Sample records for a1fi a2 b1

  1. MISR Level 1A CCD, 1B1, 1B2, and Browse Products

    Atmospheric Science Data Center

    2013-04-01

    ... ESDT Product File Name Prefix Current Quality Designations MI1B2E MISR_AM1_GRP_ELLIPSOID_GM, ... should be used. All calibration files for the life of the mission have been reprocessed using the best available calibration. ...

  2. METAL MEDIA FILTERS, AG-1 SECTION FI

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adamson, D.

    One application of metal media filters is in various nuclear air cleaning processes including applications for protecting workers, the public and the environment from hazardous and radioactive particles. To support this application the development of the ASME AG-1 FI Standard on Metal Media has been under way for more than ten years. Development of the proposed section has required resolving several difficult issues associated with operating conditions (media velocity, pressure drop, etc.), qualification testing, and quality acceptance testing. Performance characteristics of metal media are dramatically different than the glass fiber media with respect to parameters like differential pressures, operating temperatures,more » media strength, etc. These differences make existing data for a glass fiber media inadequate for qualifying a metal media filter for AG-1. In the past much work has been conducted on metal media filters at facilities such as Lawrence Livermore National Laboratory (LLNL) and Savannah River National Laboratory (SRNL) to qualify the media as High Efficiency Particulate Air (HEPA) Filters. Particle retention testing has been conducted at Oak Ridge Filter Test Facility and at Air Techniques International (ATI) to prove that the metal media meets or exceeds the 99.97% particle retention required for a HEPA Filter. Even with his testing, data was lacking to complete an AG-1 FI Standard on metal media. With funding secured by Mississippi State University (MSU) from National Nuclear Security Administration (NNSA), a research test stand is being designed and fabricated at MSU's Institute for Clean Energy Technology (ICET) Facility to obtain qualification data on metal media. This in turn will support required data needed for the FI Standard. The paper will discuss in detail how the test stand at MSU will obtain the necessary data to complete the FI Standard.« less

  3. 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.

  4. A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting--a prospective, multicenter validation study.

    PubMed

    Villar, Jesús; Pérez-Méndez, Lina; Blanco, Jesús; Añón, José Manuel; Blanch, Lluís; Belda, Javier; Santos-Bouza, Antonio; Fernández, Rosa Lidia; Kacmarek, Robert M

    2013-04-01

    The PaO2/FiO2 is an integral part of the assessment of patients with acute respiratory distress syndrome (ARDS). The American-European Consensus Conference definition does not mandate any standardization procedure. We hypothesized that the use of PaO2/FiO2 calculated under a standard ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification. We studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO2/FiO2 ≤ 200. In the derivation cohort (n = 170), we measured PaO2/FiO2 with two levels of positive end-expiratory pressure (PEEP) (≥ 5 and ≥ 10 cmH2O) and two levels of FiO2 (≥ 0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO2 response, patients were reclassified into three groups: mild (PaO2/FiO2 > 200), moderate (PaO2/FiO2 101-200), and severe (PaO2/FiO2 ≤ 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282). The only standard ventilatory setting that identified the three PaO2/FiO2 risk categories in the derivation cohort was PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001). Our method for assessing PaO2/FiO2 greatly improved risk stratification of ARDS and could be used for enrolling appropriate ARDS patients into therapeutic clinical trials.

  5. The B(E2;4^+1->2^+1) / B(E2;2^+1->0^+1) Ratio in Even-Even Nuclei

    NASA Astrophysics Data System (ADS)

    Loelius, C.; Sharon, Y. Y.; Zamick, L.; G"Urdal, G.

    2009-10-01

    We considered 207 even-even nuclei throughout the chart of nuclides for which the NNDC Tables had data on the energies and lifetimes of the 2^+1 and 4^+1 states. Using these data we calculated for each nucleus the electric quadrupole transition strengths B(E2;4^+1->2^+1) and B(E2;2^+1->0^+1), as well as their ratio. The internal conversion coefficients were obtained by using the NNDC HSICC calculator. For each nucleus we plotted the B(E2) ratio against A, N, and Z. We found that for close to 90% of the nuclei considered the ratio had values between 0.5 and 2.5. Most of the outliers had magic numbers of protons or neutrons. Our ratio results were compared with the theoretical predictions for this ratio by different models--10/7 in the rotational model and 2 in the simplest vibrational model. In the rotational regions (for 150 < A < 180 and A > 220) the ratios were indeed close to 10/7. For the few nuclei thought to be vibrational the ratios were usually less than 2. Otherwise, we got a wide scatter of ratio values. Hence other models, including the NpNn scheme, must be considered in interpreting these results.

  6. Impacts of Blast-Induced Traumatic Brain Injury on Expressions of Hepatic Cytochrome P450 1A2, 2B1, 2D1, and 3A2 in Rats.

    PubMed

    Ma, Jie; Wang, Junrui; Cheng, Jingmin; Xiao, Wenjing; Fan, Kaihua; Gu, Jianwen; Yu, Botao; Yin, Guangfu; Wu, Juan; Ren, Jiandong; Hou, Jun; Jiang, Yan; Tan, Yonghong; Jin, Weihua

    2017-01-01

    The hepatic cytochrome P450 (CYP450) enzyme superfamily is one of the most important drug-metabolizing enzyme systems, which is responsible for the metabolism of a large number of clinically relevant medications used in traumatic brain injury (TBI) therapy. Modification of CYP450 expression may have important influences on drug metabolism and lead to untoward effects on those with narrow therapeutic windows. However, the impact of blast-induced TBI (bTBI) on the expression of CYP450 has received little attention. The subfamilies of CYP1A, 2B, 2D, and 3A account for about 85 % of all human drug metabolism of clinical significance. Therefore, in this study, we investigated the expressions of hepatic CYP1A2, CYP2B1, CYP2D1, and CYP3A2 in rats suffering bTBI. Meanwhile, we also measured some important cytokines in serum after injury, and calculated the correlation between these cytokines and the expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2. The results showed that bTBI could significantly reduce mRNA expressions of CYP1A2, CYP2D1, and CYP3A2 at the early stage and induce the expressions from 48 h to 1 week after injury. The protein expressions of these CYP450s had all been downregulated from 24 to 48 h post- injury, and then began to elevate at 48 h after bTBI. The cytokines, IL-1β, IL-2, IL-6, and TNF-α, increased significantly in the early phase, and began to reduce at the delayed phase of bTBI. The serum levels of IL-1β, IL-6, and TNF-α but not IL-2 were significantly negative correlated with the mRNA expressions of CYP2B1 and CYP2D1 and the proteins expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2. In conclusion, our work has, for the first time, indicated that bTBI has significant impact on the expressions of CYP1A2, CYP2B1, CYP2D1, and CYP3A2, which may be related to the cytokines induced by the injury.

  7. Determination of aflatoxins B1, B2, G1 and G2 in spices using a multifunctional column clean-up.

    PubMed

    Akiyama, H; Goda, Y; Tanaka, T; Toyoda, M

    2001-10-12

    A rapid and simple method using a multifunctional column, which contains lipophilic and charged active sites, was developed to analyse aflatoxins B1, B2, G1 and G2 in various spices, such as red pepper and nutmeg. After extraction by acetonitrile:water (9:1) and clean-up using MultiSep #228 column, the aflatoxins and aflatoxin-TFA derivatives are determined using LC with fluorescence detection. Recoveries of each aflatoxin B1, B2, G1 and G2 spiked to red pepper, white pepper, black pepper, nutmeg and tear grass at the level of 10 ng/g were over 80-85% in all instances. The minimum detectable concentration for aflatoxins in red pepper was 0.5 ng/g.

  8. 75 FR 28188 - Airworthiness Directives; General Electric Company CF34-1A, -3A, -3A1, -3A2, -3B, and -3B1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... Frost, Aerospace Engineer, Engine Certification Office, FAA, Engine & Propeller Directorate, 12 New..., Massachusetts, on May 10, 2010. Peter A. White, Assistant Manager, Engine and Propeller Directorate, Aircraft... Airworthiness Directives; General Electric Company CF34-1A, -3A, -3A1, -3A2, -3B, and -3B1 Turbofan Engines...

  9. Pyranoflavones: a group of small-molecule probes for exploring the active site cavities of cytochrome P450 enzymes 1A1, 1A2, and 1B1.

    PubMed

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

    2013-05-23

    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 toward 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. α-Naphthoflavone-like and 5-hydroxyflavone derivatives preferentially inhibited P450 1A2, while β-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.

  10. Structure investigation of maltacine B1a, B1b, B2a and B2b: cyclic peptide lactones of the maltacine complex from Bacillus subtilis.

    PubMed

    Hagelin, Gunnar

    2005-04-01

    A new complex of cyclic peptide lactone antibiotics from Bacillus subtilis, which we named maltacines, has recently been described. The structure elucidation of four of them is reported in this paper. The amino acid sequences and structures of the peptides were found by MSn of the ring-opened linear peptides that gave uninterrupted sequences of Bn and Y''n ions. The identities of three unknown residues in the sequences were solved by a combination of derivatization with phenyl isothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange. The nature and position of the cyclic structure were revealed by a chemoselective ring opening with Na18OH and was found to be a lactone formed between a hydroxyl of residue number 4 and the C-terminal amino acid number 12. For verification of the structure of the B2+ ion, peptides with different combinations of P/Q and P/K at the N-terminus were synthesized. The structures of the four peptides were found to be as follows: B1a/B2a, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-Orn-103-Y-I-OH); and B1b/B2b, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-K-103-Y-I-OH). Copyright 2005 John Wiley & Sons, Ltd.

  11. Annexin A1, Annexin A2, and Dyrk 1B are upregulated during GAS1-induced cell cycle arrest.

    PubMed

    Pérez-Sánchez, Gilberto; Jiménez, Adriana; Quezada-Ramírez, Marco A; Estudillo, Enrique; Ayala-Sarmiento, Alberto E; Mendoza-Hernández, Guillermo; Hernández-Soto, Justino; Hernández-Hernández, Fidel C; Cázares-Raga, Febe E; Segovia, Jose

    2018-05-01

    GAS1 is a pleiotropic protein that has been investigated because of its ability to induce cell proliferation, cell arrest, and apoptosis, depending on the cellular or the physiological context in which it is expressed. At this point, we have information about the molecular mechanisms by which GAS1 induces proliferation and apoptosis; but very few studies have been focused on elucidating the mechanisms by which GAS1 induces cell arrest. With the aim of expanding our knowledge on this subject, we first focused our research on finding proteins that were preferentially expressed in cells arrested by serum deprivation. By using a proteomics approach and mass spectrometry analysis, we identified 17 proteins in the 2-DE protein profile of serum deprived NIH3T3 cells. Among them, Annexin A1 (Anxa1), Annexin A2 (Anxa2), dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B), and Eukaryotic translation initiation factor 3, F (eIf3f) were upregulated at transcriptional the level in proliferative NIH3T3 cells. Moreover, we demonstrated that Anxa1, Anxa2, and Dyrk1b are upregulated at both the transcriptional and translational levels by the overexpression of GAS1. Thus, our results suggest that the upregulation of Anxa1, Anxa2, and Dyrk1b could be related to the ability of GAS1 to induce cell arrest and maintain cell viability. Finally, we provided further evidence showing that GAS1 through Dyrk 1B leads not only to the arrest of NIH3T3 cells but also maintains cell viability. © 2017 Wiley Periodicals, Inc.

  12. 75 FR 16664 - Airworthiness Directives; Turbomeca ARRIEL 1B, 1D, 1D1, 2B, and 2B1 Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-02

    ... limited to, Eurocopter AS 350 B, AS 350 BA, AS 350 B1, AS 350 B2, AS 350 B3, and EC 130 B4 helicopters... an aviation product. The MCAI describes the unsafe condition as: During production of Arriel 1 and... by Turbom[eacute]ca. Potentially non-conforming PT blades have been traced as having been installed...

  13. Excitation of O 2(a 1Δ g, b 1Σ g+) and I( 2P 1/2) by energy transfer from I 2(A, A' 3Π 1,2u) in solid rare gases

    NASA Astrophysics Data System (ADS)

    Böhling, R.; Becker, A. C.; Minaev, B. F.; Seranski, K.; Schurath, U.

    1990-04-01

    O 2a 1Δ g, b 1Σ g+ → X 3Σ g- and I 2P 1/22P 3/4 fluorescence occurs in I 2/O 2-doped rare gas matrices when I 2 is excited with visible laser light. O 2(a 1Δ g) and I( 2P 1/2) are populated independently by near-resonant energy transfer from the metastable triplet states of I 2. The doublet splitting of the O 2a→X band, which peaks at 7879 and 7863 cm -1 in argon, is interpreted as sensitized emission from O 2 trapped in distinct nearest neighbour positions of the donor 3I 2. Annealing reverses the intensity of the doublet, showing that the sites can be interconverted. It is suggested that the a→X emission rate is enhanced by the sensitizer, causing a lifetime reduction of the a 1Δ g state from 79 s in pure argon to 21 and 3±1 s next to I 2. The long-lived O 2(a 1Δ g) state is the precursor of I 2-sensitized emission from O 2(b 1Σ g+). The lifetime of O 2(b 1Σ g+) is reduced from 24.5 ms in pure argon to 17±1 ms in the presence of I 2.

  14. Aminopyridinate-FI hybrids, their hafnium and titanium complexes, and their application in the living polymerization of 1-hexene.

    PubMed

    Haas, Isabelle; Dietel, Thomas; Press, Konstantin; Kol, Moshe; Kempe, Rhett

    2013-10-11

    Based on two well-established ligand systems, the aminopyridinato (Ap) and the phenoxyimine (FI) ligand systems, new Ap-FI hybrid ligands were developed. Four different Ap-FI hybrid ligands were synthesized through a simple condensation reaction and fully characterized. The reaction of hafnium tetrabenzyl with all four Ap-FI hybrid ligands exclusively led to mono(Ap-FI) complexes of the type [(Ap-FI)HfBn2 ]. The ligands acted as tetradentate dianionic chelates. Upon activation with tris(pentafluorophenyl)borane, the hafnium-dibenzyl complexes led to highly active catalysts for the polymerization of 1-hexene. Ultrahigh molecular weights and extremely narrow polydispersities support the living nature of this polymerization process. A possible deactivation product of the hafnium catalysts was characterized by single-crystal X-ray analysis and is discussed. The coordination modes of these new ligands were studied with the help of model titanium complexes. The reaction of titanium(IV) isopropoxide with ligand 1 led to a mono(Ap-FI) complex, which showed the desired fac-mer coordination mode. Titanium (IV) isopropoxide reacted with ligand 4 to give a complex of the type [(ApH-FI)2 Ti(OiPr)2 ], which featured the ligand in its monoanionic form. The two titanium complexes were characterized by X-ray crystal-structure analysis. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. 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

  16. 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

  17. Expression and inducibility of CYP1A1, 1A2, 1B1 by β-naphthoflavone and CYP2B22, CYP3As by rifampicin in heart regions and coronary arteries of pig.

    PubMed

    Messina, Andrea; Puccinelli, Emanuela; Gervasi, Pier Giovanni; Longo, Vincenzo

    2013-02-01

    In this study, the constitutive and inducible expression of the CYP genes (1A1, 1A2, 1B1, 2B22, 3A22, 3A29 and 3A46), related transcriptional factors (AhR, CAR, PXR, and Nrf2) and the antioxidant enzymes SOD, catalase, GSSH-reductase and GSH-peroxidase were investigated in the liver, heart regions and coronary arteries of control pigs and pigs treated with β-naphthoflavone (βNF) or with rifampicin (RIF). Real-time PCR experiments and enzymatic or immunoblot assays showed that CYP1A1 was predominantly enhanced by βNF in a similar manner in all the heart regions, whereas antioxidant enzyme activity was not affected. The rifampicin treatment resulted in an induction of CYP2B22 and CYP3As, at the transcriptional, activity and protein level in liver but not in heart nor in the coronary arteries, despite the expression of CAR and PXR in the cardiac tissues. These results obtained in vivo suggest that pig cardiac tissues may represent a useful model for humans. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer.

    PubMed

    O'Hara, F Patrick; Beck, Ernestine; Barr, Lauren K; Wong, Lily L; Kessler, Daniel S; Riddle, Robert D

    2005-07-01

    The mesencephalic and metencephalic region (MMR) of the vertebrate central nervous system develops in response to signals produced by the isthmic organizer (IsO). We have previously reported that the LIM homeobox transcription factor Lmx1b is expressed within the chick IsO, where it is sufficient to maintain expression of the secreted factor wnt1. In this paper, we show that zebrafish express two Lmx1b orthologs, lmx1b.1 and lmx1b.2, in the rostral IsO, and demonstrate that these genes are necessary for key aspects of MMR development. Simultaneous knockdown of Lmx1b.1 and Lmx1b.2 using morpholino antisense oligos results in a loss of wnt1, wnt3a, wnt10b, pax8 and fgf8 expression at the IsO, leading ultimately to programmed cell death and the loss of the isthmic constriction and cerebellum. Single morpholino knockdown of either Lmx1b.1 or Lmx1b.2 has no discernible effect on MMR development. Maintenance of lmx1b.1 and lmx1b.2 expression at the isthmus requires the function of no isthmus/pax2.1, as well as Fgf signaling. Transient misexpression of Lmx1b.1 or Lmx1b.2 during early MMR development induces ectopic wnt1 and fgf8 expression in the MMR, as well as throughout much of the embryo. We propose that Lmx1b.1- and Lmx1b.2-mediated regulation of wnt1, wnt3a, wnt10b, pax8 and fgf8 maintains cell survival in the isthmocerebellar region.

  19. Evidence for the η(b)(2S) and observation of h(b)(1P)→η(b)(1S)γ and h(b)(2P)→η(b)(1S)γ.

    PubMed

    Mizuk, R; Asner, D M; Bondar, A; Pedlar, T K; Adachi, I; Aihara, H; Arinstein, K; Aulchenko, V; Aushev, T; Aziz, T; Bakich, A M; Bay, A; Belous, K; Bhardwaj, V; Bhuyan, B; Bischofberger, M; Bonvicini, G; Bozek, A; Bračko, M; Brodzicka, J; Browder, T E; Chekelian, V; Chen, A; Chen, P; Cheon, B G; Chilikin, K; Chistov, R; Cho, I-S; Cho, K; Choi, S-K; Choi, Y; Dalseno, J; Danilov, M; Doležal, Z; Drásal, Z; Drutskoy, A; Eidelman, S; Epifanov, D; Fast, J E; Gaur, V; Gabyshev, N; Garmash, A; Golob, B; Haba, J; Hara, T; Hayasaka, K; Hayashii, H; Horii, Y; Hoshi, Y; Hou, W-S; Hsiung, Y B; Hyun, H J; Iijima, T; Ishikawa, A; Itoh, R; Iwabuchi, M; Iwasaki, Y; Iwashita, T; Jaegle, I; Julius, T; Kang, J H; Kapusta, P; Kawasaki, T; Kim, H J; Kim, H O; Kim, J H; Kim, K T; Kim, M J; Kim, Y J; Kinoshita, K; Ko, B R; Koblitz, S; Kodyš, P; Korpar, S; Kouzes, R T; Križan, P; Krokovny, P; Kuhr, T; Kumita, T; Kuzmin, A; Kwon, Y-J; Lange, J S; Lee, S-H; Li, J; Libby, J; Liu, C; Liu, Y; Liu, Z Q; Liventsev, D; Louvot, R; Matvienko, D; McOnie, S; Miyabayashi, K; Miyata, H; Mohanty, G B; Mohapatra, D; Moll, A; Muramatsu, N; Mussa, R; Nakao, M; Natkaniec, Z; Ng, C; Nishida, S; Nishimura, K; Nitoh, O; Nozaki, T; Ohshima, T; Okuno, S; Olsen, S L; Onuki, Y; Pakhlov, P; Pakhlova, G; Park, C W; Park, H; Pestotnik, R; Petrič, M; Piilonen, L E; Poluektov, A; Röhrken, M; Sakai, Y; Sandilya, S; Santel, D; Sanuki, T; Sato, Y; Schneider, O; Schwanda, C; Senyo, K; Seon, O; Sevior, M E; Shapkin, M; Shen, C P; Shibata, T-A; Shiu, J-G; Shwartz, B; Sibidanov, A; Simon, F; Smerkol, P; Sohn, Y-S; Sokolov, A; Solovieva, E; Stanič, S; Starič, M; Sumihama, M; Sumiyoshi, T; Tanida, K; Tatishvili, G; Teramoto, Y; Tikhomirov, I; Trabelsi, K; Tsuboyama, T; Uchida, M; Uehara, S; Uglov, T; Unno, Y; Uno, S; Vanhoefer, P; Varner, G; Varvell, K E; Vinokurova, A; Vorobyev, V; Wang, C H; Wang, M-Z; Wang, P; Wang, X L; Watanabe, M; Watanabe, Y; Williams, K M; Won, E; Yabsley, B D; Yamaoka, J; Yamashita, Y; Yuan, C Z; Zhang, Z P; Zhilich, V

    2012-12-07

    We report the first evidence for the η(b)(2S) using the h(b)(2P)→η(b)(2S)γ transition and the first observation of the h(b)(1P)→η(b)(1S)γ and h(b)(2P)→η(b)(1S)γ transitions. The mass and width of the η(b)(1S) and η(b)(2S) are measured to be m(η(b)(1S))=(9402.4±1.5±1.8) MeV/c(2), m(η(b)(2S))=(9999.0±3.5(-1.9)(+2.8)) MeV/c(2), and Γ(η(b)(1S))=(10.8(-3.7-2.0)(+4.0+4.5)) MeV. We also update the h(b)(1P) and h(b)(2P) mass measurements. We use a 133.4 fb(-1) data sample collected at energies near the Υ(5S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider.

  20. Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)*

    PubMed Central

    Zhou, Gang; Marathe, Gopal K.; Hartiala, Jaana; Hazen, Stanley L.; Allayee, Hooman; Tang, W. H. Wilson; McIntyre, Thomas M.

    2013-01-01

    Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10−8). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10−17). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation. PMID:23508960

  1. Effect of FiO2 in the measurement of VO2 and VCO2 using the E-COXV metabolic monitor.

    PubMed

    Ferreruela, M; Raurich, J M; Llompart-Pou, J A; Colomar, A; Ayestarán, I

    2017-11-01

    We evaluated the effect of changes in FiO 2 on the bias and accuracy of the determination of oxygen consumption (V˙O 2 ) and carbon dioxide production (V˙CO 2 ) using the E-COVX monitor in patients with mechanical ventilation. Descriptive of concordance. Intensive Care Unit. Patients with mechanical ventilation. We measured V˙O 2 and V˙CO 2 using the E-COVX monitor. Values recorded were the average in 5min. Two groups of 30 patients. We analyzed: 1) the reproducibility in the measurement of V˙O 2 and V˙CO 2 at FiO 2 0.4, and 2) the effect of the changes in FiO 2 on the measurement of V˙O 2 and V˙CO 2 . Statistical analysis was performed using Bland and Altman test. Bias and accuracy. 1) FiO 2 0.4 reproducibility: The bias in the measurement of V˙O 2 and V˙CO 2 was 1.6 and 2.1mL/min, respectively, and accuracy was 9.7 to -8.3% and 7.2 to -5.2%, respectively, and 2) effect of FiO 2 on V˙O 2 : The bias of V˙O 2 measured at FiO 2 0.4 and 0.6 was -4.0mL/min and FiO 2 0.4 and 0.8 was 5.2mL/min. Accuracy between FiO 2 0.4 and 0.6 was 11.9 to -14.1%, and between FiO 2 0.4 and 0.8 was 43.9 to -39.7%. The E-COVX monitor evaluates V˙O 2 and V˙CO 2 in critical patients with mechanical ventilation with a clinically acceptable accuracy until FiO 2 0.6. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  2. Peniciadametizine A, a Dithiodiketopiperazine with a Unique Spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] Skeleton, and a Related Analogue, Peniciadametizine B, from the Marine Sponge-Derived Fungus Penicillium adametzioides.

    PubMed

    Liu, Yang; Mándi, Attila; Li, Xiao-Ming; Meng, Ling-Hong; Kurtán, Tibor; Wang, Bin-Gui

    2015-06-05

    Peniciadametizine A (1); a new dithiodiketopiperazine derivative possessing a unique spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton, together with a highly oxygenated new analogue, peniciadametizine B (2); as well as two known compounds, brasiliamide A (3); and viridicatumtoxin (4), were isolated and identified from Penicillium adametzioides AS-53, a fungus obtained from an unidentified marine sponge. The unambiguous assignment of the relative and absolute configuration for the spiro center C-2 of compound 1 was solved by the combination of NMR and ECD measurements with Density-Functional Theory (DFT) conformational analysis and Time-Dependent Density-Functional Theory-Electronic Circular Dichroism (TDDFT-ECD) calculations. The spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton of 1 has not been reported yet among natural products and the biosynthetic pathway for 1 and 2 was discussed. Compounds 1 and 2 showed inhibitory activity against the pathogenic fungus Alternaria brassicae.

  3. Successful ABO-Incompatible Renal Transplantation:  Blood Group A1B Donor Into A2B Recipient With Anti-A1 Isoagglutinins.

    PubMed

    Fadeyi, Emmanuel A; Stratta, Robert J; Farney, Alan C; Pomper, Gregory J

    2016-08-01

    Transplantation of the blood group A2B in a recipient was successfully performed in the setting of receiving a deceased donor kidney from an "incompatible" A1B donor. The donor and recipient were both typed for ABO blood group, including ABO genotyping. The donor and recipient were tested for ABO, non-ABO, and human leukocyte antigen (HLA) antibodies. The donor and recipient were typed for HLA antigens, including T- and B-flow cytometry crossmatch tests. The recipient's RBCs were negative with A1 lectin, and immunoglobulin G anti-A1 was demonstrated in the recipient's plasma. The donor-recipient pair was a four-antigen HLA mismatch, but final T- and B-flow cytometry crossmatch tests were compatible. The transplant procedure was uneventful; the patient experienced immediate graft function with no episodes of rejection or readmissions more than 2 years later. It may be safe to transplant across the A1/A2 blood group AB mismatch barrier in the setting of low titer anti-A1 isoagglutinins without the need for pretransplant desensitization even if the antibody produced reacts with anti-human globulin. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. 7 CFR 1b.2 - Policy.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Policy. 1b.2 Section 1b.2 Agriculture Office of the Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.2 Policy. (a) All policies and programs of... environment for present and future generations. (b) Each USDA agency is responsible for compliance with this...

  5. 7 CFR 1b.2 - Policy.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Policy. 1b.2 Section 1b.2 Agriculture Office of the Secretary of Agriculture NATIONAL ENVIRONMENTAL POLICY ACT § 1b.2 Policy. (a) All policies and programs of... environment for present and future generations. (b) Each USDA agency is responsible for compliance with this...

  6. Determination of the Rate Constants for the NH 2 (X 2 B 1 ) + NH 2 (X 2 B 1 ) and NH 2 (X 2 B 1 ) + H Recombination Reactions in N 2 as a Function of Temperature and Pressure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Altinay, Gokhan; Macdonald, R. Glen

    2015-07-16

    The recombination rate constants for the reactions NH2 + NH2 → N2H4 (reaction k1b) and NH2 + H → NH3 (reaction k2b) with N2 as a third-body have been measured as a function of temperature and pressure. The temperature range was from 292 to 533 K and the pressure range from a few Torr up to 300–400 Torr, well within the pressure falloff region. The NH2 radical was produced by 193 nm pulsed-laser photolysis of NH3 in a temperature controlled flow chamber. High-resolution time-resolved laser absorption spectroscopy was used to follow the temporal concentration profiles of both NH2 and NH3, simultaneously. The NH2 radical was monitored at 14800.65 cm–1 using the 1231 (0,7,0)Ã2A1 ← 1331 (0,0,0)more » $$\\tilde{X}$$2B1 ro-vibronic transition, and NH3 monitored at 3336.39 cm–1 on the qQ3(3)s (1,0,0,0) ← (0,0,0,0) ro-vibrational transition. The necessary collisional broadening parameters for each molecule were measured in separate experiments. The pressure and temperature dependence of k1b can be represented by the Troe parameters: k0, the low-pressure three-body recombination rate constant, k0(T) = (1.14 ± 0.59) × 10–19T–(3.41±0.28) cm6 molecule–2 s–1, and Fcent, the pressure broadening parameter, Fcent = 0.15 ± 0.12, independent of temperature. The data could not be fit by three-independent parameters, and the high-pressure limiting rate constant k∞(T) = 9.33 × 10–10T–0.414 e33/T cm3 molecule–1 s–1 was taken from the high-quality theoretical calculations of Klippenstein et al. (J. Phys. Chem A 2009, 113, 10241). The pressure and temperature dependence of k2b, can be represented by the Troe parameters: k0(T) = (9.95 ± 0.58) × 10–26T(-1.76±0.092) cm6 molecule–2 s–1, Fcent = 0.5 ± 0.2, k∞ = 2.6 × 10–10 cm3 molecule–1 s–1. Again, the data could not be fit with three independent parameters, and k2b∞ was chosen to be 2.6 × 10–10 cm3 molecule–1 s–1 and fixed in the analysis.« less

  7. A role of nesfatin-1/NucB2 in dehydration-induced anorexia.

    PubMed

    Yoshimura, Mitsuhiro; Matsuura, Takanori; Ohkubo, Junichi; Maruyama, Takashi; Ishikura, Toru; Hashimoto, Hirofumi; Kakuma, Tetsuya; Mori, Masatomo; Ueta, Yoichi

    2014-07-15

    Nesfatin-1/NucB2, an anorexigenic molecule, is expressed mainly in the hypothalamus, particularly in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). Nesfatin-1/NucB2 is also expressed in the subfornical organ (SFO). Because the SON and PVN are involved in body fluid regulation, nesfatin-1/NucB2 may be involved in dehydration-induced anorexia. To clarify the effects of endogenous nesfatin-1/NucB2, we studied changes in nesfatin-1/NucB2 mRNA levels in the SFO, SON, and PVN in adult male Wistar rats after exposure to osmotic stimuli by using in situ hybridization histochemistry. Significant increases in nesfatin-1/NucB2 mRNA levels, ∼2- to 3-fold compared with control, were observed in the SFO, SON, and PVN following water deprivation for 48 h, consumption of 2% NaCl hypertonic saline in drinking water for 5 days, and polyethylene glycol-induced hypovolemia. In addition, nesfatin-1/NucB2 expression was increased in response to water deprivation in a time-dependent manner. These changes in nesfatin-1/NucB2 mRNA expression were positively correlated with plasma sodium concentration, plasma osmolality, and total protein levels in all of the examined nuclei. Immunohistochemistry for nesfatin-1/NucB2 revealed that nesfatin-1/NucB2 protein levels were also increased after 48 h of dehydration and attenuated by 24 h of rehydration. Moreover, intracerebroventricular administration of nesfatin-1/NucB2-neutralizing antibody after 48 h of water deprivation resulted in a significant increase in food intake compared with administration of vehicle alone. These results suggested that nesfatin-1/NucB2 is a crucial peptide in dehydration-induced anorexia. Copyright © 2014 the American Physiological Society.

  8. CH(X2∏, a4∑-) ... OH2 and CH2(X˜3B1, ã1A1) ... OH2 interactions. A first principles investigation

    NASA Astrophysics Data System (ADS)

    Tzeli, Demeter; Mavridis, Aristides

    We have investigated the interaction of the methylidene, CH(X2∏, a4∑-) and methylene, CH2(X˜3B1, ã1A1) with H2O, employing the (P)MPn (n = 2, 4) techniques in conjunction with the sequence of correlation consistent basis sets aug-cc-pVxZ, x = 2, 3, and 4. For the CH ... OH2 system, we have located four minima (m) and three transition states (ts) and for the CH2 ... OH2, five minima and four transition states. All our results have been corrected for zero-point energy (ZPE) and basis set superposition errors (BSSE), while for the most important m_ structures, we report complete basis set (CBS) interaction limits. We also report fully optimized geometries, harmonic frequencies, dipole moments, Mulliken charges, and potential energy curves. The highest CH(X2∏) ... OH2 (m1_2∏) and CH21A1) ... OH2 (m1_1A1) interactions are the result of electron transfer from the oxygen atom to the empty pπ orbitals of CH(X2∏) and CH21A1), respectively (ylide-like structures). At the (P)MP4/AQZ//MP2/ATZ level, including ZPE, BSSE, and CBS extrapolation, we obtain ΔE0(BSSE)+CBS = -9.36 kcal/mol at rC ... O = 1.752 Å, and -9.73 kcal/mol at rC ... O = 1.741 Å for the m1_2∏ and m1_1A1, respectively.

  9. Albumin Stimulates the Activity of the Human UDP-Glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the Effects Are Enzyme and Substrate Dependent

    PubMed Central

    Svaluto-Moreolo, Paolo; Dziedzic, Klaudyna; Yli-Kauhaluoma, Jari; Finel, Moshe

    2013-01-01

    Human UDP-glucuronosyltransferases (UGTs) are important enzymes in metabolic elimination of endo- and xenobiotics. It was recently shown that addition of fatty acid free bovine serum albumin (BSA) significantly enhances in vitro activities of UGTs, a limiting factor in in vitro–in vivo extrapolation. Nevertheless, since only few human UGT enzymes were tested for this phenomenon, we have now performed detailed enzyme kinetic analysis on the BSA effects in six previously untested UGTs, using 2–4 suitable substrates for each enzyme. We also examined some of the previously tested UGTs, but using additional substrates and a lower BSA concentration, only 0.1%. The latter concentration allows the use of important but more lipophilic substrates, such as estradiol and 17-epiestradiol. In five newly tested UGTs, 1A7, 1A8, 1A10, 2A1, and 2B15, the addition of BSA enhanced, to a different degree, the in vitro activity by either decreasing reaction’s K m, increasing its V max, or both. In contrast, the activities of UGT2B17, another previously untested enzyme, were almost unaffected. The results of the assays with the previously tested UGTs, 1A1, 1A6, 2B4, and 2B7, were similar to the published BSA only as far as the BSA effects on the reactions’ K m are concerned. In the cases of V max values, however, our results differ significantly from the previously published ones, at least with some of the substrates. Hence, the magnitude of the BSA effects appears to be substrate dependent, especially with respect to V max increases. Additionally, the BSA effects may be UGT subfamily dependent since K m decreases were observed in members of subfamilies 1A, 2A and 2B, whereas large V max increases were only found in several UGT1A members. The results shed new light on the complexity of the BSA effects on the activity and enzyme kinetics of the human UGTs. PMID:23372764

  10. Results from Evaluation of Proposed ASME AG-1 Section FI Metal Media Filters - 13063

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilson, John A.; Giffin, Paxton K.; Parsons, Michael S.

    High efficiency particulate air (HEPA) filtration technology is commonly used in Department of Energy (DOE) facilities that require control of radioactive particulate matter (PM) emissions due to treatment or management of radioactive materials. Although HEPA technology typically makes use of glass fiber media, metal and ceramic media filters are also capable of filtering efficiencies beyond the required 99.97%. Sintered metal fiber filters are good candidates for use in DOE facilities due to their resistance to corrosive environments and resilience at high temperature and elevated levels of relative humidity. Their strength can protect them from high differential pressure or pressure spikesmore » and allow for back pulse cleaning, extending filter lifetime. Use of these filters has the potential to reduce the cost of filtration in DOE facilities due to life cycle cost savings. ASME AG-1 section FI has not been approved due to a lack of protocols and performance criteria for qualifying section FI filters. The Institute for Clean Energy Technology (ICET) with the aid of the FI project team has developed a Section FI test stand and test plan capable of assisting in the qualification ASME AG-1 section FI filters. Testing done at ICET using the FI test stand evaluates resistance to rated air flow, test aerosol penetration and resistance to heated air of the section FI filters. Data collected during this testing consists of temperature, relative humidity, differential pressure, flow rate, upstream particle concentration, and downstream particle concentration. (authors)« less

  11. Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats.

    PubMed

    Ghazizadeh, Vahid; Nazıroğlu, Mustafa

    2014-09-01

    Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.

  12. CC2D1A and CC2D1B regulate degradation and signaling of EGFR and TLR4.

    PubMed

    Deshar, Rakesh; Cho, Eun-Bee; Yoon, Sungjoo Kim; Yoon, Jong-Bok

    2016-11-11

    Signaling through many transmembrane receptors is terminated by their sorting to the intraluminal vesicles (ILVs) of multivescular bodies (MVBs) and subsequent lysosomal degradation. ILV formation requires the endosomal sorting complex required for transport (ESCRT) machinery. CC2D1A and CC2D1B interact with the CHMP4 family of proteins, the major subunit of the ESCRT-III complex, however, their roles in receptor degradation and signaling are poorly defined. Here, we report that CC2D1A binds to CHMP4B polymers formed on endosomes to regulate the endosomal sorting pathway. We show that depletion of CC2D1A and B accelerates degradation of EGFR and elicits rapid termination of its downstream signaling through ERK1 and 2. Depletion of CC2D1A and B promotes sorting of EGFR to ILV leading to its rapid lysosomal degradation. In addition, we show that knockdown of CC2D1A and B has similar effects on degradation and downstream signaling of another membrane receptor, TLR4. Thus, these findings suggest that CC2D1A and B may have broad effects on transmembrane receptors by preventing premature ILV sorting and termination of signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Symbiotic effects of a lipase-secreting bacterium, Burkholderia arboris SL1B1, and a glycerol-assimilating yeast, Candida cylindracea SL1B2, on triacylglycerol degradation.

    PubMed

    Matsuoka, Hiroshi; Miura, Atsuto; Hori, Katsutoshi

    2009-04-01

    Although microbial degradation of oils and fats has been developed for application in wastewater treatment, microbial degraders are not always effective in the field, for example, in grease-traps installed for the treatment of wastewater from restaurants and food industries. Wastewater in grease-traps is usually in a pH range of 5.5 to 6.5 due to hydrolysis of triacylglycerol (TAG). Because many microorganisms commercialized for use in grease-traps cannot grow at pH 6.0, we screened oil-degrading microorganisms from the environment by growing in a medium at pH 6.0 containing canola oil as the sole carbon source. We succeeded in isolating the bacterial strain Burkholderia arboris SL1B1, which secretes lipase and assimilates fatty acids, and the yeast strain Candida cylindracea SL1B2, which assimilates glycerol. The former cannot utilize glycerol as a carbon source while the latter shows only faint lipase activity that cannot support its active growth on TAG. Canola oil was degraded rapidly by a pure culture of SL1B1 at pH 6.0. However, the degradation was markedly enhanced by a mixed culture of SL1B1 and SL1B2, although lipase activity during cultivation was similar between the pure and mixed cultures. This suggests that the reversible reaction proceeds in the direction of hydrolysis of TAG due to consumption of the reaction product, glycerol, by the symbiotic yeast strain. The optimum pH and temperature of lipase secreted by B. arboris SL1B1 were 8.0 and 60 degrees C, respectively. This lipase showed highly thermal stability; the residual activity after incubation at 70 degrees C for 2 h did not decline.

  14. Selective FLT3 inhibitor FI-700 neutralizes Mcl-1 and enhances p53-mediated apoptosis in AML cells with activating mutations of FLT3 through Mcl-1/Noxa axis.

    PubMed

    Kojima, K; Konopleva, M; Tsao, T; Andreeff, M; Ishida, H; Shiotsu, Y; Jin, L; Tabe, Y; Nakakuma, H

    2010-01-01

    Treatment using Fms-like tyrosine kinase-3 (FLT3) inhibitors is a promising approach to overcome the dismal prognosis of acute myeloid leukemia (AML) with activating FLT3 mutations. Current trials are combining FLT3 inhibitors with p53-activating conventional chemotherapy. The mechanisms of cytotoxicity of FLT3 inhibitors are poorly understood. We investigated the interaction of FLT3 and p53 pathways after their simultaneous blockade using the selective FLT3 inhibitor FI-700 and the MDM2 inhibitor Nutlin-3 in AML. We found that FI-700 immediately reduced antiapoptotic Mcl-1 levels and enhanced Nutlin-induced p53-mediated mitochondrial apoptosis in FLT3/internal tandem duplication cells through the Mcl-1/Noxa axis. FI-700 induced proteasome-mediated degradation of Mcl-1, resulting in the reduced ability of Mcl-1 to sequester proapoptotic Bim. Nutlin-3 induced Noxa, which displaced Bim from Mcl-1. The FI-700/Nutlin-3 combination profoundly activated Bax and induced apoptosis. Our findings suggest that FI-700 actively enhances p53 signaling toward mitochondrial apoptosis and that a combination strategy aimed at inhibiting FLT3 and activating p53 signaling could potentially be effective in AML.

  15. The effect of organic anion-transporting polypeptides 1B1, 1B3 and 2B1 on the antitumor activity of flavopiridol in breast cancer cells.

    PubMed

    Brenner, Stefan; Riha, Juliane; Giessrigl, Benedikt; Thalhammer, Theresia; Grusch, Michael; Krupitza, Georg; Stieger, Bruno; Jäger, Walter

    2015-01-01

    The contribution of organic anion transporting polypeptides (OATPs) to the cellular uptake of flavopiridol was investigated in OATP1B1-, OATP1B3- and OATP2B1-expressing Chinese hamster ovary (CHO) cells. Uptake of flavopiridol into these cells showed typical Michaelis-Menten kinetics with much higher transport capacity for OATP1B3 compared to OATP1B1 and OATP2B1 (Vmax/Km, 33.9 vs. 8.84 and 2.41 µl/mg/min, respectively). The predominant role of OATPs was further supported by a dramatic inhibition of flavopiridol uptake in the presence of the OATP substrate rifampicin. Uptake of flavopiridol by OATPs also seems to be an important determinant in breast cancer cells. The much higher mRNA level for OATP1B1 found in wild-type compared to ZR-75-1 OATP1B1 knockdown cells correlated with higher flavopiridol initial uptake leading to 4.6-fold decreased IC50 values in the cytotoxicity assay (IC50, 1.45 vs. 6.64 µM). Cell cycle profile also showed a clear incidence for a stronger cell cycle arrest in the G2/M phase for ZR-75-1 wild-type cells compared to OATP1B1 knockdown cells, further indicating an active uptake via OATP1B1. In conclusion, our results revealed OATP1B1, OATP1B3 and OATP2B1 as uptake transporters for flavopiridol in cancer cells, which may also apply in patients during cancer therapy.

  16. Inelastic scattering matrix elements for the nonadiabatic collision B(2P1/2)+H2(1Sigmag+,j)<-->B(2P3/2)+H2(1Sigmag+,j').

    PubMed

    Weeks, David E; Niday, Thomas A; Yang, Sang H

    2006-10-28

    Inelastic scattering matrix elements for the nonadiabatic collision B(2P1/2)+H2(1Sigmag+,j)<-->B(2P3/2)+H2(1Sigmag+,j') are calculated using the time dependent channel packet method (CPM). The calculation employs 1 2A', 2 2A', and 1 2A" adiabatic electronic potential energy surfaces determined by numerical computation at the multireference configuration-interaction level [M. H. Alexander, J. Chem. Phys. 99, 6041 (1993)]. The 1 2A' and 2 2A', adiabatic electronic potential energy surfaces are transformed to yield diabatic electronic potential energy surfaces that, when combined with the total B+H2 rotational kinetic energy, yield a set of effective potential energy surfaces [M. H. Alexander et al., J. Chem. Phys. 103, 7956 (1995)]. Within the framework of the CPM, the number of effective potential energy surfaces used for the scattering matrix calculation is then determined by the size of the angular momentum basis used as a representation. Twenty basis vectors are employed for these calculations, and the corresponding effective potential energy surfaces are identified in the asymptotic limit by the H2 rotor quantum numbers j=0, 2, 4, 6 and B electronic states 2Pja, ja=1/2, 3/2. Scattering matrix elements are obtained from the Fourier transform of the correlation function between channel packets evolving in time on these effective potential energy surfaces. For these calculations the H2 bond length is constrained to a constant value of req=1.402 a.u. and state to state scattering matrix elements corresponding to a total angular momentum of J=1/2 are discussed for j=0<-->j'=0,2,4 and 2P1/2<-->2P1/2, 2P3/2 over a range of total energy between 0.0 and 0.01 a.u.

  17. Quantitation of CYP1A1 and 1B1 mRNA in polycyclic aromatic hydrocarbon-treated human T-47D and HepG2 cells by a modified bDNA assay using fluorescence detection.

    PubMed

    Wu, Susan J; Spink, David C; Spink, Barbara C; Kaminsky, Laurence S

    2003-01-15

    The quantitation of mRNA, essential for assessing mechanisms of enzyme regulation, is normally carried out using reverse transcriptase-polymerase chain reaction (RT-PCR). An alternative method uses a signal-amplification nucleic acid probe assay, which measures RNA directly by the QuantiGene Expression Kit and incorporates branched DNA technology from Bayer and luminometer-based readings of a chemilumigenic alkaline phosphatase substrate. To broaden the utility of this assay, we investigated substitution of a fluorescent substrate, 2'-(2-benzothiazol)-6'-hydroxybenzothiazole phosphate and a fluorometer, and applied the method to quantitation of CYP1A1 and 1B1 mRNA in human T-47D and HepG2 cells following induction by benzo[a]pyrene (B[a]P) and dibenzo[a,h]anthracene (DB[a,h]A). The fluorescence response increased linearly for 200 min without photobleaching and increased linearly (r2=0.997) up to at least 0.2 microg total RNA. The data revealed that at 0.5 and 1.0 microM inducing agent, the induction of CYP1A1 mRNA in HepG2 cells by DB[a,h]A exceeded that by B[a]P by 18- and 6-fold, respectively. In T-47D cells B[a]P induced CYP1A1 mRNA by 23-fold and CYP1B1 mRNA by 3.9-fold. A B[a]P cocontaminant in the environment, arsenite, did not affect B[a]P-induced levels of CYP1A1 or 1B1 mRNA in these cells. The modified analytical system provides a rapid-throughput, reproducible, and less labor-intensive method than RT-PCR for quantifying cellular mRNA levels.

  18. Ubiquitination and sumoylation of the HTLV-2 Tax-2B protein regulate its NF-κB activity: a comparative study with the HTLV-1 Tax-1 protein

    PubMed Central

    2012-01-01

    Background Retroviruses HTLV-1 and HTLV-2 have homologous genomic structures but differ significantly in pathogenicity. HTLV-1 is associated with Adult T cell Leukemia (ATL), whereas infection by HTLV-2 has no association with neoplasia. Transformation of T lymphocytes by HTLV-1 is linked to the capacity of its oncoprotein Tax-1 to alter cell survival and cell cycle control mechanisms. Among these functions, Tax-1-mediated activation of cellular gene expression via the NF-κB pathway depends on Tax-1 post-translational modifications by ubiquitination and sumoylation. The Tax-2 protein of HTLV-2B (Tax-2B) is also modified by ubiquitination and sumoylation and activates the NF-κB pathway to a level similar to that of Tax-1. The present study aims to understand whether ubiquitination and sumoylation modifications are involved in Tax-2B-mediated activation of the NF-κB pathway. Results The comparison of Tax-1 and Tax-2B lysine to arginine substitution mutants revealed conserved patterns and levels of ubiquitination with notable difference in the lysine usage for sumoylation. Neither Tax-1 nor Tax-2B ubiquitination and sumoylation deficient mutants could activate the NF-κB pathway and fusion of ubiquitin or SUMO-1 to the C-terminus of the ubiquitination and sumoylation deficient Tax-2B mutant strikingly restored transcriptional activity. In addition, ubiquitinated forms of Tax-2B colocalized with RelA and IKKγ in prominent cytoplasmic structures associated with the Golgi apparatus, whereas colocalization of Tax-2B with the RelA subunit of NF-κB and the transcriptional coactivator p300 in punctate nuclear structures was dependent on Tax-2B sumoylation, as previously observed for Tax-1. Conclusions Both Tax-1 and Tax-2 activate the NF-κB pathway via similar mechanisms involving ubiquitination and sumoylation. Therefore, the different transforming potential of HTLV-1 and HTLV-2 is unlikely to be related to different modes of activation of the canonical NF-κB pathway

  19. Effects of Al content and annealing on the phases formation, lattice parameters, and magnetization of A lxF e2B2 (x =1.0 ,1.1 ,1.2 ) alloys

    NASA Astrophysics Data System (ADS)

    Levin, E. M.; Jensen, B. A.; Barua, R.; Lejeune, B.; Howard, A.; McCallum, R. W.; Kramer, M. J.; Lewis, L. H.

    2018-03-01

    AlF e2B2 is a ferromagnet with the Curie temperature around 300 K and has the potential to be an outstanding rare-earth free candidate for magnetocaloric applications. However, samples prepared from the melt contain additional phases which affect the functional response of the AlF e2B2 phase. We report on the effects of Al content in samples with the initial (nominal) composition of A lxF e2B2 , where x =1.0 , 1.1, and 1.2 prepared by arc-melting followed by suction casting and annealing. The as-cast A lxF e2B2 alloys contain AlF e2B2 as well as additional phases, including the primary solidifying FeB and A l13F e4 compounds, which are ferromagnetic and paramagnetic, respectively, at 300 K. The presence of these phases makes it difficult to extract the intrinsic magnetic properties of AlF e2B2 phase. Annealing of A lxF e2B2 alloys at 1040 °C for 3 days allows for reaction of the FeB with A l13F e4 to form the AlF e2B2 phase, significantly reduces the amount of additional phases, and results in nearly pure AlF e2B2 phase as confirmed with XRD, magnetization, scanning electron microscopy, and electronic transport. The values of the magnetization, effective magnetic moment per Fe atom, specific heat capacity, electrical resistivity, and Seebeck coefficient for the AlF e2B2 compound have been established.

  20. Quantum dynamics of the C(1D)+HD and C(1D)+n-D2 reactions on the ã 1A' and b 1A" surfaces.

    PubMed

    Defazio, Paolo; Gamallo, Pablo; González, Miguel; Akpinar, Sinan; Bussery-Honvault, Béatrice; Honvault, Pascal; Petrongolo, Carlo

    2010-03-14

    We present the Born-Oppenheimer, quantum dynamics of the reactions C((1)D)+HD and C((1)D)+n-D(2) on the uncoupled potential energy surfaces ã (1)A' and b (1)A", considering the Coriolis interactions and the nuclear-spin statistics. Using the real wavepacket method, we obtain initial-state-resolved probabilities, cross sections, isotopic branching ratios, and rate constants. Similarly to the C+n-H(2) reaction, the probabilities present many ã (1)A' or few b (1)A" sharp resonances, and the cross sections are very large at small collision energies and decrease at higher energies. At any initial condition, the C+HD reaction gives preferentially the CD+H products. Thermal cross sections, isotopic branching ratios, and rate constant k vary slightly with temperature and agree very well with the experimental values. At 300 K, we obtain for the various products k(CH+H)=(2.45+/-0.08) x 10(-10), k(CD+H)=(1.19+/-0.04) x 10(-10), k(CH+D)=(0.71+/-0.02) x 10(-10), k(CD+D)=(1.59+/-0.05) x 10(-10) cm(3) s(-1), and k(CD+H)/k(CH+D)=1.68+/-0.01. The b (1)A" contribution to cross sections and rate constants is always large, up to a maximum value of 62% for a rotationally resolved C+D(2) rate constant. The upper b (1)A" state is thus quite important in the C((1)D) collision with H(2) and its deuterated isotopes, as the agreement between theory and experiment shows.

  1. Heterobimetallic Pd-Sn catalysis: a Suzuki, tandem ring-closing sequence toward indeno[2,1-b]thiophenes and indeno[2,1-b]indoles.

    PubMed

    Das, Debjit; Pratihar, Sanjay; Roy, Sujit

    2012-09-21

    Indeno[2,1-b]thiophene and indeno[1,2-b]indole motifs have been obtained in moderate to good yields from easily available substituted boronic acids, 2-bromo aryl/vinyl aldehydes, and nucleophiles such as arenes/heteroarenes and others using a catalytic combination of bimetallic "Pd-Sn" and AgPF(6). This formal three-component coupling involves a Suzuki reaction followed by nucleophile assisted tandem ring closure. The sequential synthesis of substituted heterocycle-fused indenes, benzofluorene, and fluorenes was also accomplished.

  2. 18 CFR 1b.2 - Scope.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to investigations...

  3. 18 CFR 1b.2 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  4. 18 CFR 1b.2 - Scope.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to investigations...

  5. 18 CFR 1b.2 - Scope.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to investigations...

  6. Targeting Sulfotransferase (SULT) 2B1b as a Regulator of Cholesterol Metabolism in Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0588 TITLE: Targeting Sulfotransferase (SULT) 2B1b as a regulator of Cholesterol Metabolism in Prostate Cancer...October 2015 30Sep2014 - 29Sep2015 W81XWH-14-1-0588Targeting Sulfotransferase (SULT) 2B1b as a regulator of Cholesterol Metabolism in Prostate...epidemiological and experimental evidence establishes alterations in cholesterol metabolism as a key driver of prostate cancer (PCa) aggressiveness

  7. Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression.

    PubMed

    Hadjighassem, Mahmoud R; Austin, Mark C; Szewczyk, Bernadeta; Daigle, Mireille; Stockmeier, Craig A; Albert, Paul R

    2009-08-01

    Altered expression of serotonin-1A (5-HT1A) receptors, both presynaptic in the raphe nuclei and post-synaptic in limbic and cortical target areas, has been implicated in mood disorders such as major depression and anxiety. Within the 5-HT1A receptor gene, a powerful dual repressor element (DRE) is regulated by two protein complexes: Freud-1/CC2D1A and a second, unknown repressor. Here we identify human Freud-2/CC2D1B, a Freud-1 homologue, as the second repressor. Freud-2 distribution was examined with Northern and Western blot, reverse transcriptase polymerase chain reaction, and immunohistochemistry/immunofluorescence; Freud-2 function was examined by electrophoretic mobility shift, reporter assay, and Western blot. Freud-2 RNA was widely distributed in brain and peripheral tissues. Freud-2 protein was enriched in the nuclear fraction of human prefrontal cortex and hippocampus but was weakly expressed in the dorsal raphe nucleus. Freud-2 immunostaining was co-localized with 5-HT1A receptors, neuronal and glial markers. In prefrontal cortex, Freud-2 was expressed at similar levels in control and depressed male subjects. Recombinant hFreud-2 protein bound specifically to 5' or 3' human DRE adjacent to the Freud-1 site. Human Freud-2 showed strong repressor activity at the human 5-HT1A or heterologous promoter in human HEK-293 5-HT1A-negative cells and neuronal SK-N-SH cells, a model of postsynaptic 5-HT1A receptor-positive cells. Furthermore, small interfering RNA knockdown of endogenous hFreud-2 expression de-repressed 5-HT1A promoter activity and increased levels of 5-HT1A receptor protein in SK-N-SH cells. Human Freud-2 binds to the 5-HT1A DRE and represses the human 5-HT1A receptor gene to regulate its expression in non-serotonergic cells and neurons.

  8. SNMP Over Wi-Fi Wireless Networks

    DTIC Science & Technology

    2003-03-01

    headphone, 1 x microphone, 1 x AC adapter 73 Wireless connectivity IrDA, Wi-Fi (IEEE 802.11b) Power Battery installed (max) 1 x Lithium Ion battery ...headphone, 1 x microphone, 1 x AC adapter Wireless connectivity Bluetooth, IrDA, Wi-Fi Power Battery installed (max) 1 x Lithium Ion battery ...is required. However Microsoft released the new version of Embedded Visual Tool that integrated Pocket PC 2002 SDK and Smartphone 2002 SDK on

  9. HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis.

    PubMed

    Osiński, Maciej; Wirstlein, Przemysław; Wender-Ożegowska, Ewa; Mikołajczyk, Mateusz; Jagodziński, Paweł Piotr; Szczepańska, Małgorzata

    2018-01-01

    The development of endometriosis is associated with changes in the expression of genes encoding the 3β-hydroxysteroid dehydrogenase type II (HSD3B2) and 17β-hydroxysteroid dehydrogenase type II (HSD17B2), estrogen receptors 1 (ESR1) and 2 (ESR2) and the androgen receptor (AR). However, little is known about the expression of HSD3B2, HSD17B1, HSD17B2, ESR1 ESR2 and AR during the endometrial phases in eutopic endometrium from infertile women with endometriosis. Using RT-qPCR analysis, we assessed the expression of the studied genes in the follicular and luteal phases in eutopic endometrium from fertile women (n = 17) and infertile women (n = 35) with endometriosis. In the mid-follicular eutopic endometrium, we observed a significant increase in HSD3B2 transcript levels in all infertile women with endometriosis (p = 0.003), in infertile women with stage I/II endometriosis (p = 0.008) and in infertile women with stage III/IV endometriosis (p = 0.009) compared to all fertile women. There was a significant increase in ESR1 tran-scripts in all infertile women with endometriosis (p = 0.008) and in infertile women with stage I/II endometriosis (p = 0.019) and in infertile women with stage III/IV endometriosis (p = 0.023) compared to all fertile women. In the mid-luteal eutopic endometrium, we did not observe significant differences in HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR transcripts between infertile women with endometriosis and fertile women. Observed significant increase in HSD3B2 and ESR1 transcripts in follicular eutopic endometrium from infer-tile women with endometriosis may be related to abnormal biological effect of E2 in endometrium, further affecting the development of human embryos.

  10. Observation of the Hadronic transitions chi(b1,2)(2P)-->omegaUpsilon(1S).

    PubMed

    Cronin-Hennessy, D; Park, C S; Park, W; Thayer, J B; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Stroynowski, R; Artuso, M; Boulahouache, C; Blusk, S; Dambasuren, E; Dorjkhaidav, O; Mountain, R; Muramatsu, H; Nandakumar, R; Skwarnicki, T; Stone, S; Wang, J C; Mahmood, A H; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Bornheim, A; Lipeles, E; Pappas, S P; Shapiro, A; Sun, W M; Weinstein, A J; Briere, R A; Chen, G P; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Adam, N E; Alexander, J P; Berkelman, K; Boisvert, V; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Galik, R S; Gibbons, L; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Magerkurth, A; Mahlke-Krüger, H; Meyer, T O; Mistry, N B; Patterson, J R; Pedlar, T K; Peterson, D; Pivarski, J; Richichi, S J; Riley, D; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Thayer, J G; Urner, D; Wilksen, T; Warburton, A; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Potlia, V; Stoeck, H; Yelton, J; Eisenstein, B I; Gollin, G D; Karliner, I; Lowrey, N; Plager, C; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Besson, D; Gao, K Y; Gong, D T; Kubota, Y; Li, S Z; Poling, R; Scott, A W; Smith, A; Stepaniak, C J; Urheim, J; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Arms, K; Eckhart, E; Gan, K K; Gwon, C; Severini, H; Skubic, P; Dytman, S A; Mueller, J A; Nam, S; Savinov, V; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shibata, E I; Shipsey, I P J; Danko, I

    2004-06-04

    The CLEO Collaboration has made the first observations of hadronic transitions among bottomonium (bbmacr;) states other than the dipion transitions among Upsilon(nS) states. In our study of Upsilon(3S) decays, we find a significant signal for Upsilon(3S)-->gammaomegaUpsilon(1S) that is consistent with radiative decays Upsilon(3S)-->gammachi(b1,2)(2P), followed by chi(b1,2)(2P)-->omegaUpsilon(1S). The branching ratios we obtain are B[chi(b1)(2P)-->omegaUpsilon(1S)]=(1.63(+0.35+0.16)(-0.31-0.15))% and B[chi(b2)(2P)-->omegaUpsilon(1S)]=(1.10(+0.32+0.11)(-0.28-0.10))%, in which the first error is statistical and the second is systematic.

  11. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to themore » cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.« less

  12. Characterization of ursodeoxycholic and norursodeoxycholic acid as substrates of the hepatic uptake transporters OATP1B1, OATP1B3, OATP2B1 and NTCP.

    PubMed

    König, Jörg; Klatt, Sabine; Dilger, Karin; Fromm, Martin F

    2012-08-01

    Ursodeoxycholic acid (UDCA) is the only approved treatment for primary biliary cirrhosis, and norursodeoxycholic acid (norUDCA) is currently tested in clinical trials for future treatment of primary sclerosing cholangitis because of beneficial effects in cholestatic Mdr2 knock-out mice. Uptake of UDCA and norUDCA into hepatocytes is believed to be a prerequisite for subsequent metabolism and therapeutic action. However, the molecular determinants of hepatocellular uptake of UDCA and norUDCA are poorly understood. We therefore investigated whether UDCA and norUDCA are substrates of the hepatic uptake transporters OATP1B1, OATP1B3, OATP2B1 and Na(+) -taurocholate co-transporting polypeptide (NTCP), which are localized in the basolateral membrane of hepatocytes. Uptake of [(3) H]UDCA and [(14) C]norUDCA into Human embryonic kidney (HEK) cells stably expressing OATP1B1, OATP1B3, OATP2B1 or NTCP was investigated and compared with uptake into vector control cells. Uptake ratios were calculated by dividing uptake into transporter-transfected cells by uptake into respective control cells. Uptake ratios of OATP1B1-, OATP1B3- and OATP2B1-mediated UDCA and norUDCA uptake were at maximum 1.23 and 1.49, respectively. Uptake of UDCA was significantly higher into HEK-NTCP cells only at the lowest tested concentration (1 μM, p < 0.001) compared with the control cells with an uptake ratio of 1.34-fold. NorUDCA was not significantly transported by NTCP. The low uptake rates suggest that OATP1B1, OATP1B3, OATP2B1 and NTCP are not relevant for hepatocellular uptake and effects of UDCA and norUDCA in human beings. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

  13. Interactions between Cytochromes P450 2B4 (CYP2B4) and 1A2 (CYP1A2) Lead to Alterations in Toluene Disposition and P450 Uncoupling

    PubMed Central

    Reed, James R.; Cawley, George F.; Backes, Wayne L.

    2013-01-01

    The goal of this study was to characterize the effects of CYP1A2•CYP2B4 complex formation on the rates and efficiency of toluene metabolism by comparing the results from simple reconstituted systems containing P450 reductase (CPR) and a single P450 to those using a mixed system containing CPR and both P450s. In the mixed system, the rates of formation of CYP2B4-specific benzyl alcohol and p-cresol were inhibited, whereas that of CYP1A2-specific o-cresol was increased, results consistent with the formation of a CYP1A2•CYP2B4 complex where the CYP1A2 moiety has higher affinity for CPR binding. Comparison of the rates of NADPH oxidation and production of hydrogen peroxide and excess water by the simple and mixed systems indicated that excess water formed at a much lower rate in the mixed system. The commensurate increase in the rate of CYP1A2-specific product formation suggested the P450•P450 interaction increased the putative rate-limiting step of CYP1A2 catalysis, abstraction of a hydrogen radical from the substrate. Cumene hydroperoxide-supported metabolism was measured to determine whether the effects of the P450•P450 interaction required the presence of CPR. Peroxidative metabolism was not affected by the interaction of the two P450s, even with CPR present. However, CPR did stimulate peroxidative metabolism by the simple system containing CYP1A2. These results suggest the major functional effects of the P450•P450 interaction are mediated by changes in the relative abilities of the P450s to receive electrons from CPR. Furthermore, CPR may play an effector role by causing a conformation change in CYP1A2 that makes its metabolism more efficient. PMID:23675771

  14. 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...

  15. Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in Type 2 Diabetes in a Chinese population

    PubMed Central

    2010-01-01

    Background Recently, several genome-wide and candidate gene association studies have identified many novel genetic loci for type 2 diabetes (T2D); among these genes, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 are the most important. We aimed to determine the effects of these genetic loci associated with T2D in the Chinese Han population of China. Methods Single-nucleotide polymorphisms (SNPs) in or near CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 genes were genotyped in a case-control Chinese Han sample living in Beijing, China involving 1024 patients with T2D and 1005 control subjects. Results In Chinese Han, we replicated the associations between 7 genetic loci and T2D, with risk allele-specific odds ratios (ORs) as follows: 1.27 (95% CI, 1.11-1.45; p = 0.0008) for CDKAL1-rs10946398, 1.26 (95% CI, 1.08-1.47; p = 0.003) for IGF2BP2-rs4402960, 1.19 (95% CI, 1.04-1.37; p = 0.009) for SLC30A8-rs13266634, 1.22 (95% CI, 1.06-1.41; p = 0.005) for CDKN2A/B-rs10811661, 1.20 (95% CI, 1.01-1.42; p = 0.03) for HHEX-rs5015480, 1.37 (95% CI, 1.19-1.69; p = 1.0 × 10-4) for KCNQ1-rs2237892, and 1.24 (95% CI, 1.01-1.52; p = 0.046) for FTO-rs8050136 after adjustment for age, gender, and body mass index. Not only did an association between WFS1-rs6446482 and early-onset T2D exist in the subgroup analysis, but TCF2-rs7501939 and WFS1-rs6446482 were also confirmed to confer risk for T2D in this meta-analysis. Moreover, the relationship between FTO-rs8050136 and body mass index, together with the effect of CDKAL1-rs10946398 on beta cell function, was also observed in the control individuals. Conclusions Our findings support the important contribution of these genetic loci to susceptibility for T2D in the Chinese Han population in Beijing of China. PMID:20509872

  16. Transcriptional Regulation of JARID1B/KDM5B Histone Demethylase by Ikaros, Histone Deacetylase 1 (HDAC1), and Casein Kinase 2 (CK2) in B-cell Acute Lymphoblastic Leukemia*

    PubMed Central

    Wang, Haijun; Song, Chunhua; Ding, Yali; Pan, Xiaokang; Ge, Zheng; Tan, Bi-Hua; Gowda, Chandrika; Sachdev, Mansi; Muthusami, Sunil; Ouyang, Hongsheng; Lai, Liangxue; Francis, Olivia L.; Morris, Christopher L.; Abdel-Azim, Hisham; Dorsam, Glenn; Xiang, Meixian; Payne, Kimberly J.; Dovat, Sinisa

    2016-01-01

    Impaired function of the Ikaros (IKZF1) protein is associated with the development of high-risk B-cell precursor acute lymphoblastic leukemia (B-ALL). The mechanisms of Ikaros tumor suppressor activity in leukemia are unknown. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling. Here, we report that Ikaros represses transcription of the histone H3K4 demethylase, JARID1B (KDM5B). Transcriptional repression of JARID1B is associated with increased global levels of H3K4 trimethylation. Ikaros-mediated repression of JARID1B is dependent on the activity of the histone deacetylase, HDAC1, which binds to the upstream regulatory element of JARID1B in complex with Ikaros. In leukemia, JARID1B is overexpressed, and its inhibition results in cellular growth arrest. Ikaros-mediated repression of JARID1B in leukemia is impaired by pro-oncogenic casein kinase 2 (CK2). Inhibition of CK2 results in increased binding of the Ikaros-HDAC1 complex to the promoter of JARID1B, with increased formation of trimethylated histone H3 lysine 27 and decreased histone H3 Lys-9 acetylation. In cases of high-risk B-ALL that carry deletion of one Ikaros (IKZF1) allele, targeted inhibition of CK2 restores Ikaros binding to the JARID1B promoter and repression of JARID1B. In summary, the presented data suggest a mechanism through which Ikaros and HDAC1 regulate the epigenetic signature in leukemia: via regulation of JARID1B transcription. The presented data identify JARID1B as a novel therapeutic target in B-ALL and provide a rationale for the use of CK2 inhibitors in the treatment of high-risk B-ALL. PMID:26655717

  17. Effects of Al content and annealing on the phases formation, lattice parameters, and magnetization of A l x F e 2 B 2 ( x = 1.0 , 1.1 , 1.2 ) alloys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Levin, E. M.; Jensen, B. A.; Barua, R.

    AlFe 2B 2 is a ferromagnet with the Curie temperature around 300 K and has the potential to be an outstanding rare-earth free candidate for magnetocaloric applications. However, samples prepared from the melt contain additional phases which affect the functional response of the AlFe 2B 2 phase. Here, we report on the effects of Al content in samples with the initial (nominal) composition of Al xFe 2B 2 where x=1.0, 1.1, and 1.2 prepared by arc-melting followed by suction casting and annealing. The as-cast Al xFe 2B 2 alloys contain AlFe 2B 2 as well as additional phases including themore » primary solidifying FeB and Al 13Fe 4 compounds which are ferromagnetic and paramagnetic, respectively, at 300 K. The presence of these phases makes it difficult to extract the intrinsic magnetic properties of AlFe 2B 2 phase. Annealing of Al xFe 2B 2 alloys at 1040°C for 3 days allows for reaction of the FeB with Al 13Fe 4 to form the AlFe 2B 2 phase, significantly reduces the amount of additional phases, and results in nearly pure AlFe 2B2 phase as confirmed with XRD, magnetization, scanning electron microscopy, and electronic transport. The values of the magnetization, effective magnetic moment per Fe atom, specific heat capacity, electrical resistivity and Seebeck coefficient for the AlFe 2B 2 compound have been established.« less

  18. Effects of Al content and annealing on the phases formation, lattice parameters, and magnetization of A l x F e 2 B 2 ( x = 1.0 , 1.1 , 1.2 ) alloys

    DOE PAGES

    Levin, E. M.; Jensen, B. A.; Barua, R.; ...

    2018-03-26

    AlFe 2B 2 is a ferromagnet with the Curie temperature around 300 K and has the potential to be an outstanding rare-earth free candidate for magnetocaloric applications. However, samples prepared from the melt contain additional phases which affect the functional response of the AlFe 2B 2 phase. Here, we report on the effects of Al content in samples with the initial (nominal) composition of Al xFe 2B 2 where x=1.0, 1.1, and 1.2 prepared by arc-melting followed by suction casting and annealing. The as-cast Al xFe 2B 2 alloys contain AlFe 2B 2 as well as additional phases including themore » primary solidifying FeB and Al 13Fe 4 compounds which are ferromagnetic and paramagnetic, respectively, at 300 K. The presence of these phases makes it difficult to extract the intrinsic magnetic properties of AlFe 2B 2 phase. Annealing of Al xFe 2B 2 alloys at 1040°C for 3 days allows for reaction of the FeB with Al 13Fe 4 to form the AlFe 2B 2 phase, significantly reduces the amount of additional phases, and results in nearly pure AlFe 2B2 phase as confirmed with XRD, magnetization, scanning electron microscopy, and electronic transport. The values of the magnetization, effective magnetic moment per Fe atom, specific heat capacity, electrical resistivity and Seebeck coefficient for the AlFe 2B 2 compound have been established.« less

  19. O2(b1Σg+, v = 0, 1) Relative Yield in O(1D) + O2 Energy Transfer

    NASA Astrophysics Data System (ADS)

    Kostko, O.; Raj, S.; Campbell, K. M.; Pejakovic, D. A.; Slanger, T. G.; Kalogerakis, K. S.

    2012-04-01

    Energy transfer from excited O(1D) atoms to ground-state O2(X3Σg-) leads to production of O2 in the first two vibrational levels of the O2(b1Σg+) state: O(1D) + O2 → O(3P ) + O2(b1Σg+, v = 0, 1). Subsequent radiative decay of O2(b1Σg+, v = 0, 1) to the ground state results in the Atmospheric Band emission, a prominent feature of the terrestrial airglow. The relative yield for production of O2(b1Σg+, v = 0, 1) in the above process, k1/k0, is an important parameter in modeling of the observed O2 Atmospheric Band emission intensities. In the laboratory experiments, the output of a pulsed fluorine laser at 157 nm is used to photodissociate molecular oxygen in an O2/N2 mixture flowing through a heated gas cell. Photodissociation of O2 produces a ground-state O(3P ) atom and an excited O(1D) atom. O(1D) rapidly transfers energy to the remaining O2 to produce O2(b1Σg+, v = 0, 1). The populations of O2(b1Σg+, v = 0, 1) are monitored by observing emissions in the O2(b-X) 0-0 and 1-0 bands at 762 and 688 nm, respectively. The value of k1/k0 is extracted from the time-dependent O2(b1Σg+, v = 0, 1) fluorescence signals using computer simulations. We find that production of v = 1 is substantially larger than that of v = 0. We will present measurements on k1/k0 and its temperature dependence, and discuss the significance of these and other relevant laboratory measurements on the interpretation of the O2 Atmospheric Band emission. This work was supported by the US National Science Foundation (NSF) Aeronomy Program under grant AGS-0937317. The fluorine laser was purchased under grant ATM-0216583 from the NSF Major Research Instrumentation Program. The participation of Sumana Raj and Kendrick M. Campbell was supported by a Research Experiences for Undergraduates (REU) site, co-funded by the Division of Physics of the NSF and the Department of Defense in partnership with the NSF REU program (PHY-1002892).

  20. Volumetric properties under pressure for 1,2-dichlorofluoroethane (R141), 1-fluoro-1,1,2-trichloroethane (R131a), and 1,2-dichloro-1,1-difluoroethane (R132b)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Malhotra, R.; Woolf, L.A.

    1997-01-01

    The effect of pressure on the volume of R141, R131, and R132b is reported as volume ratios (the volume under pressure relative to its value at atmospheric pressure) at six temperatures covering the range 278.15 to 338.13 K and pressures up to 380 MPa for R141 and R131a. For R132b the same temperature range has been used, but above its normal boiling point experimental arrangements have limited maximum pressures to below 300 MPa, with some loss of accuracy. Densities have been measured at atmospheric pressure for each liquid. The experimental data have been used to calculate isothermal compressibilities, thermal expansivities,more » and internal pressures; the change in isobaric heat capacity from its value at atmospheric pressure has also been estimated. The volume ratios for all three compounds can be represented by a version of the Tait equation based on previously reported data for 1,2-dichloroethane and 1,1,2-trichloroethane with the inclusion of allowances of the substitution in the former of chlorine or fluorine for the hydrogens on one of the carbons.« less

  1. Investigation of the effects of distance from sources on apoptosis, oxidative stress and cytosolic calcium accumulation via TRPV1 channels induced by mobile phones and Wi-Fi in breast cancer cells.

    PubMed

    Çiğ, Bilal; Nazıroğlu, Mustafa

    2015-10-01

    TRPV1 is a Ca2+ permeable channel and gated by noxious heat, oxidative stress and capsaicin (CAP). Some reports have indicated that non-ionized electromagnetic radiation (EMR)-induces heat and oxidative stress effects. We aimed to investigate the effects of distance from sources on calcium signaling, cytosolic ROS production, cell viability, apoptosis, plus caspase-3 and -9 values induced by mobile phones and Wi-Fi in breast cancer cells MCF-7 human breast cancer cell lines were divided into A, B, C and D groups as control, 900, 1800 and 2450 MHz groups, respectively. Cells in Group A were used as control and were kept in cell culture conditions without EMR exposure. Groups B, C and D were exposed to the EMR frequencies at different distances (0 cm, 1 cm, 5 cm, 10 cm, 20 cm and 25 cm) for 1h before CAP stimulation. The cytosolic ROS production, Ca2+ concentrations, apoptosis, caspase-3 and caspase-9 values were higher in groups B, C and D than in A group at 0 cm, 1 cm and 5 cm distances although cell viability (MTT) values were increased by the distances. There was no statistically significant difference in the values between control, 20 and 25 cm. Wi-Fi and mobile phone EMR placed within 10 cm of the cells induced excessive oxidative responses and apoptosis via TRPV1-induced cytosolic Ca2+ accumulation in the cancer cells. Using cell phones and Wi-Fi sources which are farther away than 10 cm may provide useful protection against oxidative stress, apoptosis and overload of intracellular Ca2+. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. SpO2/FiO2 ratio on hospital admission is an indicator of early acute respiratory distress syndrome development among patients at risk.

    PubMed

    Festic, Emir; Bansal, Vikas; Kor, Daryl J; Gajic, Ognjen

    2015-05-01

    Oxygen saturation to fraction of inspired oxygen ratio (SpO(2)/FiO(2)) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO(2)/FiO(2) measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS. This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO(2)/FiO(2). The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death. Of the 5584 patients, we evaluated all 4646 with recorded SpO(2)/FiO(2) values. Median SpO(2)/FiO(2) in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO(2)/FiO(2) and ARDS (P ≤ .001). The SpO(2)/FiO(2) was found to be an independent predictor of ARDS in a "dose-dependent" manner; for SpO(2)/FiO(2) < 100--odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO(2)/FiO(2) 100 < 200--OR 1.75 (1.16-2.58, P = .007), and for SpO(2)/FiO(2) 200 < 300--OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively. The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk. © The Author(s) 2013.

  3. Liquid chromatography/fluorescence method for emamectin B1a and desmethylamino-emamectin B1a residues in lobster tissue.

    PubMed

    Tauber, Ronald; Gillan, Niall; Crouch, Louis; Greenhalgh, Roy

    2006-01-01

    A liquid chromatography (LC)/fluorescence procedure was validated for emamectin (EM B1a) and desmethylamino-emamectin (DMAEM B1a) residues in lobster tissue. They were extracted by shaking and sonicating with 1% ammonium acetate-methanol in the presence of sand. The extract was concentrated, partitioned with ethyl acetate, and cleaned up on a propylsulfonic cation exchange cartridge. The analytes were eluted from the cartridge with 5% ammonium hydroxide-methyl acetate, the eluate was concentrated, and the solvent was changed to dry 20% ethyl acetate-acetonitrile before derivatization with trifluoroacetic anhydride-N-methylimidizole. The products were analyzed by LC-fluorescence, and no interference [>limit of detection (LOD)] was detected in the control samples. Lobster tissues fortified with EM B1a and DMAEM B1a at 0.5, 5, 10, 25, and 50 ng/g gave overall mean recoveries of 96.7 +/- 12.4%, relative standard deviation (RSD) = 12.8% for EM B1 and 83.6 +/- 12.1%, RSD = 14.5% for DMAEM B1a. Regression analysis of the calibration data gave slopes of 0.90 (EM B1a) and 0.71 (DMAEM B1a) with an r2 = 0.99 for both compounds. The calculated LOD and limit of quantification (LOQ) for EM B1a were 1.10 and 3.32 ng/g, respectively, and for DMAEM B1a were 0.762 and 2.31 ng/g, respectively. Residues of EM B1a and DMAEM B1a in fortified lobster tissues stored at -20 degrees C showed that residues were stable for 10-12 months. No loss of EM B1a and DMAEM B1a residues was observed after 3 freeze/thaw cycles of fortified tissue in a 5-day period.

  4. A comparison of 2-phenyl-2-(1-piperidinyl)propane (ppp), 1,1',1''-phosphinothioylidynetrisaziridine (thioTEPA), clopidogrel, and ticlopidine as selective inactivators of human cytochrome P450 2B6.

    PubMed

    Walsky, Robert L; Obach, R Scott

    2007-11-01

    The use of selective chemical inhibitors of human cytochrome P450 (P450) enzymes represents a powerful method by which the relative contributions of various human P450 enzymes to the metabolism of drugs can be determined. However, the identification of CYP2B6 in the metabolism of drugs has been more challenging because of the lack of a well established inhibitor of this enzyme. In this report, we describe the selectivity of 2-phenyl-2-(1-piperidinyl)propane (PPP) as an inactivator of CYP2B6 and compare this selectivity versus other CYP2B6 inactivators: 1,1',1''-phosphinothioylidynetrisaziridine (thioTEPA), clopidogrel, and ticlopidine. Values of K(I) and k(inact) for PPP were 5.6 microM and 0.13/min for bupropion hydroxylase catalyzed by pooled human liver microsomes, and values for thioTEPA were similar (4.8 microM and 0.20/min, respectively). Intrinsic inactivation capability was considerably greater for clopidogrel because of a greater k(inact) value (1.9/min). Ticlopidine was potent with K(I) and k(inact) values of 0.32 microM and 0.43/min, respectively. The selectivity of these four agents for CYP2B6 was determined by testing their effects on other human P450 enzyme activities using conditions that yield approximately 90% inactivation of CYP2B6 activity. The results showed that preincubation of human liver microsomes with PPP at 30 microM for 30 min provided more selective inhibition for CYP2B6 than thioTEPA, clopidogrel, and ticlopidine. Furthermore, the use of clopidogrel is complicated by the observation that this agent is not stable in the presence of human liver microsomes, even without addition of NADPH. Therefore, PPP can serve as a selective chemical inactivator of CYP2B6 and be used to define the role of CYP2B6 in the metabolism of drugs.

  5. Freud-2/CC2D1B mediates dual repression of the serotonin-1A receptor gene.

    PubMed

    Hadjighassem, Mahmoud R; Galaraga, Kimberly; Albert, Paul R

    2011-01-01

    The serotonin-1A (5-HT1A) receptor functions as a pre-synaptic autoreceptor in serotonin neurons that regulates their activity, and is also widely expressed on non-serotonergic neurons as a post-synaptic heteroreceptor to mediate serotonin action. The 5-HT1A receptor gene is strongly repressed by a dual repressor element (DRE), which is recognized by two proteins: Freud-1/CC2D1A and another unknown protein. Here we identify mouse Freud-2/CC2D1B as the second repressor of the 5-HT1A-DRE. Freud-2 shares 50% amino acid identity with Freud-1, and contains conserved structural domains. Mouse Freud-2 bound specifically to the rat 5-HT1A-DRE adjacent to, and partially overlapping, the Freud-1 binding site. By supershift assay using nuclear extracts from L6 myoblasts, Freud-2-DRE complexes were distinguished from Freud-1-DRE complexes. Freud-2 mRNA and protein were detected throughout mouse brain and peripheral tissues. Freud-2 repressed 5-HT1A promoter-reporter constructs in a DRE-dependent manner in non-neuronal (L6) or 5-HT1A-expressing neuronal (NG108-15, RN46A) cell models. In NG108-15 cells, knockdown of Freud-2 using a specific short-interfering RNA reduced endogenous Freud-2 protein levels and decreased Freud-2 bound to the 5-HT1A-DRE as detected by chromatin immunoprecipitation assay, but increased 5-HT1A promoter activity and 5-HT1A protein levels. Taken together, these data show that Freud-2 is the second component that, with Freud-1, mediates dual repression of the 5-HT1A receptor gene at the DRE. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  6. Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression.

    PubMed

    Kim, H; Putt, D; Reddy, S; Hollenberg, P F; Novak, R F

    1993-11-01

    Expression of the cytochrome P450 (CYP) 2B subfamily in rat and rabbit hepatic tissues after pyridine (PY) treatment has been examined, and the molecular basis for enhanced 2B1/2B2 expression has been determined. P450 expression was monitored using metabolic activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, and the identity of the proteins was confirmed through N-terminus microsequence analysis. PY caused a dose-dependent elevation of hepatic CYP2B1/B2B levels in rats, which ranged from 4- to 22-fold over the dosing regimen of 100 to 400 mg PY/kg/day, for 3 days, respectively. PY at low dose failed to induce CYP2B in rabbit hepatic tissue, suggesting a species-dependent response in 2B expression. Anti-2B1 IgG addition to PY-induced microsomes inhibited benzphetamine N-demethylase activity by only approximately 15%, in sharp contrast to the approximately 73% inhibition observed for phenobarbital-induced microsomes, suggesting the induction of other form(s) of P450 having benzphetamine N-demethylase activity. Northern blot analysis revealed that PY treatment increased 2B1 and 2B2 poly(A)+ RNA levels approximately 69- and approximately 34-fold, respectively, whereas the 2E1 poly(A)+ RNA levels failed to increase. The results of this study show that PY induces CYP2B1/2B2 and that induction is species-dependent and kinetically distinguishable from 2E1 induction. Moreover, 2B1/2B2 induction occurs as a result of elevated mRNA levels associated with either transcriptional activation or mRNA stabilization, and it differs from the mechanism of hepatic 2E1 induction by PY.

  7. 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.

  8. Laboratory detection of a new interstellar free radical CH2CN(2B1)

    NASA Technical Reports Server (NTRS)

    Saito, Shuji; Yamamoto, Satoshi; Irvine, W. M.; Ziurys, L. M.; Suzuki, Hiroko

    1988-01-01

    An asymmetric-top free radical CH2CN with a 2B1 ground state was detected by laboratory microwave spectroscopy. The radical was produced in a free-space absorption cell by a DC glow discharge in pure CH3CN gas. About 60 fine-structure components were observed for the N = 11-10 to 14-13 a-type rotational transitions in the frequency region of 220-260 GHz. Hyperfine resolved components for the N = 4-3 and 5-4 transitions were resolved in the 80 and 100 GHz regions, respectively. Molecular constants were determined and U100602 and U80484 from Sgr B2, and U40240 and U20120 from TMC-1 were assigned to the N = 5-4, 4-3, 2-1, and 1-0 transitions with K(-1) = 0 of the CH2CN radical.

  9. Bu-2470, a new peptide antibiotic complex. I. Production, isolation and properties of Bu-2470 A, B1 and B2.

    PubMed

    Konishi, M; Sugawara, K; Tomita, K; Matsumoto, K; Miyaki, T; Fujisawa, K; Tsukiura, H; Kawaguchi, H

    1983-06-01

    A strain of Bacillus circulans produced a complex of basic peptide antibiotics designated Bu-2470, which was found to contain four active components, A, B1, B2a and B2b. Bu-2470 A specifically inhibited various Pseudomonas species including P. aeruginosa, P. maltophilia and P. putida, but otherwise its antibacterial spectrum was limited to certain Gram-negative organisms. Bu-2470 B1 and B2 (B2a + B2b) showed broad antibiotic activity against Gram-positive and Gram-negative bacteria including Pseudomonas species. The physicochemical and biological properties of Bu-2470 B1 and B2 are very similar to those of the octapeptin group of antibiotics.

  10. 76 FR 9515 - Airworthiness Directives; Turbomeca S.A. ARRIEL 2B and 2B1 Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    .... ARRIEL 2B and 2B1 Turboshaft Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice... (GG) Turbine Blade rupture occurred in service on ARRIEL 2 twin engine applications and recently one on a single engine helicopter. For the case occurring in flight on a single engine helicopter (ARRIEL...

  11. Heat shock factors HsfB1 and HsfB2b are involved in the regulation of Pdf1.2 expression and pathogen resistance in Arabidopsis.

    PubMed

    Kumar, Mukesh; Busch, Wolfgang; Birke, Hannah; Kemmerling, Birgit; Nürnberger, Thorsten; Schöffl, Friedrich

    2009-01-01

    In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes Pdf1.2a/b in mutant plants. The Pdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of Pdf1.2, which is devoid of perfect HSE consensus Hsf-binding sequences. However, changes in the formation of late HsfA2-dependent HSE binding were detected in hsfB1/B2b plants. This suggests that HsfB1/B2b may interact with class A-Hsf in regulating the shut-off of the heat shock response. The identification of Pdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses.

  12. Heat Shock Factors HsfB1 and HsfB2b Are Involved in the Regulation of Pdf1.2 Expression and Pathogen Resistance in Arabidopsis

    PubMed Central

    Kumar, Mukesh; Busch, Wolfgang; Birke, Hannah; Kemmerling, Birgit; Nürnberger, Thorsten; Schöffl, Friedrich

    2009-01-01

    In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes Pdf1.2a/b in mutant plants. The Pdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of Pdf1.2, which is devoid of perfect HSE consensus Hsf-binding sequences. However, changes in the formation of late HsfA2-dependent HSE binding were detected in hsfB1/B2b plants. This suggests that HsfB1/B2b may interact with class A-Hsf in regulating the shut-off of the heat shock response. The identification of Pdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses. PMID:19529832

  13. Effects of Wi-Fi (2.45 GHz) Exposure on Apoptosis, Sperm Parameters and Testicular Histomorphometry in Rats: A Time Course Study

    PubMed Central

    Shokri, Saeed; Soltani, Aiob; Kazemi, Mahsa; Sardari, Dariush; Mofrad, Farshid Babapoor

    2015-01-01

    Objective In today’s world, 2.45-GHz radio-frequency radiation (RFR) from industrial, scientific, medical, military and domestic applications is the main part of indoor-outdoor electromagnetic field exposure. Long-term effects of 2.45-GHz Wi-Fi radiation on male reproductive system was not known completely. Therefore, this study aimed to investigate the major cause of male infertility during short- and long-term exposure of Wi-Fi radiation. Materials and Methods This is an animal experimental study, which was conducted in the Department of Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, IRAN, from June to August 2014. Three-month-old male Wistar rats (n=27) were exposed to the 2.45 GHz radiation in a chamber with two Wi-Fi antennas on opposite walls. Animals were divided into the three following groups: I. control group (n=9) including healthy animals without any exposure to the antenna, II. 1-hour group (n=9) exposed to the 2.45 GHz Wi-Fi radiation for 1 hour per day during two months and III.7-hour group (n=9) exposed to the 2.45 GHz Wi-Fi radiation for 7 hours per day during 2 months. Sperm parameters, caspase-3 concentrations, histomorphometric changes of testis in addition to the apoptotic indexes were evaluated in the exposed and control animals. Results Both 1-hour and 7-hour groups showed a decrease in sperm parameters in a time dependent pattern. In parallel, the number of apoptosis-positive cells and caspase-3 activity increased in the seminiferous tubules of exposed rats. The seminal vesicle weight reduced significantly in both1-hour or 7-hour groups in comparison to the control group. Conclusion Regarding to the progressive privilege of 2.45 GHz wireless networks in our environment, we concluded that there should be a major concern regarding the timedependent exposure of whole-body to the higher frequencies of Wi-Fi networks existing in the vicinity of our living places. PMID:26199911

  14. Effects of Wi-Fi (2.45 GHz) Exposure on Apoptosis, Sperm Parameters and Testicular Histomorphometry in Rats: A Time Course Study.

    PubMed

    Shokri, Saeed; Soltani, Aiob; Kazemi, Mahsa; Sardari, Dariush; Mofrad, Farshid Babapoor

    2015-01-01

    In today's world, 2.45-GHz radio-frequency radiation (RFR) from industrial, scientific, medical, military and domestic applications is the main part of indoor-outdoor electromagnetic field exposure. Long-term effects of 2.45-GHz Wi-Fi radiation on male reproductive system was not known completely. Therefore, this study aimed to investigate the major cause of male infertility during short- and long-term exposure of Wi-Fi radiation. This is an animal experimental study, which was conducted in the Department of Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, IRAN, from June to August 2014. Three-month-old male Wistar rats (n=27) were exposed to the 2.45 GHz radiation in a chamber with two Wi-Fi antennas on opposite walls. Animals were divided into the three following groups: I. control group (n=9) including healthy animals without any exposure to the antenna, II. 1-hour group (n=9) exposed to the 2.45 GHz Wi-Fi radiation for 1 hour per day during two months and III.7-hour group (n=9) exposed to the 2.45 GHz Wi-Fi radiation for 7 hours per day during 2 months. Sperm parameters, caspase-3 concentrations, histomorphometric changes of testis in addition to the apoptotic indexes were evaluated in the exposed and control animals. Both 1-hour and 7-hour groups showed a decrease in sperm parameters in a time dependent pattern. In parallel, the number of apoptosis-positive cells and caspase-3 activity increased in the seminiferous tubules of exposed rats. The seminal vesicle weight reduced significantly in both1-hour or 7-hour groups in comparison to the control group. Regarding to the progressive privilege of 2.45 GHz wireless networks in our environment, we concluded that there should be a major concern regarding the timedependent exposure of whole-body to the higher frequencies of Wi-Fi networks existing in the vicinity of our living places.

  15. L1-mediated retrotransposition of murine B1 and B2 SINEs recapitulated in cultured cells.

    PubMed

    Dewannieux, Marie; Heidmann, Thierry

    2005-06-03

    SINEs are short interspersed nucleotide elements with transpositional activity, present at a high copy number (up to a million) in mammalian genomes. They are 80-400 bp long, non-coding sequences which derive either from the 7SL RNA (e.g. human Alus, murine B1s) or tRNA (e.g. murine B2s) polymerase III-driven genes. We have previously demonstrated that Alus very efficiently divert the enzymatic machinery of the autonomous L1 LINE (long interspersed nucleotide element) retrotransposons to transpose at a high rate. Here we show, using an ex vivo assay for transposition, that both B1 and B2 SINEs can be mobilized by murine LINEs, with the hallmarks of a bona fide retrotransposition process, including target site duplications of varying lengths and integrations into A-rich sequences. Despite different phylogenetic origins, transposition of the tRNA-derived B2 sequences is as efficient as that of the human Alus, whereas that of B1s is 20-100-fold lower despite a similar high copy number of these elements in the mouse genome. We provide evidence, via an appropriate nucleotide substitution within the B1 sequence in a domain essential for its intracellular targeting, that the current B1 SINEs are not optimal for transposition, a feature most probably selected for the host sake in the course of evolution.

  16. PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing.

    PubMed

    Espert, Antonio; Uluocak, Pelin; Bastos, Ricardo Nunes; Mangat, Davinderpreet; Graab, Philipp; Gruneberg, Ulrike

    2014-09-29

    The spindle assembly checkpoint (SAC) monitors correct attachment of chromosomes to microtubules, an important safeguard mechanism ensuring faithful chromosome segregation in eukaryotic cells. How the SAC signal is turned off once all the chromosomes have successfully attached to the spindle remains an unresolved question. Mps1 phosphorylation of Knl1 results in recruitment of the SAC proteins Bub1, Bub3, and BubR1 to the kinetochore and production of the wait-anaphase signal. SAC silencing is therefore expected to involve a phosphatase opposing Mps1. Here we demonstrate in vivo and in vitro that BubR1-associated PP2A-B56 is a key phosphatase for the removal of the Mps1-mediated Knl1 phosphorylations necessary for Bub1/BubR1 recruitment in mammalian cells. SAC silencing is thus promoted by a negative feedback loop involving the Mps1-dependent recruitment of a phosphatase opposing Mps1. Our findings extend the previously reported role for BubR1-associated PP2A-B56 in opposing Aurora B and suggest that BubR1-bound PP2A-B56 integrates kinetochore surveillance and silencing of the SAC. © 2014 Espert et al.

  17. Prolonged neutropenia after irinotecan-based chemotherapy in a child with polymorphisms of UGT1A1 and SLCO1B1.

    PubMed

    Sakaguchi, S; Garcia-Bournissen, F; Kim, R; Schwarz, U I; Nathan, P C; Ito, S

    2009-12-01

    Genetic polymorphisms of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and SLCO1B1 coding organic anion-transporter polypeptide 1B1, are independent risk factors known to increase irinotecan toxicity in adults. Although combined occurrence of polymorphisms in these 2 genes is likely to influence susceptibility to irinotecan toxicity, data are scarce, especially in children. We report an 11-year-old female with severe and prolonged neutropenia after irinotecan-based chemotherapy. The patient's genotyping revealed polymorphisms in both UGT1A1 and SLCO1B1. To our knowledge, this is the first case report of combined genotyping of both UGT1A1 and SLCO1B1 in a child with severe irinotecan toxicity.

  18. 76 FR 70046 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, C, D, and D1; and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ... Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, C, D, and D1; and AS355E, F, F1, F2, N... France (Eurocopter) Model AS350B, B1, B2, B3, BA, C, D, and D1 helicopters; and Model AS355E, F, F1, F2... (AD 2003- 22-06), for Eurocopter Model AS350B, B1, B2, B3, BA, C, D, and D1; and Model AS355E, F, F1...

  19. Hearing impairment related to age in Usher syndrome types 1B and 2A.

    PubMed

    Wagenaar, M; van Aarem, A; Huygen, P; Pieke-Dahl, S; Kimberling, W; Cremers, C

    1999-04-01

    To evaluate hearing impairment in 2 common genetic subtypes of Usher syndrome, USH1B and USH2A. Cross-sectional analysis of hearing threshold related to age in patients with genotypes determined by linkage and mutation analysis. Otolaryngology department, university referral center. Nineteen patients with USH1B and 27 with USH2A were examined. All participants were living in the Netherlands and Belgium. Pure tone audiometry of the best ear at last visit. The patients with USH1B had residual hearing without age dependence, with minimum thresholds of 80, 95, and 120 dB at 0.25, 0.5, and 1 to 2 kHz, respectively. Mean thresholds of patients with USH2A were about 45 to 55 dB better than these minimum values. Distinctive audiographic features of patients with USH2A were maximum hearing thresholds of 70, 80, and 100 dB at 0.25, 0.5, and 1 kHz, respectively, only at younger than 40 years. Progression of hearing impairment in USH2A was 0.7 dB/y on average for 0.25 to 4 kHz and could not be explained by presbyacusis alone. The USH1B and USH2A can be easily distinguished by hearing impairment at younger than 40 years at the low frequencies. Hearing impairment in our patients with USH2A could be characterized as progressive.

  20. KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1.

    PubMed

    Wong, Sarah J; Gearhart, Micah D; Taylor, Alexander B; Nanyes, David R; Ha, Daniel J; Robinson, Angela K; Artigas, Jason A; Lee, Oliver J; Demeler, Borries; Hart, P John; Bardwell, Vivian J; Kim, Chongwoo A

    2016-10-04

    KDM2B recruits H2A-ubiquitinating activity of a non-canonical Polycomb Repression Complex 1 (PRC1.1) to CpG islands, facilitating gene repression. We investigated the molecular basis of recruitment using in vitro assembly assays to identify minimal components, subcomplexes, and domains required for recruitment. A minimal four-component PRC1.1 complex can be assembled by combining two separately isolated subcomplexes: the DNA-binding KDM2B/SKP1 heterodimer and the heterodimer of BCORL1 and PCGF1, a core component of PRC1.1. The crystal structure of the KDM2B/SKP1/BCORL1/PCGF1 complex illustrates the crucial role played by the PCGF1/BCORL1 heterodimer. The BCORL1 PUFD domain positions residues preceding the RAWUL domain of PCGF1 to create an extended interface for interaction with KDM2B, which is unique to the PCGF1-containing PRC1.1 complex. The structure also suggests how KDM2B might simultaneously function in PRC1.1 and an SCF ubiquitin ligase complex and the possible molecular consequences of BCOR PUFD internal tandem duplications found in pediatric kidney and brain tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. A Primer for the Act-1 Language.

    DTIC Science & Technology

    1982-04-01

    Case Study. 7th Symposiumn on Operating Systems Principles, December, 1979. [Kerns 80] Kerns, B.S, Towards a Better Definition of Transactions ...1. ,X, aJ ablc as MITH Al ITI \\lFllumber 625. 1,)’lr;H fi. H. i 1,1110h)jO Abc rit I ots Of Iigs At Once W\\N OI tn Getting Con fuseCd: ! ;I’l 1,21 IIl

  2. The Pseudoenzyme PDX1.2 Sustains Vitamin B6 Biosynthesis as a Function of Heat Stress1[OPEN

    PubMed Central

    Boycheva, Svetlana

    2017-01-01

    Plants sense temperature changes and respond by altering growth and metabolic activity to acclimate to the altered environmental conditions. The B vitamins give rise to vital coenzymes that are indispensable for growth and development but their inherent reactive nature renders them prone to destruction especially under stress conditions. Therefore, plant survival strategies would be expected to include mechanisms to sustain B vitamin supply under demanding circumstances. Here, using the example of vitamin B6, we investigate the regulation of biosynthesis across eudicot and monocot species under heat stress. Most eudicots carry a pseudoenzyme PDX1.2 that is a noncatalytic homolog of the PDX1 subunit of the vitamin B6 biosynthesis protein machinery, PYRIDOXINE BIOSYNTHESIS PROTEIN1. Using Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum) as models, we show that PDX1.2 is transcriptionally regulated by the HSFA1 transcription factor family. Monocots only carry catalytic PDX1 homologs that do not respond to heat stress as demonstrated for rice (Oryza sativa) and maize (Zea mays), suggesting fundamental differences in the regulation of vitamin B6 biosynthesis across the two lineages. Investigation of the molecular mechanism of PDX1.2 transcription reveals two alternative transcriptional start sites, one of which is exclusive to heat stress. Further data suggest that PDX1.2 leads to stabilization of the catalytic PDX1s under heat stress conditions, which would serve to maintain vitamin B6 homeostasis in times of need in eudicots that carry this gene. Our analyses indicate an important abiotic stress tolerance strategy in several eudicots, which has not been evolutionarily adapted (or is not required) by monocots such as grasses. PMID:28550206

  3. Enniatin A1, enniatin B1 and beauvericin on HepG2: Evaluation of toxic effects.

    PubMed

    Juan-García, Ana; Ruiz, María-José; Font, Guillermina; Manyes, Lara

    2015-10-01

    Hepatotoxicity of three Fusarium mycotoxins, beauvericin (BEA) and two enniatins (ENNs) ENN A1 and ENN B1, in hepatocarcinoma cells (HepG2) were evaluated and compared. Concentrations used were 1.5 and 3 μM at 24, 48 and 72 h for each mycotoxin. Flow cytometry was used to examine enniatins effects on cell proliferation, to characterize the cell cycle phase where the cells blocked and to study the mitochondria role in ENNs-induced apoptosis. ENN B1 treated cells showed a time dependent G1 blockade at both concentrations used. ENN A1 and BEA decreased the apoptotic-necrotic percentage of cells comparing to control and disrupted the MMP as observed by TMRM and ToPro-3 fluorochromes signal. It is proposed a decreasing mycotoxin order by number of effects as follows: BEA > ENN B1 > ENN A1, with 47, 20 and 16%, respectively out of all situations compared. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. The discovery of 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones as a new class of respiratory syncytial virus (RSV) fusion inhibitors. Part 1.

    PubMed

    Bond, Silas; Draffan, Alistair G; Fenner, Jennifer E; Lambert, John; Lim, Chin Yu; Lin, Bo; Luttick, Angela; Mitchell, Jeffrey P; Morton, Craig J; Nearn, Roland H; Sanford, Vanessa; Stanislawski, Pauline C; Tucker, Simon P

    2015-02-15

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children and adults. Compound 1a (9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-one) was identified as an inhibitor of A and B strains of RSV targeting the fusion glycoprotein. SAR was developed by systematic exploration of the phenyl (R(1)) and benzoyl (R(2)) groups. Furthermore, introduction of a nitrogen at the 8-position of the tricyclic core resulted in active analogues with improved properties (aqueous solubility, protein binding and logD) and excellent rat pharmacokinetics (e.g., rat oral bioavailability of 89% for compound 17). Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. IRE1α links Nck1 deficiency to attenuated PTP1B expression in HepG2 cells.

    PubMed

    Li, Hui; Li, Bing; Larose, Louise

    2017-08-01

    PTP1B, a prototype of the non-receptor subfamily of the protein tyrosine phosphatase superfamily, plays a key role in regulating intracellular signaling from various receptor and non-receptor protein tyrosine kinases. Previously, we reported that silencing Nck1 in human hepatocellular carcinoma HepG2 cells enhances basal and growth factor-induced activation of the PI3K-Akt pathway through attenuating PTP1B expression. However, the underlying mechanism by which Nck1 depletion represses PTP1B expression remains unclear. In this study, we found that silencing Nck1 attenuates PTP1B expression in HepG2 cells through down-regulation of IRE1α. Indeed, we show that silencing Nck1 in HepG2 cells leads to decreased IRE1α expression and signaling. Accordingly, IRE1α depletion using siRNA in HepG2 cells enhances PI3K-dependent basal and growth factor-induced Akt activation, reproducing the effects of silencing Nck1 on activation of this pathway. In addition, depletion of IRE1α also leads to reduced PTP1B expression, which was rescued by ectopic expression of IRE1α in Nck1-depleted cells. Mechanistically, we found that silencing either Nck1 or IRE1α in HepG2 cells decreases PTP1B mRNA levels and stability. However, despite miR-122 levels, a miRNA targeting PTP1B 3' UTR and inducing PTP1B mRNA degradation in HepG2 cells, are increased in both Nck1- and IRE1α-depleted HepG2 cells, a miR-122 antagomir did not rescue PTP1B expression in these cells. Overall, this study highlights an important role for Nck1 in fine-tuning IRE1α expression and signaling that regulate PTP1B expression and subsequent activation of the PI3K-Akt pathway in HepG2 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Identification of UDP-glucuronosyltransferases 1A1, 1A3 and 2B15 as the main contributors to glucuronidation of bakuchiol, a natural biologically active compound.

    PubMed

    Li, Feng; Wang, Shuai; Lu, Danyi; Wang, Yifei; Dong, Dong; Wu, Baojian

    2017-05-01

    1. Bakuchiol, one of the main active compounds of Psoralea corylifolia, possesses a variety of pharmacological activities such as anti-tumor and anti-aging effects. Here, we aimed to characterize the glucuronidation of bakuchiol using human liver microsomes (HLM) and expressed UDP-glucuronosyltransferase (UGT) enzymes. 2. The glucuronide of bakuchiol was confirmed by liquid chromatography-mass spectrometry (LC-MS) and β-glucuronidase hydrolysis assay. Glucuronidation rates and kinetic parameters were derived by enzymatic incubation and model fitting. Activity correlation analyses were performed to identify the main UGT isoforms contributing to hepatic metabolism of bakuchiol. 3. Among the three UGT enzymes (i.e., UGT1A1, UGT1A3 and UGT2B15) capable of catalyzing bakuchiol glucuronidation, UGT2B15 showed the highest activity with a CL int value of 100 μl/min/nmol. Bakuchiol glucuronidation was strongly correlated with glucuronidation of 5-hydroxyrofecoxib (r = 0.933; p < 0.001), 3-O-glucuronidation of β-estradiol (r = 0.719; p < 0.01) and significantly correlated with 24-O-glucuronidation of CDCA (r = 0.594; p < 0.05). In addition, a marked species difference existed in hepatic glucuronidation of bakuchiol. 4. In conclusion, UGT1A1, UGT1A3 and UGT2B15 were identified as the main contributors to glucuronidation of bakuchiol.

  7. Structure of a BMI-1-Ring1B Polycomb Group Ubiquitin Ligase Complex

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li,Z.; Cao, R.; Wang, M.

    2006-01-01

    Polycomb group (PcG) proteins Bmi-1 and Ring1B are core subunits of the PRC1 complex which plays important roles in the regulation of Hox gene expression, X-chromosome inactivation, tumorigenesis and stem cell self-renewal. The RING finger protein Ring1B is an E3 ligase that participates in the ubiquitination of lysine 119 of histone H2A, and the binding of Bmi-1 stimulates the E3 ligase activity. We have mapped the regions of Bmi-1 and Ring1B required for efficient ubiquitin transfer and determined a 2.5 Angstroms structure of the Bmi-1-Ring1B core domain complex. The structure reveals that Ring1B 'hugs' Bmi-1 through extensive RING domain contactsmore » and its N-terminal tail wraps around Bmi-1. The two regions of interaction have a synergistic effect on the E3 ligase activity. Our analyses suggest a model where the Bmi-1-Ring1B complex stabilizes the interaction between the E2 enzyme and the nucleosomal substrate to allow efficient ubiquitin transfer.« less

  8. Metabolism of 1-fluoro-1,1,2-trichloroethane, 1,2-dichloro-1,1-difluoroethane, and 1,1,1-trifluoro-2-chloroethane.

    PubMed

    Yin, H; Jones, J P; Anders, M W

    1995-03-01

    1-Fluoro-1,1,2-trichloroethane (HCFC-131a), 1,2-dichloro-1,1-difluoroethane (HCFC-132b), and 1,1,1-trifluoro-2-chloroethane (HCFC-133a) were chosen as models for comparative metabolism studies on 1,1,1,2-tetrahaloethanes, which are under consideration as replacements for ozone-depleting chlorofluorocarbons (CFCs). Male Fischer 344 rats were given 10 mmol/kg ip HCFC-131a or HCFC-132b or exposed by inhalation to 1% HCFC-133a for 2 h. Urine collected in the first 24 h after exposure was analyzed by 19F NMR and GC/MS and with a fluoride-selective ion electrode for the formation of fluorine-containing metabolites. Metabolites of HCFC-131a included 2,2-dichloro-2-fluoroethyl glucuronide, 2,2-dichloro-2-fluoroethyl sulfate, dichlorofluoroacetic acid, and inorganic fluoride. Metabolites of HCFC-132b were characterized as 2-chloro-2,2-difluoroethyl glucuronide, 2-chloro-2,2-difluoroethyl sulfate, chlorodifluoroacetic acid, chlorodifluoroacetaldehyde hydrate, chlorodifluoroacetaldehyde-urea adduct, and inorganic fluoride. HCFC-133a was metabolized to 2,2,2-trifluoroethyl glucuronide, trifluoroacetic acid, trifluoroacetaldehyde hydrate, trifluoroacetaldehyde-urea adduct, inorganic fluoride, and a minor, unidentified metabolite. With HCFC-131a and HCFC-132b, glucuronide conjugates of 2,2,2-trihaloethanols were the major urinary metabolites, whereas with HCFC-133a, a trifluoroacetaldehyde-urea adduct was the major urinary metabolite. Analysis of metabolite distribution in vivo indicated that aldehydic metabolites increased as fluorine substitution increased in the order HCFC-131a < HCFC-132b < HCFC-133a. With NADPH-fortified rat liver microsomes, HCFC-133a and HCFC-132b were biotransformed to trifluoroacetaldehyde and chlorodifluoroacetaldehyde, respectively, whereas HCFC-131a was converted to dichlorofluoroacetic acid. No covalently bound metabolites were detected by 19F NMR spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Metabolism of 1-Fluro-1,1,2-trichloroethane, 1,2-dichloro-1,1-difluoroethane, and 1,1,1-trifluoro-2-chloroethane

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yin, H.; Jones, J.P.; Anders, M.W.

    1995-03-01

    1-Fluoro-1,1,2-trichloroethane (HCFC-131a), 1,2-dichloro-1,1-difluoroethane (HCFC-132b), and 1,1,1-trifluoro-2-chloroethane (HCFC-133a) were chosen as models for comparative metabolism studies on 1,1,1,2-tetrahaloethanes, which are under consideration as replacements for ozone-depleting chlorofluorocarbons (CFCs). Male Fischer 344 rats were given 10 mmol/kg ip HCFC-131a or HCFC-132b or exposed by inhalation to 1% HCFC-133a for 2 h. Urine collected in the first 24 h after exposure was analyzed by {sup 19}F NMR and GC/MS and with a fluoride-selective ion electrode for the formation of fluorine-containing metabolites. Metabolites of HCFC-131a included 2,2-dichloro-2-fluoroethyl glucuronide, 2,2-dichloro-2-fluorethyl sulfate, dichlorofluoroacetic acid, and inorganic fluoride. Metabolites of HCFC-132b were characterized as 2-chloro-2,2-difluoroethyl glucuronide, 2-chloro-2,2-difluoroethylmore » sulfate, chlorodifluoroacetic acid, chlorodifluoroacetaldehyde hydrate, chlorodifluoroacetaldehyde-urea adduct, inorganic fluoride, and a minor, unidentified metabolite. With HCFC-131a and HCFC-132b, glucuronide conjugates of 2,2,2-trihaloethanols were the major urinary metabolites, whereas with HCFC-133a, a trifluroacetaldehyde-urea adduct was the major urinary metabolite. Analysis of metabolite distribution in vivo indicated that aldehydic metabolites increased as fluorine substitution increased in the order HCFC-131a < HCFC-132b < HCFC-133a. With NADPH-fortified rat liver microsomes, HCFC-133a and HCFC-133a and HCFC-132b were biotransformed to trifluoroacetaldehyde and chlorodifluoroacetaldehyde, respectively, whereas HCFC-131a was converted to dichlorofluoroacetic acid. No covalently bound metabolites of HCFC-131a and HCFC-133a metabolites were detected by {sup 19}F NMR spectroscopy. 18 refs., 2 figs., 3 tabs.« less

  10. Temperature Dependence of O2(b1Σ ^+g, v = 0 and 1) Relative Yield in O(1D) + O2 Energy Transfer

    NASA Astrophysics Data System (ADS)

    Kostko, O.; Raj, S.; Campbell, K.; Pejakovic, D. A.; Kalogerakis, K.

    2011-12-01

    Energy transfer from excited O(1D) atoms to ground-state O2(X3Σ ^-g) leads to production of O2 in the first two vibrational levels of the O2 (b1Σ ^+g) state: O(1D) + O2 -> O(3P) + O2(b1Σ ^+g, v = 0, 1). Subsequent radiative decay of O2(b1Σ ^+g, v = 0, 1) to the ground state results in the Atmospheric Band emission, a prominent feature of the terrestrial airglow. The relative yield for production of O2(b1Σ ^+g, v = 0 and 1) in the above process, k1/k0, is an important parameter in modeling of the observed Atmospheric Band emission intensities. Recent measurements at room temperature have shown that production of O2(b1Σ ^+g, v = 1) dominates that of O2(b1Σ ^+g, v = 0), with k1/k0 having a value of approximately 3.5 [1]. In the laboratory experiments, the output of a pulsed fluorine laser at 157 nm is used to photodissociate molecular oxygen in an O2/N2 mixture flowing through a heated gas cell. Photodissociation of O2 produces a ground-state O(3P) atom and an excited O(1D) atom. O(1D) rapidly transfers energy to the remaining O2 to produce O2(b1Σ ^+g, v = 0, 1). The populations of O2(b1Σ ^+g, v = 0 and 1) are monitored by observing emissions in the O2(b--X) 0--0 and 1--0 bands at 762 and 688 nm, respectively. The value of k1/k0 is extracted from the time-dependent O2(b1Σ ^+g, v = 0 and 1) fluorescence signals using computer simulations. We will present measurements on the temperature dependence of k1/k0 and discuss their atmospheric significance. This work was supported by the US National Science Foundation (NSF) Aeronomy Program under grant AGS-0937317. The fluorine laser was purchased under grant ATM-0216583 from the NSF Major Research Instrumentation Program. S. Raj and K. M. Campbell participated in a Research Experiences for Undergraduates (REU) site, co-funded by the Division of Physics of the NSF and the Department of Defense in partnership with the NSF REU program under grant PHY-1002892. [1] K. S. Kalogerakis, D. A. Pejaković, R. A. Copeland, T. G

  11. Comparison of genetic variations of the SLCO1B1, SLCO1B3, and SLCO2B1 genes among five ethnic groups.

    PubMed

    Namgoong, Suhg; Cheong, Hyun Sub; Kim, Ji On; Kim, Lyoung Hyo; Na, Han Sung; Koh, In Song; Chung, Myeon Woo; Shin, Hyoung Doo

    2015-11-01

    Organic anion-transporting polypeptide (OATP; gene symbol, SLCO) transporters are generally involved in the uptake of multiple drugs and their metabolites at most epithelial barriers. The pattern of single-nucleotide polymorphisms (SNPs) in these transporters may be determinants of interindividual variability in drug disposition and response. The objective of this study was to define the distribution of SNPs of three SLCO genes, SLCO1B1, SLCO1B3, and SLCO2B1, in a Korean population and other ethnic groups. The study was screened using the Illumina GoldenGate assay for genomic DNA from 450 interethnic subjects, including 11 pharmacogenetic core variants and 76 HapMap tagging SNPs. The genotype distribution of the Korean population was similar to East Asian populations, but significantly different from African American and European American cohorts. These interethnic differences will be useful information for prospective studies, including genetic association and pharmacogenetic studies of drug metabolism by SLCO families. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Downregulation of kinin B1 receptor function by B2 receptor heterodimerization and signaling.

    PubMed

    Zhang, Xianming; Brovkovych, Viktor; Zhang, Yongkang; Tan, Fulong; Skidgel, Randal A

    2015-01-01

    Signaling through the G protein-coupled kinin receptors B1 (kB1R) and B2 (kB2R) plays a critical role in inflammatory responses mediated by activation of the kallikrein-kinin system. The kB2R is constitutively expressed and rapidly desensitized in response to agonist whereas kB1R expression is upregulated by inflammatory stimuli and it is resistant to internalization and desensitization. Here we show that the kB1R heterodimerizes with kB2Rs in co-transfected HEK293 cells and natively expressing endothelial cells, resulting in significant internalization and desensitization of the kB1R response in cells pre-treated with kB2R agonist. However, pre-treatment of cells with kB1R agonist did not affect subsequent kB2R responses. Agonists of other G protein-coupled receptors (thrombin, lysophosphatidic acid) had no effect on a subsequent kB1R response. The loss of kB1R response after pretreatment with kB2R agonist was partially reversed with kB2R mutant Y129S, which blocks kB2R signaling without affecting endocytosis, or T342A, which signals like wild type but is not endocytosed. Co-endocytosis of the kB1R with kB2R was dependent on β-arrestin and clathrin-coated pits but not caveolae. The sorting pathway of kB1R and kB2R after endocytosis differed as recycling of kB1R to the cell surface was much slower than that of kB2R. In cytokine-treated human lung microvascular endothelial cells, pre-treatment with kB2R agonist inhibited kB1R-mediated increase in transendothelial electrical resistance (TER) caused by kB1R stimulation (to generate nitric oxide) and blocked the profound drop in TER caused by kB1R activation in the presence of pyrogallol (a superoxide generator). Thus, kB1R function can be downregulated by kB2R co-endocytosis and signaling, suggesting new approaches to control kB1R signaling in pathological conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Downregulation of kinin B1 receptor function by B2 receptor heterodimerization and signaling

    PubMed Central

    Zhang, Xianming; Brovkovych, Viktor; Zhang, Yongkang; Tan, Fulong; Skidgel, Randal A.

    2014-01-01

    Signaling through the G protein-coupled kinin receptors B1 (kB1R) and B2 (kB2R) plays a critical role in inflammatory responses mediated by activation of the kallikrein-kinin system. The kB2R is constitutively expressed and rapidly desensitized in response to agonist whereas kB1R expression is upregulated by inflammatory stimuli and it is resistant to internalization and desensitization. Here we show that the kB1R heterodimerizes with kB2Rs in co-transfected HEK293 cells and natively expressing endothelial cells, resulting in significant internalization and desensitization of the kB1R response in cells pre-treated with kB2R agonist. However, pre-treatment of cells with kB1R agonist did not affect subsequent kB2R responses. Agonists of other G protein-coupled receptors (thrombin, lysophosphatidic acid) had no effect on a subsequent kB1R response. The loss of kB1R response after pretreatment with kB2R agonist was partially reversed with kB2R mutant Y129S, which blocks kB2R signaling without affecting endocytosis, or T342A, which signals like wild type but is not endocytosed. Co-endocytosis of the kB1R with kB2R was dependent on β-arrestin and clathrin-coated pits but not caveolae. The sorting pathway of kB1R and kB2R after endocytosis differed as recycling of kB1R to the cell surface was much slower than that of kB2R. In cytokine-treated human lung microvascular endothelial cells, pre-treatment with kB2R agonist inhibited kB1R-mediated increase in transendothelial electrical resistance (TER) caused by kB1R stimulation (to generate nitric oxide) and blocked the profound drop in TER caused by kB1R activation in the presence of pyrogallol (a superoxide generator). Thus, kB1R function can be downregulated by kB2R co-endocytosis and signaling, suggesting new approaches to control kB1R signaling in pathological conditions. PMID:25289859

  14. Rac1b enhances cell survival through activation of the JNK2/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways

    PubMed Central

    Wang, Hong; Wei, Si-Si; Chen, Jie; Chen, Yi-He; Xu, Wei-Ping; Jie, Qi-Qiang; Zhou, Qing; Li, Yi-Gang; Wei, Yi-Dong; Wang, Yue-Peng

    2016-01-01

    Rac1b is a constitutively activated, alternatively spliced form of the small GTPase Rac1. Previous studies showed that Rac1b promotes cell proliferation and inhibits apoptosis. In the present study, we used microarray analysis to detect genes differentially expressed in HEK293T cells and SW480 human colon cancer cells stably overexpressing Rac1b. We found that the pro-proliferation genes JNK2, c-JUN and cyclin-D1 as well as anti-apoptotic AKT2 and MCL1 were all upregulated in both lines. Rac1b promoted cell proliferation and inhibited apoptosis by activating the JNK2/c-JUN/cyclin-D1 and AKT2/MCL1 pathways, respectively. Very low Rac1b levels were detected in the colonic epithelium of wild-type Sprague-Dawley rats. Knockout of the rat Rac1 gene exon-3b or knockdown of endogenous Rac1b in HT29 human colon cancer cells downregulated only the AKT2/MCL1 pathway. Our study revealed that very low levels of endogenous Rac1b inhibit apoptosis, while Rac1b upregulation both promotes cell proliferation and inhibits apoptosis. It is likely the AKT2/MCL1 pathway is more sensitive to Rac1b regulation. PMID:26918455

  15. Linkage of genes for laminin B1 and B2 subunits on chromosome 1 in mouse.

    PubMed

    Elliott, R W; Barlow, D; Hogan, B L

    1985-08-01

    We have used cDNA clones for the B1 and B2 subunits of laminin to find restriction fragment length DNA polymorphisms for the genes encoding these polypeptides in the mouse. Three alleles were found for LamB2 and two for LamB1 among the inbred mouse strains. The segregation of these polymorphisms among recombinant inbred strains showed that these genes are tightly linked in the central region of mouse Chromosome 1 between Sas-1 and Ly-m22, 7.4 +/- 3.2 cM distal to the Pep-3 locus. There is no evidence in the mouse for pseudogenes for these proteins.

  16. UGT2B17 and SULT1A1 gene copy number variation (CNV) detection by LabChip microfluidic technology.

    PubMed

    Gaedigk, Andrea; Gaedigk, Roger; Leeder, J Steven

    2010-05-01

    Gene copy number variations (CNVs) are increasingly recognized to play important roles in the expression of genes and hence on their respective enzymatic activities. This has been demonstrated for a number of drug metabolizing genes, such as UDP-glucuronosyltransferases 2B17 (UGT2B17) and sulfotransferase 1A1 (SULT1A1), which are subject to genetic heterogeneity, including CNV. Quantitative assays to assess gene copy number are therefore becoming an integral part of accurate genotype assessment and phenotype prediction. In this study, we evaluated a microfluidics-based system, the Bio-Rad Experion system, to determine the power and utility of this platform to detect UGT2B17 and SULT1A1 CNV in DNA samples derived from blood and tissue. UGT2B17 is known to present with 0, 1 or 2 and SULT1A1 with up to 5 gene copies. Distinct clustering (p<0.001) into copy number groups was achieved for both genes. DNA samples derived from blood exhibited less inter-run variability compared to DNA samples obtained from liver tissue. This variability may be caused by tissue-specific PCR inhibitors as it could be overcome by using DNA from another tissue, or after the DNA had undergone whole genome amplification. This method produced results comparable to those reported for other quantitative test platforms.

  17. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

  18. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

  19. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

  20. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

  1. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

  2. Targeting Sulfotransferase (SULT) 2B1b as a regulator of Cholesterol Metabolism in Prostate Cancer

    DTIC Science & Technology

    2016-10-01

    Approved for Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and...and PCa cell lines and that genetic knock down suppresses LNCaP growth and diminishes androgen receptor ( AR ) activity. It is hypothesized that SULT2B1b...knock down suppresses LNCaP growth and diminishes androgen receptor ( AR ) activity. It is hypothesized that SULT2B1b modulates PCa growth and

  3. Canine susceptibility to human influenza viruses (A/pdm 09H1N1, A/H3N2 and B).

    PubMed

    Song, Daesub; Kim, Hyekwon; Na, Woonsung; Hong, Minki; Park, Seong-Jun; Moon, Hyoungjoon; Kang, Bokyu; Lyoo, Kwang-Soo; Yeom, Minjoo; Jeong, Dae Gwin; An, Dong-Jun; Kim, Jeong-Ki

    2015-02-01

    We investigated the infectivity and transmissibility of the human seasonal H3N2, pandemic (pdm) H1N1 (2009) and B influenza viruses in dogs. Dogs inoculated with human seasonal H3N2 and pdm H1N1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza B virus-inoculated dogs. Transmission of human H3N2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dogs. The seroprevalence study offered evidence of human H3N2 infection occurring in dogs since 2008. Furthermore, serological evidence of pdm H1N1 influenza virus infection alone and in combination with canine H3N2 virus was found in the serum samples collected from field dogs during 2010 and 2011. Our results suggest that dogs may be hosts for human seasonal H3N2 and pdm H1N1 influenza viruses. © 2015 The Authors.

  4. Compendium of Shock Wave Data. Volume 2, Revision 1. Section A2. Inorganic Compounds Section B. Hydrocarbons

    DTIC Science & Technology

    1977-06-01

    5K9AR uret 14’T17 TABLE I TUNGSTEN CARBIDE 53-23--- 1 B i 5 4fL 3 2 0 int IU aF n PAGE 4011.1 ś-1---I RUtILFr. CRYSTAL AND NATURAL (TIIANIUM OXIDCl...COtMIENTS : I I SOURCE: KOIR1ER. 5. B .. SINITSYN. M, V., ruNIIKOV. A, I., UR1. IN. V, a. AND BLINOV . A. V. SOVIET PHYS-.JIEP. VOL. 20. P. 911 119651...AO Uii Coaapendiux of* ýIoek Wave Daa.3otion A2. Inorganuic Compounds. Oection B , "r~iooarbona. ______________ I. Ca"TRACT 09GOAMY wmuimea Lawrt

  5. Vasopressor meets vasodepressor: The AT1-B2 receptor heterodimer.

    PubMed

    Quitterer, Ursula; AbdAlla, Said

    2014-04-01

    The AT1 receptor for the vasopressor angiotensin II is one of the most important drug targets for the treatment of cardiovascular diseases. Sensitization of the AT1 receptor system is a common feature contributing to the pathogenesis of many cardiovascular disorders but underlying mechanisms are not fully understood. More than a decade ago, evidence was provided for control of AT1R activation by heterodimerization with the B2 receptor for the vasodepressor peptide, bradykinin, a physiological counterpart of the vasoconstrictor angiotensin II. AT1-B2 receptor heterodimerization was shown to enhance AT1R-stimulated signaling under pathophysiological conditions such as experimental and human pregnancy hypertension. Notably, AT1R signal sensitization of patients with preeclampsia hypertension was attributed to AT1R-B2R heterodimerization. Vice versa, transgenic mice lacking the AT1-B2 receptor heterodimer due to targeted deletion of the B2R gene showed a significantly reduced AT1R-stimulated vasopressor response compared to transgenic mice with abundant AT1R-B2R heterodimerization. Biophysical methods such as BRET and FRET confirmed those data by demonstrating efficient AT1-B2 receptor heterodimerization in transfected cells and transgenic mice. Recently, a study on AT1R-specific biased agonism directed the focus to the AT1-B2 receptor heterodimer again. The β-arrestin-biased [Sar1,Ile4,Ile8]-angiotensin II promoted not only the recruitment of β-arrestin to the AT1R but also stimulated the down-regulation of the AT1R-associated B2 receptor by co-internalization. Thereby specific targeting of the AT1R-B2R heterodimer became feasible and could open the way to a new class of drugs, which specifically interfere with pathological angiotensin II-AT1 receptor system activation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Human aldo-keto reductases 1B1 and 1B10: a comparative study on their enzyme activity toward electrophilic carbonyl compounds.

    PubMed

    Shen, Yi; Zhong, Linlin; Johnson, Stephen; Cao, Deliang

    2011-05-30

    Aldo-keto reductase family 1 member B1 (AKR1B1, 1B1 in brief) and aldo-keto reductase family 1 member B10 (AKR1B10, 1B10 in brief) are two proteins with high similarities in their amino acid sequences, stereo structures, and substrate specificity. However, these two proteins exhibit distinct tissue distributions; 1B10 is primarily expressed in the gastrointestinal tract and adrenal gland, whereas 1B1 is ubiquitously present in all tissues/organs, suggesting their difference in biological functions. This study evaluated in parallel the enzyme activity of 1B1 and 1B10 toward alpha, beta-unsaturated carbonyl compounds with cellular and dietary origins, including acrolein, crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, and trans-2,4-hexadienal. Our results showed that 1B10 had much better enzyme activity and turnover rates toward these chemicals than 1B1. By detecting the enzymatic products using high-performance liquid chromatography, we measured their activity to carbonyl compounds at low concentrations. Our data showed that 1B10 efficiently reduced the tested carbonyl compounds at physiological levels, but 1B1 was less effective. Ectopically expressed 1B10 in 293T cells effectively eliminated 4-hydroxynonenal at 5 μM by reducing to 1,4-dihydroxynonene, whereas endogenously expressed 1B1 did not. The 1B1 and 1B10 both showed enzyme activity to glutathione-conjugated carbonyl compounds, but 1B1 appeared more active in general. Together our data suggests that 1B10 is more effectual in eliminating free electrophilic carbonyl compounds, but 1B1 seems more important in the further detoxification of glutathione-conjugated carbonyl compounds. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. The 2√{3}×2√{3}R30 surface reconstruction of alkali/Si(1 1 1):B semiconducting surfaces

    NASA Astrophysics Data System (ADS)

    Tournier-Colletta, C.; Chaput, L.; Tejeda, A.; Cardenas, L. A.; Kierren, B.; Malterre, D.; Fagot-Revurat, Y.; Fèvre, P. Le; Bertran, F.; Taleb-Ibrahimi, A.

    2013-02-01

    The surface structure of alkali doped Si(1 1 1):B ultra-thin films has been studied by low-energy electron diffraction (LEED), X-ray photoemission spectroscopy (XPS) and scanning tunneling microscopy (STM). A comparative study of K/Si(1 1 1)-3 × 1 and K/Si(1 1 1):B-2√{3}×2√{3}R30 interfaces allowed us to determine the saturation coverage to be 0.5 monolayer in the later case. The 2√{3}-surface reconstruction is shown to be a common property of pure K, Rb, Cs materials and K0.4Rb0.6 alloys but progressively disappears if Rb is replaced by Ca. Taking into account the existence of two distinct boron sites in the ratio 1/3 as seen from B-1s core levels spectra, LAPW-DFT calculations have been carried out in order to optimize the atomic structure. As a result, alkali adatoms are shown to form trimers leading to a large modulation of the Sisbnd B bonds accompanied by an inhomogeneous doping of the dangling bonds in agreement with voltage dependent STM images.

  8. Neuroradiological findings in GM2 gangliosidosis variant B1.

    PubMed

    Bano, Shahina; Prasad, Akhila; Yadav, Sachchida Nand; Chaudhary, Vikas; Garga, Umesh Chandra

    2011-07-01

    GM2 gangliosidosis variant B1 is a very rare lysosomal disorder. As per our knowledge, to date, only one article depicting the magnetic resonance imaging (MRI) findings of GM2 gangliosidosis variant B1 is available in the literature. We are the first to describe the neuroradiological findings in an Indian patient diagnosed with GM2 gangliosidosis variant B1.

  9. Binding of Diverse Environmental Chemicals with Human Cytochromes P450 2A13, 2A6, and 1B1 and Enzyme Inhibition

    PubMed Central

    Shimada, Tsutomu; Kim, Donghak; Murayama, Norie; Tanaka, Katsuhiro; Takenaka, Shigeo; Nagy, Leslie D.; Folkman, Lindsay M.; Foroozesh, Maryam K.; Komori, Masayuki; Yamazaki, Hiroshi; Guengerich, F. Peter

    2014-01-01

    A total of 68 chemicals including derivatives of naphthalene, phenanthrene, fluoranthene, pyrene, biphenyl, and flavone were examined for their abilities to interact with human P450s 2A13 and 2A6. Fifty-one of these 68 chemicals induced stronger Type I binding spectra (iron low- to high-spin state shift) with P450 2A13 than those seen with P450 2A6, i.e. the spectral binding intensities (ΔAmax/Ks ratio) determined with these chemicals were always higher for P450 2A13. In addition, benzo[c]phenanthrene, fluoranthene, 2,3-dihydroxy-2,3-dihydrofluoranthene, pyrene, 1-hydroxypyrene, 1-nitropyrene, 1-acetylpyrene, 2-acetylpyrene, 2,5,2’,5’-tetrachlorobiphenyl, 7-hydroxyflavone, chrysin, and galangin were found to induce a Type I spectral change only with P450 2A13. Coumarin 7-hydroxylation, catalyzed by P450 2A13, was strongly inhibited by 2’-methoxy-5,7-dihydroxyflavone, 2-ethynylnaphthalene, 2’-methoxyflavone, 2-naphththalene propargyl ether, acenaphthene, acenaphthylene, naphthalene, 1-acetylpyrene, flavanone, chrysin, 3-ethynylphenanthrene, flavone, and 7-hydroxyflavone; these chemicals induced Type I spectral changes with low Ks values. On the basis of the intensities of the spectral changes and inhibition of P450 2A13, we classified the 68 chemicals into eight groups based on the order of affinities for these chemicals and inhibition of P450 2A13. The metabolism of chemicals by P450 2A13 during the assays explained why some of the chemicals that bound well were poor inhibitors of P450 2A13. Finally, we compared the 68 chemicals for their abilities to induce Type I spectral changes of P450 2A13 with the Reverse Type I binding spectra observed with P450 1B1: 45 chemicals interacted with both P450s 2A13 and 1B1, indicating that the two enzymes have some similarty of structural features regarding these chemicals. Molecular docking analyses suggest similarities at the active sites of these P450 enzymes. These results indicate that P450 2A13, as well as Family

  10. Preparation of dimeric procyanidins B1, B2, B5, and B7 from a polymeric procyanidin fraction of black chokeberry ( Aronia melanocarpa ).

    PubMed

    Esatbeyoglu, Tuba; Winterhalter, Peter

    2010-04-28

    A semisynthetic approach has been used for the preparative formation of dimeric procyanidins B1, B2, B5, and B7. As starting material for the semisynthesis, polymeric procyanidins from black chokeberry were applied. These polymers were found to consist almost exclusively of (-)-epicatechin units. Under acidic conditions the interflavanoid linkages of the polymeric procyanidins are cleaved and the liberated (-)-epicatechin can react with nucleophiles, such as (+)-catechin or (-)-epicatechin. In this way, the polymeric procyanidins are degraded while dimeric procyanidins are formed. During this reaction only dimeric procyanidins are formed that contain (-)-epicatechin in the upper unit, that is, B1 [(-)-EC-4beta-->8-(+)-C)], B2 [(-)-EC-4beta-->8-(-)-EC], B5 [(-)-EC-4beta-->6-(-)-EC], and B7 [(-)-EC-4beta-->6-(+)-C]. The reaction mixtures of the semisynthesis can be successfully fractionated with high-speed countercurrent chromatography (HSCCC), and it is possible to isolate pure procyanidins B1, B2, B5, and B7 on a preparative scale.

  11. Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

    NASA Technical Reports Server (NTRS)

    Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

    1995-01-01

    A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

  12. Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a.

    PubMed

    Pennings, Ronald J E; Huygen, Patrick L M; Orten, Dana J; Wagenaar, Mariette; van Aarem, Annelies; Kremer, Hannie; Kimberling, William J; Cremers, Cor W R J; Deutman, August F

    2004-04-01

    To evaluate visual impairment in Usher syndrome 1b (USH1b) and Usher syndrome 2a (USH2a). We carried out a retrospective study of 19 USH1b patients and 40 USH2a patients. Cross-sectional regression analyses of the functional acuity score (FAS), functional field score (FFS) and functional vision score (FVS) related to age were performed. Statistical tests relating to regression lines and Student's t-test were used to compare between (sub)groups of patients. Parts of the available individual longitudinal data were used to obtain individual estimates of progressive deterioration and compare these to those obtained with cross-sectional analysis. Results were compared between subgroups of USH2a patients pertaining to combinations of different types of mutations. Cross-sectional analyses revealed significant deterioration of the FAS (0.7% per year), FFS (1.0% per year) and FVS (1.5% per year) with advancing age in both patient groups, without a significant difference between the USH1b and USH2a patients. Individual estimates of the deterioration rates were substantially and significantly higher than the cross-sectional estimates in some USH2a cases, including values of about 5% per year (or even higher) for the FAS (age 35-50 years), 3-4% per year for the FFS and 4-5% per year for the FVS (age > 20 years). There was no difference in functional vision score behaviour detected between subgroups of patients pertaining to different biallelic combinations of specific types of mutations. The FAS, FFS and FVS deteriorated significantly by 0.7-1.5% per year according to cross-sectional linear regression analysis in both USH1b and USH2a patients. Higher deterioration rates (3-5% per year) in any of these scores were attained, according to longitudinal data collected from individual USH2a patients. Score behaviour was similar across the patient groups and across different biallelic combinations of various types of mutations. However, more elaborate studies, preferably covering

  13. The effects of clobazam treatment in rats on the expression of genes and proteins encoding glucronosyltransferase 1A/2B (UGT1A/2B) and multidrug resistance‐associated protein-2 (MRP2), and development of thyroid follicular cell hypertrophy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miyawaki, Izuru, E-mail: izuru-miyawaki@ds-pharma.co.jp; Tamura, Akitoshi; Matsumoto, Izumi

    Clobazam (CLB) is known to increase hepatobiliary thyroxine (T4) clearance in Sprague–Dawley (SD) rats, which results in hypothyroidism followed by thyroid follicular cell hypertrophy. However, the mechanism of the acceleration of T4-clearance has not been fully investigated. In the present study, we tried to clarify the roles of hepatic UDP-glucronosyltransferase (UGT) isoenzymes (UGT1A and UGT2B) and efflux transporter (multidrug resistance–associated protein-2; MRP2) in the CLB-induced acceleration of T4-clearance using two mutant rat strains, UGT1A-deficient mutant (Gunn) and MRP2-deficient mutant (EHBR) rats, especially focusing on thyroid morphology, levels of circulating hormones (T4 and triiodothyronine (T3)) and thyroid-stimulating hormone (TSH), and mRNAmore » or protein expressions of UGTs (Ugt1a1, Ugt1a6, and Ugt2b1/2) and MRP2 (Mrp). CLB induced thyroid morphological changes with increases in TSH in SD and Gunn rats, but not in EHBR rats. T4 was slightly decreased in SD and Gunn rats, and T3 was decreased in Gunn rats, whereas these hormones were maintained in EHBR rats. Hepatic Ugt1a1, Ugt1a6, Ugt2b1/2, and Mrp2 mRNAs were upregulated in SD rats. In Gunn rats, UGT1A mRNAs (Ugt1a1/6) and protein levels were quite low, but UGT2B mRNAs (Ugt2b1/2) and protein were prominently upregulated. In SD and Gunn rats, MRP2 mRNA and protein were upregulated to the same degree. These results suggest that MRP2 is an important contributor in development of the thyroid cellular hypertrophy in CLB-treated rats, and that UGT1A and UGT2B work in concert with MRP2 in the presence of MRP2 function to enable the effective elimination of thyroid hormones. -- Highlights: ► Role of UGT and MRP2 in thyroid pathology was investigated in clobazam-treated rats. ► Clobazam induced thyroid cellular hypertrophy in SD and Gunn rats, but not EHBR rats. ► Hepatic Mrp2 gene and protein were upregulated in SD and Gunn rats, but not EHBR rats. ► Neither serum thyroid hormones

  14. Hadronic decays of Ba1(1260 )b1(1235 ) in the perturbative QCD approach

    NASA Astrophysics Data System (ADS)

    Jing, Hao-Yang; Liu, Xin; Xiao, Zhen-Jun

    2017-12-01

    We calculate the branching ratios and polarization fractions of the Ba1b1 decays in the perturbative QCD(pQCD) approach at leading order, where a1(b1) stands for the axial-vector a1(1260 )[b1(1235 )] state. By combining the phenomenological analyses with the perturbative calculations, we find the following results: (a) the large decay rates around 10-5 to 10-6 of the Ba1b1 decays dominated by the longitudinal polarization(except for the B+→b1+a10 mode) are predicted and basically consistent with those in the QCD factorization(QCDF) within errors, which are expected to be tested by the Large Hadron Collider and Belle-II experiments. The large B0→a10b10 branching ratio could provide hints to help explore the mechanism of the color-suppressed decays. (b) the rather different QCD behaviors between the a1 and b1 mesons result in the destructive(constructive) contributions in the nonfactorizable spectator diagrams with a1(b1) emission. Therefore, an interesting pattern of the branching ratios appears for the color-suppressed B0→a10a10,a10b10, and b10b10 modes in the pQCD approach, BR (B0→b10b10)>BR (B0→a10b10)≳BR (B0→a10a10), which is different from BR (B0→b10b10)˜BR (B0→a10b10)≳BR (B0→a10a10) in the QCDF and would be verified at future experiments. (c) the large naive factorization breaking effects are observed in these Ba1b1 decays. Specifically, the large nonfactorizable spectator(weak annihilation) amplitudes contribute to the B0→b1+a1-(B+→a1+b10andB+→b1+a10) mode(s), which demand confirmations via the precise measurements. Furthermore, the different phenomenologies shown among Ba1b1, Ba1a1, and Bb1b1 decays are also expected to be tested stringently, which could shed light on the typical QCD dynamics involved in these modes, even further distinguish those two popular pQCD and QCDF approaches.

  15. Differential effects of human SP-A1 and SP-A2 variants on phospholipid monolayers containing surfactant protein B

    PubMed Central

    Wang, Guirong; Taneva, Svetla; Keough, Kevin M.W.; Floros, Joanna

    2010-01-01

    Summary Surfactant protein A (SP-A), the most abundant protein in the lung alveolar surface, has multiple activities, including surfactant-related functions. SP-A is required for the formation of tubular myelin and the lung surface film. The human SP-A locus consists of two functional SP-A genes, SP-A1 and SP-A2, with a number of alleles characterized for each gene. We have found that the human in vitro expressed variants, SP-A1 (6A2) and SP-A2 (1A0), and the coexpressed SP-A1/SP-A2 (6A2/1A0) protein have a differential influence on the organization of phospholipid monolayers containing surfactant protein B (SP-B). Lipid films containing SP-B and SP-A2 (1A0) showed surface features similar to those observed in lipid films with SP-B and native human SP-A. Fluorescence images revealed the presence of characteristic fluorescent probe-excluding clusters coexisting with the traditional lipid liquid-expanded and liquid-condensed phase. Images of the films containing SP-B and SP-A1 (6A2) showed different distribution of the proteins. The morphology of lipid films containing SP-B and the coexpressed SP-A1/SP-A2 (6A2/1A0) combined features of the individual films containing the SP-A1 or SP-A2 variant. The results indicate that human SP-A1 and SP-A2 variants exhibit differential effects on characteristics of phospholipid monolayers containing SP-B. This may differentially impact surface film activity. PMID:17678872

  16. Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch Between Cortical and Striatal Interneurons

    PubMed Central

    McKinsey, Gabriel L.; Lindtner, Susan; Trzcinski, Brett; Visel, Axel; Pennacchio, Len A.; Huylebroeck, Danny; Higashi, Yujiro; Rubenstein, John L. R.

    2013-01-01

    Summary Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform towards a subtype of GABAeric striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome). PMID:23312518

  17. 2,7-Diphenyl[1]benzothieno[3,2-b]benzothiophene, a new organic semiconductor for air-stable organic field-effect transistors with mobilities up to 2.0 cm2 V(-1) s(-1).

    PubMed

    Takimiya, Kazuo; Ebata, Hideaki; Sakamoto, Katsuhiro; Izawa, Takafumi; Otsubo, Tetsuo; Kunugi, Yoshihito

    2006-10-04

    Vapor-deposited thin films of a newly developed sulfur-containing heteroarene, 2,7-diphenyl[1]benzothieno[3,2-b][1]benzothiophene (DPh-BTBT), were used as an active layer of OFETs, which showed excellent FET characteristics in ambient conditions with mobilities of approximately 2.0 cm2 V-1 s-1 and Ion/Ioff of 107.

  18. The Arrestin-selective Angiotensin AT1 Receptor Agonist [Sar1,Ile4,Ile8]-AngII Negatively Regulates Bradykinin B2 Receptor Signaling via AT1-B2 Receptor Heterodimers*

    PubMed Central

    Wilson, Parker C.; Lee, Mi-Hye; Appleton, Kathryn M.; El-Shewy, Hesham M.; Morinelli, Thomas A.; Peterson, Yuri K.; Luttrell, Louis M.; Jaffa, Ayad A.

    2013-01-01

    The renin-angiotensin and kallikrein-kinin systems are key regulators of vascular tone and inflammation. Angiotensin II, the principal effector of the renin-angiotensin system, promotes vasoconstriction by activating angiotensin AT1 receptors. The opposing effects of the kallikrein-kinin system are mediated by bradykinin acting on B1 and B2 bradykinin receptors. The renin-angiotensin and kallikrein-kinin systems engage in cross-talk at multiple levels, including the formation of AT1-B2 receptor heterodimers. In primary vascular smooth muscle cells, we find that the arrestin pathway-selective AT1 agonist, [Sar1,Ile4,Ile8]-AngII, but not the neutral AT1 antagonist, losartan, inhibits endogenous B2 receptor signaling. In a transfected HEK293 cell model that recapitulates this effect, we find that the actions of [Sar1,Ile4, Ile8]-AngII require the AT1 receptor and result from arrestin-dependent co-internalization of AT1-B2 heterodimers. BRET50 measurements indicate that AT1 and B2 receptors efficiently heterodimerize. In cells expressing both receptors, pretreatment with [Sar1,Ile4,Ile8]-AngII blunts B2 receptor activation of Gq/11-dependent intracellular calcium influx and Gi/o-dependent inhibition of adenylyl cyclase. In contrast, [Sar1,Ile4,Ile8]-AngII has no effect on B2 receptor ligand affinity or bradykinin-induced arrestin3 recruitment. Both radioligand binding assays and quantitative microscopy-based analysis demonstrate that [Sar1,Ile4,Ile8]-AngII promotes internalization of AT1-B2 heterodimers. Thus, [Sar1,Ile4,Ile8]-AngII exerts lateral allosteric modulation of B2 receptor signaling by binding to the orthosteric ligand binding site of the AT1 receptor and promoting co-sequestration of AT1-B2 heterodimers. Given the opposing roles of the renin-angiotensin and kallikrein-kinin systems in vivo, the distinct properties of arrestin pathway-selective and neutral AT1 receptor ligands may translate into different pharmacologic actions. PMID:23661707

  19. The arrestin-selective angiotensin AT1 receptor agonist [Sar1,Ile4,Ile8]-AngII negatively regulates bradykinin B2 receptor signaling via AT1-B2 receptor heterodimers.

    PubMed

    Wilson, Parker C; Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Morinelli, Thomas A; Peterson, Yuri K; Luttrell, Louis M; Jaffa, Ayad A

    2013-06-28

    The renin-angiotensin and kallikrein-kinin systems are key regulators of vascular tone and inflammation. Angiotensin II, the principal effector of the renin-angiotensin system, promotes vasoconstriction by activating angiotensin AT1 receptors. The opposing effects of the kallikrein-kinin system are mediated by bradykinin acting on B1 and B2 bradykinin receptors. The renin-angiotensin and kallikrein-kinin systems engage in cross-talk at multiple levels, including the formation of AT1-B2 receptor heterodimers. In primary vascular smooth muscle cells, we find that the arrestin pathway-selective AT1 agonist, [Sar(1),Ile(4),Ile(8)]-AngII, but not the neutral AT1 antagonist, losartan, inhibits endogenous B2 receptor signaling. In a transfected HEK293 cell model that recapitulates this effect, we find that the actions of [Sar(1),Ile(4), Ile(8)]-AngII require the AT1 receptor and result from arrestin-dependent co-internalization of AT1-B2 heterodimers. BRET50 measurements indicate that AT1 and B2 receptors efficiently heterodimerize. In cells expressing both receptors, pretreatment with [Sar(1),Ile(4),Ile(8)]-AngII blunts B2 receptor activation of Gq/11-dependent intracellular calcium influx and Gi/o-dependent inhibition of adenylyl cyclase. In contrast, [Sar(1),Ile(4),Ile(8)]-AngII has no effect on B2 receptor ligand affinity or bradykinin-induced arrestin3 recruitment. Both radioligand binding assays and quantitative microscopy-based analysis demonstrate that [Sar(1),Ile(4),Ile(8)]-AngII promotes internalization of AT1-B2 heterodimers. Thus, [Sar(1),Ile(4),Ile(8)]-AngII exerts lateral allosteric modulation of B2 receptor signaling by binding to the orthosteric ligand binding site of the AT1 receptor and promoting co-sequestration of AT1-B2 heterodimers. Given the opposing roles of the renin-angiotensin and kallikrein-kinin systems in vivo, the distinct properties of arrestin pathway-selective and neutral AT1 receptor ligands may translate into different pharmacologic

  20. [Differences in oligomerization of nucleocapsid protein of epidemic human influenza A(H1N1), A(H1N2) and B viruses].

    PubMed

    Prokudina, E N; Semenova, N P; Chumakov, V M; Burtseva, E I; Slepushkin, A N

    2003-01-01

    A comparative analysis of involving the nucleocapsid protein (NP) into shaping-up of SDS-resistant oligomers was carried out presently in circulating epidemic strains of human influenza, viruses A and B. The study results of viral isolates obtained from clinical samples and recent standard strains revealed that the involvement of NP in the SDS-resistant oligomers, which are different in various subtypes of influenza A viruses. According to this sign, the human viruses A(9H3N2) are close to the avian ones, in which, as proved by us previously, virtually the entire NP transforms itself into the oligomers resistant to SDS. About 10-20% of NP are involved in shaping-up the virus influenza A(H1N1) of SDS-resistant oligomers. No SDS-resistant NP-oligomers were detected in influenza of type B. It is suggested that the prevalence of human viruses A(H3N2) in NP-oligomers are the peculiarities of NP structure and of the presence of the PB1 protein from avian influenza virus.

  1. Coxiella burnetii Avirulent Nine Mile Phase II Induces Caspase-1-Dependent Pyroptosis in Murine Peritoneal B1a B Cells.

    PubMed

    Schoenlaub, Laura; Cherla, Rama; Zhang, Yan; Zhang, Guoquan

    2016-12-01

    Our recent study demonstrated that virulent Coxiella burnetii Nine Mile phase I (NMI) is capable of infecting and replicating within peritoneal B1a cells and that B1a cells play an important role in host defense against C. burnetii infection in mice. However, it remains unknown if avirulent Nine Mile phase II (NMII) can infect and replicate in B1a cells and whether NMI and NMII can differentially interact with B1a cells. In this study, we examined if NMI and NMII can differentially modulate host cell apoptotic signaling in B1a cells. The results showed that NMII induced dose-dependent cell death in murine peritoneal B1a cells but NMI did not, suggesting that NMI and NMII may differentially activate host cell apoptotic signaling in B1a cells. Western blotting indicated that NMII-induced B1a cell death was not dependent on either caspase-3 or PARP-1 cleavage, but cleavage of caspase-1 was detected in NMII-infected B1a cells. In addition, inhibition or deficiency of caspase-1 activity blocked NMII-induced B1a cell death. These results suggest that NMII induces a caspase-1-dependent pyroptosis in murine peritoneal B1a cells. We also found that heat-killed NMII and type 4 secretion system (T4SS) mutant NMII were unable to induce B1a cell death and that NMII infection did not induce cell death in peritoneal B1a cells from Toll-like receptor 2 (TLR-2)- or NLRP3 inflammasome-deficient mice. These data suggest that NMII-induced caspase-1-dependent pyroptosis may require its T4SS and activation of the TLR-2 and NLRP3 signaling pathways. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Organic semiconductors based on [1]benzothieno[3,2-b][1]benzothiophene substructure.

    PubMed

    Takimiya, Kazuo; Osaka, Itaru; Mori, Takamichi; Nakano, Masahiro

    2014-05-20

    The design, synthesis, and characterization of organic semiconductors applicable to organic electronic devices, such as organic field-effect transistors (OFETs) and organic photovoltaics (OPVs), had been one of the most important topics in materials chemistry in the past decade. Among the vast number of materials developed, much expectation had been placed on thienoacenes, which are rigid and planar structures formed by fusing thiophenes and other aromatic rings, as a promising candidate for organic semiconductors for high-performance OFETs. However, the thienoacenes examined as an active material in OFETs in the 1990s afforded OFETs with only moderate hole mobilities (approximately 0.1 cm(2) V(-1) s(-1)). We speculated that this was due to the sulfur atoms in the thienoacenes, which hardly contributed to the intermolecular orbital overlap in the solid state. On the other hand, we have focused on other types of thienoacenes, such as [1]benzothieno[3,2-b][1]benzothiophene (BTBT), which seem to have appropriate HOMO spatial distribution for effective intermolecular orbital overlap. In fact, BTBT derivatives and their related materials, including dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT), have turned out to be superior organic semiconductors, affording OFETs with very high mobilities. To illustrate some examples, we have developed 2,7-diphenyl BTBT (DPh-BTBT) that yields vapor-deposited OFETs having mobilities of up to 2.0 cm(2) V(-1) s(-1) under ambient conditions, highly soluble dialkyl-BTBTs (Cn-BTBTs) that afford solution-processed OFETs with mobilities higher than 1.0 cm(2) V(-1) s(-1), and DNTT and its derivatives that yield OFETs with even higher mobilities (>3.0 cm(2) V(-1) s(-1)) and stability under ambient conditions. Such high performances are rationalized by their solid-state electronic structures that are calculated based on their packing structures: the large intermolecular orbital overlap and the isotropic two-dimensional electronic

  3. Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer.

    PubMed

    Dowling, Paul; Pollard, Damian; Larkin, AnneMarie; Henry, Michael; Meleady, Paula; Gately, Kathy; O'Byrne, Kenneth; Barr, Martin P; Lynch, Vincent; Ballot, Jo; Crown, John; Moriarty, Michael; O'Brien, Emmet; Morgan, Ross; Clynes, Martin

    2015-03-01

    Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.

  4. ARID1B is a specific vulnerability in ARID1A-mutant cancers

    PubMed Central

    Helming, Katherine C.; Wang, Xiaofeng; Wilson, Boris G.; Vazquez, Francisca; Haswell, Jeffrey R.; Manchester, Haley E.; Kim, Youngha; Kryukov, Gregory V.; Ghandi, Mahmoud; Aguirre, Andrew J.; Jagani, Zainab; Wang, Zhong; Garraway, Levi A.; Hahn, William C.; Roberts, Charles W. M.

    2014-01-01

    Summary Recent studies have revealed that ARID1A is frequently mutated across a wide variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, a related but mutually exclusive homolog of ARID1A in the SWI/SNF chromatin remodeling complex, as the number one gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation. Intriguingly, we also find that ARID1A and ARID1B are frequently co-mutated in cancer, but that ARID1A-deficient cancers retain at least one ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers. PMID:24562383

  5. ARID1B is a specific vulnerability in ARID1A-mutant cancers.

    PubMed

    Helming, Katherine C; Wang, Xiaofeng; Wilson, Boris G; Vazquez, Francisca; Haswell, Jeffrey R; Manchester, Haley E; Kim, Youngha; Kryukov, Gregory V; Ghandi, Mahmoud; Aguirre, Andrew J; Jagani, Zainab; Wang, Zhong; Garraway, Levi A; Hahn, William C; Roberts, Charles W M

    2014-03-01

    Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A (SWI-like), is frequently mutated across a variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF complexes, as the number 1 gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated in cancer but that ARID1A-deficient cancers retain at least one functional ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers.

  6. Aldo-keto Reductase 1B15 (AKR1B15)

    PubMed Central

    Weber, Susanne; Salabei, Joshua K.; Möller, Gabriele; Kremmer, Elisabeth; Bhatnagar, Aruni; Adamski, Jerzy; Barski, Oleg A.

    2015-01-01

    Aldo-keto reductases (AKRs) comprise a superfamily of proteins involved in the reduction and oxidation of biogenic and xenobiotic carbonyls. In humans, at least 15 AKR superfamily members have been identified so far. One of these is a newly identified gene locus, AKR1B15, which clusters on chromosome 7 with the other human AKR1B subfamily members (i.e. AKR1B1 and AKR1B10). We show that alternative splicing of the AKR1B15 gene transcript gives rise to two protein isoforms with different N termini: AKR1B15.1 is a 316-amino acid protein with 91% amino acid identity to AKR1B10; AKR1B15.2 has a prolonged N terminus and consists of 344 amino acid residues. The two gene products differ in their expression level, subcellular localization, and activity. In contrast with other AKR enzymes, which are mostly cytosolic, AKR1B15.1 co-localizes with the mitochondria. Kinetic studies show that AKR1B15.1 is predominantly a reductive enzyme that catalyzes the reduction of androgens and estrogens with high positional selectivity (17β-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoA conjugates and exhibits strong cofactor selectivity toward NADP(H). In accordance with its substrate spectrum, the enzyme is expressed at the highest levels in steroid-sensitive tissues, namely placenta, testis, and adipose tissue. Placental and adipose expression could be reproduced in the BeWo and SGBS cell lines, respectively. In contrast, AKR1B15.2 localizes to the cytosol and displays no enzymatic activity with the substrates tested. Collectively, these results demonstrate the existence of a novel catalytically active AKR, which is associated with mitochondria and expressed mainly in steroid-sensitive tissues. PMID:25577493

  7. Cloning and functional analysis of P2X1b, a new variant in rat optic nerve that regulates the P2X1 receptor in a use-dependent manner.

    PubMed

    Rangel-Yescas, Gisela E; Vazquez-Cuevas, Francisco G; Garay, Edith; Arellano, Rogelio O

    2012-01-01

    P2X receptors are trimeric, ATP-gated cation channels. In mammals seven P2X subtypes have been reported (P2X1-P2X7), as well as several variants generated by alternative splicing. Variants confer to the homomeric or heteromeric channels distinct functional and/or pharmacological properties. Molecular biology, biochemical, and functional analysis by electrophysiological methods were used to identify and study a new variant of the P2X1 receptor named P2X1b. This new variant, identified in rat optic nerve, was also expressed in other tissues. P2X1b receptors lack amino acids 182 to 208 of native P2X1, a region that includes residues that are highly conserved among distinct P2X receptors. When expressed in Xenopus oocytes, P2X1b was not functional as a homomer; however, when co-expressed with P2X1, it downregulated the electrical response generated by ATP compared with that of oocytes expressing P2X1 alone, and it seemed to form heteromeric channels with a modestly enhanced ATP potency. A decrease in responses to ATP in oocytes co-expressing different ratios of P2X1b to P2X1 was completely eliminated by overnight pretreatment with apyrase. Thus, it is suggested that P2X1b regulates, through a use-dependent mechanism, the availability, in the plasma membrane, of receptor channels that can be operated by ATP.

  8. Optimization of chromatographic conditions for determination of aflatoxin B1, B2, G1 and G2 by using liquid chromatography-mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ramadhaningtyas, Dillani Putri; Aryana, Nurhani; Aristiawan, Yosi; Styarini, Dyah

    2017-11-01

    The optimization of instrument condition and chromatographic separation for analysis of aflatoxin B1, B2, G1 and G2 using liquid chromatography tandem with mass spectrometer detector was conducted in the aim to provide more accurate and reliable analysis results. The aflatoxin known to be serious threat for human health as it is classified as the carcinogenic compounds. The aflatoxin B1, B2, G1 and G2 were selected due to its extensive contamination in various agricultural commodities. The best chromatographic separation was obtained using C-18 column with gradient elution of solvent 5 mM ammonium acetate and 0.1% formic acid in methanol at 7 minutes runtime analysis. The linearity of the detector showed satisfied results as the coefficient determination found to be 0.9994, 0.9996, 0.9998 and 0.9987 for aflatoxin B1, G1, B2, and G2 respectively in the range concentration from 1 to 20 ng/g. The quantifier ion selected for the aflatoxin B1, B2, G1 and G2 was m/z 285.1, 259, 243 and 313 respectively. The instrument precision at these quantifier ions also showed satisfied result with %RSD was around 3.4 to 6.8%. The optimized method present in this study can be used for further sample analysis.

  9. FiO2 delivered by a turbine portable ventilator with an oxygen concentrator in an Austere environment.

    PubMed

    Bordes, Julien; Erwan d'Aranda; Savoie, Pierre-Henry; Montcriol, Ambroise; Goutorbe, Philippe; Kaiser, Eric

    2014-09-01

    Management of critically ill patients in austere environments is a logistic challenge. Availability of oxygen cylinders for the mechanically ventilated patient may be difficult in such a context. A solution is to use a ventilator able to function with an oxygen concentrator. We tested the SeQual Integra™ (SeQual, San Diego, CA) 10-OM oxygen concentrator paired with the Pulmonetic System(®) LTV 1000 ventilator (Pulmonetic Systems, Minneapolis, MN) and evaluated the delivered fraction of inspired oxygen (FiO2) across a range of minute volumes and combinations of ventilator settings. Two LTV 1000 ventilators were tested. The ventilators were attached to a test lung and FiO2 was measured by a gas analyzer. Continuous-flow oxygen was generated by the OC from 0.5 L/min to 10 L/min and injected into the oxygen inlet port of the LTV 1000. Several combinations of ventilator settings were evaluated to determine the factors affecting the delivered FiO2. The LTV 1000 ventilator is a turbine ventilator that is able to deliver high FiO2 when functioning with an oxygen concentrator. However, modifications of the ventilator settings such as increase in minute ventilation affect delivered FiO2 even if oxygen flow is constant on the oxygen concentrator. The ability of an oxygen concentrator to deliver high FiO2 when used with a turbine ventilator makes this method of oxygen delivery a viable alternative to cylinders in austere environments when used with a turbine ventilator. However, FiO2 has to be monitored continuously because delivered FiO2 decreases when minute ventilation is increased. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. 26 CFR 1.669(b)-2 - Manner of exercising election.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Manner of exercising election. 1.669(b)-2 Section 1.669(b)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Years Beginning Before January 1, 1969 § 1.669(b)-2 Manner of exercising election. (a) By whom election...

  11. 75 FR 22508 - Airworthiness Directives; Eurocopter France Model AS350B, BA, B1, B2, B3, C, D, and D1; AS 355E...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... Airworthiness Directives; Eurocopter France Model AS350B, BA, B1, B2, B3, C, D, and D1; AS 355E, F, F1, F2, N... (b) None. Applicability (c) This AD applies to Model AS350B, BA, B1, B2, B3, C, D and D1; and AS 355E..., both dated November 16, 2005, is approved by the Director of the Federal Register as of May 14, 2010...

  12. Asperentin B, a New Inhibitor of the Protein Tyrosine Phosphatase 1B.

    PubMed

    Wiese, Jutta; Aldemir, Hülya; Schmaljohann, Rolf; Gulder, Tobias A M; Imhoff, Johannes F

    2017-06-21

    In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillus sydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B ( 1 ) contains an additional phenolic hydroxy function at C-6 and exhibits an IC 50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin. Interestingly, asperentin ( 2 ) did not show any inhibition of this enzymatic activity. Asperentin B ( 1 ) is discussed as possible therapeutic agents for type 2 diabetes and sleeping sickness.

  13. Asperentin B, a New Inhibitor of the Protein Tyrosine Phosphatase 1B

    PubMed Central

    Wiese, Jutta; Aldemir, Hülya; Schmaljohann, Rolf; Gulder, Tobias A. M.; Imhoff, Johannes F.

    2017-01-01

    In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillus sydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin. Interestingly, asperentin (2) did not show any inhibition of this enzymatic activity. Asperentin B (1) is discussed as possible therapeutic agents for type 2 diabetes and sleeping sickness. PMID:28635658

  14. Imidazo[2,1-b]thiazoles and their use as pharmaceuticals: Sanofi-Aventis EP 1 923 062 A1 (equivalent to WO2008058641).

    PubMed

    Karimian, K

    2009-03-01

    Imidazothiazoles are well-known compounds and many derivatives of this fused ring system have been evaluated for potential biological activity. The present application is focused on imidazo[2,1-b]thiazoles with pharmacological ability to stimulate the expression (transcription) of the enzyme endothelial nitric oxide (NO) synthase. This invention contains two types of claims. First, several imidazo[2,1-b]thiazoles (and compositions thereof) that were not previously reported in chemical literature are claimed (claims 6 - 15). Second, the use of the claimed compounds in the treatment of several different diseases is claimed (claims 1 - 5 and 16). The claimed imidazo[2,1-b]thiazoles are synthesized by the condensation of 2-aminothiazole with an alpha-halo ketone. Evaluation of pharmacological activity of the claimed compounds is based on previously reported methodologies. Results are at their best reported in descriptive terms. The descriptive presentation of results in this application does not allow a critical evaluation of the claims. However, this does not diminish the potential commercial importance of this application. Because of the importance of nitric oxide regulation in physiological systems, more research in this area of medicinal chemistry can be anticipated.

  15. Study of infrared emission spectroscopy for the B{sup 1}Δ{sub g}–A{sup 1}Π{sub u} and B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} systems of C{sub 2}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Wang, E-mail: sc19321@s.okayama-u.ac.jp, E-mail: okakent@okayama-u.ac.jp, E-mail: pbernath@odu.edu; Kawaguchi, Kentarou, E-mail: sc19321@s.okayama-u.ac.jp, E-mail: okakent@okayama-u.ac.jp, E-mail: pbernath@odu.edu; Tang, Jian, E-mail: jtang@okayama-u.ac.jp

    Thirteen bands for the B{sup 1}Δ{sub g}–A{sup 1}Π{sub u} system and eleven bands for the B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} system of C{sub 2} were identified in the Fourier transform infrared emission spectra of hydrocarbon discharges. The B{sup ′1}Σ{sub g}{sup +} v = 4 and the B{sup 1}Δ{sub g} 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{sup 1}Δ{sub g}–A{sup 1}Π{sub u} system except for a small perturbation in the B{sup 1}Δ{sub g} v = 6more » level. The calculated rovibrational term energies up to B{sup 1}Δ{sub g} v = 12 showed that the level crossing between the B{sup 1}Δ{sub g} and d{sup 3}Π{sub g} states is responsible for many of the prominent perturbations in the Swan system observed previously. Nineteen forbidden transitions of the B{sup 1}Δ{sub g}–a{sup 3}Π{sub u} transition were identified and the off-diagonal spin-orbit interaction constant A{sub dB} between d{sup 3}Π{sub g} and B{sup 1}Δ{sub g} was derived as 8.3(1) cm{sup −1}. For the B{sup ′1}Σ{sub g}{sup +}–A{sup 1}Π{sub u} system, only individual band analyses for each vibrational level in the B′{sup 1}Σ{sub g}{sup +} state could be done satisfactorily and Dunham parameters obtained from these effective parameters showed that the anharmonic vibrational constant ω{sub e}x{sub e} is anomalously small (nearly zero). Inspection of the RKR (Rydberg-Klein-Rees) potential curves for the B{sup ′1}Σ{sub g}{sup +} and X{sup 1}Σ{sub g}{sup +} states revealed that an avoided crossing or nearly avoided crossing may occur around 30 000 cm{sup −1}, which is responsible for the anomalous molecular constants in these two states.« less

  16. Intrinsic fluorescence spectra characteristics of vitamin B1, B2, and B6

    NASA Astrophysics Data System (ADS)

    Yang, Hui; Xiao, Xue; Zhao, Xuesong; Hu, Lan; Lv, Caofang; Yin, Zhangkun

    2015-11-01

    This paper presents the intrinsic fluorescence characteristics of vitamin B1, B2 and B6 measured with 3D fluorescence Spectrophotometer. Three strong fluorescence areas of vitamin B2 locate at λex/λem=270/525nm, 370/525nm and 450/525nm, one fluorescence areas of vitamin B1 locates at λex/λem=370/460nm, two fluorescence areas of vitamin B6 locates at λex/λem=250/370nm and 325/370nm were found. The influence of pH of solution to the fluorescence profile was also discussed. Using the PARAFAC algorithm, 10 vitamin B1, B2 and B6 mixed solutions were successfully decomposed, and the emission profiles, excitation profiles, central wavelengths and the concentration of the three components were retrieved precisely through about 5 iteration times.

  17. Immunohistochemical Localization of AT1a, AT1b, and AT2 Angiotensin II Receptor Subtypes in the Rat Adrenal, Pituitary, and Brain with a Perspective Commentary

    PubMed Central

    Premer, Courtney; Lamondin, Courtney; Mitzey, Ann; Speth, Robert C.; Brownfield, Mark S.

    2013-01-01

    Angiotensin II increases blood pressure and stimulates thirst and sodium appetite in the brain. It also stimulates secretion of aldosterone from the adrenal zona glomerulosa and epinephrine from the adrenal medulla. The rat has 3 subtypes of angiotensin II receptors: AT1a, AT1b, and AT2. mRNAs for all three subtypes occur in the adrenal and brain. To immunohistochemically differentiate these receptor subtypes, rabbits were immunized with C-terminal fragments of these subtypes to generate receptor subtype-specific antibodies. Immunofluorescence revealed AT1a and AT2 receptors in adrenal zona glomerulosa and medulla. AT1b immunofluorescence was present in the zona glomerulosa, but not the medulla. Ultrastructural immunogold labeling for the AT1a receptor in glomerulosa and medullary cells localized it to plasma membrane, endocytic vesicles, multivesicular bodies, and the nucleus. AT1b and AT2, but not AT1a, immunofluorescence was observed in the anterior pituitary. Stellate cells were AT1b positive while ovoid cells were AT2 positive. In the brain, neurons were AT1a, AT1b, and AT2 positive, but glia was only AT1b positive. Highest levels of AT1a, AT1b, and AT2 receptor immunofluorescence were in the subfornical organ, median eminence, area postrema, paraventricular nucleus, and solitary tract nucleus. These studies complement those employing different techniques to characterize Ang II receptors. PMID:23573410

  18. VizieR Online Data Catalog: L1157-B1 DCN (2-1) and H13CN (2-1) datacubes (Busquet+,

    NASA Astrophysics Data System (ADS)

    Busquet, G.; Fontani, F.; Viti, S.; Codella, C.; Lefloch, B.; Benedettini, M.; Ceccarellli, C.

    2017-06-01

    IRAM NOEMA observations of DCN(2-1) and H13CN(2-1) towa brightest bow-shock B1 of the L1157 molecular outflow. All data cubes are provided in fits format smoothed to a velocity resolution of 0.5km/s. (2 data files).

  19. Determination of the rate constant for the NH2(X(2)B1) + NH2(X(2)B1) reaction at low pressure and 293 K.

    PubMed

    Bahng, Mi-Kyung; Macdonald, R Glen

    2008-12-25

    The rate constant for the reaction NH(2)(X(2)B(1)) + NH(2)(X(2)B(1)) --> products was measured in CF(4), N(2) and Ar carrier gases at 293 +/- 2 K over a pressure range from 2 to 10 Torr. The NH(2) radical was produced by the 193 nm photolysis of NH(3) dilute in the carrier gas. Both the loss of NH(3) and its subsequent recovery and the production of NH(2) and subsequent reaction were monitored simultaneously following the photolysis laser pulse. Both species were detected using quantitative time-resolved high-resolution absorption spectroscopy. The NH(3) molecule was monitored in the NIR using a rotation transition of the nu(1) + nu(3) first combination band near 1500 nm, and the NH(2) radical was monitored using the (1)2(21) <-- (1)3(31) rotational transition of the (0,7,0)A(2)A(1) <-- (0,0,0) X(2)B(1) band near 675 nm. The low-pressure rate constant showed a linear dependence on pressure. The slope of the pressure dependence was dominated by a recombination rate constant for NH(2) + NH(2) given by (8.0 +/- 0.5) x 10(-29), (5.7 +/- 0.7) x 10(-29), and (3.9 +/- 0.4) x 10(-29) cm(6) molecule(-2) s(-1) in CF(4), N(2), and Ar bath gases, respectively, where the uncertainties are +/-2sigma in the scatter of the measurements. The average of the three independent measurements of the sum of the disproportionation rate constants (the zero pressure rate constant) was (3.4 +/- 6) x 10(-13) cm(3) molecule(-1) s(-1), where the uncertainty is +/-2sigma in the scatter of the measurements.

  20. Formation of a1 Ions Directly from Oxazolone b2 Ions: an Energy-Resolved and Computational Study

    NASA Astrophysics Data System (ADS)

    Bythell, Benjamin J.; Harrison, Alex G.

    2015-05-01

    It is well-known that oxazolone b2 ions fragment extensively by elimination of CO to form a2 ions, which often fragment further to form a1 ions. Less well-known is that some oxazolone b2 ions may fragment directly to form a1 ions. The present study uses energy-resolved collision-induced dissociation experiments to explore the occurrence of the direct b2a1 fragmentation reaction. The experimental results show that the direct b2a1 reaction is generally observed when Gly is the C-terminal residue of the oxazolone. When the C-terminal residue is more complex, it is able to provide increased stability of the a2 product in the b2a2 fragmentation pathway. Our computational studies of the relative critical reaction energies for the b2a2 reaction compared with those for the b2a1 reaction provide support that the critical reaction energies are similar for the two pathways when the C-terminal residue of the oxazolone is Gly. By contrast, when the nitrogen of the oxazolone ring in the b2 ion does not bear a hydrogen, as in the Ala-Sar and Tyr-Sar (Sar = N-methylglycine) oxazolone b2 ions, a1 ions are not formed but rather neutral imine elimination from the N-terminus of the b2 ion becomes a dominant fragmentation reaction. The M06-2X/6-31+G(d,p) density functional theory calculations are in general agreement with the experimental data for both types of reaction. In contrast, the B3LYP/6-31+G(d,p) model systematically underestimates the barriers of these SN2-like b2a1 reaction. The difference between the two methods of barrier calculation are highly significant ( P < 0.001) for the b2a1 reaction, but only marginally significant ( P = 0.05) for the b2a2 reaction. The computations provide further evidence of the limitations of the B3LYP functional when describing SN2-like reactions.

  1. SLCO2B1 and SLCO1B3 May Determine Time to Progression for Patients Receiving Androgen Deprivation Therapy for Prostate Cancer

    PubMed Central

    Yang, Ming; Xie, Wanling; Mostaghel, Elahe; Nakabayashi, Mari; Werner, Lillian; Sun, Tong; Pomerantz, Mark; Freedman, Matthew; Ross, Robert; Regan, Meredith; Sharifi, Nima; Figg, William Douglas; Balk, Steven; Brown, Myles; Taplin, Mary-Ellen; Oh, William K.; Lee, Gwo-Shu Mary; Kantoff, Philip W.

    2011-01-01

    Purpose Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, SLCO2B1 and SLCO1B3, may determine time to progression on ADT. Patients and Methods A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays. Results Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P < .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (Pinteraction = .041). Conclusion Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer. PMID:21606417

  2. Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages.

    PubMed

    Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan

    2017-09-01

    Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC 50 value of 1.04μM. Results from NPOI further showed that the K on and K off of PUN-PTP1B complex were 3.38e2M -1 s -1 and 4.13e-3s -1 , respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Vapor-liquid equilibria for 1,1,1,2-tetrafluoroethane + 1-chloro-1,2,2,2-tetrafluoroethane and 1-chloro-1,2,2,2-tetrafluoroethane + 1-chloro-1,1-difluoroethane systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, J.; Lee, J.; Kim, H.

    1996-07-01

    Isothermal vapor-liquid equilibria were determined for two binary mixtures of refrigerants with a circulation type apparatus. The 1,1,1,2-tetrafluoroethane (HFC-134a) + 1-chloro-1,2,2,2-tetrafluoroethane (HCFC-124) system was studied at 296.45, 302.25, and 307.25 K. The 1-chloro-1,2,2,2-tetrafluoroethane (HCFC-124) + 1-chloro-1,1-difluoroethane (HCFC-142b) system was studied at 298.15 and 312.15 K. At each temperature, the pressure and vapor and liquid compositions were measured. Results were correlated with the Peng-Robinson equation of state.

  4. Mutant alleles of FAD2-1A and FAD2-1B combine to produce soybeans with the high oleic acid seed oil trait

    PubMed Central

    2010-01-01

    Background The alteration of fatty acid profiles in soybean [Glycine max (L.) Merr.] to improve soybean oil quality is an important and evolving theme in soybean research to meet nutritional needs and industrial criteria in the modern market. Soybean oil with elevated oleic acid is desirable because this monounsaturated fatty acid improves the nutrition and oxidative stability of the oil. Commodity soybean oil typically contains 20% oleic acid and the target for high oleic acid soybean oil is approximately 80% of the oil; previous conventional plant breeding research to raise the oleic acid level to just 50-60% of the oil was hindered by the genetic complexity and environmental instability of the trait. The objective of this work was to create the high oleic acid trait in soybeans by identifying and combining mutations in two delta-twelve fatty acid desaturase genes, FAD2-1A and FAD2-1B. Results Three polymorphisms found in the FAD2-1B alleles of two soybean lines resulted in missense mutations. For each of the two soybean lines, there was one unique amino acid change within a highly conserved region of the protein. The mutant FAD2-1B alleles were associated with an increase in oleic acid levels, although the FAD2-1B mutant alleles alone were not capable of producing a high oleic acid phenotype. When existing FAD2-1A mutations were combined with the novel mutant FAD2-1B alleles, a high oleic acid phenotype was recovered only for those lines which were homozygous for both of the mutant alleles. Conclusions We were able to produce conventional soybean lines with 80% oleic acid in the oil in two different ways, each requiring the contribution of only two genes. The high oleic acid soybean germplasm developed contained a desirable fatty acid profile, and it was stable in two production environments. The presumed causative sequence polymorphisms in the FAD2-1B alleles were developed into highly efficient molecular markers for tracking the mutant alleles. The resources

  5. Mutant alleles of FAD2-1A and FAD2-1B combine to produce soybeans with the high oleic acid seed oil trait.

    PubMed

    Pham, Anh-Tung; Lee, Jeong-Dong; Shannon, J Grover; Bilyeu, Kristin D

    2010-09-09

    The alteration of fatty acid profiles in soybean [Glycine max (L.) Merr.] to improve soybean oil quality is an important and evolving theme in soybean research to meet nutritional needs and industrial criteria in the modern market. Soybean oil with elevated oleic acid is desirable because this monounsaturated fatty acid improves the nutrition and oxidative stability of the oil. Commodity soybean oil typically contains 20% oleic acid and the target for high oleic acid soybean oil is approximately 80% of the oil; previous conventional plant breeding research to raise the oleic acid level to just 50-60% of the oil was hindered by the genetic complexity and environmental instability of the trait. The objective of this work was to create the high oleic acid trait in soybeans by identifying and combining mutations in two delta-twelve fatty acid desaturase genes, FAD2-1A and FAD2-1B. Three polymorphisms found in the FAD2-1B alleles of two soybean lines resulted in missense mutations. For each of the two soybean lines, there was one unique amino acid change within a highly conserved region of the protein. The mutant FAD2-1B alleles were associated with an increase in oleic acid levels, although the FAD2-1B mutant alleles alone were not capable of producing a high oleic acid phenotype. When existing FAD2-1A mutations were combined with the novel mutant FAD2-1B alleles, a high oleic acid phenotype was recovered only for those lines which were homozygous for both of the mutant alleles. We were able to produce conventional soybean lines with 80% oleic acid in the oil in two different ways, each requiring the contribution of only two genes. The high oleic acid soybean germplasm developed contained a desirable fatty acid profile, and it was stable in two production environments. The presumed causative sequence polymorphisms in the FAD2-1B alleles were developed into highly efficient molecular markers for tracking the mutant alleles. The resources described here for the creation

  6. 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

  7. Synthesis and Cytotoxic Evaluation of 1H-1,2,3-Triazol-1-ylmethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones.

    PubMed

    Chipoline, Ingrid C; Alves, Evelyne; Branco, Paola; Costa-Lotufo, Leticia V; Ferreira, Vitor F; Silva, Fernando C DA

    2018-01-01

    The 1,2-naphthoquinone compound was previously considered active against solid tumors. Moreover, glycosidase inhibitors such as 1,2,3-1H triazoles has been pointed out as efficient compounds in anticancer activity studies. Thus, a series of eleven 1,2-naphthoquinones tethered in C2 to 1,2,3-1H-triazoles 9a-k were designed, synthesized and their cytotoxic activity evaluated using HCT-116 (colon adenocarcinoma), MCF-7 (breast adenocarcinoma) and RPE (human nontumor cell line from retinal epithelium). The chemical synthesis was performed from C-3 allylation of lawsone followed by iodocyclization with subsequent nucleophilic displacement with sodium azide and, finally, the 1,3-dipolar cycloaddition catalyzed by Cu(I) with terminal alkynes led to the formation of 1H-1,2,3-Triazol-1-ylmethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones in good yields. Compounds containing aromatic group linked to 1,2,3-triazole ring (9c, 9d, 9e, 9i) presented superior cytotoxic activity against cancer cell lines with IC50 in the range of 0.74 to 4.4 µM indicating that the presence of aromatic rings substituents in the 1,2,3-1H-triazole moiety is probably responsible for the improved cytotoxic activity.

  8. Effective therapy for a murine model of human anaplastic large-cell lymphoma with the anti-CD30 monoclonal antibody, HeFi-1, does not require activating Fc receptors

    PubMed Central

    Zhang, Meili; Yao, Zhengsheng; Zhang, Zhuo; Garmestani, Kayhan; Goldman, Carolyn K.; Ravetch, Jeffrey V.; Janik, John; Brechbiel, Martin W.; Waldmann, Thomas A.

    2006-01-01

    CD30 is a member of the tumor necrosis factor receptor family. Overexpression of CD30 on some neoplasms versus its limited expression on normal tissues makes this receptor a promising target for antibody-based therapy. Anaplastic large-cell lymphoma (ALCL) represents a heterogeneous group of aggressive non-Hodgkin lymphomas characterized by the strong expression of CD30. We investigated the therapeutic efficacy of HeFi-1, a mouse IgG1 monoclonal antibody, which recognizes the ligand-binding site on CD30, and humanized anti-Tac antibody (daclizumab), which recognizes CD25, in a murine model of human ALCL. The ALCL model was established by intravenous injection of karpas299 cells into nonobese diabetic/severe combined immuno-deficient (SCID/NOD) wild-type or SCID/NOD Fc receptor common γ chain–deficient (FcRγ–/–) mice. HeFi-1, given at a dose of 100 μg weekly for 4 weeks, significantly prolonged survival of the ALCL-bearing SCID/NOD wild-type and SCID/NOD FcRγ–/– mice (P < .01) as compared with the control groups. In vitro studies showed that HeFi-1 inhibited the proliferation of karpas299 cells, whereas daclizumab did not inhibit cell proliferation. We demonstrated that the expression of FcRγ on polymorphonuclear leukocytes and monocytes was not required for HeFi-1–mediated tumor growth inhibition in vivo, although it was required for daclizumab. PMID:16551968

  9. Pb(B{sup {prime}}{sub 1/2}B{sup {prime}{prime}}{sub 1/2})O{sub 3}-type perovskites: Part II. Short-range order parameter as a criterion of the distinction between relaxor and normal ferroelectrics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, S.; Jang, H.M.

    1997-08-01

    A classification scheme of Pb(B{sup {prime}}{sub 1/2}B{sup {prime}{prime}}{sub 1/2})O{sub 3}-type perovskites with respect to the B-site order parameters was proposed based on the theoretical calculation of the short-range order parameter ({sigma}) using the pair-correlation model. The calculated order parameters predict that a Pb(B{sup {prime}}{sub 1/2}B{sup {prime}{prime}}{sub 1/2})O{sub 3}-type perovskite without any charge difference between B{sup {prime}} and B{sup {prime}{prime}} cations [e.g., Pb(Zr{sub 1/2}Ti{sub 1/2})O{sub 3} (PZT)] is represented by a completely disordered state with the absence of a finite coherence length. On the other hand, a Pb(B{sup {prime}}{sub 1/2}B{sup {prime}{prime}}{sub 1/2})O{sub 3} type perovskite system having different ionic charges ismore » characterized either by the short-range ordering with a nanoscale coherence length or by the macroscopic long-range ordering, depending on the magnitude of ionic charge difference between B{sup {prime}} and B{sup {prime}{prime}} ions. The normal ferroelectricity in Pb(B{sup {prime}}{sub 1/2}B{sup {prime}{prime}}{sub 1/2})O{sub 3}-type complex perovskites was then correlated either with a completely disordered state ({sigma}=0) or with a perfectly ordered state ({sigma}=1), whereas the relaxor behavior was attributed to the nanoscale short-range ordering (0{lt}{sigma}{lt}1) in the configuration of the B-site cations. {copyright} {ital 1997 Materials Research Society.}« less

  10. A first detection of singlet to triplet conversion from the 1 1B u- to the 1 3A g state and triplet internal conversion from the 1 3A g to the 1 3B u state in carotenoids: dependence on the conjugation length

    NASA Astrophysics Data System (ADS)

    Rondonuwu, Ferdy S.; Watanabe, Yasutaka; Fujii, Ritsuko; Koyama, Yasushi

    2003-07-01

    Subpicosecond time-resolved absorption spectra were recorded in the visible region for a set of photosynthetic carotenoids having different numbers of conjugated double bonds ( n), which include neurosporene ( n=9), spheroidene ( n=10), lycopene ( n=11), anhydrorhodovibrin ( n=12) and spirilloxanthin ( n=13). Singular-value decomposition and global fitting of the spectral-data matrices lead us to a branched relaxation scheme including both (1) the singlet internal conversion in the sequence of 1 1B u+ → 1 1B u- → 2 1A g- → 1 1A g-(ground), and (2) the singlet-to-triplet conversion of 1 1B u- → 1 3A g followed by triplet internal conversion of 1 3A g → 1 3B u.

  11. [In vitro study of vitamins B1, B2 and B6 adsorption on zeolite].

    PubMed

    Basić, Zorica; Kilibarda, Vesna; Dobrić, Silva; Resanović, Radmila

    2011-01-01

    Zeolites are the hydratised alumosilicates of alcali and earthalcali cations, which have a long three-dimensional crystal structure. Preparations on the basis of zeolites are used for adsorption of organic and nonorganic toxic substances and they, also, find more and more use in veterinary and human medicine and pharmacy. The aim of this study was to evaluate the possibilities of zeolite to adsorb vitamins B1, B2 and B6 in acid and neutral solutions, as well as the characteristics of the process (saturability, reversibility and competitiveness). The specific and sensitive HPLC method with fluorescent detector was used for determination of vitamins B1, B2 and B6. Analyte separation and detection were carried out by applying the reverse-phase method on column C18. An in vitro experiment was done by testing the influence of pH value (2 and 7), concentration of vitamin solution (1, 2 and 5 mg/L), the length of contact with zeolite (10-180 min) and cation competitiveness on the exchange capacity, which is achieved by media and zeolite contact, as well as a possible vitamins desorption through changing pH value of the solution at 37 degrees C. Jon competitiveness was examined by adding commercial feed mixture (grower) with a defined content of the examined vitamins in zeolite solutions the pH = 2 and pH = 7. Vitamins B1, B2 and B6 were stable in both pH=2 and pH = 7 solutions at 37 degrees C, in the defined time intervals. In acid solution concentrations of vitamins significantly declined in the first 10 min, with no significant decline in further 30 min for all the three concentrations tests. In neutral solution, after the addition of 1% zeolite, decrease in vitamins concentrations was slightly lower than in acid solution, but also significant in the first 10 min of the contact with zeolite. It was found that zeolite, which adsorbed vitamins in acid solution, transferred in the neutral one released a significant quantity of adsorbed vitamins after 30 min of extraction

  12. Premalignant Genetic and Epigenetic Alterations in Tubal Epithelium from Women with BRCA1 Mutations

    DTIC Science & Technology

    2010-10-14

    Homo sapiens , clone IMAGE:5590287, mRNA Unknown 1.8 .0044 3.0...RT-PCR W T -F T B 1- F T B 1 C an ce r 0 2 4 6 8 10 R el at iv e Q u an ti fi ca ti o n CDKN1C Array W T -F T B 1- F T B 1 C an ce r 0 100 200 300...S p o t In te n si ty CDKN1C RT-PCR W T -F T B 1- F T B 1 C an ce r 0.0 0.2 0.4 0.6 0.8 R el at iv e Q u an ti fi ca ti o n CYP3A5 Array W T

  13. Effect of Microwave Wi-Fi Radiation at Frequency of 2.4 GHz on Epileptic Behavior of Rats.

    PubMed

    A, Mahmoudi; M B, Shojaeifard; S, Nematollahii; S M J, Mortazavi; A R, Mehdizadeh

    2018-06-01

    Electromagnetic fields (EMF) with different intensities are widely used at home, offices and public places.Today, there is a growing global concern about the effects of human exposure to EMFs. Epilepsy is one of the most common chronic neurological diseases, affecting 50 million people of all ages worldwide. We aimed to investigate the effect of exposure to Wi-Fi radiation on epileptic behavior of rats. 147 male rats, weighing 200-250 g, were divided into seven groups; negative control (no intervention), sham 1(distilled water), positive control (Pentylentetrazol [PTZ]), intervention group 1 (PTZ + Wi-Fi "off"), sham 2 (distilled water + Wi-Fi "off"), sham 3 (distilled water + Wi-Fi "on"), and intervention group 2 (PTZ + Wi-Fi "on"). The rats were exposed to Wi-Fi for 2h at a distance of 30cm from a commercial Wi-Fi router. Convulsive behaviors of rats were monitored and scored based on the intensity and type by measuring latency/threshold time, number of convulsions, sum of scores and durations of seizure, and duration of score 6 seizure. Kruskal-Wallis and Mann-Whitney U-tests were used to analyze the data. Convulsion was observed in interventions Group 4 and Group 7, and positive control. The mean number of events, and sum of scores were significantly different in intervention 2 than other two groups. However, the differences in mean threshold, mean sum of durations and " time to show convulsion with score 6 " were not statistically significant (P>0.05). Due to limitations of our study including the sample size, these findings should be interpreted with caution. In this study, exposure to 2.4 GHz Wi-Fi radiation showed significant beneficial effects on the epileptic behaviour of rats. More experiments are needed to verify if these exposures can be used as a therapeutic approach for amelioration of seizures in epilepsy.

  14. Characterization of the X~ 2A1, A~ 2B1, and X~ 2Π electronic states of the Ga2H molecule and the X~ 2A' and A~ 2A'' isomerization transition states connecting the three minima

    NASA Astrophysics Data System (ADS)

    Wang, Hongyan; Wang, Suyun; Yan, Ge; Yamaguchi, Yukio; Schaefer, Henry F.

    2006-01-01

    A wide range of highly correlated ab initio methods has been used to predict the geometrical parameters of the linear (X˜Π2) and H-bridged (X˜A12 and ÃB12) Ga2H isomers and two isomerization transition states (X˜A'2 and ÃA″2) connecting the three minima. Dipole moments and vibrational frequencies are also obtained. The global minimum X˜A12 ground state of the H-bridged GaHGa isomer is predicted to lie only 1.6 [1.9 with the zero-point vibrational energy (ZPVE) corrections] kcalmol-1 below the ÃB12 state. The X˜A12 state lies 5.4kcalmol-1 below the X˜Π2 ground state of the linear GaGaH isomer at the coupled-cluster with single, double, and perturbative triple excitations [CCSD(T)] level of theory with the augmented correlation-consistent polarized valence quadruple-zeta (aug-cc-pVQZ) basis set. The full triples coupled-cluster method is found to alter these CCSD(T) predictions by as much as 0.3kcalmol-1. The forward isomerization barriers from the linear ground state to the X˜A'2 and ÃA″2 transition states are determined to be 3.3 and 5.3kcalmol-1, respectively. The reverse isomerization barrier between the X˜A12 GaHGa structure and the X˜Π2 GaGaH structure is predicted to be 8.6 (8.2 with the ZPVE corrections) kcalmol-1 at the aug-cc-pVQZ CCSD(T) level of theory.

  15. Penicillin-binding protein 1A, 2B, and 2X alterations in Canadian isolates of penicillin-resistant Streptococcus pneumoniae.

    PubMed

    Nichol, Kimberly A; Zhanel, George G; Hoban, Daryl J

    2002-10-01

    Alterations within the penicillin-binding domain of penicillin-binding protein (PBP) genes pbp1a, pbp2b, and pbp2x were determined for 15 Canadian isolates of Streptococcus pneumoniae. All penicillin-nonsusceptible S. pneumoniae isolates showed a variety of PBP 2X substitutions and contained a Thr445-Ala change after the PBP 2B SSN motif. Only isolates for which penicillin MICs were > or =0.5 micro g/ml had PBP 1A alterations near the STMK and SRN motifs. Sequence analysis revealed identical PBP 1A, PBP 2B, and PBP 2X substitution patterns among all isolates for which penicillin MICs were > or =1 micro g/ml.

  16. Penicillin-Binding Protein 1A, 2B, and 2X Alterations in Canadian Isolates of Penicillin-Resistant Streptococcus pneumoniae

    PubMed Central

    Nichol, Kimberly A.; Zhanel, George G.; Hoban, Daryl J.

    2002-01-01

    Alterations within the penicillin-binding domain of penicillin-binding protein (PBP) genes pbp1a, pbp2b, and pbp2x were determined for 15 Canadian isolates of Streptococcus pneumoniae. All penicillin-nonsusceptible S. pneumoniae isolates showed a variety of PBP 2X substitutions and contained a Thr445-Ala change after the PBP 2B SSN motif. Only isolates for which penicillin MICs were ≥0.5 μg/ml had PBP 1A alterations near the STMK and SRN motifs. Sequence analysis revealed identical PBP 1A, PBP 2B, and PBP 2X substitution patterns among all isolates for which penicillin MICs were ≥1 μg/ml. PMID:12234855

  17. SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy.

    PubMed

    Ma, Chun-Lai; Wu, Xun-Yi; Jiao, Zheng; Hong, Zhen; Wu, Zhi-Yuan; Zhong, Ming-Kang

    2015-01-01

    Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated. Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method. Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p < 0.05). Corresponding relative ln (concentration-dose ratios) values for SCN1A IVS5-91 variants differed by the genotypic order GG > GA > AA. SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

  18. 26 CFR 1.663(b)-2 - Election.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., 1968. In the case of a trust for which an election was made under prior law, the fiduciary shall make... TAXES Estates and Trusts Which May Accumulate Income Or Which Distribute Corpus § 1.663(b)-2 Election. (a) Manner and time of election; irrevocability—(1) When return is required to be filed. If a trust...

  19. Evaluation of the PaO2/FiO2 ratio after cardiac surgery as a predictor of outcome during hospital stay.

    PubMed

    Esteve, Francisco; Lopez-Delgado, Juan C; Javierre, Casimiro; Skaltsa, Konstantina; Carrio, Maria Ll; Rodríguez-Castro, David; Torrado, Herminia; Farrero, Elisabet; Diaz-Prieto, Antonio; Ventura, Josep Ll; Mañez, Rafael

    2014-09-26

    The arterial partial pressure of O2 and the fraction of inspired oxygen (PaO2/FiO2) ratio is widely used in ICUs as an indicator of oxygenation status. Although cardiac surgery and ICU scores can predict mortality, during the first hours after cardiac surgery few instruments are available to assess outcome. The aim of this study was to evaluate the usefulness of PaO2/FIO2 ratio to predict mortality in patients immediately after cardiac surgery. We prospectively studied 2725 consecutive cardiac surgery patients between 2004 and 2009. PaO2/FiO2 ratio was measured on admission and at 3 h, 6 h, 12 h and 24 h after ICU admission, together with clinical data and outcomes. All PaO2/FIO2 ratio measurements differed between survivors and non-survivors (p < 0.001). The PaO2/FIO2 at 3 h after ICU admission was the best predictor of mortality based on area under the curve (p < 0.001) and the optimum threshold estimation gave an optimal cut-off of 222 (95% Confidence interval (CI): 202-242), yielding three groups of patients: Group 1, with PaO2/FIO2 > 242; Group 2, with PaO2/FIO2 from 202 to 242; and Group 3, with PaO2/FIO2 < 202. Group 3 showed higher in-ICU mortality and ICU length of stay and Groups 2 and 3 also showed higher respiratory complication rates. The presence of a PaO2/FIO2 ratio < 202 at 3 h after admission was shown to be a predictor of in-ICU mortality (OR:1.364; 95% CI:1.212-1.625, p < 0.001) and of worse long-term survival (88.8% vs. 95.8%; Log rank p = 0.002. Adjusted Hazard ratio: 1.48; 95% CI:1.293-1.786; p = 0.004). A simple determination of PaO2/FIO2 at 3 h after ICU admission may be useful to identify patients at risk immediately after cardiac surgery.

  20. 26 CFR 1.367(b)-2 - Definitions and special rules.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

  1. 26 CFR 1.367(b)-2 - Definitions and special rules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

  2. 26 CFR 1.367(b)-2 - Definitions and special rules.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

  3. 26 CFR 1.367(b)-2 - Definitions and special rules.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

  4. 26 CFR 1.367(b)-2 - Definitions and special rules.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (QBU) (B1) in France, whose functional currency is the euro. FC2, an unrelated foreign corporation... functional currency of the combined operations of B1 and B2 is the euro. (ii) Result. FC2's acquisition of... currency of the combined operations of B1 and B2 after the exchange is the euro, B2 is deemed to have...

  5. A Novel Role for C5a in B-1 Cell Homeostasis

    PubMed Central

    Bröker, Katharina; Figge, Julia; Magnusen, Albert F.; Manz, Rudolf A.; Köhl, Jörg; Karsten, Christian M.

    2018-01-01

    B-1 cells constitute a unique subpopulation of lymphocytes residing mainly in body cavities like the peritoneal cavity (PerC) but are also found in spleen and bone marrow (BM). As innate-like B cells, they mediate first line immune defense through low-affinity natural IgM (nIgM) antibodies. PerC B-1 cells can egress to the spleen and differentiate into nIgM antibody-secreting plasma cells that recognize conserved exogenous and endogenous cellular structures. Homing to and homeostasis within the PerC are regulated by the chemokine CXCL13 released by PerC macrophages and stroma cells. However, the exact mechanisms underlying the regulation of CXCL13 and B-1 homeostasis are not fully explored. B-1 cells play important roles in the inflammatory response to infection, autoimmunity, ischemia/reperfusion injury, obesity, and atherosclerosis. Remarkably, this list of inflammatory entities has a strong overlap with diseases that are regulated by complement suggesting a link between B-1 cells and the complement system. Interestingly, up to now, no data exist regarding the role of complement in B-1 cell biology. Here, we demonstrate for the first time that C5a regulates B-1 cell steady-state dynamics within the peritoneum, the spleen, and the BM. We found decreased B-1a cell numbers in the peritoneum and the spleen of C5aR1−/− mice associated with increased B1-a and B1-b numbers in the spleen and high serum titers of nIgM antibodies directed against phosphorylcholine and several pneumococcal polysaccharides. Similarly, peritoneal B-1a cells were decreased in the peritoneum and splenic B-1a and B-1b cells were increased in C5aR2−/− mice. The decrease in peritoneal B-1 cell numbers was associated with decreased peritoneal CXCL13 levels in C5aR1−/− and C5aR2−/− mice. In search for mechanisms, we found that combined TLR2 and IL-10 receptor activation in PerC macrophages induced strong CXCL13 production, which was significantly reduced in cells from C5aR1- and C5a

  6. 26 CFR 1.167(b)-2 - Declining balance method.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Declining balance method. 1.167(b)-2 Section 1... Declining balance method. (a) Application of method. Under the declining balance method a uniform rate is... declining balance rate may be determined without resort to formula. Such rate determined under section 167(b...

  7. 26 CFR 1.167(b)-2 - Declining balance method.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 2 2011-04-01 2011-04-01 false Declining balance method. 1.167(b)-2 Section 1... Declining balance method. (a) Application of method. Under the declining balance method a uniform rate is... declining balance rate may be determined without resort to formula. Such rate determined under section 167(b...

  8. 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.

  9. Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

    PubMed Central

    Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.

    2012-01-01

    Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642

  10. 26 CFR 1.50B-2 - Electing small business corporations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 1 2012-04-01 2012-04-01 false Electing small business corporations. 1.50B-2... business corporations. (a) General rule—(1) In general. In the case of an electing small business corporation (as defined in section 1371 (b)), WIN expenses (as defined in paragraph (a) of § 1.50B-1) shall be...

  11. 26 CFR 1.50B-2 - Electing small business corporations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 1 2014-04-01 2013-04-01 true Electing small business corporations. 1.50B-2... business corporations. (a) General rule—(1) In general. In the case of an electing small business corporation (as defined in section 1371 (b)), WIN expenses (as defined in paragraph (a) of § 1.50B-1) shall be...

  12. 26 CFR 1.50B-2 - Electing small business corporations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 1 2013-04-01 2013-04-01 false Electing small business corporations. 1.50B-2... business corporations. (a) General rule—(1) In general. In the case of an electing small business corporation (as defined in section 1371 (b)), WIN expenses (as defined in paragraph (a) of § 1.50B-1) shall be...

  13. Therapeutic Administration of Broadly Neutralizing FI6 Antibody Reveals Lack of Interaction Between Human IgG1 and Pig Fc Receptors.

    PubMed

    Morgan, Sophie B; Holzer, Barbara; Hemmink, Johanneke D; Salguero, Francisco J; Schwartz, John C; Agatic, Gloria; Cameroni, Elisabetta; Guarino, Barbara; Porter, Emily; Rijal, Pramila; Townsend, Alain; Charleston, Bryan; Corti, Davide; Tchilian, Elma

    2018-01-01

    Influenza virus infection is a significant global health threat. Because of the lack of cross-protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly, cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1-H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy. Here, we show that therapeutic administration of FI6 either intravenously or by aerosol to pigs did not reduce viral load in nasal swabs or broncho-alveolar lavage, but aerosol delivery of FI6 reduced gross pathology significantly. We demonstrate that pig Fc receptors do not bind human IgG1 and that FI6 did not mediate antibody-dependent cytotoxicity (ADCC) with pig PBMC, confirming that ADCC is an important mechanism of protection by anti-stem antibodies in vivo . Enhanced respiratory disease, which has been associated with pigs with cross-reactive non-neutralizing anti-HA antibodies, did not occur after FI6 administration. Our results also show that in vitro neutralizing antibody responses are not a robust correlate of protection for the control of influenza infection and pathology in a natural host model.

  14. Synthesis and molecular crystal of 3-Chloro-2-(1-chloro-1-methyl-ethyl)-2,3-dihydro-1H-naphtho[2,1-b]oxepin-4-one

    NASA Astrophysics Data System (ADS)

    Tittal, Ram Kumar

    2018-03-01

    CuCl/TMEDA-promoted halogen atom transfer radical cyclization (HATRC) of dichloroacetic acid 1-(3-methyl-but-2-enyl)-naphthalen-2-yl ester in refluxing DCE gave chlorine containing 7-member lactone 3-Chloro-2-(1-chloro-1-methyl-ethyl)-2,3-dihydro-1H-naphtho[2,1-b]oxepin-4-one via 7-exo trig radical cyclization reaction. The structure of the Lactone was confirmed by X-ray diffraction data.

  15. External Validation of the Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) in the Scoli-RISK-1 Patient Database.

    PubMed

    Miller, Emily K; Lenke, Lawrence G; Neuman, Brian J; Sciubba, Daniel M; Kebaish, Khaled M; Smith, Justin S; Qiu, Yong; Dahl, Benny T; Pellisé, Ferran; Matsuyama, Yukihiro; Carreon, Leah Y; Fehlings, Michael G; Cheung, Kenneth M; Lewis, Stephen; Dekutoski, Mark B; Schwab, Frank J; Boachie-Adjei, Oheneba; Mehdian, Hossein; Bess, Shay; Shaffrey, Christopher I; Ames, Christopher P

    2018-05-14

    Analysis of a prospective multicenter database. To assess the ability of the recently created Adult Spinal Deformity (ASD) Frailty Index (ASD-FI) to predict odds of major complications and length of hospital stay for patients who had more severe preoperative deformity and underwent more invasive ASD surgery compared with patients in the database used to create the index. Accurate preoperative estimates of risk are necessary given the high complication rates currently associated with ASD surgery. Patients were enrolled by participating institutions in Europe, Asia, and North America from 2009 to 2011. ASD-FI scores were used to classify 267 patients as not frail (NF) (<0.3), frail (0.3-0. 5), or severely frail (SF) (>0.5). Multivariable logistic regression, adjusted for preoperative and surgical covariates such as operative time and blood loss, was performed to determine the relationship between ASD-FI category and incidence of major complications, overall incidence of complications, and length of hospital stay. The mean ASD-FI score was 0.3 (range, 0-0.7). We categorized 105 patients as NF, 103 as frail, and 59 as SF. The adjusted odds of developing a major complication were higher for SF patients (odds ratio = 4.4; 95% CI 2.0, 9.9) compared with NF patients. After adjusting for covariates, length of hospital stay for SF patients increased by 19% (95% CI 1.4%, 39%) compared with NF patients. The odds of developing a major complication or having increased length of stay were similar between frail and NF patients. Greater patient frailty, as measured by the ASD-FI, is associated with a longer hospital stay and greater risk of major complications among patients who have severe preoperative deformity and undergo invasive surgical procedures. 2.

  16. EOS MLS Level 1B Data Processing, Version 2.2

    NASA Technical Reports Server (NTRS)

    Perun, Vincent; Jarnot, Robert; Pickett, Herbert; Cofield, Richard; Schwartz, Michael; Wagner, Paul

    2009-01-01

    A computer program performs level- 1B processing (the term 1B is explained below) of data from observations of the limb of the Earth by the Earth Observing System (EOS) Microwave Limb Sounder (MLS), which is an instrument aboard the Aura spacecraft. This software accepts, as input, the raw EOS MLS scientific and engineering data and the Aura spacecraft ephemeris and attitude data. Its output consists of calibrated instrument radiances and associated engineering and diagnostic data. [This software is one of several computer programs, denoted product generation executives (PGEs), for processing EOS MLS data. Starting from level 0 (representing the aforementioned raw data, the PGEs and their data products are denoted by alphanumeric labels (e.g., 1B and 2) that signify the successive stages of processing.] At the time of this reporting, this software is at version 2.2 and incorporates improvements over a prior version that make the code more robust, improve calibration, provide more diagnostic outputs, improve the interface with the Level 2 PGE, and effect a 15-percent reduction in file sizes by use of data compression.

  17. 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.

  18. TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB.

    PubMed

    Garrison, J B; Samuel, T; Reed, J C

    2009-04-02

    Marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma is the most common extranodal non-Hodgkin lymphoma. The t(11;18)(q21;q21) translocation occurs frequently in MALT lymphomas and creates a chimeric NF-kappaB-activating protein containing the baculoviral IAP repeat (BIR) domains of c-IAP2 (inhibitor of apoptosis protein 2) fused with portions of the MALT1 protein. The BIR1 domain of c-IAP2 interacts directly with TRAF2 (TNFalpha-receptor-associated factor-2), but its role in NF-kappaB activation is still unclear. Here, we investigated the role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation. We show the BIR1 domain of c-IAP2 is essential for NF-kappaB activation, whereas BIR2 and BIR3 domains are not. Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to activate NF-kappaB showed loss of TRAF2 binding, but retention of TRAF6 binding, suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for NF-kappaB induction. In addition, a dominant-negative TRAF2 mutant or downregulation of TRAF2 achieved by small interfering RNA inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable. Comparisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell line provided evidence that TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes (c-FLIP, TRAF1), and resistance to apoptosis.

  19. Mortality prediction to hospitalized patients with influenza pneumonia: PO2 /FiO2 combined lymphocyte count is the answer.

    PubMed

    Shi, Shu Jing; Li, Hui; Liu, Meng; Liu, Ying Mei; Zhou, Fei; Liu, Bo; Qu, Jiu Xin; Cao, Bin

    2017-05-01

    Community-acquired pneumonia (CAP) severity scores perform well in predicting mortality of CAP patients, but their applicability in influenza pneumonia is powerless. The aim of our research was to test the efficiency of PO 2 /FiO 2 and CAP severity scores in predicting mortality and intensive care unit (ICU) admission with influenza pneumonia patients. We reviewed all patients with positive influenza virus RNA detection in Beijing Chao-Yang Hospital during the 2009-2014 influenza seasons. Outpatients, inpatients with no pneumonia and incomplete data were excluded. We used receiver operating characteristic curves (ROCs) to verify the accuracy of severity scores or indices as mortality predictors in the study patients. Among 170 hospitalized patients with influenza pneumonia, 30 (17.6%) died. Among those who were classified as low-risk (predicted mortality 0.1%-2.1%) by pneumonia severity index (PSI) or confusion, urea, respiratory rate, blood pressure, age ≥65 year (CURB-65), the actual mortality ranged from 5.9 to 22.1%. Multivariate logistic regression indicated that hypoxia (PO 2 /FiO 2  ≤ 250) and lymphopenia (peripheral blood lymphocyte count <0.8 × 10 9 /L) were independent risk factors for mortality, with OR value of 22.483 (95% confidence interval 4.927-102.598) and 5.853 (95% confidence interval 1.887-18.152), respectively. PO 2 /FiO 2 combined lymphocyte count performed well for mortality prediction with area under the curve (AUC) of 0.945, which was significantly better than current CAP severity scores of PSI, CURB-65 and confusion, respiratory rate, blood pressure, age ≥65 years for mortality prediction (P < 0.001). The scores or indices for ICU admission prediction to hospitalized patients with influenza pneumonia confirmed a similar pattern and PO 2 /FiO 2 combined lymphocyte count was also the best predictor for predicting ICU admission. In conclusion, we found that PO 2 /FiO 2 combined lymphocyte count is simple and reliable predictor

  20. Satellite Evidence that <fi>E. huxleyifi> Phytoplankton Blooms Weaken Marine Carbon Sinks

    NASA Astrophysics Data System (ADS)

    Kondrik, D. V.; Pozdnyakov, D. V.; Johannessen, O. M.

    2018-01-01

    Phytoplankton blooms of the coccolithophore <fi>Emiliania huxleyifi> are known to produce CO2, causing less uptake of atmospheric CO2 by the ocean, but a global assessment of this phenomenon has so far not been quantified. Therefore, here we quantify the increase in CO2 partial pressure (Δ<fi>p>CO2) at the ocean surface within <fi>E. huxleyifi> blooms for polar and subpolar seas using an 18 year ocean color time series (1998-2015). When normalized to <fi>p>CO2 in the absence of bloom, the mean and maximum Δ<fi>p>CO2 values within the bloom areas varied between 21.0%-43.3% and 31.6%-62.5%, respectively. These results might have appreciable implications for climatology, marine chemistry, and ecology.

  1. Copper-catalyzed tandem reactions of 1-(2-iodoary)-2-yn-1-ones with isocyanides for the synthesis of 4-oxo-indeno[1,2-b]pyrroles.

    PubMed

    Cai, Qian; Zhou, Fengtao; Xu, Tianfeng; Fu, Liangbing; Ding, Ke

    2011-01-21

    A novel copper-catalyzed tandem reaction of 1-(2-iodoaryl)-2-yn-1-ones with isocyanides is described. The reaction is through a formal [3 + 2] cycloaddition/coupling tandem process and leads to efficient formation of 4-oxo-indeno[1,2-b]pyrroles.

  2. Low-voltage organic field effect transistors with a 2-tridecyl[1]benzothieno[3,2-b][1]benzothiophene semiconductor layer.

    PubMed

    Amin, Atefeh Y; Khassanov, Artoem; Reuter, Knud; Meyer-Friedrichsen, Timo; Halik, Marcus

    2012-10-10

    An asymmetric n-alkyl substitution pattern was realized in 2-tridecyl[1]benzothieno[3,2-b][1]benzothiophene (C(13)-BTBT) in order to improve the charge transport properties in organic thin-film transistors. We obtained large hole mobilities up to 17.2 cm(2)/(V·s) in low-voltage operating devices. The large mobility is related to densely packed layers of the BTBT π-systems at the channel interface dedicated to the substitution motif and confirmed by X-ray reflectivity measurements. The devices exhibit promising stability in continuous operation for several hours in ambient air.

  3. Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function

    PubMed Central

    1994-01-01

    Antigen-specific T cell activation requires the engagement of the T cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. The most extensively characterized pathway of costimulation has been that involving the interaction of CD28 and CTLA4 on the T cell with B7 (now termed B7-1) on antigen presenting cells. Recently, B7-2 a second costimulatory ligand for CTLA4, was described, demonstrating the potential complexity of costimulatory interactions. This report examines and compares the expression and function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2 can be expressed by multiple cell types, including B cells, T cells, macrophages, and dendritic cells, all of which are therefore candidate populations for delivering costimulatory signals mediated by these molecules; (b) stimulating B cells with either LPS or anti-IgD-dextran induced expression of both B7- 1 and B7-2, and peak expression of both costimulatory molecules occurred after 18-42 h of culture. Expression of B7-2 on these B cell populations was significantly higher than expression of B7-1 at all times assayed after stimulation; (c) blocking of B7-2 costimulatory activity inhibited TCR-dependent T cell proliferation and cytokine production, without affecting early consequences of TCR signaling such as induction of CD69 or interleukin 2 receptor alpha (IL-2R alpha); and (d) expression of B7-1 and of B7-2 can be regulated by a variety of stimuli. Moreover, expression of B7-1 and B7-2 can be independently regulated by the same stimulus, providing an additional complexity in the mechanisms available for regulating costimulation and hence immune response. PMID:7519245

  4. Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus

    PubMed Central

    Azzouz, Doua F.; Martin, Gabriel V.; Arnoux, Fanny; Balandraud, Nathalie; Martin, Thierry; Dubucquoi, Sylvain; Hachulla, Eric; Farge-Bancel, Dominique; Tiev, Kiet; Cabane, Jean; Bardin, Nathalie; Chiche, Laurent; Martin, Marielle; Caillet, Eléonore C.; Kanaan, Sami B.; Harlé, Jean Robert; Granel, Brigitte; Diot, Elisabeth; Roudier, Jean; Auger, Isabelle; Lambert, Nathalie C.

    2016-01-01

    In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.10−4) and 60% versus 28% (P = 3.10−8). Above all, EphB2 and THEX1 revealed to be mainly recognized by SLE sera samples with respectively 56%, (P = 2.10−10) and 82% (P = 5.10−13). As anti-EphB2 and anti-THEX1 AAb were found in both diseases, an epitope mapping was realized on each protein to refine SSc and SLE diagnosis. A 15-mer peptide from EphB2 allowed to identify 35% of SLE sera samples (N = 48) versus only 5% of any other sera samples (N = 157), including SSc sera samples. AAb titers were significantly higher in SLE sera (P<0.0001) and correlated with disease activity (p<0.02). We could not find an epitope on EphB2 protein for SSc neither on THEX1 for SSc or SLE. We showed that patients with SSc or SLE have AAb against EphB2, a protein involved in angiogenesis, and THEX1, a 3’-5’ exoribonuclease involved in histone mRNA degradation. We have further identified a peptide from EphB2 as a specific and sensitive tool for SLE diagnosis. PMID:27617966

  5. Alteration of the SETBP1 gene and splicing pathway genes SF3B1, U2AF1, and SRSF2 in childhood acute myeloid leukemia.

    PubMed

    Choi, Hyun-Woo; Kim, Hye-Ran; Baek, Hee-Jo; Kook, Hoon; Cho, Duck; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun

    2015-01-01

    Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood.

  6. 39 CFR 3010.13 - Proceedings for Type 1-A and Type 1-B rate adjustment filings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Proceedings for Type 1-A and Type 1-B rate... (Type 1-A and 1-B Rate Adjustments) § 3010.13 Proceedings for Type 1-A and Type 1-B rate adjustment... include: (1) The general nature of the proceeding; (2) A reference to legal authority to which the...

  7. Cyp1b1 Regulates Ocular Fissure Closure Through a Retinoic Acid–Independent Pathway

    PubMed Central

    Williams, Antionette L.; Eason, Jessica; Chawla, Bahaar; Bohnsack, Brenda L.

    2017-01-01

    Purpose Mutations in the CYP1B1 gene are the most commonly identified genetic causes of primary infantile-onset glaucoma. Despite this disease association, the role of CYP1B1 in eye development and its in vivo substrate remain unknown. In the present study, we used zebrafish to elucidate the mechanism by which cyp1b1 regulates eye development. Methods Zebrafish eye and neural crest development were analyzed using live imaging of transgenic zebrafish embryos, in situ hybridization, immunostaining, TUNEL assay, and methylacrylate sections. Cyp1b1 and retinoic acid (RA) levels were genetically (morpholino oligonucleotide antisense and mRNA) and pharmacologically manipulated to examine gene function. Results Using zebrafish, we observed that cyp1b1 was expressed in a specific spatiotemporal pattern in the ocular fissures of the developing zebrafish retina and regulated fissure patency. Decreased Cyp1b1 resulted in the premature breakdown of laminin in the ventral fissure and altered subsequent neural crest migration into the anterior segment. In contrast, cyp1b1 overexpression inhibited cell survival in the ventral ocular fissure and prevented fissure closure via an RA-independent pathway. Cyp1b1 overexpression also inhibited the ocular expression of vsx2, pax6a, and pax6b and increased the extraocular expression of shha. Importantly, embryos injected with human wild-type but not mutant CYP1B1 mRNA also showed colobomas, demonstrating the evolutionary and functional conservation of gene function between species. Conclusions Cyp1b1 regulation of ocular fissure closure indirectly affects neural crest migration and development through an RA-independent pathway. These studies provide insight into the role of Cyp1b1 in eye development and further elucidate the pathogenesis of primary infantile-onset glaucoma. PMID:28192799

  8. Role of PTP1B in HER2 Signaling in Breast Cancer

    DTIC Science & Technology

    2011-10-01

    AD_________________ Award Number: W81XWH-10-1-1005 TITLE: Role of PTP1B in HER2 Signaling in...AND SUBTITLE 5a. CONTRACT NUMBER Role of PTP1B in HER2 Signaling in Breast Cancer 5b. GRANT NUMBER W81XWH-10-1-1005 5c. PROGRAM ELEMENT...pathways. Recent reports have shown that Protein Tyrosine Phosphatase 1B ( PTP1B ) plays a positive role in ErbB2-induced breast cancer in vitroand

  9. CD22 Promotes B-1b Cell Responses to T Cell-Independent Type 2 Antigens.

    PubMed

    Haas, Karen M; Johnson, Kristen L; Phipps, James P; Do, Cardinal

    2018-03-01

    CD22 (Siglec-2) is a critical regulator of B cell activation and survival. CD22 -/- mice generate significantly impaired Ab responses to T cell-independent type 2 (TI-2) Ags, including haptenated Ficoll and pneumococcal polysaccharides, Ags that elicit poor T cell help and activate BCR signaling via multivalent epitope crosslinking. This has been proposed to be due to impaired marginal zone (MZ) B cell development/maintenance in CD22 -/- mice. However, mice expressing a mutant form of CD22 unable to bind sialic acid ligands generated normal TI-2 Ab responses, despite significantly reduced MZ B cells. Moreover, mice treated with CD22 ligand-binding blocking mAbs, which deplete MZ B cells, had little effect on TI-2 Ab responses. We therefore investigated the effects of CD22 deficiency on B-1b cells, an innate-like B cell population that plays a key role in TI-2 Ab responses. B-1b cells from CD22 -/- mice had impaired BCR-induced proliferation and significantly increased intracellular Ca 2+ concentration responses following BCR crosslinking. Ag-specific B-1b cell expansion and plasmablast differentiation following TI-2 Ag immunization was significantly impaired in CD22 -/- mice, consistent with reduced TI-2 Ab responses. We generated CD22 -/- mice with reduced CD19 levels (CD22 -/- CD19 +/- ) to test the hypothesis that augmented B-1b cell BCR signaling in CD22 -/- mice contributes to impaired TI-2 Ab responses. BCR-induced proliferation and intracellular Ca 2+ concentration responses were normalized in CD22 -/- CD19 +/- B-1b cells. Consistent with this, TI-2 Ag-specific B-1b cell expansion, plasmablast differentiation, survival, and Ab responses were rescued in CD22 -/- CD19 +/- mice. Thus, CD22 plays a critical role in regulating TI-2 Ab responses through regulating B-1b cell signaling thresholds. Copyright © 2018 by The American Association of Immunologists, Inc.

  10. Diversity in peptide recognition by the SH2 domain of SH2B1.

    PubMed

    McKercher, Marissa A; Guan, Xiaoyang; Tan, Zhongping; Wuttke, Deborah S

    2018-02-01

    SH2B1 is a multidomain protein that serves as a key adaptor to regulate numerous cellular events, such as insulin, leptin, and growth hormone signaling pathways. Many of these protein-protein interactions are mediated by the SH2 domain of SH2B1, which recognizes ligands containing a phosphorylated tyrosine (pY), including peptides derived from janus kinase 2, insulin receptor, and insulin receptor substrate-1 and -2. Specificity for the SH2 domain of SH2B1 is conferred in these ligands either by a hydrophobic or an acidic side chain at the +3 position C-terminal to the pY. This specificity for chemically disparate species suggests that SH2B1 relies on distinct thermodynamic or structural mechanisms to bind to peptides. Using binding and structural strategies, we have identified unique thermodynamic signatures for each peptide binding mode, and several SH2B1 residues, including K575 and R578, that play distinct roles in peptide binding. The high-resolution structure of the SH2 domain of SH2B1 further reveals conformationally plastic protein loops that may contribute to the ability of the protein to recognize dissimilar ligands. Together, numerous hydrophobic and electrostatic interactions, in addition to backbone conformational flexibility, permit the recognition of diverse peptides by SH2B1. An understanding of this expanded peptide recognition will allow for the identification of novel physiologically relevant SH2B1/peptide interactions, which can contribute to the design of obesity and diabetes pharmaceuticals to target the ligand-binding interface of SH2B1 with high specificity. © 2017 Wiley Periodicals, Inc.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Do, Minh Truong; Kim, Hyung Gyun; Tran, Thi Thu Phuong

    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 andmore » 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

  12. Identification of a conserved B-cell epitope on duck hepatitis A type 1 virus VP1 protein.

    PubMed

    Wu, Xiaoying; Li, Xiaojun; Zhang, Qingshan; Wulin, Shaozhou; Bai, Xiaofei; Zhang, Tingting; Wang, Yue; Liu, Ming; Zhang, Yun

    2015-01-01

    The VP1 protein of duck hepatitis A virus (DHAV) is a major structural protein that induces neutralizing antibodies in ducks; however, B-cell epitopes on the VP1 protein of duck hepatitis A genotype 1 virus (DHAV-1) have not been characterized. To characterize B-cell epitopes on VP1, we used the monoclonal antibody (mAb) 2D10 against Escherichia coli-expressed VP1 of DHAV-1. In vitro, mAb 2D10 neutralized DHAV-1 virus. By using an array of overlapping 12-mer peptides, we found that mAb 2D10 recognized phages displaying peptides with the consensus motif LPAPTS. Sequence alignment showed that the epitope 173LPAPTS178 is highly conserved among the DHAV-1 genotypes. Moreover, the six amino acid peptide LPAPTS was proven to be the minimal unit of the epitope with maximal binding activity to mAb 2D10. DHAV-1-positive duck serum reacted with the epitope in dot blotting assay, revealing the importance of the six amino acids of the epitope for antibody-epitope binding. Competitive inhibition assays of mAb 2D10 binding to synthetic LPAPTS peptides and truncated VP1 protein fragments, detected by Western blotting, also verify that LPAPTS was the VP1 epitope. We identified LPAPTS as a VP1-specific linear B-cell epitope recognized by the neutralizing mAb 2D10. Our findings have potential applications in the development of diagnostic techniques and epitope-based marker vaccines against DHAV-1.

  13. Determination of evolutionary relationships of outbreak-associated Listeria monocytogenes strains of serotypes 1/2a and 1/2b by whole-genome sequencing

    USDA-ARS?s Scientific Manuscript database

    We used whole-genome sequencing to determine evolutionary relationships among 20 outbreak-associated clinical isolates of Listeria monocytogenes serotypes 1/2a and 1/2b. Isolates from 6 of 11 outbreaks fell outside the clonal groups or “epidemic clones” that have been previously associated with outb...

  14. Absence of B1-B2 structural transition in lithium halides under hydrostatic pressure

    NASA Astrophysics Data System (ADS)

    de Coss, Romeo; Murrieta, Gabriel

    2005-03-01

    We have investigated the B1-B2 structural transition in LiF, LiCl, LiBr, and LiI under hydrostatic pressure by means of first-principles total-energy calculations using the Full- Potential LAPW method. In order to analyze the gradient effects, we have performed calculations using the local density approximation (LDA) and the generalized gradient approximation (GGA), for the exchange and correlation potential. In agreement with the experimental observations, we find that even for pressures higher than 100 GPa, the Li halides do not present the B1-B2 structural transition. In order to understand this behavior, we have calculated the distribution of the electron densities. From the analysis of the distribution of electron densities for the Li halides in the B1 and B2 phases, we find that for this group of ionic compounds the B1 phase have a distribution of electron densities more homogeneous than in the B2 phase, preventing the B1-B2 structural transition. This work was partially supported by Consejo Nacional de Ciencia y Tecnolog'ia (CONACYT, M'exico) under Grant No. 43830-F.

  15. A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells.

    PubMed

    Hadland, Brandon K; Varnum-Finney, Barbara; Mandal, Pankaj K; Rossi, Derrick J; Poulos, Michael G; Butler, Jason M; Rafii, Shahin; Yoder, Mervin C; Yoshimoto, Momoko; Bernstein, Irwin D

    2017-06-06

    Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs). However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Test wells SF-1A, 1B, 1C, and SF-2A, 2B, 2C, Santa Fe County, New Mexico

    USGS Publications Warehouse

    Hart, D.L.

    1989-01-01

    Two well nests, SF-1 and SF-2, were drilled in Santa Fe County, New Mexico, to monitor the hydraulic head within selected zones of the aquifer. Each well nest consists of three piezometers of shallow, middle, and deep completion within the aquifer. Each set of wells was drilled to a depth of about 2,000 ft before actual construction of the piezometers. Each piezometer was completed using either 5 or 10 ft of wire-wrapped screen. These piezometers were constructed as part of a larger ongoing program with the Santa Fe Metropolitan Water Board and New Mexico State Engineer Office to establish a regional observation-well network and to define better the groundwater flow system in the vicinity of Santa Fe and Santa Fe well fields. (USGS)

  17. INTERFERON α ACTIVATES NF-κ B IN JAK1-DEFICIENT CELLS THROUGH A TYK2-DEPENDENT PATHWAY

    PubMed Central

    Yang, Chuan He; Murti, Aruna; Valentine, William J.; Du, Ziyun; Pfeffer, Lawrence M.

    2005-01-01

    In addition to activating members of the STAT transcription factor family, IFN α/β activates the NF-κ B transcription factor. To determine the role of the JAK-STAT pathway in NF-κ B activation by IFN, we examined NF-κ B activation in JAK1-deficient mutant human fibrosarcoma cells. In wild-type fibrosarcoma cells (2fTGH) IFN activates STAT1, STAT2 and STAT3, as well as NF-κB complexes comprised of p50 and p65. In contrast, in JAK1-deficient cells IFN induces NF-κB activation and NF-κB dependent gene transcription, but does not activate these STAT proteins and has no effect on STAT-dependent gene transcription. Expression of a catalytically-inactive TYK2 tyrosine kinase in JAK1-deficient cells, as well as in the highly IFN-sensitive Daudi lymphoblastoid cell line, abrogates NF-κB activation by IFN. Moreover, IFN does not promote NF-κB activation in TYK2-deficient mutant fibrosarcoma cells. Our results demonstrate a dichotomy between the classical JAK-STAT pathway and the NF-κB signaling pathway. In the IFN signaling pathway leading to STAT activation both JAK1 and TYK2 are essential, while NF-κB activation requires only TYK2. PMID:15883164

  18. Protein Phosphotyrosine Phosphatase 1B (PTP1B) in Calpain-dependent Feedback Regulation of Vascular Endothelial Growth Factor Receptor (VEGFR2) in Endothelial Cells

    PubMed Central

    Zhang, Yixuan; Li, Qiang; Youn, Ji Youn; Cai, Hua

    2017-01-01

    The VEGF/VEGFR2/Akt/eNOS/NO pathway is essential to VEGF-induced angiogenesis. We have previously discovered a novel role of calpain in mediating VEGF-induced PI3K/AMPK/Akt/eNOS activation through Ezrin. Here, we sought to identify possible feedback regulation of VEGFR2 by calpain via its substrate protein phosphotyrosine phosphatase 1B (PTP1B), and the relevance of this pathway to VEGF-induced angiogenesis, especially in diabetic wound healing. Overexpression of PTP1B inhibited VEGF-induced VEGFR2 and Akt phosphorylation in bovine aortic endothelial cells, while PTP1B siRNA increased both, implicating negative regulation of VEGFR2 by PTP1B. Calpain inhibitor ALLN induced VEGFR2 activation, which can be completely blocked by PTP1B overexpression. Calpain activation induced by overexpression or Ca/A23187 resulted in PTP1B cleavage, which can be blocked by ALLN. Moreover, calpain activation inhibited VEGF-induced VEGFR2 phosphorylation, which can be restored by PTP1B siRNA. These data implicate calpain/PTP1B negative feedback regulation of VEGFR2, in addition to the primary signaling pathway of VEGF/VEGFR2/calpain/PI3K/AMPK/Akt/eNOS. We next examined a potential role of PTP1B in VEGF-induced angiogenesis. Endothelial cells transfected with PTP1B siRNA showed faster wound closure in response to VEGF. Aortic discs isolated from PTP1B siRNA-transfected mice also had augmented endothelial outgrowth. Importantly, PTP1B inhibition and/or calpain overexpression significantly accelerated wound healing in STZ-induced diabetic mice. In conclusion, our data for the first time demonstrate a calpain/PTP1B/VEGFR2 negative feedback loop in the regulation of VEGF-induced angiogenesis. Modulation of local PTP1B and/or calpain activities may prove beneficial in the treatment of impaired wound healing in diabetes. PMID:27872190

  19. Sub-femtosecond quantum dynamics of the strong-field ionization of water to the X ̃(2)B1 and Ã(2)A1 states of the cation.

    PubMed

    Jayachander Rao, B; Varandas, A J C

    2015-03-07

    Motivated by recent efforts to achieve sub-femtosecond structural resolution in various molecular systems, we have performed a femtosecond quantum dynamics study of the water cation in the X ̃(2)B1 and Ã(2)A1 electronic states. Autocorrelation functions for H2O(+) and D2O(+) are calculated for such electronic states by solving numerically the time-dependent Schrödinger equation. From the ratio of the squared autocorrelation functions of D2O(+) and H2O(+), the high-order harmonic generation signals are calculated. Substantial vibrational dynamics is found in the Ã(2)A1 state as compared to the one in X ̃(2)B1, which supports recent experimental findings of Farrell et al., Phys. Rev. Lett., 2011, 107, 083001. Maxima in the above ratio are also predicted at ∼1.1 fs and ∼1.6 fs for the X ̃(2)B1 and Ã(2)A1 states, respectively. The expectation values of the positions of the atoms in H2O(+) as a function of time reveal a strong excitation of the bending mode in the Ã(2)A1 state, which explains the observed vibrational dynamics. The peaks in the ratios of the squared autocorrelation functions are also explained in terms of the evolving geometries of the water cation.

  20. QSAR studies in substituted 1,2,3,4,6,7,12,12a-octa-hydropyrazino[2',1':6,1]pyrido[3,4-b]indoles--a potent class of neuroleptics.

    PubMed

    Saxena, Anil K; Ram, Siya; Saxena, Mridula; Singh, Nidhi; Prathipati, Philip; Jain, Padam C; Singh, H K; Anand, Nitya

    2003-05-01

    A series of nineteen substituted 1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3, 4-b]indoles analogues of neuroleptic drug, Centbutindole have been studied using quantitative structure-activity relationship analysis. The derived models display good fits to the experimental data (r>or=0.75) having good predictive power (r(cv)>or=0.688). The best model describes a high correlation between predicted and experimental activity data (r=0.967). Statistical analysis of the equation populations indicates that hydrophobicity (as measured by pi(R), logP(o/w) and SlogP_VSA8), dipole y and structural parameters in terms of indicator variable, (In(1)) and globularity are important variables in describing the variation in the neuroleptic activity in the series.

  1. Global Profiling of hnRNP A2/B1-RNA Binding on Chromatin Highlights LncRNA Interactions.

    PubMed

    Nguyen, Eric D; Balas, Maggie M; Griffin, April M; Roberts, Justin T; Johnson, Aaron M

    2018-06-23

    Long noncoding RNAs (lncRNAs) often carry out their functions through associations with adaptor proteins. We recently identified heterogeneous ribonucleoprotein (hnRNP) A2/B1 as an adaptor of the human HOTAIR lncRNA. hnRNP A2 and B1 are splice isoforms of the same gene. The spliced version of HOTAIR preferentially associates with the B1 isoform, which we hypothesize contributes to RNA-RNA matching between HOTAIR and transcripts of target genes in breast cancer. Here we used enhanced cross-linking immunoprecipitation (eCLIP) to map the direct interactions between A2/B1 and RNA in breast cancer cells. Despite differing by only twelve amino acids, the A2 and B1 splice isoforms associate preferentially with distinct populations of RNA in vivo. Through cellular fractionation experiments we characterize the pattern of RNA association in chromatin, nucleoplasm, and cytoplasm. We find that a majority of interactions occur on chromatin, even those that do not contribute to co-transcriptional splicing. A2/B1 binding site locations on multiple RNAs hint at a contribution to the regulation and function of lncRNAs. Surprisingly, the strongest A2/B1 binding site occurs in a retained intron of HOTAIR, which interrupts an RNA-RNA interaction hotspot. In vitro eCLIP experiments highlight additional exonic B1 binding sites in HOTAIR which also surround the RNA-RNA interaction hotspot. Interestingly, a version of HOTAIR with the intron retained is still capable of making RNA-RNA interactions in vitro through the hotspot region. Our data further characterize the multiple functions of a repurposed splicing factor with isoform-biased interactions, and highlight that the majority of these functions occur on chromatin-associated RNA.

  2. BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression

    PubMed Central

    Xu, Peng; Raetz, Elizabeth A.; Kitagawa, Mayumi; Virshup, David M.; Lee, Sang Hyun

    2013-01-01

    Summary BUBR1 is a mitotic phosphoprotein essential for the maintenance of chromosome stability by promoting chromosome congression and proper kinetochore–microtubule (K-fiber) attachment, but the underlying mechanism(s) has remained elusive. Here we identify BUBR1 as a binding partner of the B56 family of Protein Phosphatase 2A regulatory subunits. The interaction between BUBR1 and the B56 family is required for chromosome congression, since point mutations in BUBR1 that block B56 binding abolish chromosome congression. The BUBR1:B56-PP2A complex opposes Aurora B kinase activity, since loss of the complex can be reverted by inhibiting Aurora B. Importantly, we show that the failure of BUBR1 to recruit B56-PP2A also contributes to the chromosome congression defects found in cells derived from patients with the Mosaic Variegated Aneuploidy (MVA) syndrome. Together, we propose that B56-PP2A is a key mediator of BUBR1's role in chromosome congression and functions by antagonizing Aurora B activity at the kinetochore for establishing stable kinetochore–microtubule attachment at the metaphase plate. PMID:23789096

  3. Effect of Microwave Wi-Fi Radiation at Frequency of 2.4 GHz on Epileptic Behavior of Rats

    PubMed Central

    A., Mahmoudi; M.B., Shojaeifard; S., Nematollahii; S.M.J., Mortazavi; A.R., Mehdizadeh

    2018-01-01

    Background: Electromagnetic fields (EMF) with different intensities are widely used at home, offices and public places.Today, there is a growing global concern about the effects of human exposure to EMFs. Epilepsy is one of the most common chronic neurological diseases, affecting 50 million people of all ages worldwide. We aimed to investigate the effect of exposure to Wi-Fi radiation on epileptic behavior of rats. Materials and Methods: 147 male rats, weighing 200-250 g, were divided into seven groups; negative control (no intervention), sham 1(distilled water), positive control (Pentylentetrazol [PTZ]), intervention group 1 (PTZ + Wi-Fi “off”), sham 2 (distilled water + Wi-Fi “off”), sham 3 (distilled water + Wi-Fi “on”), and intervention group 2 (PTZ + Wi-Fi “on”). The rats were exposed to Wi-Fi for 2h at a distance of 30cm from a commercial Wi-Fi router. Convulsive behaviors of rats were monitored and scored based on the intensity and type by measuring latency/threshold time, number of convulsions, sum of scores and durations of seizure, and duration of score 6 seizure. Kruskal-Wallis and Mann-Whitney U-tests were used to analyze the data. Results: Convulsion was observed in interventions Group 4 and Group 7, and positive control. The mean number of events, and sum of scores were significantly different in intervention 2 than other two groups. However, the differences in mean threshold, mean sum of durations and “ time to show convulsion with score 6 ” were not statistically significant (P>0.05). Conclusion: Due to limitations of our study including the sample size, these findings should be interpreted with caution. In this study, exposure to 2.4 GHz Wi-Fi radiation showed significant beneficial effects on the epileptic behaviour of rats. More experiments are needed to verify if these exposures can be used as a therapeutic approach for amelioration of seizures in epilepsy. PMID:29951445

  4. Impacts of the Glucuronidase Genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on Tamoxifen Metabolism in Breast Cancer Patients

    PubMed Central

    Romero-Lorca, Alicia; Novillo, Apolonia; Gaibar, María; Bandrés, Fernando; Fernández-Santander, Ana

    2015-01-01

    Tamoxifen is used to prevent and treat estrogen-dependent breast cancer. It is described as a prodrug since most of its antiestrogen effects are exerted through its hydroxylated metabolites 4-OH-tamoxifen and endoxifen. In prior work, we correlated optimal plasma levels of these metabolites with certain genotypes of CYP2D6 and SULT1A2. This descriptive study examines correlations between concentrations of tamoxifen's glucuronide metabolites and genotypes UGT1A4 Pro24Thr, UGT1A4 Leu48Val, UGT2B7 His268Tyr, UGT2B15 Asp85YTyr UGT2B15 Lys523Thr and UGT2B17del in 132 patients with estrogen receptor-positive breast cancer under treatment with tamoxifen. Patients were genotyped by real-time and conventional PCR-RFLP. The glucuronides 4-OH-tamoxifen-N-glucuronide, 4-OH-tamoxifen-O-glucuronide and endoxifen-O-glucuronide were isolated from blood plasma and quantified using a high-pressure liquid chromatography-tandem mass spectrometry system. Individuals who were homozygous for UGT1A448VAL showed significantly lower mean concentrations of both glucuronide metabolites compared to subjects genotyped as wt/wt plus wt/48Val (p=0.037 and p=0.031, respectively). Women homozygous for UGT2B7268Tyr also showed mean substrate/product ratios of 4-OH-tamoxifen/4-OH-tamoxifen-O-glucuronide and 4-OH-tamoxifen/4-OH-tamoxifen-N-glucuronide indicative of reduced glucuronidase activity compared to wt homozygotes or to heterozygotes for the polymorphism (p=0.005 and p=0.003, respectively). In contrast, UGT2B15 Lys523Thr and UGT2B17del were associated with possibly increased enzyme activity. Patients with at least one variant allele UGT2B15523Thr showed significantly higher 4-OH-tamoxifen-O-glucuronide and endoxifen-glucuronide levels (p=0.023 and p=0.025, respectively) indicating a variant gene-dose effect. Higher 4-OH-tamoxifen-N-glucuronide levels observed in UGT2B17del genotypes (p=0.042) could be attributed to a mechanism that compensates for the greater expression of other genes in UGT2B

  5. Genetic polymorphism of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer risk.

    PubMed

    Xu, Hua; Ding, Qiang; Jiang, Hao-Wen

    2014-01-01

    We aimed to investigate the associations between polymorphisms of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer (PCa) risk. A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to August 3, 2014 was performed. Methodological quality assessment of the trials was based on a standard quality scoring system. The meta-analysis was performed using STATA 12.0. We included 9 studies (1 study for IL-1A, 5 studies for IL-1B, and 3 studies for IL-1RN), and significant association was found between polymorphisms of IL-1B-511 (rs16944) as well as IL-1B-31 (rs1143627) and PCa risk. IL-1B-511 (rs16944) polymorphism was significantly associated with PCa risk in homozygote and recessive models, as well as allele contrast (TT vs CC: OR, 0.74; 95%CI, 0.58-0.94; P=0.012; TT vs TC+CC; OR, 0.79; 95%CI, 0.63-0.98; P=0.033; T vs C: OR, 0.86; 95%CI, 0.77-0.96; P=0.008). The association between IL-1B-31 (rs1143627) polymorphism and PCa risk was weakly significant under a heterozygote model (OR, 1.35; 95%CI, 1.00-1.80; P=0.047). Sequence variants in IL-1B-511 (rs16944) and IL-1B-31 (rs1143627) are significantly associated with PCa risk, which provides additional novel evidence that proinflammatory cytokines and inflammation play an important role in the etiology of PCa.

  6. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis.

    PubMed

    Ren, Decheng; Zhou, Yingjiang; Morris, David; Li, Minghua; Li, Zhiqin; Rui, Liangyou

    2007-02-01

    SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (alpha, beta, gamma, and/or delta) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1beta was specifically expressed in neural tissue in SH2B1-transgenic (SH2B1(Tg)) mice. SH2B1(Tg) mice were crossed with SH2B1-knockout (SH2B1(KO)) mice to generate SH2B1(TgKO) mice expressing SH2B1 only in neural tissue but not in other tissues. Systemic deletion of the SH2B1 gene resulted in metabolic disorders in SH2B1(KO) mice, including hyperlipidemia, leptin resistance, hyperphagia, obesity, hyperglycemia, insulin resistance, and glucose intolerance. Neuron-specific restoration of SH2B1beta not only corrected the metabolic disorders in SH2B1(TgKO) mice, but also improved JAK2-mediated leptin signaling and leptin regulation of orexigenic neuropeptide expression in the hypothalamus. Moreover, neuron-specific overexpression of SH2B1 dose-dependently protected against high-fat diet-induced leptin resistance and obesity. These observations suggest that neuronal SH2B1 regulates energy balance, body weight, peripheral insulin sensitivity, and glucose homeostasis at least in part by enhancing hypothalamic leptin sensitivity.

  7. Different patterns of supramolecular assembly in constitutionally similar 6-arylimidazo[2,1-b][1,3,4]thiadiazoles.

    PubMed

    Praveen, Aletti S; Yathirajan, Hemmige S; Kaur, Manpreet; Narayana, Badiadka; Hosten, Eric C; Betz, Richard; Glidewell, Christopher

    2014-09-01

    Four imidazo[2,1-b][1,3,4]thiadiazoles containing a simply-substituted 6-aryl group have been synthesized by reaction of 2-amino-1,3,4-thiadiazoles with bromoacetylarenes using microwave irradiation and brief reaction times. 6-(2-Chlorophenyl)imidazo[2,1-b][1,3,4]thiadiazole, C(10)H(6)ClN(3)S, (I), 6-(2-chlorophenyl)-2-methylimidazo[2,1-b][1,3,4]thiadiazole, C(11)H(8)ClN(3)S, (II), 6-(3,4-dichlorophenyl)imidazo[2,1-b][1,3,4]thiadiazole, C(10)H(5)Cl(2)N(3)S, (III), and 6-(4-fluoro-3-methoxyphenyl)-2-methylimidazo[2,1-b][1,3,4]thiadiazole, C(12)H(10)FN(3)OS, (IV), crystallize with Z' values of 2, 1, 1 and 2 respectively. The molecular skeletons are all nearly planar and the dihedral angles between the imidazole and aryl rings are 1.51 (8) and 7.28 (8)° in (I), 9.65 (7)° in (II), 10.44 (8)° in (III), and 1.05 (8) and 7.21 (8)° in (IV). The molecules in (I) are linked by three independent C-H...N hydrogen bonds to form ribbons containing alternating R2(2)(8) and R4(4)(18) rings, and these ribbons are linked into a three-dimensional array by three independent π-stacking interactions. Both (II) and (III) contain centrosymmetric dimers formed by π-stacking interactions but hydrogen bonds are absent, and the molecules of (IV) are linked into centrosymmetric R2(2)(8) dimers by C-H...N hydrogen bonds. Comparisons are made with a number of related compounds.

  8. Renner-Teller quantum dynamics of NH(a(1)Delta) + H reactions on the NH(2) A(2)A(1) and X(2)B(1) coupled surfaces.

    PubMed

    Defazio, P; Gamallo, P; González, M; Petrongolo, C

    2010-09-16

    Four reactions NH(a1Delta) + H′(2S) are investigated by the quantum mechanical real wavepacket method, taking into account nonadiabatic Renner-Teller (RT) and rovibronic Coriolis couplings between the involved states. We consider depletion (d) to N(2D) + H2(X1Sigmag+), exchange (e) to NH′(a1Delta) + H(2S), quenching (q) to NH(X3Sigma-) + H′(2S), and exchange-quenching (eq) to NH′(X3Sigma-) + H(2S). We extend our RT theory to a general AB + C collision using a geometry-dependent but very simple and empirical RT matrix element. Reaction probabilities, cross sections, and rate constants are presented, and RT results are compared with Born-Oppenheimer (BO), experimental, and semiclassical data. The nonadiabatic couplings open two new channels, (q) and (eq), and increase the (d) and (e) reactivity with respect to the BO one, when NH(a1Delta) is rotationally excited. In this case, the quantum cross sections are larger than the semiclassical ones at low collision energies. The calculated rate constants at 300 K are k(d) = 3.06, k(e) = 3.32, k(q) = 1.44, and k(eq) = 1.70 in 10(-11) cm3 s(-1) compared with the measured values k(d) = (3.2 =/- 1.7), k(q + eq) = (1.7 +/- 0.3), and k(total) = (4.8 +/- 1.7). The theoretical depletion rate is thus in good agreement with the experimental value, but the quenching and total rates are overestimated, because the present RT couplings are too large. This discrepancy is probably due to our simple and empirical RT matrix element.

  9. Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population.

    PubMed

    Lee, K W; Oh, D H; Lee, C; Yang, S Y

    2005-05-01

    High-resolution human leukocyte antigen (HLA) typing exposes the unique patterns of HLA allele and haplotype frequencies in each population. In this study, HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were analyzed in 485 apparently unrelated healthy Korean individuals. A total of 20 HLA-A, 43 HLA-B, 21 HLA-C, 31 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. Eleven alleles (A*0201, A*1101, A*2402, A*3303, B*1501, Cw*0102, Cw*0302, Cw*0303, DQB1*0301, DQB1*0302, and DQB1*0303) were found in more than 10% of the population. In each serologic group, a maximum of three alleles were found with several exceptions (A2, B62, DR4, DR14, and DQ6). In each serologic group exhibiting multiple alleles, two major alleles were present at 62-96% (i.e. A*0201 and A*0206 comprise 85% of A2-positive alleles). Multiple-locus haplotypes estimated by the maximum likelihood method revealed 51 A-C, 43 C-B, 52 B-DRB1, 34 DRB1-DQB1, 48 A-C-B, 42 C-B-DRB1, 46 B-DRB1-DQB1, and 30 A-C-B-DRB1-DQB1 haplotypes with frequencies of more than 0.5%. In spite of their high polymorphism in B and DRB1, identification of relatively small numbers of two-locus (B-C and DRB1-DQB1) haplotypes suggested strong associations of those two loci, respectively. Five-locus haplotypes defined by high-resolution DNA typing correlated well with previously identified serology-based haplotypes in the population. The five most frequent haplotypes were: A*3303-Cw*1403-B*4403-DRB1*1302-DQB1*0604 (4.2%), A*3303-Cw*0701/6-B*4403-DRB1*0701-DQB1*0201/2 (3.0%), A*3303-Cw*0302-B*5801-DRB1*1302-DQB1*0609 (3.0%), A*2402-Cw*0702-B*0702-DRB1*0101-DQB1*0501 (2.9%), and A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0201/2 (2.7%). Several sets of allele level haplotypes that could not be discriminated by routine HLA-A, -B, and -DRB1 low-resolution typing originated from allelic diversity of A2, B61, DR4, and DR8 serologic groups. Information obtained in this study will be useful for medical and forensic applications as well as in anthropology.

  10. 26 CFR 1.475(b)-2 - Exemptions-identification requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requirements. (a) Identification of the basis for exemption. An identification of a security as exempt from mark to market does not satisfy section 475(b)(2) if it fails to state whether the security is described in— (1) Either of the first two subparagraphs of section 475(b)(1) (identifying a security as held...

  11. Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.

    PubMed

    Gose, Tomoka; Nakanishi, Takeo; Kamo, Shunsuke; Shimada, Hiroaki; Otake, Katsumasa; Tamai, Ikumi

    2016-01-01

    Eicosapentaenoic acid (EPA)-derived prostaglandin E3 (PGE3) possesses an anti-inflammatory effect; however, information for transporters that regulate its peri-cellular concentration is limited. The present study, therefore, aimed to clarify transporters involved in local disposition of PGE3. PGE3 uptake was assessed in HEK293 cells transfected with OATP2A1/SLCO2A1, OATP1B1/SLCO1B1, OATP2B1/SLCO2B1, OAT1/SLC22A6, OCT1/SLC22A1 or OCT2/SLC22A2 genes, compared with HEK293 cells transfected with plasmid vector alone (Mock). PGE3 uptake by OATP2A1-expressing HEK293 cells (HEK/2A1) was the highest and followed by HEK/1B1, while no significantly higher uptake of PGE3 than Mock cells was detected by other transporters. Saturation kinetics in PGE3 uptake by HEK/2A1 estimated the Km as 7.202 ± 0.595 μM, which was 22 times higher than that of PGE2 (Km=0.331 ± 0.131 μM). Furthermore, tissue disposition of PGE3 was examined in wild-type (WT) and Slco2a1-deficient (Slco2a1(-/-)) mice after oral administration of EPA ethyl ester (EPA-E) when they underwent intraperitoneal injection of endotoxin (e.g., lipopolysaccharide). PGE3 concentration was significantly higher in the lung, and tended to increase in the colon, stomach, and kidney of Slco2a1(-/-), compared to WT mice. Ratio of PGE2 metabolite 15-keto PGE2 over PGE2 concentration was significantly lower in the lung and colon of Slco2a1(-/-) than that of WT mice, suggesting that PGE3 metabolism is downregulated in Slco2a1(-/-) mice. In conclusion, PGE3 was found to be a substrate of OATP2A1, and local disposition of PGE3 could be regulated by OATP2A1 at least in the lung. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. A Categorification of the Crystal Isomorphism B 1,1 B + B(Lambda i) = B(Lambdasigma (i) and a Graphical Calculus for the Shifted Symmetric Functions

    NASA Astrophysics Data System (ADS)

    Kvinge, Henry

    We prove two results at the intersection of Lie theory and the representation theory of symmetric groups, Hecke algebras, and their generalizations. The first is a categorification of the crystal isomorphism B. (1,1) tensor B1,1B(Lambdai ) ≅ B(Lambdasigma (i)). Here B(Lambdai and B(Lambda sigma(i)) are two affine type highest weight crystals of weight Lambdai and Lambdasigma (i) respectively, sigma is a specific map from the Dynkin indexing set I to itself, and B1,1 is a Kirillov-Reshetikhin crystal. We show that this crystal isomorphism is in fact the shadow of a richer module-theoretic phenomenon in the representation theory of Khovanov-Lauda-Rouquier algebras of classical affine type. Our second result identifies the center EndH'( 1) of Khovanov's Heisenberg category H', as the algebra of shifted symmetric functions Lambda* of Okounkov and Olshanski, i.e. End H'(1) ≅ Lambda*. This isomorphism provides us with a graphical calculus for Lambda*. It also allows us to describe EndH'(1) in terms of the transition and co-transition measure of Kerov and the noncommutative probability spaces of Biane.

  13. A note on 4D heterotic string vacua, FI-terms and the swampland

    NASA Astrophysics Data System (ADS)

    Aldazabal, Gerardo; Ibáñez, Luis E.

    2018-07-01

    We present a conjecture for the massless sector of perturbative 4D N = 1 heterotic (0 , 2) string vacua, including U(1) n gauge symmetries, one of them possibly anomalous (like in standard heterotic compactifications). Mathematically it states that the positive hull generated by the charges of the massless chiral multiplets spans a sublattice of the full charge lattice. We have tested this conjecture in many heterotic N = 1 compactifications in 4D. Our motivation for this conjecture is that it allows to understand a very old puzzle in (0 , 2) N = 1 heterotic compactification with an anomalous U (1). The conjecture guarantees that there is always a D-flat direction cancelling the FI-term and restoring N = 1 SUSY in a nearby vacuum. This is something that has being verified in the past in a large number of cases, but whose origin has remained obscure for decades. We argue that the existence of a lattice generated by massless states guarantees the instability of heterotic non-BPS extremal blackholes, as required by Weak Gravity Conjecture arguments. Thus the pervasive existence of these nearby FI-cancelling vacua would be connected with WGC arguments.

  14. Soliton cellular automaton associated with Dn(1)-crystal B2,s

    NASA Astrophysics Data System (ADS)

    Misra, Kailash C.; Wilson, Evan A.

    2013-04-01

    A solvable vertex model in ferromagnetic regime gives rise to a soliton cellular automaton which is a discrete dynamical system in which site variables take on values in a finite set. We study the scattering of a class of soliton cellular automata associated with the U_q(D_n^{(1)})-perfect crystal B2, s. We calculate the combinatorial R matrix for all elements of B2, s ⊗ B2, 1. In particular, we show that the scattering rule for our soliton cellular automaton can be identified with the combinatorial R matrix for U_q(A_1^{(1)}) oplus U_q(D_{n-2}^{(1)})-crystals.

  15. Complete Genome Sequences of 12 Isolates of Listeria monocytogenes Belonging to Serotypes 1/2a, 1/2b, and 4b Obtained from Food Products and Food-Processing Environments in Canada.

    PubMed

    Mottawea, Walid; Chen, Shu; Saleh-Lakha, Saleema; Belanger, Sebastien; Ogunremi, Dele

    2017-05-11

    Listeria monocytogenes is the etiological agent for an often fatal foodborne illness known as listeriosis. Here, we present the complete genome sequences of 12 L. monocytogenes isolates representing the three most common serotypes of this pathogen (1/2a, 1/2b, and 4b), collected in Canada from different food products and environmental sources. © Crown copyright 2017.

  16. Impact of a future H2-based road transportation sector on the composition and chemistry of the atmosphere - Part 1: Tropospheric composition and air quality

    NASA Astrophysics Data System (ADS)

    Wang, D.; Jia, W.; Olsen, S. C.; Wuebbles, D. J.; Dubey, M. K.; Rockett, A. A.

    2013-07-01

    Vehicles burning fossil fuel emit a number of substances that change the composition and chemistry of the atmosphere, and contribute to global air and water pollution and climate change. For example, nitrogen oxides and volatile organic compounds (VOCs) emitted as byproducts of fossil fuel combustion are key precursors to ground-level ozone and aerosol formation. In addition, on-road vehicles are major CO2 emitters. In order to tackle these problems, molecular hydrogen (H2) has been proposed as an energy carrier to substitute for fossil fuels in the future. However, before implementing any such strategy it is crucial to evaluate its potential impacts on air quality and climate. Here, we evaluate the impact of a future (2050) H2-based road transportation sector on tropospheric chemistry and air quality for several possible growth and technology adoption scenarios. The growth scenarios are based on the high and low emissions Intergovernmental Panel on Climate Change Special Report on Emissions Scenarios, A1FI and B1, respectively. The technological adoption scenarios include H2 fuel cell and H2 internal combustion engine options. The impacts are evaluated with the Community Atmospheric Model Chemistry global chemistry transport model (CAM-Chem). Higher resolution simulations focusing on the contiguous United States are also carried out with the Community Multiscale Air Quality Modeling System (CMAQ) regional chemistry transport model. For all scenarios future air quality improves with the adoption of a H2-based road transportation sector; however, the magnitude and type of improvement depend on the scenario. Model results show that the adoption of H2 fuel cells would decrease tropospheric burdens of ozone (7%), CO (14%), NOx (16%), soot (17%), sulfate aerosol (4%), and ammonium nitrate aerosol (12%) in the A1FI scenario, and would decrease those of ozone (5%), CO (4%), NOx (11%), soot (7%), sulfate aerosol (4%), and ammonium nitrate aerosol (9%) in the B1 scenario

  17. Unprecedented intramolecular [3 + 2] cycloadditions of azido-ketenimines and azido-carbodiimides. Synthesis of indolo[1,2-a]quinazolines and tetrazolo[5,1-b]quinazolines.

    PubMed

    Alajarin, Mateo; Bonillo, Baltasar; Ortin, Maria-Mar; Orenes, Raul-Angel; Vidal, Angel

    2011-10-07

    N-(2-azidomethyl)phenyl ketenimines and N-(2-azidomethyl)phenyl-N'-alkyl(aryl) carbodiimides undergo, under mild thermal conditions, intramolecular [3 + 2] cycloaddition reactions between the azido group and either the C=C or the distal C=N double bonds of the ketenimine and carbodiimide functions respectively. The reaction products are indolo[1,2-a]quinazolines and/or indolo[2,1-b]quinazolines in the case of azido-ketenimines, and tetrazolo[5,1-b]quinazolines in the case of azido-carbodiimides. The formation of the two classes of indoloquinazolines implies the ulterior dinitrogen extrusion from the non-isolated, putative [3 + 2] cycloadducts between the azide and ketenimine functions, whereas in the case of azido-carbodiimides the initial cycloadducts, tetrazoloquinazolines, were cleanly isolated and further converted into 2-aminoquinazolines by thermally induced dinitrogen extrusion.

  18. Protein Tyrosine Phosphatase 1B Regulates Pyruvate Kinase M2 Tyrosine Phosphorylation*

    PubMed Central

    Bettaieb, Ahmed; Bakke, Jesse; Nagata, Naoto; Matsuo, Kosuke; Xi, Yannan; Liu, Siming; AbouBechara, Daniel; Melhem, Ramzi; Stanhope, Kimber; Cummings, Bethany; Graham, James; Bremer, Andrew; Zhang, Sheng; Lyssiotis, Costas A.; Zhang, Zhong-Yin; Cantley, Lewis C.; Havel, Peter J.; Haj, Fawaz G.

    2013-01-01

    Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose homeostasis and adiposity and is a drug target for the treatment of obesity and diabetes. Here we identify pyruvate kinase M2 (PKM2) as a novel PTP1B substrate in adipocytes. PTP1B deficiency leads to increased PKM2 total tyrosine and Tyr105 phosphorylation in cultured adipocytes and in vivo. Substrate trapping and mutagenesis studies identify PKM2 Tyr-105 and Tyr-148 as key sites that mediate PTP1B-PKM2 interaction. In addition, in vitro analyses illustrate a direct effect of Tyr-105 phosphorylation on PKM2 activity in adipocytes. Importantly, PTP1B pharmacological inhibition increased PKM2 Tyr-105 phosphorylation and decreased PKM2 activity. Moreover, PKM2 Tyr-105 phosphorylation is regulated nutritionally, decreasing in adipose tissue depots after high-fat feeding. Further, decreased PKM2 Tyr-105 phosphorylation correlates with the development of glucose intolerance and insulin resistance in rodents, non-human primates, and humans. Together, these findings identify PKM2 as a novel substrate of PTP1B and provide new insights into the regulation of adipose PKM2 activity. PMID:23640882

  19. HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in the Serbian population.

    PubMed

    Andric, Zorana; Popadic, Dusan; Jovanovic, Barbara; Jaglicic, Ivana; Bojic, Svetlana; Simonovic, Ruzica

    2014-03-01

    This study provides the first published detailed analysis of five loci polymorphisms as well as reports of two, three and five loci haplotype frequencies in the Serbian population in a sample of 1992 volunteer bone marrow donors recruited from different part of the country. Typing was performed by PCR SSO method combined with PCR SSP techniques to resolve ambiguities. In total, 16 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1 and 5 HLA-DQB1 allelic groups were identified. The most frequent in allele groups are HLA-A(∗)02 (29.5%), HLA-A(∗)01 (14.2%), HLA-B(∗)35 (13.1%), HLA-B(∗)51 (12.8%), HLA-C(∗)07 (24.8%), HLA-DRB1(∗)11 (16.9%), HLA-DRB1(∗)13 (13.2%), HLA-DQB1(∗)03 (33.3%) and DQB1(∗)05 (33.0%). The most frequent three- and five-loci haplotypes were A(∗)01-B(∗)08-DRB1(∗)03 (5.9%) and A(∗)02-B(∗)18-DRB1(∗)11 (1.9%), A(∗)01-B(∗)08-C(∗)07-DRB1(∗)03-DQB1(∗)02 (6.6%) followed by A(∗)02-B(∗)18-C(∗)07-DRB1(∗)11-DQB1(∗)03 (2.5%), then A(∗)33-B(∗)14-C(∗)08-DRB1(∗)01-DQB1(∗)05 and A(∗)02-B(∗)35-C(∗)04-DRB1(∗)16-DQB1(∗)05 (2.2% both), respectively. The results of cluster analysis showed that the Serbian population is closely related to the populations living in central Balkan and neighboring European regions. The level of allelic diversity found in this study are relevant to facilitate searching for unrelated matched donor and provide a healthy control population from our region that should be useful in the future disease association study. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  20. Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1.

    PubMed

    Racacho, Lemuel; Byrnes, Ashley M; MacDonald, Heather; Dranse, Helen J; Nikkel, Sarah M; Allanson, Judith; Rosser, Elisabeth; Underhill, T Michael; Bulman, Dennis E

    2015-12-01

    Brachydactyly type A1 is an autosomal dominant disorder primarily characterized by hypoplasia/aplasia of the middle phalanges of digits 2-5. Human and mouse genetic perturbations in the BMP-SMAD signaling pathway have been associated with many brachymesophalangies, including BDA1, as causative mutations in IHH and GDF5 have been previously identified. GDF5 interacts directly as the preferred ligand for the BMP type-1 receptor BMPR1B and is important for both chondrogenesis and digit formation. We report pathogenic variants in BMPR1B that are associated with complex BDA1. A c.975A>C (p.(Lys325Asn)) was identified in the first patient displaying absent middle phalanges and shortened distal phalanges of the toes in addition to the significant shortening of middle phalanges in digits 2, 3 and 5 of the hands. The second patient displayed a combination of brachydactyly and arachnodactyly. The sequencing of BMPR1B in this individual revealed a novel c.447-1G>A at a canonical acceptor splice site of exon 8, which is predicted to create a novel acceptor site, thus leading to a translational reading frameshift. Both mutations are most likely to act in a dominant-negative manner, similar to the effects observed in BMPR1B mutations that cause BDA2. These findings demonstrate that BMPR1B is another gene involved with the pathogenesis of BDA1 and illustrates the continuum of phenotypes between BDA1 and BDA2.

  1. 75 FR 65222 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2... adopting a new airworthiness directive (AD) for the Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D... 14 CFR part 39 to include an AD that would apply to the Eurocopter France Model AS 350 B, BA, B1, B2...

  2. Association of HLA-A, B, DRB1 alleles and haplotypes with HIV-1 infection in Chongqing, China

    PubMed Central

    2009-01-01

    Background The human immunodeficiency virus type 1(HIV-1) epidemic in Chongqing, China, is increasing rapidly with the dominant subtype of CRF07_BC over the past 3 years. Since human leukocyte antigen (HLA) polymorphisms have shown strong association with susceptibility/resistance to HIV-1 infection from individuals with different ethnic backgrounds, a recent investigation on frequencies of HLA class I and class II alleles in a Chinese cohort also indicated that similar correlation existed in HIV infected individuals from several provinces in China, however, such information is unavailable in Chongqing, southwest China. Methods In this population-based study, we performed polymerase chain reaction analysis with sequence-specific oligonucleotide probes (PCR-SSOP) for intermediate-low-resolution HLA typing in a cohort of 549 HIV-1 infected individuals, another 2475 healthy subjects from the Han nationality in Chongqing, China, were selected as population control. We compared frequencies of HLA-A, B, DRB1 alleles, haplotypes and genotypes between the two groups, and analyzed their association with HIV-1 susceptibility or resistance. Results The genetic profile of HLA (A, B, DRB1) alleles of HIV-1 infected individuals from Chongqing Han of China was obtained. Several alleles of HLA-B such as B*46 (P = 0.001, OR = 1.38, 95%CI = 1.13-1.68), B*1501G(B62) (P = 0.013, OR = 1.42, 95%CI = 1.08-1.88), B*67 (P = 0.022, OR = 2.76, 95%CI = 1.16-6.57), B*37 (P = 0.014, OR = 1.93, 95%CI = 1.14-3.28) and B*52 (P = 0.038, OR = 1.64, 95%CI = 1.03-2.61) were observed to have association with susceptibility to HIV-1 infection in this population. In addition, the haplotype analysis revealed that A*11-B*46, A*24-B*54 and A*01-B*37 for 2-locus, and A*11-B*46-DRB1*09, A*02-B*46-DRB1*08, A*11-B*4001G-DRB1*15, A*02-B*4001G-DRB1*04, A*11-B*46-DRB1*08 and A*02-B*4001G-DRB1*12 for 3-locus had significantly overrepresented in HIV-1 infected individuals, whereas A*11-B*1502G, A*11-B*1502G-DRB1

  3. Association of HLA-A, B, DRB1 alleles and haplotypes with HIV-1 infection in Chongqing, China.

    PubMed

    Huang, Xia; Ling, Hua; Mao, Wei; Ding, Xianbin; Zhou, Quanhua; Han, Mei; Wang, Fang; Cheng, Lei; Xiong, Hongyan

    2009-12-12

    The human immunodeficiency virus type 1(HIV-1) epidemic in Chongqing, China, is increasing rapidly with the dominant subtype of CRF07_BC over the past 3 years. Since human leukocyte antigen (HLA) polymorphisms have shown strong association with susceptibility/resistance to HIV-1 infection from individuals with different ethnic backgrounds, a recent investigation on frequencies of HLA class I and class II alleles in a Chinese cohort also indicated that similar correlation existed in HIV infected individuals from several provinces in China, however, such information is unavailable in Chongqing, southwest China. In this population-based study, we performed polymerase chain reaction analysis with sequence-specific oligonucleotide probes (PCR-SSOP) for intermediate-low-resolution HLA typing in a cohort of 549 HIV-1 infected individuals, another 2475 healthy subjects from the Han nationality in Chongqing, China, were selected as population control. We compared frequencies of HLA-A, B, DRB1 alleles, haplotypes and genotypes between the two groups, and analyzed their association with HIV-1 susceptibility or resistance. The genetic profile of HLA (A, B, DRB1) alleles of HIV-1 infected individuals from Chongqing Han of China was obtained. Several alleles of HLA-B such as B*46 (P = 0.001, OR = 1.38, 95%CI = 1.13-1.68), B*1501G(B62) (P = 0.013, OR = 1.42, 95%CI = 1.08-1.88), B*67 (P = 0.022, OR = 2.76, 95%CI = 1.16-6.57), B*37 (P = 0.014, OR = 1.93, 95%CI = 1.14-3.28) and B*52 (P = 0.038, OR = 1.64, 95%CI = 1.03-2.61) were observed to have association with susceptibility to HIV-1 infection in this population. In addition, the haplotype analysis revealed that A*11-B*46, A*24-B*54 and A*01-B*37 for 2-locus, and A*11-B*46-DRB1*09, A*02-B*46-DRB1*08, A*11-B*4001G-DRB1*15, A*02-B*4001G-DRB1*04, A*11-B*46-DRB1*08 and A*02-B*4001G-DRB1*12 for 3-locus had significantly overrepresented in HIV-1 infected individuals, whereas A*11-B*1502G, A*11-B*1502G-DRB1*12 and A*33-B*58-DRB1*13 were

  4. Measurement of the production cross section ratio σ (χb2 (1 P)) / σ (χb1 (1 P)) in pp collisions at √{ s} = 8 TeV

    NASA Astrophysics Data System (ADS)

    Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Taurok, A.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Bansal, M.; Bansal, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Luyckx, S.; Ochesanu, S.; Roland, B.; Rougny, R.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Daci, N.; Heracleous, N.; Keaveney, J.; Lowette, S.; Maes, M.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Dobur, D.; Favart, L.; Gay, A. P. R.; Grebenyuk, A.; Léonard, A.; Mohammadi, A.; Perniè, L.; Reis, T.; Seva, T.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wang, J.; Adler, V.; Beernaert, K.; Benucci, L.; Cimmino, A.; Costantini, S.; Crucy, S.; Dildick, S.; Fagot, A.; Garcia, G.; Mccartin, J.; Ocampo Rios, A. A.; Ryckbosch, D.; Salva Diblen, S.; Sigamani, M.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bruno, G.; Castello, R.; Caudron, A.; Ceard, L.; Da Silveira, G. G.; Delaere, C.; du Pree, T.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Jez, P.; Komm, M.; Lemaitre, V.; Nuttens, C.; Pagano, D.; Perrini, L.; Pin, A.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Aldá Júnior, W. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Dos Reis Martins, T.; Mora Herrera, C.; Pol, M. E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santaolalla, J.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Bernardes, C. A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Aleksandrov, A.; Genchev, V.; Iaydjiev, P.; Marinov, A.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Du, R.; Jiang, C. H.; Liang, S.; Plestina, R.; Tao, J.; Wang, X.; Wang, Z.; Asawatangtrakuldee, C.; Ban, Y.; Guo, Y.; Li, Q.; Li, W.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Zhang, L.; Zou, W.; Avila, C.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Mekterovic, D.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Bodlak, M.; Finger, M.; Finger, M.; Assran, Y.; Ellithi Kamel, A.; Mahmoud, M. A.; Radi, A.; Kadastik, M.; Murumaa, M.; Raidal, M.; Tiko, A.; Eerola, P.; Fedi, G.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Baffioni, S.; Beaudette, F.; Busson, P.; Charlot, C.; Dahms, T.; Dalchenko, M.; Dobrzynski, L.; Filipovic, N.; Florent, A.; Granier de Cassagnac, R.; Mastrolorenzo, L.; Miné, P.; Mironov, C.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Paganini, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Veelken, C.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Chabert, E. C.; Collard, C.; Conte, E.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Beaupere, N.; Boudoul, G.; Bouvier, E.; Brochet, S.; Carrillo Montoya, C. A.; Chasserat, J.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Kurca, T.; Lethuillier, M.; Mirabito, L.; Perries, S.; Ruiz Alvarez, J. D.; Sabes, D.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Xiao, H.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Bontenackels, M.; Edelhoff, M.; Feld, L.; Hindrichs, O.; Klein, K.; Ostapchuk, A.; Perieanu, A.; Raupach, F.; Sammet, J.; Schael, S.; Weber, H.; Wittmer, B.; Zhukov, V.; Ata, M.; Dietz-Laursonn, E.; Duchardt, D.; Erdmann, M.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Klingebiel, D.; Knutzen, S.; Kreuzer, P.; Merschmeyer, M.; Meyer, A.; Millet, P.; Olschewski, M.; Padeken, K.; Papacz, P.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Weber, M.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Haj Ahmad, W.; Heister, A.; Hoehle, F.; Kargoll, B.; Kress, T.; Kuessel, Y.; Lingemann, J.; Nowack, A.; Nugent, I. M.; Perchalla, L.; Pooth, O.; Stahl, A.; Asin, I.; Bartosik, N.; Behr, J.; Behrenhoff, W.; Behrens, U.; Bell, A. J.; Bergholz, M.; Bethani, A.; Borras, K.; Burgmeier, A.; Cakir, A.; Calligaris, L.; Campbell, A.; Choudhury, S.; Costanza, F.; Diez Pardos, C.; Dooling, S.; Dorland, T.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Flucke, G.; Garay Garcia, J.; Geiser, A.; Gunnellini, P.; Hauk, J.; Hempel, M.; Horton, D.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Katsas, P.; Kieseler, J.; Kleinwort, C.; Krücker, D.; Lange, W.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Lutz, B.; Mankel, R.; Marfin, I.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Nayak, A.; Novgorodova, O.; Nowak, F.; Ntomari, E.; Perrey, H.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Ribeiro Cipriano, P. M.; Ron, E.; Sahin, M. Ö.; Salfeld-Nebgen, J.; Saxena, P.; Schmidt, R.; Schoerner-Sadenius, T.; Schröder, M.; Seitz, C.; Spannagel, S.; Vargas Trevino, A. D. R.; Walsh, R.; Wissing, C.; Aldaya Martin, M.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Erfle, J.; Garutti, E.; Goebel, K.; Görner, M.; Haller, J.; Hoffmann, M.; Höing, R. S.; Kirschenmann, H.; Klanner, R.; Kogler, R.; Lange, J.; Lapsien, T.; Lenz, T.; Marchesini, I.; Ott, J.; Peiffer, T.; Pietsch, N.; Poehlsen, J.; Poehlsen, T.; Rathjens, D.; Sander, C.; Schettler, H.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Seidel, M.; Sola, V.; Stadie, H.; Steinbrück, G.; Troendle, D.; Usai, E.; Vanelderen, L.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Butz, E.; Chwalek, T.; De Boer, W.; Descroix, A.; Dierlamm, A.; Feindt, M.; Frensch, F.; Giffels, M.; Hartmann, F.; Hauth, T.; Husemann, U.; Katkov, I.; Kornmayer, A.; Kuznetsova, E.; Lobelle Pardo, P.; Mozer, M. U.; Müller, Th.; Nürnberg, A.; Quast, G.; Rabbertz, K.; Ratnikov, F.; Röcker, S.; Simonis, H. J.; Stober, F. M.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weiler, T.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Markou, A.; Markou, C.; Psallidas, A.; Topsis-Giotis, I.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Stiliaris, E.; Aslanoglou, X.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Bencze, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Molnar, J.; Palinkas, J.; Szillasi, Z.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Swain, S. K.; Beri, S. B.; Bhatnagar, V.; Dhingra, N.; Gupta, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, M.; Mittal, M.; Nishu, N.; Singh, J. B.; Kumar, Ashok; Kumar, Arun; Ahuja, S.; Bhardwaj, A.; Choudhary, B. C.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, V.; Banerjee, S.; Bhattacharya, S.; Chatterjee, K.; Dutta, S.; Gomber, B.; Jain, Sa.; Jain, Sh.; Khurana, R.; Modak, A.; Mukherjee, S.; Roy, D.; Sarkar, S.; Sharan, M.; Abdulsalam, A.; Dutta, D.; Kailas, S.; Kumar, V.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Banerjee, S.; Bhowmik, S.; Chatterjee, R. M.; Dewanjee, R. K.; Dugad, S.; Ganguly, S.; Ghosh, S.; Guchait, M.; Gurtu, A.; Kole, G.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Mohanty, G. B.; Parida, B.; Sudhakar, K.; Wickramage, N.; Bakhshiansohi, H.; Behnamian, H.; Etesami, S. M.; Fahim, A.; Goldouzian, R.; Jafari, A.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Barbone, L.; Calabria, C.; Chhibra, S. S.; Colaleo, A.; Creanza, D.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Selvaggi, G.; Silvestris, L.; Singh, G.; Venditti, R.; Verwilligen, P.; Zito, G.; Abbiendi, G.; Benvenuti, A. C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Primavera, F.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Travaglini, R.; Albergo, S.; Cappello, G.; Chiorboli, M.; Costa, S.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Gallo, E.; Gonzi, S.; Gori, V.; Lenzi, P.; Meschini, M.; Paoletti, S.; Sguazzoni, G.; Tropiano, A.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Ferro, F.; Lo Vetere, M.; Robutti, E.; Tosi, S.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Gerosa, R.; Ghezzi, A.; Govoni, P.; Lucchini, M. T.; Malvezzi, S.; Manzoni, R. A.; Martelli, A.; Marzocchi, B.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Ragazzi, S.; Redaelli, N.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Fabozzi, F.; Iorio, A. O. M.; Lista, L.; Meola, S.; Merola, M.; Paolucci, P.; Azzi, P.; Bacchetta, N.; Bisello, D.; Branca, A.; Carlin, R.; Checchia, P.; Dall'Osso, M.; Dorigo, T.; Dosselli, U.; Galanti, M.; Gasparini, F.; Gasparini, U.; Giubilato, P.; Gonella, F.; Gozzelino, A.; Kanishchev, K.; Lacaprara, S.; Margoni, M.; Montecassiano, F.; Pazzini, J.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Tosi, M.; Zotto, P.; Zucchetta, A.; Zumerle, G.; Gabusi, M.; Ratti, S. P.; Riccardi, C.; Salvini, P.; Vitulo, P.; Biasini, M.; Bilei, G. M.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Mantovani, G.; Menichelli, M.; Romeo, F.; Saha, A.; Santocchia, A.; Spiezia, A.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Broccolo, G.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fiori, F.; Foà, L.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Moon, C. S.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Serban, A. T.; Spagnolo, P.; Squillacioti, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Vernieri, C.; Barone, L.; Cavallari, F.; D'imperio, G.; Del Re, D.; Diemoz, M.; Grassi, M.; Jorda, C.; Longo, E.; Margaroli, F.; Meridiani, P.; Micheli, F.; Nourbakhsh, S.; Organtini, G.; Paramatti, R.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Soffi, L.; Traczyk, P.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bellan, R.; Biino, C.; Cartiglia, N.; Casasso, S.; Costa, M.; Degano, A.; Demaria, N.; Dujany, G.; Finco, L.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Musich, M.; Obertino, M. M.; Ortona, G.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Potenza, A.; Romero, A.; Ruspa, M.; Sacchi, R.; Solano, A.; Staiano, A.; Tamponi, U.; Belforte, S.; Candelise, V.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Gobbo, B.; La Licata, C.; Marone, M.; Montanino, D.; Schizzi, A.; Umer, T.; Zanetti, A.; Chang, S.; Kropivnitskaya, A.; Nam, S. K.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Kong, D. J.; Lee, S.; Oh, Y. D.; Park, H.; Sakharov, A.; Son, D. C.; Kim, T. J.; Kim, J. Y.; Song, S.; Choi, S.; Gyun, D.; Hong, B.; Jo, M.; Kim, H.; Kim, Y.; Lee, B.; Lee, K. S.; Park, S. K.; Roh, Y.; Choi, M.; Kim, J. H.; Park, I. C.; Park, S.; Ryu, G.; Ryu, M. S.; Choi, Y.; Choi, Y. K.; Goh, J.; Kim, D.; Kwon, E.; Lee, J.; Seo, H.; Yu, I.; Juodagalvis, A.; Komaragiri, J. R.; Md Ali, M. A. B.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-de La Cruz, I.; Lopez-Fernandez, R.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Casimiro Linares, E.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Reucroft, S.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Khalid, S.; Khan, W. A.; Khurshid, T.; Shah, M. A.; Shoaib, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Brona, G.; Bunkowski, K.; Cwiok, M.; Dominik, W.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Wolszczak, W.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Nguyen, F.; Rodrigues Antunes, J.; Seixas, J.; Varela, J.; Vischia, P.; Golutvin, I.; Gorbunov, I.; Karjavin, V.; Konoplyanikov, V.; Korenkov, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Mitsyn, V. V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Skatchkov, N.; Smirnov, V.; Tikhonenko, E.; Yuldashev, B. S.; Zarubin, A.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Vorobyev, An.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Safronov, G.; Semenov, S.; Spiridonov, A.; Stolin, V.; Vlasov, E.; Zhokin, A.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Mesyats, G.; Rusakov, S. V.; Vinogradov, A.; Belyaev, A.; Boos, E.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Ekmedzic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Battilana, C.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Domínguez Vázquez, D.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Merino, G.; Navarro De Martino, E.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Albajar, C.; de Trocóniz, J. F.; Missiroli, M.; Moran, D.; Brun, H.; Cuevas, J.; Fernandez Menendez, J.; Folgueras, S.; Gonzalez Caballero, I.; Lloret Iglesias, L.; Brochero Cifuentes, J. A.; Cabrillo, I. J.; Calderon, A.; Duarte Campderros, J.; Fernandez, M.; Gomez, G.; Graziano, A.; Lopez Virto, A.; Marco, J.; Marco, R.; Martinez Rivero, C.; Matorras, F.; Munoz Sanchez, F. J.; Piedra Gomez, J.; Rodrigo, T.; Rodríguez-Marrero, A. Y.; Ruiz-Jimeno, A.; Scodellaro, L.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Auzinger, G.; Bachtis, M.; Baillon, P.; Ball, A. H.; Barney, D.; Benaglia, A.; Bendavid, J.; Benhabib, L.; Benitez, J. F.; Bernet, C.; Bianchi, G.; Bloch, P.; Bocci, A.; Bonato, A.; Bondu, O.; Botta, C.; Breuker, H.; Camporesi, T.; Cerminara, G.; Colafranceschi, S.; D'Alfonso, M.; d'Enterria, D.; Dabrowski, A.; David, A.; De Guio, F.; De Roeck, A.; De Visscher, S.; Dobson, M.; Dordevic, M.; Dupont-Sagorin, N.; Elliott-Peisert, A.; Eugster, J.; Franzoni, G.; Funk, W.; Gigi, D.; Gill, K.; Giordano, D.; Girone, M.; Glege, F.; Guida, R.; Gundacker, S.; Guthoff, M.; Hammer, J.; Hansen, M.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Kousouris, K.; Krajczar, K.; Lecoq, P.; Lourenço, C.; Magini, N.; Malgeri, L.; Mannelli, M.; Marrouche, J.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moortgat, F.; Morovic, S.; Mulders, M.; Musella, P.; Orsini, L.; Pape, L.; Perez, E.; Perrozzi, L.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Pimiä, M.; Piparo, D.; Plagge, M.; Racz, A.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Sharma, A.; Siegrist, P.; Silva, P.; Simon, M.; Sphicas, P.; Spiga, D.; Steggemann, J.; Stieger, B.; Stoye, M.; Treille, D.; Tsirou, A.; Veres, G. I.; Vlimant, J. R.; Wardle, N.; Wöhri, H. K.; Wollny, H.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Renker, D.; Rohe, T.; Bachmair, F.; Bäni, L.; Bianchini, L.; Bortignon, P.; Buchmann, M. A.; Casal, B.; Chanon, N.; Deisher, A.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dünser, M.; Eller, P.; Grab, C.; Hits, D.; Lustermann, W.; Mangano, B.; Marini, A. C.; Martinez Ruiz del Arbol, P.; Meister, D.; Mohr, N.; Nägeli, C.; Nessi-Tedaldi, F.; Pandolfi, F.; Pauss, F.; Peruzzi, M.; Quittnat, M.; Rebane, L.; Rossini, M.; Starodumov, A.; Takahashi, M.; Theofilatos, K.; Wallny, R.; Weber, H. A.; Amsler, C.; Canelli, M. F.; Chiochia, V.; De Cosa, A.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Lange, C.; Millan Mejias, B.; Ngadiuba, J.; Robmann, P.; Ronga, F. J.; Taroni, S.; Verzetti, M.; Yang, Y.; Cardaci, M.; Chen, K. H.; Ferro, C.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Volpe, R.; Yu, S. S.; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Chen, P. H.; Dietz, C.; Grundler, U.; Hou, W.-S.; Kao, K. Y.; Lei, Y. J.; Liu, Y. F.; Lu, R.-S.; Majumder, D.; Petrakou, E.; Tzeng, Y. M.; Wilken, R.; Asavapibhop, B.; Srimanobhas, N.; Suwonjandee, N.; Adiguzel, A.; Bakirci, M. N.; Cerci, S.; Dozen, C.; Dumanoglu, I.; Eskut, E.; Girgis, S.; Gokbulut, G.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Kayis Topaksu, A.; Onengut, G.; Ozdemir, K.; Ozturk, S.; Polatoz, A.; Sogut, K.; Sunar Cerci, D.; Tali, B.; Topakli, H.; Vergili, M.; Akin, I. V.; Bilin, B.; Bilmis, S.; Gamsizkan, H.; Karapinar, G.; Ocalan, K.; Sekmen, S.; Surat, U. E.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Isildak, B.; Kaya, M.; Kaya, O.; Bahtiyar, H.; Barlas, E.; Cankocak, K.; Vardarlı, F. I.; Yücel, M.; Levchuk, L.; Sorokin, P.; Brooke, J. J.; Clement, E.; Cussans, D.; Flacher, H.; Frazier, R.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Meng, Z.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Senkin, S.; Smith, V. J.; Williams, T.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Womersley, W. J.; Worm, S. D.; Baber, M.; Bainbridge, R.; Buchmuller, O.; Burton, D.; Colling, D.; Cripps, N.; Cutajar, M.; Dauncey, P.; Davies, G.; Della Negra, M.; Dunne, P.; Ferguson, W.; Fulcher, J.; Futyan, D.; Gilbert, A.; Hall, G.; Iles, G.; Jarvis, M.; Karapostoli, G.; Kenzie, M.; Lane, R.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mathias, B.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Petridis, K.; Raymond, D. M.; Rogerson, S.; Rose, A.; Seez, C.; Sharp, P.; Tapper, A.; Vazquez Acosta, M.; Virdee, T.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leggat, D.; Leslie, D.; Martin, W.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Dittmann, J.; Hatakeyama, K.; Kasmi, A.; Liu, H.; Scarborough, T.; Charaf, O.; Cooper, S. I.; Henderson, C.; Rumerio, P.; Avetisyan, A.; Bose, T.; Fantasia, C.; Lawson, P.; Richardson, C.; Rohlf, J.; Sperka, D.; St. John, J.; Sulak, L.; Alimena, J.; Berry, E.; Bhattacharya, S.; Christopher, G.; Cutts, D.; Demiragli, Z.; Ferapontov, A.; Garabedian, A.; Heintz, U.; Kukartsev, G.; Laird, E.; Landsberg, G.; Luk, M.; Narain, M.; Segala, M.; Sinthuprasith, T.; Speer, T.; Swanson, J.; Breedon, R.; Breto, G.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Gardner, M.; Ko, W.; Lander, R.; Miceli, T.; Mulhearn, M.; Pellett, D.; Pilot, J.; Ricci-Tam, F.; Searle, M.; Shalhout, S.; Smith, J.; Squires, M.; Stolp, D.; Tripathi, M.; Wilbur, S.; Yohay, R.; Cousins, R.; Everaerts, P.; Farrell, C.; Hauser, J.; Ignatenko, M.; Rakness, G.; Takasugi, E.; Valuev, V.; Weber, M.; Babb, J.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Hanson, G.; Heilman, J.; Ivova Rikova, M.; Jandir, P.; Kennedy, E.; Lacroix, F.; Liu, H.; Long, O. R.; Luthra, A.; Malberti, M.; Nguyen, H.; Olmedo Negrete, M.; Shrinivas, A.; Sumowidagdo, S.; Wimpenny, S.; Andrews, W.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; D'Agnolo, R. T.; Evans, D.; Holzner, A.; Kelley, R.; Klein, D.; Lebourgeois, M.; Letts, J.; Macneill, I.; Olivito, D.; Padhi, S.; Palmer, C.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Sudano, E.; Tadel, M.; Tu, Y.; Vartak, A.; Welke, C.; Würthwein, F.; Yagil, A.; Yoo, J.; Barge, D.; Bradmiller-Feld, J.; Campagnari, C.; Danielson, T.; Dishaw, A.; Flowers, K.; Franco Sevilla, M.; Geffert, P.; George, C.; Golf, F.; Gouskos, L.; Incandela, J.; Justus, C.; Mccoll, N.; Richman, J.; Stuart, D.; To, W.; West, C.; Apresyan, A.; Bornheim, A.; Bunn, J.; Chen, Y.; Di Marco, E.; Duarte, J.; Mott, A.; Newman, H. B.; Pena, C.; Rogan, C.; Spiropulu, M.; Timciuc, V.; Wilkinson, R.; Xie, S.; Zhu, R. Y.; Azzolini, V.; Calamba, A.; Carlson, B.; Ferguson, T.; Iiyama, Y.; Paulini, M.; Russ, J.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Ford, W. T.; Gaz, A.; Luiggi Lopez, E.; Nauenberg, U.; Smith, J. G.; Stenson, K.; Ulmer, K. A.; Wagner, S. R.; Alexander, J.; Chatterjee, A.; Chu, J.; Dittmer, S.; Eggert, N.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Ryd, A.; Salvati, E.; Skinnari, L.; Sun, W.; Teo, W. D.; Thom, J.; Thompson, J.; Tucker, J.; Weng, Y.; Winstrom, L.; Wittich, P.; Winn, D.; Abdullin, S.; Albrow, M.; Anderson, J.; Apollinari, G.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gao, Y.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hanlon, J.; Hare, D.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Kaadze, K.; Klima, B.; Kreis, B.; Kwan, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, T.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Martinez Outschoorn, V. I.; Maruyama, S.; Mason, D.; McBride, P.; Mishra, K.; Mrenna, S.; Musienko, Y.; Nahn, S.; Newman-Holmes, C.; O'Dell, V.; Prokofyev, O.; Sexton-Kennedy, E.; Sharma, S.; Soha, A.; Spalding, W. J.; Spiegel, L.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitbeck, A.; Whitmore, J.; Yang, F.; Acosta, D.; Avery, P.; Bourilkov, D.; Carver, M.; Cheng, T.; Curry, D.; Das, S.; De Gruttola, M.; Di Giovanni, G. P.; Field, R. D.; Fisher, M.; Furic, I. K.; Hugon, J.; Konigsberg, J.; Korytov, A.; Kypreos, T.; Low, J. F.; Matchev, K.; Milenovic, P.; Mitselmakher, G.; Muniz, L.; Rinkevicius, A.; Shchutska, L.; Snowball, M.; Yelton, J.; Zakaria, M.; Hewamanage, S.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, T.; Askew, A.; Bochenek, J.; Diamond, B.; Haas, J.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Prosper, H.; Veeraraghavan, V.; Weinberg, M.; Baarmand, M. M.; Hohlmann, M.; Kalakhety, H.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Bazterra, V. E.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Khalatyan, S.; Kurt, P.; Moon, D. H.; O'Brien, C.; Silkworth, C.; Turner, P.; Varelas, N.; Albayrak, E. A.; Bilki, B.; Clarida, W.; Dilsiz, K.; Duru, F.; Haytmyradov, M.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Rahmat, R.; Sen, S.; Tan, P.; Tiras, E.; Wetzel, J.; Yetkin, T.; Yi, K.; Barnett, B. A.; Blumenfeld, B.; Bolognesi, S.; Fehling, D.; Gritsan, A. V.; Maksimovic, P.; Martin, C.; Swartz, M.; Baringer, P.; Bean, A.; Benelli, G.; Bruner, C.; Gray, J.; Kenny, R. P., III; Malek, M.; Murray, M.; Noonan, D.; Sanders, S.; Sekaric, J.; Stringer, R.; Wang, Q.; Wood, J. S.; Barfuss, A. F.; Chakaberia, I.; Ivanov, A.; Khalil, S.; Makouski, M.; Maravin, Y.; Saini, L. K.; Shrestha, S.; Skhirtladze, N.; Svintradze, I.; Gronberg, J.; Lange, D.; Rebassoo, F.; Wright, D.; Baden, A.; Belloni, A.; Calvert, B.; Eno, S. C.; Gomez, J. A.; Hadley, N. J.; Kellogg, R. G.; Kolberg, T.; Lu, Y.; Marionneau, M.; Mignerey, A. C.; Pedro, K.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Barbieri, R.; Bauer, G.; Busza, W.; Cali, I. A.; Chan, M.; Di Matteo, L.; Dutta, V.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Klute, M.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Ma, T.; Paus, C.; Ralph, D.; Roland, C.; Roland, G.; Stephans, G. S. F.; Stöckli, F.; Sumorok, K.; Velicanu, D.; Veverka, J.; Wyslouch, B.; Yang, M.; Zanetti, M.; Zhukova, V.; Dahmes, B.; Gude, A.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Mans, J.; Pastika, N.; Rusack, R.; Singovsky, A.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Gonzalez Suarez, R.; Keller, J.; Knowlton, D.; Kravchenko, I.; Lazo-Flores, J.; Malik, S.; Meier, F.; Snow, G. R.; Dolen, J.; Godshalk, A.; Iashvili, I.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Haley, J.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Trocino, D.; Wang, R.-J.; Wood, D.; Zhang, J.; Hahn, K. A.; Kubik, A.; Mucia, N.; Odell, N.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Sung, K.; Velasco, M.; Won, S.; Brinkerhoff, A.; Chan, K. M.; Drozdetskiy, A.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Pearson, T.; Planer, M.; Ruchti, R.; Valls, N.; Wayne, M.; Wolf, M.; Woodard, A.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Hill, C.; Hughes, R.; Kotov, K.; Ling, T. Y.; Puigh, D.; Rodenburg, M.; Smith, G.; Winer, B. L.; Wolfe, H.; Wulsin, H. W.; Driga, O.; Elmer, P.; Hebda, P.; Hunt, A.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zenz, S. C.; Zuranski, A.; Brownson, E.; Mendez, H.; Ramirez Vargas, J. E.; Barnes, V. E.; Benedetti, D.; Bolla, G.; Bortoletto, D.; De Mattia, M.; Hu, Z.; Jha, M. K.; Jones, M.; Jung, K.; Kress, M.; Leonardo, N.; Lopes Pegna, D.; Maroussov, V.; Merkel, P.; Miller, D. H.; Neumeister, N.; Radburn-Smith, B. C.; Shi, X.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Ecklund, K. M.; Geurts, F. J. M.; Li, W.; Michlin, B.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; Covarelli, R.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Garcia-Bellido, A.; Goldenzweig, P.; Han, J.; Harel, A.; Khukhunaishvili, A.; Petrillo, G.; Vishnevskiy, D.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Lungu, G.; Mesropian, C.; Arora, S.; Barker, A.; Chou, J. P.; Contreras-Campana, C.; Contreras-Campana, E.; Duggan, D.; Ferencek, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Kaplan, S.; Lath, A.; Panwalkar, S.; Park, M.; Patel, R.; Salur, S.; Schnetzer, S.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Rose, K.; Spanier, S.; York, A.; Bouhali, O.; Castaneda Hernandez, A.; Eusebi, R.; Flanagan, W.; Gilmore, J.; Kamon, T.; Khotilovich, V.; Krutelyov, V.; Montalvo, R.; Osipenkov, I.; Pakhotin, Y.; Perloff, A.; Roe, J.; Rose, A.; Safonov, A.; Sakuma, T.; Suarez, I.; Tatarinov, A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kovitanggoon, K.; Kunori, S.; Lee, S. W.; Libeiro, T.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Sharma, M.; Sheldon, P.; Snook, B.; Tuo, S.; Velkovska, J.; Arenton, M. W.; Boutle, S.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Lin, C.; Neu, C.; Wood, J.; Clarke, C.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Dodd, L.; Duric, S.; Friis, E.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Lazaridis, C.; Levine, A.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ross, I.; Sarangi, T.; Savin, A.; Smith, W. H.; Vuosalo, C.; Woods, N.

    2015-04-01

    A measurement of the production cross section ratio σ (χb2 (1 P)) / σ (χb1 (1 P)) is presented. The χb1 (1 P) and χb2 (1 P) bottomonium states, promptly produced in pp collisions at √{ s} = 8 TeV, are detected by the CMS experiment at the CERN LHC through their radiative decays χ b 1 , 2 (1 P) → ϒ (1 S) + γ. The emitted photons are measured through their conversion to e+e- pairs, whose reconstruction allows the two states to be resolved. The ϒ (1 S) is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb-1 is used to measure the cross section ratio in a phase-space region defined by the photon pseudorapidity, |ηγ | < 1.0; the ϒ (1 S) rapidity, |yϒ | < 1.5; and the ϒ (1 S) transverse momentum, 7 < pTϒ < 40 GeV. The cross section ratio shows no significant dependence on the ϒ (1 S) transverse momentum, with a measured average value of 0.85 ± 0.07 (stat +syst) ± 0.08 (BF), where the first uncertainty is the combination of the experimental statistical and systematic uncertainties and the second is from the uncertainty in the ratio of the χb branching fractions.

  5. ATP1B3 Protein Modulates the Restriction of HIV-1 Production and Nuclear Factor κ Light Chain Enhancer of Activated B Cells (NF-κB) Activation by BST-2*

    PubMed Central

    Nishitsuji, Hironori; Sugiyama, Ryuichi; Abe, Makoto; Takaku, Hiroshi

    2016-01-01

    Here, we identify ATP1B3 and fibrillin-1 as novel BST-2-binding proteins. ATP1B3 depletion in HeLa cells (BST-2-positive cells), but not 293T cells (BST-2-negative cells), induced the restriction of HIV-1 production in a BST-2-dependent manner. In contrast, fibrillin-1 knockdown reduced HIV-1 production in 293T and HeLa cells in a BST-2-independent manner. Moreover, NF-κB activation was enhanced by siATP1B3 treatment in HIV-1- and HIV-1ΔVpu-infected HeLa cells. In addition, ATP1B3 silencing induced high level BST-2 expression on the surface of HeLa cells. These results indicate that ATP1B3 is a co-factor that accelerates BST-2 degradation and reduces BST-2-mediated restriction of HIV-1 production and NF-κB activation. PMID:26694617

  6. SLCO2B1 and SLCO1B3 as New Targets for Enhancing Androgen Deprivation Therapy for Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    that statins block DHEAS uptake by competitively binding to SLCO2B1. We examined the effect of four different statins ( atorvastatin , fluvastatin...300 pmol/mg compared to ~60 pmol/mg protein for LNCaP (Fig. 2B). 100 µM atorvastatin significantly decreased DHEAS influx by ~50% in both cell...or even 100 µM atorvastatin or simvastatin was insufficient to inhibit DHEAS uptake in LNCaP, which has a relatively low level of SLCO2B1 expression

  7. Effect of Nicotine on CYP2B1 Expression in a Glioma Animal Model and Analysis of CYP2B6 Expression in Pediatric Gliomas.

    PubMed

    Nava-Salazar, Sonia; Gómez-Manzo, Saúl; Marcial-Quino, Jaime; Marhx-Bracho, Alfonso; Phillips-Farfán, Bryan V; Diaz-Avalos, Carlos; Vanoye-Carlo, America

    2018-06-16

    Cyclophosphamide (CPA) is a pro-drug commonly used in the chemotherapeutic schemes for glioma treatment but has high toxicity and the side effects include brain damage and even death. Since CPA is activated mainly by CY2B6, over-expression of the enzyme in the tumor cells has been proposed to enhance CPA activation. In this study, we explored the induction of the Cyp2b1 (homologous to CYP2B6 ) by nicotine in an animal rat model with glioma. Gene expression and protein levels were analyzed by RT-PCR and Western blot. Nicotine treatment increased CYP2B1 protein levels in the healthy animals’ brain tissue. In the brain tissue of animals with glioma, the CYP2B1 showed a high expression, even before nicotine treatment. Nicotine did not increase significantly the CYP2B1 protein expression in the tumor, but increased its expression in the tumor vicinity, especially around blood vessels in the cortex. We also explored CY2B6 expression in glioma samples derived from pediatric patients. Tumor tissue showed a variable expression of the enzyme, which could depend on the tumor malignancy grade. Induction of the CYP2B6 in pediatric gliomas with lower expression of the enzyme, could be an alternative to improve the antitumoral effect of CPA treatment.

  8. Inhibition of PTP1B Restores IRS1-Mediated Hepatic Insulin Signaling in IRS2-Deficient Mice

    PubMed Central

    González-Rodríguez, Águeda; Gutierrez, Jose A. Mas; Sanz-González, Silvia; Ros, Manuel; Burks, Deborah J.; Valverde, Ángela M.

    2010-01-01

    OBJECTIVE Mice with complete deletion of insulin receptor substrate 2 (IRS2) develop hyperglycemia, impaired hepatic insulin signaling, and elevated gluconeogenesis, whereas mice deficient for protein tyrosine phosphatase (PTP)1B display an opposing hepatic phenotype characterized by increased sensitivity to insulin. To define the relationship between these two signaling pathways in the regulation of liver metabolism, we used genetic and pharmacological approaches to study the effects of inhibiting PTP1B on hepatic insulin signaling and expression of gluconeogenic enzymes in IRS2−/− mice. RESEARCH DESIGN AND METHODS We analyzed glucose homeostasis and insulin signaling in liver and isolated hepatocytes from IRS2−/− and IRS2−/−/PTP1B−/− mice. Additionally, hepatic insulin signaling was assessed in control and IRS2−/− mice treated with resveratrol, an antioxidant present in red wine. RESULTS In livers of hyperglycemic IRS2−/− mice, the expression levels of PTP1B and its association with the insulin receptor (IR) were increased. The absence of PTP1B in the double-mutant mice restored hepatic IRS1-mediated phosphatidylinositol (PI) 3-kinase/Akt/Foxo1 signaling. Moreover, resveratrol treatment of hyperglycemic IRS2−/− mice decreased hepatic PTP1B mRNA and inhibited PTP1B activity, thereby restoring IRS1-mediated PI 3-kinase/Akt/Foxo1 signaling and peripheral insulin sensitivity. CONCLUSIONS By regulating the phosphorylation state of IR, PTB1B determines sensitivity to insulin in liver and exerts a unique role in the interplay between IRS1 and IRS2 in the modulation of hepatic insulin action. PMID:20028942

  9. 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

  10. Protein tyrosine phosphatase-1B regulates the tyrosine phosphorylation of the adapter Grb2-associated binder 1 (Gab1) in the retina

    PubMed Central

    2013-01-01

    Background Gab1 (Grb2-associated binder 1) is a key coordinator that belongs to the insulin receptor substrate-1 like family of adaptor molecules and is tyrosine phosphorylated in response to various growth factors, cytokines, and numerous other molecules. Tyrosine phosphorylated Gab1 is able to recruit a number of signaling effectors including PI3K, SHP2 and PLC-γ. In this study, we characterized the localization and regulation of tyrosine phosphorylation of Gab1 in the retina. Results Our immuno localization studies suggest that Gab1 is expressed in rod photoreceptor inner segments. We found that hydrogen peroxide activates the tyrosine phosphorylation of Gab1 ex vivo and hydrogen peroxide has been shown to inhibit the protein tyrosine phosphatase PTP1B activity. We found a stable association between the D181A substrate trap mutant of PTP1B and Gab1. Our studies suggest that PTP1B interacts with Gab1 through Tyrosine 83 and this residue may be the major PTP1B target residue on Gab1. We also found that Gab1 undergoes a light-dependent tyrosine phosphorylation and PTP1B regulates the phosphorylation state of Gab1. Consistent with these observations, we found an enhanced Gab1 tyrosine phosphorylation in PTP1B deficient mice and also in retinas treated ex vivo with a PTP1B specific allosteric inhibitor. Conclusions Our laboratory has previously reported that retinas deficient of PTP1B are resistant to light damage compared to wild type mice. Since Gab1 is negatively regulated by PTP1B, a part of the retinal neuroprotective effect we have observed previously in PTP1B deficient mice could be contributed by Gab1 as well. In summary, our data suggest that PTP1B regulates the phosphorylation state of retinal Gab1 in vivo. PMID:23521888

  11. SAR in a child voxel phantom from exposure to wireless computer networks (Wi-Fi).

    PubMed

    Findlay, R P; Dimbylow, P J

    2010-08-07

    Specific energy absorption rate (SAR) values have been calculated in a 10 year old sitting voxel model from exposure to electromagnetic fields at 2.4 and 5 GHz, frequencies commonly used by Wi-Fi devices. Both plane-wave exposure of the model and irradiation from antennas in the near field were investigated for a variety of exposure conditions. In all situations studied, the SAR values calculated were considerably below basic restrictions. For a typical Wi-Fi exposure scenario using an inverted F antenna operating at 100 mW, a duty factor of 0.1 and an antenna-body separation of 34 cm, the maximum peak localized SAR was found to be 3.99 mW kg(-1) in the torso region. At 2.4 GHz, using a power of 100 mW and a duty factor of 1, the highest localized SAR value in the head was calculated as 5.7 mW kg(-1). This represents less than 1% of the SAR previously calculated in the head for a typical mobile phone exposure condition.

  12. Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Xuejiao; Jiaojiang District Center for Disease Control and Prevention, 518 Jingdong Rd., Taizhou 318000; Zhang, Zhan

    Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (5–80 nM) dose-more » and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80 nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced γH2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 μM nicotine (a substrate of CYP2A13) or 1 μM 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system. - Highlights: • CYP2A13 plays a critical role in low concentration of AFB1-induced DNA damage. • B-2A13 cells were more sensitive to AFB1 than B-1A2 cells and B-2A6 cells. • AFB1 dose- and time-dependently induced DNA damage in B-2A13 cells • AFB1-induced DNA adducts and damage can be inhibited by

  13. Regulation of NucB2/Nesfatin-1 throughout rat pregnancy.

    PubMed

    Garcés, María F; Poveda, Natalia E; Sanchez, Elizabeth; Sánchez, Ángel Y; Bravo, Susana B; Vázquez, María J; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E

    2014-06-22

    Nesfatin-1 is an anorexigenic neuropeptide derived by post-translational cleavage from the N-terminus region DNA binding/EF-hand/acidic amino acid rich region (NEFA)/nucleobindin2 (NucB2) protein through proteolytic prohormone convertases. This neuropeptide was originally localized in different appetite controlling areas such as the hypothalamic paraventricular nucleus, arcuate nucleus, supraoptic nucleus, lateral hypothalamic area, and nucleus tractus solitarius. The objective of this study was to determine the expression and the changes that occur to mRNA and protein of NucB2 and Nesfatin-1 serum levels during gestation. This study utilized molecular and immunological approaches to investigate the expression and regulation of NucB2/Nesfatin-1 protein throughout gestation in rat fed under ad libitum and food restricted conditions (30% nutrient restriction). NucB2 was immunolocalized in the amnion and decidua of the rat placenta. Nesfatin-1 serum levels were measured by radioimmunoassay on gestational days 12, 16, 19 and 21, showing a significant (p<0.01) decrease in serum levels after day 12 until the end of gestation in rats fed ad libitum. These results were correlated with the analysis of NucB2 mRNA, with a significant (p<0.01) reduction observed in both the mRNA and protein of NucB2 during the gestational days 12, 16 and 21. It was also observed that food restriction decreases Nesfatin-1 serum levels and NucB2 placental expression at day 16 of gestation when compared to pregnant rats fed ad libitum. This study illustrates for the first time through molecular and immunological approaches the NucB2 expression and regulation on rat placenta and that this peptide is regulated throughout pregnancy. Consistent with previous reports, our results provide additional evidence supporting the role of NucB2 protein as an anorexigenic peptide that may contribute to the regulation of feeding behavior and energy homeostasis. NucB2/Nesfatin-1 might play an important metabolic

  14. Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1-mediated metabolism to the product 4' hydroxy tangeretin.

    PubMed

    Surichan, Somchaiya; Arroo, Randolph R; Tsatsakis, Aristidis M; Androutsopoulos, Vasilis P

    2018-04-04

    Tangeretin is a polymethoxylated flavone with multifaceted anticancer activity. In the present study, the metabolism of tangeretin was evaluated in the CYP1 expressing human breast cancer cell lines MCF7 and MDA-MB-468 and in the normal breast cell line MCF10A. Tangeretin was converted to 4' OH tangeretin by recombinant CYP1 enzymes and by CYP1 enzymes expressed in MCF7 and MDA-MB-468 cells. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Tangeretin exhibited submicromolar IC50 (0.25 ± 0.15 μM) in MDA-MB-468 cells, whereas it was less active in MCF7 cells (39.3 ± 1.5 μM) and completely inactive in MCF10A cells (>100 μM). In MDA-MB-468 cells that were coincubated with the CYP1 inhibitor acacetin, an approximately 70-fold increase was noted in the IC50 (18 ± 1.6 μM) of tangeretin. In the presence of the CYP1 inhibitor acacetin, the conversion of tangeretin to 4' OH tangeretin was significantly reduced in MDA-MB-468 cells (2.55 ± 0.19 μM vs. 6.33 ± 0.12 μM). The mechanism of antiproliferative action involved cell cycle arrest at the G1 phase for MCF7 and MDA-MB-468 cells. Tangeretin was further shown to induce CYP1 enzyme activity and CYP1A1/CYP1B1 protein expression in MCF7 and MDA-MB-468 cells. These results suggest that tangeretin inhibits the proliferation of breast cancer cells via CYP1A1/CYP1B1-mediated metabolism to the product 4' hydroxy tangeretin. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1)

    DTIC Science & Technology

    2013-12-01

    2012 FEB 2012 FEB 2012 FEB 2012 Final DIOT&E flight JUL 2012 JUL 2012 JUL 2012 JUL 2012 RAA MAR 2015 MAR 2015 MAR 2016 MAR 2015 Change Explanations...None Memo RAA is defined as eight assigned aircraft modified, sufficient aircrews and maintenance personnel trained, sufficient aircrew and...incremental upgrade. Acronyms and Abbreviations DIOT&E - Dedicated Initial Operational Test and Evaluation RAA - Required Assets Available B-2 EHF Inc 1

  16. Frequency distribution of polymorphisms of CYP2C19, CYP2C9, VKORC1 and SLCO1B1 genes in the Yakut population.

    PubMed

    Vasilyev, Filipp Filippovich; Danilova, Diana Aleksandrovna; Kaimonov, Vladimir Sergeevich; Chertovskih, Yana Valerievna; Maksimova, Nadezda Romanovna

    2016-01-01

    Allele frequencies of single nucleotide polymorphisms (SNPs) are variable among different populations; therefore the study of SNPs in ethnic groups is important for establishing the clinical significance of the screening of these polymorphisms. The main goal of the research is to study the polymorphisms of CYP2C9, CYP2C19, VKORC1, and SLCO1B1 in Yakuts. Genomic DNA from 229 Yakut subjects were analyzed by real-time polymerase chain reaction (PCR) (SLCO1B1 +521T > C, VKORC1 -1639G>A, CYP2C19 +681G>A, +636G>A, CYP2C9 +430С>T, +1075A>C). Genotype frequencies of polymorphisms in the population of the Yakuts were more characteristic of the Asian population. The results have been included in the software application "Lekgen" that we developed for the interpretation of pharmacogenetic testing. The data of our study obtained on frequency carriers of polymorphisms of genes SLCO1B1, CYP2C19, CYP2C9, VKORC1 among the Yakuts may be useful in developing recommendations for a personalized therapy.

  17. Frequency distribution of polymorphisms of CYP2C19, CYP2C9, VKORC1 and SLCO1B1 genes in the Yakut population

    PubMed Central

    Vasilyev, Filipp Filippovich; Danilova, Diana Aleksandrovna; Kaimonov, Vladimir Sergeevich; Chertovskih, Yana Valerievna; Maksimova, Nadezda Romanovna

    2016-01-01

    Allele frequencies of single nucleotide polymorphisms (SNPs) are variable among different populations; therefore the study of SNPs in ethnic groups is important for establishing the clinical significance of the screening of these polymorphisms. The main goal of the research is to study the polymorphisms of CYP2C9, CYP2C19, VKORC1, and SLCO1B1 in Yakuts. Genomic DNA from 229 Yakut subjects were analyzed by real-time polymerase chain reaction (PCR) (SLCO1B1 +521T > C, VKORC1 -1639G>A, CYP2C19 +681G>A, +636G>A, CYP2C9 +430С>T, +1075A>C). Genotype frequencies of polymorphisms in the population of the Yakuts were more characteristic of the Asian population. The results have been included in the software application “Lekgen” that we developed for the interpretation of pharmacogenetic testing. The data of our study obtained on frequency carriers of polymorphisms of genes SLCO1B1, CYP2C19, CYP2C9, VKORC1 among the Yakuts may be useful in developing recommendations for a personalized therapy. PMID:27499796

  18. Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

    PubMed

    Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

    2014-01-01

    The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

  19. The Pseudoenzyme PDX1.2 Sustains Vitamin B6 Biosynthesis as a Function of Heat Stress.

    PubMed

    Dell'Aglio, Elisa; Boycheva, Svetlana; Fitzpatrick, Teresa B

    2017-08-01

    Plants sense temperature changes and respond by altering growth and metabolic activity to acclimate to the altered environmental conditions. The B vitamins give rise to vital coenzymes that are indispensable for growth and development but their inherent reactive nature renders them prone to destruction especially under stress conditions. Therefore, plant survival strategies would be expected to include mechanisms to sustain B vitamin supply under demanding circumstances. Here, using the example of vitamin B 6 , we investigate the regulation of biosynthesis across eudicot and monocot species under heat stress. Most eudicots carry a pseudoenzyme PDX1.2 that is a noncatalytic homolog of the PDX1 subunit of the vitamin B 6 biosynthesis protein machinery, PYRIDOXINE BIOSYNTHESIS PROTEIN1. Using Arabidopsis ( Arabidopsis thaliana ) and tomato ( Solanum lycopersicum ) as models, we show that PDX1 2 is transcriptionally regulated by the HSFA1 transcription factor family. Monocots only carry catalytic PDX1 homologs that do not respond to heat stress as demonstrated for rice ( Oryza sativa ) and maize ( Zea mays ), suggesting fundamental differences in the regulation of vitamin B 6 biosynthesis across the two lineages. Investigation of the molecular mechanism of PDX1 2 transcription reveals two alternative transcriptional start sites, one of which is exclusive to heat stress. Further data suggest that PDX1.2 leads to stabilization of the catalytic PDX1s under heat stress conditions, which would serve to maintain vitamin B 6 homeostasis in times of need in eudicots that carry this gene. Our analyses indicate an important abiotic stress tolerance strategy in several eudicots, which has not been evolutionarily adapted (or is not required) by monocots such as grasses. © 2017 American Society of Plant Biologists. All Rights Reserved.

  20. Measurement of the production cross section ratio σ(χ b2(1P)) / σ(χ b1(1P)) in pp collisions at √(s) = 8 TeV

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khachatryan, Vardan

    2015-02-24

    Our measurement of the production cross section ratio σ(χ b2(1P))/σ(χ b1(1P)) is presented. The χ b1(1P) and χ b2(1P) bottomonium states, promptly produced in pp collisions at √(s) = 8 TeV , are detected by the CMS experiment at the CERN LHC through their radiative decays χ b1,2(1P)→Υ(1S)+γ. The emitted photons are measured through their conversion to e +e - pairs, whose reconstruction allows the two states to be resolved. The Υ(1S) is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb -1 is used to measure the cross section ratiomore » in a phase-space region defined by the photon pseudorapidity, |η γ|<1.0; the Υ(1S) rapidity, |y Υ|<1.5; and the Υ(1S) transverse momentum, 7T Υ<40 GeV . Finally, the cross section ratio shows no significant dependence on the Υ(1S) transverse momentum, with a measured average value of 0.85± 0.07 (stat + syst) ± 0.08 (BF), where the first uncertainty is the combination of the experimental statistical and systematic uncertainties and the second is from the uncertainty in the ratio of the χ b branching fractions.« less

  1. Real-time detection of S(1D2) photofragments produced from the 1B2(1Σu+) state of CS2 by vacuum ultraviolet photoelectron imaging using 133 nm probe pulses

    NASA Astrophysics Data System (ADS)

    Horio, Takuya; Spesyvtsev, Roman; Furumido, Yu; Suzuki, Toshinori

    2017-07-01

    Ultrafast photodissociation dynamics from the 1B2(1Σu+) state of CS2 are studied by time-resolved photoelectron imaging using the fourth (4ω, 198 nm) and sixth (6ω, 133 nm) harmonics of a femtosecond Ti:sapphire laser. The 1B2 state of CS2 was prepared with the 4ω pulses, and subsequent dynamics were probed using the 6ω vacuum ultraviolet (VUV) pulses. The VUV pulses enabled real-time detection of S(1D2) photofragments, produced via CS2*(1B2(1Σu+)) → CS(X 1Σ+) + S(1D2). The photoionization signal of dissociating CS2*(1B2(1Σu+)) molecules starts to decrease at about 100 fs, while the S(1D2) fragments appear with a finite (ca. 400 fs) delay time after the pump pulse. Also discussed is the configuration interaction of the 1B2(1Σu+) state based on relative photoionization cross-sections to different cationic states.

  2. Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: a novel gene related to nuclear envelopathies.

    PubMed

    Kayman-Kurekci, Gulsum; Talim, Beril; Korkusuz, Petek; Sayar, Nilufer; Sarioglu, Turkan; Oncel, Ibrahim; Sharafi, Parisa; Gundesli, Hulya; Balci-Hayta, Burcu; Purali, Nuhan; Serdaroglu-Oflazer, Piraye; Topaloglu, Haluk; Dincer, Pervin

    2014-07-01

    We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A- and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. The Technology of LiFi: A Brief Introduction

    NASA Astrophysics Data System (ADS)

    Ramadhani, E.; Mahardika, G. P.

    2018-03-01

    Light Fidelity (LiFi) is a Visible Light Communication (VLC) based technology that making a light as a media of communication replacing the cable wire communication. LiFi is evolve to overcome the rate speed in WiFi, while using LiFi the rate speed can reach until 14 Gbps. This paper presents an introduction of the LiFi technology including the architecture, modulation, performance, and the challenges. The result of this paper can be used as a reference and knowledge to develop some of the LiFi technology.

  4. The impact of a future H2-based road transportation sector on the composition and chemistry of the atmosphere - Part 1: Tropospheric composition and air quality

    NASA Astrophysics Data System (ADS)

    Wang, D.; Jia, W.; Olsen, S. C.; Wuebbles, D. J.; Dubey, M. K.; Rockett, A. A.

    2012-08-01

    Vehicles burning fossil fuel emit a number of substances that change the composition and chemistry of the atmosphere, and contribute to global air and water pollution and climate change. For example, nitrogen oxides and volatile organic compounds (VOCs) emitted as byproducts of fossil fuel combustion are key precursors to ground-level ozone and aerosol formation. In addition, on-road vehicles are major CO2 emitters. In order to tackle these problems, molecular hydrogen (H2) has been proposed as an energy carrier to substitute for fossil fuel in the future. However, before implementing any such strategy it is crucial to evaluate its potential impacts on air quality and climate. Here we evaluate the impact of a future (2050) H2-based road transportation sector on tropospheric chemistry and air quality for several possible growth and technology adoption scenarios. The growth scenarios are based on the high and low emissions Intergovernmental Panel on Climate Change Special Report on Emissions Scenarios, A1FI and B1, respectively. The technological adoption scenarios include H2 fuel cell and H2 internal combustion engine options. The impacts are evaluated with the Community Atmospheric Model Chemistry global chemistry transport model (CAM-Chem). Higher resolution simulations focusing on the contiguous United States are also carried out with the Community Multiscale Air Quality Modeling System (CMAQ) regional chemistry transport model. For all scenarios future air quality improves with the adoption of a H2-based road transportation sector, however, the magnitude and type of improvement depend on the scenario. Model results show that with the adoption of H2 fuel cells decreases tropospheric burdens of ozone (7%), CO (14%), NOx (16%), soot (17%), sulfate aerosol (4%), and ammonium nitrate aerosol (12%) in the A1FI scenario, and decreases those of ozone (5%), CO (4%), NOx (11%), soot (7%), sulfate aerosol (4%), and ammonium nitrate aerosol (9 %) in the B1 scenario. The

  5. FK506-binding protein 1b/12.6: a key to aging-related hippocampal Ca2+ dysregulation?

    PubMed Central

    Gant, JC; Blalock, EM; K-C, Chen; Kadish, I; Porter, NM; Norris, CM; Thibault, O; Landfield, PW

    2014-01-01

    It has been recognized for some time that the Ca2+-dependent slow afterhyperpolarization (sAHP) is larger in hippocampal neurons of aged compared with young animals. In addition, extensive studies since have shown that other Ca2+-mediated electrophysiological responses are increased in hippocampus with aging, including Ca2+ transients, L-type voltage-gated Ca2+ channel activity, Ca2+ spike duration and action potential accommodation. Elevated Ca2+-induced Ca2+ release from ryanodine receptors (RyRs) appears to drive amplification of the Ca2+ responses. Components of this Ca2+ dysregulation phenotype correlate with deficits in cognitive function and plasticity, indicating they may play critical roles in aging-related impairment of brain function. However, the molecular mechanisms underlying aging-related Ca2+ dysregulation are not well understood. FK506-binding proteins 1a and 1b (FKBP1a/1b, also known as FKBP12/12.6) are immunophilin proteins that bind the immunosuppressant drugs FK506 and rapamycin. In muscle cells, FKBP1a/1b also bind RyRs and inhibits Ca2+-induced Ca2+ release, but it is not clear whether FKBPs act similarly in brain cells. Recently, we found that selectively disrupting hippocampal FKBP1b function in young rats, either by microinjecting adeno-associated viral vectors containing siRNA, or by treatment with rapamycin, increases the sAHP and recapitulates much of the hippocampal Ca2+ dysregulation phenotype. Moreover, in microarray studies, we found FKBP1b gene expression was downregulated in hippocampus of aging rats and early-stage Alzheimer’s disease subjects. These results suggest the novel hypothesis that declining FKBP function is a key factor in aging-related Ca2+ dysregulation in the brain and point to potential new therapeutic targets for counteracting unhealthy brain aging. PMID:24291098

  6. Selective increases in serotonin 5-HT1B/1D and 5-HT2A/2C binding sites in adult rat basal ganglia following lesions of serotonergic neurons.

    PubMed

    Compan, V; Segu, L; Buhot, M C; Daszuta, A

    1998-05-18

    Quantitative autoradiography was used to examine possible adaptive changes in serotonin 5-HT1B/1D and 5-HT2A/2C receptor binding sites in adult rat basal ganglia, after partial or severe lesions of serotonergic neurons produced by intraraphe injections of variable amounts of 5,7-dihydroxytryptamine. In controls, the 5-HT1B/1D sites labeled with S-CM-G[125I]TNH2 were evenly distributed in the core and the shell of the nucleus accumbens. The density of 5-HT1B/1D sites was higher in the ventral than dorsal part of the striatum and no regional differences were detected along the rostrocaudal axis of the structure. The 5-HT2A/2C sites labeled with [125I]DOI were preferentially distributed in the mediodorsal striatum and higher densities were detected in the shell than core of the nucleus accumbens. Following 5,7-dihydroxytryptamine injections, there were no changes in binding of either receptor subtype after partial lesions entailing 80-90% 5-HT depletions. After severe 5-HT depletions (over 95%), large increases in 5-HT1B/1D binding were observed in the substantia nigra (78%), but no changes took place in the globus pallidus. Increases in 5-HT1B/1D binding were also detected in the shell of the nucleus accumbens (27%). Similar sized increases in 5-HT2A/2C binding (22%) were restricted to the medial striatum. The present results suggest a preferential association between 5-HT1B/1D receptors and the striatonigral neurons containing substance P, as indicated by the striatal distribution of these receptors and their selective increases in the substantia nigra after severe 5-HT deprivation. We recently proposed a similar relationship between the 5-HT4 receptors and the striatopallidal neurons containing met-enkephalin. Moreover, the increases in 5-HT1B/1D binding in the substantia nigra and in the shell of the nucleus accumbens reinforce the view of an implication of this receptor subtype in motor functions. In contrast, the prominent increases in 5-HT2A/2C binding after

  7. Investigation of Non-Covalent Interactions of Aflatoxins (B1, B2, G1, G2, and M1) with Serum Albumin

    PubMed Central

    Poór, Miklós; Bálint, Mónika; Hetényi, Csaba; Gődér, Beatrix; Kunsági-Máté, Sándor; Lemli, Beáta

    2017-01-01

    Aflatoxins are widely spread mycotoxins produced mainly by Aspergillus species. Consumption of aflatoxin-contaminated foods and drinks causes serious health risks for people worldwide. It is well-known that the reactive epoxide metabolite of aflatoxin B1 (AFB1) forms covalent adducts with serum albumin. However, non-covalent interactions of aflatoxins with human serum albumin (HSA) are poorly characterized. Thus, in this study the complex formation of aflatoxins was examined with HSA applying spectroscopic and molecular modelling studies. Our results demonstrate that aflatoxins form stable complexes with HSA as reflected by binding constants between 2.1 × 104 and 4.5 × 104 dm3/mol. A binding free energy value of −26.90 kJ mol−1 suggests a spontaneous binding process between AFB1 and HSA at room-temperature, while the positive entropy change of 55.1 JK−1 mol−1 indicates a partial decomposition of the solvation shells of the interacting molecules. Modeling studies and investigations with site markers suggest that Sudlow’s Site I of subdomain IIA is the high affinity binding site of aflatoxins on HSA. Interaction of AFB1 with bovine, porcine, and rat serum albumins was also investigated. Similar stabilities of the examined AFB1-albumin complexes were observed suggesting the low species differences of the albumin-binding of aflatoxins. PMID:29068381

  8. Role of PTP1B in HER2 Signaling in Breast Cancer

    DTIC Science & Technology

    2012-10-01

    AD_________________ Award Number: W81XWH-10-1-1005 TITLE: Role of PTP1B in HER2 Signaling in...AND SUBTITLE 5a. CONTRACT NUMBER Role of PTP1B in HER2 Signaling in Breast Cancer 5b. GRANT NUMBER W81XWH-10-1-1005 5c. PROGRAM ELEMENT NUMBER...2009, Postdoctoral Fellowship Award W81XWH-10-1-1005, “Role of PTP1B in HER2 Signaling in Breast Cancer" INTRODUCTION  The receptor tyrosine

  9. Serological Profile of Torque Teno Sus Virus Species 1 (TTSuV1) in Pigs and Antigenic Relationships between Two TTSuV1 Genotypes (1a and 1b), between Two Species (TTSuV1 and -2), and between Porcine and Human Anelloviruses

    PubMed Central

    Huang, Yao-Wei; Harrall, Kylie K.; Dryman, Barbara A.; Opriessnig, Tanja; Vaughn, Eric M.; Roof, Michael B.

    2012-01-01

    The family Anelloviridae includes human and animal torque teno viruses (TTVs) with extensive genetic diversity. The antigenic diversity among anelloviruses has never been assessed. Using torque teno sus virus (TTSuV) as a model, we describe here the first investigation of the antigenic relationships among different anelloviruses. Using a TTSuV genotype 1a (TTSuV1a) or TTSuV1b enzyme-linked immunosorbent assay (ELISA) based on the respective putative ORF1 capsid antigen and TTSuV1-specific real-time PCR, the combined serological and virological profile of TTSuV1 infection in pigs was determined and compared with that of TTSuV2. TTSuV1 is likely not associated with porcine circovirus-associated disease (PCVAD), because both the viral loads and antibody levels were not different between affected and unaffected pigs and because there was no synergistic effect of concurrent PCV2/TTSuV1 infections. We did observe a higher correlation of IgG antibody levels between anti-TTSuV1a and -TTSuV1b than between anti-TTSuV1a or -1b and anti-TTSuV2 antibodies in these sera, implying potential antigenic cross-reactivity. To confirm this, rabbit antisera against the putative capsid proteins of TTSuV1a, TTSuV1b, or TTSuV2 were generated, and the antigenic relationships among these TTSuVs were analyzed by an ELISA and by an immunofluorescence assay (IFA) using PK-15 cells transfected with one of the three TTSuV ORF1 constructs. The results demonstrate antigenic cross-reactivity between the two genotypes TTSuV1a and TTSuV1b but not between the two species TTSuV1a or -1b and TTSuV2. Furthermore, an anti-genogroup 1 human TTV antiserum did not react with any of the three TTSuV antigens. These results have important implications for an understanding of the diversity of anelloviruses as well as for the classification and vaccine development of TTSuVs. PMID:22811540

  10. Interactions of phytochromes A, B1 and B2 in light-induced competence for adventitious shoot formation in hypocotyl of tomato (Solanum lycopersicum L.).

    PubMed

    Lercari, B; Bertram, L

    2004-02-01

    The interactions of phytochrome A (phyA), phytochrome B1 (phyB1) and phytochrome B2 (phyB2) in light-dependent shoot regeneration from the hypocotyl of tomato was analysed using all eight possible homozygous allelic combinations of the null mutants. The donor plants were pre-grown either in the dark or under red or far-red light for 8 days after sowing; thereafter hypocotyl segments (apical, middle and basal portions) were transferred onto hormone-free medium for culture under different light qualities. Etiolated apical segments cultured in vitro under white light showed a very high frequency of regeneration for all of the genotypes tested besides phyB1phyB2, phyAphyB1 and phyAphyB1phyB2 mutants. Evidence is provided of a specific interference of phyB2 with phyA-mediated HIR to far-red and blue light in etiolated explants. Pre-treatment of donor plants by growth under red light enhanced the competence of phyB1phyB2, phyAphyB1 and phyAphyB1phyB2 mutants for shoot regeneration, whereas pre-irradiation with far-red light enhanced the frequency of regeneration only in the phyAphyB1 mutant. Multiple phytochromes are involved in red light- and far-red light-dependent acquisition of competence for shoot regeneration. The position of the segments along the hypocotyl influenced the role of the various phytochromes and the interactions between them. The culture of competent hypocotyl segments under red, far-red or blue light reduced the frequency of explants forming shoots compared to those cultured under white light, with different genotypes having different response patterns.

  11. Broad-spectrum immunoaffinity cleanup for the determination of aflatoxins B1, B2, G1, G2, M1, M2 in Ophiocordyceps sinensis and its pharmaceutical preparations by ultra performance liquid chromatography tandem mass spectrometry.

    PubMed

    Sun, Shujuan; Xie, Jie; Peng, Tao; Shao, Bing; Zhu, Kui; Sun, Yuanze; Yao, Kai; Gu, Qiang; Zhang, Jing; Fan, Chunlin; Chen, Ying; Jiang, Haiyang

    2017-11-15

    An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of aflatoxins B 1 , B 2 , G 1 , G 2 , M 1 and M 2 (AFB 1 , AFB 2 , AFG 1 , AFG 2 , AFM 1 and AFM 2 ) in Ophiocordyceps sinensis and its pharmaceutical preparations. A rapid and reliable immunoaffinity column containing a broad-spectrum monoclonal antibody for six aflatoxins was used for sample cleanup. Under the optimized conditions, the home-made immunoaffinity column capacity were about 315, 319, 292, 102, 444 and 369ng/mL gel for AFB 1 , AFB 2 , AFG 1 , AFG 2 , AFM 1 and AFM 2 , respectively. Recoveries for all tested aflatoxins ranged from 79.28% to 103.42% with relative standard deviation less than 8%. The limits of quantitation were in the range of 0.008-0.045μg/kg. Among 31 real samples analyzed, one sample was contaminated with AFB 1 , AFB 2 and AFM 1 at levels of 0.483, 0.068 and 0.104μg/kg, respectively. The established method is simple, accurate, and can be effectively used to determine the aflatoxins in Ophiocordyceps sinensis and its pharmaceutical preparations. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Thermodynamic consideration and ground-state search of icosahedral boron subselenide B12(B1-xSex) 2 from a first-principles cluster expansion

    NASA Astrophysics Data System (ADS)

    Ektarawong, A.

    2018-05-01

    The phase stability of icosahedral boron subselenide B12(B1-xSex) 2 , where 0.5 ≤x ≤1 , is explored using a first-principles cluster expansion. The results shows that, instead of a continuous solid solution, B12(B1-xSex) 2 is thermodynamically stable as an individual line compound at the composition of B9.5Se . The ground-state configuration of B9.5Se is represented by a mixture of B12(Se-Se), B12(B-Se), and B12(Se-B) with a ratio of 1:1:1, where they form a periodic A B C A B C ⋯ stacking sequence of B12(Se-Se), B12(B-Se), and B12(Se-B) layers along the c axis of the hexagonal conventional unit cell. The structural and electronic properties of the ground-state B9.5Se are also derived and discussed. By comparing the derived ground-state properties of B9.5Se to the existing experimental data of boron subselenide B˜13Se , I proposed that the as-synthesized boron subselenide B˜13Se , as reported in the literature, has the actual composition of B9.5Se .

  13. Analysis of Qa-1bPeptide Binding Specificity and the Capacity of Cd94/Nkg2a to Discriminate between Qa-1–Peptide Complexes

    PubMed Central

    Kraft, Jennifer R.; Vance, Russell E.; Pohl, Jan; Martin, Amy M.; Raulet, David H.; Jensen, Peter E.

    2000-01-01

    The major histocompatibility complex class Ib protein, Qa-1b, serves as a ligand for murine CD94/NKG2A natural killer (NK) cell inhibitory receptors. The Qa-1b peptide-binding site is predominantly occupied by a single nonameric peptide, Qa-1 determinant modifier (Qdm), derived from the leader sequence of H-2D and L molecules. Five anchor residues were identified in this study by measuring the peptide-binding affinities of substituted Qdm peptides in experiments with purified recombinant Qa-1b. A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions. The results indicate that Qa-1b can bind a diverse repertoire of peptides but that Qdm has an optimal primary structure for binding Qa-1b. Flow cytometry experiments with Qa-1b tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1b complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. Our findings suggest that it may be difficult for viruses to generate decoy peptides that mimic Qdm and raise the possibility that competitive replacement of Qdm with other peptides may provide a novel mechanism for activation of NK cells. PMID:10974028

  14. New analytical techniques for mycotoxins in complex organic matrices. [Aflatoxins B1, B2, G1, and G2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bicking, M.K.L.

    1982-07-01

    Air samples are collected for analysis from the Ames Solid Waste Recovery System. The high level of airborne fungi within the processing area is of concern due to the possible presence of toxic mycotoxins, and carcinogenic fungal metabolites. An analytical method has been developed to determine the concentration of aflatoxins B1, B2, G1, and G2 in the air of the plant which produces Refuse Derived Fuel (RDF). After extraction with methanol, some components in the matrix are precipitated by dissolving the sample in 30% acetonitrile/chloroform. An aliquot of this solution is injected onto a Styragel column where the sample componentsmore » undergo simultaneous size exclusion and reverse phase partitioning. Additional studies have provided a more thorough understanding of solvent related non-exclusion effects on size exclusion gels. The Styragel column appears to have a useable lifetime of more than six months. After elution from Styragel, the sample is diverted to a second column containing Florisil which has been modified with oxalic acid and deactivated with water. Aflatoxins are eluted with 5% water/acetone. After removal of this solvent, the sample is dissolved in 150 ..mu..L of a spotting solvent and the entire sample applied to a thin layer chromatography (TLC) plate using a unique sample applicator developed here. The aflatoxins on the TLC plate are analyzed by laser fluorescence. A detection limit of 10 pg is possible for aflatoxin standards using a nitrogen laser as the excitation source. Sample concentrations are determined by comparing with an internal standard, a specially synthesized aflatoxin derivative. In two separate RDF samples, aflatoxin B1 was found at levels of 6.5 and 17.0 ppB. The analytical method has also proven useful in the analysis of contaminated corn and peanut meal samples. 42 figures, 8 tables.« less

  15. pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1.

    PubMed

    Varma, Manthena V; Rotter, Charles J; Chupka, Jonathan; Whalen, Kevin M; Duignan, David B; Feng, Bo; Litchfield, John; Goosen, Theunis C; El-Kattan, Ayman F

    2011-08-01

    The human organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) is ubiquitously expressed and may play an important role in the disposition of xenobiotics. The present study aimed to examine the role of OATP2B1 in the intestinal absorption and tissue uptake of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors (statins). We first investigated the functional affinity of statins to the transporter as a function of extracellular pH, using OATP2B1-transfeced HEK293 cells. The results indicate that OATP2B1-mediated transport is significant for rosuvastatin, fluvastatin and atorvastatin, at neutral pH. However, OATP2B1 showed broader substrate specificity as well as enhanced transporter activity at acidic pH. Furthermore, uptake at acidic pH was diminished in the presence of proton ionophore, suggesting proton gradient as the driving force for OATP2B1 activity. Notably, passive transport rates are predominant or comparable to active transport rates for statins, except for rosuvastatin and fluvastatin. Second, we studied the effect of OATP modulators on statin uptake. At pH 6.0, OATP2B1-mediated transport of atorvastatin and cerivastatin was not inhibitable, while rosuvastatin transport was inhibited by E-3-S, rifamycin SV and cyclosporine with IC(50) values of 19.7 ± 3.3 μM, 0.53 ± 0.2 μM and 2.2 ± 0.4 μM, respectively. Rifamycin SV inhibited OATP2B1-mediated transport of E-3-S and rosuvastatin with similar IC(50) values at pH 6.0 and 7.4, suggesting that the inhibitor affinity is not pH-dependent. Finally, we noted that OATP2B1-mediated transport of E-3-S, but not rosuvastatin, is pH sensitive in intestinal epithelial (Caco-2) cells. However, uptake of E-3-S and rosuvastatin by Caco-2 cells was diminished in the presence of proton ionophore. The present results indicate that OATP2B1 may be involved in the tissue uptake of rosuvastatin and fluvastatin, while OATP2B1 may play a significant role in the intestinal absorption of several

  16. SLCO1B1 variants and statin-induced myopathy--a genomewide study.

    PubMed

    Link, E; Parish, S; Armitage, J; Bowman, L; Heath, S; Matsuda, F; Gut, I; Lathrop, M; Collins, R

    2008-08-21

    Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions in cardiovascular events, and larger reductions in cholesterol may produce larger benefits. In rare cases, myopathy occurs in association with statin therapy, especially when the statins are administered at higher doses and with certain other medications. We carried out a genomewide association study using approximately 300,000 markers (and additional fine-mapping) in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12,000 participants. Replication was tested in a trial of 40 mg of simvastatin daily involving 20,000 participants. The genomewide scan yielded a single strong association of myopathy with the rs4363657 single-nucleotide polymorphism (SNP) located within SLCO1B1 on chromosome 12 (P=4x10(-9)). SLCO1B1 encodes the organic anion-transporting polypeptide OATP1B1, which has been shown to regulate the hepatic uptake of statins. The noncoding rs4363657 SNP was in nearly complete linkage disequilibrium with the nonsynonymous rs4149056 SNP (r(2)=0.97), which has been linked to statin metabolism. The prevalence of the rs4149056 C allele in the population was 15%. The odds ratio for myopathy was 4.5 (95% confidence interval [CI], 2.6 to 7.7) per copy of the C allele, and 16.9 (95% CI, 4.7 to 61.1) in CC as compared with TT homozygotes. More than 60% of these myopathy cases could be attributed to the C variant. The association of rs4149056 with myopathy was replicated in the trial of 40 mg of simvastatin daily, which also showed an association between rs4149056 and the cholesterol-lowering effects of simvastatin. No SNPs in any other region were clearly associated with myopathy. We have identified common variants in SLCO1B1 that are strongly associated with an increased risk of statin-induced myopathy. Genotyping these variants may help to achieve the benefits of statin

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

    PubMed

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

    2017-01-01

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

  18. High resolution absolute absorption cross sections of the B ̃(1)A'-X ̃(1)A' transition of the CH2OO biradical.

    PubMed

    Foreman, Elizabeth S; Kapnas, Kara M; Jou, YiTien; Kalinowski, Jarosław; Feng, David; Gerber, R Benny; Murray, Craig

    2015-12-28

    Carbonyl oxides, or Criegee intermediates, are formed from the gas phase ozonolysis of alkenes and play a pivotal role in night-time and urban area atmospheric chemistry. Significant discrepancies exist among measurements of the strong B ̃(1)A'-X ̃(1)A' electronic transition of the simplest Criegee intermediate, CH2OO in the visible/near-UV. We report room temperature spectra of the B ̃(1)A'-X ̃(1)A' electronic absorption band of CH2OO acquired at higher resolution using both single-pass broadband absorption and cavity ring-down spectroscopy. The new absorption spectra confirm the vibrational structure on the red edge of the band that is absent from ionization depletion measurements. The absolute absorption cross sections over the 362-470 nm range are in good agreement with those reported by Ting et al. Broadband absorption spectra recorded over the temperature range of 276-357 K were identical within their mutual uncertainties, confirming that the vibrational structure is not due to hot bands.

  19. Reduced expression of APC-1B but not APC-1A by the deletion of promoter 1B is responsible for familial adenomatous polyposis.

    PubMed

    Yamaguchi, Kiyoshi; Nagayama, Satoshi; Shimizu, Eigo; Komura, Mitsuhiro; Yamaguchi, Rui; Shibuya, Tetsuo; Arai, Masami; Hatakeyama, Seira; Ikenoue, Tsuneo; Ueno, Masashi; Miyano, Satoru; Imoto, Seiya; Furukawa, Yoichi

    2016-05-24

    Germline mutations in the tumor suppressor gene APC are associated with familial adenomatous polyposis (FAP). Here we applied whole-genome sequencing (WGS) to the DNA of a sporadic FAP patient in which we did not find any pathological APC mutations by direct sequencing. WGS identified a promoter deletion of approximately 10 kb encompassing promoter 1B and exon1B of APC. Additional allele-specific expression analysis by deep cDNA sequencing revealed that the deletion reduced the expression of the mutated APC allele to as low as 11.2% in the total APC transcripts, suggesting that the residual mutant transcripts were driven by other promoter(s). Furthermore, cap analysis of gene expression (CAGE) demonstrated that the deleted promoter 1B region is responsible for the great majority of APC transcription in many tissues except the brain. The deletion decreased the transcripts of APC-1B to 39-45% in the patient compared to the healthy controls, but it did not decrease those of APC-1A. Different deletions including promoter 1B have been reported in FAP patients. Taken together, our results strengthen the evidence that analysis of structural variations in promoter 1B should be considered for the FAP patients whose pathological mutations are not identified by conventional direct sequencing.

  20. B1 to B2 structural phase transition in LiF under pressure

    NASA Astrophysics Data System (ADS)

    Jain, Aayushi; Dixit, R. C.

    2018-05-01

    In the last few decades the alkali halides emerged as crystals with useful applications and their high-pressure behaviour is the most intensively studied subject in high-pressure physics/chemistry, material science, and geosciences. Most alkali halides follow the B1 (NaCl-type)→B2 (CsCl-type) phase-transition route under pressure. In the present paper, we have investigated the characteristics of structural phase transition that occurred in Lithium Florid compound under high pressure. The transition pressure of B1-B2 was calculated using an effective interionic interaction potential (EIOP). The changes of the characteristics of crystals like, Gibbs free energy, cohesive energy, volume collapse, and lattice constant are calculated for the B1 and B2 structures. These data were compared with the available experimental and theoretical data.

  1. Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent.

    PubMed

    Myagmar, Bat-Erdene; Flynn, James M; Cowley, Patrick M; Swigart, Philip M; Montgomery, Megan D; Thai, Kevin; Nair, Divya; Gupta, Rumita; Deng, David X; Hosoda, Chihiro; Melov, Simon; Baker, Anthony J; Simpson, Paul C

    2017-03-31

    It is unknown whether every ventricular myocyte expresses all 5 of the cardiac adrenergic receptors (ARs), β1, β2, β3, α1A, and α1B. The β1 and β2 are thought to be the dominant myocyte ARs. Quantify the 5 cardiac ARs in individual ventricular myocytes. We studied ventricular myocytes from wild-type mice, mice with α1A and α1B knockin reporters, and β1 and β2 knockout mice. Using individual isolated cells, we measured knockin reporters, mRNAs, signaling (phosphorylation of extracellular signal-regulated kinase and phospholamban), and contraction. We found that the β1 and α1B were present in all myocytes. The α1A was present in 60%, with high levels in 20%. The β2 and β3 were detected in only ≈5% of myocytes, mostly in different cells. In intact heart, 30% of total β-ARs were β2 and 20% were β3, both mainly in nonmyocytes. The dominant ventricular myocyte ARs present in all cells are the β1 and α1B. The β2 and β3 are mostly absent in myocytes but are abundant in nonmyocytes. The α1A is in just over half of cells, but only 20% have high levels. Four distinct myocyte AR phenotypes are defined: 30% of cells with β1 and α1B only; 60% that also have the α1A; and 5% each that also have the β2 or β3. The results raise cautions in experimental design, such as receptor overexpression in myocytes that do not express the AR normally. The data suggest new paradigms in cardiac adrenergic signaling mechanisms. © 2017 American Heart Association, Inc.

  2. Influence of nanosized amorphous silica on assimilation of vitamins B1, B2 and B6 in rats.

    PubMed

    Gmoshinsky, I V; Vrzhesinskaya, O A; Shumakova, A A; Shipelin, V A; Kodentsova, V M; Khotimchenko, S A

    2016-01-01

    Amorphous silica (SiO2) in the form of nanoparticles (NPs) is widely used as a food additive E551 in many enriched foods and food supplements. The aim of this study was to evaluate the effect of oral administration of SiO2 NPs on assimilation and metabolism of vitamins B1, B2 and B6 in laboratory rats. Amorphous SiO2 «Orisil-300 ®» was used with the size of the primary NPs 20-60 nm according to the electronic, atomic force microscopy and dynamic light scattering. The experiment was conducted on 8 groups of growing male Wistar rats (with initial body weight 70-80g) number, respectively, 7, 7, 10, 10, 12, 12, 14 and 16 animals. Animals of the 1st, 3rd, 4th and 5th groups received through­out the experiment balanced semi-synthetic diet. Animals of the 2nd group received a diet depleted of vitamins B1, B2 and B6 until day 21; animals of the 6th, 7th and 8th groups -the same diet from the 1st to the 21th day, and then, before the closure of the experiment, the diet provided with the indicated B vitamins at 100% of normal level. From day 22 of experiment and until the end at day 29 the animals of the 3rd and 6th groups received deionized water (placebo) through intragastric gavage; rat of the 4th and 7th groups -aqueous suspension of SiO2 dose of 1 mg/kg body weight /day, and the 5th and 8th group -100 mg/kg/day. Urinary excretion of thiamine, riboflavin, 4-pyridoxilic acid and liver and brain content of vitamins B1 and B2 (after acid and enzyme hydrolysis) were deter­mined by fluorimetric methods. It was found that rats in group 2 lagged in weight gain at day 21 significantly compared to group 1, and developed a marked deficiency of vitamins B1, B2 and B6 according to studied safety parameters. In groups from 6 to 8 at day 29 par­tial recovery was achieved in vitamin status. Administration of SiO2 to animal of groups 4 and 5, with normal consumption of B vitamins, had no significant effect on any param­eters of vitamin status in comparison to group 3. However

  3. Expression of the tumor suppressor genes NF2, 4.1B, and TSLC1 in canine meningiomas.

    PubMed

    Dickinson, P J; Surace, E I; Cambell, M; Higgins, R J; Leutenegger, C M; Bollen, A W; LeCouteur, R A; Gutmann, D H

    2009-09-01

    Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.

  4. Interminimum foF1 Differences and Their Physical Interpretation

    NASA Astrophysics Data System (ADS)

    Mikhailov, A. V.; Perrone, L.

    2018-01-01

    Interminimum changes of June noontime monthly median <fi>foF>1 were analyzed for European and Japanese ionosonde stations over the period of five (Moscow six) solar cycles. The magnitude of these changes is different at different stations and depends on the solar minima considered. In particular, both European and Japanese stations manifest a pronounced <fi>foF>1 change between 1996/1997 and 2008/2009 solar minima, the latter being the deepest one. For the first time, the total EUV solar flux with <fi>λ> ≤ 1,050 Å has been retrieved for the 1946-2015 period using observed June monthly median <fi>foF>1. The deep solar minimum in 2008/2009 was the lowest one among the last six solar cycles comparing the retrieved EUV. The change from 1996/1997 to 2008/2009 in the retrieved EUV is 2.0%, and this is much less than the difference of 10-12% being discussed in the literature. A 10% interminimum change in the total EUV flux results in neutral temperature and gas density, which are larger in 2008 than in 1996, and this contradicts the satellite drag neutral gas density observations. The mechanism of <fi>foF>1 interminimum changes is based on an interplay between molecular (NO+ and O2+) and O+ ions. The main contribution (>72%) to the interminimum <fi>NmF>1 change provides [M+] ions via the total ion production rate variation, the rest is provided via O+ ions. The absence (or inversed) difference in <fi>foF>1 between 1996 and 2008 minima implies that neutral temperature and density are larger in 2008 than in 1996, and this contradicts the satellite drag observations.

  5. Periaqueductal gray knockdown of V2, not V1a and V1b receptor influences nociception in the rat. yj6676@yahoo.com.

    PubMed

    Yang, Jun; Yang, Yu; Chen, Jian-Min; Wang, Gen; Xu, Hong-Tao; Liu, Wen-Yan; Lin, Bao-Cheng

    2007-01-01

    Our pervious study has proved that arginine vasopressin (AVP) in periaqueductal gray (PAG) plays a role in antinociception. After establishing a model of local special gene knockdown, the nociceptive effect of vasopressin receptor subunit in PAG was investigated in the rat. Microinjection of short-interfering RNA (siRNA) into PAG, which targeted vasopressin receptor subtypes (V(1a), V(1b) and V(2)), locally weakened the associated mRNA expression and depressed the related receptor synthesis in a dose-dependent manner, in which the significant inhibitive effect occurred on from 7th day to 14th day following 1microg or 2microg siRNA administration. PAG knockdown of V(2) receptor gene markedly decreased pain threshold in from 6th day to 13th day after siRNA administration, whereas local knockdown of either V(1a) or V(1b) receptor gene could not influence pain threshold. The data suggest that V(2) rather than V(1a) and V(1b) receptor in PAG involves in nociception.

  6. 26 CFR 1.167(b)-2 - Declining balance method.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Declining balance method. 1.167(b)-2 Section 1... Declining balance method. (a) Application of method. Under the declining balance method a uniform rate is.... While salvage is not taken into account in determining the annual allowances under this method, in no...

  7. SLCO2B1 and SLCO1B3 as New Targets for Enhancing Androgen Deprivation Therapy for Prostate Cancer

    DTIC Science & Technology

    2016-10-01

    Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as...a significantly lower level of SLCO2B1 expression, compared to those carrying the minor (risk) allele. SLCO2B1 expression levels are directly...Special Reporting Requirements…………………………………… 18 9. Appendices…………………………………………………………… .19 1 1, Introduction The androgen receptor ( AR ) plays an essential

  8. Characterisation of Translation Elongation Factor eEF1B Subunit Expression in Mammalian Cells and Tissues and Co-Localisation with eEF1A2

    PubMed Central

    Janikiewicz, Justyna; Doig, Jennifer; Abbott, Catherine M.

    2014-01-01

    Translation elongation is the stage of protein synthesis in which the translation factor eEF1A plays a pivotal role that is dependent on GTP exchange. In vertebrates, eEF1A can exist as two separately encoded tissue-specific isoforms, eEF1A1, which is almost ubiquitously expressed, and eEF1A2, which is confined to neurons and muscle. The GTP exchange factor for eEF1A1 is a complex called eEF1B made up of subunits eEF1Bα, eEF1Bδ and eEF1Bγ. Previous studies have cast doubt on the ability of eEF1B to interact with eEF1A2, suggesting that this isoform might use a different GTP exchange factor. We show that eEF1B subunits are all widely expressed to varying degrees in different cell lines and tissues, and at different stages of development. We show that ablation of any of the subunits in human cell lines has a small but significant impact on cell viability and cycling. Finally, we show that both eEF1A1 and eEF1A2 colocalise with all eEF1B subunits, in such close proximity that they are highly likely to be in a complex. PMID:25436608

  9. [Determination of aflatoxin B1, B2, G1, G2 in armeniacae semen amarum by high-performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Zheng, Run-Sheng; Xu, Hui; Wang, Wen-Li; Zhan, Ruo-Ting; Chen, Wei-Wen

    2013-10-01

    A simple, rapid and cost-effective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/ MS) method was established for simultaneous determination of aflatoxins (AFB1, AFB2, AFG1, AFG2) in Armeniacae Semen Amarum and the application was performance in 11 samples collected from different markets, medical stores and hospitals. The sample was extracted with 84% acetonitrile/water and 250 microL extraction was directly injected into a LC-MS/MS system without further purification procedure after being redissolved with methanol. The LC separation was performed on a C18 column with a linear gradient elution program of 4 mmol x L(-1) NH4 Ac-0.1% formic acid solution and menthol as the mobile phase. Selected reaction monitoring (SRM) was used for selective determination of the four aflatoxins on a triple quadruple mass spectrometer, which was operated in positive ionization modes. All the four aflatoxins showed a good linear relationship with r > 0.999 0, the average recoveries were between 87.88% and 102.9% and the matrix effect was ranged from 90.71% to 99.30% in low, intermediate and high levels. Furthermore, the higher recovery was obtained by the method reported in this study, comparing to the cleanup procedure with the Mycosep 226 purification column. Eleven samples collected were detected and the contamination levels of the AFB1 were between 1.590-2.340 microg x kg(-1) and the AF (B1 + B2 + G1 + G2) was ranged from 2.340 to 3.340 microg x kg(-1). In summary, the developed method was suitable to detect and screen AFB1, AFB2, AFG1, AFG2 in Armeniacae Semen Amarum.

  10. Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains.

    PubMed

    Shahzad, Shakeel; Ashraf, M Adnan; Sajid, M; Shahzad, Aqeel; Rafique, Azhar; Mahmood, M Shahid

    2018-02-02

    Multiple drug resistant super bugs of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) are becoming challenge for healthcare professionals. In this study, vitamins were evaluated for synergistic activity with the antibiotics. Synergistic effect between antibiotic and stock solutions of vitamins is evaluated by using Kirby-Bauer disc diffusion assay. Distilled water and propylene glycol were used as solvent for water soluble vitamins and fat-soluble vitamins respectively. The final concentration of 10mg/ml of each water-soluble vitamin B1 (Thiamine), B2 (Riboflavin), B6 (Pyridoxine) B12 (Methylcobalamin), C (Ascorbic acid) and 0.1mg/ml of each fat soluble vitamin A (retinol), D (cholecalciferol) E (αTocopherol) K (Menadione) were used with the antibiotics. The results depicted that vitamin K and E have better synergistic activity with piperacillin-tazobactam, imipenem and doripenem antibiotics against A. baumannii. While vitamin B1, B2 and B12 showed remarkable synergistic activity with linezolid against MRSA. Vitamin B1 was further tested to have better synergism with antibiotics oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K were good in synergism against Gram negative A. baumannii while water soluble vitamins as B1, B2 and B12 were effective against MRSA but not against A. baumannii. This synergistic action of vitamins with the antibiotics can be used as a tool to treat multiple drug resistant super bugs with further evaluation at molecular level. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  11. Glypican-1-antibody-conjugated Gd–Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer

    PubMed Central

    Zhu, Huanhuan; Le, Wenjun; Cui, Shaobin; Chen, Xin; Li, Wei; Zhang, Fulei; Huang, Yong; Sh, Donglu; Cui, Zheng; Shao, Chengwei; Chen, Bingdi

    2018-01-01

    Introduction Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. Materials and methods In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd–Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Results Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s−1 mM−1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s−1 mM−1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Conclusion Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC. PMID:29750031

  12. Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer.

    PubMed

    Huang, Xin; Fan, Chengqi; Zhu, Huanhuan; Le, Wenjun; Cui, Shaobin; Chen, Xin; Li, Wei; Zhang, Fulei; Huang, Yong; Sh, Donglu; Cui, Zheng; Shao, Chengwei; Chen, Bingdi

    2018-01-01

    Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd-Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s -1 mM -1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s -1 mM -1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC.

  13. Lightweight Towed Howitzer Demonstrator. Phase 1 and Partial Phase 2. Volume D1. Part 1. Structural Analysis (Less Cradle and System).

    DTIC Science & Technology

    1987-04-01

    X4Cro 7WAW,"G9 N k Y,1i ACCA . 2 JVM ly y,- L OA.0 v roo*Ler t-OAD. FA’ A /"Fi./A/a. (" -A,E’ CNAiv*6:CP A/ ’r/O’,L C4A$4P&4R.* -1MAGC.T?D0 VI.3 Moon...M- S 3D = .. = ==-=== Version 1.1 02/01/85 LTHD muzzle brate thermal load - steel Load Case 1: Loads Node F x FFM - My

  14. Characterization of the Critical Amino Acids of an Aspergillus parasiticus Cytochrome P-450 Monooxygenase Encoded by ordA That Is Involved in the Biosynthesis of Aflatoxins B1, G1, B2, and G2

    PubMed Central

    Yu, Jiujiang; Chang, Perng-Kuang; Ehrlich, Kenneth C.; Cary, Jeffrey W.; Montalbano, Beverly; Dyer, John M.; Bhatnagar, Deepak; Cleveland, Thomas E.

    1998-01-01

    The conversion of O-methylsterigmatocystin (OMST) and dihydro-O-methylsterigmatocystin to aflatoxins B1, G1, B2, and G2 requires a cytochrome P-450 type of oxidoreductase activity. ordA, a gene adjacent to the omtA gene, was identified in the aflatoxin-biosynthetic pathway gene cluster by chromosomal walking in Aspergillus parasiticus. The ordA gene was a homolog of the Aspergillus flavus ord1 gene, which is involved in the conversion of OMST to aflatoxin B1. Complementation of A. parasiticus SRRC 2043, an OMST-accumulating strain, with the ordA gene restored the ability to produce aflatoxins B1, G1, B2, and G2. The ordA gene placed under the control of the GAL1 promoter converted exogenously supplied OMST to aflatoxin B1 in Saccharomyces cerevisiae. In contrast, the ordA gene homolog in A. parasiticus SRRC 2043, ordA1, was not able to carry out the same conversion in the yeast system. Sequence analysis revealed that the ordA1 gene had three point mutations which resulted in three amino acid changes (His-400→Leu-400, Ala-143→Ser-143, and Ile-528→Tyr-528). Site-directed mutagenesis studies showed that the change of His-400 to Leu-400 resulted in a loss of the monooxygenase activity and that Ala-143 played a significant role in the catalytic conversion. In contrast, Ile-528 was not associated with the enzymatic activity. The involvement of the ordA gene in the synthesis of aflatoxins G1, and G2 in A. parasiticus suggests that enzymes required for the formation of aflatoxins G1 and G2 are not present in A. flavus. The results showed that in addition to the conserved heme-binding and redox reaction domains encoded by ordA, other seemingly domain-unrelated amino acid residues are critical for cytochrome P-450 catalytic activity. The ordA gene has been assigned to a new cytochrome P-450 gene family named CYP64 by The Cytochrome P450 Nomenclature Committee. PMID:9835571

  15. The Metastasis Efficiency Modifier Ribosomal RNA Processing 1 Homolog B (RRP1B) Is a Chromatin-associated Factor*

    PubMed Central

    Crawford, Nigel P. S.; Yang, Hailiu; Mattaini, Katherine R.; Hunter, Kent W.

    2009-01-01

    There is accumulating evidence for a role of germ line variation in breast cancer metastasis. We have recently identified a novel metastasis susceptibility gene, Rrp1b (ribosomal RNA processing 1 homolog B). Overexpression of Rrp1b in a mouse mammary tumor cell line induces a gene expression signature that predicts survival in breast cancer. Here we extend the analysis of RRP1B function by demonstrating that the Rrp1b activation gene expression signature accurately predicted the outcome in three of four publicly available breast carcinoma gene expression data sets. In addition, we provide insights into the mechanism of RRP1B. Tandem affinity purification demonstrated that RRP1B physically interacts with many nucleosome binding factors, including histone H1X, poly(ADP-ribose) polymerase 1, TRIM28 (tripartite motif-containing 28), and CSDA (cold shock domain protein A). Co-immunofluorescence and co-immunoprecipitation confirmed these interactions and also interactions with heterochromatin protein-1α and acetyl-histone H4 lysine 5. Finally, we investigated the effects of ectopic expression of an RRP1B allelic variant previously associated with improved survival in breast cancer. Gene expression analyses demonstrate that, compared with ectopic expression of wild type RRP1B in HeLa cells, the variant RRP1B differentially modulates various transcription factors controlled by TRIM28 and CSDA. These data suggest that RRP1B, a tumor progression and metastasis susceptibility candidate gene, is potentially a dynamic modulator of transcription and chromatin structure. PMID:19710015

  16. New ab initio adiabatic potential energy surfaces and bound state calculations for the singlet ground X˜ 1A1 and excited C˜ 1B2(21A') states of SO2

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

    We report new and more accurate adiabatic potential energy surfaces (PESs) for the ground X˜ 1A1 and electronically excited C˜ 1B2(21A') states of the SO2 molecule. Ab initio points are calculated using the explicitly correlated internally contracted multi-reference configuration interaction (icMRCI-F12) method. A second less accurate PES for the ground X ˜ state is also calculated using an explicitly correlated single-reference coupled-cluster method with single, double, and non-iterative triple excitations [CCSD(T)-F12]. With these new three-dimensional PESs, we determine energies of the vibrational bound states and compare these values to existing literature data and experiment.

  17. 75 FR 34062 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2... AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2, and N helicopters, with certain main... an unsafe condition for certain Eurocopter France Model AS 350 B, BA, BB, B1, B2, B3, and D, and...

  18. B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1)

    DTIC Science & Technology

    2015-12-01

    Confidence Level Confidence Level of cost estimate for current APB: 55% This APB reflects cost and funding data based on the B-2 EHF Increment I SCP...This cost estimate was quantified at the Mean (~55%) confidence level . Total Quantity Quantity SAR Baseline Production Estimate Current APB...Production Estimate Econ Qty Sch Eng Est Oth Spt Total 33.624 -0.350 1.381 0.375 0.000 -6.075 0.000 -0.620 -5.289 28.335 Current SAR Baseline to Current

  19. RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.

    PubMed

    Mitsuda, Yoshihide; Morita, Ken; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Obara, Moeka; Hirata, Masahiro; Kataoka, Tatsuki R; Muto, Manabu; Kaneda, Yasufumi; Nakahata, Tatsutoshi; Liu, Pu Paul; Adachi, Souichi; Sugiyama, Hiroshi; Kamikubo, Yasuhiko

    2018-04-23

    The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M') consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy.

  20. Mouse model of Epstein-Barr virus LMP1- and LMP2A-driven germinal center B-cell lymphoproliferative disease.

    PubMed

    Minamitani, Takeharu; Ma, Yijie; Zhou, Hufeng; Kida, Hiroshi; Tsai, Chao-Yuan; Obana, Masanori; Okuzaki, Daisuke; Fujio, Yasushi; Kumanogoh, Atsushi; Zhao, Bo; Kikutani, Hitoshi; Kieff, Elliott; Gewurz, Benjamin E; Yasui, Teruhito

    2017-05-02

    Epstein-Barr virus (EBV) is a major cause of immunosuppression-related B-cell lymphomas and Hodgkin lymphoma (HL). In these malignancies, EBV latent membrane protein 1 (LMP1) and LMP2A provide infected B cells with surrogate CD40 and B-cell receptor growth and survival signals. To gain insights into their synergistic in vivo roles in germinal center (GC) B cells, from which most EBV-driven lymphomas arise, we generated a mouse model with conditional GC B-cell LMP1 and LMP2A coexpression. LMP1 and LMP2A had limited effects in immunocompetent mice. However, upon T- and NK-cell depletion, LMP1/2A caused massive plasmablast outgrowth, organ damage, and death. RNA-sequencing analyses identified EBV oncoprotein effects on GC B-cell target genes, including up-regulation of multiple proinflammatory chemokines and master regulators of plasma cell differentiation. LMP1/2A coexpression also up-regulated key HL markers, including CD30 and mixed hematopoietic lineage markers. Collectively, our results highlight synergistic EBV membrane oncoprotein effects on GC B cells and provide a model for studies of their roles in immunosuppression-related lymphoproliferative diseases.

  1. NACA Aircraft on Lakebed - D-558-2, X-1B, and X-1E

    NASA Technical Reports Server (NTRS)

    1955-01-01

    Early NACA research aircraft on the lakebed at the High Speed Research Station in 1955: Left to right: X-1E, D-558-2, X-1B There were four versions of the original Bell X-1 rocket-powered research aircraft that flew at the NACA High-Speed Flight Research Station, Edwards, California. The bullet-shaped X-1 aircraft were built by Bell Aircraft Corporation, Buffalo, N.Y. for the U.S. Army Air Forces (after 1947, U.S. Air Force) and the National Advisory Committee for Aeronautics (NACA). The X-1 Program was originally designated the XS-1 for EXperimental Supersonic. The X-1's mission was to investigate the transonic speed range (speeds from just below to just above the speed of sound) and, if possible, to break the 'sound barrier.' Three different X-1s were built and designated: X-1-1, X-1-2 (later modified to become the X-1E), and X-1-3. The basic X-1 aircraft were flown by a large number of different pilots from 1946 to 1951. The X-1 Program not only proved that humans could go beyond the speed of sound, it reinforced the understanding that technological barriers could be overcome. The X-1s pioneered many structural and aerodynamic advances including extremely thin, yet extremely strong wing sections; supersonic fuselage configurations; control system requirements; powerplant compatibility; and cockpit environments. The X-1 aircraft were the first transonic-capable aircraft to use an all-moving stabilizer. The flights of the X-1s opened up a new era in aviation. The first X-1 was air-launched unpowered from a Boeing B-29 Superfortress on January 25, 1946. Powered flights began in December 1946. On October 14, 1947, the X-1-1, piloted by Air Force Captain Charles 'Chuck' Yeager, became the first aircraft to exceed the speed of sound, reaching about 700 miles per hour (Mach 1.06) and an altitude of 43,000 feet. The number 2 X-1 was modified and redesignated the X-1E. The modifications included adding a conventional canopy, an ejection seat, a low-pressure fuel system

  2. Vibrational wave packets in the B 1Πu and D 1Σu+ states of Cs2: Determination of improved Cs2+(X) and Cs2(B) spectroscopic constants

    NASA Astrophysics Data System (ADS)

    Oldenburg, A. L.; John, P. C.; Eden, J. G.

    2000-12-01

    Vibrational wave packets in the B 1Πu and D 1Σu+ excited states of Cs2 have been studied on the ˜100 fs time scale by pump-probe laser spectroscopy. The temporal behavior of the wave packets was monitored by photoionizing the electronically excited molecule with a time-delayed probe pulse and recording the time and energy-integrated photoelectron signal as a function of time delay between the pump and probe pulses. For the B 1Σu+ experiments, wave packets were produced by exciting the B 1Σu+←X 1Σg+ transition in the ˜740-790 nm region and subsequently detected by photoionizing the molecule at wavelengths between 565 nm and 600 nm. By simulating the experimentally observed transients with the density matrix formalism (and explicitly accounting for laser chirp and |Δv|>1 coherences), improved values for the equilibrium internuclear separation for the Cs2(B1Πu) state and Te for the Cs2+(X) state were determined to be Re(B 1Πu)=4.93±0.03 Å and Te[Cs2+(X)]=29 930±100 cm-1, respectively. Similar experiments were conducted for the D 1Σu+ state. Wave packets composed of vibrational levels (v'≈40-50) perturbed by the bound 2 3Πou state were produced on the D 1Σu+ potential surface by driving the D 1Σu+←X 1Σg+ transition in the 575-610 nm spectral interval.

  3. Differential effect of genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP) and organic anion-transporting polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors.

    PubMed

    Choi, Min-Koo; Shin, Ho Jung; Choi, Young-Lim; Deng, Jian-Wei; Shin, Jae-Gook; Song, Im-Sook

    2011-01-01

    The purpose of this study was to investigate the effect of genetic variations in organic anion-transporting polypeptide 1B1 (OATP1B1) and Na(+)/taurocholate co-transporting polypeptide (NTCP) on the uptake of various statins having different affinities for these transporters. The functional activities and simultaneous expression of NTCP and OATP1B1 were confirmed by the uptake of taurocholate and estrone-3-sulphate as representative substrates for NTCP and OATP1B1, respectively, and by an immunofluorescence analysis. The substrate specificities of NTCP and OATP1B1 for statins and the effects of genetic variations on the uptake of rosuvastatin, pitavastatin, and atorvastatin were measured. Based on the K(m) values and intrinsic clearances of the three statins, pitavastatin was taken up more efficiently than rosuvastatin and atorvastatin by OATP1B1. Consequently, the cellular accumulation of pitavastatin was modulated according to the genetic variation of OATP1B1 (OATP1B1*15), rather than NTCP*2. In contrast, NTCP*2 displayed greater transport of atorvastatin and rosuvastatin, compared with NTCP wild type. Thus, the measurements of decreased rosuvastatin and atorvastatin transport by OATP1B1*15 were confounded by the presence of NTCP and its genetic variant, NTCP*2. In conclusion, the functional consequences of genetic variants of NTCP and OATP1B1 may be different for various statins, depending on the substrate specificity of the OATP1B1 and NTCP transporters.

  4. Conditional knockdown of BCL2A1 reveals rate-limiting roles in BCR-dependent B-cell survival

    PubMed Central

    Sochalska, M; Ottina, E; Tuzlak, S; Herzog, S; Herold, M; Villunger, A

    2016-01-01

    Bcl2 family proteins control mitochondrial apoptosis and its members exert critical cell type and differentiation stage-specific functions, acting as barriers against autoimmunity or transformation. Anti-apoptotic Bcl2a1/Bfl1/A1 is frequently deregulated in different types of blood cancers in humans but its physiological role is poorly understood as quadruplication of the Bcl2a1 gene locus in mice hampers conventional gene targeting strategies. Transgenic overexpression of A1, deletion of the A1-a paralogue or constitutive knockdown in the hematopoietic compartment of mice by RNAi suggested rate-limiting roles in lymphocyte development, granulopoiesis and mast cell activation. Here we report on the consequences of conditional knockdown of A1 protein expression using a reverse transactivator (rtTA)-driven approach that highlights a critical role for this Bcl2 family member in the maintenance of mature B-cell homeostasis. Furthermore, we define the A1/Bim (Bcl-2 interacting mediator of cell death) axis as a target of key kinases mediating B-cell receptor (BCR)-dependent survival signals, such as, spleen tyrosine kinase (Syk) and Brutons tyrosine kinase (Btk). As such, A1 represents a putative target for the treatment of B-cell-related pathologies depending on hyperactivation of BCR-emanating survival signals and loss of A1 expression accounts, in part, for the pro-apoptotic effects of Syk- or Btk inhibitors that rely on the ‘BH3-only' protein Bim for cell killing. PMID:26450454

  5. [Correlation of HLA-A, B, DRB1 genes with leukemia].

    PubMed

    Du, Ying; Liang, Xiao-lan; Li, Qian; Wu, Wen-jie; Liu, Jian; Sun, Le-jing; Qiu, Lu-gui

    2013-04-01

    This study was aimed to investigate the correlation between HLA gene distribution and allele frequency of the patients with leukemia. PCR-SSP technique was used to detect the HLA genotype of 2994 umbilical cord blood units from healthy newborns (as control), the detecting result of which was compared with HLA genotypes of 1246 patients with leukemia searched in our cord blood bank. The differences between two groups were compared and analyzed. The results indicated that as compared with the control group, the allele frequencies of HLA-B*56 (0.56%), B*70 (0.24%) obviously increased (RR = 2.2546, 6.2598, χ(2) = 5, 5.98, P < 0.05), while the allele frequencies of HLA-A*03 (3.45%), A*30 (4.86%), B*13 (8.75%), B44* (3.25%), B61* (5.70%), DRB1*07 (8.23%), DRB1*15 (14.21%) obviously decreased in patients with leukemia (RR = 0.5889, 0.7187, 0.7359, 0.5713, 0.7127, 0.6242, 0.7976, χ(2) = 19.23, 9.82, 14.33, 20.48, 11.99, 33.21, 11.56, P < 0.01). It is concluded that HLA-B*56, B*70 alleles seem to be characterized by the genetic susceptibility to leukemia and may be served as risk markers for leukemia occurrence, while the HLA-A*03, A*30, B*13, B*44, B*61, DRB1*07, DRB1*15 can be considered as genetic indicators for resistance of leukemia.

  6. Molecular cloning and characterization of rat sperm surface antigen 2B1, a glycoprotein implicated in sperm-zona binding.

    PubMed

    Hou, S T; Ma, A; Jones, R; Hall, L

    1996-10-01

    The rat sperm surface antigen, 2B1, that has been proposed to play a key role in sperm adhesion to the zona pellucida, has been cloned and its entire cDNA sequenced. Northern blot analysis indicates that 2B1 is encoded by a 2.2-kb RNA transcript that is abundantly expressed in the testis. The deduced protein sequence contains 512 amino-acid residues with a strong candidate signal sequence and C-terminal transmembrane domain. Data base searches reveal a high degree of sequence similarity to guinea pig, rabbit, monkey, and human PH20 sperm surface antigens, and a lower degree of similarity to honey bee and whiteface hornet venom hyaluronidases. Rat 2B1 antigen also possesses hyaluronidase activity, suggesting that it is a bifunctional protein with putative roles in the dispersion of cumulus oophorus cells as well as zona adhesion. However, while it would appear that 2B1 is the rat homologue of the guinea pig PH20 antigen, they differ in a number of important biochemical respects (including their mode of attachment to the sperm membrane and distribution between soluble and membrane-bound fractions), as well as in their localization on the sperm membrane. Expression of regions of the 2B1 protein in recombinant bacterial cells has allowed a preliminary mapping of the 2B1 epitope, and has provided more definitive information on the endoproteolytic processing of 2B1 during epididymal transit.

  7. Biological Roles of Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11B1), HSD11B2, and Glucocorticoid Receptor (NR3C1) in Sheep Conceptus Elongation.

    PubMed

    Brooks, Kelsey; Burns, Gregory; Spencer, Thomas E

    2015-08-01

    In sheep, the elongating conceptus synthesizes and secretes interferon tau (IFNT) as well as prostaglandins (PGs) and cortisol. The enzymes, hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) and HSD11B2 interconvert cortisone and cortisol. In sheep, HSD11B1 is expressed and active in the conceptus trophectoderm as well as in the endometrial luminal epithelia; in contrast, HSD11B2 expression is most abundant in conceptus trophectoderm. Cortisol is a biologically active glucocorticoid and ligand for the glucocorticoid receptor (NR3C1 or GR) and mineralocorticoid receptor (NR3C2 or MR). Expression of MR is not detectable in either the ovine endometrium or conceptus during early pregnancy. In tissues that do not express MR, HSD11B2 protects cells from the growth-inhibiting and/or proapoptotic effects of cortisol, particularly during embryonic development. In study one, an in utero loss-of-function analysis of HSD11B1 and HSD11B2 was conducted in the conceptus trophectoderm using morpholino antisense oligonucleotides (MAOs) that inhibit mRNA translation. Elongating, filamentous conceptuses were recovered on Day 14 from ewes infused with control morpholino or HSD11B2 MAO. In contrast, HSD11B1 MAO resulted in severely growth-retarded conceptuses or conceptus fragments with apoptotic trophectoderm. In study two, clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing was used to determine the role of GR in conceptus elongation and development. Elongating, filamentous-type conceptuses (12-14 cm in length) were recovered from ewes gestating control embryos (n = 7/7) and gestating GR-edited embryos (n = 6/7). These results support the idea that the effects of HSD11B1-derived cortisol on conceptus elongation are indirectly mediated by the endometrium and are not directly mediated through GR in the trophectoderm. © 2015 by the Society for the Study of Reproduction, Inc.

  8. Life or death by NFκB, Losartan promotes survival in dy2J/dy2J mouse of MDC1A

    PubMed Central

    Elbaz, M; Yanay, N; Laban, S; Rabie, M; Mitrani-Rosenbaum, S; Nevo, Y

    2015-01-01

    Inflammation and fibrosis are well-defined mechanisms involved in the pathogenesis of the incurable Laminin α2-deficient congenital muscular dystrophy (MDC1A), while apoptosis mechanism is barely discussed. Our previous study showed treatment with Losartan, an angiotensin II type I receptor antagonist, improved muscle strength and reduced fibrosis through transforming growth factor beta (TGF-β) and mitogen-activated protein kinases (MAPK) signaling inhibition in the dy2J/dy2J mouse model of MDC1A. Here we show for the first time that Losartan treatment up-regulates and shifts the nuclear factor kappa B (NFκB) signaling pathway to favor survival versus apoptosis/damage in this animal model. Losartan treatment was associated with significantly increased serum tumor necrosis factor alpha (TNF-α) level, p65 nuclei accumulation, and decreased muscle IκB-β protein level, indicating NFκB activation. Moreover, NFκB anti-apoptotic target genes TNF receptor-associated factor 1 (TRAF1), TNF receptor-associated factor 2 (TRAF2), cellular inhibitor of apoptosis (cIAP2), and Ferritin heavy chain (FTH1) were increased following Losartan treatment. Losartan induced protein expression toward a pro-survival profile as BCL-2 expression levels were increased and Caspase-3 expression levels were decreased. Muscle apoptosis reduction was further confirmed using terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay. Thus, along with TGF-β and MAPK signaling, NFκB serves as an important regulatory pathway which following Losartan treatment promotes survival in the dy2J/dy2J mouse model of MDC1A. PMID:25766329

  9. Fate of avermectin B1a on citrus fruits. 1. Distribution and magnitude of the avermectin B sub 1a and sup 14 C residue on citrus fruits from a field study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maynard, M.S.; Iwata, Y.; Wislocki, P.G.

    An 8{mu}g/mL solution of ({sup 14}C)avermectin B{sub 1a}, the approximate field application rate, was applied to oranges, lemons, and grapefruit; a 10-fold higher rate was also applied to oranges. Immediately postapplication, {sup 14}C residues were 20-38 ng/g for the fruit treated at the field rate. Most of the residue was recovered in the surface solvent rinse at less than 2 weeks postapplication; however, after this time more of the residue was recovered from the rind fraction. The total recoveries of applied radioactivity were 61-90% and 33-50% at 1 and 12 weeks postapplication, respectively. The level of unextractable rind {sup 14}Cmore » residue from oranges treated at the 10{times} rate and harvested at 12 weeks (a worse case) was 4.9% of the applied dose (<2 ppb at the field rate). The inner pulp samples for all treatments had {sup 14}C residue levels below the detection limit of 0.4-0.8 ppb. The initial depletion half-life of avermectin B{sub 1a} was <1 week, with losses occurring within 30-40 min. For the 1-12-week postapplication period, the avermectin B{sub 1a} and {sup 14}C residue depletion half-lives were 20-38 and 56-98 days, respectively. Differences in the rate of dissipation of avermectin B{sub 1a} due to fruit type and application rate were observed.« less

  10. A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells.

    PubMed

    Stuart, Scott A; Houel, Stephane; Lee, Thomas; Wang, Nan; Old, William M; Ahn, Natalie G

    2015-06-01

    Inhibitors of oncogenic B-RAF(V600E) and MKK1/2 have yielded remarkable responses in B-RAF(V600E)-positive melanoma patients. However, the efficacy of these inhibitors is limited by the inevitable onset of resistance. Despite the fact that these inhibitors target the same pathway, combination treatment with B-RAF(V600E) and MKK1/2 inhibitors has been shown to improve both response rates and progression-free survival in B-RAF(V600E) melanoma patients. To provide insight into the molecular nature of the combinatorial response, we used quantitative mass spectrometry to characterize the inhibitor-dependent phosphoproteome of human melanoma cells treated with the B-RAF(V600E) inhibitor PLX4032 (vemurafenib) or the MKK1/2 inhibitor AZD6244 (selumetinib). In three replicate experiments, we quantified changes at a total of 23,986 phosphosites on 4784 proteins. This included 1317 phosphosites that reproducibly decreased in response to at least one inhibitor. Phosphosites that responded to both inhibitors grouped into networks that included the nuclear pore complex, growth factor signaling, and transcriptional regulators. Although the majority of phosphosites were responsive to both inhibitors, we identified 16 sites that decreased only in response to PLX4032, suggesting rare instances where oncogenic B-RAF signaling occurs in an MKK1/2-independent manner. Only two phosphosites were identified that appeared to be uniquely responsive to AZD6244. When cells were treated with the combination of AZD6244 and PLX4032 at subsaturating concentrations (30 nm), responses at nearly all phosphosites were additive. We conclude that AZD6244 does not substantially widen the range of phosphosites inhibited by PLX4032 and that the benefit of the drug combination is best explained by their additive effects on suppressing ERK1/2 signaling. Comparison of our results to another recent ERK1/2 phosphoproteomics study revealed a surprising degree of variability in the sensitivity of phosphosites to

  11. Carboxypeptidase M Is a Positive Allosteric Modulator of the Kinin B1 Receptor*

    PubMed Central

    Zhang, Xianming; Tan, Fulong; Skidgel, Randal A.

    2013-01-01

    Ligand binding to extracellular domains of G protein-coupled receptors can result in novel and nuanced allosteric effects on receptor signaling. We previously showed that the protein-protein interaction of carboxypeptidase M (CPM) and kinin B1 receptor (B1R) enhances B1R signaling in two ways; 1) kinin binding to CPM causes a conformational activation of the B1R, and 2) CPM-generated des-Arg-kinin agonist is efficiently delivered to the B1R. Here, we show CPM is also a positive allosteric modulator of B1R signaling to its agonist, des-Arg10-kallidin (DAKD). In HEK cells stably transfected with B1R, co-expression of CPM enhanced DAKD-stimulated increases in intracellular Ca2+ or phosphoinositide turnover by a leftward shift of the dose-response curve without changing the maximum. CPM increased B1R affinity for DAKD by ∼5-fold but had no effect on basal B1R-dependent phosphoinositide turnover. Soluble, recombinant CPM bound to HEK cells expressing B1Rs without stimulating receptor signaling. CPM positive allosteric action was independent of enzyme activity but depended on interaction of its C-terminal domain with the B1R extracellular loop 2. Disruption of the CPM/B1R interaction or knockdown of CPM in cytokine-treated primary human endothelial cells inhibited the allosteric enhancement of CPM on B1R DAKD binding or ERK1/2 activation. CPM also enhanced the DAKD-induced B1R conformational change as detected by increased intramolecular fluorescence or bioluminescence resonance energy transfer. Thus, CPM binding to extracellular loop 2 of the B1R results in positive allosteric modulation of B1R signaling, and disruption of this interaction could provide a novel therapeutic approach to reduce pathological B1R signaling. PMID:24108126

  12. 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.

  13. The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range

    PubMed Central

    Kalliokoski, Annikka; Neuvonen, Mikko; Neuvonen, Pertti J; Niemi, Mikko

    2008-01-01

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTOrganic anion transporting polypeptide 1B1 is an influx transporter expressed on the basolateral membrane of hepatocytes.A common single nucleotide polymorphism, c.521T→C (p.Val174Ala), of the SLCO1B1 gene has been associated with increased plasma repaglinide concentrations in healthy volunteers.Previous studies at low repaglinide doses have suggested that the effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide could be dose-dependent. WHAT THIS STUDY ADDSRepaglinide peak plasma concentration and area under the plasma concentration–time curve increased linearly along with repaglinide dose ranging from 0.25 to 2 mg in both the predominant c.521TT and rare c.521CC genotype group.The effect of SLCO1B1 c.521T→C polymorphism on repaglinide pharmacokinetics persists over a wide dose range. AIMS To establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T→C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose-dependent. METHODS Twelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25-, 0.5-, 1- or 2-mg dose of repaglinide in a dose-escalation study with a wash-out period of ≥1 week. RESULTS The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P ≤ 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC0–∞ increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT

  14. 17 CFR 240.13b2-1 - Falsification of accounting records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Falsification of accounting records. 240.13b2-1 Section 240.13b2-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Required Reports § 240.13b2-1 Falsification of accounting records. No person shall directly or indirectly...

  15. SULT2B1b Sulfotransferase: Induction by Vitamin D Receptor and Reduced Expression in Prostate Cancer

    PubMed Central

    Seo, Young-Kyo; Mirkheshti, Nooshin; Song, Chung S.; Kim, Soyoung; Dodds, Sherry; Ahn, Soon C.; Christy, Barbara; Mendez-Meza, Rosario; Ittmann, Michael M.; Abboud-Werner, Sherry

    2013-01-01

    An elevated tumor tissue androgen level, which reactivates androgen receptor in recurrent prostate cancer, arises from the intratumor synthesis of 5α-dihydrotestosterone through use of the precursor steroid dehydroepiandrosterone (DHEA) and is fueled by the steroidogenic enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD1), aldoketoreductase (AKR1C3), and steroid 5-alpha reductase, type 1 (SRD5A1) present in cancer tissue. Sulfotransferase 2B1b (SULT2B1b) (in short, SULT2B) is a prostate-expressed hydroxysteroid SULT that converts cholesterol, oxysterols, and DHEA to 3β-sulfates. DHEA metabolism involving sulfonation by SULT2B can potentially interfere with intraprostate androgen synthesis due to reduction of free DHEA pool and, thus, conversion of DHEA to androstenedione. Here we report that in prostatectomy specimens from treatment-naive patients, SULT2B expression is markedly reduced in malignant tissue (P < .001, Mann-Whitney U test) compared with robust expression in adjacent nonmalignant glands. SULT2B was detected in formalin-fixed specimens by immunohistochemistry on individual sections and tissue array. Immunoblotting of protein lysates of frozen cancer and matched benign tissue confirmed immunohistochemistry results. An in-house–developed rabbit polyclonal antibody against full-length human SULT2B was validated for specificity and used in the analyses. Ligand-activated vitamin D receptor induced the SULT2B1 promoter in vivo in mouse prostate and increased SULT2B mRNA and protein levels in vitro in prostate cancer cells. A vitamin D receptor/retinoid X receptor-α–bound DNA element (with a DR7 motif) mediated induction of the transfected SULT2B1 promoter in calcitriol-treated cells. SULT2B knockdown caused an increased proliferation rate of prostate cancer cells upon stimulation by DHEA. These results suggest that the tumor tissue SULT2B level may partly control prostate cancer growth, and its induction in a therapeutic setting may inhibit disease

  16. 76 FR 2930 - International Product Change-Global Plus 1B and 2B Negotiated Service Agreements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-18

    ... POSTAL SERVICE International Product Change--Global Plus 1B and 2B Negotiated Service Agreements... the Postal Regulatory Commission to add Global Plus 1B and 2B Negotiated Service Agreements to the... United States Postal Service to Add Global Plus 1B and 2B Negotiated Service Agreements to the...

  17. Effect of low-to-moderate-dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia.

    PubMed

    Li, Hui; Yang, Shi-Gui; Gu, Li; Zhang, Yao; Yan, Xi-Xin; Liang, Zong-An; Zhang, Wei; Jia, Hong-Yu; Chen, Wei; Liu, Meng; Yu, Kai-Jiang; Xue, Chun-Xue; Hu, Ke; Zou, Qi; Li, Lan-Juan; Cao, Bin; Wang, Chen

    2017-07-01

    The effect of corticosteroids on influenza A(H1N1)pdm09 viral pneumonia patients remains controversial, and the impact of dosage has never been studied. Using data of hospitalized adolescent and adult patients with influenza A(H1N1)pdm09 viral pneumonia, prospectively collected from 407 hospitals in mainland China, the effects of low-to-moderate-dose (25-150 mg d -1 ) and high-dose (>150 mg d -1 ) corticosteroids on 30-day mortality, 60-day mortality, and nosocomial infection were assessed with multivariate Cox regression and propensity score-matched case-control analysis. In total, 2141 patients (median age: 34 years; morality rate: 15.9%) were included. Among them, 1160 (54.2%) had PaO 2 /FiO 2 <300 mm Hg on admission, and 1055 (49.3%) received corticosteroids therapy. Corticosteroids, without consideration of dose, did not influence either 30-day or 60-day mortality. Further analysis revealed that, as compared with the no-corticosteroid group, low-to-moderate-dose corticosteroids were related to reduced 30-day mortality (adjusted hazard ratio [aHR] 0.64 [95% CI 0.43-0.96, P=.033]). In the subgroup analysis among patients with PaO 2 /FiO 2 <300 mm Hg, low-to-moderate-dose corticosteroid treatment significantly reduced both 30-day mortality (aHR 0.49 [95% CI 0.32-0.77]) and 60-day mortality (aHR 0.51 [95% CI 0.33-0.78]), while high-dose corticosteroid therapy yielded no difference. For patients with PaO 2 /FiO 2 ≥300 mm Hg, corticosteroids (irrespective of dose) showed no benefit and even increased 60-day mortality (aHR 3.02 [95% CI 1.06-8.58]). Results were similar in the propensity model analysis. Low-to-moderate-dose corticosteroids might reduce mortality of influenza A(H1N1)pdm09 viral pneumonia patients with PaO 2 /FiO 2 <300 mm Hg. Mild patients with PaO 2 /FiO 2 ≥300 mm Hg could not benefit from corticosteroid therapy. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  18. Etsrp/Etv2 is directly regulated by Foxc1a/b in the zebrafish angioblast.

    PubMed

    Veldman, Matthew B; Lin, Shuo

    2012-01-20

    Endothelial cells are developmentally derived from angioblasts specified in the mesodermal germ cell layer. The transcription factor etsrp/etv2 is at the top of the known genetic hierarchy for angioblast development. The transcriptional events that induce etsrp expression and angioblast specification are not well understood. We generated etsrp:gfp transgenic zebrafish and used them to identify regulatory regions and transcription factors critical for etsrp expression and angioblast specification from mesoderm. To investigate the mechanisms that initiate angioblast cell transcription during embryogenesis, we have performed promoter analysis of the etsrp locus in zebrafish. We describe three enhancer elements sufficient for endothelial gene expression when place in front of a heterologous promoter. The deletion of all 3 regulatory regions led to a near complete loss of endothelial expression from the etsrp promoter. One of the enhancers, located 2.3 kb upstream of etsrp contains a consensus FOX binding site that binds Foxc1a and Foxc1b in vitro by EMSA and in vivo using ChIP. Combined knockdown of foxc1a/b, using morpholinos, led to a significant decrease in etsrp expression at early developmental stages as measured by quantitative reverse transcriptase-polymerase chain reaction and in situ hybridization. Decreased expression of primitive erythrocyte genes scl and gata1 was also observed, whereas pronephric gene pax2a was relatively normal in expression level and pattern. These findings identify mesodermal foxc1a/b as a direct upstream regulator of etsrp in angioblasts. This establishes a new molecular link in the process of mesoderm specification into angioblast.

  19. Prenatal exposure to non-ionizing radiation: effects of WiFi signals on pregnancy outcome, peripheral B-cell compartment and antibody production.

    PubMed

    Sambucci, Manolo; Laudisi, Federica; Nasta, Francesca; Pinto, Rosanna; Lodato, Rossella; Altavista, Pierluigi; Lovisolo, Giorgio Alfonso; Marino, Carmela; Pioli, Claudio

    2010-12-01

    During embryogenesis, the development of tissues, organs and systems, including the immune system, is particularly susceptible to the effects of noxious agents. We examined the effects of prenatal (in utero) exposure to WiFi signals on pregnancy outcome and the immune B-cell compartment, including antibody production. Sixteen mated (plug-positive) female mice were assigned to each of the following groups: cage control, sham-exposed and microwave-exposed (WiFi signals at 2.45 GHz, whole body, SAR 4 W/kg, 2 h/day, 14 consecutive days starting 5 days after mating). No effects due to exposure to WiFi signals during pregnancy on mating success, number of newborns/mother and body weight at birth were found. Newborn mice were left to grow until 5 or 26 weeks of age, when immunological analyses were performed. No differences due to exposure were found in spleen cell number, B-cell frequency or antibody serum levels. When challenged in vitro with LPS, B cells from all groups produced comparable amounts of IgM and IgG, and proliferated at a similar level. All these findings were consistently observed in the female and male offspring at both juvenile (5 weeks) and adult (26 weeks) ages. Stress-associated effects as well as age- and/or sex-related differences were observed for several parameters. In conclusion, our results do not show any effect on pregnancy outcome or any early or late effects on B-cell differentiation and function due to prenatal exposure to WiFi signals.

  20. Pancreatic and Duodenal Homeobox Protein 1 (Pdx-1) Maintains Endoplasmic Reticulum Calcium Levels through Transcriptional Regulation of Sarco-endoplasmic Reticulum Calcium ATPase 2b (SERCA2b) in the Islet β Cell*

    PubMed Central

    Johnson, Justin S.; Kono, Tatsuyoshi; Tong, Xin; Yamamoto, Wataru R.; Zarain-Herzberg, Angel; Merrins, Matthew J.; Satin, Leslie S.; Gilon, Patrick; Evans-Molina, Carmella

    2014-01-01

    Although the pancreatic duodenal homeobox 1 (Pdx-1) transcription factor is known to play an indispensable role in β cell development and secretory function, recent data also implicate Pdx-1 in the maintenance of endoplasmic reticulum (ER) health. The sarco-endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) pump maintains a steep Ca2+ gradient between the cytosol and ER lumen. In models of diabetes, our data demonstrated loss of β cell Pdx-1 that occurs in parallel with altered SERCA2b expression, whereas in silico analysis of the SERCA2b promoter revealed multiple putative Pdx-1 binding sites. We hypothesized that Pdx-1 loss under inflammatory and diabetic conditions leads to decreased SERCA2b levels and activity with concomitant alterations in ER health. To test this, siRNA-mediated knockdown of Pdx-1 was performed in INS-1 cells. The results revealed reduced SERCA2b expression and decreased ER Ca2+, which was measured using fluorescence lifetime imaging microscopy. Cotransfection of human Pdx-1 with a reporter fused to the human SERCA2 promoter increased luciferase activity 3- to 4-fold relative to an empty vector control, and direct binding of Pdx-1 to the proximal SERCA2 promoter was confirmed by chromatin immunoprecipitation. To determine whether restoration of SERCA2b could rescue ER stress induced by Pdx-1 loss, Pdx1+/− mice were fed a high-fat diet. Isolated islets demonstrated an increased spliced-to-total Xbp1 ratio, whereas SERCA2b overexpression reduced the Xbp1 ratio to that of wild-type controls. Together, these results identify SERCA2b as a novel transcriptional target of Pdx-1 and define a role for altered ER Ca2+ regulation in Pdx-1-deficient states. PMID:25271154

  1. Influence of basis-set size on the X Σ 1 /2 +2 , A Π 1 /2 2 , A Π 3 /2 2 , and B Σ 1 /2 +2 potential-energy curves, A Π 3 /2 2 vibrational energies, and D1 and D2 line shapes of Rb+He

    NASA Astrophysics Data System (ADS)

    Blank, L. Aaron; Sharma, Amit R.; Weeks, David E.

    2018-03-01

    The X Σ 1 /2 +2 , A Π 1 /2 2 , A Π 3 /2 2 , and B2Σ1/2 + potential-energy curves for Rb+He are computed at the spin-orbit multireference configuration interaction level of theory using a hierarchy of Gaussian basis sets at the double-zeta (DZ), triple-zeta (TZ), and quadruple-zeta (QZ) levels of valence quality. Counterpoise and Davidson-Silver corrections are employed to remove basis-set superposition error and ameliorate size-consistency error. An extrapolation is performed to obtain a final set of potential-energy curves in the complete basis-set (CBS) limit. This yields four sets of systematically improved X Σ 1 /2 +2 , A Π 1 /2 2 , A Π 3 /2 2 , and B2Σ1/2 + potential-energy curves that are used to compute the A Π 3 /2 2 bound vibrational energies, the position of the D2 blue satellite peak, and the D1 and D2 pressure broadening and shifting coefficients, at the DZ, TZ, QZ, and CBS levels. Results are compared with previous calculations and experimental observation.

  2. Word Frequency Analysis. MOS: 95B. Skill Levels 1 & 2.

    DTIC Science & Technology

    1981-05-01

    uU N D 1 A C P A C K1 ? G .I A 2 1 A’J Kt I S , 1 K L S 1 BaRp IF S I ~t2iIAED 5. 1.T’ 6 BATTERY 9!j 2 BECAUSE 17 67EI 2 BEHIND 13 IL 2 RE l1󈧱 3 b1...T S :t cTt lIION 5 U It :,4t 5 F L 1%T5 &:, JC.L ME NT 5 ESTIMS4EO 5 F -4 U0 . F- "CL5 UJ 7 "S 5 F-.[377 7i (, ID󈧏CAlN5.C1DEINTS 5 I’%SER71NkG .0

  3. UGT1A and UGT2B genetic variation alters nicotine and nitrosamine glucuronidation in european and african american smokers.

    PubMed

    Wassenaar, Catherine A; Conti, David V; Das, Soma; Chen, Peixian; Cook, Edwin H; Ratain, Mark J; Benowitz, Neal L; Tyndale, Rachel F

    2015-01-01

    Identifying sources of variation in the nicotine and nitrosamine metabolic inactivation pathways is important to understanding the relationship between smoking and cancer risk. Numerous UGT1A and UGT2B enzymes are implicated in nicotine and nitrosamine metabolism in vitro; however, little is known about their roles in vivo. Within UGT1A1, UGT1A4, UGT1A9, UGT2B7, UGT2B10, and UGT2B17, 47 variants were genotyped, including UGT2B10*2 and UGT2B17*2. The association between variation in these UGTs and glucuronidation activity within European and African American current smokers (n = 128), quantified as urinary ratios of the glucuronide over unconjugated compound for nicotine, cotinine, trans-3'-hydroxycotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), was investigated in regression models assuming a dominant effect of variant alleles. Correcting for multiple testing, three UGT2B10 variants were associated with cotinine glucuronidation, rs2331559 and rs11726322 in European Americans and rs835309 in African Americans (P ≤ 0.0002). Additional variants predominantly in UGT2B10 were nominally associated with nicotine (P = 0.008-0.04) and cotinine (P = <0.001-0.02) glucuronidation in both ethnicities in addition to UGT2B10*2 in European Americans (P = 0.01, P < 0.001). UGT2B17*2 (P = 0.03) in European Americans and UGT2B7 variants (P = 0.02-0.04) in African Americans were nominally associated with 3HC glucuronidation. UGT1A (P = 0.007-0.01), UGT2B10 (P = 0.02), and UGT2B7 (P = 0.02-0.03) variants in African Americans were nominally associated with NNAL glucuronidation. Findings from this initial in vivo study support a role for multiple UGTs in the glucuronidation of tobacco-related compounds in vivo, in particular UGT2B10 and cotinine glucuronidation. Findings also provide insight into ethnic differences in glucuronidation activity, which could be contributing to ethnic disparities in the risk for smoking-related cancers. Cancer Epidemiol Biomarkers Prev

  4. Molecular Basis of Differential B-Pentamer Stability of Shiga Toxins 1 and 2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Conrady, Deborah G.; Flagler, Michael J.; Friedmann, David R.

    2012-06-27

    Escherichia coli strain O157:H7 is a major cause of food poisoning that can result in severe diarrhea and, in some cases, renal failure. The pathogenesis of E. coli O157:H7 is in large part due to the production of Shiga toxin (Stx), an AB{sub 5} toxin that consists of a ribosomal RNA-cleaving A-subunit surrounded by a pentamer of receptor-binding B subunits. There are two major isoforms, Stx1 and Stx2, which differ dramatically in potency despite having 57% sequence identity. Animal studies and epidemiological studies show Stx2 is associated with more severe disease. Although the molecular basis of this difference is unknown,more » data suggest it is associated with the B-subunit. Mass spectrometry studies have suggested differential B-pentamer stability between Stx1 and Stx2. We have examined the relative stability of the B-pentamers in solution. Analytical ultracentrifugation using purified B-subunits demonstrates that Stx2B, the more deadly isoform, shows decreased pentamer stability compared to Stx1B (EC{sub 50} = 2.3 {micro}M vs. EC{sub 50} = 0.043 {micro}M for Stx1B). X-ray crystal structures of Stx1B and Stx2B identified a glutamine in Stx2 (versus leucine in Stx1) within the otherwise strongly hydrophobic interface between B-subunits. Interchanging these residues switches the stability phenotype of the B-pentamers of Stx1 and Stx2, as demonstrated by analytical ultracentrifugation and circular dichroism. These studies demonstrate a profound difference in stability of the B-pentamers in Stx1 and Stx2, illustrate the mechanistic basis for this differential stability, and provide novel reagents to test the basis for differential pathogenicity of these toxins.« less

  5. Photochemical activation of MH3-B1/rGel: a HER2-targeted treatment approach for ovarian cancer

    PubMed Central

    Bull-Hansen, Bente; Berstad, Maria B.; Berg, Kristian; Cao, Yu; Skarpen, Ellen; Fremstedal, Ane Sofie; Rosenblum, Michael G.; Peng, Qian; Weyergang, Anette

    2015-01-01

    HER2-targeted therapy has been shown to have limited efficacy in ovarian cancer despite frequent overexpression of this receptor. Photochemical internalization (PCI) is a modality for cytosolic drug delivery, currently undergoing clinical evaluation. In the present project we studied the application of PCI in combination with the HER2-targeted recombinant fusion toxin, MH3-B1/rGel, for the treatment of ovarian cancer. The SKOV-3 cell line, resistant to trastuzumab- and MH3-B1/rGel- monotherapy, was shown to respond strongly to PCI of MH3-B1/rGel to a similar extent as observed for the treatment-sensitive SK-BR-3 breast cancer cells. Extensive hydrolytic degradation of MH3-B1/rGel in acidic endocytic vesicles was indicated as the mechanism of MH3-B1/rGel resistance in SKOV-3 cells. This was shown by the positive Pearson's correlation coefficient between Alexa488-labeled MH3-B1/rGel and Lysotracker in SKOV-3 cells in contrast to the negative Pearson's correlation coefficient in SK-BR-3 cells. The application of PCI to induce the release of MH3-B1/rGel was also demonstrated to be effective on SKOV-3 xenografts. Application of PCI with MH3-B1/rGel was further found highly effective in the HER2 expressing HOC-7 and NuTu-19 ovarian cancer cell lines. The presented results warrant future development of PCI in combination with MH3-B1/rGel as a novel therapeutic approach in preclinical models of ovarian cancer. PMID:26002552

  6. ALDH1B1 links alcohol consumption and diabetes.

    PubMed

    Singh, Surendra; Chen, Ying; Matsumoto, Akiko; Orlicky, David J; Dong, Hongbin; Thompson, David C; Vasiliou, Vasilis

    2015-08-07

    Aldehyde dehydrogenase 1B1 (ALDH1B1) is a mitochondrial enzyme sharing 65% and 72% sequence identity with ALDH1A1 and ALDH2 proteins, respectively. Compared to the latter two ALDH isozymes, little is known about the physiological functions of ALDH1B1. Studies in humans indicate that ALDH1B1 may be associated with alcohol sensitivity and stem cells. Our recent in vitro studies using human ALDH1B1 showed that it metabolizes acetaldehyde and retinaldehyde. To investigate the in vivo role of ALDH1B1, we generated and characterized a global Aldh1b1 knockout mouse line. These knockout (KO) mice are fertile and show overtly good health. However, ethanol pharmacokinetic analysis revealed ∼40% increase in blood acetaldehyde levels in KO mice. Interestingly, the KO mice exhibited higher fasting blood glucose levels. Collectively, we show for the first time the functional in vivo role of ALDH1B1 in acetaldehyde metabolism and in maintaining glucose homeostasis. This mouse model is a valuable tool to investigate the mechanism by which alcohol may promote the development of diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Word Frequency Analysis. MOS: 75C. Skill Levels 1 & 2.

    DTIC Science & Technology

    1981-05-01

    A4Fi j, A REAS . I --- - ., ARISS 12 ARMY I A~K1h ’.-L ARRANGED 64 AS I ASCERTAIN 2 .L~u Ip ASSEMBLE 12 ASSEMBLED 1 ASSEMPLY I ASSI----------------2...GOVERNING .16 GRADE ’G.; S GRAA!TET I GRfATEST I GREEN I GFEP.I .4 ( AriSS I GROUPS s GUIDANCE I G lIn (;UItES V 1 E I GUIVIS/ 3 GWPM 1-’ 1 I.AO 1 HAE

  8. The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range.

    PubMed

    Kalliokoski, Annikka; Neuvonen, Mikko; Neuvonen, Pertti J; Niemi, Mikko

    2008-12-01

    To establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T-->C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose-dependent. Twelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25-, 0.5-, 1- or 2-mg dose of repaglinide in a dose-escalation study with a wash-out period of > or =1 week. The mean area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P < or = 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC(0-infinity) increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT genotype. The effect of SLCO1B1 c.521T-->C polymorphism on the pharmacokinetics of repaglinide persists throughout the clinically relevant dose range.

  9. Metabolism of the hydrochlorofluorocarbon 1,2-dichloro-1,1-difluoroethane.

    PubMed

    Harris, J W; Anders, M W

    1991-01-01

    1,2-Dichloro-1,1-difluoroethane (HCFC-132b) is a potential substitute for some ozone-depleting chlorofluorocarbons and a model for other 1,1,1,2-tetrahaloethanes under consideration as chlorofluorocarbon substitutes. Male Fischer 344 rats were given 10 mmol/kg HCFC-132b dissolved in corn oil by intraperitoneal injection. An NMR assay for covalent binding of HCFC-132b metabolites to liver proteins was negative, whereas binding was observed in halothane-treated rats. Total urinary metabolites excreted by rats given HCFC-132b during the first 24 h amounted to 1.8 +/- 0.1% of the injected dose, as determined by 19F NMR. During the first 6 h, metabolites of HCFC-132b corresponding to 2-chloro-2,2-difluoroethyl glucuronide, unknown metabolite A, chlorodifluoroacetic acid, and chlorodifluoroacetaldehyde hydrate [both free and conjugated (unknown metabolite B)] were excreted in urine in the approximate ratio 100:9:3:7, respectively. Metabolite A is apparently an O-conjugate of 2-chloro-2,2-difluoroethanol; unconjugated 2-chloro-2,2-difluoroethanol was not detected in urine. The 19F NMR spectrum of metabolite B indicates the formation of a hemiacetal of chlorodifluoroacetaldehyde. Repeated exposure of rats to HCFC-132b significantly increased both the rate of chlorodifluoroacetic acid excretion and the relative fraction of the HCFC-132b dose excreted as chlorodifluoroacetic acid in urine. Incubation of HCFC-132b with rat hepatic microsomes yielded chlorodifluoroacetaldehyde hydrate as the only fluorinated product. The in vitro metabolism of HCFC-132b was increased in microsomes from pyridine-treated rats as compared with control rats, and HCFC-132b metabolism was inhibited by p-nitrophenol, indicating that the cytochrome P-450 isoform IIE1 is largely responsible for the initial hydroxylation of HCFC-132b.

  10. BmRobo1a and BmRobo1b control axon repulsion in the silkworm Bombyx mori.

    PubMed

    Li, Xiao-Tong; Yu, Qi; Zhou, Qi-Sheng; Zhao, Xiao; Liu, Zhao-Yang; Cui, Wei-Zheng; Liu, Qing-Xin

    2016-02-15

    The development of the nervous system is based on the growth and connection of axons, and axon guidance molecules are the dominant regulators during this course. Robo, as the receptor of axon guidance molecule Slit, plays a key role as a conserved repellent cue for axon guidance during the development of the central nervous system. However, the function of Robo in the silkworm Bombyx mori is unknown. In this study, we cloned two novel robo genes in B. mori (Bmrobo1a and Bmrobo1b). BmRobo1a and BmRobo1b lack an Ig and a FNIII domain in the extracellular region and the CC0 and CC2 motifs in the intracellular region. BmRobo1a and BmRobo1b were colocalized with BmSlit in the neuropil. Knock-down of Bmrobo1a and Bmrobo1b by RNA interference (RNAi) resulted in abnormal development of axons. Our results suggest that BmRobo1a and BmRobo1b have repulsive function in axon guidance, even though their structures are different from Robo1 of other species. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Final Environmental Assessment Test Operations at Arnold Engineering Development Center. Volumes 1 & 2

    DTIC Science & Technology

    2008-06-01

    ir Fo rc e B as e, T en ne ss ee Fi gu re 1 -2 A er od yn am ic s A er op ro pu ls io n S pa ce & M is si le In fr as...lin es /te xt - fa ci lit ie s in s ta nd by o r m ot hb al le d st at us H ea lth , S af et y an d E nv ir on m en ta l M an ag em en t S ys...yp er so ni c C A er ot he rm al C A FC L La b H E AT -H 2 C C O S

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

    PubMed Central

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

    2005-01-01

    AIM: To establish the most common vacA alleles in Helicobacter pylori (H pylori) strains isolated from Chilean patients and its relationship with gastritis and gastroduodenal ulcers. METHODS: Two hundred and forty five H pylori clinical isolates were obtained from 79 biopsies from Chilean infected patients suffering from gastrointestinal diseases. An average of 2-3 strains per patient was isolated and the vacA genotype was analyzed by PCR and 3% agarose electrophoresis. Some genotypes were checked by DNA sequencing. RESULTS: The most prevalent vacA genotype in Chilean patients was s1b m1 (76%), followed by s1a m1 (21%). In contrast, the s2 m2 genotype was scarcely represented (3%). The s1b m1 genotype was found most frequently linked to gastropathies (P<0.05) rather than ulcers. Ulcers were found more commonly in male and older patients. Curiously, patients living in cities located North and far South of Santiago, the capital and largest Chilean city, carried almost exclusively strains with the s1b m1 genotype. In contrast, patients from Santiago and cities located South of Santiago carried strains with either one or both s1a m1 and s1b m1 genotypes. Regarding the s2 m2 genotype, comparison with GenBank sequences revealed that Chilean s2 sequence was identical to those of Australian, American, and Colombian strains but quite different from those of Alaska and India. CONCLUSION: Differences in geographic distribution of the s and m vacA alleles in Chile and a relationship of s1b m1 genotype with gastritis were found. Sequence data in part support a hispanic origin for the vacA genotype. Asymmetric distribution of genotypes s1b m1 and s2 m2 recedes H Pylori strain distribution in Spain and Portugal. PMID:16419167

  13. Activation of the transcription factor nuclear factor-kappa B in uterine luminal epithelial cells by interleukin 1 Beta 2: a novel interleukin 1 expressed by the elongating pig conceptus.

    PubMed

    Mathew, Daniel J; Newsom, Emily M; Guyton, Jennifer M; Tuggle, Christopher K; Geisert, Rodney D; Lucy, Matthew C

    2015-04-01

    Conceptus mortality is greatest in mammals during the peri-implantation period, a time when conceptuses appose and attach to the uterine surface epithelium while releasing proinflammatory molecules. Interleukin 1 beta (IL1B), a master proinflammatory cytokine, is released by the primate, rodent, and pig blastocyst during the peri-implantation period and is believed to be essential for establishment of pregnancy. The gene encoding IL1B has duplicated in the pig, resulting in a novel gene. Preliminary observations indicate that the novel IL1B is specifically expressed by pig conceptuses during the peri-implantation period. To verify this, IL1B was cloned from mRNA isolated from Day 12 pig conceptuses and compared with IL1B cloned from mRNA isolated from pig peripheral blood leukocytes (PBLs). The pig conceptuses, but not the PBLs, expressed a novel IL1B, referred to here as interleukin 1 beta 2 (IL1B2). Porcine endometrium was treated with recombinant porcine interleukin 1 beta 1 (IL1B1), the prototypical cytokine, and IL1B2 proteins. Immunohistochemistry and real-time RT-PCR were used to measure activation of nuclear factor-kappa B (NFKB) and NFKB-regulated transcripts, respectively, within the endometrium. Both IL1B1 and IL1B2 activated NFKB in the uterine luminal epithelium within 4 h. The NFKB activation and related gene expression, however, were lower in endometrium treated with IL1B2, suggesting that the conceptus-derived cytokine may have reduced activity within the uterus. In conclusion, the peri-implantation pig conceptus expresses a novel IL1B that can activate NFKB within the uterine surface epithelium, likely creating a proinflammatory microenvironment during establishment of pregnancy in the pig. © 2015 by the Society for the Study of Reproduction, Inc.

  14. Determination of the rate constant for the NH2(X2B1) + NH2(X2B1) recombination reaction with collision partners He, Ne, Ar, and N2 at low pressures and 296 K. Part 1.

    PubMed

    Altinay, Gokhan; Macdonald, R Glen

    2012-02-09

    The recombination rate constant for the NH(2)(X(2)B(1)) + NH(2)(X(2)B(1)) → N(2)H(4)(X(1)A(1)) reaction in He, Ne, Ar, and N(2) was measured over the pressure range 1-20 Torr at a temperature of 296 K. The NH(2) radical was produced by 193 nm laser photolysis of NH(3) dilute in the third-body gas. The production of NH(2) and the loss of NH(3) were monitored by high-resolution continuous-wave absorption spectroscopy: NH(2) on the (1)2(21) ← (1)3(31) rotational transition of the (0,7,0)A(2)A(1) ← (0,0,0) X(2)B(1) vibronic band and NH(3) on either inversion doublet of the (q)Q(3)(3) rotational transition of the ν(1) fundamental. Both species were detected simultaneously following the photolysis laser pulse. The broader Doppler width of the NH(2) spectral transition allowed temporal concentration measurements to be extended up to 20 Torr before pressure broadening effects became significant. Fall-off behavior was identified and the bimolecular rate constants for each collision partner were fit to a simple Troe form defined by the parameters, k(0), k(inf), and F(cent). This work is the first part of a two part series in which part 2 will discuss the measurements with more efficient energy transfer collision partners CH(4), C(2)H(6), CO(2), CF(4), and SF(6). The pressure range was too limited to extract any new information on k(inf), and k(inf) was taken from the theoretical calculations of Klippenstein et al. (J. Phys. Chem A 2009, 113, 10241) as k(inf) = 7.9 × 10(-11) cm(3) molecule(-1) s(-1) at 296 K. The individual Troe parameters were: He, k(0) = 2.8 × 10(-29) and F(cent) = 0.47; Ne, k(0) = 2.7 × 10(-29) and F(cent) = 0.34; Ar, k(0) = 4.4 × 10(-29) and F(cent) = 0.41; N(2), k(0) = 5.7 × 10(-29) and F(cent) = 0.61, with units cm(6) molecule(-2) s(-1) for k(0). In the case of N(2) as the third body, it was possible to measure the recombination rate constant for the NH(2) + H reaction near 20 Torr total pressure. The pure three-body recombination rate

  15. Docking and QSAR comparative studies of polycyclic aromatic hydrocarbons and other procarcinogen interactions with cytochromes P450 1A1 and 1B1.

    PubMed

    Gonzalez, J; Marchand-Geneste, N; Giraudel, J L; Shimada, T

    2012-01-01

    To obtain chemical clues on the process of bioactivation by cytochromes P450 1A1 and 1B1, some QSAR studies were carried out based on cellular experiments of the metabolic activation of polycyclic aromatic hydrocarbons and heterocyclic aromatic compounds by those enzymes. Firstly, the 3D structures of cytochromes 1A1 and 1B1 were built using homology modelling with a cytochrome 1A2 template. Using these structures, 32 ligands including heterocyclic aromatic compounds, polycyclic aromatic hydrocarbons and corresponding diols, were docked with LigandFit and CDOCKER algorithms. Binding mode analysis highlighted the importance of hydrophobic interactions and the hydrogen bonding network between cytochrome amino acids and docked molecules. Finally, for each enzyme, multilinear regression and artificial neural network QSAR models were developed and compared. These statistical models highlighted the importance of electronic, structural and energetic descriptors in metabolic activation process, and could be used for virtual screening of ligand databases. In the case of P450 1A1, the best model was obtained with artificial neural network analysis and gave an r (2) of 0.66 and an external prediction [Formula: see text] of 0.73. Concerning P450 1B1, artificial neural network analysis gave a much more robust model, associated with an r (2) value of 0.73 and an external prediction [Formula: see text] of 0.59.

  16. Occurrence of Ochratoxins, Fumonisin B2 , Aflatoxins (B1 and B2 ), and Other Secondary Fungal Metabolites in Dried Date Palm Fruits from Egypt: A Mini-Survey.

    PubMed

    Abdallah, Mohamed F; Krska, Rudolf; Sulyok, Michael

    2018-02-01

    This study was conducted to investigate the natural co-occurrence of 295 fungal and bacterial metabolites in 28 samples of dried date palm fruits collected from different shops distributed in Assiut Governorate, Upper Egypt in 2016. Extraction and quantification of the target analytes were done using the "dilute and shoot" approach followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. In total, 30 toxic fungal metabolites were detected. Among these metabolites, 4 types of ochratoxins including ochratoxin type A and B were quantified in 3 samples (11%) with a contamination range from 1.48 to 6070 μg/kg for ochratoxin A and from 0.28 to 692 μg/kg for ochratoxin B. In addition, fumonisin B 2 was observed in 2 (7%) samples with contamination levels ranging from 4.99 to 16.2 μg/kg. The simultaneous detection of fumonisin B 2 in the same contaminated samples with ochratoxins indicates the fungal attack by Aspergillus niger species during storage. Only 1 sample was contaminated with aflatoxin B 1 (14.4 μg/kg) and B 2 (2.44 μg/kg). The highest maximum concentration (90400 μg/kg) was for kojic acid that contaminated 43% of the samples. To the best of the authors' knowledge, this is the first report of the natural co-occurrence of fumonisin B 2 and ochratoxin A and B in addition to a wide range of other fungal metabolites in date palm fruits. Mycotoxins are secondary metabolites produced by different fungi. These metabolites pose a potential risk on human health since they contaminate many food commodities. Among these, date palm fruits which are an integral part of diet in several countries. Therefore, detection of mycotoxins is a prerequisite to insure the safety of food. Here, different types of mycotoxins have been detected in levels that may have health hazard. © 2018 Institute of Food Technologists®.

  17. A 2-1-1 Research Collaboration

    PubMed Central

    Eddens, Katherine S.; Alcaraz, Kassandra I.; Kreuter, Matthew W.; Rath, Suchitra; Greer, Regina

    2012-01-01

    Background 2-1-1 serves as a lifeline in times of crises. These crises often cause a spike in call volume that can challenge 2-1-1’s ability to meet their service quality standards. For researchers gathering data through 2-1-1s, a sudden increase in call volume might reduce accrual as 2-1-1 has less time to administer study protocols. Research activities imbedded in 2-1-1 systems may directly affect 2-1-1 service quality indicators. Purpose Using data from a 2-1-1 research collaboration, this paper examines the impact of crises on call volume to 2-1-1, how call volume affects research participant accrual through 2-1-1, and how research recruitment efforts affect 2-1-1 service quality indicators. Methods t-tests were used to examine the effect of call volume on research participant accrual. Linear and logistic regressions were used to examine the effect of research participant accrual on 2-1-1 service quality indicators. Data were collected June 2010–December 2011; data were analyzed in 2012. Results Findings from this collaboration suggest that crises causing spikes in call volume adversely affect 2-1-1 service quality indicators as well as accrual of research participants. Administering a brief (2–3 minute) health risk assessment did not negatively affect service quality, but administering a longer (15–18 minute) survey had a modest adverse effect on these indicators. Conclusions In 2-1-1 research collaborations, both partners need to understand the dynamic relationship between call volume, research accrual, and service quality, and adjust expectations accordingly. If research goals include administering a longer survey, increased staffing of 2-1-1 call centers may be needed to avoid compromising service quality. PMID:23157769

  18. Aromatic derivatives of 1H-2,3-dihydropyrazolo(4,5-b)-1,5-diazepine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Orlov, V.D.; Kiroga, Kh.; Kolos, N.N.

    1987-09-01

    Aromatic derivatives of 1H-2,3-dihydropyrazole(4,5-b)-1,5-diazepine were obtained by the reaction of 1-phenyl-3-methyl-4,5-diaminopyrazole with chalcones and acetylarenes, catalyzed by acetic or sulfuric acid. The seven-membered ring in these compounds has a conformation of the boat type. The IR, UV, PMR, and mass spectra of the compounds are discussed.

  19. 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.

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

    PubMed

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

    2013-01-01

    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. 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. 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. Our data provide new information on gene polymorphisms in Greenlandic Inuit that might support evaluation of susceptibility to environmental contaminants and warrant further studies.

  1. Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b.

    PubMed

    Flisiak, Robert; Kawazoe, Seiji; Znoyko, Olga; Assy, Nimer; Gadano, Adrian; Kao, Jia-Horng; Lee, Kwan-Sik; Zwirtes, Ricardo; Portsmouth, Simon; Dong, Yuping; Xu, Dong; Kumada, Hiromitsu; Srinivasan, Subasree

    2016-11-01

    The study objective was to compare the efficacy and safety of peginterferon lambda-1a combined with ribavirin/daclatasvir (Lambda/RBV/DCV), versus peginterferon alfa-2a combined with ribavirin/telaprevir (Alfa/RBV/TVR), in patients chronically infected with hepatitis C virus (HCV), genotype 1b. This was a prospective, randomized, open-label, phase 3 study (NCT01718158) in adults (aged ≥18 years) who were treatment naïve or prior relapsers to peginterferon alfa/ribavirin therapy. The primary endpoint was sustained virologic response at post-treatment follow-up week 12 (SVR12). Patients were randomized in a 2:1 ratio to receive 24 weeks of Lambda/RBV/DCV or response-guided 24 or 48 weeks of Alfa/RBV/TVR. Overall, 440 patients were treated (294 with Lambda/RBV/DCV; 146 with Alfa/RBV/TVR). The proportion of patients achieving SVR12 was 88.8% in the Lambda/RBV/DCV arm and 70.5% in the Alfa/RBV/TVR arm (difference between arms: 18.3%; 95% confidence interval: 9.9-25.7; P < 0.0001). Patients in the Lambda/RBV/DCV group had fewer rash-related adverse events (AEs), cytopenic abnormalities, flu-like symptoms, serious AEs, and discontinuations due to AEs, but more liver abnormalities than those in the Alfa/RBV/TVR group. In conclusion, treatment with Lambda/RBV/DCV led to higher SVR12 rates and a more favorable safety profile than Alfa/RBV/TVR in patients with chronic HCV, genotype 1b infection.

  2. 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 ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.1 Definitions. For purposes of this part— (a...

  3. 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...

  4. 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...

  5. 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 ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.1 Definitions. For purposes of this part— (a...

  6. Cdc2/cyclin B1 regulates centrosomal Nlp proteolysis and subcellular localization.

    PubMed

    Zhao, Xuelian; Jin, Shunqian; Song, Yongmei; Zhan, Qimin

    2010-11-01

    The formation of proper mitotic spindles is required for appropriate chromosome segregation during cell division. Aberrant spindle formation often causes aneuploidy and results in tumorigenesis. However, the underlying mechanism of regulating spindle formation and chromosome separation remains to be further defined. Centrosomal Nlp (ninein-like protein) is a recently characterized BRCA1-regulated centrosomal protein and plays an important role in centrosome maturation and spindle formation. In this study, we show that Nlp can be phosphorylated by cell cycle protein kinase Cdc2/cyclin B1. The phosphorylation sites of Nlp are mapped at Ser185 and Ser589. Interestingly, the Cdc2/cyclin B1 phosphorylation site Ser185 of Nlp is required for its recognition by PLK1, which enable Nlp depart from centrosomes to allow the establishment of a mitotic scaffold at the onset of mitosis . PLK1 fails to dissociate the Nlp mutant lacking Ser185 from centrosome, suggesting that Cdc2/cyclin B1 might serve as a primary kinase of PLK1 in regulating Nlp subcellular localization. However, the phosphorylation at the site Ser589 by Cdc2/cyclin B1 plays an important role in Nlp protein stability probably due to its effect on protein degradation. Furthermore, we show that deregulated expression or subcellular localization of Nlp lead to multinuclei in cells, indicating that scheduled levels of Nlp and proper subcellular localization of Nlp are critical for successful completion of normal cell mitosis, These findings demonstrate that Cdc2/cyclin B1 is a key regulator in maintaining appropriate degradation and subcellular localization of Nlp, providing novel insights into understanding on the role of Cdc2/cyclin B1 in mitotic progression.

  7. Etsrp/etv2 is directly regulated by foxc1a/b in the zebrafish angioblast

    PubMed Central

    Veldman, Matthew B.; Lin, Shuo

    2012-01-01

    Rationale Endothelial cells are developmentally derived from angioblasts specified in the mesodermal germ cell layer. The transcription factor etsrp/etv2 is at the top of the known genetic hierarchy for angioblast development. The transcriptional events that induce etsrp expression and angioblast specification are not well understood. Objective We generated etsrp:gfp transgenic zebrafish and used them to identify regulatory regions and transcription factors critical for etsrp expression and angioblast specification from mesoderm. Methods and Results To investigate the mechanisms that initiate angioblast cell transcription during embryogenesis, we have performed promoter analysis of the etsrp locus in zebrafish. We describe three enhancer elements sufficient for endothelial gene expression when place in front of a heterologous promoter. The deletion of all three regulatory regions led to a near complete loss of endothelial expression from the etsrp promoter. One of the enhancers, located 2.3 kb upstream of etsrp contains a consensus FOX binding site that binds Foxc1a and Foxc1b in vitro by EMSA and in vivo using ChIP. Combined knockdown of foxc1a/b, using morpholinos, led to a significant decrease in etsrp expression at early developmental stages as measured by quantitative RT-PCR and in situ hybridization. Decreased expression of primitive erythrocyte genes scl and gata1 was also observed while pronephric gene pax2a was relatively normal in expression level and pattern. Conclusions These findings identify mesodermal foxc1a/b as a direct upstream regulator of etsrp in angioblasts. This establishes a new molecular link in the process of mesoderm specification into angioblast. PMID:22135404

  8. Consecutive thiophene-annulation approach to π-extended thienoacene-based organic semiconductors with [1]benzothieno[3,2-b][1]benzothiophene (BTBT) substructure.

    PubMed

    Mori, Takamichi; Nishimura, Takeshi; Yamamoto, Tatsuya; Doi, Iori; Miyazaki, Eigo; Osaka, Itaru; Takimiya, Kazuo

    2013-09-18

    We describe a new synthetic route to the [1]benzothieno[3,2-b][1]benzothiophene (BTBT) substructure featuring two consecutive thiophene-annulation reactions from o-ethynyl-thioanisole substrates and arylsulfenyl chloride reagents that can be easily derived from arylthiols. The method is particularly suitable for the synthesis of unsymmetrical derivatives, e.g., [1]benzothieno[3,2-b]naphtho[2,3-b]thiophene, [1]benzothieno[3,2-b]anthra[2,3-b]thiophene, and naphtho[3,2-b]thieno[3,2-b]anthra[2,3-b]thiophene, a selenium-containing derivative, [1]benzothieno[3,2-b][1]benzoselenophene. It also allows us to access largely π-extended derivatives with two BTBT substructures, e.g., bis[1]benzothieno[2,3-d:2',3'-d']benzo[1,2-b:4,5-b']dithiophene and bis[1]benzothieno[2,3-d:2',3'-d']naphtho[2,3-b:6,7-b']dithiophene (BBTNDT). It should be emphasized that these new BTBT derivatives are otherwise difficult to be synthesized. In addition, since various substrates and reagents, o-ethynyl-thioanisoles and arylthiols, respectively, can be combined, the method can be regarded as a versatile tool for the development of thienoacene-based organic semiconductors in this class. Among the newly synthesized materials, highly π-extended BBTNDT afforded very high mobility (>5 cm(2) V(-1) s(-1)) in its vapor-deposited organic field-effect transistors (OFETs), which is among the highest for unsubstituted acene- or thienoacenes-based organic semiconductors. In fact, the structural analyses of BBTNDT both in the single crystal and thin-film state indicated that an interactive two-dimensional molecular array is realized in the solid state, which rationalize the higher carrier mobility in the BBTNDT-based OFETs.

  9. Oxidation of Methyl and Ethyl Nitrosamines by Cytochromes P450 2E1 and 2B1

    PubMed Central

    Chowdhury, Goutam; Calcutt, M. Wade; Nagy, Leslie D.; Guengerich, F. Peter

    2012-01-01

    Cytochrome P450 (P450) 2E1 is the major enzyme that oxidizes N-nitrosodimethylamine (N,N-dimethylnitrosamine, DMN), a carcinogen and also a representative of some nitrosamines formed endogenously. Oxidation of DMN by rat or human P450 2E1 to HCHO showed a high apparent intrinsic kinetic deuterium isotope effect (KIE), ≥ 8. The KIE was not attenuated in non-competitive intermolecular experiments with rat liver microsomes (DV 12.5, D(V/K) 10.9, nomenclature of Northrop, D.B. (1982) Methods Enzymol. 87, 607–625) but was with purified human P450 2E1 (DV 3.3, D(V/K) 3.7), indicating that C-H bond breaking is partially rate-limiting with human P450 2E1. With N-nitrosodiethylamine (N,N-diethylnitrosamine, DEN), the intrinsic KIE was slightly lower and was not expressed (e.g., D(V/K) 1.2) in non-competitive intermolecular experiments. The same general pattern of KIEs was also seen in the D(V/K) results with DMN and DEN for the minor products resulting from the denitrosation reactions (CH3NH2, CH3CH2NH2, and NO2−). Experiments with deuterated N-nitroso-N-methyl,N-ethylamine demonstrated that the lower KIEs associated for ethyl compared to methyl oxidation could be distinguished within a single molecule. P450 2E1 oxidized DMN and DEN to aldehydes and then to the carboxylic acids. No kinetic lags were observed in acid formation; pulse-chase experiments with carrier aldehydes showed only limited equilibration with P450 2E1-bound aldehydes, indicative of processive reactions, as reported for P450 2A6 (Chowdhury, G. et al. (2010) J. Biol. Chem. 285, 8031–8044). These same features (no lag phase for HCO2H formation, lack of equilibration in pulse-chase assays) were also seen with (rat) P450 2B1, which has lower catalytic efficiency for DMN oxidation and a larger active site. Thus, the processivity of dialkylnitrosamine oxidation appears to be shared by a number of P450s. PMID:23186213

  10. Quantitative assessment of CYP11B1 and CYP11B2 expression in aldosterone-producing adenomas.

    PubMed

    Fallo, F; Pezzi, V; Barzon, L; Mulatero, P; Veglio, F; Sonino, N; Mathis, J M

    2002-12-01

    The presence and pathophysiological role of CYP11B1 (11beta-hydroxylase) gene in the zona glomerulosa of human adrenal cortex is still controversial. In order to specifically quantify CYP11B1, CYP11B2 (aldosterone synthase) and CYP17(17alpha-hydroxylase) mRNA levels, we developed a real-time RT-PCR assay and examined the expression in a series of adrenal tIssues, including six normal adrenals from patients adrenalectomized for renal cancer and twelve aldosterone-producing adenomas (APA) from patients with primary aldosteronism. CYP11B1 mRNA levels were clearly detected in normal adrenals, which comprised both zona glomerulosa and fasciculata/reticularis cells, but were also measured at a lower range (P<0.05) in APA. The levels of CYP11B2 mRNA were lower (P<0.005) in normal adrenals than in APA. CYP17 mRNAlevels were similar in normal adrenals and in APA. In patients with APA, CYP11B2 and CYP11B1 mRNA levels were not correlated either with basal aldosterone or with the change from basal aldosterone in response to posture or to dexamethasone. No correlation between CYP11B1 mRNA or CYP11B2 mRNA and the percentage of zona fasciculata-like cells was observed in APA. Real-time RT-PCR can be reliably used to quantify CYP11B1 and CYP11B2 mRNA levels in adrenal tIssues. Expression of CYP11B1 in hyperfunctioning zona glomerulosa suggests an additional formation of corticosterone via 11beta-hydroxylase, providing further substrate for aldosterone biosynthesis. CYP11B1 and CYP11B2 mRNA levels in APA are not related to the in vivo secretory activity of glomerulosa cells, where post-transcriptional factors might ultimately regulate aldosterone production.

  11. Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism.

    PubMed

    Kang, Gaeun; Bae, Kyung-Yeol; Kim, Sung-Wan; Kim, Jin; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang; Kim, Jong-Keun

    2014-06-01

    It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours (AUC0-4 ) and the peak blood concentration of EtOH (Cmax ) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results

  12. Risk stratification using SpO2/FiO2 and PEEP at initial ARDS diagnosis and after 24 h in patients with moderate or severe ARDS.

    PubMed

    Pisani, Luigi; Roozeman, Jan-Paul; Simonis, Fabienne D; Giangregorio, Antonio; van der Hoeven, Sophia M; Schouten, Laura R; Horn, Janneke; Neto, Ary Serpa; Festic, Emir; Dondorp, Arjen M; Grasso, Salvatore; Bos, Lieuwe D; Schultz, Marcus J

    2017-10-25

    We assessed the potential of risk stratification of ARDS patients using SpO 2 /FiO 2 and positive end-expiratory pressure (PEEP) at ARDS onset and after 24 h. We used data from a prospective observational study in patients admitted to a mixed medical-surgical intensive care unit of a university hospital in the Netherlands. Risk stratification was by cutoffs for SpO 2 /FiO 2 and PEEP. The primary outcome was in-hospital mortality. Patients with moderate or severe ARDS with a length of stay of > 24 h were included in this study. Patients were assigned to four predefined risk groups: group I (SpO 2 /FiO 2  ≥ 190 and PEEP < 10 cm H 2 O), group II (SpO 2 /FiO 2  ≥ 190 and PEEP ≥ 10 cm), group III (SpO 2 /FiO 2  < 190 and PEEP < 10 cm H 2 O) and group IV (SpO 2 /FiO 2  < 190 and PEEP ≥ 10 cm H 2 O). The analysis included 456 patients. SpO 2 /FiO 2 and PaO 2 /FiO 2 had a strong relationship (P < 0.001, R 2  = 0.676) that could be described in a linear regression equation (SpO 2 /FiO 2  = 42.6 + 1.0 * PaO 2 /FiO 2 ). Risk stratification at initial ARDS diagnosis resulted in groups that had no differences in in-hospital mortality. Risk stratification at 24 h resulted in groups with increasing mortality rates. The association between group assignment at 24 h and outcome was confounded by several factors, including APACHE IV scores, arterial pH and plasma lactate levels, and vasopressor therapy. In this cohort of patients with moderate or severe ARDS, SpO 2 /FiO 2 and PaO 2 /FiO 2 have a strong linear relationship. In contrast to risk stratification at initial ARDS diagnosis, risk stratification using SpO 2 /FiO 2 and PEEP after 24 h resulted in groups with worsening outcomes. Risk stratification using SpO 2 /FiO 2 and PEEP could be practical, especially in resource-limited settings.

  13. Synthesis and disulfide bond connectivity-activity studies of a kalata B1-inspired cyclopeptide against dengue NS2B-NS3 protease.

    PubMed

    Gao, Yaojun; Cui, Taian; Lam, Yulin

    2010-02-01

    Kalata B1 is a plant protein with remarkable thermal, chemical and enzymatic stability. Its potential applications could be centered on the possibility of using its cyclic structure and cystine knot motif as a scaffold for the design of stable pharmaceuticals. To discover potent dengue NS2B-NS3 protease inhibitors, we have prepared various kalata B1 analogues by varying the amino acid sequence. Mass spectrometric and biochemical investigations of these analogues revealed a cyclopeptide whose two fully oxidized forms are substrate-competitive inhibitors of the dengue viral NS2B-NS3 protease. Both oxidized forms showed potent inhibition with K(i) of 1.39+/-0.35 and 3.03+/-0.75 microM, respectively. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  14. Fermentation of 1,2-Propanediol and 1,2-Ethanediol by Some Genera of Enterobacteriaceae, Involving Coenzyme B12-Dependent Diol Dehydratase

    PubMed Central

    Toraya, Tetsuo; Honda, Susumu; Fukui, Saburo

    1979-01-01

    Klebsiella pneumoniae (Aerobacter aerogenes) ATCC 8724 was able to grow anaerobically on 1,2-propanediol and 1,2-ethanediol as carbon and energy sources. Whole cells of the bacterium grown anaerobically on 1,2-propanediol or on glycerol catalyzed conversion of 1,2-diols and aldehydes to the corresponding acids and alcohols. Glucose-grown cells also converted aldehydes, but not 1,2-diols, to acids and alcohols. The presence of activities of coenzyme B12-dependent diol dehydratase, alcohol dehydrogenase, coenzyme-A-dependent aldehyde dehydrogenase, phosphotransacetylase, and acetate kinase was demonstrated with crude extracts of 1,2-propanediol-grown cells. The dependence of the levels of these enzymes on growth substrates, together with cofactor requirements in in vitro conversion of these substrates, indicates that 1,2-diols are fermented to the corresponding acids and alcohols via aldehydes, acyl-coenzyme A, and acyl phosphates. This metabolic pathway for 1,2-diol fermentation was also suggested in some other genera of Enterobacteriaceae which were able to grow anaerobically on 1,2-propanediol. When the bacteria were cultivated in a 1,2-propanediol medium not supplemented with cobalt ion, the coenzyme B12-dependent conversion of 1,2-diols to aldehydes was the rate-limiting step in this fermentation. This was because the intracellular concentration of coenzyme B12 was very low in the cells grown in cobalt-deficient medium, since the apoprotein of diol dehydratase was markedly induced in the cells grown in the 1,2-propanediol medium. Better cell yields were obtained when the bacteria were grown anaerobically on 1,2-propanediol. Evidence is presented that aerobically grown cells have a different metabolic pathway for utilizing 1,2-propanediol. PMID:378959

  15. Retinal plasma extravasation in streptozotocin-diabetic rats mediated by kinin B1 and B2 receptors

    PubMed Central

    Abdouh, M; Talbot, S; Couture, R; Hasséssian, H M

    2008-01-01

    Background and purpose: We investigated whether or not kinin receptors play a role in diabetic blood–retinal barrier breakdown, which is a leading cause of vision loss. Experimental approach: Blood–retinal barrier breakdown was quantified using Evans blue, and expression of kinin B1 receptor mRNA was measured using quantitative reverse transcrition-PCR. Diabetic rats (streptozotocin (STZ), 65 mg kg−1) received a single intraocular injection of bradykinin (BK) or des-Arg9-BK, alone, or in combination with antagonists for B1 (des-Arg10-Hoe140, R-715) and/or B2 (Hoe140) receptors, given intraocularly or intravenously (i.v.). Key results: In control rats, BK (0.1–10 nmol) dose-dependently increased plasma extravasation, which was inhibited by Hoe140 (0.2 nmol), whereas des-Arg9-BK (0.1 and 1 nmol) was without effect. B1 receptor mRNA was markedly increased in retinas of diabetic rats, and this was prevented by N-acetyl-L-cysteine (1 g kg−1 day−1 for 7 days). Plasma extravasation in retinas of STZ-diabetic rats was higher than in controls and enhanced by des-Arg9-BK. Response to des-Arg9-BK was inhibited by intraocular or i.v. injection of B1 receptor antagonists. Diabetes-induced plasma extravasation was inhibited only by a combination of des-Arg10-Hoe140 and Hoe 140 (100 nmol kg−1, i.v. 15 min earlier) or by R-715 (1 μmol kg−1, i.v.) injected daily for 7 days. Conclusions and implications: Kinin B1 receptors are upregulated in retinas of STZ-diabetic rats through a mechanism involving oxidative stress. Both kinin B1 and B2 receptors contribute to increased plasma extravasation in diabetic retinopathy. Chronic inhibition of both kinin receptors, possibly with antioxidant adjuvants, may be a novel therapeutic strategy for diabetic retinopathy. PMID:18311190

  16. A novel method for determination of aflatoxin B1 mediated by FCLA + BSA

    NASA Astrophysics Data System (ADS)

    Chen, WenLi; Xing, Da

    2005-02-01

    As a chemiluminescence (CL) probe, 3,7-dihydro-6-{4-{2-(N"-(5-fluoresceinyl) thioureido)ethoxy}phenyl}-2-met -hylimi-dazo{1,2-a}pyrazin-3-one dosium salt (FCLA) can sensitively and specifically react with singlet oxygen (1O2 ) and superoxide(O2""). BSA (Bovine Serum Albumin) can enlarge the CL intensity of FCLA to 860%. This report presents a novel method for determination of Aflatoxin B1 (AfB1) mediated by FCLA+BSA. The concentration of AFB1 showed an obvious positive correlation with the CL intensity mediated by FCLA+BSA. This method could measure accurately ng/ml of AfB1 concentration. At the same time, the fluorescence spectrum of FCLA+BSA and FCLA+BSA+AfB1 were measured respectively, which showed that the fluorescence intensity of FCLA+BSA+AfB1 was higher than FCLA+BSA. Comparing the peak value of FCLA, FCLA+BSA and FCLA+BSA+AfB1 had a 6nm Einstein shift (red shift). The study suggested that CL method mediated by FCLA+BSA might be applicable to the determination of AfB1 concentration.

  17. Slice profile and B1 corrections in 2D magnetic resonance fingerprinting.

    PubMed

    Ma, Dan; Coppo, Simone; Chen, Yong; McGivney, Debra F; Jiang, Yun; Pahwa, Shivani; Gulani, Vikas; Griswold, Mark A

    2017-11-01

    The goal of this study is to characterize and improve the accuracy of 2D magnetic resonance fingerprinting (MRF) scans in the presence of slice profile (SP) and B 1 imperfections, which are two main factors that affect quantitative results in MRF. The SP and B 1 imperfections are characterized and corrected separately. The SP effect is corrected by simulating the radiofrequency pulse in the dictionary, and the B 1 is corrected by acquiring a B 1 map using the Bloch-Siegert method before each scan. The accuracy, precision, and repeatability of the proposed method are evaluated in phantom studies. The effects of both SP and B 1 imperfections are also illustrated and corrected in the in vivo studies. The SP and B 1 corrections improve the accuracy of the T 1 and T 2 values, independent of the shape of the radiofrequency pulse. The T 1 and T 2 values obtained from different excitation patterns become more consistent after corrections, which leads to an improvement of the robustness of the MRF design. This study demonstrates that MRF is sensitive to both SP and B 1 effects, and that corrections can be made to improve the accuracy of MRF with only a 2-s increase in acquisition time. Magn Reson Med 78:1781-1789, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  18. Dry powder inhalers of gentamicin and leucine: formulation parameters, aerosol performance and in vitro toxicity on CuFi1 cells.

    PubMed

    Aquino, R P; Prota, L; Auriemma, G; Santoro, A; Mencherini, T; Colombo, G; Russo, P

    2012-04-15

    The high hygroscopicity of gentamicin (G) as raw material hampers the production of respirable particles during aerosol generation and prevents its direct use as powder for inhalation in patients suffering from cystic fibrosis (CF). Therefore, this research aimed to design a new dry powder formulation of G studying dispersibility properties of an aminoacid, L-leucine (leu), and appropriate process conditions. Spray-dried powders were characterized as to water uptake, particle size distribution, morphology and stability, in correlation with process parameters. Aerodynamic properties were analyzed both by Single Stage Glass Impinger and Andersen Cascade Impactor. Moreover, the potential cytotoxicity on bronchial epithelial cells bearing a CFTR F508/F508 mutant genotype (CuFi1) were tested. Results indicated that leu may improve the aerosol performance of G-dried powders. The maximum fine particle fraction (FPF) of about 58.3% was obtained when water/isopropyl alcohol 7:3 system and 15-20% (w/w) of leu were used, compared to a FPF value of 13.4% for neat G-dried powders. The enhancement of aerosol efficiency was credited both to the improvement of the powder flowability, caused by the dispersibility enhancer (aminoacid), and to the modification of the particle surface due to the influence of the organic co-solvent on drying process. No significant degradation of the dry powder was observed up to 6 months of storage. Moreover, particle engineering did not affect either the cell viability or cell proliferation of CuFi1 over a 24 h period. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Polycyclic phloroglucinols as PTP1B inhibitors from Hypericum longistylum: Structures, PTP1B inhibitory activities, and interactions with PTP1B.

    PubMed

    Cao, Xiangrong; Yang, Xueyuan; Wang, Peixia; Liang, Yue; Liu, Feng; Tuerhong, Muhetaer; Jin, Da-Qing; Xu, Jing; Lee, Dongho; Ohizumi, Yasushi; Guo, Yuanqiang

    2017-12-01

    Protein tyrosine phosphatase 1B (PTP1B) has been regarded asa target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A-D (1-4) from the aerial parts of Hypericum longistylum. The structures of 1-4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1-4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin.

    PubMed

    Duan, Chaojun; Li, Minghua; Rui, Liangyou

    2004-10-15

    Leptin regulates energy homeostasis primarily by binding and activating its long form receptor (LRb). Deficiency of either leptin or LRb causes morbid obesity. Leptin stimulates LRb-associated JAK2, thus initiating multiple pathways including the Stat3 and phosphatidylinositol (PI) 3-kinase pathways that mediate leptin biological actions. Here we report that SH2-B, a JAK2-interacting protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin. SH2-B directly bound, via its PH and SH2 domain, to both IRS1 and IRS2 both in vitro and in intact cells and mediated formation of a JAK2/SH2-B/IRS1 or IRS2 tertiary complex. Consequently, SH2-B dramatically enhanced leptin-stimulated tyrosine phosphorylation of IRS1 and IRS2 in HEK293 cells stably expressing LRb, thus promoting association of IRS1 and IRS2 with the p85 regulatory subunit of PI 3-kinase and phosphorylation and activation of Akt. SH2-B mutants with lower affinity for IRS1 and IRS2 exhibited reduced ability to promote association of JAK2 with IRS1, tyrosine phosphorylation of IRS1, and association of IRS1 with p85 in response to leptin. Moreover, deletion of the SH2-B gene impaired leptin-stimulated tyrosine phosphorylation of endogenous IRS1 in mouse embryonic fibroblasts (MEF), which was reversed by reintroduction of SH2-B. Similarly, SH2-B promoted growth hormone-stimulated tyrosine phosphorylation of IRS1 in both HEK293 and MEF cells. Our data suggest that SH2-B is a novel mediator of the PI 3-kinase pathway in response to leptin or other hormones and cytokines that activate JAK2.

  1. Lubrol-RAFTs in melanoma cells: a molecular platform for tumor-promoting ephrin-B2-integrin-beta1 interaction.

    PubMed

    Meyer, Stefanie; Orsó, Evelyn; Schmitz, Gerd; Landthaler, Michael; Vogt, Thomas

    2007-07-01

    Ephrins control cell motility and matrix adhesion. These functions play a pivotal role in cancer progression, for example, in malignant melanomas. We have previously shown that the ephrin-B2-tumor-promoting action is partly mediated by integrin-beta1 interaction. However, the subcellular prerequisites for molecular interaction like molecular proximity and co-compartmentalization have not been elucidated yet. Specific cholesterol-rich microdomains, termed lipid rafts (RAFTs), are known to be essential for functional ephrin-B2 signalling and integrin-mediated effects. Therefore, we addressed the question whether RAFT co-compartmentalization of both molecules could provide the molecular platform for their tumor-promoting interaction. In this study, we show that overexpressed ephrin-B2 is not only compartmentalized to classical Triton X-100 RAFTs in B16 melanoma cells, but also to the recently defined Lubrol-RAFTs. Interestingly, in the melanoma cells investigated, integrin-beta1 is also preferentially detected in such Lubrol-RAFTs. Accordingly, the presence of ephrin-B2 and integrin-beta1 in RAFTs and their function in cell migration and matrix attachment are highly sensitive to RAFT disruption by cholesterol depletion. Confocal fluorescence microscopy analyses also support the concept of a close molecular proximity and functional interplay of ephrin-B2 and integrin-beta1 in the plasma membrane. We conclude that Lubrol-RAFTs probably represent the platform for tumor-promoting ephrin-B2-integrin-beta1 interaction, which could become an interesting target for future antitumoral therapies.

  2. 75 FR 27411 - Airworthiness Directives; Turbomeca Arriel 1B, 1D, 1D1, and 1S1 Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-17

    .... That AD requires initial and repetitive relative position checks of the gas generator 2nd stage turbine... repetitive replacements of 2nd stage turbines on Arriel 1B, 1D, and 1D1 engines. This AD requires lowering the initial and repetitive thresholds for replacement of 2nd stage turbines on Arriel 1B, 1D, and 1D1...

  3. Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291.

    PubMed

    Zhang, Peng; Li, Xiao-Ming; Mao, Xin-Xin; Mándi, Attila; Kurtán, Tibor; Wang, Bin-Gui

    2016-01-01

    A new indolyl-6,10b-dihydro-5a H -[1]benzofuro[2,3- b ]indole derivative, varioloid A ( 1 ), was isolated from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291. Its structure was elucidated on the basis of extensive analysis of 1D and 2D NMR data and the absolute configuration was determined by time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. A similar compound, whose planar structure was previously described but the relative and absolute configurations and 13 C NMR data were not reported, was also identified and was tentatively named as varioloid B ( 2 ). Both compounds 1 and 2 exhibited cytotoxicity against A549, HCT116, and HepG2 cell lines, with IC 50 values ranging from 2.6 to 8.2 µg/mL.

  4. Chemical disorder and 207Pb hyperfine fields in the magnetoelectric multiferroic Pb (F e1 /2S b1 /2 ) O3 and its solid solution with Pb (F e1 /2N b1 /2) O3

    NASA Astrophysics Data System (ADS)

    Zagorodniy, Yu. O.; Kuzian, R. O.; Kondakova, I. V.; Maryško, M.; Chlan, V.; Štěpánková, H.; Olekhnovich, N. M.; Pushkarev, A. V.; Radyush, Yu. V.; Raevski, I. P.; Zalar, B.; Laguta, V. V.; Stephanovich, V. A.

    2018-01-01

    We report on the results of magnetic susceptibility, electron paramagnetic resonance, and 207Pb nuclear magnetic resonance (NMR) studies of the magnetoelectric multiferroic Pb (F e1 /2S b1 /2 ) O3 (PFS) ceramic, as well as its solid solution with Pb (F e1 /2N b1 /2) O3 (PFN) of different degrees of the 1:1 ordering of magnetic F e3 + and nonmagnetic S b5 + ions. The ordering has been studied by x-ray diffraction (XRD) and NMR methods. In particular, two spectral lines, originating from the ordered and disordered regions, respectively, are resolved in the 207Pb NMR spectra. This demonstrates the presence of spatially heterogeneous ordering where ordered regions are embedded into a disordered matrix. Combining XRD and NMR data, we have determined both the long-range order parameter s and the volume fraction of ordered regions s' for all investigated samples. The values vary in the range s =0 -0.93 and s'=0 -1 . We have found that the 207Pb Fermi contact interaction strongly depends on the disorder in the Fe/Sb positions: whereas it reaches 7.08 MHz in the ordered lattice, it is almost zero in the disordered environment. These results are further supported by the studies of PFS-PFN solid solutions. The analysis of experimental data in terms of density functional theory reveals a noticeably higher hybridization between Pb 6s and Fe 3d orbitals in the ordered case. The ordering of magnetic and nonmagnetic ions has a strong impact on the magnetic properties of PFS, leading to a transformation of the long-range ordered antiferromagnetic phase in chemically ordered samples to the spin glass state already in partially (s =0.35 ) disordered specimens. In our opinion, the difference in the magnetic properties of PFN and PFS is related to the fact that PFN is completely disordered, in contrast to PFS, which is only partially disordered, with small ordered regions existing in the disordered matrix that prevent the percolation of the nearest-neighbor Fe-Fe exchange interaction

  5. A Survey of Client Geolocation Using Wi-Fi Positioning Services

    DTIC Science & Technology

    2014-03-01

    Master’s Thesis 4 . TITLE AND SUBTITLE A SURVEY OF CLIENT GEOLOCATION USING WI-FI POSITIONING SERVICES 5. FUNDING NUMBERS 6. AUTHOR(S) Nicholas... 4   B.   RELATED WORK ..........................................................................................5   III.   METHODOLOGY...9   4 .   Target AP Collection

  6. A revised B(E2;2+ 1 → 0+ 1) value in the semi-magic nucleus 210Po

    NASA Astrophysics Data System (ADS)

    Kocheva, D.; Rainovski, G.; Jolie, J.; Pietralla, N.; Blazhev, A.; Astier, A.; Altenkirch, R.; Ansari, S.; Braunroth, Th.; Cortés, M. L.; Dewald, A.; Diel, F.; Djongolov, M.; Fransen, C.; Gladnishki, K.; Hennig, A.; Karayonchev, V.; Keatings, J. M.; Kluge, E.; Litzinger, J.; Müller-Gatermann, C.; Petkov, P.; Rudigier, M.; Scheck, M.; Scholz, Ph.; Spagnoletti, P.; Spieker, M.; Stahl, C.; Stegmann, R.; Stoyanova, M.; Thöle, P.; Warr, N.; Werner, V.; Witt, W.; Wölk, D.; Zell, K. O.; Van Isacker, P.; Ponomarev, V. Yu.

    2017-09-01

    The lifetimes of the 2^+_1 , the 2^+_2 and the 3^-_1 states of 210Po have been measured in the 208Pb(12C,10Be)210Po transfer reaction by the Doppler-shift attenuation method. The result for the lifetime of the 2^+_1 state is about three times shorter than the adopted value. However, the new value still does not allow for a consistent description of the properties of the yrast 2^+_1 , 4^+_1 , 6^+_1 , and 8^+_1 states of 210Po in the framework of nuclear shell models. Quasi-particle Phonon Model (QPM) calculations also cannot overcome this problem thus indicating the existence of a peculiarity which is neglected in both theoretical approaches.

  7. A soluble form of IL-13 receptor alpha 1 promotes IgG2a and IgG2b production by murine germinal center B cells.

    PubMed

    Poudrier, J; Graber, P; Herren, S; Gretener, D; Elson, G; Berney, C; Gauchat, J F; Kosco-Vilbois, M H

    1999-08-01

    A functional IL-13R involves at least two cell surface proteins, the IL-13R alpha 1 and IL-4R alpha. Using a soluble form of the murine IL-13R alpha 1 (sIL-13R), we reveal several novel features of this system. The sIL-13R promotes proliferation and augmentation of Ag-specific IgM, IgG2a, and IgG2b production by murine germinal center (GC) B cells in vitro. These effects were enhanced by CD40 signaling and were not inhibited by an anti-IL4R alpha mAb, a result suggesting other ligands. In GC cell cultures, sIL-13R also promoted IL-6 production, and interestingly, sIL-13R-induced IgG2a and IgG2b augmentation was absent in GC cells isolated from IL-6-deficient mice. Furthermore, the effects of the sIL-13R molecule were inhibited in the presence of an anti-IL-13 mAb, and preincubation of GC cells with IL-13 enhanced the sIL-13R-mediated effects. When sIL-13R was injected into mice, it served as an adjuvant-promoting production to varying degrees of IgM and IgG isotypes. We thus propose that IL-13R alpha 1 is a molecule involved in B cell differentiation, using a mechanism that may involve regulation of IL-6-responsive elements. Taken together, our data reveal previously unknown activities as well as suggest that the ligand for the sIL-13R might be a component of the IL-13R complex or a counterstructure yet to be defined.

  8. 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

  9. Prognostic Significance of ESR1 Amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 Polymorphisms in Breast Cancer Patients

    PubMed Central

    Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Żaczek, Anna J.

    2013-01-01

    Introduction Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Materials and Methods Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). Results ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. Conclusions ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype. PMID:23951298

  10. Prognostic significance of ESR1 amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 polymorphisms in breast cancer patients.

    PubMed

    Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Zaczek, Anna J

    2013-01-01

    Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype.

  11. MdSOS2L1 phosphorylates MdVHA-B1 to modulate malate accumulation in response to salinity in apple.

    PubMed

    Hu, Da-Gang; Sun, Cui-Hui; Sun, Mei-Hong; Hao, Yu-Jin

    2016-03-01

    Salt-induced phosphorylation of MdVHA-B1 protein was mediated by MdSOS2L1 protein kinase, and thereby increasing malate content in apple. Salinity is an important environmental factor that influences malate accumulation in apple. However, the molecular mechanism by which salinity regulates this process is poorly understood. In this work, we found that MdSOS2L1, a novel AtSOS2-LIKE protein kinase, interacts with V-ATPase subunit MdVHA-B1. Furthermore, MdSOS2L1 directly phosphorylates MdVHA-B1 at Ser(396) site to modulate malate accumulation in response to salt stress. Meanwhile, a series of transgenic analyses in apple calli showed that the MdSOS2L1-MdVHAB1 pathway was involved in the regulation of malate accumulation. Finally, a viral vector-based transformation approach demonstrated that the MdSOS2L1-MdVHAB1 pathway also modulated malate accumulation in apple fruits with or without salt stress. Collectively, our findings provide a new insight into the mechanism by which MdSOS2L1 phosphorylates MdVHA-B1 to modulate malate accumulation in response to salinity in apple.

  12. Primary study on the lesions and specific proteins in BEAS-2B cells induced with the 2009 A (H1N1) influenza virus.

    PubMed

    Fang, Shisong; Zhang, Kaining; Wang, Ting; Wang, Xin; Lu, Xing; Peng, Bo; Wu, Weihua; Zhang, Ran; Chen, Shiju; Zhang, Renli; Xue, Hong; Yu, Muhua; Cheng, Jinquan

    2014-12-01

    In order to investigate the lesions and proteins with differential expression in cells infected with the 2009 A (H1N1) virus and to determine the specific proteins involved in cell damage, the present study has been performed. BEAS-2B cells were infected with the 2009 A (H1N1) influenza virus or the seasonal H1N1 influenza virus for 12, 24, 48, and 72 h, and cell cycle and apoptosis were analyzed with flow cytometry. Total cellular proteins were extracted and underwent two-dimensional gel electrophoresis. The differentially expressed proteins underwent mass spectrometry for identification. The results showed that after 12 h, cells infected with the virus strain sourced from severe cases had the highest apoptosis rate (P < 0.05). After 48 h, cells infected with the virus strain sourced from fatal cases and severe cases had the highest apoptosis rate (P < 0.05), and after 72 h, cells infected with virus strains from fatal cases and ordinary cases had the highest apoptosis rate (P < 0.05). All the four influenza virus strains induced cell cycle arrest mainly at the G0/G1 phase. Eighteen differentially expressed proteins were identified, including galectin-1, cofilin-1, protein DJ-1, proteasome subunit α type-5, macrophage migration inhibitory factor, translationally controlled tumor protein, profilin 1, and interferon α-2. Galectin-1 was specifically observed in BEAS-2B infected with 2009 A (H1N1) influenza viruses, and cofilin-1 was specifically observed in BEAS-2B cells in the late stage of 2009 A (H1N1) influenza virus infection. In conclusion, differential effects of the 2009 A (H1N1) influenza virus and seasonal H1N1 influenza virus were identified on the cell cycle and apoptosis, and galectin-1 may play a role in cell apoptosis induced by 2009 A (H1N1) influenza virus.

  13. 8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors.

    PubMed

    Brunschweiger, Andreas; Koch, Pierre; Schlenk, Miriam; Rafehi, Muhammad; Radjainia, Hamid; Küppers, Petra; Hinz, Sonja; Pineda, Felipe; Wiese, Michael; Hockemeyer, Jörg; Heer, Jag; Denonne, Frédéric; Müller, Christa E

    2016-11-01

    Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson's disease are, among others, the A 2A adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A 1 ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1-f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure-activity-relationships. Several compounds blocked human and rat A 1 and A 2A ARs at similar concentrations representing dual A 1 /A 2A antagonists with high selectivity versus the other AR subtypes. Among the best dual A 1 /A 2A AR antagonists were 8-(3-(4-chlorophenyl)propyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (41, K i human A 1 : 65.5nM, A 2A : 230nM; K i rat A 1 : 352nM, A 2A : 316nM) and 1,3-dimethyl-8-((2-(thiophen-2-yl)thiazol-4-yl)methyl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (57, K i human A 1 : 642nM, A 2A : 203nM; K i rat A 1 : 166nM, A 2A : 121nM). Compound 57 was found to be well water-soluble (0.7mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple-target inhibition: (R)-1,3-dimethyl-8-(2,1,3,4-tetrahydronaphthalen-1-yl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (49) was about equipotent at A 1 and A 2A ARs and at MAO-B (K i human A 1 : 393nM, human A 2A : 595nM, IC 50 human MAO-B: 210nM) thus allowing future in vivo explorations of the intended multi-target approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Combination of ALDH2 and ADH1B polymorphisms is associated with smoking initiation: A large-scale cross-sectional study in a Japanese population.

    PubMed

    Masaoka, Hiroyuki; Ito, Hidemi; Gallus, Silvano; Watanabe, Miki; Yokomizo, Akira; Eto, Masatoshi; Matsuo, Keitaro

    2017-04-01

    Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms are known to strongly influence alcohol drinking behavior. Given evidence of an association between smoking and drinking behaviors, we hypothesized that ALDH2/ADH1B polymorphisms might also be associated with smoking initiation, and conducted a cross-sectional study to examine this hypothesis. Study subjects were first-visit outpatients diagnosed not to have cancer at Aichi Cancer Center Hospital between 2001 and 2005, including 4141 never smokers and 2912 ever smokers. Unconditional logistic regression models were applied to estimate odds ratios (OR) and 95% confidence intervals (CI) for smoking initiation by comparing ever smokers with never smokers. Excessive alcohol drinking was associated with a higher likelihood of ever smoking. After adjustment for drinking behaviors, compared to individuals with ALDH2 Glu/Glu, the ORs of ever smoking were 1.71 (95% CI, 1.49-1.95) and 2.28 (1.81-2.87) among those with ALDH2 Glu/Lys and Lys/Lys, respectively. Combination of ALDH2 Lys/Lys and ADH1B His/His (i.e., the most alcohol-intolerant subpopulation) showed the highest OR [2.44 (1.84-3.23)], whereas combination of ALDH2 Glu/Glu and ADH1B Arg/Arg (i.e., the most alcohol-tolerant subpopulation) showed the lowest OR [0.83 (0.57-1.21)] compared with ALDH2 Glu/Glu and ADH1B His/His. Besides the amount and frequency of alcohol drinking, the combination of ALDH2 and ADH1B polymorphisms predicts smoking initiation. This study suggests that alcohol tolerance regulated by ALDH2 and ADH1B polymorphisms is associated with smoking initiation, and facilitates the development of targeted interventions to reduce smoking prevalence. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Bromuconazole-induced hepatotoxicity is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1 gene expression.

    PubMed

    Abdelhadya, Doaa H; El-Magd, Mohammed Abu; Elbialy, Zizy I; Saleh, Ayman A

    2017-09-01

    Despite widespread use of bromuconazole as a pesticide for food crops and fruits, limited studies have been done to evaluate its toxic effects. Here, we evaluated the hepatotoxic effect of bromuconazole using classical toxicological (biochemical analysis and histopathological examination) and gene-based molecular methods. Male rats were treated either orally or topically with bromuconazole at doses equal to no observed adverse effect level (NOAEL) and 1/10 LD50 for 90 d. Bromuconazole increased activities of liver enzymes (ALT, AST, ALP, and ACP), and levels of bilirubin. It also induced hepatic oxidative stress as evidenced by significant decrease in the activities of superoxide dismutase (SOD), and significant increase in levels of malondialdehyde (MDA) in liver. In addition, bromuconazole caused an increase in liver weights and necrobiotic changes (vacuolation and hepatocellular hypertrophy). It also strongly induced the expression of PXR and its downstream target CYP3A1 gene as well as the activity of CYP3A1. However, it inhibited the expression of CAR and its downstream target CYP2B1 gene without significant changing in CYP2B1 activity. Overall, the oral route showed higher hepatotoxic effect and molecular changes than the dermal route and all changes were dose dependent. This is the first investigation to report that bromuconazole-induced liver oxidative damage is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1.

  16. amamutdb.no: A relational database for MAN2B1 allelic variants that compiles genotypes, clinical phenotypes, and biochemical and structural data of mutant MAN2B1 in α-mannosidosis.

    PubMed

    Riise Stensland, Hilde Monica Frostad; Frantzen, Gabrio; Kuokkanen, Elina; Buvang, Elisabeth Kjeldsen; Klenow, Helle Bagterp; Heikinheimo, Pirkko; Malm, Dag; Nilssen, Øivind

    2015-06-01

    α-Mannosidosis is an autosomal recessive lysosomal storage disorder caused by mutations in the MAN2B1 gene, encoding lysosomal α-mannosidase. The disorder is characterized by a range of clinical phenotypes of which the major manifestations are mental impairment, hearing impairment, skeletal changes, and immunodeficiency. Here, we report an α-mannosidosis mutation database, amamutdb.no, which has been constructed as a publicly accessible online resource for recording and analyzing MAN2B1 variants (http://amamutdb.no). Our aim has been to offer structured and relational information on MAN2B1 mutations and genotypes along with associated clinical phenotypes. Classifying missense mutations, as pathogenic or benign, is a challenge. Therefore, they have been given special attention as we have compiled all available data that relate to their biochemical, functional, and structural properties. The α-mannosidosis mutation database is comprehensive and relational in the sense that information can be retrieved and compiled across datasets; hence, it will facilitate diagnostics and increase our understanding of the clinical and molecular aspects of α-mannosidosis. We believe that the amamutdb.no structure and architecture will be applicable for the development of databases for any monogenic disorder. © 2015 WILEY PERIODICALS, INC.

  17. FiGHTS: a preliminary screening tool for adolescent firearms-carrying.

    PubMed

    Hayes, D Neil; Sege, Robert

    2003-12-01

    Adolescent firearms-carrying is a risk factor for serious injury and death. Clinical screening tools for firearms-carrying have not yet been developed. We present the development of a preliminary screening test for adolescent firearms-carrying based on the growing body of knowledge of firearms-related risk factors. A convenience sample of 15,000 high school students from the 1999 National Youth Risk Behavior Survey was analyzed for the purpose of model building. Known risk factors for firearms-carrying were candidates for 2 models predicting recent firearms-carrying. The "brief FiGHTS score" screening tool excluded terms related to sexual behavior, significant substance abuse, or criminal behavior (Fi=fighting, G=gender, H=hurt while fighting, T=threatened, S=smoker). An "extended FiGHTS score," which included 13 items, was developed for more precise estimates. The brief FiGHTS score had a sensitivity of 82%, a specificity of 71%, and an area under the receiver operating characteristic (ROC) curve of 0.84. The extended FiGHTS score had an area under the ROC curve of 0.90. Both models performed well in a validation data set of 55,000 students. The brief and extended FiGHTS scores have high sensitivity and specificity for predicting firearms-carrying and may be appropriate for clinical testing.

  18. Regulation of HSD17B1 and SRD5A1 in lymphocytes.

    PubMed

    Zhou, Z; Speiser, P W

    1999-11-01

    We previously reported lymphocyte expression of genes encoding enzymes required for steroid metabolism; however, only 17beta-HSD and 5alpha-reductase showed significant enzyme activity. We now investigate regulation of lymphocyte expression for genes encoding 17beta-HSD and 5alpha-reductase. Cultured human T and B lymphoid cell lines and peripheral blood mononuclear cells were treated with known regulators of steroidogenic gene expression including forskolin, PMA, ionomycin, various steroids, interleukin (IL)-4, and IL-6. Treatment with 10 or 50 microM forskolin resulted in a 20-60% reduction of expression for HSD17B1 (encoding 17beta-HSD I) in T and B lymphoid cell lines and peripheral blood mononuclear cells, although such a change was not observed in the expression of SRD5A1 (encoding 5alpha-reductase I). No significant changes were found when cells were treated for 24 h with various concentrations of PMA or ionomycin. Incubation with 10(-9) to 10(-7) M androstenedione or estradiol increased expression of HSD17B1, while testosterone decreased the expression of this gene. SRD5A1 expression was increased in the presence of 5alpha-DHT although no consistent changes were observed when the cells were treated with testosterone. Other steroids, including dexamethasone, progesterone, and 6-hydroxypregnanolone, produced no effects on expression of either HSD17B1 or SRD5A1. Treatment with 0.1-10 ng/ml of IL-4 or IL-6 also did not effect significant changes in gene expression. These data implicate the involvement of the cAMP-protein kinase signal transduction pathway in regulating lymphocyte expression of HSD17B1. Furthermore, it appears that lymphocyte HSD17B1 and SRD5A1 are regulated to some extent by specific steroids. Copyright 1999 Academic Press.

  19. KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

    PubMed Central

    Farcas, Anca M; Blackledge, Neil P; Sudbery, Ian; Long, Hannah K; McGouran, Joanna F; Rose, Nathan R; Lee, Sheena; Sims, David; Cerase, Andrea; Sheahan, Thomas W; Koseki, Haruhiko; Brockdorff, Neil; Ponting, Chris P; Kessler, Benedikt M; Klose, Robert J

    2012-01-01

    CpG islands (CGIs) are associated with most mammalian gene promoters. A subset of CGIs act as polycomb response elements (PREs) and are recognized by the polycomb silencing systems to regulate expression of genes involved in early development. How CGIs function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that KDM2B (FBXL10) specifically recognizes non-methylated DNA in CGIs and recruits the polycomb repressive complex 1 (PRC1). This contributes to histone H2A lysine 119 ubiquitylation (H2AK119ub1) and gene repression. Unexpectedly, we also find that CGIs are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CGI-associated genes for susceptibility to polycomb-mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CGIs by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CGIs as mammalian PREs. DOI: http://dx.doi.org/10.7554/eLife.00205.001 PMID:23256043

  20. Antihyperalgesic activity of a novel nonpeptide bradykinin B1 receptor antagonist in transgenic mice expressing the human B1 receptor

    PubMed Central

    Fox, Alyson; Kaur, Satbir; Li, Bifang; Panesar, Moh; Saha, Uma; Davis, Clare; Dragoni, Ilaria; Colley, Sian; Ritchie, Tim; Bevan, Stuart; Burgess, Gillian; McIntyre, Peter

    2005-01-01

    We describe the properties of a novel nonpeptide kinin B1 receptor antagonist, NVP-SAA164, and demonstrate its in vivo activity in models of inflammatory pain in transgenic mice expressing the human B1 receptor. NVP-SAA164 showed high affinity for the human B1 receptor expressed in HEK293 cells (Ki 8 nM), and inhibited increases in intracellular calcium induced by desArg10kallidin (desArg10KD) (IC50 33 nM). While a similar high affinity was observed in monkey fibroblasts (Ki 7.7 nM), NVP-SAA164 showed no affinity for the rat B1 receptor expressed in Cos-7 cells. In transgenic mice in which the native B1 receptor was deleted and the gene encoding the human B1 receptor was inserted (hB1 knockin, hB1-KI), hB1 receptor mRNA was induced in tissues following LPS treatment. No mRNA encoding the mouse or human B1 receptor was detected in mouse B1 receptor knockout (mB1-KO) mice following LPS treatment. Freund's complete adjuvant-induced mechanical hyperalgesia was similar in wild-type and hB1-KI mice, but was significantly reduced in mB1-KO animals. Mechanical hyperalgesia induced by injection of the B1 agonist desArg10KD into the contralateral paw 24 h following FCA injection was similar in wild-type and hB1-KI mice, but was absent in mB1-KO animals. Oral administration of NVP-SAA164 produced a dose-related reversal of FCA-induced mechanical hyperalgesia and desArg10KD-induced hyperalgesia in hB1-KI mice, but was inactive against inflammatory pain in wild-type mice. These data demonstrate the use of transgenic technology to investigate the in vivo efficacy of species selective agents and show that NVP-SAA164 is a novel orally active B1 receptor antagonist, providing further support for the utility of B1 receptor antagonists in inflammatory pain conditions in man. PMID:15685199

  1. 75 FR 79988 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-21

    ... Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters AGENCY: Federal Aviation Administration (FAA..., 2009, for the Model AS350 B, BA, BB, B1, B2, and B3 helicopters (ASB 80.00.07); and ASB No. 80A003... authority delegated to me by the Administrator, the FAA proposes to amend 14 CFR part 39 as follows: PART 39...

  2. Targeting Sulfotransferase (SULT) 2B1b as a Regulator of Cholesterol Metabolism in Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    Roswell Park shared resource to arrange for sample analysis. Determine requirements for analysis: Completed, several samples of LNCaP with siRNA-based...SULT2b1knocked down greater than 80% were submitted to The Roswell park shared resource for lipid analysis Cell lines used: wt  LNCaP,  VCaP

  3. Preconception serum 1,1,1-trichloro-2,2,bis(p-chlorophenyl)ethane and B-vitamin status: independent and joint effects on women's reproductive outcomes1234

    PubMed Central

    Ouyang, Fengxiu; Longnecker, Matthew P; Venners, Scott A; Johnson, Sara; Korrick, Susan; Zhang, Jun; Xu, Xiping; Christian, Parul; Wang, Mei-Cheng

    2014-01-01

    Background: Although preconception 1,1,1-trichloro-2,2,bis(p-chlorophenyl)ethane (DDT) exposure and B-vitamin deficiencies have each been shown to negatively affect human reproductive outcomes, little is known about their joint effect. Objective: We sought to examine whether B-vitamin sufficiency protects against adverse effects of DDT on clinical pregnancy (CP) and subclinical early pregnancy loss (EPL). Design: We measured preconception concentrations of plasma B vitamins (vitamin B-6, vitamin B-12, and folate) and serum total DDT [sum of p,p’ and o,p’ isomers of DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] in 291 nulligravid women from Anhui, China, who were studied in 1996–1998. The women were followed prospectively from the time they stopped contraception until CP (gestational age ≥42 d) or 12 mo (whichever occurred first). EPL was identified by using daily urinary human chorionic gonadotropin. The women were categorized according to B-vitamin status (deficiency compared with sufficiency) and DDT concentration (high compared with low). Results: Of 291 study women, a total of 385 conceptions (31% of which ended in EPL) and 265 CPs occurred. Compared with women with adequate B-vitamins and low DDT, incidence rates of CP were reduced in women with B-vitamin deficiency and a high DDT concentration (P < 0.05 for all). Most notably, in women with sufficient vitamin B-12, DDT was not associated with the incidence of CP; in contrast, in women with vitamin B-12 deficiency, high DDT was associated with a lower incidence of CP (HR: 0.44; 95% CI: 0.23, 0.84); and the test for interaction was significant (P < 0.05). The odds of EPL decreased by 45% (95% CI: 21%, 62%) for each interquartile distance increase in folate in women with high DDT concentrations, and the test for interaction was significant (P = 0.006). Conclusions: Our results provide suggestive evidence that vitamin B-12 and folate sufficiency may help protect against adverse reproductive

  4. DEVELOPMENT OF AG-1 SECTION FI ON METAL MEDIA FILTERS - 9061

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adamson, D; Charles A. Waggoner, C

    Development of a metal media standard (FI) for ASME AG-1 (Code on Nuclear Air and Gas Treatment) has been under way for almost ten years. This paper will provide a brief history of the development process of this section and a detailed overview of its current content/status. There have been at least two points when dramatic changes have been made in the scope of the document due to feedback from the full Committee on Nuclear Air and Gas Treatment (CONAGT). Development of the proposed section has required resolving several difficult issues associated with scope; namely, filtering efficiency, operating conditions (mediamore » velocity, pressure drop, etc.), qualification testing, and quality control/acceptance testing. A proposed version of Section FI is currently undergoing final revisions prior to being submitted for balloting. The section covers metal media filters of filtering efficiencies ranging from medium (less than 99.97%) to high (99.97% and greater). Two different types of high efficiency filters are addressed; those units intended to be a direct replacement of Section FC fibrous glass HEPA filters and those that will be placed into newly designed systems capable of supporting greater static pressures and differential pressures across the filter elements. Direct replacements of FC HEPA filters in existing systems will be required to meet equivalent qualification and testing requirements to those contained in Section FC. A series of qualification and quality assurance test methods have been identified for the range of filtering efficiencies covered by this proposed standard. Performance characteristics of sintered metal powder vs. sintered metal fiber media are dramatically different with respect to parameters like differential pressures and rigidity of the media. Wide latitude will be allowed for owner specification of performance criteria for filtration units that will be placed into newly designed systems. Such allowances will permit use of the most

  5. Diastereoselective intramolecular Ritter reaction: generation of a cis-fused hexahydro-4aH-indeno[1,2-b]pyridine ring system with 4a,9b-diangular substituents.

    PubMed

    Van Emelen, K; De Wit, T; Hoornaert, G J; Compernolle, F

    2000-10-05

    Indanol intermediates 5, prepared via Michael addition of 1-indanone beta-ketoester and acrylonitrile followed by reduction or Grignard reaction of the ketone group, were submitted to intramolecular Ritter reaction using various acid reaction conditions to produce tricyclic lactams 4. This cis-fused hexahydro-4aH-indeno[1,2-b]pyridine ring system, substituted at both angular positions 4a and 9b, provides access to constrained analogues of non-peptide NK(1)-antagonists with monocyclic piperidine structure.

  6. Association between ALDH2 and ADH1B polymorphisms, alcohol drinking and gastric cancer: a replication and mediation analysis.

    PubMed

    Ishioka, Kuka; Masaoka, Hiroyuki; Ito, Hidemi; Oze, Isao; Ito, Seiji; Tajika, Masahiro; Shimizu, Yasuhiro; Niwa, Yasumasa; Nakamura, Shigeo; Matsuo, Keitaro

    2018-04-03

    Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant ALDH2-alcohol drinking interaction and a mediation effect of ALDH2/ADH1B through alcohol drinking on gastric cancer have remained unclear. We conducted two case-control studies to validate the interaction and to estimate the mediation effect on gastric cancer. We calculated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2/ADH1B genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways. ALDH2 Lys alleles had a higher risk with increased alcohol consumption compared with ALDH2 Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04-6.27; P for trend = 0.007), indicating a significant ALDH2-alcohol drinking interaction (P interaction  = 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38-2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76-0.92) of the ALDH2 Lys alleles with the ALDH2-alcohol drinking interaction. No significant association of ADH1B with gastric cancer was observed. The observed ALDH2-alcohol drinking interaction and the direct effect of ALDH2 Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.

  7. Detection of N-(1-deoxy-d-fructos-1-yl) Fumonisins B2 and B3 in Corn by High-Resolution LC-Orbitrap MS

    PubMed Central

    Matsuo, Yosuke; Takahara, Kentaro; Sago, Yuki; Kushiro, Masayo; Nagashima, Hitoshi; Nakagawa, Hiroyuki

    2015-01-01

    The existence of glucose conjugates of fumonisin B2 (FB2) and fumonisin B3 (FB3) in corn powder was confirmed for the first time. These “bound-fumonisins” (FB2 and FB3 bound to glucose) were identified as N-(1-deoxy-d-fructos-1-yl) fumonisin B2 (NDfrc-FB2) and N-(1-deoxy-d-fructos-1-yl) fumonisin B3 (NDfrc-FB3) respectively, based on the accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS) analysis. Treatment on NDfrc-FB2 and NDfrc-FB3 with the o-phthalaldehyde (OPA) reagent also supported that d-glucose binding to FB2 and FB3 molecules occurred to their primary amine residues. PMID:26389955

  8. 26 CFR 1.50B-2 - Electing small business corporations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 1 2011-04-01 2009-04-01 true Electing small business corporations. 1.50B-2... business corporations. (a) General rule—(1) In general. In the case of an electing small business... be apportioned separately. In determining who are shareholders of an electing small business...

  9. 26 CFR 1.50B-2 - Electing small business corporations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Electing small business corporations. 1.50B-2... business corporations. (a) General rule—(1) In general. In the case of an electing small business... be apportioned separately. In determining who are shareholders of an electing small business...

  10. Measurement of sigma chi c2 B(chi c2-->J/psi gamma)/sigma chi c1 B(chi c1 -->J/psi gamma) in pp collisions at square root s=1.96 TeV.

    PubMed

    Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Carron, S; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; Datta, M; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; DiTuro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

    2007-06-08

    We measure the ratio of cross section times branching fraction, Rp=sigma chi c2 B(chi c2-->J/psi gamma)/sigma chi c1 B(chi c1-->J/psi gamma), in 1.1 fb(-1) of pp collisions at square root s=1.96 TeV. This measurement covers the kinematic range pT(J/psi)>4.0 GeV/c, |eta(J/psi)<1.0, and pT(gamma)>1.0 GeV/c. For events due to prompt processes, we find Rp=0.395+/-0.016(stat)+/-0.015(syst). This result represents a significant improvement in precision over previous measurements of prompt chi c1,2 hadro production.

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

    PubMed Central

    Xu, Jin; Cui, Jiaxi; Del Campo, Aranzazu; Shin, Chong Hyun

    2016-01-01

    The liver and pancreas originate from overlapping embryonic regions, and single-cell lineage tracing in zebrafish has shown that Bone morphogenetic protein 2b (Bmp2b) signaling is essential for determining the fate of bipotential hepatopancreatic progenitors towards the liver or pancreas. Despite its pivotal role, the gene regulatory networks functioning downstream of Bmp2b signaling in this process are poorly understood. We have identified four and a half LIM domains 1b (fhl1b), which is primarily expressed in the prospective liver anlage, as a novel target of Bmp2b signaling. fhl1b depletion compromised liver specification and enhanced induction of pancreatic cells from endodermal progenitors. Conversely, overexpression of fhl1b favored liver specification and inhibited induction of pancreatic cells. By single-cell lineage tracing, we showed that fhl1b depletion led lateral endodermal cells, destined to become liver cells, to become pancreatic cells. Reversely, when fhl1b was overexpressed, medially located endodermal cells, fated to differentiate into pancreatic and intestinal cells, contributed to the liver by directly or indirectly modulating the discrete levels of pdx1 expression in endodermal progenitors. Moreover, loss of fhl1b increased the regenerative capacity of β-cells by increasing pdx1 and neurod expression in the hepatopancreatic ductal system. Altogether, these data reveal novel and critical functions of Fhl1b in the hepatic versus pancreatic fate decision and in β-cell regeneration. PMID:26845333

  12. 26 CFR 1.167(b)-1 - Straight line method.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 2 2014-04-01 2014-04-01 false Straight line method. 1.167(b)-1 Section 1.167(b... Straight line method. (a) In general. Under the straight line method the cost or other basis of the... may be reduced to a percentage or fraction. The straight line method may be used in determining a...

  13. Genotype and environment effects on the contents of vitamins B1, B2, B3, and B6 in wheat grain.

    PubMed

    Shewry, Peter R; Van Schaik, Frank; Ravel, Catherine; Charmet, Gilles; Rakszegi, Mariann; Bedo, Zoltan; Ward, Jane L

    2011-10-12

    The total contents of thiamine (vitamin B1), riboflavin (B2), and pyridoxine (B6) and the bioavailable forms of niacin (B3) were determined on wholemeal flours of 24 winter wheat varieties grown on four sites (United Kingdom, Poland, France, and Hungary) in 2007 and of two spring varieties grown on the same sites with the exception of Poland. The contents of vitamins B1 (5.53-13.55 μg/g dw), B2 (0.77-1.40 μg/g dw), and B6 (1.27-2.97 μg/g dw) were within the ranges reported previously, while the content of bioavailable vitamin B3 (0.16-1.74 μg/g dw) was about 10-15% of the total contents of vitamin B3 reported in previous studies. Strong correlations were observed between the contents of vitamins B1, B3, and B6, and partitioning of the variance in the contents of these three B vitamins showed that between 48 and 70% was accounted for by the environment. By contrast, the content of vitamin B2 was not correlated with the contents of other B vitamins, and 73% of the variance was ascribed to the error term, which suggests that this trait may be influenced by genotype × environment interactions. Whereas the contents of vitamins B1, B3, and B6 were correlated positively with the mean temperature from heading to harvest (r > 0.8), the content of vitamin B2 was positively correlated with precipitation during the 3 months prior to heading. These results are discussed in relation to the development of new wheat varieties with enhanced health benefits.

  14. Generation of Bayesian prediction models for OATP-mediated drug-drug interactions based on inhibition screen of OATP1B1, OATP1B1∗15 and OATP1B3.

    PubMed

    van de Steeg, E; Venhorst, J; Jansen, H T; Nooijen, I H G; DeGroot, J; Wortelboer, H M; Vlaming, M L H

    2015-04-05

    Human organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 are important hepatic uptake transporters. Early assessment of OATP1B1/1B3-mediated drug-drug interactions (DDIs) is therefore important for successful drug development. A promising approach for early screening and prediction of DDIs is computational modeling. In this study we aimed to generate a rapid, single Bayesian prediction model for OATP1B1, OATP1B1∗15 and OATP1B3 inhibition. Besides our previously generated HEK-OATP1B1 and HEK-OATP1B1∗15 cells, we now generated and characterized HEK-OATP1B3 cells. Using these cell lines we investigated the inhibitory potential of 640 FDA-approved drugs from a commercial library (10μM) on the uptake of [(3)H]-estradiol-17β-d-glucuronide (1μM) by OATP1B1, OATP1B1∗15, and OATP1B3. Using a cut-off of ⩾60% inhibition, 8% and 7% of the 640 drugs were potent OATP1B1 and OATP1B1∗15 inhibitors, respectively. Only 1% of the tested drugs significantly inhibited OATP1B3, which was not sufficient for Bayesian modeling. Modeling of OATP1B1 and OATP1B1∗15 inhibition revealed that presence of conjugated systems and (hetero)cycles with acceptor/donor atoms in- or outside the ring enhance the probability of a molecule binding these transporters. The overall performance of the model for OATP1B1 and OATP1B1∗15 was ⩾80%, including evaluation with a true external test set. Our Bayesian classification model thus represents a fast, inexpensive and robust means of assessing potential binding of new chemical entities to OATP1B1 and OATP1B1∗15. As such, this model may be used to rank compounds early in the drug development process, helping to avoid adverse effects in a later stage due to inhibition of OATP1B1 and/or OATP1B1∗15. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Identification of a new B4GalNAcT1 (GM2/GD2/GA2 synthase) isoform, and regulation of enzyme stability and intracellular transport by arginine-based motif.

    PubMed

    Shishido, Fumi; Uemura, Satoshi; Kashimura, Madoka; Inokuchi, Jin-Ichi

    2017-10-01

    Glycosphingolipids (GSLs) are abundant in plasma membranes of mammalian cells, and their synthesis is strictly regulated in the Golgi apparatus. Disruption of GSL homeostasis is the cause of numerous diseases. Hundreds of molecular species of GSLs exist, and the detailed mechanisms underlying their homeostasis remain unclear. We investigated the physiological significance of isoform production for β1,4-N-acetyl-galactosaminyl transferase 1/B4GALNT1 (B4GN1), an enzyme involved in synthesis of ganglio-series GSLs GM2/GD2/GA2. We discovered a new mRNA variant (termed variant 2) of B4GN1 through EST clone search. A new isoform, M1-B4GN1, which has an NH 2 -terminal cytoplasmic tail longer than that of previously-known isoform M2-B4GN1, is translated from variant 2. M1-B4GN1 has R-based motif (a retrograde transport signal) in the cytoplasmic tail. M1-B4GN1 is partially localized in the endoplasmic reticulum (ER) depending on the R-based motif, whereas M2-B4GN1 is localized in the Golgi. Stability of M1-B4GN1 is higher than that of M2-B4GN1 because of the R-based motif. M2-B4GN1 forms a homodimer via disulfide bonding. When M1-B4GN1 and M2-B4GN1 were co-expressed in CHO-K1 cells, the two isoforms formed a heterodimer. The M1/M2-B4GN1 heterodimer was more stable than the M2-B4GN1 homodimer, but the heterodimer was not transported from the Golgi to the ER. Our findings indicate that stabilization of M1-B4GN1 homodimer and M1/M2-B4GN1 heterodimer by R-based motif is related to prolongation of Golgi retention, but not to retrograde transport from the Golgi to the ER. Coexistence of several B4GN1 isoforms having distinctive characteristics presumably helps maintain overall enzyme stability and GSL homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mahadevan, B.; Marston, C.P.; Luch, A.

    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 revealedmore » 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.« less

  17. BPAG1a and b associate with EB1 and EB3 and modulate vesicular transport, Golgi apparatus structure, and cell migration in C2.7 myoblasts.

    PubMed

    Poliakova, Kseniia; Adebola, Adijat; Leung, Conrad L; Favre, Bertrand; Liem, Ronald K H; Schepens, Isabelle; Borradori, Luca

    2014-01-01

    BPAG1a and BPAG1b (BPAG1a/b) constitute two major isoforms encoded by the dystonin (Dst) gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5' end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3' end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts.

  18. BPAG1a and b Associate with EB1 and EB3 and Modulate Vesicular Transport, Golgi Apparatus Structure, and Cell Migration in C2.7 Myoblasts

    PubMed Central

    Poliakova, Kseniia; Adebola, Adijat; Leung, Conrad L.; Favre, Bertrand; Liem, Ronald K. H.; Schepens, Isabelle; Borradori, Luca

    2014-01-01

    BPAG1a and BPAG1b (BPAG1a/b) constitute two major isoforms encoded by the dystonin (Dst) gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5′ end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3′ end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts. PMID:25244344

  19. 75 FR 3159 - Corporate Reorganizations; Distributions Under Sections 368(a)(1)(D) and 354(b)(1)(B); Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 [TD 9475] RIN 1545-BF83 Corporate Reorganizations; Distributions Under Sections 368(a)(1)(D) and 354(b)(1)(B); Correction AGENCY... transactions as reorganizations described in section 368(a)(1)(D) where no stock and/or securities of the...

  20. Mutations in SULT2B1 Cause Autosomal-Recessive Congenital Ichthyosis in Humans.

    PubMed

    Heinz, Lisa; Kim, Gwang-Jin; Marrakchi, Slaheddine; Christiansen, Julie; Turki, Hamida; Rauschendorf, Marc-Alexander; Lathrop, Mark; Hausser, Ingrid; Zimmer, Andreas D; Fischer, Judith

    2017-06-01

    Ichthyoses are a clinically and genetically heterogeneous group of genodermatoses associated with abnormal scaling of the skin over the whole body. Mutations in nine genes are known to cause non-syndromic forms of autosomal-recessive congenital ichthyosis (ARCI). However, not all genetic causes for ARCI have been discovered to date. Using whole-exome sequencing (WES) and multigene panel screening, we identified 6 ARCI-affected individuals from three unrelated families with mutations in Sulfotransferase family 2B member 1 (SULT2B1), showing their causative association with ARCI. Cytosolic sulfotransferases form a large family of enzymes that are involved in the synthesis and metabolism of several steroids in humans. We identified four distinct mutations including missense, nonsense, and splice site mutations. We demonstrated the loss of SULT2B1 expression at RNA and protein levels in keratinocytes from individuals with ARCI by functional analyses. Furthermore, we succeeded in reconstructing the morphologic skin alterations in a 3D organotypic tissue culture model with SULT2B1-deficient keratinocytes and fibroblasts. By thin layer chromatography (TLC) of extracts from these organotypic cultures, we could show the absence of cholesterol sulfate, the metabolite of SULT2B1, and an increased level of cholesterol, indicating a disturbed cholesterol metabolism of the skin upon loss-of-function mutation in SULT2B1. In conclusion, our study reveals an essential role for SULT2B1 in the proper development of healthy human skin. Mutation in SULT2B1 leads to an ARCI phenotype via increased proliferation of human keratinocytes, thickening of epithelial layers, and altered epidermal cholesterol metabolism. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  1. A Contextual Fire Detection Algorithm for Simulated HJ-1B Imagery.

    PubMed

    Qian, Yonggang; Yan, Guangjian; Duan, Sibo; Kong, Xiangsheng

    2009-01-01

    The HJ-1B satellite, which was launched on September 6, 2008, is one of the small ones placed in the constellation for disaster prediction and monitoring. HJ-1B imagery was simulated in this paper, which contains fires of various sizes and temperatures in a wide range of terrestrial biomes and climates, including RED, NIR, MIR and TIR channels. Based on the MODIS version 4 contextual algorithm and the characteristics of HJ-1B sensor, a contextual fire detection algorithm was proposed and tested using simulated HJ-1B data. It was evaluated by the probability of fire detection and false alarm as functions of fire temperature and fire area. Results indicate that when the simulated fire area is larger than 45 m(2) and the simulated fire temperature is larger than 800 K, the algorithm has a higher probability of detection. But if the simulated fire area is smaller than 10 m(2), only when the simulated fire temperature is larger than 900 K, may the fire be detected. For fire areas about 100 m(2), the proposed algorithm has a higher detection probability than that of the MODIS product. Finally, the omission and commission error were evaluated which are important factors to affect the performance of this algorithm. It has been demonstrated that HJ-1B satellite data are much sensitive to smaller and cooler fires than MODIS or AVHRR data and the improved capabilities of HJ-1B data will offer a fine opportunity for the fire detection.

  2. A Contextual Fire Detection Algorithm for Simulated HJ-1B Imagery

    PubMed Central

    Qian, Yonggang; Yan, Guangjian; Duan, Sibo; Kong, Xiangsheng

    2009-01-01

    The HJ-1B satellite, which was launched on September 6, 2008, is one of the small ones placed in the constellation for disaster prediction and monitoring. HJ-1B imagery was simulated in this paper, which contains fires of various sizes and temperatures in a wide range of terrestrial biomes and climates, including RED, NIR, MIR and TIR channels. Based on the MODIS version 4 contextual algorithm and the characteristics of HJ-1B sensor, a contextual fire detection algorithm was proposed and tested using simulated HJ-1B data. It was evaluated by the probability of fire detection and false alarm as functions of fire temperature and fire area. Results indicate that when the simulated fire area is larger than 45 m2 and the simulated fire temperature is larger than 800 K, the algorithm has a higher probability of detection. But if the simulated fire area is smaller than 10 m2, only when the simulated fire temperature is larger than 900 K, may the fire be detected. For fire areas about 100 m2, the proposed algorithm has a higher detection probability than that of the MODIS product. Finally, the omission and commission error were evaluated which are important factors to affect the performance of this algorithm. It has been demonstrated that HJ-1B satellite data are much sensitive to smaller and cooler fires than MODIS or AVHRR data and the improved capabilities of HJ-1B data will offer a fine opportunity for the fire detection. PMID:22399950

  3. Sda1, a Cys2-His2 Zinc Finger Transcription Factor, Is Involved in Polyol Metabolism and Fumonisin B1 Production in Fusarium verticillioides

    PubMed Central

    Malapi-Wight, Martha; Smith, Jonathon; Campbell, Jacquelyn; Bluhm, Burton H.; Shim, Won-Bo

    2013-01-01

    The ubiquitous ascomycete Fusarium verticillioides causes ear rot and stalk rot of maize, both of which reduce grain quality and yield. Additionally, F. verticillioides produces the mycotoxin fumonisin B1 (FB1) during infection of maize kernels, and thus potentially compromises human and animal health. The current knowledge is fragmentary regarding the regulation of FB1 biosynthesis, particularly when considering interplay with environmental factors such as nutrient availability. In this study, SDA1 of F. verticillioides, predicted to encode a Cys-2 His-2 zinc finger transcription factor, was shown to play a key role in catabolizing select carbon sources. Growth of the SDA1 knock-out mutant (Δsda1) was completely inhibited when sorbitol was the sole carbon source and was severely impaired when exclusively provided mannitol or glycerol. Deletion of SDA1 unexpectedly increased FB1 biosynthesis, but reduced arabitol and mannitol biosynthesis, as compared to the wild-type progenitor. Trichoderma reesei ACE1, a regulator of cellulase and xylanase expression, complemented the F. verticillioides Δsda1 mutant, which indicates that Ace1 and Sda1 are functional orthologs. Taken together, the data indicate that Sda1 is a transcriptional regulator of carbon metabolism and toxin production in F. verticillioides. PMID:23844049

  4. 49 CFR Appendix A to Part 214 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... use ring bouys 1,500 (f)(i) Failure to provide skiff 1,000 2,500 (ii) Failure to use skiff 1,500 214... warning signal 1,500 3,000 (f)(1) Assignment of non-qualified person as watchman/lookout 3,000 5,000 (2... charge of providing on-track safety for a roadway work group 2,000 4,000 (e) (1) (1) (f) Roadway...

  5. Spreading of hepatitis C virus subtypes 1a and 1b through the central region of Argentina.

    PubMed

    Culasso, Andrés Carlos Alberto; Farías, Adrián; Di Lello, Federico Alejandro; Golemba, Marcelo Darío; Ré, Viviana; Barbini, Luciana; Campos, Rodolfo

    2014-08-01

    The recent history of the hepatitis C virus (HCV) subtypes 1a and 1b in the central region of Argentina is hypothesized by phylogeographic reconstruction using coalescent based Bayesian analyses. Direct partial E2 sequences from HCV 1a and 1b infected patients attending different health-care centers of the country were analyzed. The inferred date of the most recent common ancestor (tMRCA) for HCV-1a was: 1962 (between 1943 and 1977) and for HCV-1b was earlier: 1929 (between 1895 and 1953). Diverse ancestral populations were inferred from both subtypes in Córdoba and in Buenos Aires cities and after that, HCV spread within and between larger cities and to other smaller cities. The analyses suggested that HCV-1b was dispersed first and it is currently in a stationary phase whereas HCV-1a was dispersed latter and it is still in a growth phase. Finally, as it was observed in the developed countries, while the transmission of HCV-1b appears to have been somehow prevented, the HCV-1a may still represent a concern in the public health. Further work should be carried out to address their current transmission rate (and its main transmission route) in the Argentinean population. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. 75 FR 3160 - Corporate Reorganizations; Distributions Under Sections 368(a)(1)(D) and 354(b)(1)(B); Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 [TD 9475] RIN 1545-BF83 Corporate Reorganizations; Distributions Under Sections 368(a)(1)(D) and 354(b)(1)(B); Correction AGENCY... reorganizations described in section 368(a)(1)(D) where no stock and/or securities of the acquiring corporation is...

  7. A link between osteomyelitis and IL1RN and IL1B polymorphisms—a study in patients from Northeast Brazil

    PubMed Central

    Alves De Souza, Clinio; Queiroz Alves De Souza, Argos; Queiroz Alves De Souza, Maria do Socorro; Dias Leite, José Alberto; Silva De Morais, Maíra; Barem Rabenhorst, Sílvia Helena

    2017-01-01

    Background and purpose Treatment failure of osteomyelitis can result from genetic susceptibility, highlighting polymorphisms of the interleukin-1 (IL-1) family members, central mediators of innate immunity and inflammation. Polymorphisms are DNA sequence variations that are common in the population (1% or more) and represent multiple forms of a single gene. We investigated the association of IL1RNVNTR (rs2234663) and IL1B-511C > T (rs16944) polymorphisms with osteomyelitis development in patients operated on because of bone trauma. Patients and methods 153 patients who fulfilled the inclusion criteria were enrolled from a referral public hospital for trauma. All the patients were followed up daily until hospital discharge and, after this, on an outpatient basis. Patients were treated with prophylactic antimicrobials and surgery according to traumatology service protocol. The IL1RNVNTR and the IL1B-511C > T polymorphisms were determined by PCR and PCR-RFLP, respectively. Results The IL1RN*2/*2 genotype was associated (OR: 7; p < 0.001) with a higher risk of osteomyelitis and was also significantly associated with Staphylococcus aureus infection. The haplotypes (combination of different markers) *2-C and *2-T were also associated with osteomyelitis development. Interpretation IL1B-511C > T and IL1RNVNTR polymorphisms were associated with osteomyelitis development, which may have implications for patients with bone traumas. These data may be relevant for new therapeutic strategies for this disease. PMID:28682145

  8. A link between osteomyelitis and IL1RN and IL1B polymorphisms-a study in patients from Northeast Brazil.

    PubMed

    Alves De Souza, Clinio; Queiroz Alves De Souza, Argos; Queiroz Alves De Souza, Maria do Socorro; Dias Leite, José Alberto; Silva De Morais, Maíra; Barem Rabenhorst, Sílvia Helena

    2017-10-01

    Background and purpose - Treatment failure of osteomyelitis can result from genetic susceptibility, highlighting polymorphisms of the interleukin-1 (IL-1) family members, central mediators of innate immunity and inflammation. Polymorphisms are DNA sequence variations that are common in the population (1% or more) and represent multiple forms of a single gene. We investigated the association of IL1RNVNTR (rs2234663) and IL1B-511C > T (rs16944) polymorphisms with osteomyelitis development in patients operated on because of bone trauma. Patients and methods - 153 patients who fulfilled the inclusion criteria were enrolled from a referral public hospital for trauma. All the patients were followed up daily until hospital discharge and, after this, on an outpatient basis. Patients were treated with prophylactic antimicrobials and surgery according to traumatology service protocol. The IL1RNVNTR and the IL1B-511C > T polymorphisms were determined by PCR and PCR-RFLP, respectively. Results - The IL1RN*2/*2 genotype was associated (OR: 7; p < 0.001) with a higher risk of osteomyelitis and was also significantly associated with Staphylococcus aureus infection. The haplotypes (combination of different markers) *2-C and *2-T were also associated with osteomyelitis development. Interpretation - IL1B-511C > T and IL1RNVNTR polymorphisms were associated with osteomyelitis development, which may have implications for patients with bone traumas. These data may be relevant for new therapeutic strategies for this disease.

  9. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy.

    PubMed

    Porpaczy, Edit; Tripolt, Sabrina; Hoelbl-Kovacic, Andrea; Gisslinger, Bettina; Bago-Horvath, Zsuzsanna; Casanova-Hevia, Emilio; Clappier, Emmanuelle; Decker, Thomas; Fajmann, Sabine; Fux, Daniela A; Greiner, Georg; Gueltekin, Sinan; Heller, Gerwin; Herkner, Harald; Hoermann, Gregor; Kiladjian, Jean-Jacques; Kolbe, Thomas; Kornauth, Christoph; Krauth, Maria-Theresa; Kralovics, Robert; Muellauer, Leonhard; Mueller, Mathias; Prchal-Murphy, Michaela; Putz, Eva Maria; Raffoux, Emmanuel; Schiefer, Ana-Iris; Schmetterer, Klaus; Schneckenleithner, Christine; Simonitsch-Klupp, Ingrid; Skrabs, Cathrin; Sperr, Wolfgang R; Staber, Philipp Bernhard; Strobl, Birgit; Valent, Peter; Jaeger, Ulrich; Gisslinger, Heinz; Sexl, Veronika

    2018-06-14

    Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 MPN patients including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4/69 patients (5.8%) upon JAK1/2 inhibition compared to 2/557 (0.36%) with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 MPN patients. Considering primary myelofibrosis only (N=216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) versus 1/185 controls (0.54%). Lymphomas were of aggressive B-cell type, extra-nodal or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a pre-existing B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1 -/- mice: 16/24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a pre-existing B-cell clone may identify individuals at risk. Copyright © 2018 American Society of Hematology.

  10. 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...) 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...

  11. 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...

  12. Studies of molecular physics in sodium-potassium: An analysis of the 4(3)Sigma+ state and interactions between the 2(A)(1)Sigma+ and 1(b)(3)Pi states

    NASA Astrophysics Data System (ADS)

    Burns, Patrick

    2004-12-01

    In this dissertation we report the results of three experiments designed to provide new information on the structure and interactions of the NaK molecule. Specifically these experiments investigate 2(A)1Sigma +(upsilonA, J) + M → 1(b)3 pi0(upsilonb, J) + M collisional excitation transfers (where M is a collision partner), hyperfine structure of the NaK 1(b)3pi and 1(b)3pi0 ˜ 2(A)1Sigma+ spin-orbit interactions, and the structure and spectra of the NaK 43Sigma+ state, respectively. In this first experiment, populations of collisionally populated levels were recorded near the NaK 1(b)3pi0(upsilon =18, J = 44) ˜ 2(A)1Sigma+ (upsilon = 20, J = 44) center of spin-orbit perturbation. Our data indicate that population is transferred from the pumped level, 2(A) 1Sigma+(upsilon = 20, J = 49), directly to the surrounding "daughter" levels [1(b)3Sigma 0(upsilon =18, J = 45--48) and 2(A)1Sigma +(upsilon = 20, J = 45--48)]. The relative populations of the daughter levels appear anomalous, as their populations do not monotonically decrease for levels further away in energy from the pumped level. We have measured the hyperfine structure of mutually perturbing ro-vibrational levels of the 1(b)3pi0 and 2(A)1Sigma + states of the NaK molecule, using the PFOODR method with co-propagating lasers. Unperturbed 1(b)3pi0 levels are split into four hyperfine components by the Fermi contact interaction b FI·S. Mixing between the 1(b)3pi0 and 2(A)1Sigma + levels imparts hyperfine structure to the nominally singlet component, and reduces the hyperfine splitting of the nominally triplet component, of the perturbed levels. We determined a value for the Fermi constant, bF= (0.00989 +/- 0.00027) cm-1, and the magnitude of the electronic part of the 1(b)3pi 0 ˜ 2(A)1Sigma+ spin-orbit coupling, |Hel| = (15.65 +/- 0.14) cm-1 , from an analysis of the measured hyperfine splittings of the mixed singlet-triplet levels. High-resolution spectra have been observed for numerous vibrational

  13. 26 CFR 1.415(b)-2 - Multiple annuity starting dates. [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Multiple annuity starting dates. [Reserved] 1.415(b)-2 Section 1.415(b)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Multiple annuity starting dates. [Reserved] ...

  14. 49 CFR Appendix A to Part 214 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ring bouys 5,000 10,000 (ii) Failure to use ring bouys 1,500 (f)(i) Failure to provide skiff 1,000 2,500 (ii) Failure to use skiff 1,500 214.109 Scaffolding: (a)-(f) Failure to provide conforming... approach warning signal 2,000 (e) Failure to communicate proper warning signal 1,500 3,000 (f)(1...

  15. 49 CFR Appendix A to Part 214 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ring bouys 5,000 10,000 (ii) Failure to use ring bouys 1,500 (f)(i) Failure to provide skiff 1,000 2,500 (ii) Failure to use skiff 1,500 214.109 Scaffolding: (a)-(f) Failure to provide conforming... train approach warning signal 2,000 (e) Failure to communicate proper warning signal 1,500 3,000 (f)(1...

  16. 49 CFR Appendix A to Part 214 - Schedule of Civil Penalties 1

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ring bouys 5,000 10,000 (ii) Failure to use ring bouys 1,500 (f)(i) Failure to provide skiff 1,000 2,500 (ii) Failure to use skiff 1,500 214.109 Scaffolding: (a)-(f) Failure to provide conforming... approach warning signal 2,000 (e) Failure to communicate proper warning signal 1,500 3,000 (f)(1...

  17. Disruption of AP3B1 by a chromosome 5 inversion: a new disease mechanism in Hermansky-Pudlak syndrome type 2.

    PubMed

    Jones, Matthew L; Murden, Sherina L; Brooks, Claire; Maloney, Viv; Manning, Richard A; Gilmour, Kimberly C; Bharadwaj, Vandana; de la Fuente, Josu; Chakravorty, Subarna; Mumford, Andrew D

    2013-04-04

    Hermansky-Pudlak syndrome 2 (HPS2; OMIM #608233) is a rare, autosomal recessive disorder caused by loss-of-function genetic variations affecting AP3B1, which encodes the β3A subunit of the adaptor-related protein complex 3 (AP3). Phenotypic characteristics include reduced pigmentation, absent platelet dense granule secretion, neutropenia and reduced cytotoxic T lymphocyte (CTL) and natural killer (NK) cell function. To date HPS2 has been associated with non-synonymous, stop-gain or deletion-insertion nucleotide variations within the coding region of AP3B1. We describe a consanguineous female infant with reduced pigmentation, neutropenia and recurrent infections. Platelets displayed reduced aggregation and absent ATP secretion in response to collagen and ADP, indicating a platelet dense granule defect. There was increased basal surface expression of CD107a (lysosome-associated membrane protein 1(LAMP-1)) on NK cells and CTLs from the study subject and a smaller increase in the percentage of CD107a positive cells after stimulation compared to most healthy controls. Immunoblotting of protein extracts from EBV-transformed lymphoblasts from the index case showed absent expression of full-length AP-3 β3A subunit protein, confirming a phenotypic diagnosis of HPS2.The index case displayed a homozygous pericentric inv(5)(p15.1q14.1), which was also detected as a heterozygous defect in both parents of the index case. No loss of genetic material was demonstrated by microarray comparative genome hybridisation at 60kb resolution. Fluorescence in-situ hybridisation using the 189.6kb probe RP11-422I12, which maps to 5q14.1, demonstrated dual hybridisation to both 5q14.1 and 5p15.1 regions of the inverted Chr5. The RP11-422I12 probe maps from intron 1 to intron 16 of AP3B1, thus localising the 5q inversion breakpoint to within AP3B1. The probe RP11-211K15, which corresponds to an intergenic region on 5p also showed dual hybridisation, enabling localisation of the 5p inversion

  18. Laboratory diagnosis of von Willebrand disease type 1/2E (2A subtype IIE), type 1 Vicenza and mild type 1 caused by mutations in the D3, D4, B1-B3 and C1-C2 domains of the von Willebrand factor gene. Role of von Willebrand factor multimers and the von Willebrand factor propeptide/antigen ratio.

    PubMed

    Gadisseur, Alain; Berneman, Zwi; Schroyens, Wilfried; Michiels, Jan Jacques

    2009-01-01

    Autosomal dominant von Willebrand disease (VWD) type 1/2E is a quantitative/qualitative defect in the von Willebrand factor (VWF) caused by heterozygous cysteine and non-cysteine mutations in the D3 domain of the VWF gene and results in a secretion-multimerization-clearance defect in mutant VWF with the loss of large VWF multimers not due to proteolysis. The multimers of patients with dominant VWD type 1/2E due to mutations in the D3 domain show an aberrant triplet structure with lack of outer bands but with pronounced inner bands of the triplet structure combined with a relative decrease in large multimers reflecting heterozygosity for multimerization defects. There is a good response to desmopressin (DDAVP) followed by rapid clearance of VWF:antigen (Ag), factor VIII coagulant activity (FVIII:C) and VWF:ristocetin cofactor activity (RCo) as the main cause of VWD type 1 or 2 with typical 2E multimeric pattern (VWD type 1/2E). Cysteine mutations in the D3 domains (C1130, C1149 and C1190) show pronounced features of VWD 1/2E with the relative loss of large and relative increase in small VWF multimers with abnormal triplet structure in heterozygotes. Such abnormalities are less pronounced in patients with a milder form of VWD type 1 due to non-cysteine mutations W1144G, T1156M and W1120S in the D3 domain. VWD type 1 Vicenza is caused by the R1205H mutation in the D3 domain and characterized by equally low levels of FVIII:C, VWF:Ag and VWF:RCo. The response to DDAVP in VWD Vicenza is good for FVIII:C, VWF:Ag and VWF:RCo, which is followed by a rapid clearance in less than a few hours of FVIII:C and VWF parameters. The ratios for FVIII:C/VWF:Ag, VWF:RCo/Ag and VWF:CB/Ag remain normal before and after DDAVP indicating that VWD Vicenza clearly differs from VWD type 1, 1/2E and 2M. A new set of missense mutations in D4, B1-B3 and C1-C2 domains has been discovered as the cause of a mild VWD type 1 secretion defect with normal VWF multimers or smeary VWF multimeric pattern

  19. 75 FR 80293 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-22

    ... Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model AS355 E, F, F1, F2... identified in the Applicability section, Table 1, of the AD. As published, two part numbers shown in Table 1... corrected to read as follows: Table 1 Component Part No. (P/N) Serial No. (S/N) Main rotor servo-control...

  20. The Neurospora crassa PP2A Regulatory Subunits RGB1 and B56 Are Required for Proper Growth and Development and Interact with the NDR Kinase COT1

    PubMed Central

    Shomin-Levi, Hila; Yarden, Oded

    2017-01-01

    COT1 is the founding member of the highly conserved nuclear Dbf2-related (NDR) Ser/Thr kinase family and plays a role in the regulation of polar growth and development in Neurospora crassa and other fungi. Changes in COT1 phosphorylation state have been shown to affect hyphal elongation, branching, and conidiation. The function of NDR protein kinases has been shown to be regulated by type 2A protein phosphatases (PP2As). PP2As are heterotrimers comprised of a catalytic and scaffolding protein along with an interchangeable regulatory subunit involved in determining substrate specificity. Inactivation of the N. crassa PP2A regulatory subunits rgb-1 and b56 conferred severe hyphal growth defects. Partial suppression of defects observed in the rgb-1RIP strain (but not in the Δb56 mutant) was observed in cot-1 phosphomimetic mutants, demonstrating that altering COT1 phosphorylation state can bypass, at least in part, the requirement of a functional RGB1 subunit. The functional fusion proteins RGB1::GFP and B56::GFP predominantly localized to hyphal tips and septa, respectively, indicating that their primary activity is in different cellular locations. COT1 protein forms exhibited a hyperphosphorylated gel migration pattern in an rgb-1RIP mutant background, similar to that observed when the fungus was cultured in the presence of the PP2A inhibitor cantharidin. COT1 was hypophosphorylated in a Δb56 mutant background, suggesting that this regulatory subunit may be involved in determining COT1 phosphorylation state, yet in an indirect manner. Reciprocal co-immunoprecipitation analyses, using tagged COT1, PPH1, RGB1, and B56 subunits established that these proteins physically interact. Taken together, our data determine the presence of a functional and physical link between PP2A and COT1 and show that two of the PP2A regulatory subunits interact with the kinase and determine COT1 phosphorylation state. PMID:28928725

  1. Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity

    PubMed Central

    Labonté, Eric D.; Pfluger, Paul T.; Cash, James G.; Kuhel, David G.; Roja, Juan C.; Magness, Daniel P.; Jandacek, Ronald J.; Tschöp, Matthias H.; Hui, David Y.

    2010-01-01

    Decrease in fat catabolic rate on consuming a high-fat diet contributes to diet-induced obesity. This study used group 1B phospholipase A2 (Pla2g1b)-deficient mice, which are resistant to hyperglycemia, to test the hypothesis that Pla2g1b and its lipolytic product lysophospholipid suppress hepatic fat utilization and energy metabolism in promoting diet-induced obesity. The metabolic consequences of hypercaloric diet, including body weight gain, energy expenditure, and fatty acid oxidation, were compared between Pla2g1b+/+ and Pla2g1b−/− mice. The Pla2g1b−/− mice displayed normal energy balance when fed chow, but were resistant to obesity when challenged with a hypercaloric diet. Obesity resistance in Pla2g1b−/− mice is due to their ability to maintain elevated energy expenditure and core body temperature when subjected to hypercaloric diet, which was not observed in Pla2g1b+/+ mice. The Pla2g1b−/− mice also displayed increased postprandial hepatic fat utilization due to increased expression of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-δ, PPAR-γ, cd36/Fat, and Ucp2, which coincided with reduced postprandial plasma lysophospholipid levels. Lysophospholipids produced by Pla2g1b hydrolysis suppress hepatic fat utilization and down-regulate energy expenditure, thereby preventing metabolically beneficial adaptation to a high-fat diet exposure in promoting diet-induced obesity and type 2 diabetes.—Labonté, E. D., Pfluger, P. T., Cash, J. G., Kuhel, D. G., Rojas, J. C., Magness, D. P., Jandacek, R. J., Tschöp, M. H., Hui, D. Y. Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity. PMID:20215528

  2. Touch responsiveness in zebrafish requires voltage-gated calcium channel 2.1b

    PubMed Central

    Low, Sean E.; Woods, Ian G.; Lachance, Mathieu; Ryan, Joel; Saint-Amant, Louis

    2012-01-01

    The molecular and physiological basis of the touch-unresponsive zebrafish mutant fakir has remained elusive. Here we report that the fakir phenotype is caused by a missense mutation in the gene encoding voltage-gated calcium channel 2.1b (CACNA1Ab). Injection of RNA encoding wild-type CaV2.1 restores touch responsiveness in fakir mutants, whereas knockdown of CACNA1Ab via morpholino oligonucleotides recapitulates the fakir mutant phenotype. Fakir mutants display normal current-evoked synaptic communication at the neuromuscular junction but have attenuated touch-evoked activation of motor neurons. NMDA-evoked fictive swimming is not affected by the loss of CaV2.1b, suggesting that this channel is not required for motor pattern generation. These results, coupled with the expression of CACNA1Ab by sensory neurons, suggest that CaV2.1b channel activity is necessary for touch-evoked activation of the locomotor network in zebrafish. PMID:22490555

  3. Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy.

    PubMed

    Jasper, Melinda J; Care, Alison S; Sullivan, Brad; Ingman, Wendy V; Aplin, John D; Robertson, Sarah A

    2011-01-01

    Macrophages accumulate within stromal tissue subjacent to the luminal epithelium in the mouse uterus during early pregnancy after seminal fluid exposure at coitus. To investigate their role in regulating epithelial cell expression of fucosylated structures required for embryo attachment and implantation, fucosyltransferase enzymes Fut1, Fut2 (Enzyme Commission number [EC] 2.4.1.69), and Fut4 (EC 2.4.1.214) and Muc1 and Muc4 mRNAs were quantified by quantitative real-time PCR in uterine epithelial cells after laser capture microdissection in situ or after epithelial cell coculture with macrophages or macrophage-secreted factors. When uterine macrophage recruitment was impaired by mating with seminal plasma-deficient males, epithelial cell Fut2 expression on Day 3.5 postcoitus (pc) was reduced compared to intact-mated controls. Epithelial cell Fut2 was upregulated in vitro by coculture with macrophages or macrophage-conditioned medium (MCM). Macrophage-derived cytokines LIF, IL1B, and IL12 replicated the effect of MCM on Fut2 mRNA expression, and MCM-stimulated expression was inhibited by anti-LIF and anti-IL1B neutralizing antibodies. The effects of acute macrophage depletion on fucosylated structures detected with lectins Ulex europaeus 1 (UEA-1) and Lotus tetragonolobus purpureas (LTP), or LewisX immunoreactivity, were quantified in vivo in Cd11b-dtr transgenic mice. Depletion of macrophages caused a 30% reduction in luminal epithelial UEA-1 staining and a 67% reduction in LewisX staining in uterine tissues of mice hormonally treated to mimic early pregnancy. Together, these data demonstrate that uterine epithelial Fut2 mRNA expression and terminal fucosylation of embryo attachment ligands is regulated in preparation for implantation by factors including LIF and IL1B secreted from macrophages recruited during the inflammatory response to insemination.

  4. 76 FR 39254 - Airworthiness Directives; Schweizer Aircraft Corporation (Schweizer) Model 269A, A-1, B, C, C-1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-06

    ... Airworthiness Directives; Schweizer Aircraft Corporation (Schweizer) Model 269A, A-1, B, C, C-1, and TH-55... reviewed Schweizer Service Bulletins No. B-295 for Model 269A, A-1, B, and C helicopters, and No. C1B-032... citation for Part 39 continues to read as follows: Authority: 49 U.S.C. 106(g), 40113, 44701. Sec. 39.13...

  5. The B1 Protein Guides the Biosynthesis of a Lasso Peptide

    NASA Astrophysics Data System (ADS)

    Zhu, Shaozhou; Fage, Christopher D.; Hegemann, Julian D.; Mielcarek, Andreas; Yan, Dushan; Linne, Uwe; Marahiel, Mohamed A.

    2016-10-01

    Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) with a unique lariat knot-like fold that endows them with extraordinary stability and biologically relevant activity. However, the biosynthetic mechanism of these fascinating molecules remains largely speculative. Generally, two enzymes (B for processing and C for cyclization) are required to assemble the unusual knot-like structure. Several subsets of lasso peptide gene clusters feature a “split” B protein on separate open reading frames (B1 and B2), suggesting distinct functions for the B protein in lasso peptide biosynthesis. Herein, we provide new insights into the role of the RiPP recognition element (RRE) PadeB1, characterizing its capacity to bind the paeninodin leader peptide and deliver its peptide substrate to PadeB2 for processing.

  6. Novel Nine-Exon AR Transcripts (Exon 1/Exon 1b/Exons 2-8) in Normal and Cancerous Breast and Prostate Cells.

    PubMed

    Hu, Dong Gui; McKinnon, Ross A; Hulin, Julie-Ann; Mackenzie, Peter I; Meech, Robyn

    2016-12-27

    Nearly 20 different transcripts of the human androgen receptor (AR) are reported with two currently listed as Refseq isoforms in the NCBI database. Isoform 1 encodes wild-type AR (type 1 AR) and isoform 2 encodes the variant AR45 (type 2 AR). Both variants contain eight exons: they share common exons 2-8 but differ in exon 1 with the canonical exon 1 in isoform 1 and the variant exon 1b in isoform 2. Splicing of exon 1 or exon 1b is reported to be mutually exclusive. In this study, we identified a novel exon 1b (1b/TAG) that contains an additional TAG trinucleotide upstream of exon 1b. Moreover, we identified AR transcripts in both normal and cancerous breast and prostate cells that contained either exon 1b or 1b/TAG spliced between the canonical exon 1 and exon 2, generating nine-exon AR transcripts that we have named isoforms 3a and 3b. The proteins encoded by these new AR variants could regulate androgen-responsive reporters in breast and prostate cancer cells under androgen-depleted conditions. Analysis of type 3 AR-GFP fusion proteins showed partial nuclear localization in PC3 cells under androgen-depleted conditions, supporting androgen-independent activation of the AR. Type 3 AR proteins inhibited androgen-induced growth of LNCaP cells. Microarray analysis identified a small set of type 3a AR target genes in LNCaP cells, including genes known to modulate growth and proliferation of prostate cancer ( PCGEM1 , PEG3 , EPHA3 , and EFNB2 ) or other types of human cancers ( TOX3 , ST8SIA4 , and SLITRK3 ), and genes that are diagnostic/prognostic biomarkers of prostate cancer ( GRINA3 , and BCHE ).

  7. Glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) metabolism computational network analysis between chimpanzee and human left cerebrum.

    PubMed

    Sun, Lingjun; Wang, Lin; Jiang, Minghu; Huang, Juxiang; Lin, Hong

    2011-12-01

    We identified significantly higher expression of the genes glycogen debranching enzyme 6 (AGL), enolase 1 (ENOSF1), ectonucleotide pyrophosphatase 2 (ENPP2_1), glutathione S-transferase 3 (GSTM3_3) and mannosidase (MAN2B2) from human left cerebrums versus chimpanzees. Yet the distinct low- and high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism networks between chimpanzee and human left cerebrum remain to be elucidated. Here, we constructed low- and high-expression activated and inhibited upstream and downstream AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network between chimpanzee and human left cerebrum in GEO data set by gene regulatory network inference method based on linear programming and decomposition procedure, under covering AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 pathway and matching metabolism enrichment analysis by CapitalBio MAS 3.0 integration of public databases, including Gene Ontology, KEGG, BioCarta, GenMapp, Intact, UniGene, OMIM, etc. Our results show that the AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network has more activated and less inhibited molecules in chimpanzee, but less activated and more inhibited in the human left cerebrum. We inferred stronger carbohydrate, glutathione and proteoglycan metabolism, ATPase activity, but weaker base excision repair, arachidonic acid and drug metabolism as a result of inducing cell growth in low-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of chimpanzee left cerebrum; whereas stronger lipid metabolism, amino acid catabolism, DNA repair but weaker inflammatory response, cell proliferation, glutathione and carbohydrate metabolism as a result of inducing cell differentiation in high-expression AGL, ENOSF1, ENPP2_1, GSTM3_3 and MAN2B2 metabolism network of human left cerebrum. Our inferences are consistent with recent reports and computational activation and inhibition gene number patterns, respectively.

  8. Affine Kac-Moody symmetric spaces related with A1^{(1)}, A2^{(1)},} A2^{(2)}

    NASA Astrophysics Data System (ADS)

    Nayak, Saudamini; Pati, K. C.

    2014-08-01

    Symmetric spaces associated with Lie algebras and Lie groups which are Riemannian manifolds have recently got a lot of attention in various branches of Physics for their role in classical/quantum integrable systems, transport phenomena, etc. Their infinite dimensional counter parts have recently been discovered which are affine Kac-Moody symmetric spaces. In this paper we have (algebraically) explicitly computed the affine Kac-Moody symmetric spaces associated with affine Kac-Moody algebras A1^{(1)}, A2^{(1)}, A2^{(2)}. We hope these types of spaces will play similar roles as that of symmetric spaces in many physical systems.

  9. 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

    ... Corporate Reorganizations; Distributions Under Sections 368(a)(1)(D) and 354(b)(1)(B); Correction AGENCY... in section 368(a)(1)(D) where no stock and/or securities of the acquiring corporation is issued and... guidance regarding the determination of the basis of stock or securities in a reorganization described in...

  10. Word Frequency Analysis. MOS: 12B. Skill Levels 1 & 2.

    DTIC Science & Technology

    1981-05-01

    2 BURNING 16 RURNS 1 9 BJRRS- I BUP $I-ON-TARGET 9 5UJR STE R 2 RP ES I PIG PU 1 UR S11 N-TVPE...TV f 37 SHJFT ?7 STAKES 37 SUPPORT 37 SITMM 36 ADJUSTMrNT ?b.. 36 ATTACII 36- BEING .... 36 P . .. It# OIKP TIfOt 36 EXPOSED 36 IAW 16 I NSTRUICT IONS...APPENDIX lb ARTIFICIAL 16 ASSEPRLED . 6 ASLFC 16 BREAK 16 BREECH 16 BURNS 16 CA D 16 CLEARED --- to ELcCERISr- - --- -CVRT ( lb -UUI(OT ONNECTCR 1b

  11. Rapid hydrothermal synthesis of VO2 (B) and its conversion to thermochromic VO2 (M1).

    PubMed

    Popuri, Srinivasa Rao; Miclau, Marinela; Artemenko, Alla; Labrugere, Christine; Villesuzanne, Antoine; Pollet, Michaël

    2013-05-06

    The present study provides a rapid way to obtain VO2 (B) under economical and environmentally friendly conditions. VO2 (B) is one of the well-known polymorphs of vanadium dioxide and is a promising cathode material for aqueous lithium ion batteries. VO2 (B) was successfully synthesized by rapid single-step hydrothermal process using V2O5 and citric acid as precursors. The present study shows that phase-pure VO2 (B) polytype can be easily obtained at 180 °C for 2 h and 220 °C for 1 h, that is, the lowest combination of temperature and duration reported so far. The obtained VO2 (B) is characterized by X-ray powder diffraction, high-resolution scanning electron microscopy, and Fourier transform infrared spectroscopy. In addition, we present an indirect way to obtain VO2 (M1) by annealing VO2 (B) under vacuum for 1 h.

  12. B-1 phagocytes: the myeloid face of B-1 cells.

    PubMed

    Popi, Ana Flavia

    2015-12-01

    The relationship between malignant B cells and macrophages has long been established. Furthermore, evolutionary studies have demonstrated that B cells from early vertebrates have both phagocytic and antibody production capabilities. In addition to their lymphoid nature, B-1 cells retain several myeloid characteristics. Various reports have demonstrated that B-1 cells can differentiate into phagocytes. However, descriptions of B-1 cells as a novel phagocyte cell member are rarely found in the literature. This review aims to present the available data regarding B-1 cell-derived phagocytes and also discusses how their existence might be relevant to hematopoiesis and immune responses. © 2015 New York Academy of Sciences.

  13. Tooele Army Depot-North Area Suspected Releases SWMUs. Phase 1 RFI report. Volume 1. Text

    DTIC Science & Technology

    1993-12-01

    Maximum Contaminant Level MSL Mean Sea Level NEPA National Environmental Policy Act OB/OD Open Burning/Open Detonation PAH Polycyclic Aromatic...part of a pre-construction environmental assessment (EA), as required by the National Environmental Policy Act (NEPA). The following summarize the...0 1 1M*C!. 43, IV 𔃺 -4C o c a 0fi MA ao W!t 40 CD at w 4Kb CNCD 0 0 CS 40 - 0 e’A * CL m s.a Sc -~ ~ *b C CL 0 WN0 . 0 - at’ 30. qm 2 5--1 z 44

  14. The CIDA Variability Survey of Orion OB1. I. The Low-Mass Population of Ori OB1a and 1b

    NASA Astrophysics Data System (ADS)

    Briceño, Cesar; Calvet, Nuria; Hernández, J.; Vivas, A. K.; Hartmann, Lee; Downes, J. J.; Berlind, Perry

    2005-02-01

    We present results of a large-scale, multiepoch optical survey of the Orion OB1 association, carried out with the QUEST camera at the Venezuela National Astronomical Observatory. We identify for the first time the widely spread low-mass, young population in the Ori OB1a and OB1b subassociations. Candidate members were picked up by their variability in the V band and position in color-magnitude diagrams. We obtained spectra to confirm membership. In a region spanning ~68 deg2, we found 197 new young stars; of these, 56 are located in the Ori OB1a subassociation and 141 in Ori OB1b. The spatial distribution of the low-mass young stars is spatially coincident with that of the high-mass members but suggests a much sharper edge to the association. Comparison with the spatial extent of molecular gas and extinction maps indicates that the subassociation Ori OB1b is concentrated within a ringlike structure of radius ~2°(~15 pc at 440 pc), centered roughly on the star ɛ Ori in the Orion belt. The ring is apparent in 13CO and corresponds to a region with an extinction AV>=1. The stars exhibiting strong Hα emission, an indicator of active accretion, are found along this ring, whereas the center is populated with weak Hα-emitting stars. In contrast, Ori OB1a is located in a region devoid of gas and dust. We identify a grouping of stars within a ~3 deg2 area located in Ori OB1a, roughly clustered around the B2 star 25 Ori. The Herbig Ae/Be star V346 Ori is also associated with this grouping, which could be an older analog of σ Ori. Using several sets of evolutionary tracks, we find an age of 7-10 Myr for Ori OB1a and of ~4-6 Myr for Ori OB1b, consistent with previous estimates from OB stars. Indicators such as the equivalent width of Hα and near-IR excesses show that the number of accreting low-mass stars decreases sharply between Ori OB1b and Ori OB1a. These results indicate that although a substantial fraction of accreting disks remain at ages ~5 Myr, inner disks are

  15. The 590 cm-1 B_1g feature in underdoped Bi_2Sr_2CaCu_2O_8+δ

    NASA Astrophysics Data System (ADS)

    Hewitt, Kevin C.; Wang, N. L.; Irwin, J. C.; Pooke, D. M.; Pantoja, A. E.; Trodahl, H. J.

    1999-05-01

    Raman scattering studies have been performed on underdoped Bi_2Sr_2CaCu_2O_8+δ. In single crystals underdoped by oxygen removal, a 590 cm-1 peak is observed in the B_1g spectrum. The feature is observed to soften in frequency by 3.8% with isotopic exchange of ^16O by ^18O. In contrast, the 590 cm-1 peak is not observed in crystals underdoped by Y substitution which suggests that it corresponds to a disorder induced vibrational mode. We have also found that underdoping leads to a depletion of low energy spectral weight from regions of the Fermi surface located near the Brillouin zone axes.

  16. A Simple and Efficient Synthesis of 4-Arylacridinediones and 6-Aryldiindeno[1,2-b:2,1-e]pyridinediones using CuI Nanoparticles as Catalyst under Solvent-Free Conditions.

    PubMed

    Abdolmohammadi, Shahrzad; Dahi-Azar, Saman; Mohammadnejad, Mahdieh; Hosseinian, Akram

    2017-01-01

    The importance of acridine core structure and other heterocycles containing its framework is well known, as they are found in numerous compounds with a variety of biological effects. Pyridine is also an important solvent and heterocyclic nucleus for the design and synthesis of novel molecules with biological properties. It occurs in several natural compounds which are used as a precursor in agrochemicals and pharmaceuticals. The utility of nanostructured metal salts because of their small size and high surface area as catalysts in organic synthesis has drawn special attention due to their better properties such as slower reaction rate, reusability of the catalyst, and higher yields of products compared to the bulk size. Nanosized copper iodide is one reusable Lewis acid catalyst which has revealed several catalytic activities for the synthesis of organic compounds and others. As part of our recent study to develop heterocyclic syntheses using nanostructured catalysts, we now report an efficient and clean synthetic route to 4-arylacridinediones and 6-aryldiindeno[1,2-b:2,1-e]pyridinediones via a condensation reaction catalyzed by CuI nanoparticles under solvent-free conditions. The present work deals with the condensation reaction of aromatic aldehydes, ammonium acetate and active methylene compounds comprising dimedone or 1,3- indanedione in the presence of a catalytic amount of the synthesized CuI nanoparticles could be applied for the solvent-free preparation of 4-arylacridinediones and 6-aryldiindeno[1,2-b:2,1- e]pyridinediones at 70 °C within 60 min. A series of 9-aryl-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinediones and 6-aryldiindeno[1,2-b:2,1-e]pyridine-5,7-diones were synthesized in high to excellent yields via a simple one-pot three-component coupling reaction using the synthesized CuI nanoparticles as an efficient and recyclable catalyst. All synthesized compounds were well characterized by their satisfactory elemental analyses, IR, 1

  17. Plant Equipment Package Modernization Program. Volume 4-1. Model Lines. Shell, HE, M483/M107-155MM Case, Cartridge, M115B1, M148A1B1, M150B1-105MM Shell, HEAT-T, M456A1-105MM Fuze, PD, M739

    DTIC Science & Technology

    1976-04-01

    Cartridge, M115B1, M148A1B1, M15#1B1-15MM J .. Shell, HEAT-T, M456A1-105MM Fuze, PD, M739 # prepared for Project Manager Munitions Production Base...ENGINEERS PLANT EQUIPMENT PACKAGE MODERNIZATION PROGRAM Volume 4-1 Report No. 75-86-R-4- MODEL LINE DEVELOPMENT FUZE,PD, M739 prepared for Project...In preparing the model line for the manufacture of piece parts for the M739 fuze, a number of facts became obvious and affect the detailed de- [ sign

  18. Identification of high-risk Listeria monocytogenes serotypes in lineage I (serotype 1/2a, 1/2c, 3a and 3c) using multiplex PCR

    USDA-ARS?s Scientific Manuscript database

    Aims: Using molecular subtyping techniques, Listeria monocytogenes is divided into three major phylogenetic lineages, and a multiplex PCR method can differentiate five L. monocytogenes subgroups: 1/2a-3a, 1/2c-3c, 1/2b-3b-7, 4b-4d-4e, and 4a-4c. In the current study, we conducted genome comparison...

  19. Interaction of digitalis-like compounds with liver uptake transporters NTCP, OATP1B1, and OATP1B3.

    PubMed

    Gozalpour, Elnaz; Greupink, Rick; Wortelboer, Heleen M; Bilos, Albert; Schreurs, Marieke; Russel, Frans G M; Koenderink, Jan B

    2014-06-02

    Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and Na(+)-dependent taurocholate co-transporting polypeptide (NTCP) influence the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. The interaction of digoxin, digitoxin, and ouabain with hepatic uptake transporters has been studied before. However, here, we systematically investigated a much wider range of structurally related DLCs for their capability to inhibit or to be transported by these transporters in order to better understand the relation between the activity and chemical structure of this compound type. We studied the uptake and inhibitory potency of a series of 14 structurally related DLCs in Chinese hamster ovary cells expressing NTCP (CHO-NTCP) and human embryonic kidney cells expressing OATP1B1 and OATP1B3 (HEK-OATP1B1 and HEK-OATP1B3). The inhibitory effect of the DLCs was measured against taurocholic acid (TCA) uptake in CHO-NTCP cells and against uptake of β-estradiol 17-β-d-glucuronide (E217βG) in HEK-OATP1B1 and HEK-OATP1B3 cells. Proscillaridin A was the most effective inhibitor of NTCP-mediated TCA transport (IC50 = 22 μM), whereas digitoxin and digitoxigenin were the most potent inhibitors of OATP1B1 and OAPTP1B3, with IC50 values of 14.2 and 36 μM, respectively. Additionally, we found that the sugar moiety and hydroxyl groups of the DLCs play different roles in their interaction with NTCP, OATP1B1, and OATP1B3. The sugar moiety decreases the inhibition of NTCP and OATP1B3 transport activity, whereas it enhances the inhibitory potency against OATP1B1. Moreover, the hydroxyl group at position 12

  20. Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice.

    PubMed

    Lemos, Mayra Tolentino Resk; Amaral, Fabio Agostini; Dong, Karis Ester; Bittencourt, Maria Fernanda Queiroz Prado; Caetano, Ariadiny Lima; Pesquero, João Bosco; Viel, Tania Araujo; Buck, Hudson Sousa

    2010-04-01

    Under physiological conditions, elderly people present memory deficit associated with neuronal loss. This pattern is also associated with Alzheimer's disease but, in this case, in a dramatically intensified level. Kinin receptors have been involved in neurodegeneration and increase of amyloid-beta concentration, associated with Alzheimer's disease (AD). Considering these findings, this work evaluated the role of kinin receptors in memory consolidation during the aging process. Male C57Bl/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and 18-month-old - mo; n=10 per group) were submitted to an acquisition session, reinforcement to learning (24h later: test 1) and final test (7days later: test 2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar CAR were obtained among age matched animals from all strains. However, a significant decrease in CAR was observed throughout the aging process (3mo: 8.8+/-2.3%; 6mo: 4.1+/-0.6%; 12mo: 2.2+/-0.6%, 18mo: 3.6+/-0.6%, P<0.01), indicating a reduction in the learning process. In test 1, as expected, memory retention increased significantly (P<0.05) in all 3- and 6-month-old animals as well as in 12-month-old-wt and 12-month-old-koB1 (P<0.01), compared to the training session. However, 12-month-old-koB2 and all 18-month-old animals did not show an increase in memory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages showed a significant improvement in memory (P<0.05) compared to test 1. However, 12-month-old wt and koB2 mice of all ages showed no difference in memory retention. We suggest that, during the aging process, the B1 receptor could be involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is apparently acting as a neuroprotective factor. Copyright 2009 Elsevier Ltd. All rights reserved.

  1. Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1.

    PubMed

    Kang, Sung Koo; Kim, Dae Kyong; Damron, Derek S; Baek, Kwang Jin; Im, Mie-Jae

    2002-04-26

    We characterized the alpha(1B)-adrenoreceptor (alpha(1B)-AR)-mediated intracellular Ca(2+) signaling involving G alpha(h) (transglutaminase II, TGII) and phospholipase C (PLC)-delta 1 using DDT1-MF2 cell. Expression of wild-type TGII and a TGII mutant lacking transglutaminase activity resulted in significant increases in a rapid peak and a sustained level of intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to activation of the alpha(1B)-AR. Expression of a TGII mutant lacking the interaction with the receptor or PLC-delta 1 substantially reduced both the peak and sustained levels of [Ca(2+)](i). Expression of TGII mutants lacking the interaction with PLC-delta 1 resulted in a reduced capacitative Ca(2+) entry. Reduced expression of PLC-delta 1 displayed a transient elevation of [Ca(2+)](i) and a reduction in capacitative Ca(2+) entry. Expression of the C2-domain of PLC-delta 1, which contains the TGII interaction site, resulted in reduction of the alpha(1B)-AR-evoked peak increase in [Ca(2+)](i), while the sustained elevation in [Ca(2+)](i) and capacitative Ca(2+) entry remained unchanged. These findings demonstrate that stimulation of PLC-delta 1 via coupling of the alpha(1B)-AR with TGII evokes both Ca(2+) release and capacitative Ca(2+) entry and that capacitative Ca(2+) entry is mediated by the interaction of TGII with PLC-delta 1.

  2. A Comparative Study on Aflatoxin B1 Metabolism in Mice and Rats

    PubMed Central

    Steyn, M.; Pitout, M. J.; Purchase, I. F. H.

    1971-01-01

    In vivo metabolic studies on rats and mice revealed a marked difference in the fluorescent compounds produced after ingestion of aflatoxin B1. The mouse converted aflatoxin B1 to three unknown fluorescent compounds, designated x1, x2 and x3 and the known aflatoxin M1, while the rat was only capable of producing aflatoxin M1. The results suggested that metabolites x1, x2, x3 and aflatoxin M1 were not part of a major metabolic pathway, but produced independently. These unknown yellowish-green fluorescent compounds did not seem to be conjugated with sulphate or glucuronic acid. In vitro incubations of various mouse liver cell fractions with aflatoxin B1 showed that metabolites x1, x2, x3 and aflatoxin M1, could only be produced by the microsomal fraction and that NADPH was needed as a co-factor. The differences in aflatoxin metabolism by mice and rats are discussed in relation to the apparent resistance of the mouse to the carcinogenic effects of this toxin. PMID:4398926

  3. B1 gradient coherence selection using a tapered stripline.

    PubMed

    van Meerten, S G J; Tijssen, K C H; van Bentum, P J M; Kentgens, A P M

    2018-01-01

    Pulsed-field gradients are common in modern liquid state NMR pulse sequences. They are often used instead of phase cycles for the selection of coherence pathways, thereby decreasing the time required for the NMR experiment. Soft off-resonance pulses with a B 1 gradient result in a spatial encoding similar to that created by pulsed-field (B 0 ) gradients. In this manuscript we show that pulse sequences with pulsed-field gradients can easily be converted to one which uses off-resonance B 1 field gradient (OFFBEAT) pulses. The advantage of B 1 gradient pulses for coherence selection is that the chemical shift evolution during the pulses is (partially) suppressed. Therefore no refocusing echos are required to correct for evolution during the gradient pulses. A tapered stripline is shown to be a convenient tool for creating a well-defined gradient in the B 1 field strength. B 1 gradient coherence selection using a tapered stripline is a simple and cheap alternative to B 0 pulsed-field gradients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. α decay of the T = 1 ,   2 + state in B 10 and isospin symmetry breaking in the A = 10 triplet

    DOE PAGES

    Kuvin, S. A.; Wuosmaa, A. H.; Lister, C. J.; ...

    2017-10-03

    Here, the rate of the T=1, 2+ to T=1, 0 + transition in 10B ( T=1, T z=0) is compared to the analog transitions in 10Be ( T=1, T z=–1) and 10C ( T=1, T z=+1) to provide constraints on ab initio calculations using realistic nuclear forces. The relevant state in 10B, at E x=5.164 MeV, is particle unbound. Therefore, a determination of the B( E2) electromagnetic transition rate requires a precise and accurate determination of the width of the state, as well as the α-particle and γ-ray branching ratios. Previous measurements of the α-particle branching ratio are just barelymore » in agreement. We report on a new study of the α-particle branch by studying the 10B(p,p') 10B* reaction in inverse kinematics with the HELIOS spectrometer. The α-particle branching ratio that we observe, 0.144±0.027, is in good agreement with the evaluated value and improves the associated uncertainty. The resulting experimental B( E2) value is 7.0±2.2 e 2fm 4 and is more consistent with a flat trend across the A=10 triplet than previously reported. This is inconsistent with Green's function Monte Carlo predictions using realistic three-nucleon Hamiltonians, which overpredict the B(E2) value in 10C and 10B.« less

  5. Assessment of PaO2/FiO2 for stratification of patients with moderate and severe acute respiratory distress syndrome

    PubMed Central

    Villar, Jesús; Blanco, Jesús; del Campo, Rafael; Andaluz-Ojeda, David; Díaz-Domínguez, Francisco J; Muriel, Arturo; Córcoles, Virgilio; Suárez-Sipmann, Fernando; Tarancón, Concepción; González-Higueras, Elena; López, Julia; Blanch, Lluis; Pérez-Méndez, Lina; Fernández, Rosa Lidia; Kacmarek, Robert M

    2015-01-01

    Objectives A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) at ARDS onset. Since the proposal did not mandate PaO2/FiO2 calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO2/FiO2 would not provide accurate assessment of lung injury severity. Design A prospective, multicentre, observational study. Setting A network of teaching hospitals. Participants 478 patients with eligible criteria for moderate (1002/FiO2≤200) and severe (PaO2/FiO2≤100) ARDS and followed until hospital discharge. Interventions We examined physiological and ventilator parameters in association with the PaO2/FiO2 at ARDS onset, after 24 h of usual care and at 24 h under a SVS. At 24 h, patients were reclassified as severe, moderate, mild (2002/FiO2≤300) ARDS and non-ARDS (PaO2/FiO2>300). Primary and secondary outcomes Group severity and hospital mortality. Results At ARDS onset, 173 patients had a PaO2/FiO2≤100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO2/FiO2 category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO2/FiO2 and non-standardised PaO2/FiO2 at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). Conclusions Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the

  6. Characterization of the human SNM1A and SNM1B/Apollo DNA repair exonucleases.

    PubMed

    Sengerová, Blanka; Allerston, Charles K; Abu, Mika; Lee, Sook Y; Hartley, Janet; Kiakos, Konstantinos; Schofield, Christopher J; Hartley, John A; Gileadi, Opher; McHugh, Peter J

    2012-07-27

    Human SNM1A and SNM1B/Apollo have both been implicated in the repair of DNA interstrand cross-links (ICLs) by cellular studies, and SNM1B is also required for telomere protection. Here, we describe studies on the biochemical characterization of the SNM1A and SNM1B proteins. The results reveal some fundamental differences in the mechanisms of the two proteins. Both SNM1A and SNM1B digest double-stranded and single-stranded DNA with a 5'-to-3' directionality in a reaction that is stimulated by divalent cations, and both nucleases are inhibited by the zinc chelator o-phenanthroline. We find that SNM1A has greater affinity for single-stranded DNA over double-stranded DNA that is not observed with SNM1B. Although both proteins demonstrate a low level of processivity on low molecular weight DNA oligonucleotide substrates, when presented with high molecular weight DNA, SNM1A alone is rendered much more active, being capable of digesting kilobase-long stretches of DNA. Both proteins can digest past ICLs induced by the non-distorting minor groove cross-linking agent SJG-136, albeit with SNM1A showing a greater capacity to achieve this. This is consistent with the proposal that SNM1A and SNM1B might exhibit some redundancy in ICL repair. Together, our work establishes differences in the substrate selectivities of SNM1A and SNM1B that are likely to be relevant to their in vivo roles and which might be exploited in the development of selective inhibitors.

  7. Biophysical Analysis of Anopheles gambiae Leucine-Rich Repeat Proteins APL1A1, APL1B and APL1C and Their Interaction with LRIM1

    DOE PAGES

    Williams, Marni; Summers, Brady J.; Baxter, Richard H. G.; ...

    2015-03-16

    Natural infection of Anopheles gambiae by malaria-causing Plasmodium parasites is significantly influenced by the APL1 genetic locus. The locus contains three closely related leucine-rich repeat (LRR) genes, APL1A, APL1B and APL1C. Multiple studies have reported the participation of APL1A—C in the immune response of A. gambiae to invasion by both rodent and human Plasmodium isolates. APL1C forms a heterodimer with the related LRR protein LRIM1 via a C-terminal coiled-coil domain that is also present in APL1A and APL1B. The LRIM1/APL1C heterodimer protects A. gambiae from infection by binding the complement-like protein TEP1 to form a stable and active immune complex.more » We report solution x-ray scatting data for the LRIM1/APL1C heterodimer, the oligomeric state of LRIM1/APL1 LRR domains in solution and the crystal structure of the APL1B LRR domain. The LRIM1/APL1C heterodimeric complex has a flexible and extended structure in solution. In contrast to the APL1A, APL1C and LRIM1 LRR domains, the APL1B LRR domain is a homodimer. The crystal structure of APL1B-LRR shows that the homodimer is formed by an N-terminal helix that complements for the absence of an N-terminal capping motif in APL1B, which is a unique distinction within the LRIM1/APL1 protein family. Full-length APL1A 1 and APL1B form a stable complex with LRIM1. Our results support a model in which APL1A 1, APL1B and APL1C can all form an extended, flexible heterodimer with LRIM1, providing a repertoire of functional innate immune complexes to protect A. gambiae from a diverse array of pathogens.« less

  8. Biophysical Analysis of Anopheles gambiae Leucine-Rich Repeat Proteins APL1A1, APL1B and APL1C and Their Interaction with LRIM1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Williams, Marni; Summers, Brady J.; Baxter, Richard H. G.

    Natural infection of Anopheles gambiae by malaria-causing Plasmodium parasites is significantly influenced by the APL1 genetic locus. The locus contains three closely related leucine-rich repeat (LRR) genes, APL1A, APL1B and APL1C. Multiple studies have reported the participation of APL1A—C in the immune response of A. gambiae to invasion by both rodent and human Plasmodium isolates. APL1C forms a heterodimer with the related LRR protein LRIM1 via a C-terminal coiled-coil domain that is also present in APL1A and APL1B. The LRIM1/APL1C heterodimer protects A. gambiae from infection by binding the complement-like protein TEP1 to form a stable and active immune complex.more » We report solution x-ray scatting data for the LRIM1/APL1C heterodimer, the oligomeric state of LRIM1/APL1 LRR domains in solution and the crystal structure of the APL1B LRR domain. The LRIM1/APL1C heterodimeric complex has a flexible and extended structure in solution. In contrast to the APL1A, APL1C and LRIM1 LRR domains, the APL1B LRR domain is a homodimer. The crystal structure of APL1B-LRR shows that the homodimer is formed by an N-terminal helix that complements for the absence of an N-terminal capping motif in APL1B, which is a unique distinction within the LRIM1/APL1 protein family. Full-length APL1A 1 and APL1B form a stable complex with LRIM1. Our results support a model in which APL1A 1, APL1B and APL1C can all form an extended, flexible heterodimer with LRIM1, providing a repertoire of functional innate immune complexes to protect A. gambiae from a diverse array of pathogens.« less

  9. IND2, a pyrimido[1”,2”:1,5]pyrazolo[3,4-b]quinoline derivative, circumvents multi-drug resistance and causes apoptosis in colon cancer cells

    PubMed Central

    Karthikeyan, Chandrabose; Lee, Crystal; Moore, Joshua; Mittal, Roopali; Suswam, Esther A.; Abbott, Kodye L; Pondugula, Satyanarayana R.; Manne, Upender; Narayanan, Narayanan K.; Trivedi, Piyush; Tiwari, Amit K.

    2014-01-01

    Naturally occurring condensed quinolines have anticancer properties. In efforts to find active analogues, we designed and synthesized eight polycyclic heterocycles with a pyrimido[1”,2”:1,5]pyrazolo[3,4-b]quinoline framework (IND series). The compounds were evaluated for activity against colon (HCT-116 and S1-MI-80), prostate (PC3 and DU-145), breast (MCF-7 and MDAMB-231), ovarian (ov2008 and A2780), and hepatocellular (HepG2) cancer cells and against non-cancerous Madin Darby canine kidney (MDCK), mouse embryonic fibroblast (NIH/3T3), and human embryonic kidney cells (HEK293). IND-2, a 4-chloro-2-methyl pyrimido[1”,2”:1,5]pyrazolo[3,4-b]quinoline, exhibited more than tenfold selectivity and potent cytotoxic activity against colon cancer cells relative to the other cancer and non-cancer cells. With five additional colon cancer cell lines (HT-29, HCT-15, LS-180, LS-174, and LoVo), IND-2 had similar cytotoxicity and selectivity, and submicromolar concentrations caused changes in the morphology of HCT-116 and HCT-15 cells. IND-2 did not activate the transactivating function of the pregnane X receptor (PXR), indicating that it does not induce PXR-regulated ABCB1 or ABCG2 transporters. Indeed, IND-2 was not a substrate of ABCB1 or ABCG2, and it induced cytotoxicity in HEK293 cells overexpressing ABCB1 or ABCG2 to the same extent as in normal HEK293 cells. IND-2 was cytotoxic to resistant colon carcinoma S1-MI-80 cells, approximately three- and fivefold more than SN-38 and topotecan, respectively. In HCT-116 colon cancer cells, IND-2 produced concentration-dependent changes in mitochondrial membrane potential, leading to apoptosis, and sub-micromolar concentrations caused chromosomal DNA fragmentation. These findings suggest that, by increasing apoptosis, IND-2 has potential therapeutic efficacy for colorectal cancer. PMID:25537531

  10. PeaTAR1B: Characterization of a Second Type 1 Tyramine Receptor of the American Cockroach, Periplaneta americana

    PubMed Central

    Balfanz, Sabine

    2017-01-01

    The catecholamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. In insects; these neuroactive substances are functionally replaced by the phenolamines octopamine and tyramine. Phenolamines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Type 1 tyramine receptors are better activated by tyramine than by octopamine. In contrast; type 2 tyramine receptors are almost exclusively activated by tyramine. Functionally; activation of type 1 tyramine receptors leads to a decrease in the intracellular concentration of cAMP ([cAMP]i) whereas type 2 tyramine receptors can mediate Ca2+ signals or both Ca2+ signals and effects on [cAMP]i. Here; we report that the American cockroach (Periplaneta americana) expresses a second type 1 tyramine receptor (PeaTAR1B) in addition to PeaTAR1A (previously called PeaTYR1). When heterologously expressed in flpTM cells; activation of PeaTAR1B by tyramine leads to a concentration-dependent decrease in [cAMP]i. Its activity can be blocked by a series of established antagonists. The functional characterization of two type 1 tyramine receptors from P. americana; PeaTAR1A and PeaTAR1B; which respond to tyramine by changing cAMP levels; is a major step towards understanding the actions of tyramine in cockroach physiology and behavior; particularly in comparison to the effects of octopamine. PMID:29084141

  11. PeaTAR1B: Characterization of a Second Type 1 Tyramine Receptor of the American Cockroach, Periplaneta americana.

    PubMed

    Blenau, Wolfgang; Balfanz, Sabine; Baumann, Arnd

    2017-10-30

    The catecholamines norepinephrine and epinephrine regulate important physiological functions in vertebrates. In insects; these neuroactive substances are functionally replaced by the phenolamines octopamine and tyramine. Phenolamines activate specific guanine nucleotide-binding (G) protein-coupled receptors (GPCRs). Type 1 tyramine receptors are better activated by tyramine than by octopamine. In contrast; type 2 tyramine receptors are almost exclusively activated by tyramine. Functionally; activation of type 1 tyramine receptors leads to a decrease in the intracellular concentration of cAMP ([cAMP] i ) whereas type 2 tyramine receptors can mediate Ca 2+ signals or both Ca 2+ signals and effects on [cAMP] i . Here; we report that the American cockroach ( Periplaneta americana ) expresses a second type 1 tyramine receptor (PeaTAR1B) in addition to PeaTAR1A (previously called PeaTYR1). When heterologously expressed in flpTM cells; activation of PeaTAR1B by tyramine leads to a concentration-dependent decrease in [cAMP] i . Its activity can be blocked by a series of established antagonists. The functional characterization of two type 1 tyramine receptors from P. americana ; PeaTAR1A and PeaTAR1B; which respond to tyramine by changing cAMP levels; is a major step towards understanding the actions of tyramine in cockroach physiology and behavior; particularly in comparison to the effects of octopamine.

  12. CYP714B1 and CYP714B2 encode gibberellin 13-oxidases that reduce gibberellin activity in rice.

    PubMed

    Magome, Hiroshi; Nomura, Takahito; Hanada, Atsushi; Takeda-Kamiya, Noriko; Ohnishi, Toshiyuki; Shinma, Yuko; Katsumata, Takumi; Kawaide, Hiroshi; Kamiya, Yuji; Yamaguchi, Shinjiro

    2013-01-29

    Bioactive gibberellins (GAs) control many aspects of growth and development in plants. GA(1) has been the most frequently found bioactive GA in various tissues of flowering plants, but the enzymes responsible for GA(1) biosynthesis have not been fully elucidated due to the enzymes catalyzing the 13-hydroxylation step not being identified. Because of the lack of mutants defective in this enzyme, biological significance of GA 13-hydroxylation has been unknown. Here, we report that two cytochrome P450 genes, CYP714B1 and CYP714B2, encode GA 13-oxidase in rice. Transgenic Arabidopsis plants that overexpress CYP714B1 or CYP714B2 show semidwarfism. There was a trend that the levels of 13-OH GAs including GA(1) were increased in these transgenic plants. Functional analysis using yeast or insect cells shows that recombinant CYP714B1 and CYP714B2 proteins can convert GA(12) into GA(53) (13-OH GA(12)) in vitro. Moreover, the levels of 13-OH GAs including GA(1) were decreased, whereas those of 13-H GAs including GA(4) (which is more active than GA(1)) were increased, in the rice cyp714b1 cyp714b2 double mutant. These results indicate that CYP714B1 and CYP714B2 play a predominant role in GA 13-hydroxylation in rice. The double mutant plants appear phenotypically normal until heading, but show elongated uppermost internode at the heading stage. Moreover, CYP714B1 and CYP714B2 expression was up-regulated by exogenous application of bioactive GAs. Our results suggest that GA 13-oxidases play a role in fine-tuning plant growth by decreasing GA bioactivity in rice and that they also participate in GA homeostasis.

  13. Combined Palmer Type 1A and 1B Traumatic Lesions of the Triangular Fibrocartilage Complex A New Category.

    PubMed

    Nance, Erin; Ayalon, Omri; Yang, Steven

    2016-06-01

    We present a series of eight patients who underwent wrist arthroscopy for presumed solitary tears of the triangular fibrocartilage (TFC) and were, instead, found to have combined 1A (central tear) and 1B (ulnar avulsion) tears. The Palmer Classification does not currently categorize this combined pattern. All but one patient had a traumatic injury. Each subject had preoperative radiographs and MRI scans. TFC tears were evident on all MRI scans, though only one was suggestive of a combined tear pat - tern. Surgical management included arthroscopic central tear debridement and ulnar peripheral repair. Average follow-up was 22 months. Grip strength in the affected hand improved from 16% deficit as compared to the unaffected side, to 3.5% deficit postoperatively (p = 0.003), and visual analog scores (VAS) decreased from an average of 7.1/10 preoperatively to 2.3/10 postoperatively (p < 0.001). There was no statistically significant change in wrist range of motion (ROM), however. Arthroscopic debridement of the central perforation (1A lesion) with concomitant repair of the ulnar detachment (1B lesion) resulted in functional and symptomatic improvement. This combined 1A/1B TFC injury is not reliably diagnosed preoperatively and should be considered a new subset in the Palmer classification, as this will raise awareness of its presence and assist in preoperative planning of such lesions.

  14. A facile and regioselective one-pot synthesis of novel pyrazolo[1[Formula: see text],5[Formula: see text]:1,2]pyrrolo[3,4-b]quinoline-2,3-dicarboxylate hybrids via intramolecular Wittig reaction.

    PubMed

    Largani, Tahere Hosseyni; Imanzadeh, Gholamhasan; Pesyan, Nader Noroozi; Şahin, Ertan; Shamkhali, Amir Nasser; Notash, Behrouz

    2018-02-01

    The regioselective syntheses of novel pyrazolo[1[Formula: see text],5[Formula: see text]:1,2]pyrrolo[3,4-b]quinoline-2,3-dicarboxylates (6a-l) from pyrrolo([3,4-b]quinolin-2(3H)-yl)benzamides through an intramolecular Wittig reaction are described. This protocol takes advantages of mild conditions, simple workup and high yield which make this method attractive for the synthesis of these hybrid of pyrazolo[1[Formula: see text],5[Formula: see text]:1,2]pyrrolo[3,4-b]quinolines.

  15. External validation of the adult spinal deformity (ASD) frailty index (ASD-FI).

    PubMed

    Miller, Emily K; Vila-Casademunt, Alba; Neuman, Brian J; Sciubba, Daniel M; Kebaish, Khaled M; Smith, Justin S; Alanay, Ahmet; Acaroglu, Emre R; Kleinstück, Frank; Obeid, Ibrahim; Sánchez Pérez-Grueso, Francisco Javier; Carreon, Leah Y; Schwab, Frank J; Bess, Shay; Scheer, Justin K; Lafage, Virginie; Shaffrey, Christopher I; Pellisé, Ferran; Ames, Christopher P

    2018-03-30

    To assess the ability of the recently developed adult spinal deformity frailty index (ASD-FI) to predict odds of perioperative complications, odds of reoperation, and length of hospital stay after adult spinal deformity (ASD) surgery using a database other than the one used to create the index. We used the ASD-FI to calculate frailty scores for 266 ASD patients who had minimum postoperative follow-up of 2 years in the European Spine Study Group (ESSG) database. Patients were enrolled from 2012 through 2013. Using ASD-FI scores, we categorized patients as not frail (NF) (< 0.3 points), frail (0.3-0.5 points), or severely frail (SF) (> 0.5 points). Multivariable logistic regression, adjusted for preoperative and surgical factors such as operative time and blood loss, was performed to determine the relationship between ASD-FI category and odds of major complications, odds of reoperation, and length of hospital stay. We categorized 135 patients (51%) as NF, 90 patients (34%) as frail, and 41 patients (15%) as SF. Overall mean ASD-FI score was 0.29 (range 0-0.8). The adjusted odds of experiencing a major intraoperative or postoperative complication (OR 4.5, 95% CI 2.0-10) or having a reoperation (OR 3.9, 95% CI 1.7-8.9) were higher for SF patients compared with NF patients. Mean hospital stay was 2.1 times longer (95% CI 1.8-2.4) for SF patients compared with NF patients. Greater patient frailty, as measured by the ASD-FI, is associated with longer hospital stays and greater odds of major complications and reoperation. These slides can be retrieved under Electronic Supplementary Material.

  16. Overexpression of human diacylglycerol acyltransferase 1, acyl-coa:cholesterol acyltransferase 1, or acyl-CoA:cholesterol acyltransferase 2 stimulates secretion of apolipoprotein B-containing lipoproteins in McA-RH7777 cells.

    PubMed

    Liang, John J; Oelkers, Peter; Guo, Cuiying; Chu, Pi-Chun; Dixon, Joseph L; Ginsberg, Henry N; Sturley, Stephen L

    2004-10-22

    The relative importance of each core lipid in the assembly and secretion of very low density lipoproteins (VLDL) has been of interest over the past decade. The isolation of genes encoding diacylglycerol acyltransferase (DGAT) and acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) provided the opportunity to investigate the effects of isolated increases in triglycerides (TG) or cholesteryl esters (CE) on apolipoprotein B (apoB) lipoprotein biogenesis. Overexpression of human DGAT1 in rat hepatoma McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of TG. These effects were associated with decreased intracellular degradation and increased secretion of newly synthesized apoB as VLDL. Similarly, overexpression of human ACAT1 or ACAT2 in McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of CE. This led to decreased intracellular degradation and increased secretion of VLDL apoB. Overexpression of ACAT2 had a significantly greater impact upon assembly and secretion of VLDL from liver cells than did overexpression of ACAT1. The addition of oleic acid (OA) to media resulted in a further increase in VLDL secretion from cells expressing DGAT1, ACAT1, or ACAT2. VLDL secreted from DGAT1-expressing cells incubated in OA had a higher TG:CE ratio than VLDL secreted from ACAT1- and ACAT2-expressing cells treated with OA. These studies indicate that increasing DGAT1, ACAT1, or ACAT2 expression in McA-RH7777 cells stimulates the assembly and secretion of VLDL from liver cells and that the core composition of the secreted VLDL reflects the enzymatic activity that is elevated.

  17. Structural, conformational and vibrational properties of 1,1,1-Trifluoro-N-(1,1,2,2,2-pentafluoroethyl) methanesulfinimidoyl chloride, CF₃CF₂-N=S(Cl)CF₃.

    PubMed

    Robles, Norma L; Chemes, Doly M; Oberhammer, Heinz; Cutin, Edgardo H

    2015-06-15

    The structural, conformational, and configurational properties of 1,1,1-Trifluoro-N-(1,1,2,2,2-pentafluoroethyl) methanesulfinimidoyl chloride, CF3CF2NS(Cl)CF3 have been studied by vibrational spectroscopy [IR (vapor) and Raman (liquid)] and quantum chemical calculations [B3LYP, MP2 and B3PW91 levels of theory using the 6-311+G(d), 6-311+G(df) and 6-311+G(2df) basis sets]. According to these theoretical approximations, CF₃CF₂-N=S(Cl)CF₃ exists in the gas phase as a mixture of a favored anticlinal form (CN bond anticlinal with respect to the CSCl bisector) with C1 symmetry and a less abundant syn conformer showing C1 symmetry as well (ΔG° ≈ 1.20 kcal mol(-1)). Due to the small contribution only a few corresponding vibrational modes of the syn conformer could be assigned confidently in the experimental spectra. Compared to CF₃CF₂-N=S(F)CF₃, the replacement of F by Cl produces a clear change in NS bond length and the corresponding stretching frequency, without affecting the conformational properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Effect of dispersion correction on the Au(1 1 1)-H2O interface: A first-principles study

    NASA Astrophysics Data System (ADS)

    Nadler, Roger; Sanz, Javier Fdez.

    2012-09-01

    A theoretical study of the H2O-Au(1 1 1) interface based on first principles density functional theory (DFT) calculations with and without inclusion of dispersion correction is reported. Three different computational approaches are considered. First, the standard generalized gradient approximation (GGA) functional PBE is employed. Second, an additional energy term is further included that adds a semi-empirically derived dispersion correction (PBE-D2), and, finally, a recently proposed functional that includes van der Waals (vdW) interactions directly in its functional form (optB86b-vdW) was used to represent the state-of-the art of DFT functionals. The monomeric water adsorption was first considered in order to explore the dependency of geometry on the details of the model slab used to represent it (size, thickness, coverage). When the dispersion corrections are included the Au-H2O interaction is stronger, as manifested by the smaller dAu-O and stronger adsorption energies. Additionally, the interfacial region between Au(1 1 1) slab surfaces and a liquid water layer was investigated with Born-Oppenheimer molecular dynamics (BOMD) using the same functionals. Two or three interfacial orientations can be determined, depending on the theoretical methodology applied. Closest to the surface, H2O is adsorbed O-down, whereas further away it is oriented with one OH bond pointing to the surface and the molecular plane parallel to the normal direction. For the optB86b-vdW functional a third orientation is found where one H atom points into the bulk water layer and the second OH bond is oriented parallel to the metal surface. As for the water density in the first adsorption layer we find a very small increase of roughly 8%. From the analysis of vibrational spectra a weakening of the H-bond network is observed upon the inclusion of the Au(1 1 1) slab, however, no disruption of H-bonds is observed. While the PBE and PBE-D2 spectra are very similar, the optB86b-vdW spectrum shows

  19. Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population

    PubMed Central

    Millá, Elena; Mañé, Begoña; Duch, Susana; Hernan, Imma; Borràs, Emma; Planas, Ester; Dias, Miguel de Sousa; Carballo, Miguel

    2013-01-01

    Purpose To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT). Methods Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others. Results We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39Arg and p.Glu218Lys, in two families with POAG, and six previously reported MYOC mutations in seven families with POAG (four), JOAG (one), PCG (one), and normotensive glaucoma (one). CYP1B1 mutations were found in 16 index patients with PCG (nine), POAG (three), JOAG (two), and ARS (two). Conclusions The high percentage (9/25=36%) of mutations in CYP1B1 found in non-consanguineous patients with congenital glaucoma mandates genetic testing. However, the percentage of mutations (9/207=4.4%) in MYOC associated with glaucoma is relatively low in our population. The variable phenotype expression of glaucoma, even in families, cannot be explained with a digenic mechanism between MYOC and CYP1B1. PMID:23922489

  20. A low band-gap polymer based on unsubstituted benzo[1,2-b:4,5-b']dithiophene for high performance organic photovoltaics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woong Jung, Jae; Woong Jo, Jea; Liu, Feng

    2012-01-01

    A low band-gap conjugated polymer, PBDTDPP, composed of unsubstituted benzo[1,2-b:4,5-b']dithiophene and diketopyrrolo[3,4-c]pyrrole was synthesized. The deep HOMO level of PBDTDPP enhances the VOC of a PSC up to 0.82 V and exhibits a PCE of 5.16%, while alkoxy substituted PBDTDPP-OR yields a PCE of 2.24% with a VOC of 0.61 V.

  1. A cleavable signal peptide enhances cell surface delivery and heterodimerization of Cerulean-tagged angiotensin II AT1 and bradykinin B2 receptor.

    PubMed

    Quitterer, Ursula; Pohl, Armin; Langer, Andreas; Koller, Samuel; Abdalla, Said

    2011-06-10

    Heterodimerization of the angiotensin II AT1 receptor with the receptor for the vasodepressor bradykinin, B2R, is known to sensitize the AT1-stimulated response of hypertensive individuals in vivo. To analyze features of that prototypic receptor heterodimer in vitro, we established a new method that uses fluorescence resonance energy transfer (FRET) and applies for the first time AT1-Cerulean as a FRET donor. The Cerulean variant of the green fluorescent protein as donor fluorophore was fused to the C-terminus of AT1, and the enhanced yellow fluorescent protein (EYFP) as acceptor fluorophore was fused to B2R. In contrast to AT1-EGFP, the AT1-Cerulean fusion protein was retained intracellularly. To facilitate cell surface delivery of AT1-Cerulean, a cleavable signal sequence was fused to the receptor's amino terminus. The plasma membrane-localized AT1-Cerulean resembled the native AT1 receptor regarding ligand binding and receptor activation. A high FRET efficiency of 24.7% between membrane-localized AT1-Cerulean and B2R-EYFP was observed with intact, non-stimulated cells. Confocal FRET microscopy further revealed that the AT1/B2 receptor heterodimer was functionally coupled to receptor desensitization mechanisms because activation of the AT1-Cerulean/B2R-EYFP heterodimer with a single agonist triggered the co-internalization of AT1/B2R. Receptor co-internalization was sensitive to inhibition of G protein-coupled receptor kinases, GRKs, as evidenced by a GRK-specific peptide inhibitor. In agreement with efficient AT1/B2R heterodimerization, confocal FRET imaging of co-enriched receptor proteins immobilized on agarose beads also detected a high FRET efficiency of 24.0%. Taken together confocal FRET imaging revealed efficient heterodimerization of co-enriched and cellular AT1/B2R, and GRK-dependent co-internalization of the AT1/B2R heterodimer. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca2+ signaling in ventricular myocytes.

    PubMed

    Park, Seon-Ah; Hong, Bing-Zhe; Ha, Ki-Chan; Kim, Uh-Hyun; Han, Myung-Kwan; Kwak, Yong-Geun

    2017-06-02

    Cyclic ADP-ribose (cADPR) releases Ca 2+ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca 2+ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca 2+ ([Ca 2+ ] i ) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca 2+ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca 2+ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.

  3. Synthesis and redox properties of fac-BrRe(CO)3[1,2-(PPh2)2-closo-1,2-C2B10H10]: The first structurally characterized rhenium carbonyl containing a carboranyl-based diphosphine ligand

    NASA Astrophysics Data System (ADS)

    Lin, Chen-Hao; Nesterov, Vladimir N.; Richmond, Michael G.

    2018-03-01

    The diphosphine 1,2-(PPh2)2-closo-1,2-C2B10H10 reacts with BrRe(CO)5 and fac-BrRe(CO)3(THF)2 to give fac-BrRe(CO)3[1,2-(PPh2)2-closo-1,2-C2B10H10] (1) in high yields (>80%). Compound 1 is the first structurally characterized rhenium carbonyl that contains an ancillary carborane-based diphosphine ligand. 1 has been characterized in solution by IR and NMR spectroscopies (1H and 31P), and the solid-state structure has been determined by X-ray diffraction analysis. The electrochemical properties of 1 have been investigated by cyclic voltammetry, and the composition of the DFT-computed HOMO and LUMO levels are discussed relative to the electrochemical data. The thermodynamics for the formation of 1 from the rhenium precursors BrRe(CO)5 and fac-BrRe(CO)3(THF)2 have been evaluated by DFT calculations.

  4. Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer.

    PubMed

    Hiraki, Masayuki; Maeda, Takahiro; Mehrotra, Neha; Jin, Caining; Alam, Maroof; Bouillez, Audrey; Hata, Tsuyoshi; Tagde, Ashujit; Keating, Amy; Kharbanda, Surender; Singh, Harpal; Kufe, Donald

    2018-01-01

    B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression. The results show that MUC1-C activates the BCL2A1 gene by an NF-κB p65-mediated mechanism, linking this pathway with the induction of EMT. The MCL-1 anti-apoptotic protein is also of importance for the survival of TNBC cells and is an attractive target for drug development. We found that inhibiting MCL-1 with the highly specific MS1 peptide results in the activation of the MUC1-C→NF-κB→BCL2A1 pathway. In addition, selection of TNBC cells for resistance to ABT-737, which inhibits BCL-2, BCL-xL and BCL-W but not MCL-1 or BCL2A1, is associated with the upregulation of MUC1-C and BCL2A1 expression. Targeting MUC1-C in ABT-737-resistant TNBC cells suppresses BCL2A1 and induces death, which is of potential therapeutic importance. These findings indicate that MUC1-C is a target for the treatment of TNBCs unresponsive to agents that inhibit anti-apoptotic members of the BCL-2 family.

  5. Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reimers, Kerstin; Buchholz, Katja; Werchau, Hermann

    2005-01-20

    Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cellsmore » revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.« less

  6. 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)

  7. High-Resolution Synchrotron Infrared Spectroscopy of Thiophosgene: the νb{1}, νb{5}, 2νb{4}, and νb{2} + 2νb{6} bands

    NASA Astrophysics Data System (ADS)

    McKellar, Bob; Billinghurst, Brant E.

    2015-06-01

    Thiophosgene (Cl_2CS) is a favorite model system for studies of photophysics, vibrational dynamics, and intersystem interactions. But at high resolution its infrared spectrum is very congested due to hot bands and multiple isotopic species. Previously, we reported the first high resolution IR study of this molecule, analyzing the νb{2} (504 wn) and νb{4} (471 wn) fundamental bands. Here we continue, with analysis of the νb{1} (1139 wn) and νb{5} (820 wn) fundamentals for the two most abundant isotopologues, 35Cl2CS and 35Cl37ClCS, based on spectra with a resolution of about 0.001 wn obtained at the Canadian Light Source far-infrared beamline using synchrotron radiation and a Bruker IFS125 Fourier transform spectrometer. The νb{2} + νb{4} (942 wn) and νb{2} + 2νb{6} (1104 wn) bands are also studied here. But so far the νb{2} + νb{6} combination band (795 wn) resists analysis, as do the weak νb{3} (292.9 wn) and νb{6} (≈300? wn) fundamentals. A.R.W. McKellar, B.E.Billinghurst, J. Mol. Spectrosc. 260, 66 (2010).

  8. Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

    PubMed Central

    Laddha, Naresh C.; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Patel, Hetanshi H.; Agarwal, Nishtha; Shah, Anish M.; Begum, Rasheedunnisa

    2014-01-01

    Background Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. Objectives Aim of the present study was to explore NPY promoter −399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter −511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo. Methods PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B −511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. Results Genotype and allele frequencies for NPY −399T/C, +1128T/C and IL1B −511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001) between patients and controls. ‘TC’ haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001). Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029), in patients with active than stable vitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. Conclusion Our results suggest that NPY −399T/C, +1128T/C and IL1B −511C/T polymorphisms are associated with vitiligo and IL1B −511C/T SNP influences its transcript levels leading to increased risk for vitiligo in

  9. Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.

    PubMed

    Wei, Wei; Guo, Haoran; Ma, Min; Markham, Richard; Yu, Xiao-Fang

    2016-06-01

    Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution. Copyright © 2016. Published by Elsevier B.V.

  10. Asymmetric Conjugated Molecules Based on [1]Benzothieno[3,2-b][1]benzothiophene for High-Mobility Organic Thin-Film Transistors: Influence of Alkyl Chain Length.

    PubMed

    He, Keqiang; Li, Weili; Tian, Hongkun; Zhang, Jidong; Yan, Donghang; Geng, Yanhou; Wang, Fosong

    2017-10-11

    Herein, we report the synthesis and characterization of a series of [1]benzothieno[3,2-b][1]benzothiophene (BTBT)-based asymmetric conjugated molecules, that is, 2-(5-alkylthiophen-2-yl)[1]benzothieno[3,2-b][1]benzothiophene (BTBT-Tn, in which T and n represent thiophene and the number of carbons in the alkyl group, respectively). All of the molecules with n ≥ 4 show mesomorphism and display smectic A, smectic B (n = 4), or smectic E (n > 4) phases and then crystalline phases in succession upon cooling from the isotropic state. Alkyl chain length has a noticeable influence on the microstructures of vacuum-deposited films and therefore on the performance of the organic thin-film transistors (OTFTs). All molecules except for 2-(thiophen-2-yl)[1]benzothieno[3,2-b][1]benzothiophene and 2-(5-ethylthiophen-2-yl)[1]benzothieno[3,2-b][1]benzothiophene showed OTFT mobilities above 5 cm 2 V -1 s -1 . 2-(5-Hexylthiophen-2-yl)[1]benzothieno[3,2-b][1]benzothiophene and 2-(5-heptylthiophen-2-yl)[1]benzothieno[3,2-b][1]benzothiophene showed the greatest OTFT performance with reliable hole mobilities (μ) up to 10.5 cm 2 V -1 s -1 because they formed highly ordered and homogeneous films with diminished grain boundaries.

  11. Characterization of the Human SNM1A and SNM1B/Apollo DNA Repair Exonucleases*

    PubMed Central

    Sengerová, Blanka; Allerston, Charles K.; Abu, Mika; Lee, Sook Y.; Hartley, Janet; Kiakos, Konstantinos; Schofield, Christopher J.; Hartley, John A.; Gileadi, Opher; McHugh, Peter J.

    2012-01-01

    Human SNM1A and SNM1B/Apollo have both been implicated in the repair of DNA interstrand cross-links (ICLs) by cellular studies, and SNM1B is also required for telomere protection. Here, we describe studies on the biochemical characterization of the SNM1A and SNM1B proteins. The results reveal some fundamental differences in the mechanisms of the two proteins. Both SNM1A and SNM1B digest double-stranded and single-stranded DNA with a 5′-to-3′ directionality in a reaction that is stimulated by divalent cations, and both nucleases are inhibited by the zinc chelator o-phenanthroline. We find that SNM1A has greater affinity for single-stranded DNA over double-stranded DNA that is not observed with SNM1B. Although both proteins demonstrate a low level of processivity on low molecular weight DNA oligonucleotide substrates, when presented with high molecular weight DNA, SNM1A alone is rendered much more active, being capable of digesting kilobase-long stretches of DNA. Both proteins can digest past ICLs induced by the non-distorting minor groove cross-linking agent SJG-136, albeit with SNM1A showing a greater capacity to achieve this. This is consistent with the proposal that SNM1A and SNM1B might exhibit some redundancy in ICL repair. Together, our work establishes differences in the substrate selectivities of SNM1A and SNM1B that are likely to be relevant to their in vivo roles and which might be exploited in the development of selective inhibitors. PMID:22692201

  12. Congenital glaucoma and CYP1B1: an old story revisited.

    PubMed

    Alsaif, Hessa S; Khan, Arif O; Patel, Nisha; Alkuraya, Hisham; Hashem, Mais; Abdulwahab, Firdous; Ibrahim, Niema; Aldahmesh, Mohammed A; Alkuraya, Fowzan S

    2018-03-19

    Primary congenital glaucoma is a trabecular meshwork dysgenesis with resultant increased intraocular pressure and ocular damage. CYP1B1 mutations remain the most common identifiable genetic cause. However, important questions about the penetrance of CYP1B1-related congenital glaucoma remain unanswered. Furthermore, mutations in other genes have been described although their exact contribution and potential genetic interaction, if any, with CYP1B1 mutations are not fully explored. In this study, we employed modern genomic approaches to re-examine CYP1B1-related congenital glaucoma. A cohort of 193 patients (136 families) diagnosed with congenital glaucoma. We identified biallelic CYP1B1 mutations in 80.8% (87.5 and 66.1% in familial and sporadic cases, respectively, p < 0.0086). The large family size of the study population allowed us to systematically examine penetrance of all identified alleles. With the exception of c.1103G>A (p.R368H), previously reported pathogenic mutations were highly penetrant (91.2%). We conclude from the very low penetrance and genetic epidemiological analyses that c.1103G>A (p.R368H) is unlikely to be a disease-causing recessive mutation in congenital glaucoma as previously reported. All cases that lacked biallelic CYP1B1 mutations underwent whole exome sequencing. No mutations in LTBP2, MYOC or TEK were encountered. On the other hand, mutations were identified in genes linked to other ophthalmic phenotypes, some inclusive of glaucoma, highlighting conditions that might phenotypically overlap with primary congenital glaucoma (SLC4A4, SLC4A11, CPAMD8, and KERA). We also encountered candidate causal variants in genes not previously linked to human diseases: BCO2, TULP2, and DGKQ. Our results both expand and refine the genetic spectrum of congenital glaucoma with important clinical implications.

  13. Development of (6R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis

    PubMed Central

    2018-01-01

    Discovery of the potent antileishmanial effects of antitubercular 6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles and 7-substituted 2-nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazines stimulated the examination of further scaffolds (e.g., 2-nitro-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]oxazepines), but the results for these seemed less attractive. Following the screening of a 900-compound pretomanid analogue library, several hits with more suitable potency, solubility, and microsomal stability were identified, and the superior efficacy of newly synthesized 6R enantiomers with phenylpyridine-based side chains was established through head-to-head assessments in a Leishmania donovani mouse model. Two such leads (R-84 and R-89) displayed promising activity in the more stringent Leishmania infantum hamster model but were unexpectedly found to be potent inhibitors of hERG. An extensive structure–activity relationship investigation pinpointed two compounds (R-6 and pyridine R-136) with better solubility and pharmacokinetic properties that also provided excellent oral efficacy in the same hamster model (>97% parasite clearance at 25 mg/kg, twice daily) and exhibited minimal hERG inhibition. Additional profiling earmarked R-6 as the favored backup development candidate. PMID:29461823

  14. EXAFS spectrum peculiarities of Y 1- xYb xNi 2B 2C

    NASA Astrophysics Data System (ADS)

    Cortes, R.; Fomicheva, L. N.; Menushenkov, A. P.; Meyer-Klaucke, W.; Konarev, P. V.; Tsvyashchenko, A. V.

    2001-09-01

    The results on the temperature dependent EXAFS studies of the local structure peculiarities of Y 1- xYb xNi 2B 2C series synthesized at a high pressure of 8 GPa are presented. The interrelation between the local structure of Y 1- xYb xNi 2B 2C and its superconducting and magnetic properties was observed supporting the model where the contributions from all type of the nearest atoms to the electron-phonon coupling are important and cannot be neglected.

  15. Measurements of Radiofrequency Radiation with a Body-Borne Exposimeter in Swedish Schools with Wi-Fi.

    PubMed

    Hedendahl, Lena K; Carlberg, Michael; Koppel, Tarmo; Hardell, Lennart

    2017-01-01

    Wireless access to the Internet is now commonly used in schools. Many schools give each student their own laptop and utilize the laptops and wireless fidelity (Wi-Fi) connection for educational purposes. Most children also bring their own mobile phones to school. Since children are obliged by law to attend school, a safe environment is important. Lately, it has been discussed if radiofrequency (RF) radiation can have long-term adverse effects on children's health. This study conducted exposimetric measurements in schools to assess RF emissions in the classroom by measuring the teachers' RF exposure in order to approximate the children's exposure. Teachers in grades 7-12 carried a body-borne exposimeter, EME-Spy 200, in school during 1-4 days of work. The exposimeter can measure 20 different frequency bands from 87 to 5,850 MHz. Eighteen teachers from seven schools participated. The mean exposure to RF radiation ranged from 1.1 to 66.1 µW/m 2 . The highest mean level, 396.6 µW/m 2 , occurred during 5 min of a lesson when the teacher let the students stream and watch YouTube videos. Maximum peaks went up to 82,857 µW/m 2 from mobile phone uplink. Our measurements are in line with recent exposure studies in schools in other countries. The exposure levels varied between the different Wi-Fi systems, and if the students were allowed to use their own smartphones on the school's Wi-Fi network or if they were connected to GSM/3G/4G base stations outside the school. An access point over the teacher's head gave higher exposure compared with a school with a wired Internet connection for the teacher in the classroom. All values were far below International Commission on Non-Ionizing Radiation Protection's reference values, but most mean levels measured were above the precautionary target level of 3-6 µW/m 2 as proposed by the Bioinitiative Report. The length of time wireless devices are used is an essential determinant in overall exposure. Measures to minimize

  16. A WiFi public address system for disaster management.

    PubMed

    Andrade, Nicholas; Palmer, Douglas A; Lenert, Leslie A

    2006-01-01

    The WiFi Bullhorn is designed to assist emergency workers in the event of a disaster situation by offering a rapidly configurable wireless of public address system for disaster sites. The current configuration plays either pre recorded or custom recorded messages and utilizes 802.11b networks for communication. Units can be position anywhere wireless coverage exists to help manage crowds or to recall first responders from dangerous areas.

  17. A WiFi Public Address System for Disaster Management

    PubMed Central

    Andrade, Nicholas; Palmer, Douglas A.; Lenert, Leslie A.

    2006-01-01

    The WiFi Bullhorn is designed to assist emergency workers in the event of a disaster situation by offering a rapidly configurable wireless public address system for disaster sites. The current configuration plays either pre recorded or custom recorded messages and utilizes 802.11b networks for communication. Units can be position anywhere wireless coverage exists to help manage crowds or to recall first responders from dangerous areas. PMID:17238466

  18. OVA-bound nanoparticles induce OVA-specific IgG1, IgG2a, and IgG2b responses with low IgE synthesis.

    PubMed

    Yanase, Noriko; Toyota, Hiroko; Hata, Kikumi; Yagyu, Seina; Seki, Takahiro; Harada, Mitsunori; Kato, Yasuki; Mizuguchi, Junichiro

    2014-10-14

    There is an urgent requirement for a novel vaccine that can stimulate immune responses without unwanted toxicity, including IgE elevation. We examined whether antigen ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) with average diameter of 110nm would serve as an immune adjuvant. When BALB/c mice were immunized with OVA-NPs, they developed sufficient levels of OVA-specific IgG1 antibody responses with low levels of IgE synthesis, representing helper T (Th)2-mediated humoral immunity. OVA-specific IgG2a and IgG2b responses (i.e., Th1-mediated immunity) were also induced by secondary immunization with OVA-NPs. As expected, immunization with OVA in alum (OVA-alum) stimulated humoral immune responses, including IgG1 and IgE antibodies, with only low levels of IgG2a/IgG2b antibodies. CD4-positive T cells from mice primed with OVA-NPs produced substantial levels of IL-21 and IL-4, comparable to those from OVA-alum group. The irradiated mice receiving OVA-NPs-primed B cells together with OVA-alum-primed T cells exhibited enhanced anti-OVA IgG2b responses relative to OVA-alum-primed B cells and T cells following stimulation with OVA-NPs. Moreover, when OVA-NPs-primed, but not OVA-alum-primed, B cells were cultured in the presence of anti-CD40 monoclonal antibody, IL-4, and IL-21, or LPS plus TGF-β in vitro, OVA-specific IgG1 or IgG2b antibody responses were elicited, suggesting that immunization with OVA-NPs modulates B cells to generate IgG1 and IgG2b responses. Thus, OVA-NPs might exert their adjuvant action on B cells, and they represent a promising potential vaccine for generating both IgG1 and IgG2a/IgG2b antibody responses with low IgE synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Electronic Warfare Systems Career Ladder, AFSC 456X1A/B.

    DTIC Science & Technology

    1991-04-01

    En .. 𔃾- (AS L o t.. 4 - 0 L. 0 IXtC SL U41 .004- -C . W a 3 2 ) P- C XL x1. C4’ X O b .4 -J L. 0...2 Im 1m 1 AL/HRD/ID 1 1M lm/lh1 ARMY OCCUPATIONAL SURVEY BRANCH 1 CCAF/AYX 1 DEFENSE TECHNICAL INFORMATION CENTER 2 DE1 3 , USAFOMS (KEESLER AFB MS) 1...1 i HQ AFISC/DAP 2 HQ AFLC/DPMAE 3 HQ AFSC/DPAL 3 3 HQ AFSC/TTA 1 1 HQ ATC/DPAE 3 3 HQ ATC/TTOA 2 1 HQ ESC/DPTE 3 3 HQ ESC/TTA 1 1 HQ MAC/DPAT 3 3

  20. 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.

  1. 3-Phenylpropanoic acid-based phosphotyrosine (pTyr) mimetics: hit evolution to a novel orally active protein tyrosine phosphatase 1B (PTP1B) inhibitor.

    PubMed

    Tang, Yan-Bo; Liu, Jun-Zheng; Zhang, Shu-En; Du, Xin; Nie, Feilin; Tian, Jin-Ying; Ye, Fei; Huang, Kai; Hu, Jin-Ping; Li, Yan; Xiao, Zhiyan

    2014-05-01

    Protein tyrosine phosphatase 1B (PTP1B) is a promising therapeutic target for type 2 diabetes. Herein, we report the evolution of a previously identified 3-phenylpropanoic acid-based PTP1B inhibitor to an orally active lead compound. A series of 3-phenylpropanoic acid-based PTP1B inhibitors were synthesized, and three of them, 3-(4-(9H-carbazol-9-yl)phenyl)-5-(3,5-di-tert-butyl-4-methoxyphenyl)-5-oxopentanoic acid (9), 3-(4-(9H-carbazol-9-yl)phenyl)-5-(4'-bromo-[1,1'-biphenyl]-4-yl)-5-oxopentanoic acid (10) and 3-(4-(9H-carbazol-9-yl)-2-fluorophenyl)-5-(4-cyclohexylphenyl)-5-oxopentanoic acid (16), showed IC50 values at sub-micromolar level. Further in vivo evaluation indicated the sodium salt of 9 not only exhibited significant insulin-sensitizing and hypoglycemia effects, but also decreased the serum levels of triglyceride and total cholesterol in high-fat-diet-induced insulin resistance model mice. Preliminary in vivo pharmacokinetic studies on the sodium salt of 9 revealed its pharmacokinetic profile after oral administration in rats. These results provide proof-of-concept for the dual effects of PTP1B inhibitors on both glucose and lipid metabolisms. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Endophilin B1

    PubMed Central

    Cheung, Zelda H

    2009-01-01

    Endophilin B1 is a member of the endophilin family that is localized predominantly to intracellular membranes. Also known as Bax-interacting factor-1 (Bif-1), this protein has been observed to regulate the membrane dynamics of various intracellular compartments, such as the control of mitochondrial morphology and autophagosome formation in fibroblast. Endophilin B1 is expressed in the brain, but its functions in neurons had remained unknown. Recently, we have observed a novel role of endophilin B1 in neurons where it controls the trafficking of TrkA, cognate receptor for the prototypic neurotrophin nerve growth factor (NGF). Knock-down of endophilin B1 expression induces precocious targeting of NGF/TrkA to late endosomes and lysosomes, thereby leading to reduced TrkA levels. This is accompanied by marked attenuation of NGF-induced gene transcription and neurite outgrowth. Our observations suggest that endophilin B1 regulates TrkA level and downstream functions by controlling the movement of TrkA to late endosomes/lysosomes, possibly acting at the level of early endosomes. PMID:19704909

  3. Crystal structures of the coil 2B fragment and the globular tail domain of human lamin B1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ruan, Jianbin; Xu, Chao; Bian, Chuanbing

    2012-07-18

    We present here the crystal structures of human lamin B1 globular tail domain and coiled 2B domain, which adopt similar folds to Ig-like domain and coiled-coil domain of lamin A, respectively. Despite the overall similarity, we found an extra intermolecular disulfide bond in the lamin B1 coil 2B domain, which does not exist in lamin A/C. In addition, the structural analysis indicates that interactions at the lamin B1 homodimer interface are quite different from those of lamin A/C. Thus our research not only reveals the diversely formed homodimers among lamin family members, but also sheds light on understanding the importantmore » roles of lamin B1 in forming the nuclear lamina matrix.« less

  4. 26 CFR 1.410(b)-1 - Minimum coverage requirements (before 1994).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... plan satisfies section 410(b)(1) if it satisfies the requirements of paragraph (b)(1) or (b)(2) of this... this subparagraph if it benefits— (i) Seventy percent or more of all employees, or (ii) Eighty percent... requirements of section 410(b)(1) and this subparagraph if it benefits such employees as qualify under a...

  5. Engineering a Catabolic Pathway in Plants for the Degradation of 1,2-Dichloroethane1[OA

    PubMed Central

    Mena-Benitez, Gilda L.; Gandia-Herrero, Fernando; Graham, Stuart; Larson, Tony R.; McQueen-Mason, Simon J.; French, Christopher E.; Rylott, Elizabeth L.; Bruce, Neil C.

    2008-01-01

    Plants are increasingly being employed to clean up environmental pollutants such as heavy metals; however, a major limitation of phytoremediation is the inability of plants to mineralize most organic pollutants. A key component of organic pollutants is halogenated aliphatic compounds that include 1,2-dichloroethane (1,2-DCA). Although plants lack the enzymatic activity required to metabolize this compound, two bacterial enzymes, haloalkane dehalogenase (DhlA) and haloacid dehalogenase (DhlB) from the bacterium Xanthobacter autotrophicus GJ10, have the ability to dehalogenate a range of halogenated aliphatics, including 1,2-DCA. We have engineered the dhlA and dhlB genes into tobacco (Nicotiana tabacum ‘Xanthi’) plants and used 1,2-DCA as a model substrate to demonstrate the ability of the transgenic tobacco to remediate a range of halogenated, aliphatic hydrocarbons. DhlA converts 1,2-DCA to 2-chloroethanol, which is then metabolized to the phytotoxic 2-chloroacetaldehyde, then chloroacetic acid, by endogenous plant alcohol dehydrogenase and aldehyde dehydrogenase activities, respectively. Chloroacetic acid is dehalogenated by DhlB to produce the glyoxylate cycle intermediate glycolate. Plants expressing only DhlA produced phytotoxic levels of chlorinated intermediates and died, while plants expressing DhlA together with DhlB thrived at levels of 1,2-DCA that were toxic to DhlA-expressing plants. This represents a significant advance in the development of a low-cost phytoremediation approach toward the clean-up of halogenated organic pollutants from contaminated soil and groundwater. PMID:18467461

  6. Biomimetic Synthesis of Macahydantoins A and B from Lepidium meyenii, and Structure Revision of Macahydantoin B as a Class of Thiohydantoin with a 4-Methyl-hexahydropyrrolo[1,2-c]imidazole Skeleton.

    PubMed

    Zhou, Min; Ma, Hang-Ying; Xing, Huan-Huan; Li, Ping; Li, Gan-Peng; Geng, Hui-Chun; Hu, Qiu-Fen; Yang, Guang-Yu

    2017-09-15

    Phytochemical investigation on Lepidium meyenii led to the discovery of macahydantoin C (3), a new thiohydantoin with a 1,3-diazabicyclo[3.3.1]nonane core, the spectral properties of which indicate a potential structural misassignment of its previously reported analogue, macahydantoin B (2a). To probe this hypothesis, a concise, scalable, and biomimetic synthesis of the originally proposed 2a and its revised structure (2b) was efficiently accomplished using the modified Edman degradation as the key step from commercially available materials in 65% (three steps) and 52% (three steps) overall yields, respectively. These synthetic endeavors undoubtedly reassigned the structure of macahydantoin B as an unreported type of thiohydantoin featuring a 4-methyl-hexahydropyrrolo[1,2-c]imidazole scaffold.

  7. Glycyrrhetinic acid exhibits strong inhibitory effects towards UDP-glucuronosyltransferase (UGT) 1A3 and 2B7.

    PubMed

    Huang, Yin-Peng; Cao, Yun-Feng; Fang, Zhong-Ze; Zhang, Yan-Yan; Hu, Cui-Min; Sun, Xiao-Yu; Yu, Zhen-Wen; Zhu, Xu; Hong, Mo; Yang, Lu; Sun, Hong-Zhi

    2013-09-01

    The aim of the present study is to evaluate the inhibitory effects of liver UDP-glucuronosyltransferases (UGTs) by glycyrrhizic acid and glycyrrhetinic acid, which are the bioactive ingredients isolated from licorice. The results showed that glycyrrhetinic acid exhibited stronger inhibition towards all the tested UGT isoforms, indicating that the deglycosylation process played an important role in the inhibitory potential towards UGT isoforms. Furthermore, the inhibition kinetic type and parameters were determined for the inhibition of glycyrrhetinic acid towards UGT1A3 and UGT2B7. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A3 and UGT2B7 by glycyrrhetinic acid was best fit to competitive and noncompetitive type, respectively. The second plot using the slopes from Lineweaver-Burk plots versus glycyrrhetinic acid concentrations was employed to calculate the inhibition kinetic parameters (K(i)), and the values were calculated to be 0.2 and 1.7 μM for UGT1A3 and UGT2B7, respectively. All these results remind us the possibility of UGT inhibition-based herb-drug interaction. However, the explanation of these in vitro parameters should be paid more caution due to complicated factors, including the probe substrate-dependent UGT inhibition behaviour, environmental factors affecting the abundance of herbs' ingredients, and individual difference of pharmacokinetic factors. Copyright © 2012 John Wiley & Sons, Ltd.

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

    PubMed

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

    2014-12-01

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

  9. Effectiveness and predictors of success of noninvasive ventilation during H1N1 pandemics: a multicenter study.

    PubMed

    Nicolini, A; Tonveronachi, E; Navalesi, P; Antonelli, M; Valentini, I; Melotti, R M; Pigna, A; Carrassi, A; Righini, P; Ferrari Bravo, M; Pelosi, P; Nicoli, F; Cosentini, R; Vaschetto, R; Faenza, S; Nava, S

    2012-12-01

    The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure. In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO2<300 were eligible for study; 38/98 required immediate ETI, while the others received NIV as a first line therapy; 13/60 patients failed NIV and were intubated after 5.8+5.5 hours from enrolment. The remaining 47/60 patients were successfully ventilated with NIV. Hospital mortality was significantly higher in those patients who failed NIV vs. those who succeeded (53.8% vs. 2.1%; OR=0.52, P<0.001). ETI was associated with higher number of infectious complications, mainly sepsis and septic shock. The OR of having one of these events in the NIV failure group vs. NIV success was 16.7, P<0.001. According to logistic regression model, a SAPS II>29 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI. The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

  10. BPN, a marine-derived PTP1B inhibitor, activates insulin signaling and improves insulin resistance in C2C12 myotubes.

    PubMed

    Xu, Qi; Luo, Jiao; Wu, Ning; Zhang, Renshuai; Shi, Dayong

    2018-01-01

    Insulin resistance is a key feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling cascade and has attracted intensive investigation in recent T2DM therapy study. BPN, a marine-derived bromophenol compound, was isolated from the red alga Rhodomela confervoides. This study investigated the effects of BPN on the insulin signaling pathway in insulin-resistant C2C12 myotubes by inhibiting PTP1B. Molecular docking study and analysis of small- molecule interaction with PTP1B all showed BPN inhibited PTP1B activity via binding to the catalytic site through hydrogen bonds. We then found that BPN permeated into C2C12 myotubes, on the one hand, activated insulin signaling in an insulin-independent manner in C2C12 cells; on the other hand, ameliorated palmitate-induced insulin resistance through augmenting insulin sensitivity. Moreover, our studies also showed that PTP1B inhibition by BPN increased glucose uptake in normal and insulin-resistant C2C12 myotubes through glucose transporter 4 (GLUT4) translocation. Taken together, BPN activates insulin signaling and alleviates insulin resistance and represents a potential candidate for further development as an antidiabetic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. NGTS-1b: a hot Jupiter transiting an M-dwarf

    NASA Astrophysics Data System (ADS)

    Bayliss, Daniel; Gillen, Edward; Eigmüller, Philipp; McCormac, James; Alexander, Richard D.; Armstrong, David J.; Booth, Rachel S.; Bouchy, François; Burleigh, Matthew R.; Cabrera, Juan; Casewell, Sarah L.; Chaushev, Alexander; Chazelas, Bruno; Csizmadia, Szilard; Erikson, Anders; Faedi, Francesca; Foxell, Emma; Gänsicke, Boris T.; Goad, Michael R.; Grange, Andrew; Günther, Maximilian N.; Hodgkin, Simon T.; Jackman, James; Jenkins, James S.; Lambert, Gregory; Louden, Tom; Metrailler, Lionel; Moyano, Maximiliano; Pollacco, Don; Poppenhaeger, Katja; Queloz, Didier; Raddi, Roberto; Rauer, Heike; Raynard, Liam; Smith, Alexis M. S.; Soto, Maritza; Thompson, Andrew P. G.; Titz-Weider, Ruth; Udry, Stéphane; Walker, Simon R.; Watson, Christopher A.; West, Richard G.; Wheatley, Peter J.

    2018-04-01

    We present the discovery of NGTS-1b, a hot Jupiter transiting an early M-dwarf host (Teff,* = 3916 ^{+71}_{-63} K) in a P = 2.647 d orbit discovered as part of the Next Generation Transit Survey (NGTS). The planet has a mass of 0.812 ^{+0.066}_{-0.075} MJ, making it the most massive planet ever discovered transiting an M-dwarf. The radius of the planet is 1.33 ^{+0.61}_{-0.33} RJ. Since the transit is grazing, we determine this radius by modelling the data and placing a prior on the density from the population of known gas giant planets. NGTS-1b is the third transiting giant planet found around an M-dwarf, reinforcing the notion that close-in gas giants can form and migrate similar to the known population of hot Jupiters around solar-type stars. The host star shows no signs of activity, and the kinematics hint at the star being from the thick disc population. With a deep (2.5 per cent) transit around a K = 11.9 host, NGTS-1b will be a strong candidate to probe giant planet composition around M-dwarfs via James Webb Space Telescope transmission spectroscopy.

  12. B2+L2{sub 1} ordering in Co{sub 2}MnAl Heusler alloy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vinesh, A., E-mail: attatappa85@gmail.com; Sudheesh, V. D.; Lakshmi, N.

    Magnetic and structural properties of B2 ordered Co{sub 2}MnAl Heusler alloy have been studied by X-ray diffraction and DC magnetization techniques. X-ray diffractogram shows the structure is of B2 type with preferential site disorder between Mn and Al atoms and presence of a small L2{sub 1} phase. DC magnetization studies at low temperature establish that the antiferromagnetic nature arises mainly due to the antiparallel coupling of spin moments of 3d electrons of Co with Mn atoms. Curie temperature (T{sub c}) is 733 K which is close to T{sub c} of the L2{sub 1} phase.

  13. Anti-human neutrophil antigen-1a, -1b, and -2 antibodies in neonates and children with immune neutropenias analyzed by extracted granulocyte antigen immunofluorescence assay.

    PubMed

    Onodera, Rie; Kurita, Emi; Taniguchi, Kikuyo; Karakawa, Shuhei; Okada, Satoshi; Kihara, Hirotaka; Fujii, Teruhisa; Kobayashi, Masao

    2017-11-01

    Anti-human neutrophil antigen (HNA) antibodies have been implicated in the development of neonatal alloimmune neutropenia (NAN) and autoimmune neutropenia (AIN). There are many conventional assay methods that detect anti-HNA antibodies. However, a method to measure multiple samples and detect several anti-HNA antibodies simultaneously is needed. We developed a new method, the extracted granulocyte antigen immunofluorescence assay (EGIFA), to analyze anti-HNA-1a, -1b, and -2 antibodies in sera. The results obtained by EGIFA were evaluated in comparison with those from several standard assay methods. Anti-HNA antibodies in serum samples from nine familial cases with suspected NAN (n = 19) and children with suspected AIN (n = 88) were also measured by EGIFA. The evaluation of nine serum samples with anti-HNA antibodies suggested that EGIFA demonstrated equivalent specificity and superior sensitivity to monoclonal antibody-specific immobilization of granulocyte antigens and had comparable sensitivity to the granulocyte indirect immunofluorescence test. EGIFA successfully detected anti-HNA-1a or -1b antibodies in seven of nine familial cases with suspected NAN. EGIFA detected anti-HNA antibodies in 40.9% of children with suspected AIN. Among them, isolated anti-HNA-1a or -1b antibody was detected in 4.5 or 12.5% of children, respectively, and anti-HNA-2 antibody was identified in 3.4% of children. The 30.8% (16 of 52) of children negative for anti-HNA antibody by EGIFA were positive for anti-HLA antibody. EGIFA facilitated the measurement of anti-HNA-1a, -1b, and/or -2 antibodies in sera. The prompt measurement of anti-HNA antibodies will improve the diagnosis and clinical management of patients with suspected NAN or AIN. © 2017 AABB.

  14. Expression of fusion IL2-B7.1(IgV+C) and effects on T lymphocytes.

    PubMed

    Kong, Linghong; Li, Yaochen; Yang, Ye; Li, Kangsheng

    2007-12-01

    The search for an effective immunotherapeutic treatment for tumors is an important area of cancer research. To prepare a more effective form of the bifunctional fusion protein IL2-B7.1(IgV+C) and analyze its effect on the stimulation of T lymphocyte proliferation, we used DNAStar 5.03 software to predict the structural diversity and biochemical character of IL2-B7.1(IgV+C). We then prepared fusion protein IL2-B7.1(IgV+C) by establishing its prokaryotic expression system, and tested its effect on the stimulation of T lymphocytes in vitro. The results indicated that IL2-B7.1(IgV+C) correctly formed a secondary structure in which both IL2 and B7.1(IgV+C) maintained their original hydrophilicity and epitopes. Western blot analysis revealed that IL2-B7.1(IgV+C) was efficiently expressed. Our analysis of CTLL-2 and T-cell proliferation showed that recombinant human (rh) IL2-B7.1(IgV+C) exerted the combined stimulating effects of both rhIL2 and rh B7.1(IgV+C) on cell proliferation, and that these effects could be blocked by adding either anti-IL2 or anti-B7.1 monoclonal antibodies. A >2-fold increase in [3H]TdR incorporation compared with that of cells treated with recombinant protein IL2, or B7.1(IgV+C) alone, revealed that rhIL2-B7.1(IgV+C) had dose-dependent synergetic effects on T-cell activation in the presence of anti-CD3 monoclonal antibody. We concluded that the augmented potency of rhIL2-B7.1(IgV+C) resulted in a stronger stimulation of T-cell proliferation than either rhB7.1(IgV+C) or rhIL2 alone.

  15. High Throughput Synthesis of 2,3,6-Trisubstituted-5,6-Dihydroimidazo[2,1-b]thiazole Derivatives

    PubMed Central

    Li, Yangmei; Giulianotti, Marc; Houghten, Richard A.

    2011-01-01

    A facile approach to the synthesis of 2,3,6-trisubstituted-5,6-dihydroimidazo[2,1-b]thiazole was reported. A resin bound cyclic thiourea was formed by the treatment of a resin bound diamine with 1,1′-thiocarbonyldiimidazole, and then reacted with a α-haloketone to generate a resin bound isothiourea. HF treatment of the resin bound isothiourea resulted in the cleavage of the product and simultaneous formation of an enamine bond. This led to the formation of the 2,3,6-trisubstituted-5,6-dihydroimidazo[2,1-b]thiazole in high yield and purity. PMID:21461055

  16. High Throughput Synthesis of 2,3,6-Trisubstituted-5,6-Dihydroimidazo[2,1-b]thiazole Derivatives.

    PubMed

    Li, Yangmei; Giulianotti, Marc; Houghten, Richard A

    2011-02-09

    A facile approach to the synthesis of 2,3,6-trisubstituted-5,6-dihydroimidazo[2,1-b]thiazole was reported. A resin bound cyclic thiourea was formed by the treatment of a resin bound diamine with 1,1'-thiocarbonyldiimidazole, and then reacted with a α-haloketone to generate a resin bound isothiourea. HF treatment of the resin bound isothiourea resulted in the cleavage of the product and simultaneous formation of an enamine bond. This led to the formation of the 2,3,6-trisubstituted-5,6-dihydroimidazo[2,1-b]thiazole in high yield and purity.

  17. 7,12-Dimethylbenzanthracene induces apoptosis in RL95-2 human endometrial cancer cells: Ligand-selective activation of cytochrome P450 1B1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Ji Young; Medical Research Science Center, Dong-A University, Busan 602-714; Lee, Seung Gee

    2012-04-15

    7,12-Dimethylbenzanthracene (DMBA), a polycyclic aromatic hydrocarbon, exhibits mutagenic, carcinogenic, immunosuppressive, and apoptogenic properties in various cell types. To achieve these functions effectively, DMBA is modified to its active form by cytochrome P450 1 (CYP1). Exposure to DMBA causes cytotoxicity-mediated apoptosis in bone marrow B cells and ovarian cells. Although uterine endometrium constitutively expresses CYP1A1 and CYP1B1, their apoptotic role after exposure to DMBA remains to be elucidated. Therefore, we chose RL95-2 endometrial cancer cells as a model system for studying DMBA-induced cytotoxicity and cell death and hypothesized that exposure to DMBA causes apoptosis in this cell type following CYP1A1 and/ormore » CYP1B1 activation. We showed that DMBA-induced apoptosis in RL95-2 cells is associated with activation of caspases. In addition, mitochondrial changes, including decrease in mitochondrial potential and release of mitochondrial cytochrome c into the cytosol, support the hypothesis that a mitochondrial pathway is involved in DMBA-induced apoptosis. Exposure to DMBA upregulated the expression of AhR, Arnt, CYP1A1, and CYP1B1 significantly; this may be necessary for the conversion of DMBA to DMBA-3,4-diol-1,2-epoxide (DMBA-DE). Although both CYP1A1 and CYP1B1 were significantly upregulated by DMBA, only CYP1B1 exhibited activity. Moreover, knockdown of CYP1B1 abolished DMBA-induced apoptosis in RL95-2 cells. Our data show that RL95-2 cells are susceptible to apoptosis by exposure to DMBA and that CYP1B1 plays a pivotal role in DMBA-induced apoptosis in this system. -- Highlights: ► Cytotoxicity-mediated apoptogenic action of DMBA in human endometrial cancer cells. ► Mitochondrial pathway in DMBA-induced apoptosis of RL95-2 endometrial cancer cells. ► Requirement of ligand-selective activation of CYP1B1 in DMBA-induced apoptosis.« less

  18. HoxB2 binds mutant SOD1 and is altered in transgenic model of ALS.

    PubMed

    Zhai, Jinbin; Lin, Hong; Canete-Soler, Rafaela; Schlaepfer, William W

    2005-09-15

    Mutations in Cu/Zn superoxide dismutase (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis by a toxic gain of function; however, the precise mechanisms remain unclear. Here, we report the identification of HoxB2, a homeodomain-containing transcription factor, as a G93A mutant SOD1 interactive protein in a yeast two-hybrid screen. We show that HoxB2 co-precipitates and co-localizes with mutant SOD1 in neuronal cell lines, as well as in brain and spinal cord of G93A mutant SOD1 transgenic mice. Mutagenesis further shows that this interaction is mediated by the central homeodomain of HoxB2. In motor neuron-like NSC-34 cells, overexpression of HoxB2 or its homeodomain decreases the insolubility of mutant SOD1 and inhibits G93A or G86R mutant SOD1-induced neuronal cell death. In human and mouse tissues, we show that expression of HoxB2 persists in adult spinal cord and is primarily localized in nuclei of motor neurons. In G93A transgenic mice, HoxB2 co-localizes with mutant SOD1 and is redistributed to perikarya and proximal neurites of motor neurons. In addition, there is progressive accumulation of HoxB2 and mutant SOD1 as punctate inclusions in the neuropil surrounding motor neurons. Taken together, our findings demonstrate that interaction of HoxB2 with mutant SOD1 occurs in motor neurons of G93A mutant SOD1 transgenic mice and suggest that this interaction may modulate the neurotoxicity of mutant SOD1.

  19. O2(b1∑+g) relaxation in active medium of oxygen-iodine laser

    NASA Astrophysics Data System (ADS)

    Tolstov, G. I.; Zagidullin, M. V.; Khvatov, N. A.; Medvedkov, I. A.; Mikheyev, P. A.

    2018-04-01

    Rate constants for the removal of O2 b1∑+g by collisions with O2, N2, CO2 and H2O have been determined at temperature 297 K. O2(b1 ∑+g) was excited by pulses from a tunable dye laser, and the deactivation kinetics were followed by observing the temporal behavior of the b1∑+g - X3∑-g fluorescence. The removal rate constants for CO2, N2 and H2O were not strongly dependent on temperature, and could be represented by the expressions kCO2=(1.8+/-0.05)×10-16 kN2=(2.2 +/- 0.2)×10-15, and kH2O=(6.12+/-0.67)×10-12 cm3 molecule-1 s-1. Rate constant for O2(b1∑+ ) removal by O2(X), being orders of magnitude lower, represented by the fitted expression kO2=(3.67 +/- 0.06)×10-17 cm3 molecule-1 s-1. All of the rate constants measured at room temperature were found to be in good agreement with previously reported values.

  20. Novel Nine-Exon AR Transcripts (Exon 1/Exon 1b/Exons 2–8) in Normal and Cancerous Breast and Prostate Cells

    PubMed Central

    Hu, Dong Gui; McKinnon, Ross A.; Hulin, Julie-Ann; Mackenzie, Peter I.; Meech, Robyn

    2016-01-01

    Nearly 20 different transcripts of the human androgen receptor (AR) are reported with two currently listed as Refseq isoforms in the NCBI database. Isoform 1 encodes wild-type AR (type 1 AR) and isoform 2 encodes the variant AR45 (type 2 AR). Both variants contain eight exons: they share common exons 2–8 but differ in exon 1 with the canonical exon 1 in isoform 1 and the variant exon 1b in isoform 2. Splicing of exon 1 or exon 1b is reported to be mutually exclusive. In this study, we identified a novel exon 1b (1b/TAG) that contains an additional TAG trinucleotide upstream of exon 1b. Moreover, we identified AR transcripts in both normal and cancerous breast and prostate cells that contained either exon 1b or 1b/TAG spliced between the canonical exon 1 and exon 2, generating nine-exon AR transcripts that we have named isoforms 3a and 3b. The proteins encoded by these new AR variants could regulate androgen-responsive reporters in breast and prostate cancer cells under androgen-depleted conditions. Analysis of type 3 AR-GFP fusion proteins showed partial nuclear localization in PC3 cells under androgen-depleted conditions, supporting androgen-independent activation of the AR. Type 3 AR proteins inhibited androgen-induced growth of LNCaP cells. Microarray analysis identified a small set of type 3a AR target genes in LNCaP cells, including genes known to modulate growth and proliferation of prostate cancer (PCGEM1, PEG3, EPHA3, and EFNB2) or other types of human cancers (TOX3, ST8SIA4, and SLITRK3), and genes that are diagnostic/prognostic biomarkers of prostate cancer (GRINA3, and BCHE). PMID:28035996

  1. Interservice Procedures for Instructional Systems Development. Phase 1. Analyze

    DTIC Science & Technology

    1975-08-01

    exertion. 3. Kneeling or squatting . 4. Unusually cramped position. 5. Environmental conditions 1, Tropical environment. that influence task 2. Arctic...rerwuaiiiin s it tructiuna! settinqt s. -.--- No ruYle-s cni be stated that prescribe a Fi ’ spc ifir settiri for a Lask. Ho,.-ver, _"t B luidel&ines are given

  2. Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis.

    PubMed

    Jiang, Chuanhao; Xiao, Jinhong; Xie, Yafeng; Xiao, Yongjian; Wang, Chuan; Kuang, Xingxing; Xu, Man; Li, Ranhui; Zeng, Tiebing; Liu, Shuanquan; Yu, Jian; Zhao, Feijun; Wu, Yimou

    2016-02-01

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum, and accurate diagnosis is important for the prevention and treatment of syphilis. Here, to identify appropriate diagnostic antigens for serodiagnosis of syphilis, 6 recombinant proteins were expressed in Escherichia coli and purified, including flagellins (FlaB1 [Tp0868], FlaB2 [Tp0792], and FlaB3 [Tp0870]), Tp0463, Tp0751, and Tp1038. The sensitivities were determined by screening sera from individuals with primary (n=82), secondary (n=115), latent (n=105), and congenital (n=65) syphilis. The specificities were determined by screening sera from uninfected controls (n=30) and potentially cross-reactive infections including Lyme disease (n=30), leptospirosis (n=5), and hepatitis B (n=30). Our data showed that FlaB1, FlaB2, FlaB3, Tp0463, and Tp1038 exhibited higher overall sensitivities and specificities for detecting IgG antibody, with 95.4% and 98.9%, 92.6% and 95.8%, 95.1% and 95.8%, 92.6% and 97.9%, and 95.9% and 98.9%, respectively. In contrast, Tp0751 demonstrated only an overall sensitivity of 39.2%. For comparison, the sensitivity and specificity of Architect Syphilis TP were determined to be 98.1% and 93.7%, respectively. In addition, FlaB1, FlaB2, FlaB3, and Tp0463 demonstrated excellent performance for detecting IgM antibody in primary and congenital syphilis, with sensitivities of 76.8% and 83.1%, 72.0% and 87.7%, 74.4% and 89.2%, and 64.6% and 75.3%, respectively. These results indicate that FlaB1, FlaB2, FlaB3, and Tp0463 could be as novel diagnostic candidates for serodiagnosis of syphilis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    In the theory of star formation, the first hydrostatic core (FHSC) phase is a critical step in which a condensed object emerges from a prestellar core. This step lasts about one thousand years, a very short time compared with the lifetime of prestellar cores, and therefore is hard to detect unambiguously. We present IRAM Plateau de Bure observations of the Barnard 1b dense molecular core, combining detections of H2CO and CH3OH spectral lines and dust continuum at 2.3'' resolution (~500 AU). The two compact cores B1b-N and B1b-S are detected in the dust continuum at 2 mm, with fluxes that agree with their spectral energy distribution. Molecular outflows associated with both cores are detected. They are inclined relative to the direction of the magnetic field, in agreement with predictions of collapse in turbulent and magnetized gas with a ratio of mass to magnetic flux somewhat higher than the critical value, μ ~ 2-7. The outflow associated with B1b-S presents sharp spatial structures, with ejection velocities of up to ~7 km s-1 from the mean velocity. Its dynamical age is estimated to be ~2000 yr. The B1b-N outflow is smaller and slower, with a short dynamical age of ~1000 yr. The B1b-N outflow mass, mass-loss rate, and mechanical luminosity agree well with theoretical predictions of FHSC. These observations confirm the early evolutionary stage of B1b-N and the slightly more evolved stage of B1b-S. Based on observations carried out with the IRAM Plateau de Bure Interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain).Appendices are available in electronic form at http://www.aanda.orgFITS files for the H2CO and CH3OH mosaics are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/577/L2

  4. Probing the electronic properties of ternary A n M3n-1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity.

    PubMed

    Takeya, Hiroyuki; ElMassalami, Mohammed; Terrazos, Luis A; Rapp, Raul E; Capaz, Rodrigo B; Fujii, Hiroki; Takano, Yoshihiko; Doerr, Mathias; Granovsky, Sergey A

    2013-06-01

    We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh 2 B 2 -type ( Fddd ), while that of n = 3 is Ca 3 Rh 8 B 6 -type ( Fmmm ); the latter can be visualized as a stacking of structural fragments from AM 3 B 2 ( P 6/ mmm ) and AM 2 B 2 . The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol -1 K -2 , a Debye temperature θ D ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol -1 K -2 , θ D ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca 3 Rh 8 B 6 , T c = 4.0 K and H c2 = 14.5 kOe, while for Sr 3 Rh 8 B 6 , T c = 3.4 K and H c2 ≈ 4.0 kOe). These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS) calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, E F , of Ca 3 Rh 8 B 6 lies at almost the top of a pronounced local DOS peak, while that of CaRh 2 B 2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at E F , the contribution of the Rh atoms is the strongest.

  5. Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth

    PubMed Central

    KANO, YOSHIHIRO; KONNO, MASAMITSU; OHTA, KATSUYA; HARAGUCHI, NAOTSUGU; NISHIKAWA, SHIMPEI; KAGAWA, YOSHINORI; HAMABE, ATSUSHI; HASEGAWA, SHINICHIRO; OGAWA, HISATAKA; FUKUSUMI, TAKAHITO; NOGUCHI, YUKO; OZAKI, MIYUKI; KUDO, TOSHIHIRO; SAKAI, DAISUKE; SATOH, TAROH; ISHII, MASARU; MIZOHATA, EIICHI; INOUE, TAKESHI; MORI, MASAKI; DOKI, YUICHIRO; ISHII, HIDESHI

    2013-01-01

    Although esophageal cancer is highly heterogeneous and the involvement of epigenetic regulation of cancer stem cells is highly suspected, the biological significance of epigenetically modified molecules that regulate different subpopulations remains to be firmly established. Using esophageal cancer cells, we investigated the functional roles of the H3K4 demethylase Jumonji/Arid1b (Jarid1b) (Kdm5b/Plu-1/Rbp2-h1), an epigenetic factor that is required for continuous cell growth in melanoma. JARID1B knockdown resulted in the suppression of esophageal cancer cell growth, sphere formation and invasion ability and was associated with loss of epithelial marker expression. However, these inhibitory effects observed on tumor formation were reverted subsequent to subcutaneous inoculation of these cells into immune-deficient mice. These results indicated that JARID1B plays a role in maintaining cancer stem cells in the esophagus and justifies the rationale for studying the effects of continuous inhibition of this epigenetic factor in esophageal cancer. PMID:24649241

  6. The phase diagrams of a spin 1/2 core and a spin 1 shell nanoparticle with a disordered interface

    NASA Astrophysics Data System (ADS)

    Zaim, N.; Zaim, A.; Kerouad, M.

    2016-12-01

    The critical and compensation behaviors, of a spherical ferrimagnetic nanoparticle, consisting of a ferromagnetic core of spin-1/2 A atoms, a ferromagnetic shell of spin-1 B atoms and a disordered interface in between that is characterized by a random arrangement of A and B atoms of ApB1-p type and a negative A - B coupling, are studied. The ground state phase diagrams of the system have been determined in the (JAB, D/jA) and (JB, D/jA) planes. Monte Carlo simulation based on Metropolis algorithm has been used to study the effects of the concentration parameter p, the crystal field, the coupling between B - B atoms jB and the antiferromagnetic interface coupling jAB on the phase diagrams and the magnetic properties of the system. It has been found that one, two or even three compensation point(s) can appear for appropriate values of the system parameters.

  7. Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain.

    PubMed

    Gherasim, Alin; Martínez-Baz, Iván; Castilla, Jesús; Pozo, Francisco; Larrauri, Amparo

    2017-01-01

    Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010-2011 season to the 2015-2016 season in Spain. We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus.

  8. Crystal structure of (2R*,3aR*)-2-phenyl-sulfonyl-2,3,3a,4,5,6-hexa-hydro-pyrrolo-[1,2-b]isoxazole.

    PubMed

    Hernández, Yaiza; Marcos, Isidro; Garrido, Narciso M; Sanz, Francisca; Diez, David

    2017-01-01

    The title compound, C 12 H 15 NO 3 S, was prepared by 1,3-dipolar cyclo-addition of 3,4-di-hydro-2 H -pyrrole 1-oxide and phenyl vinyl sulfone. In the mol-ecule, both fused five-membered rings display a twisted conformation. In the crystal, C-H⋯O hydrogen bonds link neighbouring mol-ecules, forming chains running parallel to the b axis.

  9. Production of Autoantibodies by Murine B-1a Cells Stimulated with Helicobacter pylori Urease through Toll-Like Receptor 2 Signaling ▿ †

    PubMed Central

    Kobayashi, Fumiko; Watanabe, Eri; Nakagawa, Yohko; Yamanishi, Shingo; Norose, Yoshihiko; Fukunaga, Yoshitaka; Takahashi, Hidemi

    2011-01-01

    Helicobacter pylori infection is associated with several autoimmune diseases, in which autoantibody-producing B cells must be activated. Among these B cells, CD5-positive B-1a cells from BALB/c mice were confirmed to secrete autoantibodies when cocultured with purified H. pylori urease in the absence of T cells. To determine the mechanisms for autoantibody production, CD5-positive B-1a cells were sorted from murine spleen cells and stimulated with either purified H. pylori urease or H. pylori coated onto plates (referred to hereafter as plate-coated H. pylori), and autoantibody production was measured by enzyme-linked immunosorbent assay (ELISA). Complete urease was not secreted from H. pylori but was visually expressed over the bacterium-like endotoxin. Urease-positive plated-coated H. pylori stimulated B-1a cells to produce autoantibodies, although urease-deficient isotype-matched H. pylori did not. Autoantibody secretion by B-1a cells was inhibited when bacteria were pretreated with anti-H. pylori urease-specific antibody having neutralizing ability against urease enzymatic activity but not with anti-H. pylori urease-specific antibody without neutralizing capacity. The B-1a cells externally express various Toll-like receptors (TLRs): TLR1, TLR2, TLR4, and TLR6. Among the TLRs, blocking of TLR2 on B-1a cells with a specific monoclonal antibody (MAb), T2.5, inhibited autoantibody secretion when B-1a cells were stimulated with plate-coated H. pylori or H. pylori urease. Moreover, B-1a cells from TLR2-knockout mice did not produce those autoantibodies. The present study provides evidence that functional urease expressed on the surface of H. pylori will directly stimulate B-1a cells via innate TLR2 to produce various autoantibodies and may induce autoimmune disorders. PMID:21947775

  10. PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150

    PubMed Central

    Por, Elaine D.; Samelson, Bret K.; Belugin, Sergei; Akopian, Armen N.; Scott, John D.; Jeske, Nathaniel A.

    2011-01-01

    Activation of protein kinases and phosphatases at the plasma membrane often initiates agonist-dependent signalling events. In sensory neurons, AKAP150 (A-kinase-anchoring protein 150) orientates PKA (protein kinase A), PKC (protein kinase C) and the Ca2+/calmodulin-dependent PP2B (protein phosphatase 2B, also known as calcineurin) towards membrane-associated substrates. Recent evidence indicates that AKAP150-anchored PKA and PKC phosphorylate and sensitize the TRPV1 (transient receptor potential subfamily V type 1 channel, also known as the capsaicin receptor). In the present study, we explore the hypothesis that an AKAP150-associated pool of PP2B catalyses the dephosphorylation and desensitization of TRPV1. Biochemical, electrophysiological and cell-based experiments indicate that PP2B associates with AKAP150 and TRPV1 in cultured TG (trigeminal ganglia) neurons. Gene silencing of AKAP150 reduces basal phosphorylation of TRPV1. However, functional studies in neurons isolated from AKAP150−/− mice indicate that the anchoring protein is not required for pharmacological desensitization of TRPV1. Behavioural analysis of AKAP150−/− mice further support this notion, demonstrating that agonist-stimulated desensitization of TRPV1 is sensitive to PP2B inhibition and does not rely on AKAP150. These findings allow us to conclude that pharmacological desensitization of TRPV1 by PP2B may involve additional regulatory components. PMID:20883208

  11. PP2B/calcineurin-mediated desensitization of TRPV1 does not require AKAP150.

    PubMed

    Por, Elaine D; Samelson, Bret K; Belugin, Sergei; Akopian, Armen N; Scott, John D; Jeske, Nathaniel A

    2010-12-15

    Activation of protein kinases and phosphatases at the plasma membrane often initiates agonist-dependent signalling events. In sensory neurons, AKAP150 (A-kinase-anchoring protein 150) orientates PKA (protein kinase A), PKC (protein kinase C) and the Ca2+/calmodulin-dependent PP2B (protein phosphatase 2B, also known as calcineurin) towards membrane-associated substrates. Recent evidence indicates that AKAP150-anchored PKA and PKC phosphorylate and sensitize the TRPV1 (transient receptor potential subfamily V type 1 channel, also known as the capsaicin receptor). In the present study, we explore the hypothesis that an AKAP150-associated pool of PP2B catalyses the dephosphorylation and desensitization of TRPV1. Biochemical, electrophysiological and cell-based experiments indicate that PP2B associates with AKAP150 and TRPV1 in cultured TG (trigeminal ganglia) neurons. Gene silencing of AKAP150 reduces basal phosphorylation of TRPV1. However, functional studies in neurons isolated from AKAP150-/- mice indicate that the anchoring protein is not required for pharmacological desensitization of TRPV1. Behavioural analysis of AKAP150-/- mice further support this notion, demonstrating that agonist-stimulated desensitization of TRPV1 is sensitive to PP2B inhibition and does not rely on AKAP150. These findings allow us to conclude that pharmacological desensitization of TRPV1 by PP2B may involve additional regulatory components.

  12. Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers

    PubMed Central

    Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako; Chen, Xin; Wersto, Robert; Sen, Ranjan; Young, Howard A.; Croft, Michael; Ferrucci, Luigi; Biragyn, Arya

    2016-01-01

    B-cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL+ MHC class-IHi CD86Hi B cells of unknown origin. Here we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. The 4BL cells induce expression of 4-1BBL and IFNγR1 on B1a cells resulting in subsequent up regulation of membrane TNFα (mTNFα) and CD86. As a result, B1a cells induce expression of granzyme B in CD8+T cells by targeting TNFR2 via mTNFα while providing co-stimulation with CD86. Thus, for the first time, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8+T cells. PMID:26983789

  13. Reassortment between Influenza B Lineages and the Emergence of a Coadapted PB1–PB2–HA Gene Complex

    PubMed Central

    Dudas, Gytis; Bedford, Trevor; Lycett, Samantha; Rambaut, Andrew

    2015-01-01

    Influenza B viruses make a considerable contribution to morbidity attributed to seasonal influenza. Currently circulating influenza B isolates are known to belong to two antigenically distinct lineages referred to as B/Victoria and B/Yamagata. Frequent exchange of genomic segments of these two lineages has been noted in the past, but the observed patterns of reassortment have not been formalized in detail. We investigate interlineage reassortments by comparing phylogenetic trees across genomic segments. Our analyses indicate that of the eight segments of influenza B viruses only segments coding for polymerase basic 1 and 2 (PB1 and PB2) and hemagglutinin (HA) proteins have maintained separate Victoria and Yamagata lineages and that currently circulating strains possess PB1, PB2, and HA segments derived entirely from one or the other lineage; other segments have repeatedly reassorted between lineages thereby reducing genetic diversity. We argue that this difference between segments is due to selection against reassortant viruses with mixed-lineage PB1, PB2, and HA segments. Given sufficient time and continued recruitment to the reassortment-isolated PB1–PB2–HA gene complex, we expect influenza B viruses to eventually undergo sympatric speciation. PMID:25323575

  14. Dissemination and Persistence of blaCTX-M-9 Are Linked to Class 1 Integrons Containing CR1 Associated with Defective Transposon Derivatives from Tn402 Located in Early Antibiotic Resistance Plasmids of IncHI2, IncP1-α, and IncFI Groups

    PubMed Central

    Novais, Ângela; Cantón, Rafael; Valverde, Aránzazu; Machado, Elisabete; Galán, Juan-Carlos; Peixe, Luísa; Carattoli, Alessandra; Baquero, Fernando; Coque, Teresa M.

    2006-01-01

    This study analyzes the diversity of In60, a class 1 integron bearing CR1 and containing blaCTX-M-9, and its association with Tn402, Tn21, and classical conjugative plasmids among 45 CTX-M-9-producing clinical strains (41 Escherichia coli strains, 2 Klebsiella pneumoniae strains, 1 Salmonella enterica strain, and 1 Enterobacter cloacae strain). Forty-five patients in a Spanish tertiary care hospital were studied (1996 to 2003). The diversity of In60 and association of In60 with Tn402 or mercury resistance transposons were investigated by overlapping PCR assays and/or hybridization. Plasmid characterization included comparison of restriction fragment length polymorphism patterns and determination of incompatibility group by PCR-based replicon typing, sequencing, and hybridization. CTX-M-9 plasmids belonged to IncHI2 (n = 26), IncP-1α (n = 10), IncFI (n = 4), and IncI (n = 1) groups. Genetic platforms containing blaCTX-M-9 were classified in six types in relation to the In60 backbone and in eight subtypes in relation to Tn402 derivatives. They were associated with Tn21 sequences when located in IncP-1α or IncHI2 plasmids. Our study identified blaCTX-M-9 in a high diversity of CR1-bearing class 1 integrons linked to different Tn402 derivatives, often to Tn21, highlighting the role of recombination events in the evolution of antibiotic resistance plasmids. The presence of blaCTX-M-9 on broad-host-range IncP-1α plasmids might contribute to its dissemination to hosts that were not members of the family Enterobacteriaceae. PMID:16870767

  15. Testing Earthquake Links in Mexico From 1978 to the 2017 M = 8.1 Chiapas and M = 7.1 Puebla Shocks

    NASA Astrophysics Data System (ADS)

    Segou, Margarita; Parsons, Tom

    2018-01-01

    The <fi>M> = 8.1 Chiapas and the <fi>M> = 7.1 Puebla earthquakes occurred in the bending part of the subducting Cocos plate 11 days and 600 km apart, a range that puts them well outside the typical aftershock zone. We find this to be a relatively common occurrence in Mexico, with 14% of <fi>M> > 7.0 earthquakes since 1900 striking more than 300 km apart and within a 2 week interval, not different from a randomized catalog. We calculate the triggering potential caused by crustal stress redistribution from large subduction earthquakes over the last 40 years. There is no evidence that static stress transfer or dynamic triggering from the 8 September Chiapas earthquake promoted the 19 September earthquake. Both recent earthquakes were promoted by past thrust events instead, including delayed afterslip from the 2012 <fi>M> = 7.5 Oaxaca earthquake. A repeated pattern of shallow thrust events promoting deep intraslab earthquakes is observed over the past 40 years.

  16. Covalent Allosteric Inactivation of Protein Tyrosine Phosphatase 1B (PTP1B) by an Inhibitor-Electrophile Conjugate.

    PubMed

    Punthasee, Puminan; Laciak, Adrian R; Cummings, Andrea H; Ruddraraju, Kasi Viswanatharaju; Lewis, Sarah M; Hillebrand, Roman; Singh, Harkewal; Tanner, John J; Gates, Kent S

    2017-04-11

    Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target, but it has proven difficult to develop medicinally useful, reversible inhibitors of this enzyme. Here we explored covalent strategies for the inactivation of PTP1B using a conjugate composed of an active site-directed 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide inhibitor connected via a short linker to an electrophilic α-bromoacetamide moiety. Inhibitor-electrophile conjugate 5a caused time-dependent loss of PTP1B activity consistent with a covalent inactivation mechanism. The inactivation occurred with a second-order rate constant of (1.7 ± 0.3) × 10 2 M -1 min -1 . Mass spectrometric analysis of the inactivated enzyme indicated that the primary site of modification was C121, a residue distant from the active site. Previous work provided evidence that covalent modification of the allosteric residue C121 can cause inactivation of PTP1B [Hansen, S. K., Cancilla, M. T., Shiau, T. P., Kung, J., Chen, T., and Erlanson, D. A. (2005) Biochemistry 44, 7704-7712]. Overall, our results are consistent with an unusual enzyme inactivation process in which noncovalent binding of the inhibitor-electrophile conjugate to the active site of PTP1B protects the nucleophilic catalytic C215 residue from covalent modification, thus allowing inactivation of the enzyme via selective modification of allosteric residue C121.

  17. MiR-344b-1-3p targets TLR2 and negatively regulates TLR2 signaling pathway

    PubMed Central

    Xu, Hong; Wu, Yuting; Li, Li; Yuan, Weifeng; Zhang, Deming; Yan, Qitao; Guo, Zhenhui; Huang, Wenjie

    2017-01-01

    Objectives COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA). MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders. Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD. Materials and methods miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats. The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay. Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene. Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells. Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1β, and MIP-2, was also assessed. Results COPD rat model was successfully induced by smoke inhalation. Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene. In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1β and decreased the expression levels of MIP-2. In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition. Conclusion Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients. PMID:28243080

  18. Characterization of Human Disease Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1

    PubMed Central

    Crow, Yanick J.; Chase, Diana S.; Schmidt, Johanna Lowenstein; Szynkiewicz, Marcin; Forte, Gabriella M.A.; Gornall, Hannah L.; Oojageer, Anthony; Anderson, Beverley; Pizzino, Amy; Helman, Guy; Abdel-Hamid, Mohamed S.; Abdel-Salam, Ghada M.; Ackroyd, Sam; Aeby, Alec; Agosta, Guillermo; Albin, Catherine; Allon-Shalev, Stavit; Arellano, Montse; Ariaudo, Giada; Aswani, Vijay; Babul-Hirji, Riyana; Baildam, Eileen M.; Bahi-Buisson, Nadia; Bailey, Kathryn M.; Barnerias, Christine; Barth, Magalie; Battini, Roberta; Beresford, Michael W.; Bernard, Geneviève; Bianchi, Marika; de Villemeur, Thierry Billette; Blair, Edward M.; Bloom, Miriam; Burlina, Alberto B.; Carpanelli, Maria Luisa; Carvalho, Daniel R.; Castro-Gago, Manuel; Cavallini, Anna; Cereda, Cristina; Chandler, Kate E.; Chitayat, David A.; Collins, Abigail E.; Corcoles, Concepcion Sierra; Cordeiro, Nuno J.V.; Crichiutti, Giovanni; Dabydeen, Lyvia; Dale, Russell C.; D’Arrigo, Stefano; De Goede, Christian G.E.L.; De Laet, Corinne; De Waele, Liesbeth M.H.; Denzler, Ines; Desguerre, Isabelle; Devriendt, Koenraad; Di Rocco, Maja; Fahey, Michael C.; Fazzi, Elisa; Ferrie, Colin D.; Figueiredo, António; Gener, Blanca; Goizet, Cyril; Gowrinathan, Nirmala R.; Gowrishankar, Kalpana; Hanrahan, Donncha; Isidor, Bertrand; Kara, Bülent; Khan, Nasaim; King, Mary D.; Kirk, Edwin P.; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre; Lauffer, Heinz; Laugel, Vincent; La Piana, Roberta; Lim, Ming J.; Lin, Jean-Pierre S.-M.; Linnankivi, Tarja; Mackay, Mark T.; Marom, Daphna R.; Lourenço, Charles Marques; McKee, Shane A.; Moroni, Isabella; Morton, Jenny E.V.; Moutard, Marie-Laure; Murray, Kevin; Nabbout, Rima; Nampoothiri, Sheela; Nunez-Enamorado, Noemi; Oades, Patrick J.; Olivieri, Ivana; Ostergaard, John R.; Pérez-Dueñas, Belén; Prendiville, Julie S.; Ramesh, Venkateswaran; Rasmussen, Magnhild; Régal, Luc; Ricci, Federica; Rio, Marlène; Rodriguez, Diana; Roubertie, Agathe; Salvatici, Elisabetta; Segers, Karin A.; Sinha, Gyanranjan P.; Soler, Doriette; Spiegel, Ronen; Stödberg, Tommy I.; Straussberg, Rachel; Swoboda, Kathryn J.; Suri, Mohnish; Tacke, Uta; Tan, Tiong Y.; Naude, Johann te Water; Teik, Keng Wee; Thomas, Maya Mary; Till, Marianne; Tonduti, Davide; Valente, Enza Maria; Van Coster, Rudy Noel; van der Knaap, Marjo S.; Vassallo, Grace; Vijzelaar, Raymon; Vogt, Julie; Wallace, Geoffrey B.; Wassmer, Evangeline; Webb, Hannah J.; Whitehouse, William P.; Whitney, Robyn N.; Zaki, Maha S.; Zuberi, Sameer M.; Livingston, John H.; Rozenberg, Flore; Lebon, Pierre; Vanderver, Adeline; Orcesi, Simona; Rice, Gillian I.

    2015-01-01

    Aicardi–Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi–Goutières syndrome

  19. Critically ill infants and children with influenza A (H1N1) in pediatric intensive care units in Argentina.

    PubMed

    Farias, Julio A; Fernández, Analía; Monteverde, Ezequiel; Vidal, Nilda; Arias, Pilar; Montes, María J; Rodríguez, Gabriela; Allasia, Mariela; Ratto, Maria E; Jaén, Roxana; Meregalli, Claudia; Fiquepron, Karina; Calvo, Ana R; Siaba, Alejandro; Albano, Lidia; Poterala, Rossana; Neira, Pablo; Esteban, Andrés

    2010-06-01

    To determine the epidemiological features, course, and outcomes of critically ill pediatric patients with Influenza A (H1N1) virus. Prospective cohort of children in pediatric intensive care units (PICUs) due to Influenza A (H1N1) virus infection. Seventeen medical-surgical PICUs in tertiary care hospital in Argentina. All consecutive patients admitted to the PICUs with influenza A (H1N1) viral infection from 15 June to 31 July 2009. Of 437 patients with acute lower respiratory infection in PICUs, 147 (34%) were diagnosed with influenza A (H1N1) related to critical illness. The median age of these patients was 10 months (IQR 3-59). Invasive mechanical ventilation was used in 117 (84%) on admission. The rate of acute respiratory distress syndrome (ARDS) was 80% (118 of 147 patients). Initial non-invasive ventilation failed in 19 of 22 attempts (86%). Mortality at 28 days was 39% (n = 57). Chronic complex conditions (CCCs), acute renal dysfunction (ARD) and ratio PaO(2)/FiO(2) at day 3 on MV were independently associated with a higher risk of mortality. The odds ratio (OR) for CCCs was 3.06, (CI 95% 1.36-6.84); OR for ARD, 3.38, (CI 95% 1.45-10.33); OR for PaO(2)/FiO(2), 4 (CI 95% 1.57-9.59). The administration of oseltamivir within 24 h after admission had a protective effect: OR 0.2 (CI 95% 0.07-0.54). In children with ARDS, H1N1 as an etiologic agent confers high mortality, and the presence of CCCs in such patients increases the risk of death.

  20. The Development of the DSM-5 Cultural Formulation Interview-Fidelity Instrument (CFI-FI): A Pilot Study

    PubMed Central

    Aggarwal, Neil Krishan; Glass, Andrew; Tirado, Amilcar; Boiler, Marit; Nicasio, Andel; Alegría, Margarita; Wall, Melanie; Lewis-Fernández, Roberto

    2015-01-01

    This paper reports on the development of the Cultural Formulation Interview-Fidelity Instrument (CFI-FI) which assesses clinician fidelity to the DSM-5 Cultural Formulation Interview (CFI). The CFI consists of a manualized set of standard questions that can precede every psychiatric evaluation. It is based on the DSM-IV Outline for Cultural Formulation, the cross-cultural assessment with the most evidence in psychiatric training. Using the New York sample of the DSM-5 CFI field trial, two independent raters created and finalized items for the CFI-FI based on six audio-taped and transcribed interviews. The raters then used the final CFI-FI to rate the remaining 23 interviews. Inter-rater reliability ranged from .73 to 1 for adherence items and .52 to 1 for competence items. The development of the CFI-FI can help researchers and administrators determine whether the CFI has been implemented with fidelity, permitting future intervention research. PMID:25130248