7-trihydroxyflavones than by flavone but was weakly inhibited by 3- and 5-hydroxyflavone. Flavone and several other flavonoids produced type I binding spectra with P450 3A4, but such binding was not always related to the inhibitiory activities toward P450 3A4. These results indicate that there are different mechanisms of inhibition for P450s 1A1, 1A2, 1B1, 2C9, and 3A4 by various flavonoid derivatives and that the number and position of hydroxyl and/or methoxy groups highly influence the inhibitory actions of flavonoids toward these enzymes. Molecular docking studies suggest that there are different mechanisms involved in the interaction of various flavonoids with the active site of P450s, thus causing differences in inhibition of these P450 catalytic activities by flavonoids.

  19. Induction of CYP1A1 and CYP1B1 by benzo(k)fluoranthene and benzo(a)pyrene in T-47D human breast cancer cells: Roles of PAH interactions and PAH metabolites

    SciTech Connect

    Spink, David C. Wu, Susan J.; Spink, Barbara C.; Hussain, Mirza M.; Vakharia, Dilip D.; Pentecost, Brian T.; Kaminsky, Laurence S.

    2008-02-01

    The interactions of polycyclic aromatic hydrocarbons (PAH) and cytochromes P450 (CYP) are complex; PAHs are enzyme inducers, substrates, and inhibitors. In T-47D breast cancer cells, exposure to 0.1 to 1 {mu}M benzo(k)fluoranthene (BKF) induced CYP1A1/1B1-catalyzed 17{beta}-estradiol (E{sub 2}) metabolism, whereas BKF levels greater than 1 {mu}M inhibited E{sub 2} metabolism. Time course studies showed that induction of CYP1-catalyzed E{sub 2} metabolism persisted after the disappearance of BKF or co-exposed benzo(a)pyrene, suggesting that BKF metabolites retaining Ah receptor agonist activity were responsible for prolonged CYP1 induction. BKF metabolites were shown, through the use of ethoxyresorufin O-deethylase and CYP1A1-promoter-luciferase reporter assays to induce CYP1A1/1B1 in T-47D cells. Metabolites formed by oxidation at the C-2/C-3 region of BKF had potencies for CYP1 induction exceeding those of BKF, whereas C-8/C-9 oxidative metabolites were somewhat less potent than BKF. The activities of expressed human CYP1A1 and 1B1 with BKF as substrate were investigated by use of HPLC with fluorescence detection, and by GC/MS. The results showed that both enzymes efficiently catalyzed the formation of 3-, 8-, and 9-OHBKF from BKF. These studies indicate that the inductive effects of PAH metabolites as potent CYP1 inducers are likely to be additional important factors in PAH-CYP interactions that affect metabolism and bioactivation of other PAHs, ultimately modulating PAH toxicity and carcinogenicity.

  20. Thiamine (Vitamin B1)

    MedlinePlus

    ... B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin/niacinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin ... in appropriate amounts, although rare allergic reactions and skin irritation have occurred. It is also LIKELY SAFE ...

  1. Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 1: addressing configurational instability through scaffold modification.

    PubMed

    Fader, Lee D; Landry, Serge; Morin, Sébastien; Kawai, Stephen H; Bousquet, Yves; Hucke, Oliver; Goudreau, Nathalie; Lemke, Christopher T; Bonneau, Pierre; Titolo, Steve; Mason, Stephen; Simoneau, Bruno

    2013-06-01

    The optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly that possess a labile stereocenter at C3 is described. Quaternization of the C3 position of compound 1 in order to prevent racemization gave compound 2, which was inactive in our capsid disassembly assay. A likely explanation for this finding was revealed by in silico analysis predicting a dramatic increase in energy of the bioactive conformation upon quaternization of the C3 position. Replacement of the C3 of the diazepine ring with a nitrogen atom to give the 1,5-dihydro-benzo[f][1,3,5]triazepine-2,4-dione analog 4 was well tolerated. Introduction of a rigid spirocyclic system at the C3 position gave configurationally stable 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione analog 5, which was able to access the bioactive conformation without a severe energetic penalty and inhibit capsid assembly. Preliminary structure-activity relationships (SAR) and X-ray crystallographic data show that knowledge from the 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly can be transferred to these new scaffolds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Relationship between single nucleotide polymorphisms in CYP1A1 and CYP1B1 genes and the bone mineral density and serum lipid profiles in postmenopausal Japanese women taking hormone therapy.

    PubMed

    Quan, Jinhua; Yahata, Tetsuro; Tamura, Nozomi; Nagata, Hiroshi; Tanaka, Kenichi

    2009-01-01

    The genetic variations of the genes encoding cytochrome P-450 enzymes are considered to play an important role in the metabolism of estradiol. The objective of this study was to evaluate the relationships among single nucleotide polymorphisms (SNPs) of cytochrome P-450 genes, lumbar bone mineral density (BMD), and serum lipids and to determine the effects of hormone therapy (HT). The participants were 124 Japanese women who had been diagnosed with osteopenia or osteoporosis and were taking HT for 12 months. Seven single nucleotide polymorphisms in the CYP1A1 and CYP1B1 genes were characterized. Lumbar BMD and the levels of serum lipids were measured before and after HT. A single nucleotide polymorphism in exon 3 of CYP1B1 was found to be significantly associated with the effect of HT on BMD and low-density lipoprotein cholesterol both in univariate and multivariate analyses. In the women with the GG genotype of L432V, the responses to HT of BMD and low-density lipoprotein cholesterol markedly decreased. The serum follicle-stimulating hormone level after HT was significantly higher in the women with the GG genotype of L432V. These results suggest that the L432V polymorphism in the CYP1B1 gene could therefore be used to predict the effect of HT on lumbar BMD and low-density lipoprotein cholesterol in Japanese women.

  3. Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis.

    PubMed

    Brozek, Wolfgang; Manhardt, Teresa; Kállay, Enikö; Peterlik, Meinrad; Cross, Heide S

    2012-07-26

    Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e., CYP27B1-encoded 25-hydroxyvitamin D-1a-hydroxylase and CYP24A1-encoded 25-hydroxyvitamin D-24-hydroxylase, and inflammation-induced cyclooxygenase-2 (COX-2). Data from 105 cancer patients on CYP27B1, VDR, CYP24A1, and COX-2 mRNA expression in relation to tumor grade, anatomical location, gender and age were fit into a multivariate model of exploratory factor analysis. Nearly identical results were obtained by the principal factor and the maximum likelihood method, and these were confirmed by hierarchical cluster analysis: Within the eight mutually dependent variables studied four independent constellations were found that identify different features of colorectal cancer pathogenesis: (i) Escape of COX-2 activity from restraints by the CYP27B1/VDR system can initiate cancer growth anywhere in the colorectum regardless of age and gender; (ii) variations in COX-2 expression are mainly responsible for differences in cancer incidence in relation to tumor location; (iii) advancing age has a strong gender-specific influence on cancer incidence; (iv) progression from well differentiated to undifferentiated cancer is solely associated with a rise in CYP24A1 expression.

  4. Prenatal 3,3',4,4',5-pentachlorobiphenyl exposure modulates induction of rat hepatic CYP 1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene

    SciTech Connect

    Wakui, Shin . E-mail: wakui@azabu-u.ac.jp; Yokoo, Kiyofumi; Takahashi, Hiroyuki; Muto, Tomoko; Suzuki, Yoshihiko; Kanai, Yoshikatsu; Hano, Hiroshi; Furusato, Masakuni; Endou, Hitoshi

    2006-02-01

    We previously reported the finding that prenatal exposure to a relatively low dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a high dose decreased it. One of the most important factors determining the sensitivity to mammary carcinogenesis is the metabolic stage at administration of the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct this metabolism. We investigated the hepatic expression of CYP1 and AhR following oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 {mu}g of PCB126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1, and AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 {mu}g group) prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and immunohistochemical analyses were consistent with mRNAs changes. Because DMBA oxidation produces a highly mutagenic metabolite and is finally catalyzed by CYP1B1, a relatively low PCB126 dose might produce the biological character to potentially increase the risk of DMBA-induced mammary carcinoma.

  5. Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis

    PubMed Central

    Brozek, Wolfgang; Manhardt, Teresa; Kállay, Enikö; Peterlik, Meinrad; Cross, Heide S.

    2012-01-01

    Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e., CYP27B1-encoded 25-hydroxyvitamin D-1α-hydroxylase and CYP24A1-encoded 25-hydroxyvitamin D-24-hydroxylase, and inflammation-induced cyclooxygenase-2 (COX-2). Data from 105 cancer patients on CYP27B1, VDR, CYP24A1, and COX-2 mRNA expression in relation to tumor grade, anatomical location, gender and age were fit into a multivariate model of exploratory factor analysis. Nearly identical results were obtained by the principal factor and the maximum likelihood method, and these were confirmed by hierarchical cluster analysis: Within the eight mutually dependent variables studied four independent constellations were found that identify different features of colorectal cancer pathogenesis: (i) Escape of COX-2 activity from restraints by the CYP27B1/VDR system can initiate cancer growth anywhere in the colorectum regardless of age and gender; (ii) variations in COX-2 expression are mainly responsible for differences in cancer incidence in relation to tumor location; (iii) advancing age has a strong gender-specific influence on cancer incidence; (iv) progression from well differentiated to undifferentiated cancer is solely associated with a rise in CYP24A1 expression. PMID:24213465

  6. Cytogenetic damage in Turkish coke oven workers exposed to polycyclic aromatic hydrocarbons: Association with CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms.

    PubMed

    Ada, Ahmet Oguz; Demiroglu, Canan; Yilmazer, Meltem; Suzen, Halit Sinan; Demirbag, Ali Eba; Efe, Sibel; Alemdar, Yilmaz; Iscan, Mumtaz; Burgaz, Sema

    2013-09-01

    The aim of this study was to determine the frequencies of chromosomal aberrations (CA) and cytochalasin-blocked micronuclei (CBMN) in peripheral blood lymphocytes from Turkish coke oven workers and the influence of CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms on these biomarkers. Cytogenetic analysis showed that occupational exposure significantly increased the CA and CBMN frequencies. Gene polymorphisms, on the other hand, did not affect CA or CBMN in either exposed or control subjects. However, due to the limited sample size, our findings need to be verified in future studies with a larger sample.

  7. Chlorophyllin significantly reduces benzo[a]pyrene-DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells.

    PubMed

    Keshava, Channa; Divi, Rao L; Einem, Tracey L; Richardson, Diana L; Leonard, Sarah L; Keshava, Nagalakshmi; Poirier, Miriam C; Weston, Ainsley

    2009-03-01

    We hypothesized that chlorophyllin (CHLN) would reduce benzo[a]pyrene-DNA (BP-DNA) adduct levels. Using normal human mammary epithelial cells (NHMECs) exposed to 4 microM BP for 24 hr in the presence or absence of 5 microM CHLN, we measured BP-DNA adducts by chemiluminescence immunoassay (CIA). The protocol included the following experimental groups: BP alone, BP given simultaneously with CHLN (BP+CHLN) for 24 hr, CHLN given for 24 hr followed by BP for 24 hr (preCHLN, postBP), and CHLN given for 48 hr with BP added for the last 24 hr (preCHLN, postBP+CHLN). Incubation with CHLN decreased BPdG levels in all groups, with 87% inhibition in the preCHLN, postBP+CHLN group. To examine metabolic mechanisms, we monitored expression by Affymetrix microarray (U133A), and found BP-induced up-regulation of CYP1A1 and CYP1B1 expression, as well as up-regulation of groups of interferon-inducible, inflammation and signal transduction genes. Incubation of cells with CHLN and BP in any combination decreased expression of many of these genes. Using reverse transcription real time PCR (RT-PCR) the maximal inhibition of BP-induced gene expression, >85% for CYP1A1 and >70% for CYP1B1, was observed in the preCHLN, postBP+CHLN group. To explore the relationship between transcription and enzyme activity, the ethoxyresorufin-O-deethylase (EROD) assay was used to measure the combined CYP1A1 and CYP1B1 activities. BP exposure caused the EROD levels to double, when compared with the unexposed controls. The CHLN-exposed groups all showed EROD levels similar to the unexposed controls. Therefore, the addition of CHLN to BP-exposed cells reduced BPdG formation and CYP1A1 and CYP1B1 expression, but EROD activity was not significantly reduced.

  8. Suppressive effects of alpha-Hederin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated murine Cyp1a-1 expression in the mouse hepatoma Hepa-1c1c7 cells.

    PubMed

    Jeong, H G; Lee, S S

    1999-04-26

    Cultured mouse hepatoma cell line Hepa-1c1c7 cells were treated with alpha-Hederin to assess the role of alpha-Hederin in the process of Cyp1a-1 induction. Treatment of Hepa-1c1c7 cultures with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced Cyp1a-1, as indicated by analysis of 7-ethoxyresorufin O-deethylation (EROD) activity and Cyp1a-1 protein. When alpha-Hederin and TCDD were both added to cultures, TCDD-inducible EROD activity was greatly suppressed by alpha-Hederin in a dose-dependent manner. TCDD-induced Cyp1a-1 protein and mRNA levels were markedly reduced in the concomitant treatment of TCDD and alpha-Hederin consistent with EROD activity. Electrophoretic mobility shift assay using nuclear extraction of cells revealed that alpha-Hederin reduced transformation of the Ah receptor to a form capable of specifically binding to an oligonucleotide containing a dioxin-response element (DRE) sequence of the Cyp1a-1 gene. These results suggest that the suppressive effect of alpha-Hederin on TCDD-induced Cyp1a-1 gene expression in Hepa-1c1c7 cells might be an antagonist of the DNA binding potential of a nuclear Ah receptor.

  9. Association of common variants in/near six genes (ATP2B1, CSK, MTHFR, CYP17A1, STK39 and FGF5) with blood pressure/hypertension risk in Chinese children.

    PubMed

    Xi, B; Shen, Y; Zhao, X; Chandak, G R; Cheng, H; Hou, D; Li, Y; Ott, J; Zhang, Y; Wang, X; Mi, J

    2014-01-01

    Recent genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) that are associated with blood pressure (BP)/hypertension. In this study, we aimed to examine the established associations amongst Chinese children. We genotyped six SNPs (ATP2B1 rs17249754, CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777 and FGF5 rs16998073) in Chinese children (N=3077, age range, 6-18 years). Based on the Chinese age- and sex-specific BP standards, 619 hypertensive cases and 2458 controls with normal BP were identified. Of the six SNPs, only ATP2B1 rs17249754 SNP was significantly associated with the risk of hypertension (allelic odds ratio (OR)=1.25, 95% confidence interval (CI): 1.08-1.44, P=0.003). Although all other SNPs showed a trend towards increasing the BP values and risk of hypertension, there was no statistically significant association after false discovery rate analysis. We calculated the weighted risk score using six SNPs, for systolic BP (SBP), diastolic BP (DBP) and hypertension. Each additional weighted risk score was associated with SBP by 1.18 mm Hg (95% CI=0.62-1.73, P<0.001), but not with the DBP (β=0.28, 95% CI=(-0.15)-0.74), and overall increased the risk of hypertension by 1.19-fold (95% CI=1.04-1.35, P=0.01). The present study confirmed the significant association of ATP2B1 rs17249754 with risk of hypertension among Chinese children, but failed to replicate the association of CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777 and FGF5 rs16998073 with BP/risk of hypertension.

  10. Design, synthesis and evaluation of the inhibitory selectivity of novel trans-resveratrol analogues on human recombinant CYP1A1, CYP1A2 and CYP1B1.

    PubMed

    Mikstacka, Renata; Rimando, Agnes M; Dutkiewicz, Zbigniew; Stefański, Tomasz; Sobiak, Stanisław

    2012-09-01

    A series of trans-stilbene derivatives containing 4'-methylthio substituent were synthesized and evaluated for inhibitory activities on human recombinant cytochrome P450(s): CYP1A1, CYP1A2, and CYP1B1. CYP1A2-related metabolism of stilbene derivatives was estimated by using NADPH oxidation assay. Additionally, for CYP1A2 and CYP1B1 molecular docking analysis was carried out to provide information on enzyme-ligand interactions and putative site of metabolism. 3,4,5-Trimethoxy-4'-methylthio-trans-stilbene, an analogue of DMU-212 (3,4,5,4'-tetramethoxy-trans-stilbene) was an effective inhibitor of all CYP1 enzymes. On the other hand, 2,3,4-trimethoxy-4'-methylthio-trans-stilbene, appeared to be the most selective inhibitor of the isozymes CYP1A1 and CYP1B1, displaying extremely low affinity towards CYP1A2. Molecular modeling suggested that the most probable binding poses of the methylthiostilbene derivatives in CYP1A2 active sites are those with the methylthio substituent directed towards the heme iron. Products of CYP1A2-catalyzed oxidation of 2,4,5-trimethoxy-4'-methylthiostilbene and 3,4,5-trimethoxy-4'-methylthiostilbene were identified as monohydroxylated compounds. Other studied derivatives appeared to be poor substrates of CYP1A2. Structure-activity relationship analysis rendered better understanding of the mechanism of action of xenobiotic-metabolizing enzymes crucial at the early stage of carcinogenesis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Phase I and II metabolism and MRP2-mediated export of bosentan in a MDCKII-OATP1B1-CYP3A4-UGT1A1-MRP2 quadruple-transfected cell line

    PubMed Central

    Fahrmayr, C; König, J; Auge, D; Mieth, M; Münch, K; Segrestaa, J; Pfeifer, T; Treiber, A; Fromm, MF

    2013-01-01

    Background and Purpose Hepatic uptake (e.g. by OATP1B1), phase I and II metabolism (e.g. by CYP3A4, UGT1A1) and subsequent biliary excretion (e.g. by MRP2) are key determinants for the pharmacokinetics of numerous drugs. However, stably transfected cell models for the simultaneous investigation of transport and phase I and II metabolism of drugs are lacking. Experimental Approach A newly established quadruple-transfected MDCKII-OATP1B1-CYP3A4-UGT1A1-MRP2 cell line was used to investigate metabolism and transcellular transport of the endothelin receptor antagonist bosentan. Key Results Intracellular accumulation of bosentan equivalents (i.e. parent compound and metabolites) was significantly lower in all cell lines expressing MRP2 compared to cell lines lacking this transporter (P < 0.001). Accordingly, considerably higher amounts of bosentan equivalents were detectable in the apical compartments of cell lines with MRP2 expression (P < 0.001). HPLC and LC-MS measurements revealed that mainly unchanged bosentan accumulated in intracellular and apical compartments. Furthermore, the phase I metabolites Ro 48–5033 and Ro 47–8634 were detected intracellularly in cell lines expressing CYP3A4. Additionally, a direct glucuronide of bosentan could be identified intracellularly in cell lines expressing UGT1A1 and in the apical compartments of cell lines expressing UGT1A1 and MRP2. Conclusions and Implications These in vitro data indicate that bosentan is a substrate of UGT1A1. Moreover, the efflux transporter MRP2 mediates export of bosentan and most likely also of bosentan glucuronide in the cell system. Taken together, cell lines simultaneously expressing transport proteins and metabolizing enzymes represent additional useful tools for the investigation of the interplay of transport and metabolism of drugs. PMID:23387445

  12. Phase I and II metabolism and MRP2-mediated export of bosentan in a MDCKII-OATP1B1-CYP3A4-UGT1A1-MRP2 quadruple-transfected cell line.

    PubMed

    Fahrmayr, C; König, J; Auge, D; Mieth, M; Münch, K; Segrestaa, J; Pfeifer, T; Treiber, A; Fromm, Mf

    2013-05-01

    Hepatic uptake (e.g. by OATP1B1), phase I and II metabolism (e.g. by CYP3A4, UGT1A1) and subsequent biliary excretion (e.g. by MRP2) are key determinants for the pharmacokinetics of numerous drugs. However, stably transfected cell models for the simultaneous investigation of transport and phase I and II metabolism of drugs are lacking. A newly established quadruple-transfected MDCKII-OATP1B1-CYP3A4-UGT1A1-MRP2 cell line was used to investigate metabolism and transcellular transport of the endothelin receptor antagonist bosentan. Intracellular accumulation of bosentan equivalents (i.e. parent compound and metabolites) was significantly lower in all cell lines expressing MRP2 compared to cell lines lacking this transporter (P < 0.001). Accordingly, considerably higher amounts of bosentan equivalents were detectable in the apical compartments of cell lines with MRP2 expression (P < 0.001). HPLC and LC-MS measurements revealed that mainly unchanged bosentan accumulated in intracellular and apical compartments. Furthermore, the phase I metabolites Ro 48-5033 and Ro 47-8634 were detected intracellularly in cell lines expressing CYP3A4. Additionally, a direct glucuronide of bosentan could be identified intracellularly in cell lines expressing UGT1A1 and in the apical compartments of cell lines expressing UGT1A1 and MRP2. These in vitro data indicate that bosentan is a substrate of UGT1A1. Moreover, the efflux transporter MRP2 mediates export of bosentan and most likely also of bosentan glucuronide in the cell system. Taken together, cell lines simultaneously expressing transport proteins and metabolizing enzymes represent additional useful tools for the investigation of the interplay of transport and metabolism of drugs. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

  13. Prediction, Refinement and Persistency of Transmembrane Helix Dimers in Lipid Bilayers using Implicit and Explicit Solvent/Lipid Representations: Microsecond Molecular Dynamics Simulations of ErbB1/B2 and EphA1

    PubMed Central

    Zhang, Liqun; Sodt, Alexander J.; Venable, Richard M.; Pastor, Richard W.; Buck, Matthias

    2012-01-01

    All-atom simulations are carried out on ErbB1/B2 and EphA1 transmembrane helix dimers in lipid bilayers starting from their solution/DMPC bicelle NMR structures. Over the course of microsecond trajectories, the structures remain in close proximity to the initial configuration and satisfy the great majority of experimental tertiary contact restraints. These results further validate CHARMM protein/lipid force fields and simulation protocols on Anton. Separately, dimer conformations are generated using replica exchange in conjunction with an implicit solvent and lipid representation. The implicit model requires further improvement, and this study investigates whether lengthy all-atom molecular dynamics simulations can alleviate the shortcomings of the initial conditions. The simulations correct many of the deficiencies. For example excessive helix twisting is eliminated over a period of hundreds of nanoseconds. The helix tilt, crossing angles and dimer contacts approximate those of the NMR derived structure, although the detailed contact surface remains off-set for one of two helices in both systems. Hence, even microsecond simulations are not long enough for extensive helix rotations. The alternate structures can be rationalized with reference to interaction motifs and may represent still sought after receptor states that are important in ErbB1/B2 and EphA1 signaling. PMID:23042146

  14. Ligand-dependent regulation of the activity of the orphan nuclear receptor, small heterodimer partner (SHP), in the repression of bile acid biosynthetic CYP7A1 and CYP8B1 genes.

    PubMed

    Miao, Ji; Choi, Sung-E; Seok, Sun Mi; Yang, Linda; Zuercher, William J; Xu, Yong; Willson, Timothy M; Xu, H Eric; Kemper, Jongsook Kim

    2011-07-01

    Small heterodimer partner (SHP) plays important roles in diverse biological processes by directly interacting with transcription factors and inhibiting their activities. SHP has been designated an orphan nuclear receptor, but whether its activity can be modulated by ligands has been a long-standing question. Recently, retinoid-related molecules, including 4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3Cl-AHPC), were shown to bind to SHP and enhance apoptosis. We have examined whether 3Cl-AHPC acts as an agonist and increases SHP activity in the repression of bile acid biosynthetic CYP7A1 and CYP8B1 genes and delineated the underlying mechanisms. Contrary to this expectation, micromolar concentrations of 3Cl-AHPC increased CYP7A1 expression but indirectly via p38 kinase signaling. Nanomolar concentrations, however, repressed CYP7A1 expression and decreased bile acid levels in HepG2 cells, and little repression was observed when SHP was down-regulated by small hairpin RNA. Mechanistic studies revealed that 3Cl-AHPC bound to SHP, increased the interaction of SHP with liver receptor homologue (LRH)-1, a hepatic activator for CYP7A1 and CYP8B1 genes, and with repressive cofactors, Brahma, mammalian Sin3a, and histone deacetylase-1, and, subsequently, increased the occupancy of SHP and these cofactors at the promoters. Mutation of Leu-100, predicted to contact 3Cl-AHPC within the SHP ligand binding pocket by molecular modeling, severely impaired the increased interaction with LRH-1, and repression of LRH-1 activity mediated by 3Cl-AHPC. 3Cl-AHPC repressed SHP metabolic target genes in a gene-specific manner in human primary hepatocytes and HepG2 cells. These data suggest that SHP may act as a ligand-regulated receptor in metabolic pathways. Modulation of SHP activity by synthetic ligands may be a useful therapeutic strategy.

  15. Avermectin B1

    Integrated Risk Information System (IRIS)

    Avermectin B1 ; CASRN 65195 - 55 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  16. Spectral Modification and Catalytic Inhibition of Human Cytochromes P450 1A1, 1A2, 1B1, 2A6 and 2A13 by Four Chemopreventive Organoselenium Compounds

    PubMed Central

    Shimada, Tsutomu; Murayama, Norie; Tanaka, Katsuhiro; Takenaka, Shigeo; Guengerich, F. Peter; Yamazaki, Hiroshi; Komori, Masayuki

    2011-01-01

    Several organoselenium compounds including benzyl selenocyanate (BSC), 1,2-phenylenebis(methylene)selenocyanate (o-XSC), 1,3-phenylenebis(methylene)selenocyanate (m-XSC), and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) have been shown to prevent cancers caused by polycyclic aromatic hydrocarbons (PAHs) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in experimental animals; these chemical carcinogens are activated by human P450 1 and 2A family enzymes, respectively, to carcinogenic metabolites. In this study, we examined whether these selenium compounds interact with and inhibit human P450 1 and 2A enzymes in vitro. Four organoselenium compounds induced Reverse Type I binding spectra with P450 1A1, 1A2, and 1B1 and Type I binding spectra with P450 2A6 and 2A13. The spectral dissociation constants (Ks) for the interaction of P450 1B1 with these chemicals were 3.6–5.7 µM; the values were lower than those with seen with P450 1A1 (19–30 µM) or 1A2 (6.3–13 µM). The Ks values for Type I binding of P450 2A13 with m-XSC and BSC were both 0.20 µM; the values were very low compared to the interaction of P450 2A6 with m-XSC (5.7 µM) and BSC (2.0 µM). Four selenium compounds directly inhibited 7-ethoxyresorufin O-deethylation activities catalyzed by P450 1A1, 1A2, and 1B1 with IC50 values <1.0 µM, except for the inhibition of P450 1A2 by BSC (1.3 µM). Coumarin 7-hydroxylation activities of P450 2A13 were more inhibited by four selenium compounds than those of P450 2A6, with IC50 values of 0.22–1.4 µM for P450 2A13 and 2.4–6.2 µM for P450 2A6. Molecular docking studies of the interaction of four organoselenium compounds with human P450 enzymes suggest that these chemicals can be docked into the active sites of these human P450 enzymes and that the sites of the selenocyanate functional groups of these chemicals differ between the P450 1 and 2A family enzymes. PMID:21732699

  17. Induction of Cyp1a1 and Cyp1b1 and formation of DNA adducts in C57BL/6, Balb/c, and F1 mice following in utero exposure to 3-methylcholanthrene

    SciTech Connect

    Xu Mian; Nelson, Garret B.; Moore, Joseph E.; McCoy, Thomas P.; Dai, Jian; Manderville, Richard A.; Ross, Jeffrey A.; Miller, Mark Steven . E-mail: msmiller@wfubmc.edu

    2005-11-15

    Fetal mice are more sensitive to chemical carcinogens than are adults. Previous studies from our laboratory demonstrated differences in the mutational spectrum induced in the Ki-ras gene from lung tumors isolated from [D2 x B6D2F1]F2 mice and Balb/c mice treated in utero with 3-methylcholanthrene (MC). We thus determined if differences in metabolism, adduct formation, or adduct repair influence strain-specific responses to transplacental MC exposure in C57BL/6 (B6), Balb/c (BC), and reciprocal F1 crosses between these two strains of mice. The induction of Cyp1a1 and Cyp1b1 in fetal lung and liver tissue was determined by quantitative fluorescent real-time PCR. MC treatment caused maximal induction of Cyp1a1 and Cyp1b1 RNA 2-8 h after injection in both organs. RNA levels for both genes then declined in both fetal organs, but a small biphasic, secondary increase in Cyp1a1 was observed specifically in the fetal lung 24-48 h after MC exposure in all four strains. Cyp1a1 induction by MC at 4 h was 2-5 times greater in fetal liver (7000- to 16,000-fold) than fetal lung (2000- to 6000-fold). Cyp1b1 induction in both fetal lung and liver was similar and much lower than that observed for Cyp1a1, with induction ratios of 8- to 18-fold in fetal lung and 10- to 20-fold in fetal liver. The overall kinetics and patterns of induction were thus very similar across the four strains of mice. The only significant strain-specific effect appeared to be the relatively poor induction of Cyp1b1 in the parental strain of B6 mice, especially in fetal lung tissue. We also measured the levels of MC adducts and their disappearance from lung tissue by the P{sup 32} post-labeling assay on gestation days 18 and 19 and postnatal days 1, 4, 11, and 18. Few differences were seen between the different strains of mice; the parental strain of B6 mice had nominally higher levels of DNA adducts 2 (gestation day 19) and 4 (postnatal day 1) days after injection, although this was not statistically

  18. Theoretical Studies of Observable Transitions to Recoupled Pair Bonded States of Sulfur Halide Compounds: SF/SCl (X^2{Π}{→}A^2{Σ}^-), SF_2/SCl_2 (X^1A_1{→}1^1B_1, X^1A_1{→}1^1A_2), and SFCl (X^1A'{→}A^1A{'{'}})

    NASA Astrophysics Data System (ADS)

    Leiding, Jeff; Woon, David E.; Dunning, Thom H.; , Jr.

    2011-06-01

    In previous studies regarding the nature of hypervalent behavior, we identified low-lying excited states of SF(a^4{Σ}^-), SCl(a^4{Σ}^-), SF_2(a^3B_1,b^3A_2), SFCl(a^3A{'{'}}) and SCl_2(a^3B_1) that involve recoupled pair bonding (rpb), where the electrons of the S 3p^2 pair are made available to form bonds. While the transitions from the ground states to the quartet states of SF/SCl and the triplet states of SF_2/SFCl/SCl_2 are spin-forbidden, each of these excited states have analogs with formally spin- and dipole-allowed transitions (except ^1A_2). We performed high level MRCI+Q/aug-cc-pV(Q+d)Z calculations in order to characterize the electronic spectra, spectroscopic constants, and bonding of these species, and made comparisons to available experimental data. We found that excitation into the experimentally known and dipole-forbidden singlet rpb state, SCl_2(B^1A_2), can explain the well-known photodissociation behavior of SCl_2 used to produce SCl(X^2{Π}) radicals in the laboratory. Finally, we have also found a possible system of bond-stretch isomers on the SFCl(A^1A{'{'}}) potential energy surface that is analogous to the behavior on the triplet surface reported in our previous study. Howe, J. D.; Ashfold, M. N. R.; Morgan, R. A.;Western, C. M.; Buma, W. J.; Milan, J. B. and de Lang, C. A. J. Chem. Soc. Faraday Trans. 1995, 91, 773. Leiding, J.; Woon, D. E., and Dunning, T. H., Jr. J. Phys. Chem. A 2011, 115, 329.

  19. Induction of CYP1A1, CYP1A2, CYP1B1, increased oxidative stress and inflammation in the lung and liver tissues of rats exposed to incense smoke.

    PubMed

    Hussain, Tajamul; Al-Attas, Omar S; Al-Daghri, Nasser M; Mohammed, Arif A; De Rosas, Edgard; Ibrahim, Shebl; Vinodson, Benjamin; Ansari, Mohammed G; El-Din, Khaled I Alam

    2014-06-01

    Incense smoke is increasingly being recognized as a potential environmental contaminant and is linked to malignant and non-malignant respiratory diseases. The detoxification of environmental contaminants including polycyclic aromatic hydrocarbons (PAHs) involves the induction of cytochrome P-450 family enzymes (CYPs) by PAHs. However, the detoxification of PAHs also results in the generation of reactive and unstable intermediary metabolites which are implicated in the oxidative stress, DNA damage, and inflammation. It is unclear whether CYPs are similarly induced by incense smoke, which incidentally contains substantial amounts of PAHs. Here, we examined the impact of long-term incense smoke exposure on the induction of CYPs in male Wister Albino rats. Incense smoke exposure significantly induced the expression of CYP1A1, CYP1A2, and CYP1B1 mRNAs in both lung and liver tissues. The extent of CYP1A1 and CYP1B1 induction was significantly higher in the liver compared to that in the lung, while that of CYP1A2 was greater in the lung than in liver. Incense smoke exposure also increased malondialdehyde and reduced glutathione levels in lung and liver tissues, and the catalase activity in the liver tissues to significant levels. Furthermore incense smoke exposure led to a marked increase in TNF-α and IL-4 levels. The data demonstrate for the first time the capacity of incense smoke to induce CYP1 family enzymes in the target and non-target tissues. Induction of CYPs increased oxidative stress and inflammation appear to be intimately linked to promote the carcinogenesis and health complications in people chronically exposed to incense smoke.

  20. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) in children and adults with primary adrenal failure: ten years' experience

    PubMed Central

    Lin, Lin; Gu, Wen-Xia; Ozisik, Gokhan; To, Wing S.; Owen, Catherine J.; Jameson, J. Larry; Achermann, John C.

    2007-01-01

    Context Primary adrenal failure is a life-threatening condition that can be caused by a range of etiologies, including autoimmune, metabolic, and developmental disorders. The nuclear receptors DAX1 (NR0B1) and steroidogenic factor-1 (SF1/Ad4BP, NR5A1) play an important role in adrenal development and function, and mutations in these transcription factors have been found in patients with adrenal hypoplasia. Objective To investigate the prevalence of DAX1 and SF1 mutations in children and adults with primary adrenal failure of unknown etiology (i.e., not caused by congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune disease). Patients One-hundred and seventeen patients were included. Eighty-eight individuals presented in infancy or childhood with adrenal hypoplasia or primary adrenal failure of unknown etiology (n=64, 46,XY phenotypic males; n=17, 46,XY gonadal dysgenesis/impaired androgenization; n=7, 46,XX females). Twenty-nine individuals presented in adulthood with “Addison disease” of unknown etiology. Methods Mutational analysis of DAX1 (NR0B1) (including exon 2α/1A) and SF1 (NR5A1) by direct sequencing. Results DAX1 mutations were found in 58% (37/64) of 46,XY phenotypic boys referred with adrenal hypoplasia, and in all boys (8/8) with hypogonadotropic hypogonadism and a family history suggestive of adrenal failure in males. SF1 mutations causing adrenal failure were found only in two patients with 46,XY gonadal dysgenesis. No DAX1 or SF1 mutations were identified in the adult-onset group. Conclusions DAX1 mutations are a relatively frequent cause of adrenal failure in this group of boys. SF1 mutations causing adrenal failure in humans are rare and are more likely to be associated with significant underandrogenization and gonadal dysfunction in 46,XY individuals. PMID:16684822

  1. First analysis of the 1-v″ progression of the Ångström (B1Σ+-A1Π) band system in the rare 13C17O isotopologue.

    PubMed

    Hakalla, Rafał; Zachwieja, Mirosław; Szajna, Wojciech

    2013-11-27

    The 1-v″ progression of the Ångström band system, so far unobserved in the rare (13)C(17)O isotopologue, was obtained under high resolution as an emission spectrum using a high accuracy dispersive optical spectroscopy. In the studied region 22,700-24,500 cm(-1), 146 spectral lines were observed, among which 118 were interpreted as belonging to the 1-0 and 1-1 bands of B-A system, and the next 28 were interpreted as extra lines belonging to the 1-1 band of B(1)Σ(+)-e(3)Σ(-) intercombination system, also unobserved in the (13)C(17)O molecule so far. All those lines were precisely measured with an estimated accuracy better than 0.0025 cm(-1), and rotationally analyzed. As a result the following in the (13)C(17)O molecule were calculated for the first time: the merged rotational constants B1 = 1.790227(23) cm(-1), D1 = 6.233(47) × 10(-6) cm(-1), and ΔG1/2 = 2010.9622 (69) cm(-1) and the equilibrium constants, ωe = 2076.04(57) cm(-1), ωexe = 32.54(28) cm(-1), Be = 1.824678(15) cm(-1), αe = 2.2967(24) × 10(-2) cm(-1), De = 5.226(25) × 10(-6) cm(-1), and βe = 6.71(48) × 10(-7) cm(-1) for the B(1)Σ(+) Rydberg state, as well as the individual rotational constant B0 = 1.50485(78) cm(-1), and the equilibrium constants ωe = 1463.340(21) cm(-1), Be = 1.49902(12) cm(-1), αe = 1.7782(49) × 10(-2) cm(-1), De = 7.36(56) × 10(-6) cm(-1) for the A(1)Π state, and σe = 21,854.015(51) cm(-1), RKR turning points, Franck-Condon factors (FCF), relative intensities, and r centroids for the Ångström band system. With the help of the strong and vast A(1)Π (v = 0) ∼ e(3)Σ(-) (v = 1) interaction, the experimental parameters of the e(3)Σ(-) (v = 1) perturbing state were established in the (13)C(17)O molecule for the first time.

  2. Maternal protein restriction during lactation modulated the expression and activity of rat offspring hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1 during development.

    PubMed

    Da Costa, N Meireles; Visoni, S B C; Dos Santos, I L; Barja-Fidalgo, T C; Ribeiro-Pinto, L F

    2016-01-01

    Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring's CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8- fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities' alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development.

  3. Maternal protein restriction during lactation modulated the expression and activity of rat offspring hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2, and CYP2E1 during development

    PubMed Central

    Da Costa, N. Meireles; Visoni, S.B.C.; Dos Santos, I.L.; Barja-Fidalgo, T.C.; Ribeiro-Pinto, L.F.

    2016-01-01

    Early nutrition plays a long-term role in the predisposition to chronic diseases and influences the metabolism of several drugs. This may happen through cytochromes P450 (CYPs) regulation, which are the main enzymes responsible for the metabolism of xenobiotics. Here, we analyzed the effects of maternal protein restriction (MPR) on the expression and activity of hepatic offspring’s CYPs during 90 days after birth, using Wistar rats as a mammal model. Hepatic CYP1A1, CYP1A2, CYP2B1, CYP2B2 and CYP2E1 mRNA and protein expression, and associated catalytic activities (ECOD, EROD, MROD, BROD, PROD and PNPH) were evaluated in 15-, 30-, 60-, and 90-day-old offspring from dams fed with either a 0% protein (MPR groups) or a standard diet (C groups) during the 10 first days of lactation. Results showed that most CYP genes were induced in 60- and 90-day-old MPR offspring. The inductions detected in MPR60 and MPR90 were of 5.0- and 2.0-fold (CYP1A2), 3.7- and 2.0-fold (CYP2B2) and 9.8- and 5.8– fold (CYP2E1), respectively, and a 3.8-fold increase of CYP2B1 in MPR90. No major alterations were detected in CYP protein expression. The most relevant CYP catalytic activities’ alterations were observed in EROD, BROD and PNPH. Nevertheless, they did not follow the same pattern observed for mRNA expression, except for an induction of EROD in MPR90 (3.5-fold) and of PNPH in MPR60 (2.2-fold). Together, these results suggest that MPR during lactation was capable of altering the expression and activity of the hepatic CYP enzymes evaluated in the offspring along development. PMID:27828666

  4. Boeing XF2B-1 (F2B-1)

    NASA Technical Reports Server (NTRS)

    1931-01-01

    Boeing XF2B-1 (F2B-1): Serving as the prototype for the F2B-1 shipboard fighter, the XF2B-1 differed visually in having a pointed spinner and an unbalanced rudder. Like many aircraft of its day, the Boeing model 69 was powered by a Pratt & Whitney Wasp radial engine.

  5. Antifungal activity of the primycin complex and its main components A1, A2 and C1 on a Candida albicans clinical isolate, and their effects on the dynamic plasma membrane changes.

    PubMed

    Virág, Eszter; Belagyi, Joseph; Kocsubé, Sándor; Vágvölgyi, Csaba; Pesti, Miklós

    2013-02-01

    The in vitro antifungal activities of the macrolide lactone antibiotic complex primycin (PC) and its main components, A1 (50%), A2 (7.3%) and C1 (13%), against the opportunistic pathogenic fungus Candida albicans 33erg(+)were determined by microdilution testing. The MIC(100) (the minimal concentration required for 100% growth inhibition) values found, A2 (2 μg ml(-1)), PC (32 μg ml(-1)), A1 (32 μg ml(-1)) and C1 (64 μg ml(-1)), suggested that the biological activity of PC is highly dependent on the proportions of its constituents. In vivo measurements of the biophysical properties of plasma membranes were carried out by electron paramagnetic resonance (EPR) spectroscopic methods, using the spin probe 5-(4,4-dimethyloxazolidine-N-oxyl)stearic acid. Conventional EPR measurements demonstrated altered phase transition temperatures (Tm) of the plasma membrane of strain 33erg(+) as a consequence of treatment with PC or its constituents: for cells treated with 128 μg ml(-1) PC, A1, A2 or C1 for 15 min, Tm was 17, 21, 14.5 and 15 °C, respectively; that is significantly higher than the Tm of untreated cells, 12 °C. The molecular motions of the near-surface hydrophobic region of the plasma membrane, estimated by saturation transfer EPR spectroscopy, reflected changes in the membrane phases after the treatment. Two physiological membrane phases were detected in control samples: liquid-ordered and liquid-disordered, characterized by molecular movements ∼10(-6)-10(-8) s and ≥10(-9) s. The cells treated with the investigated compounds showed the strong presence of a non-physiological gel phase additional to the above phases, characterized by movements ≤10(-5) s.

  6. Line-shape theory of the X3Σg-→a1Δg,b1Σg+ transitions in O2-O2 collision-induced absorption

    NASA Astrophysics Data System (ADS)

    Karman, Tijs; van der Avoird, Ad; Groenenboom, Gerrit C.

    2017-08-01

    We derive the theory of collision-induced absorption for electronic transitions in the approximation of an isotropic interaction potential. We apply this theory to the spin-forbidden X3Σg-→a1Δg and X3Σg-→b1Σg+ transitions in O2-O2, which are relevant for calibration in atmospheric studies. We consider two mechanisms for breaking the spin symmetry, either by the intermolecular exchange interaction between paramagnetic collision partners or by the intramolecular spin-orbit coupling. The calculations for the exchange-based mechanism employ the diabatic potential energy surfaces and transition dipole moment surfaces reported in Paper I [T. Karman et al., J. Chem. Phys. 147, 084306 (2017)]. We show that the line shape of the theoretical absorption spectra is insensitive to the large uncertainty in the electronic transition dipole moment surfaces. We also perform calculations using a simple model of the alternative mechanism involving intramolecular spin-orbit coupling, which leads to absorption intensities which are well below the experimental results. The relative intensity of this spin-orbit-based mechanism may impact the relative contribution to the absorption by collisions with diamagnetic collision partners, such as the atmospherically relevant N2 molecule. We furthermore show that both the line shape and temperature dependence are signatures of the underlying transition mechanism.

  7. High Resolution Spectroscopy of A^1B1u ← X^1A_g 8^1_04^1_0 Band of Naphthalene Referenced to AN Optical Frequency Comb

    NASA Astrophysics Data System (ADS)

    Nakashima, Kazuki; Nishiyama, Akiko; Misono, Masatoshi

    2016-06-01

    In the excited vibronic states of naphthalene, there exist various interesting interactions such as intramolecular vibrational energy redistribution (IVR), intersystem crossing (ISC), and internal conversion (IC). More than thirty yeas ago, Beck et al. showed that IVR became remarkable when the excess energy exceeded about 2000 cm-1^, ^a. In the present study, we observe Doppler-free two-photon absorption spectra of A^1B1u ← X^1A_g 8^1_04^1_0 band of naphthalene around 34281 cm-1. The excess energy is 2261 cm-1, which is just above the threshold of IVR. Thus we expect this band is suitable to analyze the dynamics in the excited vibronic states. In our experiment, the spectral resolution is about 100 kHz, and rovibronic lines are well-resolved. To decide the transition frequencies, frequency shifts, and spectral linewidths with high accuracy and precision, we employed the comb-referenced Doppler-free two-photon absorption spectroscopic system^b. We proceed to assign the rovibronic lines in ^qQ transition, and to determine molecular constants in the excited vibronic state. ^a S. M. Beck, J. B. Hopkins, D. E. Powers, and R. E. Smalley, J. Chem. Phys. 74, 43(1981). ^b A. Nishiyama, K. Nakashima, A. Matsuba, and M. Misono, J. Mol. Spectrosc. 318, 40 (2015).

  8. Areca Nut Components Affect COX-2, Cyclin B1/cdc25C and Keratin Expression, PGE2 Production in Keratinocyte Is Related to Reactive Oxygen Species, CYP1A1, Src, EGFR and Ras Signaling

    PubMed Central

    Chang, Hsiao-Hua; Chan, Chiu-Po; Yeh, Chien-Yang; Wang, Yin-Lin; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

    2014-01-01

    Aims Chewing of betel quid (BQ) increases the risk of oral cancer and oral submucous fibrosis (OSF), possibly by BQ-induced toxicity and induction of inflammatory response in oral mucosa. Methods Primary gingival keratinocytes (GK cells) were exposed to areca nut (AN) components with/without inhibitors. Cytotoxicity was measured by 3-(4,5-dimethyl- thiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. mRNA and protein expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. PGE2/PGF2α production was measured by enzyme-linked immunosorbent assays. Results Areca nut extract (ANE) stimulated PGE2/PGF2α production, and upregulated the expression of cyclooxygenase-2 (COX-2), cytochrome P450 1A1 (CYP1A1) and hemeoxygenase-1 (HO-1), but inhibited expression of keratin 5/14, cyclinB1 and cdc25C in GK cells. ANE also activated epidermal growth factor receptor (EGFR), Src and Ras signaling pathways. ANE-induced COX-2, keratin 5, keratin 14 and cdc25C expression as well as PGE2 production were differentially regulated by α–naphthoflavone (a CYP 1A1/1A2 inhibitor), PD153035 (EGFR inhibitor), pp2 (Src inhibitor), and manumycin A (a Ras inhibitor). ANE-induced PGE2 production was suppressed by piper betle leaf (PBL) extract and hydroxychavicol (two major BQ components), dicoumarol (a NAD(P)H:Quinone Oxidoreductase - NQO1 inhibitor) and curcumin. ANE-induced cytotoxicity was inhibited by catalase and enhanced by dicoumarol, suggesting that AN components may contribute to the pathogenesis of OSF and oral cancer via induction of aberrant differentiation, cytotoxicity, COX-2 expression, and PGE2/PGF2αproduction. Conclusions CYP4501A1, reactive oxygen species (ROS), EGFR, Src and Ras signaling pathways could all play a role in ANE-induced pathogenesis of oral cancer. Addition of PBL into BQ and curcumin consumption could inhibit the ANE-induced inflammatory response. PMID:25051199

  9. Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2 production in keratinocyte is related to reactive oxygen species, CYP1A1, Src, EGFR and Ras signaling.

    PubMed

    Chang, Mei-Chi; Chen, Yi-Jane; Chang, Hsiao-Hua; Chan, Chiu-Po; Yeh, Chien-Yang; Wang, Yin-Lin; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

    2014-01-01

    Chewing of betel quid (BQ) increases the risk of oral cancer and oral submucous fibrosis (OSF), possibly by BQ-induced toxicity and induction of inflammatory response in oral mucosa. Primary gingival keratinocytes (GK cells) were exposed to areca nut (AN) components with/without inhibitors. Cytotoxicity was measured by 3-(4,5-dimethyl- thiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. mRNA and protein expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. PGE2/PGF2α production was measured by enzyme-linked immunosorbent assays. Areca nut extract (ANE) stimulated PGE2/PGF2α production, and upregulated the expression of cyclooxygenase-2 (COX-2), cytochrome P450 1A1 (CYP1A1) and hemeoxygenase-1 (HO-1), but inhibited expression of keratin 5/14, cyclinB1 and cdc25C in GK cells. ANE also activated epidermal growth factor receptor (EGFR), Src and Ras signaling pathways. ANE-induced COX-2, keratin 5, keratin 14 and cdc25C expression as well as PGE2 production were differentially regulated by α-naphthoflavone (a CYP 1A1/1A2 inhibitor), PD153035 (EGFR inhibitor), pp2 (Src inhibitor), and manumycin A (a Ras inhibitor). ANE-induced PGE2 production was suppressed by piper betle leaf (PBL) extract and hydroxychavicol (two major BQ components), dicoumarol (a Quinone Oxidoreductase--NQO1 inhibitor) and curcumin. ANE-induced cytotoxicity was inhibited by catalase and enhanced by dicoumarol, suggesting that AN components may contribute to the pathogenesis of OSF and oral cancer via induction of aberrant differentiation, cytotoxicity, COX-2 expression, and PGE2/PGF2α production. CYP4501A1, reactive oxygen species (ROS), EGFR, Src and Ras signaling pathways could all play a role in ANE-induced pathogenesis of oral cancer. Addition of PBL into BQ and curcumin consumption could inhibit the ANE-induced inflammatory response.

  10. Potential energy and dipole moment surfaces of the triplet states of the O2(X3Σg-) - O2(X3Σg-,a1Δg,b1Σg+) complex

    NASA Astrophysics Data System (ADS)

    Karman, Tijs; van der Avoird, Ad; Groenenboom, Gerrit C.

    2017-08-01

    We compute four-dimensional diabatic potential energy surfaces and transition dipole moment surfaces of O2-O2, relevant for the theoretical description of collision-induced absorption in the forbidden X3Σg- → a1Δg and X3Σg- → b1Σg+ bands at 7883 cm-1 and 13 122 cm-1, respectively. We compute potentials at the multi-reference configuration interaction (MRCI) level and dipole surfaces at the MRCI and complete active space self-consistent field (CASSCF) levels of theory. Potentials and dipole surfaces are transformed to a diabatic basis using a recent multiple-property-based diabatization algorithm. We discuss the angular expansion of these surfaces, derive the symmetry constraints on the expansion coefficients, and present working equations for determining the expansion coefficients by numerical integration over the angles. We also present an interpolation scheme with exponential extrapolation to both short and large separations, which is used for representing the O2-O2 distance dependence of the angular expansion coefficients. For the triplet ground state of the complex, the potential energy surface is in reasonable agreement with previous calculations, whereas global excited state potentials are reported here for the first time. The transition dipole moment surfaces are strongly dependent on the level of theory at which they are calculated, as is also shown here by benchmark calculations at high symmetry geometries. Therefore, ab initio calculations of the collision-induced absorption spectra cannot become quantitatively predictive unless more accurate transition dipole surfaces can be computed. This is left as an open question for method development in electronic structure theory. The calculated potential energy and transition dipole moment surfaces are employed in quantum dynamical calculations of collision-induced absorption spectra reported in Paper II [T. Karman et al., J. Chem. Phys. 147, 084307 (2017)].

  11. Potential energy and dipole moment surfaces of the triplet states of the O2(X(3)Σg(-)) - O2(X(3)Σg(-),a(1)Δg,b(1)Σg(+)) complex.

    PubMed

    Karman, Tijs; van der Avoird, Ad; Groenenboom, Gerrit C

    2017-08-28

    We compute four-dimensional diabatic potential energy surfaces and transition dipole moment surfaces of O2-O2, relevant for the theoretical description of collision-induced absorption in the forbidden X(3)Σg(-) → a(1)Δg and X(3)Σg(-) → b(1)Σg(+) bands at 7883 cm(-1) and 13 122 cm(-1), respectively. We compute potentials at the multi-reference configuration interaction (MRCI) level and dipole surfaces at the MRCI and complete active space self-consistent field (CASSCF) levels of theory. Potentials and dipole surfaces are transformed to a diabatic basis using a recent multiple-property-based diabatization algorithm. We discuss the angular expansion of these surfaces, derive the symmetry constraints on the expansion coefficients, and present working equations for determining the expansion coefficients by numerical integration over the angles. We also present an interpolation scheme with exponential extrapolation to both short and large separations, which is used for representing the O2-O2 distance dependence of the angular expansion coefficients. For the triplet ground state of the complex, the potential energy surface is in reasonable agreement with previous calculations, whereas global excited state potentials are reported here for the first time. The transition dipole moment surfaces are strongly dependent on the level of theory at which they are calculated, as is also shown here by benchmark calculations at high symmetry geometries. Therefore, ab initio calculations of the collision-induced absorption spectra cannot become quantitatively predictive unless more accurate transition dipole surfaces can be computed. This is left as an open question for method development in electronic structure theory. The calculated potential energy and transition dipole moment surfaces are employed in quantum dynamical calculations of collision-induced absorption spectra reported in Paper II [T. Karman et al., J. Chem. Phys. 147, 084307 (2017)].

  12. Development and validation of ultra-high-performance liquid chromatography-tandem mass spectrometry methods for the simultaneous determination of beauvericin, enniatins (A, A1, B, B1) and cereulide in maize, wheat, pasta and rice.

    PubMed

    Decleer, Marlies; Rajkovic, Andreja; Sas, Benedikt; Madder, Annemieke; De Saeger, Sarah

    2016-11-11

    Rapid and accurate UPLC-MS/MS methods for the simultaneous determination of beauvericin and the related enniatins (A, A1, B, B1), together with cereulide were successfully developed and validated in cereal and cereal-based food matrices such as wheat, maize, rice and pasta. Although these emerging foodborne toxins are of different microbial origin, the similar structural, toxicological and food safety features provided rationale for their concurrent detection in relevant food matrices. A Waters Acquity UPLC system coupled to a Waters Quattro Premier XE™ Mass Spectrometer operating in ESI+ mode was employed. Sample pretreatment involved a fast and simple liquid extraction of the target toxins without any further clean-up step. For all toxins the sample preparation resulted in acceptable extraction recoveries with values of 85-105% for wheat, 87-106% for maize, 84-106% for rice and 85-105% for pasta. The efficient extraction protocol, together with a fast chromatographic separation of 7min allowed substantial saving costs and time showing its robustness and performance. The validation of the developed method was performed based on Commission Decision 2002/657/EC. The obtained limits of detection ranged from 0.1 to 1.0μgkg(-1) and the limits of quantification from 0.3 to 2.9μgkg(-1) for the targeted toxins in the selected matrices. The obtained sensitivities allow detection of relevant toxicological concentrations. All relative standard deviations for repeatability (intra-day) and intermediate precision (inter-day) were lower than 20%. Trueness, expressed as the apparent recovery varied from 80 to 107%. The highly sensitive and repeatable validated method was applied to 57 naturally contaminated samples allowing detection of sub-clinical doses of the toxins. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. MRCI study on the spectroscopic parameters and molecular constants of the X1Σ+, a3Σ+, A1Π and C1Σ- electronic states of the SiO molecule.

    PubMed

    Shi, Deheng; Li, Wentao; Sun, Jinfeng; Zhu, Zunlue

    2012-02-15

    The potential energy curves (PECs) of the X(1)Σ(+), a(3)Σ(+), A(1)Π and C(1)Σ(-) electronic states of the SiO molecule are studied using an ab initio quantum chemical method. The calculations have been made employing the complete active space self-consistent field (CASSCF) method, which is followed by the valence internally contracted multireference configuration interaction (MRCI) approach in combination with several correlation-consistent basis sets. The effect on the PECs by the core-valence correlation and relativistic corrections is included. The way to consider the relativistic correction is to use the third-order Douglas-Kroll Hamiltonian approximation. The core-valence correlation correction is carried out with the cc-pCVQZ basis set, and the relativistic correction is performed at the level of the cc-pVQZ basis set. To obtain more reliable results, the PECs determined by the MRCI calculations are also corrected for size-extensivity errors by means of the Davidson modification (MRCI+Q). The PECs of these electronic states are extrapolated to the complete basis set limit by the total-energy extrapolation scheme. Employing these PECs, the spectroscopic parameters are calculated and compared with those reported in the literature. With these PECs determined by the MRCI+Q/CV+DK+56 calculations, by solving the radial Schrödinger equation of nuclear motion, 110 vibrational states for the X(1)Σ(+), 69 for the a(3)Σ(+), 54 for the A(1)Π and 67 for the C(1)Σ(-) electronic state are predicted when the rotational quantum number J equals zero. The vibrational manifolds of the first 20 vibrational states are reported and compared with the available RKR data for each electronic state. On the whole, as expected, the most accurate spectroscopic parameters and molecular constants of the SiO molecule are obtained by the MRCI+Q/CV+DK+56 calculations. And the present molecular constants of the a(3)Σ(+), C(1)Σ(-) and A(1)Π electronic states determined by the MRCI

  14. The TiO c1Φ- a1Δ (0-0) Band at Sub-Doppler Spectral Resolution: Spin-Orbit Interactions in the cState

    NASA Astrophysics Data System (ADS)

    Amiot, C.; Cheikh, M.; Luc, P.; Vetter, R.

    1996-09-01

    The c1Φ- a1Δ (0-0) band of titanium monoxide has been studied at sub-Doppler resolution by crossing a beam of TiO molecules with a cw tunable laser beam and collecting the laser-induced fluorescence. The rotational structures of the P, Q, and Rbranches have been observed up to rotational quantum numbers equal to 52, 94, and 96, respectively. The spectroscopic data have been reduced to a set of 11 effective molecular constants with a root mean squared values of the residuals equal to 7 × 10 -4cm -1. However, the necessity of including seventh order terms in the rotational development of the energy put into evidence a very strong spin-orbit interaction between the c1Φ ( v= 0) and C3Δ 3( v= 2 and v= 3) levels. The derived spin-orbit parameter allows for the reproduction of the measured wavenumbers without the introduction of higher order rotational terms into the energy development. The value of the spin-orbit parameter indicates the necessity of revisiting the configuration scheme of the involved electronic states.

  15. OH radio observations of comets P/Brorsen-Metcalf (1989o), Okazaki-Levy-Rudenko (1989r), Aarseth-Brewington (1989a1), and Austin (1989c1) at the Nancay radio telescope

    NASA Technical Reports Server (NTRS)

    Bockelee-Morvan, D.; Crovisier, J.; Gerard, E.; Bourgois, G.

    1990-01-01

    The 1667 MHz and 1665 MHz transitions of the OH radical were recently monitored in several comets with the Nancay radio telescope: P/Brorsen-Metcalf (1989o) (August 4 to October 31, 1989), Okazaki-Levy-Rudenko (1989r) (October 3 to December 2, 1989), Aarseth-Brewington (1989a1) (December 8 to 30, 1989), and Austin (1989c1) (February 15 to June 14, 1990). Present gas expansion measurements obtained from the analysis of the line shapes are presented and the long term variations of the water production rate, as measured from the OH radio lines. On October 13, 1989, the occultation of a background source by comet Okazaki-Levy-Rudenko (1989r) was fortuitously observed. A preliminary report of this observation is given. Further analysis of the data is continuing.

  16. OH radio observations of comets P/Brorsen-Metcalf (1989o), Okazaki-Levy-Rudenko (1989r), Aarseth-Brewington (1989a1), and Austin (1989c1) at the Nancay radio telescope

    NASA Technical Reports Server (NTRS)

    Bockelee-Morvan, D.; Crovisier, J.; Gerard, E.; Bourgois, G.

    1990-01-01

    The 1667 MHz and 1665 MHz transitions of the OH radical were recently monitored in several comets with the Nancay radio telescope: P/Brorsen-Metcalf (1989o) (August 4 to October 31, 1989), Okazaki-Levy-Rudenko (1989r) (October 3 to December 2, 1989), Aarseth-Brewington (1989a1) (December 8 to 30, 1989), and Austin (1989c1) (February 15 to June 14, 1990). Present gas expansion measurements obtained from the analysis of the line shapes are presented and the long term variations of the water production rate, as measured from the OH radio lines. On October 13, 1989, the occultation of a background source by comet Okazaki-Levy-Rudenko (1989r) was fortuitously observed. A preliminary report of this observation is given. Further analysis of the data is continuing.

  17. Camel Milk Modulates the Expression of Aryl Hydrocarbon Receptor-Regulated Genes, Cyp1a1, Nqo1, and Gsta1, in Murine hepatoma Hepa 1c1c7 Cells

    PubMed Central

    Korashy, Hesham M.; El Gendy, Mohamed A. M.; Alhaider, Abdulqader A.; El-Kadi, Ayman O.

    2012-01-01

    There is a traditional belief in the Middle East that camel milk may aid in prevention and treatment of numerous cases of cancer yet, the exact mechanism was not investigated. Therefore, we examined the ability of camel milk to modulate the expression of a well-known cancer-activating gene, Cytochrome P450 1a1 (Cyp1a1), and cancer-protective genes, NAD(P)H:quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase a1 (Gsta1), in murine hepatoma Hepa 1c1c7 cell line. Our results showed that camel milk significantly inhibited the induction of Cyp1a1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent Cyp1a1 inducer and known carcinogenic chemical, at mRNA, protein, and activity levels in a concentration-dependent manner. In addition, camel milk significantly decreased the xenobiotic responsive element (XRE)-dependent luciferase activity, suggesting a transcriptional mechanism is involved. Furthermore, this inhibitory effect of camel milk was associated with a proportional increase in heme oxygenase 1. On the other hand, camel milk significantly induced Nqo1 and Gsta1 mRNA expression level in a concentration-dependent fashion. The RNA synthesis inhibitor, actinomycin D, completely blocked the induction of Nqo1 mRNA by camel milk suggesting the requirement of de novo RNA synthesis through a transcriptional mechanism. In conclusion, camel milk modulates the expression of Cyp1a1, Nqo1, and Gsta1 at the transcriptional and posttranscriptional levels. PMID:22570534

  18. Camel milk modulates the expression of aryl hydrocarbon receptor-regulated genes, Cyp1a1, Nqo1, and Gsta1, in murine hepatoma Hepa 1c1c7 cells.

    PubMed

    Korashy, Hesham M; El Gendy, Mohamed A M; Alhaider, Abdulqader A; El-Kadi, Ayman O

    2012-01-01

    There is a traditional belief in the Middle East that camel milk may aid in prevention and treatment of numerous cases of cancer yet, the exact mechanism was not investigated. Therefore, we examined the ability of camel milk to modulate the expression of a well-known cancer-activating gene, Cytochrome P450 1a1 (Cyp1a1), and cancer-protective genes, NAD(P)H:quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase a1 (Gsta1), in murine hepatoma Hepa 1c1c7 cell line. Our results showed that camel milk significantly inhibited the induction of Cyp1a1 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent Cyp1a1 inducer and known carcinogenic chemical, at mRNA, protein, and activity levels in a concentration-dependent manner. In addition, camel milk significantly decreased the xenobiotic responsive element (XRE)-dependent luciferase activity, suggesting a transcriptional mechanism is involved. Furthermore, this inhibitory effect of camel milk was associated with a proportional increase in heme oxygenase 1. On the other hand, camel milk significantly induced Nqo1 and Gsta1 mRNA expression level in a concentration-dependent fashion. The RNA synthesis inhibitor, actinomycin D, completely blocked the induction of Nqo1 mRNA by camel milk suggesting the requirement of de novo RNA synthesis through a transcriptional mechanism. In conclusion, camel milk modulates the expression of Cyp1a1, Nqo1, and Gsta1 at the transcriptional and posttranscriptional levels.

  19. The influence of genetic polymorphisms in Ahr, CYP1A1, CYP1A2, CYP1B1, GST M1, GST T1 and UGT1A1 on urine 1-hydroxypyrene glucuronide concentrations in healthy subjects from Rio Grande do Sul, Brazil.

    PubMed

    Abnet, Christian C; Fagundes, Renato B; Strickland, Paul T; Kamangar, Farin; Roth, Mark J; Taylor, Philip R; Dawsey, Sanford M

    2007-01-01

    Polymorphisms in genes encoding polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes may alter metabolism of these carcinogens and contribute to inter-individual difference in urine concentrations. We investigated the influence of genetic polymorphism on PAH metabolism in urine from 199 healthy subjects from Southern Brazil. We measured urine 1-hydroxypyrene glucuronide (1-OHPG) concentrations using immunoaffinity chromatography and synchronous fluorescence spectroscopy and genotyped subjects using standard methods. Genetic variants in CYP1B1 (rs1056827, rs1800440, rs10012) were strongly associated with urine 1-OHPG with P-values < 0.010. Variants in aryl hydrocarbon receptor (Ahr) (rs4986826), CYP1A1 (rs1799814) and CYP1A2 (rs2069514) were also, although less strongly, associated with changes in urine 1-OHPG concentrations. These variants had P-values of 0.074, 0.040 and 0.025, respectively. The median urine 1-OHPG concentrations (pmol/ml) in the homozygous wild-type and homozygous variants for CYP1B1 (rs10012) and the Ahr, CYP1A1 and CYP1A2 variants listed above were 2.16 and 0.10, 2.16 and 0.41, 2.03 and 0.46, 2.19 and 2.79, respectively. We found no effect of deletions in GST M1 or GST T1, or different alleles of UGT1A1*28. Adjusting for age, sex, place of residence, tobacco smoke exposure, maté drinking, cachaça and barbeque preparation had only a minor impact on the associations. A model containing just exposure variables had an r2 of 0.21; a model with single genotypes for Ahr, CYP1A1, CYP1A2 and CYP1B1 had an r2 of 0.10; and a model combining both exposure and genotype information had a total r2 of 0.33. Our results suggest that CYP1B1 genotypes are strongly associated with urine 1-OHPG concentrations in this population.

  20. An integumentary mucin (FIM-B.1) from Xenopus laevis homologous with von Willebrand factor.

    PubMed

    Probst, J C; Gertzen, E M; Hoffmann, W

    1990-07-03

    We present a new protein from X. laevis skin termed "frog integumentary mucin B.1" (FIM-B.1) with a general structure similar to FIM-A.1 (formerly "spasmolysin"). The central region consisting of tandem repeats of 11 amino acid residues is probably a target for extensive O-glycosylation, whereas the C-terminal cysteine-rich domain shows pronounced homology with the C1-C2 domains and the C-terminal end of von Willebrand factor. Furthermore, we describe homology with antistasin, an anticoagulant peptide from a leech. We also discuss some implications concerning the evolutionary origin of von Willebrand factor. In situ hybridization studies revealed the expression of FIM-B.1 exclusively in mucous glands of the skin. This is comparable with FIM-A.1 but is in contrast to all other physiologically active peptides, which are synthesized in granular glands.

  1. Boeing F3B-1

    NASA Technical Reports Server (NTRS)

    1930-01-01

    Boeing F3B-1: While most Boeing F3B-1s served aboard the U. S. Navy aircraft carriers Lexington and Saratoga, this example flew in NACA hands at the Langley Memorial Aeronautical Laboratory in the late 1920's. Also known as the Boeing Model 77, the aircraft was powered by a Pratt & Whitney Wasp radial engine.

  2. Suppressive effects of estradiol on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated transcriptional activation of murine Cyp1a-1 in mouse hepatoma Hepa 1c1c7 cells.

    PubMed

    Jeong, H G; Lee, S S

    1998-11-27

    Cultured mouse hepatoma Hepa lclc7 cells were treated with either estradiol or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or in combination to assess the role of estradiol in the process of Cypla-1 induction. Estradiol at a concentration as high as 1 microM slightly increased the activity of Cypla-1-specific 7-ethoxyresorufin O-deethylase (EROD); in contrast, TCDD-induced EROD activity and Cypla-1 mRNA levels were markedly reduced in the concomitant treatment of TCDD and estradiol in a dose-dependent manner. Treatment with tamoxifen, an anti-estrogen which acts through the estrogen receptor, did not affect the suppressive effects of estradiol on TCDD-induced EROD activity. Electrophoretic mobility shift assay using nuclear extract of cells revealed that estradiol reduced transformation of the Ah receptor to the form capable of specifically binding to an oligonucleotide containing dioxin-response element (DRE) sequence. Consistent with this, estradiol decreased TCDD-induced increased chloramphenicol acetyltransferase (CAT) activity from a DRE-containing CAT reporter plasmid after transient transfection into the cells. The levels of the cytosolic [3H]TCDD-Ah receptor complex were reduced by estradiol in competitive Ah receptor binding assay using [3H]TCDD. This study demonstrated that estradiol acts as an antagonist to TCDD and can regulate Cyp1a-1 expression in an Ah receptor-dependent manner but not through estradiol receptor in Hepa 1c1c7 cells.

  3. Bioactive saponins and glycosides. IV. Four methyl-migrated 16,17-seco-dammarane triterpene gylcosides from Chinese natural medicine, hoveniae semen seu fructus, the seeds and fruit of Hovenia dulcis THUNB.: absolute stereostructures and inhibitory activity on histamine release of hovenidulciosides A1, A2, B1, and B2.

    PubMed

    Yoshikawa, M; Murakami, T; Ueda, T; Matsuda, H; Yamahara, J; Murakami, N

    1996-09-01

    Four bioactive methyl-migrated 16,17-seco-dammarane type triterpene glycosides called hovenidulciosides A1, A2, B1, and B2 were isolated from a Chinese natural medicine, Hoveniae Semen Seu Fructus, the seeds and fruit of Hovenia dulcis THUNB. (Rhamnaceae) together with hoduloside III and (+)-gallocatechin. The absolute stereostructures of hovenidulciosides A1, A2, B1, and B2 have been elucidated by chemical and physicochemical evidence. All were found to inhibit the histamine release from rat peritoneal exudate cells induced by compound 48/80 and calcium ionophore A-23187.

  4. ABC Transporters B1, C1 and G2 Differentially Regulate Neuroregeneration in Mice

    PubMed Central

    Schumacher, Toni; Krohn, Markus; Hofrichter, Jacqueline; Lange, Cathleen; Stenzel, Jan; Steffen, Johannes; Dunkelmann, Tina; Paarmann, Kristin; Fröhlich, Christina; Uecker, Annekathrin; Plath, Anne-Sophie; Sommer, Alexandra; Brüning, Thomas; Heinze, Hans-Jochen; Pahnke, Jens

    2012-01-01

    Background ATP-binding cassette (ABC) transporters are essential regulators of organismic homeostasis, and are particularly important in protecting the body from potentially harmful exogenous substances. Recently, an increasing number of in vitro observations have indicated a functional role of ABC transporters in the differentiation and maintenance of stem cells. Therefore, we sought to determine brain-related phenotypic changes in animals lacking the expression of distinct ABC transporters (ABCB1, ABCG2 or ABCC1). Methodology and Principal Findings Analyzing adult neurogenesis in ABC transporter-deficient animals in vivo and neuronal stem/progenitor cells in vitro resulted in complex findings. In vivo, the differentiation of neuronal progenitors was hindered in ABC transporter-deficient mice (ABCB10/0) as evidenced by lowered numbers of doublecortin+ (−36%) and calretinin+ (−37%) cells. In vitro, we confirmed that this finding is not connected to the functional loss of single neural stem/progenitor cells (NSPCs). Furthermore, assessment of activity, exploratory behavior, and anxiety levels revealed behavioral alterations in ABCB10/0 and ABCC10/0 mice, whereas ABCG20/0 mice were mostly unaffected. Conclusion and Significance Our data show that single ABC transporter-deficiency does not necessarily impair neuronal progenitor homeostasis on the single NSPC level, as suggested by previous studies. However, loss of distinct ABC transporters impacts global brain homeostasis with far ranging consequences, leading to impaired neurogenic functions in vivo and even to distinct behavioral phenotypes. In addition to the known role of ABC transporters in proteopathies such as Parkinson's disease and Alzheimer's disease, our data highlight the importance of understanding the general function of ABC transporters for the brain's homeostasis and the regeneration potential. PMID:22545122

  5. Some properties of the sum C1(h, k)

    NASA Astrophysics Data System (ADS)

    Cetin, Elif

    2017-07-01

    In [10], we have investigated properties of the sum C1(h, k). In this paper, we will give some other arithmetic properties of the sum C1(h, k). Moreover, in the light of the sum B1(h, k), which has also defined in [10], we will give specific values of the sum C1(h, k) when h + k is an odd number. Finally, we will give a relation between the sum C1(h, k) and the Hardy-Berndt sum s5(h, k) for a special case.

  6. Mercury modulates the cytochrome P450 1a1, 1a2 and 1b1 in C57BL/6J mice: in vivo and in vitro studies

    SciTech Connect

    Amara, Issa E.A.; Anwar-Mohamed, Anwar; Abdelhamid, Ghada; El-Kadi, Ayman O.S.

    2013-02-01

    In the current study C57BL/6J mice were injected intraperitoneally with Hg{sup 2+} in the absence and presence of TCDD. After 6 and 24 h the liver was harvested and the expression of Cyps was determined. In vitro, isolated hepatocytes were incubated with TCDD in the presence and absence of Hg{sup 2+}. At the in vivo level, Hg{sup 2+} significantly decreased the TCDD-mediated induction of Cyps at 6 h while potentiating their levels at 24 h. In vitro, Hg{sup 2+} significantly inhibited the TCDD-mediated induction of Cyp1a1 in a concentration- and time-dependent manner. Interestingly, Hg{sup 2+} increased the serum hemoglobin (Hb) levels in mice treated for 24 h. Upon treatment of isolated hepatocytes with Hb alone, there was an increase in the AhR-dependent luciferase activity with a subsequent increase in Cyp1a1 protein and catalytic activity levels. Importantly, when hepatocytes were treated for 2 h with Hg{sup 2+} in the presence of TCDD, then the medium was replaced with new medium containing Hb, there was potentiation of the TCDD-mediated effect. In addition, Hg{sup 2+} increased heme oxygenase-1 (HO-1) mRNA, which coincided with a decrease in the Cyp1a1 activity level. When the competitive HO-1 inhibitor, tin mesoporphyrin was applied to the hepatocytes there was a partial restoration of Hg{sup 2+}-mediated inhibition of Cyp1a1 activity. In conclusion, we demonstrate for the first time that there is a differential modulation of the TCDD-mediated induction of Cyp1a1 by Hg{sup 2+} in C57BL/6J mice livers and isolated hepatocytes. Moreover, this study implicates Hb as an in vivo specific modulator of Cyp1 family. -- Highlights: ► In vivo, Hg{sup 2+} decreased the Cyps at 6 h while potentiating their levels at 24 h. ► In vitro, Hg{sup 2+} significantly inhibited the TCDD-mediated induction of Cyps. ► Hg{sup 2+} increased the serum Hb levels in animals treated for 24 h. ► Hb potentiated the TCDD-mediated effect on Cyps. ► Tin mesoporphyrin partially

  7. A High-Calcium and Phosphate Rescue Diet and VDR-Expressing Transgenes Normalize Serum Vitamin D Metabolite Profiles and Renal Cyp27b1 and Cyp24a1 Expression in VDR Null Mice.

    PubMed

    Kaufmann, Martin; Lee, Seong Min; Pike, J Wesley; Jones, Glenville

    2015-12-01

    Vitamin D receptor (VDR)-mediated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-dependent gene expression is compromised in the VDR null mouse. The biological consequences include: hypocalcemia, hypophosphatemia, elevated parathyroid hormone (PTH) and 1,25(OH)2D3, and consequential skeletal abnormalities. CYP24A1 is a cytochrome P450 enzyme that is involved in the side chain oxidation and destruction of both 1,25(OH)2D3 and 25-hydroxyvitamin D3 (25-OH-D3). In the current studies, we used liquid chromatography-tandem mass spectrometry technology to compare the metabolic profiles of VDR null mice fed either a normal or a calcium and phosphate-enriched rescue diet and to assess the consequence of transgenic expression of either mouse or human VDR genes in the same background. Serum 1,25(OH)2D3 levels in VDR null mice on normal chow were highly elevated (>3000 pg/mL) coincident with undetectable levels of catabolites such as 24,25-(OH)2D3 and 25-OH-D3-26,23-lactone normally observed in wild-type mice. The rescue diet corrected serum Ca(++), PTH, and 1,25(OH)2D3 values and restored basal expression of Cyp24a1 as evidenced by both renal expression of Cyp24a1 and detection of 24,25-(OH)2D3 and the 25-OH-D3-26,23-lactone. Unexpectedly, this diet also resulted in supranormal levels of 3-epi-24,25-(OH)2D3 and 3-epi-25-OH-D3-26,23-lactone. The reappearance of serum 24,25-(OH)2D3 and renal Cyp24a1 expression after rescue suggests that basal levels of Cyp24a1 may be repressed by high PTH. Introduction of transgenes for either mouse or human VDR also normalized vitamin D metabolism in VDR null mice, whereas this metabolic pattern was unaffected by a transgene encoding a ligand binding-deficient mutant (L233S) human VDR. We conclude that liquid chromatography-tandem mass spectrometry-based metabolic profiling is an ideal analytical method to study mouse models with alterations in calcium/phosphate homeostasis.

  8. 40 CFR 721.5378 - 9-Phosphabicyclo[3.3.1]nonane,9,9′-(1,2-ethanediyl)bis- (9C1).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Requirements as specified in § 721.80 (f), (v)(2), (w)(2), and (y)(2). (ii) Release to water. Requirements as specified § 721.90 (a)(1), (b)(1), and (c)(1). (b) Specific requirements. The provisions of subpart A of... requirements as specified in § 721.125 (a), (b), (c), (i), and (k) are applicable to manufacturers,...

  9. 26 CFR 1.168(b)-1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 2 2013-04-01 2013-04-01 false Definitions. 1.168(b)-1 Section 1.168(b)-1... tangible, depreciable property that is placed in service after December 31, 1986 (or after July 31, 1986, if the taxpayer made an election under section 203(a)(1)(B) of the Tax Reform Act of 1986; 100...

  10. 26 CFR 301.269B-1 - Stapled foreign corporations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Stapled foreign corporations. 301.269B-1....269B-1 Stapled foreign corporations. In accordance with section 269B(a)(1), a stapled foreign corporation is subject to the same taxes that apply to a domestic corporation under Title 26 of the...

  11. Quinazoline derivatives as selective CYP1B1 inhibitors.

    PubMed

    Mohd Siddique, Mohd Usman; McCann, Glen J P; Sonawane, Vinay R; Horley, Neill; Gatchie, Linda; Joshi, Prashant; Bharate, Sandip B; Jayaprakash, Venkatesan; Sinha, Barij N; Chaudhuri, Bhabatosh

    2017-04-21

    CYP1B1 is implicated to have a role in the development of breast, ovarian, renal, skin and lung carcinomas. It has been suggested that identification of potent and specific CYP1B1 inhibitors can lead to a novel treatment of cancer. Flavonoids have a compact rigid skeleton which fit precisely within the binding cavity of CYP1B1. Systematic isosteric replacement of flavonoid 'O' atom with 'N' atom led to the prediction that a 'quinazoline' scaffold could be the basis for designing potential CYP1B1 inhibitors. A total of 20 quinazoline analogs were synthesized and screened for CYP1B1 and CYP1A1 inhibition in Sacchrosomes™. IC50 determinations of six compounds with capability of inhibiting CYP1B1 identified quinazolines 5c and 5h as the best candidates for CYP1B1 inhibition, with IC50 values in the nM range. Further selectivity studies with homologous CYPs, belonging to the CYP1, CYP2 and CYP3 family of enzymes, showed that the compounds are likely to be free from critical drug-drug interaction liability. Molecular modelling studies were performed to rationalize the observed enzymatic inhibitions. Further biological studies in live yeast and human cells, harboring CYP1A1 and CYP1B1 enzymes, have illustrated the most potent compounds' cellular permeability and capability of potently inhibiting CYP1B1 enzyme expressed within live cells.

  12. Discharged generator of singlet oxygen for oxygen-iodine laser. Transport kinetics of O2( a 1δg) and O2( b 1σ{g/+}) molecules and O(3 P) atoms in Ar:O2 and He:O2 flows excited by a 13.56-MHz discharge

    NASA Astrophysics Data System (ADS)

    Braginsky, O. V.; Vasil'Eva, A. N.; Klopovsky, K. S.; Kovalev, A. S.; Lopaev, D. V.; Rakhimova, T. V.; Rakhimov, A. T.

    2006-08-01

    To understand and reveal the basic physical factors providing the possibility of scaling of a discharged singlet oxygen generator (DSOG) in an oxygen-iodine laser, the production, and transport kinetics of metastable O2( a 1δg) and O2( b 1σ{g/+}) molecules, as well as O(3 P) atoms, were investigated in Ar:O2 and He:O2 gas flows excited by a 13.56-MHz discharge in a wide range of pressures (4-40 Torr) and oxygen percentages. It is shown that the densities and transport kinetics of O2( a 1δg), O2( b 1σ{g/+}), and O(3 P) appear similar for oxygen mixtures with argon and helium in the same conditions independent of discharge mode. Compared to pure O2, the dilution of oxygen with an inert gas allows higher energy inputs per an oxygen molecule to achieved, especially under conditions of the homogeneous discharge mode (α-mode), which gives a higher efficiency of O2( a 1δg) excitation in Ar:O2 and He:O2 mixtures. But the maximum attainable yield of singlet oxygen in Ar:O2 and He:O2 at fixed partial O2 pressure is found to be comparable with the O2( a 1δg) yield in pure oxygen at the same pressure. The reason for this is the increased three-body deactivation of O2( a 1δg) by atomic oxygen in the mixtures because of the greater total pressure. The estimation of the rate constant of O2( a 1δg) three-body quenching by O(3 P) in Ar:O2 and He:O2 mixtures as (1.5 ± 0.5) × 10-32 cm6/s was carried out from the analysis of transport kinetics of singlet and atomic oxygen in the discharge afterglow at high pressures exceeding ˜10 Torr. A similar analysis for the lower pressures has revealed that losses both of metastable O2( a 1δg) and O2( b 1σ{g/+}) molecules, and of O(3 P) atoms on the surface of the discharge tube, are determined by the density of each of the components. The obtained loss probabilities of O2( a 1δg), O2( b 1σ{g/+}), and O(3 P) on the silica surface show that the surface loss probabilities of all the species can increase noticeably under the

  13. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 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— (a...

  14. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 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— (a...

  15. 8 CFR 343b.1 - Application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Application. 343b.1 Section 343b.1 Aliens... NATURALIZATION FOR RECOGNITION BY A FOREIGN STATE § 343b.1 Application. A naturalized citizen who desires to obtain recognition as a citizen of the United States by a foreign state shall submit an application on...

  16. 45 CFR 5b.1 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Definitions. 5b.1 Section 5b.1 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT REGULATIONS § 5b.1 Definitions. As... the designee of either such officer or individual. (j) Routine use means the disclosure of a record...

  17. 34 CFR 5b.1 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Definitions. 5b.1 Section 5b.1 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.1 Definitions. As used in this part: (a... records to whom requests may be made, or the designee of either such officer or individual. (j) Routine...

  18. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  19. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  20. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  1. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  2. A Characterization of the CH 2ã1A1(1,2,0),(2,0,0),(0,5,0),(1,3,0) and b˜1B1(1,14 2,0),(0,18 0,0),(0,19 1,0) Vibronic Levels by Fourier-Transform Dispersed Fluorescence Spectroscopy

    NASA Astrophysics Data System (ADS)

    Qin, D.; Hartland, G. V.; Dai, H. L.

    1994-12-01

    The CH2ã1A1, (1, 2, 0), (2, 0, 0), (0, 5, 0), (1, 3, 0) and b˜1B1 (1, 142, 0), (0, 180, 0), (0, 191, 0) levels are characterized by Fourier-transform dispersed fluorescence spectroscopy (FTDFS). Rotational transitions in the b˜ ← ã 1102140, 2180, and 2190 fluorescence excitation bands and those of the b˜ → ã 1012162, 1012172, 1022160, 2185, 2195, 1012183 and 1102193 bands in dispersed fluorescence spectra have been assigned. The rotational constants and vibrational term values for these vibrational levels have been obtained. Due to the limits brought by Renner-Teller coupling and Franck-Condon factors, this work, along with previous studies on lower vibrational levels, has characterized almost all ã vibrational levels detectable in the b˜↔ã transitions.

  3. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL...

  4. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL...

  5. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL...

  6. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL...

  7. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... and informally any matter within the Commission's jurisdiction concerning natural gas pipelines, oil...

  8. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    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... and informally any matter within the Commission's jurisdiction concerning natural gas pipelines, oil...

  9. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... and informally any matter within the Commission's jurisdiction concerning natural gas pipelines, oil...

  10. 45 CFR 73b.1 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the Public Health Service, because of violation of the post-employment restrictions of the conflict of... 45 Public Welfare 1 2010-10-01 2010-10-01 false Scope. 73b.1 Section 73b.1 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION DEBARMENT OR SUSPENSION OF FORMER...

  11. 45 CFR 73b.1 - Scope.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the Public Health Service, because of violation of the post-employment restrictions of the conflict of... 45 Public Welfare 1 2012-10-01 2012-10-01 false Scope. 73b.1 Section 73b.1 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION DEBARMENT OR SUSPENSION OF FORMER...

  12. Specificity Determinants of CYP1B1 Estradiol Hydroxylation

    PubMed Central

    Nishida, Clinton R.; Everett, Steven

    2013-01-01

    Cytochrome P450 (P450)-catalyzed oxidation of the aromatic ring of estradiol can result in 2- or 4-hydroxylation. Which of these products is formed is biologically important, as the 4-hydroxylated metabolite is carcinogenic, whereas the 2-hydroxylated metabolite is not. Most human P450 enzymes, including CYP1A1 and CYP1A2, exhibit a high preference for estradiol 2-hydroxylation, but human CYP1B1 greatly favors 4-hydroxylation. Here we show that heterologous expression of the human, monkey, dog, rat, and mouse CYP1B1 enzymes yields active proteins that differ in their estradiol hydroxylation specificity. The monkey and dog orthologs, like the human enzyme, preferentially catalyze 4-hydroxylation, but the rat and mouse enzymes favor 2-hydroxylation. Analysis of the CYP1B1 sequences in light of these findings suggested that one residue, Val395 in human CYP1B1, could account for the differential hydroxylation specificities. In fact, mutation of this valine in human CYP1B1 to the leucine present in the rat enzyme produces a human enzyme that has the 2-hydroxylation specificity of the rat enzyme. The converse is true when the leucine in the rat enzyme is mutated to the human valine. The role of CYP1B1 in estradiol carcinogenicity thus depends on the identity of this single amino acid residue. PMID:23821647

  13. Decreased expression of CYP27B1 correlates with the increased aggressiveness of ovarian carcinomas

    PubMed Central

    BROŻYNA, ANNA A.; JÓŹWICKI, WOJCIECH; JOCHYMSKI, CEZARY; SLOMINSKI, ANDRZEJ T.

    2015-01-01

    CYP27B1 hydroxylates 25-hydroxyvitamin D3 in position C1α into biologically active 1,25-dihydroxyvitamin D3, calcitriol. CYP27B1 is expressed in normal tissues and tumors. Since calcitriol indicates anticancer activities and CYP27B1 expression can be deregulated during malignant progression, we analyzed its expression in ovarian cancers in relation to pathomorphological features of tumors and overall survival (OS). Expression of CYP27B1 was evaluated in 61 ovarian tumors, 18 metastases and 10 normal ovaries. Normal ovarian epithelium showed the highest levels CYP27B1 with a significant decrease in its expression in ovarian cancers. Both poorly differentiated primary tumors and metastases showed the lowest level of CYP27B1 expression, while non-metastasizing tumors showed a higher CYP27B1 level than tumors that developed metastases. The expression of CYP27B1 was positively correlated with a lower proliferation rate, lower dynamism of tumor growth and tumor infiltrating lymphocyte response. Furthermore, CYP27B1 expression was negatively correlated with tumor cell modeling of their microenvironment. CYP27B1 expression was also associated with longer OS time. In summary, our results suggest that local expression of CYP27B1 in ovarian tumor cells can modify their behavior and promote a less aggressive phenotype by affecting local concentrations of active of vitamin D levels within the tumor microenvironment. PMID:25501638

  14. Association of Endophilin B1 with Cytoplasmic Vesicles.

    PubMed

    Li, Jinhui; Barylko, Barbara; Eichorst, John P; Mueller, Joachim D; Albanesi, Joseph P; Chen, Yan

    2016-08-09

    Endophilins are SH3- and BAR domain-containing proteins implicated in membrane remodeling and vesicle formation. Endophilins A1 and A2 promote the budding of endocytic vesicles from the plasma membrane, whereas endophilin B1 has been implicated in vesicle budding from intracellular organelles, including the trans-Golgi network and late endosomes. We previously reported that endophilins A1 and A2 exist almost exclusively as soluble dimers in the cytosol. Here, we present results of fluorescence fluctuation spectroscopy analyses indicating that, in contrast, the majority of endophilin B1 is present in multiple copies on small, highly mobile cytoplasmic vesicles. Formation of these vesicles was enhanced by overexpression of wild-type dynamin 2, but suppressed by expression of a catalytically inactive dynamin 2 mutant. Using dual-color heterospecies partition analysis, we identified the epidermal growth factor receptor on endophilin B1 vesicles. Moreover, a proportion of endophilin B1 vesicles also contained caveolin, whereas clathrin was almost undetectable on those vesicles. These results raise the possibility that endophilin B1 participates in dynamin 2-dependent formation of a population of transport vesicles distinct from those generated by A-type endophilins. Copyright © 2016. Published by Elsevier Inc.

  15. B-1 cells temper endotoxemic inflammatory responses.

    PubMed

    Barbeiro, Denise Frediani; Barbeiro, Hermes Vieira; Faintuch, Joel; Ariga, Suely K Kubo; Mariano, Mario; Popi, Ana Flávia; de Souza, Heraldo Possolo; Velasco, Irineu Tadeu; Soriano, Francisco Garcia

    2011-03-01

    Sepsis syndrome is caused by inappropriate immune activation due to bacteria and bacterial components released during infection. This syndrome is the leading cause of death in intensive care units. Specialized B-lymphocytes located in the peritoneal and pleural cavities are known as B-1 cells. These cells produce IgM and IL-10, both of which are potent regulators of cell-mediated immunity. It has been suggested that B-1 cells modulate the systemic inflammatory response in sepsis. In this study, we conducted in vitro and in vivo experiments in order to investigate a putative role of B-1 cells in a murine model of LPS-induced sepsis. Macrophages and B-1 cells were studied in monocultures and in co-cultures. The B-1 cells produced the anti-inflammatory cytokine IL-10 in response to LPS. In the B-1 cell-macrophage co-cultures, production of proinflammatory mediators (TNF-α, IL-6 and nitrite) was lower than in the macrophage monocultures, whereas that of IL-10 was higher in the co-cultures. Co-culture of B-1 IL-10(-/-) cells and macrophages did not reduce the production of the proinflammatory mediators (TNF-α, IL-6 and nitrite). After LPS injection, the mortality rate was higher among Balb/Xid mice, which are B-1 cell deficient, than among wild-type mice (65.0% vs. 0.0%). The Balb/Xid mice also presented a proinflammatory profile of TNF-α, IL-6 and nitrite, as well as lower levels of IL-10. In the early phase of LPS stimulation, B-1 cells modulate the macrophage inflammatory response, and the main molecular pathway of that modulation is based on IL-10-mediated intracellular signaling.

  16. Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts.

    PubMed Central

    Burd, C G; Swanson, M S; Görlach, M; Dreyfuss, G

    1989-01-01

    We have isolated cDNAs for the major heterogeneous nuclear ribonucleoprotein (hnRNP) A2, B1, and C2 proteins and determined their nucleotide and deduced amino acid sequences. The A2 and B1 cDNAs are identical except for a 36-nucleotide in-frame insert in B1. Similarly, the sequence of the C2 protein cDNA is related to that of C1 in that C2 contains an extra 39 in-frame nucleotides. Therefore, the B1 amino acid sequence is identical to A2 except for the insertion of 12 amino acids near its amino terminus, and C1 and C2 are also identical to each other except for an extra 13 amino acids near the middle of C2. All three proteins are members of a large family of RNA binding proteins that contain the consensus sequence-type RNA binding domain (CS-RBD). The A2 and B1 proteins have a modular structure similar to that of the hnRNP protein A1: they contain two CS-RBDs and a glycine-rich auxiliary domain at the carboxyl terminus. The CS-RBDs of A2 and B1 have approximately 80% amino acid identity with those of A1, whereas the glycine-rich auxiliary domain is considerably more divergent with less than 30% of the amino acids being identical. These findings indicate that the addition of small peptides, probably by alternative pre-mRNA splicing, generates some of the diversity apparent among hnRNP proteins. Images PMID:2557628

  17. THE ENZYMATIC NATURE OF C'1r

    PubMed Central

    Naff, George B.; Ratnoff, Oscar D.

    1968-01-01

    Human C'1, a macromolecular complex composed of three subunits, is the zymogen for at least two distinct enzymes. Preparations of one subunit, C'1r, functioned as a protease which converted another subunit, C'1s, to C'1 esterase. The conversion of C'1s to C'1 esterase by C'1r was blocked by Liquoid, phenyl methylsulfonyl fluoride, and calcium ions, but not by soybean trypsin inhibitor, hirudin, or heparin. Preparations of C'1r also possessed two additional functions, i.e., the ability to hydrolyze certain synthetic amino acid esters and to participate in immune hemolysis. Evidence was presented which indicates that these three functions are properties of a single entity, C'1r, but not of the same portion of its molecular structure. These observations suggest that C'1r has at least two active sites, one for its reaction with C'1q, an additional subunit of C'1, and one for its reaction with C'1s; together, the three subcomponents, C'1q, C'1r, and C'1s, form a single functional unit, the first component of complement. PMID:5675434

  18. Observation of B Meson decays to b1pi and b1K.

    PubMed

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Tico, J Garra; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Pegna, D Lopes; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; Del Amo Sanchez, P; Hawkes, C M; Watson, A T; Held, T; Koch, H; Pelizaeus, M; Schroeder, T; Steinke, M; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Lombardo, V; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Vazquez, W Panduro; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Haire, M; Biesiada, J; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Ricciardi, S; Roethel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; de Monchenault, G Hamel; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Berger, N; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Hryn'ova, T; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Stelzer, J; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; van Bakel, N; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Burchat, P R; Edwards, A J; Majewski, S A; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2007-12-14

    We present the results of searches for decays of B mesons to final states with a b1 meson and a charged pion or kaon. The data, collected with the BABAR detector at the Stanford Linear Accelerator Center, represent 382x10(6) BB[over ] pairs produced in e+e- annihilation. The results for the branching fractions are, in units of 10(-6), B(B+-->b1(0)pi+)=6.7+/-1.7+/-1.0, B(B+-->b1(0)K+)=9.1+/-1.7+/-1.0, B(B0-->b1(-/+)pi(+/-))=10.9+/-1.2+/-0.9, and B(B0-->b1(-)K+)=7.4+/-1.0+/-1.0, with the assumption that B(b1-->omega pi)=1. We also measure charge and flavor asymmetries A(ch)(B+-->b1(0)pi+)=0.05+/-0.16+/-0.02, Ach(B+-->b1(0)K+)=-0.46+/-0.20+/-0.02, A(ch)(B0-->b1(-/+)pi(+/-))=-0.05+/-0.10+/-0.02, C(B0-->b1(-/+)pi(+/-))=-0.22+/-0.23+/-0.05, DeltaC(B0-->b1(-/+)pi(+/-))=-1.04+/-0.23+/-0.08, and A(ch)(B0-->b1(-)K+)=-0.07+/-0.12+/-0.02. The first error quoted is statistical, and the second systematic.

  19. MR fingerprinting with simultaneous B1 estimation

    PubMed Central

    Sawiak, Stephen J.

    2015-01-01

    Purpose MR fingerprinting (MRF) can be used for quantitative estimation of physical parameters in MRI. Here, we extend the method to incorporate B1 estimation. Methods The acquisition is based on steady state free precession MR fingerprinting with a Cartesian trajectory. To increase the sensitivity to the B1 profile, abrupt changes in flip angle were introduced in the sequence. Slice profile and B1 effects were included in the dictionary and the results from two‐ and three‐dimensional (3D) acquisitions were compared. Acceleration was demonstrated using retrospective undersampling in the phase encode directions of 3D data exploiting redundancy between MRF frames at the edges of k‐space. Results Without B1 estimation, T2 and B1 were inaccurate by more than 20%. Abrupt changes in flip angle improved B1 maps. T1 and T2 values obtained with the new MRF methods agree with classical spin echo measurements and are independent of the B1 field profile. When using view sharing reconstruction, results remained accurate (error <10%) when sampling under 10% of k‐space from the 3D data. Conclusion The methods demonstrated here can successfully measure T1, T2, and B1. Errors due to slice profile can be substantially reduced by including its effect in the dictionary or acquiring data in 3D. Magn Reson Med 76:1127–1135, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. PMID:26509746

  20. Large dynamic range relative B1+ mapping

    PubMed Central

    Hess, Aaron T.; Aljabar, Paul; Malik, Shaihan J.; Jezzard, Peter; Robson, Matthew D.; Hajnal, Joseph V.; Koopmans, Peter J.

    2015-01-01

    Purpose Parallel transmission (PTx) requires knowledge of the B1+ produced by each element. However, B1+ mapping can be challenging when transmit fields exhibit large dynamic range. This study presents a method to produce high quality relative B1+ maps when this is the case. Theory and Methods The proposed technique involves the acquisition of spoiled gradient echo (SPGR) images at multiple radiofrequency drive levels for each transmitter. The images are combined using knowledge of the SPGR signal equation using maximum likelihood estimation, yielding an image for each channel whose signal is proportional to the B1+ field strength. Relative B1+ maps are then obtained by taking image ratios. The method was tested using numerical simulations, phantom imaging, and through in vivo experiments. Results The numerical simulations demonstrated that the proposed method can reconstruct relative transmit sensitivities over a wide range of B1+ amplitudes and at several SNR levels. The method was validated at 3 Tesla (T) by comparing it with an alternative B1+ mapping method, and demonstrated in vivo at 7T. Conclusion Relative B1+ mapping in the presence of large dynamic range has been demonstrated through numerical simulations, phantom imaging at 3T and experimentally at 7T. The method will enable PTx to be applied in challenging imaging scenarios at ultrahigh field. Magn Reson Med 76:490–499, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:26308375

  1. Bioactive constituents from chinese natural medicines. XXIV. Hypoglycemic effects of Sinocrassula indica in sugar-loaded rats and genetically diabetic KK-A(y) mice and structures of new acylated flavonol glycosides, sinocrassosides A(1), A(2), B(1), and B(2).

    PubMed

    Yoshikawa, Masayuki; Wang, Tao; Morikawa, Toshio; Xie, Haihui; Matsuda, Hisashi

    2007-09-01

    The methanolic extract from the whole plant of Sinocrassula indica (Crassulaceae) was found to inhibit the increase in serum glucose levels in oral administration of sucrose and glucose in rats at a dose of 250 mg/kg (p.o.). However, the extract did not inhibit the increase in serum glucose levels after intraperitoneal administration of glucose in these animals but did partly inhibit the gastric emptying. On the other hand, this extract significantly inhibited the increase in serum glucose levels after administration for 2 weeks in KK-A(y) mice, a genetically type II diabetic mice, at a dose of 250 mg/kg/d (p.o.) without significant changes of the weights of body, liver, and visceral fat. From the extract, four new acylated flavonol glycosides, sinocrassosides A(1), A(2), B(1), and B(2), were isolated together with 11 flavonoids and 2 megastigmanes. The absolute stereostructures of the four new compounds were elucidated on the basis of chemical and physicochemical evidence.

  2. B-1a Lymphocytes Attenuate Insulin Resistance

    PubMed Central

    Shen, Lei; Chng, MH; Alonso, Michael N.; Yuan, Robert

    2015-01-01

    Obesity-associated insulin resistance, a common precursor of type 2 diabetes, is characterized by chronic inflammation of tissues, including visceral adipose tissue (VAT). Here we show that B-1a cells, a subpopulation of B lymphocytes, are novel and important regulators of this process. B-1a cells are reduced in frequency in obese high-fat diet (HFD)-fed mice, and EGFP interleukin-10 (IL-10) reporter mice show marked reductions in anti-inflammatory IL-10 production by B cells in vivo during obesity. In VAT, B-1a cells are the dominant producers of B cell–derived IL-10, contributing nearly half of the expressed IL-10 in vivo. Adoptive transfer of B-1a cells into HFD-fed B cell–deficient mice rapidly improves insulin resistance and glucose tolerance through IL-10 and polyclonal IgM-dependent mechanisms, whereas transfer of B-2 cells worsens metabolic disease. Genetic knockdown of B cell–activating factor (BAFF) in HFD-fed mice or treatment with a B-2 cell–depleting, B-1a cell–sparing anti-BAFF antibody attenuates insulin resistance. These findings establish B-1a cells as a new class of immune regulators that maintain metabolic homeostasis and suggest manipulation of these cells as a potential therapy for insulin resistance. PMID:25249575

  3. Expression of ATP-Binding Cassette Transporters B1 and C1 after Severe Traumatic Brain Injury in Humans

    PubMed Central

    Willyerd, F. Anthony; Empey, Philip E.; Philbrick, Ashley; Ikonomovic, Milos D.; Puccio, Ava M.; Kochanek, Patrick M.; Okonkwo, David O.

    2016-01-01

    Abstract Adenosine triphosphate-binding cassette (ABC) transport proteins ABCC1 and ABCB1 (also known as multidrug resistance-associated protein 1 and p-glycoprotein, respectively), are key membrane efflux transporters of drugs and endogenous substrates, including in the brain. The impact of traumatic brain injury (TBI) on ABCC1 and ABCB1 expression in humans is unknown. We hypothesized that ABCC1 and ABCB1 expression would be altered in brain tissue from patients acutely after severe TBI. Archived TBI samples (n=10) from our Brain Trauma Research Center and control samples (n=7) from our Alzheimer Disease Research Center were obtained under Institutional Review Board approval. Protein was extracted from fresh frozen cortical brain tissue for Western blot analysis and sections were obtained from fixed cortical tissue for immunohistochemistry. Relative abundance of ABCC1 was increased in samples from TBI versus controls (2.8±2.5 fold; p=0.005). ABCC1 immunohistochemistry was consistent with Western blot data, with increased immunoreactivity in cerebral blood vessel walls, as well as cells with the morphological appearance of neurons and glia in TBI versus controls. Relative abundance of ABCB1 was similar between TBI and controls (p=0.76), and ABCB1 immunoreactivity was primarily associated with cerebral blood vessels in both groups. These human data show that TBI increases ABCC1 expression in the brain, consistent with possible implications for both patients receiving pharmacological inhibitors and/or substrates of ABCC1 after TBI. PMID:25891836

  4. Aflatoxin B1 in common Egyptian foods.

    PubMed

    Selim, M I; Popendorf, W; Ibrahim, M S; el Sharkawy, S; el Kashory, E S

    1996-01-01

    Samples of common Egyptian foods (17 nuts and seeds, 10 spices, 31 herbs and medicinal plants, 12 dried vegetables, and 28 cereal grains) were collected from markets in Cairo and Giza. A portion of each sample was extracted with chloroform, and the concentrated extract was cleaned by passing through a silica gel column. Aflatoxin B1 was determined by reversed-phase liquid chromatography with UV detection. The highest prevalence of aflatoxin B1 was in nuts and seeds (82%), followed by spices (40%), herbs and medicinal plants (29%), dried vegetables (25%), and cereal grains (21%). The highest mean concentration of aflatoxin B1 was in herb and medicinal plants (49 ppb), followed by cereals (36 ppb), spices (25 ppb), nuts and seeds (24 ppb), and dried vegetables (20 ppb). Among nuts and seeds, the prevalence of aflatoxin B1 was highest (100%) in watermelon seeds, inshell peanuts, and unshelled peanuts. The lowest prevalence and concentrations were in hommos (garbanzo beans). The highest concentrations of aflatoxin B1 were detected in foods that had no potential for field contamination but required drying during processing and storage, such as pomegranate peel, watermelon seeds, and molokhia.

  5. Curtiss XSO3C-1 Seagull

    NASA Technical Reports Server (NTRS)

    1940-01-01

    Curtiss XSO3C-1 Seagull: Although drag reduction was very important to radial engined aircraft, it was no less important to aircraft such as this inline Ranger powered Curtiss XSO3C-1 Seagull. Here the Seagull is shown in the 30 x 60 Full Scale Tunnel in October of 1940. The XSO3C-1 was also undergoing study to improve engine cooling. Published in Aircraft; FST; Curtiss XSO3C-1 Seagull; Full Scale Tunnel; Nicklas

  6. C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles.

    PubMed

    Mossberg, Maria; Ståhl, Anne-Lie; Kahn, Robin; Kristoffersson, Ann-Charlotte; Tati, Ramesh; Heijl, Caroline; Segelmark, Mårten; Leeb-Lundberg, L M Fredrik; Karpman, Diana

    2017-08-01

    The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P<0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor-depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation. Copyright © 2017 by the American Society of Nephrology.

  7. 29 CFR 2575.502c-1 - Adjusted civil penalty under section 502(c)(1).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Adjusted civil penalty under section 502(c)(1). 2575.502c-1 Section 2575.502c-1 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY... ERISA Title I § 2575.502c-1 Adjusted civil penalty under section 502(c)(1). In accordance with...

  8. 7 CFR 1b.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.1 Purpose. (a) This part supplements the regulations for implementation of the National Environmental Policy Act (NEPA), for which regulations were published by the Council on Environmental Quality (CEQ) in 40 CFR parts 1500 through 1508. This...

  9. 7 CFR 1b.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.1 Purpose. (a) This part supplements the regulations for implementation of the National Environmental Policy Act (NEPA), for which regulations were published by the Council on Environmental Quality (CEQ) in 40 CFR parts 1500 through 1508. This part...

  10. 7 CFR 1b.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.1 Purpose. (a) This part supplements the regulations for implementation of the National Environmental Policy Act (NEPA), for which regulations were published by the Council on Environmental Quality (CEQ) in 40 CFR parts 1500 through 1508. This part...

  11. 7 CFR 1b.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.1 Purpose. (a) This part supplements the regulations for implementation of the National Environmental Policy Act (NEPA), for which regulations were published by the Council on Environmental Quality (CEQ) in 40 CFR parts 1500 through 1508. This part...

  12. 7 CFR 1b.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.1 Purpose. (a) This part supplements the regulations for implementation of the National Environmental Policy Act (NEPA), for which regulations were published by the Council on Environmental Quality (CEQ) in 40 CFR parts 1500 through 1508. This part...

  13. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed... to conduct the business of the Uniformed Services University of the Health Sciences, and designated this body “the Board of Regents of the Uniformed Services University of the Health Sciences,” referred...

  14. Development of an In Vitro Model to Screen CYP1B1-Targeted Anticancer Prodrugs.

    PubMed

    Wang, Zhiying; Chen, Yao; Drbohlav, Laura M; Wu, Judy Qiju; Wang, Michael Zhuo

    2016-12-01

    Cytochrome P450 1B1 (CYP1B1) is an anticancer therapeutic target due to its overexpression in a number of steroid hormone-related cancers. One anticancer drug discovery strategy is to develop prodrugs specifically activated by CYP1B1 in malignant tissues to cytotoxic metabolites. Here, we aimed to develop an in vitro screening model for CYP1B1-targeted anticancer prodrugs using the KLE human endometrial carcinoma cell line. KLE cells demonstrated superior stability of CYP1B1 expression relative to transiently transfected cells and did not express any appreciable amount of cognate CYP1A1 or CYP1A2, which would have compromised the specificity of the screening assay. The effect of two CYP1B1-targeted probe prodrugs on KLE cells was evaluated in the absence and presence of a CYP1B1 inhibitor to chemically "knock out" CYP1B1 activity (CYP1B1 inhibited). Both probe prodrugs were more toxic to KLE cells than to CYP1B1-inhibited KLE cells and significantly induced G0/G1 arrest and decreased the S phase in KLE cells. They also exhibited pro-apoptotic effects in KLE cells, which were attenuated in CYP1B1-inhibited KLE cells. In summary, a KLE cell-based model has been characterized to be suitable for identifying CYP1B1-targeted anticancer prodrugs and should be further developed and employed for screening chemical libraries.

  15. B1 bradykinin receptors and sensory neurones.

    PubMed Central

    Davis, C. L.; Naeem, S.; Phagoo, S. B.; Campbell, E. A.; Urban, L.; Burgess, G. M.

    1996-01-01

    1. The location of the B1 bradykinin receptors involved in inflammatory hyperalgesia was investigated. 2. No specific binding of the B1 bradykinin receptor ligand [3H]-des-Arg10-kallidin was detected in primary cultures of rat dorsal root ganglion neurones, even after treatment with interleukin-1 beta (100 iu ml-1). 3. In dorsal root ganglion neurones, activation of B2 bradykinin receptors stimulated polyphosphoinositidase C. In contrast, B1 bradykinin receptor agonists (des-Arg9-bradykinin up to 10 microM and des-Arg10-kallidin up to 1 microM) failed to activate polyphosphoinositidase C, even in neurones that had been treated with interleukin-1 beta (100 iu ml-1), prostaglandin E2 (1 microM) or prostaglandin I2 (1 microM). 4. Dorsal root ganglion neurones removed from rats (both neonatal and 14 days old) that had been pretreated with inflammatory mediators (Freund's complete adjuvant, or carrageenan) failed to respond to B1 bradykinin receptor selective agonists (des-Arg9-bradykinin up to 10 microM and des-Arg10-kallidin up to 1 microM). 5. Bradykinin (25 nM to 300 nM) evoked ventral root responses when applied to peripheral receptive fields or central terminals of primary afferents in the neonatal rat spinal cord and tail preparation. In contrast, des-Arg9-bradykinin (50 nM to 500 nM) failed to evoke ventral root depolarizations in either control rats or in animals that developed inflammation following ultraviolet irradiation of the tail skin. 6. The results of the present study imply that the B1 bradykinin receptors that contribute to hypersensitivity in models of persistent inflammatory hyperalgesia are located on cells other than sensory neurones where they may be responsible for releasing mediators that sensitize or activate the nociceptors. PMID:8832074

  16. Expression of staphylococcal enterotoxin C1 in Escherichia coli.

    PubMed Central

    Bohach, G A; Schlievert, P M

    1987-01-01

    The structural gene encoding staphylococcal enterotoxin C1 was cloned into Escherichia coli and localized on a 1.5-kilobase HindIII-ClaI DNA fragment by subcloning. The toxin was partially purified from E. coli clones and shown to be immunologically identical to enterotoxin C1 from Staphylococcus aureus. The cloned toxin also had the same molecular weight (26,000) and charge heterogeneity as staphylococcus-derived enterotoxin. Toxins from both sources were equally biologically active. Images PMID:3542834

  17. Alcohol binding in the C1 (C1A + C1B) domain of protein kinase C epsilon

    PubMed Central

    Pany, Satyabrata; Das, Joydip

    2015-01-01

    Background Alcohol regulates the expression and function of protein kinase C epsilon (PKCε). In a previous study we identified an alcohol binding site in the C1B, one of the twin C1 subdomains of PKCε. Methods In this study, we investigated alcohol binding in the entire C1 domain (combined C1A and C1B) of PKCε. Fluorescent phorbol ester, SAPD and fluorescent diacylglycerol (DAG) analog, dansyl-DAG were used to study the effect of ethanol, butanol, and octanol on the ligand binding using fluorescence resonance energy transfer (FRET). To identify alcohol binding site(s), PKCεC1 was photolabeled with 3-azibutanol and 3-azioctanol, and analyzed by mass spectrometry. The effects of alcohols and the azialcohols on PKCε were studied in NG108-15 cells. Results In the presence of alcohol, SAPD and dansyl-DAG showed different extent of FRET, indicating differential effects of alcohol on the C1A and C1B subdomains. Effects of alcohols and azialcohols on PKCε in NG108-15 cells were comparable. Azialcohols labeled Tyr-176 of C1A and Tyr-250 of C1B. Inspection of the model structure of PKCεC1 reveals that these residues are 40 Å apart from each other indicating that these residues form two different alcohol binding sites. Conclusions The present results provide evidence for the presence of multiple alcohol-binding sites on PKCε and underscore the importance of targeting this PKC isoform in developing alcohol antagonists. PMID:26210390

  18. C1 inhibitor: quantification and purification.

    PubMed

    Varga, Lilian; Dobó, József

    2014-01-01

    C1 inhibitor is a multipotent serpin capable of inhibiting the classical and the lectin pathways of complement, the fibrinolytic system, and contact/kinin system of coagulation. Deficiency of C1 inhibitor manifest as hereditary angioedema (HAE), an autosomal dominant hereditary disease. Measuring the C1 inhibitor level is of vital importance for the diagnosis of HAE and also for monitoring patients receiving C1 inhibitor for therapy. Determination of the antigenic C1 inhibitor level by the radial immunodiffusion (RID) technique is described in detail in this chapter. The presented purification method of plasma C1 inhibitor is primarily based on its high carbohydrate content and its affinity to the lectin jacalin.

  19. B-1B excels in conventional role

    SciTech Connect

    Scott, W.B.

    1992-07-01

    A report is presented of an observational flight performed in a USAF B-1B to better understand the operational aspects of the aircraft's new conventional bombing mission as an integral element of a multiaircraft tactical strike package. The basic flight plan consisted of a standard takeoff and climb, cruising to the training area at 22,000 ft, descending for a 400 ft low-level run, making two simulated bomb drops, and climbing back to 25,000 ft for the return to base. Attention is given the new/enhanced avionics, the ALQ-161 defensive electronic warfare system and ripple-release Mk. 82 bombing procedures.

  20. Feasibility Study B-1 Power Controller.

    DTIC Science & Technology

    1979-11-01

    Study performed by the Autonetics Strategic Systems Division ( ASSD ) of Rockwell International on Contract N62269-79-C-0294. The objective of this study...Modify the design of the ASSD B-1 SSPC, Part Number 12880-507-1, to be a 115 Vac quadruple SSPC unit, with a SOSTEL compatible interface. 3.1.2 115 Vac...Primary Power Modifications. The ASSD SSPC Unit, Appendix A, contains four identical PC’s operating from 230 Vac primary power. Referring to Figure 1

  1. C1 neurons: the body's EMTs

    PubMed Central

    Stornetta, Ruth L.; Bochorishvili, Genrieta; DePuy, Seth D.; Burke, Peter G. R.; Abbott, Stephen B. G.

    2013-01-01

    The C1 neurons reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM, IVLM). They use glutamate as a fast transmitter and synthesize catecholamines plus various neuropeptides. These neurons regulate the hypothalamic pituitary axis via direct projections to the paraventricular nucleus and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The presympathetic C1 cells, located in the RVLM, are probably organized in a roughly viscerotopic manner and most of them regulate the circulation. C1 cells are variously activated by hypoglycemia, infection or inflammation, hypoxia, nociception, and hypotension and contribute to most glucoprivic responses. C1 cells also stimulate breathing and activate brain stem noradrenergic neurons including the locus coeruleus. Based on the various effects attributed to the C1 cells, their axonal projections and what is currently known of their synaptic inputs, subsets of C1 cells appear to be differentially recruited by pain, hypoxia, infection/inflammation, hemorrhage, and hypoglycemia to produce a repertoire of stereotyped autonomic, metabolic, and neuroendocrine responses that help the organism survive physical injury and its associated cohort of acute infection, hypoxia, hypotension, and blood loss. C1 cells may also contribute to glucose and cardiovascular homeostasis in the absence of such physical stresses, and C1 cell hyperactivity may contribute to the increase in sympathetic nerve activity associated with diseases such as hypertension. PMID:23697799

  2. B-1 AFT Nacelle Flow Visualization Study

    NASA Technical Reports Server (NTRS)

    Celniker, Robert

    1975-01-01

    A 2-month program was conducted to perform engineering evaluation and design tasks to prepare for visualization and photography of the airflow along the aft portion of the B-1 nacelles and nozzles during flight test. Several methods of visualizing the flow were investigated and compared with respect to cost, impact of the device on the flow patterns, suitability for use in the flight environment, and operability throughout the flight. Data were based on a literature search and discussions with the test personnel. Tufts were selected as the flow visualization device in preference to several other devices studied. A tuft installation pattern has been prepared for the right-hand aft nacelle area of B-1 air vehicle No.2. Flight research programs to develop flow visualization devices other than tufts for use in future testing are recommended. A design study was conducted to select a suitable motion picture camera, to select the camera location, and to prepare engineering drawings sufficient to permit installation of the camera. Ten locations on the air vehicle were evaluated before the selection of the location in the horizontal stabilizer actuator fairing. The considerations included cost, camera angle, available volume, environmental control, flutter impact, and interference with antennas or other instrumentation.

  3. SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid.

    PubMed

    Tornio, Aleksi; Vakkilainen, Juha; Neuvonen, Mikko; Backman, Janne T; Neuvonen, Pertti J; Niemi, Mikko

    2015-08-01

    Organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1 gene) is a hepatic uptake transporter, and its genetic variability is associated with pharmacokinetics and muscle toxicity risk of simvastatin. We examined the possible effects of variations in the SLCO1B1 gene on the pharmacokinetics of lovastatin in a prospective genotype panel study. Seven healthy volunteers with the SLCO1B1*1B/*1B genotype, five with the SLCO1B1*5/*15 or *15/*15 genotype, and 15 with the SLCO1B1*1A/*1A genotype (controls) were recruited. Each study participant ingested a single 40-mg dose of lovastatin. Plasma concentrations of lovastatin (inactive lactone) and its active metabolite lovastatin acid were measured up to 24 h. In the SLCO1B1*5/*15 or *15/*15 genotype group, the geometric mean Cmax and AUC0-24 of lovastatin acid were 340 and 286% of the corresponding values in the SLCO1B1*1A/*1A (reference) genotype group (P<0.005). In contrast, the AUC0-24 of lovastatin acid in the SLCO1B1*1B/*1B genotype group was only 68% of that in the reference genotype group (P=0.03). No statistically significant association was observed between the SLCO1B1 genotype and the pharmacokinetics of lovastatin lactone. SLCO1B1*5/*15 and *15/*15 genotypes markedly increase the exposure to active lovastatin acid, but have no significant effect on lovastatin lactone, similar to their effects on simvastatin and simvastatin acid. Accordingly, it is probable that the risk of muscle toxicity during lovastatin treatment is increased in individuals carrying the SLCO1B1*5 or *15 allele. The SLCO1B1*1B/*1B genotype is associated with reduced lovastatin acid concentrations, consistent with enhanced hepatic uptake.

  4. 17 CFR 270.12b-1 - Distribution of shares by registered open-end management investment company.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... registered open-end management investment company. 270.12b-1 Section 270.12b-1 Commodity and Securities... 1940 § 270.12b-1 Distribution of shares by registered open-end management investment company. (a)(1... the printing and mailing of sales literature; (b) A registered, open-end management investment...

  5. 17 CFR 270.12b-1 - Distribution of shares by registered open-end management investment company.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... registered open-end management investment company. 270.12b-1 Section 270.12b-1 Commodity and Securities... 1940 § 270.12b-1 Distribution of shares by registered open-end management investment company. (a)(1) Except as provided in this section, it shall be unlawful for any registered open-end...

  6. 17 CFR 270.12b-1 - Distribution of shares by registered open-end management investment company.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... registered open-end management investment company. 270.12b-1 Section 270.12b-1 Commodity and Securities... 1940 § 270.12b-1 Distribution of shares by registered open-end management investment company. (a)(1) Except as provided in this section, it shall be unlawful for any registered open-end...

  7. 17 CFR 270.12b-1 - Distribution of shares by registered open-end management investment company.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... registered open-end management investment company. 270.12b-1 Section 270.12b-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.12b-1 Distribution of shares by registered open-end management investment company. (a)(1...

  8. 118-B-1 excavation treatability test plan

    SciTech Connect

    Not Available

    1994-07-01

    The Hanford 118-B-1 Burial Ground Treatability Study has been required by milestone change request {number_sign}M-15-93-04, dated September 30, 1993. The change request requires that a treatability test be conducted at the 100-B Area to obtain additional engineering information for remedial design of burial grounds receiving waste from 100 Area removal actions. This treatability study has two purposes: (1) to support development of the Proposed Plan (PP) and Record of Decision (ROD), which will identify the approach to be used for burial ground remediation, and (2) to provide specific engineering information for receiving waste generated from the 100 Area removal actions. Data generated from this test also will provide critical performance and cost information necessary for remedy evaluation in the detailed analysis of alternatives during preparation of the focused feasibility study (FFS). This treatability testing supports the following 100 Area alternatives: (1) excavation and disposal, and (2) excavation, sorting, (treatment), and disposal.

  9. 118-B-1 excavation treatability test procedures

    SciTech Connect

    Frain, J.M.

    1994-08-01

    This treatability study has two purposes: to support development of the approach to be used for burial ground remediation, and to provide specific engineering information for the design of burial grounds receiving waste generated from the 100 Area removal actions. Data generated from this test will also provide performance and cost information necessary for detailed analysis of alternatives for burial ground remediation. Further details on the test requirements, milestones and data quality objectives are described in detail in the 118-B-1 Excavation Treatability Test Plan (DOE/RL-94-43). These working procedures are intended for use by field personnel to implement the requirements of the milestone. A copy of the detailed Test Plan will be kept on file at the on-site field support trailer, and will be available for review by field personnel.

  10. Bell 206B-1 Directional Control in Low Airspeed Flight.

    DTIC Science & Technology

    1981-05-01

    left pedal control margins are minimal and a requirement for additional power may cause rpm droop. 25. Increasing Main Rotor Torque. In the low ...AO-A09 500 AIRCRAFT KRKA*CH AN EWL[PENT UNIT £EDOWI*ASU (AUS-Y¢ P,6 inBELL 060-1 DIRECTIONAL CONTROL IN LOW AIRSPEED PLIGHT.4U) MAY A1 L R WARD...AIR FORCE AIRCRAFT RESEARCH AND DEVELOPMENT UNIT EDINBURGH, SOUTH AUSTRALIA TECHNICAL INVESTIGATION NO 721 BELL 206B-1 DIRECTIONAL CONTROL IN LOW

  11. Differential effects of Glycyrrhiza species on genotoxic estrogen metabolism: licochalcone A downregulates P450 1B1 whereas isoliquiritigenin stimulates

    PubMed Central

    Dunlap, Tareisha L.; Wang, Shuai; Simmler, Charlotte; Chen, Shao-Nong; Pauli, Guido F.; Dietz, Birgit M.; Bolton, Judy L.

    2015-01-01

    Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by up-regulating P450 1B1. The present study tested the three authenticated medicinal species of licorice, [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)], used by women as dietary supplements, for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI > GG > GU and LigC ≅ LicA > LigF. The Michael acceptor chalcone LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as non-toxic and 4-MeOE1 as genotoxic biomarkers in the non-tumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 μg/mL), and LigC (1 μM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-α and IFN-γ). LicA (1 μM, 10 μM) decreased cytokine- and TCDD-induced, P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50=12.3 μM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 μg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women’s health. Additionally

  12. Wiseman conducts BCAT-C1 experiment

    NASA Image and Video Library

    2014-07-25

    ISS040-E-076505 (25 July 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, conducts a session with the Binary Colloidal Alloy Test-C1, or BCAT-C1, experiment in the Kibo laboratory of the International Space Station. Results from this ongoing investigation of colloids ? mixtures of small particles distributed throughout a liquid ? will help materials scientists to develop new consumer products with unique properties and longer shelf lives.

  13. Wiseman conducts BCAT-C1 experiment

    NASA Image and Video Library

    2014-07-25

    ISS040-E-076507 (25 July 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, conducts a session with the Binary Colloidal Alloy Test-C1, or BCAT-C1, experiment in the Kibo laboratory of the International Space Station. Results from this ongoing investigation of colloids ? mixtures of small particles distributed throughout a liquid ? will help materials scientists to develop new consumer products with unique properties and longer shelf lives.

  14. Wiseman conducts BCAT-C1 experiment

    NASA Image and Video Library

    2014-07-25

    ISS040-E-076510 (25 July 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, conducts a session with the Binary Colloidal Alloy Test-C1, or BCAT-C1, experiment in the Kibo laboratory of the International Space Station. Results from this ongoing investigation of colloids ? mixtures of small particles distributed throughout a liquid ? will help materials scientists to develop new consumer products with unique properties and longer shelf lives.

  15. Phylogeography of E1b1b1b-M81 haplogroup and analysis of its subclades in Morocco.

    PubMed

    Reguig, Ahmed; Harich, Nourdin; Barakat, Abdelhamid; Rouba, Hassan

    2014-01-01

    In this study we analyzed 295 unrelated Berber-speaking men from northern, central, and southern Morocco to characterize frequency of the E1b1b1b-M81 haplogroup and to refine the phylogeny of its subclades: E1b1b1b1-M107, E1b1b1b2-M183, and E1b1b1b2a-M165. For this purpose, we typed four biallelic polymorphisms: M81, M107, M183, and M165. A large majority of the Berber-speaking male lineages belonged to the Y-chromosomal E1b1b1b-M81 haplogroup. The frequency ranged from 79.1% to 98.5% in all localities sampled. E1b1b1b2-M183 was the most dominant subclade in our samples, ranging from 65.1% to 83.1%. In contrast, the E1b1b1b1-M107 and E1b1b1b2a-M165 subclades were not found in our samples. Our results suggest a predominance of the E1b1b1b-M81 haplogroup among Moroccan Berber-speaking males with a decreasing gradient from south to north. The most prevalent subclade in this haplogroup was E1b1b1b2-M183, for which diffferences among these three groups were statistically significant between central and southern groups. Copyright © 2014 Wayne State University Press, Detroit, Michigan 48201-1309.

  16. 29 CFR 2575.502c-1 - Adjusted civil penalty under section 502(c)(1).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-1 Adjusted civil penalty under section 502(c)(1). In accordance with the... section 502(c)(1) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  17. 29 CFR 2575.502c-1 - Adjusted civil penalty under section 502(c)(1).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-1 Adjusted civil penalty under section 502(c)(1). In accordance with the... section 502(c)(1) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  18. 29 CFR 2575.502c-1 - Adjusted civil penalty under section 502(c)(1).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-1 Adjusted civil penalty under section 502(c)(1). In accordance with the... section 502(c)(1) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  19. 29 CFR 2575.502c-1 - Adjusted civil penalty under section 502(c)(1).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ACT OF 1974 ADJUSTMENT OF CIVIL PENALTIES UNDER ERISA TITLE I Adjustment of Civil Penalties Under ERISA Title I § 2575.502c-1 Adjusted civil penalty under section 502(c)(1). In accordance with the... section 502(c)(1) of the Employee Retirement Income Security Act of 1974, as amended (ERISA), is...

  20. Effect of vitamin B1 and mixtures of B1 with other vitamins on cytostatic efficiency of sanazole under irradiation. A study in vitro

    NASA Astrophysics Data System (ADS)

    Heinrich, Edith; Getoff, Nikola

    2003-06-01

    Experiments in vitro, using bacteria Escherichia coli (AB 1157) as a biological model, showed that the cytostatic efficiency of sanazole (AK-2123, a nitrotriazole-type radiosensitizer) in radiation treatment can be strongly influenced by the presence of various vitamins. In airfree media the sanazole action is increased by a factor of 2.5 in the presence of vitamin (vit.) B1, vit. C E-acetate and β-carotene, whereas vit. B1 used individually possesses a 2.7-times higher cytostatic activity than sanazole itself. In media containing air the highest increase of sanazole action is observed in the presence of vit. B1 and C, whereas the individual use of vit. B1 shows a radiation protection effect. In media saturated with N 2O the addition of the vit. B1 and C causes a 1.8-times larger sanazole activity, but the application of vit. B1 alone brings about a very high radiation protection. From studies of vit. B1-radiolysis it can be concluded that OH radicals are the major primary transients leading to substrate degradation. The results are of interest for the radiation therapy of cancer.

  1. In vivo Metabolism of Hydrolyzed Fumonisin B1 and Fumonisin B1

    USDA-ARS?s Scientific Manuscript database

    Fumonisin B1 (FB1) is the most prevalent fumonisin mycotoxin found in corn and corn-based foods. It inhibits ceramide synthase, disrupts sphingolipid metabolism and function, is toxic to animals, causes cancer in rodents, and induces neural tube defects in some mouse strains. Its human health effect...

  2. Vitamin B1 (thiamine) and dementia.

    PubMed

    Gibson, Gary E; Hirsch, Joseph A; Fonzetti, Pasquale; Jordan, Barry D; Cirio, Rosanna T; Elder, Jessica

    2016-03-01

    The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer's disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine decline, and a decrease in their levels could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD.

  3. Vitamin B1 (thiamine) and dementia

    PubMed Central

    Gibson, Gary E.; Hirsch, Joseph A.; Fonzetti, Pasquale; Jordon, Barry D.; Cirio, Rosanna T.; Elder, Jessica

    2016-01-01

    The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer’s disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine deficiency, and their decline could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs, or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD. PMID:26971083

  4. Systematic Errors in measurement of b1

    NASA Astrophysics Data System (ADS)

    Wood, S. A.

    2014-10-01

    A class of spin observables can be obtained from the relative difference of or asymmetry between cross sections of different spin states of beam or target particles. Such observables have the advantage that the normalization factors needed to calculate absolute cross sections from yields often divide out or cancel to a large degree in constructing asymmetries. However, normalization factors can change with time, giving different normalization factors for different target or beam spin states, leading to systematic errors in asymmetries in addition to those determined from statistics. Rapidly flipping spin orientation, such as what is routinely done with polarized beams, can significantly reduce the impact of these normalization fluctuations and drifts. Target spin orientations typically require minutes to hours to change, versus fractions of a second for beams, making systematic errors for observables based on target spin flips more difficult to control. Such systematic errors from normalization drifts are discussed in the context of the proposed measurement of the deuteron b1 structure function at Jefferson Lab.

  5. SLE and C1q: A quantitative ELISA for determining C1q levels in serum

    PubMed Central

    Dillon, Skyler P.; D’Souza, Anil; Kurien, Biji T.; Scofield, R. Hal

    2010-01-01

    C1q is of interest in SLE research due to deficiencies in its activity being associated with the disease. Current published protocols for measuring C1q vary greatly in their results and ease of reproducibility. Due to this, average C1q concentrations have been reported between 56 and 276 µg/ml in non-SLE serum. We present an improved method for quantifying C1q concentrations that employs a sandwich ELISA. This method has improved precision, cost efficiency, up-scaling, reproducibility, and uses significantly lesser volumes of serum sample when compared to RID and other methods for quantifying C1q. We report an average concentration of 113±40 µg/ml for C1q in non-SLE serum. The assay designed here will be useful in the high-throughput measurement of serum C1q in SLE cases. PMID:19370710

  6. Local perturbations of conservative C 1 diffeomorphisms

    NASA Astrophysics Data System (ADS)

    Buzzi, Jérôme; Crovisier, Sylvain; Fisher, Todd

    2017-09-01

    A number of techniques have been developed to perturb the dynamics of C 1-diffeomorphisms and to modify the properties of their periodic orbits. For instance, one can locally linearize the dynamics, change the tangent dynamics, or create local homoclinic orbits. These techniques have been crucial for the understanding of C 1 dynamics, but their most precise forms have mostly been shown in the dissipative setting. This work extends these results to volume-preserving and especially symplectic systems. These tools underlie our study of the entropy of C 1-diffeomorphisms in Buzzi et al (2016 (arXiv:1606.01765)). We also give an application to the approximation of transitive invariant sets without genericity assumptions.

  7. Fumonisin B(1): a neurotoxic mycotoxin.

    PubMed

    Domijan, Ana-Marija

    2012-12-01

    Fumonisin B(1) (FB(1)) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB(1) is the most abundant and toxicologically the most significant one. FB(1) has a wide range of toxic effects, depending on animal species. In horses FB(1) causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB(1) is linked with higher incidence of primary liver cancer and oesophageal cancer, which are frequent in certain regions of the world (such as Transkei region in South Africa) where maize is staple food. The occurrence of neural tube defect in children in some countries of Central America (such as Mexico and Honduras) is connected with the consumption of FB(1)-contaminated maize-based food. However, possible involvement of FB(1) in the development of human diseases is not clear. Nevertheless, the International Agency for Research on Cancer (IARC) has classified FB(1) as a possible carcinogen to humans (group 2B). FB(1) is a causative agent of ELEM, a brain disorder in equines, indicating that brain is a target organ of FB(1) toxicity. Several studies on experimental animals or on cell cultures of neural origin have established that FB(1) has a neurodegenerative potential, although the mechanism of its neurotoxicity is still vague. The aim of this article is to give an overview of available literature on FB(1) neurotoxicity and involved mechanisms, and to offer a new perspective for future studies.

  8. On orientifolds of c=1 orbifolds

    NASA Astrophysics Data System (ADS)

    Dijkstra, T. P. T.; Gato-Rivera, B.; Riccioni, F.; Schellekens, A. N.

    2004-10-01

    The aim of this paper is to study orientifolds of c=1 conformal field theories. A systematic analysis of the allowed orientifold projections for c=1 orbifold conformal field theories is given. We compare the Klein bottle amplitudes obtained at rational points with the orientifold projections that we claim to be consistent for any value of the orbifold radius. We show that the recently obtained Klein bottle amplitudes corresponding to exceptional modular invariants, describing bosonic string theories at fractional square radius, are also in agreement with those orientifold projections.

  9. Hereditary angioedema with normal C1 inhibitor.

    PubMed

    Bork, Konrad

    2013-11-01

    Until recently it was assumed that hereditary angioedema was a disease that results exclusively from a genetic deficiency of the C1 inhibitor. In 2000, families with hereditary angioedema, normal C1 inhibitor activity, and protein in plasma were described. Since then, numerous patients and families with that condition have been reported. Most of the patients were women. In many of the affected women, oral contraceptives, hormone replacement therapy containing estrogens, and pregnancies triggered the clinical symptoms. In some families mutations in the coagulation factor XII (Hageman factor) gene were detected.

  10. Global gene profiling of aging lungs in Atp8b1 mutant mice

    PubMed Central

    Soundararajan, Ramani; Stearns, Timothy M.; Czachor, Alexander; Fukumoto, Jutaro; Turn, Christina; Westermann-Clark, Emma; Breitzig, Mason; Tan, Lee; Lockey, Richard F.; King, Benjamin L.; Kolliputi, Narasaiah

    2016-01-01

    Objective Recent studies implicate cardiolipin oxidation in several age-related diseases. Atp8b1 encoding Type 4 P-type ATPases is a cardiolipin transporter. Mutation in Atp8b1 gene or inflammation of the lungs impairs the capacity of Atp8b1 to clear cardiolipin from lung fluid. However, the link between Atp8b1 mutation and age-related gene alteration is unknown. Therefore, we investigated how Atp8b1 mutation alters age-related genes. Methods We performed Affymetrix gene profiling of lungs isolated from young (7-9 wks, n=6) and aged (14 months, 14 M, n=6) C57BL/6 and Atp8b1 mutant mice. In addition, Ingenuity Pathway Analysis (IPA) was performed. Differentially expressed genes were validated by quantitative real-time PCR (qRT-PCR). Results Global transcriptome analysis revealed 532 differentially expressed genes in Atp8b1 lungs, 157 differentially expressed genes in C57BL/6 lungs, and 37 overlapping genes. IPA of age-related genes in Atp8b1 lungs showed enrichment of Xenobiotic metabolism and Nrf2-mediated signaling pathways. The increase in Adamts2 and Mmp13 transcripts in aged Atp8b1 lungs was validated by qRT-PCR. Similarly, the decrease in Col1a1 and increase in Cxcr6 transcripts was confirmed in both Atp8b1 mutant and C57BL/6 lungs. Conclusion Based on transcriptome profiling, our study indicates that Atp8b1 mutant mice may be susceptible to age-related lung diseases. PMID:27689529

  11. Synthesis and biological evaluation of bradykinin B(1)/B(2) and selective B(1) receptor antagonists.

    PubMed

    Amblard, M; Bedos, P; Olivier, C; Daffix, I; Luccarini, J M; Dodey, P; Pruneau, D; Paquet, J L; Martinez, J

    2000-06-15

    We recently described a potent bradykinin B(2) receptor agonist (JMV1116) obtained by replacing the D-Tic-Oic dipeptide moiety of HOE140 by a (3S)-amino-5-(carbonylmethyl)-2,3-dihydro-1, 5-benzothiazepin-4(5H)-one (D-BT) moiety. This compound inhibited the specific binding of [(3)H]BK on membranes of CHO cells expressing the human cloned B(2) receptor with nanomolar affinity and contracted both isolated rat uterus and human umbilical vein. These data demonstrated that D-BT could be a good mimic of the Pro-Phe dipeptide. In the present study we characterized B(1) receptor antagonists containing the D-BT moiety. We prepared an analogue of compound JMV1116 deleting the C-terminal arginine residue. The resulting compound (1) had an affinity of 83 nM for the human cloned B(1) receptor. The most remarkable property of 1 is its ability to bind also the B(2) receptor with an affinity of 4.4 nM despite the absence of the C-terminal arginine residue. Modifications at the N-terminal part of 1 associated with the substitution of the thienylalanine residue by alpha-(2-indanyl)glycine resulted in analogues selectively binding to the B(1) receptor with an affinity in the picomolar range.

  12. Caged ceramide 1-phosphate (C1P) analogs: Novel tools for studying C1P biology.

    PubMed

    Gomez-Muñoz, Antonio; Gangoiti, Patricia; Rivera, Io-Guané; Presa, Natalia; Gomez-Larrauri, Ana; Ordoñez, Marta

    2016-01-01

    Ceramide 1-phosphate (C1P) is a bioactive sphingolipid metabolite that is produced in cells by the action of ceramide kinase (CerK) acting upon ceramide, and is also found in the circulation. C1P was first demonstrated to be mitogenic and antiapoptotic in different cell types, and was later shown to induce cell migration. Understanding the precise mechanisms by which C1P exerts its biological effects has been possible using specific photosensitive caged C1P analogues synthesized by Robert Bittman's group. These compounds are cell permeable, bypass cell plasma membrane receptors, and can be released into the cytosol upon light irradiation, thereby allowing precise determination of the intracellular mechanisms of actions of C1P. Two derivatives of N-palmitoyl-ceramide 1-phosphate have been used in most studies. In one C1P derivative the cage was 7-(N,N-diethylamino)coumarin (DECM-C1P) while in the other it was a 4-bromo-5-hydroxy-2-nitrobenzhydryl moiety (BHNB-C1P). The uncaging process released C1P in the cytosol, and this was accompanied by stimulation of cell proliferation, inhibition of apoptosis, and production of low levels of reactive oxygen species. However, intracellular accumulation of C1P did not affect chemotaxis. The caged C1P analogues allowed distinction between the extracellular events evoked by C1P, as for example through interaction with a putative cell-surface receptor, from its intracellular effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Tumor-specific expression of cytochrome P450 CYP1B1.

    PubMed

    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.

  14. Terminal complement complexes and C1/C1 inhibitor complexes in autoimmune thyroid disease.

    PubMed Central

    Weetman, A P; Cohen, S B; Oleesky, D A; Morgan, B P

    1989-01-01

    The potential role of complement activation and the membrane attack complex in the pathogenesis of Graves' disease and Hashimoto's thyroiditis has been investigated by measuring serum concentrations of the C1r-C1s-C1 inhibitor complex (C1/C1-inh) and the terminal complement complex (TCC), and by studying the binding to thyroid tissue of monoclonal and polyclonal antibodies against TCC neoantigens. Serum C1/C1-inh and TCC concentrations were significantly increased in 29 patients with untreated Graves' disease compared with 47 healthy subjects (P less than 0.001 for both), and decreased significantly after carbimazole treatment in 18 of these patients for whom post-treatment samples were available (P less than 0.01 and P less than 0.02, respectively). The serum TCC concentration, but not that of C1/C1-inh, was also significantly increased in 15 patients with Hashimoto's thyroiditis compared with the 47 healthy subjects (P less than 0.001). TCCs were identified by immunohistochemical staining around the thyroid follicles in thyroidectomy specimens from patients with Graves' disease (six out of six) and Hashimoto's thyroiditis (two out of two); normal thyroid tissue from two subjects showed no staining. These results suggest a role for complement, in particular the membrane attack complex in the pathogenesis of autoimmune thyroid disease. Images Fig. 3 PMID:2766576

  15. 12 CFR 261b.1 - Basis and scope.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Basis and scope. 261b.1 Section 261b.1 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM RULES REGARDING PUBLIC OBSERVATION OF MEETINGS § 261b.1 Basis and scope. This part is issued by the Board of...

  16. 26 CFR 1.643(b)-1 - Definition of income.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Definition of income. 1.643(b)-1 Section 1.643(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.643(b)-1 Definition of income...

  17. 40 CFR Figure B-1 to Subpart B of... - Example

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Example B Figure B-1 to Subpart B of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... of Automated Methods for SO2, CO, O3, and NO2 Pt. 53, Subpt. B, Fig. B-1 Figure B-1 to Subpart B...

  18. 40 CFR Figure B-1 to Subpart B of... - Example

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 6 2012-07-01 2012-07-01 false Example B Figure B-1 to Subpart B of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... of Automated Methods for SO2, CO, O3, and NO2 Pt. 53, Subpt. B, Fig. B-1 Figure B-1 to Subpart B...

  19. 40 CFR Figure B-1 to Subpart B of... - Example

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Example B Figure B-1 to Subpart B of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... of Automated Methods for SO2, CO, O3, and NO2 Pt. 53, Subpt. B, Fig. B-1 Figure B-1 to Subpart B...

  20. 29 CFR 2520.104b-1 - Disclosure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... sponsor's electronic information system is an integral part of those duties; or (ii) A participant... 29 Labor 9 2010-07-01 2010-07-01 false Disclosure. 2520.104b-1 Section 2520.104b-1 Labor... REPORTING AND DISCLOSURE Disclosure Requirements § 2520.104b-1 Disclosure. (a) General...

  1. 26 CFR 1.7702B-1 - Consumer protection provisions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Consumer protection provisions. 1.7702B-1 Section 1.7702B-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.7702B-1 Consumer...

  2. 26 CFR 1.367(b)-1 - Other transfers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Other transfers. 1.367(b)-1 Section 1.367(b)-1...) INCOME TAXES Effects on Corporation § 1.367(b)-1 Other transfers. (a) Scope. The regulations promulgated... earnings and profits, basis of stock or securities, basis of assets, or other relevant tax attributes....

  3. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 3 2014-04-01 2014-04-01 false Relationships. 1.267(b)-1 Section 1.267(b)-1...) INCOME TAXES (CONTINUED) Items Not Deductible § 1.267(b)-1 Relationships. (a) In general. (1) The persons... partnership separately. Therefore, if the other person and a partner are within any one of the relationships...

  4. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Relationships. 1.267(b)-1 Section 1.267(b)-1...) INCOME TAXES Items Not Deductible § 1.267(b)-1 Relationships. (a) In general. (1) The persons referred to... partnership separately. Therefore, if the other person and a partner are within any one of the relationships...

  5. 26 CFR 1.7702B-1 - Consumer protection provisions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Consumer protection provisions. 1.7702B-1 Section 1.7702B-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.7702B-1 Consumer protection...

  6. Combined traumatic occiput-C1 and C1-C2 dissociation: 2 case reports.

    PubMed

    Gould, Stephen; Hishmeh, Shuriz; McKinney, Bart; Stephen, Mark

    2010-08-01

    Occiput-C1 and C1-C2 dissociations and dislocations have been well documented in the literature. However, after thorough review of the literature, we found very little in the literature regarding combined occiput-C1 and C1-C2 dissociations in adults who survived. We present 2 case reports describing the clinical presentation, initial management, operative treatment, and postoperative course of 2 patients who sustained traumatic combined occiput-C1 and C1-C2 dissociations. After initial stabilization, both patients underwent open reduction and posterior occipital-cervical fusion with segmental fixation. At recent follow-up, both patients maintain good sagittal alignment without loss of reduction, and they have radiographic progression to fusion, minimal pain, and improved neurologic function. Combined occiput-C1 and C1-C2 dissociations are rare but serious injuries. Incomplete dissociations may not be evident on initial radiographs. Computed tomography or magnetic resonance imaging is recommended for formal diagnosis. A traumatic dural tear may be present. We recommend open reduction and posterior occipital-cervical fusion with segmental fixation for these patients.

  7. Cooperative Research in C1 Chemistry

    SciTech Connect

    Gerald P. Huffman

    2000-10-27

    C1 chemistry refers to the conversion of simple carbon-containing materials that contain one carbon atom per molecule into valuable products. The feedstocks for C1 chemistry include natural gas, carbon dioxide, carbon monoxide, methanol and synthesis gas (a mixture of carbon monoxide and hydrogen). Synthesis gas, or syngas, is produced primarily by the reaction of natural gas, which is principally methane, with steam. It can also be produced by gasification of coal, petroleum coke, or biomass. The availability of syngas from coal gasification is expected to increase significantly in the future because of increasing development of integrated gasification combined cycle (IGCC) power generation. Because of the abundance of remote natural gas, the advent of IGCC, and environmental advantages, C1 chemistry is expected to become a major area of interest for the transportation fuel and chemical industries in the relatively near future. The CFFLS will therefore perform a valuable national service by providing science and engineering graduates that are trained in this important area. Syngas is the source of most hydrogen. Approximately 10 trillion standard cubic feet (SCF) of hydrogen are manufactured annually in the world. Most of this hydrogen is currently used for the production of ammonia and in a variety of refining and chemical operations. However, utilization of hydrogen in fuel cells is expected to grow significantly in the next century. Syngas is also the feedstock for all methanol and Fischer-Tropsch plants. Currently, world consumption of methanol is over 25 million tons per year. There are many methanol plants in the U.S. and throughout the world. Methanol and oxygenated transportation fuel products play a significant role in the CFFLS C1 program. Currently, the only commercial Fischer-Tropsch plants are overseas, principally in South Africa (SASOL). However, new plants are being built or planned for a number of locations. One possible location for future F

  8. Notes on Liouville theory at c{<=}1

    SciTech Connect

    McElgin, Will

    2008-03-15

    The continuation of the Liouville conformal field theory to c{<=}1 is considered. The viability of an interpretation involving a timelike boson which is the conformal factor for two-dimensional asymptotically de Sitter geometries is examined. The conformal bootstrap leads to a three-point function with a unique analytic factor which is the same as that which appears along with the fusion coefficients in the minimal models. A corresponding nonanalytic factor produces a well-defined metric on fields only when the central charge is restricted to those of the topological minimal models, and when the conformal dimensions satisfy h>(c-1)/24. However, the theories considered here have a continuous spectrum which excludes the degenerate representations appearing in the minimal models. The c=1 theory has been investigated previously using similar techniques, and is identical to a nonrational conformal field theory (CFT) which arises as a limit of unitary minimal models. When coupled to unitary matter fields, the nonunitary theories with c{<=}-2 produce string amplitudes which are similar to those of the minimal string.

  9. Somatic overgrowth associated with homozygous mutations in both MAN1B1 and SEC23A

    PubMed Central

    Gupta, Swati; Fahiminiya, Somayyeh; Wang, Tracy; Dempsey Nunez, Laura; Rosenblatt, David S.; Gibson, William T.; Gilfix, Brian; Bergeron, John J. M.; Jerome-Majewska, Loydie A.

    2016-01-01

    Using whole-exome sequencing, we identified homozygous mutations in two unlinked genes, SEC23A c.1200G>C (p.M400I) and MAN1B1 c.1000C>T (p.R334C), associated with congenital birth defects in two patients from a consanguineous family. Patients presented with carbohydrate-deficient transferrin, tall stature, obesity, macrocephaly, and maloccluded teeth. The parents were healthy heterozygous carriers for both mutations and an unaffected sibling with tall stature carried the heterozygous mutation in SEC23A only. Mutations in SEC23A are responsible for craniolenticosultura dysplasia (CLSD). CLSD patients are short, have late-closing fontanels, and have reduced procollagen (pro-COL1A1) secretion because of abnormal pro-COL1A1 retention in the endoplasmic reticulum (ER). The mutation we identified in MAN1B1 was previously associated with reduced MAN1B1 protein and congenital disorders of glycosylation (CDG). CDG patients are also short, are obese, and have abnormal glycan remodeling. Molecular analysis of fibroblasts from the family revealed normal levels of SEC23A in all cells and reduced levels of MAN1B1 in cells with heterozygous or homozygous mutations in SEC23A and MAN1B1. Secretion of pro-COL1A1 was increased in fibroblasts from the siblings and patients, and pro-COL1A1 was retained in Golgi of heterozygous and homozygous mutant cells, although intracellular pro-COL1A1 was increased in patient fibroblasts only. We postulate that increased pro-COL1A1 secretion is responsible for tall stature in these patients and an unaffected sibling, and not previously discovered in patients with mutations in either SEC23A or MAN1B1. The patients in this study share biochemical and cellular characteristics consistent with mutations in MAN1B1 and SEC23A, indicating a digenic disease. PMID:27148587

  10. Circulating SerpinB1 levels and clinical features in patients with type 2 diabetes.

    PubMed

    Takebayashi, Kohzo; Hara, Kenji; Terasawa, Tomoko; Naruse, Rika; Suetsugu, Mariko; Tsuchiya, Takafumi; Inukai, Toshihiko

    2016-01-01

    The main purpose of this study was to investigate the association of serum SerpinB1 levels and various parameters in patients with type 2 diabetes. The effect of canagliflozin (a sodium glucose cotransporter 2 (SGLT2) inhibitor), which can decrease circulating insulin levels, on serum SerpinB1 levels was also investigated. A recent study suggests that the serum levels of SerpinB1, also known as monocyte neutrophil elastase inhibitor, increase with insulin resistance, may have a protective effect for pancreatic β cells, and may decrease insulin resistance. The study included 30 patients with type 2 diabetes hospitalized for glycemic control and 10 control subjects. SerpinB1 levels were significantly higher in patients with type 2 diabetes, compared with that in heathy control subjects (10.01±3.59 vs 5.69±1.64 ng/mL, p<0.0001). Serum SerpinB1 levels had a significant negative correlation with low-density lipoprotein cholesterol (LDL-C) (p=0.0123). Serum SerpinB1 levels had a significant positive association or trend toward a positive association with age and with hemoglobin A1c (HbA1c), and significant negative association with LDL-C levels in some multiple regression analysis models. Patients treated with statins had a tendency toward higher serum SerpinB1 levels, compared with those patients not treated with statins. During a 3-day observation period both with and without canagliflozin treatment, the serum SerpinB1 levels did not change. Serum SerpinB1 levels are elevated in patients with type 2 diabetes compared with that in healthy subjects and are negatively correlated with serum LDL-C.

  11. Circulating SerpinB1 levels and clinical features in patients with type 2 diabetes

    PubMed Central

    Takebayashi, Kohzo; Hara, Kenji; Terasawa, Tomoko; Naruse, Rika; Suetsugu, Mariko; Tsuchiya, Takafumi; Inukai, Toshihiko

    2016-01-01

    Objective The main purpose of this study was to investigate the association of serum SerpinB1 levels and various parameters in patients with type 2 diabetes. The effect of canagliflozin (a sodium glucose cotransporter 2 (SGLT2) inhibitor), which can decrease circulating insulin levels, on serum SerpinB1 levels was also investigated. A recent study suggests that the serum levels of SerpinB1, also known as monocyte neutrophil elastase inhibitor, increase with insulin resistance, may have a protective effect for pancreatic β cells, and may decrease insulin resistance. Research design and methods The study included 30 patients with type 2 diabetes hospitalized for glycemic control and 10 control subjects. Results SerpinB1 levels were significantly higher in patients with type 2 diabetes, compared with that in heathy control subjects (10.01±3.59 vs 5.69±1.64 ng/mL, p<0.0001). Serum SerpinB1 levels had a significant negative correlation with low-density lipoprotein cholesterol (LDL-C) (p=0.0123). Serum SerpinB1 levels had a significant positive association or trend toward a positive association with age and with hemoglobin A1c (HbA1c), and significant negative association with LDL-C levels in some multiple regression analysis models. Patients treated with statins had a tendency toward higher serum SerpinB1 levels, compared with those patients not treated with statins. During a 3-day observation period both with and without canagliflozin treatment, the serum SerpinB1 levels did not change. Conclusions Serum SerpinB1 levels are elevated in patients with type 2 diabetes compared with that in healthy subjects and are negatively correlated with serum LDL-C. PMID:27933185

  12. Effects of Aflatoxin B1 and Fumonisin B1 on Blood Biochemical Parameters in Broilers

    PubMed Central

    Tessari, Eliana N. C.; Kobashigawa, Estela; Cardoso, Ana Lúcia S. P.; Ledoux, David R.; Rottinghaus, George E.; Oliveira, Carlos A. F.

    2010-01-01

    The individual and combined effects of dietary aflatoxin B1 (AFB1) and fumonisin B1 (FB1) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 × 3 factorial arrangement with three levels of AFB1 (0, 50 and 200 μg AFB1/kg), and three levels of FB1 (0, 50 and 200 mg FB1/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB1 only, concentrations of AST were higher (p < 0.05) in all other treatment groups when compared with controls. Plasma TP was lower (p < 0.05) at six days post feeding in groups fed 200 μg AFB1/kg alone or in combination with FB1. At day 33 days post feeding, with the exception of birds fed the highest combination of AFB1 and FB1 which had higher plasma TP than control birds, plasma TP of birds fed other dietary treatments were similar to controls. Broilers receiving the highest levels of AFB1 and FB1 had bile duct proliferation and trabecular disorder in liver samples. AFB1 singly or in combination with FB at the levels studied, caused liver damage and an increase in serum levels of AST. PMID:22069595

  13. Effects of aflatoxin B(1) and fumonisin B(1) on blood biochemical parameters in broilers.

    PubMed

    Tessari, Eliana N C; Kobashigawa, Estela; Cardoso, Ana Lúcia S P; Ledoux, David R; Rottinghaus, George E; Oliveira, Carlos A F

    2010-04-01

    The individual and combined effects of dietary aflatoxin B(1 )(AFB(1)) and fumonisin B(1) (FB(1)) on liver pathology, serum levels of aspartate amino-transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 × 3 factorial arrangement with three levels of AFB(1 )(0, 50 and 200 μg AFB(1)/kg), and three levels of FB(1 )(0, 50 and 200 mg FB(1)/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB(1 )only, concentrations of AST were higher (p < 0.05) in all other treatment groups when compared with controls. Plasma TP was lower (p < 0.05) at six days post feeding in groups fed 200 μg AFB(1)/kg alone or in combination with FB(1). At day 33 days post feeding, with the exception of birds fed the highest combination of AFB(1 )and FB(1 )which had higher plasma TP than control birds(, )plasma TP of birds fed other dietary treatments were similar to controls. Broilers receiving the highest levels of AFB(1) and FB(1) had bile duct proliferation and trabecular disorder in liver samples. AFB(1) singly or in combination with FB at the levels studied, caused liver damage and an increase in serum levels of AST.

  14. Further characterization of the electrogenicity and pH sensitivity of the human organic anion-transporting polypeptides OATP1B1 and OATP1B3.

    PubMed

    Martinez-Becerra, Pablo; Briz, Oscar; Romero, Marta R; Macias, Rocio I R; Perez, Maria J; Sancho-Mateo, Carlos; Lostao, Maria P; Fernandez-Abalos, Jose M; Marin, Jose J G

    2011-03-01

    Organic anion-transporting polypeptides (OATPs) are involved in the liver uptake of many endogenous and xenobiotic compounds, such as bile acids and drugs, respectively. Using Xenopus laevis oocytes and Chinese hamster ovary (CHO) cells expressing rat Oatp1a1, human OATP1B1, or OATP1B3, the sensitivity of these transporters to extracellular/intracellular pH (pHo/pHi) and changes in plasma membrane potential (ΔΨ) was investigated. In X. laevis oocytes, nonspecific plasma membrane permeability increased only at pHo below 4.5. Above this value, both using oocytes and CHO cells, extracellular acidification affected differently the specific transport of taurocholic acid (TCA) and estradiol 17β-d-glucuronide (E(2)17βG) by Oatp1a1 (stimulation), OATP1B1 (inhibition), and OATP1B3 (stimulation). Changes in substrate uptake in the presence of valinomycin (K(+)-ionophore), carbonyl cyanide 3-chlorophenylhydrazone and nigericin (protonophores), and amiloride (Na(+)/H(+)-inhibitor) and cation replacement in the medium were studied with fluorescent probes for measuring substrate uptake (cholylglycyl amidofluorescein) and changes in pHi (SNARF-4F) and ΔΨ [DilC(1)(5)]. The results suggest that activity of these three carriers is sodium/potassium-independent and affected differently by changes in pHo and ΔΨ: Oatp1a1 was confirmed to be an electroneutral anion exchanger, whereas the function of both OATP1B1 and OATP1B3 was markedly affected by the magnitude of ΔΨ. Moreover, electrophysiological measurements revealed the existence of a net anion influx associated to OATP1B1/OATP1B3-mediated transport of TCA, E(2)17βG, and estrone-3-sulfate. Furthermore, a leakage of Na(+) through OATP1B1 and OATP1B3, which is not coupled to substrate transport, was found. In conclusion, these results suggest that OATP1B1 and OATP1B3 are electrogenic transporters whose activity may be strongly affected under circumstances of displacement of local pH.

  15. Interindividual and interethnic variability in drug disposition: polymorphisms in organic anion transporting polypeptide 1B1 (OATP1B1; SLCO1B1).

    PubMed

    Lee, Hannah H; Ho, Richard H

    2017-06-01

    OATP1B1 (SLCO1B1) is predominantly expressed at the basolateral membrane of hepatocytes and is critically important for the hepatic uptake and clearance of numerous drug substrates and endogenous compounds. In general, the organic anion transporting polypeptides (OATP; SLCO) represent a superfamily of uptake transporters that mediate the sodium-independent transport of a diverse range of amphipathic organic compounds including bile salts, steroid conjugates, thyroid hormones, anionic peptides, numerous drugs and other xenobiotic substances. OATP1B1 is highly polymorphic and a number of relevant and ethnically dependent polymorphisms have been identified and functionally characterized. In particular, the SLCO1B1 521T>C and 388A>G polymorphisms are commonly occurring variants in ethnically diverse populations and numerous in vitro and clinical studies have evaluated the consequences of these variants to interindividual differences in drug disposition and response. OATP1B1 is particularly important for the disposition of HMG-CoA reductase inhibitors, or statins, as it is known to efficiently transport most statins to their site of action within hepatocytes. Many studies have focused on the consequences of OATP1B1 variants to statin disposition in vitro and in vivo and would suggest that genetic variability in SLCO1B1 has important implications for statin pharmacokinetics, risk for statin-induced myopathy, and modulation of statin treatment response. This review describes what is currently known regarding SLCO1B1 genotype, OATP1B1 protein expression and interindividual and interethnic consequences to drug disposition, with particular focus on statin pharmacokinetics and implications for drug response and toxicity. © 2016 The British Pharmacological Society.

  16. Rapid modulation of the organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) function by protein kinase C-mediated internalization.

    PubMed

    Köck, Kathleen; Koenen, Anna; Giese, Bernd; Fraunholz, Martin; May, Karen; Siegmund, Werner; Hammer, Elke; Völker, Uwe; Jedlitschky, Gabriele; Kroemer, Heyo K; Grube, Markus

    2010-04-09

    Members of the organic anion transporting polypeptide (OATP) family are involved in various pharmacological, pathophysiological, and physiological processes, such as hepatic drug uptake, progress of cancer, or transport of hormones. Although variability in expression and function of OATPs has been investigated in detail, data concerning regulation are rather limited. Here, we report a novel mechanism for rapid regulation of OATP2B1 mediated by protein kinase C (PKC) resulting in significant changes of transport activity. PKC activation by the phorbol ester (phorbol 12-myristate 13-acetate, PMA) resulted in increased phosphorylation of OATP2B1 as well as reduced OATP2B1 transport activity with a decrease in V(max) of E(1)S uptake (288 +/- 21 (control) versus 165 +/- 16 pmol/min/mg of protein (PMA)). This effect was sensitive to the PKC inhibitor bisindolylmaleimide I (BIM-I). Confocal microscopy, fluorescence-based internalization assay, and live-cell imaging using green fluorescent protein-tagged OATP2B1 revealed that transport inhibition was due to internalization of the transporter. Furthermore, colocalization with LAMP-2 and chloroquine-sensitive degradation of OATP2B1 suggest that the internalized protein is targeted to a lysosomal degradation pathway. With regard to the underlying mechanism inhibition of caveolin/lipid raft-mediated endocytosis failed to prevent OATP2B1 internalization, whereas inhibition of clathrin-mediated processes blocked OATP2B1 sequestration. However, small interfering RNA-mediated clathrin knock-down affected general trafficking of OATP2B1 and resulted in intracellular accumulation in the absence of PMA. In conclusion, our data demonstrate that OATP2B1 function is regulated by PKC-mediated, clathrin-dependent internalization and followed by lysosomal degradation. Furthermore, internalization could be shown in an ex vivo placenta perfusion. Our findings represent a new, rapid mechanism in regulation of human OATPs.

  17. The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner

    PubMed Central

    Vikis, Haris G.; Li, Weiquan; He, Zhigang; Guan, Kun-Liang

    2000-01-01

    Semaphorin molecules serve as axon guidance signals that regulate the navigation of neuronal growth cones. Semaphorins have also been implicated in other biological processes, including the immune response. Plexins, acting either alone or in complex with neuropilins, have recently been identified as functional semaphorin receptors. However, the mechanisms of signal transduction by plexins remain largely unknown. We have demonstrated a direct interaction between plexin-B1 and activated Rac. Rac specifically interacts with the cytosolic domain of plexin-B1, but not with that of plexin-A3 or -C1. Neither RhoA nor Cdc42 interacts with plexin-B1, indicating that the Rac/plexin-B1 interaction is highly specific. The binding of GTP and the integrity of the Rac effector domain are required for the interaction with plexin-B1. Furthermore, we have identified that a Cdc42/Rac interactive binding (CRIB) motif in the cytosolic domain of plexin-B1 is essential for its interaction with active Rac. We have also observed that the semaphorin CD100, a ligand for plexin-B1, stimulates the interaction between plexin-B1 and active Rac. Our results support a model by which activated Rac plays a role in mediating semaphorin signals, resulting in reorganization of actin cytoskeletal structure. PMID:11035813

  18. Determinants of Human Cyclin B1 Association with Mitotic Chromosomes

    PubMed Central

    Pfaff, Kathleen L.; King, Randall W.

    2013-01-01

    Cyclin B1–CDK1 activity is essential for mitotic entry, but questions remain regarding how the activity of this kinase is spatially regulated. Previous studies showed that the cyclin B1 subunit localizes to several compartments of a mitotic cell, including the centrosomes, mitotic spindle, kinetochores and chromosomes via distinct sequence elements. Mitotic chromosome association occurs through the unstructured N-terminal domain of cyclin B1 and is independent of CDK1 binding. Here, we use live cell imaging of human cyclin B1 fused to GFP to precisely define the sequence elements within cyclin B1 that mediate its association with condensed mitotic chromosomes. We find that a short, evolutionarily conserved N-terminal motif is required for cyclin B1 to localize to mitotic chromosomes. We further reveal a role for arginine residues within and near the destruction box sequence in the chromosome association of cyclin B1. Additionally, our data suggest that sequences further downstream in cyclin B1, such as the cytoplasmic retention sequence and the cyclin box, may negatively modulate chromosome association. Because multiple basic residues are required for cyclin B1 association with mitotic chromosomes, electrostatic interactions with DNA may facilitate cyclin B1 localization to chromosomes. PMID:23505570

  19. Molecular genetics of C1 inhibitor.

    PubMed

    Tosi, M

    1998-08-01

    More than 100 different C1 inhibitor gene mutations have been described in hereditary angioedema (HAE) patients. Sixty-nine mutations have been reported in patients with the quantitative C1 inhibitor defect (type 1 HAE) in two recent large-scale studies. These changes were found distributed over all exons and exon/intron boundaries. The molecular defects can be divided as follows: Alu-repeat-mediated deletions or duplications (accounting for 21% of all cases), missense mutations (> 36%), frameshifts (14%), Stop codon mutations (10%), promoter variants (4%), splice site mutations (7-10%), deletions of a few amino acids (less than 3%). Several recent studies indicate that up to 25% of these changes are found in patients without a family history of angioedema and represent de novo mutations. Pathogenic amino acid substitutions were found distributed over the entire length of the coding sequence, except for the 100 amino-acid-long glycosylated amino-terminal extension, whose sequence tolerates extensive variation, as indicated by comparisons across species. Functional studies have been carried out only on a fraction of these amino acid substitutions and indicate that defects affecting intracellular transport are often at the basis of type 1 hereditary angioedema. An interesting promoter variant (a C to T transition at position -103) was found in an exceptional family with recessive transmission of the disease. Regulatory elements in the promoter region and in intron 1 were revealed by their sequence conservation in mouse and man and by functional studies. C1 inhibitor "minigene" constructs directing correct mRNA and protein synthesis in transgenic mice have provided valuable information on hormonal control and cell-type specificity of gene expression.

  20. COOPERATIVE RESEARCH IN C1 CHEMISTRY

    SciTech Connect

    Gerald P. Huffman

    2001-04-30

    Faculty and students from five universities (Kentucky, West Virginia, Utah, Pittsburgh and Auburn) are collaborating on a basic research program to develop novel C1 chemistry processes for the production of clean, high quality transportation fuel. An Industrial Advisory Board (IAB) with members from Chevron, Eastman Chemical, Energy International, Teir Associates, and the Department of Defense has been formed to provide practical guidance to the program. The program has two principal objectives. (1) Develop technology for conversion of C1 source materials (natural gas, synthesis gas, carbon dioxide and monoxide, and methanol) into clean, high efficiency transportation fuel. (2) Develop novel processes for producing hydrogen from natural gas and other hydrocarbons. Some of the principal accomplishments of the program in its first two years are: (1) The addition of acetylenic compounds in Fischer-Tropsch synthesis is found to produce significant amounts of oxygenated products in FT diesel fuels. Such oxygenated products should decrease particulate matter (PM) emissions. (2) Nanoscale, binary, Fe-based catalysts supported on alumina have been shown to have significant activity for the decomposition of methane into pure hydrogen and potentially valuable multi-walled carbon nanotubes. (3) Catalytic synthesis processes have been developed for synthesis of diethyl carbonate, higher ethers, and higher alcohols from C1 source materials. Testing of the effect of adding these oxygenates to diesel fuel on PM emissions has begun using a well-equipped small diesel engine test facility. (4) Supercritical fluid (SCF) FT synthesis has been conducted under SCF hexane using both Fe and Co catalysts. There is a marked effect on the hydrocarbon product distribution, with a shift to higher carbon number products. These and other results are summarized.

  1. Theoretical Insights into C1 Surface Chemistry

    NASA Astrophysics Data System (ADS)

    Neurock, Matthew

    2008-03-01

    Reforming and partial oxidation of methane as well as other C1 fuels are important processes in the production of hydrogen and synthesis gas and will likely play important roles future energy strategies. Herein we use theory and simulation to examine the reactivity of methane, methanol and dimethyl ether with CO2, H2O, or O2 over supported transition metals. We systematically probe the elementary C-H bond activation as well as the oxidation pathways involved in both reforming as the oxidation of methane and other C1 intermediates over well defined transition metal surfaces, metal alloys and metal nanoparticles. The calculations demonstrate well-established trends in C-H bond activation as the result of changes in the metal, the activating molecule (methane, methanol, and DME) as well as the reaction conditions. The reaction conditions ultimately dictate the surface coverage of carbon and oxygen which have important consequences on the surface reactivity. The theoretical and simulation results are compared with well defined experiments carried out at Berkeley over supported particles.

  2. MAN1B1 Deficiency: An Unexpected CDG-II

    PubMed Central

    Millón, María B.; Race, Valérie; Sturiale, Luisa; Garozzo, Domenico; Mills, Philippa; Clayton, Peter; Asteggiano, Carla G.; Quelhas, Dulce; Cansu, Ali; Martins, Esmeralda; Nassogne, Marie-Cécile; Gonçalves-Rocha, Miguel; Topaloglu, Haluk; Jaeken, Jaak; Foulquier, François; Matthijs, Gert

    2013-01-01

    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. PMID:24348268

  3. Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites

    PubMed Central

    Bally, Isabelle; Ancelet, Sarah; Moriscot, Christine; Gonnet, Florence; Mantovani, Alberto; Daniel, Régis; Schoehn, Guy; Arlaud, Gérard J.; Thielens, Nicole M.

    2013-01-01

    Complement C1q is a hexameric molecule assembled from 18 polypeptide chains of three different types encoded by three genes. This versatile recognition protein senses a wide variety of immune and nonimmune ligands, including pathogens and altered self components, and triggers the classical complement pathway through activation of its associated proteases C1r and C1s. We report a method for expression of recombinant full-length human C1q involving stable transfection of HEK 293-F mammalian cells and fusion of an affinity tag to the C-terminal end of the C chain. The resulting recombinant (r) C1q molecule is similar to serum C1q as judged from biochemical and structural analyses and exhibits the characteristic shape of a bunch of flowers. Analysis of its interaction properties by surface plasmon resonance shows that rC1q retains the ability of serum C1q to associate with the C1s-C1r-C1r-C1s tetramer, to recognize physiological C1q ligands such as IgG and pentraxin 3, and to trigger C1r and C1s activation. Functional analysis of rC1q variants carrying mutations of LysA59, LysB61, and/or LysC58, in the collagen-like stems, demonstrates that LysB61 and LysC58 each play a key role in the interaction with C1s-C1r-C1r-C1s, with LysA59 being involved to a lesser degree. We propose that LysB61 and LysC58 both form salt bridges with outer acidic Ca2+ ligands of the C1r and C1s CUB (complement C1r/C1s, Uegf, bone morphogenetic protein) domains. The expression method reported here opens the way for deciphering the molecular basis of the unusual binding versatility of C1q by mapping the residues involved in the sensing of its targets and the binding of its receptors. PMID:23650384

  4. Loss of endophilin-B1 exacerbates Alzheimer's disease pathology.

    PubMed

    Wang, David B; Kinoshita, Yoshito; Kinoshita, Chizuru; Uo, Takuma; Sopher, Bryce L; Cudaback, Eiron; Keene, C Dirk; Bilousova, Tina; Gylys, Karen; Case, Amanda; Jayadev, Suman; Wang, Hong-Gang; Garden, Gwenn A; Morrison, Richard S

    2015-07-01

    Endophilin-B1, also known as Bax-interacting factor 1 (Bif-1, and encoded by SH3GLB1), is a multifunctional protein involved in apoptosis, autophagy and mitochondrial function. We recently described a unique neuroprotective role for neuron-specific alternatively spliced isoforms of endophilin-B1. To examine whether endophilin-B1-mediated neuroprotection could be a novel therapeutic target for Alzheimer's disease we used a double mutant amyloid precursor protein and presenilin 1 (APPswe/PSEN1dE9) mouse model of Alzheimer's disease and observed that expression of neuron-specific endophilin-B1 isoforms declined with disease progression. To determine if this reduction in endophilin-B1 has a functional role in Alzheimer's disease pathogenesis, we crossed endophilin-B1(-/-) mice with APPswe/PSEN1dE9 mice. Deletion of endophilin-B1 accelerated disease onset and progression in 6-month-old APPswe/PSEN1dE9/endophilin-B1(-/-) mice, which showed more plaques, astrogliosis, synaptic degeneration, cognitive impairment and mortality than APPswe/PSEN1dE9 mice. In mouse primary cortical neuron cultures, overexpression of neuron-specific endophilin-B1 isoforms protected against amyloid-β-induced apoptosis and mitochondrial dysfunction. Additionally, protein and mRNA levels of neuron-specific endophilin-B1 isoforms were also selectively decreased in the cerebral cortex and in the synaptic compartment of patients with Alzheimer's disease. Flow sorting of synaptosomes from patients with Alzheimer's disease demonstrated a negative correlation between amyloid-β and endophilin-B1 levels. The importance of endophilin-B1 in neuronal function was further underscored by the development of synaptic degeneration and cognitive and motor impairment in endophilin-B1(-/-) mice by 12 months. Our findings suggest that endophilin-B1 is a key mediator of a feed-forward mechanism of Alzheimer's disease pathogenesis where amyloid-β reduces neuron-specific endophilin-B1, which in turn enhances amyloid

  5. X (3872 ) , Xb , and the χb 1(3 P ) state

    NASA Astrophysics Data System (ADS)

    Karliner, Marek; Rosner, Jonathan L.

    2015-01-01

    We discuss the possible production and discovery channels in e+e- and p p machines of the Xb, the bottomonium counterpart of X (3872 ) and the putative isoscalar analogue of the charged bottomoniumlike states Zb discovered by Belle. We suggest that the Xb may be close in mass to the bottomonium state χb 1(3 P ), mixing with it and sharing its decay channels, just as X (3872 ) is likely a mixture of a D ¯D* molecule and χc 1(2 P ) . Consequently, the experiments which reported observing χb 1(3 P ) might have actually discovered the Xb, or a mixture of the two states.

  6. 26 CFR 48.4061(b)-1 - Imposition of tax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 16 2013-04-01 2013-04-01 false Imposition of tax. 48.4061(b)-1 Section 48.4061... EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Motor Vehicles, Tires, Tubes, Tread Rubber, and Taxable Fuel Automotive and Related Items § 48.4061(b)-1 Imposition of tax. (a) In general. Section...

  7. 26 CFR 48.4061(b)-1 - Imposition of tax.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Imposition of tax. 48.4061(b)-1 Section 48.4061... EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Motor Vehicles, Tires, Tubes, Tread Rubber, and Taxable Fuel Automotive and Related Items § 48.4061(b)-1 Imposition of tax. (a) In general. Section 4061(b...

  8. 77 FR 46419 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  9. 77 FR 46417 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  10. 78 FR 26326 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  11. 77 FR 52698 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  12. 78 FR 26330 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  13. 77 FR 35363 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  14. 76 FR 72184 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-22

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  15. 77 FR 53180 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. ] This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  16. 76 FR 77809 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-14

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  17. 78 FR 48424 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-08

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  18. 76 FR 72182 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-22

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  19. 78 FR 78941 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  20. 76 FR 79658 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-22

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  1. 76 FR 76954 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  2. 76 FR 69707 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  3. 78 FR 26324 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  4. 78 FR 78939 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  5. 78 FR 49482 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-14

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  6. 76 FR 65701 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-24

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  7. 76 FR 68432 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  8. 77 FR 46415 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  9. 76 FR 66044 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  10. 76 FR 66046 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  11. 78 FR 26328 - 36(b)(1) Arms Sales Notification

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    2013-05-06

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  12. 77 FR 53182 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-31

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  13. 77 FR 49430 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B....

  14. 77 FR 49434 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  15. 78 FR 46579 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English,...

  16. 26 CFR 1.643(b)-1 - Definition of income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Definition of income. 1.643(b)-1 Section 1.643(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX... of subparts A through D, part I, subchapter J, chapter 1 of the Internal Revenue Code, “income,”...

  17. 26 CFR 31.6011(b)-1 - Employers' identification numbers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Employers' identification numbers. 31.6011(b)-1... Subtitle F, Internal Revenue Code of 1954) § 31.6011(b)-1 Employers' identification numbers. (a... Insurance Contributions Act, but who prior to such day neither has been assigned an identification number...

  18. 26 CFR 1.669(b)-1 - Information requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Information requirements. 1.669(b)-1 Section 1... Beginning Before January 1, 1969 § 1.669(b)-1 Information requirements. The election of a beneficiary who is... following information with respect to the operation and accounts of the foreign trust created by a U.S...

  19. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Relationships. 1.267(b)-1 Section 1.267(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED... interest are accrued. (3) Under section 267(b)(9), the control of certain educational and...

  20. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Relationships. 1.267(b)-1 Section 1.267(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED... interest are accrued. (3) Under section 267(b)(9), the control of certain educational and...

  1. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Relationships. 1.267(b)-1 Section 1.267(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED... interest are accrued. (3) Under section 267(b)(9), the control of certain educational and...

  2. 26 CFR 11.410(b)-1 - Minimum coverage requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Minimum coverage requirements. 11.410(b)-1 Section 11.410(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) TEMPORARY INCOME TAX REGULATIONS UNDER THE EMPLOYEE RETIREMENT INCOME SECURITY ACT...

  3. 26 CFR 48.4061(b)-1 - Imposition of tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Imposition of tax. 48.4061(b)-1 Section 48.4061(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Motor Vehicles, Tires, Tubes, Tread Rubber,...

  4. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise...

  5. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise...

  6. 77 FR 65185 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-25

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA...

  7. SerpinB1 Promotes Pancreatic β Cell Proliferation

    SciTech Connect

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

    2016-01-01

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

  8. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise allowable...

  9. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 3 2014-04-01 2014-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise...

  10. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise...

  11. 76 FR 60467 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...: a Foreign Military Sales Order II (FMSO II) to provide funds for blanket order requisitions,...

  12. 76 FR 56181 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security... a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section.... (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None. (vii) Sensitivity...

  13. 26 CFR 1.269B-1 - Stapled foreign corporations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Stapled foreign corporations. 1.269B-1 Section 1... (CONTINUED) INCOME TAXES Items Not Deductible § 1.269B-1 Stapled foreign corporations. (a) Treatment as a domestic corporation—(1) General rule. Except as otherwise provided, if a foreign corporation is a...

  14. 26 CFR 1.677(b)-1 - Trusts for support.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Trusts for support. 1.677(b)-1 Section 1.677(b... (CONTINUED) INCOME TAXES Grantors and Others Treated As Substantial Owners § 1.677(b)-1 Trusts for support. (a) Section 677(b) provides that a grantor is not treated as the owner of a trust merely because...

  15. 17 CFR 260.10b-1 - Calculation of percentages.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Calculation of percentages. 260.10b-1 Section 260.10b-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Calculation of percentages. The percentages of voting securities and other securities specified in section...

  16. 76 FR 103 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-03

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated 21 July 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English...

  17. 76 FR 107 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-03

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated 21 July 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English...

  18. 76 FR 30670 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated 21 July 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English...

  19. 76 FR 30676 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated 21 July 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English...

  20. Hereditary C1q deficiency: a new family with C1qA deficiency.

    PubMed

    Sun-Tan, Cağman; Ozgür, Tuba Turul; Kilinç, Gamze; Topaloğlu, Rezan; Gököz, Ozay; Ersoy-Evans, Sibel; Sanal, Ozden

    2010-01-01

    Hereditary deficiency of complement component C1q is a rare genetic disorder with susceptibility to recurrent infections with polysaccharide-containing encapsulated microorganisms and a high prevalence of autoimmune diseases, most often systemic lupus erythematosus (SLE). Here, we report a 29-month-old boy who presented with facial rash and history of early death of a sibling with infections, who was found to have a selective deficiency of C1q. The facial rash was composed of patchy erythematous plaques and centrally hypopigmented macules and desquamation. Two siblings had died of severe bacterial infections and his uncle had died of meningitis. Molecular study disclosed a homozygous point mutation in the C1qA chain gene. Five members of the family, including the parents and three healthy siblings, were heterozygous for this mutation.

  1. CYP1B1 and hormone-induced cancer.

    PubMed

    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.

  2. The Role of B-1 Cells in Inflammation

    PubMed Central

    Aziz, Monowar; Holodick, Nichol E.; Rothstein, Thomas L.; Wang, Ping

    2015-01-01

    B-1 lymphocytes exhibit unique phenotypic, ontogenic, and functional characteristics that differ from the conventional B-2 cells. B-1 cells spontaneously secrete germline-like, repertoire skewed polyreactive natural antibody, which acts as a first line of defense by neutralizing a wide range of pathogens before launching of the adaptive immune response. Immunomodulatory molecules, such as interleukin-10 (IL-10), adenosine, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-35 are also produced by B-1 cells in the presence or absence of stimulation, which regulate acute and chronic inflammatory diseases. Considerable progress has been made during the past three decades since the discovery of B-1 cells, which has not only improved our understanding of their phenotypic and ontogenic uniqueness but also their role in various inflammatory diseases including influenza, pneumonia, sepsis, atherosclerosis, inflammatory bowel disease (IBD), autoimmunity, obesity and diabetes mellitus. Recent identification of human B-1 cells widens the scope of this field, leading to novel innovations that can be implemented from bench to bedside. Among the vast number of studies on B-1 cells, we have carried out a literature review highlighting current trends in the study of B-1 cell involvement during inflammation, which may result in a paradigm shift towards sustainable therapeutics in various inflammatory diseases. PMID:26427372

  3. Structural and functional aspects of C1-inhibitor.

    PubMed

    Bos, Ineke G A; Hack, C Erik; Abrahams, Jan Pieter

    2002-09-01

    C1-Inh is a serpin that inhibits serine proteases from the complement and the coagulation pathway. C1-Inh consists of a serpin domain and a unique N-terminal domain and is heavily glycosylated. Non-functional mutants of C1-Inh can give insight into the inhibitory mechanism of C1-Inh. This review describes a novel 3D model of C1-Inh, based on a newly developed homology modelling method. This model gives insight into a possible potentiation mechanism of C1-Inh and based on this model the essential residues for efficient inhibition by C1-Inh are discussed.

  4. Flavopiridol Pharmacogenetics: Clinical and Functional Evidence for the Role of SLCO1B1/OATP1B1 in Flavopiridol Disposition

    PubMed Central

    Ni, Wenjun; Ji, Jia; Dai, Zunyan; Papp, Audrey; Johnson, Amy J.; Ahn, Sunjoo; Farley, Katherine L.; Lin, Thomas S.; Dalton, James T.; Li, Xiaobai; Jarjoura, David; Byrd, John C.; Sadee, Wolfgang; Grever, Michael R.; Phelps, Mitch A.

    2010-01-01

    Background Flavopiridol is a cyclin-dependent kinase inhibitor in phase II clinical development for treatment of various forms of cancer. When administered with a pharmacokinetically (PK)-directed dosing schedule, flavopiridol exhibited striking activity in patients with refractory chronic lymphocytic leukemia. This study aimed to evaluate pharmacogenetic factors associated with inter-individual variability in pharmacokinetics and outcomes associated with flavopiridol therapy. Methodology/Principal Findings Thirty-five patients who received single-agent flavopiridol via the PK-directed schedule were genotyped for 189 polymorphisms in genes encoding 56 drug metabolizing enzymes and transporters. Genotypes were evaluated in univariate and multivariate analyses as covariates in a population PK model. Transport of flavopiridol and its glucuronide metabolite was evaluated in uptake assays in HEK-293 and MDCK-II cells transiently transfected with SLCO1B1. Polymorphisms in ABCC2, ABCG2, UGT1A1, UGT1A9, and SLCO1B1 were found to significantly correlate with flavopiridol PK in univariate analysis. Transport assay results indicated both flavopiridol and flavopiridol-glucuronide are substrates of the SLCO1B1/OATP1B1 transporter. Covariates incorporated into the final population PK model included bilirubin, SLCO1B1 rs11045819 and ABCC2 rs8187710. Associations were also observed between genotype and response. To validate these findings, a second set of data with 51 patients was evaluated, and overall trends for associations between PK and PGx were found to be consistent. Conclusions/Significance Polymorphisms in transport genes were found to be associated with flavopiridol disposition and outcomes. Observed clinical associations with SLCO1B1 were functionally validated indicating for the first time its relevance as a transporter of flavopiridol and its glucuronide metabolite. A second 51-patient dataset indicated similar trends between genotype in the SLCO1B1 and other

  5. CYP1B1: a unique gene with unique characteristics.

    PubMed

    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.

  6. Differential Effects of Glycyrrhiza Species on Genotoxic Estrogen Metabolism: Licochalcone A Downregulates P450 1B1, whereas Isoliquiritigenin Stimulates It.

    PubMed

    Dunlap, Tareisha L; Wang, Shuai; Simmler, Charlotte; Chen, Shao-Nong; Pauli, Guido F; Dietz, Birgit M; Bolton, Judy L

    2015-08-17

    Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by upregulating P450 1B1. The present study tested the three authenticated medicinal species of licorice [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)] used by women as dietary supplements for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI-specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI ≫ GG > GU and LigC ≅ LicA ≫ LigF. The Michael acceptor chalcone, LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as nontoxic and 4-MeOE1 as genotoxic biomarkers in the nontumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 μg/mL), and LigC (1 μM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-α and IFN-γ). LicA (1, 10 μM) decreased cytokine- and TCDD-induced P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50 = 12.3 μM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 μg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that, of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women's health. Additionally, the

  7. MISR Level 1B1 Radiance Data (MI1B1_V1)

    NASA Technical Reports Server (NTRS)

    Diner, David J. (Principal Investigator)

    summary, the Level 1B1 Product contains the Data Numbers (DNs) radiometrically-scaled to radiances with no geometric resampling. [Location=GLOBAL] [Temporal_Coverage: Start_Date=2000-02-24; Stop_Date=] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=275 m for red band only; Longitude_Resolution=275 m for red band only; Horizontal_Resolution_Range=250 meters - < 500 meters; Temporal_Resolution=about 15 orbits/day; Temporal_Resolution_Range=Daily - < Weekly, about 15 orbits/day, Daily - < Weekly].

  8. MISR Level 1B1 Radiance Data (MI1B1_V2)

    NASA Technical Reports Server (NTRS)

    Diner, David J. (Principal Investigator)

    summary, the Level 1B1 Product contains the Data Numbers (DNs) radiometrically-scaled to radiances with no geometric resampling. [Temporal_Coverage: Start_Date=2000-02-24; Stop_Date=] [Spatial_Coverage: Southernmost_Latitude=-90; Northernmost_Latitude=90; Westernmost_Longitude=-180; Easternmost_Longitude=180] [Data_Resolution: Latitude_Resolution=1.1 km; Longitude_Resolution=1.1 km; Temporal_Resolution=about 15 orbits/day; Temporal_Resolution_Range=about 15 orbits/day].

  9. Interaction of A1B1 and BRCA1 in the Development of Breast Cancer

    DTIC Science & Technology

    2008-03-01

    ERα transcriptional activity MCF-7 cells were plated in 5% charcoal-stripped serum in IMEM for 3 days prior to transfection. Cells were transfected...plated in IMEM containing 10% fetal bovine serum. After the cells were attached, the media was changed to serum-free IMEM . The cells were transfected

  10. Characterization of C1 inhibitor binding to neutrophils.

    PubMed Central

    Chang, N S; Boackle, R J; Leu, R W

    1991-01-01

    In a previous study we have isolated neutrophil membrane proteins that non-covalently bind to native C1-INH (105,000 MW) and a non-functional, degraded C1-INH (88,000 MW; C1-INH-88). To further characterize the binding nature, we have designed a novel kinetic C1 titration assay which enables not only a quantification of the removal of fluid-phase C1-INH by neutrophils, but also a concomitant measure of residual C1-INH function. Native C1-INH, when adsorbed to EDTA-pretreated neutrophils, lost its function in the inhibition of fluid-phase C1. The non-functional C1-INH-88, which is probably devoid of a reactive centre, was found to block the binding of native C1-INH to neutrophils. Pretreatment of neutrophils with serine esterase inhibitors did not abrogate binding capacity of the cells for C1-INH, whereas the binding affinity for C1-INH was lost when the cells were pretreated with trypsin. An array of human peripheral blood leucocytes and several lymphoid cell lines has surface binding sites for C1-INH, but not on human erythrocytes and U937 cells. Binding was further confirmed using (i) C1-INH-microsphere beads to neutrophils, in which the binding was blocked when pretreating neutrophils with excess C1-INH or with trypsin, and (ii) radiolabelled C1-INH to neutrophils, which was competitively blocked by unlabelled non-functional C1-INH-88. Desialylation of C1-INH significantly reduced its binding affinity for neutrophils, indicating that the membrane receptor sites on neutrophils could be specific for the binding of sialic acid residues on C1-INH. Overall, our studies indicate that neutrophils or other leucocytes possess specific surface binding sites for the sialic acid-containing portion of C1-INH. PMID:2045131

  11. 26 CFR 31.3302(b)-1 - Additional credit against tax.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Additional credit against tax. 31.3302(b)-1... credit against tax. (a) In general. In addition to the credit against the tax allowable for contributions actually paid to State unemployment funds (see § 31.3302(a)-1), the taxpayer may be entitled to a...

  12. 26 CFR 31.3302(b)-1 - Additional credit against tax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Additional credit against tax. 31.3302(b)-1... credit against tax. (a) In general. In addition to the credit against the tax allowable for contributions actually paid to State unemployment funds (see § 31.3302(a)-1), the taxpayer may be entitled to a...

  13. 26 CFR 31.3302(b)-1 - Additional credit against tax.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Additional credit against tax. 31.3302(b)-1... credit against tax. (a) In general. In addition to the credit against the tax allowable for contributions actually paid to State unemployment funds (see § 31.3302(a)-1), the taxpayer may be entitled to a...

  14. 26 CFR 31.3302(b)-1 - Additional credit against tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Additional credit against tax. 31.3302(b)-1... credit against tax. (a) In general. In addition to the credit against the tax allowable for contributions actually paid to State unemployment funds (see § 31.3302(a)-1), the taxpayer may be entitled to a credit...

  15. Classical complement pathway component C1q: purification of human C1q, isolation of C1q collagen-like and globular head fragments and production of recombinant C1q-derivatives. Functional characterization.

    PubMed

    Kojouharova, Mihaela

    2014-01-01

    The classical complement pathway (CCP) activation is a multimolecular complex, composed of three subcomponents namely C1q, C1r, and C1s. C1q is the recognition subunit of this complex and its binding to the specific targets leads to the formation of active C1, which in turn activates the CCP in an immunoglobulin-dependent or -independent manner. C1q is a hexameric glycoprotein composed of 18 polypeptide chains of three different types (A, B, and C), organized in two fragments-collagen-like (CLR) and globular head (gC1q) possessing different functional activity. The contemporary knowledge of the C1q structure allows the isolation and purification of a C1q molecule from serum by combination of different chromatography procedures including ion-exchange, size-exclusion, and affinity chromatography, as well as the isolation of CLR and gC1q by limited enzymatic hydrolysis of the native C1q molecule. In this chapter, we described methods for purification of human C1q and its CLR and gC1q fragments, as well as methods for their biochemical and functional characterization. The production and purification of recombinant C1q derivatives ghA, ghB, and ghC (globular fragments of the individual C1q chains) are also presented.

  16. 76 FR 46754 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-03

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21,...

  17. 78 FR 36538 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21,...

  18. 78 FR 41039 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-09

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21,...

  19. Supercritical Fluid Extraction of Aflatoxin B 1 from Soil

    EPA Science Inventory

    This research describes the development of a Supercritical Fluid Extraction (SFE) method to recover aflatoxin B1 from fortified soil. The effects of temperature, pressure, modifier (identity and percentage), and extraction type were assessed. Using the optimized SFE conditions, ...

  20. B-1 cells as a source of IgA.

    PubMed

    Meyer-Bahlburg, Almut

    2015-12-01

    Immunoglobulin A (IgA) is the most abundantly produced immunoglobulin found primarily on mucosal surfaces. The generation of IgA and its involvement in mucosal immune responses have been intensely studied over the past years. IgA can be generated in T cell-dependent and T cell-independent pathways, and it has an important impact on maintaining homeostasis within the mucosal immune system. There is good evidence that B-1 cells contribute substantially to the production of mucosal IgA and thus play an important role in regulating commensal microbiota. However, whether B-1 cells produce antigen-specific or only nonspecific IgA remains to be determined. This review will discuss what is currently known about IgA production by B-1 cells and the functional relevance of B-1 cell-derived IgA both in vitro and in vivo. © 2015 New York Academy of Sciences.

  1. Properties of L=1 B(1) and B(2)* mesons.

    PubMed

    Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Ahn, S H; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Anastasoaie, M; Ancu, L S; Andeen, T; Anderson, S; Andrieu, B; Anzelc, M S; Arnoud, Y; Arov, M; Arthaud, M; Askew, A; Asman, B; Assis Jesus, A C S; Atramentov, O; Autermann, C; Avila, C; Ay, C; Badaud, F; Baden, A; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Banerjee, P; Barberis, E; Barfuss, A-F; Bargassa, P; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Berntzon, L; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Biscarat, C; Blazey, G; Blekman, F; Blessing, S; Bloch, D; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Borissov, G; Bos, K; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Buchanan, N J; Buchholz, D; Buehler, M; Buescher, V; Burdin, S; Burke, S; Burnett, T H; Buszello, C P; Butler, J M; Calfayan, P; Calvet, S; Cammin, J; Caron, S; Carvalho, W; Casey, B C K; Cason, N M; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chan, K; Chandra, A; Charles, F; Cheu, E; Chevallier, F; Cho, D K; Choi, S; Choudhary, B; Christofek, L; Christoudias, T; Cihangir, S; Claes, D; Clément, C; Clément, B; Coadou, Y; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Crépé-Renaudin, S; Cutts, D; Cwiok, M; da Motta, H; Das, A; Davies, G; De, K; de Jong, S J; de Jong, P; De La Cruz-Burelo, E; Martins, C De Oliveira; Degenhardt, J D; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dong, H; Dudko, L V; Duflot, L; Dugad, S R; Duggan, D; Duperrin, A; Dyer, J; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Evans, H; Evdokimov, A; Evdokimov, V N; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Ford, M; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Gallas, E; Galyaev, E; Garcia, C; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Gelé, D; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Gollub, N; Gómez, B; Goussiou, A; Grannis, P D; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, J; Guo, F; Gutierrez, P; Gutierrez, G; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Hanagaki, K; Hansson, P; Harder, K; Harel, A; Harrington, R; Hauptman, J M; Hauser, R; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinmiller, J M; Heinson, A P; Heintz, U; Hensel, C; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hobbs, J D; Hoeneisen, B; Hoeth, H; Hohlfeld, M; Hong, S J; Hooper, R; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jarvis, C; Jesik, R; Johns, K; Johnson, C; Johnson, M; Jonckheere, A; Jonsson, P; Juste, A; Käfer, D; Kahn, S; Kajfasz, E; Kalinin, A M; Kalk, J R; Kalk, J M; Kappler, S; Karmanov, D; Kasper, J; Kasper, P; Katsanos, I; Kau, D; Kaur, R; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y M; Khatidze, D; Kim, H; Kim, T J; Kirby, M H; Kirsch, M; Klima, B; Kohli, J M; Konrath, J-P; Kopal, M; Korablev, V M; Kothari, B; Kozelov, A V; Krop, D; Kryemadhi, A; Kuhl, T; Kumar, A; Kunori, S; Kupco, A; Kurca, T; Kvita, J; Lacroix, F; Lam, D; Lammers, S; Landsberg, G; Lazoflores, J; Lebrun, P; Lee, W M; Leflat, A; Lehner, F; Lellouch, J; Lesne, V; Leveque, J; Lewis, P; Li, J; Li, Q Z; Li, L; Lietti, S M; Lima, J G R; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobo, L; Lobodenko, A; Lokajicek, M; Lounis, A; Love, P; Lubatti, H J; Lyon, A L; Maciel, A K A; Mackin, D; Madaras, R J; Mättig, P; Magass, C; Magerkurth, A; Makovec, N; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Mao, H S; Maravin, Y; Martin, B; McCarthy, R; Melnitchouk, A; Mendes, A; Mendoza, L; Mercadante, P G; Merkin, M; Merritt, K W; Meyer, J; Meyer, A; Michaut, M; Millet, T; Mitrevski, J; Molina, J; Mommsen, R K; Mondal, N K; Moore, R W; Moulik, T; Muanza, G S; Mulders, M; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Naumann, N A; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nomerotski, A; Novaes, S F; Nunnemann, T; O'Dell, V; O'Neil, D C; Obrant, G; Ochando, C; Onoprienko, D; Oshima, N; Osta, J; Otec, R; Y Garzón, G J Otero; Owen, M; Padley, P; Pangilinan, M; Parashar, N; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Penning, B; Perea, P M; Peters, K; Peters, Y; Pétroff, P; Petteni, M; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M-E; Polozov, P; Pompos, A; Pope, B G; Popov, A V; Potter, C; da Silva, W L Prado; Prosper, H B; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rakitine, A; Rangel, M S; Rani, K J; Ranjan, K; Ratoff, P N; Renkel, P; Reucroft, S; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rodrigues, R F; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Santoro, A; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schieferdecker, P; Schliephake, T; Schmitt, C; Schwanenberger, C; Schwartzman, A; Schwienhorst, R; Sekaric, J; Sengupta, S; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Shpakov, D; Siccardi, V; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Smith, R P; Snow, J; Snow, G R; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Souza, M; Spurlock, B; Stark, J; Steele, J; Stolin, V; Stone, A; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, M; Strauss, E; Ströhmer, R; Strom, D; Strovink, M; Stutte, L; Sumowidagdo, S; Svoisky, P; Sznajder, A; Talby, M; Tamburello, P; Tanasijczuk, A; Taylor, W; Telford, P; Temple, J; Tiller, B; Tissandier, F; Titov, M; Tokmenin, V V; Tomoto, M; Toole, T; Torchiani, I; Trefzger, T; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, S; Uvarov, L; Uzunyan, S; Vachon, B; van den Berg, P J; van Eijk, B; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vartapetian, A; Vasilyev, I A; Vaupel, M; Verdier, P; Vertogradov, L S; Verzocchi, M; Villeneuve-Seguier, F; Vint, P; Vokac, P; Von Toerne, E; Voutilainen, M; Vreeswijk, M; Wagner, R; Wahl, H D; Wang, L; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, M; Weber, G; Weerts, H; Wenger, A; Wermes, N; Wetstein, M; White, A; Wicke, D; Wilson, G W; Williams, M R J; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Yacoob, S; Yamada, R; Yan, M; Yasuda, T; Yatsunenko, Y A; Yip, K; Yoo, H D; Youn, S W; Yu, J; Yu, C; Yurkewicz, A; Zatserklyaniy, A; Zeitnitz, C; Zhang, D; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zieminski, A; Zivkovic, L; Zutshi, V; Zverev, E G

    2007-10-26

    This Letter presents the first strong evidence for the resolution of the excited B mesons B(1) and B(2)* as two separate states in fully reconstructed decays to B(+)(*)pi(-). The mass of B(1) is measured to be 5720.6+/-2.4+/-1.4 MeV/c(2) and the mass difference DeltaM between B(2)* and B(1) is 26.2+/-3.1+/-0.9 MeV/c;{2}, giving the mass of the B(2)* as 5746.8+/-2.4+/-1.7 MeV/c(2). The production rate for B(1) and B(2)* mesons is determined to be a fraction (13.9+/-1.9+/-3.2)% of the production rate of the B+ meson.

  2. 76 FR 68434 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996.

  3. 77 FR 37881 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-25

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996.

  4. 77 FR 37879 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-25

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996.

  5. 76 FR 66048 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996.

  6. 26 CFR 31.3401(b)-1 - Payroll period.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Payroll period. 31.3401(b)-1 Section 31.3401(b... Collection of Income Tax at Source § 31.3401(b)-1 Payroll period. (a) The term payroll period means the period of service for which a payment of wages is ordinarily made to an employee by his employer. It is...

  7. Benzodiazepines as potent and selective bradykinin B1 antagonists.

    PubMed

    Wood, Michael R; Kim, June J; Han, Wei; Dorsey, Bruce D; Homnick, Carl F; DiPardo, Robert M; Kuduk, Scott D; MacNeil, Tanya; Murphy, Kathy L; Lis, Edward V; Ransom, Richard W; Stump, Gary L; Lynch, Joseph J; O'Malley, Stacey S; Miller, Patricia J; Chen, Tsing-Bau; Harrell, Charles M; Chang, Raymond S L; Sandhu, Punam; Ellis, Joan D; Bondiskey, Peter J; Pettibone, Douglas J; Freidinger, Roger M; Bock, Mark G

    2003-05-08

    Antagonism of the bradykinin B(1) receptor was demonstrated to be a potential treatment for chronic pain and inflammation. Novel benzodiazepines were designed that display subnanomolar affinity for the bradykinin B(1) receptor (K(i) = 0.59 nM) and high selectivity against the bradykinin B(2) receptor (K(i) > 10 microM). In vivo efficacy, comparable to morphine, was demonstrated for lead compounds in a rodent hyperalgesia model.

  8. [Study on the frontier orbital and Raman spectra of Aflatoxin B1 and isomer].

    PubMed

    Li, Tao; Tang, Yan-lin; Ling, Zhi-gang; Long, Zheng-wen

    2014-08-01

    Through computation, this paper obtained Aflatoxin B1 and its trans-isomer molecules stable structure which was rarely reported by the density functional theory(DFT) with B3LYP complex function and 6-311 + g(d, p) basis set. Through a single point calculations and geometry analysis, we know that the cis-structure is more stable than trans-structure. On the basis of this, Raman spectra of two molecules are calculated by the same method and basis set. compared with the Aflatoxin B1 cis-structure powder experimental Raman spectra, it was informed that numerical results with experimental results combined with a better. While 1582, 3065, 1626 means to take the strongest of the three peaks of cis-structure raman characteristics, 1616, 3065, 1659 cm(-1) is indicated for the strongest of the three peaks of trans-structure raman characteristics. Use the Hirshfeld atom division method combined with Multiwfn software to analyze the composition of frontier orbital based on optimization calculation, and it was informed that the electrophilic ability of two monlecules was stronger than the nucleophilic ability. The proportion of C1 atoms in LUMO orbital are respectively 21.48 percent, 20.62 percent by calculating, thus it is predicted that C1 atom is most main position spot depriving of the electronic in DNA to cause cancer. The above-mentioned research has certain theoretical directive significance in detection, transformation and toxicity inhibition of the cis-trans isomers.

  9. Hematopoietic stem cell-independent B-1a lineage.

    PubMed

    Ghosn, Eliver Eid Bou; Yang, Yang

    2015-12-01

    The accepted dogma has been that a single long-term hematopoietic stem cell (LT-HSC) can reconstitute all components of the immune system. However, our single-cell transfer studies have shown that highly purified LT-HSCs selectively fail to reconstitute B-1a cells in otherwise fully reconstituted hosts (i.e., LT-HSCs fully reconstitute follicular, marginal zone, and B-1b B cells, but not B-1a cells). These results suggest that B-1a cells are a separate B cell lineage that develops independently of classical LT-HSCs. We provide an evolutionary two-pathway development model (HSC independent versus HSC dependent), and suggest that this lineage separation is employed not only by B cells but by all hematopoietic lineages. Collectively, these findings challenge the current notion that LT-HSCs can reconstitute all components of the immune system and raise key questions about human HSC transplantation. We discuss the implications of these findings in light of our recent studies demonstrating the ability of B-1a cells to elicit antigen-specific responses that differ markedly from those mounted by follicular B cells. These findings have implications for vaccine development, in particular vaccines that may elicit the B-1a repertoire.

  10. B1(+) interferometry for the calibration of RF transmitter arrays.

    PubMed

    Brunner, David O; Pruessmann, Klaas P

    2009-06-01

    Multiple-channel RF transmission holds great promise for MRI, especially for human applications at high fields. For calibration it requires mapping the effective RF magnetic fields, B(1) (+), of the transmitter array. This is challenging to do accurately and fast due to the large dynamic range of B(1) (+) and tight SAR constraints. In the present work, this problem is revisited and solved by a novel mapping approach relying on an interference principle. The B(1) (+) fields of individual transmitter elements are measured indirectly by observing their interference with a SAR-efficient baseline RF field. In this fashion even small RF fields can be observed in the B(1) (+) -sensitive large-flip-angle regime. Based on a set of such experiments B(1) (+) maps of the individual transmitter channels are obtained by solving a linear inverse problem. Confounding relaxation and off-resonance effects are addressed by an extended signal model and nonlinear fitting. Using the novel approach, 2D mapping of an 8-channel transmitter array was accomplished in less than a minute. For validation it is demonstrated that mapping results do not vary with T(1) or parameters of the mapping sequence. In RF shimming experiments it is shown that the measured B(1) (+) maps accurately reflect the linearity of RF superposition.

  11. CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma.

    PubMed

    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.

  12. CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma

    PubMed Central

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

    2015-01-01

    ABSTRACT 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. PMID:26997841

  13. Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity

    PubMed Central

    Baradaran-Heravi, Alireza; Niesser, Jürgen; Balgi, Aruna D.; Choi, Kunho; Zimmerman, Carla; South, Andrew P.; Anderson, Hilary J.; Strynadka, Natalie C.; Bally, Marcel B.; Roberge, Michel

    2017-01-01

    Nonsense mutations underlie about 10% of rare genetic disease cases. They introduce a premature termination codon (PTC) and prevent the formation of full-length protein. Pharmaceutical gentamicin, a mixture of several related aminoglycosides, is a frequently used antibiotic in humans that can induce PTC readthrough and suppress nonsense mutations at high concentrations. However, testing of gentamicin in clinical trials has shown that safe doses of this drug produce weak and variable readthrough activity that is insufficient for use as therapy. In this study we show that the major components of pharmaceutical gentamicin lack PTC readthrough activity but the minor component gentamicin B1 (B1) is a potent readthrough inducer. Molecular dynamics simulations reveal the importance of ring I of B1 in establishing a ribosome configuration that permits pairing of a near-cognate complex at a PTC. B1 induced readthrough at all three nonsense codons in cultured cancer cells with TP53 (tumor protein p53) mutations, in cells from patients with nonsense mutations in the TPP1 (tripeptidyl peptidase 1), DMD (dystrophin), SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), and COL7A1 (collagen type VII alpha 1 chain) genes, and in an in vivo tumor xenograft model. The B1 content of pharmaceutical gentamicin is highly variable and major gentamicins suppress the PTC readthrough activity of B1. Purified B1 provides a consistent and effective source of PTC readthrough activity to study the potential of nonsense suppression for treatment of rare genetic disorders. PMID:28289221

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

    PubMed Central

    Eder, Christiane; Frankenberger, Marion; Stanzel, Franz; Seidel, Albrecht; Schramm, Karl-Werner; Ziegler-Heitbrock, Loems; Hofer, Thomas PJ

    2009-01-01

    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. PMID:19835593

  15. Constituents of Dragon's Blood. 5. Dracoflavans B1, B2, C1, C2, D1, and D2, new A-type deoxyproanthocyanidins.

    PubMed

    Arnone, A; Nasini, G; Vajna de Pava, O; Merlini, L

    1997-10-01

    From Dragon's Blood, a resin produced by plants of the genus Daemonorops (Palmae), six new A-type flavanoid deoxyproanthocyanidins have been isolated. Their structure and stereochemistry, established by chemical degradation and extensive NMR analysis, is consistent with a mechanism of formation common to other constituents of the resin, which involves oxidation of a 6-methylflavan to a quinonemethide, followed by coupling with another flavan moiety.

  16. Investigating Criterial Discourse Features across Second Language Development: Lexical Bundles in Rated Learner Essays, CEFR B1, B2 and C1

    ERIC Educational Resources Information Center

    Chen, Yu-Hua; Baker, Paul

    2016-01-01

    In this study, we investigated criterial discourse features in L2 writing through the use of recurrent word combinations, a.k.a. lexical bundles, taking a corpus-driven and expert-judged approach by examining L2 English data across various proficiency levels from L1 Chinese learners. Proficiency was determined by a robust rating procedure which is…

  17. Proteolytic inactivation of plasma C1- inhibitor in sepsis.

    PubMed Central

    Nuijens, J H; Eerenberg-Belmer, A J; Huijbregts, C C; Schreuder, W O; Felt-Bersma, R J; Abbink, J J; Thijs, L G; Hack, C E

    1989-01-01

    Activation of both the complement system and the contact system of intrinsic coagulation is implicated in the pathophysiology of sepsis. Because C1 inhibitor (C1-Inh) regulates the activation of both cascade systems, we studied the characteristics of plasma C1-Inh in 48 patients with severe sepsis on admission to the Intensive Care Unit at the Free University of Amsterdam. The ratio between the level of functional and antigenic C1-Inh (functional index) was significantly reduced in the patients with sepsis compared with healthy volunteers (P = 0.004). The assessment of modified (cleaved), inactive C1-Inh (iC1-Inh), and complexed forms of C1-Inh (nonfunctional C1-Inh species) revealed that the reduced functional index was mainly due to the presence of iC1-Inh. On SDS-PAGE, iC1-Inh species migrated with a lower apparent molecular weight (Mr 98,000, 91,000, and 86,000) than native C1-Inh (Mr 110,000). Elevated iC1-Inh levels (greater than or equal to 0.13 microM) were found in 81% of all patients, sometimes up to 1.6 microM. Levels of iC1-Inh on admission appeared to be of prognostic value: iC1-Inh was higher in 27 patients who died than in 21 patients who survived (P = 0.003). The mortality in 15 patients with iC1-Inh levels up to 0.2 microM was 27%, but in 12 patients with plasma iC1-Inh exceeding 0.44 microM, the mortality was 83%. The overall mortality in the patients with sepsis was 56%. We propose that the cleavage of C1-Inh in patients with sepsis reflects processes that play a major role in the development of fatal complications during sepsis. Images PMID:2668333

  18. C1 inhibitor functional deficiency in systemic lupus erythematosus (SLE).

    PubMed Central

    Jazwinska, E C; Gatenby, P A; Dunckley, H; Serjeantson, S W

    1993-01-01

    C1 inhibitor (C1-inh) was assayed in eight SLE patients presenting with consistently low levels of intact C4. C1-inh antigenic levels were normal in all patients; however, the function of the C1-inh tested against C1s and C1r was variable and outside the normal functional range in seven of the eight patients. The molecular weight of patients' C1-inh protein was 105 kD, corresponding to the size of the intact molecule. The C1-inh gene was analysed in all patients. Restriction fragments generated with TaqI, PstI and HgiAI gave no indication of a major C1-inh gene rearrangement. Direct genomic sequencing of exon VIII revealed three polymorphic point mutations, but there were no changes from the normal gene in or around the reactive-centre residue of C1-inh. Furthermore, we found no evidence for a C1-inh autoantibody in patients which could affect normal C1-inh function in vitro. These results indicate that the etiology of C1-inh dysfunction in SLE is heterogeneous and distinct from that reported in either hereditary or acquired angioedema. PMID:8485912

  19. Evidence for the eta_b(1S) in the Decay Upsilon(2S)-> gamma eta_b(1S)

    SciTech Connect

    Aubert, B.; Bona, M.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Lopez, L.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Battaglia, M.; Brown, D.N.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G.; /LBL, Berkeley /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UCLA /UC, Riverside /UC, San Diego /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /Harvard U. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa U. /Iowa State U. /Johns Hopkins U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Karlsruhe U., EKP /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT, LNS /McGill U. /INFN, Milan /Milan U. /INFN, Milan /INFN, Milan /Milan U. /Mississippi U. /Montreal U. /Mt. Holyoke Coll. /INFN, Naples /Naples U. /INFN, Naples /INFN, Naples /Naples U. /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /INFN, Padua /Padua U. /INFN, Padua /INFN, Padua /Padua U. /Paris U., VI-VII /Pennsylvania U. /INFN, Perugia /Perugia U. /INFN, Pisa /Pisa U. /INFN, Pisa /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /Rostock U. /Rutherford /DSM, DAPNIA, Saclay /South Carolina U. /SLAC /Stanford U., Phys. Dept. /SUNY, Albany /Tennessee U. /Texas U. /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U., IFIC /Victoria U. /Warwick U. /Wisconsin U., Madison

    2009-12-14

    We have performed a search for the {eta}{sub b}(1S) meson in the radiative decay of the {Upsilon}(2S) resonance using a sample of 91.6 million {Upsilon}(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at E{sub {gamma}} = 610.5{sub -4.3}{sup +4.5}(stat) {+-} 1.8(syst) MeV, corresponding to an {eta}{sub b}(1S) mass of 9392.9{sub -4.8}{sup +4.6}(stat) {+-} 1.9(syst) MeV/c{sup 2}. The branching fraction for the decay {Upsilon}(2S) {yields} {gamma}{eta}{sub b}(1S) is determined to be (4.2{sub -1.0}{sup +1.1}(stat) {+-} 0.9(syst)) x 10{sup -4}. The ratio {Beta}({Upsilon}(2S) {yields} {gamma}{eta}{sub b}(1S))/{Beta}({Upsilon}(3S) {yields} {gamma}{eta}{sub b}(1S)) = 0.89{sub -0.23}{sup +0.25}(stat){sub -0.16}{sup +0.12}(syst) is consistent with the ratio expected for magnetic dipole transitions to the {eta}{sub b}(1S) meson.

  20. The 1990 vertical distribution of two important halons (F-12B1 and F-13B1) in the tropics

    NASA Technical Reports Server (NTRS)

    Singh, O. N.; Borchers, R.; Lal, Shyam; Subbarya, B. H.; Krueger, Bernd C.; Fabian, Peter

    1994-01-01

    The first vertical profiles of F-12B1 and F-13B1 had been obtained in the tropical troposphere and stratosphere by us in 1987. The measurement of these substances responsible for almost the entire anthropogenic contribution to the stratospheric BrO(x) budget is important in the tropics, as tropical upwelling provides their injection along with that of other pollutants, into the stratosphere. To ascertain the trends of these distributions and foster the data, the 1987 experiment was repeated in April 1990. Like 1987, the MPAE cryogenic whole air sampler was launched on a balloon from Hyderabad, India (17.5 deg N), and 14 samples were collected between 10 and 35 km altitude. The results obtained by means of GC and GC-MS analyses showed that the atmospheric abundance of both F-12B1 and F-13B1 is increasing at a fast rate, respectively by about 15 percent and 10 percent per year. From 1987 to 1990, F-12B1 and F-13B1 tropospheric mixing ratios have been growing from 1.2 and 1.3 ppt to 1.8 and 1.7 ppt, respectively. The vertical profiles will be discussed.

  1. Plasma levels of C1- inhibitor complexes and cleaved C1- inhibitor in patients with hereditary angioneurotic edema.

    PubMed Central

    Cugno, M; Nuijens, J; Hack, E; Eerenberg, A; Frangi, D; Agostoni, A; Cicardi, M

    1990-01-01

    C1- inhibitor (C1(-)-Inh) catabolism in plasma of patients with hereditary angioneurotic edema (HANE) was assessed by measuring the complexes formed by C1(-)-Inh with its target proteases (C1-s, Factor XIIa, and kallikrein) and a modified (cleaved) inactive form of C1(-)-Inh (iC1(-)-Inh). This study was performed in plasma from 18 healthy subjects and 30 patients with HANE in remission: 20 with low antigen concentration (type I) and 10 (from 5 different kindreds) with dysfunctional protein (type II). Both type-I and type-II patients had increased C1(-)-C1(-)-Inh complexes (P less than 0.0001), which in type I inversely correlated with the levels of C1(-)-Inh (P less than 0.001). iC1(-)-Inh was normal in all type-I patients and in type-II patients from three families with increased C1(-)-Inh antigen, whereas iC1(-)-Inh was higher than 20 times the normal values in patients from the remaining two families with C1(-)-Inh antigen in the normal range. None of the subjects had an increase of either Factor XIIa-C1(-)-Inh or kallikrein-C1(-)-Inh complexes. This study shows that the hypercatabolism of C1(-)-Inh in HANE patients at least in part occurs via the formation of complexes with C1- and that genetically determined differences in catabolism of dysfunctional C1(-)-Inh proteins are present in type-II patients. Images PMID:2318974

  2. SerpinB1 Promotes Pancreatic β Cell Proliferation.

    PubMed

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A; De Jesus, Dario F; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O'Donnell, Eileen; Kulkarni, Rohit N

    2016-01-12

    Although compensatory islet hyperplasia in response to insulin resistance is a recognized feature in diabetes, the factor(s) that promote β cell proliferation have been elusive. We previously reported that the liver is a source for such factors in the liver insulin receptor knockout (LIRKO) mouse, an insulin resistance model that manifests islet hyperplasia. Using proteomics we show that serpinB1, a protease inhibitor, which is abundant in the hepatocyte secretome and sera derived from LIRKO mice, is the liver-derived secretory protein that regulates β cell proliferation in humans, mice, and zebrafish. Small-molecule compounds, that partially mimic serpinB1 effects of inhibiting elastase activity, enhanced proliferation of β cells, and mice lacking serpinB1 exhibit attenuated β cell compensation in response to insulin resistance. Finally, SerpinB1 treatment of islets modulated proteins in growth/survival pathways. Together, these data implicate serpinB1 as an endogenous protein that can potentially be harnessed to enhance functional β cell mass in patients with diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Occurrence of aflatoxin B1 in natural products

    PubMed Central

    Prado, Guilherme; Altoé, Aline F.; Gomes, Tatiana C. B.; Leal, Alexandre S.; Morais, Vanessa A. D.; Oliveira, Marize S.; Ferreira, Marli B.; Gomes, Mateus B.; Paschoal, Fabiano N.; von S. Souza, Rafael; Silva, Daniela A.; Cruz Madeira, Jovita E. G.

    2012-01-01

    The media claims for the consumption of natural resource-based food have gradually increased in both developing and developed countries. The interest in the safety of these products is partially due to the possible presence of toxigenic fungi acting as mycotoxin producers, such as aflatoxins produced during the secondary metabolism of Aspergillus flavus, A. parasiticus and A. nomius. Aflatoxins, mainly aflatoxin B1, are directly associated with liver cancer in human beings. This paper is aimed at evaluating the presence of aflatoxin B1 in a few vegetable drugs, dried plant extracts and industrialized products traded in 2010 in the city of Belo Horizonte, State of Minas Gerais, Brazil. The method used for the quantification of aflatoxin B1 was based on extraction through acetone:water (85:15), immunoaffinity column purification followed by separation and detection in high efficiency liquid chromatography. Under the conditions of analysis, the Limits of Detection and Quantification were 0.6 µg kg-1 and 1.0 µg kg-1 respectively. The complete sets of analyses were carried out in duplicate. Aflatoxin B1 was noticed in a single sample (< 1.0 µg kg-1). The results revealed low aflatoxin B1 contamination in the products under analysis. However, it is required to establish a broad monitoring program in order to obtain additional data and check up on the actual extension of contamination. PMID:24031973

  4. B-1 cells and concomitant immunity in Ehrlich tumour progression.

    PubMed

    Azevedo, M C; Palos, M C; Osugui, L; Laurindo, M F; Masutani, D; Nonogaki, S; Bachi, A L L; Melo, F H M; Mariano, M

    2014-05-01

    Concomitant immunity is a phenomenon in which a tumour-bearing host is resistant to the growth of an implanted secondary tumour. Metastases are considered to be secondary tumours that develop spontaneously during primary tumour growth, suggesting the involvement of concomitant immunity in controlling the rise of metastases. It has been demonstrated that B-1 cells, a subset of B-lymphocytes found predominantly in pleural and peritoneal cavities, not only increase the metastatic development of murine melanoma B16F10, but also are capable of differentiating into mononuclear phagocytes, modulating inflammatory responses in wound healing, in oral tolerance and in Paracoccidiose brasiliensis infections. Here, we studied B-1 cells' participation in concomitant immunity during Ehrlich tumour progression. Our results show that B-1 cells obtained from BALB/c mice previously injected with Ehrlich tumour in the footpad were able to protect BALB/c and BALB/Xid mice against Ehrlich tumour challenge. In addition, it was demonstrated that BALB/Xid show faster tumour growth and have lost concomitant immunity, and that this state can be partially restored by reconstituting these animals with B-1 cells. However, further researches are required to establish the mechanism involving B-1 cells in Ehrlich tumour growth. Copyright © 2014 Elsevier GmbH. All rights reserved.

  5. B1 Mapping by Bloch-Siegert Shift

    PubMed Central

    Sacolick, Laura I.; Wiesinger, Florian; Hancu, Ileana; Vogel, Mika W.

    2010-01-01

    A novel method for B1+ field mapping based on the Bloch-Siegert shift is presented. Unlike conventionally applied double-angle or other signal magnitude-based methods it encodes the B1 information into signal phase, resulting in important advantages in terms of acquisition speed, accuracy and robustness. The Bloch Siegert frequency shift is caused by irradiating with an off-resonance RF pulse following conventional spin excitation. When applying the off-resonance RF in the kHz range, spin nutation can be neglected and the primarily observed effect is a spin precession frequency shift. This shift is proportional to the square of the RF field magnitude B12. Adding gradient image encoding following the off-resonance pulse allows one to acquire spatially resolved B1 maps. The frequency shift from the Bloch-Siegert effect gives a phase shift in the image that is proportional to B12. The phase difference of two acquisitions, with the RF pulse applied at two frequencies symmetrically around the water resonance is used to eliminate undesired off-resonance effects due to B0 inhomogeneity and chemical shift. In-vivo Bloch Siegert B1 mapping with 25 seconds / slice is demonstrated to be quantitatively comparable to a 21 minute double-angle map. As such this method enables robust, high resolution B1+ mapping in a clinically acceptable time frame. PMID:20432302

  6. The neural guidance receptor Plexin C1 delays melanoma progression

    PubMed Central

    Chen, Y; Soong, J; Mohanty, S; Xu, L; Scott, G

    2013-01-01

    Plexin C1 is a type I transmembrane receptor with intrinsic R-Ras GTPase activity, which regulates cytoskeletal remodeling and adhesion in normal human melanocytes. Melanocytes are pigment-producing cells of the epidermis, precursors for melanoma, and express high levels of Plexin C1, which is lost in melanoma in vitro and in vivo. To determine if Plexin C1 is a tumor suppressor for melanoma, we introduced Plexin C1 into a primary human melanoma cell line, and phenotypes including migration, apoptosis, proliferation and tumor growth in mice were analyzed. Complimentary studies in which Plexin C1 was silenced in human melanocytes were performed. Plexin C1 significantly inhibited migration and proliferation in melanoma, whereas in melanocytes, loss of Plexin C1 increased migration and proliferation. In mouse xenografts, Plexin C1 delayed tumor growth of melanoma at early time points, but tumors eventually escaped the suppressive effects of Plexin C1, due to Plexin C1-dependent activation of the pro-survival protein Akt. R-Ras activation stimulates melanoma migration. Plexin C1 lowered R-Ras activity in melanoma and melanocytes, consistent with inhibitory effects of Plexin C1 on migration of melanocytes and melanoma. To determine if R-Ras is expressed in melanocytic lesions in vivo, staining of tissue microarrays of nevi and melanoma were performed. R-Ras expression was highly limited in melanocytic lesions, being essentially confined to primary melanoma, and almost completely absent in nevi and metastatic melanoma. These data suggest that loss of Plexin C1 in melanoma may promote early steps in melanoma progression through suppression of migration and proliferation, but pro-survival effects of Plexin C1 ultimately abrogate the tumor suppressive effects of Plexin C1. In primary melanoma, loss of Plexin C1 may function in early steps of melanoma progression by releasing inhibition of R-Ras activation, and stimulating migration. PMID:23160370

  7. The neural guidance receptor Plexin C1 delays melanoma progression.

    PubMed

    Chen, Y; Soong, J; Mohanty, S; Xu, L; Scott, G

    2013-10-10

    Plexin C1 is a type I transmembrane receptor with intrinsic R-Ras GTPase activity, which regulates cytoskeletal remodeling and adhesion in normal human melanocytes. Melanocytes are pigment-producing cells of the epidermis, precursors for melanoma, and express high levels of Plexin C1, which is lost in melanoma in vitro and in vivo. To determine if Plexin C1 is a tumor suppressor for melanoma, we introduced Plexin C1 into a primary human melanoma cell line, and phenotypes including migration, apoptosis, proliferation and tumor growth in mice were analyzed. Complimentary studies in which Plexin C1 was silenced in human melanocytes were performed. Plexin C1 significantly inhibited migration and proliferation in melanoma, whereas in melanocytes, loss of Plexin C1 increased migration and proliferation. In mouse xenografts, Plexin C1 delayed tumor growth of melanoma at early time points, but tumors eventually escaped the suppressive effects of Plexin C1, due to Plexin C1-dependent activation of the pro-survival protein Akt. R-Ras activation stimulates melanoma migration. Plexin C1 lowered R-Ras activity in melanoma and melanocytes, consistent with inhibitory effects of Plexin C1 on migration of melanocytes and melanoma. To determine if R-Ras is expressed in melanocytic lesions in vivo, staining of tissue microarrays of nevi and melanoma were performed. R-Ras expression was highly limited in melanocytic lesions, being essentially confined to primary melanoma, and almost completely absent in nevi and metastatic melanoma. These data suggest that loss of Plexin C1 in melanoma may promote early steps in melanoma progression through suppression of migration and proliferation, but pro-survival effects of Plexin C1 ultimately abrogate the tumor suppressive effects of Plexin C1. In primary melanoma, loss of Plexin C1 may function in early steps of melanoma progression by releasing inhibition of R-Ras activation, and stimulating migration.

  8. Horseshoe and entropy for C1 surface diffeomorphisms

    NASA Astrophysics Data System (ADS)

    Gan, Shaobo

    2002-05-01

    Let M be a two-dimensional closed Riemannian manifold and denote by Diff1(M) the set of C1 diffeomorphisms on M. Then, the C1 interior of {f in Diff1(M):h(f) = 0} is equal to the C1 interior of the closure of the Morse-Smale systems and equal to the C1 interior of the set of diffeomorphisms having no horseshoe.

  9. The Kinematic and Chemical Properties of a Potential Core-forming Clump: Perseus B1-E

    NASA Astrophysics Data System (ADS)

    Sadavoy, S. I.; Shirley, Y.; Di Francesco, J.; Henning, Th.; Currie, M. J.; André, Ph.; Pezzuto, S.

    2015-06-01

    We present 13CO and {{C}18}O (1-0), (2-1), and (3-2) maps toward the core-forming Perseus B1-E clump using observations from the James Clerk Maxwell Telescope, the Submillimeter Telescope of the Arizona Radio Observatory, and the IRAM 30 m telescope. We find that the 13CO and {{C}18}O line emission both have very complex velocity structures, indicative of multiple velocity components within the ambient gas. The (1-0) transitions reveal a radial velocity gradient across B1-E of ˜ 1 km {{s}-1} p{{c}-1} that increases from northwest to southeast, whereas the majority of the Perseus cloud has a radial velocity gradient increasing from southwest to northeast. In contrast, we see no evidence of a velocity gradient associated with the denser Herschel-identified substructures in B1-E. Additionally, the denser substructures have much lower systemic motions than the ambient clump material, which indicates that they are likely decoupled from the large-scale gas. Nevertheless, these substructures themselves have broad line widths (˜0.4 km {{s}-1}) similar to that of the {{C}18}O gas in the clump, which suggests they inherited their kinematic properties from the larger-scale, moderately dense gas. Finally, we find evidence of {{C}18}O depletion only toward one substructure, B1-E2, which is also the only object with narrow (transonic) line widths. We suggest that as prestellar cores form, their chemical and kinematic properties are linked in evolution, such that these objects must first dissipate their turbulence before they deplete in CO.

  10. 26 CFR 1.682(c)-1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Definitions. 1.682(c)-1 Section 1.682(c)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Miscellaneous § 1.682(c)-1 Definitions. For definitions of the terms “husband” and “wife” as...

  11. C1q Deficiency and Neuropsychiatric Systemic Lupus Erythematosus.

    PubMed

    van Schaarenburg, Rosanne A; Magro-Checa, César; Bakker, Jaap A; Teng, Y K Onno; Bajema, Ingeborg M; Huizinga, Tom W; Steup-Beekman, Gerda M; Trouw, Leendert A

    2016-01-01

    C1q deficiency is a rare immunodeficiency, which is strongly associated with the development of systemic lupus erythematosus (SLE). A mutation in one of the C1q genes can either lead to complete deficiency or to low C1q levels with C1q polypeptide in the form of low-molecular weight (LMW) C1q. Patients with C1q deficiency mainly present with cutaneous and renal involvement. Although less frequent, neuropsychiatric (NP) involvement has also been reported in 20% of the C1q-deficient patients. This involvement appears to be absent in other deficiencies of early components of the complement classical pathway (CP) (C1r/C1s, C2, or C4 deficiencies). We describe a new case with C1q deficiency with a homozygous G34R mutation in C1qC-producing LMW-C1q presenting with a severe SLE flare with NP involvement. The serum of this patient contained very low levels of a LMW variant of C1q polypeptides. Cell lysates contained the three chains of C1q, but no intact C1q was detected, consistent with the hypothesis of the existence of a LMW-C1q. Furthermore, we provide a literature overview of NP-SLE in C1q deficiency and hypothesize about the potential role of C1q in the pathogenesis of NP involvement in these patients. The onset of NP-SLE in C1q-deficient individuals is more severe when compared with complement competent NP-SLE patients. An important number of cases present with seizures and the most frequent findings in neuroimaging are changes in basal ganglia and cerebral vasculitis. A defective CP, because of non-functional C1q, does not protect against NP involvement in SLE. The absence of C1q and, subsequently, some of its biological functions may be associated with more severe NP-SLE.

  12. C1q Deficiency and Neuropsychiatric Systemic Lupus Erythematosus

    PubMed Central

    van Schaarenburg, Rosanne A.; Magro-Checa, César; Bakker, Jaap A.; Teng, Y. K. Onno; Bajema, Ingeborg M.; Huizinga, Tom W.; Steup-Beekman, Gerda M.; Trouw, Leendert A.

    2016-01-01

    C1q deficiency is a rare immunodeficiency, which is strongly associated with the development of systemic lupus erythematosus (SLE). A mutation in one of the C1q genes can either lead to complete deficiency or to low C1q levels with C1q polypeptide in the form of low-molecular weight (LMW) C1q. Patients with C1q deficiency mainly present with cutaneous and renal involvement. Although less frequent, neuropsychiatric (NP) involvement has also been reported in 20% of the C1q-deficient patients. This involvement appears to be absent in other deficiencies of early components of the complement classical pathway (CP) (C1r/C1s, C2, or C4 deficiencies). We describe a new case with C1q deficiency with a homozygous G34R mutation in C1qC-producing LMW-C1q presenting with a severe SLE flare with NP involvement. The serum of this patient contained very low levels of a LMW variant of C1q polypeptides. Cell lysates contained the three chains of C1q, but no intact C1q was detected, consistent with the hypothesis of the existence of a LMW-C1q. Furthermore, we provide a literature overview of NP-SLE in C1q deficiency and hypothesize about the potential role of C1q in the pathogenesis of NP involvement in these patients. The onset of NP-SLE in C1q-deficient individuals is more severe when compared with complement competent NP-SLE patients. An important number of cases present with seizures and the most frequent findings in neuroimaging are changes in basal ganglia and cerebral vasculitis. A defective CP, because of non-functional C1q, does not protect against NP involvement in SLE. The absence of C1q and, subsequently, some of its biological functions may be associated with more severe NP-SLE. PMID:28082982

  13. Bu-2470, a new peptide antibiotic complex. II. Structure determination of Bu-2470 A, B1, B2a and B2b.

    PubMed

    Sugawara, K; Yonemoto, T; Konishi, M; Matsumoto, K; Miyaki, T; Kawaguchi, H

    1983-06-01

    The structures of Bu-2470 A, B1, B2a, and B2b have been determined. Bu-2470 A is a simple octapeptide having no fatty acid moiety, while Bu-2470 B1, B2a and B2b are octapeptides that have been acylated with a beta-hydroxy C11 or C10 fatty acid. The octapeptide structure of Bu-2470 components was found identical with that of octapeptin C1, hence generic names of octapeptin C0, C2, C3 and C4 are proposed for Bu-2470 A, B1, B2a and B2b, respectively.

  14. Evaluation of particulate air samplers for airborne aflatoxin B1

    SciTech Connect

    Silas, J.C.; Harrison, M.A.; Carpenter, J.A.

    1986-01-01

    Five air samplers (Millipore, all-glass impinger, centrifugal, Andersen, and absorbent cotton) were evaluated for their ability to collect airborne grain particles contaminated with aflatoxin B1. Corn dust containing 100 micrograms aflatoxin B1/g was aerosolized within a containment system. Each device sampled 100 I air, thus exchanging the air in the chamber two times. Aflatoxin B1 was extracted from all sampling matrices and was detected and quantitated with thin-layer chromatography and scanning fluorodensitometry. The highest efficiency was obtained with the Millipore sampler, while the efficiencies of the centrifugal and the cotton samplers were almost identical. Efficiency of an Andersen was less, with no toxin recovered from an all-glass impinger. Measurement of particle size was accomplished with the Andersen sampler.

  15. B1-Metallo-beta-Lactamases: Where do we stand?

    PubMed Central

    Mojica, Maria F.; Bonomo, Robert A.; Fast, Walter

    2015-01-01

    Metallo-beta-Lactamases (MBLs) are class B β-lactamases that hydrolyze almost all clinically-available β-lactam antibiotics. MBLs feature the distinctive αβ/βα sandwich fold of the metallo-hydrolase / oxidoreductase superfamily and possess a shallow active-site groove containing one or two divalent zinc ions, flanked by flexible loops. According to sequence identity and zinc ion dependence, MBLs are classified into three subclasses (B1, B2 and B3), of which the B1 subclass enzymes have emerged as the most clinically significant. Differences among the active site architectures, the nature of zinc ligands, and the catalytic mechanisms have limited the development of a common inhibitor. In this review, we will describe the molecular epidemiology and structural studies of the most prominent representatives of class B1 MBLs (NDM-1, IMP-1 and VIM-2) and describe the implications for inhibitor design to counter this growing clinical threat. PMID:26424398

  16. Slice-by-slice B1+ shimming at 7 T.

    PubMed

    Curtis, Andrew T; Gilbert, Kyle M; Klassen, L Martyn; Gati, Joseph S; Menon, Ravi S

    2012-10-01

    Parallel transmission has been used to reduce the inevitable inhomogeneous radiofrequency fields produced in human high-field MRI greater than 3 T. Further improvements in the transmit homogeneity and efficiency are possible by leveraging the additional degree of freedom permitted by multislice acquisitions. Compared to simple scaling of the flip angle to compensate for B1+ falloff along the radiofrequency coil, calculation of B1+ shim solutions on a slice-by-slice basis can markedly improve homogeneity and/or reduce transmitted power and global SAR. Performance measures were acquired at 7 T with a 15-channel head-only transceive array featuring elements distributed over all three logical axes, facilitating B1+ shimming over arbitrary orientations. Compared to a circularly polarized volume mode of the same coil, shimming to maximize excitation efficiency on a slice-by-slice basis yielded improvements in mean B1+ by 12.8±2.4% and a reduction in standard deviation of B1+ of 16.3±6.8%, while reducing relative SAR by 6.2±3.1%. When shimming for greater uniformity, the mean and standard deviation of B1+ were further improved by 15.9±2.6% and 26.2±10.4%, respectively, at the expense of a 135±8% increase in global SAR. Robust multislice-shim solutions are demonstrated that can be quickly calculated, applied in real time, and reliably improve on volume coil modes. Copyright © 2011 Wiley Periodicals, Inc.

  17. Thymoma type B1 arising in a giant supradiaphragmatic thymolipoma.

    PubMed

    Kaplan, Tevfik; Han, Serdar; Han, Unsal; Atac, Gokce Kaan; Yanik, Serdar

    2014-11-01

    Thymolipomas are uncommon tumors of the anterior mediastinum. They may extend into, but rarely stem from, the chest cavity. Furthermore, thymoma arising in a thymolipoma is extremely rare. We report a unique case of thymoma type B1 that originated form a giant thymolipoma located in the chest cavity, which was resected by a lateral thoracotomy in a 23-year-old woman. To our knowledge, this is the first reported case of thymoma type B1 arising within a giant thymolipoma. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. 26 CFR 1.1244(c)-1 - Section 1244 stock defined.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 11 2012-04-01 2012-04-01 false Section 1244 stock defined. 1.1244(c)-1 Section....1244(c)-1 Section 1244 stock defined. (a) In general. For purposes of §§ 1.1244(a)-1 to 1.1244(e)-1, inclusive: (1) The term pre-November 1978 stock means stock issued after June 30, 1958, and on or...

  19. 26 CFR 1.669(b)-1 - Information requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Beginning Before January 1, 1969 § 1.669(b)-1 Information requirements. The election of a beneficiary who is... unless the beneficiary, at or before the time the election is made, supplies, in a letter addressed to.... person for each of the preceding taxable years, on the last day of which an amount is deemed...

  20. 76 FR 18726 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD ACTION: Notice SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  1. 75 FR 41820 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of five section...

  2. 76 FR 55651 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-08

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of... foreign policy and national security of the United States by helping to improve the security of a...

  3. 75 FR 76415 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  4. 76 FR 27022 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  5. 75 FR 20571 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of two section...

  6. 75 FR 69953 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  7. 76 FR 32958 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  8. 75 FR 51445 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  9. 75 FR 29998 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-28

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  10. 76 FR 40703 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  11. 75 FR 69922 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  12. 75 FR 69957 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  13. 76 FR 17111 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  14. 75 FR 69938 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  15. 75 FR 47275 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of two section...

  16. 75 FR 61440 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of three...

  17. 76 FR 28956 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  18. 75 FR 69931 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  19. 75 FR 76412 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  20. 75 FR 5971 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of six section...

  1. 75 FR 60424 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of two section...

  2. 76 FR 27026 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  3. 77 FR 71401 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-30

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... proposed sale will contribute to the foreign policy and national security of the United States by helping to improve the security of a friendly country that has been, and continues to be, an important...

  4. 75 FR 81993 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... [Federal Register Volume 75, Number 249 (Wednesday, December 29, 2010)] [Notices] [Pages 81993-81998] [FR Doc No: 2010-32755] DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 10-62] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation...

  5. 78 FR 42758 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-17

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of... $250 million. This proposed sale will contribute to the foreign policy and national security of...

  6. 75 FR 74014 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  7. 76 FR 26707 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  8. 75 FR 11865 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  9. 75 FR 23247 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  10. 76 FR 8716 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  11. 76 FR 37078 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  12. 76 FR 18731 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  13. 75 FR 76418 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  14. 77 FR 32599 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-01

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of... security of the United States by enabling the Bangladesh Air Force (BAF) to use its C-130 fleet to...

  15. 75 FR 74011 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  16. 76 FR 38371 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  17. 78 FR 36534 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... security of the United States, by helping to improve the security of a friendly country which has been,...

  18. 77 FR 40028 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of... contribute to the foreign policy and national security of the United States by helping to improve...

  19. 75 FR 69971 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  20. 76 FR 43659 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  1. 75 FR 76408 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  2. 75 FR 69926 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  3. 76 FR 29212 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  4. 78 FR 41040 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-09

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... sale will contribute to the foreign policy and national security of the United States by helping to improve the security of a friendly country that has been, and continues to be, an important force...

  5. 75 FR 69947 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  6. 76 FR 30667 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  7. 78 FR 36536 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency... contribute to the foreign policy and national security of the United States by helping to improve the security of a friendly country which has been, and continues to be, an important force for...

  8. 75 FR 69960 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  9. 76 FR 35188 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  10. 76 FR 37075 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  11. 76 FR 37071 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  12. 75 FR 27314 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  13. 75 FR 9182 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section...

  14. 75 FR 48646 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of three...

  15. 77 FR 60391 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office.... ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public...

  16. 77 FR 60387 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office.... ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public...

  17. 78 FR 54242 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office..., Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of...

  18. 78 FR 76112 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office... Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section...

  19. 77 FR 60384 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office.... ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public...

  20. In vivo formation of N-acyl-fumonisin B1

    USDA-ARS?s Scientific Manuscript database

    Fumonisins are fungal toxins found in corn and in corn-based foods. Fumonisin B1 (FB1) is the most common and is toxic to animals, causes cancer in rodents, and is a suspected risk factor for cancer and birth defects in humans. The hydrolyzed form of FB1 (HFB1) also occurs in foods and is metabolize...

  1. 26 CFR 31.6302(b)-1 - Method of collection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Method of collection. 31.6302(b)-1 Section 31... TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Administrative Provisions of Special Application to Employment Taxes (Selected Provisions of Subtitle F, Internal...

  2. 26 CFR 31.6302(b)-1 - Method of collection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Method of collection. 31.6302(b)-1 Section 31... TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Administrative Provisions of Special Application to Employment Taxes (Selected Provisions of Subtitle F, Internal...

  3. βB1-Crystallin: Thermodynamic Profiles of Molecular Interactions

    PubMed Central

    Dolinska, Monika B.; Wingfield, Paul T.; Sergeev, Yuri V.

    2012-01-01

    Background β-Crystallins are structural proteins maintaining eye lens transparency and opacification. Previous work demonstrated that dimerization of both βA3 and βB2 crystallins (βA3 and βB2) involves endothermic enthalpy of association (∼8 kcal/mol) mediated by hydrophobic interactions. Methodology/Principal Findings Thermodynamic profiles of the associations of dimeric βA3 and βB1 and tetrameric βB1/βA3 were measured using sedimentation equilibrium. The homo- and heteromolecular associations of βB1 crystallin are dominated by exothermic enthalpy (−13.3 and −24.5 kcal/mol, respectively). Conclusions/Significance Global thermodynamics of βB1 interactions suggest a role in the formation of stable protein complexes in the lens via specific van der Waals contacts, hydrogen bonds and salt bridges whereas those β-crystallins which associate by predominately hydrophobic forces participate in a weaker protein associations. PMID:22238594

  4. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for topics not addressed in §§ 54.4980B-1 through 54.4980B-10? A-2: For purposes of section 4980B, for topics relating to the COBRA continuation coverage requirements of section 4980B that are not...

  5. 26 CFR 1.7702B-1 - Consumer protection provisions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... coverage, policy summaries, and notices will be considered satisfied for a contract subject to the law of... insurance contracts and issuers of those contracts are required to satisfy certain provisions of the Long... January 1993. The requirements for qualified long-term care insurance contracts under section 7702B(b)(1...

  6. 77 FR 51780 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  7. 78 FR 62600 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  8. 78 FR 62590 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text...

  9. 78 FR 62588 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  10. 77 FR 75617 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  11. 78 FR 15004 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  12. 78 FR 62592 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Office of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified...

  13. 26 CFR 301.6229(b)-1 - Extension by agreement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) PROCEDURE AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6229(b)-1 Extension by... assessment period with respect to all partners; (2) Identify the partnership and the person being authorized... years for which the authorization is effective; and (4) Be signed by all persons who were general...

  14. 78 FR 66338 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-05

    ... Section 36(b)(1) of the Arms Export Control Act, as amended (i) Prospective Purchaser: Republic of Korea... Section 47(6) of the Arms Export Control Act. ] POLICY JUSTIFICATION The Republic of Korea--Patriot Anti-Tactical Missiles The Republic of Korea (ROK) has requested a possible sale to procure 112 Patriot Anti...

  15. Role of Lamin B1 in Chromatin Instability

    PubMed Central

    Butin-Israeli, Veronika; Adam, Stephen A.; Jain, Nikhil; Otte, Gabriel L.; Neems, Daniel; Wiesmüller, Lisa; Berger, Shelly L.

    2014-01-01

    Nuclear lamins play important roles in the organization and structure of the nucleus; however, the specific mechanisms linking lamin structure to nuclear functions are poorly defined. We demonstrate that reducing nuclear lamin B1 expression by short hairpin RNA-mediated silencing in cancer cell lines to approximately 50% of normal levels causes a delay in the cell cycle and accumulation of cells in early S phase. The S phase delay appears to be due to the stalling and collapse of replication forks. The double-strand DNA breaks resulting from replication fork collapse were inefficiently repaired, causing persistent DNA damage signaling and the assembly of extensive repair foci on chromatin. The expression of multiple factors involved in DNA replication and repair by both nonhomologous end joining and homologous repair is misregulated when lamin B1 levels are reduced. We further demonstrate that lamin B1 interacts directly with the promoters of some genes associated with DNA damage response and repair, including BRCA1 and RAD51. Taken together, the results suggest that the maintenance of lamin B1 levels is required for DNA replication and repair through regulation of the expression of key factors involved in these essential nuclear functions. PMID:25535332

  16. 26 CFR 1.512(b)-1 - Modifications.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) INCOME TAXES (CONTINUED) Taxation of Business Income of Certain Exempt Organizations § 1.512(b)-1... properly allocable to the land and building. Under these circumstances, A shall not take into account in... with rates or other charges charged for such services by persons not exempt from taxation. Rates or...

  17. 77 FR 781 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-06

    .../DBO/CFM, (703) 601-3740. The following is a copy of a letter to the Speaker of the House of... Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as amended (i) Prospective... Services Program (SESP) for the past 20 years. The ESP provides material support to Saudi's defense...

  18. 75 FR 4785 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b... July 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. Dated...

  19. 75 FR 48947 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b... July 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY...

  20. 75 FR 30787 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-02

    ... of the Secretary 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b... July 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. The following...