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Sample records for salar p47phox p67phox

  1. Colitis susceptibility in p47(phox-/-) mice is mediated by the microbiome.

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    Falcone, E Liana; Abusleme, Loreto; Swamydas, Muthulekha; Lionakis, Michail S; Ding, Li; Hsu, Amy P; Zelazny, Adrian M; Moutsopoulos, Niki M; Kuhns, Douglas B; Deming, Clay; Quiñones, Mariam; Segre, Julia A; Bryant, Clare E; Holland, Steven M

    2016-04-05

    Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. Although CGD mice do not spontaneously develop colitis, we demonstrate that p47(phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47(phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47(phox+/-) mice and standardizing the microflora between littermate p47(phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47(phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47(phox-/-) and B6Tac mice treated with Citrobacter rodentium. Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.

  2. PKCδ-dependent p47phox activation mediates methamphetamine-induced dopaminergic neurotoxicity.

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    Dang, Duy-Khanh; Shin, Eun-Joo; Kim, Dae-Joong; Tran, Hai-Quyen; Jeong, Ji Hoon; Jang, Choon-Gon; Ottersen, Ole Petter; Nah, Seung-Yeol; Hong, Jau-Shyong; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2018-02-01

    Protein kinase C (PKC) has been recognized to activate NADPH oxidase (PHOX). However, the interaction between PKC and PHOX in vivo remains elusive. Treatment with methamphetamine (MA) resulted in a selective increase in PKCδ expression out of PKC isoforms. PKCδ co-immunoprecipitated with p47phox, and facilitated phosphorylation and membrane translocation of p47phox. MA-induced increases in PHOX activity and reactive oxygen species were attenuated by knockout of p47phox or PKCδ. In addition, MA-induced impairments in the Nrf-2-related glutathione synthetic system were also mitigated by knockout of p47phox or PKCδ. Glutathione-immunoreactivity was co-localized in Iba-1-labeled microglial cells and in NeuN-labeled neurons, but not in GFAP-labeled astrocytes, reflecting the necessity for self-protection against oxidative stress by mainly microglia. Buthionine-sulfoximine, an inhibitor of glutathione biosynthesis, potentiated microglial activation and pro-apoptotic changes, leading to dopaminergic losses. These neurotoxic processes were attenuated by rottlerin, a pharmacological inhibitor of PKCδ, genetic inhibitions of PKCδ [i.e., PKCδ knockout mice (KO) and PKCδ antisense oligonucleotide (ASO)], or genetic inhibition of p47phox (i.e., p47phox KO or p47phox ASO). Rottlerin did not exhibit any additive effects against the protective activity offered by genetic inhibition of p47phox. Therefore, we suggest that PKCδ is a critical regulator for p47phox activation induced by MA, and that Nrf-2-dependent GSH induction via inhibition of PKCδ or p47phox, is important for dopaminergic protection against MA insult. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Caracterización molecular en pacientes con enfermedad granulomatosa crónica por deficiencia en p47 phox Molecular characterization in patients with chronic granulomatous disease due to p47phox deficiency

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    Pablo Javier Patiño Grajales

    1998-01-01

    Full Text Available El sistema NAOPH oxidasa es un complejo enzimático transportador de electrones localizado en la membrana de las células fagocíticas. Oe este sistema hacen parte varias proteínas; un flavocitocromo b558' el cual está conformado por una cadena b (gp91-phox y una cadena a (p22-phox y poral menos 3 proteínas citosólicas (p47-phox, p67- phox, p40-phox. Una alteración gen ética en cualquiera de estas proteínas causa el síndrome de Enfermedad Granulomatosa Crónica (EGC. La caracterizaciÓn de las mutaciones de los pacientes con EGC ha sido fundamental para dilucidar la estructura y función de los componentes del sistema NAOPH oxidasa. En el caso de la p47-phox, se han obtenido hallazgos importantes que la hacen un modelo interesante para estudiar el mecanismo molecular involucrado en regular la expresión y función bioquímica de este sistema. En los pacientes con defecto en la p47-phox investigados hasta ahora, se ha hallado una deleción del dinucleótido GT al comienzo del exón 2 , siendo la mayoría de ellos homocigóticos para esta deleción, la cual posiblemente se debe a eventos de recombinación entre el gen p47 -phox normal y un seudogen recientemente descrito. En el diagnóstico de pacientes no homocigóticos, cualquier mutación encontrada en el análisis del ONA (gONA o cONA puede representar un cambio sufrido por el seudogen. Por lo tanto, para la identificación precisa del defecto gen ético es necesario separar el gen normal del seudogen y analizar las secuencias en forma individual. Los pacientes no homocigóticos posiblemente deben tener una segunda mutación en el alelo tipo silvestre diferente a la deleción GT. De otro lado, a través de mutagénesis sitio-dirigida se pueden modificar algunos de los aminoácidos o dominios de la p47-phox, los cuales pueden ser esenciales para su funcionamiento y su relación con la EGC. Con esta metodología, es posible introducir cambios en un gen cuya secuencia es totalmente

  4. Caracterización molecular de las proteínas p47phox y p40phox del sistema NADPH oxidasa mediante mutagénesis sitio dirigida

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    Juan Alvaro López

    2000-02-01

    Full Text Available <p class="MsoNormal">Los neutrófilos responden a diferentes estímulos con un fenómeno conocido como “explosión respiratoria” la cual depende del sistema NADPH oxidasa. La importancia de este sistema para la actividad microbicida de las células fagocíticas es evidente en pacientes con Enfermedad Granulomatosa Crónica (EGC, los cuales sufren un incremento en la susceptibilidad a infecciones por hongos y bacterias debido a una deficiencia en la producción de agentes oxidantes por los fagocitos. El sistema NADPH oxidasa está formado por seis componentes esenciales: p40phox, p47phox, p67phox, p22phox y gp91phox. Una sexta proteína implicada en la activación del sistema es la proteína p21rac, de la familia de las GTPasas relacionadas con Ras. El centro funcional de este sistema se encuentra en el flavocitocromo b558, compuesto por las subunidades gp91phox y p22phox ubicadas en la membrana de las vesículas secretorias y gránulos específicos, las cuales aceptan electrones del NADPH citosólico y lo donan al oxígeno molecular que se encuentra en la vacuola fagocítica. p> <p class

  5. La p67-PHOX como un elemento esencial del sistema NADPH oxidasa de las células fagocíticas

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    Pablo Javier Patiño Grajales

    1999-01-01

    Full Text Available Las células fagocíticas cumplen un papel fundamental en la defensa innata del huésped contra la invasión de microorganismos. Luego de ser fagocitados, uno de lo~ mecanismos utilizados para destruir dichos microorganismos es la producción de metabolitos intermedios del oxígeno generados a través del sistema NADPH oxidasa. Los radicales libres del oxígeno están al mismo tiempo involucrados en el daño tisular, que ocurre en muchas condiciones inflamatorias. La NADPH oxidasa es un complejo proteico conformado por varios componentes: gp91-phox y p22-phox, los cuales forman un heterodímero llamado citocromo b5581 que se encuentra en la membrana de las células fagocíticas, y por las proteínas p47-phox, p67-phox y p40-phox que forman un complejo macromolecular localizado en el citoplasma. Durante la activación de las células fagocíticas los componentes citosólicos del sistema se translocan a la membrana y se unen al citocromo b558' conformando así el complejo enzimático activo de la NADPH oxidasa cuya importancia biológica se ha evidenciado en las últimas cuatro décadas gracias al estudio de la enfermedad granulomatosa crónica (EGC. Ésta es una inmunodeficiencia primaria caracterizada por infecciones recurrentes y severas. Todos los casos de EGC reportados hasta ahora tienen que ver con una alteración en los genes que codifican las proteínas gp91-phox, p22-phox, p67-phoxy p47-phox. La p67 -phox es uno de los componentes del sistema NADPH oxidasa que más ha llamado la atención en los últimos años, pues tiene un papel fundamental en la activación del flujo de electrones desde el citoplasma a la vacuola fagocítica. En este articulo se hace una revisión acerca de lo que hasta ahora se conoce de la estructura y función de la p67-phox. Además se revisarán las diversas mutaciones identificadas en su gen, que debido a su alto grado de heterogeneidad son de gran utilidad para el entendimiento de la estructura y función del

  6. Nox2 and p47phox modulate compensatory growth of primary collateral arteries

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    DiStasi, Matthew R.; Unthank, Joseph L.

    2014-01-01

    The role of NADPH oxidase (Nox) in both the promotion and impairment of compensatory collateral growth remains controversial because the specific Nox and reactive oxygen species involved are unclear. The aim of this study was to identify the primary Nox and reactive oxygen species associated with early stage compensatory collateral growth in young, healthy animals. Ligation of the feed arteries that form primary collateral pathways in rat mesentery and mouse hindlimb was used to assess the role of Nox during collateral growth. Changes in mesenteric collateral artery Nox mRNA expression determined by real-time PCR at 1, 3, and 7 days relative to same-animal control arteries suggested a role for Nox subunits Nox2 and p47phox. Administration of apocynin or Nox2ds-tat suppressed collateral growth in both rat and mouse models, suggesting the Nox2/p47phox interaction was involved. Functional significance of p47phox expression was assessed by evaluation of collateral growth in rats administered p47phox small interfering RNA and in p47phox−/− mice. Diameter measurements of collateral mesenteric and gracilis arteries at 7 and 14 days, respectively, indicated no significant collateral growth compared with control rats or C57BL/6 mice. Chronic polyethylene glycol-conjugated catalase administration significantly suppressed collateral development in rats and mice, implying a requirement for H2O2. Taken together, these results suggest that Nox2, modulated at least in part by p47phox, mediates early stage compensatory collateral development via a process dependent upon peroxide generation. These results have important implications for the use of antioxidants and the development of therapies for peripheral arterial disease. PMID:24633549

  7. The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice

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    Flávia Rezende

    2018-05-01

    Innovation and conclusion: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.

  8. The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.

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    Rezende, Flávia; Moll, Franziska; Walter, Maria; Helfinger, Valeska; Hahner, Fabian; Janetzko, Patrick; Ringel, Christian; Weigert, Andreas; Fleming, Ingrid; Weissmann, Norbert; Kuenne, Carsten; Looso, Mario; Rieger, Michael A; Nawroth, Peter; Fleming, Thomas; Brandes, Ralf P; Schröder, Katrin

    2018-05-01

    NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes. In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice. ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. The dehydrogenase region of the NADPH oxidase component Nox2 acts as a protein disulfide isomerase (PDI) resembling PDIA3 with a role in the binding of the activator protein p67phox

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    Bechor, Edna; Dahan, Iris; Fradin, Tanya; Berdichevsky, Yevgeny; Zahavi, Anat; Rafalowski, Meirav; Federman-Gross, Aya; Pick, Edgar

    2015-02-01

    The superoxide (O2.-)-generating NADPH oxidase of phagocytes consists of a membrane component, cytochrome b558 (a heterodimer of Nox2 and p22phox), and four cytosolic components, p47phox, p67phox, p40phox, and Rac. The catalytic component, responsible for O2.- generation, is Nox2. It is activated by the interaction of the dehydrogenase region (DHR) of Nox2 with the cytosolic components, principally with p67phox. Using a peptide-protein binding assay, we found that Nox2 peptides containing a 369CysGlyCys371 triad (CGC) bound p67phox with high affinity, dependent upon the establishment of a disulfide bond between the two cysteines. Serially truncated recombinant Nox2 DHR proteins bound p67phox only when they comprised the CGC triad. CGC resembles the catalytic motif (CGHC) of protein disulfide isomerases (PDIs). This led to the hypothesis that Nox2 establishes disulfide bonds with p67phox via a thiol-dilsulfide exchange reaction and, thus, functions as a PDI. Evidence for this was provided by the following: 1. Recombinant Nox2 protein, which contained the CGC triad, exhibited PDI-like disulfide reductase activity; 2. Truncation of Nox2 C-terminal to the CGC triad or mutating C369 and C371 to R, resulted in loss of PDI activity; 3. Comparison of the sequence of the DHR of Nox2 with PDI family members revealed three small regions of homology with PDIA3; 4. Two monoclonal anti-Nox2 antibodies, with epitopes corresponding to regions of Nox2/PDIA3 homology, reacted with PDIA3 but not with PDIA1; 5. A polyclonal anti-PDIA3 (but not an anti-PDIA1) antibody reacted with Nox2; 6. p67phox, in which all cysteines were mutated to serines, lost its ability to bind to a Nox2 peptide containing the CGC triad and had an impaired capacity to support oxidase activity in vitro. We propose a model of oxidase assembly in which binding of p67phox to Nox2 via disulfide bonds, by virtue of the intrinsic PDI activity of Nox2, stabilizes the primary interaction between the two components.

  10. Producción de la proteína p67 phox recombinante del sistema NADPH oxidasa mediante el sistema baculovirus

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    Pablo Patiño

    2001-04-01

    la producción de anión superóxido (O2 -. Este sistema está formado por cinco proteínas: gp91 phox, p22 phox, p47 phox, p67 phox y p40 phox, y mutaciones en cuatro de estas proteínas (gp91 phox, p22 phox, p47phox, p67phox conducen a una inmunodeficiencia primaria conocida como Enfermedad Granulomatosa Crónica.p>

  11. Gene transfer and expression in human neutrophils. The phox homology domain of p47phox translocates to the plasma membrane but not to the membrane of mature phagosomes

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    Brzezinska Agnieszka A

    2006-12-01

    Full Text Available Abstract Background Neutrophils are non-dividing cells with poor survival after isolation. Consequently, exogenous gene expression in neutrophils is challenging. We report here the transfection of genes and expression of active proteins in human primary peripheral neutrophils using nucleofection. Results Exogenous gene expression in human neutrophils was achieved 2 h post-transfection. We show that neutrophils transfected by nucleofection are functional cells, able to respond to soluble and particulate stimuli. They conserved the ability to undergo physiological processes including phagocytosis. Using this technique, we were able to show that the phox homology (PX domain of p47phox localizes to the plasma membrane in human neutrophils. We also show that RhoB, but not the PX domain of p47phox, is translocated to the membrane of mature phagosomes. Conclusion We demonstrated that cDNA transfer and expression of exogenous protein in human neutrophils is compatible with cell viability and is no longer a limitation for the study of protein function in human neutrophils.

  12. Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

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    Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

    2016-08-01

    Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice. Copyright © 2016 the American Physiological Society.

  13. A founder effect for p47(phox)Trp193Ter chronic granulomatous disease in Kavkazi Jews

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    de Boer, Martin; Tzur, Shay; van Leeuwen, Karin; Dencher, Paula C. D.; Skorecki, Karl; Wolach, Baruch; Gavrieli, Ronit; Nasidze, Ivane; Stoneking, Mark; Tanck, Michael W. T.; Roos, Dirk

    2015-01-01

    Chronic granulomatous disease (CGD) is a rare congenital immune deficiency caused by mutations in any of the five genes encoding NADPH oxidase subunits. One of these genes is NCF1, encoding the p47(phox) protein. A group of 39 patients, 14 of whom are of Kavkazi Jewish descent, was investigated for

  14. Priming of the neutrophil NADPH oxidase activation: role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane.

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    El-Benna, Jamel; Dang, Pham My-Chan; Gougerot-Pocidalo, Marie-Anne

    2008-07-01

    Neutrophils play an essential role in host defense against microbial pathogens and in the inflammatory reaction. Upon activation, neutrophils produce superoxide anion (O*2), which generates other reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical (OH*) and hypochlorous acid (HOCl), together with microbicidal peptides and proteases. The enzyme responsible for O2* production is called the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two trans-membrane proteins (p22phox and gp91phox/NOX2, which form the cytochrome b558), three cytosolic proteins (p47phox, p67phox, p40phox) and a GTPase (Rac1 or Rac2), which assemble at membrane sites upon cell activation. NADPH oxidase activation in phagocytes can be induced by a large number of soluble and particulate factors. Three major events accompany NAPDH oxidase activation: (1) protein phosphorylation, (2) GTPase activation, and (3) translocation of cytosolic components to the plasma membrane to form the active enzyme. Actually, the neutrophil NADPH oxidase exists in different states: resting, primed, activated, or inactivated. The resting state is found in circulating blood neutrophils. The primed state can be induced by neutrophil adhesion, pro-inflammatory cytokines, lipopolysaccharide, and other agents and has been characterized as a "ready to go" state, which results in a faster and higher response upon exposure to a second stimulus. The active state is found at the inflammatory or infection site. Activation is induced by the pathogen itself or by pathogen-derived formylated peptides and other agents. Finally, inactivation of NADPH oxidase is induced by anti-inflammatory agents to limit inflammation. Priming is a "double-edged sword" process as it contributes to a rapid and efficient elimination of the pathogens but can also induce the generation of large quantities of toxic ROS by hyperactivation of

  15. Andrographolide, a Novel NF-κB Inhibitor, Induces Vascular Smooth Muscle Cell Apoptosis via a Ceramide-p47phox-ROS Signaling Cascade

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    Yu-Ying Chen

    2013-01-01

    Full Text Available Atherosclerosis is linked with the development of many cardiovascular complications. Abnormal proliferation of vascular smooth muscle cells (VSMCs plays a crucial role in the development of atherosclerosis. Accordingly, the apoptosis of VSMCs, which occurs in the progression of vascular proliferation, may provide a beneficial strategy for managing cardiovascular diseases. Andrographolide, a novel nuclear factor-κB inhibitor, is the most active and critical constituent isolated from the leaves of Andrographis paniculata. Recent studies have indicated that andrographolide is a potential therapeutic agent for treating cancer through the induction of apoptosis. In this study, the apoptosis-inducing activity and mechanisms in andrographolide-treated rat VSMCs were characterized. Andrographolide significantly induced reactive oxygen species (ROS formation, p53 activation, Bax, and active caspase-3 expression, and these phenomena were suppressed by pretreating the cells with N-acetyl-L-cysteine, a ROS scavenger, or diphenylene iodonium, a nicotinamide adenine dinucleotide phosphate (NADPH oxidase (Nox inhibitor. Furthermore, p47phox, a Nox subunit protein, was phosphorylated in andrographolide-treated rat VSMCs. However, pretreatment with 3-O-methyl-sphingomyelin, a neutral sphingomyelinase inhibitor, significantly inhibited andrographolide-induced p47phox phosphorylation as well as Bax and active caspase-3 expression. Our results collectively demonstrate that andrographolide-reduced cell viability can be attributed to apoptosis in VSMCs, and this apoptosis-inducing activity was associated with the ceramide-p47phox-ROS signaling cascade.

  16. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

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    Thewarid Berkban

    2015-06-01

    Full Text Available The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day for five weeks. L-NAME induced high systolic blood pressure (SBP and increased heart rate (HR, hindlimb vascular resistance (HVR and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability.

  17. Impaired compensation to femoral artery ligation in diet-induced obese mice is primarily mediated via suppression of collateral growth by Nox2 and p47phox.

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    DiStasi, Matthew R; Mund, Julie A; Bohlen, H Glenn; Miller, Steven J; Ingram, David A; Dalsing, Michael C; Unthank, Joseph L

    2015-10-01

    The present study was undertaken to establish the role of NADPH oxidase (Nox) in impaired vascular compensation to arterial occlusion that occurs in the presence of risk factors associated with oxidative stress. Diet-induced obese (DIO) mice characterized by multiple comorbidities including diabetes and hyperlipidemia were used as a preclinical model. Arterial occlusion was induced by distal femoral artery ligation in lean and DIO mice. Proximal collateral arteries were identified as the site of major (∼70%) vascular resistance to calf perfusion by distal arterial pressures, which decreased from ∼80 to ∼30 mmHg with ligation in both lean and DIO mice. Two weeks after ligation, significant vascular compensation occurred in lean but not DIO mice as evidenced by increased perfusion (147 ± 48% vs. 49 ± 29%) and collateral diameter (151 ± 30% vs. 44 ± 17%). Vascular mRNA expression of p22(phox), Nox2, Nox4, and p47(phox) were all increased in DIO mice. Treatment of DIO mice with either apocynin or Nox2ds-tat or with whole body ablation of either Nox2 or p47(phox) ameliorated the impairment in both collateral growth and hindlimb perfusion. Multiparametric flow cytometry analysis demonstrated elevated levels of circulating monocytes in DIO mice without impaired mobilization and demargination after femoral artery ligation. These results establish collateral resistance as the major limitation to calf perfusion in this preclinical model, demonstrate than monocyte mobilization and demarginatin is not suppressed, implicate Nox2-p47(phox) interactions in the impairment of vascular compensation to arterial occlusion in DIO mice, and suggest that selective Nox component suppression/inhibition may be effective as either primary or adjuvant therapy for claudicants. Copyright © 2015 the American Physiological Society.

  18. Identification of NoxD/Pro41 as the homologue of the p22phox NADPH oxidase subunit in fungi.

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    Lacaze, Isabelle; Lalucque, Hervé; Siegmund, Ulrike; Silar, Philippe; Brun, Sylvain

    2015-03-01

    NADPH oxidases (Nox) are membrane complexes that produce O2(-). Researches in mammals, plants and fungi highlight the involvement of Nox-generated ROS in cell proliferation, differentiation and defense. In mammals, the core enzyme gp91(phox)/Nox2 is associated with p22(phox) forming the flavocytochrome b558 ready for activation by a cytosolic complex. Intriguingly, no homologue of the p22(phox) gene has been found in fungal genomes, questioning how the flavoenzyme forms. Using whole genome sequencing combined with phylogenetic analysis and structural studies, we identify the fungal p22(phox) homologue as being mutated in the Podospora anserina mutant IDC(509). Functional studies show that the fungal p22(phox), PaNoxD, acts along PaNox1, but not PaNox2, a second fungal gp91(phox) homologue. Finally, cytological analysis of functional tagged versions of PaNox1, PaNoxD and PaNoxR shows clear co-localization of PaNoxD and PaNox1 and unravel a dynamic assembly of the complex in the endoplasmic reticulum and in the vacuolar system. © 2014 John Wiley & Sons Ltd.

  19. Resveratrol strongly enhances the retinoic acid-induced superoxide generating activity via up-regulation of gp91-phox gene expression in U937 cells.

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    Kikuchi, Hidehiko; Mimuro, Hitomi; Kuribayashi, Futoshi

    2018-01-01

    The membrane bound cytochrome b 558 composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O 2 - )-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dramatically activates the O 2 - -generating system during retinoic acid (RA)-induced differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. When U937 cells were cultured in the presence of RA and resveratrol, the O 2 - -generating activity increased more than 5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and resveratrol strongly enhanced transcription of the gp91-phox compared with those of the RA-treatment only. On the other hand, immunoblot analysis revealed that co-treatment with RA and resveratrol caused remarkable accumulation of protein levels of gp91-phox (to 4-fold), p22-phox (to 5-fold) and p47-phox (to 4-fold) compared with those of the RA-treatment alone. In addition, ChIP assay suggested that resveratrol participates in enhancing the gene expression of gp91-phox via promoting acetylation of Lys-9 residues and Lys-14 residues of histone H3 within chromatin around the promoter regions of the gene. These results suggested that resveratrol strongly enhances the RA-induced O 2 - -generating activity via up-regulation of gp91-phox gene expression in U937 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Role of Nox2 and p22phox in Persistent Postoperative Hypertension in Aldosterone-Producing Adenoma Patients after Adrenalectomy

    Directory of Open Access Journals (Sweden)

    Xiaojing Geng

    2016-01-01

    Full Text Available Adrenal aldosterone-producing adenoma (APA, producing the salt-retaining hormone aldosterone, commonly causes secondary hypertension, which often persists after unilateral adrenalectomy. Although persistent hypertension was correlated with residual hormone aldosterone, the in vivo mechanism remains unclear. NADPH oxidase is the critical cause of aldosterone synthesis in vitro. Nox2 and p22phox comprise the NADPH oxidase catalytic core, serving to initiate a reactive oxygen species (ROS cascade that may participate in the pathology. mRNAs of seven NADPH oxidase isoforms in APA were evaluated by RT-PCR and Q-PCR and their proteins by immunohistochemistry and Western blotting. NADPH oxidase activity was also detected. Nox2 and p22phox were especially abundant in APA. Particularly higher Nox2 and p22phox gene and protein levels were seen in APA than controls. Significant correlations between Nox2 mRNA and aldosterone synthase (CYP11B2 mRNA (R=0.66, P<0.01 and Nox2 protein and baseline plasma aldosterone concentration (PAC (R=0.503, P<0.01 were detected in APA; however, none were found between p22phox mRNA, CYP11B2 mRNA, p22phox protein, and baseline PAC. Importantly, we found that Nox2 localized specifically in hyperplastic zona glomerulosa cells. In conclusion, our results highlight that Nox2 and p22phox may be directly involved in pathological aldosterone production and zona glomerulosa cell proliferation after APA resection.

  1. A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites

    DEFF Research Database (Denmark)

    Dang, Pham My-Chan; Stensballe, Allan; Boussetta, Tarek

    2006-01-01

    mass spectrometry to show that GM-CSF and TNF-alpha induce phosphorylation of Ser345 on p47phox, a cytosolic component of NADPH oxidase, in human neutrophils. As Ser345 is located in the MAPK consensus sequence, we tested the effects of MAPK inhibitors. Inhibitors of the ERK1/2 pathway abrogated GM......Neutrophil NADPH oxidase plays a key role in host defense and in inflammation by releasing large amounts of superoxide and other ROSs. Proinflammatory cytokines such as GM-CSF and TNF-alpha prime ROS production by neutrophils through unknown mechanisms. Here we used peptide sequencing by tandem...

  2. Novel p47phox-related organizers regulate NADPH oxidase 1 (Nox1) activity and localization

    Science.gov (United States)

    Gianni, Davide; Diaz, Begoña; Taulet, Nicolas; Fowler, Bruce; Courtneidge, Sara A.; Bokoch, Gary M.

    2010-01-01

    The mechanisms that determine localized formation of reactive oxygen species (ROS) via NADPH oxidases (Nox) in nonphagocytic cells are unknown. We show that the c-Src substrate proteins Tks4 and Tks5 are functional members of a p47phox-related organizer superfamily. Tks proteins selectively support Nox1 and Nox3 (vs. Nox2 and Nox4) activity in reconstituted cellular systems, and interact with the NoxA1 activator protein through an SH3-mediated interaction. Endogenous Tks4 is required for Rac GTPase-dependent ROS production by DLD1 colon cancer cells. Tks4 recruits Nox1 to invadopodia that form in DLD1 cells in a Tks- and Nox-dependent fashion. We propose that Tks organizers represent novel members of an organizer superfamily that link Nox to localized ROS formation. PMID:19755710

  3. Novel p47(phox)-related organizers regulate localized NADPH oxidase 1 (Nox1) activity.

    Science.gov (United States)

    Gianni, Davide; Diaz, Begoña; Taulet, Nicolas; Fowler, Bruce; Courtneidge, Sara A; Bokoch, Gary M

    2009-09-15

    The mechanisms that determine localized formation of reactive oxygen species (ROS) through NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase (Nox) family members in nonphagocytic cells are unknown. We show that the c-Src substrate proteins Tks4 (tyrosine kinase substrate with four SH3 domains) and Tks5 are functional members of a p47(phox)-related organizer superfamily. Tks proteins selectively support Nox1 and Nox3 (and not Nox2 and Nox4) activity in reconstituted cellular systems and interact with the NoxA1 activator protein through an Src homology 3 domain-mediated interaction. Endogenous Tks4 is required for Rac guanosine triphosphatase- and Nox1-dependent ROS production by DLD1 colon cancer cells. Our results are consistent with the Tks-mediated recruitment of Nox1 to invadopodia that form in DLD1 cells in a Tks- and Nox-dependent fashion. We propose that Tks organizers represent previously unrecognized members of an organizer superfamily that link Nox to localized ROS formation.

  4. Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47phox component of the phagocyte NADPH oxidase

    NARCIS (Netherlands)

    Roos, Dirk; de Boer, Martin; Köker, M. Yavuz; Dekker, Jan; Singh-Gupta, Vinita; Ahlin, Anders; Palmblad, Jan; Sanal, Ozden; Kurenko-Deptuch, Magdalena; Jolles, Stephen; Wolach, Baruch

    2006-01-01

    Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by defects in any of four genes encoding components of the leukocyte nicotinamide dinucleotide phosphate, reduced (NADPH) oxidase. One of these is the autosomal neutrophil cytosolic factor 1 (NCF1) gene encoding the p47phox

  5. Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47phox pathway

    International Nuclear Information System (INIS)

    Tsai, Ming-Horng; Lin, Zih-Chan; Liang, Chan-Jung; Yen, Feng-Lin; Chiang, Yao-Chang; Lee, Chiang-Wen

    2014-01-01

    Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production associated with increased COX-2 expression in Hs68 cells. This effect was blocked by eupafolin, TLR-4 antibody, antioxidants (APO and NAC), as well as inhibitors, including U0126 (ERK1/2), SB202190 (p38), SP600125 (JNK1/2), and Tanshinone IIA (AP-1). In gene regulation level, qPCR and promoter assays revealed that COX-2 expression was attenuated by eupafolin. In addition, eupafolin also ameliorated LPS-induced p47 phox activation and decreased reactive oxygen species (ROS) generation and NADPH oxidase (Nox) activity. Moreover, pretreatment with eupafolin and APO led to reduced LPS-induced phosphorylation of ERK1/2, JNK, and p38. Further, eupafolin attenuated LPS-induced increase in AP-1 transcription factor binding activity as well as the increase in the phosphorylation of c-Jun and c-Fos. In vivo studies have shown that in dermal fibroblasts of LPS treated mice, eupafolin exerted anti-inflammation effects by decreasing COX-2 protein levels. Our results reveal a novel mechanism for anti-inflammatory and anti-oxidative effects of eupafolin that involved inhibition of LPS-induced ROS generation, suppression of MAPK phosphorylation, diminished DNA binding activity of AP-1 and attenuated COX-2 expression leading to reduced production of prostaglandin E2 (PGE2). Our results demonstrate that eupafolin may be used to treat inflammatory responses associated with dermatologic diseases. - Highlights: • LPS activates the Nox2/p47 phox /JNK/AP-1 and induces COX2 expression in Hs68 cells. • Eupafolin inhibits LPS-induced COX-2 expression via Nox2/p47 phox inhibition. • Eupafolin may be used in the treatment of skin diseases involving inflammation

  6. Eupafolin inhibits PGE2 production and COX2 expression in LPS-stimulated human dermal fibroblasts by blocking JNK/AP-1 and Nox2/p47{sup phox} pathway

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Ming-Horng [Department of Pediatrics, Division of Neonatology and Pediatric Hematology/Oncology, Chang Gung Memorial Hospital, Yunlin, Taiwan (China); Lin, Zih-Chan [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liang, Chan-Jung [Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yen, Feng-Lin [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Institute of Biomedical Sciences, Sun Yat-Sen University, 70 Lienhai Rd., Kaohsiung, Taiwan (China); Chiang, Yao-Chang [Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan (China); China Medical University, Taichung, Taiwan (China); Lee, Chiang-Wen, E-mail: cwlee@gw.cgust.edu.tw [Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi, Taiwan (China); Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan (China); Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan (China)

    2014-09-01

    Eupafolin, a major active component found in the methanol extracts of Phyla nodiflora, has been used to treat inflammation of skin. We examined its effects on cyclooxygenase-2 (COX-2) expression in LPS-treated human dermal fibroblasts. Lipopolysaccharide (LPS) significantly increased prostaglandin-E2 (PGE2) production associated with increased COX-2 expression in Hs68 cells. This effect was blocked by eupafolin, TLR-4 antibody, antioxidants (APO and NAC), as well as inhibitors, including U0126 (ERK1/2), SB202190 (p38), SP600125 (JNK1/2), and Tanshinone IIA (AP-1). In gene regulation level, qPCR and promoter assays revealed that COX-2 expression was attenuated by eupafolin. In addition, eupafolin also ameliorated LPS-induced p47 phox activation and decreased reactive oxygen species (ROS) generation and NADPH oxidase (Nox) activity. Moreover, pretreatment with eupafolin and APO led to reduced LPS-induced phosphorylation of ERK1/2, JNK, and p38. Further, eupafolin attenuated LPS-induced increase in AP-1 transcription factor binding activity as well as the increase in the phosphorylation of c-Jun and c-Fos. In vivo studies have shown that in dermal fibroblasts of LPS treated mice, eupafolin exerted anti-inflammation effects by decreasing COX-2 protein levels. Our results reveal a novel mechanism for anti-inflammatory and anti-oxidative effects of eupafolin that involved inhibition of LPS-induced ROS generation, suppression of MAPK phosphorylation, diminished DNA binding activity of AP-1 and attenuated COX-2 expression leading to reduced production of prostaglandin E2 (PGE2). Our results demonstrate that eupafolin may be used to treat inflammatory responses associated with dermatologic diseases. - Highlights: • LPS activates the Nox2/p47{sup phox}/JNK/AP-1 and induces COX2 expression in Hs68 cells. • Eupafolin inhibits LPS-induced COX-2 expression via Nox2/p47{sup phox} inhibition. • Eupafolin may be used in the treatment of skin diseases involving inflammation.

  7. INF-γ Enhances Nox2 Activity by Upregulating phox Proteins When Applied to Differentiating PLB-985 Cells but Does Not Induce Nox2 Activity by Itself.

    Directory of Open Access Journals (Sweden)

    Michael A Ellison

    Full Text Available The cytokine and drug interferon-γ enhances superoxide anion production by the antimicrobicidal Nox2 enzyme of neutrophils. Because mature neutrophils have a short lifespan, we hypothesized that the effects of interferon-γ on these cells might be mediated by its prolonged exposure to differentiating neutrophil precursors in the bone marrow rather than its brief exposure to mature circulating neutrophils. Effects of INF-Γ on NOX2 activity: To address this possibility we exposed the myeloid PLB-985 cell line to interferon-γ for 3 days in the presence of dimethyl sulfoxide which induces terminal differentiation of these cells. Interferon-γ was found to enhance superoxide production by Nox2 in a concentration dependent manner. In contrast, application of interferon-γ alone for 3 days failed to induce detectible Nox2 activity. Additionally, application of interferon-γ for 3 hours to pre-differentiated PLB-985 cells, which models studies using isolated neutrophils, was much less effective at enhancing superoxide anion production. Effects of INF-Γ on phox protein levels: Addition of interferon-γ during differentiation was found to upregulate the Nox2 proteins gp91phox and p47phox in concert with elevated transcription of their genes. The p22phox protein was upregulated in the absence of increased transcription presumably reflecting stabilization resulting from binding to the elevated gp91phox. Thus, increased levels of gp91phox, p47phox and p22phox likely account for the interferon-γ mediated enhancement of dimethyl sulfoxide-induced Nox2 activity. In contrast, although interferon-γ alone also increased various phox proteins and their mRNAs, the pattern was very different to that seen with interferon-γ plus dimethyl sulfoxide. In particular, p47phox was not induced thus explaining the inability of interferon -γ alone to enhance Nox2 activity. Short application of interferon-γ to already differentiated cells failed to increase any phox

  8. Relación de la transición A G en la posición –21 del intrón 10 del gen NCF-2 con la expresión de la proteína p67-phox

    Directory of Open Access Journals (Sweden)

    Pablo Patiño

    2001-04-01

    Full Text Available <p>El sistema NADPH oxidasa de las células fagocíticas es esencial
    para la producción de metabolitos reactivos de oxígeno que tienen
    acción microbicida importante. La proteína p67-phox, codificada por
    el gen NCF-2, tiene un papel importante en este sistema (1. Previamente nuestro grupo reportó algunos cambios nucleotídicos en regiones no codificadoras del gen NCF-2. Uno de estos corresponde a la
    transición de una adenina (A por una guanina (G en el intrón 10, 21
    nucleótidos antes del inicio del exón 11, sitio importante para la eliminación de este intrón y unión de los exones 10 y 11 durante el procesamiento del ARNm.
    En este proyecto se pretende determinar si existe alguna modificación
    en la expresión de p67-phox inducida por la transición A -►G en la posición -21 del intrón 10 en el gen NCF-2.p>

     

     >

  9. Investigation of association between donors' and recipients' NADPH oxidase p22(phox) C242T polymorphism and acute rejection, delayed graft function and blood pressure in renal allograft recipients.

    Science.gov (United States)

    Mandegary, Ali; Rahmanian-Koshkaki, Sara; Mohammadifar, Mohammad-Amir; Pourgholi, Leila; Mehdipour, Mohammad; Etminan, Abbas; Ebadzadeh, Mohammad-Reza; Fazeli, Faramarz; Azmandian, Jalal

    2015-01-01

    Production of reactive oxygen species (ROS) and thereby induction of oxidative stress seem to be one of the major mediators of inflammatory adverse outcomes after renal transplantation. p22(phox) is a polymorphic subunit of NAD(P)H-oxidase that is critical for activation and stabilization of the enzyme. This enzyme is involved in the production of superoxide that triggers inflammatory injuries to the kidney. So in this study, the association between donors and recipients' C242T polymorphism of p22(phox) and acute rejection (AR), delayed graft function (DGF), creatinine clearance (CrCl), and blood pressure in renal-allograft recipients was studied. One hundred ninety six donor-recipient pairs were studied. The C242T polymorphism of p22(phox) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to p22 genotype, the subjects were divided in wild-type (CC) and T allele carriers (CT+TT). Transplantation outcomes were determined using acute rejection and delayed graft function criteria. The mean arterial pressure was also measured monthly after transplantation. There was a significant association between the recipients' p22(phox) polymorphism and DGF occurrence (OR=2.5, CI: 1.2-4.9, p=0.0009). No significant association was detected between donors' p22(phox) polymorphism and AR and DGF events. CrCl during the six months follow-up after transplantation was lower in the patients who received allograft from donors carrying 242T allele (B=-12.8, CI: -22.9-12.8 (-22.9 to -2.6)). Changes in the blood pressure were not different among the patients having different genotypes of p22(phox). These results suggest that the recipients' p22(phox) C242T polymorphism may be a major risk factor for DGF in renal transplantation. Moreover, the donors' 242T allele seems to affect the rate of CrCl in the renal allograft recipients. Copyright © 2014. Published by Elsevier B.V.

  10. NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

    Directory of Open Access Journals (Sweden)

    Jaroslav Padevět

    2016-06-01

    Full Text Available A synthesis of new NeoPHOX ligands derived from serine or threonine has been developed. The central intermediate is a NeoPHOX derivative bearing a methoxycarbonyl group at the stereogenic center next to the oxazoline N atom. The addition of methylmagnesium chloride leads to a tertiary alcohol, which can be acylated or silylated to produce NeoPHOX ligands with different sterical demand. The new NeoPHOX ligands were tested in the iridium-catalyzed asymmetric hydrogenation and palladium-catalyzed allylic substitution. In both reactions high enantioselectivities were achieved, that were comparable to the enantioselectivities obtained with the up to now best NeoPHOX ligand derived from expensive tert-leucine.

  11. The C242T polymorphism of the p22-phox gene (CYBA is associated with higher left ventricular mass in Brazilian hypertensive patients

    Directory of Open Access Journals (Sweden)

    Krieger José E

    2011-08-01

    Full Text Available Abstract Background Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA on left ventricular structure in Brazilian hypertensive subjects. Methods We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441 and Vitória (n = 120] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample. Results Genotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height2.7 than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m2.7; p = 0.009, and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m2.7; p = 0.023 samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03. Conclusions The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height2.7 and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.

  12. Utility of Phox2b immunohistochemical stain in neural crest tumours and non-neural crest tumours in paediatric patients.

    Science.gov (United States)

    Warren, Mikako; Matsuno, Ryosuke; Tran, Henry; Shimada, Hiroyuki

    2018-03-01

    This study evaluated the utility of Phox2b in paediatric tumours. Previously, tyrosine hydroxylase (TH) was the most widely utilised sympathoadrenal marker specific for neural crest tumours with neuronal/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity. Phox2b immunohistochemistry (IHC) was performed on 159 paediatric tumours, including (group 1) 65 neural crest tumours with neuronal differentiation [peripheral neuroblastic tumours (pNT)]: 15 neuroblastoma undifferentiated (NB-UD), 10 NB poorly differentiated (NB-PD), 10 NB differentiating (NB-D), 10 ganglioneuroblastoma intermixed (GNBi), 10 GNB nodular (GNBn) and 10 ganglioneuroma (GN); (group 2) 23 neural crest tumours with neuroendocrine differentiation [pheochromocytoma/paraganglioma (PCC/PG)]; (group 3) 27 other neural crest tumours including one composite rhabdomyosarcoma/neuroblastoma; and (group 4) 44 non-neural crest tumours. TH IHC was performed on groups 1, 2 and 3. Phox2b was expressed diffusely in pNT (n = 65 of 65), strongly in NB-UD and NB-PD and with less intensity in NB-D, GNB and GN. Diffuse TH was seen in all NB-PD, NB-D, GNB and GN, but nine of 15 NB-UD and a nodule in GNBn did not express TH (n = 55 of 65). PCC/PG expressed diffuse Phox2b (n = 23 of 23) and diffuse TH, except for one tumour (n = 22 of 23). In composite rhabdomyosarcoma, TH was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumours were negative for Phox2b (n = none of 44). Phox2b was a specific and sensitive marker for pNT and PCC/PG, especially useful for identifying NB-UD often lacking TH. Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural crest origin. © 2017 John Wiley & Sons Ltd.

  13. Association between NADPH oxidase p22(phox C242T polymorphism and ischemic cerebrovascular disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Bing-Hu Li

    Full Text Available BACKGROUND: Epidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH oxidase p22(phox C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD, but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies. METHODOLOGY/PRINCIPAL FINDINGS: Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7 and Stata (Version 11.0. The pooled odds ratios (ORs with 95% confidence intervals (95%CIs were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22(phox C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93-1.26; additive model: OR = 1.33, 95%CI = 0.81-2.17; dominant model: OR = 1.00, 95%CI = 0.86-1.15; recessive model: OR = 1.06, 95%CI = 0.77-1.45. Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88-1.41; additive model: OR = 1.36, 95%CI = 0.60-3.09; dominant model: OR = 1.25, 95%CI = 0.74-2.11; recessive model: OR = 2.17, 95%CI = 1.11-4.23. No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup were all lower than 80%. CONCLUSIONS/SIGNIFICANCE: This meta-analysis indicates that NADPH oxidase p22(phox C242T polymorphism is more associated

  14. A Phox2b BAC Transgenic Rat Line Useful for Understanding Respiratory Rhythm Generator Neural Circuitry.

    Directory of Open Access Journals (Sweden)

    Keiko Ikeda

    Full Text Available The key role of the respiratory neural center is respiratory rhythm generation to maintain homeostasis through the control of arterial blood pCO2/pH and pO2 levels. The neuronal network responsible for respiratory rhythm generation in neonatal rat resides in the ventral side of the medulla and is composed of two groups; the parafacial respiratory group (pFRG and the pre-Bötzinger complex group (preBötC. The pFRG partially overlaps in the retrotrapezoid nucleus (RTN, which was originally identified in adult cats and rats. Part of the pre-inspiratory (Pre-I neurons in the RTN/pFRG serves as central chemoreceptor neurons and the CO2 sensitive Pre-I neurons express homeobox gene Phox2b. Phox2b encodes a transcription factor and is essential for the development of the sensory-motor visceral circuits. Mutations in human PHOX2B cause congenital hypoventilation syndrome, which is characterized by blunted ventilatory response to hypercapnia. Here we describe the generation of a novel transgenic (Tg rat harboring fluorescently labeled Pre-I neurons in the RTN/pFRG. In addition, the Tg rat showed fluorescent signals in autonomic enteric neurons and carotid bodies. Because the Tg rat expresses inducible Cre recombinase in PHOX2B-positive cells during development, it is a potentially powerful tool for dissecting the entire picture of the respiratory neural network during development and for identifying the CO2/O2 sensor molecules in the adult central and peripheral nervous systems.

  15. C242T Polymorphism in CYBA Gene (p22phox and Risk of Coronary Artery Disease in a Population of Caucasian Italians

    Directory of Open Access Journals (Sweden)

    Sabina Nasti

    2006-01-01

    Full Text Available Background: specific polymorphisms of genes regulating intracellular redox balance and oxidative stress are related to atherogenesis. Some studies have identified a relationship between progression of atherosclerosis and C242T mutation in CYBA gene coding for p22phox, a subunit of the NADH/NADPH oxidase system.

  16. PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours.

    Science.gov (United States)

    Hung, Yin P; Lee, John P; Bellizzi, Andrew M; Hornick, Jason L

    2017-11-01

    Neuroblastoma shows considerable histological overlap with other small round blue cell tumours. PHOX2B, a transcription factor that is essential for autonomic nervous system development, has been reported as an immunohistochemical marker for neuroblastoma. The aim of this study was to validate the specificity and diagnostic utility of PHOX2B for peripheral neuroblastic tumours. We evaluated 240 cases (133 in whole-tissue sections; 107 in tissue microarrays), including 76 peripheral neuroblastic tumours (median age 2 years; including four adults) and 164 other tumours: 44 Wilms tumours; 20 Ewing sarcomas; 10 each of CIC-rearranged round cell sarcomas, poorly differentiated synovial sarcomas, lymphoblastic lymphomas, alveolar rhabdomyosarcomas, embryonal rhabdomyosarcomas, mesenchymal chondrosarcomas, Merkel cell carcinomas, olfactory neuroblastomas, and melanomas; and five each of NUT midline carcinomas and desmoplastic small round cell tumours. Immunohistochemistry for PHOX2B was performed with a rabbit monoclonal antibody. PHOX2B positivity was defined as the presence of nuclear immunoreactivity in ≥5% of cells. PHOX2B was positive in 70 (92%) peripheral neuroblastic tumours, including 68 of 72 (94%) paediatric and two of four (50%) adult cases. Furthermore, PHOX2B was consistently negative in all non-peripheral neuroblastic tumours, with staining being absent in 160 cases and limited in four cases. PHOX2B is a highly sensitive and specific immunohistochemical marker for peripheral neuroblastic tumours, including neuroblastoma. PHOX2B reliably distinguishes neuroblastoma from histological mimics such as Wilms tumour, Ewing sarcoma, and CIC-rearranged round cell sarcoma. PHOX2B negativity in two of four adult neuroblastoma cases raises the possibility that some adult neuroblastomas are of a different lineage than paediatric cases. © 2017 John Wiley & Sons Ltd.

  17. Substance P enhances tissue factor release from granulocyte-macrophage colony-stimulating factor-dependent macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway.

    Science.gov (United States)

    Yamaguchi, Rui; Yamamoto, Takatoshi; Sakamoto, Arisa; Ishimaru, Yasuji; Narahara, Shinji; Sugiuchi, Hiroyuki; Yamaguchi, Yasuo

    2016-03-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF-dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole-cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, β-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/β-arrestin 2/Rho A signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Impaired ventilatory and thermoregulatory responses to hypoxic stress in newborn Phox2b heterozygous knockout mice

    Directory of Open Access Journals (Sweden)

    Nelina eRamanantsoa

    2011-09-01

    Full Text Available The Phox2b gene is necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b+/- pups and their wild-type littermates (Phox2b+/+ to hypoxia (10% O2 or hypercapnia (8% CO2 under thermoneutral (33°C or cold (26°C conditions. We found that Phox2b+/- pups showed less normoxic ventilation (VE in the cold than Phox2b+/+ pups. Phox2b+/- pups also showed lower oxygen consumption (VO2 in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b+/- pups. Finally, because serotonin (5-HT neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high-pressure liquid chromatography, and found that it was altered in Phox2b+/- pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments.

  19. Clinical, functional, and genetic characterization of chronic granulomatous disease in 89 Turkish patients

    NARCIS (Netherlands)

    Köker, Mustafa Yavuz; Camcıoğlu, Yıldız; van Leeuwen, Karin; Kılıç, Sara Şebnem; Barlan, Işıl; Yılmaz, Mustafa; Metin, Ayşe; de Boer, Martin; Avcılar, Hüseyin; Patıroğlu, Türkan; Yıldıran, Alişan; Yeğin, Olcay; Tezcan, Ilhan; Sanal, Ozden; Roos, Dirk

    2013-01-01

    Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes resulting in impaired killing of bacteria and fungi. A mutation in one of the 4 genes encoding the components p22(phox), p47(phox), p67(phox), and p40(phox) of the leukocyte nicotinamide dinucleotide

  20. Distinctive features of Phox2b-expressing neurons in the rat reticular formation dorsal to the trigeminal motor nucleus.

    Science.gov (United States)

    Nagoya, Kouta; Nakamura, Shiro; Ikeda, Keiko; Onimaru, Hiroshi; Yoshida, Atsushi; Nakayama, Kiyomi; Mochizuki, Ayako; Kiyomoto, Masaaki; Sato, Fumihiko; Kawakami, Kiyoshi; Takahashi, Koji; Inoue, Tomio

    2017-09-01

    Phox2b encodes a paired-like homeodomain-containing transcription factor essential for development of the autonomic nervous system. Phox2b-expressing (Phox2b + ) neurons are present in the reticular formation dorsal to the trigeminal motor nucleus (RdV) as well as the nucleus of the solitary tract and parafacial respiratory group. However, the nature of Phox2b + RdV neurons is still unclear. We investigated the physiological and morphological properties of Phox2b + RdV neurons using postnatal day 2-7 transgenic rats expressing yellow fluorescent protein under the control of Phox2b. Almost all of Phox2b + RdV neurons were glutamatergic, whereas Phox2b-negative (Phox2b - ) RdV neurons consisted of a few glutamatergic, many GABAergic, and many glycinergic neurons. The majority (48/56) of Phox2b + neurons showed low-frequency firing (LF), while most of Phox2b - neurons (35/42) exhibited high-frequency firing (HF) in response to intracellularly injected currents. All, but one, Phox2b + neurons (55/56) did not fire spontaneously, whereas three-fourths of the Phox2b - neurons (31/42) were spontaneously active. K + channel and persistent Na + current blockers affected the firing of LF and HF neurons. The majority of Phox2b + (35/46) and half of the Phox2b - neurons (19/40) did not respond to stimulations of the mesencephalic trigeminal nucleus, the trigeminal tract, and the principal sensory trigeminal nucleus. Biocytin labeling revealed that about half of the Phox2b + (5/12) and Phox2b - RdV neurons (5/10) send their axons to the trigeminal motor nucleus. These results suggest that Phox2b + RdV neurons have distinct neurotransmitter phenotypes and firing properties from Phox2b - RdV neurons and might play important roles in feeding-related functions including suckling and possibly mastication. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Impaired Ventilatory and Thermoregulatory Responses to Hypoxic Stress in Newborn Phox2b Heterozygous Knock-Out Mice

    Science.gov (United States)

    Ramanantsoa, Nelina; Matrot, Boris; Vardon, Guy; Lajard, Anne-Marie; Voituron, Nicolas; Dauger, Stéphane; Denjean, André; Hilaire, Gérard; Gallego, Jorge

    2011-01-01

    The Phox2b genesis necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b+/− pups and their wild-type littermates (Phox2b+/+) to hypoxia (10% O2) or hypercapnia (8% CO2) under thermoneutral (33°C) or cold (26°C) conditions. We found that Phox2b+/− pups showed less normoxic ventilation (VE) in the cold than Phox2b+/+ pups. Phox2b+/− pups also showed lower oxygen consumption (VO2) in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b+/− pups. Finally, because serotonin (5-HT) neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high pressure liquid chromatography, and found that it was altered in Phox2b+/− pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments. PMID:21977017

  2. Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression.

    Science.gov (United States)

    McKallip, Robert J; Jia, Wentao; Schlomer, Jerome; Warren, James W; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2006-09-01

    In the current study, we examined the effects of the nonpsychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of leukemia cells to cannabidiol led to cannabinoid receptor 2 (CB2)-mediated reduction in cell viability and induction in apoptosis. Furthermore, cannabidiol treatment led to a significant decrease in tumor burden and an increase in apoptotic tumors in vivo. From a mechanistic standpoint, cannabidiol exposure resulted in activation of caspase-8, caspase-9, and caspase-3, cleavage of poly(ADP-ribose) polymerase, and a decrease in full-length Bid, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome c. It is noteworthy that cannabidiol exposure led to an increase in reactive oxygen species (ROS) production as well as an increase in the expression of the NAD(P)H oxidases Nox4 and p22(phox). Furthermore, cannabidiol-induced apoptosis and reactive oxygen species (ROS) levels could be blocked by treatment with the ROS scavengers or the NAD(P)H oxidase inhibitors. Finally, cannabidiol exposure led to a decrease in the levels of p-p38 mitogen-activated protein kinase, which could be blocked by treatment with a CB2-selective antagonist or ROS scavenger. Together, the results from this study reveal that cannabidiol, acting through CB2 and regulation of Nox4 and p22(phox) expression, may be a novel and highly selective treatment for leukemia.

  3. Prenatal Diagnosis of Chronic Granulomatous Disease in a Male Fetus

    NARCIS (Netherlands)

    Yavuz Köker, M.; Metin, Ayşe; Ozgür, Tuba T.; de Boer, Martin; Roos, Dirk

    2009-01-01

    Mutations in any of four known NADPH-oxidase components lead to CGD. X-linked CGD (X-CGD) is caused by defects in CYBB, the gene that encodes gp91-phox. Autosomal recessive (AR) CGD is caused by defects in the genes for p47 phox, p22-phox or p67-phox. The aim of this study was to screen the

  4. Impaired Ventilatory and Thermoregulatory Responses to Hypoxic Stress in Newborn Phox2b Heterozygous Knock-Out Mice

    OpenAIRE

    Ramanantsoa, Nelina; Matrot, Boris; Vardon, Guy; Lajard, Anne-Marie; Voituron, Nicolas; Dauger, Stéphane; Denjean, André; Hilaire, Gérard; Gallego, Jorge

    2011-01-01

    The Phox2b genesis necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b +/? pups and their wild-type littermates (Phox2b +/+) to...

  5. Expresión y actividad de posibles polimorfismos provenientes de individuos normales en la proteína de 67 kd del sistema NADPH oxidasa utilizando el sistema COSphox.

    Directory of Open Access Journals (Sweden)

    Andrés Augusto Arias

    2004-09-01

    Full Text Available El sistema NADPH oxidasa de las células fagocíticas cumple una función importante durante la respuesta antimicrobiana del organismo. La activación de este sistema está precedida por la translocación de las proteínas citosólicas p67phox, p47phox y p40phox hacia la membrana para ponerse en contacto con el flavocitocromo b558, lo que induce la generación del anión superóxido, un precursor de agentes microbicidas oxidantes. El presente trabajo presenta un análisis funcional del sistema NADPH oxidasa basado en los hallazgos de polimorfismos encontrados en el gen de p67phox de individuos sanos. Para esto se generaron mutaciones en el cADN que codifica la p67phox y se expresaron en el sistema de células COSphox. Los datos obtenidos en el presente trabajo indican que los cambios Val166?Ile, Pro329?Ser y His389?Gln no generan alteraciones en el funcionamiento de la p67phox cuando su función se analizó en el sistema transgénico basado en células COS-7. Por lo tanto, estos polimorfismos no generan ningún riesgo genético de producir deficiencias en la activación del sistema NADPH oxidasa. Además, se demuestra que el modelo de células COSphox representa un nuevo sistema celular, fácilmente transfectable que permite estudiar la función del sistema NADPH oxidasa de las células fagocíticas y sus particularidades genéticas. Finalmente, los hallazgos con estos polimorfismos nos permiten avanzar en el conocimiento sobre los mecanismos moleculares involucrados en la activación del sistema NADPH oxidasa células fagocíticas.

  6. Análisis de la localización, dinámica intracelular y producción de 02 - por el sistema NADPH oxidasa de las células fagocíticas

    Directory of Open Access Journals (Sweden)

    Pablo Patiño

    2001-04-01

    Full Text Available <p>El sistema NADPH oxidasa, un sistema encargado de producir
    anión superóxido (O2 - en las células fagocíticas, está formado por las proteínas: gp91 phox, p22 phox, p47 phox, p67 phox, p40 phox y la proteína Rac. Las células COS-7, una línea celular de riñón de simio, que expresa endógenamente Rac1, y que por transfección estable expresan gp91 phox, p47 phox y p22 phox, pueden ser cotransfectadas adicionalmente con vectores episomales pGFP-N3, pEGFP-C1 y pCDNA3.1zeo(+ que contengan el cDNA tipo silvestre y mutante de la proteína p67 phox obtenidos por mutagénesis sitio-dirigida. Estos vectores contienen el gen de la proteína verde fluorescente (GFP, útil para explorar la localización intracelular y la dinámica de los componentes del sistema oxidasa. Después de la cotransfección, se estimulan las células con PMA y se determina la producción de O2
    - y la señal de fluorescencia generada por GFP de forma directa en células vivas por microscopía confocal.p>

     

     >

  7. Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22phox expression

    International Nuclear Information System (INIS)

    Wang, Chaoyun; He, Yanhao; Yang, Ming; Sun, Hongliu; Zhang, Shuping; Wang, Chunhua

    2013-01-01

    Intracellular reactive oxygen species (ROS) are derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Angiotensin II (Ang II) can cause endothelial dysfunction by promoting intracellular ROS generation. Safflor yellow B (SYB) effectively inhibits ROS generation by upregulating Bcl-2 expression. In this study, we examined the effects of SYB on Ang II-induced injury to human umbilical vein endothelial cells (HUVECs), and elucidated the roles of NADPH oxidase and Bcl-2. We treated cultured HUVECs with Ang II, SYB, and Bcl-2 siRNA, and determined NADPH oxidase activity and ROS levels. Furthermore, cellular and mitochondrial physiological states were evaluated, and the expression levels of target proteins were analyzed. Ang II significantly enhanced intracellular ROS levels, caused mitochondrial membrane dysfunction, and decreased cell viability, leading to apoptosis. This was associated with increased expression of AT1R and p22 phox , increased NADPH oxidase activity, and an increased ratio of Bax/Bcl-2, leading to decreases in antioxidant enzyme activities, which were further strengthened after blocking Bcl-2. Compared to Ang II treatment alone, co-treatment with SYB significantly reversed HUVEC injury. Taken together, these results demonstrate that SYB could significantly protect endothelial cells from Ang II-induced cell damage, and that it does so by upregulating Bcl-2 expression and inhibiting ROS generation. - Highlights: • Angiotensin II depresses mitochondria physiological function. • Angiotensin II activates NADPH oxidase via up-regulating expresion of p22 phox . • Bcl-2 plays a pivotal role in improving mitochondria function and regulates ROS level. • Inhibitor of Bcl-2 promotes angiotensin II mediated HUVEC injury. • SYB attenuates angiotensin II mediated HUVEC injury via up regulating Bcl-2 expression

  8. Long-Term Effects of Maternal Deprivation on Redox Regulation in Rat Brain: Involvement of NADPH Oxidase

    Directory of Open Access Journals (Sweden)

    Branka Marković

    2017-01-01

    Full Text Available Maternal deprivation (MD causes perinatal stress, with subsequent behavioral changes which resemble the symptoms of schizophrenia. The NADPH oxidase is one of the major generators of reactive oxygen species, known to play a role in stress response in different tissues. The aim of this study was to elucidate the long-term effects of MD on the expression of NADPH oxidase subunits (gp91phox, p22phox, p67phox, p47phox, and p40phox. Activities of cytochrome C oxidase and respiratory chain Complex I, as well as the oxidative stress parameters using appropriate spectrophotometric techniques were analyzed. Nine-day-old Wistar rats were exposed to a 24 h maternal deprivation and sacrificed at young adult age. The structures affected by perinatal stress, cortex, hippocampus, thalamus, and caudate nuclei were investigated. The most prominent findings were increased expressions of gp91phox in the cortex and hippocampus, increased expression of p22phox and p40phox, and decreased expression of gp91phox, p22phox, and p47phox in the caudate nuclei. Complex I activity was increased in all structures except cortex. Content of reduced glutathione was decreased in all sections while region-specific changes of other oxidative stress parameters were found. Our results indicate the presence of long-term redox alterations in MD rats.

  9. Structural features of PhoX, one of the phosphate-binding proteins from Pho regulon of Xanthomonas citri

    Science.gov (United States)

    Pegos, Vanessa R.; Santos, Rodrigo M. L.; Medrano, Francisco J.

    2017-01-01

    In Escherichia coli, the ATP-Binding Cassette transporter for phosphate is encoded by the pstSCAB operon. PstS is the periplasmic component responsible for affinity and specificity of the system and has also been related to a regulatory role and chemotaxis during depletion of phosphate. Xanthomonas citri has two phosphate-binding proteins: PstS and PhoX, which are differentially expressed under phosphate limitation. In this work, we focused on PhoX characterization and comparison with PstS. The PhoX three-dimensional structure was solved in a closed conformation with a phosphate engulfed in the binding site pocket between two domains. Comparison between PhoX and PstS revealed that they originated from gene duplication, but despite their similarities they show significant differences in the region that interacts with the permeases. PMID:28542513

  10. Smooth Muscle Specific Overexpression of p22phox Potentiates Carotid Artery Wall Thickening in Response to Injury

    Directory of Open Access Journals (Sweden)

    Michael R. Manogue

    2015-01-01

    Full Text Available We hypothesized that transgenic mice overexpressing the p22phox subunit of the NADPH oxidase selectively in smooth muscle (Tgp22smc would exhibit an exacerbated response to transluminal carotid injury compared to wild-type mice. To examine the role of reactive oxygen species (ROS as a mediator of vascular injury, the injury response was quantified by measuring wall thickness (WT and cross-sectional wall area (CSWA of the injured and noninjured arteries in both Tgp22smc and wild-type animals at days 3, 7, and 14 after injury. Akt, p38 MAPK, and Src activation were evaluated at the same time points using Western blotting. WT and CSWA following injury were significantly greater in Tgp22smc mice at both 7 and 14 days after injury while noninjured contralateral carotids were similar between groups. Apocynin treatment attenuated the injury response in both groups and rendered the response similar between Tgp22smc mice and wild-type mice. Following injury, carotid arteries from Tgp22smc mice demonstrated elevated activation of Akt at day 3, while p38 MAPK and Src activation was elevated at day 7 compared to wild-type mice. Both increased activation and temporal regulation of these signaling pathways may contribute to enhanced vascular growth in response to injury in this transgenic model of elevated vascular ROS.

  11. Libyan Boy with Autosomal Recessive Trait (P22-phox Defect of Chronic Granulomatous Disease

    Directory of Open Access Journals (Sweden)

    Ilka Schulze

    2006-09-01

    Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency disorder of the phagocytes. In this disorder, phagocytic cells (polymorphonuclear leukocytes and monocytes cannot produce active oxygen metabolites, and therefore, cannot destroy the ingested intracellular bacteria. Clinically, patients with CGD usually have recurrent bacterial and fungal infections causing abscess and granuloma formation in the skin, lymph nodes and visceral organs.In this report, we present a boy from Libya with a rare autosomal recessive trait of CGD (defect of p22-phox who has chronic lung disease following multiple severe pneumonia attacks. The case we present suffered from bloody diarrhea since the third month of his life. He also had recurrent episodes of fever, and later, developed persistent cervical lymphadenitis and failure to gain weight. CGD is a very rare condition worldwide. It is also not recognized here in Libya, and usually not in the list of differential diagnosis for chronic pulmonary infections. We advise that pediatricians and general practitioners who treat chronic cases of lung diseases (with or without chronic diarrhea should consider primary immunodeficiency disorders in the hope that early diagnosis and treatment may prevent chronic complications especially of the respiratory tract. Furthermore, we state that, to the best of our knowledge, this is the first documented case of CGD from Libya.

  12. Learning Photogrammetry with Interactive Software Tool PhoX

    Directory of Open Access Journals (Sweden)

    T. Luhmann

    2016-06-01

    Full Text Available Photogrammetry is a complex topic in high-level university teaching, especially in the fields of geodesy, geoinformatics and metrology where high quality results are demanded. In addition, more and more black-box solutions for 3D image processing and point cloud generation are available that generate nice results easily, e.g. by structure-from-motion approaches. Within this context, the classical approach of teaching photogrammetry (e.g. focusing on aerial stereophotogrammetry has to be reformed in order to educate students and professionals with new topics and provide them with more information behind the scene. Since around 20 years photogrammetry courses at the Jade University of Applied Sciences in Oldenburg, Germany, include the use of digital photogrammetry software that provide individual exercises, deep analysis of calculation results and a wide range of visualization tools for almost all standard tasks in photogrammetry. During the last years the software package PhoX has been developed that is part of a new didactic concept in photogrammetry and related subjects. It also serves as analysis tool in recent research projects. PhoX consists of a project-oriented data structure for images, image data, measured points and features and 3D objects. It allows for almost all basic photogrammetric measurement tools, image processing, calculation methods, graphical analysis functions, simulations and much more. Students use the program in order to conduct predefined exercises where they have the opportunity to analyse results in a high level of detail. This includes the analysis of statistical quality parameters but also the meaning of transformation parameters, rotation matrices, calibration and orientation data. As one specific advantage, PhoX allows for the interactive modification of single parameters and the direct view of the resulting effect in image or object space.

  13. Learning Photogrammetry with Interactive Software Tool PhoX

    Science.gov (United States)

    Luhmann, T.

    2016-06-01

    Photogrammetry is a complex topic in high-level university teaching, especially in the fields of geodesy, geoinformatics and metrology where high quality results are demanded. In addition, more and more black-box solutions for 3D image processing and point cloud generation are available that generate nice results easily, e.g. by structure-from-motion approaches. Within this context, the classical approach of teaching photogrammetry (e.g. focusing on aerial stereophotogrammetry) has to be reformed in order to educate students and professionals with new topics and provide them with more information behind the scene. Since around 20 years photogrammetry courses at the Jade University of Applied Sciences in Oldenburg, Germany, include the use of digital photogrammetry software that provide individual exercises, deep analysis of calculation results and a wide range of visualization tools for almost all standard tasks in photogrammetry. During the last years the software package PhoX has been developed that is part of a new didactic concept in photogrammetry and related subjects. It also serves as analysis tool in recent research projects. PhoX consists of a project-oriented data structure for images, image data, measured points and features and 3D objects. It allows for almost all basic photogrammetric measurement tools, image processing, calculation methods, graphical analysis functions, simulations and much more. Students use the program in order to conduct predefined exercises where they have the opportunity to analyse results in a high level of detail. This includes the analysis of statistical quality parameters but also the meaning of transformation parameters, rotation matrices, calibration and orientation data. As one specific advantage, PhoX allows for the interactive modification of single parameters and the direct view of the resulting effect in image or object space.

  14. Organizers and activators: Cytosolic Nox proteins impacting on vascular function.

    Science.gov (United States)

    Schröder, Katrin; Weissmann, Norbert; Brandes, Ralf P

    2017-08-01

    NADPH oxidases of the Nox family are important enzymatic sources of reactive oxygen species (ROS) in the cardiovascular system. Of the 7 members of the Nox family, at least three depend for their activation on specific cytosolic proteins. These are p47phox and its homologue NoxO1 and p67phox and its homologue NoxA1. Also the Rho-GTPase Rac is important but as this protein has many additional functions, it will not be covered here. The Nox1 enzyme is preferentially activated by the combination of NoxO1 with NoxA1, whereas Nox2 gains highest activity with p47phox together with p67phox. As p47phox, different to NoxO1 contains an auto inhibitory region it has to be phosphorylated prior to complex formation. In the cardio-vascular system, all cytosolic Nox proteins are expressed but the evidence for their contribution to ROS production is not well established. Most data have been collected for p47phox, whereas NoxA1 has basically not yet been studied. In this article the specific aspects of cytosolic Nox proteins in the cardiovascular system with respect to Nox activation, their expression and their importance will be reviewed. Finally, it will be discussed whether cytosolic Nox proteins are suitable pharmacological targets to tamper with vascular ROS production. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Tiziana Bachetti

    Full Text Available BACKGROUND: Neuroblastoma (NB is a severe pediatric tumor originating from neural crest derivatives and accounting for 15% of childhood cancer mortality. The heterogeneous and complex genetic etiology has been confirmed with the identification of mutations in two genes, encoding for the receptor tyrosine kinase Anaplastic Lymphoma Kinase (ALK and the transcription factor Paired-like Homeobox 2B (PHOX2B, in a limited proportion of NB patients. Interestingly, these two genes are overexpressed in the great majority of primary NB samples and cell lines. These observations led us to test the hypothesis of a regulatory or functional relationship between ALK and PHOX2B underlying NB pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Following this possibility, we first confirmed a striking correlation between the transcription levels of ALK, PHOX2B and its direct target PHOX2A in a panel of NB cell lines. Then, we manipulated their expression in NB cell lines by siRNA-mediated knock-down and forced over-expression of each gene under analysis. Surprisingly, PHOX2B- and PHOX2A-directed siRNAs efficiently downregulated each other as well as ALK gene and, consistently, the enhanced expression of PHOX2B in NB cells yielded an increment of ALK protein. We finally demonstrated that PHOX2B drives ALK gene transcription by directly binding its promoter, which therefore represents a novel PHOX2B target. CONCLUSIONS/SIGNIFICANCE: These findings provide a compelling explanation of the concurrent involvement of these two genes in NB pathogenesis and are going to foster a better understanding of molecular interactions at the base of the disease. Moreover, this work opens new perspectives for NBs refractory to conventional therapies that may benefit from the design of novel therapeutic RNAi-based approaches for multiple gene targets.

  16. Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome.

    Science.gov (United States)

    Amiel, Jeanne; Laudier, Béatrice; Attié-Bitach, Tania; Trang, Ha; de Pontual, Loïc; Gener, Blanca; Trochet, Delphine; Etchevers, Heather; Ray, Pierre; Simonneau, Michel; Vekemans, Michel; Munnich, Arnold; Gaultier, Claude; Lyonnet, Stanislas

    2003-04-01

    Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a life-threatening disorder involving an impaired ventilatory response to hypercarbia and hypoxemia. This core phenotype is associated with lower-penetrance anomalies of the autonomic nervous system (ANS) including Hirschsprung disease and tumors of neural-crest derivatives such as ganglioneuromas and neuroblastomas. In mice, the development of ANS reflex circuits is dependent on the paired-like homeobox gene Phox2b. Thus, we regarded its human ortholog, PHOX2B, as a candidate gene in CCHS. We found heterozygous de novo mutations in PHOX2B in 18 of 29 individuals with CCHS. Most mutations consisted of 5-9 alanine expansions within a 20-residue polyalanine tract probably resulting from non-homologous recombination. We show that PHOX2B is expressed in both the central and the peripheral ANS during human embryonic development. Our data support an essential role of PHOX2B in the normal patterning of the autonomous ventilation system and, more generally, of the ANS in humans.

  17. Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl bromides with secondary phosphine oxides

    KAUST Repository

    McDougal, Nolan T.

    2010-10-01

    Herein an efficient and direct copper-catalyzed coupling of oxazoline-containing aryl bromides with electron-deficient secondary phosphine oxides is reported. The resulting tertiary phosphine oxides can be reduced to prepare a range of PHOX ligands. The presented strategy is a useful alternative to known methods for constructing PHOX derivatives.

  18. Rapid synthesis of an electron-deficient t-BuPHOX ligand: cross-coupling of aryl bromides with secondary phosphine oxides

    KAUST Repository

    McDougal, Nolan T.; Streuff, Jan; Mukherjee, Herschel; Virgil, Scott C.; Stoltz, Brian M.

    2010-01-01

    Herein an efficient and direct copper-catalyzed coupling of oxazoline-containing aryl bromides with electron-deficient secondary phosphine oxides is reported. The resulting tertiary phosphine oxides can be reduced to prepare a range of PHOX ligands. The presented strategy is a useful alternative to known methods for constructing PHOX derivatives.

  19. The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO2

    DEFF Research Database (Denmark)

    Ruffault, Pierre Louis; D’Autréaux, Fabien; Hayes, John A.

    2015-01-01

    . Photostimulation of these neurons entrains the respiratory rhythm. Conversely, abrogating expression of Atoh1 or Phox2b or glutamatergic transmission in these cells curtails the phrenic nerve response to low pH in embryonic preparations and abolishes the respiratory chemoreflex in behaving animals. Thus, the RTN...

  20. [The X+ chronic granulomatous disease as a fabulous model to study the NADPH oxidase complex activation].

    Science.gov (United States)

    Stasia, Marie-José

    2007-05-01

    Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack NADPH oxidase activity. Patients with CGD suffer from recurrent bacterial and fungal infections because of the absence of superoxide anions (O2- degrees ) generatingsystem. The NADPH oxidase complex is composed of a membranous cytochrome b558, cytosolic proteins p67phox, p47phox, p40phox and two small GTPases Rac2 and Rap1A. Cytochrome b558 consists of two sub-units gp91phox and p22phox. The most common form of CGD is due to mutations in CYBB gene encoding gp91phox. In some rare cases, the mutated gp91phox is normally expressed but is devoided of oxidase activity. These variants called X+ CGD, have provided interesting informations about oxidase activation mechanisms. However modelization of such variants is necessary to obtain enough biological material for studies at the molecular level. A cellular model (knock-out PLB-985 cells) has been developed for expressing recombinant mutated gp91phox for functional analysis of the oxidase complex. Recent works demonstrated that this cell line genetically deficient in gp91phox is a powerful tool for functional analysis of the NADPH oxidase complex activation.

  1. Khz-cp (crude polysaccharide extract obtained from the fusion of Ganoderma lucidum and Polyporus umbellatus mycelia) induces apoptosis by increasing intracellular calcium levels and activating P38 and NADPH oxidase-dependent generation of reactive oxygen species in SNU-1 cells.

    Science.gov (United States)

    Kim, Tae Hwan; Kim, Ju Sung; Kim, Zoo Haye; Huang, Ren Bin; Chae, Young Lye; Wang, Ren Sheng

    2014-07-10

    Khz-cp is a crude polysaccharide extract that is obtained after nuclear fusion in Ganoderma lucidum and Polyporus umbellatus mycelia (Khz). It inhibits the growth of cancer cells. Khz-cp was extracted by solvent extraction. The anti-proliferative activity of Khz-cp was confirmed by using Annexin-V/PI-flow cytometry analysis. Intracellular calcium increase and measurement of intracellular reactive oxygen species (ROS) were performed by using flow cytometry and inverted microscope. SNU-1 cells were treated with p38, Bcl-2 and Nox family siRNA. siRNA transfected cells was employed to investigate the expression of apoptotic, growth and survival genes in SNU-1 cells. Western blot analysis was performed to confirm the expression of the genes. In the present study, Khz-cp induced apoptosis preferentially in transformed cells and had only minimal effects on non-transformed cells. Furthermore, Khz-cp was found to induce apoptosis by increasing the intracellular Ca2+ concentration ([Ca2+]i) and activating P38 to generate reactive oxygen species (ROS) via NADPH oxidase and the mitochondria. Khz-cp-induced apoptosis was caspase dependent and occurred via a mitochondrial pathway. ROS generation by NADPH oxidase was critical for Khz-cp-induced apoptosis, and although mitochondrial ROS production was also required, it appeared to occur secondary to ROS generation by NADPH oxidase. Activation of NADPH oxidase was shown by the translocation of the regulatory subunits p47phox and p67phox to the cell membrane and was necessary for ROS generation by Khz-cp. Khz-cp triggered a rapid and sustained increase in [Ca2+]i that activated P38. P38 was considered to play a key role in the activation of NADPH oxidase because inhibition of its expression or activity abrogated membrane translocation of the p47phox and p67phox subunits and ROS generation. In summary, these data indicate that Khz-cp preferentially induces apoptosis in cancer cells and that the signaling mechanisms involve an

  2. Dynamics of phosphorus and bacterial phoX genes during the decomposition of Microcystis blooms in a mesocosm.

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    Jiangyu Dai

    Full Text Available Cyanobacterial blooms are a worldwide environmental problem and frequently occur in eutrophic lakes. Organophosphorus mineralization regulated by microbial alkaline phosphatase provides available nutrients for bloom regeneration. To uncover the dynamics of bacterial alkaline phosphatase activity and microbial backgrounds in relation to organophosphorus mineralization during the decomposition process of cyanobacterial blooms, the response of alkaline phosphatase PhoX-producing bacteria were explored using a 23-day mesocosm experiment with three varying densities of Microcystis biomass from eutrophic Lake Taihu. Our study found large amounts of soluble reactive phosphorus and dissolved organophosphorus were released into the lake water during the decomposition process. Bacterial alkaline phosphatase activity showed the peak values during days 5~7 in groups with different chlorophyll-a densities, and then all decreased dramatically to their initial experimental levels during the last stage of decomposition. Bacterial phoX abundances in the three experimental groups increased significantly along with the decomposition process, positively related to the dissolved organic carbon and organophosphorus released by the Microcystis blooms. The genotypes similar to the phoX genes of Alphaproteobacteria were dominant in all groups, whereas the genotypes most similar to the phoX genes of Betaproteobacteria and Cyanobacteria were also abundant in the low density (~15 μg L-1 chlorophyll-a group. At the end of the decomposition process, the number of genotypes most similar to the phoX of Betaproteobacteria and Cyanobacteria increased in the medium (~150 μg L-1 chlorophyll-a and high (~1500 μg L-1 chlorophyll-a density groups. The released organophosphorus and increased bacterial phoX abundance after decomposition of Microcystis aggregates could potentially provide sufficient nutrients and biological conditions for algal proliferation and are probably related

  3. Association of genetic variants in the promoter region of genes encoding p22phox (CYBA and glutamate cysteine ligase catalytic subunit (GCLC and renal disease in patients with type 1 diabetes mellitus

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    Pavin Elizabeth J

    2011-09-01

    Full Text Available Abstract Background Oxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the CYBA gene. Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs in genes involved in the generation of NADPH-dependent O2•- (-675 T → A in CYBA, unregistered and in glutathione metabolism (-129 C → T in GCLC [rs17883901] and -65 T → C in GPX3 [rs8177412] confer susceptibility to renal disease in type 1 diabetes patients. Methods 401 patients were sorted into two groups according to the presence (n = 104 or absence (n = 196 of overt diabetic nephropathy or according to glomerular filtration rate (GFR estimated by Modification of Diet in Renal Disease (MDRD equation: ≥ 60 mL (n = 265 or 2 (n = 136 and were genotyped. Results No differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR CYBA genotypes T/A+A/A (18.7% than in the group carrying the T/T genotype (35.3% (P = 0.0143 and the frequency of GFR GCLC genotypes C/T+T/T (47.1% than in the group carrying the C/C genotype (31.1% (p = 0.0082. Logistic regression analysis identified the presence of at least one A allele of the CYBA SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, p = 0.0354 and the presence of at least one T allele of the GCLC rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, p = 0.0068. Conclusions The functional SNPs CYBA -675 T → A and

  4. Asymmetrical distribution of non-conserved regulatory sequences at PHOX2B is reflected at the ENCODE loci and illuminates a possible genome-wide trend

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    McCallion Andrew S

    2009-01-01

    Full Text Available Abstract Background Transcriptional regulatory elements are central to development and interspecific phenotypic variation. Current regulatory element prediction tools rely heavily upon conservation for prediction of putative elements. Recent in vitro observations from the ENCODE project combined with in vivo analyses at the zebrafish phox2b locus suggests that a significant fraction of regulatory elements may fall below commonly applied metrics of conservation. We propose to explore these observations in vivo at the human PHOX2B locus, and also evaluate the potential evidence for genome-wide applicability of these observations through a novel analysis of extant data. Results Transposon-based transgenic analysis utilizing a tiling path proximal to human PHOX2B in zebrafish recapitulates the observations at the zebrafish phox2b locus of both conserved and non-conserved regulatory elements. Analysis of human sequences conserved with previously identified zebrafish phox2b regulatory elements demonstrates that the orthologous sequences exhibit overlapping regulatory control. Additionally, analysis of non-conserved sequences scattered over 135 kb 5' to PHOX2B, provides evidence of non-conserved regulatory elements positively biased with close proximity to the gene. Furthermore, we provide a novel analysis of data from the ENCODE project, finding a non-uniform distribution of regulatory elements consistent with our in vivo observations at PHOX2B. These observations remain largely unchanged when one accounts for the sequence repeat content of the assayed intervals, when the intervals are sub-classified by biological role (developmental versus non-developmental, or by gene density (gene desert versus non-gene desert. Conclusion While regulatory elements frequently display evidence of evolutionary conservation, a fraction appears to be undetected by current metrics of conservation. In vivo observations at the PHOX2B locus, supported by our analyses of in

  5. The role of oxidative stress and NADPH oxidase in the pathogenesis of atherosclerosis

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    Dorota Bryk

    2017-01-01

    Full Text Available Reactive oxygen species (ROS play a key role in the pathogenesis of atherosclerosis. The main mechanisms which are involved are low-density lipoprotein oxidative modification, inactivation of nitric oxide and modulation of redox-sensitive signaling pathways. ROS contribute to several aspects of atherosclerosis including endothelial cell dysfunction, monocyte/macrophage recruitment and activation, stimulation of inflammation, and inducing smooth muscle cell migration and proliferation. NADPH oxidase is the main source of ROS in the vasculature. This enzyme consists of a membrane-bound heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox, p67phox and p40phox, and small GTP-binding proteins rac1 and rac 2. Seven distinct isoforms of this enzyme have been identified, of which four (NOX1, 2, 4 and 5 may have cardiovascular function. In this paper, we review the current state of knowledge concerning the role of oxidative stress and NOX enzymes in pathogenesis of atherosclerosis. Moreover, we analyze the experimental studies that explore the relationship between the NOX family and atherosclerosis.

  6. Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells

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    Lee I-Ta

    2012-11-01

    Full Text Available Abstract Background In bacteria-induced glomerulonephritis, Toll-like receptor 4 (TLR4 activation by lipopolysaccharide (LPS, a key component of the outer membranes of Gram-negative bacteria can increase oxidative stress and the expression of vascular cell adhesion molecule-1 (VCAM-1, which recruits leukocytes to the glomerular mesangium. However, the mechanisms underlying VCAM-1 expression induced by LPS are still unclear in human renal mesangial cells (HRMCs. Results We demonstrated that LPS induced VCAM-1 mRNA and protein levels associated with an increase in the promoter activity of VCAM-1, determined by Western blot, RT-PCR, and promoter assay. LPS-induced responses were inhibited by transfection with siRNAs of TLR4, myeloid differentiation factor 88 (MyD88, Nox2, Nox4, p47phox, c-Src, p38 MAPK, activating transcription factor 2 (ATF2, and p300 or pretreatment with the inhibitors of reactive oxygen species (ROS, edaravone, NADPH oxidase [apocynin (APO or diphenyleneiodonium chloride (DPI], c-Src (PP1, p38 MAPK (SB202190, and p300 (GR343. LPS induced NADPH oxidase activation, ROS production, and p47phox translocation from the cytosol to the membrane, which were reduced by PP1 or c-Src siRNA. We observed that LPS induced TLR4, MyD88, c-Src, and p47phox complex formation determined by co-immunoprecipitation and Western blot. We further demonstrated that LPS stimulated ATF2 and p300 phosphorylation and complex formation via a c-Src/NADPH oxidase/ROS/p38 MAPK pathway. Up-regulation of VCAM-1 led to enhancing monocyte adhesion to HRMCs challenged with LPS, which was inhibited by siRNAs of c-Src, p47phox, p38 MAPK, ATF2, and p300 or pretreatment with an anti-VCAM-1 neutralizing antibody. Conclusions In HRMCs, LPS-induced VCAM-1 expression was, at least in part, mediated through a TLR4/MyD88/ c-Src/NADPH oxidase/ROS/p38 MAPK-dependent p300 and ATF2 pathway associated with recruitment of monocyte adhesion to kidney. Blockade of these pathways may

  7. Enfermedad granulomatosa crónica: Aspectos actuales Chronic granulomatous disease: Current aspects

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    Yanelkys Cos Padrón

    2004-12-01

    Full Text Available La enfermedad granulomatosa crónica (EGC es una inmunodeficiencia primaria causada por mutaciones en los genes que codifican para cualquiera de las 4 subunidades que conforman a la enzima adenina dinucleótido fosfato oxidasa (NADPH oxidasa, encargada de regular la producción de especies oxidantes microbicidas que constituyen la primera vía de defensa del organismo contra los microorganismos infecciosos. Esta es una deficiencia muy heterogénea clasificada en EGC ligada al cromosoma X (subunidad gp91-phox y autosómica recesiva, donde puede estar afectada cualquiera de las siguientes subunidades de la enzima: p22-phox, p47-phox y p67-phox. Dentro de los hallazgos clínicos más frecuentes se encuentran entre otros la linfadenopatía, hepatoesplenomegalia, neumonía. Para el tratamiento de la enfermedad se utilizan antibióticos de amplio espectro y el interferón gamma para el tratamiento de infecciones severas en la EGC ligada al cromosoma X. Actualmente se están realizando estudios para utilizar la terapia génica somática como posible cura de la enfermedadChronic granulomatous disease is a primary immunodeficiency caused by mutations in genes encoding any of the 4 subunits that make up adenine dinucleotide phosphate oxidase (NADPH oxidase, the enzyme that regulates the production of microbial oxidizing species that are the first defensive pathway of the body against infectious microorganisms. This is a very heterogeneous deficiency classified as X chromosome-linked CGD (gp91-phox subunit and as autosomal recessive chronic granulomatous disease, where any of the subunits of the enzyme, that is, p22-phox, p47-phox and p67-phox, may be affected. The most frequent clinical findings include, among others, lymphadenopathy, splenohepatomegaly and pneumonia. Broad-spectrum antibiotics for the treatment of the disease and gamma interferon for the treatment of severe infections are used in X chromosome-linked chronic granulomatous disease. At

  8. Acute Ethanol Intake Induces NAD(P)H Oxidase Activation and Rhoa Translocation in Resistance Arteries.

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    Simplicio, Janaina A; Hipólito, Ulisses Vilela; Vale, Gabriel Tavares do; Callera, Glaucia Elena; Pereira, Camila André; Touyz, Rhian M; Tostes, Rita de Cássia; Tirapelli, Carlos R

    2016-11-01

    The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(P)H oxidase-derived reactive oxygen species (ROS) on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(P)H oxidase activation. Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage) or water (control). Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days) before administration of water or ethanol. The mesenteric arterial bed (MAB) was collected 30 min after ethanol administration. Vitamin C prevented ethanol-induced increase in superoxide anion (O2-) generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2) levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt) and eNOS (Ser1177 or Thr495 residues) or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(P)H oxidase by inducing p47phox translocation by a redox-sensitive mechanism. O mecanismo da disfunção vascular induzido pelo consumo de etanol não é totalmente compreendido. Justifica-se, assim a identificação de mecanismos bioquímicos e moleculares que poderiam explicar tais efeitos. Investigar se a ingestão aguda de etanol ativa a via vascular RhoA/Rho quinase

  9. Constitutive NADPH-Dependent Electron Transferase Activity of the Nox4 Dehydrogenase Domain?

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    Nisimoto, Yukio; Jackson, Heather M.; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J. David

    2010-01-01

    NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47 phox and p67 phox and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K m for NADPH of 55 ? 10 ?M. The concentration of Nox4 in cell lysates was esti...

  10. NADPH oxidase-2 derived ROS dictates murine DC cytokine-mediated cell fate decisions during CD4 T helper-cell commitment.

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    Meghan A Jendrysik

    Full Text Available NADPH oxidase-2 (Nox2/gp91(phox and p47(phox deficient mice are prone to hyper-inflammatory responses suggesting a paradoxical role for Nox2-derived reactive oxygen species (ROS as anti-inflammatory mediators. The molecular basis for this mode of control remains unclear. Here we demonstrate that IFNγ/LPS matured p47(phox-/--ROS deficient mouse dendritic cells (DC secrete more IL-12p70 than similarly treated wild type DC, and in an in vitro co-culture model IFNγ/LPS matured p47(phox-/- DC bias more ovalbumin-specific CD4(+ T lymphocytes toward a Th1 phenotype than wild type (WT DC through a ROS-dependent mechanism linking IL-12p70 expression to regulation of p38-MAPK activation. The Nox2-dependent ROS production in DC negatively regulates proinflammatory IL-12 expression in DC by constraining p38-MAPK activity. Increasing endogenous H(2O(2 attenuates p38-MAPK activity in IFNγ/LPS stimulated WT and p47(phox-/- DC, which suggests that endogenous Nox 2-derived ROS functions as a secondary messenger in the activated p38-MAPK signaling pathway during IL-12 expression. These findings indicate that ROS, generated endogenously by innate and adaptive immune cells, can function as important secondary messengers that can regulate cytokine production and immune cell cross-talk to control during the inflammatory response.

  11. PHOX2B mutation-confirmed congenital central hypoventilation syndrome in a Chinese family: presentation from newborn to adulthood.

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    Lee, Peilin; Su, Yi-Ning; Yu, Chong-Jen; Yang, Pan-Chyr; Wu, Huey-Dong

    2009-02-01

    Congenital central hypoventilation syndrome (CCHS) is characterized by compromised chemoreflexes resulting in sleep hypoventilation. We report a Chinese family with paired-like homeobox 2B (PHOX2B) mutation-confirmed CCHS, with a clinical spectrum from newborn to adulthood, to increase awareness of its various manifestations. After identifying central hypoventilation in an adult man (index case), clinical evaluation was performed on the complete family, which consisted of the parents, five siblings, and five offspring. Pulmonary function tests, overnight polysomnography, arterial blood gas measurements, hypercapnia ventilatory response, and PHOX2B gene mutation screening were performed on living family members. Brain MRI, 24-h Holter monitoring, and echocardiography were performed on members with clinically diagnosed central hypoventilation. The index patient and four offspring manifested clinical features of central hypoventilation. The index patients had hypoxia and hypercapnia while awake, polycythemia, and hematocrit levels of 70%. The first and fourth children had frequent cyanotic spells, and both died of respiratory failure. The second and third children remained asymptomatic until adulthood, when they experienced impaired hypercapnic ventilatory response. The third child had nocturnal hypoventilation with nadir pulse oximetric saturation of 59%. Adult-onset CCHS with PHOX2B gene mutation of the + 5 alanine expansions were confirmed in the index patient and the second and third children. The index patient and the third child received ventilator support system bilevel positive airway pressure treatment, which improved the hypoxemia, hypercapnia, and polycythemia without altering their chemosensitivity. Transmission of late-onset CCHS is autosomal-dominant. Genetic screening of family members of CCHS probands allows for early diagnosis and treatment.

  12. Activation of endothelial cells after exposure to ambient ultrafine particles: The role of NADPH oxidase

    International Nuclear Information System (INIS)

    Mo Yiqun; Wan Rong; Chien Sufan; Tollerud, David J.; Zhang Qunwei

    2009-01-01

    Several studies have shown that ultrafine particles (UFPs) may pass from the lungs to the circulation because of their very small diameter, and induce lung oxidative stress with a resultant increase in lung epithelial permeability. The direct effects of UFPs on vascular endothelium remain unknown. We hypothesized that exposure to UFPs leads to endothelial cell O 2 ·- generation via NADPH oxidase and results in activation of endothelial cells. Our results showed that UFPs, at a non-toxic dose, induced reactive oxygen species (ROS) generation in mouse pulmonary microvascular endothelial cells (MPMVEC) that was inhibited by pre-treatment with the ROS scavengers or inhibitors, but not with the mitochondrial inhibitor, rotenone. UFP-induced ROS generation in MPMVEC was abolished by p67 phox siRNA transfection and UFPs did not cause ROS generation in MPMVEC isolated from gp91 phox knock-out mice. UFP-induced ROS generation in endothelial cells was also determined in vivo by using a perfused lung model with imaging. Moreover, Western blot and immunofluorescence staining results showed that MPMVEC treated with UFPs resulted in the translocation of cytosolic proteins of NADPH oxidase, p47 phox , p67 phox and rac 1, to the plasma membrane. These results demonstrate that NADPH oxidase in the pulmonary endothelium is involved in ROS generation following exposure to UFPs. To investigate the activation of endothelial cells by UFP-induced oxidative stress, we determined the activation of the mitogen-activated protein kinases (MAPKs) in MPMVEC. Our results showed that exposure of MPMVEC to UFPs caused increased phosphorylation of p38 and ERK1/2 MAPKs that was blocked by pre-treatment with DPI or p67 phox siRNA. Exposure of MPMVEC obtained from gp91 phox knock-out mice to UFPs did not cause increased phosphorylation of p38 and ERK1/2 MAPKs. These findings confirm that UFPs can cause endothelial cells to generate ROS directly via activation of NADPH oxidase. UFP-induced ROS lead to

  13. Prodigiosin inhibits gp91phox and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia–ischemia

    International Nuclear Information System (INIS)

    Chang, Chia-Che; Wang, Yea-Hwey; Chern, Chang-Ming; Liou, Kuo-Tong; Hou, Yu-Chang; Peng, Yu-Ta; Shen, Yuh-Chiang

    2011-01-01

    This study aimed to explore the mechanisms by which prodigiosin protects against hypoxia-induced oxidative/nitrosative brain injury induced by middle cerebral artery occlusion/reperfusion (MCAo/r) injury in mice. Hypoxia in vitro was modeled using oxygen–glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone MCAo/r injury with prodigiosin (10 and 100 μg/kg, i.v.) at 1 h after hypoxia ameliorated MCAo/r-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. MCAo/r induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (gp91 phox ), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b leukocytes due to breakdown of blood–brain barrier (BBB) by activation of nuclear factor-kappa B (NF-κB). All these changes were significantly diminished by prodigiosin. In BV-2 cells, OGD induced ROS and nitric oxide production by up-regulating gp91 phox and iNOS via activation of the NF-κB pathway, and these changes were suppressed by prodigiosin. In conclusion, our results indicate that prodigiosin reduces gp91 phox and iNOS expression possibly by impairing NF-κB activation. This compromises the activation of microglial and/or inflammatory cells, which then, in turn, mediates prodigiosin's protective effect in the MCAo/r mice. -- Highlights: ► Prodigiosin ameliorated brain infarction and deficits. ► Prodigiosin protected against hypoxia/reperfusion-induced brain injury. ► Prodigiosin diminished oxidative/nitrosativestress and leukocytes infiltration. ► Prodigiosin reduced BBB breakdown. ► Prodigiosin down-regulated gp91 phox and iNOS by inhibiting NF-κB activation.

  14. Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury.

    Science.gov (United States)

    Shen, Jia; Bai, Xiao-Yin; Qin, Yuan; Jin, Wei-Wei; Zhou, Jing-Yin; Zhou, Ji-Ping; Yan, Ying-Gang; Wang, Qiong; Bruce, Iain C; Chen, Jiang-Hua; Xia, Qiang

    2011-06-15

    Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Generation of X-CGD cells for vector evaluation from healthy donor CD34+ HSCs by shRNA-mediated knock down of gp91phox

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    Christian Brendel

    2014-01-01

    Full Text Available Innovative approaches for the treatment of rare inherited diseases are hampered by limited availability of patient derived samples for preclinical research. This also applies for the evaluation of novel vector systems for the gene therapy of monogenic hematological diseases like X-linked chronic granulomatous disease (X-CGD, a severe primary immunodeficiency caused by mutations in the gp91phox subunit of the phagocytic NADPH oxidase. Since current gene therapy protocols involve ex vivo gene modification of autologous CD34+ hematopoietic stem cells (HSC, the ideal preclinical model should simulate faithfully this procedure. However, the low availability of patient-derived CD34+ cells limits the feasibility of this approach. Here, we describe a straightforward experimental strategy that circumvents this limitation. The knock down of gp91phox expression upon lentiviral delivery of shRNAs into CD34+ cells from healthy donors generates sufficient amounts of X-CGD CD34+ cells which subsequently can be used for the evaluation of novel gene therapeutic strategies using a codon-optimized gp91phox transgene. We have used this strategy to test the potential of a novel gene therapy vector for X-CGD.

  16. Microvascular Endothelial Dysfunction in Sedentary, Obese Humans is mediated by NADPH Oxidase; Influence of Exercise Training

    Science.gov (United States)

    La Favor, Justin D.; Dubis, Gabriel S.; Yan, Huimin; White, Joseph D.; Nelson, Margaret A.M.; Anderson, Ethan J.; Hickner, Robert C.

    2016-01-01

    Objective The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and to determine the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results Young, sedentary men and women were divided into lean (BMI 18–25; n=14), intermediate (BMI 28–32.5; n=13), and obese (BMI 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralis of obese compared to both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase (Nox) inhibitor, lowered (normalized) H2O2 and superoxide levels and reversed microvascular endothelial dysfunction in obese subjects. Following 8-weeks of exercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the Nox subunits p22phox, p47phox, and p67phox were increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions This study implicates Nox as a source of excessive ROS production in skeletal muscle of obese individuals, and links excessive Nox derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies. PMID:27765769

  17. The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma

    International Nuclear Information System (INIS)

    Revet, Ingrid; Huizenga, Gerda; Chan, Alvin; Koster, Jan; Volckmann, Richard; Sluis, Peter van; Ora, Ingrid; Versteeg, Rogier; Geerts, Dirk

    2008-01-01

    Neuroblastoma is an embryonal tumour of the peripheral sympathetic nervous system (SNS). One of the master regulator genes for peripheral SNS differentiation, the homeobox transcription factor PHOX2B, is mutated in familiar and sporadic neuroblastomas. Here we report that inducible expression of PHOX2B in the neuroblastoma cell line SJNB-8 down-regulates MSX1, a homeobox gene important for embryonic neural crest development. Inducible expression of MSX1 in SJNB-8 caused inhibition of both cell proliferation and colony formation in soft agar. Affymetrix micro-array and Northern blot analysis demonstrated that MSX1 strongly up-regulated the Delta-Notch pathway genes DLK1, NOTCH3, and HEY1. In addition, the proneural gene NEUROD1 was down-regulated. Western blot analysis showed that MSX1 induction caused cleavage of the NOTCH3 protein to its activated form, further confirming activation of the Delta-Notch pathway. These experiments describe for the first time regulation of the Delta-Notch pathway by MSX1, and connect these genes to the PHOX2B oncogene, indicative of a role in neuroblastoma biology. Affymetrix micro-array analysis of a neuroblastic tumour series consisting of neuroblastomas and the more benign ganglioneuromas showed that MSX1, NOTCH3 and HEY1 are more highly expressed in ganglioneuromas. This suggests a block in differentiation of these tumours at distinct developmental stages or lineages

  18. Cellular antioxidant effects of atorvastatin in vitro and in vivo.

    Science.gov (United States)

    Wassmann, Sven; Laufs, Ulrich; Müller, Kirsten; Konkol, Christian; Ahlbory, Katja; Bäumer, Anselm T; Linz, Wolfgang; Böhm, Michael; Nickenig, Georg

    2002-02-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert direct effects on vascular cells and beneficially influence endothelial dysfunction. Because reactive oxygen species (ROS) may lead to vascular damage and dysfunction, we investigated the effect of atorvastatin on ROS production and the underlying mechanisms in vitro and in vivo. Cultured rat aortic vascular smooth muscle cells were incubated with 10 micromol/L atorvastatin. Angiotensin II-induced and epidermal growth factor-induced ROS production were significantly reduced by atorvastatin (dichlorofluorescein fluorescence laser microscopy). Atorvastatin downregulated mRNA expression of the NAD(P)H oxidase subunit nox1, whereas p22phox mRNA expression was not significantly altered (reverse transcription-polymerase chain reaction, Northern analysis). Membrane translocation of rac1 GTPase, which is required for the activation of NAD(P)H oxidase, was inhibited by atorvastatin (Western blot). mRNA expression of superoxide dismutase isoforms and glutathione peroxidase was not modified by atorvastatin, whereas catalase expression was upregulated at mRNA and protein levels, resulting in an increased enzymatic activity. Effects of atorvastatin on ROS production and nox1, rac1, and catalase expression were inhibited by L-mevalonate but not by 25-hydroxycholesterol. In addition, spontaneously hypertensive rats were treated with atorvastatin for 30 days. ROS production in aortic segments was significantly reduced in statin-treated rats (lucigenin chemiluminescence). Treatment with atorvastatin reduced vascular mRNA expression of p22phox and nox1 and increased aortic catalase expression. mRNA expression of superoxide dismutases, glutathione peroxidase, and NAD(P)H oxidase subunits gp91phox, p40phox, p47phox, and p67phox remained unchanged. Translocation of rac1 from the cytosol to the cell membrane was also reduced in vivo. Thus, atorvastatin exerts cellular antioxidant effects in cultured rat

  19. Prodigiosin inhibits gp91{sup phox} and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia-ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Chia-Che [Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Agricultural Biotechnology Center, National Chung-Hsing University, Taichung, Taiwan (China); Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan (China); Wang, Yea-Hwey [Department of Nursing, College of Medicine and Nursing, Hungkuang University, Taichung, Taiwan (China); Chern, Chang-Ming [Division of Neurovascular Disease, Neurological Institute, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Liou, Kuo-Tong [Department of Chinese Martial Arts, Chinese Culture University, Taipei, Taiwan (China); Hou, Yu-Chang [Department of Chinese Medicine, Taoyuan General Hospital, Department of Health, Taiwan (China); Department of Nursing, Yuanpei University, Hsinchu, Taiwan (China); Department of Bioscience Technology, Chuan-Yuan Christian University, Taoyuan, Taiwan (China); Peng, Yu-Ta [Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan (China); Shen, Yuh-Chiang, E-mail: yuhcs@nricm.edu.tw [National Research Institute of Chinese Medicine, Taipei, Taiwan (China); Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan (China)

    2011-11-15

    This study aimed to explore the mechanisms by which prodigiosin protects against hypoxia-induced oxidative/nitrosative brain injury induced by middle cerebral artery occlusion/reperfusion (MCAo/r) injury in mice. Hypoxia in vitro was modeled using oxygen-glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone MCAo/r injury with prodigiosin (10 and 100 {mu}g/kg, i.v.) at 1 h after hypoxia ameliorated MCAo/r-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. MCAo/r induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (gp91{sup phox}), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b leukocytes due to breakdown of blood-brain barrier (BBB) by activation of nuclear factor-kappa B (NF-{kappa}B). All these changes were significantly diminished by prodigiosin. In BV-2 cells, OGD induced ROS and nitric oxide production by up-regulating gp91{sup phox} and iNOS via activation of the NF-{kappa}B pathway, and these changes were suppressed by prodigiosin. In conclusion, our results indicate that prodigiosin reduces gp91{sup phox} and iNOS expression possibly by impairing NF-{kappa}B activation. This compromises the activation of microglial and/or inflammatory cells, which then, in turn, mediates prodigiosin's protective effect in the MCAo/r mice. -- Highlights: Black-Right-Pointing-Pointer Prodigiosin ameliorated brain infarction and deficits. Black-Right-Pointing-Pointer Prodigiosin protected against hypoxia/reperfusion-induced brain injury. Black-Right-Pointing-Pointer Prodigiosin diminished oxidative/nitrosativestress and leukocytes infiltration. Black-Right-Pointing-Pointer Prodigiosin reduced BBB breakdown. Black

  20. Ginsenoside Re protects against phencyclidine-induced behavioral changes and mitochondrial dysfunction via interactive modulation of glutathione peroxidase-1 and NADPH oxidase in the dorsolateral cortex of mice.

    Science.gov (United States)

    Tran, The-Vinh; Shin, Eun-Joo; Dang, Duy-Khanh; Ko, Sung Kwon; Jeong, Ji Hoon; Nah, Seung-Yeol; Jang, Choon-Gon; Lee, Yu Jeung; Toriumi, Kazuya; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2017-12-01

    We investigated whether ginsenoside Re (Re) modulates phencyclidine (PCP)-induced sociability deficits and recognition memory impairments to extend our recent finding. We examined the role of GPx-1 gene in the pharmacological activity of Re against mitochondrial dysfunction induced by PCP in the dorsolateral cortex of mice. Since mitochondrial oxidative stress activates NADPH oxidase (PHOX), we applied PHOX inhibitor apocynin for evaluating interactive modulation between GPx-1 and PHOX against PCP neurotoxicity. Sociability deficits and recognition memory impairments induced by PCP were more pronounced in GPx-1 knockout (KO) than in wild type (WT) mice. PCP-induced mitochondrial oxidative stress, mitochondrial dysfunction, and membrane translocation of p47phox were more evident in GPx-1 KO than in WT. Re treatment significantly attenuated PCP-induced neurotoxic changes. Re also significantly attenuated PCP-induced sociability deficits and recognition memory impairments. The attenuation by Re was comparable to that by apocynin. The attenuation was more obvious in GPx-1 KO than in WT. Importantly, apocynin did not show any additional positive effects on the neuroprotective activity of Re, indicating that PHOX is a molecular target for therapeutic activity of Re. Our results suggest that Re requires interactive modulation between GPx activity and PHOX (p47phox) to exhibit neuroprotective potentials against PCP insult. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade.

    Science.gov (United States)

    Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A; Hamilton, Elisha J; Figtree, Gemma A; Rasmussen, Helge H

    2015-09-01

    Dysregulated nitric oxide (NO)- and superoxide (O2 (·-))-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na(+)-K(+) pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na(+)-K(+) pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47(phox) and membranous p22(phox) NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47(phox) to p22(phox) with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na(+)-K(+) pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22(phox) with p47(phox), abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na(+)-K(+) pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na(+)-K(+) pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes. Copyright © 2015 the American Physiological Society.

  2. Functional Assembly of Soluble and Membrane Recombinant Proteins of Mammalian NADPH Oxidase Complex.

    Science.gov (United States)

    Souabni, Hajer; Ezzine, Aymen; Bizouarn, Tania; Baciou, Laura

    2017-01-01

    Activation of phagocyte cells from an innate immune system is associated with a massive consumption of molecular oxygen to generate highly reactive oxygen species (ROS) as microbial weapons. This is achieved by a multiprotein complex, the so-called NADPH oxidase. The activity of phagocyte NADPH oxidase relies on an assembly of more than five proteins, among them the membrane heterodimer named flavocytochrome b 558 (Cytb 558 ), constituted by the tight association of the gp91 phox (also named Nox2) and p22 phox proteins. The Cytb 558 is the membrane catalytic core of the NADPH oxidase complex, through which the reducing equivalent provided by NADPH is transferred via the associated prosthetic groups (one flavin and two hemes) to reduce dioxygen into superoxide anion. The other major proteins (p47 phox , p67 phox , p40 phox , Rac) requisite for the complex activity are cytosolic proteins. Thus, the NADPH oxidase functioning relies on a synergic multi-partner assembly that in vivo can be hardly studied at the molecular level due to the cell complexity. Thus, a cell-free assay method has been developed to study the NADPH oxidase activity that allows measuring and eventually quantifying the ROS generation based on optical techniques following reduction of cytochrome c. This setup is a valuable tool for the identification of protein interactions, of crucial components and additives for a functional enzyme. Recently, this method was improved by the engineering and the production of a complete recombinant NADPH oxidase complex using the combination of purified proteins expressed in bacterial and yeast host cells. The reconstitution into artificial membrane leads to a fully controllable system that permits fine functional studies.

  3. Angiotensin II inhibits the Na+-K+ pump via PKC-dependent activation of NADPH oxidase.

    Science.gov (United States)

    White, Caroline N; Figtree, Gemma A; Liu, Chia-Chi; Garcia, Alvaro; Hamilton, Elisha J; Chia, Karin K M; Rasmussen, Helge H

    2009-04-01

    The sarcolemmal Na(+)-K(+) pump, pivotal in cardiac myocyte function, is inhibited by angiotensin II (ANG II). Since ANG II activates NADPH oxidase, we tested the hypothesis that NADPH oxidase mediates the pump inhibition. Exposure to 100 nmol/l ANG II increased superoxide-sensitive fluorescence of isolated rabbit ventricular myocytes. The increase was abolished by pegylated superoxide dismutase (SOD), by the NADPH oxidase inhibitor apocynin, and by myristolated inhibitory peptide to epsilon-protein kinase C (epsilonPKC), previously implicated in ANG II-induced Na(+)-K(+) pump inhibition. A role for epsilonPKC was also supported by an ANG II-induced increase in coimmunoprecipitation of epsilonPKC with the receptor for the activated kinase and with the cytosolic p47(phox) subunit of NADPH oxidase. ANG II decreased electrogenic Na(+)-K(+) pump current in voltage-clamped myocytes. The decrease was abolished by SOD, by the gp91ds inhibitory peptide that blocks assembly and activation of NADPH oxidase, and by epsilonPKC inhibitory peptide. Since colocalization should facilitate NADPH oxidase-dependent regulation of the Na(+)-K(+) pump, we examined whether there is physical association between the pump subunits and NADPH oxidase. The alpha(1)-subunit coimmunoprecipitated with caveolin 3 and with membrane-associated p22(phox) and cytosolic p47(phox) NADPH oxidase subunits at baseline. ANG II had no effect on alpha(1)/caveolin 3 or alpha(1)/p22(phox) interaction, but it increased alpha(1)/p47(phox) coimmunoprecipitation. We conclude that ANG II inhibits the Na(+)-K(+) pump via PKC-dependent NADPH oxidase activation.

  4. NADPH oxidase-mediated generation of reactive oxygen species: A new mechanism for X-ray-induced HeLa cell death

    International Nuclear Information System (INIS)

    Liu Qing; He Xiaoqing; Liu Yongsheng; Du Bingbing; Wang Xiaoyan; Zhang Weisheng; Jia Pengfei; Dong Jingmei; Ma Jianxiu; Wang Xiaohu; Li Sha; Zhang Hong

    2008-01-01

    Oxidative damage is an important mechanism in X-ray-induced cell death. Radiolysis of water molecules is a source of reactive oxygen species (ROS) that contribute to X-ray-induced cell death. In this study, we showed by ROS detection and a cell survival assay that NADPH oxidase has a very important role in X-ray-induced cell death. Under X-ray irradiation, the upregulation of the expression of NADPH oxidase membrane subunit gp91 phox was dose-dependent. Meanwhile, the cytoplasmic subunit p47 phox was translocated to the cell membrane and localized with p22 phox and gp91 phox to form reactive NADPH oxidase. Our data suggest, for the first time, that NADPH oxidase-mediated generation of ROS is an important contributor to X-ray-induced cell death. This suggests a new target for combined gene transfer and radiotherapy.

  5. Contribution of PPARγ in modulation of acrolein-induced inflammatory signaling in gp91phox knock-out mice.

    Science.gov (United States)

    Yousefipour, Zivar; Chug, Neha; Marek, Katarzyna; Nesbary, Alicia; Mathew, Joseph; Ranganna, Kasturi; Newaz, Mohammad A

    2017-08-01

    Oxidative stress and inflammation are major contributors to acrolein toxicity. Peroxisome proliferator activated receptor gamma (PPARγ) has antioxidant and anti-inflammatory effects. We investigated the contribution of PPARγ ligand GW1929 to the attenuation of oxidative stress in acrolein-induced insult. Male gp91 phox knock-out (KO) mice were treated with acrolein (0.5 mg·(kg body mass) -1 by intraperitoneal injection for 7 days) with or without GW1929 (GW; 0.5 mg·(kg body mass) -1 ·day -1 , orally, for 10 days). The livers were processed for further analyses. Acrolein significantly increased 8-isoprostane and reduced PPARγ activity (P acrolein-treated WT mice, and was reduced by GW1929 (by 65%). KO mice exhibited higher xanthine oxidase (XO). Acrolein increased XO and COX in WT mice and XO in KO mice. GW1929 significantly reduced COX in WT and KO mice and reduced XO in KO mice. Acrolein significantly reduced the total antioxidant status in WT and KO mice (P acrolein-treated WT mice. GW1929 reduced NF-κB levels (by 51%) in KO mice. Acrolein increased CD36 in KO mice (by 43%), which was blunted with GW1929. Data confirms that the generation of free radicals by acrolein is mainly through NAD(P)H, but other oxygenates play a role too. GW1929 may alleviate the toxicity of acrolein by attenuating NF-κB, COX, and CD36.

  6. NADPH Oxidase Isoform 2 (NOX2 Is Involved in Drug Addiction Vulnerability in Progeny Developmentally Exposed to Ethanol

    Directory of Open Access Journals (Sweden)

    Marcela L. Contreras

    2017-06-01

    Full Text Available Ethanol exposure increases oxidative stress in developing organs, including the brain. Antioxidant treatment during maternal ethanol ingestion improves behavioral deficits in rodent models of fetal alcohol spectrum disorder (FASD. However, the impact of general antioxidant treatment in their adult offspring and the Specific Reactive Species (ROS-dependent mechanism, are not fully understood. We hypothesized that pre and early postnatal ethanol exposure (PEE modifies redox homeostasis, in particular NOX2 function during reward signaling in the mesocorticolimbic pathway, which reinforces the effects of alcohol. We developed a FASD rat model which was evaluated during adolescence (P21 and adulthood (P70. We first studied whether redox homeostasis is affected in PEE animals, by analyzing mRNA expression of SOD1, CAT, and Gpx1. We found that PEE reduced the mRNA levels of these three anti-oxidant enzymes in PFC and HIPP at P21 and in the VTA at P70. We also analyzed basal mRNA and protein expression of NOX2 subunits such as gp91phox, p22 phox, and p47 phox, in mesocorticolimbic brain areas of PEE rat brains. At P21, gp91 phox, and p47 phox levels in the VTA were decreased. At P70, gp91 phox mRNA levels was decreased in HIPP and both mRNA and protein levels were decreased in PFC. Since NOX2 is regulated by the N-methyl-D-aspartate Receptor (NMDAR, we analyzed NMDAR mRNA expression and found differential expression of NMDAR subunits (NR1 and NR2B in the PFC that was age dependent, with levels decreased at P21 and increased at P70. The analysis also revealed decreased NR2B mRNA expression in HIPP and VTA at P70. Offspring from maternal ethanol users consumed 25% more ethanol in a free choice alcohol consumption test than control rats, and showed place preference for an alcohol-paired compartment. In vivo inhibition of NOX2 using apocynin in drinking water, or infusion of blocked peptide gp91 phox ds in the VTA normalized alcohol place preference

  7. NADPH Oxidase Isoform 2 (NOX2) Is Involved in Drug Addiction Vulnerability in Progeny Developmentally Exposed to Ethanol.

    Science.gov (United States)

    Contreras, Marcela L; de la Fuente-Ortega, Erwin; Vargas-Roberts, Sofía; Muñoz, Daniela C; Goic, Carolina A; Haeger, Paola A

    2017-01-01

    Ethanol exposure increases oxidative stress in developing organs, including the brain. Antioxidant treatment during maternal ethanol ingestion improves behavioral deficits in rodent models of fetal alcohol spectrum disorder (FASD). However, the impact of general antioxidant treatment in their adult offspring and the Specific Reactive Species (ROS)-dependent mechanism, are not fully understood. We hypothesized that pre and early postnatal ethanol exposure (PEE) modifies redox homeostasis, in particular NOX2 function during reward signaling in the mesocorticolimbic pathway, which reinforces the effects of alcohol. We developed a FASD rat model which was evaluated during adolescence (P21) and adulthood (P70). We first studied whether redox homeostasis is affected in PEE animals, by analyzing mRNA expression of SOD1, CAT, and Gpx1. We found that PEE reduced the mRNA levels of these three anti-oxidant enzymes in PFC and HIPP at P21 and in the VTA at P70. We also analyzed basal mRNA and protein expression of NOX2 subunits such as gp91phox, p22 phox, and p47 phox, in mesocorticolimbic brain areas of PEE rat brains. At P21, gp91 phox, and p47 phox levels in the VTA were decreased. At P70, gp91 phox mRNA levels was decreased in HIPP and both mRNA and protein levels were decreased in PFC. Since NOX2 is regulated by the N-methyl-D-aspartate Receptor (NMDAR), we analyzed NMDAR mRNA expression and found differential expression of NMDAR subunits (NR1 and NR2B) in the PFC that was age dependent, with levels decreased at P21 and increased at P70. The analysis also revealed decreased NR2B mRNA expression in HIPP and VTA at P70. Offspring from maternal ethanol users consumed 25% more ethanol in a free choice alcohol consumption test than control rats, and showed place preference for an alcohol-paired compartment. In vivo inhibition of NOX2 using apocynin in drinking water, or infusion of blocked peptide gp91 phox ds in the VTA normalized alcohol place preference, suggesting that NOX

  8. Ebselen and congeners inhibit NADPH oxidase 2-dependent superoxide generation by interrupting the binding of regulatory subunits.

    Science.gov (United States)

    Smith, Susan M E; Min, Jaeki; Ganesh, Thota; Diebold, Becky; Kawahara, Tsukasa; Zhu, Yerun; McCoy, James; Sun, Aiming; Snyder, James P; Fu, Haian; Du, Yuhong; Lewis, Iestyn; Lambeth, J David

    2012-06-22

    NADPH oxidases (Nox) are a primary source of reactive oxygen species (ROS), which function in normal physiology and, when overproduced, in pathophysiology. Recent studies using mice deficient in Nox2 identify this isoform as a novel target against Nox2-implicated inflammatory diseases. Nox2 activation depends on the binding of the proline-rich domain of its heterodimeric partner p22phox to p47phox. A high-throughput screen that monitored this interaction via fluorescence polarization identified ebselen and several of its analogs as inhibitors. Medicinal chemistry was performed to explore structure-activity relationships and to optimize potency. Ebselen and analogs potently inhibited Nox1 and Nox2 activity but were less effective against other isoforms. Ebselen also blocked translocation of p47phox to neutrophil membranes. Thus, ebselen and its analogs represent a class of compounds that inhibit ROS generation by interrupting the assembly of Nox2-activating regulatory subunits. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Urotensin II inhibits skeletal muscle glucose transport signaling pathways via the NADPH oxidase pathway.

    Directory of Open Access Journals (Sweden)

    Hong-Xia Wang

    Full Text Available Our previous studies have demonstrated that the urotensin (UII and its receptor are up-regulated in the skeletal muscle of mice with type II diabetes mellitus (T2DM, but the significance of UII in skeletal muscle insulin resistance remains unknown. The purpose of this study was to investigate the effect of UII on NADPH oxidase and glucose transport signaling pathways in the skeletal muscle of mice with T2DM and in C2C12 mouse myotube cells. KK/upj-AY/J mice (KK mice were divided into the following groups: KK group, with saline treatment for 2 weeks; KK+ urantide group, with daily 30 µg/kg body weight injections over the same time period of urantide, a potent urotensin II antagonist peptide; Non-diabetic C57BL/6J mice were used as normal controls. After urantide treatment, mice were subjected to an intraperitoneal glucose tolerance test, in addition to measurements of the levels of ROS, NADPH oxidase and the phosphorylated AKT, PKC and ERK. C2C12 cells were incubated with serum-free DMEM for 24 hours before conducting the experiments, and then administrated with 100 nM UII for 2 hours or 24 hours. Urantide treatment improved glucose tolerance, decreased the translocation of the NADPH subunits p40-phox and p47-phox, and increased levels of the phosphorylated PKC, AKT and ERK. In contrast, UII treatment increased ROS production and p47-phox and p67-phox translocation, and decreased the phosphorylated AKT, ERK1/2 and p38MAPK; Apocynin abrogated this effect. In conclusion, UII increased ROS production by NADPH oxidase, leading to the inhibition of signaling pathways involving glucose transport, such as AKT/PKC/ERK. Our data imply a role for UII at the molecular level in glucose homeostasis, and possibly in skeletal muscle insulin resistance in T2DM.

  10. Downregulation of B-myb promotes senescence via the ROS-mediated p53/p21 pathway, in vascular endothelial cells.

    Science.gov (United States)

    Zhou, Zhihui; Yin, Yanlin; Chang, Qun; Sun, Guanqun; Lin, Jiahui; Dai, Yalei

    2017-04-01

    To reveal whether B-myb is involved in preventing senescence of vascular endothelial cells, and if so, to identify possible mechanisms for it. C57/BL6 male mice and primary human aortic endothelial cells (HAECs) were used. Bleomycin was applied to induce stress-related premature senescence. B-myb knockdown was achieved using an siRNA technique and cell senescence was assessed using the senescence-associated β-galactosidase (SA-β-gal) assay. Intracellular reactive oxygen species (ROS) production was analysed using an ROS assay kit and cell proliferation was evaluated using KFluor488 EdU kit. Capillary tube network formation was determined by Matrigel assay. Expressions of mRNA and protein levels were detected by real-time PCR and western blotting. B-myb expression significantly decreased, while p53 and p21 expressions increased in the aortas of aged mice. This expression pattern was also found in replicative senescent HAECs and senescent HAECs induced by bleomycin. B-myb knockdown resulted in upregulation of p22 phox , ROS accumulation and cell senescence of HAECs. Downregulation of B-myb significantly inhibited cell proliferation and capillary tube network formation and activated the p53/p21 signalling pathway. Blocking ROS production or inhibiting p53 activation remarkably attenuated SA-β-gal activity and delayed cell senescence induced by B-myb-silencing. Downregulation of B-myb induced senescence by upregulation of p22 phox and activation of the ROS/p53/p21 pathway, in our vascular endothelial cells, suggesting that B-myb may be a novel candidate for regulating cell senescence to protect against endothelial senescence-related cardiovascular diseases. © 2016 John Wiley & Sons Ltd.

  11. Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells.

    Science.gov (United States)

    Batchuluun, Battsetseg; Inoguchi, Toyoshi; Sonoda, Noriyuki; Sasaki, Shuji; Inoue, Tomoaki; Fujimura, Yoshinori; Miura, Daisuke; Takayanagi, Ryoichi

    2014-01-01

    Metformin and glucagon like peptide-1 (GLP-1) prevent diabetic cardiovascular complications and atherosclerosis. However, the direct effects on hyperglycemia-induced oxidative stress in endothelial cells are not fully understood. Thus, we aimed to evaluate the effects of metformin and a GLP-1 analog, liraglutide on high glucose-induced oxidative stress. Production of reactive oxygen species (ROS), activation of protein kinase C (PKC) and NAD(P)H oxidase, and changes in signaling molecules in response to high glucose exposure were evaluated in human aortic endothelial cells with and without treatment of metformin and liraglutide, alone or in combination. PKC-NAD(P)H oxidase pathway was assessed by translocation of GFP-fused PKCβ2 isoform and GFP-fused p47phox, a regulatory subunit of NAD(P)H oxidase, in addition to endogenous PKC phosphorylation and NAD(P)H oxidase activity. High glucose-induced ROS overproduction was blunted by metformin or liraglutide treatment, with a further decrease by a combination of these drugs. Exposure to high glucose caused PKCβ2 translocation and a time-dependent phosphorylation of endogenous PKC but failed to induce its translocation and phosphorylation in the cells treated with metformin and liraglutide. Furthermore, both drugs inhibited p47phox translocation and NAD(P)H oxidase activation, and prevented the high glucose-induced changes in intracellulalr diacylglycerol (DAG) level and phosphorylation of AMP-activated protein kinase (AMPK). A combination of these drugs further enhanced all of these effects. Metformin and liraglutide ameliorate high glucose-induced oxidative stress by inhibiting PKC-NAD(P)H oxidase pathway. A combination of these two drugs provides augmented protective effects, suggesting the clinical usefulness in prevention of diabetic vascular complications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition.

    Science.gov (United States)

    Chia, Karin K M; Liu, Chia-Chi; Hamilton, Elisha J; Garcia, Alvaro; Fry, Natasha A; Hannam, William; Figtree, Gemma A; Rasmussen, Helge H

    2015-08-15

    Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na(+)-K(+) pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na(+)-K(+) pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na(+)-K(+) pump current (Ip). Coexposure to 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na(+)-K(+) pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47(phox) NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22(phox) subunit, and it decreased O2 (·-)-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47(phox) indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22(phox) and p47(phox) NADPH oxidase subunits and decrease β1-Na(+)-K(+) pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo. Copyright © 2015 the American Physiological Society.

  13. High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery.

    Science.gov (United States)

    Yang, Qian; Wu, Wei; Li, Qian; Chen, Chan; Zhou, Ronghua; Qiu, Yanhua; Luo, Ming; Tan, Zhaoxia; Li, Shen; Chen, Gang; Zhou, Wentao; Liu, Jiaxin; Yang, Chengmin; Liu, Jin; Li, Tao

    2015-01-01

    Objective. Ischemia/reperfusion (I/R) injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB). This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb), a hemoglobin-based oxygen carrier (HBOC), can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v) provided a significant protection on the I/R heart, whereas the high-dose PolyPHb (3%, w/v) did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs) to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, and elevated malonaldehyde (MDA) formation. Consistent with the increased oxidative stress, the NAD(P)H oxidase activity and subunits expression, including gp91(phox), p47(phox), p67(phox), and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(P)H oxidase-induced ROS and resultant endothelial dysfunction.

  14. Ultrafine carbon particles promote rotenone-induced dopamine neuronal loss through activating microglial NADPH oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yinxi; Liu, Dan; Zhang, Huifeng; Wang, Yixin [Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, 100191 (China); Wei, Ling [Beijing Center for Physical & Chemical Analysis, Beijing 100089 (China); Liu, Yutong [School of Life Science, Beijing Normal University, Beijing 100875 (China); Liao, Jieying [Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361024 (China); Gao, Hui-Ming [Model Animal Research Center of Nanjing University, Nanjing 211800 (China); Zhou, Hui, E-mail: hardhui@gmail.com [Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, 100191 (China)

    2017-05-01

    Background: Atmospheric ultrafine particles (UFPs) and pesticide rotenone were considered as potential environmental risk factors for Parkinson's disease (PD). However, whether and how UFPs alone and in combination with rotenone affect the pathogenesis of PD remains largely unknown. Methods: Ultrafine carbon black (ufCB, a surrogate of UFPs) and rotenone were used individually or in combination to determine their roles in chronic dopaminergic (DA) loss in neuron-glia, and neuron-enriched, mix-glia cultures. Immunochemistry using antibody against tyrosine hydroxylase was performed to detect DA neuronal loss. Measurement of extracellular superoxide and intracellular reactive oxygen species (ROS) were performed to examine activation of NADPH oxidase. Genetic deletion and pharmacological inhibition of NADPH oxidase and MAC-1 receptor in microglia were employed to examine their role in DA neuronal loss triggered by ufCB and rotenone. Results: In rodent midbrain neuron-glia cultures, ufCB and rotenone alone caused neuronal death in a dose-dependent manner. In particularly, ufCB at doses of 50 and 100 μg/cm{sup 2} induced significant loss of DA neurons. More importantly, nontoxic doses of ufCB (10 μg/cm{sup 2}) and rotenone (2 nM) induced synergistic toxicity to DA neurons. Microglial activation was essential in this process. Furthermore, superoxide production from microglial NADPH oxidase was critical in ufCB/rotenone-induced neurotoxicity. Studies in mix-glia cultures showed that ufCB treatment activated microglial NADPH oxidase to induce superoxide production. Firstly, ufCB enhanced the expression of NADPH oxidase subunits (gp91{sup phox}, p47{sup phox} and p40{sup phox}); secondly, ufCB was recognized by microglial surface MAC-1 receptor and consequently promoted rotenone-induced p47{sup phox} and p67{sup phox} translocation assembling active NADPH oxidase. Conclusion: ufCB and rotenone worked in synergy to activate NADPH oxidase in microglia, leading to

  15. Ultrafine carbon particles promote rotenone-induced dopamine neuronal loss through activating microglial NADPH oxidase

    International Nuclear Information System (INIS)

    Wang, Yinxi; Liu, Dan; Zhang, Huifeng; Wang, Yixin; Wei, Ling; Liu, Yutong; Liao, Jieying; Gao, Hui-Ming; Zhou, Hui

    2017-01-01

    Background: Atmospheric ultrafine particles (UFPs) and pesticide rotenone were considered as potential environmental risk factors for Parkinson's disease (PD). However, whether and how UFPs alone and in combination with rotenone affect the pathogenesis of PD remains largely unknown. Methods: Ultrafine carbon black (ufCB, a surrogate of UFPs) and rotenone were used individually or in combination to determine their roles in chronic dopaminergic (DA) loss in neuron-glia, and neuron-enriched, mix-glia cultures. Immunochemistry using antibody against tyrosine hydroxylase was performed to detect DA neuronal loss. Measurement of extracellular superoxide and intracellular reactive oxygen species (ROS) were performed to examine activation of NADPH oxidase. Genetic deletion and pharmacological inhibition of NADPH oxidase and MAC-1 receptor in microglia were employed to examine their role in DA neuronal loss triggered by ufCB and rotenone. Results: In rodent midbrain neuron-glia cultures, ufCB and rotenone alone caused neuronal death in a dose-dependent manner. In particularly, ufCB at doses of 50 and 100 μg/cm 2 induced significant loss of DA neurons. More importantly, nontoxic doses of ufCB (10 μg/cm 2 ) and rotenone (2 nM) induced synergistic toxicity to DA neurons. Microglial activation was essential in this process. Furthermore, superoxide production from microglial NADPH oxidase was critical in ufCB/rotenone-induced neurotoxicity. Studies in mix-glia cultures showed that ufCB treatment activated microglial NADPH oxidase to induce superoxide production. Firstly, ufCB enhanced the expression of NADPH oxidase subunits (gp91 phox , p47 phox and p40 phox ); secondly, ufCB was recognized by microglial surface MAC-1 receptor and consequently promoted rotenone-induced p47 phox and p67 phox translocation assembling active NADPH oxidase. Conclusion: ufCB and rotenone worked in synergy to activate NADPH oxidase in microglia, leading to oxidative damage to DA neurons. Our

  16. Reactive oxygen species generation mediated by NADPH oxidase and PI3K/Akt pathways contribute to invasion of Streptococcus agalactiae in human endothelial cells.

    Science.gov (United States)

    Oliveira, Jessica Silva Santos de; Santos, Gabriela da Silva; Moraes, João Alfredo; Saliba, Alessandra Mattos; Barja-Fidalgo, Thereza Christina; Mattos-Guaraldi, Ana Luíza; Nagao, Prescilla Emy

    2018-01-01

    BACKGROUND Streptococcus agalactiae can causes sepsis, pneumonia, and meningitis in neonates, the elderly, and immunocompromised patients. Although the virulence properties of S. agalactiae have been partially elucidated, the molecular mechanisms related to reactive oxygen species (ROS) generation in infected human endothelial cells need further investigation. OBJECTIVES This study aimed to evaluate the influence of oxidative stress in human umbilical vein endothelial cells (HUVECs) during S. agalactiae infection. METHODS ROS production during S. agalactiae-HUVEC infection was detected using the probe CM-H2DCFDA. Microfilaments labelled with phalloidin-FITC and p47phox-Alexa 546 conjugated were analysed by immunofluorescence. mRNA levels of p47phox (NADPH oxidase subunit) were assessed using Real Time qRT-PCR. The adherence and intracellular viability of S. agalactiae in HUVECs with or without pre-treatment of DPI, apocynin (NADPH oxidase inhibitors), and LY294002 (PI3K inhibitor) were evaluated by penicillin/gentamicin exclusion. Phosphorylation of p47phox and Akt activation by S. agalactiae were evaluated by immunoblotting analysis. FINDINGS Data showed increased ROS production 15 min after HUVEC infection. Real-Time qRT-PCR and western blotting performed in HUVEC infected with S. agalactiae detected alterations in mRNA levels and activation of p47phox. Pre-treatment of endothelial cells with NADPH oxidase (DPI and apocynin) and PI3K/Akt pathway (LY294002) inhibitors reduced ROS production, bacterial intracellular viability, and generation of actin stress fibres in HUVECs infected with S. agalactiae. CONCLUSIONS ROS generation via the NADPH oxidase pathway contributes to invasion of S. agalactiae in human endothelial cells accompanied by cytoskeletal reorganisation through the PI3K/Akt pathway, which provides novel evidence for the involvement of oxidative stress in S. agalactiae pathogenesis.

  17. Andrographolide inhibits TNFα-induced ICAM-1 expression via suppression of NADPH oxidase activation and induction of HO-1 and GCLM expression through the PI3K/Akt/Nrf2 and PI3K/Akt/AP-1 pathways in human endothelial cells.

    Science.gov (United States)

    Lu, Chia-Yang; Yang, Ya-Chen; Li, Chien-Chun; Liu, Kai-Li; Lii, Chong-Kuei; Chen, Haw-Wen

    2014-09-01

    Andrographolide, the major bioactive component of Andrographis paniculata, has been demonstrated to have various biological properties including anti-inflammation, antioxidation, and anti-hepatotoxicity. Oxidative stress is considered a major risk factor in aging, inflammation, cancer, atherosclerosis, and diabetes mellitus. NADPH oxidase is a major source of endogenous reactive oxygen species (ROS). In this study, we used EA.hy926 endothelial-like cells to explore the anti-inflammatory activity of andrographolide. Andrographolide attenuated TNFα-induced ROS generation, Src phosphorylation, membrane translocation of the NADPH oxidase subunits p47(phox) and p67(phox), and ICAM-1 gene expression. In the small hairpin RNA interference assay, shp47(phox) abolished TNFα-induced p65 nuclear translocation, ICAM-1 gene expression, and adhesion of HL-60 cells. Andrographolide induced the gene expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase modifier subunit (GCLM) in a time-dependent manner. Cellular glutathione (GSH) content was increased by andrographolide. shGCLM attenuated the andrographolide-induced increase in GSH content and reversed the andrographolide inhibition of HL-60 adhesion. shHO-1 showed a similar effect on andrographolide inhibition of HL-60 adhesion to shGCLM. The mechanism underlying the up-regulation of HO-1 and GCLM by andrographolide was dependent on the PI3K/Akt pathway, and both the Nrf2 and AP-1 transcriptional factors were involved. Our results suggest that andrographolide attenuates TNFα-induced ICAM-1 expression at least partially through suppression of NADPH oxidase activation and induction of HO-1 and GCLM expression, which is PI3K/Akt pathway-dependent. Copyright © 2014. Published by Elsevier Inc.

  18. ATP mediates NADPH oxidase/ROS generation and COX-2/PGE2 expression in A549 cells: role of P2 receptor-dependent STAT3 activation.

    Directory of Open Access Journals (Sweden)

    Shin-Ei Cheng

    Full Text Available BACKGROUND: Up-regulation of cyclooxygenase (COX-2 and its metabolite prostaglandin E(2 (PGE(2 are frequently implicated in lung inflammation. Extracellular nucleotides, such as ATP have been shown to act via activation of P2 purinoceptors, leading to COX-2 expression in various inflammatory diseases, such as lung inflammation. However, the mechanisms underlying ATP-induced COX-2 expression and PGE(2 release remain unclear. PRINCIPAL FINDINGS: Here, we showed that ATPγS induced COX-2 expression in A549 cells revealed by western blot and real-time PCR. Pretreatment with the inhibitors of P2 receptor (PPADS and suramin, PKC (Gö6983, Gö6976, Ro318220, and Rottlerin, ROS (Edaravone, NADPH oxidase [diphenyleneiodonium chloride (DPI and apocynin], Jak2 (AG490, and STAT3 [cucurbitacin E (CBE] and transfection with siRNAs of PKCα, PKCι, PKCμ, p47(phox, Jak2, STAT3, and cPLA(2 markedly reduced ATPγS-induced COX-2 expression and PGE(2 production. In addition, pretreatment with the inhibitors of P2 receptor attenuated PKCs translocation from the cytosol to the membrane in response to ATPγS. Moreover, ATPγS-induced ROS generation and p47(phox translocation was also reduced by pretreatment with the inhibitors of P2 receptor, PKC, and NADPH oxidase. On the other hand, ATPγS stimulated Jak2 and STAT3 activation which were inhibited by pretreatment with PPADS, suramin, Gö6983, Gö6976, Ro318220, GF109203X, Rottlerin, Edaravone, DPI, and apocynin in A549 cells. SIGNIFICANCE: Taken together, these results showed that ATPγS induced COX-2 expression and PGE(2 production via a P2 receptor/PKC/NADPH oxidase/ROS/Jak2/STAT3/cPLA(2 signaling pathway in A549 cells. Increased understanding of signal transduction mechanisms underlying COX-2 gene regulation will create opportunities for the development of anti-inflammation therapeutic strategies.

  19. High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery

    Directory of Open Access Journals (Sweden)

    Qian Yang

    2015-01-01

    Full Text Available Objective. Ischemia/reperfusion (I/R injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB. This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb, a hemoglobin-based oxygen carrier (HBOC, can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v provided a significant protection on the I/R heart, whereas the high-dose PolyPHb (3%, w/v did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS production, reduced superoxide dismutase (SOD activity, and elevated malonaldehyde (MDA formation. Consistent with the increased oxidative stress, the NAD(PH oxidase activity and subunits expression, including gp91phox, p47phox, p67phox, and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(PH oxidase-induced ROS and resultant endothelial dysfunction.

  20. Efferocytosis is impaired in Gaucher macrophages.

    Science.gov (United States)

    Aflaki, Elma; Borger, Daniel K; Grey, Richard J; Kirby, Martha; Anderson, Stacie; Lopez, Grisel; Sidransky, Ellen

    2017-04-01

    Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide-laden macrophages resulting from impaired digestion of aged erythrocytes or apoptotic leukocytes. Studies of macrophages from patients with type 1 Gaucher disease with genotypes N370S/N370S, N370S/L444P or N370S/c.84dupG revealed that Gaucher macrophages have impaired efferocytosis resulting from reduced levels of p67 phox and Rab7. The decreased Rab7 expression leads to impaired fusion of phagosomes with lysosomes. Moreover, there is defective translocation of p67 phox to phagosomes, resulting in reduced intracellular production of reactive oxygen species. These factors contribute to defective deposition and clearance of apoptotic cells in phagolysosomes, which may have an impact on the inflammatory response and contribute to the organomegaly and inflammation seen in patients with Gaucher disease. Copyright© Ferrata Storti Foundation.

  1. Rac-1 as a new therapeutic target in cerebro- and cardio-vascular diseases.

    Science.gov (United States)

    Carrizzo, Albino; Forte, Maurizio; Lembo, Maria; Formisano, Luigi; Puca, Annibale A; Vecchione, Carmine

    2014-01-01

    Growing evidence indicates that overproduction of reactive oxygen species (ROS) plays a prominent role in the development of cardio- and cerebro-vascular diseases. Among the mechanisms identified to produce oxidative stress in the vascular wall, those mediated by membrane-bound NAD(P)H oxidases represent a major one. NAD(P)H oxidases are a family of enzymes that generate ROS both in phagocytic and non-phagocytic cell types. Vascular NAD(P)H oxidase contains the membrane-bound subunits Nox1, Nox2 (gp91phox), Nox4 and p22phox, the catalytic site of the oxidase, and the cytosolic components p47phox and p67phox. Rac1 (Ras-related C3 botulinum toxin substrate1) is a small GTPase essential for the assembly and activation of NADPH oxidase. Several molecular and cellular studies have reported the involvement of Rac1 in different cardiovascular pathologies, such as vascular smooth muscle proliferation, cardiomyocyte hypertrophy, endothelial cell shape change, atherosclerosis and endothelial dysfunction in hypertension. In addition, increased activation of NADPH oxidase by Rac1 has been reported in animals and humans after myocardial infarction and heart failure. The Rac1/NADPH pathway has also been found involved in different pathologies of the cerebral district, such as ischemic stroke, cognitive impairment, subaracnoid hemorrhage and neuronal oxidative damage typical of several neurodegenerative disorders. In addition, thrombotic events are an important step in the onset of cardio- and cerebrovascular diseases. Rac1 has been found involved also in platelet activation, inducing actin polymerization and lamellipodia formation, which are necessary steps for platelet aggregation. Taken together, the evidence candidates Rac1 as a new pharmacological target of cardiovascular and cerebrovascular diseases. Although the involvement of Rac1 in the beneficial pleiotropic effects of drugs such as statins is well known, and the onset of numerous side effects has raised concern for the

  2. TASK-2 Channels Contribute to pH Sensitivity of Retrotrapezoid Nucleus Chemoreceptor Neurons

    Science.gov (United States)

    Wang, Sheng; Benamer, Najate; Zanella, Sébastien; Kumar, Natasha N.; Shi, Yingtang; Bévengut, Michelle; Penton, David; Guyenet, Patrice G.; Lesage, Florian

    2013-01-01

    Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN) display properties expected of central respiratory chemoreceptors; they are directly activated by CO2/H+ via an unidentified pH-sensitive background K+ channel and, in turn, facilitate brainstem networks that control breathing. Here, we used a knock-out mouse model to examine whether TASK-2 (K2P5), an alkaline-activated background K+ channel, contributes to RTN neuronal pH sensitivity. We made patch-clamp recordings in brainstem slices from RTN neurons that were identified by expression of GFP (directed by the Phox2b promoter) or β-galactosidase (from the gene trap used for TASK-2 knock-out). Whereas nearly all RTN cells from control mice were pH sensitive (95%, n = 58 of 61), only 56% of GFP-expressing RTN neurons from TASK-2−/− mice (n = 49 of 88) could be classified as pH sensitive (>30% reduction in firing rate from pH 7.0 to pH 7.8); the remaining cells were pH insensitive (44%). Moreover, none of the recorded RTN neurons from TASK-2−/− mice selected based on β-galactosidase activity (a subpopulation of GFP-expressing neurons) were pH sensitive. The alkaline-activated background K+ currents were reduced in amplitude in RTN neurons from TASK-2−/− mice that retained some pH sensitivity but were absent from pH-insensitive cells. Finally, using a working heart–brainstem preparation, we found diminished inhibition of phrenic burst amplitude by alkalization in TASK-2−/− mice, with apneic threshold shifted to higher pH levels. In conclusion, alkaline-activated TASK-2 channels contribute to pH sensitivity in RTN neurons, with effects on respiration in situ that are particularly prominent near apneic threshold. PMID:24107938

  3. Targeting NADPH oxidase decreases oxidative stress in the transgenic sickle cell mouse penis.

    Science.gov (United States)

    Musicki, Biljana; Liu, Tongyun; Sezen, Sena F; Burnett, Arthur L

    2012-08-01

    Sickle cell disease (SCD) is a state of chronic vasculopathy characterized by endothelial dysfunction and increased oxidative stress, but the sources and mechanisms responsible for reactive oxygen species (ROS) production in the penis are unknown. We evaluated whether SCD activates NADPH oxidase, induces endothelial nitric oxide synthase (eNOS) uncoupling, and decreases antioxidants in the SCD mouse penis. We further tested the hypothesis that targeting NADPH oxidase decreases oxidative stress in the SCD mouse penis. SCD transgenic (sickle) mice were used as an animal model of SCD. Hemizygous (hemi) mice served as controls. Mice received an NADPH oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Penes were excised at baseline for molecular studies. Markers of oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NADPH oxidase subunits p67(phox) , p47(phox) , and gp91(phox) ), and enzymatic antioxidants (superoxide dismutase [SOD]1, SOD2, catalase, and glutathione peroxidase-1 [GPx1]) were measured by Western blot in penes. Sources of ROS, oxidative stress, and enzymatic antioxidants in the SCD penis. Relative to hemi mice, SCD increased (Ppenis. Apocynin treatment of sickle mice reversed (P0.05) prevented eNOS uncoupling in the penis. Apocynin treatment of hemi mice did not affect any of these parameters. NADPH oxidase and eNOS uncoupling are sources of oxidative stress in the SCD penis; decreased GPx1 further contributes to oxidative stress. Inhibition of NADPH oxidase upregulation decreases oxidative stress, implying a major role for NADPH oxidase as a ROS source and a potential target for improving vascular function in the SCD mouse penis. © 2012 International Society for Sexual Medicine.

  4. Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia.

    Science.gov (United States)

    Shi, Guang-Xia; Wang, Xue-Rui; Yan, Chao-Qun; He, Tian; Yang, Jing-Wen; Zeng, Xiang-Hong; Xu, Qian; Zhu, Wen; Du, Si-Qi; Liu, Cun-Zhi

    2015-12-10

    In the current study, we aimed to investigate whether NADPH oxidase, a major ROS-producing enzyme, was involved in the antioxidant effect of acupuncture on cognitive impairment after cerebral ischaemia. The cognitive function, infract size, neuron cell loss, level of superoxide anion and expression of NADPH oxidase subunit in hippocampus of two-vessel occlusion (2VO) rats were determined after 2-week acupuncture. Furthermore, the cognitive function and production of O2(-) were determined in the presence and absence of NADPH oxidase agonist (TBCA) and antagonist (Apocynin). The effect of acupuncture on cognitive function after cerebral ischaemia in gp91phox-KO mice was evaluated by Morris water maze. Acupuncture reduced infarct size, attenuated overproduction of O2(-), and reversed consequential cognitive impairment and neuron cell loss in 2VO rats. The elevations of gp91phox and p47phox after 2VO were significantly decreased after acupuncture treatment. However, no differences of gp91phox mRNA were found among any experimental groups. Furthermore, these beneficial effects were reversed by TBCA, whereas apocynin mimicked the effect of acupuncture by improving cognitive function and decreasing O2(-) generation. Acupuncture failed to improve the memory impairment in gp91phox KO mice. Full function of the NADPH oxidase enzyme plays an important role in neuroprotective effects against cognitive impairment via inhibition of NAPDH oxidase-mediated oxidative stress.

  5. Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy

    Science.gov (United States)

    Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Veeraveedu, Punniyakoti T; Nakamura, Takashi; Arozal, Wawaimuli; Sari, Flori R; Giridharan, Vijayasree V; Soetikno, Vivian; Palaniyandi, Suresh S; Harima, Meilei; Suzuki, Kenji; Nagata, Masaki; Kodama, Makoto; Watanabe, Kenichi

    2012-01-01

    Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47phox, p67phox, gp91phox and Nox4), fibrosis markers (TGF-β1 and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis. PMID:22268705

  6. Volume-sensitive NADPH oxidase activity and taurine efflux in NIH3T3 mouse fibroblasts

    DEFF Research Database (Denmark)

    Friis, Martin Barfred; Vorum, Katrine Gribel; Lambert, Ian Henry

    2008-01-01

    Reactive oxygen species (ROS) are produced in NIH3T3 fibroblasts during hypotonic stress, and H(2)O(2) potentiates the concomitant release of the organic osmolyte taurine (Lambert IH. J Membr Biol 192: 19-32, 2003). The increase in ROS production [5-(and-6)-carboxy-2', 7'-dichlorodihydrofluorescein......+-mobilizing agonist ATP (10 microM) potentiates the release of taurine but has no effect on ROS production under hypotonic conditions. On the other hand, addition of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 100 nM) or the lipid messenger lysophosphatidic acid (LPA, 10 n......M) potentiates the swelling-induced taurine release as well as the ROS production. Overexpression of Rac1 or p47 phox or p47 phox knockdown [small interfering (si)RNA] had no effect on the swelling-induced ROS production or taurine release. NOX4 knockdown (siRNA) impairs the increase in the ROS production...

  7. Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

    Science.gov (United States)

    Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

    2013-01-01

    The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

  8. Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation.

    Directory of Open Access Journals (Sweden)

    Elaine Hatanaka

    Full Text Available The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47 (phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47 (phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts.

  9. NCBI nr-aa BLAST: CBRC-OPRI-01-1187 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-1187 ref|XP_344240.3| PREDICTED: similar to Paired mesoderm homeobox p...rotein 2B (Paired-like homeobox 2B) (PHOX2B homeodomain protein) (Neuroblastoma Phox) (NBPhox) [Rattus norvegicus] XP_344240.3 8.8 38% ...

  10. Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis.

    Science.gov (United States)

    Matyas, Csaba; Varga, Zoltan V; Mukhopadhyay, Partha; Paloczi, Janos; Lajtos, Tamas; Erdelyi, Katalin; Nemeth, Balazs T; Nan, Mintong; Hasko, Gyorgy; Gao, Bin; Pacher, Pal

    2016-06-01

    Alcoholic cardiomyopathy in humans develops in response to chronic excessive alcohol consumption; however, good models of alcohol-induced cardiomyopathy in mice are lacking. Herein we describe mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH) feeding and characterize detailed hemodynamic alterations, mitochondrial function, and redox signaling in these models. Mice were fed a liquid diet containing 5% EtOH for 10, 20, and 40 days (d) combined with single or multiple EtOH binges (5 g/kg body wt). Isocalorically pair-fed mice served as controls. Left ventricular (LV) function and morphology were assessed by invasive pressure-volume conductance approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, 3-nitrotyrosine (3-NT) levels, gene expression of markers of oxidative stress (gp91phox, p47phox), mitochondrial biogenesis (PGC1α, peroxisome proliferator-activated receptor α), and fibrosis were examined. Cardiac steatosis and fibrosis were investigated by histological/immunohistochemical methods. Chronic and binge EtOH feeding (already in 10 days EtOH plus single binge group) was characterized by contractile dysfunction (decreased slope of end-systolic pressure-volume relationship and preload recruitable stroke work), impaired relaxation (decreased time constant of LV pressure decay and maximal slope of systolic pressure decrement), and vascular dysfunction (impaired arterial elastance and lower total peripheral resistance). This was accompanied by enhanced myocardial oxidative/nitrative stress (3-NT; gp91phox; p47phox; angiotensin II receptor, type 1a) and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, excessive cardiac steatosis, and higher mortality. Collectively, chronic plus binge EtOH feeding in mice leads to alcohol-induced cardiomyopathies (National Institute on Alcohol Abuse and Alcoholism models) characterized by increased myocardial oxidative

  11. Empirical algorithms to estimate water column pH in the Southern Ocean

    Science.gov (United States)

    Williams, N. L.; Juranek, L. W.; Johnson, K. S.; Feely, R. A.; Riser, S. C.; Talley, L. D.; Russell, J. L.; Sarmiento, J. L.; Wanninkhof, R.

    2016-04-01

    Empirical algorithms are developed using high-quality GO-SHIP hydrographic measurements of commonly measured parameters (temperature, salinity, pressure, nitrate, and oxygen) that estimate pH in the Pacific sector of the Southern Ocean. The coefficients of determination, R2, are 0.98 for pH from nitrate (pHN) and 0.97 for pH from oxygen (pHOx) with RMS errors of 0.010 and 0.008, respectively. These algorithms are applied to Southern Ocean Carbon and Climate Observations and Modeling (SOCCOM) biogeochemical profiling floats, which include novel sensors (pH, nitrate, oxygen, fluorescence, and backscatter). These algorithms are used to estimate pH on floats with no pH sensors and to validate and adjust pH sensor data from floats with pH sensors. The adjusted float data provide, for the first time, seasonal cycles in surface pH on weekly resolution that range from 0.05 to 0.08 on weekly resolution for the Pacific sector of the Southern Ocean.

  12. NOX2 Inhibition Impairs Early Muscle Gene Expression Induced by a Single Exercise Bout.

    Science.gov (United States)

    Henríquez-Olguín, Carlos; Díaz-Vegas, Alexis; Utreras-Mendoza, Yildy; Campos, Cristian; Arias-Calderón, Manuel; Llanos, Paola; Contreras-Ferrat, Ariel; Espinosa, Alejandra; Altamirano, Francisco; Jaimovich, Enrique; Valladares, Denisse M

    2016-01-01

    Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg) or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47(phox) levels were significantly upregulated by exercise in flexor digitorum brevis (FDB). Moreover, exercise significantly increased NOX2 complex assembly (p47(phox)-gp91(phox) interaction) demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx), citrate synthase (CS), mitochondrial transcription factor A (tfam) and interleukin-6 (IL-I6) in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p < 0.001). These results were corroborated using gp91-dstat in an in vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

  13. Functional and genetic characterization of two extremely rare cases of Williams-Beuren syndrome associated with chronic granulomatous disease

    NARCIS (Netherlands)

    Stasia, Marie J.; Mollin, Michele; Martel, Cecile; Satre, Veronique; Coutton, Charles; Amblard, Florence; Vieville, Gaelle; van Montfrans, Joris M.; Boelens, Jaap J.; Veenstra-Knol, Hermine E.; van Leeuwen, Karen; de Boer, Martin; Brion, Jean-Paul; Roos, Dirk

    2013-01-01

    Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder with multi-systemic manifestations, caused by a heterozygous segmental deletion of 1.55-1.83Mb at chromosomal band 7q11.23. The deletion can include the NCF1 gene that encodes the p47(phox) protein, a component of the leukocyte NADPH

  14. Event-free survival of infants and toddlers enrolled in the HR-NBL-1/SIOPEN trial is associated with the level of neuroblastoma mRNAs at diagnosis.

    Science.gov (United States)

    Corrias, Maria V; Parodi, Stefano; Tchirkov, Andrei; Lammens, Tim; Vicha, Ales; Pasqualini, Claudia; Träger, Catarina; Yáñez, Yania; Dallorso, Sandro; Varesio, Luigi; Luksch, Roberto; Laureys, Genevieve; Valteau-Couanet, Dominique; Canete, Adela; Pöetschger, Ulrike; Ladenstein, Ruth; Burchill, Susan A

    2018-07-01

    The purpose of this study was to evaluate whether levels of neuroblastoma mRNAs in bone marrow and peripheral blood from stage M infants (≤12 months of age at diagnosis, MYCN amplified) and toddlers (between 12 and 18 months, any MYCN status) predict event-free survival (EFS). Bone marrow aspirates and peripheral blood samples from 97 infants/toddlers enrolled in the European High-Risk Neuroblastoma trial were collected at diagnosis in PAXgene ™ blood RNA tubes. Samples were analyzed by reverse transcription quantitative polymerase chain reaction according to standardized procedures. Bone marrow tyrosine hydroxylase (TH) or paired-like homeobox 2b (PHOX2B) levels in the highest tertile were associated with worse EFS; hazard ratios, adjusted for age and MYCN status, were 1.5 and 1.8 respectively. Expression of both TH and PHOX2B in the highest tertile predicted worse outcome (p = 0.015), and identified 20 (23%) infants/toddlers with 5-year EFS of 20% (95%CI: 4%-44%). Prognostic significance was maintained after adjusting for over-fitting bias (p = 0.038), age and MYCN status. In peripheral blood, PHOX2B levels in the highest tertile predicted a two-fold increased risk of an event (p = 0.032), and identified 23 (34%) infants/toddlers with 5-year EFS of 29% (95%CI: 12%-48%). Time-dependent receiver operating characteristic analysis confirmed the prognostic value of combined TH and PHOX2B in bone marrow and of PHOX2B in peripheral blood during the first year of follow-up. High levels of bone marrow TH and PHOX2B and of peripheral blood PHOX2B at diagnosis allow early identification of a group of high-risk infant and toddlers with neuroblastoma who may be candidates for alternative treatments. Integration with additional biomarkers, as well as validation in additional international trials is warranted. © 2018 Wiley Periodicals, Inc.

  15. Detection of non-ΔGT NCF-1 mutations in chronic granulomatous disease

    DEFF Research Database (Denmark)

    Jakobsen, Marianne Antonius; Pedersen, Svend Stenvang; Barington, Torben

    2009-01-01

    to have mutations in NCF-1 encoding p47-phox, which is part of the cytosolic component of NADPH oxidase. More than 94% of these patients share the same mutation, a 2 bp GT deletion in the GTGT dinucleotide repeat in the start of exon 2. The presence of two pseudogenes more than 98% homologous...

  16. Combination Therapy with Losartan and Pioglitazone Additively Reduces Renal Oxidative and Nitrative Stress Induced by Chronic High Fat, Sucrose, and Sodium Intake

    Directory of Open Access Journals (Sweden)

    Xiang Kong

    2012-01-01

    Full Text Available We recently showed that combination therapy with losartan and pioglitazone provided synergistic effects compared with monotherapy in improving lesions of renal structure and function in Sprague-Dawley rats fed with a high-fat, high-sodium diet and 20% sucrose solution. This study was designed to explore the underlying mechanisms of additive renoprotection provided by combination therapy. Losartan, pioglitazone, and their combination were orally administered for 8 weeks. The increased level of renal malondialdehyde and expression of nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox and nitrotyrosine as well as the decreased total superoxide dismutase activity and copper, zinc-superoxide dismutase expression were tangible evidence for the presence of oxidative and nitrative stress in the kidney of model rats. Treatment with both drugs, individually and in combination, improved these abnormal changes. Combination therapy showed synergistic effects in reducing malondialdehyde level, p47phox, and nitrotyrosine expression to almost the normal level compared with monotherapy. All these results suggest that the additive renoprotection provided by combination therapy might be attributed to a further reduction of oxidative and nitrative stress.

  17. Geomorphology of comet 67P/Churyumov–Gerasimenko

    Science.gov (United States)

    Birch, Samuel P. D.; Tang, Y.; Hayes, A. G.; Kirk, Randolph L.; Bodewitz, D.; Campins, H.; Fernandez, Y.; de Freitas Bart, R.; Kutsop, N. W.; Sierks, H.; Soderblom, J. M.; Squyres, S. W.; Vincent, J.-B.

    2017-01-01

    We present a global geomorphological map of comet 67P/Churyumov–Gerasimenko (67P/C-G) using data acquired by the Rosetta Orbiter’s OSIRIS Narrow Angle Camera. The images used in our study were acquired between 2014 August and 2015 May, before 67P/C-G passed through perihelion. Imagery of the Southern hemisphere was included in our study, allowing us to compare the contrasting hemispheres of 67P/C-G in a single study. Our work also puts into greater context the morphologies studied in previous works, and also the morphologies observed on previously visited cometary nuclei. Relative to other nuclei, 67P/C-G appears most similar to 81P/Wild 2, with a topographically heterogeneous surface dominated by smooth-floored pits. Our mapping describes the landscapes of 67P/C-G when they were first observed by Rosetta, and our map can be used to detect changes in surface morphologies after its perihelion passage. Our mapping reveals strong latitudinal dependences for emplaced units and a highly heterogeneous surface. Layered bedrock units that represent the exposed nucleus of 67P/C-G are dominant at southern latitudes, while topographically smooth, dust covered regions dominate the Northern hemisphere. Equatorial latitudes are dominated by smooth terrain units that show evidence for flow structures. We observe no obvious differences between the comet’s two lobes, with the only longitudinal variations being the Imhotep and Hatmehit basins. These correlations suggest a strong seasonal forcing on the surface evolution of 67P/C-G, where materials are transported from the Southern hemisphere to Northern hemisphere basins over multiple orbital time-scales.

  18. NOX2 inhibition impairs early muscle gene expression induced by a single exercise bout

    Directory of Open Access Journals (Sweden)

    Carlos Henríquez-Olguín

    2016-07-01

    Full Text Available Reactive oxygen species (ROS participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2 in the molecular response to physical exercise in skeletal muscle. BALB/c mice, pre-treated with a NOX2 inhibitor, apocynin, (3 mg/kg or vehicle for 3 days, were swim-exercised for 60 min. Phospho-p47phox levels were significantly upregulated by exercise in flexor digitorum brevis (FDB. Moreover, exercise significantly increased NOX2 complex assembly (p47phox-gp91phox interaction demonstrated by both proximity ligation assay and co-immunoprecipitation. Exercise-induced NOX2 activation was completely inhibited by apocynin treatment. As expected, exercise increased the mRNA levels of manganese superoxide dismutase (MnSOD, glutathione peroxidase (GPx, citrate synthase (CS, mitochondrial transcription factor A (tfam and interleukin-6 (IL-6 in FDB muscles. Moreover, the apocynin treatment was associated to a reduced activation of p38 MAP kinase, ERK 1/2, and NF-κB signaling pathways after a single bout of exercise. Additionally, the increase in plasma IL-6 elicited by exercise was decreased in apocynin-treated mice compared with the exercised vehicle-group (p<0.001. These results were corroborated using gp91-dstat in an in-vitro exercise model. In conclusion, NOX2 inhibition by both apocynin and gp91dstat, alters the intracellular signaling to exercise and electrical stimuli in skeletal muscle, suggesting that NOX2 plays a critical role in molecular response to an acute exercise.

  19. 67P Through the Lens of Art

    Science.gov (United States)

    Smirnova, Ekaterina; ESA, The Open University, OSIRIS

    2016-10-01

    I am an artist, who is deeply inspired by science. Since the landing of the robotic probe Philae on the comet I have been working on an art project called 67P. Having a goal of discovering our place in the universe, I chose ESA's Rosetta mission as a successful example of such discovery. During the conference I'd like to expand the dialogue to include an artistic research of the comet 67P. I invite the participants to explore 67P through the lens of art and create inspirational reciprocity in between two spheres, creative and scientific. New ideas often originate when two vocabularies are smashed together. Via this path we perhaps will be able to get a new way of exploring the topic of cometary science.During the conference I'd like to present:- 67p artwork in the art section- poster outlining the major focuses of my projectArt project focuses:- 67P water:In the art studio I re-create water that is close in composition to the water on the comet, by enriching it with D2O. With this water I paint large scale paintings, based on the photographs by Rosetta (OSIRIS, Nav. Cam.).- spectroscopic data:Inspired by data from OSIRIS, I create an additional layer to my work using augmented reality to reveal a "hidden" from the view layer. I am making a parallel with the idea that some scientific information could be viewed only by using special instruments, in this case - instruments on board of Rosetta spacecraft, such as OSIRIS. You will be able to see a virtual layer on top of my paintings using a readily available instrument - your cellphone. Red, Green and Blue colors, of particular wavelength, will be introduced to the monochromatic paintings.- magnetometer readings:International music collaboration inspired by the "Singing comet" composition, based on the magnetometer data of 67P will be offered for any interested spectators.- 67P smell:In collaboration with The Open University, UK, postcards with a smell of the comet were created, introducing the chemical components of

  20. Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages.

    Science.gov (United States)

    Kim, Jun Sub; Kim, Jae Gyu; Jeon, Chan Young; Won, Ha Young; Moon, Mi Young; Seo, Ji Yeon; Kim, Jong Il; Kim, Jaebong; Lee, Jae Yong; Choi, Soo Young; Park, Jinseu; Yoon Park, Jung Han; Ha, Kwon Soo; Kim, Pyeung Hyeun; Park, Jae Bong

    2005-12-31

    Rac1 and Rac2 are essential for the control of oxidative burst catalyzed by NADPH oxidase. It was also documented that Rho is associated with the superoxide burst reaction during phagocytosis of serum- (SOZ) and IgG-opsonized zymosan particles (IOZ). In this study, we attempted to reveal the signal pathway components in the superoxide formation regulated by Rho GTPase. Tat-C3 blocked superoxide production, suggesting that RhoA is essentially involved in superoxide formation during phagocytosis of SOZ. Conversely SOZ activated both RhoA and Rac1/2. Inhibition of RhoA-activated kinase (ROCK), an important downstream effector of RhoA, by Y27632 and myosin light chain kinase (MLCK) by ML-7 abrogated superoxide production by SOZ. Extracellular signaling-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were activated during phagocytosis of SOZ, and Tat-C3 and SB203580 reduced ERK1/2 and p38 MAPK activation, suggesting that RhoA and p38 MAPK may be upstream regulators of ERK1/2. Inhibition of ERK1/2, p38 MAPK, phosphatidyl inositol 3-kinase did not block translocation of RhoA to membranes, suggesting that RhoA is upstream to these kinases. Inhibition of RhoA by Tat-C3 blocked phosphorylation of p47(PHOX). Taken together, RhoA, ROCK, p38MAPK, ERK1/2, and p47(PHOX) may be subsequently activated, leading to activation of NADPH oxidase to produce superoxide.

  1. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  2. Time course investigation of PPARα- and Kupffer cell-dependent effects of WY-14,643 in mouse liver using microarray gene expression

    International Nuclear Information System (INIS)

    Woods, Courtney G.; Kosyk, Oksana; Bradford, Blair U.; Ross, Pamela K.; Burns, Amanda M.; Cunningham, Michael L.; Qu Pingping; Ibrahim, Joseph G.; Rusyn, Ivan

    2007-01-01

    Administration of peroxisome proliferators to rodents causes proliferation of peroxisomes, induction of β-oxidation enzymes, hepatocellular hypertrophy and hyperplasia, with chronic exposure ultimately leading to hepatocellular carcinomas. Many responses associated with peroxisome proliferators are nuclear receptor-mediated events involving peroxisome proliferators-activated receptor alpha (PPARα). A role for nuclear receptor-independent events has also been shown, with evidence of Kupffer cell-mediated free radical production, presumably through NAPDH oxidase, induction of redox-sensitive transcription factors involved in cytokine production and cytokine-mediated cell replication following acute treatment with peroxisome proliferators in rodents. Recent studies have demonstrated, by using p47 phox -null mice which are deficient in NADPH oxidase, that this enzyme is not related to the phenotypic events caused by prolonged administration of peroxisome proliferators. In an effort to determine the timing of the transition from Kupffer cell-to PPARα-dependent modulation of peroxisome proliferator effects, gene expression was assessed in liver from Pparα-null, p47 phox -null and corresponding wild-type mice following treatment with 4-chloro-6-(2,3-xylidino)-pyrimidynylthioacetic acid (WY-14,643) for 8 h, 24 h, 72 h, 1 week or 4 weeks. WY-14,643-induced gene expression in p47 phox -null mouse liver differed substantially from wild-type mice at acute doses and striking differences in baseline expression of immune related genes were evident. Pathway mapping of genes that respond to WY-14,643 in a time- and dose-dependent manner demonstrates suppression of immune response, cell death and signal transduction and promotion of lipid metabolism, cell cycle and DNA repair. Furthermore, these pathways were largely dependent on PPARα, not NADPH oxidase demonstrating a temporal shift in response to peroxisome proliferators. Overall, this study shows that NADPH oxidase

  3. Neoplasias astrocitárias e correlação com as proteínas p53 mutada e Ki-67 Astrocytic neoplasms and correlation with mutate p53 and Ki-67 proteins

    Directory of Open Access Journals (Sweden)

    Gustavo Rassier Isolan

    2005-12-01

    Full Text Available As neoplasias astrocitárias correspondem a 60% dos tumores do sistema nervoso central, sendo o estudo da biologia molecular um importante passo para a compreensão da gênese e comportamento biológico destas doenças. As proteínas Ki-67, que é um marcador de proliferação celular, e p53, que é o produto do gene supressor de tumor de mesmo nome, são importantes marcadores tumorais. O objetivo deste estudo foi identificar e quantificar as proteínas Ki-67 e produto do gene supressor de tumor TP53 em diferentes graus de malignidade das neoplasias astrocitárias, bem como analisar suas relações com idade e sexo. Foram estudadas por imuno-histoquímica as proteínas Ki-67 e p53 em 47 pacientes com neoplasias astrocitárias ressecadas cirurgicamente, classificadas previamente e revisadas quanto ao grau de malignidade, de acordo com o proposto pela Organização Mundial da Saúde. Os núcleos celulares imunomarcados foram quantificados no programa Imagelab-softium pela razão paramétrica absoluta entre os núcleos de células positivas e o número total de células tumorais, sendo contadas 1000 células. O delineamento utilizado foi transversal não controlado. Para análise estatística as variáveis foram divididas em grupos, que para a Ki-67 foram ausente, 5% e para a p53 foram ausente (0, The astrocytic neoplasms respond by 60% of the central nervous system tumors, being the study of the molecular biology an important step for the understanding of the genesis and biological behavior of these diseases. The Ki-67 proteins, which are markers of the cellular proliferation, and p53, which is the product of the tumor suppressor gene TP53, are both important tumoral markers. This study intends to identify and quantify the Ki-67 and p53 proteins in astrocytic tumors of different grades of malignancy, as well as to analyze their relations with age and gender. Ki-67 and p53 proteins in 47 patients with surgically resected astrocytic neoplasms were

  4. Hepatoprotective Effects of Ixora parviflora Extract against Exhaustive Exercise-Induced Oxidative Stress in Mice

    Directory of Open Access Journals (Sweden)

    Chi-Chang Huang

    2013-09-01

    Full Text Available Ixora parviflora, a species of the Rubiaceae, is rich in polyphenols and flavonoids, and has been traditionally used as a folk medicine. An I. parviflora extract (IPE has great antioxidant activity in vitro, including a scavenging effect on superoxide radicals, reducing power, and ferrous ion-chelating ability. However, whether IPE is efficacious against oxidative damage in vivo is not known. The purpose of this study was to determine the protective effects of IPE treatment on hepatic oxidative stress and antioxidant defenses after exhaustive exercise in mice. Fifty male C57BL/6 mice (6 week old were randomly divided into five groups and designated a sedentary control with vehicle (C, and exhaustive exercise with vehicle (IPE0, low dosage (IPE10, medium dosage (IPE50 and high dosage (IPE100 of IPE at 0, 10, 50, and 100 mg/kg, respectively. After a single bout of exhaustive swimming exercise challenge, levels of blood ammonia and creatine kinase (CK, and hepatic superoxide dismutase (SOD protein expression, thiobarbituric acid-reactive substance (TBARS, and gp91phox, p22phox, and p47phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH oxidase expressions in the IPE0 group were significantly affected compared to those of the C group, but they were all significantly inhibited by the IPE treatments. Results of the present in vivo study in mice indicate that I. parviflora extract possesses antioxidative and hepatoprotective potential following exhaustive exercise.

  5. Squamosamide derivative FLZ protects dopaminergic neurons against inflammation-mediated neurodegeneration through the inhibition of NADPH oxidase activity

    Directory of Open Access Journals (Sweden)

    Wilson Belinda

    2008-05-01

    Full Text Available Abstract Background Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD through over-activation of microglia, which consequently causes the excessive production of proinflammatory and neurotoxic factors, and impacts surrounding neurons and eventually induces neurodegeneration. Hence, prevention of microglial over-activation has been shown to be a prime target for the development of therapeutic agents for inflammation-mediated neurodegenerative diseases. Methods For in vitro studies, mesencephalic neuron-glia cultures and reconstituted cultures were used to investigate the molecular mechanism by which FLZ, a squamosamide derivative, mediates anti-inflammatory and neuroprotective effects in both lipopolysaccharide-(LPS- and 1-methyl-4-phenylpyridinium-(MPP+-mediated models of PD. For in vivo studies, a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-(MPTP- induced PD mouse model was used. Results FLZ showed potent efficacy in protecting dopaminergic (DA neurons against LPS-induced neurotoxicity, as shown in rat and mouse primary mesencephalic neuronal-glial cultures by DA uptake and tyrosine hydroxylase (TH immunohistochemical results. The neuroprotective effect of FLZ was attributed to a reduction in LPS-induced microglial production of proinflammatory factors such as superoxide, tumor necrosis factor-α (TNF-α, nitric oxide (NO and prostaglandin E2 (PGE2. Mechanistic studies revealed that the anti-inflammatory properties of FLZ were mediated through inhibition of NADPH oxidase (PHOX, the key microglial superoxide-producing enzyme. A critical role for PHOX in FLZ-elicited neuroprotection was further supported by the findings that 1 FLZ's protective effect was reduced in cultures from PHOX-/- mice, and 2 FLZ inhibited LPS-induced translocation of the cytosolic subunit of p47PHOX to the membrane and thus inhibited the activation of PHOX. The neuroprotective effect of FLZ demonstrated in primary neuronal

  6. TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation.

    Science.gov (United States)

    Wang, Haibo; Han, Xiaokun; Wittchen, Erika S; Hartnett, M Elizabeth

    2016-01-01

    -catenin transcriptional inhibitors, XAV939 or JW67, or transfection with p22phox siRNA and compared to appropriate controls. Compared to the non-lasered control, TNF-α and VEGF protein were increased in the RPE/choroids in a murine laser-induced CNV model (pROS generation and increased activation of NOX4, an isoform of NADPH oxidase; both were prevented by pretreatment with the apocynin or VAS2870 or knockdown of p22phox, a subunit of NADPH oxidase. TNF-α treatment increased VEGF expression (pROS-dependent activation of β-catenin signaling. These results provide mechanisms of crosstalk between inflammatory mediator, TNF-α, and ROS in RPE cells.

  7. Effects of telmisartan on the expression of NADPH oxidase subunits in the myocardium of type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Jia-wei LI

    2011-10-01

    Full Text Available Objective To explore the effect of telmisartan on the expression of NADPH oxidase subunits p22phox and NOX4 in the myocardiam of type 2 diabetic rats.Methods Thirty-six male Wistar rats were randomly divided into two groups: normal control group(group A,n=10,diabetic model group(n=26.Type 2 diabetic model was established by high-fat and high-sugar diet followed by intraperitoneal injection of a low dose of streptozotocin(STZ.After the model was reproduced successfully,20 diabetic rats were randomly divided into diabetic subgroup(group B,n=10 and telmisartan-treated subgroup(group C,n=10.Rats in group C were orally administered telmisartan(5mg/kg/d,and rats in group A and B were given equivalent volume of normal saline.All rats were sacrificed 12 weeks after treatment.The mRNA expressions of myocardial p22phox and NOX4 were detected by real-time fluorescence quantitative PCR,and the protein expressions of myocardial connective tissue growth factor(CTGF and copper-zinc-superoxide dismutase(Cu-Zn-SOD were detected by immunohistochemical staining.Results Compared with group A,the ratio of heart/body weight,the mRNA expression of myocardial p22phox and NOX4,and the protein expression of myocardial CTGF increased significantly in group B,and the protein expression of myocardial Cu-Zn-SOD decreased significantly(P 0.05.Conclusions Telmisartan can down-regulate the over-expression of myocardial NOX4 and p22phox mRNA in type 2 diabetic rats,lessen the myocardial damage induced by oxidative stress,thus plays a protective role in the myocardium of diabetic rats.

  8. Molecular biology based assessment of green tea effects on oxidative stress and cardiac remodelling in dialysis patients.

    Science.gov (United States)

    Calo, Lorenzo A; Vertolli, Ugo; Davis, Paul A; Maso, Lucia Dal; Pagnin, Elisa; Ravarotto, Verdiana; Maiolino, Giuseppe; Lupia, Mario; Seccia, Teresa M; Rossi, Gian Paolo

    2014-06-01

    Cardiovascular disease, the most common cause for morbidity and mortality in end-stage renal disease (ESRD), has prompted the exploration of multiple approaches to improve outcomes. Cardiovascular risk factors such as oxidative stress (OxSt) and cardiac remodelling are common in ESRD and dialysis patients. Green tea (GT) is well recognized as reducing OxSt. This 6 months study evaluated in 20 ESRD patients under chronic dialysis, the effect of GT treatment (1 g/day as commercially available capsule) on cellular and plasma OxSt and proliferation related markers using a molecular biology approach. Mononuclear cell p22(phox), Haeme Oxygenase (HO)-1 protein expression, and phosphorylated ERK1/2 status were evaluated in dialysis patients at baseline, after 3 and 6 months of GT treatment by Western blot analysis and plasma oxLDL by ELISA. Cardiac remodelling was assessed by echocardiographic left ventricular (LV) mass determination at baseline and at the end of the study. GT treatment reduced p22(phox) and pERK1/2 from baseline while HO-1 increased. At baseline, LV mass correlated with both p22(phox) and oxLDL. GT treatment decreased LV mass from baseline, which correlated with oxLDL. 9 patients had LV hypertrophy at baseline, which, at 6 months, was normalized in 5 and reduced in 3, showing a parallel decrease of p22(phox), pERK1/2, oxLDL and increase of HO-1. Treatment with GT decreased the expression of OxSt-related proteins tightly associated with cardiovascular disease and decreased LV mass. It appears highly likely that the addition of GT can provide a benefit in terms of cardiovascular protection in dialysis patients. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  9. NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

    2018-05-26

    Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

  10. 67P, Singing Comet

    Science.gov (United States)

    Smirnova, Ekaterina

    2017-04-01

    I would like to propose to present a short science-art-music collaboration film called "67P, Singing Comet" (5:27 min). If time of the session will allow, prior to the film I would like to make a slide show introduction to this project, highlighting the inspiration - the mission Rosetta by the European Space Agency (ESA) - and the artistic collaboration that took place in creating this piece. Inspired by the ESA Rosetta mission to the comet 67P, Ekaterina Smirnova (artist and project director, New York), Lee Mottram (clarinetist, Wales), Takuto Fukuda (composer, Japan) and Brian Hekker (video editor, New York) collaborated to create a unique atmospheric piece. Water and the origins of life throughout the Universe (specifically the Earth) is an element of the mission and the focus of Ekaterina's artistic vision. Ekaterina literally and figuratively paints a sensory assemblage using a combination of synthetic and natural elements to shape this artistic creation. To paint her watercolor works she is using a replica of the water found on the comet and implementing her own heartbeat into the music to create a recognizable inward sound of life. The Electro-Acoustic composition by Takuto Fukuda features an electronically manipulated performance by clarinetist Lee Mottram. The piece ceremoniously begins with reverberant bursts of low-register atonal bells transporting the listener to their ethereal inner origins of body and mind. The imagination takes the experience to an unknown destination as it gains speed gliding through the visual and audible textures of space and time. The comet's water similarly reacts with an ebb and flow thawing ice to potentially give life a chance as it is thrust along an orbit around the Sun. Near then far from the heat the comet forms frozen particles from vapors as it reaches it's furthest stretches creating an aerodynamic tail of icicles that slowly dissipate in a cycle that repeats itself until the comet's ultimate collision with an

  11. Neurodegenerative evidence in mice brains with cecal ligation and puncture-induced sepsis: preventive effect of the free radical scavenger edaravone.

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    Hiroki Yokoo

    Full Text Available Sepsis is a major clinical challenge and septic encephalopathy is its nasty complication. The pathogenesis and underlying mechanisms of septic encephalopathy are not well understood. This study sought to fully characterize sepsis-associated biochemical and histopathological changes in brains of mice after cecal ligation and puncture, regarded as a highly clinically relevant animal model of polymicrobial sepsis. Real-time PCR analysis showed that gene expression levels of proinflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, were significantly up-regulated in brain tissues from septic mice, but to a much lesser extent when compared with those in peripheral tissues such as lungs. Blood-brain barrier (BBB permeability was significantly increased in septic mice, as determined by the measurement of sodium fluorescein and Evans blue content. Sepsis resulted in increases in NADPH oxidase activity and expression of p47(phox and p67(phox and up-regulation of inducible nitric oxide (NO synthase in brains, indicating that superoxide, produced by NADPH oxidase, reacts with NO to form peroxynitrite, that maybe lead to the loss of BBB integrity. Light and electron microscopic examination of septic mouse brain showed serious neuronal degeneration, as indicated by hyperchromatic, shrunken, pyknotic, and electron-dense neurons. These histopathological changes were prevented by treatment with the free radical scavenger edaravone. Together, these results suggest that sepsis can lead to rapid neurodegenerative changes in brains via free radical species production and possibly subsequent injury to the BBB. We may also provide a potentially useful therapeutic tool for treating septic encephalopathy.

  12. Effect of GLP-1 on the expression of NADPH oxidase subunits in the kidney of type 1 diabetic rats

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    Jin-jin LIU

    2013-09-01

    Full Text Available Objective To observe the effect of exenatide, a glucagon-like peptide-1 (GLP-1 receptor agonist, on the expression of NADPH oxidase subunits NOX4 and p22phox and connective tissue growth factor (CTGF in the kidney of streptozotocin (STZ-induced type 1 diabetic rats, and explore the protective effects and mechanisms of exenatide on the kidney of diabetic rats. Methods Thirty male Sprague-Dawley (SD rats were divided into control group (group A, n=7 and diabetic model group (n=23. Type 1 diabetic model was reproduced by intraperitoneal injection of streptozotocin. It was successful in 19 rats. Diabetic rats were randomly divided into diabetic control group (group B, n=10 and diabetic with treatment of exenatide group (group C, n=9. Rats in group C were injected subcutaneously with exenatide in dose of 5μg/kg twice daily. Rats in group A and B were given equivalent volume of normal saline by subcutaneous injection. All rats were sacrificed after eight weeks. The mRNA expression of renal p22phox and NOX4 were detected by real-time fluorescence quantitative PCR. The protein expression of CTGF was detected by immunohistochemical staining. Results The levels of blood glucose, lipids, creatinine, and urea nitrogen, the albumin excretion rate, kidney index, the mRNA expressions of renal NOX4 and p22phox, and the protein expression of renal CTGF were significantly increased in group B compared with that in group A (P0.05. Conclusion Exenatide can decrease the expressions of renal NOX4, p22phox and CTGF, decline the index of urinary protein, and alleviate the kidney hypertrophy in type 1 diabetic rats, implying that exenatide exerted a protective effect on the kidney.

  13. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

    International Nuclear Information System (INIS)

    Wang, Xianwei; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L.

    2012-01-01

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22 phox , p47 phox , p67 phox , NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H 2 O 2 . Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen

  14. Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

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    Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L., E-mail: MehtaJL@UAMS.edu

    2012-03-15

    Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac

  15. Chromatin preferences of the perichromosomal layer constituent pKi-67.

    Science.gov (United States)

    Traut, Walther; Endl, Elmar; Garagna, Silvia; Scholzen, Thomas; Schwinger, Eberhard; Gerdes, Johannes; Winking, Heinz

    2002-01-01

    The proliferation-associated nuclear protein pKi-67 relocates from the nucleolus to the chromosome surface during the G2/M transition of the cell cycle and contributes to the formation of the 'perichromosomal layer'. We investigated the in-vivo binding preferences of pKi-67 for various chromatin blocks of the mitotic chromosomes from the human and two mouse species, Mus musculus and M. caroli. All chromosomes were decorated with pKi-67 but displayed a gap of pKi-67 decoration in the centromere and NOR regions. pKi-67 distribution in a rearranged mouse chromosome showed that the formation of the centromeric gap was controlled by the specific chromatin in that region. While most chromatin served as a substrate for direct or indirect binding of pKi-67, we identified three types of chromatin that bound less or no pKi-67. These were: (1) the centromeric heterochromatin defined by the alpha satellite DNA in the human, by the mouse minor satellite in M. musculus and the 60- and 79-bp satellites in M. caroli; (2) the pericentromeric heterochromatin in M. musculus defined by the mouse major satellite, and (3) NORs in the human and in M. musculus defined by rDNA repeats. In contrast, the conspicuous blocks of pericentromeric heterochromatin in human chromosomes 1, 9 and 16 containing the 5-bp satellite showed intense pKi-67 decoration. The centromeric gap may have a biological significance for the proper attachment of the chromosomes to the mitotic spindle. In this context, our results suggest a new role for centromeric heterochromatin: the control of the centromeric gap in the perichromosomal layer.

  16. Conformational changes in the AAA ATPase p97–p47 adaptor complex

    Science.gov (United States)

    Beuron, Fabienne; Dreveny, Ingrid; Yuan, Xuemei; Pye, Valerie E; Mckeown, Ciaran; Briggs, Louise C; Cliff, Matthew J; Kaneko, Yayoi; Wallis, Russell; Isaacson, Rivka L; Ladbury, John E; Matthews, Steve J; Kondo, Hisao; Zhang, Xiaodong; Freemont, Paul S

    2006-01-01

    The AAA+ATPase p97/VCP, helped by adaptor proteins, exerts its essential role in cellular events such as endoplasmic reticulum-associated protein degradation or the reassembly of Golgi, ER and the nuclear envelope after mitosis. Here, we report the three-dimensional cryo-electron microscopy structures at ∼20 Å resolution in two nucleotide states of the endogenous hexameric p97 in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins involved in membrane fusion. Depending on the nucleotide state, we observe the p47 trimer to be in two distinct arrangements on top of the p97 hexamer. By combining the EM data with NMR and other biophysical measurements, we propose a model of ATP-dependent p97(N) domain motions that lead to a rearrangement of p47 domains, which could result in the disassembly of target protein complexes. PMID:16601695

  17. PREVAILING DUST-TRANSPORT DIRECTIONS ON COMET 67P/CHURYUMOV–GERASIMENKO

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, Tobias; Noack, Matthias [Konrad-Zuse-Zentrum für Informationstechnik, Takustrasse 7, D-14195 Berlin (Germany)

    2015-11-10

    Dust transport and deposition behind larger boulders on the comet 67P/Churyumov–Gerasimenko (67P/C–G) have been observed by the Rosetta mission. We present a mechanism for dust-transport vectors based on a homogeneous surface activity model incorporating in detail the topography of 67P/C–G. The combination of gravitation, gas drag, and Coriolis force leads to specific dust transfer pathways, which for higher dust velocities fuel the near-nucleus coma. By distributing dust sources homogeneously across the whole cometary surface, we derive a global dust-transport map of 67P/C–G. The transport vectors are in agreement with the reported wind-tail directions in the Philae descent area.

  18. Intermittent Hypoxia Affects the Spontaneous Differentiation In Vitro of Human Neutrophils into Long-Lived Giant Phagocytes

    Directory of Open Access Journals (Sweden)

    Larissa Dyugovskaya

    2016-01-01

    Full Text Available Previously we identified, for the first time, a new small-size subset of neutrophil-derived giant phagocytes (Gϕ which spontaneously develop in vitro without additional growth factors or cytokines. Gϕ are CD66b+/CD63+/MPO+/LC3B+ and are characterized by extended lifespan, large phagolysosomes, active phagocytosis, and reactive oxygen species (ROS production, and autophagy largely controls their formation. Hypoxia, and particularly hypoxia/reoxygenation, is a prominent feature of many pathological processes. Herein we investigated Gϕ formation by applying various hypoxic conditions. Chronic intermittent hypoxia (IH (29 cycles/day for 5 days completely abolished Gϕ formation, while acute IH had dose-dependent effects. Exposure to 24 h (56 IH cycles decreased their size, yield, phagocytic ability, autophagy, mitophagy, and gp91-phox/p22-phox expression, whereas under 24 h sustained hypoxia (SH the size and expression of LC3B and gp91-phox/p22-phox resembled Gϕ formed in normoxia. Diphenyl iodide (DPI, a NADPH oxidase inhibitor, as well as the PI3K/Akt and autophagy inhibitor LY294002 abolished Gϕ formation at all oxygen conditions. However, the potent antioxidant, N-acetylcysteine (NAC abrogated the effects of IH by inducing large CD66b+/LC3B+ Gϕ and increased both NADPH oxidase expression and phagocytosis. These findings suggest that NADPH oxidase, autophagy, and the PI3K/Akt pathway are involved in Gϕ development.

  19. Effects of monascin on anti-inflammation mediated by Nrf2 activation in advanced glycation end product-treated THP-1 monocytes and methylglyoxal-treated wistar rats.

    Science.gov (United States)

    Lee, Bao-Hong; Hsu, Wei-Hsuan; Huang, Tao; Chang, Yu-Ying; Hsu, Ya-Wen; Pan, Tzu-Ming

    2013-02-13

    Hyperglycemia is associated with advanced glycation end products (AGEs). This study was designed to evaluate the inhibitory effects of monascin on receptor for advanced glycation end product (RAGE) signal and THP-1 monocyte inflammation after treatment with S100b, a specific ligand of RAGE. Monascin inhibited cytokine production by S100b-treated THP-1 monocytes via up-regulation of nuclear factor-erythroid 2-related factor-2 (Nrf2) and alleviated p47phox translocation to the membrane. Methylglyoxal (MG, 600 mg/kg bw) was used to induce diabetes in Wistar rats. Inhibitions of RAGE and p47phox by monascin were confirmed by peripheral blood mononuclear cells (PBMCs) of MG-induced rats. Silymarin (SM) was used as a positive control group. It was found that monascin promoted heme oxygenase-1 (HO-1) expression mediated by Nrf2. Suppressions of AGEs, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-β) in serum of MG-induced rats were attenuated in the monascin administration group treated with retinoic acid (RA). RA treatment resulted in Nrf2 inactivation by increasing RA receptor-α (RARα) activity, suggesting that RA acts as an inhibitor of Nrf2. The results showed that monascin exerted anti-inflammatory and antioxidative effects mediated by Nrf2 to prevent the development of diseases such as type 2 diabetes caused by inflammation.

  20. Benazepril, an angiotensin-converting enzyme inhibitor, alleviates renal injury in spontaneously hypertensive rats by inhibiting advanced glycation end-product-mediated pathways.

    Science.gov (United States)

    Liu, Xue-Ping; Pang, Yue-Jiu; Zhu, Wei-Wei; Zhao, Ting-Ting; Zheng, Min; Wang, Yi-Bing; Sun, Zhi-Jian; Sun, Siao-Jing

    2009-03-01

    1. Advanced glycation end-products (AGE) and their receptors (RAGE) have been implicated in renal damage in diabetes. The aim of the present study was to investigate the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI), on the formation of AGE, the expression RAGE and other associated components in the oxidative stress pathway in spontaneously hypertensive rats (SHR). 2. Groups of SHR were treated with or without 10 mg/kg per day benazepril for 12 weeks. Systolic blood pressure (SBP) and angiotensin (Ang) II levels were evaluated in SHR and control Wistar-Kyoto (WKY) rats. Renal function was investigated by determining levels of proteinuria and glomerulosclerosis. Furthermore, reactive oxygen species (ROS) in the rat renal cortex were analysed using an H(2)O(2)-based hydroxyl radical-detection assay and the renal content of AGE, RAGE, NADPH oxidase p47phox, nuclear factor (NF)-kappaB p65, phosphorylated (p-) NF-kappaB p65, vascular cell adhesion molecule (VCAM)-1 and transforming growth factor (TGF)-beta1 was determined by immunohistochemistry, quantitative real-time polymerase chain reaction and western blot analysis. 3. Treatment with benazepril inhibited the formation of AngII, reduced SBP and alleviated renal lesions in SHR compared with both untreated SHR and control WKY rats. Benazepril treatment significantly suppressed the accumulation of AGE and expression of RAGE in the kidney of SHR. In addition, benazepril treatment reduced the upregulation of NADPH oxidase p47phox, ROS generation and NF-kappaB p65, p-NF-kappaB p65, VCAM-1 and TGF-beta1 expression in the kidney of SHR compared with both untreated SHR and control WKY rats. 4. The results of the present study provide new insights into the regulation by the renin-angiotensin system of AGE-RAGE, oxidative stress and nephropathy, increasing our understanding of the role of the RAS in nephropathy.

  1. Cluster Differentiating 36 (CD36) Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart.

    Science.gov (United States)

    Gharib, Mohamed; Tao, Huan; Fungwe, Thomas V; Hajri, Tahar

    2016-01-01

    Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS) leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36) protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear. The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity. Studies were conducted in control (Lean), obese leptin-deficient (Lepob/ob) and leptin-CD36 double null (Lepob/obCD36-/-) mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA) uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase-dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity. CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress.

  2. Generation of reactive oxygen species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate

    International Nuclear Information System (INIS)

    Arana, Lide; Gangoiti, Patricia; Ouro, Alberto; Rivera, Io-Guané; Ordoñez, Marta; Trueba, Miguel; Lankalapalli, Ravi S.; Bittman, Robert; Gomez-Muñoz, Antonio

    2012-01-01

    We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P. ROS production was dependent upon prior activation of NADPH oxidase by C1P, which was determined by measuring phosphorylation of the p40phox subunit and translocation of p47phox from the cytosol to the plasma membrane. In addition, C1P activated cytosolic calcium-dependent phospholipase A 2 and protein kinase C-α, and NADPH oxidase activation was blocked by selective inhibitors of these enzymes. These inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all of these C1P actions are caused by intracellular C1P. It can be concluded that the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived macrophages is NADPH oxidase, and that this enzyme is downstream of PKC-α and cPLA 2 -α in this pathway. -- Highlights: ► Ceramide 1-phosphate (C1P) stimulates reactive oxygen species (ROS) formation. ► The enzyme responsible for ROS generation by C1P in macrophages is NADPH oxidase. ► NADPH oxidase lies downstream of cPLA 2 -α and PKC-α in this pathway. ► ROS generation is essential for the stimulation of macrophage proliferation by C1P.

  3. Testosterone improves erectile function through inhibition of reactive oxygen species generation in castrated rats

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    Rui Li

    2016-05-01

    Full Text Available Testosterone is overwhelmingly important in regulating erectile physiology. However, the associated molecular mechanisms are poorly understood. The purpose of this study was to explore the effects and mechanisms of testosterone in erectile dysfunction (ED in castrated rats. Forty male Sprague-Dawley rats were randomized to four groups (control, sham-operated, castration and castration-with-testosterone-replacement. Reactive oxygen species (ROS production was measured by dihydroethidium (DHE staining. Erectile function was assessed by the recording of intracavernous pressure (ICP and mean arterial blood pressure (MAP. Protein expression levels were examined by western blotting. We found that castration reduced erectile function and that testosterone restored it. Nitric oxide synthase (NOS activity was decrease in the castrated rats, and testosterone administration attenuated this decrease (each p < 0.05. The testosterone, dihydrotestosterone, cyclic guanosine monophosphate (cGMP and cyclic adenosine monophosphate (cAMP concentrations were lower in the castrated rats, and testosterone restored these levels (each p < 0.05. Furthermore, the cyclooxygenase-2 (COX-2 and prostacyclin synthase (PTGIS expression levels and phospho-endothelial nitric oxide synthase (p-eNOS, Ser1177/endothelial nitric oxide synthase (eNOS ratio were reduced in the castrated rats compared with the controls (each p < 0.05. In addition, the p40phox and p67phox expression levels were increased in the castrated rats, and testosterone reversed these changes (each p < 0.05. Overall, our results demonstrate that testosterone ameliorates ED after castration by reducing ROS production and increasing the activity of the eNOS/cGMP and COX-2/PTGIS/cAMP signaling pathways.

  4. Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome.

    Science.gov (United States)

    Yanes, Licy L; Romero, Damian G; Moulana, Mohaddetheh; Lima, Roberta; Davis, Deborah D; Zhang, Huimin; Lockhart, Rachel; Racusen, Lorraine C; Reckelhoff, Jane F

    2011-04-01

    Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated. This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined. Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

  5. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Yogi, Alvaro; Callera, Glaucia E. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Mecawi, André S. [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Batalhão, Marcelo E.; Carnio, Evelin C. [Department of General and Specialized Nursing, College of Nursing of Ribeirão Preto, USP, São Paulo (Brazil); Antunes-Rodrigues, José [Department of Physiology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP (Brazil); Queiroz, Regina H. [Department of Clinical, Toxicological and Food Science Analysis, Faculty of Pharmaceutical Sciences, USP, São Paulo (Brazil); Touyz, Rhian M. [Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario (Canada); Tirapelli, Carlos R., E-mail: crtirapelli@eerp.usp.br [Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, USP, Ribeirão Preto, SP (Brazil)

    2012-11-01

    Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT{sub 1} receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase‐mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation.

  6. Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes

    Directory of Open Access Journals (Sweden)

    Gi Soo Youn

    2017-08-01

    Full Text Available Histone deacetylase 6 (HDAC6 likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat activates NADPH oxidase resulting in generation of reactive oxygen species (ROS, leading to extensive neuro-inflammation in the central nervous system. We investigated the correlation of HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6 knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N-acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10. Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent expression of chemokines. The collective results point to the potential crosstalk between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for relief of HIV-1 Tat-mediated neuro-inflammation. Keywords: HIV-1 Tat, HDAC6, NADPH oxidase, ROS, Inflammation, Astrocytes

  7. Dissecting the hydrogenase expression and activity of transformed escherichia coli with the bidirectional NiFe-hydrogenase from synechocystis sp. PCC 6803

    International Nuclear Information System (INIS)

    Moon, Yu Ran; Lee, Min Hee; An, Byung Chull; Chung, Byung Yeoup; Kim, Jae Sung; Kim, Jin Hong; Park, Youn Il; Kim, Cha Soon

    2009-01-01

    Synechocystis bidirectional hydrogenase genes (hoxEFUYH) and their putative promoter regions and transformed into E. coli. The hox genes were transcribed in the E. coli cells carrying the vector construct of pCCIFOS::phox::hox or pCCIFOS::pT7::hox and translated into HoxEFUYH proteins, suggesting that the putative hox promoter can be constitutively activated in E. coli. Accordingly, the total hydrogenase activity was markedly increased up to 192% or 169% in the transformed cells, while the hydrogen uptake was decreased up to about 30% of the negative control. Although the gene expression of LexA, the only one transcription regulator proven for the hox genes, was substantially decreased in the pCCIFOS::phox::hox cells after γ-irradiation of 30 Gy, the expression levels of HoxEFUYH proteins were not altered significantly. Thus, it is also suggested that other transcription regulators as well as LexA might contribute to activation of the hox promoter in E. coli

  8. Proliferation marker pKi-67 occurs in different isoforms with various cellular effects.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Finniss, Susan; Bögler, Oliver; Duchrow, Michael

    2004-04-15

    The Ki-67 antigen, pKi-67, is a commonly used proliferation marker in research and pathology. It has been recognized that the protein exists in two different splice variants that differ in one exon. In the current work, we present three new splice variants of human pKi-67 consisting of two naturally occurring isoforms and one atypical version. Additionally, data is presented indicating that alternative splicing of the pKi-67 N-terminus is common in tumor cell lines. Analyzing 93 tissues mainly consisting of brain tumor specimens, we found evidence that long and short isoform can be expressed independently of each other. Induction of mitosis in human peripheral blood mononuclear cells revealed that short pKi-67 appears earlier in the cell cycle than the long isoform and reaches its expression maximum when transcription of the latter sets in. Finally, transfection of mammalian culture cells with exon 7 (specific for the long pKi-67 isoform and not present in the short isoform) in a tetracycline regulated expression system decreased the rate of cell proliferation without affecting the cell cycle. In summary, we present evidence that the pKi-67 N-terminus is differentially spliced resulting in at least five different isoforms with different functions. Copyright 2004 Wiley-Liss, Inc.

  9. Suppression of cell division by pKi-67 antisense-RNA and recombinant protein.

    Science.gov (United States)

    Duchrow, M; Schmidt, M H; Zingler, M; Anemüller, S; Bruch, H P; Broll, R

    2001-01-01

    The human antigen defined by the monoclonal antibody Ki-67 (pKi-67) is a human nuclear protein strongly associated with cell proliferation and found in all tissues studied. It is widely used as a marker of proliferating cells, yet its function is unknown. To investigate its function we suppressed pKi-67 expression by antisense RNA and overexpressed a partial structure of pKi-67 in HeLa cells. A BrdU-incorporation assay showed a significant decrease in DNA synthesis after antisense inhibition. Cell cycle analysis indicated a higher proportion of cells in G1 phase and a lower proportion of cells in S phase while the number of G(2)/M phase cells remained constant. Overexpression of a recombinant protein encoding three of the repetitive elements from exon 13 of pKi-67 had a similar effect to that obtained by antisense inhibition. The similarity of the effect of expressing 'Ki-67 repeats' and pKi-67 antisense RNA could be explained by a negative effect on the folding of the endogenous protein in the endoplasmatic reticulum. Furthermore excessive self-association of pKi-67 via the repeat structure could inhibit its nuclear transport, preventing it from getting to its presumptive site of action. We conclude that the Ki-67 protein has an important role in the regulation of the cell cycle, which is mediated in part by its repetitive elements. Copyright 2001 S. Karger AG, Basel

  10. Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation.

    Science.gov (United States)

    Wang, Su Bin; Jang, Ji Yong; Chae, Yun Hee; Min, Ji Hyun; Baek, Jin Young; Kim, Myunghee; Park, Yunjeong; Hwang, Gwi Seo; Ryu, Jae-Sang; Chang, Tong-Shin

    2015-06-01

    Reactive oxygen species (ROS) generated upon collagen stimulation act as second messengers to propagate various platelet-activating events. Among the ROS-generating enzymes, NADPH oxidase (NOX) plays a prominent role in platelet activation. Thus, NOX has been suggested as a novel target for anti-platelet drug development. Although kaempferol has been identified as a NOX inhibitor, the influence of kaempferol on the activation of platelets and the underlying mechanism have never been investigated. Here, we studied the effects of kaempferol on NOX activation, ROS-dependent signaling pathways, and functional responses in collagen-stimulated platelets. Superoxide anion generation stimulated by collagen was significantly inhibited by kaempferol in a concentration-dependent manner. More importantly, kaempferol directly bound p47(phox), a major regulatory subunit of NOX, and significantly inhibited collagen-induced phosphorylation of p47(phox) and NOX activation. In accordance with the inhibition of NOX, ROS-dependent inactivation of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) was potently protected by kaempferol. Subsequently, the specific tyrosine phosphorylation of key components (Syk, Vav1, Btk, and PLCγ2) of collagen receptor signaling pathways was suppressed by kaempferol. Kaempferol also attenuated downstream responses, including cytosolic calcium elevation, P-selectin surface exposure, and integrin-αIIbβ3 activation. Ultimately, kaempferol inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. This study shows that kaempferol impairs collagen-induced platelet activation through inhibition of NOX-derived ROS production and subsequent oxidative inactivation of SHP-2. This effect suggests that kaempferol has therapeutic potential for the prevention and treatment of thrombovascular diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Maspin, p53, p63, and Ki-67 in epithelial lesions of the tongue: from hyperplasia through dysplasia to carcinoma.

    Science.gov (United States)

    Vered, Marilena; Allon, Irit; Dayan, Dan

    2009-03-01

    The pattern of changes in the expression of mammary serine protease inhibitor (maspin) tumor suppressor protein in tongue epithelial lesions [hyperplasia (HP), mild dysplasia (MD), moderate-to-severe dysplasia (MSD) and squamous cell carcinoma (SCC)] was investigated and correlated to the expression of maspin-regulating factors p53 and p63, and the proliferation marker Ki-67. Cases of HP (n = 16), MD (n = 12), MSD (n = 11), and SCC (n = 22) were immunostained for maspin, p53, p63, and Ki-67. Maspin expression was scored separately for the basal, middle, and upper thirds of the epithelial width, and as the total sum of all 'thirds' (maspin-total). p53, p63, and Ki-67 were immuno-morphometrically assessed for the entire epithelial width. Maspin expression was differential and progressive extending to higher epithelial layers as dysplastic changes aggravated and culminated in carcinoma. Strong expression was related to MSD in the middle third and to carcinoma in the upper third. It was frequently lost at the invasion front, where the tumor was less differentiated. The changes in mean scores of maspin-total in the different study groups were positively correlated to the mean scores of p63 (r = 0.5, P < 0.001), p53 (r = 0.4, P = 0.004), and Ki-67 (r = 0.5, P < 0.001). Strong expression of maspin in the middle third of the epithelium may be considered a diagnostic sign of mild-to-moderate dysplasia and an indication of carcinoma in the upper third. The correlations between maspin and controlling factors (e.g. p63 and p53) may be events with key roles in the development of tongue carcinoma.

  12. Fatty acid oxidation changes and the correlation with oxidative stress in different preeclampsia-like mouse models.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Ding

    Full Text Available BACKGROUND: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD expression is decreased in placenta of some cases of preeclampsia (PE which may result in free fatty acid (FFA increased. High FFA level will induce oxidative stress, so abnormal long-chain fatty acid-oxidation may participate in the pathogenesis of PE through oxidative stress pathway. METHODS: PE-like groups were ApoC3 transgenic mice with abnormal fatty acid metabolism, classical PE-like models with injection of Nw-nitro-L-arginine-methyl ester (L-NA or lipopolysaccharide (LPS and the antiphospholipid syndrome (APS mouse model with β2GPI injection (ApoC3+NS, ApoC3+L-NA, L-NA, LPS and β2GPI groups. The control group was wild-type mice with normal saline injection. Except for β2GPI mice, the other mice were subdivided into pre-implantation (Pre and mid-pregnancy (Mid subgroups by injection time. RESULTS: All PE-like groups showed hypertension and proteinuria except ApoC3+NS mice only showed hypertension. Serum FFA levels increased significantly except in LPS group compared to controls (P<0.05. LCHAD mRNA and protein expression in the liver and placenta was significantly higher for ApoC3+NS, ApoC3+L-NA and β2GPI mice and lower for L-NA mice than controls (P<0.05 but did not differ between LPS mice and controls. P47phox mRNA and protein expression in the liver significantly increased in all PE-like groups except LPS group, while P47phox expression in the placenta only significantly increased in L-NA and β2GPI groups. CONCLUSIONS: Abnormal long-chain fatty acid-oxidation may play a different role in different PE-like models and in some cases participate in the pathogenesis of PE through oxidative stress pathway.

  13. Proliferation marker pKi-67 affects the cell cycle in a self-regulated manner.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Duchrow, Michael

    2002-01-01

    The proliferation marker pKi-67 is commonly used in research and pathology to detect proliferating cells. In a previous work, we found the protein to be associated with regulators of the cell cycle, controlling S-phase progression, as well as entry into and exit from mitosis. Here we investigate whether pKi-67 has a regulative effect on the cell cycle itself. For that purpose we cloned four fragments of pKi-67, together representing nearly the whole protein, and an N-terminal pKi-67 antisense oligonucleotide into a tetracycline inducible gene expression system. The sense fragments were C-terminally modified by addition of either a nuclear localization sequence (NLS) or a STOP codon to address the impact of their intracellular distribution. FACS based cell cycle analysis revealed that expression of nearly all pKi-67 domains and the antisense oligonucleotide led to a decreased amount of cells in S-phase and an increased number of cells in G(2)/M- and G(1)-phase. Subsequent analysis of the endogenous pKi-67 mRNA and protein levels revealed that the constructs with the most significant impact on the cell cycle were able to silence pKi-67 transcription as well. We conclude from the data that pKi-67 influences progression of S-phase and mitosis in a self-regulated manner and, therefore, effects the cell cycle checkpoints within both phases. Furthermore, we found pKi-67 mediates an anti-apoptotic effect on the cell and we verified that this marker, although it is a potential ribosomal catalyst, is not expressed in differentiated tissues with a high transcriptional activity. Copyright 2002 Wiley-Liss, Inc.

  14. Equol Effectively Inhibits Toxic Activity of Human Neutrophils without Influencing Their Viability

    Czech Academy of Sciences Publication Activity Database

    Pažoureková, S.; Lucová, M.; Nosál, R.; Drábiková, K.; Harmatha, Juraj; Šmidrkal, J.; Jančinová, V.

    2016-01-01

    Roč. 97, 3/4 (2016), s. 138-145 ISSN 0031-7012 Institutional support: RVO:61388963 Keywords : neutrophils * equol * chemiluminescence * reactive oxygen species * p40(phox) * apoptosis Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.442, year: 2016

  15. Lipidation of BmAtg8 is required for autophagic degradation of p62 bodies containing ubiquitinated proteins in the silkworm, Bombyx mori.

    Science.gov (United States)

    Ji, Ming-Ming; Lee, Jae Man; Mon, Hiroaki; Iiyama, Kazuhiro; Tatsuke, Tsuneyuki; Morokuma, Daisuke; Hino, Masato; Yamashita, Mami; Hirata, Kazuma; Kusakabe, Takahiro

    2017-10-01

    p62/Sequestosome-1 (p62/SQSTM1, hereafter referred to as p62) is a major adaptor that allows ubiquitinated proteins to be degraded by autophagy, and Atg8 homologs are required for p62-mediated autophagic degradation, but their relationship is still not understood in Lepidopteran insects. Here it is clearly demonstrated that the silkworm homolog of mammalian p62, Bombyx mori p62 (Bmp62), forms p62 bodies depending on its Phox and Bem1p (PB1) and ubiquitin-associated (UBA) domains. These two domains are associated with Bmp62 binding to ubiquitinated proteins to form the p62 bodies, and the UBA domain is essential for the binding, but Bmp62 still self-associates without the PB1 or UBA domain. The p62 bodies in Bombyx cells are enclosed by BmAtg9-containing membranes and degraded via autophagy. It is revealed that the interaction between the Bmp62 AIM motif and BmAtg8 is critical for the autophagic degradation of the p62 bodies. Intriguingly, we further demonstrate that lipidation of BmAtg8 is required for the Bmp62-mediated complete degradation of p62 bodies by autophagy. Our results should be useful in future studies of the autophagic mechanism in Lepidopteran insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis.

    Science.gov (United States)

    Rahmanzadeh, R; Hüttmann, G; Gerdes, J; Scholzen, T

    2007-06-01

    Expression of the nuclear Ki-67 protein (pKi-67) is strongly associated with cell proliferation. For this reason, antibodies against this protein are widely used as prognostic tools for the assessment of cell proliferation in biopsies from cancer patients. Despite this broad application in histopathology, functional evidence for the physiological role of pKi-67 is still missing. Recently, we proposed a function of pKi-67 in the early steps of ribosomal RNA (rRNA) synthesis. Here, we have examined the involvement of pKi-67 in this process by photochemical inhibition using chromophore-assisted light inactivation (CALI). Anti-pKi-67 antibodies were labelled with the fluorochrome fluorescein 5(6)-isothiocyanate and were irradiated after binding to their target protein. Performing CALI in vitro on cell lysates led to specific cross-linking of pKi-67. Moreover, the upstream binding factor (UBF) necessary for rRNA transcription was also partly subjected to cross-link formation, indicating a close spatial proximity of UBF and pKi-67. CALI in living cells, using micro-injected antibody, caused a striking relocalization of UBF from foci within the nucleoli to spots located at the nucleolar rim or within the nucleoplasm. pKi-67-CALI resulted in dramatic inhibition of RNA polymerase I-dependent nucleolar rRNA synthesis, whereas RNA polymerase II-dependent nucleoplasmic RNA synthesis remained almost unaltered. Our data presented here argue for a crucial role of pKi-67 in RNA polymerase I-dependent nucleolar rRNA synthesis.

  17. What's Causing the Activity on Comet 67P?

    Science.gov (United States)

    Kohler, Susanna

    2015-09-01

    Comet 67P/ChuryumovGerasimenko made famous by the explorations of the Rosetta mission has been displaying puzzling activity as it hurtles toward the Sun. However, recent modeling of the comet by a group of scientists from the Cte dAzur University may now explain whats causing 67Ps activity.Shadowed ActivityA model of comet 67P, with the colors indicating the rate of change of the temperature on the comets surface. The most rapid temperature changes are seen at the comets neck, in the same locations as the early activity seen in the Rosetta images. [Al-Lagoa et al. 2015] Between June and September of 2014, Rosetta observed comet 67P displaying early activity in the form of jets of dust emitted from near the neck of the comet (its narrowest point). Such activity is usually driven by the sublimation of volatiles from the comets surface as a result of sun exposure. But the neck of the comet is frequently shadowed as the comet rotates, and it receives significantly less sunlight than the rest of the comet. So why would the early activity originate from the comets neck?The authors of a recent study, led by Victor Al-Lagoa, hypothesize that its precisely because the neck is receiving alternating sunlight/shadows that its displaying activity. They suggest that thermal cracking of the surface of the comet is happening faster in this region, due to the rapid changes in temperature that result from the shadows cast by the surrounding terrain. The cracking exposes subsurface ices in the neck faster than in other regions, and the ensuing sublimation of that ice is what creates the activity were seeing.Temperature Models: To test their hypothesis, the authors study the surface temperatures on comet 67P by means of a thermophysical model a model used to calculate the temperatures on an airless body, both on and below the surface. The model takes into account factors like thermal inertia (how quickly the bodys temperature responds to changes in the incident energy), shadowing, and

  18. Comet 67P Through the Lens of Art

    Science.gov (United States)

    Smirnova, Ekaterina

    2017-04-01

    My proposal is to share my artistic exploration of a comet through the bodily senses, while finding inspiration in scientific data. I will present my artwork as a slideshow, showcasing: large scale paintings, ceramic sculptures, music and interactive augmented reality. The Rosetta mission of the European Space Agency (ESA) to comet 67P/ Churyumov-Gerasimenko is remarkable. The scientific investigation of the comet's composition, atmosphere, dust, vapor, surface and internal structure are crucial to help researchers understand the origin of the solar system and our own planet. Sight: Paintings Rosetta mission discovered that the water on the comet is different from the water on Earth; as measured with the ROSINA-DFMS instrument on Rosetta, water on 67P contains approximately 3 times more hydrogen­deuterium oxide - HDO, than found in Earth's oceans. In the art studio I re-create water that is close in composition to the water on the comet, by concentrating the level of HDO. With this water I paint large scale watermedia paintings, based on the photographs by Rosetta (OSIRIS, Nav. Cam.). Touch: Sculptures While exploring the comet's three-dimensional form, I focus more deeply on the composition of the comet. Stoneware clay and my choice of a glaze both include iron oxide, a common constituent of meteorites and comets. Hearing: Music An audio piece "A Singing Comet", by Manuel Senfft, based on the Rosetta Plasma Consortium data, inspired me to make a musical piece. In collaboration with clarinetist Lee Mottram (Wales) and composer Takuto Fukuda (Japan) we created an electro­acoustic composition in which we tell the story of comets visiting our Solar System, repeating their cycle, curving around the sun and releasing water, carrying away dust to form their tails. Smell In collaboration with The Open University, UK, postcards with a smell of the comet were created, introducing the chemical components of the comet. The smell was recreated by combining several molecules

  19. Water chemistry and its effects on the physiology and survival of Atlantic salmon Salmo salar smolts

    Science.gov (United States)

    Liebich, T.; McCormick, S.D.; Kircheis, D.; Johnson, K.; Regal, R.; Hrabik, T.

    2011-01-01

    The physiological effects of episodic pH fluctuations on Atlantic salmon Salmo salar smolts in eastern Maine, U.S.A., were investigated. During this study, S. salar smolts were exposed to ambient stream-water chemistry conditions at nine sites in four catchments for 3 and 6 day intervals during the spring S. salar smolt migration period. Plasma chloride, plasma glucose, gill aluminium and gill Na+- and K+-ATPase levels in S. salar smolts were assessed in relation to ambient stream-water chemistry during this migration period. Changes in both plasma chloride and plasma glucose levels of S. salar smolts were strongly correlated with stream pH, and S. salar smolt mortality occurred in one study site with ambient stream pH between 5??6 and 5??8 during the study period. The findings from this study suggest that physiological effects on S. salar smolts are strongly correlated with stream pH and that in rivers and streams with low dissolved organic carbon (DOC) concentrations the threshold for physiological effects and mortality probably occurs at a higher pH and shorter exposure period than in rivers with higher DOC. Additionally, whenever an acidification event in which pH drops below 5??9 coincides with S. salar smolt migration in eastern Maine rivers, there is potential for a significant reduction in plasma ions of S. salar smolts. ?? 2011 The Fisheries Society of the British Isles.

  20. Diagnostic value of p53 and M67 immunostaining for distinguishing benign from malignant serous effusions

    International Nuclear Information System (INIS)

    Hafez, N.H.; Tahoun, N.S.

    2011-01-01

    The differentiation of benign mesothelial cells from malignant tumor cells, primary, or metastatic, in serous effusions based on cytomorphologic features alone can be problematic. Purpose: This study was conducted to evaluate the utility of p53 and ki67 imrminocytochemical markers in differentiating benign from malignant tumor cells in serous effusions. Patients and methods: Archival Papanicolaou-stained smears of 91 pleura and peritoneal effusions were retrieved from Cytology Unit, Pathology Department, NCI, Cairo University between 2008 and 2010. Forty-one cases were positive for malignant cells and 50 cases were benign based on cytomorphologic features. Cases having doubt were excluded from the study. The slides were de stained and subjected to immunocytochemical staining for p53 and ki67. Histologic sections of colonic carcinoma and tonsillar tissue were used as positive control for p53 and ki67, respectively. Smears having > 5% positively stained nuclei for p53 were taken as positive and labeling index 10% of ki67 was considered positive. Frequencies of the individual immunocytochemical stains; p53 and ki67, in benign and malignant effusion as well as the combination of both stains were calculated. Results: p53 immunostaining showed nuclear positivity in 31 out of 41 malignant effusions (75.6%) and in 3 out of 50 benign effusions (6%), p < 0.005. p53 had 75.6% sensitivity, 94% specificity, 91.2% PPV, and 82.5% NPV. ki67 immunostaining was positive in 30 out of 41 malignant effusions (73.2%) and in 17 out of 50 benign effusions (34%), p < 0.05. ki67 had 73.2% sensitivity, 66% specificity, 63.8% PPV, and 75% NPV. Cases were then analyzed for combined immuno profile of p3 and ki67. Among the 24 cases that coexpressed both antigens, 22 cases (91.7%) were malignant. Thirty two out of 34 cases (94.1%) that showed negative results for both antigens were benign. For the cases that showed p53 immunostaining only, 9 out of 10 cases (90%) were malignant. Fifteen out of

  1. The Rosetta Mission to Comet 67P/ Churyumov-Gerasimenko

    Science.gov (United States)

    Buratti, Bonnie J.

    2017-06-01

    As remnant bodies left over from the formation of the Solar System, comets offer clues to the physical conditions and architecture of the protosolar nebula. The Rosetta spacecraft, which included an orbiter and a lander that were built and managed by the European Space Agency with NASA contributing four instruments and scientific expertise, was the first mission to orbit and study a comet through a perihelion passage. The targeted Jupiter-family comet 67P/ Churyumov-Gerasimenko, is seemingly two distinct planetesimals stuck together. The comet has not melted or been processed substantially, except for its outer layers, which consist of reaccreted dust and a crust of heated, devolatized, and annealed refractory materials and organics. The exceptionally low density (0.53 gm/cc) of 67P/ implies it is a rubble pile. The comet also appears to contain a hierarchy of building blocks: smaller spherically shaped meter-sized bodies can be seen in its interior, and even smaller cm-sized pebbles were imaged by the camera as the spacecraft made a soft crash landing on the comet’s surface on 30 September 2016. The unexpected discovery of molecular oxygen, nitrogen, and hydrogen imply that 67P/ was formed under cold conditions not exceeding 30K. The discovery of many organic compounds, including the amino acid glycine, lends support to the idea that comets, which originate in the Kuiper Belt and the Oort Cloud, brought the building blocks of life to Earth. More laboratory data on organic compounds would help to identify additional organic compounds on the comet. The differences between cometary and terrestrial D/H ratios suggest that comets are not the primary source of terrestrial water, although data on more comets is needed to confirm this result.Besides being primordial objects offering a window into the formation of solar systems, comets are astrophysical laboratories, ejecting dust and charged particles into the plasma comprising the solar wind. Several unusual phenomena

  2. Expression and significance of VEGF, CD34, Ki-67 and p21 in pterygium

    Directory of Open Access Journals (Sweden)

    Li-Bo Wang

    2014-07-01

    Full Text Available AIM: To investigate the expression of VEGF, CD34, Ki-67 and p21 in pterygium as well as the correlation between their expression and clinical pathological characteristics; explore its pathogenesis. METHODS: Immunohistochemical S-P staining method was adopted in detecting the expression of VEGF, CD34, Ki-67 and p21 in 62 cases of pterygia and 20 cases of normal conjunctival tissues. Relationship between these markers and clinical pathological characteristics was analyzed. RESULTS:(1The positive expression of VEGF, CD34, Ki-67 and p21 in 62 cases of pterygia was 74.2%(46/62, 77.4%(48/62, 66.1%(41/62and 40.3%(25/62respectively. The differences were statistically significant compared with normal conjunctival tissues(PPP>0.05; the expression of Ki-67 was correlated with clinical stages(PP>0.05; the expression of p21 was correlated with clinical stages and pterygium characters(PP>0.05.(3Spearman correlation showed that there was a positive correlation between VEGF and Ki-67(r=0.279, Pr=0.299, Pr=-0.267, PP>0.05.CONCLUSION:(1Overexpression of VEGF, Ki-67, CD34 and low expression of p21 suggest that these markers are concerned with the development and progression of pterygium.(2Expression of VEGF and CD34 increases along with the increase of clinical types and stages, expression of Ki-67 increases along with the increase of clinical stages, and expression of p21 decreases along with the improvement of clinical types or stages; they suggest that these markers may play important roles in the development and recurrence of pterygium.(3There is positive correlation between VEGF and Ki-67, VEGF and CD34 as well as negative correlation between VEGF and p21. They suggest that there may be synergistic action between two factors during the development and progression of pterygium.

  3. Sesamin Ameliorates Advanced Glycation End Products-Induced Pancreatic β-Cell Dysfunction and Apoptosis

    Directory of Open Access Journals (Sweden)

    Xiang Kong

    2015-06-01

    Full Text Available Advanced glycation end products (AGEs, the direct modulators of β-cells, have been shown to cause insulin-producing β-cell dysfunction and apoptosis through increase of intracellular reactive oxygen species (ROS production. Sesamin has been demonstrated to possess antioxidative activity. This study was designed to investigate whether sesamin protects against AGEs-evoked β-cell damage via its antioxidant property. The effects of sesamin were examined in C57BL/6J mice and MIN6 cell line. In in vivo studies, mice were intraperitoneally injected with AGEs (120 mg/kg and orally treated with sesamin (160 mg/kg for four weeks. Intraperitoneal glucose tolerance and insulin releasing tests were performed. Insulin content, ROS generation and β-cell apoptosis in pancreatic islets were also measured. In in vitro studies, MIN6 cells were pretreated with sesamin (50 or 100 μM and then exposed to AGEs (200 mg/L for 24 h. Insulin secretion, β-cell death, ROS production as well as expression and activity of NADPH oxidase were determined. Sesamin treatment obviously ameliorated AGE-induced β-cell dysfunction and apoptosis both in vivo and in vitro. These effects were associated with decreased ROS production, down-regulated expression of p67phox and p22phox, and reduced NADPH oxidase activity. These results suggest that sesamin protects β-cells from damage caused by AGEs through suppressing NADPH oxidase-mediated oxidative stress.

  4. Sinomenine, a natural dextrorotatory morphinan analog, is anti-inflammatory and neuroprotective through inhibition of microglial NADPH oxidase

    Directory of Open Access Journals (Sweden)

    Wilson Belinda

    2007-09-01

    Full Text Available Abstract Background The mechanisms involved in the induction and regulation of inflammation resulting in dopaminergic (DA neurotoxicity in Parkinson's disease (PD are complex and incompletely understood. Microglia-mediated inflammation has recently been implicated as a critical mechanism responsible for progressive neurodegeneration. Methods Mesencephalic neuron-glia cultures and reconstituted cultures were used to investigate the molecular mechanisms of sinomenine (SN-mediated anti-inflammatory and neuroprotective effects in both the lipopolysaccharide (LPS- and the 1-methyl-4-phenylpyridinium (MPP+-mediated models of PD. Results SN showed equivalent efficacy in protecting against DA neuron death in rat midbrain neuron-glial cultures at both micro- and sub-picomolar concentrations, but no protection was seen at nanomolar concentrations. The neuroprotective effect of SN was attributed to inhibition of microglial activation, since SN significantly decreased tumor necrosis factor-α (TNF-α, prostaglandin E2 (PGE2 and reactive oxygen species (ROS production by microglia. In addition, from the therapeutic point of view, we focused on sub-picomolar concentration of SN for further mechanistic studies. We found that 10-14 M of SN failed to protect DA neurons against MPP+-induced toxicity in the absence of microglia. More importantly, SN failed to show a protective effect in neuron-glia cultures from mice lacking functional NADPH oxidase (PHOX, a key enzyme for extracellular superoxide production in immune cells. Furthermore, we demonstrated that SN reduced LPS-induced extracellular ROS production through the inhibition of the PHOX cytosolic subunit p47phoxtranslocation to the cell membrane. Conclusion Our findings strongly suggest that the protective effects of SN are most likely mediated through the inhibition of microglial PHOX activity. These findings suggest a novel therapy to treat inflammation-mediated neurodegenerative diseases.

  5. The Mechanism of Sevoflurane Preconditioning-Induced Protections against Small Intestinal Ischemia Reperfusion Injury Is Independent of Mast Cell in Rats

    Directory of Open Access Journals (Sweden)

    Xiaoliang Gan

    2013-01-01

    Full Text Available The study aimed to investigate whether sevoflurane preconditioning can protect against small intestinal ischemia reperfusion (IIR injury and to explore whether mast cell (MC is involved in the protections provided by sevoflurane preconditioning. Sprague-Dawley rats exposed to sevoflurane or treated with MC stabilizer cromolyn sodium (CS were subjected to 75-minute superior mesenteric artery occlusion followed by 2-hour reperfusion in the presence or absence of MC degranulator compound 48/80 (CP. Small intestinal ischemia reperfusion resulted in severe intestinal injury as demonstrated by significant elevations in intestinal injury scores and p47phox and gp91phox, ICAM-1 protein expressions and malondialdehyde and IL-6 contents, and MPO activities as well as significant reductions in SOD activities, accompanied with concomitant increases in mast cell degranulation evidenced by significant increases in MC counts, tryptase expression, and β-hexosaminidase concentrations, and those alterations were further upregulated in the presence of CP. Sevoflurane preconditioning dramatically attenuated the previous IIR-induced alterations except MC counts, tryptase, and β-hexosaminidase which were significantly reduced by CS treatment. Furthermore, CP exacerbated IIR injury was abrogated by CS but not by sevoflurane preconditioning. The data collectively indicate that sevoflurane preconditioning confers protections against IIR injury, and MC is not involved in the protective process.

  6. Three-dimensional organization of pKi-67: a comparative fluorescence and electron tomography study using FluoroNanogold.

    Science.gov (United States)

    Cheutin, Thierry; O'Donohue, Marie-Françoise; Beorchia, Adrien; Klein, Christophe; Kaplan, Hervé; Ploton, Dominique

    2003-11-01

    The monoclonal antibody (MAb) Ki-67 is routinely used in clinical studies to estimate the growth fraction of tumors. However, the role of pKi-67, the protein detected by the Ki-67 MAb, remains elusive, although some biochemical data strongly suggest that it might organize chromatin. To better understand the functional organization of pKi-67, we studied its three-dimensional distribution in interphase cells by confocal microscopy and electron tomography. FluoroNanogold, a single probe combining a dense marker with a fluorescent dye, was used to investigate pKi-67 organization at the optical and ultrastructural levels. Observation by confocal microscopy followed by 3D reconstruction showed that pKi-67 forms a shell around the nucleoli. Double labeling experiments revealed that pKi-67 co-localizes with perinucleolar heterochromatin. Electron microscopy studies confirmed this close association and demonstrated that pKi-67 is located neither in the fibrillar nor in the granular components of the nucleolus. Finally, spatial analyses by electron tomography showed that pKi-67 forms cords 250-300 nm in diameter, which are themselves composed of 30-50-nm-thick fibers. These detailed comparative in situ analyses strongly suggest the involvement of pKi-67 in the higher-order organization of perinucleolar chromatin.

  7. ORIGIN OF MOLECULAR OXYGEN IN COMET 67P/CHURYUMOV–GERASIMENKO

    Energy Technology Data Exchange (ETDEWEB)

    Mousis, O.; Ronnet, T.; Brugger, B.; Vernazza, P. [Aix Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388, Marseille (France); Ozgurel, O.; Pauzat, F.; Ellinger, Y.; Markovits, A. [Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Univ. Paris 06, CNRS UMR 7616, F-75252 Paris CEDEX 05 (France); Maggiolo, R. [Royal Institute for Space Aeronomy, 3 Avenue Circulaire, Brussels (Belgium); Wurz, P.; Altwegg, K.; Bieler, A.; Rubin, M. [Physikalisches Institut, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland); Lunine, J. I. [Department of Astronomy and Carl Sagan Institute, Space Sciences Building Cornell University, Ithaca, NY 14853 (United States); Luspay-Kuti, A.; Mandt, K. E., E-mail: olivier.mousis@lam.fr [Department of Space Research, Southwest Research Institute, 6220 Culebra Rd., San Antonio, TX 78228 (United States)

    2016-06-01

    Molecular oxygen has been detected in the coma of comet 67P/Churyumov–Gerasimenko with abundances in the 1%–10% range by the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis-Double Focusing Mass Spectrometer instrument on board the Rosetta spacecraft. Here we find that the radiolysis of icy grains in low-density environments such as the presolar cloud may induce the production of large amounts of molecular oxygen. We also show that molecular oxygen can be efficiently trapped in clathrates formed in the protosolar nebula (PSN), and that its incorporation as crystalline ice is highly implausible, because this would imply much larger abundances of Ar and N{sub 2} than those observed in the coma. Assuming that radiolysis has been the only O{sub 2} production mechanism at work, we conclude that the formation of comet 67P/Churyumov–Gerasimenko is possible in a dense and early PSN in the framework of two extreme scenarios: (1) agglomeration from pristine amorphous icy grains/particles formed in ISM and (2) agglomeration from clathrates that formed during the disk’s cooling. The former scenario is found consistent with the strong correlation between O{sub 2} and H{sub 2}O observed in comet 67P/Churyumov-Gerasimenko’s coma while the latter scenario requires that clathrates formed from ISM icy grains that crystallized when entering the PSN.

  8. ORIGIN OF MOLECULAR OXYGEN IN COMET 67P/CHURYUMOV–GERASIMENKO

    International Nuclear Information System (INIS)

    Mousis, O.; Ronnet, T.; Brugger, B.; Vernazza, P.; Ozgurel, O.; Pauzat, F.; Ellinger, Y.; Markovits, A.; Maggiolo, R.; Wurz, P.; Altwegg, K.; Bieler, A.; Rubin, M.; Lunine, J. I.; Luspay-Kuti, A.; Mandt, K. E.

    2016-01-01

    Molecular oxygen has been detected in the coma of comet 67P/Churyumov–Gerasimenko with abundances in the 1%–10% range by the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis-Double Focusing Mass Spectrometer instrument on board the Rosetta spacecraft. Here we find that the radiolysis of icy grains in low-density environments such as the presolar cloud may induce the production of large amounts of molecular oxygen. We also show that molecular oxygen can be efficiently trapped in clathrates formed in the protosolar nebula (PSN), and that its incorporation as crystalline ice is highly implausible, because this would imply much larger abundances of Ar and N_2 than those observed in the coma. Assuming that radiolysis has been the only O_2 production mechanism at work, we conclude that the formation of comet 67P/Churyumov–Gerasimenko is possible in a dense and early PSN in the framework of two extreme scenarios: (1) agglomeration from pristine amorphous icy grains/particles formed in ISM and (2) agglomeration from clathrates that formed during the disk’s cooling. The former scenario is found consistent with the strong correlation between O_2 and H_2O observed in comet 67P/Churyumov-Gerasimenko’s coma while the latter scenario requires that clathrates formed from ISM icy grains that crystallized when entering the PSN.

  9. Impact of the Ki-67 labeling index and p53 expression status on disease-free survival in pT1 urothelial carcinoma of the bladder.

    Science.gov (United States)

    Vetterlein, Malte W; Roschinski, Julia; Gild, Philipp; Marks, Phillip; Soave, Armin; Doh, Ousman; Isbarn, Hendrik; Höppner, Wolfgang; Wagner, Walter; Shariat, Shahrokh F; Brausi, Maurizio; Büscheck, Franziska; Sauter, Guido; Fisch, Margit; Rink, Michael

    2017-12-01

    The identification of protein biomarkers to guide treatment decisions regarding adjuvant therapies for high-risk non-muscle-invasive bladder cancer (NMIBC) has been of increasing interest. Evidence of the impact of tumor suppressor gene product p53 and cell proliferation marker Ki-67 on oncologic outcomes in bladder cancer patients at highest risk of recurrence and progression is partially contradictory. We sought to mirror contemporary expression patterns of p53 and Ki-67 in a select cohort of patients with pT1 bladder cancer. Patients from four Northern German institutions with a primary diagnosis of pT1 bladder cancer between 2009 and 2016 and complete data regarding p53 or Ki-67 expression status were included for final analyses. Baseline patient characteristics (age, gender, age-adjusted Charlson comorbidity index) and tumor characteristics [diagnostic sequence, tumor focality, concomitant carcinoma in situ, 1973 World Health Organization (WHO) grading, lymphovascular invasion, adjuvant instillation therapy] were abstracted by retrospective chart review. Immunohistochemistry for detection of p53 and Ki-67 expression was performed according to standardized protocols. Microscopic analyses were performed by central pathologic review. First, we compared patients with positive vs. negative p53 expression and Ki-67 labeling index [>40% vs. ≤40%; cutoffs based on best discriminative ability in univariable Cox regression analysis with disease-free survival (DFS) as endpoint] with regard to baseline and tumor characteristics. Second, we evaluated the effect of biomarker positivity on DFS by plotting univariable Kaplan-Meier curves and performing uni- and multivariable Cox regression analyses. Of 102 patients with complete information on p53 status, 44 (43.1%) were p53 positive, and they more often harbored concomitant carcinoma in situ (50.0% vs. 27.6%; P=0.032) and 1973 WHO grade 3 (97.7% vs. 69.0%; P=0.001) compared to their p53 negative counterparts. Of 79

  10. Limb Remote Ischemic Postconditioning Reduces Ischemia-Reperfusion Injury by Inhibiting NADPH Oxidase Activation and MyD88-TRAF6-P38MAP-Kinase Pathway of Neutrophils

    Directory of Open Access Journals (Sweden)

    Gangling Chen

    2016-11-01

    Full Text Available Limb remote ischemic postconditioning (LRIP has been confirmed to reduce the ischemia-reperfusion injury but its mechanisms are still not clear. This study clarified the mechanism of LRIP based on the nicotinamide-adenine dinucleotide phosphate (NADPH oxidase and Myeloid differentiation factor 88 (MyD88-Tumor necrosis factor (TNF receptor-associated factor 6 (TRAF6-P38 pathway of neutrophils. Rat middle cerebral artery occlusion (MCAO model was used in this study. Ischemia-reperfusion injury was carried out by MCAO 1.5 h followed by 24 h reperfusion. LRIP operation was performed to the left femoral artery at 0, 1 or 3 h after reperfusion. Behavioral testing, including postural reflex test, vibrissae-elicited forelimb placing test and tail hang test, showed that LRIP operated at 0 h of reperfusion could significantly ameliorate these behavioral scores. Pathological examinations, infarct size, Myeloperoxidase (MPO activity showed that LRIP operated at 0 h of reperfusion could significantly ameliorate the pathological scores, reduce the infarct size and MPO activity in the brain and increase the MPO activity in the left leg. By using Neutrophil counting, immunofluorescence and real-time PCR techniques, we found that LRIP operated at 0 h of reperfusion could reduce neutrophil counts in the peripheral blood and downregulate the activation of neutrophil in the peripheral blood and rat brain. Western blots revealed that MyD88, TRAF6, p38 mitogen-activated protein kinase (p38-MAPK in neutrophils and the phosphorylation of p47phox (Ser 304 and Ser 345 in neutrophil could be downregulated by LRIP. Our study suggests that LRIP inhibits the number and activation of neutrophils in the rat brain and peripheral blood linked to down-regulating the activation of NADPH oxidase in neutrophils by MyD88/TRAF6/p38-MAPK pathway.

  11. Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats

    Directory of Open Access Journals (Sweden)

    Serizawa Ken-ichi

    2011-11-01

    Full Text Available Abstract Background Nicorandil, an anti-angina agent, reportedly improves outcomes even in angina patients with diabetes. However, the precise mechanism underlying the beneficial effect of nicorandil on diabetic patients has not been examined. We investigated the protective effect of nicorandil on endothelial function in diabetic rats because endothelial dysfunction is a major risk factor for cardiovascular disease in diabetes. Methods Male Sprague-Dawley rats (6 weeks old were intraperitoneally injected with streptozotocin (STZ, 40 mg/kg, once a day for 3 days to induce diabetes. Nicorandil (15 mg/kg/day and tempol (20 mg/kg/day, superoxide dismutase mimetic were administered in drinking water for one week, starting 3 weeks after STZ injection. Endothelial function was evaluated by measuring flow-mediated dilation (FMD in the femoral arteries of anaesthetised rats. Cultured human coronary artery endothelial cells (HCAECs were treated with high glucose (35.6 mM, 24 h and reactive oxygen species (ROS production with or without L-NAME (300 μM, apocynin (100 μM or nicorandil (100 μM was measured using fluorescent probes. Results Endothelial function as evaluated by FMD was significantly reduced in diabetic as compared with normal rats (diabetes, 9.7 ± 1.4%; normal, 19.5 ± 1.7%; n = 6-7. There was a 2.4-fold increase in p47phox expression, a subunit of NADPH oxidase, and a 1.8-fold increase in total eNOS expression in diabetic rat femoral arteries. Nicorandil and tempol significantly improved FMD in diabetic rats (nicorandil, 17.7 ± 2.6%; tempol, 13.3 ± 1.4%; n = 6. Nicorandil significantly inhibited the increased expressions of p47phox and total eNOS in diabetic rat femoral arteries. Furthermore, nicorandil significantly inhibited the decreased expression of GTP cyclohydrolase I and the decreased dimer/monomer ratio of eNOS. ROS production in HCAECs was increased by high-glucose treatment, which was prevented by L-NAME and nicorandil

  12. Porosity Gradient at the Surface of Comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Christou, C.; Dadzie, S. K.; Thomas, N.; Hartogh, P.; Jorda, L.; Kuhrt, E.; Wright, I.; Zarnecki, J.

    2017-12-01

    The Rosetta mission has provided invaluable and unexpected information about our knowledge and understanding of comets until now. The on-board instruments, ROSINA and VIRTIS showed the non-uniformly outgassing of H2O over the surface of the nucleus. After Philae landing in a small lobe and the attempt to intrude MUPUS into the surface led to estimate the minimum compressive strength of material > 4MPa. This high strength of material (at least locally) along with different porosity ranges that have been presented for the 67P/Churyumov-Gerasimenko (67P) challenge our understanding of the surface and outgassing processes. Here we used the micro computed tomography (micro-CT) technology to represent 3D Earth rock samples with different porosity to investigate outgassing in the near surface boundary layer. The Direct Simulation of Monte Carlo (DSMC) method is used to simulate the rarefied cometary atmosphere. We presented results with H2O outgassing at a maximum production rate near perihelion. We show that an existence of a possible porosity gradient at the surface of the comet may explain some of the structures observed on 67P.

  13. Stemcell Information: SKIP000629 [SKIP Stemcell Database[Archive

    Lifescience Database Archive (English)

    Full Text Available PS0335 and HPS0336 are derived from the same patient. ... p47欠損型慢性肉芽腫症患者由来iPS細胞株。HPS...hronic granulomatous disease (CGD), p47phox-deficiency 233700 ... -- -- Japanese Japanese Yes No Disease specific iPS cell...所バイオリソースセンター http://www2.brc.riken.jp/lab/cell/detail.cgi?cell_no=HPS0334 ... ...0R or MMC) 1-1.5x10^(6) cells/100mm dish DMEM/HamF12(2mM L-Glutamine)+20%KSR+0.1mM NEAA+0.1mM 2-Mercaptoetha...0335、HPS0336と同一人由来。 human ES-like Research Grade Sendai virus Oct3/4, Sox2, Klf4, c-Myc ... Yes MEF (X-rays:500

  14. Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.

    Science.gov (United States)

    Schäfer, Nicola; Lohmann, Christine; Winnik, Stephan; van Tits, Lambertus J; Miranda, Melroy X; Vergopoulos, Athanasios; Ruschitzka, Frank; Nussberger, Jürg; Berger, Stefan; Lüscher, Thomas F; Verrey, François; Matter, Christian M

    2013-12-01

    Aldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. Obesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

  15. Necrotizing Liver Granuloma/Abscess and Constrictive Aspergillosis Pericarditis with Central Nervous System Involvement: Different Remarkable Phenotypes in Different Chronic Granulomatous Disease Genotypes

    Directory of Open Access Journals (Sweden)

    Sanem Eren Akarcan

    2017-01-01

    Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency causing predisposition to infections with specific microorganisms, Aspergillus species and Staphylococcus aureus being the most common ones. A 16-year-old boy with a mutation in CYBB gene coding gp91phox protein (X-linked disease developed a liver abscess due to Staphylococcus aureus. In addition to medical therapy, surgical treatment was necessary for the management of the disease. A 30-month-old girl with an autosomal recessive form of chronic granulomatous disease (CYBA gene mutation affecting p22phox protein had invasive aspergillosis causing pericarditis, pulmonary abscess, and central nervous system involvement. The devastating course of disease regardless of the mutation emphasizes the importance of early diagnosis and intervention of hematopoietic stem cell transplantation as soon as possible in children with CGD.

  16. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  17. A designated centre for people with disabilities operated by Stewarts Care Ltd, Dublin 20

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  18. Constitutive NADPH-dependent electron transferase activity of the Nox4 dehydrogenase domain.

    Science.gov (United States)

    Nisimoto, Yukio; Jackson, Heather M; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J David

    2010-03-23

    NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47(phox) and p67(phox) and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K(m) for NADPH of 55 +/- 10 microM. The concentration of Nox4 in cell lysates was estimated using Western blotting and allowed calculation of a turnover of approximately 200 mol of H(2)O(2) min(-1) (mol of Nox4)(-1). A chimeric protein (Nox2/4) consisting of the Nox2 transmembrane (TM) domain and the Nox4 dehydrogenase (DH) domain showed H(2)O(2) production in the absence of cytosolic regulatory subunits. In contrast, chimera Nox4/2, consisting of the Nox4 TM and Nox2 DH domains, exhibited PMA-dependent activation that required coexpression of regulatory subunits. Nox DH domains from several Nox isoforms were purified and evaluated for their electron transferase activities. Nox1 DH, Nox2 DH, and Nox5 DH domains exhibited barely detectable activities toward artificial electron acceptors, while the Nox4 DH domain exhibited significant rates of reduction of cytochrome c (160 min(-1), largely superoxide dismutase-independent), ferricyanide (470 min(-1)), and other electron acceptors (artificial dyes and cytochrome b(5)). Rates were similar to those observed for H(2)O(2) production by the Nox4 holoenzyme in cell lysates. The activity required added FAD and was seen with NADPH but not NADH. These results indicate that the Nox4 DH domain exists in an intrinsically activated state and that electron transfer from NADPH to FAD is likely to be rate-limiting in the NADPH-dependent reduction of oxygen by holo-Nox4.

  19. Transcriptional patterns identify resource controls on the diazotroph Trichodesmium in the Atlantic and Pacific oceans.

    Science.gov (United States)

    Rouco, Mónica; Frischkorn, Kyle R; Haley, Sheean T; Alexander, Harriet; Dyhrman, Sonya T

    2018-02-28

    The N 2 -fixing cyanobacterium Trichodesmium is intensely studied because of the control this organism exerts over the cycling of carbon and nitrogen in the low nutrient ocean gyres. Although iron (Fe) and phosphorus (P) bioavailability are thought to be major drivers of Trichodesmium distributions and activities, identifying resource controls on Trichodesmium is challenging, as Fe and P are often organically complexed and their bioavailability to a single species in a mixed community is difficult to constrain. Further, Fe and P geochemistries are linked through the activities of metalloenzymes, such as the alkaline phosphatases (APs) PhoX and PhoA, which are used by microbes to access dissolved organic P (DOP). Here we identified significant correlations between Trichodesmium-specific transcriptional patterns in the North Atlantic (NASG) and North Pacific Subtropical Gyres (NPSG) and patterns in Fe and P biogeochemistry, with the relative enrichment of Fe stress markers in the NPSG, and P stress markers in the NASG. We also observed the differential enrichment of Fe-requiring PhoX transcripts in the NASG and Fe-insensitive PhoA transcripts in the NPSG, suggesting that metalloenzyme switching may be used to mitigate Fe limitation of DOP metabolism in Trichodesmium. This trait may underpin Trichodesmium success across disparate ecosystems.

  20. Outbursts and diamagnetic cavities in comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Voelzke, M. R.

    2018-03-01

    On 2014 August 06 the Rosetta spacecraft arrived at comet 67P/Churyumov-Gerasimenko. Since then, the spacecraft accompanied the comet on its journey around the Sun (Glassmeier et al. 2007), until the end of the mission on 2016 September 30. This work tries to understand the possible connections between the 665 reported diamagnetic regions (Goetz et al. 2016), detected from April 2015 to February 2016 around the comet 67P/Churyumov-Gerasimenko, with the fluxgate magnetometer of the Rosetta Plasma Consortium (RPC-MAG), when the heliocentric distance of the comet from the sun varied from 1.8 to 2.4 AU and the 34 reported outbursts (Vincent et al. 2016), detected from July to September 2015, with the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras, when the ESA's Rosetta spacecraft changed the cometocentric distance from 155 to 817 km.

  1. Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation.

    Science.gov (United States)

    Hsieh, Chia-Jung; Kuo, Po-Lin; Hsu, Ying-Chan; Huang, Ya-Fang; Tsai, Eing-Mei; Hsu, Ya-Ling

    2014-02-01

    This study investigates the anticancer effect of arctigenin (ATG), a natural lignan product of Arctium lappa L., in human breast cancer MDA-MB-231 cells. Results indicate that ATG inhibits MDA-MB-231 cell growth by inducing apoptosis in vitro and in vivo. ATG triggers the mitochondrial caspase-independent pathways, as indicated by changes in Bax/Bcl-2 ratio, resulting in AIF and EndoG nuclear translocation. ATG increased cellular reactive oxygen species (ROS) production by increasing p22(phox)/NADPH oxidase 1 interaction and decreasing glutathione level. ATG clearly increases the activation of p38 MAPK, but not JNK and ERK1/2. Antioxidant EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, significantly decreases ATG-mediated p38 activation and apoptosis. Blocking p38 with a specific inhibitor suppresses ATG-mediated Bcl-2 downregulation and apoptosis. Moreover, ATG activates ATF-2, a transcription factor activated by p38, and then upregulates histone H3K9 trimethylation in the Bcl-2 gene promoter region, resulting in Bcl-2 downregulation. Taken together, the results demonstrate that ATG induces apoptosis of MDA-MB-231 cells via the ROS/p38 MAPK pathway and epigenetic regulation of Bcl-2 by upregulation of histone H3K9 trimethylation. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  2. Association of pKi-67 with satellite DNA of the human genome in early G1 cells.

    Science.gov (United States)

    Bridger, J M; Kill, I R; Lichter, P

    1998-01-01

    pKi-67 is a nucleolar antigen that provides a specific marker for proliferating cells. It has been shown previously that pKi-67's distribution varies in a cell cycle-dependent manner: it coats all chromosomes during mitosis, accumulates in nuclear foci during G1 phase (type I distribution) and localizes within nucleoli in late G1 S and G2 phase (type II distribution). Although no function has as yet been ascribed to pKi-67, it has been found associated with centromeres in G1. In the present study the distribution pattern of pKi-67 during G1 in human dermal fibroblasts (HDFs) was analysed in more detail. Synchronization experiments show that in very early G1 cells pKi-67 coincides with virtually all satellite regions analysed, i.e. with centromeric (alpha-satellite), telomeric (minisatellite) and heterochromatic blocks (satellite III) on chromosomes 1 and Y (type Ia distribution). In contrast, later in the G1 phase, a smaller fraction of satellite DNA regions are found collocalized with pKi-67 foci (type Ib distribution). When all pKi-67 becomes localized within nucleoli, even fewer satellite regions remain associated with the pKi-67 staining. However, all centromeric and short arm regions of the acrocentric chromosomes, which are in very close proximity to or even contain the rRNA genes, are collocalized with anti-pKi-67 staining throughout the remaining interphase of the cell cycle. Thus, our data demonstrate that during post-mitotic reformation and nucleogenesis there is a progressive decline in the fraction of specific satellite regions of DNA that remain associated with pKi-67. This may be relevant to nucleolar reformation following mitosis.

  3. Aluminum exposure impacts brain plasticity and behavior in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Grassie, C; Braithwaite, V A; Nilsson, J; Nilsen, T O; Teien, H-C; Handeland, S O; Stefansson, S O; Tronci, V; Gorissen, M; Flik, G; Ebbesson, L O E

    2013-08-15

    Aluminum (Al) toxicity occurs frequently in natural aquatic ecosystems as a result of acid deposition and natural weathering processes. Detrimental effects of Al toxicity on aquatic organisms are well known and can have consequences for survival. Fish exposed to Al in low pH waters will experience physiological and neuroendocrine changes that disrupt homeostasis and alter behavior. To investigate the effects of Al exposure on both the brain and behavior, Atlantic salmon (Salmo salar) kept in water treated with Al (pH 5.7, 0.37±0.04 μmol 1(-1) Al) for 2 weeks were compared with fish kept in under control conditions (pH 6.7, salmon, and may impair the ability to cope with new environments.

  4. Human Cytomegalovirus pUL47 Modulates Tegumentation and Capsid Accumulation at the Viral Assembly Complex

    Science.gov (United States)

    Cappadona, Ilaria; Villinger, Clarissa; Schutzius, Gabi; Mertens, Thomas

    2015-01-01

    ABSTRACT Human cytomegalovirus (HCMV) tegument protein pUL47 is an interaction partner of pUL48 and highly conserved among herpesviruses. It is closely associated with the capsid and has an important function early in infection. Here, we report a specific role of pUL47 in the tegumentation of capsids in the cytoplasm. A newly generated mutant virus (TB-47stop), in which expression of pUL47 is blocked, exhibited a severe impairment in cell-to-cell spread and release of infectivity from infected cells. Ultrastructural analysis of TB-47stop-infected cells clearly showed cytoplasmic accumulations of nonenveloped capsids that were only partially tegumented, indicating that these capsids failed to complete tegumentation. Nevertheless, these accumulations were positive for HCMV inner tegument proteins pp150 and pUL48, suggesting that their attachment to capsids occurs independently of pUL47. Despite these morphological alterations, fully enveloped virus particles were found in the extracellular space and at the viral assembly complex (vAC) of TB-47stop-infected cells, indicating that pUL47 is not essential for the generation of virions. We confirmed findings that incorporation of pUL48 into virions is impaired in the absence of pUL47. Interestingly, pUL47 exhibited a strong nuclear localization in transfected cells, whereas it was found exclusively at the vAC in the context of virus infection. Colocalization of pUL47 and pUL48 at the vAC is consistent with their interaction. We also found a shift to a more nuclear localization of pUL47 when the expression of pUL48 was reduced. Summarizing our results, we hypothesize that pUL48 directs pUL47 to the vAC to promote tegumentation and secondary envelopment of capsids. IMPORTANCE Generation of infectious HCMV particles requires an organized and multistep process involving the action of several viral and cellular proteins as well as protein-protein interactions. A better understanding of these processes is important for

  5. Flow- and acetylcholine-induced dilation in small arteries from rats with renovascular hypertension - effect of tempol treatment

    DEFF Research Database (Denmark)

    Christensen, Frank Holden; Stankevicius, Edgaras; Hansen, Thomas

    2007-01-01

    -treated animals, while only the relaxation was improved by the NO donor, S-nitroso-N-acetylpenicillamine (SNAP). In conclusion renovascular hypertension selectively inhibits flow-induced NO-mediated vasodilatation, while EDHF-type vasodilatation remains unaffected, suggesting that high blood pressure leads...... blood pressure and tempol treatment. Simultaneous measurements of NO-concentration and relaxation were performed in isolated coronary arteries from the same animals. As compared to vehicle-treated rats, both acetylcholine-induced relaxation and NO-concentration increased in arteries from tempol......-induced dilatation remained normal. Measured by dihydroethidium staining there was an increased amount of superoxide in arteries from vehicle-treated rats, but not from tempol-treated rats. Expression by immunoblotting of endothelial NO synthase and the NAD(P)H oxidase subunit p47phox remained unaffected by high...

  6.  Immunohistochemical Expression of ki-67 and p53 in Colorectal Adenomas: A Clinicopathological Study

    Directory of Open Access Journals (Sweden)

    Hussam Hasson Ali

    2011-07-01

    Full Text Available  Objectives: To evaluate the significance of P53 and Ki-67 expression as immunohistochemical markers in early detection of premalignant changes in different types of colorectal adenomas. Also, to correlate immunohistochemical expression of the two markers with different clinicopathological parameters including; age, and sex of the patient, type, site, size and grade of dysplasia of colorectal adenomas.Methods: Forty-seven polypectomy specimens of colorectal adenomas were retrieved from the archival materials of the Gastrointestinal and Hepatic Diseases Teaching Hospital in Baghdad from 2009 - 2010. Four µm section specimens were stained by immunohistochemical technique with Ki-67 and P53 tumor markers. P-values <0.05 were considered statistically significant.Results: Immunohistochemical expressions of Ki-67 and P53 had a significant correlation with the size and grade of dysplasia in colorectal adenomas. However, there was no significant correlation among the immunohistochemical expression of Ki-67 and P53 with the age and gender of the patient, and the type and site of colorectal adenomas. There was no significant correlation between Ki-67 and P53 expressions in colorectal adenomas. Villous adenomas of colorectum showed a significant correlation with the grade of dysplasia, while there was no significant correlation between size and site of colorectal adenoma with the grade of dysplasia.Conclusion: High grade dysplasia with significant positive immunohistochemical markers of Ki-67 and P53 could be valuable parameters for selecting from the total colorectal adenoma population, those most deserving of close surveillance in follow-up cancer prevention programs. It is closely linked with increasing age particularly in patients with a large size adenoma of villous component in their histology.

  7. Angiotensin-(1–7 inhibits inflammation and oxidative stress to relieve lung injury induced by chronic intermittent hypoxia in rats

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    W. Lu

    2016-01-01

    Full Text Available Obstructive sleep apnea is associated with inflammation and oxidative stress in lung tissues and can lead to metabolic abnormalities. We investigated the effects of angiotensin1–7 [Ang-(1–7] on lung injury in rats induced by chronic intermittent hypoxia (CIH. We randomly assigned 32 male Sprague-Dawley rats (180–200 g to normoxia control (NC, CIH-untreated (uCIH, Ang-(1–7-treated normoxia control (N-A, and Ang-(1–7-treated CIH (CIH-A groups. Oxidative stress biomarkers were measured in lung tissues, and expression of NADPH oxidase 4 (Nox4 and Nox subunits (p22phox, and p47phox was determined by Western blot and reverse transcription-polymerase chain reaction. Pulmonary pathological changes were more evident in the uCIH group than in the other groups. Enzyme-linked immunosorbent assays and immunohistochemical staining showed that inflammatory factor concentrations in serum and lung tissues in the uCIH group were significantly higher than those in the NC and N-A groups. Expression of inflammatory factors was significantly higher in the CIH-A group than in the NC and N-A groups, but was lower than in the uCIH group (P<0.01. Oxidative stress was markedly higher in the uCIH group than in the NC and N-A groups. Expression of Nox4 and its subunits was also increased in the uCIH group. These changes were attenuated upon Ang-(1–7 treatment. In summary, treatment with Ang-(1-7 reversed signs of CIH-induced lung injury via inhibition of inflammation and oxidative stress.

  8. NADPH oxidase is not an essential mediator of oxidative stress or liver injury in murine MCD diet-induced steatohepatitis.

    Science.gov (United States)

    dela Peña, Aileen; Leclercq, Isabelle A; Williams, Jacqueline; Farrell, Geoffrey C

    2007-02-01

    Hepatic oxidative stress is a key feature of metabolic forms of steatohepatitis, but the sources of pro-oxidants are unclear. The NADPH oxidase complex is critical for ROS generation in inflammatory cells; loss of any one component (e.g., gp91phox) renders NADPH oxidase inactive. We tested whether activated inflammatory cells contribute to oxidant stress in steatohepatitis. gp91phox-/- and wildtype (wt) mice were fed a methionine and choline-deficient (MCD) diet. Serum ALT, hepatic triglycerides, histopathology, lipid peroxidation, activation of NF-kappaB, expression of NF-kappaB-regulated genes and macrophage chemokines were measured. After 10 days of MCD dietary feeding, gp91phox-/- and wt mice displayed equivalent hepatocellular injury. After 8 weeks, there were fewer activated macrophages in livers of gp91phox-/- mice than controls, despite similar mRNA levels for MCP and MIP chemokines, but fibrosis was similar. NF-kappaB activation and increased expression of ICAM-1, TNF-alpha and COX-2 mRNA were evident in both genotypes, but in gp91phox-/- mice, expression of these genes was confined to hepatocytes. A functional NADPH oxidase complex does not contribute importantly to oxidative stress in this model and therefore is not obligatory for induction or perpetuation of dietary steatohepatitis.

  9. Tensile strength of 67P/Churyumov-Gerasimenko nucleus material from overhangs

    Science.gov (United States)

    Attree, N.; Groussin, O.; Jorda, L.; Nébouy, D.; Thomas, N.; Brouet, Y.; Kührt, E.; Preusker, F.; Scholten, F.; Knollenberg, J.; Hartogh, P.; Sierks, H.; Barbieri, C.; Lamy, P.; Rodrigo, R.; Koschny, D.; Rickman, H.; Keller, H. U.; A'Hearn, M. F.; Auger, A.-T.; Barucci, M. A.; Bertaux, J.-L.; Bertini, I.; Bodewits, D.; Boudreault, S.; Cremonese, G.; Da Deppo, V.; Davidsson, B.; Debei, S.; De Cecco, M.; Deller, J.; El-Maarry, M. R.; Fornasier, S.; Fulle, M.; Gutiérrez, P. J.; Güttler, C.; Hviid, S.; Ip, W.-H.; Kovacs, G.; Kramm, J. R.; Küppers, M.; Lara, L. M.; Lazzarin, M.; Lopez Moreno, J. J.; Lowry, S.; Marchi, S.; Marzari, F.; Mottola, S.; Naletto, G.; Oklay, N.; Pajola, M.; Toth, I.; Tubiana, C.; Vincent, J.-B.; Shi, X.

    2018-03-01

    We directly measured twenty overhanging cliffs on the surface of comet 67P/Churyumov-Gerasimenko extracted from the latest shape model and estimated the minimum tensile strengths needed to support them against collapse under the comet's gravity. We find extremely low strengths of around 1 Pa or less (1 to 5 Pa, when scaled to a metre length). The presence of eroded material at the base of most overhangs, as well as the observed collapse of two features andthe implied previous collapse of another, suggests that they are prone to failure and that the true material strengths are close to these lower limits (although we only consider static stresses and not dynamic stress from, for example, cometary activity). Thus, a tensile strength of a few pascals is a good approximation for the tensile strength of the 67P nucleus material, which is in agreement with previous work. We find no particular trends in overhang properties either with size over the 10-100 m range studied here or location on the nucleus. There are no obvious differences, in terms of strength, height or evidence of collapse, between the populations of overhangs on the two cometary lobes, suggesting that 67P is relatively homogenous in terms of tensile strength. Low material strengths are supportive of cometary formation as a primordial rubble pile or by collisional fragmentation of a small body (tens of km).

  10. Exercise training protects against atherosclerotic risk factors through vascular NADPH oxidase, extracellular signal-regulated kinase 1/2 and stress-activated protein kinase/c-Jun N-terminal kinase downregulation in obese rats.

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    Touati, Sabeur; Montezano, Augusto C I; Meziri, Fayçal; Riva, Catherine; Touyz, Rhian M; Laurant, Pascal

    2015-02-01

    Exercise training reverses atherosclerotic risk factors associated with metabolic syndrome and obesity. The aim of the present study was to determine the molecular anti-inflammatory, anti-oxidative and anti-atherogenic effects in aorta from rats with high-fat diet-induced obesity. Male Sprague-Dawley rats were placed on a high-fat (HFD) or control (CD) diet for 12 weeks. The HFD rats were then divided into four groups: (i) sedentary HFD-fed rats (HFD-S); (ii) exercise trained (motor treadmill 5 days/week, 60 min/day, 12 weeks) HFD-fed rats (HFD-Ex); (iii) modified diet (HFD to CD) sedentary rats (HF/CD-S); and (iv) an exercise-trained modified diet group (HF/CD-Ex). Tissue levels of NADPH oxidase (activity and expression), NADPH oxidase (Nox) 1, Nox2, Nox4, p47(phox) , superoxide dismutase (SOD)-1, angiotensin AT1 and AT2 receptors, phosphorylated mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase (ERK) 1/2, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the aorta. Plasma cytokines (tumour necrosis factor (TNF)-α and interleukin (IL)-6) levels were also measured. Obesity was accompanied by increases in NADPH oxidase activity, p47(phox) translocation, Nox4 and VCAM-1 protein expression, MAPK (ERK1/2, SAPK/JNK) phosphorylation and plasma TNF-α and IL-6 levels. Exercise training and switching from the HFD to CD reversed almost all these molecular changes. In addition, training increased aortic SOD-1 protein expression and decreased ERK1/2 phosphorylation. These findings suggest that protective effects of exercise training on atherosclerotic risk factors induced by obesity are associated with downregulation of NADPH oxidase, ERK1/2 and SAPK/JNK activity and increased SOD-1 expression. © 2014 Wiley Publishing Asia Pty Ltd.

  11. Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

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    Bo Hu

    2018-02-01

    Full Text Available Background/Aims: Renal ischemia/reperfusion (I/R injury (RI/RI is a common complication of diabetes, and it may be involved in altering intracellular calcium concentrations at its onset, which can result in inflammation, abnormal lipid metabolism, the production of reactive oxygen species (ROS, and nitroso-redox imbalance. The calcium-sensing receptor (CaSR is a G-protein coupled receptor, however, the functional involvement of CaSR in diabetic RI/ RI remains unclear. The present study was intended to investigate the role of CaSR on RI/RI in diabetes mellitus (DM. Methods: The bilateral renal arteries and veins of streptozotocin (STZ-induced diabetic rats were subjected to 45-min ischemia followed by 2-h reperfusion with or without R-568 (agonist of CaSR and NPS-2143 (antagonist of CaSR at the beginning of I/R procedure. DM without renal I/R rats served as control group. The expressions of CaSR, calmodulin (CaM, and p47phox in the renal tissue were analyzed by qRT-PCR and Western blot. The renal pathomorphology, renal function, oxidative stress, inflammatory response, and calcium disorder were evaluated by detection of a series of indices by hematoxylin-eosin (HE staining, transmission electron microscope (TEM, commercial kits, enzyme-linked immunosorbent assay (ELISA, and spectrophotofluorometry, respectively. Results: Results showed that the expressions of CaSR, CaM, and p47phox in I/R group were significantly up-regulated as compared with those in DM group, which were accompanied by renal tissue injury, increased calcium, oxidative stress, inflammation, and nitroso-redox imbalance. Conclusion: These results suggest that activation of CaSR is involved in the induction of damage of renal tubular epithelial cell during diabetic RI/RI, resulting in lipid peroxidation, inflammatory response, nitroso-redox imbalance, and apoptosis.

  12. Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions.

    Science.gov (United States)

    Kim, Arang; Lee, Wooje; Yun, Jung-Mi

    2017-10-01

    Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

  13. Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions.

    Science.gov (United States)

    Byers, Heather M; Chen, Maida; Gelfand, Andrew S; Ong, Bruce; Jendras, Marisa; Glass, Ian A

    2018-04-25

    Congenital central hypoventilation syndrome (CCHS) is a neurocristopathy caused by pathogenic heterozygous variants in the gene paired-like homeobox 2b (PHOX2B). It is characterized by severe infantile alveolar hypoventilation. Individuals may also have diffuse autonomic nervous system dysfunction, Hirschsprung disease and neural crest tumors. We report three individuals with CCHS due to an 8-base pair duplication in PHOX2B; c.691_698dupGGCCCGGG (p.Gly234Alafs*78) with a predominant enteral and neural crest phenotype and a relatively mild respiratory phenotype. The attenuated respiratory phenotype reported here and elsewhere suggests an emergent genotype:phenotype correlation which challenges the current paradigm of invoking mechanical ventilation for all infants diagnosed with CCHS. Best treatment requires careful clinical judgment and ideally the assistance of a care team with expertise in CCHS. © 2018 Wiley Periodicals, Inc.

  14. Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening.

    Science.gov (United States)

    Wentzensen, Nicolas; Fetterman, Barbara; Tokugawa, Diane; Schiffman, Mark; Castle, Philip E; Wood, Shannon N; Stiemerling, Eric; Poitras, Nancy; Lorey, Thomas; Kinney, Walter

    2014-12-01

    Dual-stain cytology for p16 and Ki-67 has been proposed as a biomarker in cervical cancer screening. The authors evaluated the reproducibility and accuracy of dual-stain cytology among 10 newly trained evaluators. In total, 480 p16/Ki-67-stained slides from human papillomavirus-positive women were evaluated in masked fashion by 10 evaluators. None of the evaluators had previous experience with p16 or p16/Ki-67 cytology. All participants underwent p16/Ki-67 training and subsequent proficiency testing. Reproducibility of dual-stain cytology was measured using the percentage agreement, individual and aggregate κ values, as well as McNemar statistics. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was evaluated for each individual evaluator and for all evaluators combined compared with the reference evaluation by a cytotechnologist who had extensive experience with dual-stain cytology. The percentage agreement of individual evaluators with the reference evaluation ranged from 83% to 91%, and the κ values ranged from 0.65 to 0.81. The combined κ value was 0.71 for all evaluators and 0.73 for cytotechnologists. The average sensitivity and specificity for the detection of CIN2+ among novice evaluators was 82% and 64%, respectively; whereas the reference evaluation had 84% sensitivity and 63% specificity, respectively. Agreement on dual-stain positivity increased with greater numbers of p16/Ki-67-positive cells on the slides. Good to excellent reproducibility of p16/Ki-67 dual-stain cytology was observed with almost identical clinical performance of novice evaluators compared with reference evaluations. The current findings suggest that p16/Ki-67 dual-stain evaluation can be implemented in routine cytology practice with limited training. © 2014 American Cancer Society.

  15. Genetics Home Reference: congenital central hypoventilation syndrome

    Science.gov (United States)

    ... Kravis EM, Zhou L, Rand CM, Weese-Mayer DE. Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype. Am J Respir Crit ... BA, Leurgans SE, Berry-Kravis EM, Weese-Mayer DE. Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death. Pediatr ...

  16. SUBSURFACE CHARACTERIZATION OF 67P/CHURYUMOV–GERASIMENKO’S ABYDOS SITE

    Energy Technology Data Exchange (ETDEWEB)

    Brugger, B.; Mousis, O.; Jorda, L.; Lamy, P.; Vernazza, P. [Aix Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388, Marseille (France); Morse, A.; Andrews, D.; Barber, S.; Morgan, G.; Sheridan, S.; Wright, I. P. [Planetary and Space Sciences, Department of Physics, The Open University, Walton Hall, Milton Keynes MK7 6AA (United Kingdom); Marboeuf, U. [Physikalishes Institut, Center for Space and Habitability, University of Bern (Switzerland); Guilbert-Lepoutre, A. [Institut UTINAM, UMR 6213 CNRS-Université de Franche-Comté, Besançon (France); Luspay-Kuti, A.; Mandt, K., E-mail: bastien.brugger@lam.fr [Department of Space Science, Southwest Research Institute, 6220 Culebra Road, San Antonio, TX 78228 (United States)

    2016-05-10

    On 2014 November 12, the ESA/ Rosetta descent module Philae landed on the Abydos site of comet 67P/Churyumov–Gerasimenko. Aboard this module, the Ptolemy mass spectrometer measured a CO/CO{sub 2} ratio of 0.07 ± 0.04, which differs substantially from the value obtained in the coma by the Rosetta /ROSINA instrument, suggesting a heterogeneity in the comet nucleus. To understand this difference, we investigated the physicochemical properties of the Abydos subsurface, leading to CO/CO{sub 2} ratios close to that observed by Ptolemy at the surface of this region. We used a comet nucleus model that takes into account different water ice phase changes (amorphous ice, crystalline ice, and clathrates) as well as diffusion of molecules throughout the pores of the matrix. The input parameters of the model were optimized for the Abydos site, and the ROSINA CO/CO{sub 2} measured ratio is assumed to correspond to the bulk value in the nucleus. We find that all considered structures of water ice are able to reproduce the Ptolemy observation with a time difference not exceeding ∼50 days, i.e., lower than ∼2% on 67P/Churyumov–Gerasimenko’s orbital period. The suspected heterogeneity of 67P/Churyumov–Gerasimenko’s nucleus is also found possible only if it is constituted of crystalline ices. If the icy phase is made of amorphous ice or clathrates, the difference between Ptolemy and ROSINA’s measurements would rather originate from the spatial variations in illumination on the nucleus surface. An eventual new measurement of the CO/CO{sub 2} ratio at Abydos by Ptolemy could be decisive to distinguish between the three water ice structures.

  17. Extracellular proteases from the Antarctic marine Pseudoalteromonas sp. P96-47 strain Proteasas extracelulares de la cepa marina antártica Pseudoalteromonas sp. P96-47

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    S.C. Vázquez

    2008-03-01

    Full Text Available The extracellular protease-production capacity of 33 bacterial isolates taken from marine biotopes in King George Island, Antarctica, was evaluated in liquid cultures. The P96-47 isolate was selected due to its high production capacity and was identified as Pseudoalteromonas sp. The optimal growth temperature was 20 °C and the optimal for protease production was 15 °C. Proteases were purified from culture supernatants, developing a multiple-band profile in zymograms. They were classified as neutral metalloproteases and worked optimally at 45 °C with an Eact of 47 kJ/ mol. Their stability was higher at neutral pH, retaining more than 80% of activity at pH 6-10 after 3 h incubation at 4 °C. After 90 min incubation at 40 and 50 °C, the percentages of residual activities were 78% and 44%. These results contribute to the basic knowledge of Antarctic marine proteases and also help evaluate the probable industrial applications of P96-47 proteases.La capacidad productora de proteasas extracelulares de 33 aislamientos bacterianos tomados de biotopos marinos en la Isla Rey Jorge, Antártida, fue evaluada en cultivo líquido. El aislamiento P96-47 fue seleccionado debido a su alta capacidad productora y fue identificado como Pseudoalteromonas sp. La temperatura óptima de crecimiento fue de 20 °C y la de producción de 15 °C. Las proteasas fueron purificadas a partir del sobrenadante de cultivo, y en los zimogramas desarrollaron un perfil de múltiples bandas. Estas proteasas fueron clasificadas como metaloproteasas neutras y se observó que trabajan óptimamente a 45 °C, con una Eact de 47 kJ/ mol. Su estabilidad fue superior a pH neutro y retuvieron más del 80% de su actividad a pH 6-10 después de 3 h de incubación a 4 °C. Luego de 90 min de incubación a 40 y 50 °C, las actividades residuales fueron 78% y 44%, respectivamente. Los resultados que se presentan en este trabajo contribuyen al conocimiento básico de las proteasas marinas ant

  18. Advanced Glycation End-Products Induce Apoptosis of Vascular Smooth Muscle Cells: A Mechanism for Vascular Calcification

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    Sayo Koike

    2016-09-01

    Full Text Available Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD. To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs stimulated calcium deposition in vascular smooth muscle cells (VSMCs through excessive oxidative stress and phenotypic transition into osteoblastic cells. Since AGEs can induce apoptosis, in this study we investigated its role on VSMC apoptosis, focusing mainly on the underlying mechanisms. A rat VSMC line (A7r5 was cultured, and treated with glycolaldehyde-derived AGE-bovine serum albumin (AGE3-BSA. Apoptotic cells were identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. To quantify apoptosis, an enzyme-linked immunosorbent assay (ELISA for histone-complexed DNA fragments was employed. Real-time PCR was performed to determine the mRNA levels. Treatment of A7r5 cells with AGE3-BSA from 100 µg/mL concentration markedly increased apoptosis, which was suppressed by Nox inhibitors. AGE3-BSA significantly increased the mRNA expression of NAD(PH oxidase components including Nox4 and p22phox, and these findings were confirmed by protein levels using immunofluorescence. Dihydroethidisum assay showed that compared with cBSA, AGE3-BSA increased reactive oxygen species level in A7r5 cells. Furthermore, AGE3-induced apoptosis was significantly inhibited by siRNA-mediated knockdown of Nox4 or p22phox. Double knockdown of Nox4 and p22phox showed a similar inhibitory effect on apoptosis as single gene silencing. Thus, our results demonstrated that NAD(PH oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD.

  19. Assessment of p21, p53 expression, and Ki-67 proliferative activities in the gastric mucosa of children with Helicobacter pylori gastritis.

    Science.gov (United States)

    Saf, Coskun; Gulcan, Enver Mahir; Ozkan, Ferda; Cobanoglu Saf, Seyhan Perihan; Vitrinel, Ayca

    2015-02-01

    Helicobacter pylori that is generally acquired in childhood and infects the gastric mucosa is considered to be responsible for many pathobiological changes that are linked to the pathogenesis of gastric cancer. Although the majority of studies on the subject have been carried out in adults, there are a limited number of studies on children that reflect the early period of infection and may be of greater significance. We aimed to determine the role of H. pylori infection and/or gastritis in several histopathological changes, p53, p21, and cell proliferation-associated Ki-67 antigen expression in the gastric mucosa. We studied 60 patients with a mean age of 7.5 ± 4.5 years at referral. On the basis of endoscopic appearance and the evaluation of the gastric antral specimens, the patients were divided into three groups: patients without gastritis, patients with H. pylori-positive gastritis, and patients with H. pylori-negative gastritis. To determine the expression of p53, Ki-67, and p21 in gastric biopsy specimens, immunohistochemical stains were performed. The incidence of neutrophil activity, which was one of our histopathologic parameters, was significantly higher in the H. pylori-positive gastritis group than the other two groups. The presence of lymphoid aggregate was more frequent in H. pylori ± gastritis groups than the nongastritis group. p53 expression was found to be significantly higher in the H. pylori-positive gastritis group than the nongastritis group. Ki-67 and p21 expressions were significantly more frequent in the H. pylori-positive gastritis group than the other two groups. When we evaluated the density of H. pylori, as the density of bacteria increases, we found that the expressions of p53, p21, and Ki-67 increased significantly. Expression of the studied precancerous markers in significant amounts indicates the importance of childhood H. pylori infection in the constitution of gastric cancer in adulthood.

  20. Adiponectin attenuates angiotensin II-induced vascular smooth muscle cell remodeling through nitric oxide and the RhoA/ROCK pathway.

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    Wared eNour-Eldine

    2016-04-01

    Full Text Available INTRODUCTION: Adiponectin (APN, an adipocytokine, exerts protective effects on cardiac remodeling, while angiotensin II (Ang II induces hypertension and vascular remodeling. The potential protective role of APN on the vasculature during hypertension has not been fully elucidated yet. Here, we evaluate the molecular mechanisms of the protective role of APN in the physiological response of the vascular wall to Ang II.METHODS AND RESULTS: Rat aortic tissues were used to investigate the effect of APN on Ang II-induced vascular remodeling and hypertrophy. We investigated whether nitric oxide (NO, the RhoA/ROCK pathway, actin cytoskeleton remodeling, and reactive oxygen species (ROS mediate the anti-hypertrophic effect of APN. Ang II-induced protein synthesis was attenuated by pre-treatment with APN, NO donor (SNAP, or cGMP. The hypertrophic response to Ang II was associated with a significant increase in RhoA activation and vascular force production, which were prevented by APN and SNAP. NO was also associated with inhibition of Ang II-induced phosphorylation of cofilin. In addition, immunohistochemistry revealed that 24 hr Ang II treatment increased the F- to G-actin ratio, an effect that was inhibited by SNAP. Ang II-induced ROS formation and upregulation of p22phox mRNA expression were inhibited by APN and NO. Both compounds failed to inhibit Nox1 and p47phox expression. CONCLUSIONS: Our results suggest that the anti-hypertrophic effects of APN are due, in part, to NO-dependent inhibition of the RhoA/ROCK pathway and ROS formation.

  1. A 6-gene signature identifies four molecular subgroups of neuroblastoma

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    Kogner Per

    2011-04-01

    Full Text Available Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB; Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples. Four distinct clusters were identified by Principal Components Analysis (PCA in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics.

  2. Immunohistochemical characteristic of expression levels of Kі-67, p16INK4a, HPV16 in cervical intraepithelial neoplasia and cervical cancer

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    V. A. Tumanskiy

    2017-08-01

    Full Text Available Squamous cervical cancer (SCC is a common tumor in women, which is preceded by the series of pathological processes, among which the key role is played by cervical intraepithelial neoplasia (CIN. Aim. To study the characteristics of immunohistochemical (IHC expression of Ki-67, p16INK4a, HPV16 in squamous cervical epithelium (SCE with dysplastic changes of varying degree (CIN I–III and also in the tumor cells of SCC. Materials and methods. Pathohistological and IHC studies of uterine cervix biopsies from 53 patients (the age ranged from 18 to 45 years were performed. Results. It was found that SCE with CIN I is characterized by the low Ki-67 expression level (Me = 17.87 % (13.76, 22.44 and the extremely low p16INK4a expression level (Me = 0.00 CUOD (0.00; 29.64. The proportion of HPV16-positive patients with CIN I is 27.27 %. CIN II is characterized by the average proliferation level in SCE (Me = 44.96 % (34.91, 55.41 and the moderate p16INK4a expression level (Me = 75.71 CUOD (51.24, 82, 41. The proportion of HPV16-positive patients with CIN II is 71.43 %. CIN III is characterized by the high proliferation level (Me = 74.62 % (68.50, 84.67 and by the high p16INK4a expression level of in SCE (Me = 117.47 CUOD (95.38, 123, 93; the proportion of HPV16-positive patients with CIN III is 77.78%. In all the patients with SСС, nuclear and cytoplasmic expression of HPV16 was detected in the tumor cells. High expression levels of Ki-67 and p16INK4a were detected in the tumor cells. There are direct correlations between the expression levels of Ki-67, p16INK4a, HPV16 and CIN degree. Conclusions. These data indicate that the expression levels of Ki-67, p16INK4a and HPV16 increase with the increasing of CIN grade. The absence of statistically significant differences between the expression levels of Ki-67, p16INK4a and HPV16 in CIN III and the same levels in the tumor cells of SCC indicates that these markers cannot be used for differential diagnosis

  3. Expression of PPARγ, p27 and Ki67 in Cervical Cancer and its Clinical Significance

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    Peng-li LI

    2015-03-01

    Full Text Available Objective: To investigate the expression of peroxisome proliferation-activated receptor γ (PPARγ, p27 and Ki67 in cervical cancer and its clinical significance. Methods: The expression of PPARγ, p27 and Ki67 in the tissues of 42 patients with cervical cancer, 28 with cervical intraepithelial neoplasia (CIN and 12 with normal cervix was detected using immunohistochemistry. Results:The positive rate of PPARγ protein in cervical cancer tissue (76.2% was significantly higher than in CIN (53.6% and normal cervical tissue (8.3% (P<0.05 orP<0.01, which was also evidently higher in CIN than in normal cervical tissue (P<0.05. The positive rate of p27 protein in cervical cancer tissue (31.0% was significantly lower than in CIN (57.1% and normal cervical tissue (83.3% (P<0.05 or P<0.01, and that in CIN had a markedly lower tendency compared with normal cervical tissue (P<0.05. The positive rate of Ki67 protein in cervical cancer tissue (100.0% was apparently higher than in CIN (85.7% and normal cervical tissue (33.3% (P<0.05 or P<0.01, which was also markedly higher in CIN than in normal cervical tissue (P<0.01. The expression of PPARγ, p27 and Ki67 proteins was not associated with the clinicopathological features of patients, including the age, histological types, pathological grading and clinical staging (P>0.05.Conclusion: Abnormal expression of PPARγ, p27 and Ki67 may play important roles in occurrence and progression of cervical cancer, and hence, joint detection of PPARγ, p27 and Ki67 can be used to diagnose early CIN and cervical cancer.

  4. CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

    Directory of Open Access Journals (Sweden)

    Ming-Horng Tsai

    2017-08-01

    Full Text Available Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9 induced migration of human aortic smooth muscle cells (HASMCs is the most common and basic pathological feature. Carbon monoxide (CO, a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2 on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47phox, Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed. Keywords: Angiotensin II, Carbon monoxide, Human aortic smooth muscle cell, Inflammation, Matrix metallopeptidase

  5. Cosmochemical implications of CONSERT permittivity characterization of 67P/C-G

    Science.gov (United States)

    Levasseur-Regourd, A.; Hérique, Alain; Kofman, Wlodek; Beck, Pierre; Bonal, Lydie; Buttarazzi, Ilaria; Heggy, Essam; Lasue, Jeremie; Quirico, Eric; Zine, Sonia

    2016-10-01

    Unique information about the internal structure of the nucleus of comet 67P/C-G was provided by the CONSERT bistatic radar on-board Rosetta and Philae [1]. Analysis of the propagation of its signal throughout the small lobe indicated that the real part of the permittivity at 90 MHz is of (1.27±0.05). The first interpretation of this value using dielectric properties of mixtures of dust and ices (H2O, CO2), led to the conclusion that the comet porosity ranges between 75-85%. In addition, the dust/ice ratio was found to range between 0.4-2.6 and the permittivity of dust (including 30% of porosity) was determined to be lower than 2.9.The dust permittivity estimate is now reduced by taking into account the updated values of nucleus density and of dust/ice ratio, in order of providing further insights into the nature of the constituents of comet 67P/C-G [2]. We adopt a systematic approach: i) determination of the dust permittivity as a function of the ice (I) to dust (D) and vacuum (V) volume fraction; ii) comparison with the permittivity of meteoritic, mineral and organic materials from literature and laboratory measurements; iii) test of several composition models of the nucleus, corresponding to cosmochemical end members of 67P/C-G. For each of these models the location in the ternary I/D/V diagram is calculated based on available dielectric measurements, and confronted to the locus of 67P/C-G. The number of compliant models is small and the cosmochemical implications of each are discussed [2]. An important fraction of carbonaceous material is required in the dust in order to match CONSERT permittivity observations, establishing that comets represent a massive carbon reservoir.Support from Centre National d'Études Spatiales (CNES, France) for this work, based on observations with CONSERT on board Rosetta, is acknowledged. The CONSERT instrument was designed, built and operated by IPAG, LATMOS and MPS and was financially supported by CNES, CNRS, UJF/UGA, DLR and MPS

  6. High-level mRNA quantification of proliferation marker pKi-67 is correlated with favorable prognosis in colorectal carcinoma.

    Science.gov (United States)

    Ihmann, Thomas; Liu, Jian; Schwabe, Wolfgang; Häusler, Peter; Behnke, Detlev; Bruch, Hans-Peter; Broll, Rainer; Windhövel, Ute; Duchrow, Michael

    2004-12-01

    The present study retrospectively examines the expression of pKi-67 mRNA and protein in colorectal carcinoma and their correlation to the outcome of patients. Immunohistochemistry and quantitative RT-PCR were used to analyze the expression of pKi-67 in 43 archival specimens of patients with curatively resected primary colorectal carcinoma, who were not treated with neo-adjuvant therapy. We determined a median pKi-67 (MIB-1) labeling index of 31.3% (range 10.3-66.4%), and a mean mRNA level of 0.1769 (DeltaC(T): range 0.01-0.69); indices and levels did not correlate. High pKi-67 mRNA DeltaC(T) values were associated with a significantly favorable prognosis, while pKi-67 labeling indices were not correlated to prognostic outcome. A multivariate analysis of clinical and biological factors indicated that tumor stage (UICC) and pKi-67 mRNA expression level were independent prognostic factors. Quantitatively determined pKi-67 mRNA can be a good and new prognostic indicator for primary resected colorectal carcinoma.

  7. [Expression of Ki-67 and P53 protein in oral squamous cell carcinoma and its clinical significance].

    Science.gov (United States)

    He, Wei; Xiao, Yan; Chen, Wei-min

    2015-04-01

    To investigate the clinical and pathological features and its relationship with the expression of Ki-67 and p53 protein in oral squamous cell carcinoma. Immunohistochemical SP staining method was used to quantify the protein expression levels of Ki-67 and p53 protein in 10 cases of normal oral mucosa, 16 cases of oral leukoplakia (OLK) tissue, and 48 cases of oral squamous cell carcinoma. The relationship of the expression of Ki-67 and p53 protein to clinical and pathological data was analyzed, and SPSS17.0 software package was used for statistical analysis. The positive expression rate of Ki-67 protein in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma was 30%, 56.3% and 79.2%, respectively; The positive expression rate of p53 was 0%, 43.8%, and 70.8%, respectively; Ki-67 and p53 expression had significant difference among normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma (Poral squamous cell carcinoma (Poral squamous cell carcinoma tissues may play an important role in the development of oral squamous cell carcinoma.

  8. Preparation of carrier-free 67Cu by the 68Zn(γ,p) reaction

    International Nuclear Information System (INIS)

    Yagi, M.; Kondo, K.

    1978-01-01

    The preparation of pure, carrier-free 67 Cu using the 68 Zn(γ, p) reaction with an isotopically enriched 68 Zn(98.97%) target is described. The production rates of 67 Cu and contaminants were determined as a function of the maximum bremsstrahlung energies between 30 and 60 MeV. The chemical separation of the carrier-free 67 Cu and the recovery of the 68 Zn target were also studied. (author)

  9. Evaluated (n,p) cross sections of 46Ti, 47Ti and 48Ti

    International Nuclear Information System (INIS)

    Philis, C.; Bersillon, O.; Smith, D.; Smith, A.

    1977-01-01

    Microscopic evaluated neutron cross sections for the reactions 46 Ti(n;p) 46 Sc, 47 Ti(n;p) 47 Sc and 48 Ti(n;p) 48 Sc are obtained from threshold (or zero energy) to 20 MeV. The results are presented in graphical and numerical (ENDF format) form. The microscopic evaluated cross sections are compared with measured fission-spectrum-averaged values

  10. The proliferation marker pKi-67 becomes masked to MIB-1 staining after expression of its tandem repeats.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Duchrow, Michael

    2002-11-01

    The Ki-67 antigen, pKi-67, is one of the most commonly used markers of proliferating cells. The protein can only be detected in dividing cells (G(1)-, S-, G(2)-, and M-phase) but not in quiescent cells (G(0)). The standard antibody to detect pKi-67 is MIB-1, which detects the so-called 'Ki-67 motif' FKELF in 9 of the protein's 16 tandem repeats. To investigate the function of these repeats we expressed three of them in an inducible gene expression system in HeLa cells. Surprisingly, addition of a nuclear localization sequence led to a complete absence of signal in the nuclei of MIB-1-stained cells. At the same time antibodies directed against different epitopes of pKi-67 did not fail to detect the protein. We conclude that the overexpression of the 'Ki-67 motif', which is present in the repeats, can lead to inability of MIB-1 to detect its antigen as demonstrated in adenocarcinoma tissue samples. Thereafter, in order to prevent the underestimation of Ki-67 proliferation indices in MIB-1-labeled preparations, additional antibodies (for example, MIB-21) should be used. Additionally, we could show in a mammalian two-hybrid assay that recombinant pKi-67 repeats are capable of self-associating with endogenous pKi-67. Speculating that the tandem repeats are intimately involved in its protein-protein interactions, this offers new insights in how access to these repeats is regulated by pKi-67 itself.

  11. CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

    Directory of Open Access Journals (Sweden)

    Sarah A. Abd El-Aal

    2017-10-01

    Full Text Available Statins were reported to lower the Coenzyme Q10 (CoQ10 content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg, CoQ10 (10 mg/kg and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase. They also opposed the upregulation of gp91phox, and p47phox subunits of NADPH oxidase. Meanwhile, both agents reduced content/expression of TNF-α, iNOS, NF-κBp65, ICAM-1, and MPO. Besides, all regimens abated cytochrome c, caspase-3 and Bax, but increased Bcl-2 in favor of cell survival. On the molecular level, they increased p-Akt and its downstream target p-FOXO3A, with the inhibition of the nuclear content of FOXO3A to downregulate the expression of Bim, a pro-apoptotic gene. Additionally, both treatments downregulate the JNK3/c-Jun signaling pathway. The effect of the combination regimen overrides that of either treatment alone. These effects were reflected on the alleviation of the hippocampal damage in CA1 region inflicted by I/R. Together, these findings accentuate the neuroprotective potentials of both treatments against global I/R by virtue of their rigorous multi-pronged actions, including suppression of hippocampal oxidative stress, inflammation, and apoptosis with the involvement of the Akt/FOXO3A/Bim and JNK3/c-Jun/Bax signaling pathways. The study also nominates CoQ10 as an adds-on therapy with statins.

  12. Evaluation of Ki-67 Antigen and Protein P53 Expression in Orthokratinized and Parakratinized Odontogenic Keratocyst

    Directory of Open Access Journals (Sweden)

    F. Baghaei

    2004-06-01

    Full Text Available Statement of Problem: Odontogenic Keratocysts (OKC make up 10-12% of all developmental cysts with dental origin. OKCs are classified into parakeratotic and orthokeratotic types, with completely different clinical features. In order to investigate biological behavior of OKCs, an immunohistochemical study was designed, using Ki-67 antigen as proliferation marker and P53 protein as tumor suppressor gene.Purposes: The aim of the present study was to investigate the expression of P53 and Ki-67 markers in two types of OKCs and to determine their relationship with the biological behaviour of OKC.Materials and Methods: A total of 20 OKCs (parakeratotic n=10, orthokeratotic n=10were stained immunohistochemically for Ki-67 and P53 protein by Biotin – Streptavidine method. Then, slides were studied quantitatively through optical lense (magnification=X10and the number of positively stained cells was counted/mm BM.Results: The average number of Positively stained cells for Ki-67 were 62.30±11.96 cells/mm BM in parakeratotic, and 29.90±4.90 cells/mmBM in orthokeratotic OKCs (P<0.05. Positive cells for Ki-67 were dominantly located in parabasal layer. Mean stainedcells for P53 were 4.30± 2.21cells/mmBM in parakeratinized and 4.80±1.75 cells/mmBM in orthokeratotic types that was not statistically significant. (P<0.58Parakeratotic OKCs mostly occur in the lower jaw (90%, whereas just 50% of orthokeratotic OKCs occur in mandible (P=0.05Conclusion: Regarding other clinical features and the existence of daughter cysts, no significant statistical difference was found between two types of OKCs.

  13. Systematics of proton absorption deduced from ( p,p) and ( p,n) cross sectionsfor 2.0- to 6.7-MeV protons on /sup 107,109/Ag and 115In

    International Nuclear Information System (INIS)

    Hershberger, R.L.; Flynn, D.S.; Gabbard, F.; Johnson, C.H.

    1980-01-01

    The ( p,p) and ( p,n) cross sections were measured to accuracies of +- 2% and +- 3%, respectively, for 2.0- to 6.7-MeV protons on /sup 107,109/Ag and 115 In. Hauser-Feshbach calculations, which included γ-ray emission channels, were used to convert the ( p,n) cross sections to proton absorption cross sections. Analysis of the ( p,p) and deduced proton absorption cross sections were made simultaneously using a conventional optical-model potential. The measured cross sections can be described using parameters extrapolated from the Sn region in a systematic way, except for a large increase required for the depth of the absorptive potential

  14. Resveratrol efficiently improves pulmonary function via stabilizing mast cells in a rat intestinal injury model.

    Science.gov (United States)

    Huang, Xiaolei; Zhao, Weicheng; Hu, Dan; Han, Xue; Wang, Hanbin; Yang, Jianyu; Xu, Yang; Li, Yuantao; Yao, Weifeng; Chen, Chaojin

    2017-09-15

    Intestinal ischemia/reperfusion (IIR) leads to acute lung injury (ALI) distally by aggravating pulmonary oxidative stress. Resveratrol is effective in attenuating ALI through its antioxidant capacity. This study aimed to determine the effects of resveratrol on IIR-induced ALI and to explore the role of mast cells (MCs) activation in a rat model of IIR. Adult Sprague-Dawley rats were subjected to IIR by occluding the superior mesenteric artery for 60min followed by 4-hour reperfusion. Resveratrol was intraperitoneally injected at a dose of 15mg/kg for 5days before IIR. MCs stabilizer/inhibitor cromolyn sodium and degranulator compound 48/80 were used to explore the interaction between resveratrol and MCs. Lung tissues were collected for pathological detection and MCs staining. Pulmonary protein expression of surfactant protein-C (SP-C), tryptase, p47 phox and gp91 phox (two NADPH oxidase subunits), ICAM-1(intercellular adhesion molecule-1) and P-selectin were detected. The levels of oxidative stress markers (SOD, MDA, H 2 O 2 and MPO) and β-hexosaminidase were also measured. At the end of IIR, lung injury was significantly increased and was associated with decreased expression of SP-C and increased lung oxidative stress. Increased inflammation as well as activation of MCs was also observed in the lungs after IIR. All these changes were prevented or reversed by resveratrol pretreatment or MCs inhibition with cromolyn sodium. However, these protective effects of resveratrol or cromolyn sodium were reduced by MCs degranulator compound 48/80. These findings reveal that resveratrol attenuates IIR-induced ALI by reducing NADPH oxidase protein expression and inflammation through stabilizing MCs. Copyright © 2017. Published by Elsevier Inc.

  15. Activation of cAMP-dependent signaling induces oxidative modification of the cardiac Na+-K+ pump and inhibits its activity.

    Science.gov (United States)

    White, Caroline N; Liu, Chia-Chi; Garcia, Alvaro; Hamilton, Elisha J; Chia, Karin K M; Figtree, Gemma A; Rasmussen, Helge H

    2010-04-30

    Cellular signaling can inhibit the membrane Na(+)-K(+) pump via protein kinase C (PKC)-dependent activation of NADPH oxidase and a downstream oxidative modification, glutathionylation, of the beta(1) subunit of the pump alpha/beta heterodimer. It is firmly established that cAMP-dependent signaling also regulates the pump, and we have now examined the hypothesis that such regulation can be mediated by glutathionylation. Exposure of rabbit cardiac myocytes to the adenylyl cyclase activator forskolin increased the co-immunoprecipitation of NADPH oxidase subunits p47(phox) and p22(phox), required for its activation, and increased superoxide-sensitive fluorescence. Forskolin also increased glutathionylation of the Na(+)-K(+) pump beta(1) subunit and decreased its co-immunoprecipitation with the alpha(1) subunit, findings similar to those already established for PKC-dependent signaling. The decrease in co-immunoprecipitation indicates a decrease in the alpha(1)/beta(1) subunit interaction known to be critical for pump function. In agreement with this, forskolin decreased ouabain-sensitive electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange ratio) of voltage-clamped, internally perfused myocytes. The decrease was abolished by the inclusion of superoxide dismutase, the inhibitory peptide for the epsilon-isoform of PKC or inhibitory peptide for NADPH oxidase in patch pipette solutions that perfuse the intracellular compartment. Pump inhibition was also abolished by inhibitors of protein kinase A and phospholipase C. We conclude that cAMP- and PKC-dependent inhibition of the cardiac Na(+)-K(+) pump occurs via a shared downstream oxidative signaling pathway involving NADPH oxidase activation and glutathionylation of the pump beta(1) subunit.

  16. Groundbased investigation of comet 67p/churyumov- gerasimenko, target of the spacecraft Mission Rosetta

    Science.gov (United States)

    de Almeida, A. A.; Trevisan Sanzovo, D.; Sanzovo, G. C.; Boczko, R.; Miguel Torres, R.

    In this work, we make a comparative study of Comet 67P/Churyumov-Gerasimenko, target of Mission Rosetta, with Comets 1P/Halley and Hyakutake(C/1996 B2). Water and gas) release rates are derived from visual magnitudes (mv), determined mostly by amateur astronomers, and listed in several issues of International Comet Quarterly(ICQ). We make a systematic and uniform analysis of continuum fluxes obtained at visual wavelengths and, using the framework of photometric theory of Newburn & Spinrad (1985, 1989), we estimate dust release rates, qd (in g/s), effective particle sizes, a (in micron), and dust-to-gas mass ratios, for this important sample of comets. We also determine the color excess of the dust particles, CE, relative to the Sun at wavelength ranges 477.0-524.0 nm in the 1996 return of Comet 67P/Churyumov-Gerasimenko, and 365.0-484.5 nm for Comets 1P/Halley and C/1996 B2.

  17. Structural analysis of the yeast exosome Rrp6p–Rrp47p complex by small-angle X-ray scattering

    Energy Technology Data Exchange (ETDEWEB)

    Dedic, Emil; Seweryn, Paulina; Jonstrup, Anette Thyssen; Flygaard, Rasmus Koch [Centre for mRNP Biogenesis and Metabolism, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Department of Molecular Biology and Genetics, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Fedosova, Natalya U. [Department of Biomedicine, Ole Worms Allé 6, Aarhus University, DK-8000 Aarhus C (Denmark); Hoffmann, Søren Vrønning [Institute for Storage Ring Facilities (ISA), Department of Physics and Astronomy, Ny Munkegade 120, Aarhus University, DK-8000 Aarhus C (Denmark); Boesen, Thomas [Centre for Membrane Pumps in Cells and Disease – PUMPKIN, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Department of Molecular Biology and Genetics, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Brodersen, Ditlev Egeskov, E-mail: deb@mb.au.dk [Centre for mRNP Biogenesis and Metabolism, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark); Department of Molecular Biology and Genetics, Gustav Wieds Vej 10c, Aarhus University, DK-8000 Aarhus C (Denmark)

    2014-07-18

    Highlights: • We show that S. cerevisiae Rrp6p and Rrp47p stabilise each other in vitro. • We determine molecular envelopes of the Rrp6p–Rrp47p complex by SAXS. • Rrp47p binds at the top of the Rrp6p exonuclease domain. • Rrp47p modulates the activity of Rrp6p on a variety of RNA substrates. • Rrp47p does not affect RNA affinity by Rrp6p. - Abstract: The RNase D-type 3′–5′ exonuclease Rrp6p from Saccharomyces cerevisiae is a nuclear-specific cofactor of the RNA exosome and associates in vivo with Rrp47p (Lrp1p). Here, we show using biochemistry and small-angle X-ray scattering (SAXS) that Rrp6p and Rrp47p associate into a stable, heterodimeric complex with an elongated shape consistent with binding of Rrp47p to the nuclease domain and opposite of the HRDC domain of Rrp6p. Rrp47p reduces the exonucleolytic activity of Rrp6p on both single-stranded and structured RNA substrates without significantly altering the affinity towards RNA or the ability of Rrp6p to degrade RNA secondary structure.

  18. Structural analysis of the yeast exosome Rrp6p–Rrp47p complex by small-angle X-ray scattering

    International Nuclear Information System (INIS)

    Dedic, Emil; Seweryn, Paulina; Jonstrup, Anette Thyssen; Flygaard, Rasmus Koch; Fedosova, Natalya U.; Hoffmann, Søren Vrønning; Boesen, Thomas; Brodersen, Ditlev Egeskov

    2014-01-01

    Highlights: • We show that S. cerevisiae Rrp6p and Rrp47p stabilise each other in vitro. • We determine molecular envelopes of the Rrp6p–Rrp47p complex by SAXS. • Rrp47p binds at the top of the Rrp6p exonuclease domain. • Rrp47p modulates the activity of Rrp6p on a variety of RNA substrates. • Rrp47p does not affect RNA affinity by Rrp6p. - Abstract: The RNase D-type 3′–5′ exonuclease Rrp6p from Saccharomyces cerevisiae is a nuclear-specific cofactor of the RNA exosome and associates in vivo with Rrp47p (Lrp1p). Here, we show using biochemistry and small-angle X-ray scattering (SAXS) that Rrp6p and Rrp47p associate into a stable, heterodimeric complex with an elongated shape consistent with binding of Rrp47p to the nuclease domain and opposite of the HRDC domain of Rrp6p. Rrp47p reduces the exonucleolytic activity of Rrp6p on both single-stranded and structured RNA substrates without significantly altering the affinity towards RNA or the ability of Rrp6p to degrade RNA secondary structure

  19. Role of Met80 and Tyr67 in the low-pH conformational equilibria of cytochrome c.

    Science.gov (United States)

    Battistuzzi, Gianantonio; Bortolotti, Carlo Augusto; Bellei, Marzia; Di Rocco, Giulia; Salewski, Johannes; Hildebrandt, Peter; Sola, Marco

    2012-07-31

    The low-pH conformational equilibria of ferric yeast iso-1 cytochrome c (ycc) and its M80A, M80A/Y67H, and M80A/Y67A variants were studied from pH 7 to 2 at low ionic strength through electronic absorption, magnetic circular dichroism, and resonance Raman spectroscopies. For wild-type ycc, the protein structure, axial heme ligands, and spin state of the iron atom convert from the native folded His/Met low-spin (LS) form to a molten globule His/H(2)O high-spin (HS) form and a totally unfolded bis-aquo HS state, in a single cooperative transition with an apparent pK(a) of ~3.0. An analogous cooperative transition occurs for the M80A and M80A/Y67H variants. This is preceded by protonation of heme propionate-7, with a pK(a) of ~4.2, and by an equilibrium between a His/OH(-)-ligated LS and a His/H(2)O-ligated HS conformer, with a pK(a) of ~5.9. In the M80A/Y67A variant, the cooperative low-pH transition is split into two distinct processes because of an increased stability of the molten globule state that is formed at higher pH values than the other species. These data show that removal of the axial methionine ligand does not significantly alter the mechanism of acidic unfolding and the ranges of stability of low-pH conformers. Instead, removal of a hydrogen bonding partner at position 67 increases the stability of the molten globule and renders cytochrome c more susceptible to acid unfolding. This underlines the key role played by Tyr67 in stabilizing the three-dimensional structure of cytochrome c by means of the hydrogen bonding network connecting the Ω loops formed by residues 71-85 and 40-57.

  20. The proliferation marker pKi-67 organizes the nucleolus during the cell cycle depending on Ran and cyclin B.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Bögler, Oliver; Duchrow, Michael

    2003-01-01

    The proliferation marker pKi-67 ('Ki-67 antigen') is commonly used in clinical and research pathology to detect proliferating cells, as it is only expressed during cell-cycle progression. Despite the fact that this antigen has been known for nearly two decades, there is still no adequate understanding of its function. This study has therefore identified proteins that interact with pKi-67, using a yeast two-hybrid system. A mammalian two-hybrid system and immunoprecipitation studies were used to verify these interactions. Among other cell-cycle regulatory proteins, two binding partners associated with the small GTPase Ran were identified. In addition, DNA-structural and nucleolus-associated proteins binding to pKi-67 were found. Moreover, it was demonstrated that the N-terminal domain of pKi-67 is capable of self-binding to its own repeat region encoded by exon 13. Since RanBP, a protein involved in the transport of macromolecules over the nuclear lamina, was found to be a binding partner, a possible effect of pKi-67 on the localization of cell-cycle regulatory proteins was proposed. To test this hypothesis, a tetracycline-responsive gene expression system was used to induce the pKi-67 fragments previously used for the two-hybrid screens in HeLa cells. Subsequent immunostaining revealed the translocation of cyclin B1 from cytoplasm to nucleoli in response to this expression. It is suggested that pKi-67 is a Ran-associated protein with a role in the disintegration and reformation of the nucleolus and thereby in entry into and exit from the M-phase. Copyright 2002 John Wiley & Sons, Ltd.

  1. Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study.

    Science.gov (United States)

    Viprey, Virginie F; Gregory, Walter M; Corrias, Maria V; Tchirkov, Andrei; Swerts, Katrien; Vicha, Ales; Dallorso, Sandro; Brock, Penelope; Luksch, Roberto; Valteau-Couanet, Dominique; Papadakis, Vassilios; Laureys, Genevieve; Pearson, Andrew D; Ladenstein, Ruth; Burchill, Susan A

    2014-04-01

    To evaluate the hypothesis that detection of neuroblastoma mRNAs by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4 neuroblastoma are clinically useful biomarkers of risk. RTqPCR for paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR-NBL1/SIOPEN) was performed at diagnosis and after induction therapy. High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly predicted for worse event-free survival (EFS) and overall survival (OS) in a cohort of 290 children. After induction therapy, high levels of these mRNAs predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) PB cohorts, high TH (log10TH > 0.8) or high PHOX2B (log10PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38% (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in mRNA level between diagnosis and postinduction therapy in BM or PB was not of additional predictive value. High levels of TH and PHOX2B mRNA in PB at diagnosis objectively identify children with ultrahigh-risk disease who may benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in BM and/or PB at diagnosis might contribute to an algorithm to improve stratification of children for treatment.

  2. Impact of Radiogenic Heating on the Formation Conditions of Comet 67P/Churyumov–Gerasimenko

    International Nuclear Information System (INIS)

    Mousis, O.; Drouard, A.; Vernazza, P.; Le Deun, T.; Lunine, J. I.; Monnereau, M.; Rème, H.; Maggiolo, R.; Cessateur, G.; De Keyser, J.; Gasc, S.; Altwegg, K.; Balsiger, H.; Rubin, M.; Tzou, C.-Y.; Berthelier, J.-J.; Fuselier, S. A.; Korth, A.; Mall, U.; Marty, B.

    2017-01-01

    Because of the high fraction of refractory material present in comets, the heat produced by the radiogenic decay of elements such as aluminum and iron can be high enough to induce the loss of ultravolatile species such as nitrogen, argon, or carbon monoxide during their accretion phase in the protosolar nebula (PSN). Here, we investigate how heat generated by the radioactive decay of "2"6Al and "6"0Fe influences the formation of comet 67P/Churyumov–Gerasimenko, as a function of its accretion time and the size of its parent body. We use an existing thermal evolution model that includes various phase transitions, heat transfer in the ice-dust matrix, and gas diffusion throughout the porous material, based on thermodynamic parameters derived from Rosetta observations. Two possibilities are considered: either, to account for its bilobate shape, 67P/Churyumov–Gerasimenko was assembled from two primordial ∼2 km sized planetesimals, or it resulted from the disruption of a larger parent body with a size corresponding to that of comet Hale–Bopp (∼70 km). To fully preserve its volatile content, we find that either 67P/Churyumov–Gerasimenko’s formation was delayed between ∼2.2 and 7.7 Myr after that of Ca–Al-rich Inclusions in the PSN or the comet’s accretion phase took place over the entire time interval, depending on the primordial size of its parent body and the composition of the icy material considered. Our calculations suggest that the formation of 67P/Churyumov–Gerasimenko is consistent with both its accretion from primordial building blocks formed in the nebula or from debris issued from the disruption of a Hale–Bopp-like body.

  3. Impact of Radiogenic Heating on the Formation Conditions of Comet 67P/Churyumov–Gerasimenko

    Energy Technology Data Exchange (ETDEWEB)

    Mousis, O.; Drouard, A.; Vernazza, P.; Le Deun, T. [Aix Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388, Marseille (France); Lunine, J. I. [Department of Astronomy and Carl Sagan Institute, Space Sciences Building Cornell University, Ithaca, NY 14853 (United States); Monnereau, M.; Rème, H. [Université de Toulouse, UPS-OMP-CNRS, IRAP, Toulouse (France); Maggiolo, R.; Cessateur, G.; De Keyser, J.; Gasc, S. [Royal Belgian Institute for Space Aeronomy, BIRA-IASB, Ringlaan 3, B-1180 Brussels (Belgium); Altwegg, K.; Balsiger, H.; Rubin, M.; Tzou, C.-Y. [Physikalisches Institut, University of Bern, Sidlerstr. 5, CH-3012 Bern (Switzerland); Berthelier, J.-J. [LATMOS/IPSL-CNRS-UPMC-UVSQ, 4 Avenue de Neptune F-94100, Saint-Maur (France); Fuselier, S. A. [Department of Space Science, Southwest Research Institute, 6220 Culebra Road, San Antonio, TX 78228 (United States); Korth, A.; Mall, U. [Max-Planck-Institut für Sonnensystemforschung, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany); Marty, B., E-mail: olivier.mousis@lam.fr [Centre de Recherches Pétrographiques et Géochimiques, CRPG-CNRS, Université de Lorraine, 15 rue Notre Dame des Pauvres, BP 20, F-54501 Vandoeuvre lès Nancy (France); and others

    2017-04-10

    Because of the high fraction of refractory material present in comets, the heat produced by the radiogenic decay of elements such as aluminum and iron can be high enough to induce the loss of ultravolatile species such as nitrogen, argon, or carbon monoxide during their accretion phase in the protosolar nebula (PSN). Here, we investigate how heat generated by the radioactive decay of {sup 26}Al and {sup 60}Fe influences the formation of comet 67P/Churyumov–Gerasimenko, as a function of its accretion time and the size of its parent body. We use an existing thermal evolution model that includes various phase transitions, heat transfer in the ice-dust matrix, and gas diffusion throughout the porous material, based on thermodynamic parameters derived from Rosetta observations. Two possibilities are considered: either, to account for its bilobate shape, 67P/Churyumov–Gerasimenko was assembled from two primordial ∼2 km sized planetesimals, or it resulted from the disruption of a larger parent body with a size corresponding to that of comet Hale–Bopp (∼70 km). To fully preserve its volatile content, we find that either 67P/Churyumov–Gerasimenko’s formation was delayed between ∼2.2 and 7.7 Myr after that of Ca–Al-rich Inclusions in the PSN or the comet’s accretion phase took place over the entire time interval, depending on the primordial size of its parent body and the composition of the icy material considered. Our calculations suggest that the formation of 67P/Churyumov–Gerasimenko is consistent with both its accretion from primordial building blocks formed in the nebula or from debris issued from the disruption of a Hale–Bopp-like body.

  4. ON THE ORIGIN OF INNER COMA STRUCTURES OBSERVED BY ROSETTA DURING A DIURNAL ROTATION OF COMET 67P/CHURYUMOV–GERASIMENKO

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, Tobias; Noack, Matthias [Konrad-Zuse-Zentrum für Informationstechnik, Takustr. 7, D-14195 Berlin (Germany)

    2016-05-20

    The Rosetta probe around comet 67P/Churyumov–Gerasimenko (67P) reveals an anisotropic dust distribution of the inner coma with jet-like structures. The physical processes leading to jet formation are under debate, with most models for cometary activity focusing on localized emission sources, such as cliffs or terraced regions. Here we suggest, by correlating high-resolution simulations of the dust environment around 67P with observations, that the anisotropy and the background dust density of 67P originate from dust released across the entire sunlit surface of the nucleus rather than from few isolated sources. We trace back trajectories from coma regions with high local dust density in space to the non-spherical nucleus and identify two mechanisms of jet formation: areas with local concavity in either two dimensions or only one. Pits and craters are examples of the first case; the neck region of the bi-lobed nucleus of 67P is an example of the latter case. The conjunction of multiple sources, in addition to dust released from all other sunlit areas, results in a high correlation coefficient (∼0.8) of the predictions with observations during a complete diurnal rotation period of 67P.

  5. ON THE ORIGIN OF INNER COMA STRUCTURES OBSERVED BY ROSETTA DURING A DIURNAL ROTATION OF COMET 67P/CHURYUMOV–GERASIMENKO

    International Nuclear Information System (INIS)

    Kramer, Tobias; Noack, Matthias

    2016-01-01

    The Rosetta probe around comet 67P/Churyumov–Gerasimenko (67P) reveals an anisotropic dust distribution of the inner coma with jet-like structures. The physical processes leading to jet formation are under debate, with most models for cometary activity focusing on localized emission sources, such as cliffs or terraced regions. Here we suggest, by correlating high-resolution simulations of the dust environment around 67P with observations, that the anisotropy and the background dust density of 67P originate from dust released across the entire sunlit surface of the nucleus rather than from few isolated sources. We trace back trajectories from coma regions with high local dust density in space to the non-spherical nucleus and identify two mechanisms of jet formation: areas with local concavity in either two dimensions or only one. Pits and craters are examples of the first case; the neck region of the bi-lobed nucleus of 67P is an example of the latter case. The conjunction of multiple sources, in addition to dust released from all other sunlit areas, results in a high correlation coefficient (∼0.8) of the predictions with observations during a complete diurnal rotation period of 67P.

  6. Rosetta/VIRTIS-M spectral data: Comet 67P/CG compared to other primitive small bodies.

    Science.gov (United States)

    De Sanctis, M. C.; Capaccioni, F.; Filacchione, G.; Erard, S.; Tosi, F.; Ciarniello, M.; Raponi, A.; Piccioni, G.; Leyrat, C.; Bockelée-Morvan, D.; Drossart, P.; Fornasier, S.

    2014-12-01

    VIRTIS-M, the Visible InfraRed Thermal Imaging Spectrometer, onboard the Rosetta Mission orbiter (Coradini et al., 2007) acquired data of the comet 67P/Churyumov-Gerasimenko in the 0.25-5.1 µm spectral range. The initial data, obtained during the first mission phases to the comet, allow us to derive albedo and global spectral properties of the comet nucleus as well as spectra of different areas on the nucleus. The characterization of cometary nuclei surfaces and their comparison with those of related populations such as extinct comet candidates, Centaurs, near-Earth asteroids (NEAs), trans-Neptunian objects (TNOs), and primitive asteroids is critical to understanding the origin and evolution of small solar system bodies. The acquired VIRTIS data are used to compare the global spectral properties of comet 67P/CG to published spectra of other cometary nuclei observed from ground or visited by space mission. Moreover, the spectra of 67P/Churyumov-Gerasimenko are also compared to those of primitive asteroids and centaurs. The comparison can give us clues on the possible common formation and evolutionary environment for primitive asteroids, centaurs and Jupiter-family comets. Authors acknowledge the funding from Italian and French Space Agencies. References: Coradini, A., Capaccioni, F., Drossart, P., Arnold, G., Ammannito, E., Angrilli, F., Barucci, A., Bellucci, G., Benkhoff, J., Bianchini, G., Bibring, J. P., Blecka, M., Bockelee-Morvan, D., Capria, M. T., Carlson, R., Carsenty, U., Cerroni, P., Colangeli, L., Combes, M., Combi, M., Crovisier, J., De Sanctis, M. C., Encrenaz, E. T., Erard, S., Federico, C., Filacchione, G., Fink, U., Fonti, S., Formisano, V., Ip, W. H., Jaumann, R., Kuehrt, E., Langevin, Y., Magni, G., McCord, T., Mennella, V., Mottola, S., Neukum, G., Palumbo, P., Piccioni, G., Rauer, H., Saggin, B., Schmitt, B., Tiphene, D., Tozzi, G., Space Science Reviews, Volume 128, Issue 1-4, 529-559, 2007.

  7. Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study.

    Science.gov (United States)

    Meyer, Hans Jonas; Höhn, Annekathrin; Surov, Alexey

    2018-04-06

    Functional imaging modalities like Diffusion-weighted imaging are increasingly used to predict tumor behavior like cellularity and vascularity in different tumors. Histogram analysis is an emergent imaging analysis, in which every voxel is used to obtain a histogram and therefore statistically information about tumors can be provided. The purpose of this study was to elucidate possible associations between ADC histogram parameters and several immunhistochemical features in rectal cancer. Overall, 11 patients with histologically proven rectal cancer were included into the study. There were 2 (18.18%) females and 9 males with a mean age of 67.1 years. KI 67-index, expression of p53, EGFR, VEGF, and Hif1-alpha were semiautomatically estimated. The tumors were divided into PD1-positive and PD1-negative lesions. ADC histogram analysis was performed as a whole lesion measurement using an in-house matlab application. Spearman's correlation analysis revealed a strong correlation between EGFR expression and ADCmax (p=0.72, P=0.02). None of the vascular parameters (VEGF, Hif1-alpha) correlated with ADC parameters. Kurtosis and skewness correlated inversely with p53 expression (p=-0.64, P=0.03 and p=-0.81, P=0.002, respectively). ADCmedian and ADCmode correlated with Ki67 (p=-0.62, P=0.04 and p=-0.65, P=0.03, respectively). PD1-positive tumors showed statistically significant lower ADCmax values in comparison to PD1-negative tumors, 1.93 ± 0.36 vs 2.32 ± 0.47×10 -3 mm 2 /s, p=0.04. Several associations were identified between histogram parameter derived from ADC maps and EGFR, KI 67 and p53 expression in rectal cancer. Furthermore, ADCmax was different between PD1 positive and PD1 negative tumors indicating an important role of ADC parameters for possible future treatment prediction.

  8. Tea polyphenols alleviate high fat and high glucose-induced endothelial hyperpermeability by attenuating ROS production via NADPH oxidase pathway.

    Science.gov (United States)

    Zuo, Xuezhi; Tian, Chong; Zhao, Nana; Ren, Weiye; Meng, Yi; Jin, Xin; Zhang, Ying; Ding, Shibin; Ying, Chenjiang; Ye, Xiaolei

    2014-03-02

    Hyperglycemia-induced endothelial hyperpermeability is crucial to cardiovascular disorders and macro-vascular complications in diabetes mellitus. The objective of this study is to investigate the effects of green tea polyphenols (GTPs) on endothelial hyperpermeability and the role of nicotinamide adenine dinucleotide phosphate (NADPH) pathway. Male Wistar rats fed on a high fat diet (HF) were treated with GTPs (0, 0.8, 1.6, 3.2 g/L in drinking water) for 26 weeks. Bovine aortic endothelial cells (BAECs) were treated with high glucose (HG, 33 mmol/L) and GTPs (0.0, 0.4, or 4 μg/mL) for 24 hours in vitro. The endothelial permeabilities in rat aorta and monolayer BAECs were measured by Evans blue injection method and efflux of fluorescein isothiocyanate (FITC)-dextran, respectively. The reactive oxygen species (ROS) levels in rat aorta and monolayer BAECs were measured by dihydroethidium (DHE) and 2', 7'-dichloro-fluorescein diacetate (DCFH-DA) fluorescent probe, respectively. Protein levels of NADPH oxidase subunits were determined by Western-blot. HF diet-fed increased the endothelial permeability and ROS levels in rat aorta while HG treatments increased the endothelial permeability and ROS levels in cultured BAECs. Co-treatment with GTPs alleviated those changes both in vivo and in vitro. In in vitro studies, GTPs treatments protected against the HG-induced over-expressions of p22phox and p67phox. Diphenylene iodonium chloride (DPI), an inhibitor of NADPH oxidase, alleviated the hyperpermeability induced by HG. GTPs could alleviate endothelial hyperpermeabilities in HF diet-fed rat aorta and in HG treated BAECs. The decrease of ROS production resulting from down-regulation of NADPH oxidase contributed to the alleviation of endothelial hyperpermeability.

  9. Characteristics of circular features on comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Deller, J. F.; Güttler, C.; Tubiana, C.; Hofmann, M.; Sierks, H.

    2017-09-01

    Comet 67P/Churyumov-Gerasimenko shows a large variety of circular structures such as pits, elevated roundish features in Imhotep, and even a single occurrence of a plausible fresh impact crater. Imaging the pits in the Ma'at region, aiming to understand their structure and origin drove the design of the final descent trajectory of the Rosetta spacecraft. The high-resolution images obtained during the last mission phase allow us to study these pits as exemplary circular features. A complete catalogue of circular features gives us the possibility to compare and classify these structures systematically.

  10. Incorporation of p-53 mutation status and Ki-67 proliferating index in ...

    African Journals Online (AJOL)

    Ayesha Ahmed

    2018-04-26

    Apr 26, 2018 ... gastric cancer. p-53 mutation status and Ki-67 proliferation index are established prognostic ... could not only be predictive in patientLs prognostics but could also form a basis of molecular ... a similar status to Her2-neu in gastric cancer, yet no ..... HER2-based biology in 1,006 cases of gastric cancer in.

  11. Surface Activity Distributions of Comet 67P/Churyumov-Gerasimenko Derived from VIRTIS Images

    Science.gov (United States)

    Fougere, Nicolas; Combi, Michael R.; Tenishev, Valeriy; Migliorini, Alessandra; Bockelee-Morvan, Dominique; Fink, Uwe; Filacchione, Gianrico; Rinaldi, Giovanna; Capaccioni, Fabrizio; Toth, Gabor; Gombosi, T. I.; Hansen, Kenneth C.; Huang, Zhenguang; Shou, Yinsi; VIRTIS Team

    2017-10-01

    The outgassing mechanism of comets still remains a critical question to better understand these objects. The Rosetta mission gave some insight regarding the potential activity distribution from the surface of the nucleus of comet 67P/Churyumov-Gerasimenko, Fougere et al. (2016, Astronomy & Astrophysics, Volume 588, id.A134, 11 pp and Monthly Notices of the Royal Astronomical Society, Volume 462, Issue Suppl_1, p.S156-S169) used a spherical harmonics inversion scheme with in-situ measurements from the ROSINA instrument to derive mapping of the broad distribution of potential activity at the surface of the nucleus. Marschall et al. (2016, Astronomy & Astrophysics, doi: 10.1051/0004-6361/201730849) based on the appearance of dust active areas suggested that the so-called “neck” region and regions with fractured cliffs and locally steep slopes show more activity than the rest of comet 67P’s nucleus. Using in situ ROSINA measurements from a distance makes it difficult to distinguish between these two scenarios because the fast expansion of the gas and large molecular mean free paths prevents distinguishing small outgassing features even when the spacecraft was in bound orbits within 10 km from the nucleus. In this paper, we present a similar numerical inversion approach using VIRTIS images, which should better probe the very inner coma of comet 67P and give more detailed information about the outgassing activity. Support from contracts JPL #1266314 and #1266313 from the US Rosetta Project and grant NNX14AG84G from the NASA Planetary Atmospheres Program are gratefully acknowledged.

  12. Inhibition of overexpression of Giα proteins and nitroxidative stress contribute to sodium nitroprusside-induced attenuation of high blood pressure in SHR.

    Science.gov (United States)

    Hossain, Ekhtear; Sarkar, Oli; Li, Yuan; Anand-Srivastava, Madhu B

    2018-03-01

    We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit enhanced expression of Giα proteins which was attributed to the decreased levels of nitric oxide (NO), because elevation of the intracellular levels of NO by NO donors; sodium nitroprusside (SNP) and S-Nitroso-N-acetyl-DL-penicillamine (SNAP), attenuated the enhanced expression of Giα proteins. Since the enhanced expression of Giα proteins is implicated in the pathogenesis of hypertension, the present study was undertaken to investigate if treatment of SHR with SNP could also attenuate the development of high blood pressure (BP) and explore the underlying molecular mechanisms. Intraperitoneal injection of SNP at a concentration of 0.5 mg/kg body weight twice a week for 2 weeks into SHR attenuated the high blood pressure by about 80 mmHg without affecting the BP in WKY rats. SNP treatment also attenuated the enhanced levels of superoxide anion (O 2 - ), hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO - ), and NADPH oxidase activity in VSMC from SHR to control levels. In addition, the overexpression of different subunits of NADPH oxidase; Nox-1, Nox-2, Nox-4, P 22phox , and P 47phox , and Giα proteins in VSMC from SHR were also attenuated by SNP treatment. On the other hand, SNP treatment augmented the decreased levels of intracellular NO, eNOS, and cGMP in VSMC from SHR. These results suggest that SNP treatment attenuates the development of high BP in SHR through the elevation of intracellular levels of cGMP and inhibition of the enhanced levels of Giα proteins and nitroxidative stress. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  13. Cambogin exerts anti-proliferative and pro-apoptotic effects on breast adenocarcinoma through the induction of NADPH oxidase 1 and the alteration of mitochondrial morphology and dynamics.

    Science.gov (United States)

    Shen, Kaikai; Lu, Fangfang; Xie, Jianling; Wu, Minfeng; Cai, Bo; Liu, Yurong; Zhang, Hong; Tan, Hongsheng; Pan, Yingyi; Xu, Hongxi

    2016-08-02

    Cambogin, a bioactive polycyclic polyprenylated acylphoroglucinol (PPAP) derived from the Garcinia genus, possesses proapoptotic effect in medulloblastoma and breast cancer cells. We have previously demonstrated that the proapoptotic effect of cambogin is driven by the production of reactive oxygen species (ROS). Here we have shown that the inhibitory effect of cambogin on cell proliferation is associated with the loss of mitochondrial transmembrane potential (ΔΨm) and mitochondrial fragmentation. Cambogin also promotes the mutual complex formation of the membrane-bound subunit p22phox of NADPH oxidase 1 (NOX1), as well as the phosphorylation of the cytosolic subunit p47phox, subsequently enhancing membrane-bound NOX1 activity, which leads to increases in intracellular and mitochondrial levels of O2.- and H2O2. Pharmacological inhibition of NOX1 using apocynin (pan-NOX inhibitor), ML171 (NOX1 inhibitor) or siRNA against NOX1 prevents the increases in O2.- and H2O2 levels and the anti-proliferative effect of cambogin. Antioxidants, including SOD (superoxide dismutase), CAT (catalase) and EUK-8, are also able to restore cell viability in the presence of cambogin. Besides, cambogin increases the dissociation of thioredoxin-1 (Trx1) from ASK1, switching the inactive form of ASK1 to the active kinase, subsequently leads to the phosphorylation of JNK/SAPK, which is abolished upon ML171 treatment. The proapoptotic effect of cambogin in breast cancer cells is also aggravated upon knocking down Trx1 in MCF-7 cells. Taken in conjunction, these data indicate that the anti-proliferative and pro-apoptotic effect of cambogin is mediated via inducing NOX1-dependent ROS production and the dissociation of ASK1 and Trx1.

  14. EPA:DHA 6:1 prevents angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase- and COX-derived oxidative stress.

    Science.gov (United States)

    Niazi, Zahid Rasul; Silva, Grazielle C; Ribeiro, Thais Porto; León-González, Antonio J; Kassem, Mohamad; Mirajkar, Abdur; Alvi, Azhar; Abbas, Malak; Zgheel, Faraj; Schini-Kerth, Valérie B; Auger, Cyril

    2017-12-01

    Eicosapentaenoic acid:docosahexaenoic acid (EPA:DHA) 6:1, an omega-3 polyunsaturated fatty acid formulation, has been shown to induce a sustained formation of endothelial nitric oxide (NO) synthase-derived NO, a major vasoprotective factor. This study examined whether chronic intake of EPA:DHA 6:1 prevents hypertension and endothelial dysfunction induced by angiotensin II (Ang II) in rats. Male Wister rats received orally corn oil or EPA:DHA 6:1 (500 mg kg -1 per day) before chronic infusion of Ang II (0.4 mg kg -1 per day). Systolic blood pressure was determined by tail cuff sphingomanometry, vascular reactivity using a myograph, oxidative stress using dihydroethidium and protein expression by immunofluorescence and western blot analysis. Ang II-induced hypertension was associated with reduced acetylcholine-induced relaxations of secondary branch mesenteric artery rings affecting the endothelium-dependent hyperpolarization (EDH)- and the NO-mediated relaxations, both of which were improved by the NADPH oxidase inhibitor VAS-2870. The Ang II treatment induced also endothelium-dependent contractile responses (EDCFs), which were abolished by the cyclooxygenase (COX) inhibitor indomethacin. An increased level of vascular oxidative stress and expression of NADPH oxidase subunits (p47 phox and p22 phox ), COX-1 and COX-2, endothelial NO synthase and Ang II type 1 receptors were observed in the Ang II group, whereas SK Ca and connexin 37 were downregulated. Intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction by improving both the NO- and EDH-mediated relaxations, and by reducing EDCFs and the expression of target proteins. The present findings indicate that chronic intake of EPA:DHA 6:1 prevented the Ang II-induced hypertension and endothelial dysfunction in rats, most likely by preventing NADPH oxidase- and COX-derived oxidative stress.

  15. Protein kinase-dependent oxidative regulation of the cardiac Na+-K+ pump: evidence from in vivo and in vitro modulation of cell signalling.

    Science.gov (United States)

    Galougahi, Keyvan Karimi; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A S; Hamilton, Elisha J; Rasmussen, Helge H; Figtree, Gemma A

    2013-06-15

    The widely reported stimulation of the cardiac Na(+)-K(+) pump by protein kinase A (PKA) should oppose other effects of PKA to increase contractility of the normal heart. It should also reduce harmful raised myocyte Na(+) levels in heart failure, yet blockade of the β1 adrenergic receptor (AR), coupled to PKA signalling, is beneficial. We treated rabbits with the β1 AR antagonist metoprolol to modulate PKA activity and studied cardiac myocytes ex vivo. Metoprolol increased electrogenic pump current (Ip) in voltage clamped myocytes and reduced glutathionylation of the β1 pump subunit, an oxidative modification causally related to pump inhibition. Activation of adenylyl cyclase with forskolin to enhance cAMP synthesis or inclusion of the catalytic subunit of PKA in patch pipette solutions abolished the increase in Ip in voltage clamped myocytes induced by treatment with metoprolol, supporting cAMP/PKA-mediated pump inhibition. Metoprolol reduced myocardial PKA and protein kinase C (PKC) activities, reduced coimmunoprecipitation of cytosolic p47(phox) and membranous p22(phox) NADPH oxidase subunits and reduced myocardial O2(•-)-sensitive dihydroethidium fluorescence. Treatment also enhanced coimmunoprecipitation of the β1 pump subunit with glutaredoxin 1 that catalyses de-glutathionylation. Since angiotensin II induces PKC-dependent activation of NADPH oxidase, we examined the effects of angiotensin-converting enzyme inhibition with captopril. This treatment had no effect on PKA activity but reduced the activity of PKC, reduced β1 subunit glutathionylation and increased Ip. The PKA-induced Na(+)-K(+) pump inhibition we report should act with other mechanisms that enhance contractility of the normal heart but accentuate the harmful effects of raised cytosolic Na(+) in the failing heart. This scheme is consistent with the efficacy of β1 AR blockade in the treatment of heart failure.

  16. Protein kinase-dependent oxidative regulation of the cardiac Na+–K+ pump: evidence from in vivo and in vitro modulation of cell signalling

    Science.gov (United States)

    Galougahi, Keyvan Karimi; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A S; Hamilton, Elisha J; Rasmussen, Helge H; Figtree, Gemma A

    2013-01-01

    The widely reported stimulation of the cardiac Na+–K+ pump by protein kinase A (PKA) should oppose other effects of PKA to increase contractility of the normal heart. It should also reduce harmful raised myocyte Na+ levels in heart failure, yet blockade of the β1 adrenergic receptor (AR), coupled to PKA signalling, is beneficial. We treated rabbits with the β1 AR antagonist metoprolol to modulate PKA activity and studied cardiac myocytes ex vivo. Metoprolol increased electrogenic pump current (Ip) in voltage clamped myocytes and reduced glutathionylation of the β1 pump subunit, an oxidative modification causally related to pump inhibition. Activation of adenylyl cyclase with forskolin to enhance cAMP synthesis or inclusion of the catalytic subunit of PKA in patch pipette solutions abolished the increase in Ip in voltage clamped myocytes induced by treatment with metoprolol, supporting cAMP/PKA-mediated pump inhibition. Metoprolol reduced myocardial PKA and protein kinase C (PKC) activities, reduced coimmunoprecipitation of cytosolic p47phox and membranous p22phox NADPH oxidase subunits and reduced myocardial O2•−-sensitive dihydroethidium fluorescence. Treatment also enhanced coimmunoprecipitation of the β1 pump subunit with glutaredoxin 1 that catalyses de-glutathionylation. Since angiotensin II induces PKC-dependent activation of NADPH oxidase, we examined the effects of angiotensin-converting enzyme inhibition with captopril. This treatment had no effect on PKA activity but reduced the activity of PKC, reduced β1 subunit glutathionylation and increased Ip. The PKA-induced Na+–K+ pump inhibition we report should act with other mechanisms that enhance contractility of the normal heart but accentuate the harmful effects of raised cytosolic Na+ in the failing heart. This scheme is consistent with the efficacy of β1 AR blockade in the treatment of heart failure. PMID:23587884

  17. Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology

    DEFF Research Database (Denmark)

    Ikenberg, Hans; Bergeron, Christine; Schmidt, Dietmar

    2013-01-01

    Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections...

  18. Differences in Expression of EGFR, Ki67 and p-EPK in Oral Cavity ...

    African Journals Online (AJOL)

    Purpose: To evaluate the expression of EGFR, Ki67, and p-EPK in oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. Methods: One hundred patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in a Chinese People's ...

  19. Interpretación de procesos redox en suelos sulfatados ácidos del distrito de riego del alto chicamocha, boyacá

    OpenAIRE

    Gómez, Manuel Iván; Castro, Hugo E.; Malagón, Dimas

    2010-01-01

    La génesis de suelos sulfatados ácidos (SSA) ubicados en el valle fluvio-lacustre de la cuenca alta del Río Chicamocha (Boyacá, Colombia) fue de­terminada mediante la oxidorreducción del hierro y el azufre, procesos que promueven una acidificación y modificación extremas de las características fisico­químicas del medio. Mediante el comportamiento de los parámetros: Eh (mV), pH (pH en agua, 1:1), pHox (pH en peróxido de hidrógeno al 30%, 1:1) y Al+3, se estableció la existencia de una degradac...

  20. Physical Modeling Modular Boxes: PHOXES

    DEFF Research Database (Denmark)

    Gelineck, Steven; Serafin, Stefania

    2010-01-01

    This paper presents the development of a set of musical instruments, which are based on known physical modeling sound synthesis techniques. The instruments are modular, meaning that they can be combined in various ways. This makes it possible to experiment with physical interaction and sonic...

  1. In vivo dynamics and kinetics of pKi-67: transition from a mobile to an immobile form at the onset of anaphase.

    Science.gov (United States)

    Saiwaki, Takuya; Kotera, Ippei; Sasaki, Mitsuho; Takagi, Masatoshi; Yoneda, Yoshihiro

    2005-08-01

    A cell proliferation marker protein, pKi-67, distributes to the chromosome periphery during mitosis and nucleolar heterochromatin in the interphase. We report here on the structural domains of pKi-67 that are required for its correct distribution. While both the LR domain and the conserved domain were involved in localization to the nucleolar heterochromatin, both the LR domain and the Ki-67 repeat domain were required for its distribution to the mitotic chromosome periphery. Using in vivo time-lapse microscopy, GFP-pKi-67 was dynamically tracked from the mitotic chromosome periphery to reforming nucleoli via prenucleolar bodies (PNBs). The signals in PNBs then moved towards and fused into the reforming nucleoli with a thin string-like fluorescence during early G1 phase. An analysis of the in vivo kinetics of pKi-67 using photobleaching indicated that the association of pKi-67 with chromatin was progressively altered from "loose" to "tight" after the onset of anaphase. These findings indicate that pKi-67 dynamically alters the nature of the interaction with chromatin structure during the cell cycle, which is closely related to the reformation process of the interphase nucleolar chromatin.

  2. In vivo dynamics and kinetics of pKi-67: Transition from a mobile to an immobile form at the onset of anaphase

    International Nuclear Information System (INIS)

    Saiwaki, Takuya; Kotera, Ippei; Sasaki, Mitsuho; Takagi, Masatoshi; Yoneda, Yoshihiro

    2005-01-01

    A cell proliferation marker protein, pKi-67, distributes to the chromosome periphery during mitosis and nucleolar heterochromatin in the interphase. We report here on the structural domains of pKi-67 that are required for its correct distribution. While both the LR domain and the conserved domain were involved in localization to the nucleolar heterochromatin, both the LR domain and the Ki-67 repeat domain were required for its distribution to the mitotic chromosome periphery. Using in vivo time-lapse microscopy, GFP-pKi-67 was dynamically tracked from the mitotic chromosome periphery to reforming nucleoli via prenucleolar bodies (PNBs). The signals in PNBs then moved towards and fused into the reforming nucleoli with a thin string-like fluorescence during early G1 phase. An analysis of the in vivo kinetics of pKi-67 using photobleaching indicated that the association of pKi-67 with chromatin was progressively altered from 'loose' to 'tight' after the onset of anaphase. These findings indicate that pKi-67 dynamically alters the nature of the interaction with chromatin structure during the cell cycle, which is closely related to the reformation process of the interphase nucleolar chromatin

  3. Nox regulation of smooth muscle contraction

    OpenAIRE

    Ritsick, Darren R.; Edens, William A.; Finnerty, Victoria; Lambeth, J. David

    2007-01-01

    The catalytic subunit, gp91phox (a.k.a., Nox2) of the NADPH-oxidase of mammalian phagocytes is activated by microbes and immune mediators to produce large amounts of reactive oxygen species (ROS) which participate in microbial killing. Homologs of gp91phox, the Nox and Duox enzymes, were recently described in a range of organisms, including plants, vertebrates, and invertebrates such as Drosophila melanogaster. While their enzymology and cell biology is being extensively studied in many labor...

  4. Hall effect in the coma of 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Huang, Z.; Tóth, G.; Gombosi, T. I.; Jia, X.; Combi, M. R.; Hansen, K. C.; Fougere, N.; Shou, Y.; Tenishev, V.; Altwegg, K.; Rubin, M.

    2018-04-01

    Magnetohydrodynamics simulations have been carried out in studying the solar wind and cometary plasma interactions for decades. Various plasma boundaries have been simulated and compared well with observations for comet 1P/Halley. The Rosetta mission, which studies comet 67P/Churyumov-Gerasimenko, challenges our understanding of the solar wind and comet interactions. The Rosetta Plasma Consortium observed regions of very weak magnetic field outside the predicted diamagnetic cavity. In this paper, we simulate the inner coma with the Hall magnetohydrodynamics equations and show that the Hall effect is important in the inner coma environment. The magnetic field topology becomes complex and magnetic reconnection occurs on the dayside when the Hall effect is taken into account. The magnetic reconnection on the dayside can generate weak magnetic field regions outside the global diamagnetic cavity, which may explain the Rosetta Plasma Consortium observations. We conclude that the substantial change in the inner coma environment is due to the fact that the ion inertial length (or gyro radius) is not much smaller than the size of the diamagnetic cavity.

  5. Analysis of p53- immunoreactivity in astrocytic brain tumors

    Directory of Open Access Journals (Sweden)

    Shinkarenko T.V.

    2016-12-01

    Full Text Available P53 is an antioncogene with the frequently occured mutations in human tumor cells, leading to corresponding protein overexpression which can be detected by immunohistochemistry. Researches dedicated to the investigation of possibilities of using this technique gave controversial results. The authors investigated features of p53 protein expression in astrocytic brain tumors with different degrees of malignancy. Analyzed the relationship of the expression level of p53 by tumor cells with clinical parameters and Ki-67 proliferation index (PI as well. Tissues were collected from 52 cases with diagnosed astrocytic brain tumors. The sections were immunohistochemically stained with p53 and Ki-67. For each marker, 1000 tumor cells were counted and the ratio of positive tumor cells was calculated using software package ImageJ 1,47v. In normal brain tissue p53- expression was not identified. p53-immunoreactive tumor cells were detected in 25% (1/4 pilocytic astrocytomas, 33.3% (2/6 of diffuse astrocytomas, 53.8% (7/13 anaplastic astrocytomas, 58.6% (17/29 glioblastomas. A high proportion of p53-immunoreactive cells (> 30% was observed only in glioblastomas. The level of p53-imunoreactivity was not related to the age, gender and Grade WHO (p> 0,05. Spearman correlation coefficient between the relative quantity of ki-67- and p53-immunoreactive nuclei showed weak direct correlation (0.023, but the one was not statistically significant (p> 0,05. The level of p53-imunoreactivity is not dependent from age and sex of patients, Grade (WHO and proliferative activity (p>0,05 but the high level of p53-immunoreactive cells (>30% is found in glioblastoma specimens only, that may be due to the accumulation of mutations in DNA of tumor cells. There is insignificant weak relationship between relative quantities of ki-67- and p53-immunoreactive tumor cells (p>0,05.

  6. Refractive Index Sensing of Green Fluorescent Proteins in Living Cells Using Fluorescence Lifetime Imaging Microscopy

    Science.gov (United States)

    van Manen, Henk-Jan; Verkuijlen, Paul; Wittendorp, Paul; Subramaniam, Vinod; van den Berg, Timo K.; Roos, Dirk; Otto, Cees

    2008-01-01

    We show that fluorescence lifetime imaging microscopy (FLIM) of green fluorescent protein (GFP) molecules in cells can be used to report on the local refractive index of intracellular GFP. We expressed GFP fusion constructs of Rac2 and gp91phox, which are both subunits of the phagocyte NADPH oxidase enzyme, in human myeloid PLB-985 cells and showed by high-resolution confocal fluorescence microscopy that GFP-Rac2 and GFP-gp91phox are targeted to the cytosol and to membranes, respectively. Frequency-domain FLIM experiments on these PLB-985 cells resulted in average fluorescence lifetimes of 2.70 ns for cytosolic GFP-Rac2 and 2.31 ns for membrane-bound GFP-gp91phox. By comparing these lifetimes with a calibration curve obtained by measuring GFP lifetimes in PBS/glycerol mixtures of known refractive index, we found that the local refractive indices of cytosolic GFP-Rac2 and membrane-targeted GFP-gp91phox are ∼1.38 and ∼1.46, respectively, which is in good correspondence with reported values for the cytosol and plasma membrane measured by other techniques. The ability to measure the local refractive index of proteins in living cells by FLIM may be important in revealing intracellular spatial heterogeneities within organelles such as the plasma and phagosomal membrane. PMID:18223002

  7. Intermittent hypoxia-induced cognitive deficits are mediated by NADPH oxidase activity in a murine model of sleep apnea.

    Directory of Open Access Journals (Sweden)

    Deepti Nair

    Full Text Available In rodents, exposure to intermittent hypoxia (IH, a hallmark of obstructive sleep apnea (OSA, is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Excessive NADPH oxidase activity may play a role in IH-induced CNS dysfunction.The effect of IH during light period on two forms of spatial learning in the water maze and well as markers of oxidative stress was assessed in mice lacking NADPH oxidase activity (gp91phox(_/Y and wild-type littermates. On a standard place training task, gp91phox(_/Y displayed normal learning, and were protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to IH as compared to room air (RA controls, while no changes emerged in gp91phox(_/Y mice. Additionally, wild-type mice, but not gp91phox(_/Y mice had significantly elevated levels of NADPH oxidase expression and activity, as well as MDA and 8-OHDG in cortical and hippocampal lysates following IH exposures.The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by excessive NADPH oxidase activity, and thus pharmacological agents targeting NADPH oxidase may provide a therapeutic strategy in sleep-disordered breathing.

  8. Hanhaqimei,a Salar Woman

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    The Salar nationality,with apopulation of 87,697,mainly settles in Xunhua Salar Nationality Autonomous County in eastern Qinghai Province.The Salar have their own spoken language,but no written script.Most of the Salar use Mandarin Chinese.According to legend and historians,their ancestors movde to Xunhua from Middle Asia in the 13th century.The Salar living by the Yellow River engage in agriculture and animal husbandry as their Primary means of support. The Salar believe in Islam and are also greatly influenced by confucian culture developed by the Han nationality.

  9. Breastfeeding and Immunohistochemical Expression of ki-67, p53 and BCL2 in Infiltrating Lobular Breast Carcinoma.

    Directory of Open Access Journals (Sweden)

    Angel Gonzalez-Sistal

    Full Text Available Invasive lobular breast carcinoma is the second most common type of breast cancer after invasive ductal carcinoma. According to the American Cancer Society, more than 180,000 women in the United States find out they have invasive breast cancer each year. Personal history of breast cancer and certain changes in the breast are correlated with an increased breast cancer risk. The aim of this work was to analyze breastfeeding in patients with infiltrating lobular breast carcinoma, in relation with: 1 clinicopathological parameters, 2 hormonal receptors and 3 tissue-based tumor markers.The study included 80 women with ILC, 46 of which had breastfeed their children. Analyzed parameters were: age, tumor size, axillary lymph node (N, distant metastasis (M, histological grade (HG, estrogen receptor (ER, progesterone receptor (PR, androgen receptor (AR, Ki-67, p53 and BCL2.ILC of non-lactating women showed a larger (p = 0.009, lymph node involvement (p = 0.051 and distant metastasis (p = 0.060. They were also more proliferative tumors measured by Ki-67 (p = 0.053. Breastfeeding history did not influence the subsequent behavior of the tumor regardless of histological subtype.Lactation seems to influence the biological characteristics of ILC defining a subgroup with more tumor size, axillary lymph node involvement, distant metastasis and higher proliferation measured by ki-67 expression.

  10. A PROTOSOLAR NEBULA ORIGIN FOR THE ICES AGGLOMERATED BY COMET 67P/CHURYUMOV–GERASIMENKO

    Energy Technology Data Exchange (ETDEWEB)

    Mousis, O.; Vernazza, P. [Aix Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388 Marseille (France); Lunine, J. I. [Center For Radiophysics And Space Research, Space Sciences Building Cornell University, Ithaca, NY 14853 (United States); Luspay-Kuti, A.; Hässig, M.; Waite, J. H. [Department of Space Research, Southwest Research Institute, 6220 Culebra Road, San Antonio, TX 78228 (United States); Guillot, T. [Laboratoire J.-L. Lagrange, Université de Nice-Sophia Antipolis, CNRS, Observatoire de la Côte d’Azur, BP 4229, F-06304 Nice (France); Marty, B. [CRPG-CNRS, Nancy-Université, 15 rue Notre Dame des Pauvres, F-54501 Vandoeuvre-lès-Nancy (France); Ali-Dib, M. [Université de Franche-Comté, Institut UTINAM, CNRS/INSU, UMR 6213, Besançon Cedex (France); Wurz, P.; Altwegg, K.; Bieler, A.; Rubin, M., E-mail: olivier.mousis@lam.fr [Physikalisches Institut, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland)

    2016-03-10

    The nature of the icy material accreted by comets during their formation in the outer regions of the protosolar nebula (PSN) is a major open question in planetary science. Some scenarios of comet formation predict that these bodies agglomerated from crystalline ices condensed in the PSN. Concurrently, alternative scenarios suggest that comets accreted amorphous ice originating from the interstellar cloud or from the very distant regions of the PSN. On the basis of existing laboratory and modeling data, we find that the N{sub 2}/CO and Ar/CO ratios measured in the coma of the Jupiter-family comet 67P/Churyumov–Gerasimenko by the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis instrument on board the European Space Agency’s Rosetta spacecraft match those predicted for gases trapped in clathrates. If these measurements are representative of the bulk N{sub 2}/CO and Ar/CO ratios in 67P/Churyumov–Gerasimenko, it implies that the ices accreted by the comet formed in the nebula and do not originate from the interstellar medium, supporting the idea that the building blocks of outer solar system bodies have been formed from clathrates and possibly from pure crystalline ices. Moreover, because 67P/Churyumov–Gerasimenko is impoverished in Ar and N{sub 2}, the volatile enrichments observed in Jupiter’s atmosphere cannot be explained solely via the accretion of building blocks with similar compositions and require an additional delivery source. A potential source may be the accretion of gas from the nebula that has been progressively enriched in heavy elements due to photoevaporation.

  11. [Sorting role of p16(INK4a)/Ki-67 double immunostaining in the cervical cytology specimens of ASCUS and LSIL cases].

    Science.gov (United States)

    Yu, J; Zhu, H T; Zhao, J J; Su, J Z; Xia, Y D

    2017-05-08

    Objective: To investigate the sorting effect of p16(INK4a)/Ki-67 double immunostaining method in patients with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology results. Methods: Four-hundred and twenty cases collected during April 2014 to February 2015 of cervical cytology of ASCUS ( n =318) and LSIL ( n =102) were selected, and residual liquid-based cytology specimens were used for p16(INK4a)/Ki-67 double immunostaining. The sensitivity and specificity of the detection of cervical precancerous lesions and cervical cancer were calculated, and the results were compared with high risk HPV. Taking histological follow-up as the gold standard, the test was considered positive when at least one cell exhibited p16(INK4a)/Ki-67 co-staining, without requirement of adjunct morphologic interpretation of positive cells. Results: Further screening CIN2+ in cytology ASCUS and LSIL group , the sensitivity of p16(INK4a)/Ki-67 double immunostaining was slightly lower than high risk HPV (84.2% vs . 94.7%), while the specificity was higher (84.0% vs . 53.9%). For ASCUS patients, the sensitivity of p16(INK4a)/Ki-67 double immunostaining and high risk HPV was 82.6% and 91.3%, and the specificity was 88.8% and 63.7%, respectively. For LSIL patients, the sensitivity of p16(INK4a)/Ki-67 double immunostaining and high risk HPV was 86.7% and 100.0%, and the specificity was 67.8% and 20.7%, respectively. For patients younger and older than 30 years, specificity of p16(INK4a)/Ki-67 double immunostaining was both higher than that of high risk HPV (80.8% vs . 42.3%; 84.6% vs . 56.9%). Conclusions: p16(INK4a)/Ki-67 double immunostaining can effectively identify the high risk population in ASCUS or LSIL, with higher specificity than high risk HPV test. p16(INK4a)/Ki-67 double immunostaining may benefit patients younger than 30 years of age as a preliminary or potential cytology-combining screening tool.

  12. Immunostimulation of Salmo salar L., and its effect on Lepeophtheirus salmonis (Krøyer) P-glycoprotein mRNA expression following subsequent emamectin benzoate exposure.

    Science.gov (United States)

    Igboeli, O O; Purcell, S L; Wotton, H; Poley, J; Burka, J F; Fast, M D

    2013-03-01

    Control of sea lice, Lepeophtheirus salmonis, on farmed Atlantic salmon, Salmo salar, relies heavily on chemotherapeutants. However, reduced efficacy of many treatments and need for integrated sea lice management plans require innovative strategies. Resistance to emamectin benzoate (EMB), a major sea lice parasiticide, has been linked with P-glycoprotein (P-gp) expression. We hypothesized that host immunostimulation would complement EMB treatment outcome. Lepeophtheirus salmonis-infected Atlantic salmon were fed immunostimulatory or control feeds. Sea lice were collected for 24-h EMB bioassays 1 and 2 weeks prior to commencement of EMB treatment of the fish. Two weeks after cessation of immunostimulant-treated feed, EMB was administered at 150 μg kg(-1) fish biomass for 7 days. The bioassay revealed stage, gender and immunostimulant-related differences in EMB EC(50) . Sea lice attached to salmon with a history of immunostimulation exhibited significantly greater survival than those on control feeds, despite similar levels of EMB in host tissues. Lepeophtheirus salmonis from salmon with a history of immunostimulation also exhibited higher P-gp mRNA expression as well as greater survivability compared to controls. Administration of immunostimulants prior to EMB treatment caused increased expression of P-gp mRNA which could have consequently caused decreased efficacy of the parasiticide. © 2013 Blackwell Publishing Ltd.

  13. Expression of p53, Bcl-2, VEGF, Ki67 and PCNA and prognostic significance in hepatocellular carcinoma.

    Science.gov (United States)

    Stroescu, Cezar; Dragnea, Adrian; Ivanov, Bogdan; Pechianu, Catalin; Herlea, Vlad; Sgarbura, Olivia; Popescu, Andra; Popescu, Irinel

    2008-12-01

    Hepatocellular carcinoma is one of the most common malignant tumors that carry a poor prognosis. To improve the long-term outlook for HCC, an accurate prognosis is important. To study the immunohistochemical expressions of p53, Ki67, Bcl-2, VEGF and PCNA and their potential role as prognostic factors in patients with radical resection of hepatocellular carcinoma. Forty-seven formalin-fixed paraffin-embedded tumor samples from patients with HCC receiving liver resection were investigated immunohistochemically for the expression of cellular proliferation markers PCNA, Ki67, p53, Bcl-2 and VEGF and their correlation with tumor characteristics and survival time after resection. p53 was expressed in a higher percentage (85.7 vs. 42.1%) in undifferentiated histological tumor grades (Edmondson Steiner G3/G4 vs. G1/G2). Patients with p53 accumulating tumors showed a worse survival than patients with p53 non-accumulating tumors (median 9.5 vs. 16.5 months). Over-expression of VEGF was found in 38.3% of all HCCs. VEGF expression was significantly correlated with p53 expression and recurrence rates. The results showed that the labeling index of PCNA and expression of p53 are correlated. The high labeling index of PCNA or over-expression of p53 resulted in high risk of tumor recurrence, more aggressive growth and poor survival. High labeling index of PCNA, p53 nuclear accumulation and VEGF high expression are associated with poor survival in patients with HCC.

  14. Telomeric 1p36.3 deletion and Ki-67 expression in B-Non-Hodgkin's Lymphoma patients associated with chronic hepatitis C virus infection.

    Science.gov (United States)

    Mosad, E; Said Abd El-Rahman Allam, M; Moustafa, H M; Mohammed, A Eliaw; El kebeer, A M; Abdel-Moneim, S S

    2014-12-01

    The hepatitis C virus (HCV) core protein is able to accumulate genetic p53 mutations and may be considered co-oncogenic. This study investigates 1p36.3 telomere deletion in B-non-Hodgkin's lymphoma (NHL) patients with chronic HCV infection using fluorescence in situ hybridization (FISH) in relation to survival to assess Ki-67 antigen expression. A study group and a control group of 100 patients with B-NHL (50 HCV positive and 50 HCV negative) and 60 control bone marrow biopsies were subjected to FISH for the detection of 1P36.3 deletion and to immunohistochemical staining with Ki-67 antigens. 1p36.3 deletion by FISH was detected in 40% of the study group, and Ki-67 was expressed in approximately 74% of patients. A significant difference was found between positive and negative HCV patients in their overall survival, the qualitative expression of Ki-67 and the quantitative detection of 1p36.3 deletion by FISH. The overall survival was shorter with the presence of an 1p36 deletion by FISH and HCV positive. We concluded that the coexistence of Ki-67 positivity, HCV positivity and 1p36.3 deletion may contribute to infection-related cancers at the 1p36.3 locus. © 2014 John Wiley & Sons Ltd.

  15. Coma morphology of comet 67P controlled by insolation over irregular nucleus

    Science.gov (United States)

    Shi, X.; Hu, X.; Mottola, S.; Sierks, H.; Keller, H. U.; Rose, M.; Güttler, C.; Fulle, M.; Fornasier, S.; Agarwal, J.; Pajola, M.; Tubiana, C.; Bodewits, D.; Barbieri, C.; Lamy, P. L.; Rodrigo, R.; Koschny, D.; Barucci, M. A.; Bertaux, J.-L.; Bertini, I.; Boudreault, S.; Cremonese, G.; Da Deppo, V.; Davidsson, B.; Debei, S.; De Cecco, M.; Deller, J.; Groussin, O.; Gutiérrez, P. J.; Hviid, S. F.; Ip, W.-H.; Jorda, L.; Knollenberg, J.; Kovacs, G.; Kramm, J.-R.; Kührt, E.; Küppers, M.; Lara, L. M.; Lazzarin, M.; Lopez-Moreno, J. J.; Marzari, F.; Naletto, G.; Oklay, N.; Toth, I.; Vincent, J.-B.

    2018-05-01

    While the structural complexity of cometary comae is already recognizable from telescopic observations1, the innermost region, within a few radii of the nucleus, was not resolved until spacecraft exploration became a reality2,3. The dust coma displays jet-like features of enhanced brightness superposed on a diffuse background1,4,5. Some features can be traced to specific areas on the nucleus, and result conceivably from locally enhanced outgassing and/or dust emission6-8. However, diffuse or even uniform activity over topographic concavity can converge to produce jet-like features9,10. Therefore, linking observed coma morphology to the distribution of activity on the nucleus is difficult11,12. Here, we study the emergence of dust activity at sunrise on comet 67P/Churyumov-Gerasimenko using high-resolution, stereo images from the OSIRIS camera onboard the Rosetta spacecraft, where the sources and formation of the jet-like features are resolved. We perform numerical simulations to show that the ambient dust coma is driven by pervasive but non-uniform water outgassing from the homogeneous surface layer. Physical collimations of gas and dust flows occur at local maxima of insolation and also via topographic focusing. Coma structures are projected to exhibit jet-like features that vary with the perspective of the observer. For an irregular comet such as 67P/Churyumov-Gerasimenko, near-nucleus coma structures can be concealed in the shadow of the nucleus, which further complicates the picture.

  16. Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion

    International Nuclear Information System (INIS)

    Bubb, Robbin S.; Komaki, Ritsuko; Hachiya, Tsutomu; Milas, Ivan; Ro, Jae Y.; Langford, Lauren; Sawaya, Raymond; Putnam, Joe B.; Allen, Pamela; Cox, James D.; McDonnell, Timothy J.; Brock, William; Hong, Waun K.; Roth, Jack A.; Milas, Luka

    2002-01-01

    Purpose: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar. Methods and Materials: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis. Results: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p=0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p=0.04), and these patients had a higher rate of nonbrain distant metastases (p=0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p=0.01). There was a positive correlation in the expression of Ki-67 (p=0.02) (r 2 =0.1608), as well as p53 (p 2 =0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive. Conclusion: Differences in biomarker expression between the

  17. Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas.

    Science.gov (United States)

    Sheikh, Rafiq A; Min, Byung Hee; Yasmeen, Shagufta; Teplitz, Raymond; Tesluk, Henry; Ruebner, Boris Henry; Tobi, Martin; Hatfield, James; Fligiel, Suzanne; Lawson, Michael J

    2003-01-01

    Variations of Ki-67, p53, and Adnab-9 monoclonal antibody reactions in colonic adenomas may be associated with colonic cancer risk. We studied the predictive value of these markers for adverse behavior in severely dysplastic colorectal adenomas, such as an associated carcinoma, multiplicity of adenomas, and subsequent development of adenomas. For this purpose we compared theclinical, gross, and histologic characteristics of highly dysplastic index polyps in 42 patients with Ki 67, p53, and Adnab-9 immunostaining and other molecular markers. Polyps were removed endoscopically, and severely dysplastic polyps were stained immunohistochemically with Ki-67, Adnab-9, and p53 protein by the avidin biotin conjugate (ABC) technique. Quantitative DNA (QDNA) was analyzed by computer-assisted image analysis. Ki-67 immunohistochemistry showed reversal of normal distribution of nuclear staining from the normal basal position to the upper third of the colonic crypts. This abnormality of immunostaining in dysplastic adenomas was the earliest detected by the panel we used. A statistically significant correlation was seen between invasiveness of carcinoma in the index polyp and polyp size (P = 0.003), sessile morphology (P = 0.037), and villous or tubulovillous histology (P = 0.019). In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025). Although p53 positivity and aneuploidy were correlated with invasiveness of carcinoma in the index polyp (P = 0.025), Adnab-9 positivity was not. However, Adnab-9 positivity in the index polyp was associated with multiplicity of adenomas (P = 0.04) as well as recurrence of adenomas (P < 0.024). In conclusion, in addition to the morphologic and histologic markers already known, Ki-67, Adnab-9 antibody, and p53 protein may be prognostic indicators useful in follow-up of patients

  18. Laboratory simulations of the Vis-NIR spectra of comet 67P using sub-μm sized cosmochemical analogues

    Science.gov (United States)

    Rousseau, B.; Érard, S.; Beck, P.; Quirico, É.; Schmitt, B.; Brissaud, O.; Montes-Hernandez, G.; Capaccioni, F.; Filacchione, G.; Bockelée-Morvan, D.; Leyrat, C.; Ciarniello, M.; Raponi, A.; Kappel, D.; Arnold, G.; Moroz, L. V.; Palomba, E.; Tosi, F.; Virtis Team

    2018-05-01

    Laboratory spectral measurements of relevant analogue materials were performed in the framework of the Rosetta mission in order to explain the surface spectral properties of comet 67P. Fine powders of coal, iron sulphides, silicates and their mixtures were prepared and their spectra measured in the Vis-IR range. These spectra are compared to a reference spectrum of 67P nucleus obtained with the VIRTIS/Rosetta instrument up to 2.7 μm, excluding the organics band centred at 3.2 μm. The species used are known to be chemical analogues for cometary materials which could be present at the surface of 67P. Grain sizes of the powders range from tens of nanometres to hundreds of micrometres. Some of the mixtures studied here actually reach the very low reflectance level observed by VIRTIS on 67P. The best match is provided by a mixture of sub-micron coal, pyrrhotite, and silicates. Grain sizes are in agreement with the sizes of the dust particles detected by the GIADA, MIDAS and COSIMA instruments on board Rosetta. The coal used in the experiment is responsible for the spectral slope in the visible and infrared ranges. Pyrrhotite, which is strongly absorbing, is responsible for the low albedo observed in the NIR. The darkest components dominate the spectra, especially within intimate mixtures. Depending on sample preparation, pyrrhotite can coat the coal and silicate aggregates. Such coating effects can affect the spectra as much as particle size. In contrast, silicates seem to play a minor role.

  19. Associação entre a expressão das proteínas p53 e Ki-67 e os achados clínico-patológicos em pacientes com carcinoma invasor do colo uterino Association between p53 and Ki-67 expression and clinicopathologic features in patients with carcinoma of the cervix

    Directory of Open Access Journals (Sweden)

    Agnaldo L. Silva-Filho

    2005-05-01

    Full Text Available OBJETIVO: avaliar a associação da expressão das proteínas p53 e Ki-67 no tumor com achados clínico-patológicos em pacientes com carcinoma invasor de colo uterino. MÉTODOS: foram estudadas amostras de tumor obtidas de 36 pacientes submetidas a histerectomia radical para tratamento de carcinoma invasor do colo uterino estádio IB (FIGO. Amostras do tumor foram fixadas em formol e incluídas em parafina. O material foi analisado pela histopatologia (hematoxilina e eosina e processado para marcação imuno-histoquímica por anticorpos monoclonais contra as proteínas p53 e Ki-67. Os dados foram analisados pelo teste de chi2 para a avaliação das diferenças entre os grupos. RESULTADOS: a idade das pacientes variou de 27 a 73 anos (48,7±10,4 anos. O estadiamento clínico (FIGO foi IB1 em 27 casos (75% e IB2 em 9 casos (25%. A expressão tumoral da proteína p53 foi positiva em metade dos casos. Em relação à expressão do Ki-67, foi evidenciado alto grau de proliferação celular em 73,3% dos casos. Não houve associação da expressão das proteínas p53 e Ki-67 no tumor com idade (p=0,091 e 0,900, estadiamento (p=0,054 e 0,667, tipo histológico (p=0,674 e 0,674, grau de diferenciação (p=0,07 e 0,282, presença de invasão linfovascular (p=0,248 e 0,667, acometimento parametrial (p=0,729 e 0,763 e metástases para os linfonodos pélvicos (p=0,729 e 0,636, respectivamente. CONCLUSÕES: a expressão tumoral das proteínas p53 e Ki-67 não se associou com achados clínico-patológicos em pacientes com carcinoma invasor do colo uterino estádio IB.PURPOSE: to evaluate the association between p53 and Ki-67 expression in the tumor and clinicopathological features in patients with carcinoma of the cervix. METHODS: samples were taken from the tumor of 36 patients with stage IB (FIGO cervical carcinoma submitted to radical hysterectomy. Tissue samples were taken from the tumor, fixed in formalin and embedded in paraffin. The specimens were

  20. Degradation of YRA1 Pre-mRNA in the cytoplasm requires translational repression, multiple modular intronic elements, Edc3p, and Mex67p.

    Directory of Open Access Journals (Sweden)

    Shuyun Dong

    2010-04-01

    Full Text Available Intron-containing pre-mRNAs are normally retained and processed in the nucleus but are sometimes exported to the cytoplasm and degraded by the nonsense-mediated mRNA decay (NMD pathway as a consequence of their inclusion of intronic in-frame termination codons. When shunted to the cytoplasm by autoregulated nuclear export, the intron-containing yeast YRA1 pre-mRNA evades NMD and is targeted by a cytoplasmic decay pathway mediated by the decapping activator Edc3p. Here, we have elucidated this transcript-specific decay mechanism, showing that Edc3p-mediated YRA1 pre-mRNA degradation occurs independently of translation and is controlled through five structurally distinct but functionally interdependent modular elements in the YRA1 intron. Two of these elements target the pre-mRNA as an Edc3p substrate and the other three mediate transcript-specific translational repression. Translational repression of YRA1 pre-mRNA also requires the heterodimeric Mex67p/Mtr2p general mRNA export receptor, but not Edc3p, and serves to enhance Edc3p substrate specificity by inhibiting the susceptibility of this pre-mRNA to NMD. Collectively, our data indicate that YRA1 pre-mRNA degradation is a highly regulated process that proceeds through translational repression, substrate recognition by Edc3p, recruitment of the Dcp1p/Dcp2p decapping enzyme, and activation of decapping.

  1. Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Guo Zhixin

    2012-08-01

    Full Text Available Abstract Background Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2 and nicotinamide adenine dinucleotide phosphate (NADPH oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1 in aorta in type 2 diabetic rats. Methods Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ. Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4, monocyte chemoattractant protein-1(MCP-1 and connective tissue growth factor (CTGFin the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-κB in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d by gavage for 12 weeks. Results Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P Conclusions Our results suggest that telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-κB in the abdominal aorta in diabetic rats.

  2. Effect of initial pH and temperature of iron salt solutions on formation of magnetite nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Gnanaprakash, G. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Mahadevan, S. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Jayakumar, T. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Kalyanasundaram, P. [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Philip, John [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India)]. E-mail: philip@igcar.gov.in; Raj, Baldev [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India)

    2007-05-15

    We report the effect of initial pH and temperature of iron salt solutions on formation of magnetite (Fe{sub 3}O{sub 4}) nanoparticles during co-precipitation. We synthesized nanoparticles by keeping the initial pH at 0.7, 1.5, 3.0, 4.7, 5.7, 6.7 for two different temperatures of 30 and 60 deg. C. When the initial pH (prior to alkali addition) of the salt solution was below 5, the nanoparticles formed were 100% spinel iron oxide. Average size of the magnetite particles increases with initial pH until ferrihydrite is formed at a pH of 3 and the size remains the same till 4.7 pH. The percentage of goethite formed along with non-stoichiometric magnetite was 35 and 78%, respectively, when the initial pH of the solution was 5.7 and 6.7. As the reaction temperature was increased to 60 deg. C, maintaining a pH of 6.7, the amount of goethite increased from 78 to 100%. These results show that the initial pH and temperature of the ferrous and ferric salt solution before initiation of the precipitation reaction are critical parameters controlling the composition and size of nanoparticles formed. We characterize the samples using X-ray diffraction, transmission electron microscopy and vibrating sample magnetometer. The results of the present work provide the right conditions to synthesis pure magnetite nanoparticles, without goethite impurities, through co-precipitation technique for ferrofluid applications.

  3. Effects of buffers and pH on in vitro binding of 67Ga by L1210 leukemic cells

    International Nuclear Information System (INIS)

    Glickson, J.D.; Webb, J.; Gams, R.A.

    1974-01-01

    The effect of sodium nitrate and a series of buffers on in vitro 67 Ga binding to L1210 leukemic cells at pH 6.8 +- 0.2 and 37 0 at concentrations of 10 -7 to 10 -2 M has been investigated. The relative ability of these agents to inhibit cellular incorporation of 67 Ga is given. Inhibition probably results from formation of gallium(III) complexes which are either impermeable to the tumor membrane or which compete with intracellular receptor complexes. However, direct interaction of buffers with the cell membrane or with gallium(III) receptors, as well as effects of buffers on cellular metabolism, have not been excluded. A monotonic decrease in the cellular incorporation of 67 Ga occurs between pH 6.2 and 7.8 in the presence of the inert buffer, 10 -2 M morpholinopropane sulfonic acid. (U.S.)

  4. The Noble Gas Abundances in the Coma of Comet 67P/Churyumov-Gerasimenko from Rosetta/ROSINA

    Science.gov (United States)

    Rubin, M.; Altwegg, K.; Balsiger, H. R.; Berthelier, J. J.; Briois, C.; Combi, M. R.; De Keyser, J.; Fiethe, B.; Fuselier, S. A.; Gasc, S.; Gombosi, T. I.; Hansen, K. C.; Jäckel, A.; Kopp, E.; Korth, A.; Mall, U.; Marty, B.; Mousis, O.; Owen, T.; Reme, H.; Schuhmann, M.; Schroeder, I. R. H. G.; Semon, T.; Tzou, C. Y.; Waite, J. H., Jr.; Wurz, P.

    2017-12-01

    The Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA), the mass spectrometer suite on board the European Space Agency's Rosetta mission, was dedicated to the measurement of the volatiles in the coma of comet 67P/Churyumov-Gerasimenko (67P) [1]. Among many other species, ROSINA DFMS, the Double Focusing Mass Spectrometer, detected and quantified the three noble gases argon, krypton, and xenon including their major isotopes [2,3]. Noble gases provide important clues to the physical and chemical conditions during and possibly even before and after the comet's formation in the early solar system. Furthermore, measurements of the isotope ratios provide constraints on the amount of cometary material brought to Earth and its early atmosphere. In this presentation, we will report on the measured coma densities and derived nucleus bulk abundances of these three noble gases and investigate correlations with other volatiles. Furthermore, we will discuss the measured isotope ratios and the implications of these results. AcknowledgementsUoB was funded by the State of Bern, the Swiss National Science Foundation and by the European Space Agency PRODEX Programme. Work at MPS was funded by the Max-Planck Gesellschaft and BMWI (contract 50QP1302), at Southwest Research institute by Jet Propulsion Laboratory (subcontract #1496541 and JPL subcontract to JWH NAS703001TONMO710889), at the University of Michigan by NASA (contract JPL-1266313). This work has been supported through the A*MIDEX project from the French National Research Agency (ANR) (n° ANR-11-IDEX- 0001-02) and by CNES grants at IRAP, LATMOS, LPC2E, LAM, CRPG, by the European Research Council (grant no. 267255 to B. Marty) and at BIRA-IASB by the Belgian Science Policy Office via PRODEX/ROSINA PEA C4000107705. References[1] Balsiger, H., et al., Rosina - Rosetta orbiter spectrometer for ion and neutral analysis. Space Science Reviews. 128, 745-801, 2007. [2] Balsiger, H., et al., Detection of argon in the

  5. Meter-scale thermal contraction crack polygons on the nucleus of comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Auger, A.-T.; Groussin, O.; Jorda, L.; El-Maarry, M. R.; Bouley, S.; Séjourné, A.; Gaskell, R.; Capanna, C.; Davidsson, B.; Marchi, S.; Höfner, S.; Lamy, P. L.; Sierks, H.; Barbieri, C.; Rodrigo, R.; Koschny, D.; Rickman, H.; Keller, H. U.; Agarwal, J.; A'Hearn, M. F.; Barucci, M. A.; Bertaux, J.-L.; Bertini, I.; Cremonese, G.; Da Deppo, V.; Debei, S.; De Cecco, M.; Fornasier, S.; Fulle, M.; Gutiérrez, P. J.; Güttler, C.; Hviid, S.; Ip, W.-H.; Knollenberg, J.; Kramm, J.-R.; Kührt, E.; Küppers, M.; Lara, L. M.; Lazzarin, M.; Lopez Moreno, J. J.; Marzari, F.; Massironi, M.; Michalik, H.; Naletto, G.; Oklay, N.; Pommerol, A.; Sabau, L.; Thomas, N.; Tubiana, C.; Vincent, J.-B.; Wenzel, K.-P.

    2018-02-01

    We report on the detection and characterization of more than 6300 polygons on the surface of the nucleus of comet 67P/Churyumov-Gerasimenko, using images acquired by the OSIRIS camera onboard Rosetta between August 2014 and March 2015. They are found in consolidated terrains and grouped in localized networks. They are present at all latitudes (from North to South) and longitudes (head, neck, and body), sometimes on pit walls or following lineaments. About 1.5% of the observed surface is covered by polygons. Polygons have an homogeneous size across the nucleus, with 90% of them in the size range 1 - 5 m and a mean size of 3.0 ± 1.4 m. They show different morphologies, depending on the width and depth of their trough. They are found in networks with 3- or 4-crack intersection nodes. The polygons observed on 67P are consistent with thermal contraction crack polygons formed by the diurnal or seasonal temperature variations in a hard (MPa) and consolidated sintered layer of water ice, located a few centimeters below the surface. Our thermal analysis shows an evolution of thermal contraction crack polygons according to the local thermal environment, with more evolved polygons (i.e. deeper and larger troughs) where the temperature and the diurnal and seasonal temperature range are the highest. Thermal contraction crack polygons are young surface morphologies that probably formed after the injection of 67P in the inner solar system, typically 100,000 years ago, and could be as young as a few orbital periods, following the decreasing of its perihelion distance in 1959 from 2.7 to 1.3 a.u. Meter scale thermal contraction crack polygons should be common features on the nucleus of Jupiter family comets.

  6. NUMERICAL SIMULATION OF DUST IN A COMETARY COMA: APPLICATION TO COMET 67P/CHURYUMOV-GERASIMENKO

    International Nuclear Information System (INIS)

    Tenishev, Valeriy; Combi, Michael R.; Rubin, Martin

    2011-01-01

    The Rosetta spacecraft is en route to comet 67P/Churyumov-Gerasimenko for a rendezvous, landing, and extensive orbital phase beginning in 2014. With a limited amount of available observational data, planning of the mission as well as the interpretation of measurements obtained by instruments on board the spacecraft requires modeling of the dusty/gas environment of the comet. During the mission, the collision regime in the inner coma will change starting from transitional to fully collisionless. As a result, a physically correct model has to be valid at conditions that are far from equilibrium and account for the kinetic nature of the processes occurring in the coma. A study of the multi-species coma of comet 67P/Churyumov-Gerasimenko is presented in our previous paper, where we describe our kinetic model and discuss the results of its application to cases that correspond to the different stages during the mission. In this work, we focus on numerical modeling of the dust phase in the coma of comet 67P/Churyumov-Gerasimenko and its interaction with the surrounding gas. The basic phenomena that govern the dynamics and energy balance of the dust grains are outlined. The effect of solar radiation pressure and the nucleus gravity in limiting the maximum liftable mass of the grains is discussed. The distribution of the terminal velocity of the dust grains as a function of subsolar angle is derived in the paper. We have found that in the regions with high gradients of the gas density, spike-like features can form in the dust flow. The obtained results represent the state of the coma in the vicinity of the nucleus for a series of stages throughout the Rosetta mission. The implications of the model results for future measurements by the GIADA instrument are discussed.

  7. Statistical analysis of dust signals observed by ROSINA/COPS onboard of the Rosetta spacecraft at comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Tzou, Chia-Yu; altwegg, kathrin; Bieler, Andre; Calmonte, Ursina; Gasc, Sébastien; Le Roy, Léna; Rubin, Martin

    2016-10-01

    ROSINA is the in situ Rosetta Orbiter Spectrometer for Ion and Neutral Analysis on board of Rosetta, one of the corner stone missions of the European Space Agency (ESA) to land and orbit the Jupiter family comet 67P/Churyumov-Gerasimenko (67P). ROSINA consists of two mass spectrometers and a pressure sensor. The Reflectron Time of Flight Spectrometer (RTOF) and the Double Focusing Mass Spectrometer (DFMS) complement each other in mass and time resolution.The Comet Pressure Sensor (COPS) provides density measurements of the neutral molecules in the cometary coma of 67P. COPS has two gauges, a nude gauge that measures the total neutral density and a ram gauge that measures the dynamic pressure from the comet. Combining the two COPS is also capable of providing gas dynamic information such as gas velocity and gas temperature of the coma.While Rosetta started orbiting around 67P in August 2014, COPS observed diurnal and seasonal variations of the neutral gas density in the coma. Surprisingly, additional to these major density variation patterns, COPS occasionally observed small spikes in the density that are associated with dust. These dust signals can be interpreted as a result of cometary dust releasing volatiles while heated up near COPS. A statistical analysis of dust signals detected by COPS will be presented.

  8. Assessment and optimization of theileria parva sporozoite full-length p67 antigen expression in mammalian cells

    Science.gov (United States)

    Delivery of various forms of recombinant Theileria parva sporozoite antigen (p67) has been shown to elicit antibody responses in cattle capable of providing protection against East Coast fever, the clinical disease caused by T. parva. Previous formulations of full-length and shorter recombinant vers...

  9. Spectral response modeling and analysis of p–n–p In0.53Ga0.47As/InP HPTs

    International Nuclear Information System (INIS)

    Chen Jun; Lv Jiabing

    2016-01-01

    We report our results on the modeling of the spectral response of the near-infrared (NIR) lattice-matched p–n–p In 0.53 Ga 0.47 As/InP heterojunction phototransistors (HPTs). The spectral response model is developed from the solution of the steady state continuity equations that dominate the excess optically generated minority-carriers in the active regions of the HPTs with accurate boundary conditions. In addition, a detailed optical-power absorption profile is constructed for the device modeling. The calculated responsivity is in good agreement with the measured one for the incident radiation at 980 nm, 1310 nm, and 1550 nm. Furthermore, the variation in the responsivity of the device with the base region width is analyzed. (paper)

  10. Solar wind interaction with comet 67P: Impacts of corotating interaction regions

    Science.gov (United States)

    Edberg, N. J. T.; Eriksson, A. I.; Odelstad, E.; Vigren, E.; Andrews, D. J.; Johansson, F.; Burch, J. L.; Carr, C. M.; Cupido, E.; Glassmeier, K.-H.; Goldstein, R.; Halekas, J. S.; Henri, P.; Koenders, C.; Mandt, K.; Mokashi, P.; Nemeth, Z.; Nilsson, H.; Ramstad, R.; Richter, I.; Wieser, G. Stenberg

    2016-02-01

    We present observations from the Rosetta Plasma Consortium of the effects of stormy solar wind on comet 67P/Churyumov-Gerasimenko. Four corotating interaction regions (CIRs), where the first event has possibly merged with a coronal mass ejection, are traced from Earth via Mars (using Mars Express and Mars Atmosphere and Volatile EvolutioN mission) to comet 67P from October to December 2014. When the comet is 3.1-2.7 AU from the Sun and the neutral outgassing rate ˜1025-1026 s-1, the CIRs significantly influence the cometary plasma environment at altitudes down to 10-30 km. The ionospheric low-energy (˜5 eV) plasma density increases significantly in all events, by a factor of >2 in events 1 and 2 but less in events 3 and 4. The spacecraft potential drops below -20 V upon impact when the flux of electrons increases. The increased density is likely caused by compression of the plasma environment, increased particle impact ionization, and possibly charge exchange processes and acceleration of mass-loaded plasma back to the comet ionosphere. During all events, the fluxes of suprathermal (˜10-100 eV) electrons increase significantly, suggesting that the heating mechanism of these electrons is coupled to the solar wind energy input. At impact the magnetic field strength in the coma increases by a factor of 2-5 as more interplanetary magnetic field piles up around the comet. During two CIR impact events, we observe possible plasma boundaries forming, or moving past Rosetta, as the strong solar wind compresses the cometary plasma environment. We also discuss the possibility of seeing some signatures of the ionospheric response to tail disconnection events.

  11. Cell-cycle-dependent three-dimensional redistribution of nuclear proteins, P 120, pKi-67, and SC 35 splicing factor, in the presence of the topoisomerase I inhibitor camptothecin.

    Science.gov (United States)

    Elias, Emmanuel; Lalun, Nathalie; Lorenzato, Marianne; Blache, Laurent; Chelidze, Pavel; O'Donohue, Marie-Françoise; Ploton, Dominique; Bobichon, Hélène

    2003-11-15

    Topoisomerase I (Topo I) is mostly known for its role in DNA relaxation, which is required for duplication and transcription. Topo I acts as a protein kinase mainly directed to the mRNA splicing factor SC35. Camptothecin is one of the specific Topo I inhibitors and is effective on the two functions of the enzyme. In this study we demonstrated that treatment of KB cells with camptothecin for only 30 min induced the 3D reorganization and redistribution of three proteins involved in the nucleus machinery, P 120, pKi-67, and SC 35, and this occurred in a cell cycle-dependent manner. Our data were obtained from confocal microscopic studies after immunolabeling, 3D reconstruction, and measurement of the nuclear components volumes. In the presence of camptothecin, P 120, which occupied the nucleolar volume, lost its reticulation and pKi-67 was redistributed within the nucleoplasm and even into the cytoplasm. Finally, for SC 35 the fusion of its dots into bigger volumes was observed specifically during the G1 phase. Variations of volumes were also observed for the nucleolus and for the nucleus. These results pointed out that, depending on the cell cycle phase, Topo I functions were selective toward the three different proteins.

  12. Cholesterol Removal from Adult Skeletal Muscle impairs Excitation-Contraction Coupling and Aging reduces Caveolin-3 and alters the Expression of other Triadic Proteins

    Directory of Open Access Journals (Sweden)

    Genaro eBarrientos

    2015-04-01

    Full Text Available Cholesterol and caveolin are integral membrane components that modulate the function/location of many cellular proteins. Skeletal muscle fibers, which have unusually high cholesterol levels in transverse tubules, express the caveolin-3 isoform but its association with transverse tubules remains contentious. Cholesterol removal impairs excitation-contraction coupling in amphibian and mammalian fetal skeletal muscle fibers. Here, we show that treating single muscle fibers from adult mice with the cholesterol removing agent methyl-β-cyclodextrin decreased fiber cholesterol by 26%, altered the location pattern of caveolin-3 and of the voltage dependent calcium channel Cav1.1, and suppressed or reduced electrically evoked Ca2+ transients without affecting membrane integrity or causing sarcoplasmic reticulum calcium depletion. We found that transverse tubules from adult muscle and triad fractions that contain ~10% attached transverse tubules, but not sarcoplasmic reticulum membranes, contained caveolin-3 and Cav1.1; both proteins partitioned into detergent-resistant membrane fractions highly enriched in cholesterol. Aging entails significant deterioration of skeletal muscle function. We found that triad fractions from aged rats had similar cholesterol and RyR1 protein levels compared to triads from young rats, but had lower caveolin-3 and glyceraldehyde 3-phosphate dehydrogenase and increased Na+/K+-ATPase protein levels. Both triad fractions had comparable NADPH oxidase (NOX activity and protein content of NOX2 subunits (p47phox and gp91phox, implying that NOX activity does not increase during aging. These findings show that partial cholesterol removal impairs excitation-contraction coupling and alters caveolin-3 and Cav1.1 location pattern, and that aging reduces caveolin-3 protein content and modifies the expression of other triadic proteins. We discuss the possible implications of these findings for skeletal muscle function in young and aged

  13. Purple sweet potato color attenuates domoic acid-induced cognitive deficits by promoting estrogen receptor-α-mediated mitochondrial biogenesis signaling in mice.

    Science.gov (United States)

    Lu, Jun; Wu, Dong-Mei; Zheng, Yuan-Lin; Hu, Bin; Cheng, Wei; Zhang, Zi-Feng

    2012-02-01

    Recent findings suggest that endoplasmic reticulum stress may be involved in the pathogenesis of domoic acid-induced neurodegeneration. Purple sweet potato color, a class of naturally occurring anthocyanins, has beneficial health and biological effects. Recent studies have also shown that anthocyanins have estrogenic activity and can enhance estrogen receptor-α expression. In this study, we evaluated the effect of purple sweet potato color on cognitive deficits induced by hippocampal mitochondrial dysfunction in domoic acid-treated mice and explored the potential mechanisms underlying this effect. Our results showed that the oral administration of purple sweet potato color to domoic acid-treated mice significantly improved their behavioral performance in a step-through passive avoidance task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of estrogen receptor-α-mediated mitochondrial biogenesis signaling and by decreases in the expression of p47phox and gp91phox. Decreases in reactive oxygen species and protein carbonylation were also observed, along with a blockade of the endoplasmic reticulum stress pathway. Furthermore, purple sweet potato color significantly suppressed endoplasmic reticulum stress-induced apoptosis, which prevented neuron loss and restored the expression of memory-related proteins. However, knockdown of estrogen receptor-α using short hairpin RNA only partially blocked the neuroprotective effects of purple sweet potato color in the hippocampus of mice cotreated with purple sweet potato color and domoic acid, indicating that purple sweet potato color acts through multiple pathways. These results suggest that purple sweet potato color could be a possible candidate for the prevention and treatment of cognitive deficits in excitotoxic and other brain disorders. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  14. Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells.

    Science.gov (United States)

    Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

    2016-01-01

    We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy.

  15. Structural alterations in embryos and alevins of the Atlantic salmon, Salmo salar 1. , induced by continuous or short-term exposure to acidic levels of pH

    Energy Technology Data Exchange (ETDEWEB)

    Daye, P.G.; Garside, E.T.

    1980-01-01

    Embryos of the Atlantic Salmon, salmo salar l., were incubated continuously from fertilization, at pH 6.8 (control), 5.0, 4.5, 4.3, 4.0, and 3.7, at 5-6 degrees C. The subsequent alvins in these environments were maintained at these levels for 40 days after hatching. Generally, lethal and sublethal injuries were separable only as to degree and distribution. Sublethal alterations occurred in the integument, gill blood, and blood vascular structures of all live alevins incubated at pH 5.0 and lower. At pH 4.5 and lower, injuries also occurred in brain, optic retina, kidney, and spleen. Some tissue regeneration occurred in the embryonal rudimentary integument at pH 4.5 and lower. Regeneration also occurred but to a lesser degree in pseudobranch, kidney, spleen, and erythrocytes. Injury of the integument was the apparent cause of death in prehatching embryos since it is the major site of respiration and ion exchange. As gills expand in posthatching alevins, they assume these functions and destruction of branchial epithelium then becomes the prime cause of death. The nature of cell injury and consequent dysgenesis at tissue and organ levels are not ascribable uniquely to acidic stress. Some injuries are similar to those caused variously by heavy metals, detergents, halogenated organic compounds, some petroleum fractions, and chronic and acute high temperature in postalevin stages of several species of fish.

  16. Thermophotovoltaic cells based on In0.53Ga0.47As/InP heterostructures

    International Nuclear Information System (INIS)

    Karlina, L. B.; Vlasov, A. S.; Kulagina, M. M.; Timoshina, N. Kh.

    2006-01-01

    Reflection of infrared radiation from n-InP substrates with a rear MgF 2 /Au mirror is investigated in the wavelength range 1000-2200 nm. It is found that the reflectance weakly depends on substrate thickness and free-carrier concentration in the (0.1-6) x 10 18 cm -3 range. Thermophotovoltaic cells based on the InP/In 0.53 Ga 0.47 As lattice-matched heterostructure of p-n and n-p are fabricated by liquid-phase epitaxy and Zn and P diffusion from a gas phase. The characteristics of p-n and n-p thermophotovoltaic cells with an identical configuration of the contacts of 1 cm 2 area are determined. These characteristics are the open-circuit voltage U oc = 0.465 V, the filling factor FF = 64% at the current density of 1 A/cm 2 , and the reflectance R = 76-80% for wavelengths longer than 1.86 μm

  17. NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice.

    Science.gov (United States)

    Bast, Antje; Kubis, Helen; Holtfreter, Birte; Ribback, Silvia; Martin, Heiner; Schreiner, Helen C; Dominik, Malte J; Breitbach, Katrin; Dombrowski, Frank; Kocher, Thomas; Steinmetz, Ivo

    2017-02-01

    Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans-induced periodontitis. NADPH oxidase-deficient (gp91 phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional micro-computed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91 phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91 phox KO mice. Only infected gp91 phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis. Copyright © 2017 American Society for Microbiology.

  18. A Polyprotein-Expressing Salmonid Alphavirus Replicon Induces Modest Protection in Atlantic Salmon (Salmo Salar Against Infectious Pancreatic Necrosis

    Directory of Open Access Journals (Sweden)

    Azila Abdullah

    2015-01-01

    Full Text Available Vaccination is an important strategy for the control and prevention of infectious pancreatic necrosis (IPN in farmed Atlantic salmon (Salmo salar in the post-smolt stage in sea-water. In this study, a heterologous gene expression system, based on a replicon construct of salmonid alphavirus (SAV, was used for in vitro and in vivo expression of IPN virus proteins. The large open reading frame of segment A, encoding the polyprotein NH2-pVP2-VP4-VP3-COOH, as well as pVP2, were cloned and expressed by the SAV replicon in Chinook salmon embryo cells (CHSE-214 and epithelioma papulosum cyprini (EPC cells. The replicon constructs pSAV/polyprotein (pSAV/PP and pSAV/pVP2 were used to immunize Atlantic salmon (Salmo salar by a single intramuscular injection and tested in a subsequent IPN virus (IPNV challenge trial. A low to moderate protection against IPN was observed in fish immunized with the replicon vaccine that encoded the pSAV/PP, while the pSAV/pVP2 construct was not found to induce protection.

  19. PACA_Rosetta67P: Global Amateur Observing Support for ESA/Rosetta Mission

    Science.gov (United States)

    Yanamandra-Fisher, Padma A.; Alexander, Claudia; Morales, Efrain; Feliciano-Rivera, Christiana

    2015-11-01

    The PACA (Professional - Amateur Collaborative Astronomy) Project is an ecosystem of several social media platforms (Facebook, Pinterest, Twitter, Flickr, Vimeo) that takes advantage of the global and immediate connectivity amongst amateur astronomers worldwide, that can be galvanized to participate in a given observing campaign. The PACA Project has participated in organized campaigns such as Comet Observing Campaign (CIOC_ISON) in 2013 and Comet Siding Spring (CIOC_SidingSpring)in 2014. Currently the PACA Project is supporting ESA/Rosetta mission with ground-based observations of the comet 67P/Churyumov-Gerasimenko (CG) through its perihelion in August 2015 and beyond; providing baseline observations of magnitude and evolution from locations around the globe. Comet 67P/CG will reach its brightest post-perihelion and pass closest to Earth in November 2015. We will present the various benefits of our professional - amateur collaboration: developing and building a core astronomer community; defining an observing campaign from basic information of the comet from its previous apparitions; coordinating with professionals and the mission to acquire observations, albeit low-resolution, but on a long timeline; while addressing the creation of several science products such as the variation of its magnitude over time and the changing morphology. We will present some of our results to date and compare with observations from professionals and previous apparations of the comet. We shall also highlight the challenges faced in building a successful collaborative partnership between the professional and amateur observers and their resolution. With the popularity of mobile platforms and instant connections with peers globally, the multi-faceted social universe has become a vital part of engagement of multiple communities for collaborative scientific partnerships and outreach. We shall also highlight other cometary observing campaigns that The PACA Project has initiated to evolve

  20. Immunohistochemical study of p53, pRb, p16 in esophageal cancer

    International Nuclear Information System (INIS)

    Zo, Jae Ill; Zo, Kyung Ja; Park, Jong Ho; Kim, Mi Hee

    1998-01-01

    To confirm the expression of molecular genetic alterations of p53, pRb, p16 in esophageal cancer and to investigate the expression of p53, pRb, p16 in esophageal cancer according to the pathologic steps of carcinogenesis, immuno-histochemistry was performed in 15 resected esophageal cancer specimens with multiple separated lesions after pathologic mapping. The accumulation of mutant p53 was observed in 60 % of dysplasia and 47 % of invasive cancer, while pRb was not detected in 91 % of dysplasia and 72.7 % of invasive cancer. But p16 was not observed in 0 % in dysplasia and 7 % of invasive cancer. But p16 was not observed in 0 % in dysplasia and 28.6 % in invasive cancer. There was no simultaneous negative pRb and p16 expression. There was no relations between p53 and p16, pRb. As a results, the expression of p53, pRb, p16 was co-related well with molecular genetic changes and inactivation of p53, pRb, p16 was co-related well with molecular genetic changes and inactivation of p53 and pRb was common and early event in esophageal carcinogenesis in Korea, but inactivation of p16 was a infrequent change. (author). 17 refs., 2 tabs., 7 figs

  1. Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox/Duox family of enzymes

    Directory of Open Access Journals (Sweden)

    Lambeth J David

    2007-07-01

    Full Text Available Abstract Background NADPH-oxidases (Nox and the related Dual oxidases (Duox play varied biological and pathological roles via regulated generation of reactive oxygen species (ROS. Members of the Nox/Duox family have been identified in a wide variety of organisms, including mammals, nematodes, fruit fly, green plants, fungi, and slime molds; however, little is known about the molecular evolutionary history of these enzymes. Results We assembled and analyzed the deduced amino acid sequences of 101 Nox/Duox orthologs from 25 species, including vertebrates, urochordates, echinoderms, insects, nematodes, fungi, slime mold amoeba, alga and plants. In contrast to ROS defense enzymes, such as superoxide dismutase and catalase that are present in prokaryotes, ROS-generating Nox/Duox orthologs only appeared later in evolution. Molecular taxonomy revealed seven distinct subfamilies of Noxes and Duoxes. The calcium-regulated orthologs representing 4 subfamilies diverged early and are the most widely distributed in biology. Subunit-regulated Noxes represent a second major subdivision, and appeared first in fungi and amoeba. Nox5 was lost in rodents, and Nox3, which functions in the inner ear in gravity perception, emerged the most recently, corresponding to full-time adaptation of vertebrates to land. The sea urchin Strongylocentrotus purpuratus possesses the earliest Nox2 co-ortholog of vertebrate Nox1, 2, and 3, while Nox4 first appeared somewhat later in urochordates. Comparison of evolutionary substitution rates demonstrates that Nox2, the regulatory subunits p47phox and p67phox, and Duox are more stringently conserved in vertebrates than other Noxes and Nox regulatory subunits. Amino acid sequence comparisons identified key catalytic or regulatory regions, as 68 residues were highly conserved among all Nox/Duox orthologs, and 14 of these were identical with those mutated in Nox2 in variants of X-linked chronic granulomatous disease. In addition to

  2. Absolute differential cross sections for π±p elastic scattering at 30 ≤ Tπ ≤ 67 MeV

    International Nuclear Information System (INIS)

    Brack, J.T.; Ristinen, R.A.; Kraushaar, J.J.

    1989-11-01

    Absolute π±p differential cross sections have been measured at incident pion energies of 30.0, 45.0, and 66.8 MeV, using active targets of scintillator plastic (CH 1.1 ) to detect recoil protons in coincidence with scattered pions. Statistical uncertainties are typically ±3%; systematic uncertainties are ±2%. The results are consistent with two earlier measurements by this group employing different experimental techniques at 67 MeV and higher incident pion energies. The π - p cross sections are in good agreement with currently accepted phase-shift analyses, but the corresponding π + p predictions are typically 15% higher at large angles than the π + p data reported here

  3. Evidence for episodic acidification effects on migrating Atlantic salmon Salmo salar smolts

    Science.gov (United States)

    Kelly, John T; Lerner, Darrren T.; O'Dea, Michael F.; Regish, Amy M.; Monette, Michelle Y.; Hawkes, J.P.; Nislow, Keith H.; McCormick, Stephen

    2015-01-01

    Field studies were conducted to determine levels of gill aluminium as an index of acidification effects on migrating Atlantic salmon Salmo salar smolts in the north-eastern U.S.A. along mainstem river migration corridors in several major river basins. Smolts emigrating from the Connecticut River, where most (but not all) tributaries were well buffered, had low or undetectable levels of gill aluminium and high gill Na+/K+-ATPase (NKA) activity. In contrast, smolts emigrating from the upper Merrimack River basin where most tributaries are characterized by low pH and high inorganic aluminium had consistently elevated gill aluminium and lower gill NKA activity, which may explain the low adult return rates of S. salar stocked into the upper Merrimack catchment. In the Sheepscot, Narraguagus and Penobscot Rivers in Maine, river and year-specific effects on gill aluminium were detected that appeared to be driven by underlying geology and high spring discharge. The results indicate that episodic acidification is affecting S. salar smolts in poorly buffered streams in New England and may help explain variation in S. salar survival and abundance among rivers and among years, with implications for the conservation and recovery of S. salar in the north-eastern U.S.A. These results suggest that the physiological condition of outmigrating smolts may serve as a large-scale sentinel of landscape-level recovery of atmospheric pollution in this and other parts of the North Atlantic region.

  4. a salar elahi

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics. A SALAR ELAHI. Articles written in Pramana – Journal of Physics. Volume 87 Issue 5 November 2016 pp 81 Regular. Analysis of tokamak plasma confinement modes using the fast Fourier transformation · S R MIRMOEINI A SALAR ELAHI M GHORANNEVISS · More Details ...

  5. Evaluation of Some (n,n'), (n,γ), (n,p), (n,2n) and (n,3n) Reaction Excitation Functions for Fission and Fusion Reactor Dosimetry Applications; Evaluation of the Excitation Functions for the 54Fe(n,p)54Mn, 58Ni(n,2n)57Ni, 67Zn(n,p)67Cu, 92Mo(n,p)92mNb, 93Nb(n,γ)94Nb, 113In(n,n')113mIn, 115In(n,γ) 116mIn, and 169Tm(n,3n)167Tm Reactions. Progress Report on Research Contract No 16242

    International Nuclear Information System (INIS)

    Zolotarev, K.I.; Zolotarev, P.K.

    2013-12-01

    Cross section data for the 54 Fe(n,p) 54 Mn, 58 Ni(n,2n) 57 Ni, 67 Zn(n,p) 67 Cu, 92 Mo(n,p) 92m Nb, 93 Nb(n,γ) 94 Nb, 113 In(n,n') 113m In, 115 In(n,γ) 116m In, 169 Tm(n,3n) 167 Tm reactions are needed to solve a wide spectrum of scientific and technical tasks. Activation detectors based on these reactions may be used in the field of reactor dosimetry. Furthermore, the 54 Fe(n,p) 54 Mn reaction is often used in experimental nuclear physics as a monitor reaction for measurements of unknown cross sections by means of the activation method over the neutron energy range from 5 to 15 MeV. The 93 Nb(n,γ) 94 Nb reaction is also very promising for using in retrospective neutron dosimetry for determination of total neutron fluence during a campaign of a reactor. In the existing version of the International Reactor Dosimetry File and the new extended version named as IRDFF data for excitation functions of 67 Zn(n,p) 67 Cu, 92 Mo(n,p) 92m Nb, 113 In(n,n') 113m In, and 169 Tm(n,3n) 167 Tm reactions are absent. Data for these reactions are also absent in the JENDL/D-99 dosimetry file. Excitation functions of 67 Zn(n,p) 67 Cu and 169 Tm(n,3n) 167 Tm are presented in the TENDL-2012, EAF-2010, JENDL-4.0, JEFF-3.1/A, MENDL-2 libraries. Cross section data for the 67 Zn(n,p) 67 Cu reaction up to 20 MeV are given also in the JENDL/HE-2007 library. Excitation functions of the 92 Mo(n,p) 92m Nb and 113 In(n,n') 113m In reactions are evaluated in the EAF-2010 and JEFF-3.1/A libraries. Cross section data for the 113 In(n,n') 113m In reaction are given also in the TENDL-2010 library. It is necessary to note that neutron data in the JEFF-3.1/A and JENDL-4.0 libraries were evaluated up to 20 MeV. Neutron data in the TENDL-2012, EAF-2010, MENDL-2 and TENDL-2010 libraries had been evaluated up to 30 MeV, 60 MeV, 100 MeV and 200 MeV, respectively. Neutron cross sections in the MENDL-2, TENDL-2010 and TENDL-2012 libraries had been obtained on the basis of pure theoretical model calculations

  6. Solar-insolation-induced changes in the coma morphology of comet 67P/Churyumov-Gerasimenko. Optical monitoring with the Nordic Optical Telescope

    Science.gov (United States)

    Zaprudin, B.; Lehto, H. J.; Nilsson, K.; Somero, A.; Pursimo, T.; Snodgrass, C.; Schulz, R.

    2017-07-01

    Context. 67P/Churyumov-Gerasimenko (67P/C-G) is a short-period Jupiter family comet with an orbital period of 6.55 yr. Being the target comet of ESA's Rosetta mission, 67P/C-G has become one of the most intensively studied minor bodies of the solar system. The Rosetta Orbiter and the Philae Lander have brought us unique information about the structure and activity of the comet nucleus, as well as its activity along the orbit, composition of gas, and dust particles emitted into the coma. However, as Rosetta stayed in very close proximity to the cometary nucleus (less than 500 km with a few short excursions reaching up to 1500 km), it could not see the global picture of a coma at the scales reachable by telescopic observations (103 - 105 km). Aims: In this work we aim to connect in-situ observations made by Rosetta with the morphological evolution of the coma structures monitored by the ground-based observations. In particular, we concentrate on causal relationships between the coma morphology and evolution observed with the Nordic Optical Telescope (NOT) in the Canary Islands, and the seasonal changes of the insolation and the activity of the comet observed by the Rosetta instruments. Methods: Comet 67P/C-G was monitored with the NOT in imaging mode in two colors. Imaging optical observations were performed roughly on a weekly basis, which provides good coverage of short- and long-term variability. With the three dimensional modeling of the coma produced by active regions on the southern hemisphere, we aim to qualify the observed morphology by connecting it to the activity observed by Rosetta. Results: During our monitoring program, we detected major changes in the coma morphology of comet 67P/C-G. These were long-term and long-lasting changes. They do not represent any sudden outburst or short transient event, but are connected to seasonal changes of the surface insolation and the emergence of new active regions on the irregular shaped comet nucleus. We have also

  7. Microbial diversity of the hypersaline and lithium-rich Salar de Uyuni, Bolivia.

    Science.gov (United States)

    Haferburg, Götz; Gröning, Janosch A D; Schmidt, Nadja; Kummer, Nicolai-Alexeji; Erquicia, Juan Carlos; Schlömann, Michael

    2017-06-01

    Salar de Uyuni, situated in the Southwest of the Bolivian Altiplano, is the largest salt flat on Earth. Brines of this athalassohaline hypersaline environment are rich in lithium and boron. Due to the ever- increasing commodity demand, the industrial exploitation of brines for metal recovery from the world's biggest lithium reservoir is likely to increase substantially in the near future. Studies on the composition of halophilic microbial communities in brines of the salar have not been published yet. Here we report for the first time on the prokaryotic diversity of four brine habitats across the salar. The brine is characterized by salinity values between 132 and 177 PSU, slightly acidic to near-neutral pH and lithium and boron concentrations of up to 2.0 and 1.4g/L, respectively. Community analysis was performed after sequencing the V3-V4 region of the 16S rRNA genes employing the Illumina MiSeq technology. The mothur software package was used for sequence processing and data analysis. Metagenomic analysis revealed the occurrence of an exclusively archaeal community comprising 26 halobacterial genera including only recently identified genera like Halapricum, Halorubellus and Salinarchaeum. Despite the high diversity of the halobacteria-dominated community in sample P3 (Shannon-Weaver index H'=3.12 at 3% OTU cutoff) almost 40% of the Halobacteriaceae-assigned sequences could not be classified on the genus level under stringent filtering conditions. Even if the limited taxonomic resolution of the V3-V4 region for halobacteria is considered, it seems likely to discover new, hitherto undescribed genera of the family halobacteriaceae in this particular habitat of Salar de Uyuni in future. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. InterProScan Result: FS904599 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available R001683 Phox-like Molecular Function: protein binding (GO:0005515)|Biological Process: cell communication (GO:0007154)|Molecular Function: phosphoinositide binding (GO:0035091) ...

  9. InterProScan Result: DC541645 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available IPR001683 Phox-like Molecular Function: protein binding (GO:0005515)|Biological Process: cell communication (GO:0007154)|Molecular Function: phosphoinositide binding (GO:0035091) ...

  10. InterProScan Result: FS724649 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available IPR001683 Phox-like Molecular Function: protein binding (GO:0005515)|Biological Process: cell communication (GO:0007154)|Molecular Function: phosphoinositide binding (GO:0035091) ...

  11. InterProScan Result: FS912773 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available R001683 Phox-like Molecular Function: protein binding (GO:0005515)|Biological Process: cell communication (GO:0007154)|Molecular Function: phosphoinositide binding (GO:0035091) ...

  12. Congenital central hypoventilation syndrome: diagnostic and management challenges

    Directory of Open Access Journals (Sweden)

    Kasi AS

    2016-08-01

    Full Text Available Ajay S Kasi,1 Iris A Perez,1,2 Sheila S Kun,1 Thomas G Keens1,2 1Division of Pediatric Pulmonology and Sleep Medicine, Children’s Hospital Los Angeles, 2Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA Abstract: Congenital central hypoventilation syndrome (CCHS is a rare genetic disorder with failure of central control of breathing and of the autonomic nervous system function due to a mutation in the paired-like homeobox 2B (PHOX2B gene. Affected patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxemia, and they do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis of CCHS must be confirmed with PHOX2B gene mutation. Generally, the PHOX2B mutation genotype can aid in anticipating the severity of the phenotype. They require ventilatory support for life. Home assisted ventilation options include positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and diaphragm pacing via phrenic nerve stimulation, but each strategy has its associated limitations and challenges. Since all the clinical manifestations of CCHS may not manifest at birth, periodic monitoring and early intervention are necessary to prevent complications and improve outcome. Life-threatening arrhythmias can manifest at different ages and a normal cardiac monitoring study does not exclude future occurrences leading to the dilemma of timing and frequency of cardiac rhythm monitoring and treatment. Given the rare incidence of CCHS, most health care professionals are not experienced with managing CCHS patients, particularly those with diaphragm pacers. With early diagnosis and advances in home mechanical ventilation and monitoring strategies, many CCHS children are surviving into adulthood presenting new challenges in their care. Keywords: congenital central hypoventilation syndrome, PHOX2B, home mechanical ventilation, diaphragm

  13. Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs.

    Science.gov (United States)

    Feng, Qiaoli; Lu, Chengzhi; Wang, Li; Song, Lijun; Li, Chao; Uppada, Ravi Chandra

    2017-02-17

    This study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action. Eighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47 phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1-7) [Ang(1-7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively. We found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47 phox ,ACE2, Ang(1-7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0

  14. EXAFS study of Mn1.28Fe0.67P0.46Si0.54 compound with first-order phase transition

    International Nuclear Information System (INIS)

    L, Yingjie; Huliyageqi, B; Haschaolu, W; Song, Zhiqiang; Tegus, O; Nakai, Ikuo

    2014-01-01

    Highlights: • We have investigated the Fe and Mn K edge XAFS spectra of the Mn 1.28 Fe 0.67 P 0.46 Si 0.54 compound at 25 K and 295 K. • The site occupation of the Fe and Mn atoms and local structure of Mn 1.28 Fe 0.67 P 0.46 Si 0.54 are determined. • The atomic distances between Fe–Fe in c-plane for the ferromagnetic state are larger than those in the paramagnetic state. - Abstract: The Fe 2 P-type MnFe(P,Si) compounds are investigated by means of magnetic measurements and X-ray absorption fine structure spectroscopy. Magnetic measurements show that the Mn 1.28 Fe 0.67 P 0.46 Si 0.54 compound undergoes a first-order phase transition at the Curie temperature of 254 K. The Fe K-edge and Mn K-edge X-ray absorption fine structure spectra show that Mn atom mainly located at the 3g sites, while the 3f sites are occupied by Fe atoms and Mn atom randomly. The distances between the Fe atom and its nearest neighbor atoms in a triangle Fe–Mn–Fe change from 2.80 Å at 25 K to 2.74 Å at 300 K. On the other hand, the distances between Fe atom and its second neighbor atoms change from 4.06 Å at 25 K to 4.02 Å at 300 K

  15. Aging increases oxidative stress and renal expression of oxidant and antioxidant enzymes that are associated with an increased trend in systolic blood pressure.

    Science.gov (United States)

    Gomes, Pedro; Simão, Sónia; Silva, Elisabete; Pinto, Vanda; Amaral, João S; Afonso, Joana; Serrão, Maria Paula; Pinho, Maria João; Soares-da-Silva, Patrício

    2009-01-01

    The aim of this study was to investigate whether the effects of aging on oxidative stress markers and expression of major oxidant and antioxidant enzymes associate with impairment of renal function and increases in blood pressure. To explore this, we determined age-associated changes in lipid peroxidation (urinary malondialdehyde), plasma and urinary hydrogen peroxide (H(2)O(2)) levels, as well as renal H(2)O(2) production, and the expression of oxidant and antioxidant enzymes in young (13 weeks) and old (52 weeks) male Wistar Kyoto (WKY) rats. Urinary lipid peroxidation levels and H(2)O(2) production by the renal cortex and medulla of old rats were higher than their young counterparts. This was accompanied by overexpression of NADPH oxidase components Nox4 and p22(phox) in the renal cortex of old rats. Similarly, expression of superoxide dismutase (SOD) isoforms 2 and 3 and catalase were increased in the renal cortex from old rats. Renal function parameters (creatinine clearance and fractional excretion of sodium), diastolic blood pressure and heart rate were not affected by aging, although slight increases in systolic blood pressure were observed during this 52-week period. It is concluded that overexpression of renal Nox4 and p22(phox) and the increases in renal H(2)O(2) levels in aged WKY does not associate with renal functional impairment or marked increases in blood pressure. It is hypothesized that lack of oxidative stress-associated effects in aged WKY rats may result from increases in antioxidant defenses that counteract the damaging effects of H(2)O(2).

  16. Expressão imuno-histoquímica dos marcadores pcna, KI67 e p53 em carcinomas epidermóides do trato aerodigestivo superior

    Directory of Open Access Journals (Sweden)

    João Paulo Esposito

    Full Text Available OBJETIVO: Os carcinomas epidermóides do trato aerodigestivo superior são tumores de comportamento biológico heterogêneo. O objetivo deste trabalho é verificar se a expressão imuno-histoquímica dos marcadores Ki67, PCNA e P53 apresenta correlações com parâmetros prognósticos clínico-patológicos. MÉTODOS: Determinação da expressão imuno-histoquímica dos antígenos Ki67, PCNA e P53 em espécimes tumorais fixados e embebidos em parafina de 53 pacientes com carcinoma epidermóide em diferentes sítios primários do trato aerodigestivo superior. RESULTADOS: Os marcadores tiveram altos índices de expressão imuno-histoquímica, sendo 46,5% para o Ki67, 66,5% para o PCNA e 36,5% para o P53. Não houve correlação da expressão do Ki67 e do PCNA com o estadiamento TNM (AJCC, nem com o grau de malignidade. A expressão do Ki67 apresentou correlação positiva com a expressão do PCNA (p = 0,037. O mesmo aconteceu para o PCNA e o número de mitoses por campo (p = 0,001. CONCLUSÕES: De acordo com estes resultados, concluiu-se que a determinação da imunorreatividade dos marcadores Ki67 e PCNA é um método objetivo e quantificável para avaliar proliferação celular que pode subsidiar as informações prognósticas.

  17. Time variability and heterogeneity in the coma of 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Hässig, M.; Altwegg, K.; Balsiger, H.; Bar-Nun, A.; Berthelier, J. J.; Bieler, A.; Bochsler, P.; Briois, C.; Calmonte, U.; Combi, M.; De Keyser, J.; Eberhardt, P.; Fiethe, B.; Fuselier, S. A.; Galand, M.; Gasc, S.; Gombosi, T. I.; Hansen, K. C.; Jäckel, A.; Keller, H. U.; Kopp, E.; Korth, A.; Kührt, E.; Le Roy, L.; Mall, U.; Marty, B.; Mousis, O.; Neefs, E.; Owen, T.; Rème, H.; Rubin, M.; Sémon, T.; Tornow, C.; Tzou, C.-Y.; Waite, J. H.; Wurz, P.

    2015-01-01

    Comets contain the best-preserved material from the beginning of our planetary system. Their nuclei and comae composition reveal clues about physical and chemical conditions during the early solar system when comets formed. ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) onboard the Rosetta spacecraft has measured the coma composition of comet 67P/Churyumov-Gerasimenko with well-sampled time resolution per rotation. Measurements were made over many comet rotation periods and a wide range of latitudes. These measurements show large fluctuations in composition in a heterogeneous coma that has diurnal and possibly seasonal variations in the major outgassing species: water, carbon monoxide, and carbon dioxide. These results indicate a complex coma-nucleus relationship where seasonal variations may be driven by temperature differences just below the comet surface.

  18. Functions and regulation of the Nox family in the filamentous fungus Podospora anserina: a new role in cellulose degradation.

    Science.gov (United States)

    Brun, Sylvain; Malagnac, Fabienne; Bidard, Frédérique; Lalucque, Hervé; Silar, Philippe

    2009-10-01

    NADPH oxidases are enzymes that produce reactive oxygen species. Studies in mammals, plants and fungi have shown that they play important roles in differentiation, defence, host/pathogen interaction and mutualistic symbiosis. In this paper, we have identified a Podospora anserina mutant strain impaired for processes controlled by PaNox1 and PaNox2, the two Nox isoforms characterized in this model ascomycete. We show that the gene mutated is PaNoxR, the homologue of the gene encoding the regulatory subunit p67(phox), conserved in mammals and fungi, and that PaNoxR regulates both PaNox1 and PaNox2. Genome sequence analysis of P. anserina reveals that this fungus posses a third Nox isoform, PaNox3, related to human Nox5/Duox and plant Rboh. We have generated a knock-out mutant of PaNox3 and report that PaNox3 plays a minor role in P. anserina, if any. We show that PaNox1 and PaNox2 play antagonist roles in cellulose degradation. Finally, we report for the first time that a saprobic fungus, P. anserina, develops special cell structures dedicated to breach and to exploit a solid cellulosic substrate, cellophane. Importantly, as for similar structures present in some plant pathogens, their proper differentiation requires PaNox1, PaNox2, PaNoxR and the tetraspanin PaPls1.

  19. Heterogeneities of 67P nucleus seen by CONSERT in the vicinity of Abydos

    Science.gov (United States)

    Ciarletti, Valerie; Lasue, Jéremie; Hérique, Alain; Kofman, Wlodek; Levasseur-Regourd, Anny-Chantal; Lemmonier, Florentin; Guiffaut, Christophe; Plettemeier, Dirk

    2016-04-01

    Since their arrival at comet 67P in August 2014, a number of instruments onboard Rosetta's main spacecraft and Philae lander have been observing the surface of the nucleus and have revealed details of amazing structures. This information was complemented by information about the nucleus internal structure collected by the CONSERT (Comet Nucleus Sounding Experiment by Radiowave Transmission) experiment in order to constrain the nucleus formation and evolution. The CONSERT experiment is a bistatic radar with receivers and transmitters on-board both Rosetta's main spacecraft and Philae lander. The instrument makes use of electromagnetic waves at 90 MHz that propagated, during the First Science Sequence, between Philae and Rosetta through the small lobe of 67P over distances ranging from approximately 200 to 800 m depending on the spacecraft location. The data used here have been collected at depths that reach a maximum of about one hundred of meters nucleus in the vicinity of Abydos. The data collected by CONSERT provide an estimate of the permittivity mean value and information about its spatial variability inside the sounded volume. Thanks to the 10 MHz frequency bandwidth of the signal used by the instrument a spatial resolution around 10m is obtained inside the sounded volume of the nucleus. In this paper, we specifically focus on local variations in the nucleus subsurface permittivity. A number of electromagnetic simulations corresponding to the CONSERT operations have been performed for a variety of subsurface permittivity models. The effect of local vertical and horizontal large scale variations as well as smaller scale random fractal structure of the permittivity values around the landing site will be presented and discussed in comparison with CONSERT's experimental data collected in the same configurations. Possible interpretations of the results will be presented as well as potential consequences for the nucleus structure in connection with observations made

  20. SPITZER OBSERVATIONS OF COMET 67P/CHURYUMOV-GERASIMENKO AT 5.5-4.3 AU FROM THE SUN

    International Nuclear Information System (INIS)

    Kelley, Michael S.; Wooden, Diane H.; Tubiana, Cecilia; Boehnhardt, Hermann; Woodward, Charles E.; Harker, David E.

    2009-01-01

    We report Spitzer Space Telescope observations of comet 67P/Churyumov-Gerasimenko at 5.5 and 4.3 AU from the Sun, post-aphelion. Comet 67P is the primary target of the European Space Agency's Rosetta mission. The Rosetta spacecraft will rendezvous with the nucleus at heliocentric distances similar to our observations. Rotationally resolved observations at 8 and 24 μm (at a heliocentric distance, r h , of 4.8 AU) that sample the size and color-temperature of the nucleus are combined with aphelion R-band light curves observed at the Very Large Telescope (VLT) and yield a mean effective radius of 2.04 ± 0.11 km, and an R-band geometric albedo of 0.054 ± 0.006. The amplitudes of the R-band and mid-infrared light curves agree, which suggests that the variability is dominated by the shape of the nucleus. We also detect the dust trail of the comet at 4.8 and 5.5 AU, constrain the grain sizes to be ∼ h = 4 AU in 2014.

  1. Preparation and Properties of Nanoparticles of Calcium Phosphates With Various Ca/P Ratios.

    Science.gov (United States)

    Sun, Limin; Chow, Laurence C; Frukhtbeyn, Stanislav A; Bonevich, John E

    2010-01-01

    This study aimed at preparing and studying the properties of nanoparticles of calcium phosphate (nCaP) with Ca/P ratios ranging from 1.0 to 1.67 using a spray-drying technique. Micro-structural analyses suggested that the nCaPs with Ca/P ratios of 1.67 to 1.33 were nano-sized amorphous calcium phosphate (ACP) containing varying amounts of acid phosphate and carbonate. The nCaP with Ca/P ratio of 1 contained only nano-sized low crystalline dicalcium phosphate (DCP). BET measurements of the nCaPs showed specific surface areas of (12 ± 2 to 50 ± 1) m(2)/g, corresponding to estimated equivalent spherical diameters of (38 to 172) nm. However, dynamic light scattering measurements revealed much larger particles of (380 ± 49 to 768 ± 111) nm, owing to agglomeration of the smaller primary nano particles as revealed by Scanning Electron Microscopy (SEM). Thermodynamic solubility measurements showed that the nCaPs with Ca/P ratio of 1.33 - 1.67 all have similar solubility behavior. The materials were more soluble than the crystalline hydroxyapatite (HA) at pH greater than about 4.7, and more soluble than β-tricalcium phosphate (β-TCP), octacalcium phosphate (OCP) and DCP at pH above 5.5. Their solubility approached that of α-tricalcium phosphate (α-TCP) at about pH 7. These nCaPs, which cannot be readily prepared by other currently available methods for nanoparticle preparation, have potential biomedical applications.

  2. Immunohistochemical Expression of Ki67 and p53 in Wilms Tumor and Its Relationship with Tumor Histology and Stage at Presentation

    Science.gov (United States)

    Krishna, O. H. Radhika; Kayla, Geetha; Abdul Aleem, Mohammed; Malleboyina, Ramani; Reddy Kota, Ramesh

    2016-01-01

    Aim. Evaluate tumor proliferation marker (Ki67) and p53 tumor suppressor marker in Wilms tumor and correlate with histology, anaplasia, and staging. Design. Prospective, hospital based study conducted at a tertiary pediatric referral centre in south India. Setting. Wilms tumor is the most common childhood renal malignancy worldwide. Anaplasia on histology is associated with treatment resistance but not with aggressiveness clinical presentation. Chemotherapy for Wilms tumor is based on histology and staging. Most patients respond to current chemotherapy protocol. However, a small fraction relapses or metastasizes. Affordable prognostic markers are needed for histopathological evaluation of this tumor. Subjects. Cases of histologically confirmed Wilms tumor over five years. Cases after chemotherapy were excluded as the immunostaining was inconsistent in necrotic areas. Methods. The clinical and radiological findings of 31 cases of Wilms tumor were documented at a tertiary pediatric referral hospital over five years. In addition to Hematoxylin and Eosin staining, Ki67 proliferation index and p53 expression were correlated with tumor histology and staging. Results. Age incidence was 3–8 years with female preponderance. Significant correlation was noted between Ki67 proliferation index and tumor staging. p53 expression was not useful in stratification of Wilms tumor. Conclusion. Ki67 was cost-effective immunohistochemical marker for prognostication of pediatric Wilms tumor. PMID:26904359

  3. Immunohistochemical Expression of Ki67 and p53 in Wilms Tumor and Its Relationship with Tumor Histology and Stage at Presentation

    Directory of Open Access Journals (Sweden)

    O. H. Radhika Krishna

    2016-01-01

    Full Text Available Aim. Evaluate tumor proliferation marker (Ki67 and p53 tumor suppressor marker in Wilms tumor and correlate with histology, anaplasia, and staging. Design. Prospective, hospital based study conducted at a tertiary pediatric referral centre in south India. Setting. Wilms tumor is the most common childhood renal malignancy worldwide. Anaplasia on histology is associated with treatment resistance but not with aggressiveness clinical presentation. Chemotherapy for Wilms tumor is based on histology and staging. Most patients respond to current chemotherapy protocol. However, a small fraction relapses or metastasizes. Affordable prognostic markers are needed for histopathological evaluation of this tumor. Subjects. Cases of histologically confirmed Wilms tumor over five years. Cases after chemotherapy were excluded as the immunostaining was inconsistent in necrotic areas. Methods. The clinical and radiological findings of 31 cases of Wilms tumor were documented at a tertiary pediatric referral hospital over five years. In addition to Hematoxylin and Eosin staining, Ki67 proliferation index and p53 expression were correlated with tumor histology and staging. Results. Age incidence was 3–8 years with female preponderance. Significant correlation was noted between Ki67 proliferation index and tumor staging. p53 expression was not useful in stratification of Wilms tumor. Conclusion. Ki67 was cost-effective immunohistochemical marker for prognostication of pediatric Wilms tumor.

  4. Chemical composition of the semi-volatile grains of comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Wurz, Peter; Altwegg, Kathrin; Balsiger, Hans; Berthelier, Jean-Jacques; Bieler, André; Calmonte, Ursina; De Keyser, Johan; Fiethe, Björn; Fuselier, Stefan; Gasc, Sébastien; Gombosi, Tamas; Jäckel, Annette; Korth, Axel; Le Roy, Lena; Mall, Urs; Rème, Henri; Rubin, Martin; Tzou, Chia-Yu

    2017-04-01

    The European Space Agency's Rosetta spacecraft (Glassmeier et al., 2007) has been in orbit of the comet 67P/Churyumov-Gerasimenko (67P/C-G) since August 2014. On board is the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) instrument suite (Balsiger et al., 2007). ROSINA consists of two mass spectrometers, the Double Focusing Mass Spectrometer (DFMS) and the Reflectron-type Time-Of-Flight (RTOF) (Scherer et al., 2006), as well as the COmet Pressure Sensor (COPS). ROSINA is designed to detect and monitor the neutral gas and thermal plasma environment in the comet's coma by in situ investigation. The two mass spectrometers have high dynamic ranges and complement each other with high mass resolution (DFMS) and high time resolution and large mass range (RTOF). Especially the unprecedented sensitivity and mass resolution of DFMS together with the large mass range of RTOF allow determining precisely light species (e.g. isotopologues) as well as detecting heavy organic species. The pressure sensor COPS measures total gas densities, bulk velocities, and gas temperatures. ROSINA has been collecting data on the composition of the coma and activity of the comet from 3.5 AU to pericentre and out again to 3.5 AU. The Rosetta mission presents a unique opportunity to directly sample the parent species in the thin cometary atmosphere of a Kuiper-belt object at distances in excess of 2.5 AU from the Sun all the way to the pericentre of the cometary orbit at 1.24 AU. The ROSINA experiment continuously measured the chemical composition of the gases in the cometary coma. Occasionally, a dust grain of cometary origin enters the ion source of a ROSINA instrument where the volatile part evaporates since these ion sources are hot. We will report on the first measurements of the volatile inventory of such dust grains. Volatile release from cometary dust grains was observed with all three ROSINA instruments on several occasions. Because the volatile content of such a dust

  5. Measurement of the 64Zn,47Ti(n,p) cross sections using a DD neutron generator for medical isotope studies

    Science.gov (United States)

    Voyles, A. S.; Basunia, M. S.; Batchelder, J. C.; Bauer, J. D.; Becker, T. A.; Bernstein, L. A.; Matthews, E. F.; Renne, P. R.; Rutte, D.; Unzueta, M. A.; van Bibber, K. A.

    2017-11-01

    Cross sections for the 47Ti(n,p)47Sc and 64Zn(n,p)64Cu reactions have been measured for quasi-monoenergetic DD neutrons produced by the UC Berkeley High Flux Neutron Generator (HFNG). The HFNG is a compact neutron generator designed as a "flux-trap" that maximizes the probability that a neutron will interact with a sample loaded into a specific, central location. The study was motivated by interest in the production of 47Sc and 64Cu as emerging medical isotopes. The cross sections were measured in ratio to the 113In(n,n‧)113mIn and 115In(n,n‧)115mIn inelastic scattering reactions on co-irradiated indium samples. Post-irradiation counting using an HPGe and LEPS detectors allowed for cross section determination to within 5% uncertainty. The 64Zn(n,p)64Cu cross section for 2.76-0.02+0.01 MeV neutrons is reported as 49.3 ± 2.6 mb (relative to 113In) or 46.4 ± 1.7 mb (relative to 115In), and the 47Ti(n,p)47Sc cross section is reported as 26.26 ± 0.82 mb. The measured cross sections are found to be in good agreement with existing measured values but with lower uncertainty (neutron sources for nuclear data measurements and potentially the production of radionuclides for medical applications.

  6. p53 and Ki-67 in Barrett's carcinoma: is there any value to predict recurrence after circumferential endoscopic mucosal resection? p53 e Ki-67 no carcinoma do esôfago de Barrett: algum valor na predição da recurrência após mucosectomia endoscópica circunferencial?

    Directory of Open Access Journals (Sweden)

    César Vivian Lopes

    2007-12-01

    Full Text Available BACKGROUND: There are situations in which the specimens obtained after endoscopic mucosal resection of superficial adenocarcinoma arising from Barrett's esophagus are not adequate for histopathological assessment of the margins. In these cases, immunohistochemistry might be an useful tool for predicting cancer recurrence. AIM: To evaluate the value of p53 and Ki-67 immunohistochemistry in predicting the cancer recurrence in patients with Barrett's esophagus-related cancer referred to circumferential endoscopic mucosal resection. METHODS: Mucosectomy specimens from 41 patients were analyzed. All endoscopic biopsies prior to endoscopic mucosal resection presented high-grade dysplasia and cancer was detected in 23 of them. Positive reactions were considered the intense coloration in the nuclei of at least 90% of the cells in each high-power magnification field, and immunostaining could be classified as superficial or diffuse according to the mucosal distribution of the stained nuclei. RESULTS: Endoscopic mucosal resection samples detected cancer in 21 cases. In these cases, p53 immunohistochemistry revealed a diffuse positivity for the great majority of these cancers (90.5% vs. 20%, and Ki-67 showed a diffuse pattern for all cases (100% vs. 30%; conversely, patients without cancer revealed a superficial or negative pattern for p53 (80% vs. 9.5% and Ki-67 (70% vs. 0%. During a mean follow-up of 31.6 months, 5 (12.2% patients developed six episodes of recurrent cancer. Endoscopic mucosal resection specimens did not show any significant difference in the p53 and Ki-67 expression for patients developing cancer after endoscopic treatment. CONCLUSIONS: p53 and Ki-67 immunohistochemistry were useful to confirm the cancer; however, they had not value for predicting the recurrent carcinoma after circumferential endoscopic mucosal resection of Barrett's carcinoma.RACIONAL: Há situações nas quais o material obtido após mucosectomia endoscópica do

  7. Molecular beam epitaxy of InP single junction and InP/In0.53Ga0.47As monolithically integrated tandem solar cells using solid phosphorous source material

    International Nuclear Information System (INIS)

    Delaney, A.; Chin, K.; Street, S.; Newman, F.; Aguilar, L.; Ignatiev, A.; Monier, C.; Velela, M.; Freundlich, A.

    1998-01-01

    This work reports the first InP solar cells, InP/In 0.53 Ga 0.47 As tandem solar cells and InP tunnel junctions to be grown using a solid phosphorous source cracker cell in a molecular beam epitaxy system. High p-type doping achieved with this system allowed for the development of InP tunnel junctions. These junctions which allow for improved current matching in subsequent monolithically integrated tandem devices also do not absorb photons which can be utilized in the InGaAs structure. Photocurrent spectral responses compared favorably to devices previously grown in a chemical beam epitaxy system. High resolution x-ray scans demonstrated good lattice matching between constituent parts of the tandem cell. AM0 efficiencies of both InP and InP/InGaAs tandem cells are reported

  8. Involvement of histone H3 phosphorylation via the activation of p38 MAPK pathway and intracellular redox status in cytotoxicity of HL-60 cells induced by Vitex agnus-castus fruit extract.

    Science.gov (United States)

    Kikuchi, Hidetomo; Yuan, Bo; Yuhara, Eisuke; Imai, Masahiko; Furutani, Ryota; Fukushima, Shin; Hazama, Shingo; Hirobe, Chieko; Ohyama, Kunio; Takagi, Norio; Toyoda, Hiroo

    2014-08-01

    We have demonstrated that an extract from the ripe fruit of Vitex angus-castus (Vitex), might be a promising anticancer candidate. In order to further provide a molecular rationale for clinical development in anticancer therapy, a detailed mechanism underlying the efficacy of Vitex against HL-60 cells was investigated. Vitex induced a dose- and time-dependent decrease in cell viability associated with induction of apoptosis and G(2)/M cell cycle arrest, both of which were suppressed by the addition of SB203580, an inhibitor for p38 MAPK. Furthermore, SB203580 significantly suppressed Vitex-induced phosphorylation of histone H3, a downstream molecule of p38 MAPK known to be involved in apoptosis induction in tumor cells. Notably, Vitex induced upregulation of intracellular ATP, known to bind its binding pocket inside activated p38 MAPK and to be required for the activation of p38 MAPK pathway. These results, thus, suggest that upregulation of intracellular ATP and phosphorylation of histone H3 are closely associated with the activation of p38 MAPK pathway, consequently contributing to Vitex-mediated cytotoxicity. Intriguingly, a significant decrease of intracellular ROS levels and downregulation of expression level of gp91(phox), an important component of NADPH oxidase, were observed in Vitex-treated cells. A greater decline in ROS levels along with enhanced apoptosis was observed after treatment with Vitex in combination with SnPP, an inhibitor specific for HO-1. Since NADPH oxidase and HO-1 are closely correlated to redox status associated with intracellular ROS levels, the two enzymes are suggested to be implicated in Vitex-mediated cytotoxicity in HL-60 cells by regulating ROS generation. We also suggest that activation of the p38 MAPK pathway may be dependent on the alterations of intracellular ATP levels, rather than that of intracellular ROS levels. These results may have important implications for appropriate clinical uses of Vitex and provide novel insights

  9. PLASMA ENVIRONMENT AROUND COMET 67P/CHURYUMOV–GERASIMENKO AT PERIHELION: MODEL COMPARISON WITH ROSETTA DATA

    Energy Technology Data Exchange (ETDEWEB)

    Madanian, H.; Cravens, T. E. [Department of Physics and Astronomy, University of Kansas, Lawrence, KS (United States); Burch, J.; Goldstein, R. [Southwest Research Institute, San Antonio, Texas (United States); Rubin, M.; Altwegg, K. [Physikalisches Institut, University of Bern, CH-3012 Bern (Switzerland); Nemeth, Z. [Wigner Research Centre for Physics, Budapest (Hungary); Goetz, C.; Koenders, C., E-mail: cravens@ku.edu [Institut für Geophysik und extraterrestrische Physik, Technische Universität Braunschweig, Mendelssohnstr. 3, D-38106 Braunschweig (Germany)

    2017-01-01

    The plasma environment near comet 67P/Churyumov–Gerasimenko (67P/CG) is dynamically affected by various factors, including the incident solar wind and outgassing from the nucleus. The Rosetta spacecraft MAGnetometer (MAG) instrument observations near perihelion showed crossing events into a magnetic field-free region at about 170 km from the nucleus in 2015 July at 1.26 au from the Sun. At each crossing, the magnitude of the magnetic field dropped by more than 20 nT to near zero. We compared the Ion and Electron Sensor (IES) electron differential flux energy spectrum inside and outside the crossing boundaries. The IES observations show a modest but consistent drop in electron flux for energies between 40 eV and a few hundred eV at each cavity crossing event. This drop in the electron spectra might be due to the absence or attenuation of solar wind electrons inside the observed diamagnetic regions, which might or might not be a diamagnetic cavity. There is no apparent simple linear correlation between the electron count rate measured by the IES at different energies and the magnitude of the magnetic field, however; at all energies, the highest electron count rates are recorded at the highest magnetic field magnitudes. From model-data comparisons it seems that inside diamagnetic regions, pure coma photoelectrons are not sufficient to explain the observations and that a trapping mechanism and/or infused solar wind electrons are necessary to explain the observed electron fluxes.

  10. 2',3-dihydroxy-5-methoxybiphenyl suppresses fMLP-induced superoxide anion production and cathepsin G release by targeting the β-subunit of G-protein in human neutrophils.

    Science.gov (United States)

    Liao, Hsiang-Ruei; Chen, Ih-Sheng; Liu, Fu-Chao; Lin, Shinn-Zhi; Tseng, Ching-Ping

    2018-06-15

    This study investigates the effect and the underlying mechanism of 2',3-dihydroxy-5-methoxybiphenyl (RIR-2), a lignan extracted from the roots of Rhaphiolepis indica (L.) Lindl. ex Ker var. tashiroi Hayata ex Matsum. & Hayata (Rosaceae), on N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced respiratory burst and cathepsin G in human neutrophils. Signaling pathways regulated by RIR-2 which modulated fMLP-induced respiratory burst were evaluated by an interaction between β subunit of G-protein (Gβ) with downstream signaling induced by fMLP and by immunoblotting analysis of the downstream targets of Gβ-protein. RIR-2 inhibited fMLP-induced superoxide anion production (IC 50 :2.57 ± 0.22 μM), cathepsin G release (IC 50 :18.72 ± 3.76 μM) and migration in a concentration dependent manner. RIR-2 specifically suppresses fMLP-induced Src family kinases phosphorylation by inhibiting the interaction between Gβ-protein with Src kinases without inhibiting Src kinases activities, therefore, RIR-2 attenuated the downstream targets of Src kinase, such as phosphorylation of Raf/ERK, AKT, P38, PLCγ2, PKC and translocation Tec, p47 ph ° x and P40 ph ° x from the cytosol to the inner leaflet of the plasma membrane. Furthermore, RIR-2 attenuated fMLP-induced intracellular calcium mobilization by inhibiting the interaction between Gβ-protein with PLCβ2. RIR-2 was not a competitive or allosteric antagonist of fMLP. On the contrary, phorbol 12-myristate 13-acetate (PMA)-induced phosphorylation of Src, AKT, P38, PKC and membrane localization of p47 ph ° x and P40 ph ° x remained unaffected. RIR-2 specifically modulates fMLP-mediated neutrophil superoxide anion production and cathepsin G release by inhibiting the interaction between Gβ-protein with downstream signaling which subsequently interferes with the activation of intracellular calcium, PLCγ2, AKT, p38, PKC, ERK, p47 ph ° x and p40 phox . Copyright © 2018 Elsevier B.V. All rights reserved.

  11. NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation

    Directory of Open Access Journals (Sweden)

    Fabio eCavaliere

    2013-12-01

    Full Text Available Multipotent cells from the juvenile subventricular zone (SVZ possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.

  12. Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

    Science.gov (United States)

    Marachelian, Araz; Villablanca, Judith G; Liu, Cathy W; Liu, Betty; Goodarzian, Fariba; Lai, Hollie A; Shimada, Hiroyuki; Tran, Hung C; Parra, Jaime A; Gallego, Richard; Bedrossian, Nora; Young, Sabrina; Czarnecki, Scarlett; Kennedy, Rebekah; Weiss, Brian D; Goldsmith, Kelly; Granger, Meaghan; Matthay, Katherine K; Groshen, Susan; Asgharzadeh, Shahab; Sposto, Richard; Seeger, Robert C

    2017-09-15

    Purpose: We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma. Experimental Design: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, Δ C t , for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, 123 I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between Δ C t and progression-free survival (PFS). Results: NB-mRNA was detectable in 83% of bone marrow (185/223) and 63% (89/142) of blood specimens, and their Δ C t values were correlated (Spearman r = 0.67, P neuroblastoma. Clin Cancer Res; 23(18); 5374-83. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Evolution of H2O related species in the neutral coma of 67P

    Science.gov (United States)

    Bieler, A. M.; Altwegg, K.; Balsiger, H. R.; Bar-Nun, A.; Berthelier, J. J.; Bochsler, P. A.; Briois, C.; Calmonte, U.; Combi, M. R.; De Keyser, J.; van Dishoeck, E.; Fiethe, B.; Fuselier, S. A.; Gasc, S.; Gombosi, T. I.; Hansen, K. C.; Hässig, M.; Jäckel, A.; Kopp, E.; Korth, A.; Le Roy, L.; Mall, U.; Maggiolo, R.; Marty, B.; Mousis, O.; Owen, T. C.; Reme, H.; Rubin, M.; Sémon, T.; Tzou, C. Y.; Waite, J. H., Jr.; Walsh, C.; Wurz, P.

    2015-12-01

    The ROSINA-DFMS mass spectrometer has been probing the coma of 67Psince the spacecraft arrived at the comet in August 2014.The acquired data set covers a large range of viewing geometries forthe ever changing conditions of 67P along its journey to pericenter. With the high temporal resolutionof ROSINA-DFMS we are able to examine diurnal and seasonal changesof different species in the gaseous coma.Large scale heterogeneities in the coma have been reported since the very first measurements of the neutral inventory at 67P.Many of the minor species are seen to follow one of the major compounds,H2O, CO or CO2.In this paper we will present the latest results on H2O related species.We will discuss the possible trapping/building mechanisms responsible for these species and why it is different from other species such asCO, N2 or CO2. Acknowledgements:Work at the University of Michigan was funded by NASA contract JPL-1266313.Work at UoB was funded by the State of Bern, the Swiss National Science Foundationand the European Space Agency PRODEX Program. Work at MPS was funded by the Max-Planck Society and BMWI contract 50QP1302. Work at Southwest Research institute was supported by subcontract #1496541 from the Jet Propulsion Laboratory. Work at BIRA-IASB was supported by the Belgian Science Policy Office via PRODEX/ROSINA PEA 90020. This work has been carried out thanks to the support of the A*MIDEX project (n° ANR-11-IDEX-0001-02) funded by the « Investissements d'Avenir » French Government program, managed by the French National Research Agency (ANR). This work was supported by CNES grants at IRAP, LATMOS, LPC2E, UTINAM, CRPG, and by the European Research Council (grant no. 267255 to B. Marty). A. Bar-Nun thanks the Ministry of Science and the Israel Space agency. Work by JHW at Southwest Research Institute was funded by the NASA JPL subcontract NAS703001TONMO710889. EvD and CW are supported by A-ERC grant 291141 CHEMPLAN and an NWO Veni award. We acknowledge herewith the

  14. The frequency of p53, Ki67, CD99 and Fli-1 protein expression in paraffin-embedded tissue blocks in Ewing’s sarcoma

    Directory of Open Access Journals (Sweden)

    Bagheri Hossein-Abadi Z

    2011-06-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Ewing sarcoma family tumors (ESFTs are among the most malignant tumors in children and young adults. ESFTs include Ewing sarcoma (ES and peripheral primitive neuroectodermal tumors (pPNETs. As there seemed to be few studies on the molecular biology of ESFTs, we investigated the frequency of CD99, Ki67, p53 and Fli-1 protein expression in 15 Iranian patients with ESFTs. In addition, the correlation between expression rate of these proteins and various clinical factors, including age, sex and survival was computed."n"nMethods: The expression of the aforesaid proteins was studied by immunohisto-chemistry in formalin-fixed and paraffin-embedded blocks of 15 ESFTs specimens. Stained sections were classified according to the percentage of stained tumor cells."n"nResults: The results showed the membrane expression of CD99 protein in all of the specimens. The nuclear expression of Fli-1 protein was observed in 86.7% and the over-expression of p53 nuclear protein was seen in 53.3% of the specimens. The expression rate of Ki67 protein was 60%. Although a significant correlation was not shown between the expression levels of Ki67, p53 or Fli-1 proteins with age, sex or survival of the patients, there was a significant

  15. p16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL papanicolaou cytology: results from the European equivocal or mildly abnormal Papanicolaou cytology study.

    Science.gov (United States)

    Schmidt, Dietmar; Bergeron, Christine; Denton, Karin J; Ridder, Ruediger

    2011-06-25

    The objective of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-stain protocol, which simultaneously detects p16(INK4a) and Ki-67 expression in cervical cytology samples, for identifying high-grade cervical intraepithelial neoplasia (CIN2+) in women with Papanicolaou (Pap) cytology results categorized as atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL). Residual liquid-based cytology material from 776 retrospectively collected ASCUS/LSIL cases that were available from a recent study evaluating p16 cytology and HPV testing were subjected to p16/Ki-67 dual staining. The presence of 1 or more double-immunoreactive cell(s) was regarded as a positive test outcome, irrespective of morphology. Test results were correlated to histology follow-up. Sensitivity of p16/Ki-67 dual-stain cytology for biopsy-confirmed CIN2+ was 92.2% (ASCUS) and 94.2% (LSIL), while specificity rates were 80.6% (ASCUS) and 68.0% (LSIL), respectively. Similar sensitivity/specificity profiles were found for both age groups of women aged aged ≥30 years. Dual-stain cytology showed comparable sensitivity, but significantly higher specificity, when compared with human papillomavirus (HPV) testing. The results of this study show that p16/Ki-67 dual-stain cytology provided a high sensitivity for the detection of underlying CIN2+ in women with ASCUS or LSIL Pap cytology results, comparable to the rates previously reported for HPV testing and p16 single-stain cytology. However, the specificity of this morphology-independent interpretation of p16/Ki-67 dual-stain cytology testing was further improved compared with the earlier p16 single-stain cytology approach, which required morphology interpretation, and it is significantly higher when compared with HPV testing. Copyright © 2011 American Cancer Society.

  16. Rosetta/Alice Measurements of Atomic and Molecular Abundances in the Coma of 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Vervack, R. J., Jr.; Weaver, H. A., Jr.; Knight, M. M.; Feldman, P.; Stern, A.; Parker, J. W.; Feaga, L. M.; Steffl, A.; Bertaux, J. L.; A'Hearn, M. F.; Keeney, B. A.

    2017-12-01

    During the Rosetta orbital phase from August 2014 through September 2016, the Alice far-ultraviolet (FUV) imaging spectrograph routinely monitored the FUV emission from the coma of 67P/Churyumov-Gerasimenko (67P). These data, spanning 700-2050 Å, provide both spatial and temporal information on the evolution of the coma composition throughout the encounter. Emissions from hydrogen (Lyman beta at 1025 Å), oxygen (1304 Å triplet, 1356 Å), sulfur (1429 Å and 1479 Å multiplets, 1814 Å triplet), and carbon (1561 Å, 1657 Å) were regularly observed, as well as emission from the CO Fourth Positive and Cameron bands. We present a preliminary analysis of these emissions with a focus on the abundances in the coma and a mapping of the temporal and spatial variations. Both short-term (days) and long-term (months) variations will be discussed in the context of rotational and seasonal timeframes. We also present ratios among various species with the goal of identifying the dominant processes at work in the coma as a function of time. Rosetta is an ESA mission with contributions from its member states and NASA. The Alice team acknowledges continuing support from NASA's Jet Propulsion Laboratory through contract 1336850 to the Southwest Research Institute. RJV's work was supported by a subcontract from Southwest Research Institute to the Johns Hopkins University Applied Physics Laboratory.

  17. /bar p/p collider physics

    International Nuclear Information System (INIS)

    Green, D.

    1989-03-01

    This note encompasses a set of six lectures given at the summer school held at Campos Do Jordao in January of 1989 near Sao Paulo, Brazil. The intent of the lectures was to describe the physics of /bar p/p at CERN and Fermilab. Particular attention has been paid to making a self contained presentation to a prospective audience of graduate students. Since large Monte Carlo codes might not be available to all members of this audience, great reliance was placed on ''back of the envelope estimates.'' Emphasis was also placed on experimental data rather than theoretical speculation, since predictions for, for example, supersymmetric particle production are easily obtained by transcription of formulae already obtained. 9 refs., 67 figs., 2 tabs

  18. A quantitative history of precipitation and hydrologic variability for the last 45 ka: Lake Titicaca, Salar de Coipasa and Salar de Uyuni, Peru and Bolivia

    Science.gov (United States)

    Nunnery, A.; Baker, P. A.; Coe, M. T.; Fritz, S. C.; Rigsby, C. A.

    2011-12-01

    Precipitation on the Bolivian/Peruvian Altiplano is dominantly controlled by the South American summer Monsoon (SASM). Over long timescales moisture transport to the Altiplano by the SASM fluctuates in intensity due to precessional insolation forcing as well as teleconnections to millennial scale abrupt temperature shifts in the North Atlantic. These long-term changes in moisture transport have been observed in multiple paleoclimate and paleo-lake level records as advances and retreats of large lakes in the terminal basin (the Salar de Uyuni). Several previous studies using energy/water balance models have been applied to paleoclimate records in attempts to provide quantitative constraints on past precipitation and temperature (P and T). For example, Blodgett et al. concluded that high paleolake stands, first dated at ca. 16,000 cal. yr BP, required P 20% higher and T 5°C colder than modern. We expand on this work conducting two experiments. The first uses a latitudinal paleohydrologic profile to reconstruct hydrological history. The second uses a terrestrial hydrology model (THMB) to "predict" lake level given changes in P and T. The profile is constructed using records from Lake Titicaca (LT), Salar de Coipasa (SC) and Salar de Uyuni (SU). LT carbonate and diatom records indicate a deep, overflowing lake for much of the last 100 ka with a distinct dry, closed-basin phase in the early to mid Holocene. A continuous sediment core from SC indicates lake level fluctuations between deep and shallow phases for the last 45 ka. A natural gamma radiation log from SU, where large paleolakes alternated with shallow salt pans characteristic of drier and/or warmer periods, shows alternation between wet and dry phases through time. These three records give evidence to the complex nature of Altiplano hydrology, most notably the ability to sustain lakes in the SC basin while exhibiting dry conditions in SU. For the second experiment, THMB, which estimates water balance and

  19. Linking surface morphology, composition and activity on the 67P/Churyumov-Gerasimenko’s nucleus

    Science.gov (United States)

    Fornasier, Sonia; Hoang, Van Hong; Hasselmann, Pedro H.; Barucci, Maria Antonieta; Feller, Clement; Prasanna Deshapriya, Jasinghege Don; Keller, Horst Uwe; OSIRIS Team

    2017-10-01

    The Rosetta mission orbited around the comet 67P/Churyumov-Gerasimenko for more than 2 years, getting an incredible amount of unique data of the comet nucleus and inner coma. This has enabled us to study its activity continuously from 4 AU inbound to 3.6 AU outbound, including the perihelion passage at 1.25 AU.This work focuses on the identification of the regions sources of faint jets and outbursts, and on the study of their spectrophotometric properties, from observations acquired with the OSIRIS/NAC camera during the July-October 2015 period, i.e. close to perihelion. More than 150 jets of different intensities were identified directly on the nucleus from NAC color sequences acquired in 7-11 filters covering the 250-1000 nm wavelength range, and their spectrophotometric properties studied for the first time. Some spectacular outbursts appear dominated by water ice particles, while fainter jets often show colors redder than the nucleus and appear dominated by dusty particles. Some jets are very faint and were identified on the nucleus thanks to the unprecedented spatial and temporal resolution of the ROSETTA/OSIRIS observations. Some of them have an extremely short lifetime, appearing on the cometary surface during the color sequence observations, reaching their peak in flux and then vanishing in less than a couple of minutes.We will present the results on the location, duration, and colors of active sources on the 67P nucleus from the relatively low resolution (i.e. 6-10 m/pixel) images acquired close to the perihelion passage. Some of this active regions were observed and investigated in higher resolution (up to few dm per pixel) during other phases of the mission. These observations allow us to study the morphological and spectral evolution of the regions found to be active and to further investigate the link between morphology, composition, and activity on cometary nuclei.

  20. P R Sarma

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics. P R Sarma. Articles written in Pramana – Journal of Physics. Volume 67 Issue 3 September 2006 pp 477-486 Research Articles. Experimental study of the dependence of beam current on injection magnetic field in 6.4 GHz ECR ion source · G S Taki P R Sarma D K ...

  1. Observation of a new type of low-frequency waves at comet 67P/Churyumov-Gerasimenko

    Directory of Open Access Journals (Sweden)

    I. Richter

    2015-08-01

    Full Text Available We report on magnetic field measurements made in the innermost coma of 67P/Churyumov-Gerasimenko in its low-activity state. Quasi-coherent, large-amplitude (δ B/B ~ 1, compressional magnetic field oscillations at ~ 40 mHz dominate the immediate plasma environment of the nucleus. This differs from previously studied cometary interaction regions where waves at the cometary ion gyro-frequencies are the main feature. Thus classical pickup-ion-driven instabilities are unable to explain the observations. We propose a cross-field current instability associated with newborn cometary ion currents as a possible source mechanism.

  2. Usefulness of p16ink4a, ProEX C, and Ki-67 for the diagnosis of glandular dysplasia and adenocarcinoma of the cervix uteri.

    Science.gov (United States)

    Negri, Giovanni; Bellisano, Giulia; Carico, Elisabetta; Faa, Gavino; Kasal, Armin; Antoniazzi, Sonia; Egarter-Vigl, Eduard; Piccin, Andrea; Dalla Palma, Paolo; Vittadello, Fabio

    2011-07-01

    Although the diagnostic criteria of in-situ and invasive adenocarcinomas of the cervix uteri are well established, the differentiation from benign mimics may be difficult and the morphologic features of the precursors of endocervical adenocarcinoma are still debated. In this study, we evaluated the usefulness of p16ink4a (p16), ProEX C, and Ki-67 for the diagnosis of endocervical adenocarcinoma and its precursors. Immunohistochemistry with p16, ProEX C, and Ki-67 was performed in 82 glandular lesions including 15 invasive adenocarcinomas, 29 adenocarcinomas in situ (AIS), 22 non-neoplastic samples, and 16 cases of glandular dysplasia (GD), which showed significant nuclear abnormalities but did not meet the diagnostic criteria for AIS. The immunohistochemical expression pattern was scored according to the percentage of the stained cells (0, 1+, 2+, and 3+ when 0% to 5%, 6% to 25%, 26% to 50%, and more than 50% of the cells were stained, respectively) and was evaluated for each antibody. p16 was at least focally expressed (1+ or more) in 14 of 15 invasive adenocarcinomas, in all AIS and in 7 negative samples. ProEX C and Ki-67 both scored 1+ or more in all adenocarcinomas and AIS and in 8 and 6 negative samples, respectively. Of the GD 15, 14, and 15 expressed p16, ProEX C, and Ki-67, respectively. The score differences between neoplastic and non-neoplastic samples were highly significant for each marker (Pcervix uteri and may also improve the diagnostic accuracy of endocervical GD. In particularly problematic cases, the combination of p16 and a proliferation marker can provide additional help for the interpretation of these lesions.

  3. Experimental study of the $^{66}$Ni$(d,p)^{67}$Ni one-neutron transfer reaction

    CERN Document Server

    Diriken, J.; Andreyev, A.N.; Antalic, S.; Bildstein, V.; Blazhev, A.; Darby, I.G.; De Witte, H.; Eberth, J.; Elseviers, J.; Fedosseev, V.N.; Flavigny, F.; Fransen, Ch.; Georgiev, G.; Gernhauser, R.; Hess, H.; Huyse, M.; Jolie, J.; Kröll, Th.; Krücken, R.; Lutter, R.; Marsh, B.A.; Mertzimekis, T.; Muecher, D.; Orlandi, R.; Pakou, A.; Raabe, R.; Randisi, G.; Reiter, P.; Roger, T.; Seidlitz, M.; Seliverstov, M.; Sotty, C.; Tornqvist, H.; Van De Walle, J.; Van Duppen, P.; Voulot, D.; Warr, N.; Wenander, F.; Wimmer, K.

    2015-01-01

    The quasi-SU(3) sequence of the positive parity $νg_{9/2}, d_{5/2}, s_{1/2}$ orbitals above the N=40 shell gap are assumed to induce strong quadrupole collectivity in the neutron-rich Fe (Z=26) and Cr (Z=24) isotopes below the nickel region. In this paper the position and strength of these single-particle orbitals are characterized in the neighborhood of $^{68}$Ni (Z=28,N=40) through the $^{66}$Ni($d,p$)$^{67}$Ni one-neutron transfer reaction at 2.95 MeV/nucleon in inverse kinematics, performed at the REX-ISOLDE facility in CERN. A combination of the Miniball $\\gamma$-array and T-REX particle-detection setup was used and a delayed coincidence technique was employed to investigate the 13.3-$\\mu$s isomer at 1007 keV in $^{67}$Ni. Excited states up to an excitation energy of 5.8 MeV have been populated. Feeding of the $νg_{9/2}$ (1007 keV) and $νd_{5/2}$ (2207 keV and 3277 keV) positive-parity neutron states and negative parity ($νpf$) states have been observed at low excitation energy. The extracted relativ...

  4. Comet 67p/Churyumov-Gerasimenko, possible origin of the depression Hatmehit

    Science.gov (United States)

    Kossacki, Konrad J.; Czechowski, Leszek

    2018-05-01

    On the nucleus of comet 67P/Churyumov-Gerasimenko numerous pits and depressions of different sizes are identified. In the present work the origin of depression Hatmehit is investigated. We propose a mechanism that includes recession of the surface due to sub-dust sublimation together with formation of cavities. Recession of the surface is calculated taking into account the sub-dust sublimation of water ice with volatile organic components, formation of a strengthened ice-dust crust due to sintering of ice grains and the increase of the gas pressure in pores due to release of gaseous CO. Our simulations indicate, that the formation of a 300 m deep depression due to the sub-dust sublimation of ice can take as little as 50 orbital periods assuming that the heliocentric distance at perihelion is close to its present value (Ip. et al., 2016). When amorphous water ice is present at small depth the release of gaseous CO may cause either compression of low-strength material beneath the strengthened crust, or ejection of the crust. In both cases a cavity is formed and grows due to the sublimation of ice from the wall and the floor.

  5. Broadband permittivity measurements on porous planetary regoliths simulants, in relation with the Rosetta mission to 67P/C-G

    Science.gov (United States)

    Brouet, Yann; Levasseur-Regourd, Anny-Chantal; Encrenaz, Pierre; Sabouroux, Pierre; Heggy, Essam; Kofman, Wlodek; Thomas, Nick

    2015-04-01

    The Rosetta mission has successfully rendezvous comet 67P/Churyumov-Gerasimenko (hereafter 67P) last year and landed Philae module on its nucleus on 12 November it 2014. Among instruments onboard Rosetta, MIRO [1], composed of two radiometers, with receivers at 190 GHz and 563 GHz (center-band), is dedicated to the measurements of the subsurface and surface brightness temperatures. These values depend on the complex relative permittivity (hereafter permittivity) with ɛ' and ɛ'' the real and imaginary parts. The permittivity of the material depends on frequency, bulk density/porosity, composition and temperature [2]. Considering the very low bulk density of 67P nucleus (about 450 kg.m-3 [3]) and the suspected presence of a dust mantle in many areas of the nucleus [4], investigations on the permittivity of porous granular samples are needed to support the interpretation of MIRO data, as well as of other microwave experiments onboard Rosetta, e.g. CONSERT [5], a bistatic penetrating radar working at 90 MHz. We have developed a programme of permittivity measurements on porous granular samples over a frequency range from 50 MHz to 190 GHz under laboratory conditions (e.g. [6] and [7]). We present new results obtained on JSC-1A lunar soil simulant and ashes from Etna. The samples were split into several sub-samples with different size ranges covering a few to 500 μm. Bulk densities of the sub-samples were carefully measured and found to be in the 800-1400 kg.m-3 range. Sub-samples were also dried and volumetric moisture content was found to be below 0.6%. From 50 MHz to 6 GHz and at 190 GHz, the permittivity has been determined, respectively with a coaxial cell and with a quasi-optical bench mounted in transmission, both connected to a vector network analyzer. The results demonstrate the dispersive behaviours of ɛ' between 50 MHz and 190 GHz. Values of ɛ' remain within the 3.9-2.6 range for all sub-samples. At CONSERT frequency, ɛ'' is within the 0.01-0.09 range

  6. The effect of orexin-A on cardiac dysfunction mediated by NADPH oxidase-derived superoxide anion in ventrolateral medulla.

    Directory of Open Access Journals (Sweden)

    Jun Chen

    Full Text Available Hypocretin/orexin-producing neurons, located in the perifornical region of the lateral hypothalamus area (LHA and projecting to the brain sites of rostral ventrolateral medulla (RVLM, involve in the increase of sympathetic activity, thereby regulating cardiovascular function. The current study was designed to test the hypothesis that the central orexin-A (OXA could be involved in the cardiovascular dysfunction of acute myocardial infarction (AMI by releasing NAD(PH oxidase-derived superoxide anion (O2 (- generation in RVLM, AMI rat model established by ligating the left anterior descending (LAD coronary artery to induce manifestation of cardiac dysfunction, monitored by the indicators as heart rate (HR, heart rate variability (HRV, mean arterial pressure (MAP and left intraventricular pressure. The results showed that the expressions of OXA in LHA and orexin 1 receptor (OX1R increased in RVLM of AMI rats. The double immunofluorescent staining indicated that OX1R positive cells and NAD(PH oxidative subunit gp91phox or p47phox-immunoreactive (IR cells were co-localized in RVLM. Microinjection of OXA into the cerebral ventricle significantly increased O2 (- production and mRNA expression of NAD(PH oxidase subunits when compared with aCSF-treated ones. Exogenous OXA administration in RVLM produced pressor and tachycardiac effects. Furthermore, the antagonist of OX1R and OX2R (SB-408124 and TCS OX2 29, respectively or apocynin (APO, an inhibitor of NAD(PH oxidase, partly abolished those cardiovascular responses of OXA. HRV power spectral analysis showed that exogenous OXA led to decreased HF component of HRV and increased LF/HF ratio in comparison with aCSF, which suggested that OXA might be related to sympathovagal imbalance. As indicated by the results, OXA might participate in the central regulation of cardiovascular activities by disturbing the sympathovagal balance in AMI, which could be explained by the possibility that OXR and NAD(PH-derived O

  7. Nifedipine treatment reduces resting calcium concentration, oxidative and apoptotic gene expression, and improves muscle function in dystrophic mdx mice.

    Directory of Open Access Journals (Sweden)

    Francisco Altamirano

    Full Text Available Duchenne Muscular Dystrophy (DMD is a recessive X-linked genetic disease, caused by mutations in the gene encoding dystrophin. DMD is characterized in humans and in mdx mice by a severe and progressive destruction of muscle fibers, inflammation, oxidative/nitrosative stress, and cell death. In mdx muscle fibers, we have shown that basal ATP release is increased and that extracellular ATP stimulation is pro-apoptotic. In normal fibers, depolarization-induced ATP release is blocked by nifedipine, leading us to study the potential therapeutic effect of nifedipine in mdx muscles and its relation with extracellular ATP signaling. Acute exposure to nifedipine (10 µM decreased [Ca(2+]r, NF-κB activity and iNOS expression in mdx myotubes. In addition, 6-week-old mdx mice were treated with daily intraperitoneal injections of nifedipine, 1 mg/Kg for 1 week. This treatment lowered the [Ca(2+]r measured in vivo in the mdx vastus lateralis. We demonstrated that extracellular ATP levels were higher in adult mdx flexor digitorum brevis (FDB fibers and can be significantly reduced after 1 week of treatment with nifedipine. Interestingly, acute treatment of mdx FDB fibers with apyrase, an enzyme that completely degrades extracellular ATP to AMP, reduced [Ca(2+]r to a similar extent as was seen in FDB fibers after 1-week of nifedipine treatment. Moreover, we demonstrated that nifedipine treatment reduced mRNA levels of pro-oxidative/nitrosative (iNOS and gp91(phox/p47(phox NOX2 subunits and pro-apoptotic (Bax genes in mdx diaphragm muscles and lowered serum creatine kinase (CK levels. In addition, nifedipine treatment increased muscle strength assessed by the inverted grip-hanging test and exercise tolerance measured with forced swimming test in mdx mice. We hypothesize that nifedipine reduces basal ATP release, thereby decreasing purinergic receptor activation, which in turn reduces [Ca(2+]r in mdx skeletal muscle cells. The results in this work open new

  8. ER, PgR, Ki67, p27Kip1, and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab

    International Nuclear Information System (INIS)

    Kurozumi, Sasagu; Inoue, Kenichi; Takei, Hiroyuki; Matsumoto, Hiroshi; Kurosumi, Masafumi; Horiguchi, Jun; Takeyoshi, Izumi; Oyama, Tetsunari

    2015-01-01

    Neoadjuvant chemotherapy (NAC) with taxanes followed by fluorouracil, epirubicin, and cyclophosphamide (FEC), and concurrent trastuzumab is a potent regimen for HER2 over-expressing breast cancer. A high pathological complete response (pCR) rate has been achieved using this regimen; however, the predictive factors and prognostic effects of pCR currently remain unclear. In the present study, we determined whether pCR was related to histological grade (HG) and several biological factors including p27 Kip1 . We also assessed the prognosis of the pCR and non-pCR groups, and expected differences between those positive and negative for lymph node metastasis after chemotherapy. A total of 129 Japanese women with HER2-positive invasive breast cancer received either paclitaxel or docetaxel followed by FEC, with the concomitant administration of trastuzumab. The statuses of HG, ER, PgR, Ki67, and p27 Kip1 were evaluated to determine their relationship with pCR. Relapse-free survival (RFS) and overall survival (OS) were also analyzed for their relationship with pCR and pathological nodal involvement. pCR was obtained in 84 out of 129 patients and the pCR rate was 65.1 %. The pCR rates related to 5 factors were as follows: HG (grade 3, 70.0 % vs. grades 1–2, 36.8 %), ER (negative, 78.6 % vs. positive, 40.0 %), PgR (negative, 75.3 % vs. positive, 38.9 %), Ki67 (high, 72.0 % vs. low, 47.2 %), and p27 Kip1 (low, 71.0 % vs. high, 50.0 %). RFS was significantly better in the pCR group than in the non-pCR group (p = 0.018). Patients with remaining nodal disease in the pCR group had worse OS (p = 0.0002). High-HG, low-ER, low-PgR, high-Ki67, and low-p27 Kip1 were identified as predictive factors of pCR in NAC with trastuzumab, while pCR and negative nodes were predictive of better survivals. The online version of this article (doi:10.1186/s12885-015-1641-y) contains supplementary material, which is available to authorized users

  9. Defect States in InP/InGaAs/InP Heterostructures by Current-Voltage Characteristics and Deep Level Transient Spectroscopy.

    Science.gov (United States)

    Vu, Thi Kim Oanh; Lee, Kyoung Su; Lee, Sang Jun; Kim, Eun Kyu

    2018-09-01

    We studied defect states in In0.53Ga0.47As/InP heterojunctions with interface control by group V atoms during metalorganic chemical vapor (MOCVD) deposition. From deep level transient spectroscopy (DLTS) measurements, two defects with activation energies of 0.28 eV (E1) and 0.15 eV (E2) below the conduction band edge, were observed. The defect density of E1 for In0.53Ga0.47As/InP heterojunctions with an addition of As and P atoms was about 1.5 times higher than that of the heterojunction added P atom only. From the temperature dependence of current- voltage characteristics, the thermal activation energies of In0.53Ga0.47As/InP of heterojunctions were estimated to be 0.27 and 0.25 eV, respectively. It appeared that the reverse light current for In0.53Ga0.47As/InP heterojunction added P atom increased only by illumination of a 940 nm-LED light source. These results imply that only the P addition at the interface can enhance the quality of InGaAs/InP heterojunction.

  10. The effect of pH on the uptake and toxicity of the bivalent weak base chloroquine tested on Salix viminalis and Daphnia magna

    DEFF Research Database (Denmark)

    Rendal, Cecilie; Kusk, Kresten Ole; Trapp, Stefan

    2011-01-01

    , and therefore a higher toxicity can be expected. The current study examines the pHdependent toxicity and bioaccumulation of the bivalent weak base chloroquine (pKa: 10.47 and 6.33, log KOW 4.67) tested on Salix viminalis (basket willow) and Daphnia magna (water flea). The transpiration rates of hydroponically...

  11. Epithelial Label-Retaining Cells Are Absent during Tooth Cycling in Salmo salar and Polypterus senegalus.

    Directory of Open Access Journals (Sweden)

    Sam Vandenplas

    Full Text Available The Atlantic salmon (Salmo salar and African bichir (Polypterus senegalus are both actinopterygian fish species that continuously replace their teeth without the involvement of a successional dental lamina. Instead, they share the presence of a middle dental epithelium: an epithelial tier enclosed by inner and outer dental epithelium. It has been hypothesized that this tier could functionally substitute for a successional dental lamina and might be a potential niche to house epithelial stem cells involved in tooth cycling. Therefore, in this study we performed a BrdU pulse chase experiment on both species to (1 determine the localization and extent of proliferating cells in the dental epithelial layers, (2 describe cell dynamics and (3 investigate if label-retaining cells are present, suggestive for the putative presence of stem cells. Cells proliferate in the middle dental epithelium, outer dental epithelium and cervical loop at the lingual side of the dental organ to form a new tooth germ. Using long chase times, both in S. salar (eight weeks and P. senegalus (eight weeks and twelve weeks, we could not reveal the presence of label-retaining cells in the dental organ. Immunostaining of P. senegalus dental organs for the transcription factor Sox2, often used as a stem cell marker, labelled cells in the zone of outer dental epithelium which grades into the oral epithelium (ODE transition zone and the inner dental epithelium of a successor only. The location of Sox2 distribution does not provide evidence for epithelial stem cells in the dental organ and, more specifically, in the middle dental epithelium. Comparison of S. salar and P. senegalus reveals shared traits in tooth cycling and thus advances our understanding of the developmental mechanism that ensures lifelong replacement.

  12. Study of the coma of comet 67P/Churyumov-Gerasimenko based on the ROSINA/RTOF instrument onboard Rosetta

    Science.gov (United States)

    Hoang, M.; Garnier, P.; Lasue, J.; Reme, H.; Altwegg, K.; Balsiger, H. R.; Bieler, A. M.; Calmonte, U.; Fiethe, B.; Galli, A.; Gasc, S.; Gombosi, T. I.; Jäckel, A.; Mall, U.; Le Roy, L.; Rubin, M.; Tzou, C. Y.; Waite, J. H., Jr.; Wurz, P.

    2015-12-01

    The ROSETTA spacecraft of ESA is in the environment of comet 67P/Churyumov-Gerasimenko since August 2014. Among the experiments onboard the spacecraft, the ROSINA experiment (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) includes two mass spectrometers (DFMS and RTOF) to analyze the composition of neutrals and ions, and a pressure sensor (COPS) to monitor the density and velocity of neutrals in the coma [1]. We will here analyze and discuss the data of the ROSINA/RTOF instrument during the comet escort phase. The Reflectron-type Time-Of-Flight (RTOF) mass spectrometer possesses a wide mass range and a high temporal resolution [1,2]. It was designed to measure cometary neutral gas as well as cometary ions. A detailed description of the main volatiles (H2O, CO2, CO) dynamics and of the heterogeneities of the coma will then be provided. The influence of various parameters on the coma measurements is investigated on a statistical basis, with the parameters being distance to the comet, heliocentric distance, longitude and latitude of nadir point. Our analysis of the northern hemisphere summer season shows the presence of water vapor mostly in the illuminated northern hemisphere near the neck region with cyclic diurnal variations whereas CO2 was confined to the cold southern hemisphere with a more spatially homogeneous composition, in agreement with previous observations of 67P [2] or Hartley 2 [3]. A comparison will also be provided with the COPS total density and DFMS abundance measurements. [1] Balsiger et al., "ROSINA - Rosetta Orbiter Spectrometer for Ion and Neutral Analysis", Space Sci. Rev., 2007. [2] Scherer et al., "A novel principle for an ion mirror design in time-of-flight mass spectrometry," Int. Jou. Mass Spectr., 2006. [3] Hässig et al., "Time variability and heterogeneity in the coma of 67P/Churyumov-Gerasimenko", Science, 2015. [4] A'Hearn et al., "EPOXI at comet Hartley 2", Science, 2011.

  13. Thermal fracturing on comets. Applications to 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Attree, N.; Groussin, O.; Jorda, L.; Rodionov, S.; Auger, A.-T.; Thomas, N.; Brouet, Y.; Poch, O.; Kührt, E.; Knapmeyer, M.; Preusker, F.; Scholten, F.; Knollenberg, J.; Hviid, S.; Hartogh, P.

    2018-03-01

    We simulate the stresses induced by temperature changes in a putative hard layer near the surface of comet 67P/Churyumov-Gerasimenko with a thermo-viscoelastic model. Such a layer could be formed by the recondensation or sintering of water ice (and dust grains), as suggested by laboratory experiments and computer simulations, and would explain the high compressive strength encountered by experiments on board the Philae lander. Changes in temperature from seasonal insolation variation penetrate into the comet's surface to depths controlled by the thermal inertia, causing the material to expand and contract. Modelling this with a Maxwellian viscoelastic response on a spherical nucleus, we show that a hard, icy layer with similar properties to Martian permafrost will experience high stresses: up to tens of MPa, which exceed its material strength (a few MPa), down to depths of centimetres to a metre. The stress distribution with latitude is confirmed qualitatively when taking into account the comet's complex shape but neglecting thermal inertia. Stress is found to be comparable to the material strength everywhere for sufficient thermal inertia (≳50 J m-2 K-1 s-1/2) and ice content (≳45% at the equator). In this case, stresses penetrate to a typical depth of 0.25 m, consistent with the detection of metre-scale thermal contraction crack polygons all over the comet. Thermal fracturing may be an important erosion process on cometary surfaces which breaks down material and weakens cliffs.

  14. Progress of the correlation study between mammographic appearances and expression of p53, Ki-67 in patients with breast cancer

    International Nuclear Information System (INIS)

    Liu Jie; Liu Peifang

    2013-01-01

    Breast cancer is one of the most common female malignant tumors. The occurrence and development of breast cancer are often accompanied by abnormal gene expression. It has been well accepted that p53, Ki -67 are the commonly used biological indicators for clinical endocrine therapy and prognosis prediction. The oncogene expression reflects the malignant biological behavior of breast cancer from different perspectives. Those aggressive behaviors cause a variety of changes in histopathology and thus in imaging. Therefore, the imaging features of breast cancer may indirectly demonstrate the status of p53, Ki-67. Until now, because of its facility, low cost and high accuracy, mammography is still the preferred method in breast cancer screening and diagnosis. The relationship of mammographic appearances and gene expression in patients with breast cancer has potential clinical value in preoperative evaluation and planning of non-surgical treatment for those who are not able to perform immunohistochemistry. (authors)

  15. Excitation function of (p,α) nuclear reaction on enriched {sup 67}Zn. Possibility of production of {sup 64}Cu at low energy cyclotron

    Energy Technology Data Exchange (ETDEWEB)

    Szelecsenyi, Ferenc; Kovacs, Zoltan [Hungarian Academy of Sciences, Debrecen (Hungary). Cyclotron Application Dept.; Nagatsu, Kotaro; Zhang, Ming-Rong; Suzuki, Kazutosi [National Institute of Radiological Sciences, Chiba (Japan). Molecular Imaging Center

    2014-09-01

    The potential for production of the medically relevant {sup 64}Cu has been investigated by proton irradiation of highly enriched {sup 67}Zn targets. The excitation function of the {sup 67}Zn(p,α){sup 64}Cu a nuclear reaction was measured by the stacked-foil technique up to 30 MeV. The prediction of the TALYS code was also compared to the measured cross section results. Based on the improved database of the {sup 67}Zn(p,α){sup 64}Cu reaction, thick target yield as a function of energy was also deduced. Production possibility of {sup 64}Cu is discussed in detail, employing different energy proton beams and with regards to the {sup 61}Cu and {sup 67}Cu contamination levels as a function of the target enrichment level. By using 1 μA beam intensity, 6.3505 h irradiation time and enriched {sup 67}Zn target ({sup 64}Zn ≤ 0.5%, {sup 66}Zn ≤ 9%, {sup 67}Zn ≥ 80%, {sup 68}Zn ≤ 10% and {sup 70}Zn ≤ 0.5%), the expected EOB (End Of bombardment) yields are 43.66, 88.80 and 156.14MBq/μA at 12, 15 and 18 MeV proton energies, respectively. Application time-frames were also deduced where the total radio-copper contamination level remains below 1%. (orig.)

  16. p16(INK4a) /Ki-67 dual labelling as a marker for the presence of high-grade cancer cells or disease progression in urinary cytopathology.

    Science.gov (United States)

    Piaton, E; Advenier, A S; Carré, C; Decaussin-Petrucci, M; Mege-Lechevallier, F; Ruffion, A

    2013-10-01

    Overexpression of p16(INK4a) independent of the presence of E6-E7 oncoproteins of high-risk papillomaviruses has been identified in bladder carcinoma in situ lesions with or without concurrent papillary or invasive high-grade (HG) urothelial carcinoma. As p16(INK4a) and Ki-67 co-expression clearly indicates deregulation of the cell cycle, the aim of this study was to investigate the frequency of p16(INK4a) /Ki-67 dual labelling in urinary cytology samples. Immunolabelling was performed in demounted, destained Papanicolaou slides after ThinPrep(®) processing. A total of 84 urinary cytology samples (18 negative, 10 low grade, 19 atypical urothelial cells and 37 high grade) were analysed for p16(INK4a) /Ki-67 co-expression. We assessed underlying urothelial malignancy with cystoscopy, histopathology and follow-up data in every case. Compared with raw histopathological results, p16 (INK4a) /Ki-67 dual labelling was observed in 48 out of 55 (87.3%) HG lesions and in 11 out of 29 (37.9%) negative, papillary urothelial neoplasia of low malignant potential or low-grade carcinomas (P = 0.05). All cases with high-grade/malignant cytology were dual labelled. Sixteen out of 17 (94.1%) carcinoma in situ cases and eight out of 14 (57.1%) cases with atypical urothelial cells matching with HG lesions were dual labelled. Extended follow-up allowed three cases of progression to be diagnosed in dual-labelled cases with negative/low-grade cytology results after a 9- to 11-months delay. The data show that p16(INK4a) /Ki-67 co-expression allows most HG cancer cells to be detected initially and in the follow-up period. Additional studies are needed in order to determine whether dual labelling can be used as a triage tool for atypical urothelial cells in the urine. © 2012 John Wiley & Sons Ltd.

  17. Single-cell Raman and fluorescence microscopy reveal the association of lipid bodies with phagosomes in leukocytes

    Science.gov (United States)

    van Manen, Henk-Jan; Kraan, Yvonne M.; Roos, Dirk; Otto, Cees

    2005-01-01

    Cellular imaging techniques based on vibrational spectroscopy have become powerful tools in cell biology because the molecular composition of subcellular compartments can be visualized without the need for labeling. Using high-resolution, nonresonant confocal Raman microscopy on individual cells, we demonstrate here that lipid bodies (LBs) rich in arachidonate as revealed by their Raman spectra associate with latex bead-containing phagosomes in neutrophilic granulocytes. This finding was corroborated in macrophages and in PLB-985 cells, which can be induced to differentiate into neutrophil-like cells, by selective staining of LBs and visualization by confocal fluorescence microscopy. We further show that the accumulation of LBs near phagosomes is mediated at least in part by the flavohemoprotein gp91phox (in which “phox” is phagocyte oxidase), because different LB distributions around phagocytosed latex beads were observed in WT and gp91phox-deficient PLB-985 cells. gp91phox, which accumulates in the phagosomal membrane, is the catalytic subunit of the leukocyte NADPH oxidase, a critical enzyme in the innate immune response. Finally, time-lapse fluorescence microscopy experiments on neutrophils revealed that the LB-phagosome association is transient, similar to the “kiss-and-run” behavior displayed by endosomes involved in phagosome maturation. Because arachidonic acid (AA) has been shown to be involved in NADPH oxidase activation and phagosome maturation in neutrophils and macrophages, respectively, the findings reported here suggest that LBs may provide a reservoir of AA for local activation of these essential leukocyte functions. PMID:16002471

  18. Comet 67P/Churyumov-Gerasimenko Surface Composition as a Playground for Radiative Transfer Modeling and Laboratory Measurements: an international ISSI team

    Science.gov (United States)

    Stephan, K.; Ciarniello, M.; Beck, P.; Filacchione, G.; Moroz, L.; Pilorget, C.; Pommerol, A.; Quirico, E.; Raponi, A.; Schröder, S.; Kappel, D.; Vinogradoff, V.; Istiqomah, I.; Rousseau, B.

    2017-12-01

    Remote sensing observations at visible-infrared (VIS-IR) wavelengths of the nucleus of comet 67P/Churyumov-Gerasimenko performed by VIRTIS (Coradini et al., 2007) aboard the Rosetta mission have revealed a surface ubiquitously covered by low-albedo material (Capaccioni et al., 2015; Ciarniello et al., 2015), characterized by the presence of refractory and semi-volatile organics and dark opaque phases (Capaccioni et al., 2015; Quirico et al., 2016). However, a quantitative determination of the physical properties (grain size, porosity) and chemical composition of the surface regolith, from spectrophotometric analysis, is still missing. This subject will be investigated within an international team hosted by ISSI (International Space Science Institute), taking advantage of available and dedicated laboratory reflectance measurements on cometary analogue samples and radiative transfer models (Hapke, 2012; Shkuratov et al., 1999; Monte Carlo ray-tracing), applied to Rosetta spectrophotometric observations of the nucleus. The convergence between models and measurements will allow us to provide a thorough characterization of 67P/Churyumov-Gerasimenko surface. At the same time, the comparison of theoretical predictions with results from laboratory reflectance spectroscopy on powders of analog materials give us the possibility to constrain the capability of the models to characterize their composition (endmember abundances and mixing modalities) and physical properties. We report about the state of the art of laboratory reflectance spectroscopy and spectral modeling applied to 67P/Churyumov-Gerasimenko VIS-IR spectrum as well as preliminary results of the team activity and planned future work. Acknowledgements: the team thanks ISSI-Switzerland for the logistic and financial support.

  19. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  20. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  1. Inhibition of WNT signaling reduces differentiation and induces sensitivity to doxorubicin in human malignant neuroblastoma SH-SY5Y cells.

    Science.gov (United States)

    Suebsoonthron, Junjira; Jaroonwitchawan, Thiranut; Yamabhai, Montarop; Noisa, Parinya

    2017-06-01

    Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme. XAV939 treatment led to the reduction of β-catenin within the cells, confirming its inhibitory effect of WNT. The inhibition of WNT signaling by XAV939 did not affect cell morphology, survival, and proliferation; however, the differentiation and sensitivity to anticancer drugs of human neuroblastoma cells were altered. The treatment of XAV939 resulted in the downregulation of mature neuronal markers, including β-tubulin III, PHOX2A, and PHOX2B, whereas neural progenitor markers (PAX6, TFAP2α, and SLUG) were upregulated. In addition, the combination of XAV939 significantly enhanced the sensitivity of SH-SY5Y and IMR-32 cells to doxorubicin in both 2D and 3D culture systems. Microarray gene expression profiling suggested numbers of candidate target genes of WNT inhibition by XAV939, in particular, p21, p53, ubiquitin C, ZBED8, MDM2, CASP3, and FZD1, and this explained the enhanced sensitivity of SH-SY5Y cells to doxorubicin. Altogether, these results proposed that the altered differentiation of human malignant neuroblastoma cells by inhibiting WNT signaling sensitized the cells to anticancer drugs. This approach could thus serve as an effective treatment option for aggressive brain malignancy.

  2. Prevention of age-related endothelial dysfunction by habitual aerobic exercise in healthy humans: possible role of nuclear factor κB.

    Science.gov (United States)

    Walker, Ashley E; Kaplon, Rachelle E; Pierce, Gary L; Nowlan, Molly J; Seals, Douglas R

    2014-12-01

    Habitual aerobic exercise prevents age-related impairments in endothelium-dependent dilation (EDD). We have hypothesized that the pro-inflammatory transcription factor nuclear factor κB (NF-κB) impairs EDD with sedentary aging, and habitual aerobic exercise prevents this age-related suppression of EDD by NF-κB. To test this hypothesis, we have inhibited NF-κB signalling via oral salsalate administration in healthy older aerobic exercise-trained adults (OT, n=14, 58 ± 2 years), older non-exercising adults (ON, n=16, 61 ± 1 years) and young non-exercising controls (YN, n=8, 23 ± 1 years). Salsalate reduced endothelial cell expression of NF-κB p65 by ~25% in ON (P0.05). EDD, assessed by brachial artery flow-mediated dilation (FMD), was improved by salsalate in ON (4.0 ± 0.7% compared with 6.8 ± 0.7%, placebo compared with salsalate, P0.05). Endothelium-independent dilation was not affected by salsalate in any group (P>0.05). In ON, vitamin C infusion improved FMD by ~30% during placebo (P0.05). In OT and YN, vitamin C infusion did not affect FMD during either placebo or salsalate (P>0.05). Salsalate reduced endothelial cell nitrotyrosine content by ~25% and NADPH oxidase p47phox expression by ~30% in ON (P0.05). Our results suggest that endothelial NF-κB signalling is associated with oxidative stress-related impairment of EDD in healthy non-exercising but not aerobically exercising older adults. This may be a key mechanism by which regular aerobic exercise preserves endothelial function and reduces cardiovascular risk with aging.

  3. Cometary science. Time variability and heterogeneity in the coma of 67P/Churyumov-Gerasimenko.

    Science.gov (United States)

    Hässig, M; Altwegg, K; Balsiger, H; Bar-Nun, A; Berthelier, J J; Bieler, A; Bochsler, P; Briois, C; Calmonte, U; Combi, M; De Keyser, J; Eberhardt, P; Fiethe, B; Fuselier, S A; Galand, M; Gasc, S; Gombosi, T I; Hansen, K C; Jäckel, A; Keller, H U; Kopp, E; Korth, A; Kührt, E; Le Roy, L; Mall, U; Marty, B; Mousis, O; Neefs, E; Owen, T; Rème, H; Rubin, M; Sémon, T; Tornow, C; Tzou, C-Y; Waite, J H; Wurz, P

    2015-01-23

    Comets contain the best-preserved material from the beginning of our planetary system. Their nuclei and comae composition reveal clues about physical and chemical conditions during the early solar system when comets formed. ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) onboard the Rosetta spacecraft has measured the coma composition of comet 67P/Churyumov-Gerasimenko with well-sampled time resolution per rotation. Measurements were made over many comet rotation periods and a wide range of latitudes. These measurements show large fluctuations in composition in a heterogeneous coma that has diurnal and possibly seasonal variations in the major outgassing species: water, carbon monoxide, and carbon dioxide. These results indicate a complex coma-nucleus relationship where seasonal variations may be driven by temperature differences just below the comet surface. Copyright © 2015, American Association for the Advancement of Science.

  4. Plasminogen activator inhibitor-2 polymorphism associates with recurrent coronary event risk in patients with high HDL and C-reactive protein levels.

    Directory of Open Access Journals (Sweden)

    James P Corsetti

    Full Text Available The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C and C-reactive protein (CRP and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2 were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1, a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095 and LRP-1 (LRP1, rs1800156 as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272, p22phox (CYBA, rs4673, and thrombospondin-4 (THBS4, rs1866389. Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014 along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked

  5. Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Cass, Jamaica D. [Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston K7L 3N6 (Canada); Varma, Sonal [Department of Pathology and Molecular Medicine, Queen’s University, Kingston K7L 3N6 (Canada); Day, Andrew G. [Kingston General Hospital, Kingston K7L 2V7 (Canada); Sangrar, Waheed [Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston K7L 3N6 (Canada); Rajput, Ashish B. [Department of Pathology and Molecular Medicine, Queen’s University, Kingston K7L 3N6 (Canada); Raptis, Leda H.; Squire, Jeremy [Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston K7L 3N6 (Canada); Madarnas, Yolanda [Department of Oncology, Queen’s University, Kingston K7L 3N6 (Canada); SenGupta, Sandip K. [Department of Pathology and Molecular Medicine, Queen’s University, Kingston K7L 3N6 (Canada); Elliott, Bruce E., E-mail: elliottb@queensu.ca [Division of Cancer Biology and Genetics, Cancer Research Institute, Queen’s University, Kingston K7L 3N6 (Canada); Department of Pathology and Molecular Medicine, Queen’s University, Kingston K7L 3N6 (Canada)

    2012-07-18

    There is critical need for improved biomarker assessment platforms which integrate traditional pathological parameters (TNM stage, grade and ER/PR/HER2 status) with molecular profiling, to better define prognostic subgroups or systemic treatment response. One roadblock is the lack of semi-quantitative methods which reliably measure biomarker expression. Our study assesses reliability of automated immunohistochemistry (IHC) scoring compared to manual scoring of five selected biomarkers in a tissue microarray (TMA) of 63 human breast cancer cases, and correlates these markers with clinico-pathological data. TMA slides were scanned into an Ariol Imaging System, and histologic (H) scores (% positive tumor area x staining intensity 0–3) were calculated using trained algorithms. H scores for all five biomarkers concurred with pathologists’ scores, based on Pearson correlation coefficients (0.80–0.90) for continuous data and Kappa statistics (0.55–0.92) for positive vs. negative stain. Using continuous data, significant association of pERK expression with absence of LVI (p = 0.005) and lymph node negativity (p = 0.002) was observed. p53 over-expression, characteristic of dysfunctional p53 in cancer, and Ki67 were associated with high grade (p = 0.032 and 0.0007, respectively). Cyclin D1 correlated inversely with ER/PR/HER2-ve (triple negative) tumors (p = 0.0002). Thus automated quantitation of immunostaining concurs with pathologists’ scoring, and provides meaningful associations with clinico-pathological data.

  6. Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics

    International Nuclear Information System (INIS)

    Cass, Jamaica D.; Varma, Sonal; Day, Andrew G.; Sangrar, Waheed; Rajput, Ashish B.; Raptis, Leda H.; Squire, Jeremy; Madarnas, Yolanda; SenGupta, Sandip K.; Elliott, Bruce E.

    2012-01-01

    There is critical need for improved biomarker assessment platforms which integrate traditional pathological parameters (TNM stage, grade and ER/PR/HER2 status) with molecular profiling, to better define prognostic subgroups or systemic treatment response. One roadblock is the lack of semi-quantitative methods which reliably measure biomarker expression. Our study assesses reliability of automated immunohistochemistry (IHC) scoring compared to manual scoring of five selected biomarkers in a tissue microarray (TMA) of 63 human breast cancer cases, and correlates these markers with clinico-pathological data. TMA slides were scanned into an Ariol Imaging System, and histologic (H) scores (% positive tumor area x staining intensity 0–3) were calculated using trained algorithms. H scores for all five biomarkers concurred with pathologists’ scores, based on Pearson correlation coefficients (0.80–0.90) for continuous data and Kappa statistics (0.55–0.92) for positive vs. negative stain. Using continuous data, significant association of pERK expression with absence of LVI (p = 0.005) and lymph node negativity (p = 0.002) was observed. p53 over-expression, characteristic of dysfunctional p53 in cancer, and Ki67 were associated with high grade (p = 0.032 and 0.0007, respectively). Cyclin D1 correlated inversely with ER/PR/HER2-ve (triple negative) tumors (p = 0.0002). Thus automated quantitation of immunostaining concurs with pathologists’ scoring, and provides meaningful associations with clinico-pathological data

  7. Protection against Ischemia-Induced Oxidative Stress Conferred by Vagal Stimulation in the Rat Heart: Involvement of the AMPK-PKC Pathway

    Directory of Open Access Journals (Sweden)

    Wei-Jin Zang

    2012-11-01

    Full Text Available Reactive oxygen species (ROS production is an important mechanism in myocardial ischemia and nicotinamide adenine dinucleotide phosphate (NADPH oxidase is one of major sources of ROS in the heart. Previous studies showed that vagus nerve stimulation (VNS is beneficial in treating ischemic heart diseases. However, the effect of VNS on ROS production remains elusive. In this study, we investigated the role of VNS onischemia-induced ROS production. Our results demonstrated that VNS alleviated the myocardial injury, attenuated the cardiac dysfunction, reserved the antioxidant enzyme activity and inhibited the formation of ROS as evidenced by the decreased NADPH oxidase (Nox activity and superoxide fluorescence intensity as well as the expression of p67phox, Rac1 and nitrotyrosine. Furthermore, VNS resulted in the phosphorylation and activation of adenosine monophosphate activated protein kinase (AMPK, which in turn led to an inactivation of Nox by protein kinase C (PKC; however, the phenomena were repressed by the administration of a muscarinic antagonist atropine. Taken together, these data indicate that VNS decreases ROS via AMPK-PKC-Nox pathway; this may have potential importance for the treatment of ischemic heart diseases.

  8. EXAFS study of Mn{sub 1.28}Fe{sub 0.67}P{sub 0.46}Si{sub 0.54} compound with first-order phase transition

    Energy Technology Data Exchange (ETDEWEB)

    L, Yingjie; Huliyageqi, B; Haschaolu, W; Song, Zhiqiang [Inner Mongolia Key Laboratory for Physics and Chemistry of Functional Materials, Physics and Electronic Information College, Inner Mongolia Normal University, Hohhot 010022 (China); Tegus, O, E-mail: tegusph@imnu.edu.cn [Inner Mongolia Key Laboratory for Physics and Chemistry of Functional Materials, Physics and Electronic Information College, Inner Mongolia Normal University, Hohhot 010022 (China); Nakai, Ikuo [Department of Electrical and Electronic Engineering, Tottori University, Tottori 680-8552 (Japan)

    2014-10-15

    Highlights: • We have investigated the Fe and Mn K edge XAFS spectra of the Mn{sub 1.28}Fe{sub 0.67}P{sub 0.46}Si{sub 0.54} compound at 25 K and 295 K. • The site occupation of the Fe and Mn atoms and local structure of Mn{sub 1.28}Fe{sub 0.67}P{sub 0.46}Si{sub 0.54} are determined. • The atomic distances between Fe–Fe in c-plane for the ferromagnetic state are larger than those in the paramagnetic state. - Abstract: The Fe{sub 2}P-type MnFe(P,Si) compounds are investigated by means of magnetic measurements and X-ray absorption fine structure spectroscopy. Magnetic measurements show that the Mn{sub 1.28}Fe{sub 0.67}P{sub 0.46}Si{sub 0.54} compound undergoes a first-order phase transition at the Curie temperature of 254 K. The Fe K-edge and Mn K-edge X-ray absorption fine structure spectra show that Mn atom mainly located at the 3g sites, while the 3f sites are occupied by Fe atoms and Mn atom randomly. The distances between the Fe atom and its nearest neighbor atoms in a triangle Fe–Mn–Fe change from 2.80 Å at 25 K to 2.74 Å at 300 K. On the other hand, the distances between Fe atom and its second neighbor atoms change from 4.06 Å at 25 K to 4.02 Å at 300 K.

  9. Investigating the correlations between water coma emissions and active regions in comet 67P/ Churyumov-Gerasimenko

    Science.gov (United States)

    Migliorini, Alessandra; Filacchione, Gianrico; Capaccioni, Fabrizio; Piccioni, Giuseppe; Bockelee-Morvan, Dominique; Érard, Stéphane; Leyrat, Cedric; Combi, Michael R.; Fougere, Nicolas; Rinaldi, Giovanna; VIRTIS Team

    2016-10-01

    Vibrational emission lines of H2O and CO2 at 2.67 and 4.27 μm, respectively, were identified by the VIRTIS spectrometer (Bockelée-Morvan et al., 2015; Migliorini et al., 2016; Fink et al., 2016) and mapped from the surface up to about 10 km altitude with a spatial resolution on the order of tens of meters per pixel (Migliorini et al., 2016).Data acquired in April 2015 with the VIRTIS spectrometer on board the Rosetta mission, provided information on the possible correlation between the H2O emission in the inner coma and the exposed water deposits detected in the Hapi region on the 67P/Churyumov-Gerasimenko surface (Migliorini et al., 2106; De Sanctis et al., 2015). Further bright spots attributed to exposed water ice have been identified in other regions by OSIRIS at visible wavelengths (Pommerol, et al., 2015) and confirmed in the infrared by VIRTIS-M in the Imothep region (Filacchione et al., 2016). The small dimensions of these icy spots - approximately 100x100 m (Filacchione et al., 2016) - and the relatively small amount of water ice (about 5%) make uncertain the correlation with the strong emissions in the coma.However, VIRTIS data show that the distribution of jet-like emissions seems to follow the distribution of cliffs and exposed areas identified in the North hemisphere with OSIRIS camera (Vincent et al., 2015). These areas are mainly concentrated in correspondence of comet's rough terrains, while a lack of active regions is observed in the comet's neck. Nevertheless, strong H2O emission is observed above the neck with VIRTIS. This might be a consequence of gas jets that are originated in the surrounding of the neck but converging towards the neck itself. This gaseous activity is the main driver of the dust upwelling (Migliorini et al, 2016; Rinaldi et al., in preparation)In this paper, we investigate the relationship between H2O vapour observed with VIRTIS within 5 km from the 67P/C-G nucleus and the exposed regions identified by OSIRIS on the surface

  10. Insight into molecular interactions between two PB1 domains

    NARCIS (Netherlands)

    van Drogen-Petit, A.; Zwahlen, C.; Peter, M.; Bonvin, A.M.J.J.

    2004-01-01

    Specific protein–protein interactions play crucial roles in the regulation of any biological process. Recently, a new protein–protein interaction domain termed PB1 (Phox and Bem1) was identified, which is conserved throughout evolution and present in diverse proteins functioning in signal

  11. Inclusive π+d →pp ) process and the η N scattering length

    Science.gov (United States)

    Garcilazo, Humberto

    2018-02-01

    The cross section of the inclusive process π+d →pp ) is calculated as a function of the η p invariant mass when the detected proton is moving in the forward direction. The incident pion has a momentum of plab=898.47 MeV/c for which the η p pair are left at rest in the laboratory system which allows one to study the effect of the η p →η p final-state interaction in the region of the N (1535 ) S11 resonance. The sensitivity of the inclusive cross section to different parametrizations of the η N final-state interaction is discussed.

  12. Dust mass distribution around comet 67P/Churyumov-Gerasimenko determined via parallax measurements using Rosetta's OSIRIS cameras

    Science.gov (United States)

    Ott, T.; Drolshagen, E.; Koschny, D.; Güttler, C.; Tubiana, C.; Frattin, E.; Agarwal, J.; Sierks, H.; Bertini, I.; Barbieri, C.; Lamy, P. I.; Rodrigo, R.; Rickman, H.; A'Hearn, M. F.; Barucci, M. A.; Bertaux, J.-L.; Boudreault, S.; Cremonese, G.; Da Deppo, V.; Davidsson, B.; Debei, S.; De Cecco, M.; Deller, J.; Feller, C.; Fornasier, S.; Fulle, M.; Geiger, B.; Gicquel, A.; Groussin, O.; Gutiérrez, P. J.; Hofmann, M.; Hviid, S. F.; Ip, W.-H.; Jorda, L.; Keller, H. U.; Knollenberg, J.; Kovacs, G.; Kramm, J. R.; Kührt, E.; Küppers, M.; Lara, L. M.; Lazzarin, M.; Lin, Z.-Y.; López-Moreno, J. J.; Marzari, F.; Mottola, S.; Naletto, G.; Oklay, N.; Pajola, M.; Shi, X.; Thomas, N.; Vincent, J.-B.; Poppe, B.

    2017-07-01

    The OSIRIS (optical, spectroscopic and infrared remote imaging system) instrument on board the ESA Rosetta spacecraft collected data of 67P/Churyumov-Gerasimenko for over 2 yr. OSIRIS consists of two cameras, a Narrow Angle Camera and a Wide Angle Camera. For specific imaging sequences related to the observation of dust aggregates in 67P's coma, the two cameras were operating simultaneously. The two cameras are mounted 0.7 m apart from each other, as a result this baseline yields a parallax shift of the apparent particle trails on the analysed images directly proportional to their distance. Thanks to such shifts, the distance between observed dust aggregates and the spacecraft was determined. This method works for particles closer than 6000 m to the spacecraft and requires very few assumptions. We found over 250 particles in a suitable distance range with sizes of some centimetres, masses in the range of 10-6-102 kg and a mean velocity of about 2.4 m s-1 relative to the nucleus. Furthermore, the spectral slope was analysed showing a decrease in the median spectral slope of the particles with time. The further a particle is from the spacecraft the fainter is its signal. For this reason, this was counterbalanced by a debiasing. Moreover, the dust mass-loss rate of the nucleus could be computed as well as the Afρ of the comet around perihelion. The summed-up dust mass-loss rate for the mass bins 10-4-102 kg is almost 8300 kg s-1.

  13. p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women.

    Science.gov (United States)

    Wentzensen, Nicolas; Fetterman, Barbara; Castle, Philip E; Schiffman, Mark; Wood, Shannon N; Stiemerling, Eric; Tokugawa, Diane; Bodelon, Clara; Poitras, Nancy; Lorey, Thomas; Kinney, Walter

    2015-12-01

    Human papillomavirus (HPV)-based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women. One thousand five hundred and nine HPV-positive women screened with HPV/cytology cotesting at Kaiser Permanente California were enrolled into a prospective observational study in 2012. Dual stain cytology was performed on residual Surepath material, and slides were evaluated for dual stain-positive cells. Disease endpoints were ascertained from the clinical database at KPNC. We evaluated the clinical performance of the assay among all HPV-positive women and among HPV-positive, cytology-negative women. We used internal benchmarks for clinical management to evaluate the clinical relevance of the dual stain assay. We evaluated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the dual stain compared with Pap cytology. All statistical tests were two-sided. The dual stain had lower positivity (45.9%) compared with cytology at an ASC-US threshold (53.4%). For detection of CIN2+, the dual stain had similar sensitivity (83.4% vs 76.6%, P = .1), and statistically higher specificity (58.9% vs 49.6%, P < .001), PPV (21.0% vs 16.6%, P < .001), and NPV (96.4% vs 94.2%, P = .01) compared with cytology. Similar patterns were observed for CIN3+. Women with a positive test had high enough risk for referral to colposcopy, while the risk for women with negative tests was below a one-year return threshold based on current US management guidelines. Dual stain cytology showed good risk stratification for all HPV-positive women and for HPV-positive women with normal cytology. Additional follow-up is needed to determine how long dual stain negative women remain at low risk of precancer. Published by Oxford University Press 2015. This work is written by (a

  14. Arctigenin reduces blood pressure by modulation of nitric oxide synthase and NADPH oxidase expression in spontaneously hypertensive rats.

    Science.gov (United States)

    Liu, Ying; Wang, Guoyuan; Yang, Mingguang; Chen, Haining; zhao, Yan; Yang, Shucai; Sun, Changhao

    2015-12-25

    Arctigenin is a bioactive constituent from dried seeds of Arctium lappa L., which was traditionally used as medicine. Arctigenin exhibits various bioactivities, but its effects on blood pressure regulation are still not widely studied. In this study, we investigated antihypertensive effects of arctigenin by long-term treatment in spontaneously hypertensive rats (SHRs). Arctigenin (50 mg/kg) or vehicle was administered to SHRs or Wistar rats as negative control by oral gavage once a day for total 8 weeks. Nifedipine (3 mg/kg) was used as a positive drug control. After treatment, hemodynamic and physical parameters, vascular reactivity in aorta, the concentration of plasma arctigenin and serum thromboxane B2, NO release and vascular p-eNOS, p-Akt, caveolin-1 protein expression, and vascular superoxide anion generation and p47phox protein expression were detected and analyzed. The results showed that arctigenin significantly reduced systolic blood pressure and ameliorated endothelial dysfunction of SHRs. Arctigenin reduced the levels of thromboxane B2 in plasma and superoxide anion in thoracic aorta of SHRs. Furthermore, arctigenin increased the NO production by enhancing the phosphorylation of Akt and eNOS (Ser 1177), and inhibiting the expression of NADPH oxidase in thoracic aorta of SHRs. Our data suggested that antihypertensive mechanisms of arctigenin were associated with enhanced eNOS phosphorylation and decreased NADPH oxidase-mediated superoxide anion generation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Lymphoblast-derived integration-free iPSC line AD-TREM2-1 from a 67 year-old Alzheimer's disease patient expressing the TREM2 p.R47H variant

    Directory of Open Access Journals (Sweden)

    Soraia Martins

    2018-05-01

    Full Text Available Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs by over-expressing episomal-based plasmids harbouring OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. AD-TREM2–1 was defined as pluripotent based on (i expression of pluripotency-associated markers (ii embryoid body-based differentiation into cell types representative of the three germ layers and (iii the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0.947.

  16. Effects of 42 deg. C hyperthermia on intracellular pH in ovarian carcinoma cells during acute or chronic exposure to low extracellular pH

    International Nuclear Information System (INIS)

    Wahl, Miriam L.; Bobyock, Suzanne B.; Leeper, Dennis B.; Owen, Charles S.

    1997-01-01

    Purpose: To determine whether intracellular pH (pH i ) is affected during hyperthermia in substrate-attached cells and whether acute extracellular acidification potentiates the cytotoxicity of hyperthermia via an effect on pH i . Methods and Materials: The pH i was determined in cells attached to extracellular matrix proteins loaded with the fluorescent indicator dye BCECF at 37 deg. C and during 42 deg. C hyperthermia at an extracellular pH (pH e ) of 6.7 or 7.3 in cells. Effects on pH i during hyperthermia are compared to effects on clonogenic survival after hyperthermia at pH e 7.3 and 6.7 of cells grown at pH e 7.3, or of cells grown and monitored at pH e 6.7. Results: The results show that pH i values are affected by substrate attachments. Cells attached to extracellular matrix proteins had better signal stability, low dye leakage and evidence of homeostatic regulation of pH i during heating. The net decrease in pH i in cells grown and assayed at pH e = 7.3 during 42 deg. C hyperthermia was 0.28 units and the decrease in low pH adapted cells heated at pH e = 6.7 was 0.14 units. Acute acidification from pH e = 7.3 to pH e = 6.7 at 37 deg. C caused an initial reduction of 0.5-0.8 unit in pH i , but a partial recovery followed during the next 60-90 min. Concurrent 42 deg. C hyperthermia caused the same initial reduction in pH i in acutely acidified cells, but inhibited the partial recovery that occurred during the next 60-90 min at 37 deg. C. After 4 h at 37 deg. C, the net change in pH i in acutely acidified cells was 0.30 pH unit, but at 42 deg. C is 0.63 pH units. The net change in pH i correlated inversely with clonogenic survival. Conclusions: Hyperthermia causes a pH i reduction in cells which was smaller in magnitude by 50% in low pH adapted cells. Hyperthermia inhibited the partial recovery from acute acidification that was observed at 37 deg. C in substrate attached cells, in parallel with a lower subsequent clonogenic survival

  17. The ALMA-PILS survey: the sulphur connection between protostars and comets: IRAS 16293-2422 B and 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Drozdovskaya, Maria N.; van Dishoeck, Ewine F.; Jørgensen, Jes K.; Calmonte, Ursina; van der Wiel, Matthijs H. D.; Coutens, Audrey; Calcutt, Hannah; Müller, Holger S. P.; Bjerkeli, Per; Persson, Magnus V.; Wampfler, Susanne F.; Altwegg, Kathrin

    2018-06-01

    The evolutionary past of our Solar system can be pieced together by comparing analogous low-mass protostars with remnants of our Protosolar Nebula - comets. Sulphur-bearing molecules may be unique tracers of the joint evolution of the volatile and refractory components. ALMA Band 7 data from the large unbiased Protostellar Interferometric Line Survey are used to search for S-bearing molecules in the outer disc-like structure, ˜60 au from IRAS 16293-2422 B, and are compared with data on 67P/Churyumov-Gerasimenko (67P/C-G) stemming from the ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instrument aboard Rosetta. Species such as SO2, SO, OCS, CS, H2CS, H2S, and CH3SH are detected via at least one of their isotopologues towards IRAS 16293-2422 B. The search reveals a first-time detection of OC33S towards this source and a tentative first-time detection of C36S towards a low-mass protostar. The data show that IRAS 16293-2422 B contains much more OCS than H2S in comparison to 67P/C-G; meanwhile, the SO/SO2 ratio is in close agreement between the two targets. IRAS 16293-2422 B has a CH3SH/H2CS ratio in range of that of our Solar system (differences by a factor of 0.7-5.3). It is suggested that the levels of UV radiation during the initial collapse of the systems may have varied and have potentially been higher for IRAS 16293-2422 B due to its binary nature; thereby, converting more H2S into OCS. It remains to be conclusively tested if this also promotes the formation of S-bearing complex organics. Elevated UV levels of IRAS 16293-2422 B and a warmer birth cloud of our Solar system may jointly explain the variations between the two low-mass systems.

  18. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Science.gov (United States)

    2011-01-01

    Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p INSS stage 4 and/or dead of disease, p < 0.05, Fisher's exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics. PMID:21492432

  19. Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of the yeast RNase MRP and RNase P RNAs.

    Science.gov (United States)

    Perederina, Anna; Esakova, Olga; Koc, Hasan; Schmitt, Mark E; Krasilnikov, Andrey S

    2007-10-01

    Pop6 and Pop7 are protein subunits of Saccharomyces cerevisiae RNase MRP and RNase P. Here we show that bacterially expressed Pop6 and Pop7 form a soluble heterodimer that binds the RNA components of both RNase MRP and RNase P. Footprint analysis of the interaction between the Pop6/7 heterodimer and the RNase MRP RNA, combined with gel mobility assays, demonstrates that the Pop6/7 complex binds to a conserved region of the P3 domain. Binding of these proteins to the MRP RNA leads to local rearrangement in the structure of the P3 loop and suggests that direct interaction of the Pop6/7 complex with the P3 domain of the RNA components of RNases MRP and P may mediate binding of other protein components. These results suggest a role for a key element in the RNase MRP and RNase P RNAs in protein binding, and demonstrate the feasibility of directly studying RNA-protein interactions in the eukaryotic RNases MRP and P complexes.

  20. Phosphorus flux due to Atlantic salmon (Salmo salar) in an oligotrophic upland stream: effects of management and demography

    Science.gov (United States)

    Keith H. Nislow; John D. Armstrong; Simon. McKelvey

    2004-01-01

    Little is known concerning the role of Atlantic salmon (Salmo salar) in the transport of nutrients to and from river systems. We used demographic data from the River Bran, an oligotrophic river in Scotland, UK, to construct a budget for the transport of phosphorus (P) and applied it to investigate the effects of management strategies and demographic...

  1. Suprathermal electron environment of comet 67P/Churyumov-Gerasimenko: Observations from the Rosetta Ion and Electron Sensor

    Science.gov (United States)

    Clark, G.; Broiles, T. W.; Burch, J. L.; Collinson, G. A.; Cravens, T.; Frahm, R. A.; Goldstein, J.; Goldstein, R.; Mandt, K.; Mokashi, P.; Samara, M.; Pollock, C. J.

    2015-11-01

    Context. The Rosetta spacecraft is currently escorting comet 67P/Churyumov-Gerasimenko until its perihelion approach at 1.2 AU. This mission has provided unprecedented views into the interaction of the solar wind and the comet as a function of heliocentric distance. Aims: We study the interaction of the solar wind and comet at large heliocentric distances (>2 AU) using data from the Rosetta Plasma Consortium Ion and Electron Sensor (RPC-IES). From this we gain insight into the suprathermal electron distribution, which plays an important role in electron-neutral chemistry and dust grain charging. Methods: Electron velocity distribution functions observed by IES fit to functions used to previously characterize the suprathermal electrons at comets and interplanetary shocks. We used the fitting results and searched for trends as a function of cometocentric and heliocentric distance. Results: We find that interaction of the solar wind with this comet is highly turbulent and stronger than expected based on historical studies, especially for this weakly outgassing comet. The presence of highly dynamical suprathermal electrons is consistent with observations of comets (e.g., Giacobinni-Zinner, Grigg-Skjellerup) near 1 AU with higher outgassing rates. However, comet 67P/Churyumov-Gerasimenko is much farther from the Sun and appears to lack an upstream bow shock. Conclusions: The mass loading process, which likely is the cause of these processes, plays a stronger role at large distances from the Sun than previously expected. We discuss the possible mechanisms that most likely are responsible for this acceleration: heating by waves generated by the pick-up ion instability, and the admixture of cometary photoelectrons.

  2. p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Zhang, Shanxiang; Li, Xin

    2016-01-01

    with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6...... was likely due to the association of p63 expression with high-risk IPI, and potential presence of ∆Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53 antagonize...

  3. Origin of adenocarcinoma in Barrett's esophagus: P53 and Ki67 expression and histopathologic background Origem do adenocarcinoma no esôfago de Barrett: bases histopathológicas e expressão dos genes p53 e Ki67

    Directory of Open Access Journals (Sweden)

    Sergio Szachnowicz

    2005-04-01

    Full Text Available Barrett's esophagus is the substitution of squamous epithelium of the distal esophagus by columnar epithelium. Intestinal metaplasia in Barrett's esophagus is considered to be the main risk factor for the development of adenocarcinoma. Diffuse adenocarcinoma and Barrett's esophagus without intestinal metaplasia are rare, and reports on the subject are scarce. PURPOSE AND METHOD: To estimate the prevalence of adenocarcinoma in 297 patients with Barrett's esophagus, during the period of 1990 to 2002, and in 13 patients undergoing surgery, to conduct detailed macroscopic and microscopic analysis, with performance of immunohistochemical tests for p53 and Ki67, correlating the type of tumor with its adjacent epithelium. RESULTS: In our patients with Barrett's esophagus, there was a prevalence of 5.7% of adenocarcinoma. The tumors developed only when the Barrett's esophagus segment was long (>3.0 cm. Tumors were located close to the squamous-columnar junction. The histological study revealed 2 patients (15.4% with Barrett's esophagus adjacent to a tumor with gastric metaplasia without the presence of intestinal metaplasia. Tumors were classified according to Nakamura's classification (23% differentiated pattern, and 77% undifferentiated pattern and to Lauren's classification (61% intestinal and 39% diffuse. The difference is due to the migration of microtubular and foveolar tumors of undifferentiated (gastric pattern in Nakamuras classification to the Lauren's intestinal type. The immunohistochemical test for Ki67 was strongly positive in all the patients, thus evidencing intense cell proliferation in both the columnar epithelium and tumor. Expression of p53 was negative in 67% of the adjacent columnar epithelia and 42% of the tumors, without any correlation between the tissue types. CONCLUSION: Adenocarcinoma develops from mixed columnar epithelium, either intestinal or gastric, showing both the gastric and the intestinal patterns; thus, tumors can

  4. Investigating the role of dimensions of UPPS-P model of impulsivity and age increasing in men’s emotion dysregulation

    Directory of Open Access Journals (Sweden)

    Hashem Jebraeili

    2018-04-01

    Results: The findings showed that there were significant coloration between all dimensions of impulsivity, with the exception of sensation seeking, and age with emotion dysregulation. Results of regression analysis showed that dimensions of impulsivity and age have significant role in prediction of emotion dysregulation and explain 47 percent of total variance of it (F=40.67, P

  5. Exiled by Definition:The Salar of Northwest China

    Directory of Open Access Journals (Sweden)

    David SG Goodman

    2005-03-01

    Full Text Available The reform of state socialism came relatively late to Qinghai Province in the Northwest of the People’s Republic of China. One of Qinghai’s most dynamic groups in the social leadership of reform has been the Salar. The Salar were one of the officially recognized nationalities identified in the People’s Republic of China during the 1950s. A relatively small group of some 100,000 currently live along the upper reaches of the Yellow River, on the borders of Qinghai and Gansu Provinces. The Salar are characterised by their commitment to both Islam and China, and by their belief that they live in permanent exile, though there is considerable uncertainty about their origins. The evidence of recent research in Qinghai suggests the perspective of being Chinese citizens, yet a people in exile, significantly shapes recent Salar social and economic activism.

  6. Influence of fluoride on aluminum toxicity to Atlantic salmon (Salmo salar)

    Science.gov (United States)

    Hamilton, Steven J.; Haines, Terry A.

    1995-01-01

    Atlantic salmon (Salmo salar) alevins were exposed to various aluminum (0–4700 μg/L) and four fluoride (0–500 μg/L) concentrations at two pH values (5.5 and 6.5) for 4- and 30-d periods. In the 4-d tests, aluminum with fluoride was less toxic at pH 6.5 than at pH 5.5, whereas without fluoride, pH had no effect. In the 30-d test, mortality in all treatments was 17–21% at pH 5.5, but only 3–7% at pH 6.5. Fish length and weight after 30 d were reduced in all fluoride–aluminum treatments at pH 5.5, but only in the 200-μg/L aluminum without fluoride treatment at pH 6.5. At pH 5.5 and 6.5 without aluminum, histomorphological examinations revealed no abnormalities in gill tissue. However, in aluminum exposure with no fluoride, gill filaments and secondary lamellae were swollen and thickened. Addition of fluoride at pH 6.5 alleviated some gill damage. At pH 5.5 and 200 μg/L aluminum, addition of 100 μg/L fluoride reduced swelling of gill lamellae, but 200 μg/L fluoride did not reduce swelling. Low fluoride concentrations (fluoride concentrations (> 100 μg/L) may not reduce aluminum-induced effects.

  7. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

    Science.gov (United States)

    Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

    2017-09-01

    Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

  8. Inactivation of p16INK4a, with retention of pRB and p53/p21cip1 function, in human MRC5 fibroblasts that overcome a telomere-independent crisis during immortalization.

    Science.gov (United States)

    Taylor, Lisa M; James, Alexander; Schuller, Christine E; Brce, Jesena; Lock, Richard B; Mackenzie, Karen L

    2004-10-15

    Recent investigations, including our own, have shown that specific strains of fibroblasts expressing telomerase reverse transcriptase (hTERT) have an extended lifespan, but are not immortal. We previously demonstrated that hTERT-transduced MRC5 fetal lung fibroblasts (MRC5hTERTs) bypassed senescence but eventually succumbed to a second mortality barrier (crisis). In the present study, 67 MRC5hTERT clones were established by limiting dilution of a mass culture. Whereas 39/67 clones had an extended lifespan, all 39 extended lifespan clones underwent crisis. 11 of 39 clones escaped crisis and were immortalized. There was no apparent relationship between the fate of clones at crisis and the level of telomerase activity. Telomeres were hyperextended in the majority of the clones analyzed. There was no difference in telomere length of pre-crisis compared with post-crisis and immortal clones, indicating that hyperextended telomeres were conducive for immortalization and confirming that crisis was independent of telomere length. Immortalization of MRC5hTERT cells was associated with repression of the cyclin-dependent kinase inhibitor p16INK4a and up-regulation of pRB. However, the regulation of pRB phosphorylation and the response of the p53/p21cip1/waf1 pathway were normal in immortal cells subject to genotoxic stress. Overexpression of oncogenic ras failed to de-repress p16INK4a in immortal cells. Furthermore, expression of ras enforced senescent-like growth arrest in p16INK4a-positive, but not p16INK4a-negative MRC5hTERT cells. Immortal cells expressing ras formed small, infrequent colonies in soft agarose, but were non-tumorigenic. Overall, these results implicate the inactivation of p16INK4a as a critical event for overcoming telomere-independent crisis, immortalizing MRC5 fibroblasts and overcoming ras-induced premature senescence.

  9. P67

    Directory of Open Access Journals (Sweden)

    O. Bryzgunova

    2015-11-01

    Thus, microparticles, isolated from urine of PCa patients represent a valuable source of diagnostically significant miRNAs. To investigate miR-19b, a large testing cohort is required. Search for other potential miRNA-markers by microarray profiling of cell-free miRNA isolated from urine of PCa patients is also required to reveal a sold set of markers for confident PCa diagnostics.

  10. How pristine is the interior of the comet 67P/Churyumov-Gerasimenko?

    Science.gov (United States)

    Capria, Maria Teresa; Capaccioni, Fabrizio; Filacchione, Gianrico; Tosi, Federico; De Sanctis, Maria Cristina; Mottola, Stefano; Ciarniello, Mauro; Formisano, Michelangelo; Longobardo, Andrea; Migliorini, Alessandra; Palomba, Ernesto; Raponi, Andrea; Kührt, Ekkehard; Bockelée-Morvan, Dominique; Erard, Stéphane; Leyrat, Cedric; Zinzi, Angelo

    2017-07-01

    Comets are usually considered to be the most primitive bodies in the Solar System. The level of truth of this paradigm, however, is a matter of debate, especially if by primitive we mean that they represent a sample of intact, unprocessed material. We now have the possibility of analysing the comet 67P/Churyumov-Gerasimenko with an unprecedented level of detail, but its interior remains largely unprobed and unknown. The questions we address in this paper concern the depth of the processed layers, and whether the comet nucleus, under these processed layers, is really representative of the original material. We applied the Rome model for the thermal evolution and differentiation of nuclei to give an estimation of the evolution and depth of the active layers and of the interplay between the erosion process and the penetration of the heat wave. In order to characterize the illumination regime and the activity on the nucleus, two locations with very different illumination histories were chosen for the simulation. For both locations, the bulk of the activity tends to be concentrated around the perihelion time, giving rise to a high erosion rate. As a consequence, the active layers tend to remain close to the surface, and the interior of the comet, below a layer of few tens of centimetres, can be considered as pristine.

  11. Diagnostic significance of pleural fluid pH and pCO2

    Directory of Open Access Journals (Sweden)

    K.E. Sobhey

    2015-10-01

    Results: We conducted this study on 50 patients with pleural effusions of different causes. The patients were classified into 5 groups according to the cause. For all the patients, measurement of pleural pH, pCO2, pO2, HCO3, protein, LDH, glucose and WBC was done. We observed lowest pH in complicated parapneumonic effusion (empyema 6.80 ± 0.15 and highest pH was observed in transudative effusion 7.47 ± 0.07. Tuberculous effusion has pH lower than pH of malignant effusion 7.17 ± 0.017 and 7.39 ± 0.08, respectively. Post pleurodesis malignant effusion has pH lower than pH of malignant effusion 7.28 ± 0.17 and 7.39 ± 0.08, respectively. There is a strong inverse correlation between pH and pCO2, WBC, LDH and protein (r = −0.813 and p < 0.001, (r = −0.796 and p, 0.001, (r = −0.829 and p, 0.001 and (r = −.837 and p, 0.001, respectively. While there is a weak correlation between pH and glucose of pleural fluid (r = 0.249 and p = 0.066. The highest increase of PNL numbers was in empyema (20169 ± 8094.8 cells/cc.The highest increase of lymphocytes was in malignant effusions (4285.00 ± 2948.20 cells/cc and tuberculous effusion (3977.7 ± 3169 cells/cc.

  12. Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB

    NARCIS (Netherlands)

    Wolach, Baruch; Scharf, Yitshak; Gavrieli, Ronit; de Boer, Martin; Roos, Dirk

    2005-01-01

    Most patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91(phox), a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme

  13. Refractive index sensing of green fluorescent proteins in living cells using fluorescence lifetime imaging microscopy

    NARCIS (Netherlands)

    van Manen, Henk-Jan; Verkuijlen, Paul; Wittendorp, Paul; Subramaniam, Vinod; van den Berg, Timo K; Roos, Dirk; Otto, Cees

    2008-01-01

    We show that fluorescence lifetime imaging microscopy (FLIM) of green fluorescent protein (GFP) molecules in cells can be used to report on the local refractive index of intracellular GFP. We expressed GFP fusion constructs of Rac2 and gp91(phox), which are both subunits of the phagocyte NADPH

  14. Ethnoarchéologie du salar d'Uyuni: sel et cultures régionales inter salar

    Directory of Open Access Journals (Sweden)

    1985-01-01

    Full Text Available Le sel a toujours été l'une des denrées fondamentalement indispensables à la vie quotidienne des hommes. Abondant dans les hauts plateaux des Andes centrales, il constitue l'une des principales richesses des populations locales. Transporté par caravanes de lamas vers d'autres écozones où il est troqué, littoral pacifique, moyennes et basses vallées orientales, il permet à chaque communauté d'acquérir les matières premières complémentaires nécessaires à sa propre subsistance: maïs, piment, coca ou algues... En Bolivie, les grands salars d'Uyuni et de Coipasa sont les principaux centres d'approvisionnement en sel. Leur exploitation à l'échelle régionale semblerait remonter bien avant la colonisation espagnole? La zone 'inter salar,' comprise entre ces deux grandes salines proches de la frontière chilienne, est la mieux localisée pour essayer de déterminer l'exploitation dont elles ont pu faire l'objet par les diverses cultures régionales anciennes ou plus contemporaines. Cette interrogation est à la base du projet d'ethnoarchéologie commencé sur cette région. Cet article présente les premiers résultats de la prospection archéologique menée du 15 novembre au 15 décembre 1983 dans le cadre de ce programme. Il révèle l'existence de nombreux sites fortifiés ou d'inhumations pré-inca correspondant, dans leur ensemble, à des cultures ou grandes chefferies régionales ou 'señoríos' post-Tiwanaku, pouvant être liés au salar et au commerce du sel? Il met l'accent sur les problèmes soulevés par cette étude, les possibilités d'interprétation que nous pouvons avancer et les orientations souhaitées pour compléter ce projet. Siempre la sal ha sido uno de los productos fundamentalmente necesarios para la vida cotidiana del ser humano. Muy abundante en el altiplano de los Andes centrales, la sal constituye, para las poblaciones locales, una de sus riquezas más valiosas. Cargada y trasladada por caravanas de

  15. Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse.

    Science.gov (United States)

    Vincent, Jean-Baptiste; Bodewits, Dennis; Besse, Sébastien; Sierks, Holger; Barbieri, Cesare; Lamy, Philippe; Rodrigo, Rafael; Koschny, Detlef; Rickman, Hans; Keller, Horst Uwe; Agarwal, Jessica; A'Hearn, Michael F; Auger, Anne-Thérèse; Barucci, M Antonella; Bertaux, Jean-Loup; Bertini, Ivano; Capanna, Claire; Cremonese, Gabriele; Da Deppo, Vania; Davidsson, Björn; Debei, Stefano; De Cecco, Mariolino; El-Maarry, Mohamed Ramy; Ferri, Francesca; Fornasier, Sonia; Fulle, Marco; Gaskell, Robert; Giacomini, Lorenza; Groussin, Olivier; Guilbert-Lepoutre, Aurélie; Gutierrez-Marques, P; Gutiérrez, Pedro J; Güttler, Carsten; Hoekzema, Nick; Höfner, Sebastian; Hviid, Stubbe F; Ip, Wing-Huen; Jorda, Laurent; Knollenberg, Jörg; Kovacs, Gabor; Kramm, Rainer; Kührt, Ekkehard; Küppers, Michael; La Forgia, Fiorangela; Lara, Luisa M; Lazzarin, Monica; Lee, Vicky; Leyrat, Cédric; Lin, Zhong-Yi; Lopez Moreno, Josè J; Lowry, Stephen; Magrin, Sara; Maquet, Lucie; Marchi, Simone; Marzari, Francesco; Massironi, Matteo; Michalik, Harald; Moissl, Richard; Mottola, Stefano; Naletto, Giampiero; Oklay, Nilda; Pajola, Maurizio; Preusker, Frank; Scholten, Frank; Thomas, Nicolas; Toth, Imre; Tubiana, Cecilia

    2015-07-02

    Pits have been observed on many cometary nuclei mapped by spacecraft. It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments and models cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts. Alternative mechanisms like explosive activity have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface.

  16. Yogurt made from milk heated at different pH values.

    Science.gov (United States)

    Ozcan, Tulay; Horne, David S; Lucey, John A

    2015-10-01

    Milk for yogurt manufacture is subjected to high heat treatment to denature whey proteins. Low milk pH values (≤ 6.5) at heating result in most denatured whey proteins becoming associated with casein micelles, whereas high milk pH values (≥ 7.0) at heating result in the formation of mostly soluble (nonmicellar) denatured whey protein complexes. There are conflicting reports on the relative importance of soluble and casein-bound whey protein aggregates on the properties of acid gels. Prior studies investigating the effect of pH of milk at heating used model gels in which milk was acidified by glucono-δ-lactone; in this study, we prepared yogurt gels using commercial starter cultures. Model acid gels can have very different texture and physical properties from those made by fermentation with starter cultures. In this study, we investigated the effects of different pH values of milk at heating on the rheological, light backscatter, and microstructural properties of yogurt gels. Reconstituted skim milk was adjusted to pH values 6.2, 6.7, and 7.2 and heated at 85°C for 30 min. A portion of the heated milk samples was readjusted back to pH 6.7 after heating. Milks were inoculated with 3% (wt/wt) yogurt starter culture and incubated at 40°C until pH 4.6. Gel formation was monitored using dynamic oscillatory rheology, and parameters measured included the storage modulus (G') and loss tangent (LT) values. Light-backscattering properties, such as the backscatter ratio (R) and the first derivative of light backscatter ratio (R'), were also monitored during fermentation. Fluorescence microscopy was used to observe gel microstructure. The G' values at pH 4.6 were highest in gels made from milk heated at pH 6.7 and lowest in milk heated at pH 6.2, with or without pH adjustment after heating. The G' values at pH 4.6 were lower in samples after adjustment back to pH 6.7 after heating. No maximum in the LT parameter was observed during gelation for yogurts made from milk

  17. Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk

    Science.gov (United States)

    Broderick, Peter; Chen, Bowang; Johnson, David C; Försti, Asta; Vijayakrishnan, Jayaram; Migliorini, Gabriele; Dobbins, Sara E; Holroyd, Amy; Hose, Dirk; Walker, Brian A; Davies, Faith E; Gregory, Walter A; Jackson, Graham H; Irving, Julie A; Pratt, Guy; Fegan, Chris; Fenton, James AL; Neben, Kai; Hoffmann, Per; Nöthen, Markus M; Mühleisen, Thomas W; Eisele, Lewin; Ross, Fiona M; Straka, Christian; Einsele, Hermann; Langer, Christian; Dörner, Elisabeth; Allan, James M; Jauch, Anna; Morgan, Gareth J; Hemminki, Kari; Houlston, Richard S; Goldschmidt, Hartmut

    2016-01-01

    To identify variants for multiple myeloma risk, we conducted a genome-wide association study with validation in additional series totaling 4,692 cases and 10,990 controls. We identified four risk loci at 3q26.2 (rs10936599, P=8.70x10-14), 6p21.33 (rs2285803, PSORS1C2; P= 9.67x10-11), 17p11.2 (rs4273077, TNFRSF13B; P=7.67x10-9) and 22q13.1 (rs877529, CBX7; P=7.63x10-16). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy and insight into the biological basis of predisposition. PMID:23955597

  18. Measurement of the $B^+\\rightarrow p \\bar{p} K^{+}$ Branching Fraction and Study of the Decay Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.; Barate, R.; Boutigny, D.; Couderc, F.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Tisserand, V.; Zghiche, A.; /Annecy, LAPP; Grauges, E.; /Barcelona, IFAE; Palano, A.; Pappagallo, M.; Pompili, A.; /Bari U. /INFN, Bari; Chen, J.C.; Qi, N.D.; Rong, G.; Wang, P.; Zhu, Y.S.; /Beijing, Inst. High Energy Phys.; Eigen, G.; Ofte, I.; Stugu, B.

    2005-07-06

    With a sample of 232 x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} events collected with the BABAR detector, we study the decay B{sup +} {yields} p{bar p}K{sup +} excluding charmonium decays to p{bar p}. We measure a branching fraction {Beta}(B{sup +} {yields} p{bar p}K{sup +}) = (6.7 {+-} 0.5 {+-} 0.4) x 10{sup -6}. An enhancement at low p{bar p} mass is observed and the Dalitz plot asymmetry suggests dominance of the penguin amplitude in this B decay. We search for a pentaquark candidate {Theta}*{sup ++} decaying into pK{sup +} in the mass range 1.43 to 2.00 GeV/c{sup 2} and set limits on {Beta}(B{sup +} {yields} {Theta}*{sup ++} {bar p}) x {Beta}({Theta}*{sup ++} {yields} pK{sup +}) at the 10{sup -7} level.

  19. Antifungal activity of the basil (Ocimmum basilicum L. extract on Penicillium aurantiogriseum, P. glabrum, P. chrysogenum, and P. brevicompactum

    Directory of Open Access Journals (Sweden)

    Kocić-Tanackov Sunčica D.

    2012-01-01

    Full Text Available This study was aimed at investigating the antifungal potential of basil (Ocimmum basilicum L. extract against toxin-producing Penicillium spp. (P. aurantiogriseum, P. glabrum, P. chrysogenum, and P. brevicompactum isolated from food. The basil extract composition was determined by the GC-MS method. The major component identified in the extract was estragole (86.72%. The determination of the antifungal activity of basil extract on Penicillium spp. was performed using the agar plate method. Basil extract reduced the growth of Penicillium spp. at all applied concentration levels (0.16, 0.35, 0.70, and 1.50 mL/100mL with the colony growth inhibition from 3.6 (for P. glabrum to 100% (for P. chrysogenum. The highest sensitivity showed P. chrysogenum, where the growth was completely inhibited at the basil extract concentration of 1.50 mL/100mL. The growth of other Penicillium spp. was partially inhibited with the colony growth inhibition of 63.4 % (P. brevicompactum, 67.5% (P. aurantiogriseum, and 71.7% (P. glabrum. Higher concentrations (0.70 and 1.50 mL/100mL reduced the growth of the aerial mycelium of all tested Penicillium species. In addition, at the same extract concentrations, the examination of microscopic preparation showed the deformation of hyphae with the frequent occurrence of fragmentations and thickenings, occurrence of irregular vesicle, frequently without metulae and phialides, enlarged metulae. The results obtained in this investigation point to the possibility of using basil extract for the antifungal food protection. [Projekat Ministarstva nauke Republike Srbije, br. TR-31017

  20. Enhanced Adsorption of p-Arsanilic Acid from Water by Amine-Modified UiO-67 as Examined Using Extended X-ray Absorption Fine Structure, X-ray Photoelectron Spectroscopy, and Density Functional Theory Calculations.

    Science.gov (United States)

    Tian, Chen; Zhao, Jian; Ou, Xinwen; Wan, Jieting; Cai, Yuepeng; Lin, Zhang; Dang, Zhi; Xing, Baoshan

    2018-03-20

    p-Arsanilic acid ( p-ASA) is an emerging organoarsenic pollutant comprising both inorganic and organic moieties. For the efficient removal of p-ASA, adsorbents with high adsorption affinity are urgently needed. Herein, amine-modified UiO-67 (UiO-67-NH 2 ) metal-organic frameworks (MOFs) were synthesized, and their adsorption affinities toward p-ASA were 2 times higher than that of the pristine UiO-67. Extended X-ray absorption fine structure (EXAFS), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculation results revealed adsorption through a combination of As-O-Zr coordination, hydrogen bonding, and π-π stacking, among which As-O-Zr coordination was the dominant force. Amine groups played a significant role in enhancing the adsorption affinity through strengthening the As-O-Zr coordination and π-π stacking, as well as forming new adsorption sites via hydrogen bonding. UiO-67-NH 2 s could remove p-ASA at low concentrations (<5 mg L -1 ) in simulated natural and wastewaters to an arsenic level lower than that of the drinking water standard of World Health Organization (WHO) and the surface water standard of China, respectively. This work provided an emerging and promising method to increase the adsorption affinity of MOFs toward pollutants containing both organic and inorganic moieties, via modifying functional groups based on the pollutant structure to achieve synergistic adsorption effect.

  1. Phosphorylation of p37 is important for Golgi disassembly at mitosis

    International Nuclear Information System (INIS)

    Kaneko, Yayoi; Tamura, Kaori; Totsukawa, Go; Kondo, Hisao

    2010-01-01

    Research highlights: → p37 is phosphorylated on Serine-56 and Threonine-59 by Cdc2 at mitosis. → Phosphorylated p37 does not bind to Golgi membranes. → p37 phosphorylation inhibits p97/p37-mediated Golgi membrane fusion. -- Abstract: In mammals, the Golgi apparatus is disassembled at early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 by Cdc2 results in mitotic inhibition of the p97/p47 pathway . In this study, we demonstrate that p37 is phosphorylated on Serine-56 and Threonine-59 by Cdc2 at mitosis, and this phosphorylated p37 does not bind to Golgi membranes. Using an in vitro Golgi reassembly assay, we show that mutated p37(S56D, T59D), which mimics mitotic phosphorylation, does not cause any cisternal regrowth, indicating that p37 phosphorylation inhibits the p97/p37 pathway. Our results demonstrate that p37 phosphorylation on Serine-56 and Threonine-59 is important for Golgi disassembly at mitosis.

  2. Triple-axis X-ray reciprocal space mapping of In{sub y}Ga{sub 1-y}As thermophotovoltaic diodes grown on (1 0 0) InP substrates

    Energy Technology Data Exchange (ETDEWEB)

    Dashiell, M.W.; Ehsani, H.; Sander, P.C. [Lockheed Martin Corporation, Schenectady, NY 12301-1072 (United States); Newman, F.D. [Emcore Corporation, Albuquerque, NM 87123 (United States); Wang, C.A. [MIT Lincoln Laboratory, Lexington, MA 02420 (United States); Shellenbarger, Z.A. [Sarnoff Corporation, Princeton NJ, 08543-5300 (United States); Donetski, D.; Gu, N.; Anikeev, S. [Department of Electrical Engineering, State University of New York, Stony Brook, NY 11794-2350 (United States)

    2008-09-15

    Analysis of the composition, strain-relaxation, layer-tilt, and the crystalline quality of In{sub y}Ga{sub 1-y}As/InP{sub 1-x}As{sub x} thermophotovoltaic (TPV) diodes grown by metal-organic vapor phase epitaxy (MOVPE) is demonstrated using triple-axis X-ray reciprocal space mapping techniques. In{sub 0.53}Ga{sub 0.47}As (E{sub gap}=0.74 eV) n/p junction diodes are grown lattice matched (LM) to InP substrates and lattice-mismatched (LMM) In{sub 0.67}Ga{sub 0.33}As (E{sub gap}=0.6 eV) TPV diodes are grown on three-step InP{sub 1-x}As{sub x} (0P substrates. X-ray reciprocal space maps about the symmetric (4 0 0) and asymmetric (5 3 3) reciprocal lattice points (RELPs) determine the in-plane and out-of-plane lattice parameters and strain of the In{sub y}Ga{sub 1-y}As TPV active layer and underlying InP{sub 1-x}As{sub x} buffers. Triple-axis X-ray rocking curves about the LMM In{sub 0.67}Ga{sub 0.33}As RELP show an order of magnitude increase of its full-width at half-maximum (FWHM) compared to that from the LM In{sub 0.53}Ga{sub 0.47}As (250 vs. 30 arcsec). Despite the significant RELP broadening, the photovoltaic figure of merits show that the electronic quality of the LMM In{sub 0.67}Ga{sub 0.33}As approaches that of the LM diode material. This indicates that misfit-related crystalline imperfections are not dominating the photovoltaic response of the optimized LMM In{sub 0.67}Ga{sub 0.33}As material compared with the intrinsic recombination processes and/or recombination through native point defects, which would be present in both LMM and LM diode material. However, additional RELP broadening in non-optimized LMM In{sub 0.67}Ga{sub 0.33}As n/p junction diodes does correspond to significant degradation of TPV diode open-circuit voltage and minority carrier lifetime demonstrating that there is correlation between X-ray FWHM and the electronic performance of the LMM TPV diodes. (author)

  3. Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Prencipe, E.; Prudent, X.; Tisserand, V.; /Annecy, LAPP; Garra Tico, J.; Grauges, E.; /Barcelona U., ECM; Martinelli, M.; Palano, A.; Pappagallo, M.; /INFN, Bari /Bari U.; Eigen, G.; Stugu, B.; Sun, L.; /Bergen U.; Battaglia, M.; Brown, D.N.; Hooberman, B.; Kerth, L.T.; Kolomensky, Yu.G.; Lynch, G. /LBL, Berkeley /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UC, Riverside /UC, San Diego /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /INFN, Ferrara /INFN, Ferrara /Ferrara U. /Frascati /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /INFN, Genoa /INFN, Genoa /Genoa U. /Harvard U. /Heidelberg U. /Humboldt U., Berlin /Imperial Coll., London /Iowa U. /Iowa State U. /Johns Hopkins U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Mainz U., Inst. Kernphys. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT, LNS /McGill U. /INFN, Milan /Milan U. /INFN, Milan /INFN, Milan /Milan U. /Mississippi U. /Montreal U. /Mt. Holyoke Coll. /INFN, Naples /Naples U. /INFN, Naples /INFN, Naples /Naples U. /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /INFN, Padua /Padua U. /INFN, Padua /INFN, Padua /Padua U. /Paris U., VI-VII /Pennsylvania U. /INFN, Perugia /Perugia U. /INFN, Pisa /Pisa U. /INFN, Pisa /Pisa, Scuola Normale Superiore /INFN, Pisa /Pisa U. /INFN, Pisa /Princeton U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /INFN, Rome /Rome U. /INFN, Rome /Rostock U. /Rutherford /DAPNIA, Saclay /SLAC /South Carolina U. /Stanford U., Phys. Dept. /SUNY, Albany /Tel Aviv U. /Tennessee U. /Texas U. /Texas U., Dallas /INFN, Turin /Turin U. /INFN, Trieste /Trieste U. /Valencia U., IFIC /Victoria U. /Warwick U. /Wisconsin U., Madison

    2009-10-17

    We present a study of ten B-meson decays to a D{sup (*)}, a proton-antiproton pair, and a system of up to two pions using BABAR's data set of 455 x 10{sup 6} B{bar B} pairs. Four of the modes {bar B}{sup 0} {yields} D{sup 0}p{bar p}, {bar B}{sup 0} {yields} D*{sup 0}p{bar p}, {bar B}{sup 0} {yields} D{sup +}p{bar p}{pi}{sup -}, {bar B}{sup 0} {yields} D{sup ast+}p{bar p}{pi}{sup -} are studied with improved statistics compared to previous measurements; six of the modes (B{sup -} {yields} D{sup 0}p{bar p}{pi}{sup -}, B{sup -} {yields} D*{sup 0}p{bar p}{pi}{sup -}, {bar B}{sup 0} {yields} D{sup 0}p{bar p}{pi}{sup -}{pi}{sup +}, {bar B}{sup 0} {yields} D*{sup 0}p{bar p}{pi}{sup -}{pi}{sup +}, B{sup -} {yields} D{sup +}p{bar p}{pi}{sup -}{pi}{sup -}, B{sup -} {yields} D{sup ast+}p{bar p}{pi}{sup -}{pi}{sup -}) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p{bar p}) and m(D{sup (*)0}p) in the Dalitz plots. For 4-body decays, m(p{pi}{sup -}) mass projections show a narrow peak with mass and full width of (1497.4 {+-} 3.0 {+-} 0.9)MeV/c{sup 2} and (47 {+-} 12 {+-} 4)MeV/c{sup 2}, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.

  4. Physical process in the coma of comet 67P derived from narrowband imaging of fragment species

    Science.gov (United States)

    Perez Lopez, F.; Küppers, M.; Marín-Yaseli de la Parra, J.; Besse, S.; Moissl, R.

    2017-09-01

    During the rendezvous of the Rosetta spacecraft with comet 67P/Churyumov-Gerasimenko, the OSIRIS scientific cameras monitored the near-nucleus gas environment in various narrow-band filters, observing various fragment species. It turned out that the excitation processes in the innermost coma are significantly different from the overall coma, as observed from the ground [1]. In particular, some of the observed emissions of fragments (daughter molecules) are created by direct dissociation of parent molecules, and in those cases the spatial distribution of the emission directly maps the distribution of parent molecules. We investigate the evolution of the brightness and distribution of the emissions over time to improve our understanding of the underlying emission mechanisms and to derive the spatial distribution of H2O and CO2. The outcome will provide constraints on the homogeneity of the cometary nucleus.

  5. High-resolution array CGH profiling identifies Na/K transporting ATPase interacting 2 (NKAIN2) as a predisposing candidate gene in neuroblastoma.

    Science.gov (United States)

    Romania, Paolo; Castellano, Aurora; Surace, Cecilia; Citti, Arianna; De Ioris, Maria Antonietta; Sirleto, Pietro; De Mariano, Marilena; Longo, Luca; Boldrini, Renata; Angioni, Adriano; Locatelli, Franco; Fruci, Doriana

    2013-01-01

    Neuroblastoma (NB), the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH) analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2) locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation.

  6. High-resolution array CGH profiling identifies Na/K transporting ATPase interacting 2 (NKAIN2 as a predisposing candidate gene in neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Paolo Romania

    Full Text Available Neuroblastoma (NB, the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2 locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation.

  7. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    International Nuclear Information System (INIS)

    Su, Qing; Qin, Da-Nian; Wang, Fu-Xin; Ren, Jun; Li, Hong-Bao; Zhang, Meng; Yang, Qing; Miao, Yu-Wang; Yu, Xiao-Jing; Qi, Jie; Zhu, Zhiming; Zhu, Guo-Qing; Kang, Yu-Ming

    2014-01-01

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91 phox (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91 phox , ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension

  8. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Wang, Fu-Xin [Department of Neurology, The First Affiliated Hospital of Jiamusi University, Jiamusi 154002 (China); Ren, Jun [Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071 (United States); Li, Hong-Bao; Zhang, Meng; Yang, Qing; Miao, Yu-Wang; Yu, Xiao-Jing; Qi, Jie [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Zhiming [Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, The Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-04-15

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91{sup phox} (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91{sup phox}, ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension.

  9. Characterizing the interior of 67P in the vicinity of Abydos

    Science.gov (United States)

    Ciarletti, V.; Lasue, J.; Lemonnier, F.; Herique, A.; Kofman, W. W.; Guiffaut, C.; Levasseur-Regourd, A. C.; Plettemeier, D.

    2016-12-01

    Since the arrival of Rosetta at comet 67P, numerous pictures have been delivered by the cameras onboard both the main spacecraft and the Philae lander. They revealed, at the nucleus' surface and inside the walls of the deep pits, few-meters scale repeating structures, thus providing hints about the internal structure of the nucleus, and suggesting that primordial 'cometesimals' may be objects around 3m in size. The CONSERT (Comet Nucleus Sounding Experiment by Radiowave Transmission) experiment is a radar that has been designed to specifically sound the interior of the nucleus and to provide information on the nucleus internal structure. The work presented here is based on the CONSERT data collected during the First Science Sequence (FSS) and marginally during Philae's Separation Descent and Landing (SDL) for comparison. During FFS, the smaller lobe of the nucleus in the vicinity of Abydos has been actually sounded by CONSERT's electromagnetic waves at 90 MHz with a spatial resolution around 10 m. The propagation delays measured during FSS are consistent with a very low bulk permittivity value for the investigated cometary material, which confirms the high porosity of the nucleus. The sharp shape of the received pulses indicates that the electromagnetic waves suffered weak scattering when propagating through the nucleus. This suggests that the sounded part nucleus is thus fairly homogeneous on a spatial scale of tens of meters. We will present further results on the variation of the CONSERT's pulse shape transmitted through the small lobe of the nucleus. For a more accurate analysis and interpretation of the data, we split the FSS data into two distinct sets corresponding to soundings performed West and East of Philae in order to investigate potential differences. Tentative interpretation in terms of nucleus internal structure based on propagation simulations performed in non-homogeneous nucleus numerical models will be presented.

  10. In-beam γ-ray Spectroscopy of {sup 30}P via the {sup 28}Si({sup 3}He,pγ){sup 30}P Reaction

    Energy Technology Data Exchange (ETDEWEB)

    Mcneice, E.; Setoodehnia, K. [Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1 (Canada); Singh, B., E-mail: ndgroup@mcmaster.ca [Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1 (Canada); Abe, Y. [Institute of Physics, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8577 (Japan); Binh, D.N. [Center for Nuclear Study (CNS), the University of Tokyo, Wako Branch at RIKEN, Wako, Saitama 351-0198 (Japan); Chen, A.A.; Chen, J. [Department of Physics and Astronomy, McMaster University, Hamilton, ON L8S 4M1 (Canada); Cherubini, S. [INFN-Laboratori Nazionali del Sud and Dipartimento di Fisica ed Astronomia, Università di Catania, 95123 Catania (Italy); Center for Nuclear Study (CNS), the University of Tokyo, Wako Branch at RIKEN, Wako, Saitama 351-0198 (Japan); Fukuoka, S. [Institute of Physics, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8577 (Japan); Hashimoto, T. [Center for Nuclear Study (CNS), the University of Tokyo, Wako Branch at RIKEN, Wako, Saitama 351-0198 (Japan); Hayakawa, T. [Japan Atomic Energy Agency (JAEA), Tokai–mura, Ibaraki 319-1195 (Japan); Ishibashi, Y.; Ito, Y. [Institute of Physics, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8577 (Japan); Kahl, D. [Center for Nuclear Study (CNS), the University of Tokyo, Wako Branch at RIKEN, Wako, Saitama 351-0198 (Japan); Komatsubara, T. [Institute of Physics, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8577 (Japan); Kubono, S. [Nishina Center, the Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198 (Japan); Moriguchi, T.; Nagae, D.; Nishikiori, R.; Niwa, T. [Institute of Physics, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8577 (Japan); and others

    2014-06-15

    The level structure of {sup 30}P up to 8.25 MeV was investigated via in-beam γ-ray spectroscopy using the {sup 28}Si({sup 3}He,pγ){sup 30}P reaction at 9 MeV at the University of Tsukuba Tandem Accelerator Complex in Japan. An energy level scheme was deduced from γ-γ coincidence measurements. 47 new transitions have been observed from the previously known states (mostly resonances), thereby reducing the uncertainties in the excitation energies of 17 states from 3 to 10 keV to values of < 1 keV. Furthermore, spin assignments based on measurements of γ-ray angular distributions and γ-γ directional correlation of oriented nuclei (DCO ratios) were made for several observed levels of {sup 30}P.

  11. PEER REVIEW (Correlation between GATA-3, Ki67 and p53 expressions to Histopathology grading of Breast Cancer bin Makassar, Indonesia)

    OpenAIRE

    Islam, Andi Asadul

    2016-01-01

    - PEER REVIEW Judul karya Ilmiah (artikel): Correlation between GATA-3, Ki67 and p53 expressions to Histopathology grading of Breast Cancer bin Makassar, Indonesia : 9 Orang : Penulis Ketiga : a. Nama Jurnal : Cancer Research Journal b. Nomor ISSN : 2330-8192, E: 2330-8214 c. Volume,nomor, bulan, tahun : Volume 4, No. 3 Tahun 2016 d. Penerbit : Science PG e. DOI artikel (Jika ada) : 10.11648/j.crj .20160403.11 f. Alamat web Jurnal : www.sciencepublishingg...

  12. Peptides-Derived from Thai Rice Bran Improves Endothelial Function in 2K-1C Renovascular Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Orachorn Boonla

    2015-07-01

    Full Text Available In recent years, a number of studies have investigated complementary medical approaches to the treatment of hypertension using dietary supplements. Rice bran protein hydrolysates extracted from rice is a rich source of bioactive peptides. The present study aimed to investigate the vasorelaxation and antihypertensive effects of peptides-derived from rice bran protein hydrolysates (RBP in a rat model of two kidney-one clip (2K-1C renovascular hypertension. 2K-1C hypertension was induced in male Sprague-Dawley rats by placing a silver clip around the left renal artery, whereas sham-operated rats were served as controls. 2K-1C and sham-operated rats were intragastrically administered with RBP (50 mg kg−1 or 100 mg kg−1 or distilled water continuously for six weeks. We observed that RBP augmented endothelium-dependent vasorelaxation in all animals. Administration of RBP to 2K-1C rats significantly reduced blood pressure and decreased peripheral vascular resistance compared to the sham operated controls (p < 0.05. Restoration of normal endothelial function and blood pressure was associated with reduced plasma angiotensin converting enzyme (ACE, decreased superoxide formation, reduced plasma malondialdehyde and increased plasma nitrate/nitrite (p < 0.05. Up-regulation of eNOS protein and down-regulation of p47phox protein were found in 2K-1C hypertensive rats-treated with RBP. Our results suggest that RBP possesses antihypertensive properties which are mainly due to the inhibition of ACE, and its vasodilatory and antioxidant activity.

  13. p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) repress prostate specific antigen levels in human prostate cancer cell lines.

    Science.gov (United States)

    Wong, Lilian I L; Labrecque, Mark P; Ibuki, Naokazu; Cox, Michael E; Elliott, John E; Beischlag, Timothy V

    2015-03-25

    Despite stringent restrictions on their use by many countries since the 1970s, the endocrine disrupting chemicals, DDT and DDE are still ubiquitous in the environment. However, little attention has been directed to p,p'-DDT and the anti-androgen, p,p'-DDE on androgen receptor (AR) target gene transcription in human cells. Inhibitors of androgenic activity may have a deleterious clinical outcome in prostate cancer screens and progression, therefore we determined whether environmentally relevant concentrations of p,p'-DDT and p,p'-DDE negatively impact AR-regulated expression of prostate-specific antigen (PSA), and other AR target genes in human LNCaP and VCaP prostate cancer cells. Quantitative real-time PCR and immuno-blotting techniques were used to measure intracellular PSA, PSMA and AR mRNA and protein levels. We have shown for the first time that p,p'-DDT and p,p'-DDE repressed R1881-inducible PSA mRNA and protein levels in a dose-dependent manner. Additionally, we used the fully automated COBAS PSA detection system to determine that extracellular PSA levels were also significantly repressed. These chemicals achieve this by blocking the recruitment of AR to the PSA promoter region at 10 μM, as demonstrated by the chromatin immunoprecipitation (ChIP) in LNCaP cells. Both p,p'-DDT and p,p'-DDE repressed R1881-inducible AR protein accumulation at 10 μM. Thus, we conclude that men who have been exposed to either DDT or DDE may produce a false-negative PSA test when screening for prostate cancer, resulting in an inaccurate clinical diagnosis. More importantly, prolonged exposure to these anti-androgens may mimic androgen ablation therapy in individuals with prostate cancer, thus exacerbating the condition by inadvertently forcing adaptation to this stress early in the disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Energy Dependence of Nuclear Transparency in C (p,2p) Scattering

    Science.gov (United States)

    Leksanov, A.; Alster, J.; Asryan, G.; Averichev, Y.; Barton, D.; Baturin, V.; Bukhtoyarova, N.; Carroll, A.; Heppelmann, S.; Kawabata, T.; Makdisi, Y.; Malki, A.; Minina, E.; Navon, I.; Nicholson, H.; Ogawa, A.; Panebratsev, Yu.; Piasetzky, E.; Schetkovsky, A.; Shimanskiy, S.; Tang, A.; Watson, J. W.; Yoshida, H.; Zhalov, D.

    2001-11-01

    The transparency of carbon for (p,2p) quasielastic events was measured at beam momenta ranging from 5.9 to 14.5 GeV/c at 90° c.m. The four-momentum transfer squared (Q2) ranged from 4.7 to 12.7 (GeV/c)2. We present the observed beam momentum dependence of the ratio of the carbon to hydrogen cross sections. We also apply a model for the nuclear momentum distribution of carbon to obtain the nuclear transparency. We find a sharp rise in transparency as the beam momentum is increased to 9 GeV/c and a reduction to approximately the Glauber level at higher energies.

  15. First evidence for the two-body charmless baryonic decay $B^0 \\to p \\bar{p}$

    CERN Document Server

    INSPIRE-00258707; Adeva, B; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves Jr, A A; Amato, S; Amerio, S; Amhis, Y; Anderlini, L; Anderson, J; Andreassen, R; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Baesso, C; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bauer, Th; Bay, A; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M -O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Burducea, I; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chen, P; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Couturier, B; Cowan, G A; Cowie, E; Craik, D C; Cunliffe, S; Currie, R; D'Ambrosio, C; David, P; David, P N Y; Davis, A; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Dogaru, M; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Falabella, A; Färber, C; Fardell, G; Farinelli, C; Farry, S; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Furcas, S; Furfaro, E; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garofoli, J; Garosi, P; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gorbounov, P; Gordon, H; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hartmann, T; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Hess, M; Hicheur, A; Hicks, E; Hill, D; Hoballah, M; Hombach, C; Hopchev, P; Hulsbergen, W; Hunt, P; Huse, T; Hussain, N; Hutchcroft, D; Hynds, D; Iakovenko, V; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Kenyon, I R; Ketel, T; Keune, A; Khanji, B; Kochebina, O; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J -P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Li Gioi, L; Liles, M; Lindner, R; Linn, C; Liu, B; Liu, G; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lu, H; Lucchesi, D; Luisier, J; Luo, H; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Maratas, J; Marconi, U; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martins Tostes, D; Martynov, A; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Maurice, E; Mazurov, A; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M -N; Molina Rodriguez, J; Monteil, S; Moran, D; Morawski, P; Mordà, A; Morello, M J; Mountain, R; Mous, I; Muheim, F; Müller, K; Muresan, R; Muryn, B; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neubert, S; Neufeld, N; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Nomerotski, A; Novoselov, A; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palczewski, T; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Phan, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Playfer, S; Plo Casasus, M; Polci, F; Polok, G; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Powell, A; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rademacker, J H; Rakotomiaramanana, B; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redford, S; Reid, M M; dos Reis, A C; Ricciardi, S; Richards, A; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Roberts, D A; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanmartin Sedes, B; Sannino, M; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schaack, P; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M -H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Senderowska, K; Sepp, I; Serra, N; Serrano, J; Seyfert, P; Shapkin, M; Shapoval, I; Shatalov, P; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, N A; Smith, E; Smith, J; Smith, M; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Straticiuc, M; Straumann, U; Subbiah, V K; Sun, L; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szumlak, T; T'Jampens, S; Teklishyn, M; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Urner, D; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Van Dijk, M; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; Waldi, R; Wallace, C; Wallace, R; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wicht, J; Wiechczynski, J; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Yang, Z; Young, R; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

    2013-01-01

    The results of a search for the rare two-body charmless baryonic decays $B^0 \\to p \\bar{p}$ and $B_s^0 \\to p \\bar{p}$ are reported. The analysis uses a data sample, corresponding to an integrated luminosity of 0.9 fb$^{-1}$, of $pp$ collision data collected by the LHCb experiment at a centre-of-mass energy of 7 TeV. An excess of $B^0 \\to p \\bar{p}$ candidates with respect to background expectations is seen with a statistical significance of 3.3 standard deviations. This is the first evidence for a two-body charmless baryonic $B^0$ decay. No significant $B_s^0 \\to p \\bar{p}$ signal is observed, leading to an improvement of three orders of magnitude over previous bounds. If the excess events are interpreted as signal, the 68.3\\% confidence level intervals on the branching fractions are \\begin{eqnarray} \\cal{B}(\\rm{B}^0 \\to p \\bar{p}) & = & ( 1.47 \\,^{+0.62}_{-0.51} \\,^{+0.35}_{-0.14} ) \\times 10^{-8} \\,, \

  16. Optimization of urinary dipstick pH: Are multiple dipstick pH readings reliably comparable to commercial 24-hour urinary pH?

    Science.gov (United States)

    Abbott, Joel E; Miller, Daniel L; Shi, William; Wenzler, David; Elkhoury, Fuad F; Patel, Nishant D; Sur, Roger L

    2017-09-01

    Accurate measurement of pH is necessary to guide medical management of nephrolithiasis. Urinary dipsticks offer a convenient method to measure pH, but prior studies have only assessed the accuracy of a single, spot dipstick. Given the known diurnal variation in pH, a single dipstick pH is unlikely to reflect the average daily urinary pH. Our goal was to determine whether multiple dipstick pH readings would be reliably comparable to pH from a 24-hour urine analysis. Kidney stone patients undergoing a 24-hour urine collection were enrolled and took images of dipsticks from their first 3 voids concurrently with the 24-hour collection. Images were sent to and read by a study investigator. The individual and mean pH from the dipsticks were compared to the 24-hour urine pH and considered to be accurate if the dipstick readings were within 0.5 of the 24-hour urine pH. The Bland-Altman test of agreement was used to further compare dipstick pH relative to 24-hour urine pH. Fifty-nine percent of patients had mean urinary pH values within 0.5 pH units of their 24-hour urine pH. Bland-Altman analysis showed a mean difference between dipstick pH and 24-hour urine pH of -0.22, with an upper limit of agreement of 1.02 (95% confidence interval [CI], 0.45-1.59) and a lower limit of agreement of -1.47 (95% CI, -2.04 to -0.90). We concluded that urinary dipstick based pH measurement lacks the precision required to guide medical management of nephrolithiasis and physicians should use 24-hour urine analysis to base their metabolic therapy.

  17. Sphingosine 1-Phosphate-Induced ICAM-1 Expression via NADPH Oxidase/ROS-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells

    Science.gov (United States)

    Lin, Chih-Chung; Yang, Chien-Chung; Cho, Rou-Ling; Wang, Chen-Yu; Hsiao, Li-Der; Yang, Chuen-Mao

    2016-01-01

    The intercellular adhesion molecule-1 (ICAM-1) expression is frequently correlated with the lung inflammation. In lung injury, sphingosine-1-phosphate (S1P, bioactive sphingolipid metabolite), participate gene regulation of adhesion molecule in inflammation progression and aggravate tissue damage. To investigate the transduction mechanisms of the S1P in pulmonary epithelium, we demonstrated that exposure of HPAEpiCs (human pulmonary alveolar epithelial cells) to S1P significantly induces ICAM-1 expression leading to increase monocyte adhesion on the surface of HPAEpiCs. These phenomena were effectively attenuated by pretreatments with series of inhibitors such as Rottlerin (PKCδ), PF431396 (PYK2), diphenyleneiodonium chloride (DPI), apocynin (NADPH oxidase), Edaravone (ROS), and Bay11-7082 (NF-κB). Consistently, knockdown with siRNA transfection of PKCδ, PYK2, p47phox, and p65 exhibited the same results. Pretreatment with both Gq-coupled receptor antagonist (GPA2A) and Gi/o-coupled receptor antagonist (GPA2) also blocked the upregulation of ICAM-1 protein and mRNA induced by S1P. We observed that S1P induced PYK2 activation via a Gq-coupled receptor/PKCδ-dependent pathway. In addition, S1P induced NADPH oxidase activation and intracellular ROS generation, which were also reduced by Rottlerin or PF431396. We demonstrated that S1P induced NF-κB p65 phosphorylation and nuclear translocation in HPAEpiCs. Activated NF-κB was blocked by Rottlerin, PF431396, APO, DPI, or Edaravone. Besides, the results of monocyte adhesion assay indicated that S1P-induced ICAM-1 expression on HPAEpiCs can enhance the monocyte attachments. In the S1P-treated mice, we found that the levels of ICAM-1 protein and mRNA in the lung fractions, the pulmonary hematoma and leukocyte count in bronchoalveolar lavage fluid were enhanced through a PKCδ/PYK2/NADPH oxidase/ROS/NF-κB signaling pathway. We concluded that S1P-accelerated lung damage is due to the ICAM-1 induction associated with

  18. Carbon monoxide releasing molecule-2 ameliorates IL-1β-induced IL-8 in human gastric cancer cells

    International Nuclear Information System (INIS)

    Lian, Sen; Xia, Yong; Ung, Trong Thuan; Khoi, Pham Ngoc; Yoon, Hyun Joong; Kim, Nam Ho; Kim, Kyung Keun; Jung, Young Do

    2016-01-01

    Carbon monoxide (CO), a byproduct of heme oxygenase (HO), presents antioxidant, anti-inflammatory, and anti-tumor properties. Accumulating evidence supports that interleukin (IL)-8 contribute to the vascularity of human gastric cancer. However, the inhibition of IL-8 expression by CO is yet to be elucidated. Here, we utilized CO releasing molecule-2 (CORM-2) to investigate the effect of CO on IL-1β-induced IL-8 expression and the underlying molecular mechanisms in human gastric cancer AGS cells. CORM-2 dose-dependently suppressed IL-1β-induced IL-8 mRNA and protein expression as well as IL-8 promoter activity. IL-1β induced the translocation of p47 phox to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Moreover, IL-1β activated MAPKs (Erk1/2, JNK1/2, and p38 MAPK) and promoted nuclear factor (NF)-kB and activator protein (AP)-1 binding activities. Pharmacological inhibition and mutagenesis studies indicated that NOX, ROS, Erk1/2, and p38 MAPK are involved in IL-1β-induced IL-8 expression. Transient transfection of deletion mutant constructs of the IL-8 promoter in cells suggested that NF-kB and AP-1 are critical for IL-1β-induced IL-8 transcription. NOX-derived ROS and MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. CORM-2 pretreatment significantly mitigated IL-1β-induced activation of ROS/NF-kB and Erk1/2/AP-1 cascades, blocking IL-8 expression and thus significantly reducing endothelial cell proliferation in the tumor microenvironment.

  19. Rapid Temperature Changes and the Early Activity on Comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Alí-Lagoa, V.; Delbo', M.; Libourel, G.

    2015-09-01

    The so-called “early activity” of comet 67P/Churyumov-Gerasimenko has been observed to originate mostly in parts of the concave region or “neck” between its two lobes. Since activity is driven by the sublimation of volatiles, this is a puzzling result because this area is less exposed to the Sun and is therefore expected to be cooler on average. We used a thermophysical model that takes into account thermal inertia, global self-heating, and shadowing, to compute surface temperatures of the comet. We found that, for every rotation in the 2014 August-December period, some parts of the neck region undergo the fastest temperature variations of the comet’s surface precisely because they are shadowed by their surrounding terrains. Our work suggests that these fast temperature changes are correlated to the early activity of the comet, and we put forward the hypothesis that erosion related to thermal cracking is operating at a high rate on the neck region due to these rapid temperature variations. This may explain why the neck contains some ice—as opposed to most other parts of the surface—and why it is the main source of the comet’s early activity. In a broader context, these results indicate that thermal cracking can operate faster on atmosphereless bodies with significant concavities than implied by currently available estimates.

  20. Dynamic unmagnetized plasma in the diamagnetic cavity around comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Hajra, Rajkumar; Henri, Pierre; Vallières, Xavier; Moré, Jerome; Gilet, Nicolas; Wattieaux, Gaetan; Goetz, Charlotte; Richter, Ingo; Tsurutani, Bruce T.; Gunell, Herbert; Nilsson, Hans; Eriksson, Anders I.; Nemeth, Zoltan; Burch, James L.; Rubin, Martin

    2018-04-01

    The Rosetta orbiter witnessed several hundred diamagnetic cavity crossings (unmagnetized regions) around comet 67P/Churyumov-Gerasimenko during its two year survey of the comet. The characteristics of the plasma environment inside these diamagnetic regions are studied using in situ measurements by the Rosetta Plasma Consortium instruments. Although the unmagnetized plasma density has been observed to exhibit little dynamics compared to the very dynamical magnetized cometary plasma, we detected several localized dynamic plasma structures inside those diamagnetic regions. These plasma structures are not related to the direct ionization of local cometary neutrals. The structures are found to be steepened, asymmetric plasma enhancements with typical rising-to-descending slope ratio of ˜2.8 (±1.9), skewness ˜0.43 (±0.36), mean duration of ˜2.7 (±0.9) min and relative density variation ΔN/N of ˜0.5 (±0.2), observed close to the electron exobase. Similar steepened plasma density enhancements were detected at the magnetized boundaries of the diamagnetic cavity as well as outside the diamagnetic region. The plausible scalelength and propagation direction of the structures are estimated from simple plasma dynamics considerations. It is suggested that they are large-scale unmagnetized plasma enhancements, transmitted from the very dynamical outer magnetized region to the inner magnetic field-free cavity region.

  1. Analysis of the immunohistochemical expressions of p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and their correlations with the prognostic factors Análise das expressões imunoistoquímicas da p53, bcl-2 e Ki-67 no adenocarcinoma colorretal e suas correlações com os fatores prognósticos

    Directory of Open Access Journals (Sweden)

    Hunaldo Lima de Menezes

    2010-06-01

    Full Text Available CONTEXT: Search of tumors markers that allow treatment with higher survival rates, and indicate the response to treatment and recurrence of cancer OBJECTIVE: To analyze the immunoexpression of the proteins p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and correlate them with the clinical-pathological prognostic factors. METHOD: Tissue microarray paraffin blocks were made from colorectal adenocarcinoma tissue resected from 82 patients who had undergone surgery but not chemotherapy or radiotherapy, at "Hospital São Paulo", São Paulo, SP, Brazil, between 2002 and 2005. Thin sections (4 µm were subjected to immunohistochemical reactions, and immunoexpression staining scores were obtained. The scores were correlated with the degree of cell differentiation, staging, disease-free interval, recurrence, survival and specific mortality. The study variables were analyzed using the chi-square and Kaplan-Meier tests to investigate associations with the markers. The significance of the differences between the curves of the disease-free interval and survival was analyzed using the Logrank and Wilcoxon tests. RESULTS: The immunohistochemical expression of p53 was positive in 70 tumors (85.4% and negative in 12 (14.6%. The expression of bcl-2 was positive in 26 (31.7% and negative in 56 (68.3%. The expression of Ki-67 was positive in 62 (75.6% and negative in 20 (24.4%. There was no statistically significant correlation between the expressions of these markers separately or in conjunction, in relation to the degree of cell differentiation, staging, disease-free interval, survival and specific mortality. In relation to recurrence, there was a statistically significant correlation with positive expression of Ki-67 (P = 0.035. CONCLUSION: The immunohistochemical expression of Ki-67 in colorectal cancer is associated with recurrence of this disease.CONTEXTO: Pesquisa de marcadores tumorais que permitam tratamento com maiores índices de sobrevida, além de

  2. Overexpression of c-myc and loss of heterozigosity on 2p, 3p, 5q, 17p and 18q in sporadic colorectal carcinoma Sobreexpresión de c-myc y pérdida de heterozigosidad en 2p, 3p, 5q, 17p y 18q en carcinoma colorrectal esporádico

    Directory of Open Access Journals (Sweden)

    A. Sánchez-Pernaute

    2005-03-01

    Full Text Available Aim: the aim of the present study is to evaluate the prognostic influence of loss of heterozygosity on 2p, 3p, 5q, 17p and 18q, and c-myc overexpression on surgically treated sporadic colorectal carcinoma. Methods: tumor and non-tumor tissue samples from 153 patients were analyzed. Fifty-one percent of patients were male, and mean age in the series was 67 years. Tumors were located in the proximal colon in 37 cases, in the distal bowel in 37, and in the rectum in 79 patients. c-myc overexpression was studied by means of Northern blot analysis, and loss of heterozigosity through microsatellite analysis. Results: c-myc overexpression was detected in 25% of cases, and loss of heterozygosity in at least one of the studied regions in 48%. There was no association between clinical and pathologic features, and genetic alterations. The disease-free interval was significantly shorter for patients with both genetic alterations; the presence of both events was an independent prognostic factor for poor outcome in the multivariate analysis (RR: 4.34, p Objetivo: el objetivo del presente trabajo es evaluar la importancia pronóstica de la pérdida de heterozigosidad en las regiones 2p, 3p, 5q, 17p y 18q y de la sobreexpresión del gen c-myc en el carcinoma colorrectal esporádico, mediante el estudio de la supervivencia libre de enfermedad tras cirugía potencialmente curativa. Métodos: se han analizado muestras tumorales y no tumorales de mucosa colónica de 153 pacientes. El 51% de los pacientes eran varones y la edad media de la serie fue 67 años. Los tumores fueron proximales en 37 casos, distales en 37 y localizados en recto en 79. Se analizó la sobreexpresión del RNA de c-myc por Northern blot, y la presencia de pérdida de heterozigosidad en las diferentes regiones consideradas por análisis de microsatélites. Resultados: se detectó sobreexpresión de c-myc en el 25% de los casos, y pérdida de heterozigosidad en alguna de las regiones estudiadas

  3. Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

    Science.gov (United States)

    Carter, D A; Choong, Y-T; Connelly, A A; Bassi, J K; Hunter, N O; Thongsepee, N; Llewellyn-Smith, I J; Fong, A Y; McDougall, S J; Allen, A M

    2017-10-01

    Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT 1A R) most widely expressed in adult neurons. Activation of the AT 1 R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT 1 R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT 1A R-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT 1A R promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT 1A R-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT 1A R-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT 1A R-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT 1A R-GFP neurons and TH-GFP neurons showed similar AT 1A R-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT 1A R-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing. Copyright © 2017 the American Physiological Society.

  4. Study of the $^{44}$Ti$(\\alpha,p)^{47}$V47 reaction and implications for core collapse supernovae

    CERN Document Server

    Margerin, V; Davinson, T; Dressler, R; Fallis, J; Kankainen, A; Laird, A M; Lotay, G; Mountford, D J; Murphy, C D; Seiffert, C; Schumann, D; Stowasser, T; Stora, T; Wang, C H -T; Woods, P J

    2014-01-01

    The underlying physics triggering core collapse supernovae is not fully understood but observations of material ejected during such events helps to solve this puzzle. In particular, several satellite based γ -ray observations of the isotope 44 Ti have been reported recently. Conveniently, the amount of this isotope in stellar ejecta is thought to depend critically on the explosion mechanism. The most influential reaction to the amount of 44 Ti in supernovae is 44 Ti ( α , p ) 47 V. Here we report on a direct study of this reaction conducted at the REX-ISOLDE facility, CERN. The experiment was performed with a 44 Ti beam at E lab = 2 . 16 MeV / u, corresponding to an energy distribution, for reacting α -particles, centred on E cm = 4 . 15 with a 1 σ width of 0.23 MeV. This is, for the first time, well within the Gamow window for core collapse supernovae. The material from which the 44 Ti beam was extracted originates from highly irradiated components of the SINQ spallation neutron source of the Paul Scherr...

  5. NoxO1 Controls Proliferation of Colon Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Franziska Moll

    2018-05-01

    Full Text Available AimReactive oxygen species (ROS produced by enzymes of the NADPH oxidase family serve as second messengers for cellular signaling. Processes such as differentiation and proliferation are regulated by NADPH oxidases. In the intestine, due to the exceedingly fast and constant renewal of the epithelium both processes have to be highly controlled and balanced. Nox1 is the major NADPH oxidase expressed in the gut, and its function is regulated by cytosolic subunits such as NoxO1. We hypothesize that the NoxO1-controlled activity of Nox1 contributes to a proper epithelial homeostasis and renewal in the gut.ResultsNoxO1 is highly expressed in the colon. Knockout of NoxO1 reduces the production of superoxide in colon crypts and is not subsidized by an elevated expression of its homolog p47phox. Knockout of NoxO1 increases the proliferative capacity and prevents apoptosis of colon epithelial cells. In mouse models of dextran sulfate sodium (DSS-induced colitis and azoxymethane/DSS induced colon cancer, NoxO1 has a protective role and may influence the population of natural killer cells.ConclusionNoxO1 affects colon epithelium homeostasis and prevents inflammation.

  6. The 2H(p,2p)n reaction at 508 MeV. Part I

    International Nuclear Information System (INIS)

    Punjabi, V.; Perdrisat, C.F.; Aniol, K.A.; Epstein, M.B.; Huber, J.P.; Margaziotis, D.J.; Bracco, A.; Davis, C.A.; Gubler, H.P.; Lee, W.P.; Poffenberger, P.R.; van Oers, W.T.H.; Postma, H.; Sebel, H.J.; Stetz, A.W.

    1988-09-01

    Differential cross sections for the reaction 2 H(p,2p)n at T p = 507 and 508 MeV are presented. The proton angle pairs chosen were 41.5 degrees with 41.4 and 50.0, 30.1 degrees with 44.0, 53,75, 61.0, and 68.0, 38.1 degrees -38.0 degrees, 44.1 degrees - 44.0 degrees, 47.1 degrees - 47.0 degrees and 50.0 degrees - 50.0 degrees. The data range over an energy window 100 MeV wide on one of the proton energies, the second energy being defined by the kinematic condition of a single neutron recoiling. The data are compared with the impulse approximation (IA) prediction and with the results of a nonrelativistic calculation of the six lowest-order Feynman diagrams describing the reaction. A previously known missing strength for the reaction in the small neutron recoil region is confirmed with much smaller experimental uncertainty; the missing strength persists up to 150 MeV/c neutron recoil. The onset of a systematic section excess relative to the IA near neutron recoil momentum 200 MeV is explored in detail. (Author) (37 refs., 17 figs.)

  7. Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest

    Science.gov (United States)

    Vincentz, Joshua W.; Firulli, Beth A.; Lin, Andrea; Spicer, Douglas B.; Howard, Marthe J.; Firulli, Anthony B.

    2013-01-01

    Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages. PMID:23555309

  8. Congenital central hypoventilation syndrome: four families.

    Science.gov (United States)

    Trivedi, Amit; Waters, Karen; Suresh, Sadasivam; Nair, Rashmi

    2011-12-01

    Congenital central hypoventilation syndrome (CCHS) is a rare condition that usually presents soon after birth and is potentially life-shortening if not treated. The defining abnormality is hypoventilation during sleep which requires life-long treatment with artificial ventilation. This syndrome may also be associated with generalised dysfunction of the autonomic nervous system and a sub-group with associated Hirschsprung's disease. The genetic basis of CCHS has been identified as mutations in the PHOX2B gene. We present four families, three with autosomal dominant inheritance and familial clustering, and one with a de novo mutation resulting in CCHS. We demonstrate that nasal mask ventilation from birth can provide adequate treatment and improved quality of life for these children. Phenotypic variability in expression of disease is seen in families with the same mutations in PHOX2B gene. The psychosocial costs of the disease and the unrecognised 'morbidity barter' that is part of current management needs to be factored into in all stages of management from childhood to adolescence to adulthood.

  9. A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

    International Nuclear Information System (INIS)

    Gallì, Paola; Boccia, Stefania; Cadoni, Gabriella; Volante, Mariangela; De Feo, Emma; Amore, Rosarita; Giorgio, Arianna; Arzani, Dario; Paludetti, Gaetano; Ricciardi, Gualtiero

    2009-01-01

    The purpose of this study is to analyze the combined effects of selected p53 and p73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population. Two hundred and eighty-three cases and 295 hospital controls were genotyped for p53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and p73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the p53 polymorphisms, and a gene-gene interaction analysis for the combined effects of p73 G4C14-to-A4T14 and p53 polymorphisms. We found a significant increased risk of SCCHN among individuals with combined p73 exon 2 G4A and p53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the p53 exon 4-p53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying p73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among p53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16). Our study provides for the first time evidence that individuals carrying p53 exon 4 and p53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of p73 exon 2 G4C14-to-A4T14 and p53 intron 3 variant allele. Larger studies are required to confirm these findings

  10. 40 CFR 704.33 - P-tert-butylbenzoic acid (P-TBBA), p-tert-butyltoluene (P-TBT) and p-tert-butylbenzaldehyde (P-TBB).

    Science.gov (United States)

    2010-07-01

    ...-tert-butyltoluene (P-TBT) and p-tert-butylbenzaldehyde (P-TBB). 704.33 Section 704.33 Protection of... (P-TBBA), p-tert-butyltoluene (P-TBT) and p-tert-butylbenzaldehyde (P-TBB). (a) Definitions. (1) P..., CAS No. 98-73-7. (2) P-TBT means the substance p-tert-butyltoluene, also identified as 1-(1,1...

  11. Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Groome, Michelle J; Koen, Anthonet; Fix, Alan; Page, Nicola; Jose, Lisa; Madhi, Shabir A; McNeal, Monica; Dally, Len; Cho, Iksung; Power, Maureen; Flores, Jorge; Cryz, Stanley

    2017-08-01

    enrolled in the expanded cohort between Nov 3, 2014, and March 20, 2015, and all 162 infants (12 assigned to 10 μg, 50 to 30 μg, 50 to 60 μg, and 50 to placebo) were included in the safety analysis. Serum IgA seroresponses were observed in 38 (81%, 95% CI 67-91) of 47 infants in the 30 μg group and 32 (68%, 53-81) of 47 in the 60 μg group, compared with nine (20%, 10-35) of 45 in the placebo group; adjusted IgG seroresponses were seen in 46 (98%, 89-100) of 47 infants in the 30 μg group and 47 (100%; 92-100) of 47 in the 60 μg group, compared with four (9%, 2·5-21) of 45 in the placebo group; and adjusted neutralising antibody seroresponses against the homologous Wa-strain were seen in 40 (85%, 72-94) of 47 infants in both the 30 μg and 60 μg groups, compared with three (7%, 1·4-18) of 45 participants in the placebo group. Solicited reactions following any injection occurred with similar frequency and severity in participants receiving vaccine and those receiving placebo. Unsolicited adverse events were mostly mild and occurred at a similar frequency between groups. Eight serious adverse events (one with placebo, two with 30 μg, and five with 60 μg) occurred in seven infants within 28 days of any study injection, none of which were deemed related to study treatment. The parenteral P2-VP8-P[8] vaccine was well tolerated and immunogenic in infants, providing a novel approach to vaccination against rotavirus disease. On the basis of these results, a phase 1/2 trial of a trivalent P2-VP8 (P[4], P[6], and P[8]) subunit vaccine is underway at three sites in South Africa. Bill & Melinda Gates Foundation. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

  12. HPLC confirmatory method development for the determination of seven quinolones in salmon tissue (Salmo salar L.) validated according to the European Union Decision 2002/657/EC.

    Science.gov (United States)

    Evaggelopoulou, Evaggelia N; Samanidou, Victoria F

    2013-01-15

    A confirmatory high pressure liquid chromatographic method for the determination of seven quinolone antibiotics in tissue of Atlantic salmon (Salmo salar L.) was developed. Ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR), sarafloxacin (SAR), oxolinic acid (OXO), nalidixic acid (NAL) and flumequine (FLU) were separated on a Perfectsil ODS-2 120 (250 mm × 4 mm, 5 μm) column by gradient elution with a mobile phase consisting of 0.1% trifluoroacetic acid (pH=1), acetonitrile and methanol at 25°C within 22 min. Analytes were monitored at 255 nm (for the determination of OXO, NAL and FLU) and 275 nm (for CIP, DAN, ENR and SAR) by means of photodiode array detector. Examined quinolones were isolated from salmon tissue by extraction with citrate buffer solution (pH=4.7) and purified by solid phase extraction using Oasis HLB (200mg/6 mL) cartridges. The developed method was fully validated in terms of selectivity, linearity, accuracy, precision, stability and sensitivity according to the European Union Decision 2002/657/EC. The accuracy of the method was additionally proved by its application to certified reference material of salmon tissue (BCR® 725). Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. P-type Oxide Semiconductors for Transparent & Energy Efficient Electronics

    KAUST Repository

    Wang, Zhenwei

    2018-01-01

    , the performance of p-type counterparts is lag behind. However, after years of discovery, several p-type TSOs are confirmed with promising performance, for example, tin monoxide (SnO). By using p-type SnO, excellent transistor field-effect mobility of 6.7 cm2 V-1 s

  14. Multiparticle jets from π+/K+/p p collisions at 147 GeV/C compared to e+e- annihilations

    International Nuclear Information System (INIS)

    Ratti, S.P.

    1981-01-01

    The data presented here have been collected by the International Hybrid Spectrometer Consortium in the 30'' B.C. hybrid spectrometer exposed to a 147 GeV/C positive tagged beam made of 47% π + ; 45% p; 8% K + (root-bars = 16.7 GeV) at Fermilab. The sample consists of 15802 events with at least 4 prongs (11822 events with at least 6 prongs) fully measured and reconstructed with an accuracy Δp/p 2 /sub i/delta/sub alphabeta/-p/sup α//sub i/p/sup β//sub i/]; α,β = x,y,z; p/sup x//sub i/,p/sup y//sub i/,p/sup z//sub i/ are the c.m. momentum components of particle i (x-direction along the beam). Their use in hardron hadron physics was suggested long ago

  15. Environmental controls of C, N and P biogeochemistry in peatland pools.

    Science.gov (United States)

    Arsenault, Julien; Talbot, Julie; Moore, Tim R

    2018-08-01

    Pools are common in northern peatlands but studies have seldom focused on their nutrient biogeochemistry, especially in relation to their morphological characteristics and through seasons. We determined the environmental characteristics controlling carbon (C), nitrogen (N) and phosphorus (P) biogeochemistry in pools and assessed their evolution over the course of the 2016 growing season in a subboreal ombrotrophic peatland of eastern Canada. We showed that water chemistry variations in 62 pools were significantly explained by depth (81.9%) and the surrounding vegetation type (14.8%), but not by pool area or shape. Shallow pools had larger dissolved organic carbon (DOC) and total nitrogen (TN) concentrations and lower pH than deep pools, while pools surrounded by coniferous trees had more recalcitrant DOC than pools where vegetation was dominated by mosses. The influence of depth on pool biogeochemistry was confirmed by the seasonal survey of pools of different sizes with 47.1% of the variation in pool water chemistry over time significantly explained. Of this, 67.3% was explained by the interaction between time and pool size and 32.7% by pool size alone. P concentrations were small in all pools all summer long and combined with high N:P ratios, are indicative of P-limitation. Our results show that pool biogeochemistry is influenced by internal processes and highlight the spatial and temporal heterogeneity of nutrient biogeochemistry in ombrotrophic peatlands. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Heterologous expression of pyrroloquinoline quinone (pqq) gene cluster confers mineral phosphate solubilization ability to Herbaspirillum seropedicae Z67.

    Science.gov (United States)

    Wagh, Jitendra; Shah, Sonal; Bhandari, Praveena; Archana, G; Kumar, G Naresh

    2014-06-01

    Gluconic acid secretion mediated by the direct oxidation of glucose by pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase (GDH) is responsible for mineral phosphate solubilization in Gram-negative bacteria. Herbaspirillum seropedicae Z67 (ATCC 35892) genome encodes GDH apoprotein but lacks genes for the biosynthesis of its cofactor PQQ. In this study, pqqE of Erwinia herbicola (in plasmid pJNK1) and pqq gene clusters of Pseudomonas fluorescens B16 (pOK53) and Acinetobacter calcoaceticus (pSS2) were over-expressed in H. seropedicae Z67. Transformants Hs (pSS2) and Hs (pOK53) secreted micromolar levels of PQQ and attained high GDH activity leading to secretion of 33.46 mM gluconic acid when grown on 50 mM glucose while Hs (pJNK1) was ineffective. Hs (pJNK1) failed to solubilize rock phosphate, while Hs (pSS2) and Hs (pOK53) liberated 125.47 μM and 168.07 μM P, respectively, in minimal medium containing 50 mM glucose under aerobic conditions. Moreover, under N-free minimal medium, Hs (pSS2) and Hs (pOK53) not only released significant P but also showed enhanced growth, biofilm formation, and exopolysaccharide (EPS) secretion. However, indole acetic acid (IAA) production was suppressed. Thus, the addition of the pqq gene cluster, but not pqqE alone, is sufficient for engineering phosphate solubilization in H. seropedicae Z67 without compromising growth under nitrogen-fixing conditions.

  17. Identification and characterisation of the IL-27 p28 subunits in fish: Cloning and comparative expression analysis of two p28 paralogues in Atlantic salmon Salmo salar.

    Science.gov (United States)

    Husain, Mansourah; Martin, Samuel A M; Wang, Tiehui

    2014-11-01

    Interleukin (IL)-27 is an IL-6/IL-12 family member with pro-inflammatory and anti-inflammatory properties. It is a heterodimeric cytokine composed of an α-chain p28 and a β-chain Ebi3 (Epstein-Barr virus induce gene 3). The p28 subunit can also be secreted as a monomer and function as IL-30 that acts as an inhibitor of IL-27 signalling. At present, the p28 gene has only been described in mammals. Thus, for the first time outwith mammals, we have identified seven p28 molecules in six divergent teleost fish species, Atlantic salmon, two cichlids, two cyprinids and a yellowtail. The fish p28 molecules have higher similarities to mammalian p28 than other IL-6/12 family members. Critical residues involved in the interaction with Ebi3 and the receptor gp130 are highly conserved. The prediction that these are true orthologues is supported by phylogenetic and synteny analysis. Two p28 paralogues (p28a and p28b) sharing 72% aa identity have been identified and characterised in Atlantic salmon. There are multiple upstream ATGs in the 5'-UTR and ATTTA motifs in the 3'-UTR of both cDNA sequences, suggesting regulation at the post-transcriptional and translational level. Both salmon p28 genes are highly expressed in immune relevant tissues, such as thymus, gills, spleen and head kidney. Conversely salmon Ebi3 is highly expressed in other organs, such as liver and caudal kidney. The expression of p28 but not Ebi3 was induced by PAMPs and recombinant cytokines in head kidney cells, and in spleen by Poly I:C challenge in vivo. The dissociation of the expression and modulation of p28 and Ebi3 suggest that both p28 and Ebi3 may be secreted alone or with other partners. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. InP tunnel junctions for InP/InGaAs tandem solar cells

    Science.gov (United States)

    Vilela, Mauro F.; Freundlich, Alex; Renaud, P.; Medelci, N.; Bensaoula, A.

    1996-01-01

    We report, for the first time, an epitaxially grown InP p(+)/n(++) tunnel junction. A diode with peak current densities up to 1600 A/cm and maximum specific resistivities (Vp/Ip - peak voltage to peak current ratio) in the range of 10(exp -4)Omega cm(exp 2) is obtained. This peak current density is comparable to the highest results previously reported for lattice matched In(0.53)Ga(0.47)As tunnel junctions. Both results were obtained using chemical beam epitaxy (CBE). In this paper we discuss the electrical characteristics of these tunnel diodes and how the growth conditions influence them.

  19. PREDICTION OF FORBIDDEN ULTRAVIOLET AND VISIBLE EMISSIONS IN COMET 67P/CHURYUMOV–GERASIMENKO

    International Nuclear Information System (INIS)

    Raghuram, Susarla; Galand, Marina; Bhardwaj, Anil

    2016-01-01

    Remote observation of spectroscopic emissions is a potential tool for the identification and quantification of various species in comets. The CO Cameron band (to trace CO 2 ) and atomic oxygen emissions (to trace H 2 O and/or CO 2 , CO) have been used to probe neutral composition in the cometary coma. Using a coupled-chemistry-emission model, various excitation processes controlling the CO Cameron band and different atomic oxygen and atomic carbon emissions have been modeled in comet 67P/Churyumov–Gerasimenko at 1.29 AU (perihelion) and at 3 AU heliocentric distances, which is being explored by ESA's Rosetta mission. The intensities of the CO Cameron band, atomic oxygen, and atomic carbon emission lines as a function of projected distance are calculated for different CO and CO 2 volume mixing ratios relative to water. Contributions of different excitation processes controlling these emissions are quantified. We assess how CO 2 and/or CO volume mixing ratios with respect to H 2 O can be derived based on the observed intensities of the CO Cameron band, atomic oxygen, and atomic carbon emission lines. The results presented in this work serve as baseline calculations to understand the behavior of low out-gassing cometary coma and compare them with the higher gas production rate cases (e.g., comet Halley). Quantitative analysis of different excitation processes governing the spectroscopic emissions is essential to study the chemistry of inner coma and to derive neutral gas composition

  20. Differences in Expression of EGFR, Ki67 and p-EPK in Oral Cavity ...

    African Journals Online (AJOL)

    significantly higher in oral cavity cancers than in oropharyngeal cancers (p = 0.005 and p = 0.001, respectively). Loss of ... serine/threonine kinase and a downstream target of Akt, is ... protease digestion, and then hybridizes the tissue with a ...

  1. p63 protein is essential for the embryonic development of vibrissae and teeth

    International Nuclear Information System (INIS)

    Rufini, Alessandro; Weil, Miguel; McKeon, Frank; Barlattani, Alberto; Melino, Gerry; Candi, Eleonora

    2006-01-01

    Development of skin appendages strongly depends on epithelial-mesenchymal interactions. One of the genes involved in this process is p63, a member of the p53 family of transcription factors, essential for ectodermal development, as elucidated by the phenotype of p63 knock-out mice. Surprisingly, no information on p63 expression in tooth and hair is yet available. Here, we show p63 expression during teeth and vibrissae morphogenesis in mouse embryos and we also show a correlation with the expression patterns of the epithelial marker keratin 5 and the proliferation marker Ki67. Our results show that p63 colocalizes with both K5 and Ki67 in the epithelium of developing vibrissae, while in teeth p63 is expressed, together with K5, in the undifferentiated ectoderm (enamel organ), and in ameloblasts, a subpopulation of differentiated ectodermal cells. Moreover, p63 expression in tooth seems not to be fully colocalized with nuclear Ki67 expression

  2. 2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47) decreases progesterone synthesis through cAMP-PKA pathway and P450scc downregulation in mouse Leydig tumor cells

    International Nuclear Information System (INIS)

    Han, Xiumei; Tang, Rong; Chen, Xiaojiao; Xu, Bo; Qin, Yufeng; Wu, Wei; Hu, Yanhui; Xu, Bin; Song, Ling; Xia, Yankai; Wang, Xinru

    2012-01-01

    Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in textiles, plastics and electronics and represent a group of persistent environmental contaminants. They have been found to accumulate in human and marine mammals. Previous studies have shown that PBDEs have endocrine-disrupting properties and reproductive toxicity. However, the mechanisms under the reproductive disruptions are still not well understood. In this study, we explored the effects of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) on progesterone biosynthesis and possible mechanisms in mouse Leydig tumor cells (mLTC-1). Our results showed that BDE-47 could reduce progesterone production and decrease the intracellular cAMP level induced by hCG or forskolin. These suggested that BDE-47 decreasing progesterone production in mLTC-1 cells may be associated with the decline of intracellular cAMP level. Moreover, our data also indicated that the site G protein in cAMP-PKA pathway may be involved in this process. Furthermore, the addition of cAMP analog, 8-Br-cAMP, could not reverse the decrease of progesterone biosynthesis, indicating that a post-cAMP site (or sites) might be involved into the BDE-47-decreased progesterone production. In addition, we found BDE-47 reduced the activity of P450 side chain cleavage enzyme (P450scc), which was companied with the decline of P450scc mRNA and protein level in mLTC-1 cells. Put all together, these results suggested that progesterone synthesis decrease induced by BDE-47 may be associated with attenuation of cAMP generation and reduction of P450scc activity.

  3. Evaluation of LANDSAT-2 (ERTS) images applied to geologic structures and mineral resources of South America. [Salar de Coposa, Chile and Salar of Uyuni, Bolivia

    Science.gov (United States)

    Carter, W. D. (Principal Investigator); Kowalik, W. S.

    1976-01-01

    The author has identified the following significant results. The Salar of Coposa is located in northern Chile along the frontier with Bolivia. The surface was divided into six general classes of materials. Analysis of LANDSAT image 1243-14001 by use of interactive multispectral computer (Image 100) enabled accurate repetition of these general classes based on reflectance. The Salar of Uyuni is the largest of the South American evaporite deposits. Using image 1243-13595, and parallel piped computer classification of reflectance units, the Salar was divided into nine classes ranging from deep to shallow water, water over salt, salt saturated with water, and several classes of dry salt.

  4. Total (p,n), (p,γ), (p,p'γ) and differential (p,p) cross-sections measurements for /sup 61,64/Ni

    International Nuclear Information System (INIS)

    Hershberger, R.L.; Gabbard, F.; Laird, C.E.

    1985-01-01

    Absolute total (p,n) and differential elastic (p,p) cross sections have been measured for /sup 61,64/Ni in the energy range of E/sub p/ = 2 to 7 MeV. The (p,γ) and (p,p'γ) cross sections were measured from as low an energy as feasible to approximately one MeV above the (p,n) threshold. Standard optical potentials have been used with a Hauser-Feshbach model to analyze the data. The adopted model values are used to deduce a total proton strength function which displays features of the 3s single particle resonance

  5. MicroRNAs as Potential Mediators for Cigarette Smoking Induced Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yuka Yokoyama

    2018-04-01

    Full Text Available Smoking increases the risk of atherosclerosis-related events, such as myocardial infarction and ischemic stroke. Recent studies have examined the expression levels of altered microRNAs (miRNAs in various diseases. The profiles of tissue miRNAs can be potentially used in diagnosis or prognosis. However, there are limited studies on miRNAs following exposure to cigarette smoke (CS. The present study was designed to dissect the effects and cellular/molecular mechanisms of CS-induced atherosclerogenesis. Apolipoprotein E knockout (ApoE KO mice were exposed to CS for five days a week for two months at low (two puffs/min for 40 min/day or high dose (two puffs/min for 120 min/day. We measured the area of atherosclerotic plaques in the aorta, representing the expression of miRNAs after the exposure period. Two-month exposure to the high dose of CS significantly increased the plaque area in aortic arch, and significantly upregulated the expression of atherosclerotic markers (VCAM-1, ICAM-1, MCP1, p22phox, and gp91phox. Exposure to the high dose of CS also significantly upregulated the miRNA-155 level in the aortic tissues of ApoE KO mice. Moreover, the expression level of miR-126 tended to be downregulated and that of miR-21 tended to be upregulated in ApoE KO mice exposed to the high dose of CS, albeit statistically insignificant. The results suggest that CS induces atherosclerosis through increased vascular inflammation and NADPH oxidase expression and also emphasize the importance of miRNAs in the pathogenesis of CS-induced atherosclerosis. Our findings provide evidence for miRNAs as potential mediators of inflammation and atherosclerosis induced by CS.

  6. Predictive effect of p53 and p21 alteration on chemotherapy response and survival in locally advanced adenocarcinoma of the esophagus

    NARCIS (Netherlands)

    Heeren, PAM; Kloppenberg, FWH; Hollema, H; Mulder, NH; Nap, RE; Plukker, JTM

    2004-01-01

    Background: Cell cycle regulating proteins (p53/p21) and proliferation index Ki-67 have been associated with prognosis and response to chemotherapy. The aim of this study was to determine the significance of these molecular markers on tumor response and prognostic effect in a group of esophageal

  7. Structural insights into the p97-Ufd1-Npl4 complex

    Science.gov (United States)

    Pye, Valerie E.; Beuron, Fabienne; Keetch, Catherine A.; McKeown, Ciaran; Robinson, Carol V.; Meyer, Hemmo H.; Zhang, Xiaodong; Freemont, Paul S.

    2007-01-01

    p97/VCP (Cdc48 in yeast) is an essential and abundant member of the AAA+ family of ATPases and is involved in a number of diverse cellular pathways through interactions with different adaptor proteins. The two most characterized adaptors for p97 are p47 and the Ufd1 (ubiquitin fusion degradation 1)-Npl4 (nuclear protein localization 4) complex. p47 directs p97 to membrane fusion events and has been shown to be involved in protein degradation. The Ufd1-Npl4 complex directs p97 to an essential role in endoplasmic reticulum-associated degradation and an important role in mitotic spindle disassembly postmitosis. Here we describe the structural features of the Ufd1-Npl4 complex and its interaction with p97 with the aid of EM and other biophysical techniques. The Ufd1-Npl4 heterodimer has an elongated bilobed structure that is ≈80 × 30 Å in dimension. One Ufd1-Npl4 heterodimer is shown to interact with one p97 hexamer to form the p97-Ufd1-Npl4 complex. The Ufd1-Npl4 heterodimer emanates from one region on the periphery of the N-D1 plane of the p97 hexamer. Intriguingly, the p97-p47 and the p97-Ufd1-Npl4 complexes are significantly different in stoichiometry, symmetry, and quaternary arrangement, reflecting their specific actions and their ability to interact with additional cofactors that cooperate with p97 in diverse cellular pathways. PMID:17202270

  8. Title VI in '76: Review of Projects Funded Under P.L. 91-230 Title VI-B, Education of the Handicapped Act, as Amended by P.L. 93-380 and P.L. 94-142. Fiscal Year 1976.

    Science.gov (United States)

    Florida State Dept. of Education, Tallahassee.

    Summarized are 89 projects which served exceptional students in all 67 Florida school districts and were funded during the 1975-76 school year under P.L. 91-230 Title VI B (Education of the Handicapped Act) as ammended by P.L. 93-380 and P.L. 94-142. Projects are divided into the following major areas; Florida Learning Resources System,…

  9. PREDICTION OF FORBIDDEN ULTRAVIOLET AND VISIBLE EMISSIONS IN COMET 67P/CHURYUMOV–GERASIMENKO

    Energy Technology Data Exchange (ETDEWEB)

    Raghuram, Susarla; Galand, Marina [Department of Physics, Imperial College London, Prince Consort Road, London SW7 2AZ (United Kingdom); Bhardwaj, Anil, E-mail: raghuramsusarla@gmail.com [Space Physics Laboratory, Vikram Sarabhai Space Centre, Trivandrum, 695022 (India)

    2016-02-20

    Remote observation of spectroscopic emissions is a potential tool for the identification and quantification of various species in comets. The CO Cameron band (to trace CO{sub 2}) and atomic oxygen emissions (to trace H{sub 2}O and/or CO{sub 2}, CO) have been used to probe neutral composition in the cometary coma. Using a coupled-chemistry-emission model, various excitation processes controlling the CO Cameron band and different atomic oxygen and atomic carbon emissions have been modeled in comet 67P/Churyumov–Gerasimenko at 1.29 AU (perihelion) and at 3 AU heliocentric distances, which is being explored by ESA's Rosetta mission. The intensities of the CO Cameron band, atomic oxygen, and atomic carbon emission lines as a function of projected distance are calculated for different CO and CO{sub 2} volume mixing ratios relative to water. Contributions of different excitation processes controlling these emissions are quantified. We assess how CO{sub 2} and/or CO volume mixing ratios with respect to H{sub 2}O can be derived based on the observed intensities of the CO Cameron band, atomic oxygen, and atomic carbon emission lines. The results presented in this work serve as baseline calculations to understand the behavior of low out-gassing cometary coma and compare them with the higher gas production rate cases (e.g., comet Halley). Quantitative analysis of different excitation processes governing the spectroscopic emissions is essential to study the chemistry of inner coma and to derive neutral gas composition.

  10. Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease.

    Science.gov (United States)

    Chamilos, Georgios; Akoumianaki, Tonia; Kyrmizi, Irene; Brakhage, Axel; Beauvais, Anne; Latge, Jean-Paul

    2016-05-03

    Intracellular swelling of conidia of the major human airborne fungal pathogen Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen-associated molecular patterns (PAMPs) and triggers activation of a specialized autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal killing. We have recently discovered that, apart from PAMPs exposure, cell wall melanin removal during germination of A. fumigatus is a prerequisite for activation of LAP. Importantly, melanin promotes fungal pathogenicity via targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence upon conditional inactivation of Atg5 in hematopoietic cells of mice. Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering with signaling regulating cytokine responses. Notably, inhibition of LAP is a general property of melanin pigments, a finding with broad physiological implications.

  11. A Catalytic, Asymmetric Formal Synthesis of (+)-Hamigeran B

    KAUST Repository

    Mukherjee, Herschel

    2011-03-04

    A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B.

  12. A Catalytic, Asymmetric Formal Synthesis of (+)-Hamigeran B

    KAUST Repository

    Mukherjee, Herschel; McDougal, Nolan T.; Virgil, Scott C.; Stoltz, Brian M.

    2011-01-01

    A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B.

  13. Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C.

    Science.gov (United States)

    Siqueira, Erika Rabelo Forte de; Pereira, Luciano Beltrao; Stefano, Jose Tadeu; Patente, Thiago; Cavaleiro, Ana Mercedes; Silva Vasconcelos, Luydson Richardson; Carmo, Rodrigo Feliciano; Moreira Beltrao Pereira, Leila Maria; Carrilho, Flair Jose; Corrêa-Giannella, Maria Lucia; Oliveira, Claudia P

    2015-03-28

    Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV. One hundred seventy eight naïve HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and -675 T → A in CYBA. No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 ± 6.34 U/L versus CC = 100.22 ± 9.85; mean ± SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 ± 6.77 U/L versus TA + AA = 109.67 ± 18.37 U/L; mean ± SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025). The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.

  14. Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap(®) System.

    Science.gov (United States)

    Koziolek, Mirko; Grimm, Michael; Becker, Dieter; Iordanov, Ventzeslav; Zou, Hans; Shimizu, Jeff; Wanke, Christoph; Garbacz, Grzegorz; Weitschies, Werner

    2015-09-01

    Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated in two studies with each 10 healthy human subjects using the IntelliCap(®) system. This telemetric drug delivery device enabled the determination of gastric emptying time, small bowel transit time, and colon arrival time by significant pH and temperature changes. The study results revealed high variability of GI pH and transit times. The gastric transit of IntelliCap(®) was characterized by high fluctuations of the pH with mean values ranging from pH 1.7 to pH 4.7. Gastric emptying was observed after 7-202 min (median: 30 min). During small bowel transit, which had a duration of 67-532 min (median: 247 min), pH values increased slightly from pH 5.9-6.3 in proximal parts to pH 7.4-7.8 in distal parts. Colonic pH conditions were characterized by values fluctuating mainly between pH 5 and pH 8. The pH profiles and transit times described in this work are highly relevant for the comprehension of drug delivery of solid oral dosage forms comprising ionizable drugs and excipients with pH-dependent solubility. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. New production cross sections for the theranostic radionuclide 67Cu

    Science.gov (United States)

    Pupillo, Gaia; Sounalet, Thomas; Michel, Nathalie; Mou, Liliana; Esposito, Juan; Haddad, Férid

    2018-01-01

    The cross sections of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were measured at the ARRONAX facility by using the 70 MeV cyclotron, with particular attention to the production of the theranostic radionuclide 67Cu. Enriched 68Zn material was electroplated on silver backing and exposed to a low-intensity proton beam by using the stacked-foils target method. Since 67Cu and 67Ga radionuclides have similar half-lives and same γ-lines (they both decay to 67Zn), a radiochemical process aimed at Cu/Ga separation was mandatory to avoid interferences in γ-spectrometry measurements. A simple chemical procedure having a high separation efficiency (>99%) was developed and monitored during each foil processing, thanks to the tracer isotopes 61Cu and 66Ga. Nuclear cross sections were measured in the energy range 35-70 MeV by using reference reactions recommended by the International Atomic Energy Agency (IAEA) to monitor beam flux. In comparison with literature data a general good agreement on the trend of the nuclear reactions was noted, especially with latest measurements, but slightly lower values were obtained in case of 67Cu. Experimental results of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were also compared with the theoretical values estimated by using the software TALYS. The production yield of the theranostic radionuclide 67Cu was estimated considering the results obtained in this work.

  16. NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joonghoon; Park, Eok; Ahn, Bong-Hyun; Kim, Hyoung Jin [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Park, Ji-hoon [Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, 301-747 (Korea, Republic of); Koo, Sun Young; Kwak, Hyo-Shin; Park, Heui Sul; Kim, Dong Wook; Song, Myoungsub; Yim, Hyeon Joo; Seo, Dong Ook [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of); Kim, Soon Ha, E-mail: shakim@lgls.com [LG Life Sciences Ltd., R and D Park, Daejeon, 305-380 (Korea, Republic of)

    2012-08-15

    Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC{sub 50} = 0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p < 0.05). Microarray analysis revealed that 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in ‘Production of reactive oxygen species’ (p = 0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. -- Highlights: ► NecroX-7 prevented tert-butyl hydroperoxide-induced in vitro cardiac cell death. ► NecroX-7 ameliorated doxorubicin-induced in vivo cardiomyopathy. ► NecroX-7 prevented oxidative stress and necrosis-enriched transcriptional changes. ► NecroX-7 effectively inhibited NADPH oxidase activation. ► Cardioprotection of Necro-7 was brought on by modulation of NADPH oxidase activity.

  17. Gamma radiation effect in iso-P P/at-P P blends

    International Nuclear Information System (INIS)

    Bettini, S.H.P.; Bittencourt, E.

    1993-01-01

    This work studied the behaviour of iso-P P/at-P P blends when submitted to various radiation doses, between 0 and 10 Mrad. Structural modifications were accompanied by load-deformation tests, infrared spectroscopy and thermal analyses. Aging of the non-irradiated samples and those irradiated at 3,5 Mrad were analyzed by measuring the carbonyl bands in the infrared spectra. (author)

  18. Multiplicity and asymmetric fireballs from π+p, K+p, γp, e-p, and μ-p reactions

    International Nuclear Information System (INIS)

    Hoang, T.F.; Chew, C.K.; Phua, K.K.

    1979-01-01

    Negative-pion multiplicities produced by asymmetric fireballs are investigated in terms of the fireball mass M*, related to the Feynman-Yang scaling. Assuming approx. M* and making use of results of the previous analysis on pp and p-barp data, it is found that only one parameter is needed for both π + p and K + p reactions and another one for γp, e - p, and μ - p reactions. An attempt is made to analyze π production by e + e - in analogy with the analysis of p-barp annihilation in a previous work

  19. Trastorno de pánico y memoria

    OpenAIRE

    Andrés Gómez, Javier de

    2014-01-01

    El trastorno de pánico afecta al 4.7% de las personas a lo largo de su vida. Sin embargo desconocemos cómo este trastorno afecta a la memoria. Se analizan los distintos modelos explicativos neuro-anatómicos, neuropsicológicos y etológicos sobre el trastorno de pánico y, cómo este trastorno afecta a la memoria

  20. WISE/NEOWISE PRELIMINARY ANALYSIS AND HIGHLIGHTS OF THE 67P/CHURYUMOV-GERASIMENKO NEAR NUCLEUS ENVIRONS

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, James M.; Kramer, Emily; Mainzer, A. K.; Stevenson, Rachel; Masiero, Joseph R.; Weissman, Paul R. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, MS 183-401, Pasadena, CA 91109 (United States); Grav, Tommy [Planetary Science Institute, 1700 East Fort Lowell, Suite 106, Tucson, AZ 85719-2395 (United States); Walker, Russell G. [Monterey Institute for Research in Astronomy, 200 Eighth Street, Marina, CA 93933 (United States); Fernandez, Yan R. [Department of Physics, University of Central Florida, 4000 Central Florida Boulevard, P.S. Building, Orlando, FL 32816-2385 (United States); Meech, Karen J. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Manoa, HI 96822 (United States); Lisse, Carey M. [Applied Physics Laboratory, Johns Hopkins University, 11100 Johns Hopkins Road, Laurel, MD 20723-6099 (United States); Cutri, Roc M.; Dailey, John W.; Masci, Frank J.; Pearman, George [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Tholen, David J. [NASA Astrobiology Institute, University of Hawaii, Manoa, HI 96822 (United States); Wright, Edward L., E-mail: bauer@scn.jpl.nasa.gov [Department of Physics and Astronomy, University of California, P.O. Box 91547, Los Angeles, CA 90095-1547 (United States); Collaboration: WISE Team

    2012-10-10

    On 2010 January 18-19 and June 28-29, the Wide-field Infrared Survey Explorer (WISE) spacecraft imaged the Rosetta mission target, comet 67P/Churyumov-Gerasimenko. We present a preliminary analysis of the images, which provide a characterization of the dust environment at heliocentric distances similar to those planned for the initial spacecraft encounter, but on the outbound leg of its orbit rather than the inbound. Broadband photometry yields low levels of CO{sub 2} production at a comet heliocentric distance of 3.32 AU and no detectable production at 4.18 AU. We find that at these heliocentric distances, large dust grains with mean grain diameters on the order of a millimeter or greater dominate the coma and evolve to populate the tail. This is further supported by broadband photometry centered on the nucleus, which yield an estimated differential dust particle size distribution with a power-law relation that is considerably shallower than average. We set a 3{sigma} upper limit constraint on the albedo of the large-grain dust at {<=}0.12. Our best estimate of the nucleus radius (1.82 {+-} 0.20 km) and albedo (0.04 {+-} 0.01) are in agreement with measurements previously reported in the literature.

  1. The phase function and density of the dust observed at comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Fulle, Marco; Bertini, I.; Della Corte, V.; Güttler, C.; Ivanovski, S.; La Forgia, F.; Lasue, J.; Levasseur-Regourd, A. C.; Marzari, F.; Moreno, F.; Mottola, S.; Naletto, G.; Palumbo, P.; Rinaldi, G.; Rotundi, A.; Sierks, H.; Barbieri, C.; Lamy, P. L.; Rodrigo, R.; Koschny, D.; Rickman, H.; Barucci, M. A.; Bertaux, J.-L.; Bodewits, D.; Cremonese, G.; Da Deppo, V.; Davidsson, B.; Debei, S.; De Cecco, M.; Deller, J.; Fornasier, S.; Groussin, O.; Gutiérrez, P. J.; Hviid, H. S.; Ip, W. H.; Jorda, L.; Keller, H. U.; Knollenberg, J.; Kramm, J. R.; Kührt, E.; Küppers, M.; Lara, M. L.; Lazzarin, M.; López-Moreno, J. J.; Shi, X.; Thomas, N.; Tubiana, C.

    2018-05-01

    The OSIRIS camera onboard Rosetta measured the phase function of both the coma dust and the nucleus. The two functions have a very different slope versus the phase angle. Here, we show that the nucleus phase function should be adopted to convert the brightness to the size of dust particles larger than 2.5 mm only. This makes the dust bursts observed close to Rosetta by OSIRIS, occurring about every hour, consistent with the fragmentation on impact with Rosetta of parent particles, whose flux agrees with the dust flux observed by GIADA. OSIRIS also measured the antisunward acceleration of the fragments, thus providing the first direct measurement of the solar radiation force acting on the dust fragments and thus of their bulk density, excluding any measurable rocket effect by the ice sublimation from the dust. The obtained particle density distribution has a peak matching the bulk density of most COSIMA particles, and represents a subset of the density distribution measured by GIADA. This implies a bias in the elemental abundances measured by COSIMA, which thus are consistent with the 67P dust mass fractions inferred by GIADA, i.e. (38 ± 8) {per cent} of hydrocarbons versus the (62 ± 8) {per cent} of sulphides and silicates.

  2. P(o-chlorophenol–co-o-hydroxyphenol: kinetic formation studies and pH-sensor application

    Directory of Open Access Journals (Sweden)

    Said M. Sayyah

    2017-03-01

    Full Text Available Electrochemical copolymerization of o-chlorophenol (o-ClPh with o-hydroxyphenol (o-HOPh was conducted in aqueous H2SO4 using cyclic voltammetry technique at the Pt electrode. The reaction rate was found to be of the second order in the monomer concentration and first order in the acid concentration. The activation energy, enthalpy, and entropy for the copolymerization were found to be 20.20 kJ mol-1, 19.24 kJ mol-1 and -281.47 J K-1 mol-1, respectively. The obtained copolymer films show smooth feature with amorphous nature. Copolymer films adhere Pt electrode very well and show less reactivity in the H2SO4 medium. The pH sensitivity of the poly(oClPh-co-HOPh-modified electrode has been investigated potentiometrically using different polymer thicknesses. The potentiometric responses to pH change of the poly(oClPh-co-HOPh-modified electrode appeared reversible and linear in the range from pH 2-11 with a maximum sub-Nernstian potentiometric response slope of 40.7 mV/pH (30 °C. The slope became close to 56.2 mV/pH in the range from pH 4 to 9 at (30 °C. The poly(oClPh-co-HOPh-modified electrode readily responded to pH change but was not stable with time.

  3. Exploring the effective photon management by InP nanoparticles: Broadband light absorption enhancement of InP/In0.53Ga0.47As/InP thin-film photodetectors

    International Nuclear Information System (INIS)

    Fu, Dong; Zhu, Xi; Li, Jian; Xu, Yun; Song, Guofeng; Wei, Xin; Liu, Jietao

    2015-01-01

    High-index dielectric and semiconductor nanoparticles with the characteristics of low absorption loss and strong scattering have attracted more and more attention for improving performance of thin-film photovoltaic devices. In this paper, we focus our attention on InP nanoparticles and study the influence of the substrate and the geometrical configurations on their scattering properties. We demonstrate that, compared with the InP sphere, the InP cylinder has higher coupling efficiency due to the stronger interactions between the optical mode in the nanoparticle and its induced mirror image in the substrate. Moreover, we propose novel thin-film InGaAs photodetectors integrated with the periodically arranged InP nanoparticles on the substrate. Broadband light absorption enhancement is achieved over the wavelength range between 1.0 μm and 1.7 μm. The highest average absorption enhancement of 59.7% is realized for the photodetector with the optimized cylinder InP nanoparticles. These outstanding characteristics attribute to the preferentially forward scattering of single InP nanoparticle along with the effective coupling of incident light into the guided modes through the collective diffraction effect of InP nanoparticles array

  4. Chronic infusion of epigallocatechin-3-O-gallate into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation by restoring neurotransmitters and cytokines.

    Science.gov (United States)

    Yi, Qiu-Yue; Li, Hong-Bao; Qi, Jie; Yu, Xiao-Jing; Huo, Chan-Juan; Li, Xiang; Bai, Juan; Gao, Hong-Li; Kou, Bo; Liu, Kai-Li; Zhang, Dong-Dong; Chen, Wen-Sheng; Cui, Wei; Zhu, Guo-Qing; Shi, Xiao-Lian; Kang, Yu-Ming

    2016-11-16

    Reactive oxygen species (ROS) in the brain are involved in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG), one of the active compounds in green tea, has anti-oxidant, anti-inflammatory and vascular protective properties. This study was designed to determine whether chronic infusion of EGCG into the hypothalamic paraventricular nucleus (PVN) attenuates ROS and sympathetic activity and delays the progression of hypertension by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs) and decreasing nuclear factor-kappa B (NF-κB) activity, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar-Kyoto (WKY) rats and SHR received bilateral PVN infusion of EGCG (20μg/h) or vehicle via osmotic minipumps for 4 weeks. SHR showed higher mean arterial pressure, plasma proinflammatory cytokines and circulating norepinephrine (NE) levels compared with WKY rats. SHR also had higher PVN levels of the subunit of NAD(P)H oxidase (gp91 phox ), ROS, tyrosine hydroxylase, and PICs; increased NF-κB activity; and lower PVN levels of interleukin-10 (IL-10) and 67kDa isoform of glutamate decarboxylase (GAD67) than WKY rats. PVN infusion of EGCG attenuated all these changes in SHR. These findings suggest that SHR have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN. Chronic inhibition of ROS in the PVN restores the balance of neurotransmitters and cytokines in the PVN, thereby attenuating hypertensive response and sympathetic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Measurement of (vapor + liquid) equilibrium for the systems {methanol + dimethyl carbonate} and {methanol + dimethyl carbonate + tetramethylammonium bicarbonate} at p = (34.43, 67.74) kPa

    International Nuclear Information System (INIS)

    Yang Changsheng; Zeng Hao; Yin Xia; Ma Shengyong; Sun Feizhong; Li Yafei; Li Jiao

    2012-01-01

    Highlights: ► VLE data for the binary system and the ternary system were measured. ► Methanol, dimethyl carbonate, and tetramethylammonium bicarbonate were studied. ► Isobaric experimental data were measured at p = (34.43, 67.74) kPa. ► VLE data of binary system were correlated with the Wilson, NRTL, and UNIQUAC models. ► The salt effect of TMAB on the VLE of {methanol + DMC} system was investigated. - Abstract: Isobaric (vapor + liquid) equilibrium (VLE) data for the binary system (methanol + dimethyl carbonate) and the ternary system (methanol + dimethyl carbonate + tetramethylammonium bicarbonate) have been measured at p = (34.43, 67.74) kPa using a modified Rose–Williams still. The experimental data for the binary system were well correlated by Wilson, NRTL, and UNIQUAC activity-coefficient models at the two reduced pressures. All the experimental results of the binary system passed the thermodynamic consistency test by the area test of Redlich–Kister and the point test of Van Ness et al. The experimental results of ternary system show that the salt tetramethylammonium bicarbonate has a salting-in effect on methanol. And this effect enhances when the salt concentration increases.

  6. Mitotic phosphorylation of VCIP135 blocks p97ATPase-mediated Golgi membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Totsukawa, Go; Matsuo, Ayaka; Kubota, Ayano; Taguchi, Yuya; Kondo, Hisao, E-mail: hk228@med.kyushu-u.ac.jp

    2013-04-05

    Highlights: •VCIP135 is mitotically phosphorylated on Threonine-760 and Serine-767 by Cdc2. •Phosphorylated VCIP135 does not bind to p97ATPase. •The phosphorylation of VCIP135 inhibits p97ATPase-mediated Golgi membrane fusion. -- Abstract: In mammals, the Golgi apparatus is disassembled early mitosis and reassembled at the end of mitosis. For Golgi disassembly, membrane fusion needs to be blocked. Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. We previously reported that p47 phosphorylation on Serine-140 and p37 phosphorylation on Serine-56 and Threonine-59 result in mitotic inhibition of the p97/p47 and the p97/p37 pathways, respectively [11,14]. In this study, we show another mechanism of mitotic inhibition of p97-mediated Golgi membrane fusion. We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. An in vitro Golgi reassembly assay revealed that VCIP135(T760E, S767E), which mimics mitotic phosphorylation, caused no cisternal regrowth. Our results indicate that the phosphorylation of VCIP135 on Threonine-760 and Serine-767 inhibits p97-mediated Golgi membrane fusion at mitosis.

  7. Discovery of ferromagnetism with large magnetic anisotropy in ZrMnP and HfMnP

    Energy Technology Data Exchange (ETDEWEB)

    Lamichhane, Tej N.; Taufour, Valentin; Kaluarachchi, Udhara S.; Bud' ko, Sergey L.; Canfield, Paul C. [Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011 (United States); The Ames Laboratory, US Department of Energy, Iowa State University, Ames, Iowa 50011 (United States); Masters, Morgan W. [Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011 (United States); Parker, David S. [Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Thimmaiah, Srinivasa [The Ames Laboratory, US Department of Energy, Iowa State University, Ames, Iowa 50011 (United States)

    2016-08-29

    ZrMnP and HfMnP single crystals are grown by a self-flux growth technique, and structural as well as temperature dependent magnetic and transport properties are studied. Both compounds have an orthorhombic crystal structure. ZrMnP and HfMnP are ferromagnetic with Curie temperatures around 370 K and 320 K, respectively. The spontaneous magnetizations of ZrMnP and HfMnP are determined to be 1.9 μ{sub B}/f.u. and 2.1 μ{sub B}/f.u., respectively, at 50 K. The magnetocaloric effect of ZrMnP in terms of entropy change (ΔS) is estimated to be −6.7 kJ m{sup −3} K{sup −1} around 369 K. The easy axis of magnetization is [100] for both compounds, with a small anisotropy relative to the [010] axis. At 50 K, the anisotropy field along the [001] axis is ∼4.6 T for ZrMnP and ∼10 T for HfMnP. Such large magnetic anisotropy is remarkable considering the absence of rare-earth elements in these compounds. The first principle calculation correctly predicts the magnetization and hard axis orientation for both compounds, and predicts the experimental HfMnP anisotropy field within 25%. More importantly, our calculations suggest that the large magnetic anisotropy comes primarily from the Mn atoms, suggesting that similarly large anisotropies may be found in other 3d transition metal compounds.

  8. Discovery of ferromagnetism with large magnetic anisotropy in ZrMnP and HfMnP

    International Nuclear Information System (INIS)

    Lamichhane, Tej N.; Taufour, Valentin; Kaluarachchi, Udhara S.; Bud'ko, Sergey L.; Canfield, Paul C.; Masters, Morgan W.; Parker, David S.; Thimmaiah, Srinivasa

    2016-01-01

    ZrMnP and HfMnP single crystals are grown by a self-flux growth technique, and structural as well as temperature dependent magnetic and transport properties are studied. Both compounds have an orthorhombic crystal structure. ZrMnP and HfMnP are ferromagnetic with Curie temperatures around 370 K and 320 K, respectively. The spontaneous magnetizations of ZrMnP and HfMnP are determined to be 1.9 μ_B/f.u. and 2.1 μ_B/f.u., respectively, at 50 K. The magnetocaloric effect of ZrMnP in terms of entropy change (ΔS) is estimated to be −6.7 kJ m"−"3 K"−"1 around 369 K. The easy axis of magnetization is [100] for both compounds, with a small anisotropy relative to the [010] axis. At 50 K, the anisotropy field along the [001] axis is ∼4.6 T for ZrMnP and ∼10 T for HfMnP. Such large magnetic anisotropy is remarkable considering the absence of rare-earth elements in these compounds. The first principle calculation correctly predicts the magnetization and hard axis orientation for both compounds, and predicts the experimental HfMnP anisotropy field within 25%. More importantly, our calculations suggest that the large magnetic anisotropy comes primarily from the Mn atoms, suggesting that similarly large anisotropies may be found in other 3d transition metal compounds.

  9. Evaluation of feed and feeding regime on growth performance, flesh quality and fecal viscosity of Atlantic salmon ( Salmo salar L.) in recirculating aquaculture systems

    Science.gov (United States)

    Sun, Guoxiang; Liu, Ying; Li, Yong; Li, Xian; Wang, Shunkui

    2015-10-01

    The effects of different feeds and feeding regimes on growth performance, flesh quality and fecal viscosity of Atlantic salmon ( Salmo salar L.) in recirculating aquaculture systems (RAS) were investigated. Fish (initial body weight of 1677 g ± 157 g) were fed with four commercial feeds (Nosan salmon-NS, Aller gold-AG, Skretting salmon-SS and Han ye-HY) in two feeding regimes (80% and 100% satiation) for 78 d. The results showed that salmon specific growth ratio (SGR) and weight gain ratio (WGR) were significantly affected by feed type and feeding regime ( P vitamin E, hydroxyproline (HYP), liquid loss and muscle pH among all groups showed significant differences ( P important quality attributes of Atlantic salmon.

  10. p p mahulikar

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. P P MAHULIKAR. Articles written in Bulletin of Materials Science. Volume 41 Issue 2 April 2018 pp 44. 3D Architectured polyazomethine gel synthesis: its self-assembled intercalating complexation with nitro aromatic acceptor · D S RAGHUVANSHI N B SHIRSATH P P ...

  11. Influencia del α-tocoferol en la incorporación y peroxidación del ácido araquidónico en alevines parr de salmón del Atlántico (Salmo salar L. Influence of α-tocopherol on arachidonic acid deposition and peroxidation in Atlantic salmon (Salmo salar L. fingerlings

    Directory of Open Access Journals (Sweden)

    Patricio Dantagnan

    2012-09-01

    Full Text Available Se evaluó el efecto sinérgico del ácido araquidónico (ARA (20:4n-6 y el α-tocoferol en la acumulación de estos nutrientes y su peroxidación en el músculo e hígado en juveniles de salmón del Atlántico (Salmo salar. Grupos por triplicado se alimentaron por 12 semanas con ocho dietas experimentales que contenían diferentes niveles de ácido araquidónico y α-tocoferol. Los parámetros productivos no se vieron afectados (P > 0,05 por las dietas suministradas. La acumulación del ARA en el músculo e hígado mostró diferencias significativas (P The synergistic effect of arachidonic acid (ARA (20:4n-6 and α-tocopherol on the accumulation of fatty acids and the peroxidation of lipids in liver and muscle was evaluated in Atlantic salmon (Salmo salar juveniles. Triplicate groups were fed during 12 weeks with eight experimental diets with different levels of ARA and α-tocopherol. In all experimental diets the productive parameters were not affected (P > 0.05. ARA accumulation in muscle and liver showed significant differences (P < 0.05 between treatments. The synergic relationship between ARAAx4ocopherol was influenced (P < 0.05 only in the liver, showing that high levels of α-tocopherol and ARA favored the fatty acids accumulation in this organ. Results indicate that a dietary concentration up to 0.6% ARA, the increment of α-tocopherol is not necessary. The data obtained in this study demonstrated that the interaction between the ARA and α-tocopherol influenced the accumulation of fatty acids in the liver.

  12. Nuclear effects in protonium formation low-energy three-body reaction: p̄ + (pμ1s → (p̄pα + μ−: Strong p̄–p interaction in p̄ + (pμ1s

    Directory of Open Access Journals (Sweden)

    Sultanov Renat A.

    2016-01-01

    Full Text Available A three-charge-particle system (p̄, μ−, p+ with an additional matter-antimatter, i.e. p̄–p+, nuclear interaction is the subject of this work. Specifically, we carry out a few-body computation of the following protonium formation reaction: p̄ + (p+μ−1s → (p̄p+1s + μ−, where p+ is a proton, p̄ is an antiproton, μ− is a muon, and a bound state of p+ and its counterpart p̄ is a protonium atom: Pn = (p̄p+. The low-energy cross sections and rates of the Pn formation reaction are computed in the framework of a Faddeev-like equation formalism. The strong p̄–p+ interaction is approximately included in this calculation.

  13. Puzzling Two-Proton Decay of 67Kr

    Science.gov (United States)

    Wang, S. M.; Nazarewicz, W.

    2018-05-01

    Ground-state two-proton (2 p ) radioactivity is a rare decay mode found in a few very proton-rich isotopes. The 2 p decay lifetime and properties of emitted protons carry invaluable information on nuclear structure in the presence of a low-lying proton continuum. The recently measured 2 p decay of 67Kr turned out to be unexpectedly fast. Since 67Kr is expected to be a deformed system, we investigate the impact of deformation effects on the 2 p radioactivity. We apply the recently developed Gamow coupled-channel framework, which allows for a precise description of three-body systems in the presence of rotational and vibrational couplings. This is the first application of a three-body approach to a two-nucleon decay from a deformed nucleus. We show that deformation couplings significantly increase the 2 p decay width of 67Kr; this finding explains the puzzling experimental data. The calculated angular proton-proton correlations reflect a competition between 1 p and 2 p decay modes in this nucleus.

  14. The cross section measurement for the reactions of 48,46Ti(n,p) 48,46Sc, 50Ti(n, α)47Ca and 58Ni (n, 2n)57Ni, 58Ni(n,p)58m+gCo

    International Nuclear Information System (INIS)

    Yuan Junqian; Wang Yongchang; Kong Xiangzhong; Yang Jingkang

    1992-01-01

    The cross sections for the 50 Ti(n, α) 47 Ca, 46 Ti(n, p) 46 Sc, 48 Ti(n, p) 48 Sc and 58 Ni(n, 2n) 57 Ni, 58 Ni(n, p) 58m+g Co reactions have been measured by using the activation method relative to the cross sections of the 27 Al(n, α) 24 Na reaction in the neutron energy range of 13.50-14.81 MeV. The neutron energies were determined by the cross section ratios of the 90 Zr(n, 2n) 89m+g Zr and 93 Nb(n, 2n) 92m Nb reactions. The results obtained are compared with the published and to be published data of several authors

  15. Neuroprotective effects of glyceryl nonivamide against microglia-like cells and 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells.

    Science.gov (United States)

    Lin, Yi-Chin; Uang, Hao-Wei; Lin, Rong-Jyh; Chen, Ing-Jun; Lo, Yi-Ching

    2007-12-01

    Glyceryl nonivamide (GLNVA), a vanilloid receptor (VR) agonist, has been reported to have calcitonin gene-related peptide-associated vasodilatation and to prevent subarachnoid hemorrhage-induced cerebral vasospasm. In this study, we investigated the neuroprotective effects of GLNVA on activated microglia-like cell mediated- and proparkinsonian neurotoxin 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. In coculture conditions, we used lipopolysaccharide (LPS)-stimulated BV-2 cells as a model of activated microglia. LPS-induced neuronal death was significantly inhibited by diphenylene iodonium (DPI), an inhibitor of NADPH oxidase. However, capsazepine, the selective VR1 antagonist, did not block the neuroprotective effects of GLNVA. GLNVA reduced LPS-activated microglia-mediated neuronal death, but it lacked protection in DPI-pretreated cultures. GLNVA also decreased LPS activated microglia induced overexpression of neuronal nitric-oxide synthase (nNOS) and glycoprotein 91 phagocyte oxidase (gp91(phox)) on SH-SY5Y cells. Pretreatment of BV-2 cells with GLNVA diminished LPS-induced nitric oxide production, overexpression of inducible nitric-oxide synthase (iNOS), and gp91(phox) and intracellular reactive oxygen species (iROS). GLNVA also reduced cyclooxygenase (COX)-2 expression, inhibitor of nuclear factor (NF)-kappaB (IkappaB)alpha/IkappaBbeta degradation, NF-kappaB activation, and the overproduction of tumor necrosis factor-alpha, interleukin (IL)-1beta, and prostaglandin E2 in BV-2 cells. However, GLNVA augmented anti-inflammatory cytokine IL-10 production on LPS-stimulated BV-2 cells. Furthermore, in 6-OHDA-treated SH-SY5Y cells, GLNVA rescued the changes in condensed nuclear and apoptotic bodies, prevented the decrease in mitochondrial membrane potential, and reduced cells death. GLNVA also suppressed accumulation of iROS and up-regulated heme oxygenase-1 expression. 6-OHDA-induced overexpression of nNOS, i

  16. Clonal progression during the T cell-dependent B cell antibody response depends on the immunoglobulin DH gene segment repertoire.

    Directory of Open Access Journals (Sweden)

    Ahmad eTrad

    2014-08-01

    Full Text Available The diversity of the third complementarity determining region of the Ig H chain is constrained by natural selection of immunoglobulin diversity (DH sequence. To test the functional significance of this constraint in the context of thymus-dependent (TD immune responses, we immunized BALB/c mice with WT or altered DH sequence with 2-phenyloxazolone-coupled chicken serum albumin (phOx-CSA. We chose this antigen because studies of the humoral immune response to the hapten phOx were instrumental in the development of the current theoretical framework on which our understanding of the forces driving TD responses is based. To allow direct comparison, we used the classic approach of generating monoclonal Ab (mAb from various stages of the immune response to phOx to assess the effect of changing the sequence of the DH on clonal expansion, class switching and affinity maturation, which are hallmarks of TD responses. Compared to WT, TD-induced humoral IgM as well as IgG antibody production in the D-altered D-DFS and D-iD strains were significantly reduced. An increased prevalence of IgM producing hybridomas from late primary, secondary, and tertiary memory responses suggested either impaired class switch recombination (CSR or impaired clonal expansion of class switched B cells with phOx reactivity. Neither of the D-altered strains demonstrated the restriction in the VH/VL repertoire, the elimination of VH1 family-encoded antibodies, the focusing of the distribution of CDR-H3 lengths, or the selection for the normally dominant Ox1 clonotype which all are hallmarks of the anti-phOx response in WT mice. These changes in clonal selection and expansion as well as class switch recombination indicate that the genetic constitution of the DH locus, which has been selected by evolution, can strongly influence the functional outcome of a TD humoral response.

  17. Superoxide Mediates Depressive Effects Induced by Hydrogen Sulfide in Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Haiyun Yu

    2015-01-01

    Full Text Available Hydrogen sulfide (H2S plays a crucial role in the regulation of blood pressure and oxidative stress. In the present study, we tested the hypothesis that H2S exerts its cardiovascular effects by reducing oxidative stress via inhibition of NADPH oxidase activity in the rostral ventrolateral medulla (RVLM. We examined cell distributions of cystathionine-β-synthase (CBS and effects of H2S on reactive oxygen species (ROS and mean arterial blood pressure (MAP in spontaneously hypertensive rats (SHRs. We found that CBS was expressed in neurons of the RVLM, and the expression was lower in SHRs than in Wistar-Kyoto rats. Microinjection of NaHS (H2S donor, S-adenosyl-l-methionine (SAM, a CBS agonist, or Apocynin (NADPH oxidase inhibitor into the RVLM reduced the ROS level, NADPH oxidase activity, and MAP, whereas microinjection of hydroxylamine hydrochloride (HA, a CBS inhibitor increased MAP. Furthermore, intracerebroventricular infusion of NaHS inhibited phosphorylation of p47phox, a key step of NADPH oxidase activation. Since decreasing ROS level in the RVLM reduces MAP and heart rate and increasing H2S reduces ROS production, we conclude that H2S exerts an antihypertensive effect via suppressing ROS production. H2S, as an antioxidant, may be a potential target for cardiovascular diseases.

  18. Hu-Lu-Ba-Wan Attenuates Diabetic Nephropathy in Type 2 Diabetic Rats through PKC-α/NADPH Oxidase Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Lishan Zhou

    2013-01-01

    Full Text Available Hu-Lu-Ba-Wan (HLBW is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH and protein kinase C-alpha (PKC-α related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47phox, and the protein expression of phosphorylated PKC-α in renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-α/NADPH oxidase signaling pathway.

  19. Periplasmic Cu,Zn superoxide dismutase and cytoplasmic Dps concur in protecting Salmonella enterica serovar Typhimurium from extracellular reactive oxygen species.

    Science.gov (United States)

    Pacello, Francesca; Ceci, Pierpaolo; Ammendola, Serena; Pasquali, Paolo; Chiancone, Emilia; Battistoni, Andrea

    2008-02-01

    Several bacteria possess periplasmic Cu,Zn superoxide dismutases which can confer protection from extracellular reactive oxygen species. Thus, deletion of the sodC1 gene reduces Salmonella enterica serovar Typhimurium ability to colonize the spleens of wild type mice, but enhances virulence in p47phox mutant mice. To look into the role of periplamic Cu,Zn superoxide dismutase and into possible additive effects of the ferritin-like Dps protein involved in hydrogen peroxide detoxification, we have analyzed bacterial survival in response to extracellular sources of superoxide and/or hydrogen peroxide. Exposure to extracellular superoxide of Salmonella Typhimurium mutant strains lacking the sodC1 and sodC2 genes and/or the dps gene does not cause direct killing of bacteria, indicating that extracellular superoxide is poorly bactericidal. In contrast, all mutant strains display a sharp hydrogen peroxide-dependent loss of viability, the dps,sodC1,sodC2 mutant being less resistant than the dps or the sodC1,sodC2 mutants. These findings suggest that the role of Cu,Zn superoxide dismutase in bacteria is to remove rapidly superoxide from the periplasm to prevent its reaction with other reactive molecules. Moreover, the nearly additive effect of the sodC and dps mutations suggests that localization of antioxidant enzymes in different cellular compartments is required for bacterial resistance to extracytoplasmic oxidative attack.

  20. Possible involvement of 12-lipoxygenase activation in glucose-deprivation/reload-treated neurons.

    Science.gov (United States)

    Nagasawa, Kazuki; Kakuda, Taichi; Higashi, Youichirou; Fujimoto, Sadaki

    2007-12-18

    The aim of this study was to clarify whether 12-lipoxygenase (12-LOX) activation was involved in reactive oxygen species (ROS) generation, extensive poly(ADP-ribose) polymerase (PARP) activation and neuronal death induced by glucose-deprivation, followed by glucose-reload (GD/R). The decrease of neuronal viability and accumulation of poly(ADP-ribose) induced by GD/R were prevented 3-aminobenzamide, a representative PARP inhibitor, demonstrating this treatment protocol caused the same oxidative stress with the previously reported one. The PARP activation, ROS generation and decrease of neuron viability induced by GD/R treatment were almost completely abolished by an extracellular zinc chelator, CaEDTA. p47(phox), a cytosolic component of NADPH oxidase was translocated the membrane fraction by GD/R, indicating its activation, but it did not generate detectable ROS. Surprisingly, pharmacological inhibition of NADPH oxidase with apocynin and AEBSF further decreased the decreased neuron viability induced by GD/R. On the other hand, AA861, a 12-LOX inhibitor, prevented ROS generation and decrease of neuron viability caused by GD/R. Interestingly, an antioxidant, N-acetyl-l-cysteine rescued the neurons from GD/R-induced oxidative stress, implying effectiveness of antioxidant administration. These findings suggested that activation of 12-LOX, but not NADPH oxidase, following to zinc release might play an important role in ROS generation and decrease of viability in GD/R-treated neurons.

  1. Antecedentes hidroquímicos del Salar de Aguas Calientes I (Chile

    Directory of Open Access Journals (Sweden)

    Ingrid Garcés Millas

    2012-01-01

    Full Text Available El Salar de Aguas Calientes I es un sistema salino del Altiplano chileno, situado a4.280 m.s.n.m, expuesto a condiciones ambientales áridas. El presente trabajo da cuenta del estudio hidroquímico de las soluciones superficiales existentes en el salar, tanto de soluciones diluidas como concentradas en surgencias y acumulaciones lacustres, así como de la mineralogía de las sales precipitadas por evaporación de estas aguas lacustres. Los principales aportes de agua al salar ingresan por la zona norte y por el sector sur, siendo estos últimos de carácter termal. Los restantes aportes se limitan a escasas precipitaciones en forma de escorrentía superficial o subsuperficial. Todas estas aguas circulan hacia las zonas más bajas del salar, y se acumulan en distintos puntos a lo largo de su sector occidental como consecuencia de un ligero basculamiento en su superficie. Los resultados del análisis químico indican que, a pesar de tratarse de aguas con grados de concentración variable y que oscilan entre muy diluidas y altamente concentradas, todas ellas pertenecen al tipo químico Na-Cl, debido a la interacción de las aguas con los depósitos salinos preexistentes en el salar, en los que predominan halita y yeso. Además, todas las soluciones mostraron elevados contenidos en elementos químicos asociados a actividad hidrotermal como son Li, B y As, encontrándose este último en rangos de toxicidad incluso en las muestras diluidas. En el margen norte del salar, las aguas de una surgencia no termal caracterizadas por ser de muy baja concentración en sales minerales, discurren hacia el salar,alimentando una zona de bofedal en la que se desarrolla importante vida vegetal y sirven de sustento a los rebaños de camélidos del área. En cambio, las aguas de los sectores central y meridional (donde se encuentra una surgencia de carácter termal son mucho más concentradas, acumulándose en lagunas desprovistas de desarrollo vegetal. El an

  2. Evolutionary origin and function of NOX4-art, an arthropod specific NADPH oxidase.

    Science.gov (United States)

    Gandara, Ana Caroline Paiva; Torres, André; Bahia, Ana Cristina; Oliveira, Pedro L; Schama, Renata

    2017-03-29

    NADPH oxidases (NOX) are ROS producing enzymes that perform essential roles in cell physiology, including cell signaling and antimicrobial defense. This gene family is present in most eukaryotes, suggesting a common ancestor. To date, only a limited number of phylogenetic studies of metazoan NOXes have been performed, with few arthropod genes. In arthropods, only NOX5 and DUOX genes have been found and a gene called NOXm was found in mosquitoes but its origin and function has not been examined. In this study, we analyzed the evolution of this gene family in arthropods. A thorough search of genomes and transcriptomes was performed enabling us to browse most branches of arthropod phylogeny. We have found that the subfamilies NOX5 and DUOX are present in all arthropod groups. We also show that a NOX gene, closely related to NOX4 and previously found only in mosquitoes (NOXm), can also be found in other taxonomic groups, leading us to rename it as NOX4-art. Although the accessory protein p22-phox, essential for NOX1-4 activation, was not found in any of the arthropods studied, NOX4-art of Aedes aegypti encodes an active protein that produces H 2 O 2 . Although NOX4-art has been lost in a number of arthropod lineages, it has all the domains and many signature residues and motifs necessary for ROS production and, when silenced, H 2 O 2 production is considerably diminished in A. aegypti cells. Combining all bioinformatic analyses and laboratory work we have reached interesting conclusions regarding arthropod NOX gene family evolution. NOX5 and DUOX are present in all arthropod lineages but it seems that a NOX2-like gene was lost in the ancestral lineage leading to Ecdysozoa. The NOX4-art gene originated from a NOX4-like ancestor and is functional. Although no p22-phox was observed in arthropods, there was no evidence of neo-functionalization and this gene probably produces H 2 O 2 as in other metazoan NOX4 genes. Although functional and present in the genomes of many

  3. Deregulated expression of p16INK4a and p53 pathway members in benign and malignant myoepithelial tumours of the salivary glands

    NARCIS (Netherlands)

    Vékony, H.; Röser, K.; Löning, T.; Raaphorst, F.M.; Leemans, C.R.; van der Waal, I.; Bloemena, E.

    2008-01-01

    Aims: Myoepithelial salivary gland tumours are uncommon and follow an unpredictable biological course. The aim was to examine their molecular background to acquire a better understanding of their clinical behaviour. Methods and results: Expression of protein (E2F1, p16INK4a, p53, cyclin D1, Ki67 and

  4. Cometary science. The organic-rich surface of comet 67P/Churyumov-Gerasimenko as seen by VIRTIS/Rosetta.

    Science.gov (United States)

    Capaccioni, F; Coradini, A; Filacchione, G; Erard, S; Arnold, G; Drossart, P; De Sanctis, M C; Bockelee-Morvan, D; Capria, M T; Tosi, F; Leyrat, C; Schmitt, B; Quirico, E; Cerroni, P; Mennella, V; Raponi, A; Ciarniello, M; McCord, T; Moroz, L; Palomba, E; Ammannito, E; Barucci, M A; Bellucci, G; Benkhoff, J; Bibring, J P; Blanco, A; Blecka, M; Carlson, R; Carsenty, U; Colangeli, L; Combes, M; Combi, M; Crovisier, J; Encrenaz, T; Federico, C; Fink, U; Fonti, S; Ip, W H; Irwin, P; Jaumann, R; Kuehrt, E; Langevin, Y; Magni, G; Mottola, S; Orofino, V; Palumbo, P; Piccioni, G; Schade, U; Taylor, F; Tiphene, D; Tozzi, G P; Beck, P; Biver, N; Bonal, L; Combe, J-Ph; Despan, D; Flamini, E; Fornasier, S; Frigeri, A; Grassi, D; Gudipati, M; Longobardo, A; Markus, K; Merlin, F; Orosei, R; Rinaldi, G; Stephan, K; Cartacci, M; Cicchetti, A; Giuppi, S; Hello, Y; Henry, F; Jacquinod, S; Noschese, R; Peter, G; Politi, R; Reess, J M; Semery, A

    2015-01-23

    The VIRTIS (Visible, Infrared and Thermal Imaging Spectrometer) instrument on board the Rosetta spacecraft has provided evidence of carbon-bearing compounds on the nucleus of the comet 67P/Churyumov-Gerasimenko. The very low reflectance of the nucleus (normal albedo of 0.060 ± 0.003 at 0.55 micrometers), the spectral slopes in visible and infrared ranges (5 to 25 and 1.5 to 5% kÅ(-1)), and the broad absorption feature in the 2.9-to-3.6-micrometer range present across the entire illuminated surface are compatible with opaque minerals associated with nonvolatile organic macromolecular materials: a complex mixture of various types of carbon-hydrogen and/or oxygen-hydrogen chemical groups, with little contribution of nitrogen-hydrogen groups. In active areas, the changes in spectral slope and absorption feature width may suggest small amounts of water-ice. However, no ice-rich patches are observed, indicating a generally dehydrated nature for the surface currently illuminated by the Sun. Copyright © 2015, American Association for the Advancement of Science.

  5. InP tunnel junction for InGaAs/InP tandem solar cells

    Science.gov (United States)

    Vilela, M. F.; Freundlich, A.; Bensaoula, A.; Medelci, N.; Renaud, P.

    1995-01-01

    Chemical beam epitaxy (CBE) has been shown to allow the growth of high quality materials with reproducible complex compositional and doping profiles. The main advantage of CBE compared to metalorganic chemical vapor deposition (MOCVD), the most popular technique for InP-based photovoltaic device fabrication, is the ability to grow high purity epilayers at much lower temperatures (450-530 C). We have previously shown that CBE is perfectly suited toward the fabrication of complex photovoltaic devices such as InP/InGaAs monolithically integrated tandem solar cells, because its low process temperature preserves the electrical characteristics of the InGaAs tunnel junction commonly used as an ohmic interconnect. In this work using CBE for the fabrication of optically transparent (with respect to the bottom cell) InP tunnel diodes is demonstrated. Epitaxial growth were performed in a Riber CBE 32 system using PH3 and TMIn as III and V precursors. Solid Be (p-type) and Si (n-type) have been used as doping sources, allowing doping levels up to 2 x 10(exp -19)/cu cm and 1 x 10(exp -19)/cu cm for n and p type respectively. The InP tunnel junction characteristics and the influence of the growth's conditions (temperature, growth rate) over its performance have been carefully investigated. InP p(++)/n(++) tunnel junction with peak current densities up to 1600 A/sq cm and maximum specific resistivities (V(sub p)/I(sub p) - peak voltage to peak current ratio) in the range of 10(exp -4) Omega-sq cm were obtained. The obtained peak current densities exceed the highest results previously reported for their lattice matched counterparts, In(0.53)Ga( 0.47)As and should allow the realization of improved minimal absorption losses in the interconnect InP/InGaAs tandem devices for Space applications. Owing to the low process temperature required for the top cell, these devices exhibit almost no degradation of its characteristics after the growth of subsequent thick InP layer suggesting

  6. Sphingosine 1-phosphate-induced ICAM-1 expression via NADPH oxidase/ROS-dependent NF-kappaB cascade on human pulmonary alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Chin-Chung eLin

    2016-03-01

    Full Text Available The intercellular adhesion molecule-1 (ICAM-1 expression is frequently correlated with the lung inflammation. A bioactive sphingolipid metabolite, sphingosine-1-phosphate (S1P, was involved in inflammation through the adhesion molecules induction, and then caused lung injury. However, the transduction mechanisms of the S1P stimulation to induce ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs remain unclear. Here, we demonstrated that exposure of HPAEpiCs to S1P significantly induces ICAM-1 expression leading to increase monocyte adhesion on the surface of HPAEpiCs. These phenomena were effectively attenuated by pretreatments with series of inhibitors such as Rottlerin (PKCdelta, PF431396 (PYK2, diphenyleneiodonium chloride (DPI, apocynin (NADPH oxidase, Edaravone (ROS, and Bay11-7082 (NF-kappaB. Consistently, knockdown with siRNA transfection of PKCdelta, PYK2, p47phox, and p65 exhibited the same results. Pretreatment with both Gq-coupled receptor antagonist (GPA2A and Gi/o-coupled receptor antagonist (GPA2 also blocked S1P-induced ICAM-1 protein and mRNA expression. We observed that S1P induced PYK2 activation via a Gq-coupled receptor/PKCdelta-dependent pathway. In addition, S1P induced NADPH oxidase activation and intracellular ROS generation, which were also reduced by Rottlerin or PF431396. We demonstrated that S1P induced NF-kappaB p65 phosphorylation and translocation from the cytosol to the nucleus in HPAEpiCs, which was inhibited by Rottlerin, PF431396, APO, DPI, or Edaravone. In the in vitro study, we established that S1P induced monocyte adhesion via an ICAM-1-dependent pathway. In the in vivo study, we found that S1P induced ICAM-1 protein and mRNA levels in the lung fractions, pulmonary hematoma, and leukocyte (mainly eosinophils and neutrophils count in bronchoalveolar lavage (BAL fluid in mice via a PKCdelta/PYK2/NADPH oxidase/ROS/NF-kappaB signaling pathway. We concluded that S1P may induce lung

  7. pH-adjustment strategy for volatile fatty acid production from high-strength wastewater for biological nutrient removal.

    Science.gov (United States)

    Xie, Li; Liu, Hui; Chen, Yin-Guang; Zhou, Qi

    2014-01-01

    Volatile fatty acid (VFA) production from three types of high-strength organic wastewater (cassava thin stillage, starch wastewater and yellow-wine processing wastewater) were compared. The results showed that cassava thin stillage was the most suitable substrate, based on its high specific VFA production (0.68 g chemical oxygen demand (COD)/g initial soluble chemical oxygen demand (SCOD)) and yield (0.72 g COD/g SCOD) as well as low nutrient content in the substrate and fermented liquid. The acid fermented cassava thin stillage was evaluated and compared with sodium acetate in a sequencing batch reactor system. Total nitrogen removal efficiency was higher with fermented cassava thin stillage than with the sodium acetate. The effects of pH and a pH-adjustment strategy on VFA production and composition were determined using cassava thin stillage. At an initial pH range of 7-11, a relatively high VFA concentration of about 9 g COD/L was obtained. The specific VFA production (g COD/g initial SCOD) increased from 0.27 to 0.47 to 0.67 at pH 8 and from 0.26 to 0.68 to 0.81 at pH 9 (initial pH, interval pH, and constant pH adjustment, respectively). The dominant VFA species changed significantly with the increasing frequency of the pH adjustment. Further studies will examine the metabolic pathways responsible for VFA composition.

  8. Multiparticle jets from π+/K+/p p collisions at 147 GeV/C compared to e+e- annihilations

    Science.gov (United States)

    Ratti, Sergio P.

    1981-02-01

    The data presented here have been collected by the International Hybrid Spectrometer Consortium in the 30″ B.C. hybrid spectrometer exposed to a 147 GeV/C positive tagged beam made of 47% π+; 45% p; 8% K+(?s = 16.7 GeV) at Fermilab. The sample consists of 15802 events with at least 4 prongs (11822 events with at least 6 prongs) fully measured and reconstructed with an accuracy Δp/phardron hadron physics was suggested long ago.

  9. Attenuation of short-period P, PcP, ScP, and pP waves in the earth's mantle

    International Nuclear Information System (INIS)

    Bock, G.; Clements, J.R.

    1982-01-01

    The parameter t* (ratio of body wave travel time to the average quality factor Q) was estimated under various assumptions of the nature of the earthquake sources for short-period P, PcP, and ScP phases originating from earthquakes in the Fiji-Tonga region and recorded at the Warramunga Seismic Array at Tennant Creek (Northern Territory, Australia). Spectral ratios were calculated for the amplitudes of PcP to P and of pP to P. The data reveal a laterally varying Q structure in the Fiji-Tonga region. The high-Q lithosphere descending beneath the Tonga Island arc is overlain above 350 km depth by a wedgelike zone of high attenuation with an average Q/sub α/ between 120 and 200 at short periods. The upper mantle farther to the west of the Tonga island arc is less attenuating, with Q/sub α/, between 370 and 560. Q/sub α/ is about 500 in the upper mantle on the oceanic side of the subduction zone. The t* estimates of this study are much smaller than estimates from the free oscillation model SL8. This can be partly explained by regional variations of Q in the upper mantle. If no lateral Q variations occur in the lower mantle, a frequency-dependent Q can make the PcP and ScP observations consistent with model SL8. Adopting the absorption band model to describe the frequency dependence of Q, the parameter tau 2 , the cut-off period of the high-frequency end of the absorption band, was determined. For different source models with finite corner frequencies, the average tau 2 for the mantle is between 0.01 and 0.10 s (corresponding to frequencies between 16 and 1.6 Hz) as derived from the PcP data, and between 0.06 and 0.12 s (2.7 and 1.3 Hz), as derived from the ScP data

  10. Correlation between p53 expression and clinical-pathological characteristics of gastric cancer

    Directory of Open Access Journals (Sweden)

    Radovanović Dragče

    2011-01-01

    Full Text Available Backgraund/Aim. Gene p53, or “cell genome keeper”, has a preventive effect on the occurrence of genetic aberrations and prevents abnormal expansion of (tumor cells. In gastric cancer cells in most cases we register high expression of mutated p53 gene, which correlates with prognosis and specific clinicalpathological characteristics of gastric cancer. Methods. Using the imunohistochemical method we determined the level of expression of p53 protein in 62 gastric cancers and 30 precancerous conditions (intestinal metaplasia of the stomach. We analyzed the relationship of the level of p53 expression and clinical pathological characteristics of gastric cancer. Results. Expression of p53 was positive in 42 (67.7% tumor cases and in 7 (14.3% cases of intestinal metaplasia. Expression of P53 and stomach cancer were in direct correlation (p = 0.000. Sensitivity for p53 in stomach cancer cases was 67.7% (42/62, and specifility was 76.7% (23/30. Expression of mutated p53 protein was in direct correlation with the invasion of lymph nodes (p = 0.034 and with invasion of blood vessels by carcinoma cells (p = 0.042. Conclusion. There is a direct correlation between p53 expression and gastric cancer and it indicates the ability of carcinoma cells to invade blood vessels.

  11. Speciation, uptake and toxicity of uranium in Atlantic Salmon (Salmo salar)

    Energy Technology Data Exchange (ETDEWEB)

    Teien, Hans-Christian; Hertel-Aas, Turid; Lind, Ole Christian; Skipperud, Lindis; Oughton, Deborah H.; Salbu, Brit [Norwegian University of Life Sciences (NMBU), Center of Excellence in Environmental Radioactivity (CERAD). P.O. Box 5003, N-1432 Aas (Norway); Thoerring, Haavard [Norwegian Radiation Protection Authority (NRPA), P.O. Box 55, N-1332 Oesteraas (Norway)

    2014-07-01

    To obtain information about the bioavailability of uranium (U) and its chemical toxicity, a significant number of Atlantic Salmon (Salmo salar) juveniles (in total about 800 fish) were exposure to commercial available depleted uranium (DU) in controlled experiments conducted in accordance with the OECD guidelines for acute toxicity tests. Speciation, gill accumulation and induced toxicity of U as a function of varying water concentrations of H{sup +}, Ca{sup 2+}, Mg{sup 2+}, Na{sup +} and K{sup +} as well as U were studied. In addition to recording mortality, blood samples were collected and analysed for general stress parameters (plasma Cl and glucose) prior to fish dissection and collection of different tissues. The observed dose-response demonstrated that varying concentrations of K{sup +}, Na{sup +} or Mg{sup 2+} had no apparent effect on the U induced toxicity in terms of 96 h LC50-values. U toxicity was, however, strongly dependent on pH. Reducing pH from about 6.7 to 6.0 or 5.5 reduced the LC50-value from 3.1 to 1.4 mg U/l. However, by increasing pH to 7.9, LC50-values increased to 25 mg/L. Fractionation of the exposure waters, demonstrated that U was present as dissolved species less than 10 kDa in size predominantly as anion, and that a fraction (30%) was present as U colloids ( 3-10 kDa). Furthermore, U accumulated in fish gills, and the accumulation of U in the fish gills increased with increasing U concentration in the water. U accumulation at >50 μg U/g dry weight gill was correlated with ion regulation problems and stress response in fish, reflected by reduced plasma Cl concentration and increased blood glucose, and mortality was observed at concentration levels >300 μg/g gill dry weight. Thus, toxic effects in fish were correlated to U concentration in gills, and the concentration of U in gills was highly dependent upon pH in water and the U speciation. As presented in detail on a poster at the present conference (Cagno et al.), U did not only

  12. 30 pJ/b, 67 Mbps, Centimeter-to-Meter Range Data Telemetry With an IR-UWB Wireless Link.

    Science.gov (United States)

    Ebrazeh, Ali; Mohseni, Pedram

    2015-06-01

    This paper reports an energy-efficient, impulse radio ultra wideband (IR-UWB) wireless link operating in 3-5 GHz for data telemetry over centimeter-to-meter range distances at rates extended to tens of Mbps. The link comprises an all-digital, integrated transmitter (TX) fabricated in 90 nm 1P/9M CMOS that incorporates a waveform-synthesis pulse generator and a timing generator for on-off-keying (OOK) pulse modulation and phase scrambling. The link also incorporates an energy-detection receiver (RX) realized with commercial off-the-shelf (COTS) components that performs radio-frequency (RF) filtering, amplification, logarithmic power detection for data demodulation and automatic level control for robust operation in the presence of distance variations. Employing a miniaturized, UWB, chip antenna for the TX and RX, wireless transmission of pseudo-random binary sequence (PRBS) data at rates up to 50 Mbps over 10 cm-1 m is shown. Further, employing a high-gain horn antenna for the RX, wireless transmission of PRBS data at rates up to 67 Mbps over 50 cm-4 m is shown with a TX energy consumption of 30 pJ/b (i.e., power consumption of 2 mW) from 1.2 V. The measured bit error rate (BER) in both cases is wireless recording of the background current of a carbon-fiber microelectrode (CFM) in one fast-scan cyclic voltammetry (FSCV) scan using the IR-UWB link are also included, exhibiting excellent match with those obtained from a conventional frequency-shift-keyed (FSK) link at ~433 MHz.

  13. Di-μ-iodido-bis{[(R-(+-2,2′-bis(diphenylphosphanyl-1,1′-binaphthyl-κ2P,P′]copper(I} 0.67-hydrate

    Directory of Open Access Journals (Sweden)

    Daniel Volz

    2012-04-01

    Full Text Available The structure of the title compound, [Cu2I2(C44H32P22]·0.67H2O, has been determined because of its interesting catalytic and optical features. The molecule, which has non-crystallographic C2-symmetry, consists of a core structure of two CuI ions, bridged by two iodide ions. Each CuI ion is also coordinated by one equivalent of the chiral bidentate (R-BINAP ligand [BINAP = 2,2′-bis(diphenylphosphanyl-1,1′-binaphthyl]. Thus, both cations show a distorted tetrahedral geometry being surrounded by two I atoms and two P atoms from the (R-BINAP ligands. The complex consists of isolated butterfly-shaped molecules featuring an angle of 146.11 (2° between adjacent CuI2 planes. The structure displays intramolecular C—H...I hydrogen bonding and contains disordered water. The absolute configuration of this chiral complex was determined by anomalous dispersion effects.

  14. Accurate accelerator energy calibration using selected resonances in proton elastic scattering and in (p,γ) and (p,p‧γ) reactions

    Science.gov (United States)

    Paneta, V.; Kokkoris, M.; Lagoyannis, A.; Preketes-Sigalas, K.

    2017-09-01

    The present work aims at contributing to the field of Ion Beam Analysis by providing a set of standard, high-accuracy nuclear resonance reaction data points to be used for accelerator energy calibration up to 4.6 MeV, more specifically with the use of the 27Al(p,γ), 13C(p,γ), 12C(p,p0) and 32S(p,p‧γ) resonant reactions, as a result of a comprehensive investigation in two different laboratories. The use of resonances at higher energies, namely up to 6 MeV, is also discussed. The measurements have been performed at two different electrostatic accelerators, namely at the 5.5 MV HV TN-11 of NCSR "Demokritos", Greece, and at the 5 MV 15SDH-2 Pelletron Tandem accelerator at Uppsala University in Uppsala, Sweden. Common points were used to normalize and validate the data. The possible use of the 16O(p,p0) resonance at 3.47 MeV is also discussed and analyzed.

  15. Chromogenic In Situ Hybridization and p16/Ki67 Dual Staining on Formalin-Fixed Paraffin-Embedded Cervical Specimens: Correlation with HPV-DNA Test, E6/E7 mRNA Test, and Potential Clinical Applications

    Directory of Open Access Journals (Sweden)

    Roberta Zappacosta

    2013-01-01

    Full Text Available Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise. In this study, we investigated the possible use of a novel HPV tyramide-based chromogenic in situ hybridization (CISH technology to locate HPV on tissue specimens. Then, we evaluate the potential usefulness of p16INK4a/Ki-67 double stain on histological samples, to identify cervical cells expressing HPV E6/E7 oncogenes. In our series, CISH showed a clear signal in 95.2% of the specimens and reached a sensitivity of 86.5%. CISH positivity always matched with HPV-DNA positivity, while 100% of cases with punctated signal joined with cervical intraepithelial neoplasia grade 2 or worse (CIN2+. p16/Ki67 immunohistochemistry gave an interpretable result in 100% of the cases. The use of dual stain significantly increased the agreement between pathologists, which reached 100%. Concordance between dual stain and E6/E7 mRNA test was 89%. In our series, both CISH and p16INK4a/Ki67 dual stain demonstrated high grade of performances. In particular, CISH would help to distinguish episomal from integrated HPV, in order to allow conclusions regarding the prognosis of the lesion, while p16INK4a/Ki67 dual stain approach would confer a high level of standardization to the diagnostic procedure.

  16. Chromogenic In Situ Hybridization and p16/Ki67 Dual Staining on Formalin-Fixed Paraffin-Embedded Cervical Specimens: Correlation with HPV-DNA Test, E6/E7 mRNA Test, and Potential Clinical Applications

    Science.gov (United States)

    Zappacosta, Roberta; Colasante, Antonella; Viola, Patrizia; D'Antuono, Tommaso; Lattanzio, Giuseppe; Capanna, Serena; Gatta, Daniela Maria Pia; Rosini, Sandra

    2013-01-01

    Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV) infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise. In this study, we investigated the possible use of a novel HPV tyramide-based chromogenic in situ hybridization (CISH) technology to locate HPV on tissue specimens. Then, we evaluate the potential usefulness of p16INK4a/Ki-67 double stain on histological samples, to identify cervical cells expressing HPV E6/E7 oncogenes. In our series, CISH showed a clear signal in 95.2% of the specimens and reached a sensitivity of 86.5%. CISH positivity always matched with HPV-DNA positivity, while 100% of cases with punctated signal joined with cervical intraepithelial neoplasia grade 2 or worse (CIN2+). p16/Ki67 immunohistochemistry gave an interpretable result in 100% of the cases. The use of dual stain significantly increased the agreement between pathologists, which reached 100%. Concordance between dual stain and E6/E7 mRNA test was 89%. In our series, both CISH and p16INK4a/Ki67 dual stain demonstrated high grade of performances. In particular, CISH would help to distinguish episomal from integrated HPV, in order to allow conclusions regarding the prognosis of the lesion, while p16INK4a/Ki67 dual stain approach would confer a high level of standardization to the diagnostic procedure. PMID:24369532

  17. Polarization measurements for P-12C elastic scattering between 40-75 MeV

    International Nuclear Information System (INIS)

    Kato, S.; Okada, K.; Kondo, M.; Shimizu, A.; Hosono, K.; Saito, T.; Matsuoka, N.; Nagamachi, S.; Nisimura, K.; Tamura, N.

    1980-01-01

    Absolute values of the polarization in p- 12 C elastic scattering have been measured at 60.0 and 64.5 MeV at 47.5 0 in the laboratory system using a double scattering method and a method to measure an asymmetry with a polarized beam. The results are P(60.0 MeV, 47.5 0 ) = 0.965 +- 0.011 and P(64.5 MeV, 47.5 0 ) = 0.975 +- 0.011. Based on these values, the polarization measurements have been extended to the energy range from 40-75 MeV at several angles around 47.5 0 using the polarized proton beam and the energy degrader. Differential cross sections and polarizations from 15-115 0 are also presented at 65 MeV. These data will be valuable for the monitoring of beam polarization in this energy region. (orig.)

  18. Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells

    Directory of Open Access Journals (Sweden)

    Sahla Belhadj

    2018-03-01

    Full Text Available Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (−48%, p < 0.001 and disruption of insulin secretion (p < 0.001 associated with of reactive oxygen species (ROS production and a modulation of pro-oxidant and antioxidant signaling pathway. Cell pre-treatments with extracts considerably increased cell viability (+86% p < 0.001 for simmondsin and +74% (p < 0.001 for aqueous extract and insulin secretion. The extracts also markedly decreased ROS (−69% (p < 0.001 for simmondsin and −59% (p < 0.001 for aqueous extract and caspase-3 activation and improved antioxidant defense, inhibiting p22phox and increasing nuclear factor (erythroid-derived 2-like 2 (Nrf2 levels (+70%, p < 0.001 for aqueous extract. Simmondsin had no impact on Nrf2 levels. The richness and diversity of molecules present in jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia.

  19. Análisis multivariado de recidiva y progresión en el carcinoma de células transicionales de vejiga en estadio T1: Valor pronóstico de p53 y ki67

    OpenAIRE

    Rodríguez Alonso, A.; Pita Fernández, S.; González Carreró, J.; Nogueira March, J.L.

    2003-01-01

    OBJETIVO: Establecer los factores pronósticos de recidiva y progresión en el carcinoma de células transicionales de vejiga en estadio T1, prestando especial atención al valor pronóstico de p53 y ki67. MATERIAL Y MÉTODOS: 175 pacientes con tumor vesical incidente de la categoría T1. El estudio inmunohistoquímico fue realizado con los anticuerpos monoclonales DO7, para p53 y MIB-1, para ki67. Se utilizó la metodología de Kaplan-Meier y se realizó un análisis multivariado de regresión de Cox, pa...

  20. Skin pH, Atopic Dermatitis, and Filaggrin Mutations

    DEFF Research Database (Denmark)

    Bandier, Josefine; Johansen, Jeanne Duus; Petersen, Lars Jelstrup

    2014-01-01

    mutations may influence skin pH. OBJECTIVE: We aimed to determine the epidermal pH in different groups stratified by filaggrin mutations and atopic dermatitis. Further, we investigated the changes in pH according to severity of mutational status among patients with dermatitis, irrespective of skin condition....... METHODS: pH was measured with a multiprobe system pH probe (PH 905), and the study population was composed of 67 individuals, who had all been genotyped for 3 filaggrin mutations (R501X, 2282del4, R2447X). RESULTS: We found no clear pattern in relation to filaggrin mutation carrier status. Individuals...... with wild-type filaggrin displayed both the most acidic and most alkaline values independent of concomitant skin disease; however, no statistical differences between the groups were found. CONCLUSIONS: The lack of significant diversity in skin pH in relation to filaggrin mutation carrier status suggests...

  1. Dawn-dusk asymmetry induced by the Parker spiral angle in the plasma dynamics around comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Behar, E.; Tabone, B.; Nilsson, H.

    2018-05-01

    When interacting, the solar wind and the ionised atmosphere of a comet exchange energy and momentum. Our aim is to understand the influence of the average Parker spiral configuration of the solar wind magnetic field on this interaction. We compare the theoretical expectations of an analytical generalised gyromotion with Rosetta observations at comet 67P/Churyumov-Gerasimenko. A statistical approach allows one to overcome the lack of upstream solar wind measurement. We find that additionally to their acceleration along (for cometary pick-up ions) or against (for solar wind ions) the upstream electric field orientation and sense, the cometary pick-up ions are drifting towards the dawn side of the coma, while the solar wind ions are drifting towards the dusk side of the coma, independent of the heliocentric distance. The dynamics of the interaction is not taking place in a plane, as often assumed in previous works.

  2. Nuclear data for production of the therapeutic radionuclides {sup 32}P, {sup 64}Cu, {sup 67}Cu, {sup 89}Sr, {sup 9}Y and {sup 153}Sm via the (n,p) reaction: Evaluation of excitation function and its validation via integral cross-section measurement using a 14 MeV d(Be) neutron source

    Energy Technology Data Exchange (ETDEWEB)

    Al-Abyad, M. [Institut fuer Nuklearchemie, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany); Cyclotron Facility, Nuclear Research Center, Atomic Energy Authority, Cairo 13759 (Egypt); Spahn, I. [Institut fuer Nuklearchemie, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany); Institute of Experimental Physics, University of Debrecen, H-4010 Debrecen (Hungary); Sudar, S. [Institut fuer Nuklearchemie, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany); Institute of Experimental Physics, University of Debrecen, H-4010 Debrecen (Hungary); Morsy, M. [Cyclotron Facility, Nuclear Research Center, Atomic Energy Authority, Cairo 13759 (Egypt); Comsan, M.N.H. [Cyclotron Facility, Nuclear Research Center, Atomic Energy Authority, Cairo 13759 (Egypt); Csikai, J. [Institute of Experimental Physics, University of Debrecen, H-4010 Debrecen (Hungary); Qaim, S.M. [Institut fuer Nuklearchemie, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany)]. E-mail: s.m.qaim@fz-juelich.de; Coenen, H.H. [Institut fuer Nuklearchemie, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany)

    2006-06-15

    Nuclear data for production of the therapeutic radionuclides {sup 32}P, {sup 64}Cu, {sup 67}Cu, {sup 89}Sr, {sup 9}Y and {sup 153}Sm via (n,p) reactions on the target nuclei {sup 32}S, {sup 64}Zn, {sup 67}Zn, {sup 89}Y, {sup 9}Zr and {sup 153}Eu, respectively, are discussed. The available information on each excitation function was analysed. From the recommended data set for each reaction the average integrated cross section for a standard 14 MeV d(Be) neutron field was deduced. The spectrum-averaged cross section was also measured experimentally. A comparison of the integrated value with the integral measurement served to validate the excitation function within about 15%. A fast neutron source appears to be much more effective than a fission reactor for production of the above-mentioned radionuclides in a no-carrier-added form via the (n,p) process. In particular, the possibility of production of high specific activity {sup 153}Sm is discussed.

  3. Phenomenological study of the p p →π+p n reaction

    Science.gov (United States)

    Fäldt, G.; Wilkin, C.

    2018-02-01

    Fully constrained bubble chamber data on the p p →π+p n and p p →π+d reactions are used to investigate the ratio of the counting rates for the two processes as function of the p n excitation energy Q . Though it is important to include effects associated with the p -wave nature of pion production, the data are insufficient to establish unambiguously the dependence on Q . The angular distributions show the presence of higher partial waves which seem to be anomalously large at small Q . The dispersion relation method to determine scattering lengths is extended to encompass cases where, as for the p p →π+p n reaction, there is a bound state and, in a test example, it is shown that the values deduced for the low-energy neutron-proton scattering parameters are significantly influenced by the pion p -wave behavior.

  4. MOLECULAR OXYGEN IN OORT CLOUD COMET 1P/HALLEY

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, M.; Altwegg, K. [Physikalisches Institut, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland); Dishoeck, E. F. van [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands); Schwehm, G. [ESA (retired) Science Operations Department, ESTEC, Keplerlaan 1, 2201 AZ Noordwijk (Netherlands)

    2015-12-10

    Recently, the ROSINA mass spectrometer suite on board the European Space Agency's Rosetta spacecraft discovered an abundant amount of molecular oxygen, O{sub 2}, in the coma of Jupiter family comet 67P/Churyumov–Gerasimenko of O{sub 2}/H{sub 2}O = 3.80 ± 0.85%. It could be shown that O{sub 2} is indeed a parent species and that the derived abundances point to a primordial origin. Crucial questions are whether the O{sub 2} abundance is peculiar to comet 67P/Churyumov–Gerasimenko or Jupiter family comets in general, and also whether Oort cloud comets such as comet 1P/Halley contain similar amounts of molecular oxygen. We investigated mass spectra obtained by the Neutral Mass Spectrometer instrument during the flyby by the European Space Agency's Giotto probe of comet 1P/Halley. Our investigation indicates that a production rate of O{sub 2} of 3.7 ± 1.7% with respect to water is indeed compatible with the obtained Halley data and therefore that O{sub 2} might be a rather common and abundant parent species.

  5. Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation.

    Directory of Open Access Journals (Sweden)

    Naadiya Carrim

    Full Text Available We have previously shown the presence of a TRAF4/p47phox/Hic5/Pyk2 complex associated with the platelet collagen receptor, GPVI, consistent with a potential role of this complex in GPVI-dependent ROS formation. In other cell systems, NOX-dependent ROS formation is facilitated by Pyk2, which along with its closely related homologue FAK are known to be activated and phosphorylated downstream of ligand binding to GPVI.To evaluate the relative roles of Pyk2 and FAK in GPVI-dependent ROS formation and to determine their location within the GPVI signaling pathway.Human and mouse washed platelets (from WT or Pyk2 KO mice were pre-treated with pharmacological inhibitors targeting FAK or Pyk2 (PF-228 and Tyrphostin A9, respectively and stimulated with the GPVI-specific agonist, CRP. FAK, but not Pyk2, was found to be essential for GPVI-dependent ROS production and aggregation. Subsequent human platelet studies with PF-228 confirmed FAK is essential for GPVI-mediated phosphatidylserine exposure, α-granule secretion (P-selectin (CD62P surface expression and integrin αIIbβ3 activation. To determine the precise location of FAK within the GPVI pathway, we analyzed the effect of PF-228 inhibition in CRP-stimulated platelets in conjunction with immunoprecipitation and pulldown analysis to show that FAK is downstream of Lyn, Spleen tyrosine kinase (Syk, PI3-K and Bruton's tyrosine kinase (Btk and upstream of Rac1, PLCγ2, Ca2+ release, PKC, Hic-5, NOX1 and αIIbβ3 activation.Overall, these data suggest a novel role for FAK in GPVI-dependent ROS formation and platelet activation and elucidate a proximal signaling role for FAK within the GPVI pathway.

  6. Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions.

    Science.gov (United States)

    Balajthy, Zoltán; Csomós, Krisztián; Vámosi, György; Szántó, Attila; Lanotte, Michel; Fésüs, László

    2006-09-15

    Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.

  7. P P Kundu

    Indian Academy of Sciences (India)

    Synthesis and characterization of saturated polyester and nanocomposites derived from glycolyzed PET waste with varied compositions · Sunain Katoch Vinay Sharma P P Kundu · More Details Abstract Fulltext PDF. Saturated polyester resin, derived from the glycolysis of polyethyleneterephthalate (PET) was examined as ...

  8. pH-sensitive pHluorins as a molecular sensor for in situ monitoring of enzyme-catalyzed prodrug activation.

    Science.gov (United States)

    Liu, Hui; Cao, Xiaodan; Wang, Ping; Ma, Xingyuan

    2017-07-01

    This work examines the feasibility of using a pH-sensitive fluorescent protein as a molecular reporter for enzyme-catalyzed prodrug activation reaction. Specifically, a ratiometric pHluorins was examined for detection of the activity of horseradish peroxidase (HRP) for the activation of indole-3-acetic acid. The pHluorins and HRP were conjugated chemically, forming a biocatalyst with a self-reporting function. Results showed that the characteristic fluorescence intensity ratio of the conjugate shifted from 1.47 to 1.40 corresponding to the progress of the prodrug activation reaction. The effectiveness of applying the conjugate for inhibition of the growth of Bcap-37 cells was also demonstrated simultaneously with reaction monitoring. The results reveal a very promising approach to realizing in situ monitoring of enzyme activities based on pH shifting for enzyme-based prodrug therapy applications. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  9. Astrophysical s-factor measurements for 120Te(p,γ)121I and 120Te(p,n)120I reactions

    International Nuclear Information System (INIS)

    Gueray, R. T.; Oezkan, N.; Yalcin, C.; Goerres, J.; DeBoer, R.; Palumbo, A.; Tan, W. P.; Wiescher, M.; Fueloep, Zs.; Somorjai, E.; Lee, H. Y.

    2009-01-01

    Astrophysical S-factors for the 1 20Te(p,γ) 1 21I and 1 20Te(p,n) 1 20I reactions have been measured in the effective center-of-mass energies between 2.47 MeV and 7.93 MeV. Experimental data have been compared with the Hauser-Fesbach statistical model calculations obtained with the model codes NON-SMOKER and TALYS. The discrepancies between the experimental results and calculations can mainly be attributed to the optical model potentials used in the codes.

  10. Chemical Composition of the Semi-Volatile Grains of Comet 67P/Churyumov-Gerasimenko

    Science.gov (United States)

    Wurz, P.; Altwegg, K.; Balsiger, H. R.; Berthelier, J. J.; De Keyser, J.; Fiethe, B.; Fuselier, S. A.; Gasc, S.; Gombosi, T. I.; Korth, A.; Mall, U.; Reme, H.; Rubin, M.; Tzou, C. Y.

    2017-12-01

    Rosetta was in orbit of comet 67P/Churyumov-Gerasimenko from August 2014 to September 2016. On board is the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) experiment that has been continuously collecting data on the chemical composition and activity of the coma from 3.5 AU to pericentre at 1.24 AU and out again to 3.5 AU. ROSINA consists of two mass spectrometers, the Double Focusing Mass Spectrometer (DFMS) and the Reflectron-type Time-Of-Flight (RTOF), as well as the COmet Pressure Sensor (COPS). ROSINA recorded the neutral gas and thermal plasma in the comet's coma. The two mass spectrometers have high dynamic ranges and complement each other with high mass resolution, and high time resolution and large mass range. COPS measures total gas densities, bulk velocities, and gas temperatures. Occasionally, a dust grain of cometary origin enters the ion source of a ROSINA instrument where the volatile part evaporates since these ion sources are hot. The release of volatiles from cometary dust grains was observed with all three ROSINA instruments on several occasions. Because the volatile content of such a dust grain is completely evaporated after a few seconds, the RTOF instrument is best suited for the investigation of its chemical composition since complete mass spectra are recorded during this time. During the mission 9 dust grains were observed with RTOF during the October 2014 to July 2016 time period. It is estimated that these grains contain about 10-15 g of volatiles. The mass spectra were interpreted with a set of 75 molecules, with the major groups of chemical species being hydrocarbons, oxygenated hydrocarbons, nitrogen-bearing molecules, sulphur-bearing molecules, halogenated molecules and others. About 70% of these grains are depleted in water compared to the comet coma, thus, can be considered as semi-volatile dust grains, and the other about 30% are water grains. The chemical composition varies considerably from grain to grain

  11. Salars evaporation rates evaluation using isotope techniques, Bellavista Salar, Chile

    International Nuclear Information System (INIS)

    Grilli, A.; Ortiz, J.

    1989-01-01

    Long term evaporation rates are evaluated in different soil conditions at Bellavista Salar, using environmental isotope profiles (oxygen-18) of the unsaturated soil zone. The Barnes and Allison model was adapted to stratified soils under non-saturation conditions and for a non-isothermal permanent regime. To apply the proposed model, field data of the different variables were used and the evaporation rates were obtained adjunting the δ 18 O values generated by the model to those experimentally measured in the water extracted from the soil profile of the unsaturated soil zone. (author). 13 refs, 8 figs

  12. Clinical significance of cyclin-dependent kinase inhibitor p27Kip1 expression and proliferation in non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Skjødt, Karsten; Mortensen, Leif Spange

    1999-01-01

    The cyclin-dependent kinase inhibitor p27Kip1 is a negative cell cycle regulator linking extracellular growth-regulatory signals to the cell cycle machinery in G1. We investigated the pattern and prognostic value of p27Kip1 expression in a population-based group of 203 non-Hodgkin's lymphoma (NHL...... between p27Kip1 and Ki-67 expression. Low expression of p27Kip1, defined as nuclear p27Kip1 expression in lymphomas behaved differently as those with low p27Kip1...... expression tended to do better. Likewise, a high proliferation rate (Ki-67 >40%) was associated with poor survival in indolent and aggressive lymphomas. Multivariate analysis using the proportional hazards model showed that only p27Kip1, and not Ki-67, maintained independent prognostic significance...

  13. Interpretación de procesos redox en suelos sulfatados ácidos del distrito de riego del Alto Chicamocha, Boyacá

    Directory of Open Access Journals (Sweden)

    Gómez Manuel Iván

    2005-06-01

    Full Text Available <p class="MsoNormal" style="margin: 0cm 0cm 10pt; text-align: justify;">La génesis de suelos sulfatados ácidos (SSA ubicados en el valle fluvio-lacustre de la cuenca alta del Río Chicamocha (Boyacá, Colombia fue de­terminada mediante la oxidorreducción del hierro y el azufre, procesos que promueven una acidificación y modificación extremas de las características fisico­químicas del medio. Mediante el comportamiento de los parámetros: Eh (mV, pH (pH en agua, 1:1, pHox (pH en peróxido de hidrógeno al 30%, 1:1 y Al+3, se estableció la existencia de una degradación severa de estos SSA que se relacionó con la presencia de materiales orgánicos o minerales que forman parte de horizontes sulfúricos diagnósticos. La mayor parte de los horizontes sulfúricos estudiados coinciden con Eh (mV positivos >400; pH menores <3,7 y Al3+ >5 cmol· kg-1, indicadores que demuestran una fuerte evolución (oxidación y determinan las limitantes de productividad agrícola presentes en los SSA del dis­trito de riego del Alto Chicamocha.p>

  14. n-GaAs/InGaP/p-GaAs core-multishell nanowire diodes for efficient light-to-current conversion

    Energy Technology Data Exchange (ETDEWEB)

    Gutsche, Christoph; Lysov, Andrey; Regolin, Ingo; Keller, Gregor; Prost, Werner; Tegude, Franz-Josef [Department of Solid-State Electronics and CeNIDE University of Duisburg-Essen, Duisburg (Germany); Braam, Daniel; Li, Zi-An; Geller, Martin; Spasova, Marina [Department of Experimental Physics and CeNIDE University of Duisburg-Essen, Duisburg (Germany)

    2012-03-07

    Heterostructure n-GaAs/InGaP/p-GaAs core-multishell nanowire diodes are synthesized by metal-organic vapor-phase epitaxy. This structure allows a reproducible, selective wet etching of the individual shells and therefore a simplified contacting of single nanowire p-i-n junctions. Nanowire diodes show leakage currents in a low pA range and at a high rectification ratio of 3500 (at {+-}1V). Pronounced electroluminescence at 1.4 eV is measured at room temperature and gives evidence of the device quality. Photocurrent generation is demonstrated at the complete area of the nanowire p-i-n junction by scanning photocurrent microscopy. A solar-conversion efficiency of 4.7%, an open-circuit voltage of 0.5 V and a fill factor of 52% are obtained under AM 1.5G conditions. These results will guide the development of nanowire-based photonic and photovoltaic devices. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  15. Temporal Evolution of Comet 67P/Churyumov-Gerasimenko Surface Properties as Observed by VIRTIS-M from Pre-Perihelion to Post-Perihelion

    Science.gov (United States)

    Ciarniello, M.; Filacchione, G.; Capaccioni, F.; Raponi, A.; De Sanctis, M. C.; Tosi, F.; Migliorini, A.; Piccioni, G.; Cerroni, P.; Capria, M. T.; Erard, S.; Bockelee-Morvan, D.; Leyrat, C.; Arnold, G.; Barucci, M. A.; Schmitt, B.; Quirico, E.; Fornasier, S.; Kappel, D.; Longobardo, A.; Rousseau, B.; Mottola, S.

    2017-04-01

    Introduction: The Visible and Infrared Thermal Imaging Spectrometer [1] on board the Rosetta spacecraft acquired disk-resolved images of the nucleus of comet 67P/Churyumov-Gerasimenko for more than two years from August 2014 to September 2016. The observation campaigns have been carried out using both the visible (VIS) and infrared (IR) channels of the instrument covering the 0.25-5.1 μm spectral range up to May 2015 and by means of the sole VIS channel (0.25-1 μm) for the remaining part of the mission. This allowed monitoring the spectral properties of the comet surface as a function of the heliocentric distance for the inbound part of the orbit from 3.6 AU to perihelion (1.3 AU) and the outbound part up to 3.3 AU. Throughout this period the surface evolution was further complicated by the combination of the relatively large orbital eccentricity, of the irregular shape of 67P/CG's nucleus and of the inclination of its rotational axis (52° [2]) which amplify the seasonal effects. Method: The long-term variability of 67P's nucleus is described by means of spectral indicators as defined in [3] which are represented by the spectral slopes in the VIS (0.55-0.8 μm) and IR (1.2-2.0 μm) spectral ranges, the single scattering albedo at 0.55 μm [4] and the band area and band center of the 3.2 μm absorption feature [5]. These quantities are computed from photometrically corrected spectra [4], in order to remove observation geometry effects [5]. The spectral indicators are projected onto latitude-longitude maps of the nucleus at different times, in order to monitor both spatial and temporal variations. In parallel, the evolution of selected areas on 67P/CG's surface as selected by [3] is followed to monitor local variability. Preliminary results: The analysis of the VIS slope from observations taken from August 2014 to June 2016, corresponding to the Rosetta mission Medium Term Planning (MTP) observation phases from MTP006 to MTP030, indicates a progressive reduction

  16. Co-existence of t(6;13)(p21;q14.1) and trisomy 12 in chronic lymphocytic leukemia.

    Science.gov (United States)

    de Oliveira, Fábio Morato; de Figueiredo Pontes, Lorena Lobo; Bassi, Sarah Cristina; Dalmazzo, Leandro Felipe Figueiredo; Falcão, Roberto Passetto

    2012-06-01

    We report a case of a 57-year-old man diagnosed with chronic lymphocytic leukemia (CLL) and presence of a rare t(6;13)(p21;q14.1) in association with an extra copy of chromosome 12. Classical cytogenetic analysis using the immunostimulatory combination of DSP30 and IL-2 showed the karyotype 47,XY,t(6;13)(p21;q14.1), +12 in 75% of the metaphase cells. Spectral karyotype analysis (SKY) confirmed the abnormality previously seen by G-banding. Additionally, interphase fluorescence in situ hybridization using an LSI CEP 12 probe performed on peripheral blood cells without any stimulant agent showed trisomy of chromosome 12 in 67% of analyzed cells (134/200). To the best of our knowledge, the association of t(6;13)(p21;q14.1) and +12 in CLL has never been described. The prognostic significance of these new findings in CLL remains to be elucidated. However, the patient has been followed up since 2009 without any therapeutic intervention and has so far remained stable.

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

    Science.gov (United States)

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

    2009-01-07

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

  18. Variable developmental delays and characteristic facial features-A novel 7p22.3p22.2 microdeletion syndrome?

    Science.gov (United States)

    Yu, Andrea C; Zambrano, Regina M; Cristian, Ingrid; Price, Sue; Bernhard, Birgitta; Zucker, Marc; Venkateswaran, Sunita; McGowan-Jordan, Jean; Armour, Christine M

    2017-06-01

    Isolated 7p22.3p22.2 deletions are rarely described with only two reports in the literature. Most other reported cases either involve a much larger region of the 7p arm or have an additional copy number variation. Here, we report five patients with overlapping microdeletions at 7p22.3p22.2. The patients presented with variable developmental delays, exhibiting relative weaknesses in expressive language skills and relative strengths in gross, and fine motor skills. The most consistent facial features seen in these patients included a broad nasal root, a prominent forehead a prominent glabella and arched eyebrows. Additional variable features amongst the patients included microcephaly, metopic ridging or craniosynostosis, cleft palate, cardiac defects, and mild hypotonia. Although the patients' deletions varied in size, there was a 0.47 Mb region of overlap which contained 7 OMIM genes: EIP3B, CHST12, LFNG, BRAT1, TTYH3, AMZ1, and GNA12. We propose that monosomy of this region represents a novel microdeletion syndrome. We recommend that individuals with 7p22.3p22.2 deletions should receive a developmental assessment and a thorough cardiac exam, with consideration of an echocardiogram, as part of their initial evaluation. © 2017 Wiley Periodicals, Inc.

  19. Germline but macrophage-tropic CYBB mutations in kindreds with X-linked predisposition to tuberculous mycobacterial diseases

    OpenAIRE

    2011-01-01

    Abstract Germline mutations in the human CYBB gene, encoding the gp91phox subunit of the phagocyte NADPH oxidase, impair the respiratory burst of phagocytes and result in X-linked chronic granulomatous disease. We report two kindreds in which otherwise healthy male adults show X-linked recessive Mendelian susceptibility to mycobacterial diseases. These patients harbor mutations in CYBB that profoundly reduce the respiratory burst in monocyte-derived macrophages, but not in monocyte...

  20. Effects of pH upon the environmental fate of [14C]fenitrothion in an aquatic microcosm

    International Nuclear Information System (INIS)

    Fisher, S.W.

    1985-01-01

    The environmental fate of [ 14 C]fenitrothion was evaluated in aquatic microcosms held at pH 8.3 or 6.7. No general effect attributable to pH was observed; however, several significant interactions were identified. Of these, the findings that statistically higher amounts of radioactivity were present in water held at pH 6.7 and that significantly less metabolism of the parent compound occurred in the organisms at pH 8.3 were preeminent. These differences seen in metabolism and environmental fate between pH values are relatively minor and do not compromise the safety of the compound