Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients.

Science.gov (United States)

Wright, Adam; Mahaut-Smith, Martyn; Symon, Fiona; Sylvius, Nicolas; Ran, Shaun; Bafadhel, Mona; Muessel, Michelle; Bradding, Peter; Wardlaw, Andrew; Vial, Catherine

2016-06-15

Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist α,β-methylene ATP (α,β-meATP; 10 μM) evoked rapidly activating and desensitizing inward currents (peak 18 ± 3 pA/pF at -60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3 ± 2 pA/pF). α,β-meATP-evoked currents were smaller in eosinophils from asthmatic patients (8 ± 2 versus 27 ± 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 ± 5 pA/pF for 10 IU/ml and 11 ± 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. α,β-meATP (10 μM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 ± 21% and 108 ± 11% of control response, respectively). Furthermore, α,β-meATP increased healthy (18 ± 2% compared with control 10 ± 1%) but not asthmatic (13 ± 1% versus 10 ± 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration. Copyright © 2016 by The American Association of Immunologists, Inc.

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

Science.gov (United States)

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

2014-01-01

Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

Interstitial deletion 1p as a result of a de novo reciprocal 1p;2p translocation

DEFF Research Database (Denmark)

Hertz, Jens Michael; Jensen, P H

1985-01-01

A 5-month-old female patient with psychomotor retardation and minor dysmorphisms is described. Cytogenetic analysis using high-resolution banding technique revealed an interstitial deletion of the short arm of one chromosome 1 (p21----p22.2) resulting from a de novo translocation t(1;2)(p22;p25)....

The temperature dependence of 1/f noise in InP

NARCIS (Netherlands)

Chen, X.Y.; Hooge, F.N.; Leijs, M.R.

1997-01-01

Noise spectra were measured on CBE grown InP samples in the frequency range from 1 Hz to 104 kHz at temperatures from 77 to 500 K. The experimental results show that llfnoise stems from the lattice scattering. The 1/f noise in InP is well characterised by a parameter CtL~,, in this temperature

Frequency metrology on the 4s(2)S(1/2)-4p(2)P(1/2) transition in Ca-40(+) for a comparison with quasar data

NARCIS (Netherlands)

Wolf, A.L.; van den Berg, S.A.; Gohle, C.; Salumbides, E.J.; Ubachs, W.M.G.; Eikema, K.S.E.

2008-01-01

High accuracy frequency metrology on the 4s S 12 2 -4p P 12 2 transition in calcium ions is performed using laser cooled and crystallized ions in a linear Paul trap. Calibration is performed with a frequency comb laser, resulting in a transition frequency of f=755 222 766.2 (1.7) MHz. The accuracy

MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription factor in the context of anticancer chemotherapy resistance

Science.gov (United States)

Lai, Xin; Gupta, Shailendra K; Schmitz, Ulf; Marquardt, Stephan; Knoll, Susanne; Spitschak, Alf; Wolkenhauer, Olaf; Pützer, Brigitte M; Vera, Julio

2018-01-01

High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach for treating patients showing chemoresistance. Methods: We integrated bioinformatics, structural and kinetic modelling, and experiments to study cooperative regulation of E2F1 by microRNA (miRNA) pairs in the context of anticancer chemotherapy resistance. Results: We showed that an enhanced E2F1 repression efficiency can be achieved in chemoresistant tumour cells through two cooperating miRNAs. Sequence and structural information were used to identify potential miRNA pairs that can form tertiary structures with E2F1 mRNA. We then employed molecular dynamics simulations to show that among the identified triplexes, miR-205-5p and miR-342-3p can form the most stable triplex with E2F1 mRNA. A mathematical model simulating the E2F1 regulation by the cooperative miRNAs predicted enhanced E2F1 repression, a feature that was verified by in vitro experiments. Finally, we integrated this cooperative miRNA regulation into a more comprehensive network to account for E2F1-related chemoresistance in tumour cells. The network model simulations and experimental data indicate the ability of enhanced expression of both miR-205-5p and miR-342-3p to decrease tumour chemoresistance by cooperatively repressing E2F1. Conclusions: Our results suggest that pairs of cooperating miRNAs could be used as potential RNA therapeutics to reduce E2F1-related chemoresistance. PMID:29464002

Alfalfa mosaic virus replicase proteins, P1 and P2, localize to the tonoplast in the presence of virus RNA

International Nuclear Information System (INIS)

Ibrahim, Amr; Hutchens, Heather M.; Howard Berg, R.; Sue Loesch-Fries, L.

2012-01-01

To identify the virus components important for assembly of the Alfalfa mosaic virus replicase complex, we used live cell imaging of Arabidopsis thaliana protoplasts that expressed various virus cDNAs encoding native and GFP-fusion proteins of P1 and P2 replicase proteins and full-length virus RNAs. Expression of P1-GFP alone resulted in fluorescent vesicle-like bodies in the cytoplasm that colocalized with FM4-64, an endocytic marker, and RFP-AtVSR2, RabF2a/Rha1-mCherry, and RabF2b/Ara7-mCherry, all of which localize to multivesicular bodies (MVBs), which are also called prevacuolar compartments, that mediate traffic to the lytic vacuole. GFP-P2 was driven from the cytosol to MVBs when expressed with P1 indicating that P1 recruited GFP-P2. P1-GFP localized on the tonoplast, which surrounds the vacuole, in the presence of infectious virus RNA, replication competent RNA2, or P2 and replication competent RNA1 or RNA3. This suggests that a functional replication complex containing P1, P2, and a full-length AMV RNA assembles on MVBs to traffic to the tonoplast.

Alfalfa mosaic virus replicase proteins, P1 and P2, localize to the tonoplast in the presence of virus RNA

Energy Technology Data Exchange (ETDEWEB)

Ibrahim, Amr [Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47907 (United States); Present address: Genomics Facility, Agricultural Genetic Engineering Research Institute, Agricultural Research Center, Giza 12619 (Egypt); Hutchens, Heather M. [Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47907 (United States); Howard Berg, R. [Integrated Microscopy Facility, Donald Danforth Plant Science Center, Saint Louis, MO 63132 (United States); Sue Loesch-Fries, L., E-mail: loeschfr@purdue.edu [Department of Botany and Plant Pathology, Purdue University, West Lafayette, IN 47907 (United States)

2012-11-25

To identify the virus components important for assembly of the Alfalfa mosaic virus replicase complex, we used live cell imaging of Arabidopsis thaliana protoplasts that expressed various virus cDNAs encoding native and GFP-fusion proteins of P1 and P2 replicase proteins and full-length virus RNAs. Expression of P1-GFP alone resulted in fluorescent vesicle-like bodies in the cytoplasm that colocalized with FM4-64, an endocytic marker, and RFP-AtVSR2, RabF2a/Rha1-mCherry, and RabF2b/Ara7-mCherry, all of which localize to multivesicular bodies (MVBs), which are also called prevacuolar compartments, that mediate traffic to the lytic vacuole. GFP-P2 was driven from the cytosol to MVBs when expressed with P1 indicating that P1 recruited GFP-P2. P1-GFP localized on the tonoplast, which surrounds the vacuole, in the presence of infectious virus RNA, replication competent RNA2, or P2 and replication competent RNA1 or RNA3. This suggests that a functional replication complex containing P1, P2, and a full-length AMV RNA assembles on MVBs to traffic to the tonoplast.

Measurement of the 22S1/2-22P3/2 fine structure interval in muonium

International Nuclear Information System (INIS)

Kettell, S.H.

1990-08-01

The (2 2 S 1/2 - 2 2 P 3/2 ) fine structure transition in muonium has been observed for the first time. The measured value is 9895 -30 +35 MHz. This measurement, when included with the theoretical value for the 2 2 P 1/2 - 2 2 P 3/2 fine structure interval, gives a value for the Lamb shift (2 2 S 1/2 - 2 2 P 1/2 ) independent of previous direct measurements. From the theoretical value for the fine structure interval, 10921.833(3) MHz, the value for the Lamb shift determined from this experiment is 1027 -35 +30 MHz and is in agreement with the prediction of quantum electrodynamics (QED) of 1047.5(3) MHz. Previous experimental values for the Lamb shift (2 2 S 1/2 -2 2 P 1/2 ) in muonium are 1070 -15 + 12 MHz and 1042 -23 +21 MHz. Combining this result with these previous results gives a new experimental value of 1058 -12 +10 for the Lamb shift in muonium. Muonium, the bound state of two structureless leptons (μ + e - ), is an ideal system for testing bound state QED because of the lack of hadronic structure as exists in the hydrogen system. The measurement makes use of the techniques of atomic beam microwave spectroscopy. Muonium atoms (μ + e - ) in the 2S states are produced by the beam-foil technique at the Clinton P. Anderson Meson Physics Facility with a low momentum, sub-surface muon beam. A variable frequency microwave field is applied to drive the atoms from the 2S to the 2P states, with the subsequent observation of the Lyman alpha photon from the decay of the 2P state to the 1S ground state. The frequency is varied from 9.0--11.0 GHz, driving the F = 0 → F = 1, F = 1, F = 1 and F = 1 → F = 2 transitions

Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest

Directory of Open Access Journals (Sweden)

Harrison David J

2007-11-01

Full Text Available Abstract Background TGFβ is critical to control hepatocyte proliferation by inducing G1-growth arrest through multiple pathways leading to inhibition of E2F transcription activity. The retinoblastoma protein pRb is a key controller of E2F activity and G1/S transition which can be inhibited in viral hepatitis. It is not known whether the impairment of pRb would alter the growth inhibitory potential of TGFβ in disease. We asked how Rb-deficiency would affect responses to TGFβ-induced cell cycle arrest. Results Primary hepatocytes isolated from Rb-floxed mice were infected with an adenovirus expressing CRE-recombinase to delete the Rb gene. In control cells treatment with TGFβ prevented cells to enter S phase via decreased cMYC activity, activation of P16INK4A and P21Cip and reduction of E2F activity. In Rb-null hepatocytes, cMYC activity decreased slightly but P16INK4A was not activated and the great majority of cells continued cycling. Rb is therefore central to TGFβ-induced cell cycle arrest in hepatocytes. However some Rb-null hepatocytes remained sensitive to TGFβ-induced cell cycle arrest. As these hepatocytes expressed very high levels of P21Cip1 and P53 we investigated whether these proteins regulate pRb-independent signaling to cell cycle arrest by evaluating the consequences of disruption of p53 and p21Cip1. Hepatocytes deficient in p53 or p21Cip1 showed diminished growth inhibition by TGFβ. Double deficiency had a similar impact showing that in cells containing functional pRb; P21Cip and P53 work through the same pathway to regulate G1/S in response to TGFβ. In Rb-deficient cells however, p53 but not p21Cip deficiency had an additive effect highlighting a pRb-independent-P53-dependent effector pathway of inhibition of E2F activity. Conclusion The present results show that otherwise genetically normal hepatocytes with disabled p53, p21Cip1 or Rb genes respond less well to the antiproliferative effects of TGFβ. As the function of

Electron impact excitation-autoionisation of the (2s2)1S, (2p2)1D and (2s2p)1P autoionising states of helium

International Nuclear Information System (INIS)

Samardzic, O.; Hurn, J.A.; Weigold, E.; Brunger, M.J.

1994-01-01

The electron impact excitation of the (2s 2 ) 1 S, (2p 2 ) 1 D and (2s2p) 1 P autoionising states of helium and their subsequent radiationless decay was studied by observation of the ejected electrons. The present work was carried out at an incident energy of 94.6 eV and for ejected electron scattering angles in the range 25-135 deg C. The lineshapes observed in the present ejected electron spectra are analysed using the Shore-Balashov parametrisation. As part of the analysis procedure, numerically rigorous confidence limits were determined for the derived parameters. No previous experimental or theoretical work has been undertaken at the incident energy of the present investigation but, where possible, the resulting parameters are qualitatively compared against the 80 eV results of other experiments and theory. 37 refs., 4 figs

An interesting charmonium state formation and decay: p p-bar → 1 D2 → 1 P1γ

International Nuclear Information System (INIS)

Anselmino, M.; Caruso, F.; Universidade do Estado, Rio de Janeiro, RJ; Murgia, F.; Negrao, M.R.

1994-01-01

Massless perturbative QCD forbids, at leading order, the exclusive annihilation of proton-antiproton into some charmonium states, which however, have been observed in the pp channel, indicating the significance of higher order and non perturbative effects in the few GeV energy region. The most well known cases are those of the 1 S 0 (η c ) and the 1 P 1 . The case of the 1 D 2 is considered here and a way of detecting such a state through its typical angular distribution in the radiative decay 1 D 2 -> 1 D 2 -> 1 P 1 γ is suggested. Estimates of the branching ratio BR( 1 D 2 ->pp), as given by a quark-diquark model of the nucleon, mass corrections and an instanton induced process are presented. (author). 15 refs

E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair

Directory of Open Access Journals (Sweden)

David G. Johnson

2012-10-01

Full Text Available Many of the biochemical details of nucleotide excision repair (NER have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure. Interestingly, many of the players involved in modifying chromatin at sites of DNA damage were originally identified as regulators of transcription. These include ATP-dependent chromatin remodelers, histone modifying enzymes and several transcription factors. The p53 and E2F1 transcription factors are well known for their abilities to regulate gene expression in response to DNA damage. This review will highlight the underappreciated, transcription-independent functions of p53 and E2F1 in modifying chromatin structure in response to DNA damage to promote global NER.

1-[[sup 18]F]fluoro-2-propanol p-toluenesulfonate: a synthon for the preparation of N-([[sup 18]F]fluoroisopropyl)amines

Energy Technology Data Exchange (ETDEWEB)

Groot, T.J. de; Elsinga, P.H.; Visser, G.M.; Vaalburg, W. (Groningen Univ. (Netherlands). PET Center and GCCS)

1992-11-01

The new radiochemical synthon 1-[[sup 18]F]fluoro-2-propanol p-toluenesulfonate is prepared with a radiochemical yield of 45% [corrected for decay to beginning of synthesis, synthesis time 40 min]. This compound is used to prepare the [[sup 18]F]fluoroisopropyl-alkylated derivatives of benzylamine and norephedrine with a yield of 7 and 2% respectively, (synthesis time 90 min). This alkylation reaction a good perspective for the preparation of [[sup 18]F]fluoro-labelled analogues of [beta][sub 1]-adrenergic receptor binding ligands for PET. (Author).

E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.

Science.gov (United States)

Carcagno, Abel L; Marazita, Mariela C; Ogara, María F; Ceruti, Julieta M; Sonzogni, Silvina V; Scassa, María E; Giono, Luciana E; Cánepa, Eduardo T

2011-01-01

A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity.

E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.

Directory of Open Access Journals (Sweden)

Abel L Carcagno

Full Text Available BACKGROUND: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. CONCLUSIONS/SIGNIFICANCE: The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell

^2H(^18F,p)^19F Study at 6 MeV/u

Science.gov (United States)

Kozub, R. L.; Nesaraja, C. D.; Moazen, B. H.; Scott, J. P.; Bardayan, D. W.; Blackmon, J. C.; Gross, C. J.; Shapira, D.; Smith, M. S.; Batchelder, J. C.; Brune, C. R.; Champagne, A. E.; Sahin, L.; Cizewski, J. A.; Thomas, J. S.; Davinson, T.; Woods, P. J.; Greife, U.; Jewett, C.; Livesay, R. J.; Ma, Z.; Parker, P. D.

2003-04-01

The degree to which the (p,α) and (p,γ) reactions destroy ^18F at temperatures ˜1-4 x 10^8 K is important for understanding the synthesis of nuclei in nova explosions and for using ^18F as a monitor of nova mechanisms in gamma ray astronomy. The reactions are dominated by low-lying proton resonances near the ^18F+p threshold (E_x=6.411 MeV excitation energy in ^19Ne). To gain further information about these resonances, we have used the inverse ^18F(d,p)^19F neutron transfer reaction at the Holifield Radioactive Ion Beam Facility to selectively populate corresponding mirror states in ^19F. Proton angular distributions were measured for states in ^19F in the excitation energy range 0-9 MeV. Results and implications for the ^18F+p reactions and nuclear structure will be presented. ^1Supported by DOE. ^2ORNL is managed by UT-Battelle, LLC, for the USDOE.

Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression.

Science.gov (United States)

Xie, Chu-Hai; Cao, Yan-Ming; Huang, Yan; Shi, Qun-Wei; Guo, Jian-Hong; Fan, Zi-Wen; Li, Ju-Gen; Chen, Bin-Wei; Wu, Bo-Yi

2016-11-01

Recent studies have shown that long non-coding RNAs (lncRNAs) have critical roles in tumorigenesis, including osteosarcoma. The lncRNA taurine-upregulated gene 1 (TUG1) was reported to be involved in the progression of osteosarcoma. Here, we investigated the role of TUG1 in osteosarcoma cells and the underlying mechanism. TUG1 expression was measured in osteosarcoma cell lines and human normal osteoblast cells by quantitative real-time PCR (qRT-PCR). The effects of TUG1 on osteosarcoma cells were studied by RNA interference in vitro and in vivo. The mechanism of competing endogenous RNA (ceRNA) was determined using bioinformatic analysis and luciferase assays. Our data showed that TUG1 knockdown inhibited cell proliferation and colony formation, and induced G0/G1 cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Besides, we found that TUG1 acted as an endogenous sponge to directly bind to miR-9-5p and downregulated miR-9-5p expression. Moreover, TUG1 overturned the effect of miR-9-5p on the proliferation, colony formation, cell cycle arrest, and apoptosis in osteosarcoma cells, which involved the derepression of POU class 2 homeobox 1 (POU2F1) expression. In conclusion, our study elucidated a novel TUG1/miR-9-5p/POU2F1 pathway, in which TUG1 acted as a ceRNA by sponging miR-9-5p, leading to downregulation of POU2F1 and facilitating the tumorigenesis of osteosarcoma. These findings may contribute to the lncRNA-targeted therapy for human osteosarcoma.

A de-novo interstitial microduplication involving 2p16.1-p15 and mirroring 2p16.1-p15 microdeletion syndrome: Clinical and molecular analysis.

Science.gov (United States)

Mimouni-Bloch, Aviva; Yeshaya, Josepha; Kahana, Sarit; Maya, Idit; Basel-Vanagaite, Lina

2015-11-01

Microdeletions of various sizes in the 2p16.1-p15 chromosomal region have been grouped together under the 2p16.1-p15 microdeletion syndrome. Children with this syndrome generally share certain features including microcephaly, developmental delay, facial dysmorphism, urogenital and skeletal abnormalities. We present a child with a de-novo interstitial 1665 kb duplication of 2p16.1-p15. Clinical features of this child are distinct from those of children with the 2p16.1-p15 microdeletion syndrome, specifically the head circumference which is within the normal range and mild intellectual disability with absence of autistic behaviors. Microduplications many times bear milder clinical phenotypes in comparison with corresponding microdeletion syndromes. Indeed, as compared to the microdeletion syndrome patients, the 2p16.1-p15 microduplication seems to have a milder cognitive effect and no effect on other body systems. Limited information available in genetic databases about cases with overlapping duplications indicates that they all have abnormal developmental phenotypes. The involvement of genes in this location including BCL11A, USP34 and PEX13, affecting fundamental developmental processes both within and outside the nervous system may explain the clinical features of the individual described in this report. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Tables of Shore and Fano parameters for the helium resonances 2s/sup 2/ /sup 1/S, 2p/sup 2/ /sup 1/D, and 2s 2p /sup 1/P excited in p-He collisions E/sub p/ = 33 to 150 keV

Energy Technology Data Exchange (ETDEWEB)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Merchez, H.

1976-02-01

Absolute values of Shore and Fano parameters are tabulated for the helium atom 2s/sup 2/ /sup 1/S, 2p/sup 2/ /sup 1/D, and 2s 2p /sup 1/P resonances produced by a proton beam. Observations were made on the spectra of ejected electrons. The important variation of the shape of the resonances with ejection angle is illustrated for E/sub p/ = 100 keV; the variation with proton energy is shown at 30/sup 0/.

Phosphorylation of a specific cdk site in E2F-1 affects its electrophoretic mobility and promotes pRB-binding in vitro

DEFF Research Database (Denmark)

Peeper, D S; Keblusek, P; Helin, K

1995-01-01

of the retinoblastoma gene (pRB). We find that E2F-1 proteins are heterogeneously phosphorylated in insect cells, as a result of which they migrate as a doublet on SDS-polyacrylamide gels. This electrophoretic shift is shown to be dependent upon specific phosphorylation of E2F-1 on serine-375 (S375), near the p...

Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

International Nuclear Information System (INIS)

Zou, Yang; Liu, Fa-Ying; Liu, Huai; Wang, Feng; Li, Wei; Huang, Mei-Zhen; Huang, Yan; Yuan, Xiao-Qun; Xu, Xiao-Yun; Huang, Ou-Ping; He, Ming

2014-01-01

The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively

Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Zou, Yang; Liu, Fa-Ying; Liu, Huai; Wang, Feng [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Li, Wei [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Huang, Mei-Zhen [Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); Huang, Yan; Yuan, Xiao-Qun [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Xu, Xiao-Yun [Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); Huang, Ou-Ping, E-mail: huangouping@gmail.com [Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); He, Ming, E-mail: jxhm56@hotmail.com [Department of Pharmacology and Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang 330006 (China)

2014-03-15

The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively

Preclinical evaluation of [{sup 18}F]2FNQ1P as the first fluorinated serotonin 5-HT{sub 6} radioligand for PET imaging

Energy Technology Data Exchange (ETDEWEB)

Becker, Guillaume [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); Colomb, Julie [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); Sgambato-Faure, Veronique; Tremblay, Leon [Universite Claude Bernard Lyon 1, CNRS, Cognitive Neuroscience Center, Bron (France); Billard, Thierry [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France); Zimmer, Luc [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France)

2014-10-21

Brain serotonin 6 receptor (5-HT{sub 6}) is one of the most recently identified serotonin receptors. It is a potent therapeutic target for psychiatric and neurological diseases, e.g. schizophrenia and Alzheimer's disease. Since no specific fluorinated radioligand has yet been successfully used to study this receptor by positron emission tomography (PET) neuroimaging, the objective of the present study was to study the first 5-HT{sub 6} {sup 18}F-labelled radiotracer. 2FNQ1P, inspired by the quinolone core of a previous radiotracer candidate, GSK215083, was selected according its 5-HT{sub 6} affinity and selectivity and was radiolabelled by {sup 18}F nucleophilic substitution. The cerebral distribution of [{sup 18}F]2FNQ1P was studied in vivo in rats, cats and macaque monkeys. The chemical and radiochemical purities of [{sup 18}F]2FNQ1P were >98 %. In rats, in vitro competition with the 5-HT{sub 6} antagonist, SB258585, revealed that the radioligand was displaced dose dependently. Rat microPET studies showed low brain uptake of [{sup 18}F]2FNQ1P, reversed by the P-glycoprotein inhibitor, cyclosporin. On the contrary, PET scans in cats showed good brain penetration and specific striatal binding blocked after pretreatment with unlabelled 2FNQ1P. PET scans in macaque monkeys confirmed high specific binding in both cortical and subcortical regions, specifically decreased by pretreatment with the 5-HT{sub 6} receptor antagonist, SB258585. 2FNQ1P was initially selected because of its suitable characteristics for 5-HT{sub 6} receptor probing in vitro in terms of affinity and specificity. Although in vivo imaging in rats cannot be considered as predictive of the clinical characteristics of the radiotracer, [{sup 18}F]2FNQ1P appeared to be a suitable 5-HT{sub 6} PET tracer in feline and primate models. These preclinical results encourage us to pursue the clinical development of this first fluorinated 5-HT{sub 6} PET radiotracer. (orig.)

Quantum state-to-state dynamics for the quenching process of Br(2P1/2) + H2(v(i) = 0, 1, j(i) = 0).

Science.gov (United States)

Xie, Changjian; Jiang, Bin; Xie, Daiqian; Sun, Zhigang

2012-03-21

Quantum state-to-state dynamics for the quenching process Br((2)P(1/2)) + H(2)(v(i) = 0, 1, j(i) = 0) → Br((2)P(3/2)) + H(2)(v(f), j(f)) has been studied based on two-state model on the recent coupled potential energy surfaces. It was found that the quenching probabilities have some oscillatory structures due to the interference of reflected flux in the Br((2)P(1/2)) + H(2) and Br((2)P(3/2)) + H(2) channels by repulsive potential in the near-resonant electronic-to-vibrational energy transfer process. The final vibrational state resolved integral cross sections were found to be dominated by the quenching process Br((2)P(1/2)) + H(2)(v) → Br((2)P(3/2)) + H(2)(v+1) and the nonadiabatic reaction probabilities for Br((2)P(1/2)) + H(2)(v = 0, 1, j(i) = 0) are quite small, which are consistent with previous theoretical and experimental results. Our calculated total quenching rate constant for Br((2)P(1/2)) + H(2)(v(i) = 0, j(i) = 0) at room temperature is in good agreement with the available experimental data. © 2012 American Institute of Physics

u-Constacyclic codes over F_p+u{F}_p and their applications of constructing new non-binary quantum codes

Science.gov (United States)

Gao, Jian; Wang, Yongkang

2018-01-01

Structural properties of u-constacyclic codes over the ring F_p+u{F}_p are given, where p is an odd prime and u^2=1. Under a special Gray map from F_p+u{F}_p to F_p^2, some new non-binary quantum codes are obtained by this class of constacyclic codes.

Measurement of the $\\chi_b(3P)$ mass and of the relative rate of $\\chi_{b1}(1P)$ and $\\chi_{b2}(1P)$ production

CERN Document Server

Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; van den Brand, Johannes; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cojocariu, Lucian; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gavrilov, Gennadii; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Lespinasse, Mickael; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Roa Romero, Diego; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wu, Suzhi; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

2014-10-14

The production of $\\chi_b$ mesons in proton-proton collisions is studied using a data sample collected by the LHCb detector, at centre-of-mass energies of $\\sqrt{s}=7$ and $8$ TeV and corresponding to an integrated luminosity of 3.0 fb$^{-1}$. The $\\chi_b$ mesons are identified through their decays to $\\Upsilon(1S)\\gamma$ and $\\Upsilon(2S)\\gamma$ using photons that converted to $e^+e^-$ pairs in the detector. The $\\chi_b(3P)$ meson mass, and the relative prompt production rate of $\\chi_{b1}(1P)$ and $\\chi_{b2}(1P)$ mesons as a function of the $\\Upsilon(1S)$ transverse momentum in the $\\chi_b$ rapidity range 2.0< $y$<4.5, are measured. Assuming a mass splitting between the $\\chi_{b1}(3P)$ and the $\\chi_{b2}(3P)$ states of 10.5 MeV/$c^2$, the mass of the $\\chi_{b1}(3P)$ meson is \\begin{equation*} m(\\chi_{b1}(3P))= 10515.7^{+2.2}_{-3.9}(stat) ^{+1.5}_{-2.1}(syst) MeV/c^2. \\end{equation*}

A Novel Regulatory Mechanism of Smooth Muscle α-Actin Expression by NRG-1/circACTA2/miR-548f-5p Axis.

Science.gov (United States)

Sun, Yan; Yang, Zhan; Zheng, Bin; Zhang, Xin-Hua; Zhang, Man-Li; Zhao, Xue-Shan; Zhao, Hong-Ye; Suzuki, Toru; Wen, Jin-Kun

2017-09-01

Neuregulin-1 (NRG-1) includes an extracellular epidermal growth factor-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor-β1, its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB (erythroblastic leukemia viral oncogene homolog) receptor. However, NRG-1-ICD function in VSMCs remains unknown. Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs. Immunofluorescence staining, Western blotting, and quantitative real-time polymerase chain reaction showed that NRG-1 was expressed in rat, mouse, and human VSMCs and was upregulated and cleaved in response to transforming growth factor-β1. In the cytoplasm of HASMCs (human aortic smooth muscle cells), the NRG-1-ICD participated in filamentous actin formation by interacting with α-SMA (smooth muscle α-actin). In the nucleus, the Nrg-1-ICD induced circular ACTA2 (alpha-actin-2; circACTA2) formation by recruitment of the zinc-finger transcription factor IKZF1 (IKAROS family zinc finger 1) to the first intron of α-SMA gene. We further confirmed that circACTA2, acting as a sponge binding microRNA (miR)-548f-5p, interacted with miR-548f-5p targeting 3' untranslated region of α-SMA mRNA, which in turn relieves miR-548f-5p repression of the α-SMA expression and thus upregulates α-SMA expression, thereby facilitating stress fiber formation and cell contraction in HASMCs. Accordingly, in vivo studies demonstrated that the localization of the interaction of circACTA2 with miR-548f-5p is significantly decreased in human intimal hyperplastic arteries compared with normal arteries, implicating that dysregulation of circACTA2 and miR-548f-5p expression is involved in intimal hyperplasia. These results suggest that circACTA2 mediates NRG-1-ICD regulation of α-SMA expression in HASMCs via the NRG-1-ICD/circACTA2/miR-548f-5p axis. Our data provide a molecular

S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Science.gov (United States)

Fang, Chao; Bian, Ganlan; Ren, Pan; Xiang, Jie; Song, Jun; Yu, Caiyong; Zhang, Qian; Liu, Ling; Chen, Kun; Liu, Fangfang; Zhang, Kun; Wu, Chunfeng; Sun, Ruixia; Hu, Dan; Ju, Gong; Wang, Jian

2018-02-08

Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Saccharomyces cerevisiae GTPase complex: Gtr1p-Gtr2p regulates cell-proliferation through Saccharomyces cerevisiae Ran-binding protein, Yrb2p

International Nuclear Information System (INIS)

Wang Yonggang; Nakashima, Nobutaka; Sekiguchi, Takeshi; Nishimoto, Takeharu

2005-01-01

A Gtr1p GTPase, the GDP mutant of which suppresses both temperature-sensitive mutants of Saccharomyces cerevisiae RanGEF/Prp20p and RanGAP/Rna1p, was presently found to interact with Yrb2p, the S. cerevisiae homologue of mammalian Ran-binding protein 3. Gtr1p bound the Ran-binding domain of Yrb2p. In contrast, Gtr2p, a partner of Gtr1p, did not bind Yrb2p, although it bound Gtr1p. A triple mutant: yrb2Δ gtr1Δ gtr2Δ was lethal, while a double mutant: gtr1Δ gtr2Δ survived well, indicating that Yrb2p protected cells from the killing effect of gtr1Δ gtr2Δ. Recombinant Gtr1p and Gtr2p were purified as a complex from Escherichia coli. The resulting Gtr1p-Gtr2p complex was comprised of an equal amount of Gtr1p and Gtr2p, which inhibited the Rna1p/Yrb2 dependent RanGAP activity. Thus, the Gtr1p-Gtr2p cycle was suggested to regulate the Ran cycle through Yrb2p

Role of dopants in LiF:Mg,Cu, LiF:Mg,P and LiF:Mg,Cu,P detectors

International Nuclear Information System (INIS)

Mohammadi, Kh.; Moussavi Zarandi, A.; Afarideh, H.; Shahmaleki, S.

2013-01-01

In this study, electronic structure of LiF crystal doped with Mg,Cu,P impurities was studied with WIEN2k code on the basis of FPLAPW+lo method. Results show that in Mg-doped LiF composition, an electronic trap was created with impurity concentration of 1.56% and 3.125%. In this condition, the electronic trap with increasing the percentage of the impurities up to 4.687% is annihilated. It was found, that by doping of Mg and Cu or P simultaneously, a hole-trap is created in valence band. It was realized that in LiF:Mg,Cu, LiF:Mg,P and LiF:Mg,Cu,P, Cu impurity and Li atom, have a key role in creation of levels which lead to create electronic and hole traps. Mg impurity and F atom, only have a role in creation of electronic traps. In addition, P impurity has a main role in creation of the electronic and hole traps in LiF:Mg,Cu,P. The activation energy of electronic and hole trap in LiF:Mg,Cu, LiF:Mg,P and LiF:Mg,Cu,P crystalline lattice were obtained as 0.3 and 5.5 eV, 0.92 and 3.4 eV and 0.75 and 3.1 eV, respectively. - Graphical abstract: Figure (a) and (b) shows changes in electronic structure and band gap energy of LiF crystal due to presence of Mg and Cu, Mg and P ions respectively. - Highlights: • Electronic structure of LiF, LiF:Mg,Cu, LiF:Mg,P and LiF:Mg,Cu,P materials were studied with WIEN2K code. • In LiF:Mg,Cu and LiF:Mg,Cu,P, Li atom and Cu impurity have a key role in creation of levels. • F atom and Mg impurity only have a role in creation of electronic traps. • In LiF:Mg,Cu,P, P impurity has a main role in creation of electronic and hole traps

P2X1 receptors and the endothelium

Directory of Open Access Journals (Sweden)

LS Harrington

2005-03-01

Full Text Available Adenosine triphosphate (ATP is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted that ATP induces a bi-phasic response in arteries, inducing contraction via the P2X and P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y receptors located on the endothelium. However, a number of recent studies have placed P2X1 receptors on the endothelium of some arteries. The use of a specific P2X1 receptor ligand, a, b methylene ATP has demonstrated that P2X1 receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is therefore dependant on its location, inducing contraction when located on the smooth muscle cells, and dilation when expressed on the endothelium, comparable to that of P2Y receptors.

p21(Waf1/Cip1) expression and the p53/MDM2 feedback loop in gastric carcinogenesis

NARCIS (Netherlands)

Craanen, M. E.; Blok, P.; Offerhaus, G. J.; Meijer, G. A.; Dekker, W.; Kuipers, E. J.; Meuwissen, S. G.

1999-01-01

Data are non-existent regarding coincidental alterations in the expression of p53 and its downstream target genes MDM2 and p21(Waf1/Cip1) in gastric carcinogenesis. An immunohistochemical study was therefore performed to examine the interrelationships of p53, MDM2, and p21(Waf1/Cip1) expression in a

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

Science.gov (United States)

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

2016-08-26

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

The f2(1565) in pbar-p -> (omega-omega)pizero interactions at rest

CERN Document Server

Baker, C.A.; Batty, C.J.; Braune, K.; Bugg, D.V.; Cramer, O.; Crede, V.; Djaoshvili, N.; Dunnweber, W.; Faessler, M.A.; Hessey, N.P.; Hidas, P.; Hodd, C.; Jamnik, D.; Kilinowsky, H.; Kisiel, J.; Klempt, E.; Kolo, C.; Montanet, L.; Pick, B.; Roethel, W.; Sarantsev, A.; Scott, I.; Strassburger, C.; Thoma, U.; Volcker, C.; Wallis, S.; Walther, D.; Wittmack, K.; Zou, B.S.

2011-01-01

Data are presented on the reaction pbar-p -> omega-omega-pizero at rest from the Crystal Barrel detector. These data identify a strong signal due to f2(1565) -> omega-omega. The relative production from initial pbar-p states 3P2, 3P1 and 1S0 is well determined from omega-omega decay angular correlations; P-state annihilation dominates strongly. A combined fit is made with data on pbar-p -> 3pizero at rest, where f2(1565) -> pizero-pizero is observed.

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

Science.gov (United States)

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

2016-01-27

Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

Quenching of I(2P1/2) by O3 and O(3P).

Science.gov (United States)

Azyazov, Valeriy N; Antonov, Ivan O; Heaven, Michael C

2007-04-26

Oxygen-iodine lasers that utilize electrical or microwave discharges to produce singlet oxygen are currently being developed. The discharge generators differ from conventional chemical singlet oxygen generators in that they produce significant amounts of atomic oxygen. Post-discharge chemistry includes channels that lead to the formation of ozone. Consequently, removal of I(2P1/2) by O atoms and O3 may impact the efficiency of discharge driven iodine lasers. In the present study, we have measured the rate constants for quenching of I(2P1/2) by O(3P) atoms and O3 using pulsed laser photolysis techniques. The rate constant for quenching by O3, (1.8 +/- 0.4) x 10(-12) cm3 s-1, was found to be a factor of 5 smaller than the literature value. The rate constant for quenching by O(3P) was (1.2 +/- 0.2) x 10(-11) cm3 s-1.

The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

Science.gov (United States)

Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

2008-01-01

Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

The tumor suppressors p33ING1 and p33ING2 interact with alien in vivo and enhance alien-mediated gene silencing.

Science.gov (United States)

Fegers, Inga; Kob, Robert; Eckey, Maren; Schmidt, Oliver; Goeman, Frauke; Papaioannou, Maria; Escher, Niko; von Eggeling, Ferdinand; Melle, Christian; Baniahmad, Aria

2007-11-01

The tumor suppressor p33ING1 is involved in DNA repair and cell cycle regulation. Furthermore, p33ING1 is a transcriptional silencer that recognizes the histone mark for trimethylated lysine 4 at histone H3. Interestingly, expression of p33ING1 and p33ING2 is able to induce premature senescence in primary human fibroblasts. The corepressor Alien is involved in gene silencing mediated by selected members of nuclear hormone receptors. In addition, Alien acts as a corepressor for E2F1, a member of the E2F cell cycle regulatory family. Furthermore, recent findings suggest that Alien is complexed with transcription factors participating in DNA repair and chromatin. Here, using a proteomic approach by surface-enhanced laser desorption ionization and mass spectrometry (SELDI-MS) combined with immunological techniques, we show that Alien interacts in vivo with the tumor suppressor p33ING1 as well as with the related tumor suppressor candidate p33ING2. The interaction of Alien with p33ING1 and p33ING2 was confirmed in vitro with GST-pull-down, suggesting a direct binding of Alien to these factors. The binding domain was mapped to a central region of Alien. Functionally, the expression of p33ING1 or p33ING2 enhances the Alien-mediated silencing, suggesting that the interaction plays a role in transcriptional regulation. Thus, the findings suggest that the identified interaction between Alien and the tumor suppressors p33ING1 and p33ING2 reveals a novel cellular protein network.

PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

Science.gov (United States)

Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

2013-11-01

We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells. © 2013.

Microglia P2Y13 Receptors Prevent Astrocyte Proliferation Mediated by P2Y1 Receptors

Directory of Open Access Journals (Sweden)

Clara Quintas

2018-05-01

Full Text Available Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog. In astrocyte cultures, ADPβS increased cell proliferation through activation of P2Y1 and P2Y12 receptors, an effect abolished in co-cultures (of astrocytes with ∼12.5% microglia. The possibility that the loss of the ADPβS-mediated effect could have been caused by a microglia-induced degradation of ADPβS or by a preferential microglial localization of P2Y1 or P2Y12 receptors was excluded. Since ADPβS also activates P2Y13 receptors, the contribution of microglial P2Y13 receptors to prevent the proliferative effect of ADPβS in co-cultures was investigated. The results obtained indicate that P2Y13 receptors are low expressed in astrocytes and mainly expressed in microglia. Furthermore, in co-cultures, ADPβS induced astroglial proliferation in the presence of the selective P2Y13 antagonist MRS 2211 (3 μM and of the selective P2Y12 antagonist AR-C66096 (0.1 μM, suggesting that activation of microglial P2Y12 and P2Y13 receptors may induce the release of messengers that inhibit astroglial proliferation mediated by P2Y1,12 receptors. In this microglia-astrocyte paracrine communication, P2Y12 receptors exert opposite effects in astroglial proliferation as a result of its cellular localization: cooperating in astrocytes with P2Y1 receptors to directly stimulate proliferation and in

Improved wavelengths for the 1s2s3S1-1s2p3P0,2 transitions in helium-like Si12+

International Nuclear Information System (INIS)

Armour, I.A.; Myers, E.G.; Silver, J.D.; Traebert, E.; Oxford Univ.

1979-01-01

The wavelengths of the 1s2s 3 S 1 -1s2p 3 P 0 , 2 transitions in He-like Si 12+ have been remaesured to be 87.86 +- 0.01 nm and 81.48 +- 0.01 nm. The use of Rydberg lines for the calibration of fast beam spectra is discussed. (orig.)

The sphingosine 1-phosphate receptor S1P(2) triggers hepatic wound healing

NARCIS (Netherlands)

Serriere-Lanneau, Valerie; Teixeira-Clerc, Fatima; Li, Liying; Schippers, Marlies; de Wries, Willie; Julien, Boris; Tran-Van-Nhieu, Jeanne; Manin, Sylvie; Poelstra, Klaas; Chun, Jerold; Carpentier, Stephane; Levade, Thierry; Mallat, Ariane; Lotersztajn, Sophie

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK1 and 2). We previously showed that S1P receptors (S1P(1), S1P(2), and S1P(3)) are expressed in hepatic myofibroblasts (hMF), a population of cells that triggers matrix remodeling during liver injury. Here

E2F1 induces p19INK4d, a protein involved in the DNA damage response, following UV irradiation.

Science.gov (United States)

Carcagno, Abel L; Giono, Luciana E; Marazita, Mariela C; Castillo, Daniela S; Pregi, Nicolás; Cánepa, Eduardo T

2012-07-01

Central to the maintenance of genomic integrity is the cellular DNA damage response. Depending on the type of genotoxic stress and through the activation of multiple signaling cascades, it can lead to cell cycle arrest, DNA repair, senescence, and apoptosis. p19INK4d, a member of the INK4 family of CDK inhibitors, plays a dual role in the DNA damage response, inhibiting cell proliferation and promoting DNA repair. Consistently, p19INK4d has been reported to become upregulated in response to UV irradiation and a great variety of genotoxic agents. Here, this induction is shown to result from a transcriptional stimulatory mechanism that can occur at every phase of the cell cycle except during mitosis. Moreover, evidence is presented that demonstrates that E2F1 is involved in the induction of p19INK4d following UV treatment, as it is prevented by E2F1 protein ablation and DNA-binding inhibition. Specific inhibition of this regulation using triplex-forming oligonucleotides that target the E2F response elements present in the p19INK4d promoter also block p19INK4d upregulation and sensitize cells to DNA damage. These results constitute the first description of a mechanism for the induction of p19INK4d in response to UV irradiation and demonstrate the physiological relevance of this regulation following DNA damage.

Collisions of halogen (2P) and rare gas (1S) atoms

International Nuclear Information System (INIS)

Becker, C.H.

1978-12-01

Differential cross sections I (THETA) at several collision energies measured in crossed molecular beam experiments are reported for several combinations of halogen atoms ( 2 P) scattered off rare gas-rare gas atoms ( 1 S 0 ), namely, F + Ne, F + Ar, F + Kr, F + Xe, C1 + Xe. The scattering is described by an elastic model appropriate to Hund's case c coupling. With the use of this model, the X 1/2, I 3/2, and II 1/2 interaction potential energy curves are derived by fitting calculated differential cross sections, based on analytic representations of the potentials, to the data. The F - Xe X 1/2 potential shows a significant bonding qualitatively different than for the other F-rare gases. The I 3/2 and II 1/2 potentials closely resemble the van der Waals interactions of the one electron richer ground state rare gas-rare gas systems. Coupled-channel scattering calculations are carried out for F + Ar, F + Xe, and C1 + Xe using the realistic potential curves derived earlier. The results justify the use of the elastic model, and give additional information on intramultiplet and intermultiplet transitions. The transitions are found to be governed by the crossing of the two Ω = 1/2 potentials in the complex plane. The measured I (theta) and I (THETA) derived from the coupled-channel computations show small oscillations or perturbations (Stueckelberg oscillations) though quantitative agreement is not obtained.The nature of the anomalous F - Xe X 1/2 potential is discussed as is the approximation of a constant spin orbit coupling over the experimentally accessible range of internuclear distances for these open shell molecules. 55 references

Clinical Significance of POU5F1P1 rs10505477 Polymorphism in Chinese Gastric Cancer Patients Receving Cisplatin-Based Chemotherapy after Surgical Resection

Directory of Open Access Journals (Sweden)

Lili Shen

2014-07-01

Full Text Available This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1 rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944 gastric cancer patients who received gastrectomy. The association of rs10505477 G > A polymorphism with the progression and prognosis in gastric cancer patients was statistically analyzed using the SPSS version 18.0 for Windows. The results reveal that rs10505477 polymorphism has a negatively effect on the overall survival of gastric cancer patients in cisplatin-based chemotherapy subgroup (HR = 1.764, 95% CI = 1.069–2.911, p = 0.023. Our preliminary study indicates for the first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer patients who receving cisplatin-based chemotherapy after gastrectomy. Further studies are warranted to investigate the mechanism and to verify our results in different populations.

Lost P1 allele in sh2 sweet corn: quantitative effects of p1 and a1 genes on concentrations of maysin, apimaysin, methoxymaysin, and chlorogenic acid in maize silk.

Science.gov (United States)

Guo, B Z; Zhang, Z J; Butrón, A; Widstrom, N W; Snook, M E; Lynch, R E; Plaisted, D

2004-12-01

In the United States, insecticide is used extensively in the production of sweet corn due to consumer demand for zero damage to ears and to a sweet corn genetic base with little or no resistance to ear-feeding insects. Growers in the southern United States depend on scheduled pesticide applications to control ear-feeding insects. In a study of quantitative genetic control over silk maysin, AM-maysin (apimaysin and methoxymaysin), and chlorogenic acid contents in an F2 population derived from GE37 (dent corn, P1A1) and 565 (sh2 sweet corn, p1a1), we demonstrate that the P1 allele from field corn, which was selected against in the development of sweet corn, has a strong epistatic interaction with the a1 allele in sh2 sweet corn. We detected that the p1 gene has significant effects (P silk maysin concentrations but also on AM-maysin, and chlorogenic acid concentrations. The a1 gene also has significant (P silk antibiotic chemicals. Successful selection from the fourth and fifth selfed backcrosses for high-maysin individuals of sweet corn homozygous for the recessive a1 allele (tightly linked to sh2) and the dominant P1 allele has been demonstrated. These selected lines have much higher (2 to 3 times) concentrations of silk maysin and other chemicals (AM-maysin and chlorogenic acid) than the donor parent GE37 and could enhance sweet corn resistance to corn earworm and reduce the number of applications of insecticide required to produce sweet corn.

When is f(x1,x2,... ,xn)

Indian Academy of Sciences (India)

R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

When is f(x1,x2,... ,xn) = u1(x1) + u2(x2) +···+ un(xn)? ... (i) there exist non-zero integers p1,p2,... ,pk such that ..... probability measure for the countable collection of functions 1Ai , i = 1, 2, 3,. .... For question (B) a sufficient condition is that.

PET-CT imaging with [18F]-gefitinib to measure Abcb1a/1b (P-gp) and Abcg2 (Bcrp1) mediated drug–drug interactions at the murine blood–brain barrier

International Nuclear Information System (INIS)

Vlaming, Maria L.H.; Läppchen, Tilman; Jansen, Harm T.; Kivits, Suzanne; Driel, Andy van; Steeg, Evita van de; Hoorn, José W. van der; Sio, Charles F.; Steinbach, Oliver C.; DeGroot, Jeroen

2015-01-01

Introduction: The efflux transporters P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) are expressed at the blood–brain barrier (BBB), and can limit the access of a wide range of drugs to the brain. In this study we developed a PET-CT imaging method for non-invasive, quantitative analysis of the effect of ABCB1 and ABCG2 on brain penetration of the anti-cancer drug gefitinib, and demonstrated the applicability of this method for identification and quantification of potential modulators of ABCB1 and ABCB2 using the dual inhibitor elacridar. Methods: In vitro cellular accumulation studies with [ 14 C]-gefitinib were conducted in LLC-PK1, MDCKII, and the corresponding ABCB1/Abcb1a and ABCG2/Abcg2 overexpressing cell lines. Subsequently, in vivo brain penetration of [ 18 F]-gefitinib was quantified by PET-CT imaging studies in wild-type, Abcg2 −/− , Abcb1a/1b −/− , and Abcb1a/1b;Abcg2 −/− mice. Results: In vitro studies showed that [ 14 C]-gefitinib is a substrate of the human ABCB1 and ABCG2 transporters. After i.v. administration of [ 18 F]-gefitinib (1 mg/kg), PET-CT imaging showed 2.3-fold increased brain levels of [ 18 F]-gefitinib in Abcb1a/1b;Abcg2 −/− mice, compared to wild-type. Levels in single knockout animals were not different from wild-type, showing that Abcb1a/1b and Abcg2 together limit access of [ 18 F]-gefitinib to the brain. Furthermore, enhanced brain accumulation of [ 18 F]-gefitinib after administration of the ABCB1 and ABCG2 inhibitor elacridar (10 mg/kg) could be quantified with PET-CT imaging. Conclusions: PET-CT imaging with [ 18 F]-gefitinib is a powerful tool to non-invasively assess potential ABCB1- and ABCG2-mediated drug–drug interactions (DDIs) in vivo. Advances in knowledge and implications for patient care: This minimally-invasive, [ 18 F]-based PET-CT imaging method shows the interplay of ABCB1 and ABCG2 at the BBB in vivo. The method may be applied in the future to assess ABCB1 and

Diffractive production of {pi}{sup -}f{sub 1} in {pi}{sup -}p interactions at COMPASS(CERN)

Energy Technology Data Exchange (ETDEWEB)

Yang, Hao

2012-11-06

Diffractive dissociation of a {pi}{sup -} beam(190 GeV/c) on a proton target was measured at the COMPASS spectrometer. During a run in 2008, a large number of events with {pi}{sup -}{pi}{sup -}{pi}{sup +}{eta} in the final state was recorded. Partial wave analyses(PWA) of these data are being performed, concentrating on the kinematic domain of momentum transfer t' from 0.1 to 1.0 GeV{sup 2}/c{sup 2}. Subject of this thesis is the diffractive production of X from {pi}{sup -}p{yields}Xp with the subsequent decays X{yields}{pi}{sup -}f{sub 1} and f{sub 1}{yields}{pi}{sup -}{pi}{sup +}{eta}. Two different decays of the {eta} were selected: {eta}{yields}{pi}{sup -}{pi}{sup +}{pi}{sup 0}({gamma}{gamma}) and {eta}{yields}{gamma}{gamma}. A kinematic fitting routine was used to improve the data selection. In order to do the PWA, a Monte Carlo(MC) simulation is needed to account for the detector acceptance. In the mass-independent PWA the angular distributions of the real events are compared with the event distributions imposed on Monte Carlo(MC) events in order to determine the production amplitudes of different assumed partial waves in mass bins of 50 MeV/c{sup 2} of the invariant mass m{sub X} of X in the range 1.3 < m{sub X} < 3.0 GeV/c{sup 2}, by means of a maximum-likelihood-fit. Then a simplified mass-dependent fit of Breit-Wigner amplitudes has been applied to the distributions of production intensities as a function of m{sub X} in order to determine the contributions of known or presumed resonances. In the {pi}{sup -}f{sub 1} channel, we focus on the S, P and D wave i.e. orbital angular momentum L=0, 1, 2 between {pi}{sup -} and f{sub 1}. Significant intensity and phase motion are observed for the following J{sup PC}M{sup {epsilon}} combinations, where J, P, C, M and {epsilon} stand for the total angular momentum, parity and charge conjugation, total spin projection and reflectivity: 1{sup -+}1{sup +} (S wave), 1{sup ++}0{sup +} (P wave), 2{sup -+}0{sup +} (D

Calculations of resonances parameters for the ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) doubly excited states of helium-like ions with Z≤10 using a complex rotation method implemented in Scilab

Science.gov (United States)

Gning, Youssou; Sow, Malick; Traoré, Alassane; Dieng, Matabara; Diakhate, Babacar; Biaye, Mamadi; Wagué, Ahmadou

2015-01-01

In the present work a special computational program Scilab (Scientific Laboratory) in the complex rotation method has been used to calculate resonance parameters of ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) states of helium-like ions with Z≤10. The purpose of this study required a mathematical development of the Hamiltonian applied to Hylleraas wave function for intrashell states, leading to analytical expressions which are carried out under Scilab computational program. Results are in compliance with recent theoretical calculations.

31P NMR Spectroscopy Revealed Adenylate kinase-like Activity and Phosphotransferase-like Activity from F1-ATPase of Escherichia coli

International Nuclear Information System (INIS)

Kim, Hyun Won

2011-01-01

Adenylate kinase-like activity and phosphotransferase-like activity from F 1 -ATPase of Escherichia coli was revealed by 31 P NMR spectroscopy. Incubation of F 1 -ATPase with ADP in the presence of Mg 2+ shows the appearance of 31 P resonances from AMP and Pi, suggesting generation of AMP and ATP by adenylate kinase-like activity and the subsequent hydrolysis to Pi. Incubation of F1-ATPase with ADP in the presence of methanol shows additional peak from methyl phosphate, suggesting phosphotransferase-like activity of F 1 -ATPase. Both adenylate kinase-like activity and phosphotransferase-like activity has not been reported from F 1 -ATPase of Escherichia coli. 31 P NMR could be a valuable tool for the investigation of phosphorous related enzyme

Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms

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Stefan Bittner

2015-07-01

Full Text Available Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (TASK2; KCNK5 channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K2P5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K2P5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K2P5.1 knockout (K2P5.1−/− mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K2P5.1−/− mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K2P3.1 and KV1.3 seems to counterbalance the deletion of K2P5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K2P5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K2P5.1-targeting drugs.

Reduction of Aromatic and Heterocyclic Aromatic N-Hydroxylamines by Human Cytochrome P450 2S1

Science.gov (United States)

Wang, Kai; Guengerich, F. Peter

2013-01-01

Many aromatic amines and heterocyclic aromatic amines (HAAs) are known carcinogens for animals and there is also strong evidence for some in human cancer. The activation of these compounds, including some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 enzymes (P450) in Family 1 (1A2, 1A1, and 1B1). We previously demonstrated that the bioactivation product of the anti-cancer agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203), an N-hydroxylamine, can be reduced by P450 2S1 to its amine precursor under anaerobic conditions and, to a lesser extent, under aerobic conditions (Wang, K., and Guengerich, F. P. (2012) Chem. Res. Toxicol. 25, 1740–1751). In the present study, we tested the hypothesis that P450 2S1 is involved in the reductive biotransformation of known carcinogenic aromatic amines and HAAs. The N-hydroxylamines of 4-aminobiphenyl (4-ABP), 2-naphthylamine (2-NA), and 2-aminofluorene (2-AF) were synthesized and found to be reduced by P450 2S1 under both anaerobic and aerobic conditions. The formation of amines due to P450 2S1 reduction also occurred under aerobic conditions but was less apparent because the competitive disproportionation reactions (of the N-hydroxylamines) also yielded amines. Further, some nitroso and nitro derivatives of the arylamines could also be reduced by P450 2S1. None of the amines tested were oxidized by P450 2S1. These results suggest that P450 2S1 may be involved in the reductive detoxication of several of the activated products of carcinogenic aromatic amines and HAAs. PMID:23682735

Hal2p functions in Bdf1p-involved salt stress response in Saccharomyces cerevisiae.

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Lei Chen

Full Text Available The Saccharomyces cerevisiae Bdf1p associates with the basal transcription complexes TFIID and acts as a transcriptional regulator. Lack of Bdf1p is salt sensitive and displays abnormal mitochondrial function. The nucleotidase Hal2p detoxifies the toxic compound 3' -phosphoadenosine-5'-phosphate (pAp, which blocks the biosynthesis of methionine. Hal2p is also a target of high concentration of Na(+. Here, we reported that HAL2 overexpression recovered the salt stress sensitivity of bdf1Δ. Further evidence demonstrated that HAL2 expression was regulated indirectly by Bdf1p. The salt stress response mechanisms mediated by Bdf1p and Hal2p were different. Unlike hal2Δ, high Na(+ or Li(+ stress did not cause pAp accumulation in bdf1Δ and methionine supplementation did not recover its salt sensitivity. HAL2 overexpression in bdf1Δ reduced ROS level and improved mitochondrial function, but not respiration. Further analyses suggested that autophagy was apparently defective in bdf1Δ, and autophagy stimulated by Hal2p may play an important role in recovering mitochondrial functions and Na(+ sensitivity of bdf1Δ. Our findings shed new light towards our understanding about the molecular mechanism of Bdf1p-involved salt stress response in budding yeast.

Branching ratio and angular distribution of ejected electrons from Eu 4f76p1/2 n d auto-ionizing states

International Nuclear Information System (INIS)

Wu Xiao-Rui; Shen Li; Zhang Kai; Dai Chang-Jian; Yang Yu-Na

2016-01-01

The branching ratios of ions and the angular distributions of electrons ejected from the Eu 4f 7 6p 1/2 n d auto-ionizing states are investigated with the velocity-map-imaging technique. To populate the above auto-ionizing states, the relevant bound Rydberg states have to be detected first. Two new bound Rydberg states are identified in the region between 41150 cm −1 and 44580 cm −1 , from which auto-ionization spectra of the Eu 4f 7 6p 1/2 n d states are observed with isolated core excitation method. With all preparations above, the branching ratios from the above auto-ionizing states to different final ionic states and the angular distributions of electrons ejected from these processes are measured systematically. Energy dependence of branching ratios and anisotropy parameters within the auto-ionization spectra are carefully analyzed, followed by a qualitative interpretation. (paper)

The deexcitation of the Ar (3P2, 3p1 and 1P1) states as measured by absorption both in pure argon and in the presence of additives

International Nuclear Information System (INIS)

Dutuit, Odile

1974-01-01

The de-excitation of the 3 P 2 , 3 p 1 and 1 P 1 states of argon was studied in pure argon between 10 and 200 torr and in Ar + CO and Ar + H 2 mixtures. These states are populated after excitation of the gas by a short (20 ns) pulse of 500 keV electrons (FEBETRON). Under our experimental conditions, the relation between the measured optical density of the lines studied and the concentration of absorbing species was found to be: DO = log I 0 /I ∝ (lC) n with n = 0,4. The three body rate constants k 2 were measured for the two resonant states 3 p 1 (k 2 = (1,65 ± 0,3) x 10 -32 cm 6 s -1 ) and 1 P 1 (k 2 = (1,0 ± 0,2) x 10 -32 cm 6 s -1 ); they had not been considered in previous low pressure studies. For the metastable state 3 P 2 , the measured value of k 2 ((1,6 ± 0,3) x 10 -32 cm 6 s -1 ) is in good agreement with those found in the literature. However, our two body rate constant k 1 is about ten times higher than that found in measurements at low pressure. This difference could be due to a collision-induced emission process at high pressure. The rate constants for the quenching by CO and H 2 were measured for the metastable state 3 P 2 (1,85 and 10,5 x 10 -11 cm 3 s -1 ) and for the resonant states 3 P 1 (4,5 and 20 x 10 -11 cm 3 s -1 ) and 1 P 1 (8,5 and 33 X 10 -11 cm 3 s -1 ). Comparison of the de-excitation cross sections of resonant and metastable states should lead to a better understanding of energy transfer processes from these latter. (author) [fr

Excitation mechanisms of 2s1/2-2p3/2 and 2p1/2-2p3/2 transitions in U82+ through U89+

International Nuclear Information System (INIS)

Decaux, V.; Beiersdorfer, P.; Osterheld, A.

1994-01-01

A model based on detailed calculations of the electron-impact excitation of n = 2 electrons in the Li- to Ne-like uranium ions was developed to interpret and explain measurements on EBIT (Electron Beam Ion Trap). While only considering the direct excitation process provided a good model for the electric dipole (El) transitions, it was necessary for the magnetic dipole (Ml) spectrum to include various additional excitation processes in the model. In particular, the model was expanded to include electron-impact excitation of n = 3 levels followed by radiative cascades. Moreover, excitation by the ionization of 2s 1/2 , 2p 1/2 , and 2p 3/2 electrons and by radiative capture of beam electrons into excited levels was added. The new model demonstrates that the dipole-forbidden lines are almost exclusively produced by indirect excitation processes

A lifetime measurement of the 1s2p 3P1 level in helium-like Mg and Al

International Nuclear Information System (INIS)

Armour, I.A.; Silver, J.D.; Traebert, E.; Oxford Univ.

1981-01-01

The lifetimes of the 1s2p 3 P 1 levels of helium-like magnesium and aluminium have been measured by the beam-foil decay curve technique. The 1s 2 -1s2p transitions were observed with a curved-crystal x-ray spectrometer. Decay curves taken under systematically varied conditions have been evaluated using several techniques including a cascade model. The results are in agreement with most of the theoretical predictions. (author)

An unusual methylene aziridine refined in P2(1)/c and the nonstandard setting P2(1)/n.

Science.gov (United States)

Feast, George C; Haestier, James; Page, Lee W; Robertson, Jeremy; Thompson, Amber L; Watkin, David J

2009-12-01

The unusual methylene aziridine 6-tert-butyl-3-oxa-2-thia-1-azabicyclo[5.1.0]oct-6-ene 2,2-dioxide, C(9)H(15)NO(3)S, was found to crystallize with two molecules in the asymmetric unit. The structure was solved in both the approximately orthogonal and the oblique settings of space group No. 14, viz. P2(1)/n and P2(1)/c, respectively. A comparison of these results clearly displayed an increase in the correlation between coordinates in the ac plane for the oblique cell. The increase in the corresponding covariances makes a significant contribution to the standard uncertainties of derived parameters, e.g. bond lengths. Since there is yet no CIF definition for the full variance-covariance matrix, there are clear advantages to reporting the structure in the nonstandard space-group setting.

Excitation of the (2p2)1D and (2s2p)1P autoionizing states of helium by 200 eV electron impact

International Nuclear Information System (INIS)

Godunov, A.L.; McGuire, J.H.; Schipakov, V.S.; Crowe, A.

2002-01-01

We report full second Born calculations with inclusion of post-collision interactions for excitation of the (2p 2 ) 1 D and (2s2p) 1 P autoionizing states of helium by 200 eV electron impact. The calculations are compared to (e, 2e) measurements of McDonald and Crowe (McDonald D G and Crowe A 1993 J. Phys. B: At. Mol. Opt. Phys. 26 2887-97) and Lower and Weigold (Lower J and Weigold E 1990 J. Phys. B: At. Mol. Opt. Phys. 23 2819-45). It is shown that post-collision interactions or Coulomb interactions in the final state between the scattered particle, the ejected electron and the recoil ion have a strong influence on both the direct ionization and resonance profiles around the binary lobe. The second-order terms in the amplitude of double electron excitation also play an observable role under these kinematic conditions. Reasonable agreement is found between the full-scale calculations and the experimental data. (author). Letter-to-the-editor

The 4s- and 4p- XPS spectra of Xe, XeF2 and XeF4

International Nuclear Information System (INIS)

Ohno, Masahide

2003-01-01

The 4s- and 4p- XPS spectra of Xe gas, XeF 2 molecule and XeF 4 molecule are calculated by an ab-initio atomic many-body theory. The 4s-peak and the prominent '4p'-peak are predicted well by the present theory. In XeF 2 and XeF 4 the spectral lines observed below the 4d-double ionization threshold are the 4d -2 4f multiplet states strongly perturbed by the interaction with the initial 4p 1/2 -hole state. They are very similar to the spectral lines which emerge with an increase in atomic number (e.g. Ba)

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

Science.gov (United States)

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

2014-07-01

The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates. Copyright © 2014 Elsevier Inc. All rights reserved.

Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.

Directory of Open Access Journals (Sweden)

Kaipeng Huang

Full Text Available The accumulation of glomerular extracellular matrix (ECM is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1-sphingosine 1- phosphate (S1P signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG and simultaneously inhibited S1P2 receptor-mediated FN overproduction. Further, BBR also obviously suppressed the activation of NF-κB induced by HG, which was accompanied by reduced S1P2 receptor and FN expression. Taken together, our findings suggest that BBR reduces FN expression by acting on the S1P2 receptor in the mesangium under diabetic condition. The role of BBR in S1P2 receptor expression regulation could closely associate with its inhibitory effect on NF-κB activation.

The pMSSM10 after LHC Run 1

International Nuclear Information System (INIS)

De Vries, K.J.; Buchmueller, O.

2015-04-01

We present a frequentist analysis of the parameter space of the pMSSM10, in which the following 10 soft SUSY-breaking parameters are specified independently at the mean scalar top mass scale M SUSY ≡√(m t 1 m t 2 ): the gaugino masses M 1,2,3 , the 1st-and 2nd-generation squark masses m q 1 =m q 2 , the third-generation squark mass m q 3 , a common slepton mass M l and a common trilinear mixing parameter A, the Higgs mixing parameter μ, the pseudoscalar Higgs mass M A and tan β. We use the MultiNest sampling algorithm with ∝1.2 x 10 9 points to sample the pMSSM10 parameter space. A dedicated study shows that the sensitivities to strongly-interacting SUSY masses of ATLAS and CMS searches for jets, leptons+E T signals depend only weakly on many of the other pMSSM10 parameters. With the aid of the Atom and Scorpion codes, we also implement the LHC searches for EW-interacting sparticles and light stops, so as to confront the pMSSM10 parameter space with all relevant SUSY searches. In addition, our analysis includes Higgs mass and rate measurements using the HiggsSignals code, SUSY Higgs exclusion bounds, the measurements B-physics observables, EW precision observables, the CDM density and searches for spin-independent DM scattering. We show that the pMSSM10 is able to provide a SUSY interpretation of (g-2) μ , unlike the CMSSM, NUHM1 and NUHM2. As a result, we find (omitting Higgs rates) that the minimum χ 2 /d.o.f.=20.5/18 in the pMSSM10, corresponding to a χ 2 probability of 30.8 %, to be compared with χ 2 /d.o.f.=32.8/24(31.1/23)(30.3/22) in the CMSSM (NUHM1) (NUHM2). We display 1-dimensional likelihood functions for SUSY masses, and show that they may be significantly lighter in the pMSSM10 than in the CMSSM, NUHM1 and NUHM2. We discuss the discovery potential of future LHC runs, e + e - colliders and direct detection experiments.

Identification of 6H1 as a P2Y purinoceptor: P2Y5.

Science.gov (United States)

Webb, T E; Kaplan, M G; Barnard, E A

1996-02-06

We have determined the identity of the orphan G-protein coupled receptor cDNA, 6H1, present in activated chicken T cells, as a subtype of P2Y purinoceptor. This identification is based on first on the degree of sequence identity shared with recently cloned members of the P2Y receptor family and second on the pharmacological profile. Upon transient expression in COS-7 cells the 6H1 receptor bound the radiolabel [35S]dATP alpha S specifically and with high affinity (Kd, 10 nM). This specific binding could be competitively displaced by a range of ligands active at P2 purinoceptors, with ATP being the most active (K (i)), 116 nM). Such competition studies have established the following rank order of activity: ATP ADP 2-methylthioATP alpha, beta-methylene ATP, UTP, thus confirming 6H1 as a member of the growing family of P2Y purinoceptors. As the fifth receptor of this type to be identified we suggest that it be named P2Y5.

Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis

International Nuclear Information System (INIS)

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

2012-01-01

Highlights: ► The effect of a newly developed S1P 1 -selective antagonist on angiogenic responses. ► S1P 1 is a critical component of VEGF-related angiogenic responses. ► S1P 1 -selective antagonist showed in vitro activity to inhibit angiogenesis. ► S1P 1 -selective antagonist showed in vivo activity to inhibit angiogenesis. ► The efficacy of S1P 1 -selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P 1 ) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P 1 and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P 1 -selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P 1 antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P 1 is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

Tunneling magnetoresistance sensor with pT level 1/f magnetic noise

Science.gov (United States)

Deak, James G.; Zhou, Zhimin; Shen, Weifeng

2017-05-01

Magnetoresistive devices are important components in a large number of commercial electronic products in a wide range of applications including industrial position sensors, automotive sensors, hard disk read heads, cell phone compasses, and solid state memories. These devices are commonly based on anisotropic magnetoresistance (AMR) and giant magnetoresistance (GMR), but over the past few years tunneling magnetoresistance (TMR) has been emerging in more applications. Here we focus on recent work that has enabled the development of TMR magnetic field sensors with 1/f noise of less than 100 pT/rtHz at 1 Hz. Of the commercially available sensors, the lowest noise devices have typically been AMR, but they generally have the largest die size. Based on this observation and modeling of experimental data size and geometry dependence, we find that there is an optimal design rule that produces minimum 1/f noise. This design rule requires maximizing the areal coverage of an on-chip flux concentrator, providing it with a minimum possible total gap width, and tightly packing the gaps with MTJ elements, which increases the effective volume and decreases the saturation field of the MTJ freelayers. When properly optimized using this rule, these sensors have noise below 60 pT/rtHz, and could possibly replace fluxgate magnetometers in some applications.

MiRNA-362-3p induces cell cycle arrest through targeting of E2F1, USF2 and PTPN1 and is associated with recurrence of colorectal cancer

DEFF Research Database (Denmark)

Christensen, Lise Lotte; Tobiasen, Heidi; Holm, Anja

2013-01-01

Colorectal cancer (CRC) is one of the leading causes of cancer deaths in Western countries. A significant number of CRC patients undergoing curatively intended surgery subsequently develop recurrence and die from the disease. MicroRNAs (miRNAs) are aberrantly expressed in cancers and appear to have......-3p in a second independent cohort of 43 CRC patients, using single TaqMan® microRNA assays. In vitro functional analysis showed that over-expression of miR-362-3p in colon cancer cell lines reduced cell viability, and proliferation mainly due to cell cycle arrest. E2F1, USF2 and PTPN1 were identified...... as potential miR-362-3p targets by mRNA profiling of HCT116 cells over-expressing miR-362-3p. Subsequently, these genes were confirmed as direct targets by Luciferase reporter assays and their knockdown in vitro phenocopied the effects of miR-362-3p over-expression. We conclude that miR-362-3p may be a novel...

Toxicology and carcinogenesis studies of p,p'-dichlorophenyl sulfone (CAS No. 80-07-9) in F344/N rats and B6C3F1 mice (feed studies).

Science.gov (United States)

2001-09-01

p,pN-Dichlorodiphenyl sulfone is used as a starting material in the production of polysulfones and polyethersulfones and as a component in reactive dyes in the textile industry; it is also a by-product of pesticide production. p,pN-Dichlorodiphenyl sulfone was nominated for study by the National Cancer Institute because of its history of high production and use, the prospect of increased production and use, and the absence of adequate toxicity testing. Male and female F344/N rats and B6C3F1 mice were exposed top,pN-dichlorodiphenyl sulfone (greater than 99% pure)in feed for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium,cultured Chinese hamster ovary cells, and mouse bone marrow. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm p,pN-dichlorodiphenyl sulfone (equivalent to average daily doses of approximately 2, 6, 19, 65, or 200 mgp,pN-dichlorodiphenyl sulfone/kg body weight) for 14 weeks. All rats survived until the end of the study. Mean body weights of groups exposed to 300 ppm or greater were significantly less than those of the controls. Liver weights of groups exposed to 100 ppm or greater and kidney weights of 1,000 and 3,000 ppm male rats were significantly greater than those of the controls. Centrilobular hepatocyte hypertrophy of the liver was observed in most male rats exposed to 100 ppm or greater and in all female rats exposed to 300 ppm or greater, and the severities were increased in 300 ppm males and 1,000 and 3,000 ppm males and females. The incidences of nephropathy in 1,000 and 3,000 ppm female rats were significantly increased. Dose-related increases in severity of nephropathy were observed in male rats. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were fed diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm p,pN-dichlorodiphenyl sulfone (equivalent to average daily doses of approximately 3.5, 15, 50

Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

Science.gov (United States)

Quint, Patrick; Ruan, Ming; Pederson, Larry; Kassem, Moustapha; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

2013-01-01

Normal bone turnover requires tight coupling of bone resorption and bone formation to preserve bone quantity and structure. With aging and during several pathological conditions, this coupling breaks down, leading to either net bone loss or excess bone formation. To preserve or restore normal bone metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed that osteoclasts produce the chemokine sphingosine 1-phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) cell chemotaxis. S1P treatment of mesenchymal (skeletal) cells activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1P receptors, S1PR1 and S1PR2, coordinately promoted migration through activation of the JAK/STAT3 and FAK/PI3K/AKT signaling pathways, respectively. These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways. PMID:23300082

Crossed molecular beam-tunable laser determination of velocity dependence of intramultiplet mixing: K(4p2P1/2)+He →K(4p2P3/2)+He

International Nuclear Information System (INIS)

Anderson, R.W.; Goddard, T.P.; Parravano, C.; Warner, J.

1976-01-01

The velocity dependence of intramultiplet mixing, K(4p 2 P 1 / 2 ) +He→K(4p 2 P 3 / 2 )+He, has been measured over the relative velocity range v=1.3--3.4 km/sec. The cross section appears to fit a linear function Q (v) =A (v-v 0 ), where a=6.3 x 10 -4 A 2 and v 0 = 7.9 x 10 4 cm/sec. The value of A is obtained by normalization to the literature thermal average cross section. The intramultiplet mixing theory of Nikitin is modified to yield Q (v) for the process. The modified theory correctly exhibits detailed balancing, and it is normalized to provide a very good fit to the observed Q (v). The magnitude of the normalization factor, however, is larger than that predicted from recent pseudopotential calculations of the excited state potentials. The temperature dependence of intramultiplet mixing is predicted. The use of laser polarization to determine the m/subj/ dependence of the process K(4p 2 P 3 / 2 +He→K(4p 2 P 1 / 2 )+He and other collision processes of excited 2 P 3 / 2 states is examined

Calculations of resonances parameters for the ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) doubly excited states of helium-like ions with Z≤10 using a complex rotation method implemented in Scilab

International Nuclear Information System (INIS)

Gning, Youssou; Sow, Malick; Traoré, Alassane; Dieng, Matabara; Diakhate, Babacar; Biaye, Mamadi; Wagué, Ahmadou

2015-01-01

In the present work a special computational program Scilab (Scientific Laboratory) in the complex rotation method has been used to calculate resonance parameters of ((2s 2 ) 1 S e , (2s2p) 1,3 P 0 ) and ((3s 2 ) 1 S e , (3s3p) 1,3 P 0 ) states of helium-like ions with Z≤10. The purpose of this study required a mathematical development of the Hamiltonian applied to Hylleraas wave function for intrashell states, leading to analytical expressions which are carried out under Scilab computational program. Results are in compliance with recent theoretical calculations. - Highlights: • Resonance energy and widths computed for doubly excited states of helium-like ions. • Well-comparable results to the theoretical literature values up to Z=10. • Satisfactory agreements with theoretical calculations for widths

Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness

International Nuclear Information System (INIS)

Young, Nicholas; Van Brocklyn, James R.

2007-01-01

Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of five G-protein-coupled receptors, termed S1P 1-5 . S1P stimulates growth and invasiveness of glioma cells, and high expression levels of the enzyme that forms S1P, sphingosine kinase-1, correlate with short survival of glioma patients. In this study we examined the mechanism of S1P stimulation of glioma cell proliferation and invasion by either overexpressing or knocking down, by RNA interference, S1P receptor expression in glioma cell lines. S1P 1 , S1P 2 and S1P 3 all contribute positively to S1P-stimulated glioma cell proliferation, with S1P 1 being the major contributor. Stimulation of glioma cell proliferation by these receptors correlated with activation of ERK MAP kinase. S1P 5 blocks glioma cell proliferation, and inhibits ERK activation. S1P 1 and S1P 3 enhance glioma cell migration and invasion. S1P 2 inhibits migration through Rho activation, Rho kinase signaling and stress fiber formation, but unexpectedly, enhances glioma cell invasiveness by stimulating cell adhesion. S1P 2 also potently enhances expression of the matricellular protein CCN1/Cyr61, which has been implicated in tumor cell adhesion, and invasion as well as tumor angiogenesis. A neutralizing antibody to CCN1 blocked S1P 2 -stimulated glioma invasion. Thus, while S1P 2 decreases glioma cell motility, it may enhance invasion through induction of proteins that modulate glioma cell interaction with the extracellular matrix

Optical frequency measurements of 6s 2S1/2-6p 2P3/2 transition in a 133Cs atomic beam using a femtosecond laser frequency comb

International Nuclear Information System (INIS)

Gerginov, V.; Tanner, C.E.; Diddams, S.; Bartels, A.; Hollberg, L.

2004-01-01

Optical frequencies of the hyperfine components of the D 2 line in 133 Cs are determined using high-resolution spectroscopy and a femtosecond laser frequency comb. A narrow-linewidth probe laser excites the 6s 2 S 1/2 (F=3,4)→6p 2 P 3/2 (F=2,3,4,5) transition in a highly collimated atomic beam. Fluorescence spectra are taken by scanning the laser frequency over the excited-state hyperfine structure. The laser optical frequency is referenced to a Cs fountain clock via a reference laser and a femtosecond laser frequency comb. A retroreflected laser beam is used to estimate and minimize the Doppler shift due to misalignment between the probe laser and the atomic beam. We achieve an angular resolution on the order of 5x10 -6 rad. The final uncertainties (∼±5 kHz) in the frequencies of the optical transitions are a factor of 20 better than previous results [T. Udem et al., Phys. Rev. A 62, 031801 (2000).]. We find the centroid of the 6s 2 S 1/2 →6p 2 P 3/2 transition to be f D2 =351 725 718.4744(51) MHz

Influence of P-Glycoprotein Inhibition or Deficiency at the Blood-Brain Barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ( (18)F-FDG) Brain Kinetics.

Science.gov (United States)

Tournier, Nicolas; Saba, Wadad; Goutal, Sébastien; Gervais, Philippe; Valette, Héric; Scherrmann, Jean-Michel; Bottlaender, Michel; Cisternino, Salvatore

2015-05-01

The fluorinated D-glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact (18)F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate (18)F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of (18)F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for (18)F-FDG brain kinetics were then assessed using (i) (18)F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg(-1) h(-1)) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled D-glucose exposure to the brain. In vitro, the time course of (18)F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of D-glucose but not in the presence of high D-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1, k 2, k 3, V T , and CMRGlc. The lack of P-gp effect on in vivo (18)F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates (18)F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. (18)F-FDG is not a P-gp substrate at the BBB and (18)F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

HAT-P-49b: a 1.7 M {sub J} planet transiting a bright 1.5 M {sub ☉} F-star

Energy Technology Data Exchange (ETDEWEB)

Bieryla, A.; Latham, D. W.; Buchhave, L. A.; Béky, B.; Falco, E.; Torres, G.; Noyes, R. W.; Berlind, P.; Calkins, M. C.; Esquerdo, G. A. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Hartman, J. D.; Bakos, G. Á.; Bhatti, W.; Csubry, Z.; Penev, K.; De Val-Borro, M. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Kovács, G. [Konkoly Observatory, Budapest 1121 (Hungary); Boisse, I. [Centro de Astrofísica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Lázár, J.; Papp, I., E-mail: abieryla@cfa.harvard.edu, E-mail: gbakos@astro.princeton.edu [Hungarian Astronomical Association (HAA), Budapest 1461 (Hungary); and others

2014-04-01

We report the discovery of the transiting extrasolar planet HAT-P-49b. The planet transits the bright (V = 10.3) slightly evolved F-star HD 340099 with a mass of 1.54 M {sub ☉} and a radius of 1.83 R {sub ☉}. HAT-P-49b is orbiting one of the 25 brightest stars to host a transiting planet which makes this a favorable candidate for detailed follow-up. This system is an especially strong target for Rossiter-McLaughlin follow-up due to the host star's fast rotation, 16 km s{sup –1}. The planetary companion has a period of 2.6915 days, mass of 1.73 M {sub J}, and radius of 1.41 R {sub J}. The planetary characteristics are consistent with that of a classical hot Jupiter but we note that this is the fourth most massive star to host a transiting planet with both M{sub p} and R{sub p} well determined.

The (2p, 2p) 11Δg state of 6Li2: Fourier transform spectrum of the 11Δg-B1IIu transition

International Nuclear Information System (INIS)

Linton, C.; Martin, F.; Crozet, P.; Ross, A.J.; Bacis, R.

1993-01-01

The 1 1 Δ g -B 1 II u transition of 6 Li 2 has been observed in collisionally induced fluorescence following single frequency optical-optical double resonance excitation of the F 1 Σ g + state using a ring dye laser with DCM dye. Spectra of the s and a symmetry levels were obtained separately, at high resolution, in the near-infrared region using a Fourier transform spectrometer. The molecular constants (Dunham coefficients) of the 1 1 Δ g state have been calculated. Comparison of the constants and dissociation energy with ab initio calculations has shown that the 1 1 Δ g state correlates with Li(2p) + Li(2p) and has a dissociation energy of 9,579 ± 1 cm -1 . The energy transfer process responsible for excitation of the 1 1 Δ g state is discussed

Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase.

Directory of Open Access Journals (Sweden)

Evgeny V Berdyshev

Full Text Available BACKGROUND: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P induces migration of human pulmonary artery endothelial cells (HPAECs through the activation of S1P(1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs and S1P lyase (S1PL, that regulate intracellular S1P accumulation, in HPAEC motility. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino-4-(p-Chlorophenyl Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1P(int, and attenuated S1P(ext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1P(int and potentiated motility of HPAECs to S1P(ext or serum. S1P(ext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting "inside-out" signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs. Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1P(ext or 4-deoxypyridoxine-dependent endothelial cell motility. CONCLUSIONS/SIGNIFICANCE: These results suggest S1P(ext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL.

LMFBR transducer performance in SLSF tests P1 and P2

International Nuclear Information System (INIS)

English, J.J.; Anderson, T.T.; Kuzay, T.M.; Wilson, R.E.; Pedersen, D.R.; Kaiser, W.C.; Klingler, W.B.

1977-01-01

The reliability and problem areas of sodium-immersed thermocouples, pressure transducers and flowmeters are presented for experiments P1 and P2 of the Sodium Loop Safety Facility (SLSF). The SLSF is a doubly-contained sodium loop situated in a core position of the Engineering Test Reactor at the Idaho National Engineering Laboratory

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

Science.gov (United States)

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

2016-02-01

At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. © 2016 Yamamoto, Yako, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells.

Science.gov (United States)

Uehara, Norihisa; Yoshizawa, Katsuhiko; Tsubura, Airo

2012-07-01

Vorinostat is a histone deacetylase inhibitor that blocks cancer cell proliferation through the regulation of cyclin-dependent kinase inhibitors. We, herein, examined the involvement of S-phase kinase-associated protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1), the components of the SCFSkp2-Cks1 (Skp1/Cul1/F-box protein) ubiquitin ligase complex, in the regulation of p27 and p21 during vorinostat-induced growth arrest of MDA-MB-231 and MCF-7 human breast cancer cells. Vorinostat significantly reduced BrdU incorporation in MDA-MB-231 and MCF-7 cells, which was associated with increased p27 and p21 protein levels without concomitant induction of p27 mRNA. Vorinostat-induced accumulation of p27 and p21 proteins was inversely correlated with the mRNA and protein levels of Skp2 and Cks1. Cycloheximide chase analysis revealed that vorinostat increased the half-life of p27 and p21 proteins. The accumulation of p27 and p21 proteins was attenuated by forced expression of Skp2 and Cks1, which conferred resistance to the vorinostat-induced S-phase reduction. These results suggest that vorinostat-induced growth arrest may be in part due to the enhanced protein stability of p27 and p21 through the downregulation of Skp2 and Cks1.

Neuropharmacology of purinergic receptors in human submucous plexus: Involvement of P2X₁, P2X₂, P2X₃ channels, P2Y and A₃ metabotropic receptors in neurotransmission.

Science.gov (United States)

Liñán-Rico, A; Wunderlich, J E; Enneking, J T; Tso, D R; Grants, I; Williams, K C; Otey, A; Michel, K; Schemann, M; Needleman, B; Harzman, A; Christofi, F L

2015-08-01

The role of purinergic signaling in human ENS is not well understood. We sought to further characterize the neuropharmacology of purinergic receptors in human ENS and test the hypothesis that endogenous purines are critical regulators of neurotransmission. LSCM-Fluo-4/(Ca(2+))-imaging of postsynaptic Ca(2+) transients (PSCaTs) was used as a reporter of synaptic transmission evoked by fiber tract electrical stimulation in human SMP surgical preparations. Pharmacological analysis of purinergic signaling was done in 1,556 neurons (identified by HuC/D-immunoreactivity) in 235 ganglia from 107 patients; P2XR-immunoreactivity was evaluated in 19 patients. Real-time MSORT (Di-8-ANEPPS) imaging tested effects of adenosine on fast excitatory synaptic potentials (fEPSPs). Synaptic transmission is sensitive to pharmacological manipulations that alter accumulation of extracellular purines: Apyrase blocks PSCaTs in a majority of neurons. An ecto-NTPDase-inhibitor 6-N,N-diethyl-D-β,γ-dibromomethyleneATP or adenosine deaminase augments PSCaTs. Blockade of reuptake/deamination of eADO inhibits PSCaTs. Adenosine inhibits fEPSPs and PSCaTs (IC50 = 25 µM), sensitive to MRS1220-antagonism (A3AR). A P2Y agonist ADPβS inhibits PSCaTs (IC50 = 111 nM) in neurons without stimulatory ADPbS responses (EC50 = 960 nM). ATP or a P2X1,2,2/3 (α,β-MeATP) agonist evokes fast, slow, biphasic Ca(2+) transients or Ca(2+) oscillations (ATP,EC50 = 400 mM). PSCaTs are sensitive to P2X1 antagonist NF279. Low (20 nM) or high (5 µM) concentrations of P2X antagonist TNP-ATP block PSCaTs in different neurons; proportions of neurons with P2XR-immunoreactivity follow the order P2X2 > P2X1 > P2X3; P2X1 + P2X2 and P2X3 + P2X2 are co-localized. RT-PCR identified mRNA-transcripts for P2X1-7, P2Y1,2,12-14R. Purines are critical regulators of neurotransmission in human ENS. Purinergic signaling involves P2X1, P2X2, P2X3 channels, P2X1 + P2X2 co-localization and inhibitory P2Y or A3 receptors. These are

[Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes].

Science.gov (United States)

Bao, X H; Li, H X; Tao, J; Li, X M; Yang, Y N; Ma, Y T; Chen, B D

2016-05-24

To study the role and mechanism of sphingosine-1-phosphate (S1P)/ sphingosine-1-phosphate receptor 1(S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes. Neonatal rat cardiomyocytes were isolated and cultured, then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy. Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning. Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected: (1) IPost group (hypoxia+ postconditioning); (2) IPost+ S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost); (3) IPost+ W-146+ S1P group (cells in IPost+ W-146+ S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min); (4) IPost+ PD98059+ S1P group (cells in IPost+ S1P group were pretreated with MAPK antagonist PD98059 (125 μmol/L) for 20 min); (5) IPost+ LY-294002+ S1P group (cells in IPost+ S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min). Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot. (1)Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90±4.49)% group compared with normal control group (7.97±2.18)%, which could be significantly reduced in IPost group (15.90±1.77)% (all PS1P and IPost+ S1P+ LY-294002 groups than in IPost and IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 group (all PS1P and IPost+ S1P+ LY-294002 group than in IPost and IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 group (all PS1P+ W-146 and IPost+ S1P+ PD98059 groups. p-ERK1/2 and p-Akt levels in IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 were similar as in IPost group. S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and

Phase diagram of ZnCr2pA12-2pS(Se)4 and Zn1-pCdpCr2S(Se)4

International Nuclear Information System (INIS)

Afif, K.; Benyoussef, A.; Hamedoun, M.; Hourmatallah, A.

1999-06-01

We compute the phase diagram of the nonmetallic compounds ZnCr2 p A1 2-2p S(Se) 4 (I[S,Se]) and Zn 1-p Cd p Cr 2 S(Se) 4 (II[S,Se]). We consider the bond-diluted Ising model on the spinel B site (S.B.S.) lattice with competitive exchange interactions, i.e. the ferromagnetic exchange interaction J 1 between nearest neighbours (n.n.) and the antiferromagnetic superexchange interaction J 2 between next-nearest neighbours' (n.n.n.) (and/or the more distant superexchange interactions J i (i > 1). Dilution and competition are found to be responsible for the spill glass phase and the percolation behaviour. (author)

The Polerovirus F box protein P0 targets ARGONAUTE1 to suppress RNA silencing.

Science.gov (United States)

Bortolamiol, Diane; Pazhouhandeh, Maghsoud; Marrocco, Katia; Genschik, Pascal; Ziegler-Graff, Véronique

2007-09-18

Plants employ post-transcriptional gene silencing (PTGS) as an antiviral defense response. In this mechanism, viral-derived small RNAs are incorporated into the RNA-induced silencing complex (RISC) to guide degradation of the corresponding viral RNAs. ARGONAUTE1 (AGO1) is a key component of RISC: it carries the RNA slicer activity. As a counter-defense, viruses have evolved various proteins that suppress PTGS. Recently, we showed that the Polerovirus P0 protein carries an F box motif required to form an SCF-like complex, which is also essential for P0's silencing suppressor function. Here, we investigate the molecular mechanism by which P0 impairs PTGS. First we show that P0's expression does not affect the biogenesis of primary siRNAs in an inverted repeat-PTGS assay, but it does affect their activity. Moreover, P0's expression in transformed Arabidopsis plants leads to various developmental abnormalities reminiscent of mutants affected in miRNA pathways, which is accompanied by enhanced levels of several miRNA-target transcripts, suggesting that P0 acts at the level of RISC. Interestingly, ectopic expression of P0 triggered AGO1 protein decay in planta. Finally, we provide evidence that P0 physically interacts with AGO1. Based on these results, we propose that P0 hijacks the host SCF machinery to modulate gene silencing by destabilizing AGO1.

Identification of the 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole inner-shell satellite line in the Ar16+ K-shell x-ray spectrum

Science.gov (United States)

Beiersdorfer, P.; Bitter, M.; Hey, D.; Reed, K. J.

2002-09-01

We have identified the dipole-forbidden 1s2s2p 4P5/2-->1s22s 2S1/2 transition in lithiumlike Ar15+ in high-resolution K-shell x-ray emission spectra recorded at the Livermore EBIT-II electron-beam ion trap and the Princeton National Spherical Tokamak Experiment. Unlike other Ar15+ satellite lines, which can be excited by dielectronic recombination, the line is exclusively excited by electron-impact excitation. Its predicted radiative rate is comparable to that of the well-known 1s2p 3P1-->1s2 1S0 magnetic quadrupole transition in heliumlike Ar16+. As a result, it can also only be observed in low-density plasma. We present calculations of the electron-impact excitation cross sections of the innershell excited Ar15+ satellite lines, including the magnetic sublevels needed for calculating the linear line polarization. We compare these calculations to the relative magnitudes of the observed 1s2s2p-->1s22s transitions and find good agreement, confirming the identification of the lithiumlike 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole line.

Observation of the hadronic transitions χb1,2(2P)→ωΥ(1S)

International Nuclear Information System (INIS)

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.

2004-01-01

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

Alfalfa mosaic virus replicase proteins P1 and P2 interact and colocalize at the vacuolar membrane

NARCIS (Netherlands)

Heijden, van der M.W.; Carette, J.E.; Reinhoud, P.J.; Haegi, A.; Bol, J.F.

2001-01-01

Replication of Alfalfa mosaic virus (AMV) RNAs depends on the virus-encoded proteins P1 and P2. P1 contains methyltransferase- and helicase-like domains, and P2 contains a polymerase-like domain. Coimmunoprecipitation experiments revealed an interaction between in vitro translated-P1 and P2 and

Pregnane X receptor-dependent induction of the CYP3A4 gene by o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane.

Science.gov (United States)

Medina-Díaz, Irma M; Arteaga-Illán, Georgina; de León, Mario Bermudez; Cisneros, Bulmaro; Sierra-Santoyo, Adolfo; Vega, Libia; Gonzalez, Frank J; Elizondo, Guillermo

2007-01-01

CYP3A4, the predominant cytochrome P450 (P450) expressed in human liver and intestine, contributes to the metabolism of approximately half the drugs in clinical use today. CYP3A4 catalyzes the 6beta-hydroxylation of a number of steroid hormones and is involved in the bioactivation of environmental procarcinogens. The expression of CYP3A4 is affected by several stimuli, including environmental factors such as insecticides and pesticides. The o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane (DDT) isomer of DDT comprises approximately 20% of technical grade DDT, which is an organochloride pesticide. We have recently shown that o,p'-DDT exposure increases CYP3A4 mRNA levels in HepG2 cells. To determine the mechanism by which o,p'-DDT induces CYP3A4 expression, transactivation and electrophoretic mobility shift assays were carried out, revealing that o,p'-DDT activates the CYP3A4 gene promoter through the pregnane X receptor (PXR). CYP3A4 gene promoter activation resulted in both an increase in CYP3A4 mRNA levels and an increase in the total CYP3A4 activity in HepG2 cells. We also observed induction of CYP3A4 and mouse Cyp3a11 mRNA in the intestine of CYP3A4-transgenic mice after exposure to 1 mg/kg o,p'-DDT. At higher doses, a decrease of CYP3A4 inducibility was observed together with an increase in levels of interleukin 6 mRNA, a proinflammatory cytokine that strongly represses CYP3A4 transcription. The present study indicates that regulation of other genes under PXR control may be altered by o,p'-DDT exposure.

Effects of perinatal combined exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and tributyltin (TBT) on rat female reproductive system.

Science.gov (United States)

Makita, Yuji

2008-05-01

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is the most prevalent metabolite of DDT used as a pesticide before and tributyltin (TBT) compounds are used primarily as antifouling agents on vessels, ships, and aqua culture facilities, as they exert biocidal actions. Currently, p,p'-DDE and TBT are ubiquitously distributed in the environment and bio-accumulated in marine products, especially fish or shellfish. Thus, oral p,p'-DDE and TBT intake through marine products is demonstrated to be rather high in Japan. Consequently, the fetus and neonate will be exposed to p,p'-DDE and TBT via mother. Therefore, effects of perinatal combined exposure to p,p'-DDE and TBT on the female reproductive system after maturation have been investigated in rat female offspring of dams ingesting 125ppm p,p'-DDE (approximately 10mg/kg) and 25ppm TBT (approximately 2mg/kg) during the perinatal period from gestation to lactation. In the present study, no deleterious reproductive outcomes were recognized in p,p'-DDE and/or TBT-treated dams. In contrast, growth retardation had developed in rat female offspring following perinatal exposure to TBT and sustained even after cessation of exposures. Further, reduced ovarian weights with elevated serum follicle-stimulating hormone (FSH) concentrations were observed in the reproductive system of matured female offspring following perinatal exposure to TBT. At present, biological relevance of these alterations remains unknown, but there is a possibility that these alterations lead to reproductive malfunctions in matured female offspring. Copyright © 2007 Elsevier B.V. All rights reserved.

Search for excited and exotic muons in the mu gamma decay channel in p anti-p collisions at s**(1/2) = 1.96-TeV

Energy Technology Data Exchange (ETDEWEB)

Abulencia, A.; Acosta, D.; Adelman, Jahred A.; Affolder, T.; Akimoto, T.; Albrow, M.G.; Ambrose, D.; Amerio, S.; Amidei, D.; Anastassov, A.; Anikeev, K.; /Taiwan, Inst.

2006-06-01

The authors present a search for excited and exotic muon states {mu}*, conducted using an integrated luminosity of 371 pb{sup -1} of data collected in p{bar p} collisions at {radical}s = 1.96 TeV at the Tevatron with the CDF II detector. They search for associated production of {mu}{mu}* followed by the decay {mu}* {yields} {mu}{gamma}, resulting in the {mu}{mu}{gamma} final state. They compare the data to model predictions as a function of the mass of the excited muon M{sub {mu}*}, the compositeness energy scale {Lambda}, and the gauge coupling factor f. No signal above the standard model expectation is observed in the {mu}{gamma} mass spectrum. In the contact interaction model, they exclude 107 < M{sub {mu}*} < 853 GeV/c{sup 2} for {Lambda} = M{sub {mu}*}; in the gauge-mediated model, they exclude 100 < M{sub {mu}*} < 410 GeV/c{sup 2} for f/{Lambda} = 10{sup -2} GeV{sup -1}. These 95% confidence level exclusions extend previous limits and are the first hadron collider results on {mu}* production in the gauge-mediated model.

Comparative modeling and docking studies of p16ink4/Cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1

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e Zahra Syeda Naqsh

2013-01-01

Full Text Available Abstract Background Lung cancer is the major cause of mortality worldwide. Major signalling pathways that could play significant role in lung cancer therapy include (1 Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase (2 Growth inhibitory pathways (p53/Rb/P14ARF, STK11 (3 Apoptotic pathways (Bcl-2/Bax/Fas/FasL. Insilico strategy was implemented to solve the mystery behind selected lung cancer pathway by applying comparative modeling and molecular docking studies. Results YASARA [v 12.4.1] was utilized to predict structural models of P16-INK4 and RB1 genes using template 4ELJ-A and 1MX6-B respectively. WHAT CHECK evaluation tool demonstrated overall quality of predicted P16-INK4 and RB1 with Z-score of −0.132 and −0.007 respectively which showed a strong indication of reliable structure prediction. Protein-protein interactions were explored by utilizing STRING server, illustrated that CDK4 and E2F1 showed strong interaction with P16-INK4 and RB1 based on confidence score of 0.999 and 0.999 respectively. In order to facilitate a comprehensive understanding of the complex interactions between candidate genes with their functional interactors, GRAMM-X server was used. Protein-protein docking investigation of P16-INK4 revealed four ionic bonds illustrating Arg47, Arg80,Cys72 and Met1 residues as actively participating in interactions with CDK4 while docking results of RB1 showed four hydrogen bonds involving Glu864, Ser567, Asp36 and Arg861 residues which interact strongly with its respective functional interactor E2F1. Conclusion This research may provide a basis for understanding biological insights of P16-INK4 and RB1 proteins which will be helpful in future to design a suitable drug to inhibit the disease pathogenesis as we have determined the interacting amino acids which can be targeted in order to design a ligand in-vitro to propose a drug for clinical trials. Protein -protein docking of

Regulation of P2Y1 receptor traffic by sorting Nexin 1 is retromer independent.

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Nisar, Shaista; Kelly, Eamonn; Cullen, Pete J; Mundell, Stuart J

2010-04-01

The activity and traffic of G-protein coupled receptors (GPCRs) is tightly controlled. Recent work from our laboratory has shown that P2Y(1) and P2Y(12) responsiveness is rapidly and reversibly modulated in human platelets and that the underlying mechanism requires receptor trafficking as an essential part of this process. However, little is known about the molecular mechanisms underlying P2Y receptor traffic. Sorting nexin 1 (SNX1) has been shown to regulate the endosomal sorting of cell surface receptors either to lysosomes where they are downregulated or back to the cell surface. These functions may in part be due to interactions of SNX1 with the mammalian retromer complex. In this study, we investigated the role of SNX1 in P2Y receptor trafficking. We show that P2Y(1) receptors recycle via a slow recycling pathway that is regulated by SNX1, whereas P2Y(12) receptors return to the cell surface via a rapid route that is SNX1 independent. SNX1 inhibition caused a dramatic increase in the rate of P2Y(1) receptor recycling, whereas inhibition of Vps26 and Vps35 known to be present in retromer had no effect, indicating that SNX1 regulation of P2Y(1) receptor recycling is retromer independent. In addition, inhibition of SNX4, 6 and 17 proteins did not affect P2Y(1) receptor recycling. SNX1 has also been implicated in GPCR degradation; however, we provide evidence that P2Y receptor degradation is SNX1 independent. These data describe a novel function of SNX1 in the regulation of P2Y(1) receptor recycling and suggest that SNX1 plays multiple roles in endocytic trafficking of GPCRs.

Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis.

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Dai, Lan; Liu, Yixuan; Xie, Lei; Wu, Xia; Qiu, Lihua; Di, Wen

2017-09-26

Sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) signaling pathway has been implicated in a variety of pathological processes of ovarian cancer. However, the function of this axis in ovarian cancer angiogenesis remains incompletely defined. Here we provided the first evidence that SphK1/S1P/S1PR 1/3 pathway played key roles in ovarian cancer angiogenesis. The expression level of SphK1, but not SphK2, was closely correlated with the microvascular density (MVD) of ovarian cancer tissue. In vitro , the angiogenic potential and angiogenic factor secretion of ovarian cancer cells could be attenuated by SphK1, but not SphK2, blockage and were restored by the addition of S1P. Moreover, in these cells, we found S1P stimulation induced the angiogenic factor secretion via S1PR 1 and S1PR 3 , but not S1PR 2 . Furthermore, inhibition of S1PR 1/3 , but not S1PR 2 , attenuated the angiogenic potential and angiogenic factor secretion of the cells. in vivo , blockage of SphK or S1PR 1/3 could attenuate ovarian cancer angiogenesis and inhibit angiogenic factor expression in mouse models. Collectively, the current study showed a novel role of SphK1/S1P/S1PR 1/3 axis within the ovarian cancer, suggesting a new target to block ovarian cancer angiogenesis.

The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1

DEFF Research Database (Denmark)

Jenal, Mathias; Trinh, Emmanuelle; Britschgi, Christian

2009-01-01

to the HIC1 promoter was shown by chromatin immunoprecipitation assays in human TIG3 fibroblasts expressing tamoxifen-activated E2F1. In agreement, activation of E2F1 in TIG3-E2F1 cells markedly increased HIC1 expression. Interestingly, expression of E2F1 in the p53(-/-) hepatocellular carcinoma cell line...

Sphingosine-1-Phosphate (S1P)-Related Response of Human Conjunctival Fibroblasts After Filtration Surgery for Glaucoma.

Science.gov (United States)

Aoyama-Araki, Yuka; Honjo, Megumi; Uchida, Takatoshi; Yamagishi, Reiko; Kano, Kuniyuki; Aoki, Junken; Aihara, Makoto

2017-04-01

To investigate levels of sphingosine-1-phosphate (S1P) in aqueous fluid samples taken before and after filtration surgery and S1P-induced human conjunctival fibroblast (HCF) responses. Levels of S1P and its related sphingophospholipids in aqueous fluid obtained immediately before and after filtration surgery were determined by liquid chromatography-tandem mass spectrometry. HCFs were used for all in vitro experiments. The expression of five S1P receptor subtypes in HCFs was examined by quantitative real-time PCR. The effect of S1P and receptor-specific antagonists on HCF viability and cell migration was assessed by WST-1 assay and scratch migration assay, respectively. Differentiation to myofibroblasts and extracellular matrix production was evaluated by examining changes in F-actin, α-smooth muscle actin (αSMA), and collagen expression with immunocytochemistry, Western blotting, and collagen accumulation assay, respectively. No significant S1P levels in the aqueous fluid samples were detectable immediately before surgery, but postoperative levels of several lysophospholipids, including S1P, dehydro-S1P, and sphingosine, were significantly increased to bioactive concentrations in aqueous fluid in the blebs (P S1P receptor subtypes was detected in HCFs. Although S1P levels did not influence HCF proliferation, S1P enhanced cell migration, which could be inhibited by the S1P2 antagonist JTE 013. F-actin, αSMA, and collagen expression was significantly increased by S1P stimulation and was reduced by JTE 013. Bioactive S1P concentrations were present in the aqueous fluid at the end of filtration surgery. S1P activated HCFs via S1P2 receptors. These results revealed the potential of S1P2 antagonists in preventing scarring after glaucoma filtration surgery.

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

Energy Technology Data Exchange (ETDEWEB)

Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

2012-03-23

Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

Quasimolecular emission near the Xe(5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance lines induced by collisions with He atoms

Science.gov (United States)

Alekseeva, O. S.; Devdariani, A. Z.; Grigorian, G. M.; Lednev, M. G.; Zagrebin, A. L.

2017-02-01

This study is devoted to the theoretical investigation of the quasimolecular emission of Xe*-He and Kr*-He collision pairs near the Xe (5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance atomic lines. The potential curves of the quasimolecules Xe(5p 56s) + He and Kr(4p 55s) + He have been obtained with the use of the effective Hamiltonian and pseudopotential methods. Based on these potential curves the processes of quasimolecular emission of Xe*+He and Kr*+He mixtures have been considered and the spectral distributions I(ħΔω) of photons emitted have been obtained in the framework of quasistatic approximation.

Cytochrome P2A13 and P1A1 gene polymorphisms are associated with the occurrence of uterine leiomyoma.

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Herr, D; Bettendorf, H; Denschlag, D; Keck, C; Pietrowski, D

2006-10-01

To investigate the association between the occurrence of uterine leiomyoma and two SNPs of the CYP 2A13 and CYP 1A1 genes. Prospective case control study with 132 women with clinically and surgically diagnosed uterine leiomyoma and 260 controls. Genotyping was performed by polymerase chain reaction (PCR) based amplification of CYP 2A13 and CYP 1A1 genes, and restriction fragment length polymorphism (RFLP) analysis. Comparing women with uterine leiomyoma and controls, we demonstrate statistical significant differences of allele frequency and genotype distribution for the CYP 1A1 polymorphism (P = 0.025 and P = 0.046, respectively). Furthermore, for the CYP 2A13 polymorphism we found a significant difference concerning allele frequency (P = 0.033). However, for the genotype distribution, only borderline significance was observed (P = 0.064). The CYP 2A13 and CYP 1A1 SNPs are associated with uterine leiomyoma in a Caucasian population and may contribute to the understanding of the pathogenic mechanisms of uterine leiomyoma.

Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

Science.gov (United States)

Berdyshev, Evgeny V.; Gorshkova, Irina; Usatyuk, Peter; Kalari, Satish; Zhao, Yutong; Pyne, Nigel J.; Pyne, Susan; Sabbadini, Roger A.; Garcia, Joe G. N.; Natarajan, Viswanathan

2011-01-01

Background Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility. Methodology/Principal Findings Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino)-4-(p-Chlorophenyl) Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1Pint, and attenuated S1Pext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1Pint and potentiated motility of HPAECs to S1Pext or serum. S1Pext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting “inside-out” signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs). Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1Pext or 4-deoxypyridoxine-dependent endothelial cell motility. Conclusions/Significance These results suggest S1Pext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL. PMID:21304987

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

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

2015-06-01

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

Triaxiality and alternating M1 strengths in f-p-g shell nuclei

Energy Technology Data Exchange (ETDEWEB)

Tabor, S L; Johnson, T D; Holcombe, J W; Womble, P C; Doring, J; Nazarewicz, W [Florida State Univ., Tallahassee, FL (United States). Dept. of Physics

1992-08-01

The appearance of alternating patterns in B(M1) strengths in f-p-g shell nuclei is surveyed. The M1 alternations in a sequence of N= 41 isotones, in conjunction with particle-rotor model calculations, is shown to provide information about changing {gamma} deformation. In addition to other odd-A nuclei, several odd-odd nuclei are shown to exhibit alternating B(M1) values and signature inversion. alternations have also been reported in a 4 quasiparticle band in {sup 86}Zr, where they have been interpreted in terms of the interacting boson model. (author). 15 refs., 1 tab., 6 figs.

Growth, straightness and survival at age 32 in a Pinus strobus x P. wallichiana F1 hybrid population (Experiment 1

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Ioan Blada

2013-11-01

. The narrow-sensefamily heritability estimates were 0.657 for diameter, 0.586 for height, 0.505 for volume, 0.705 for stem straightness and 0.734 for tree survival. The individual-tree narrow-sense heritability estimates were 0.336 for diameter, 0.253 for height, 0.205 for volume and 0.121 for stem straightness. Assuming selection of 5, 10, or 15 familiesout of the 28 tested ones and sexual propagation, a genetic gain of 9.5%, 6.8% and 4.8% in diameter, and 11.2%, 8.1% and 5.7% in volume and 16.4%, 11.8% and 8.4% in tree survival, respectively, might be achieved. Selecting the most outstanding 5%, 10%, or 15% individual F1 hybrids would yield a genetic progress of 9.7%, 8.3% and 7,4% in diameter and 10.2%, 8.8% and 7.8% in volume growth rate. The hybrid population mean surpassed in tree survival the open pollinated eastern white pine mean by 70.7% while the eastern white pine, surpassed the hybrid in all growth traits. The F1 hybrid and P. strobus open pollinated parent species averaged 0.993 and 1.069 m3 volume per tree, respectively. By extrapolation the yield results from the hybrid trial area to 1 ha results in a yield of 559.9 m3 per hectare for hybrids and 602.5 m3 for P. strobus female parent species. In conclusion, hybrids should be taken into consideration and used in plantation programs in high-blister-rust-hazard areas.

The subcellular distribution of the human ribosomal "stalk" components: P1, P2 and P0 proteins

DEFF Research Database (Denmark)

Tchórzewski, Marek; Krokowski, Dawid; Rzeski, Wojciech

2003-01-01

The ribosomal "stalk" structure is a distinct lateral protuberance located on the large ribosomal subunit in prokaryotic, as well as in eukaryotic cells. In eukaryotes, this ribosomal structure is composed of the acidic ribosomal P proteins, forming two hetero-dimers (P1/P2) attached...

Sphingosine-1-Phosphate Mediates ICAM-1-Dependent Monocyte Adhesion through p38 MAPK and p42/p44 MAPK-Dependent Akt Activation

Science.gov (United States)

Lin, Chih-Chung; Lee, I-Ta; Hsu, Chun-Hao; Hsu, Chih-Kai; Chi, Pei-Ling; Hsiao, Li-Der; Yang, Chuen-Mao

2015-01-01

Up-regulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation. Sphingosine-1-phosphate (S1P) has been shown to play a key role in inflammation via adhesion molecules induction, and then causes lung injury. However, the mechanisms underlying S1P-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear. The effect of S1P on ICAM-1 expression was determined by Western blot and real-time PCR. The involvement of signaling pathways in these responses was investigated by using the selective pharmacological inhibitors and transfection with siRNAs. S1P markedly induced ICAM-1 expression and monocyte adhesion which were attenuated by pretreatment with the inhibitor of S1PR1 (W123), S1PR3 (CAY10444), c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), PI3K (LY294002), or AP-1 (Tanshinone IIA) and transfection with siRNA of S1PR1, S1PR3, c-Src, EGFR, PDGFR, p38, p42, JNK1, c-Jun, or c-Fos. We observed that S1P-stimulated p42/p44 MAPK and p38 MAPK activation was mediated via a c-Src/EGFR and PDGFR-dependent pathway. S1P caused the c-Src/EGFR/PDGFR complex formation. On the other hand, we demonstrated that S1P induced p42/p44 MAPK and p38 MAPK-dependent Akt activation. In addition, S1P-stimulated JNK1/2 phosphorylation was attenuated by SP600125 or PP1. Finally, S1P enhanced c-Fos mRNA levels and c-Jun phosphorylation. S1P-induced c-Jun activation was reduced by PP1, AG1478, AG1296, U0126, SP600125, SB202190, or LY294002. These results demonstrated that S1P-induced ICAM-1 expression and monocyte adhesion were mediated through S1PR1/3/c-Src/EGFR, PDGFR/p38 MAPK, p42/p44 MAPK/Akt-dependent AP-1 activation. PMID:25734900

pH-dependent inhibition of K2P3.1 prolongs atrial refractoriness in whole hearts

DEFF Research Database (Denmark)

Skarsfeldt, Mark A; Jepps, Thomas A; Bomholtz, Sofia H

2016-01-01

In isolated human atrial cardiomyocytes, inhibition of K2P3.1 K(+) channels results in action potential (action potential duration (APD)) prolongation. It has therefore been postulated that K2P3.1 (KCNK3), together with K2P9.1 (KCNK9), could represent novel drug targets for the treatment of atrial...... fibrillation (AF). However, it is unknown whether these findings in isolated cells translate to the whole heart. The purposes of this study were to investigate the expression levels of KCNK3 and KCNK9 in human hearts and two relevant rodent models and determine the antiarrhythmic potential of K2P3.1 inhibition...... displayed a more uniform expression of KCNK3 between atria and ventricle. In voltage-clamp experiments, ML365 and A293 were found to be potent and selective inhibitors of K2P3.1, but at pH 7.4, they failed to prolong atrial APD and refractory period (effective refractory period (ERP)) in isolated perfused...

Production of psi(2S) Mesons in p anti-p Collisions at 1.96-TeV

Energy Technology Data Exchange (ETDEWEB)

Aaltonen, T.; /Helsinki Inst. of Phys.; Adelman, Jahred A.; /Chicago U., EFI; Akimoto, T.; /Tsukuba U.; Alvarez Gonzalez, B.; /Cantabria Inst. of Phys.; Amerio, S.; /INFN, Padua; Amidei, Dante E.; /Michigan U.; Anastassov, A.; /Northwestern U.; Annovi, Alberto; /Frascati; Antos, Jaroslav; /Comenius U.; Apollinari, G.; /Fermilab; Apresyan, A.; /Purdue U. /Waseda U.

2009-05-01

The authors have measured the differential cross section for the inclusive production of {psi}(2S) mesons decaying to {mu}{sup +}{mu}{sup -} that were produced in prompt or B-decay processes from p{bar p} collisions at 1.96 TeV. These measurements have been made using a data set from an integrated luminosity of 1.1 fb{sup -1} collected by the CDF II detector at Fermilab. For events with transverse momentum p{sub T}({psi}(2S)) > 2 GeV/c and rapidity |y({psi}(2S))| < 0.6 we measure the integrated inclusive cross section {sigma}(p{bar p} {yields} {psi}(2S)X) {center_dot} Br({psi}(2S) {yields} {mu}{sup +}{mu}{sup -}) to be 3.29 {+-} 0.04(stat.) {+-} 0.32(syst.) nb.

Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma.

Science.gov (United States)

Rodriguez, A M; Graef, A J; LeVine, D N; Cohen, I R; Modiano, J F; Kim, J-H

2015-01-01

Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs. S1P/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA). Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used. This was a retrospective case series and in vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography/mass spectrometry. S1P signaling was evaluated by intracellular Ca(2+) mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining. Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1 , decreased S1P1 protein expression and induced apoptosis of HSA cells. S1P/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Bis{2-[(diisopropylphosphanylamino]pyridine-κ2N1,P}copper(I hexafluoridophosphate

Directory of Open Access Journals (Sweden)

Özgür Öztopcu

2010-07-01

Full Text Available The crystal structure of the title compound, [Cu(C11H19N2P2]PF6, is composed of discrete [Cu(PN-iPr2]+ cations [PN-iPr is 2-(diisopropylphosphanylaminopyridine] and PF6− anions. The Cu(I atom is bis-chelated by two independent PN-iPr ligands. It has a distorted tetrahedral coordination by two P atoms [Cu—P = 2.2277 (4 and 2.2257 (4 Å] and two pyridine N atoms [Cu—N = 2.0763 (11 and 2.0845 (12 Å]. Bond angles about Cu vary from 85.11 (3 (P—Cu—N to 130.37 (2° (P—Cu—P. In the crystal, N—H...F hydrogen bonds link the Cu complexes and the PF6− anions into continuous chains, which show a cross-bedded spatial arrangement. In addition, several weaker C—H...F interactions contribute to the coherence of the structure.

Inclusive f2(1270) meson production in νp and anti νp charged current interactions

International Nuclear Information System (INIS)

Jones, G.T.; Jones, R.W.L.; Kennedy, B.W.; Morrison, D.R.O.; Mobayyen, M.M.; Wainstein, S.; Aderholz, M.; Hantke, D.; Hoffmann, E.; Katz, U.F.; Kern, J.; Schmitz, N.; Wittek, W.; Borner, H.P.; Myatt, G.; Radojicic, D.; Burke, S.

1991-01-01

Using data obtained with the bubble chamber BEBC at CERN, the inclusive f 2 (1270) meson production in νp and anti νp charged current reactions is studied. It is found that f 2 production occurs mainly in events with a hadronic invariant mass W> or approx.7 GeV. In these events, the average f 2 multiplicity is about half the average ρ 0 multiplicity, and the x F and p T 2 distributions of the f 2 agree in shape with those of the ρ 0 . The predictions of a semi-empirical model (Wells model) are in accord with the measured multiplicities at W>7 GeV, whereas at lower W the model predicts too large f 2 multiplicities. (orig.)

Static and dynamic 18F-FET PET for the characterization of gliomas defined by IDH and 1p/19q status

International Nuclear Information System (INIS)

Verger, Antoine; Stoffels, Gabriele; Lohmann, Philipp; Neumaier, Bernd; Bauer, Elena K.; Blau, Tobias; Fink, Gereon R.; Shah, Nadim J.; Langen, Karl-Josef; Galldiks, Norbert

2018-01-01

The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET parameters in gliomas with or without IDH mutation or 1p/19q co-deletion. Ninety patients with newly diagnosed and untreated gliomas with a static and dynamic 18 F-FET PET scan prior to evaluation of tumor tissue according to the 2016 WHO classification were identified retrospectively. Mean and maximum tumor-to-brain ratios (TBR mean/max ), as well as dynamic parameters (time-to-peak and slope) of 18 F-FET uptake were calculated. Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBR mean , TBR max , TTP and slope discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P < 0.01). TBR mean showed the best diagnostic performance (cut-off 1.95; sensitivity, 89%; specificity, 67%; accuracy, 81%). None of the parameters discriminated between oligodendrogliomas (IDH mutated, 1p/19q co-deleted) and glioblastomas or astrocytomas. Furthermore, TBR mean , TBR max , TTP, and slope discriminated between gliomas with and without IDH mutation (p < 0.01). The best diagnostic performance was obtained for the combination of TTP with TBR max or slope (accuracy, 73%). Data suggest that static and dynamic 18 F-FET PET parameters may allow determining non-invasively the IDH mutation status. However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be differentiated from glioblastomas and astrocytomas by 18 F-FET PET. (orig.)

The F1 -ATPase from Trypanosoma brucei is elaborated by three copies of an additional p18-subunit.

Science.gov (United States)

Gahura, Ondřej; Šubrtová, Karolína; Váchová, Hana; Panicucci, Brian; Fearnley, Ian M; Harbour, Michael E; Walker, John E; Zíková, Alena

2018-02-01

The F-ATPases (also called the F 1 F o -ATPases or ATP synthases) are multi-subunit membrane-bound molecular machines that produce ATP in bacteria and in eukaryotic mitochondria and chloroplasts. The structures and enzymic mechanisms of their F 1 -catalytic domains are highly conserved in all species investigated hitherto. However, there is evidence that the F-ATPases from the group of protozoa known as Euglenozoa have novel features. Therefore, we have isolated pure and active F 1 -ATPase from the euglenozoan parasite, Trypanosoma brucei, and characterized it. All of the usual eukaryotic subunits (α, β, γ, δ, and ε) were present in the enzyme, and, in addition, two unique features were detected. First, each of the three α-subunits in the F 1 -domain has been cleaved by proteolysis in vivo at two sites eight residues apart, producing two assembled fragments. Second, the T. brucei F 1 -ATPase has an additional subunit, called p18, present in three copies per complex. Suppression of expression of p18 affected in vitro growth of both the insect and infectious mammalian forms of T. brucei. It also reduced the levels of monomeric and multimeric F-ATPase complexes and diminished the in vivo hydrolytic activity of the enzyme significantly. These observations imply that p18 plays a role in the assembly of the F 1 domain. These unique features of the F 1 -ATPase extend the list of special characteristics of the F-ATPase from T. brucei, and also, demonstrate that the architecture of the F 1 -ATPase complex is not strictly conserved in eukaryotes. © 2017 Federation of European Biochemical Societies.

Tables of Shore and Fano parameters for the helium resonances 2s21S, 2p21D, and 2s 2p 1P excited in p-He collisions E/sub p/ = 33 to 150 keV

International Nuclear Information System (INIS)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Merchez, H.

1976-01-01

Absolute values of Shore and Fano parameters are tabulated for the helium atom 2s 2 1 S, 2p 2 1 D, and 2s 2p 1 P resonances produced by a proton beam. Observations were made on the spectra of ejected electrons. The important variation of the shape of the resonances with ejection angle is illustrated for E/sub p/ = 100 keV; the variation with proton energy is shown at 30 0

Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae*

Science.gov (United States)

Effelsberg, Daniel; Cruz-Zaragoza, Luis Daniel; Tonillo, Jason; Schliebs, Wolfgang; Erdmann, Ralf

2015-01-01

Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD+ salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. PMID:26276932

Functional and molecular evidence for heteromeric association of P2Y1 receptor with P2Y2 and P2Y4 receptors in mouse granulocytes.

Science.gov (United States)

Ribeiro-Filho, Antonio Carlos; Buri, Marcus Vinicius; Barros, Carlos Castilho; Dreyfuss, Juliana Luporini; Nader, Helena Bonciani; Justo, Giselle Zenker; Craveiro, Rogério Bastos; Pesquero, João Bosco; Miranda, Antonio; Ferreira, Alice Teixeira; Paredes-Gamero, Edgar Julian

2016-07-07

All hematopoietic cells express P2 receptors, however pharmacological characteristics such as expression and affinity in granulocytes are unknown. Pharmacological characteristics of P2 receptors were evaluated by Ca(2+) measurements using Fura-2 fluorophore. P2 receptors expression were analyzed by flow cytometry and RT-PCR. P2 interaction were shown by coimmunoprecipitation, western blotting and FRET. Granulocytes were responsive to P2Y agonists, whereas P2X agonists were ineffective. Ca(2+) increase, elicited by ADP and UTP was dependent on intracellular stocks and sensitive to G-coupled receptor inhibition. Moreover, MRS2179, a specific antagonist of the P2Y1 receptor, abolished ADP response. Interestingly, ADP and UTP exhibited full heterologous desensitization, suggesting that these agonists interact with the same receptor. The heteromeric association between P2Y1 receptor and the P2Y2 and P2Y4 receptors was shown by immunoprecipitation and FRET analysis. Clear evidence of heteromeric association of P2Y receptors was found during the evaluation of P2 receptors present in mice granulocytes, which could impact in the classical pharmacology of P2Y receptors in granulocytes.

Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

International Nuclear Information System (INIS)

Neuffer, D.B.

1977-05-01

Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

Suppression in the electrical hysteresis by using CaF2 dielectric layer for p-GaN MIS capacitors

Science.gov (United States)

Sang, Liwen; Ren, Bing; Liao, Meiyong; Koide, Yasuo; Sumiya, Masatomo

2018-04-01

The capacitance-voltage (C-V) hysteresis in the bidirectional measurements of the p-GaN metal-insulator-semiconductor (MIS) capacitor is suppressed by using a CaF2 dielectric layer and a post annealing treatment. The density of trapped charge states at the CaF2/p-GaN interface is dramatically reduced from 1.3 × 1013 cm2 to 1.1 × 1011/cm2 compared to that of the Al2O3/p-GaN interface with a large C-V hysteresis. It is observed that the disordered oxidized interfacial layer can be avoided by using the CaF2 dielectric. The downward band bending of p-GaN is decreased from 1.51 to 0.85 eV as a result of the low-density oxides-related trap states. Our work indicates that the CaF2 can be used as a promising dielectric layer for the p-GaN MIS structures.

Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae.

Science.gov (United States)

Effelsberg, Daniel; Cruz-Zaragoza, Luis Daniel; Tonillo, Jason; Schliebs, Wolfgang; Erdmann, Ralf

2015-10-16

Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD(+) salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)

DEFF Research Database (Denmark)

Hsu, Jerry Y; Reimann, Julie D R; Sørensen, Claus S

2002-01-01

. At the G1-S transition, hEmi1 is transcriptionally induced by the E2F transcription factor, much like cyclin A. hEmi1 overexpression accelerates S phase entry and can override a G1 block caused by overexpression of Cdh1 or the E2F-inhibitor p105 retinoblastoma protein (pRb). Depleting cells of hEmi1...

Induction of DNA synthesis and apoptosis are separable functions of E2F-1

DEFF Research Database (Denmark)

Phillips, A C; Bates, S; Ryan, K M

1997-01-01

The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic...... response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant...... apoptosis in the absence of p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E...

Suppression of Zeeman relaxation in cold collisions of 2P1/2 atoms

International Nuclear Information System (INIS)

Tscherbul, T. V.; Dalgarno, A.; Buchachenko, A. A.; Lu, M.-J.; Weinstein, J. D.

2009-01-01

We present a combined experimental and theoretical study of angular momentum depolarization in cold collisions of 2 P atoms in the presence of an external magnetic field. We show that collision-induced Zeeman relaxation of Ga( 2 P 1/2 ) and In( 2 P 1/2 ) atoms in cold 4 He gas is dramatically suppressed compared to atoms in 2 P 3/2 states. Using rigorous quantum-scattering calculations based on ab initio interaction potentials, we demonstrate that Zeeman transitions in collisions of atoms in 2 P 1/2 electronic states occur via couplings to the 2 P 3/2 state induced by the anisotropy of the interaction potential. Our results suggest the feasibility of sympathetic cooling and magnetic trapping of 2 P 1/2 -state atoms, such as halogens, thereby opening up exciting areas of research in precision spectroscopy and cold-controlled chemistry.

Wolf-Hirschhorn (4p-) syndrome: prenatal diagnosis, molecular cytogenetic characterization and association with a 1.2-Mb microduplication at 8p22-p21.3 and a 1.1-Mb microduplication at 10p15.3 in a fetus with an apparently pure 4p deletion.

Science.gov (United States)

Chen, Chih-Ping; Su, Yi-Ning; Chen, Yi-Yung; Su, Jun-Wei; Chern, Schu-Rern; Chen, Yu-Ting; Chen, Wen-Lin; Chen, Li-Feng; Wang, Wayseen

2011-12-01

To present prenatal diagnosis and molecular cytogenetic characterization of Wolf-Hirschhorn syndrome (WHS) associated with microduplications at 8p and 10p in a fetus with an apparently pure 4p deletion. A 35-year-old gravida 2, para 1 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Her husband was 38 years of age. There was no family history of congenital malformations. Amniocentesis revealed a karyotype of 46,XY,del(4p16.1). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 6.5-Mb deletion at 4p16.3-p16.1, a 1.2-Mb microduplication at 8p22-p21.3, and a 1.1-Mb microduplication at 10p15.3, or arr cgh 4p16.3p16.1 (0-6,531,998 bp)×1, 8p22p21.3 (18,705,388-19,940,445 bp)×3, 10p15.3 (0-1,105,065 bp)×3. Polymorphic DNA marker analysis confirmed a paternal origin of 4p deletion. Prenatal ultrasound revealed facial dysmorphism and hypospadias. The aCGH analysis of the parents revealed no genomic imbalance. Fluorescence in situ hybridization study showed an unbalanced reciprocal translocation between chromosomes 4 and 10 at bands 4p16.1 and 10p15.3. The cytogenetic result, thus, was 46,XY,der(4)t(4;10)(p16.1;p15.3),dup(8)(p21.3p22). The parents elected to terminate the pregnancy, and a 470-g malformed fetus was delivered. The present case provides evidence that an apparently pure 4p deletion can be associated with subtle chromosome imbalances in other chromosomes. Copyright © 2011. Published by Elsevier B.V.

Scutellarin inhibits cytochrome P450 isoenzyme 1A2 (CYP1A2) in rats.

Science.gov (United States)

Jian, Tun-Yu; He, Jian-Chang; He, Gong-Hao; Feng, En-Fu; Li, Hong-Liang; Bai, Min; Xu, Gui-Li

2012-08-01

Scutellarin is the most important flavone glycoside in the herbal drug Erigeron breviscapus (Vant.) Hand.-Mazz. It is used frequently in the clinic to treat ischemic vascular diseases in China. However, the direct relationship between scutellarin and cytochrome P450 (CYP450) is unclear. The present study investigated the in vitro and in vivo effects of scutellarin on cytochrome P450 1A2 (CYP 1A2) metabolism. According to in vitro experiments, scutellarin (10-250 µM) decreased the formation of 4-acetamidophenol in a concentration-dependent manner, with an IC₅₀ value of 108.20 ± 0.657 µM. Furthermore, scutellarin exhibited a weak mixed-type inhibition against the activity of CYP1A2 in rat liver microsomes, with a K(i) value of 95.2 µM. Whereas in whole animal studies, scutellarin treatment for 7 days (at 5, 15, 30 mg/kg, i.p.) decreased the clearance (CL), and increased the T(1/2) (at 15, 30 mg/kg, i.p.), it did not affect the V(d) of phenacetin. Scutellarin treatment (at 5, 15, 30 mg/kg, i.p.) increased the AUC(0-∞) by 14.3%, 67.3% and 159.2%, respectively. Scutellarin at 30 mg/kg also weakly inhibited CYP1A2 activity, in accordance with our in vitro study. Thus, the results indicate that CYP1A2 is inhibited directly, but weakly, by scutellarin in vivo, and provide useful information on the safe and effective use of scutellarin in clinical practice. Copyright © 2012 John Wiley & Sons, Ltd.

Measurements of the ground-state ionization energy and wavelengths for the 1snp {sup 1}P{sub 1}{sup *}-1s{sup 2} {sup 1}S{sub 0} (n=4-9) lines of Mg XI and F VIII

Energy Technology Data Exchange (ETDEWEB)

Pal' chikov, V.G. [Multicharged Ions Spectra Data Centre of VNIIFTRI, Mendeleevo (Russian Federation)). E-mail: vitpal@mail.ru; Ya Faenov, A.; Yu Skobelev, I. [Multicharged Ions Spectra Data Centre of VNIIFTRI, Mendeleevo (RU)] [and others

2002-06-28

The wavelengths of the 1snp {sup 1}P{sub 1}{sup 0}-1s{sup 2} {sup 1}S{sub 0} transitions in the He-like Mg XI (n = 4-9) and F VIII (n=4-8) have been measured in laser-produced plasmas. The accuracy of the present measurements (0.4-1.6 mA) is a large improvement over previous results. The Rydberg series is used to determine the ground-state ionization energy of F VIII and Mg XI: E{sub i}on (F VIII) 953.96{+-}0.11 eV, E{sub i}on (Mg XI)=1761.88{+-}0.15 eV. These experimental results are compared with theoretical data calculated by the 1/Z-expansion method and the HFR and MCDF approaches. Fairly good agreement between theory and experiment is observed with a precision up to 5x10{sup -5}. Radiative corrections to the 1s{sup 2} {sup 1}S{sub 0} state are analysed and compared with experiments. It is found that QED corrections to the ground-state ionization energy are significant at the present level of experimental accuracy. (author)

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

Science.gov (United States)

Tsai, Hsing-Chuan; Han, May H

2016-07-01

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

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

Science.gov (United States)

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

2016-10-01

Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function. The S1PL inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile was used to determine the relationship in rats between drug concentration, S1P levels in select tissues, and circulating lymphocytes. Repeated oral doses of the S1PL inhibitor fully depleted circulating lymphocytes after 3 to 4 days of treatment in rats. Full lymphopenia corresponded to increased levels of S1P of 100- to 1000-fold in lymph nodes, 3-fold in blood (but with no change in plasma), and 9-fold in cardiac tissue. Repeated oral dosing of the S1PL inhibitor in telemeterized, conscious rats resulted in significant bradycardia within 48 hours of drug treatment, comparable in magnitude to the bradycardia induced by 3 mg/kg fingolimod. These results suggest that S1PL inhibition modulates cardiac function and does not provide immune suppression with an improved cardiovascular safety profile over fingolimod in rats. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Growth, straightness and survival at age 32 in a Pinus strobus x P. wallichiana F1 hybrid population (Experiment 1

Directory of Open Access Journals (Sweden)

Ioan Blada

2013-12-01

in a breeding program. The narrow-sense family heritability estimates were 0.657 for diameter, 0.586 for height, 0.505 for volume, 0.705 for stem straightness and 0.734 for tree survival. The individual-tree narrow-sense heritability estimates were 0.336 for diameter, 0.253 for height, 0.205 for volume and 0.121 for stem straightness. Assuming selection of 5, 10, or 15 families out of the 28 tested ones and sexual propagation, a genetic gain of 9.5%, 6.8% and 4.8% in diameter, and 11.2%, 8.1% and 5.7% in volume and 16.4%, 11.8% and 8.4% in tree survival, respectively, might be achieved. Selecting the most outstanding 5%, 10%, or 15% individual F1 hybrids would yield a genetic progress of 9.7%, 8.3% and 7,4% in diameter and 10.2%, 8.8% and 7.8% in volume growth rate. The hybrid population mean surpassed in tree survival the open pollinated eastern white pine mean by 70.7% while the eastern white pine, surpassed the hybrid in all growth traits. The F1 hybrid and P. strobus open pollinated parent species averaged 0.993 and 1.069 m3 volume per tree, respectively. By extrapolation the yield results from the hybrid trial area to 1 ha results in a yield of 559.9 m3 per hectare for hybrids and 602.5 m3 for P. strobus female parent species. In conclusion, hybrids should be taken into consideration and used in plantation programs in high-blister-rust-hazard areas.

Arithmetically Cohen-Macaulay sets of points in P^1 x P^1

CERN Document Server

Guardo, Elena

2015-01-01

This brief presents a solution to the interpolation problem for arithmetically Cohen-Macaulay (ACM) sets of points in the multiprojective space P^1 x P^1.  It collects the various current threads in the literature on this topic with the aim of providing a self-contained, unified introduction while also advancing some new ideas.  The relevant constructions related to multiprojective spaces are reviewed first, followed by the basic properties of points in P^1 x P^1, the bigraded Hilbert function, and ACM sets of points.  The authors then show how, using a combinatorial description of ACM points in P^1 x P^1, the bigraded Hilbert function can be computed and, as a result, solve the interpolation problem.  In subsequent chapters, they consider fat points and double points in P^1 x P^1 and demonstrate how to use their results to answer questions and problems of interest in commutative algebra.  Throughout the book, chapters end with a brief historical overview, citations of related results, and, where relevan...

Static and dynamic 18F-FET PET for the characterization of gliomas defined by IDH and 1p/19q status.

Science.gov (United States)

Verger, Antoine; Stoffels, Gabriele; Bauer, Elena K; Lohmann, Philipp; Blau, Tobias; Fink, Gereon R; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

2018-03-01

The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET parameters in gliomas with or without IDH mutation or 1p/19q co-deletion. Ninety patients with newly diagnosed and untreated gliomas with a static and dynamic 18 F-FET PET scan prior to evaluation of tumor tissue according to the 2016 WHO classification were identified retrospectively. Mean and maximum tumor-to-brain ratios (TBR mean/max ), as well as dynamic parameters (time-to-peak and slope) of 18 F-FET uptake were calculated. Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBR mean , TBR max , TTP and slope discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P dynamic 18 F-FET PET parameters may allow determining non-invasively the IDH mutation status. However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be differentiated from glioblastomas and astrocytomas by 18 F-FET PET.

Isotope shift of 40,42,44,48Ca in the 4s 2S1/2 → 4p 2P3/2 transition

Science.gov (United States)

Gorges, C.; Blaum, K.; Frömmgen, N.; Geppert, Ch; Hammen, M.; Kaufmann, S.; Krämer, J.; Krieger, A.; Neugart, R.; Sánchez, R.; Nörtershäuser, W.

2015-12-01

We report on improved isotope shift measurements of the isotopes {}{40,42,{44,48}}Ca in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}3/2 (D2) transition using collinear laser spectroscopy. Accurately known isotope shifts in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}1/2(D1) transition were used to calibrate the ion beam energy with an uncertainty of {{Δ }}U≈ +/- 0.25 {{V}}. The accuracy in the D2 transition was improved by a factor of 5-10. A King-plot analysis of the two transitions revealed that the field shift factor in the D2 line is about 1.8(13)% larger than in the D1 transition which is ascribed to relativistic contributions of the 4{{{p}}}1/2 wave function.

Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p–Rnr4p

Energy Technology Data Exchange (ETDEWEB)

Ainsworth, William B. [Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, LA 70803 (United States); Hughes, Bridget Todd; Au, Wei Chun; Sakelaris, Sally [Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Kerscher, Oliver [Biology Department, The College of William and Mary, Williamsburg, VA 23185 (United States); Benton, Michael G., E-mail: benton@lsu.edu [Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, LA 70803 (United States); Basrai, Munira A., E-mail: basraim@mail.nih.gov [Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

2013-10-04

Highlights: •Hug1p overexpression sensitizes wild-type cells to DNA damage and hydroxyurea (HU). •Expression of Hug1p in response to HU treatment is delayed relative to Rnr3p. •MEC1 pathway genes are required for cytoplasmic localization of Hug1p. •Hug1p subcellular compartmentalization to the cytoplasm coincides with Rnr2p–Rnr4p. -- Abstract: The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p–Rnr4p subunits and inactivation of negative regulators Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p–Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p–Rnr4p.

Exclusive interactions in p anti-p collisions at s**(1/2) = 1.96 TeV

International Nuclear Information System (INIS)

Hamilton, Andrew; Alberta U.

2006-01-01

This thesis presents two exclusive production processes in p(bar p) collisions at √s = 1.96 TeV, using the Collider Detector Facility at Fermi National Accelerator Laboratory. An observation of exclusive e + e - production through γγ → e + e - is presented, as well as evidence for exclusive production of γγ through gg → γγ (via a quark loop). The exclusive e + e - production observation is based on 16 candidate events, with a background estimate of 2.1 -0.3 +0.7 . Each event has an e + e - pair (E T (e) > 5 GeV, |η(e)| -0.3 +0.5 (stat) ± 0.3(sys) pb, while the predicted cross section is 1.711 ± 0.008 pb. The kinematic properties of the events are consistent with the predictions of the LPAIR Monte Carlo. The evidence for exclusive γγ production consists of 3 candidate events, with a background estimate of 0.0 -0.0 +0.2 events. Each event has two photons (E T γ) > 5 GeV, |η(γ)| -0.04 +0.14 (stat) ± (sys) pb. It agrees with the theoretical prediction of 0.04 pb with a factor 3 to 5 theoretical uncertainty

J/ψ production in p anti p collisions at √s = 1.8 TeV

International Nuclear Information System (INIS)

Abachi, S.

1995-07-01

The authors have studied J/ψ production in p anti p collisions at √s = 1.8 TeV with the D0 detector at Fermilab, using a μ + μ - data sample corresponding to an integrated luminosity of 13 pb -1 . They have measured the inclusive J/ψ production cross section as a function of J/ψ transverse momentum p T . For the kinematic range p T > 8 GeV/c and |η| + μ - ) · σ(p anti p → J/ψ + X) = 1.93 ± 0.16(stat) ± 0.43(syst) nb. Using the muon impact parameter they have estimated the fraction of J/ψ mesons coming from B meson decays to be f b = 0.35 ± 0.09 (stat) ± 0.10 (syst) and inferred the inclusive b production cross section. From the information on the event topology a fraction of non-isolated J/ψ events has been measured to be f non-isol = 0.64 ± 0.09(stat) ± 0.06(syst). They have also obtained the fraction of events resulting from radiative decays of χ c states as f χ = 0.30 ± 0.07(stat) ± 0.07(syst). They discuss the implications of the measurements for charmonium production processes

Overexpression of HDAC1 induces cellular senescence by Sp1/PP2A/pRb pathway

International Nuclear Information System (INIS)

Chuang, Jian-Ying; Hung, Jan-Jong

2011-01-01

Highlights: → Overexpression of HDAC1 induces Sp1 deacetylation and raises Sp1/p300 complex formation to bind to PP2Ac promoter. → Overexpression of HDAC1 strongly inhibits the phosphorylation of pRb through up-regulation of PP2A. → Overexpressed HDAC1 restrains cell proliferaction and induces cell senescence though a novel Sp1/PP2A/pRb pathway. -- Abstract: Senescence is associated with decreased activities of DNA replication, protein synthesis, and cellular division, which can result in deterioration of cellular functions. Herein, we report that the growth and division of tumor cells were significantly repressed by overexpression of histone deacetylase (HDAC) 1 with the Tet-off induced system or transient transfection. In addition, HDAC1 overexpression led to senescence through both an accumulation of hypophosphorylated active retinoblastoma protein (pRb) and an increase in the protein level of protein phosphatase 2A catalytic subunit (PP2Ac). HDAC1 overexpression also increased the level of Sp1 deacetylation and elevated the interaction between Sp1 and p300, and subsequently that Sp1/p300 complex bound to the promoter of PP2Ac, thus leading to induction of PP2Ac expression. Similar results were obtained in the HDAC1-Tet-off stable clone. Taken together, these results indicate that HDAC1 overexpression restrained cell proliferation and induced premature senescence in cervical cancer cells through a novel Sp1/PP2A/pRb pathway.

Overexpression of HDAC1 induces cellular senescence by Sp1/PP2A/pRb pathway

Energy Technology Data Exchange (ETDEWEB)

Chuang, Jian-Ying [Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan (China); Hung, Jan-Jong, E-mail: petehung@mail.ncku.edu.tw [Department of Pharmacology, National Cheng-Kung University, Tainan 701, Taiwan (China); Institute of Bioinformatics and Biosignal Transduction, National Cheng-Kung University, Tainan 701, Taiwan (China)

2011-04-15

Highlights: {yields} Overexpression of HDAC1 induces Sp1 deacetylation and raises Sp1/p300 complex formation to bind to PP2Ac promoter. {yields} Overexpression of HDAC1 strongly inhibits the phosphorylation of pRb through up-regulation of PP2A. {yields} Overexpressed HDAC1 restrains cell proliferaction and induces cell senescence though a novel Sp1/PP2A/pRb pathway. -- Abstract: Senescence is associated with decreased activities of DNA replication, protein synthesis, and cellular division, which can result in deterioration of cellular functions. Herein, we report that the growth and division of tumor cells were significantly repressed by overexpression of histone deacetylase (HDAC) 1 with the Tet-off induced system or transient transfection. In addition, HDAC1 overexpression led to senescence through both an accumulation of hypophosphorylated active retinoblastoma protein (pRb) and an increase in the protein level of protein phosphatase 2A catalytic subunit (PP2Ac). HDAC1 overexpression also increased the level of Sp1 deacetylation and elevated the interaction between Sp1 and p300, and subsequently that Sp1/p300 complex bound to the promoter of PP2Ac, thus leading to induction of PP2Ac expression. Similar results were obtained in the HDAC1-Tet-off stable clone. Taken together, these results indicate that HDAC1 overexpression restrained cell proliferation and induced premature senescence in cervical cancer cells through a novel Sp1/PP2A/pRb pathway.

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

Science.gov (United States)

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

2014-05-01

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

Thermonuclear reaction rate of 17O(p,γ)18F

International Nuclear Information System (INIS)

Fox, C.; Iliadis, C.; Champagne, A.E.; Fitzgerald, R.P.; Longland, R.; Newton, J.; Pollanen, J.; Runkle, R.

2005-01-01

The 17 O(p,γ) 18 F and 17 O(p,α) 14 N reactions have a profound influence on hydrogen-burning nucleosynthesis in a number of stellar sites, including red giants, asymptotic giant branch (AGB) stars, massive stars, and classical novae. Previously evaluated thermonuclear rates for both reactions carry large uncertainties. We investigated the proton-capture reaction on 17 O in the bombarding energy range of E p lab = 180-540 keV. We observed a previously undiscovered resonance at E R lab = 193.2 ± 0.9 keV. The resonance strength amounts to (ωγ) pγ (1.2±0.2)x10 -6 eV. With this value, the uncertainties of the 17 O(p,γ) 18 F reaction rates are reduced by orders of magnitude in the peak temperature range of classical novae (T=0.1-0.4 GK). We also report on a reevaluation of the 17 O(p,γ) 18 F reaction rates at lower temperatures that are pertinent to red giants, AGB stars, or massive stars. The present work establishes the 17 O(p,γ) 18 F reaction rates over a temperature range of T= 0.01-1.5 GK with statistical uncertainties of 10-50%. The new recommended reaction rates deviate from the previously accepted values by an order of magnitude around T≅0.2 GK and by factors of 2-3 at T < 0.1 GK

The three-loop splitting functions P{sup (2)}{sub qg} and P{sup (2,N{sub F})}{sub gg}

Energy Technology Data Exchange (ETDEWEB)

Ablinger, J.; Schneider, C. [Johannes Kepler Univ., Linz (Austria). Research Inst. for Symbolic Computation (RISC); Behring, A. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); RWTH Aachen Univ. (Germany). Inst. fuer Theoretische Teilchenphysik und Kosmologie; Bluemlein, J.; Freitas, A. de [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Von Manteuffel, A. [Michigan State Univ., East Lansing, MI (United States). Dept. of Physics and Astronomy

2017-04-15

We calculate the unpolarized twist-2 three-loop splitting functions P{sup (2)}{sub qg}(x) and P{sup (2,N{sub F})}{sub gg}(x) and the associated anomalous dimensions using massive three-loop operator matrix elements. While we calculate P{sup (2,N{sub F})}{sub gg}(x) directly, P{sup (2)}{sub qg}(x) is computed from 1200 even moments, without any structural prejudice, using a hierarchy of recurrences obtained for the corresponding operator matrix element. The largest recurrence to be solved is of order 12 and degree 191. We confirm results in the foregoing literature.

The effect of lycopene on the total cytochrome P450, CYP1A2 and CYP2E1

Directory of Open Access Journals (Sweden)

Melva Louisa

2009-12-01

Full Text Available Aim: Some carotenoids such as canthaxantin, astaxanthin and beta apo-8’-carotenal were reported to have modulatoryeffect on the cytochrome P450. The present study was conducted to investigate the effects of lycopene, a nonprovitamin A carotenoid, on microsomal cytochrome P450, CYP1A2 and CYP2E1.Methods: Total cytochrome P450 levels, CYP1A2 and CYP2E1-catalyzed reactions (acetanilide 4-hydroxylation and p-nitrophenol hydroxylation were studied in the liver microsomes of male Sprague Dawley rats. Microsomes were prepared using differential centrifugation combined with calcium aggregation method. Lycopene was orally administered in the dosages of 0, 25, 50 or 100 mg/kgBW/day for 14 days in a repeated fashion. Data were analyzed using ANOVA test.Results: Total cytochrome P450 level and acetanilide 4-hydroxylase activity were unaffected by any of the treatments. The CYP2E1 probe enzyme (p-nitrophenol hydroxylase was significantly reduced by repeated administration of 100mg/ kgBW/day lycopene (7.88 + 2.04 vs 12.26 + 2.77 n mol/min/mg prot.Conclusion: The present results suggest that lycopene does not affect the total cytochrome P450 or CYP1A2 activity but it inhibits the activity of CYP2E1 (p-nitrophenol hydroxylase in the rat. (Med J Indones 2009; 18: 233-8Keywords: lycopene, cytochrome P450, CYP1A2, CYP2E1

Familial partial duplication (1)(p21p31)

Energy Technology Data Exchange (ETDEWEB)

Hoechstetter, L.; Soukup, S.; Schorry, E.K. [Children`s Hospital Research Foundation, Cincinnati, OH (United States)

1995-11-20

A partial duplication (1)(p21p31), resulting from a maternal direct insertion (13,1) (q22p21p31), was found in a 30-year-old woman with mental retardation, cleft palate, and multiple minor anomalies. Two other affected and deceased relatives were presumed to have the same chromosome imbalance. Duplication 1p cases are reviewed. 8 refs., 5 figs., 1 tab.

The 2s1/2 → 2p1/2 + one photon transition in hydrogen and hydrogenlike ions

International Nuclear Information System (INIS)

Kelsey, E.J.

1977-01-01

The 2s 1 / 2 → 2p 1 / 2 + one photon transition rate is calculated and discussed for hydrogen and hydrogenlike ions. It is noted that the induced transition rather than the spontaneous transition is of primary importance since it is the basis of many of the precision Lamb-shift measurements. The lack of a calculation of the transition rate other than a heuristic nonrelativistic derivation which requires a nontrivial assumption motivates the calculation presented here based on the external field approximation to quantum electrodynamics. It is found that the heuristic answer is correct in lowest order. In this derivation we see that the 2s 1 / 2 → 2p 1 / 2 + one photon transition gives an apparent contradiction to the often-stated remark that for the electric dipole matrix element there exist three equivalent representations, the ''length,'' ''velocity,'' and ''acceleration'' forms. The difficulties of an experimental determination of this transition rate using induced transitions in hydrogenlike ions are briefly noted as well as the somewhat different case of heavy muonic atoms where the spontaneous 2s 1 / 2 → 2p 1 / 2 + one photon transition has been observed

Optimization of 1.3-μm InGaAsP/InP Electro-Absorption Modulator

International Nuclear Information System (INIS)

Wang Hui-Tao; Zhou Dai-Bing; Zhang Rui-Kang; Lu Dan; Zhao Ling-Juan; Zhu Hong-Liang; Wang Wei; Ji Chen

2015-01-01

We report the simulation and experimental results of 1.3-μm InGaAsP/InP multiple quantum well (MQW) electro-absorption modulators (EAMs). In this work, the quantum confined Stark effect of the EAM is systematically analyzed through the finite element method. An optimized structure of the 1.3-μm InGaAsP/InP QW EAM is proposed for applications in 100 G ethernet. Then 1.3-μm InGaAsP/InP EAMs with f_−_3 _d_B bandwidth of over 20 GHz and extinction ratio over 20 dB at 3 V bias voltage are demonstrated. (paper)

Near-threshold electron-impact excitation of the (2p53s2)2P3/2,1/2 autoionizing states in sodium

International Nuclear Information System (INIS)

Borovik, A; Zatsarinny, O; Bartschat, K

2008-01-01

The ejected-electron excitation functions of the J = 3/2, 1/2 components of the (2p 5 3s 2 ) 2 P leading autoionizing doublet in sodium atoms were measured at an incident electron energy resolution of 0.25 eV over the incident electron energy range from the lowest excitation threshold up to 36 eV. On the basis of 56-state R-matrix (close-coupling) calculations, the observed strong near-threshold structures were classified as negative-ion resonances with likely configurations 2p 5 3s 2 3p and 2p 5 3s3p 2

Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p

Directory of Open Access Journals (Sweden)

Greenblatt Jack F

2007-09-01

Full Text Available Abstract Background Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4. Results Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC. While mutational inactivation of the histone acetyltransferase (HAT gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2 exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork. Conclusion We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p. The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.

Observation of the 1P1 state of charmonium

International Nuclear Information System (INIS)

Armstrong, T.A.; Bettoni, D.; Bharadwaj, V.; Biino, C.; Borreani, G.; Broemmelsiek, D.; Buzzo, A.; Calabrese, R.; Ceccucci, A.; Cester, R.; Church, M.; Dalpiaz, P.; Dalpiaz, P.F.; Dibenedetto, R.; Dimitroyannis, D.; Fabbri, M.G.; Fast, J.; Gianoli, A.; Ginsburg, C.M.; Gollwitzer, K.; Hahn, A.; Hasan, M.; Hsueh, S.; Lewis, R.; Luppi, E.; Macri, M.; Majewska, A.M.; Mandelkern, M.; Marchetto, F.; Marinelli, M.; Marques, J.; Marsh, W.; Martini, M.; Masuzawa, M.; Menichetti, E.; Migliori, A.; Mussa, R.; Palestini, S.; Pallavicini, M.; Pastrone, N.; Patrignani, C.; Peoples, J. Jr.; Pesando, L.; Petrucci, F.; Pia, M.G.; Pordes, S.; Rapidis, P.; Ray, R.; Reid, J.; Rinaudo, G.; Roccuzzo, B.; Rosen, J.; Santroni, A.; Sarmiento, M.; Savrie, M.; Scalisi, A.; Schultz, J.; Seth, K.K.; Smith, A.; Smith, G.A.; Sozzi, M.; Trokenheim, S.; Weber, M.F.; Werkema, S.; Zhang, Y.; Zhao, J.; Zioulas, G.

1992-01-01

We have performed a search for the 1 P 1 state of charmonium resonantly formed in bar pp annihilations, close to the center of gravity of the 3 P J states. We report results from the study of the J/ψ+π 0 and J/ψ+2π final states. We have observed a statistically significant enhancement in the bar p+p→J/ψ+π 0 cross section at √s congruent 3526.2 MeV. This enhancement has the characteristics of a narrow resonance of mass, total width, and production cross section consistent with what is expected for the 1 P 1 state. In our search we have found no candidates for the reactions bar p+p→J/ψ+π 0 +π 0 and bar p+p→J/ψ+π + +π -

Posttranscriptional regulation of the karyogamy gene by Kem1p/Xrn1p exoribonuclease and Rok1p RNA helicase of Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Kim, Jaehee; Jeon, Soonmee; Yang, Yun-Seok; Kim, Jinmi

2004-01-01

The major biochemical activities ascribed to Kem1p/Xrn1p of Saccharomyces cerevisiae are 5'-3' exoribonuclease functioning in RNA turnover and a microtubule-binding protein. Mutational analysis has shown that Kem1p/Xrn1p participates in microtubule-related functions such as nuclear fusion (karyogamy) during mating, chromosome transmission, and spindle pole body duplication. Here, evidence is presented that Kem1p plays a specific role in nuclear fusion by affecting, at the posttranscriptional level, the pheromone induction of the karyogamy-specific transcription factor Kar4p and the expression of Rok1p, a putative RNA helicase. We found that Rok1p itself also affects the pheromone induction of Kar4p and thereby participates in nuclear fusion. Analysis of the active-site mutations, xrn1-D206A or D208A, shows that nuclear fusion as well as the Rok1p synthesis do not require the exoribonuclease activity of Kem1p. Our data provide an important insight into the gene-specific regulatory function mediated by the general RNA-modulating enzymes

DRD2 A1 allele and P300 abnormalities in obesity

Energy Technology Data Exchange (ETDEWEB)

Blum, K. [Univ. of Texas Health Science Center, San Antonio, TX (United States)]|[PATH Foundation, Princeton, NJ (United States); Wood, R.; Sheridan, L.P.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

1994-09-01

Obesity is a heterogeneous and prevalent disorder having both inheritable and environmental components. The role of the dopamine system in P300 has been implicated. We genotyped 193 neuropsychiatrically ill patients with and without comorbid drug and alcohol/abuse/dependence and obesity for the prevalence of the A1 allele of the DRD2 gene. We found a significant linear trend ({chi}{sup 2} = 40.4, df=1, p<0.00001) where the percent prevalence of the A1 increased with increasing polysubstance abuse. Where the A1 allele was found in 44% of 40 obese subjects, the A1 allele prevalence was found in as much as 91% of 11 obese subjects with comorbid polysubstance abuse. 53 obese subjects having a mean body weight (BMI) of 34.6{+-}8.2 were mapped for brain electrical activity and compared with 15 controls with a BMI of 22.3{+-}3.0 (P<.001). The P3 amplitude was significantly different (two tailed; t=3.24, df=16.2, P = 0.005), whereas P3 latency was not significant. Preliminarily, we found a significant decreased P3 amplitude correlated with parental polysubstance abuse (p=0.4) with prolongation of P3 latency correlated with the three risk factors of parental substance abuse, chemical dependency and carbohydrate bingeing (P<0.02). Finally, in a small sample, the A1 allele was present in 25% of probands having 0 risk compared to 66% in those obese subjects with any risk. This work represents the first electrophysiological data to implicate P3 abnormalities in a subset of obesity and further confirms an association of the DRD2 gene and a electrophysiological marker previously indicated to have predictive value in vulnerability to addictive behaviors.

PLASMA DIAGNOSTIC POTENTIAL OF 2p4f IN N{sup +}—ACCURATE WAVELENGTHS AND OSCILLATOR STRENGTHS

Energy Technology Data Exchange (ETDEWEB)

Shen, Xiaozhi [School of Physics Science and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); Li, Jiguang; Wang, Jianguo [Data Center for High Energy Density Physics, Institute of Applied Physics and Computational Mathematics, P.O. Box 8009, Beijing 100088 (China); Jönsson, Per, E-mail: Li_Jiguang@iapcm.ac.cn [Materials Science and Applied Mathematics, Malmö University, SE-20506 Malmö (Sweden)

2015-03-10

Radiative emission lines from nitrogen and its ions are often observed in nebula spectra, where the N{sup 2+} abundance can be inferred from lines of the 2p4f configuration. In addition, intensity ratios between lines of the 2p3p-2p3s and 2p4f-2p3d transition arrays can serve as temperature diagnostics. To aid abundance determinations and plasma diagnostics, wavelengths and oscillator strengths were calculated with high precision for electric dipole (E1) transitions from levels in the 2p4f configuration of N{sup +}. Electron correlation and relativistic effects, including the Breit interaction, were systematically taken into account within the framework of the multiconfiguration Dirac-Hartree-Fock method. Except for the 2p4f-2p4d transitions with quite large wavelengths and the two-electron-one-photon 2p4f-2s2p {sup 3} transitions, the uncertainties of the present calculations were controlled to within 3% and 5% for wavelengths and oscillator strengths, respectively. We also compared our results with other theoretical and experimental values when available. Discrepancies were found between our calculations and previous calculations due to the neglect of relativistic effects in the latter.

Modulation of the E2F1-driven cancer cell fate by the DNA damage response machinery and potential novel E2F1 targets in osteosarcomas

DEFF Research Database (Denmark)

Liontos, Michalis; Niforou, Katerina; Velimezi, Georgia

2009-01-01

Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies...... in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network...

Static and dynamic {sup 18}F-FET PET for the characterization of gliomas defined by IDH and 1p/19q status

Energy Technology Data Exchange (ETDEWEB)

Verger, Antoine [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, INM-4, INM-5), Juelich (Germany); Lorraine University, Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy, Nancy (France); Lorraine University, IADI, INSERM, UMR 947, Nancy (France); Service de Medecine Nucleaire, Vandoeuvre-les-Nancy (France); Stoffels, Gabriele; Lohmann, Philipp; Neumaier, Bernd [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, INM-4, INM-5), Juelich (Germany); Bauer, Elena K. [University Hospital Cologne, Department of Neurology, Cologne (Germany); Blau, Tobias [University Hospital Cologne, Department of Neuropathology, Cologne (Germany); Fink, Gereon R. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, INM-4, INM-5), Juelich (Germany); University Hospital Cologne, Department of Neurology, Cologne (Germany); Shah, Nadim J. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, INM-4, INM-5), Juelich (Germany); RWTH Aachen University Hospital, Department of Neurology, Aachen (Germany); Section JARA-Brain, Juelich-Aachen Research Alliance (JARA), Juelich (Germany); Langen, Karl-Josef [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, INM-4, INM-5), Juelich (Germany); Section JARA-Brain, Juelich-Aachen Research Alliance (JARA), Juelich (Germany); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany); Galldiks, Norbert [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, INM-4, INM-5), Juelich (Germany); University Hospital Cologne, Department of Neurology, Cologne (Germany); Universities of Cologne and Bonn, Center of Integrated Oncology (CIO), Cologne (Germany)

2018-03-15

The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2-{sup 18}F-fluoroethyl)-L-tyrosine ({sup 18}F-FET) PET parameters in gliomas with or without IDH mutation or 1p/19q co-deletion. Ninety patients with newly diagnosed and untreated gliomas with a static and dynamic {sup 18}F-FET PET scan prior to evaluation of tumor tissue according to the 2016 WHO classification were identified retrospectively. Mean and maximum tumor-to-brain ratios (TBR{sub mean/max}), as well as dynamic parameters (time-to-peak and slope) of {sup 18}F-FET uptake were calculated. Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBR{sub mean}, TBR{sub max}, TTP and slope discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P < 0.01). TBR{sub mean} showed the best diagnostic performance (cut-off 1.95; sensitivity, 89%; specificity, 67%; accuracy, 81%). None of the parameters discriminated between oligodendrogliomas (IDH mutated, 1p/19q co-deleted) and glioblastomas or astrocytomas. Furthermore, TBR{sub mean}, TBR{sub max}, TTP, and slope discriminated between gliomas with and without IDH mutation (p < 0.01). The best diagnostic performance was obtained for the combination of TTP with TBR{sub max} or slope (accuracy, 73%). Data suggest that static and dynamic {sup 18}F-FET PET parameters may allow determining non-invasively the IDH mutation status. However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be differentiated from glioblastomas and astrocytomas by {sup 18}F-FET PET. (orig.)

Search for stopped gluinos from p-anti-p collisions at s**(1/2) = 1.96 TeV

Czech Academy of Sciences Publication Activity Database

Abazov, V. M.; Abbott, B.; Abolins, M.; Kupčo, Alexander; Lokajíček, Miloš; Šimák, Vladislav

2007-01-01

Roč. 99, č. 13 (2007), 131801/1-131801/7 ISSN 0031-9007 R&D Projects: GA MŠk 1P04LA210; GA MŠk 1P05LA257 Institutional research plan: CEZ:AV0Z10100502 Keywords : supersymmetry * gluino * neutralino * D0 * DZero Subject RIV: BF - Elementary Particle s and High Energy Physics Impact factor: 6.944, year: 2007

Measurements of the ground-state ionization energy and wavelengths for the 1snp 1P1*-1s21S0 (n=4-9) lines of Mg XI and F VIII

International Nuclear Information System (INIS)

Pal'chikov, V.G.; Ya Faenov, A.; Yu Skobelev, I.

2002-01-01

The wavelengths of the 1snp 1 P 1 0 -1s 2 1 S 0 transitions in the He-like Mg XI (n = 4-9) and F VIII (n=4-8) have been measured in laser-produced plasmas. The accuracy of the present measurements (0.4-1.6 mA) is a large improvement over previous results. The Rydberg series is used to determine the ground-state ionization energy of F VIII and Mg XI: E i on (F VIII) 953.96±0.11 eV, E i on (Mg XI)=1761.88±0.15 eV. These experimental results are compared with theoretical data calculated by the 1/Z-expansion method and the HFR and MCDF approaches. Fairly good agreement between theory and experiment is observed with a precision up to 5x10 -5 . Radiative corrections to the 1s 2 1 S 0 state are analysed and compared with experiments. It is found that QED corrections to the ground-state ionization energy are significant at the present level of experimental accuracy. (author)

VARIABILIDAD GENÉTICA DE PARENTALES Y POBLACIONES F1 INTER E INTRAESPECÍFICAS DE Physalis peruviana L. Y P. floridana Rydb.

Directory of Open Access Journals (Sweden)

JHON ALEXANDER BERDUGO CELY

2015-03-01

Full Text Available RESUMEN La uchuva, Physalis peruviana, es un frutal andino de importancia para la exportación; el principal limitante de su producción en Colombia es el marchitamiento vascular ocasionado por Fusarium oxysporum. En el presente trabajo se propuso generar poblaciones F1 entre parentales contrastantes por su respuesta a éste patógeno y evaluarlas molecularmente como apoyo al conocimiento y uso de los recursos genéticos de la especie. Para ello, cuatro genotipos de P. peruviana y uno de la especie relacionada P. floridana, fueron caracterizados a nivel morfo-agronómico empleando 34 variables cualitativas y 20 cuantitativas, y a nivel molecular con 328 marcadores tipoCOSII y 154 IRGs. Dichos genotipos se utilizaron como parentales para la generación y caracterización molecular de poblaciones F1. Las variables cuantitativas permitieron diferenciar las especies P. floridana y P. peruviana así como genotipos cultivados y silvestres dentro de P. peruviana. Se encontró un 100% de viabilidad en cruces F1 intraespecíficos y un 50% en interespecíficos, siendo viables aquellos donde P. floridana fue receptor de polen. A nivel molecular no se identificaron polimorfismos dentro de P. peruviana pero sí entre P. floridana y P. Peruviana. En una población F1 de 51 individuos generada entre las especies se encontró un total de 127 alelos con un promedio de 3,18 por locus, un PIC de 0,358 y altos valores de heterocigocidad (Ho: 0,737 y He: 0,449. Los análisis de PCA y agrupamiento permitieron discriminar la población F1 en tres grupos, en su mayoría con mayor similitud al parental P. floridana. Lo anterior se reflejó en una distorsión mendeliana del 75% favorecida por la presencia de un 63,75% de alelos maternos. El estudio aporta conocimiento sobre la cruzabilidad en uchuva y la variabilidad genética de genotipos parentales y poblaciones F1.

The effect of P-glycoprotein on 18F-FDG uptake in vitro

International Nuclear Information System (INIS)

Yu Chunjing; Zhang Bin; Deng Shengming; Wan Weixing; Wu Yiwei

2013-01-01

Objective: To evaluate the effect of P-gp inhibitors of verapamil (VER) and GF120918 on 18 F-FDG uptake in Bcap37 and Bcap37/multidrug resistance (MDR)1 cell lines in vitro, and to explore the relationship between 18 F-FDG uptake and P-gp expression at cellular level. Methods: Bcap37 and Bcap37/MDR1 cells were seeded into 6-well plates at a density of 1 × 10 6 per well. Three days later,37 kBq/ml 18 F-FDG, or 37 kBq/ml 18 F-FDG + 100 μmol/L VER, or 37 kBq/ml 18 F-FDG + 50 μmol/L GF120918 were added into each well. After incubated for 10, 30, 60 and 120 min at 37 ℃ and in 5% CO 2 , the medium was removed and the cells were washed three times with 1 ml ice-cold PBS immediately. The radioactivity of 18 F-FDG was measured using a gamma counter. The uptake of 18 F-FDG was expressed as the ratio of 18 F-FDG radioactivity in Bcap37 or Bcap37/MDR1 cells and the overall radioactivity added to the cells in each well.The t test was used for statistical analysis. Results: 18 F-FDG uptake was higher in Bcap37/MDR1 cells than that in Bcap37 cells after incubated for 10 min. The uptake rate was (1.88 ±0.19) % in Bcap37/MDR1 cells and (1.37 ± 0.18) % in Bcap37 cells (t=7.832, P<0.05). On the contrary, 18 F-FDG uptake was significantly higher in Bcap37 cells than that in Bcap37/MDR1 cells after incubated for 60 and 120 min. The uptake rates were (2.29 ±0.23)% and (2.34 ±0.15)% in Bcap37 cells, (1.47 ±0.14)% and (1.53 ±0.22)% in Bcap37/MDR1 cells (t=8.437, 8.283, both P<0.05). 18 F-FDG uptake was significantly higher with VER or GF120918 in Bcap37/MDR1 cells than that without VER or GF120918 after the incubation of 60 and 120 min (t=9.032, 9.243 and 8.765, 8.803, all P<0.05). The uptake rates with VER or GF120918 were (2.45 ±0.21)% and (2.46 ±0.25)%, (2.50 ±0.24)% and (2.48 ±0.27)%. There was no significant difference of 18 F-FDG uptake in Bcap37 cells with or without VER or GF120918. Conclusions: 18 F-FDG is a substrate of P-gp at cellular level. P-gp may act as an

Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

International Nuclear Information System (INIS)

Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

2015-01-01

Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death

Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

Energy Technology Data Exchange (ETDEWEB)

Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

2015-09-25

Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death.

Heavy particle excitation of the 2s22p52P3/2-2s22p52P1/2 transition in fluorine-like Fe XVIII and Ni XX

International Nuclear Information System (INIS)

Keenan, F.P.; Reid, R.H.G.

1989-01-01

Cross sections and rate coefficients for excitation of the 2s 2 2p 52 P 3/2 -2s 2 2p 52 P 1/2 transition in fluorine-like Fe XVIII and Ni XX by proton (p), deuteron (d), triton (t) and α-particle (α) impact have been calculated using the close-coupled impact parameter method. At temperatures close to or below those of maximum Fe XVIII and Ni XX fractional abundance in ionisation equilibrium, the p,d and t rates are found to be comparable and are much greater than the rates due to α collisions. However, at high temperatures the situation is reversed, with the α rates being about a factor of two larger than those due to the other particles. The effects of adopting the present atomic data in calculations of the electron density or ion temperature sensitive emission line ratios are briefly discussed. (author)

Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation

DEFF Research Database (Denmark)

Helin, K; Wu, C L; Fattaey, A R

1993-01-01

the hypophosphorylated form of the retinoblastoma protein (pRB). The other protein, murine DP-1, was purified from an E2F DNA-affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 and DP-1, we have now isolated a cDNA for the human...

[μ-1,2-Bis(diphenylphosphinoethane-κ2P:P′]bis{[1,2-bis(diphenylphosphinoethane-κ2P,P′]cyanidocopper(I} methanol disolvate

Directory of Open Access Journals (Sweden)

Rong Wang

2010-08-01

Full Text Available The title centrosymmetric complex, [Cu2(CN2(C26H24P23]·2CH3OH, consists of two five-membered [Cu(dppeCN] rings [dppe is 1,2-bis(diphenylphosphinoethane] bridged by one μ2-dppe ligand, and two methanol solvent molecules. The angles around the central metal atom indicate that each CuI atom is located in the center of a distorted tetrahedron. The coordination sphere of each CuI atom is formed by three P atoms from two dppe ligands, and one C atom from the cyanide ligand. The crystal structure is stabilized by O—H...N hydrogen bonds, which are formed by the O—H donor group from methanol and the N-atom acceptor from a cyanide ligand.

The amino terminal end determines the stability and assembling capacity of eukaryotic ribosomal stalk proteins P1 and P2.

Science.gov (United States)

Camargo, Hendricka; Nusspaumer, Gretel; Abia, David; Briceño, Verónica; Remacha, Miguel; Ballesta, Juan P G

2011-05-01

The eukaryotic ribosomal proteins P1 and P2 bind to protein P0 through their N-terminal domain to form the essential ribosomal stalk. A mutational analysis points to amino acids at positions 2 and 3 as determinants for the drastic difference of Saccharomyces cerevisiae P1 and P2 half-life, and suggest different degradation mechanisms for each protein type. Moreover, the capacity to form P1/P2 heterodimers is drastically affected by mutations in the P2β four initial amino acids, while these mutations have no effect on P1β. Binding of P2β and, to a lesser extent, P1β to the ribosome is also seriously affected showing the high relevance of the amino acids in the first turn of the NTD α-helix 1 for the stalk assembly. The negative effect of some mutations on ribosome binding can be reversed by the presence of the second P1/P2 couple in the ribosome, indicating a stabilizing structural influence between the two heterodimers. Unexpectedly, some mutations totally abolish heterodimer formation but allow significant ribosome binding and, therefore, a previous P1 and P2 association seems not to be an absolute requirement for stalk assembly. Homology modeling of the protein complexes suggests that the mutated residues can affect the overall protein conformation. © The Author(s) 2011. Published by Oxford University Press.

Changes in the F0F1-ATPase activity of irradiated Lactobacillus acidophilus in the presence of ceftazidime at low pH

International Nuclear Information System (INIS)

Kalantaryan, V.P.; Trchounian, A.H.; Soghomonyan, D.R.

2014-01-01

The aim of this study was the investigation of the effects of low intensity electromagnetic irradiation (EMI) at the frequencies of 51.8 and 53 GHz and of antibiotic ceftazidime on the N,N'-dicyclohexylcarbodiimide (DCCD) inhibited ATPase activity of membrane vesicles of lactic acid bacteria Lactobacillus acidophilus grown at low pH (pH 4.0 or 6.5) and assayed at the same pH. It was shown that both frequencies EMI stimulated ATPase activity of L. acidophilus grown at pH 4.0, but EMI combined with ceftazidime and DCCD decreased ATPase activity at pH 4.0 and pH 6.5. It was suggested that the F 0 F 1 -ATPase might be a target for EMI even at low pH

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

Science.gov (United States)

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

2017-01-01

Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. . Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement of the production cross section ratio $\\sigma(\\chi_{b2}(1\\mathrm{P}))/ \\sigma(\\chi_{b1}(1\\mathrm{P}))$ in pp collisions at $\\sqrt{s}$ = 8 TeV

CERN Document Server

Khachatryan, Vardan; Tumasyan, Armen; Adam, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Erö, Janos; Fabjan, Christian; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Kiesenhofer, Wolfgang; Knünz, Valentin; Krammer, Manfred; Krätschmer, Ilse; Liko, Dietrich; Mikulec, Ivan; Rabady, Dinyar; Rahbaran, Babak; Rohringer, Herbert; Schöfbeck, Robert; Strauss, Josef; Taurok, Anton; Treberer-Treberspurg, Wolfgang; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Alderweireldt, Sara; Bansal, Monika; Bansal, Sunil; Cornelis, Tom; De Wolf, Eddi A; Janssen, Xavier; Knutsson, Albert; Luyckx, Sten; Ochesanu, Silvia; Roland, Benoit; Rougny, Romain; Van De Klundert, Merijn; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Blekman, Freya; Blyweert, Stijn; D'Hondt, Jorgen; Daci, Nadir; Heracleous, Natalie; Keaveney, James; Lowette, Steven; Maes, Michael; Olbrechts, Annik; Python, Quentin; Strom, Derek; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Villella, Ilaria; Caillol, Cécile; Clerbaux, Barbara; De Lentdecker, Gilles; Dobur, Didar; Favart, Laurent; Gay, Arnaud; Grebenyuk, Anastasia; Léonard, Alexandre; Mohammadi, Abdollah; Perniè, Luca; Reis, Thomas; Seva, Tomislav; Thomas, Laurent; Vander Velde, Catherine; Vanlaer, Pascal; Wang, Jian; Adler, Volker; Beernaert, Kelly; Benucci, Leonardo; Cimmino, Anna; Costantini, Silvia; Crucy, Shannon; Dildick, Sven; Fagot, Alexis; Garcia, Guillaume; Mccartin, Joseph; Ocampo Rios, Alberto Andres; Ryckbosch, Dirk; Salva Diblen, Sinem; Sigamani, Michael; Strobbe, Nadja; Thyssen, Filip; Tytgat, Michael; Yazgan, Efe; Zaganidis, Nicolas; Basegmez, Suzan; Beluffi, Camille; Bruno, Giacomo; Castello, Roberto; Caudron, Adrien; Ceard, Ludivine; Da Silveira, Gustavo Gil; Delaere, Christophe; Du Pree, Tristan; Favart, Denis; Forthomme, Laurent; Giammanco, Andrea; Hollar, Jonathan; Jez, Pavel; Komm, Matthias; Lemaitre, Vincent; Nuttens, Claude; Pagano, Davide; Perrini, Lucia; Pin, Arnaud; Piotrzkowski, Krzysztof; Popov, Andrey; Quertenmont, Loic; Selvaggi, Michele; Vidal Marono, Miguel; Vizan Garcia, Jesus Manuel; Beliy, Nikita; Caebergs, Thierry; Daubie, Evelyne; Hammad, Gregory Habib; Aldá Júnior, Walter Luiz; Alves, Gilvan; Brito, Lucas; Correa Martins Junior, Marcos; Dos Reis Martins, Thiago; Mora Herrera, Clemencia; Pol, Maria Elena; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Malbouisson, Helena; Matos Figueiredo, Diego; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santaolalla, Javier; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Vilela Pereira, Antonio; Bernardes, Cesar Augusto; Dogra, Sunil; Tomei, Thiago; De Moraes Gregores, Eduardo; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Aleksandrov, Aleksandar; Genchev, Vladimir; Iaydjiev, Plamen; Marinov, Andrey; Piperov, Stefan; Rodozov, Mircho; Stoykova, Stefka; Sultanov, Georgi; Tcholakov, Vanio; Vutova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Hadjiiska, Roumyana; Kozhuharov, Venelin; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Du, Ran; Jiang, Chun-Hua; Liang, Song; Plestina, Roko; Tao, Junquan; Wang, Xianyou; Wang, Zheng; Asawatangtrakuldee, Chayanit; Ban, Yong; Guo, Yifei; Li, Qiang; Li, Wenbo; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Zhang, Linlin; Zou, Wei; Avila, Carlos; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; Gomez Moreno, Bernardo; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Polic, Dunja; Puljak, Ivica; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Kadija, Kreso; Luetic, Jelena; Mekterovic, Darko; Sudic, Lucija; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Bodlak, Martin; Finger, Miroslav; Finger Jr, Michael; Assran, Yasser; Ellithi Kamel, Ali; Mahmoud, Mohammed; Radi, Amr; Kadastik, Mario; Murumaa, Marion; Raidal, Martti; Tiko, Andres; Eerola, Paula; Fedi, Giacomo; Voutilainen, Mikko; Härkönen, Jaakko; Karimäki, Veikko; Kinnunen, Ritva; Kortelainen, Matti J; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Peltola, Timo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Favaro, Carlotta; Ferri, Federico; Ganjour, Serguei; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Locci, Elizabeth; Malcles, Julie; Rander, John; Rosowsky, André; Titov, Maksym; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Charlot, Claude; Dahms, Torsten; Dalchenko, Mykhailo; Dobrzynski, Ludwik; Filipovic, Nicolas; Florent, Alice; Granier de Cassagnac, Raphael; Mastrolorenzo, Luca; Miné, Philippe; Mironov, Camelia; Naranjo, Ivo Nicolas; Nguyen, Matthew; Ochando, Christophe; Paganini, Pascal; Regnard, Simon; Salerno, Roberto; Sauvan, Jean-Baptiste; Sirois, Yves; Veelken, Christian; Yilmaz, Yetkin; Zabi, Alexandre; Agram, Jean-Laurent; Andrea, Jeremy; Aubin, Alexandre; Bloch, Daniel; Brom, Jean-Marie; Chabert, Eric Christian; Collard, Caroline; Conte, Eric; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Goetzmann, Christophe; Le Bihan, Anne-Catherine; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Beaupere, Nicolas; Boudoul, Gaelle; Bouvier, Elvire; Brochet, Sébastien; Carrillo Montoya, Camilo Andres; Chasserat, Julien; Chierici, Roberto; Contardo, Didier; Depasse, Pierre; El Mamouni, Houmani; Fan, Jiawei; Fay, Jean; Gascon, Susan; Gouzevitch, Maxime; Ille, Bernard; Kurca, Tibor; Lethuillier, Morgan; Mirabito, Laurent; Perries, Stephane; Ruiz Alvarez, José David; Sabes, David; Sgandurra, Louis; Sordini, Viola; Vander Donckt, Muriel; Verdier, Patrice; Viret, Sébastien; Xiao, Hong; Tsamalaidze, Zviad; Autermann, Christian; Beranek, Sarah; Bontenackels, Michael; Edelhoff, Matthias; Feld, Lutz; Hindrichs, Otto; Klein, Katja; Ostapchuk, Andrey; Perieanu, Adrian; Raupach, Frank; Sammet, Jan; Schael, Stefan; Weber, Hendrik; Wittmer, Bruno; Zhukov, Valery; Ata, Metin; Dietz-Laursonn, Erik; Duchardt, Deborah; Erdmann, Martin; Fischer, Robert; Güth, Andreas; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Klingebiel, Dennis; Knutzen, Simon; Kreuzer, Peter; Merschmeyer, Markus; Meyer, Arnd; Millet, Philipp; Olschewski, Mark; Padeken, Klaas; Papacz, Paul; Reithler, Hans; Schmitz, Stefan Antonius; Sonnenschein, Lars; Teyssier, Daniel; Thüer, Sebastian; Weber, Martin; Cherepanov, Vladimir; Erdogan, Yusuf; Flügge, Günter; Geenen, Heiko; Geisler, Matthias; Haj Ahmad, Wael; Heister, Arno; Hoehle, Felix; Kargoll, Bastian; Kress, Thomas; Kuessel, Yvonne; Lingemann, Joschka; Nowack, Andreas; Nugent, Ian Michael; Perchalla, Lars; Pooth, Oliver; Stahl, Achim; Asin, Ivan; Bartosik, Nazar; Behr, Joerg; Behrenhoff, Wolf; Behrens, Ulf; Bell, Alan James; Bergholz, Matthias; Bethani, Agni; Borras, Kerstin; Burgmeier, Armin; Cakir, Altan; Calligaris, Luigi; Campbell, Alan; Choudhury, Somnath; Costanza, Francesco; Diez Pardos, Carmen; Dooling, Samantha; Dorland, Tyler; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Flucke, Gero; Garay Garcia, Jasone; Geiser, Achim; Gunnellini, Paolo; Hauk, Johannes; Hempel, Maria; Horton, Dean; Jung, Hannes; Kalogeropoulos, Alexis; Kasemann, Matthias; Katsas, Panagiotis; Kieseler, Jan; Kleinwort, Claus; Krücker, Dirk; Lange, Wolfgang; Leonard, Jessica; Lipka, Katerina; Lobanov, Artur; Lohmann, Wolfgang; Lutz, Benjamin; Mankel, Rainer; Marfin, Ihar; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mittag, Gregor; Mnich, Joachim; Mussgiller, Andreas; Naumann-Emme, Sebastian; Nayak, Aruna; Novgorodova, Olga; Nowak, Friederike; Ntomari, Eleni; Perrey, Hanno; Pitzl, Daniel; Placakyte, Ringaile; Raspereza, Alexei; Ribeiro Cipriano, Pedro M; Ron, Elias; Sahin, Mehmet Özgür; Salfeld-Nebgen, Jakob; Saxena, Pooja; Schmidt, Ringo; Schoerner-Sadenius, Thomas; Schröder, Matthias; Seitz, Claudia; Spannagel, Simon; Vargas Trevino, Andrea Del Rocio; Walsh, Roberval; Wissing, Christoph; Aldaya Martin, Maria; Blobel, Volker; Centis Vignali, Matteo; Draeger, Arne-Rasmus; Erfle, Joachim; Garutti, Erika; Goebel, Kristin; Görner, Martin; Haller, Johannes; Hoffmann, Malte; Höing, Rebekka Sophie; Kirschenmann, Henning; Klanner, Robert; Kogler, Roman; Lange, Jörn; Lapsien, Tobias; Lenz, Teresa; Marchesini, Ivan; Ott, Jochen; Peiffer, Thomas; Pietsch, Niklas; Poehlsen, Jennifer; Pöhlsen, Thomas; Rathjens, Denis; Sander, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schmidt, Alexander; Seidel, Markus; Sola, Valentina; Stadie, Hartmut; Steinbrück, Georg; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Barth, Christian; Baus, Colin; Berger, Joram; Böser, Christian; Butz, Erik; Chwalek, Thorsten; De Boer, Wim; Descroix, Alexis; Dierlamm, Alexander; Feindt, Michael; Frensch, Felix; Giffels, Manuel; Hartmann, Frank; Hauth, Thomas; Husemann, Ulrich; Katkov, Igor; Kornmayer, Andreas; Kuznetsova, Ekaterina; Lobelle Pardo, Patricia; Mozer, Matthias Ulrich; Müller, Thomas; Nürnberg, Andreas; Quast, Gunter; Rabbertz, Klaus; Ratnikov, Fedor; Röcker, Steffen; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Ulrich, Ralf; Wagner-Kuhr, Jeannine; Wayand, Stefan; Weiler, Thomas; Wolf, Roger; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Giakoumopoulou, Viktoria Athina; Kyriakis, Aristotelis; Loukas, Demetrios; Markou, Athanasios; Markou, Christos; Psallidas, Andreas; Topsis-Giotis, Iasonas; Kesisoglou, Stilianos; Panagiotou, Apostolos; Saoulidou, Niki; Stiliaris, Efstathios; Aslanoglou, Xenofon; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Kokkas, Panagiotis; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Bencze, Gyorgy; Hajdu, Csaba; Hidas, Pàl; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Karancsi, János; Molnar, Jozsef; Palinkas, Jozsef; Szillasi, Zoltan; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Swain, Sanjay Kumar; Beri, Suman Bala; Bhatnagar, Vipin; Dhingra, Nitish; Gupta, Ruchi; Bhawandeep, Bhawandeep; Kalsi, Amandeep Kaur; Kaur, Manjit; Mittal, Monika; Nishu, Nishu; Singh, Jasbir; Kumar, Ashok; Kumar, Arun; Ahuja, Sudha; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Ranjan, Kirti; Sharma, Varun; Banerjee, Sunanda; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dutta, Suchandra; Gomber, Bhawna; Jain, Sandhya; Jain, Shilpi; Khurana, Raman; Modak, Atanu; Mukherjee, Swagata; Roy, Debarati; Sarkar, Subir; Sharan, Manoj; Abdulsalam, Abdulla; Dutta, Dipanwita; Kailas, Swaminathan; Kumar, Vineet; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Banerjee, Sudeshna; Bhowmik, Sandeep; Chatterjee, Rajdeep Mohan; Dewanjee, Ram Krishna; Dugad, Shashikant; Ganguly, Sanmay; Ghosh, Saranya; Guchait, Monoranjan; Gurtu, Atul; Kole, Gouranga; Kumar, Sanjeev; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mohanty, Gagan Bihari; Parida, Bibhuti; Sudhakar, Katta; Wickramage, Nadeesha; Bakhshiansohi, Hamed; Behnamian, Hadi; Etesami, Seyed Mohsen; Fahim, Ali; Goldouzian, Reza; Jafari, Abideh; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Rezaei Hosseinabadi, Ferdos; Safarzadeh, Batool; Zeinali, Maryam; Felcini, Marta; Grunewald, Martin; Abbrescia, Marcello; Barbone, Lucia; Calabria, Cesare; Chhibra, Simranjit Singh; Colaleo, Anna; Creanza, Donato; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; My, Salvatore; Nuzzo, Salvatore; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Selvaggi, Giovanna; Silvestris, Lucia; Singh, Gurpreet; Venditti, Rosamaria; Verwilligen, Piet; Zito, Giuseppe; Abbiendi, Giovanni; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Montanari, Alessandro; Navarria, Francesco; Perrotta, Andrea; Primavera, Federica; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Travaglini, Riccardo; Albergo, Sebastiano; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Gallo, Elisabetta; Gonzi, Sandro; Gori, Valentina; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Ferro, Fabrizio; Lo Vetere, Maurizio; Robutti, Enrico; Tosi, Silvano; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Gerosa, Raffaele; Ghezzi, Alessio; Govoni, Pietro; Lucchini, Marco Toliman; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Martelli, Arabella; Marzocchi, Badder; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Di Guida, Salvatore; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lista, Luca; Meola, Sabino; Merola, Mario; Paolucci, Pierluigi; Azzi, Patrizia; Bacchetta, Nicola; Bisello, Dario; Branca, Antonio; Carlin, Roberto; Checchia, Paolo; Dall'Osso, Martino; Dorigo, Tommaso; Dosselli, Umberto; Galanti, Mario; Gasparini, Fabrizio; Gasparini, Ugo; Giubilato, Piero; Gonella, Franco; Gozzelino, Andrea; Kanishchev, Konstantin; Lacaprara, Stefano; Margoni, Martino; Montecassiano, Fabio; Pazzini, Jacopo; Pozzobon, Nicola; Ronchese, Paolo; Simonetto, Franco; Tosi, Mia; Zotto, Pierluigi; Zucchetta, Alberto; Zumerle, Gianni; Gabusi, Michele; Ratti, Sergio P; Riccardi, Cristina; Salvini, Paola; Vitulo, Paolo; Biasini, Maurizio; Bilei, Gian Mario; Ciangottini, Diego; Fanò, Livio; Lariccia, Paolo; Mantovani, Giancarlo; Menichelli, Mauro; Romeo, Francesco; Saha, Anirban; Santocchia, Attilio; Spiezia, Aniello; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Broccolo, Giuseppe; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Donato, Silvio; Fiori, Francesco; Foà, Lorenzo; Giassi, Alessandro; Grippo, Maria Teresa; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Moon, Chang-Seong; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Serban, Alin Titus; Spagnolo, Paolo; Squillacioti, Paola; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Vernieri, Caterina; Barone, Luciano; Cavallari, Francesca; D'imperio, Giulia; Del Re, Daniele; Diemoz, Marcella; Grassi, Marco; Jorda, Clara; Longo, Egidio; Margaroli, Fabrizio; Meridiani, Paolo; Micheli, Francesco; Nourbakhsh, Shervin; Organtini, Giovanni; Paramatti, Riccardo; Rahatlou, Shahram; Rovelli, Chiara; Santanastasio, Francesco; Soffi, Livia; Traczyk, Piotr; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Casasso, Stefano; Costa, Marco; Degano, Alessandro; Demaria, Natale; Dujany, Giulio; Finco, Linda; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Musich, Marco; Obertino, Maria Margherita; Ortona, Giacomo; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Pinna Angioni, Gian Luca; Potenza, Alberto; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Solano, Ada; Staiano, Amedeo; Tamponi, Umberto; Belforte, Stefano; Candelise, Vieri; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; La Licata, Chiara; Marone, Matteo; Montanino, Damiana; Schizzi, Andrea; Umer, Tomo; Zanetti, Anna; Chang, Sunghyun; Kropivnitskaya, Anna; Nam, Soon-Kwon; Kim, Dong Hee; Kim, Gui Nyun; Kim, Min Suk; Kong, Dae Jung; Lee, Sangeun; Oh, Young Do; Park, Hyangkyu; Sakharov, Alexandre; Son, Dong-Chul; Kim, Tae Jeong; Kim, Jae Yool; Song, Sanghyeon; Choi, Suyong; Gyun, Dooyeon; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Yongsun; Lee, Byounghoon; Lee, Kyong Sei; Park, Sung Keun; Roh, Youn; Choi, Minkyoo; Kim, Ji Hyun; Park, Inkyu; Park, Sangnam; Ryu, Geonmo; Ryu, Min Sang; Choi, Young-Il; Choi, Young Kyu; Goh, Junghwan; Kim, Donghyun; Kwon, Eunhyang; Lee, Jongseok; Seo, Hyunkwan; Yu, Intae; Juodagalvis, Andrius; Komaragiri, Jyothsna Rani; Md Ali, Mohd Adli Bin; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-de La Cruz, Ivan; Lopez-Fernandez, Ricardo; Sánchez Hernández, Alberto; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Pedraza, Isabel; Salazar Ibarguen, Humberto Antonio; Casimiro Linares, Edgar; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Reucroft, Steve; Ahmad, Ashfaq; Ahmad, Muhammad; Hassan, Qamar; Hoorani, Hafeez R; Khalid, Shoaib; Khan, Wajid Ali; Khurshid, Taimoor; Shah, Mehar Ali; Shoaib, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Zalewski, Piotr; Brona, Grzegorz; Bunkowski, Karol; Cwiok, Mikolaj; Dominik, Wojciech; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Olszewski, Michał; Wolszczak, Weronika; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Nguyen, Federico; Rodrigues Antunes, Joao; Seixas, Joao; Varela, Joao; Vischia, Pietro; Golutvin, Igor; Gorbunov, Ilya; Karjavin, Vladimir; Konoplyanikov, Viktor; Korenkov, Vladimir; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Mitsyn, Valeri Valentinovitch; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Skatchkov, Nikolai; Smirnov, Vitaly; Tikhonenko, Elena; Yuldashev, Bekhzod S; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Vorobyev, Andrey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Safronov, Grigory; Semenov, Sergey; Spiridonov, Alexander; Stolin, Viatcheslav; Vlasov, Evgueni; Zhokin, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Rusakov, Sergey V; Vinogradov, Alexey; Belyaev, Andrey; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Klyukhin, Vyacheslav; Kodolova, Olga; Lokhtin, Igor; Obraztsov, Stepan; Petrushanko, Sergey; Savrin, Viktor; Snigirev, Alexander; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Ekmedzic, Marko; Milosevic, Jovan; Rekovic, Vladimir; Alcaraz Maestre, Juan; Battilana, Carlo; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Domínguez Vázquez, Daniel; Escalante Del Valle, Alberto; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Merino, Gonzalo; Navarro De Martino, Eduardo; Pérez Calero Yzquierdo, Antonio María; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Senghi Soares, Mara; Albajar, Carmen; de Trocóniz, Jorge F; Missiroli, Marino; Moran, Dermot; Brun, Hugues; Cuevas, Javier; Fernandez Menendez, Javier; Folgueras, Santiago; Gonzalez Caballero, Isidro; Lloret Iglesias, Lara; Brochero Cifuentes, Javier Andres; Cabrillo, Iban Jose; Calderon, Alicia; Duarte Campderros, Jordi; Fernandez, Marcos; Gomez, Gervasio; Graziano, Alberto; Lopez Virto, Amparo; Marco, Jesus; Marco, Rafael; Martinez Rivero, Celso; Matorras, Francisco; Munoz Sanchez, Francisca Javiela; Piedra Gomez, Jonatan; Rodrigo, Teresa; Rodríguez-Marrero, Ana Yaiza; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Bachtis, Michail; Baillon, Paul; Ball, Austin; Barney, David; Benaglia, Andrea; Bendavid, Joshua; Benhabib, Lamia; Benitez, Jose F; Bernet, Colin; Bianchi, Giovanni; Bloch, Philippe; Bocci, Andrea; Bonato, Alessio; Bondu, Olivier; Botta, Cristina; Breuker, Horst; Camporesi, Tiziano; Cerminara, Gianluca; Colafranceschi, Stefano; D'Alfonso, Mariarosaria; D'Enterria, David; Dabrowski, Anne; David Tinoco Mendes, Andre; De Guio, Federico; De Roeck, Albert; De Visscher, Simon; Dobson, Marc; Dordevic, Milos; Dupont-Sagorin, Niels; Elliott-Peisert, Anna; Eugster, Jürg; Franzoni, Giovanni; Funk, Wolfgang; Gigi, Dominique; Gill, Karl; Giordano, Domenico; Girone, Maria; Glege, Frank; Guida, Roberto; Gundacker, Stefan; Guthoff, Moritz; Hammer, Josef; Hansen, Magnus; Harris, Philip; Hegeman, Jeroen; Innocente, Vincenzo; Janot, Patrick; Kousouris, Konstantinos; Krajczar, Krisztian; Lecoq, Paul; Lourenco, Carlos; Magini, Nicolo; Malgeri, Luca; Mannelli, Marcello; Marrouche, Jad; Masetti, Lorenzo; Meijers, Frans; Mersi, Stefano; Meschi, Emilio; Moortgat, Filip; Morovic, Srecko; Mulders, Martijn; Musella, Pasquale; Orsini, Luciano; Pape, Luc; Perez, Emmanuelle; Perrozzi, Luca; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Pierini, Maurizio; Pimiä, Martti; Piparo, Danilo; Plagge, Michael; Racz, Attila; Rolandi, Gigi; Rovere, Marco; Sakulin, Hannes; Schäfer, Christoph; Schwick, Christoph; Sharma, Archana; Siegrist, Patrice; Silva, Pedro; Simon, Michal; Sphicas, Paraskevas; Spiga, Daniele; Steggemann, Jan; Stieger, Benjamin; Stoye, Markus; Treille, Daniel; Tsirou, Andromachi; Veres, Gabor Istvan; Vlimant, Jean-Roch; Wardle, Nicholas; Wöhri, Hermine Katharina; Wollny, Heiner; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; Kotlinski, Danek; Langenegger, Urs; Renker, Dieter; Rohe, Tilman; Bachmair, Felix; Bäni, Lukas; Bianchini, Lorenzo; Bortignon, Pierluigi; Buchmann, Marco-Andrea; Casal, Bruno; Chanon, Nicolas; Deisher, Amanda; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Dünser, Marc; Eller, Philipp; Grab, Christoph; Hits, Dmitry; Lustermann, Werner; Mangano, Boris; Marini, Andrea Carlo; Martinez Ruiz del Arbol, Pablo; Meister, Daniel; Mohr, Niklas; Nägeli, Christoph; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pauss, Felicitas; Peruzzi, Marco; Quittnat, Milena; Rebane, Liis; Rossini, Marco; Starodumov, Andrei; Takahashi, Maiko; Theofilatos, Konstantinos; Wallny, Rainer; Weber, Hannsjoerg Artur; Amsler, Claude; Canelli, Maria Florencia; Chiochia, Vincenzo; De Cosa, Annapaola; Hinzmann, Andreas; Hreus, Tomas; Kilminster, Benjamin; Lange, Clemens; Millan Mejias, Barbara; Ngadiuba, Jennifer; Robmann, Peter; Ronga, Frederic Jean; Taroni, Silvia; Verzetti, Mauro; Yang, Yong; Cardaci, Marco; Chen, Kuan-Hsin; Ferro, Cristina; Kuo, Chia-Ming; Lin, Willis; Lu, Yun-Ju; Volpe, Roberta; Yu, Shin-Shan; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Dietz, Charles; Grundler, Ulysses; Hou, George Wei-Shu; Kao, Kai-Yi; Lei, Yeong-Jyi; Liu, Yueh-Feng; Lu, Rong-Shyang; Majumder, Devdatta; Petrakou, Eleni; Tzeng, Yeng-Ming; Wilken, Rachel; Asavapibhop, Burin; Srimanobhas, Norraphat; Suwonjandee, Narumon; Adiguzel, Aytul; Bakirci, Mustafa Numan; Cerci, Salim; Dozen, Candan; Dumanoglu, Isa; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Kayis Topaksu, Aysel; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Sogut, Kenan; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Mehmet; Akin, Ilina Vasileva; Bilin, Bugra; Bilmis, Selcuk; Gamsizkan, Halil; Karapinar, Guler; Ocalan, Kadir; Sekmen, Sezen; Surat, Ugur Emrah; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Isildak, Bora; Kaya, Mithat; Kaya, Ozlem; Bahtiyar, Hüseyin; Barlas, Esra; Cankocak, Kerem; Vardarli, Fuat Ilkehan; Yücel, Mete; Levchuk, Leonid; Sorokin, Pavel; Brooke, James John; Clement, Emyr; Cussans, David; Flacher, Henning; Frazier, Robert; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Meng, Zhaoxia; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Senkin, Sergey; Smith, Vincent J; Williams, Thomas; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Womersley, William John; Worm, Steven; Baber, Mark; Bainbridge, Robert; Buchmuller, Oliver; Burton, Darren; Colling, David; Cripps, Nicholas; Cutajar, Michael; Dauncey, Paul; Davies, Gavin; Della Negra, Michel; Dunne, Patrick; Ferguson, William; Fulcher, Jonathan; Futyan, David; Gilbert, Andrew; Hall, Geoffrey; Iles, Gregory; Jarvis, Martyn; Karapostoli, Georgia; Kenzie, Matthew; Lane, Rebecca; Lucas, Robyn; Lyons, Louis; Magnan, Anne-Marie; Malik, Sarah; Mathias, Bryn; Nash, Jordan; Nikitenko, Alexander; Pela, Joao; Pesaresi, Mark; Petridis, Konstantinos; Raymond, David Mark; Rogerson, Samuel; Rose, Andrew; Seez, Christopher; Sharp, Peter; Tapper, Alexander; Vazquez Acosta, Monica; Virdee, Tejinder; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Leggat, Duncan; Leslie, Dawn; Martin, William; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Dittmann, Jay; Hatakeyama, Kenichi; Kasmi, Azeddine; Liu, Hongxuan; Scarborough, Tara; Charaf, Otman; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; Avetisyan, Aram; Bose, Tulika; Fantasia, Cory; Lawson, Philip; Richardson, Clint; Rohlf, James; Sperka, David; St John, Jason; Sulak, Lawrence; Alimena, Juliette; Berry, Edmund; Bhattacharya, Saptaparna; Christopher, Grant; Cutts, David; Demiragli, Zeynep; Ferapontov, Alexey; Garabedian, Alex; Heintz, Ulrich; Kukartsev, Gennadiy; Laird, Edward; Landsberg, Greg; Luk, Michael; Narain, Meenakshi; Segala, Michael; Sinthuprasith, Tutanon; Speer, Thomas; Swanson, Joshua; Breedon, Richard; Breto, Guillermo; Calderon De La Barca Sanchez, Manuel; Chauhan, Sushil; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Gardner, Michael; Ko, Winston; Lander, Richard; Miceli, Tia; Mulhearn, Michael; Pellett, Dave; Pilot, Justin; Ricci-Tam, Francesca; Searle, Matthew; Shalhout, Shalhout; Smith, John; Squires, Michael; Stolp, Dustin; Tripathi, Mani; Wilbur, Scott; Yohay, Rachel; Cousins, Robert; Everaerts, Pieter; Farrell, Chris; Hauser, Jay; Ignatenko, Mikhail; Rakness, Gregory; Takasugi, Eric; Valuev, Vyacheslav; Weber, Matthias; Babb, John; Burt, Kira; Clare, Robert; Ellison, John Anthony; Gary, J William; Hanson, Gail; Heilman, Jesse; Ivova Rikova, Mirena; Jandir, Pawandeep; Kennedy, Elizabeth; Lacroix, Florent; Liu, Hongliang; Long, Owen Rosser; Luthra, Arun; Malberti, Martina; Nguyen, Harold; Olmedo Negrete, Manuel; Shrinivas, Amithabh; Sumowidagdo, Suharyo; Wimpenny, Stephen; Andrews, Warren; Branson, James G; Cerati, Giuseppe Benedetto; Cittolin, Sergio; D'Agnolo, Raffaele Tito; Evans, David; Holzner, André; Kelley, Ryan; Klein, Daniel; Lebourgeois, Matthew; Letts, James; Macneill, Ian; Olivito, Dominick; Padhi, Sanjay; Palmer, Christopher; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Sudano, Elizabeth; Tadel, Matevz; Tu, Yanjun; Vartak, Adish; Welke, Charles; Würthwein, Frank; Yagil, Avraham; Yoo, Jaehyeok; Barge, Derek; Bradmiller-Feld, John; Campagnari, Claudio; Danielson, Thomas; Dishaw, Adam; Flowers, Kristen; Franco Sevilla, Manuel; Geffert, Paul; George, Christopher; Golf, Frank; Gouskos, Loukas; Incandela, Joe; Justus, Christopher; Mccoll, Nickolas; Richman, Jeffrey; Stuart, David; To, Wing; West, Christopher; Apresyan, Artur; Bornheim, Adolf; Bunn, Julian; Chen, Yi; Di Marco, Emanuele; Duarte, Javier; Mott, Alexander; Newman, Harvey B; Pena, Cristian; Rogan, Christopher; Spiropulu, Maria; Timciuc, Vladlen; Wilkinson, Richard; Xie, Si; Zhu, Ren-Yuan; Azzolini, Virginia; Calamba, Aristotle; Carlson, Benjamin; Ferguson, Thomas; Iiyama, Yutaro; Paulini, Manfred; Russ, James; Vogel, Helmut; Vorobiev, Igor; Cumalat, John Perry; Ford, William T; Gaz, Alessandro; Luiggi Lopez, Eduardo; Nauenberg, Uriel; Smith, James; Stenson, Kevin; Ulmer, Keith; Wagner, Stephen Robert; Alexander, James; Chatterjee, Avishek; Chu, Jennifer; Dittmer, Susan; Eggert, Nicholas; Mirman, Nathan; Nicolas Kaufman, Gala; Patterson, Juliet Ritchie; Ryd, Anders; Salvati, Emmanuele; Skinnari, Louise; Sun, Werner; Teo, Wee Don; Thom, Julia; Thompson, Joshua; Tucker, Jordan; Weng, Yao; Winstrom, Lucas; Wittich, Peter; Winn, Dave; Abdullin, Salavat; Albrow, Michael; Anderson, Jacob; Apollinari, Giorgio; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Burkett, Kevin; Butler, Joel Nathan; Cheung, Harry; Chlebana, Frank; Cihangir, Selcuk; Elvira, Victor Daniel; Fisk, Ian; Freeman, Jim; Gao, Yanyan; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Hanlon, Jim; Hare, Daryl; Harris, Robert M; Hirschauer, James; Hooberman, Benjamin; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Kaadze, Ketino; Klima, Boaz; Kreis, Benjamin; Kwan, Simon; Linacre, Jacob; Lincoln, Don; Lipton, Ron; Liu, Tiehui; Lykken, Joseph; Maeshima, Kaori; Marraffino, John Michael; Martinez Outschoorn, Verena Ingrid; Maruyama, Sho; Mason, David; McBride, Patricia; Mishra, Kalanand; Mrenna, Stephen; Musienko, Yuri; Nahn, Steve; Newman-Holmes, Catherine; O'Dell, Vivian; Prokofyev, Oleg; Sexton-Kennedy, Elizabeth; Sharma, Seema; Soha, Aron; Spalding, William J; Spiegel, Leonard; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vidal, Richard; Whitbeck, Andrew; Whitmore, Juliana; Yang, Fan; Acosta, Darin; Avery, Paul; Bourilkov, Dimitri; Carver, Matthew; Cheng, Tongguang; Curry, David; Das, Souvik; De Gruttola, Michele; Di Giovanni, Gian Piero; Field, Richard D; Fisher, Matthew; Furic, Ivan-Kresimir; Hugon, Justin; Konigsberg, Jacobo; Korytov, Andrey; Kypreos, Theodore; Low, Jia Fu; Matchev, Konstantin; Milenovic, Predrag; Mitselmakher, Guenakh; Muniz, Lana; Rinkevicius, Aurelijus; Shchutska, Lesya; Snowball, Matthew; Yelton, John; Zakaria, Mohammed; Hewamanage, Samantha; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Adams, Todd; Askew, Andrew; Bochenek, Joseph; Diamond, Brendan; Haas, Jeff; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Prosper, Harrison; Veeraraghavan, Venkatesh; Weinberg, Marc; Baarmand, Marc M; Hohlmann, Marcus; Kalakhety, Himali; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Bazterra, Victor Eduardo; Berry, Douglas; Betts, Russell Richard; Bucinskaite, Inga; Cavanaugh, Richard; Evdokimov, Olga; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Khalatyan, Samvel; Kurt, Pelin; Moon, Dong Ho; O'Brien, Christine; Silkworth, Christopher; Turner, Paul; Varelas, Nikos; Albayrak, Elif Asli; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Duru, Firdevs; Haytmyradov, Maksat; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Penzo, Aldo; Rahmat, Rahmat; Sen, Sercan; Tan, Ping; Tiras, Emrah; Wetzel, James; Yetkin, Taylan; Yi, Kai; Barnett, Bruce Arnold; Blumenfeld, Barry; Bolognesi, Sara; Fehling, David; Gritsan, Andrei; Maksimovic, Petar; Martin, Christopher; Swartz, Morris; Baringer, Philip; Bean, Alice; Benelli, Gabriele; Bruner, Christopher; Gray, Julia; Kenny III, Raymond Patrick; Malek, Magdalena; Murray, Michael; Noonan, Daniel; Sanders, Stephen; Sekaric, Jadranka; Stringer, Robert; Wang, Quan; Wood, Jeffrey Scott; Barfuss, Anne-Fleur; Chakaberia, Irakli; Ivanov, Andrew; Khalil, Sadia; Makouski, Mikhail; Maravin, Yurii; Saini, Lovedeep Kaur; Shrestha, Shruti; Skhirtladze, Nikoloz; Svintradze, Irakli; Gronberg, Jeffrey; Lange, David; Rebassoo, Finn; Wright, Douglas; Baden, Drew; Belloni, Alberto; Calvert, Brian; Eno, Sarah Catherine; Gomez, Jaime; Hadley, Nicholas John; Kellogg, Richard G; Kolberg, Ted; Lu, Ying; Marionneau, Matthieu; Mignerey, Alice; Pedro, Kevin; Skuja, Andris; Tonjes, Marguerite; Tonwar, Suresh C; Apyan, Aram; Barbieri, Richard; Bauer, Gerry; Busza, Wit; Cali, Ivan Amos; Chan, Matthew; Di Matteo, Leonardo; Dutta, Valentina; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Gulhan, Doga; Klute, Markus; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Ma, Teng; Paus, Christoph; Ralph, Duncan; Roland, Christof; Roland, Gunther; Stephans, George; Stöckli, Fabian; Sumorok, Konstanty; Velicanu, Dragos; Veverka, Jan; Wyslouch, Bolek; Yang, Mingming; Zanetti, Marco; Zhukova, Victoria; Dahmes, Bryan; Gude, Alexander; Kao, Shih-Chuan; Klapoetke, Kevin; Kubota, Yuichi; Mans, Jeremy; Pastika, Nathaniel; Rusack, Roger; Singovsky, Alexander; Tambe, Norbert; Turkewitz, Jared; Acosta, John Gabriel; Oliveros, Sandra; Avdeeva, Ekaterina; Bloom, Kenneth; Bose, Suvadeep; Claes, Daniel R; Dominguez, Aaron; Gonzalez Suarez, Rebeca; Keller, Jason; Knowlton, Dan; Kravchenko, Ilya; Lazo-Flores, Jose; Malik, Sudhir; Meier, Frank; Snow, Gregory R; Dolen, James; Godshalk, Andrew; Iashvili, Ia; Kharchilava, Avto; Kumar, Ashish; Rappoccio, Salvatore; Alverson, George; Barberis, Emanuela; Baumgartel, Darin; Chasco, Matthew; Haley, Joseph; Massironi, Andrea; Morse, David Michael; Nash, David; Orimoto, Toyoko; Trocino, Daniele; Wang, Ren-Jie; Wood, Darien; Zhang, Jinzhong; Hahn, Kristan Allan; Kubik, Andrew; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Pozdnyakov, Andrey; Schmitt, Michael Henry; Stoynev, Stoyan; Sung, Kevin; Velasco, Mayda; Won, Steven; Brinkerhoff, Andrew; Chan, Kwok Ming; Drozdetskiy, Alexey; Hildreth, Michael; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Lannon, Kevin; Luo, Wuming; Lynch, Sean; Marinelli, Nancy; Pearson, Tessa; Planer, Michael; Ruchti, Randy; Valls, Nil; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Antonelli, Louis; Brinson, Jessica; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Hill, Christopher; Hughes, Richard; Kotov, Khristian; Ling, Ta-Yung; Puigh, Darren; Rodenburg, Marissa; Smith, Geoffrey; Winer, Brian L; Wolfe, Homer; Wulsin, Howard Wells; Driga, Olga; Elmer, Peter; Hebda, Philip; Hunt, Adam; Koay, Sue Ann; Lujan, Paul; Marlow, Daniel; Medvedeva, Tatiana; Mooney, Michael; Olsen, James; Piroué, Pierre; Quan, Xiaohang; Saka, Halil; Stickland, David; Tully, Christopher; Werner, Jeremy Scott; Zenz, Seth Conrad; Zuranski, Andrzej; Brownson, Eric; Mendez, Hector; Ramirez Vargas, Juan Eduardo; Barnes, Virgil E; Benedetti, Daniele; Bolla, Gino; Bortoletto, Daniela; De Mattia, Marco; Hu, Zhen; Jha, Manoj; Jones, Matthew; Jung, Kurt; Kress, Matthew; Leonardo, Nuno; Lopes Pegna, David; Maroussov, Vassili; Merkel, Petra; Miller, David Harry; Neumeister, Norbert; Radburn-Smith, Benjamin Charles; Shi, Xin; Shipsey, Ian; Silvers, David; Svyatkovskiy, Alexey; Wang, Fuqiang; Xie, Wei; Xu, Lingshan; Yoo, Hwi Dong; Zablocki, Jakub; Zheng, Yu; Parashar, Neeti; Stupak, John; Adair, Antony; Akgun, Bora; Ecklund, Karl Matthew; Geurts, Frank JM; Li, Wei; Michlin, Benjamin; Padley, Brian Paul; Redjimi, Radia; Roberts, Jay; Zabel, James; Betchart, Burton; Bodek, Arie; Covarelli, Roberto; de Barbaro, Pawel; Demina, Regina; Eshaq, Yossof; Ferbel, Thomas; Garcia-Bellido, Aran; Goldenzweig, Pablo; Han, Jiyeon; Harel, Amnon; Khukhunaishvili, Aleko; Petrillo, Gianluca; Vishnevskiy, Dmitry; Ciesielski, Robert; Demortier, Luc; Goulianos, Konstantin; Lungu, Gheorghe; Mesropian, Christina; Arora, Sanjay; Barker, Anthony; Chou, John Paul; Contreras-Campana, Christian; Contreras-Campana, Emmanuel; Duggan, Daniel; Ferencek, Dinko; Gershtein, Yuri; Gray, Richard; Halkiadakis, Eva; Hidas, Dean; Kaplan, Steven; Lath, Amitabh; Panwalkar, Shruti; Park, Michael; Patel, Rishi; Salur, Sevil; Schnetzer, Steve; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Rose, Keith; Spanier, Stefan; York, Andrew; Bouhali, Othmane; Castaneda Hernandez, Alfredo; Eusebi, Ricardo; Flanagan, Will; Gilmore, Jason; Kamon, Teruki; Khotilovich, Vadim; Krutelyov, Vyacheslav; Montalvo, Roy; Osipenkov, Ilya; Pakhotin, Yuriy; Perloff, Alexx; Roe, Jeffrey; Rose, Anthony; Safonov, Alexei; Sakuma, Tai; Suarez, Indara; Tatarinov, Aysen; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; Dragoiu, Cosmin; Dudero, Phillip Russell; Faulkner, James; Kovitanggoon, Kittikul; Kunori, Shuichi; Lee, Sung Won; Libeiro, Terence; Volobouev, Igor; Appelt, Eric; Delannoy, Andrés G; Greene, Senta; Gurrola, Alfredo; Johns, Willard; Maguire, Charles; Mao, Yaxian; Melo, Andrew; Sharma, Monika; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Arenton, Michael Wayne; Boutle, Sarah; Cox, Bradley; Francis, Brian; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Li, Hengne; Lin, Chuanzhe; Neu, Christopher; Wood, John; Clarke, Christopher; Harr, Robert; Karchin, Paul Edmund; Kottachchi Kankanamge Don, Chamath; Lamichhane, Pramod; Sturdy, Jared; Belknap, Donald; Carlsmith, Duncan; Cepeda, Maria; Dasu, Sridhara; Dodd, Laura; Duric, Senka; Friis, Evan; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Lanaro, Armando; Lazaridis, Christos; Levine, Aaron; Loveless, Richard; Mohapatra, Ajit; Ojalvo, Isabel; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ross, Ian; Sarangi, Tapas; Savin, Alexander; Smith, Wesley H; Vuosalo, Carl; Woods, Nathaniel

2015-04-09

A measurement of the production cross section ratio $\\sigma(\\chi_{b2}(1\\mathrm{P}))/ \\sigma(\\chi_{b1}(1\\mathrm{P}))$ is presented. The $\\chi_{b1}(1\\mathrm{P})$ and $\\chi_{b2}(1\\mathrm{P})$ bottomonium states, promptly produced in pp collisions at $\\sqrt{s}$= 8 TeV, are detected by the CMS experiment at the CERN LHC through their radiative decays $\\chi_{b1,2}(1\\mathrm{P}) \\rightarrow \\Upsilon(1\\mathrm{S}) + \\gamma$. The emitted photons are measured through their conversion to e$^+$e$^-$ pairs, whose reconstruction allows the two states to be resolved. The $\\Upsilon(1\\mathrm{S})$ 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, |$\\eta^\\gamma$| < 1.0; the $\\Upsilon(1\\mathrm{S})$ rapidity, |$y^\\Upsilon$| < 1.5; and the $\\Upsilon(1\\mathrm{S})$ transverse momentum, 7 < $p_{\\mathrm{T}}^\\Upsilon$ < 40 GeV. The cross section ratio sh...

Modulation of the TGF-β1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells.

Science.gov (United States)

Zuccarini, Mariachiara; Giuliani, Patricia; Buccella, Silvana; Di Liberto, Valentina; Mudò, Giuseppa; Belluardo, Natale; Carluccio, Marzia; Rossini, Margherita; Condorelli, Daniele Filippo; Rathbone, Michel Piers; Caciagli, Francesco; Ciccarelli, Renata; Di Iorio, Patrizia

2017-12-01

Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling. The stimulation of A2A receptor reduced the overexpression of the EMT-related markers, mainly through the cAMP-dependent PKA pathway, as confirmed by cell pre-treatment with Myr-PKI. Both A1 and P2Y1 receptor stimulation exacerbated the TGF-β1-driven effects, which were reduced by cell pre-treatment with the MAPK inhibitor PD98059, according to the increased ERK1/2 phosphorylation upon receptor activation. The effects induced by P2Y11 receptor activation were oppositely modulated by PKA or MAPK inhibition, in line with the dual nature of the Gs- and Gq-coupled receptor. Differently, P2X7 receptor induced, per se, similar and not additive effects compared to TGF-β1, after prolonged cell exposure to BzATP. These results suggest a putative role of purine receptors as target for anti-fibrotic agents.

Gln3p and Nil1p regulation of invertase activity and SUC2 expression in Saccharomyces cerevisiae.

Science.gov (United States)

Oliveira, Edna Maria Morais; Mansure, José João; Bon, Elba Pinto da Silva

2005-04-01

In Saccharomyces cerevisiae, sensing and signalling pathways regulate gene expression in response to quality of carbon and nitrogen sources. One such system, the target of rapamycin (Tor) proteins, senses nutrients and uses the GATA activators Gln3p and Nil1p to regulate translation in response to low-quality carbon and nitrogen. The signal transduction, triggered in response to nitrogen nutrition that is sensed by the Tor proteins, operates via a regulatory pathway involving the cytoplasmic factor Ure2p. When carbon and nitrogen are abundant, the phosphorylated Ure2p anchors the also phosphorylated Gln3p and Nil1p in the cytoplasm. Upon a shift from high- to low-quality nitrogen or treatment with rapamycin all three proteins are dephosphorylated, causing Gln3p and Nil1p to enter the nucleus and promote transcription. The genes that code for yeast periplasmic enzymes with nutritional roles would be obvious targets for regulation by the sensing and signalling pathways that respond to quality of carbon and nitrogen sources. Indeed, previous results from our laboratory had shown that the GATA factors Gln3p, Nil1p, Dal80p, Nil2p and also the protein Ure2 regulate the expression of asparaginase II, coded by ASP3. We also had observed that the activity levels of the also periplasmic invertase, coded by SUC2, were 6-fold lower in ure2 mutant cells in comparison to wild-type cells collected at stationary phase. These results suggested similarities between the signalling pathways regulating the expression of ASP3 and SUC2. In the present work we showed that invertase levels displayed by the single nil1 and gln3 and by the double gln3nil1 mutant cells, cultivated in a sucrose-ammonium medium and collected at the exponential phase, were 6-, 10- and 60-fold higher, respectively, in comparison to their wild-type counterparts. RT-PCR data of SUC2 expression in the double-mutant cells indicated a 10-fold increase in the mRNA(SUC2) levels.

Characterization of a recurrent t(1;2)(p36;p24) in human uterine leiomyoma.

NARCIS (Netherlands)

Rijk, A. van; Sweers, M.A.; Huys, E.; Kersten, M.; Merkx, G.F.M.; Geurts van Kessel, A.H.M.; Debiec-Rychter, M.; Schoenmakers, E.F.P.M.

2009-01-01

Uterine leiomyomas are the most common neoplasms in women of reproductive age. Approximately 40% of these neoplasms show recurring structural cytogenetic anomalies, including del(7)(q22), t(12;14)(q15;q24), t(1;2)(p36;p24), and anomalies affecting 6p21 or 10q22. Using positional cloning strategies,

Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4

DEFF Research Database (Denmark)

Farkas, Thomas; Hansen, Klaus; Holm, Karin

2002-01-01

The "pocket proteins" pRb (retinoblastoma tumor suppressor protein), p107, and p130 regulate cell proliferation via phosphorylation-sensitive interactions with E2F transcription factors and other proteins. We previously identified 22 in vivo phosphorylation sites in human p130, including three...

P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

Science.gov (United States)

Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

2015-09-01

HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF

Optogalvanic transients in the 1s2,4→2p1,3 excitations of radio frequency neon plasma

International Nuclear Information System (INIS)

Yao, X.; Kumar, D.; McGlynn, S.P.

1999-01-01

The optogalvanic effects (OGE) induced by pulsed laser excitation of Ne 1s 2,4 →2p 1,3 transitions in a low power, ∼30 MHz radio frequency Ne discharge at ∼5 Torr are described. The polarity (sign) of the OGE signal is controlled by perturbations of the 1s j populations. The steady state 1s 4 population is ∼10 1 times larger than the 1s 2 population and the OGE signals for 1s 4 →2p 1,3 excitations are correspondingly stronger than those for 1s 2 →2p 1,3 excitations. The plasma temperature is found to be ∼1000 K. The excitations 1s 2,4 →2p 3 are more efficient at signal production than the 1s 2,4 →2p 1 excitations, which is contrary to prediction. The OGE signals are consequences of: (1) perturbation and reequilibration of the metastable 1s 3 and 1s 5 populations; (2) radiatively trapped 1s 2 → 1 S 0 photons; and (3) collisionally induced 1s 2 , 1s 4 ↔1s 3 , 1s 5 energy transfer. The OGE signal components, both the ionization and photoacoustic constituents, are temporally coincident only when the immediate causative agents are trapped photons. When otherwise produced, the photoacoustic part is delayed relative to the ionization component by the time required for the acoustic wave to travel from the locus of excitation to the sensitive region(s) of the plasma. copyright 1999 American Institute of Physics

Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Arun K.; Sean Fyvie, W.; Brindisi, Margherita; Steffey, Melinda; Agniswamy, Johnson; Wang, Yuan-Fang; Aoki, Manabu; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

2017-11-01

Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki = 13.2 nM, IC50 = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki = 62 pM and 14 pM, respectively) and antiviral activity (IC50 = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.

A Genome-wide Association Study Provides Evidence of Sex-specific Involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 With Diabetic Neuropathic Pain

Directory of Open Access Journals (Sweden)

Weihua Meng

2015-10-01

Full Text Available Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0% than in females (14.7%. This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 with the disorder, indicating the need for further research.

The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation.

Science.gov (United States)

Martins, Telma S; Pereira, Clara; Canadell, David; Vilaça, Rita; Teixeira, Vítor; Moradas-Ferreira, Pedro; de Nadal, Eulàlia; Posas, Francesc; Costa, Vítor

2018-01-01

Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Electron Excitation Rate Coefficients for Transitions from the IS21S Ground State to the 1S2S1,3S and 1S2P1,3P0 Excited States of Helium

Science.gov (United States)

Aggarwal, K. M.; Kingston, A. E.; McDowell, M. R. C.

1984-03-01

The available experimental and theoretical electron impact excitation cross section data for the transitions from the 1s2 1S ground state to the 1s2s 1,3S and 1s2p 1,3P0 excited states of helium are assessed. Based on this assessed data, excitation rate coefficients are calculated over a wide electron temperature range below 3.0×106K. A comparison with other published results suggests that the rates used should be lower by a factor of 2 or more.

Polarization dependence of double-resonance optical pumping and electromagnetically induced transparency in the 5S1/2-5P3/2-5D5/2 transition of 87Rb atoms

International Nuclear Information System (INIS)

Moon, Han Seb; Noh, Heung-Ryoul

2011-01-01

The polarization dependence of double-resonance optical pumping (DROP) in the ladder-type electromagnetically induced transparency (EIT) of the 5S 1/2 -5P 3/2 -5D 5/2 transition of 87 Rb atoms is studied. The transmittance spectra in the 5S 1/2 (F=2)-5P 3/2 (F'=3)-5D 5/2 (F''=2,3,4) transition were observed as caused by EIT, DROP, and saturation effects in the various polarization combinations between the probe and coupling lasers. The features of the double-structure transmittance spectra in the 5S 1/2 (F=2)-5P 3/2 (F'=3)-5D 5/2 (F''=4) cycling transition were attributed to the difference in saturation effect according to the transition routes between the Zeeman sublevels and the EIT according to the two-photon transition probability.

[1,3-Bis(diphenylphosphinopropane-κ2P,P′]diiodido(perfluoropropylrhodium(III dichloromethane solvate

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Andreas Franken

2008-10-01

Full Text Available The structure of the title compound, [RhI2(C3F7(C27H26P2]·CH2Cl2, at 110 (2 K is an unusual example of a structurally characterized square-based pyramidal alkyl complex of rhodium(III. The Rh—C bond is relatively short at 1.996 (6 Å. This short metal–carbon bond length is typical of perfluoro complexes of transition metals and illustrates the enhanced bond strength in these compounds.

Identification of rabbit cytochromes P450 2C1 and 2C2 as arachidonic acid epoxygenases.

Science.gov (United States)

Laethem, R M; Koop, D R

1992-12-01

Microsomes prepared from COS-1 cells transiently expressing rabbit cytochromes P450 2C1 and 2C2 catalyzed the metabolism of arachidonic acid to predominantly 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) when microsomal epoxide hydrolase activity was inhibited by 0.2 mM 1,2-epoxy-3,3,3-trichloropropane. P450 2C2 catalyzed the formation of 11,12-EET and 14,15-EET at a ratio of 3.0 and also produced 19-hydroxyeicosatetraenoic acid (19-HETE). The 11,12-EET, 14,15-EET, and 19-HETE represented 48.3, 15.9, and 12.8%, respectively, of the total metabolites formed. P450 2C1 produced a similar but distinct ratio of 11,12-EET to 14,15-EET (2.0) and did not produce any detectable 19-HETE. The 11,12-EET and 14,15-EET represented 63.0 and 31.1%, respectively, of the total metabolites formed. The 8,9- and 5,6-EETs were not detected with either enzyme. The ratio of the 11,12-EET to 14,15-EET was 1.5 with P450 2CAA, a P450 arachidonic acid epoxygenase (P450 2CAA) that had an amino-terminal sequence identical to that of P450 2C2 [J. Biol. Chem. 267:5552-5559 (1992)]. P450 2C1, 2C2, and 2CAA metabolized lauric acid. The ratio of omega-1- to omega-hydroxylated laurate was 3.6, 3.4, and 2.4 for P450 2CAA, P450 2C2, and P450 2C1, respectively. Purified P450 2CAA had a slightly greater apparent molecular weight than expressed P450 2C2 on sodium dodecyl sulfate-polyacrylamide gels. The results clearly establish that rabbit P450 2C1 and 2C2 are arachidonic acid epoxygenases, and they suggest that P450 2CAA and 2C2 are very similar but may not be identical isoforms.

Tumor protein 53-induced nuclear protein 1 (TP53INP1 enhances p53 function and represses tumorigenesis

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Jeyran eShahbazi

2013-05-01

Full Text Available Tumor protein 53-induced nuclear protein 1 (TP53INP1 is a stress-induced p53 target gene whose expression is modulated by transcription factors such as p53, p73 and E2F1. TP53INP1 gene encodes two isoforms of TP53INP1 proteins, TP53INP1α and TP53INP1β, both of which appear to be key elements in p53 function. When associated with homeodomain-interacting protein kinase-2 (HIPK2, TP53INP1 phosphorylates p53 protein at Serine 46, enhances p53 protein stability and its transcriptional activity, leading to transcriptional activation of p53 target genes such as p21, PIG-3 and MDM2, cell growth arrest and apoptosis upon DNA damage stress. The anti-proliferative and pro-apoptotic activities of TP53INP1 indicate that TP53INP1 has an important role in cellular homeostasis and DNA damage response. Deficiency in TP53INP1 expression results in increased tumorigenesis; while TP53INP1 expression is repressed during early stages of cancer by factors such as miR-155. This review aims to summarize the roles of TP53INP1 in blocking tumor progression through p53-dependant and p53-independent pathways, as well as the elements which repress TP53INP1 expression, hence highlighting its potential as a therapeutic target in cancer treatment.

μ-1,2-Bis(diphenylphosphinoethane-κ2P:P′-bis{[1,2-bis(diphenylphosphinoethane-κ2P,P′]bromidocopper(I} acetone disolvate

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Wen-Juan Shi

2008-10-01

Full Text Available In the crystal structure of the title compound, [Cu2Br2(dppe3]·2CH3COCH3 [dppe is 1,2-bis(diphenylphosphinoethane, C26H24P2], the two Cu centers are bridged by a dppe ligand and each metal center carries one chelating dppe unit, with the fourth coordination site available for the Br− anion. The molecule is centrosymmetric, with the center of symmetry located between the methylene C atoms of the bridging dppe ligand. The crystal structure is stabilized by intramolecular C—H...Br hydrogen bonds and intermolecular π–π interactions, with a centroid-to-centroid distance of 3.2055 (1 Å.

The selective antagonism of P2X7 and P2Y1 receptors prevents synaptic failure and affects cell proliferation induced by oxygen and glucose deprivation in rat dentate gyrus.

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Giovanna Maraula

Full Text Available Purinergic P2X and P2Y receptors are broadly expressed on both neurons and glial cells in the central nervous system (CNS, including dentate gyrus (DG. The aim of this research was to determine the synaptic and proliferative response of the DG to severe oxygen and glucose deprivation (OGD in acute rat hippocampal slices and to investigate the contribution of P2X7 and P2Y1 receptor antagonism to recovery of synaptic activity after OGD. Extracellular field excitatory post-synaptic potentials (fEPSPs in granule cells of the DG were recorded from rat hippocampal slices. Nine-min OGD elicited an irreversible loss of fEPSP and was invariably followed by the appearance of anoxic depolarization (AD. Application of MRS2179 (selective antagonist of P2Y1 receptor and BBG (selective antagonist of P2X7 receptor, before and during OGD, prevented AD appearance and allowed a significant recovery of neurotransmission after 9-min OGD. The effects of 9-min OGD on proliferation and maturation of cells localized in the subgranular zone (SGZ of slices prepared from rats treated with 5-Bromo-2'-deoxyuridine (BrdU were investigated. Slices were further incubated with an immature neuron marker, doublecortin (DCX. The number of BrdU+ cells in the SGZ was significantly decreased 6 hours after OGD. This effect was antagonized by BBG, but not by MRS2179. Twenty-four hours after 9-min OGD, the number of BrdU+ cells returned to control values and a significant increase of DCX immunofluorescence was observed. This phenomenon was still evident when BBG, but not MRS2179, was applied during OGD. Furthermore, the P2Y1 antagonist reduced the number of BrdU+ cells at this time. The data demonstrate that P2X7 and P2Y1 activation contributes to early damage induced by OGD in the DG. At later stages after the insult, P2Y1 receptors might play an additional and different role in promoting cell proliferation and maturation in the DG.

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

Science.gov (United States)

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

2014-06-01

We previously reported sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF) augment endothelial cell (EC) barrier function and attenuate murine acute lung inury (ALI). While the mechanisms underlying these effects are not fully understood, S1P and HGF both transactivate the S1P receptor, S1PR1 and integrin β4 (ITGB4) at membrane caveolin-enriched microdomains (CEMs). In the current study, we investigated the roles of S1PR2 and S1PR3 in S1P/HGF-mediated EC signaling and their associations with ITGB4. Our studies confirmed ITGB4 and S1PR2/3 are recruited to CEMs in human lung EC in response to either S1P (1 µM, 5 min) or HGF (25 ng/ml, 5 min). Co-immunoprecipitation experiments identified an S1P/HGF-mediated interaction of ITGB4 with both S1PR2 and S1PR3. We then employed an in situ proximity ligation assay (PLA) to confirm a direct ITGB4-S1PR3 association induced by S1P/HGF although a direct association was not detectable between S1PR2 and ITGB4. S1PR1 knockdown (siRNA), however, abrogated S1P/HGF-induced ITGB4-S1PR2 associations while there was no effect on ITGB4-S1PR3 associations. Moreover, PLA confirmed a direct association between S1PR1 and S1PR2 induced by S1P and HGF. Finally, silencing of S1PR2 significantly attenuated S1P/HGF-induced EC barrier enhancement as measured by transendothelial resistance while silencing of S1PR3 significantly augmented S1P/HGF-induced barrier enhancement. These results confirm an important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4. Our findings elucidate novel mechanisms of EC barrier regulation that may ultimately lead to new therapeutic targets for disorders characterized by increased vascular permeability including ALI. © 2013 Wiley Periodicals, Inc.

MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells.

Science.gov (United States)

Kalhori, Veronica; Törnquist, Kid

2015-03-15

The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.