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Sample records for alpha induced nuclear

  1. Cross sections of nuclear reactions induced by protons, deuterons, and alpha particles. Pt.6. Phosphorus

    International Nuclear Information System (INIS)

    Tobailem, Jacques.

    1981-11-01

    Cross sections are reviewed for nuclear reactions induced by protons, deuterons, and alpha particles on phosphorus targets. When necessary, published experimental data are corrected, and, when possible, excitation functions are proposed [fr

  2. Nuclear reactions induced by high-energy alpha particles

    Science.gov (United States)

    Shen, B. S. P.

    1974-01-01

    Experimental and theoretical studies of nuclear reactions induced by high energy protons and heavier ions are included. Fundamental data needed in the shielding, dosimetry, and radiobiology of high energy particles produced by accelerators were generated, along with data on cosmic ray interaction with matter. The mechanism of high energy nucleon-nucleus reactions is also examined, especially for light target nuclei of mass number comparable to that of biological tissue.

  3. Cross section measurement of alpha particle induced nuclear reactions on natural cadmium up to 52 MeV

    OpenAIRE

    Ditrói, F.; Takács, S.; Haba, H.; Komori, Y.; Aikawa, M.

    2016-01-01

    Cross sections of alpha particle induced nuclear reactions have been measured on thin natural cadmium targets foils in the energy range from 11 to 51.2 MeV. This work was a part of our systematic study on excitation functions of light ion induced nuclear reactions on different target materials. Regarding the cross sections, the alpha induced reactions are not deeply enough investigated. Some of the produced isotopes are of medical interest, others have application in research and industry. Th...

  4. Thresholds and Q values of nuclear reactions induced by neutrons, protons, deuterons, tritons, 3He ions, alpha particles, and photons

    International Nuclear Information System (INIS)

    Howerton, R.J.

    1981-01-01

    The 1977 Wapstra and Bos nuclear mass data tables were used to derive tables for thresholds and Q values of nuclear reactions induced by neutrons, protons, deuterons, tritons, 3 He ions, alpha particles, and photons. The tables are displayed on microfiche included with the report

  5. Investigation of activation cross-sections of alpha-induced nuclear reactions on natural cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Khandaker, Mayeen Uddin [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Department of Physics, University of Malaya, 50603 Kuala Lumpur (Malaysia); Kim, Kwangsoo [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Manwoo [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Research Center, Dongnam Institute of Radiological and Medical Science, Busan 619-953 (Korea, Republic of); Kim, Guinyun, E-mail: gnkim@knu.ac.kr [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2014-08-15

    We measured production cross-sections of Sn, In, and Cd radionuclides from alpha-induced reactions on {sup nat}Cd from their respective threshold to 45 MeV by using a stacked-foil activation technique at the MC-50 cyclotron of the Korea Institute of Radiological and Medical Sciences. The results were compared with the earlier measurements as well as with the theoretical values obtained from the TENDL-2012 library based on the TALYS 1.4 code. Our measurements for the {sup 110,113g,117m}Sn, {sup 108m,108g,109g,110m,110g,111g,113m,114m,115m,116m,117m,117g}In, and {sup 111m,115g}Cd radionuclides in the energy region from the threshold energy to 45 MeV are in general good agreement with the other experimental data and calculated results. The integral yields for thick target were also deduced using the measured cross-sections and the stopping power of natural cadmium target and found in agreement with the directly measured yields available in the literature. The measured cross-sections find importance in various practical applications including nuclear medicine and improvement of nuclear model calculations.

  6. Cross section measurement of alpha particle induced nuclear reactions on natural cadmium up to 52MeV.

    Science.gov (United States)

    Ditrói, F; Takács, S; Haba, H; Komori, Y; Aikawa, M

    2016-12-01

    Cross sections of alpha particle induced nuclear reactions have been measured on thin natural cadmium targets foils in the energy range from 11 to 51.2MeV. This work was a part of our systematic study on excitation functions of light ion induced nuclear reactions on different target materials. Regarding the cross sections, the alpha induced reactions are not deeply enough investigated. Some of the produced isotopes are of medical interest, others have application in research and industry. The radioisotope 117m Sn is a very important theranostic (therapeutic + diagnostic) radioisotope, so special care was taken to the results for that isotope. The well-established stacked foil technique followed by gamma-spectrometry with HPGe gamma spectrometers were used. The target and monitor foils in the stack were commercial high purity metal foils. From the irradiated targets 117m Sn, 113 Sn, 110 Sn, 117m,g In, 116m In, 115m In, 114m In, 113m In, 111 In, 110m,g In, 109m In, 108m,g In, 115g Cd and 111m Cd were identified and their excitation functions were derived. The results were compared with the data of the previous measurements from the literature and with the results of the theoretical nuclear reaction model code calculations TALYS 1.8 (TENDL-2015) and EMPIRE 3.2 (Malta). From the cross section curves thick target yields were calculated and compared with the available literature data. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. In-beam study of the rotational states in actinides after alpha-induced nuclear reactions

    International Nuclear Information System (INIS)

    Hardt, K.

    1983-01-01

    In the experiments described in this thesis the ground state rotational bands of a whole series of actinide isotopes has been studied by means of α-induced nuclear reactions. The rotational bands studied in the even isotopes could be identified up to a spin of about 16 (h/2π). With this data it was now possible to establish a broad systematic of the rotational energies up to relatively high angular momenta. Also in the odd isotopes 233 U and 239 Pu it was possible to follow the ground state rotational bands up to higher spins and to compare them with predictions of the rotational model. By means of the (α,α'2n) reaction the nuclei 230 Th and especially 228 Th could by populated. (orig./HSI) [de

  8. The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Beggs, Kevin M., E-mail: kbeggs2@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, 4052 HLSIC, Kansas City, KS 66160 (United States); McGreal, Steven R., E-mail: smcgreal@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, 4052 HLSIC, Kansas City, KS 66160 (United States); McCarthy, Alex [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, 4052 HLSIC, Kansas City, KS 66160 (United States); Gunewardena, Sumedha, E-mail: sgunewardena@kumc.edu [Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, 2027 HLSIC, Kansas City, KS 66160 (United States); Lampe, Jed N., E-mail: jlampe@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, 4052 HLSIC, Kansas City, KS 66160 (United States); Lau, Christoper, E-mail: lau.christopher@epa.gov [Developmental Toxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Apte, Udayan, E-mail: uapte@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, 4052 HLSIC, Kansas City, KS 66160 (United States)

    2016-08-01

    Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), chemicals present in a multitude of consumer products, are persistent organic pollutants. Both compounds induce hepatotoxic effects in rodents, including steatosis, hepatomegaly and liver cancer. The mechanisms of PFOA- and PFOS-induced hepatic dysfunction are not completely understood. We present evidence that PFOA and PFOS induce their hepatic effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α). Human hepatocytes treated with PFOA and PFOS at a concentration relevant to occupational exposure caused a decrease in HNF4α protein without affecting HNF4α mRNA or causing cell death. RNA sequencing analysis combined with Ingenuity Pathway Analysis of global gene expression changes in human hepatocytes treated with PFOA or PFOS indicated alterations in the expression of genes involved in lipid metabolism and tumorigenesis, several of which are regulated by HNF4α. Further investigation of specific HNF4α target gene expression revealed that PFOA and PFOS could promote cellular dedifferentiation and increase cell proliferation by down regulating positive targets (differentiation genes such as CYP7A1) and inducing negative targets of HNF4α (pro-mitogenic genes such as CCND1). Furthermore, in silico docking simulations indicated that PFOA and PFOS could directly interact with HNF4α in a similar manner to endogenous fatty acids. Collectively, these results highlight HNF4α degradation as novel mechanism of PFOA and PFOS-mediated steatosis and tumorigenesis in human livers. - Highlights: • PFOA and PFOS cause decreased HNF4α protein expression in human hepatocytes. • PFOA and PFOS promote changes associated with lipid metabolism and carcinogenesis. • PFOA and PFOS induced changes in gene expression associated with cellular dedifferentiation. • PFOA and PFOS induce expression of Nanog, a transcription factor involved in stem cell development.

  9. Hantaan Virus Nucleocapsid Protein Binds to Importin alpha Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B

    Science.gov (United States)

    2008-11-19

    Microbiology . All Rights Reserved. Hantaan Virus Nucleocapsid Protein Binds to Importin Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced...Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702,1 and Department of Microbiology , Mount Sinai...34–36. 32. Prescott , J., C. Ye, G. Sen, and B. Hjelle. 2005. Induction of innate immune response genes by Sin Nombre hantavirus does not require

  10. Additional evaluation of alpha induced neutron production nuclear data. 9Be, 27Al, 28,29,30Si

    International Nuclear Information System (INIS)

    Murata, Toru; Shibata, Keiichi

    2005-01-01

    Alpha particle induced neutron production cross sections, emitted neutron energy spectrum and angular distributions were evaluated for the target nucleus 9 Be, 27 Al and Si isotopes; 28 Si, 29 Si and 30 Si in the incident energy region below 15 MeV. (author)

  11. Depletion of nuclear import protein karyopherin alpha 7 (KPNA7) induces mitotic defects and deformation of nuclei in cancer cells.

    Science.gov (United States)

    Vuorinen, Elisa M; Rajala, Nina K; Ihalainen, Teemu O; Kallioniemi, Anne

    2018-03-27

    Nucleocytoplasmic transport is a tightly regulated process carried out by specific transport machinery, the defects of which may lead to a number of diseases including cancer. Karyopherin alpha 7 (KPNA7), the newest member of the karyopherin alpha nuclear importer family, is expressed at a high level during embryogenesis, reduced to very low or absent levels in most adult tissues but re-expressed in cancer cells. We used siRNA-based knock-down of KPNA7 in cancer cell lines, followed by functional assays (proliferation and cell cycle) and immunofluorescent stainings to determine the role of KPNA7 in regulation of cancer cell growth, proper mitosis and nuclear morphology. In the present study, we show that the silencing of KPNA7 results in a dramatic reduction in pancreatic and breast cancer cell growth, irrespective of the endogenous KPNA7 expression level. This growth inhibition is accompanied by a decrease in the fraction of S-phase cells as well as aberrant number of centrosomes and severe distortion of the mitotic spindles. In addition, KPNA7 depletion leads to reorganization of lamin A/C and B1, the main nuclear lamina proteins, and drastic alterations in nuclear morphology with lobulated and elongated nuclei. Taken together, our data provide new important evidence on the contribution of KPNA7 to the regulation of cancer cell growth and the maintenance of nuclear envelope environment, and thus deepens our understanding on the impact of nuclear transfer proteins in cancer pathogenesis.

  12. Production of medically useful bromine isotopes via alpha-particle induced nuclear reactions

    Science.gov (United States)

    Breunig, Katharina; Scholten, Bernhard; Spahn, Ingo; Hermanne, Alex; Spellerberg, Stefan; Coenen, Heinz H.; Neumaier, Bernd

    2017-09-01

    The cross sections of α-particle induced reactions on arsenic leading to the formation of 76,77,78Br were measured from their respective thresholds up to 37 MeV. Thin sediments of elemental arsenic powder were irradiated together with Al degrader and Cu monitor foils using the established stacked-foil technique. For determination of the effective α-particle energies and of the effective beam current through the stacks the cross-section ratios of the monitor nuclides 67Ga/66Ga were used. This should help resolve discrepancies in existing literature data. Comparison of the data with the available excitation functions shows some slight energy shifts as well as some differences in curve shapes. The calculated thick target yields indicate, that 77Br can be produced in the energy range Eα = 25 → 17 MeV free of isotopic impurities in quantities sufficient for medical application.

  13. Production of medically useful bromine isotopes via alpha-particle induced nuclear reactions

    Directory of Open Access Journals (Sweden)

    Breunig Katharina

    2017-01-01

    Full Text Available The cross sections of α-particle induced reactions on arsenic leading to the formation of 76,77,78Br were measured from their respective thresholds up to 37 MeV. Thin sediments of elemental arsenic powder were irradiated together with Al degrader and Cu monitor foils using the established stacked-foil technique. For determination of the effective α-particle energies and of the effective beam current through the stacks the cross-section ratios of the monitor nuclides 67Ga/66Ga were used. This should help resolve discrepancies in existing literature data. Comparison of the data with the available excitation functions shows some slight energy shifts as well as some differences in curve shapes. The calculated thick target yields indicate, that 77Br can be produced in the energy range Eα = 25 → 17 MeV free of isotopic impurities in quantities sufficient for medical application.

  14. Understanding of the mechanical and structural changes induced by alpha particles and heavy ions in the French simulated nuclear waste glass

    Energy Technology Data Exchange (ETDEWEB)

    Karakurt, G., E-mail: karakurt_gokhan@yahoo.fr [SUBATECH, UMR 6457CNRS-IN2P3, Ecole des Mines de Nantes, 4 rue Alfred Kastler, 44307 Nantes (France); Abdelouas, A. [SUBATECH, UMR 6457CNRS-IN2P3, Ecole des Mines de Nantes, 4 rue Alfred Kastler, 44307 Nantes (France); Guin, J.-P.; Nivard, M. [Institut de Physique de Rennes, Université de Rennes 1 – UMR 62051 IPR, 263 avenue du Général Leclerc, 35042 Rennes (France); Sauvage, T. [Laboratoire CEMHTI (Conditions Extrêmes et Matériaux: Haute Température et Irradiation), CNRS UPR, 3079 Orléans (France); Paris, M. [Institut des Matériaux Jean ROUXEL, Université de Nantes, UMR 6502 CNRS, 2 rue de la Houssinière, BP 32229, 44322 Nantes Cedex 03 (France); Bardeau, J.-F. [Institut des Molécules et Matériaux du Mans, UMR CNRS 6283, avenue Olivier Messiaen, 72085 Le Mans (France)

    2016-07-15

    Borosilicate glasses are considered for the long-term confinement of high-level nuclear wastes. External irradiations with 1 MeV He{sup +} ions and 7 MeV Au{sup 5+} ions were performed to simulate effects produced by alpha particles and by recoil nuclei in the simulated SON68 nuclear waste glass. To better understand the structural modifications, irradiations were also carried out on a 6-oxides borosilicate glass, a simplified version of the SON68 glass (ISG glass). The mechanical and macroscopic properties of the glasses were studied as function of the deposited electronic and nuclear energies. Alpha particles and gold ions induced a volume change up to −0.7% and −2.7%, respectively, depending on the glass composition. Nano-indentations tests were used to determine the mechanical properties of the irradiated glasses. A decrease of about −22% to −38% of the hardness and a decrease of the reduced Young's modulus by −8% were measured after irradiations. The evolution of the glass structure was studied by Raman spectroscopy, and also {sup 11}B and {sup 27}Al Nuclear Magnetic Resonance (MAS-NMR) on a 20 MeV Kr irradiated ISG glass powder. A decrease of the silica network connectivity after irradiation with alpha particles and gold ions is deduced from the structural changes observations. NMR spectra revealed a partial conversion of BO{sub 4} to BO{sub 3} units but also a formation of AlO{sub 5} and AlO{sub 6} species after irradiation with Kr ions. The relationships between the mechanical and structural changes are also discussed. - Highlights: • Mechanical and structural properties of two borosilicate glass compositions irradiated with alpha particles and heavy ions were investigated. • Both kinds of particles induced a decrease of the hardness, reduced Young's modulus and density. • Electronic and nuclear interactions are responsible for the changes observed. • The evolution of the mechanical properties under irradiation is linked

  15. Understanding of the mechanical and structural changes induced by alpha particles and heavy ions in the French simulated nuclear waste glass

    International Nuclear Information System (INIS)

    Karakurt, G.; Abdelouas, A.; Guin, J.-P.; Nivard, M.; Sauvage, T.; Paris, M.; Bardeau, J.-F.

    2016-01-01

    Borosilicate glasses are considered for the long-term confinement of high-level nuclear wastes. External irradiations with 1 MeV He + ions and 7 MeV Au 5+ ions were performed to simulate effects produced by alpha particles and by recoil nuclei in the simulated SON68 nuclear waste glass. To better understand the structural modifications, irradiations were also carried out on a 6-oxides borosilicate glass, a simplified version of the SON68 glass (ISG glass). The mechanical and macroscopic properties of the glasses were studied as function of the deposited electronic and nuclear energies. Alpha particles and gold ions induced a volume change up to −0.7% and −2.7%, respectively, depending on the glass composition. Nano-indentations tests were used to determine the mechanical properties of the irradiated glasses. A decrease of about −22% to −38% of the hardness and a decrease of the reduced Young's modulus by −8% were measured after irradiations. The evolution of the glass structure was studied by Raman spectroscopy, and also 11 B and 27 Al Nuclear Magnetic Resonance (MAS-NMR) on a 20 MeV Kr irradiated ISG glass powder. A decrease of the silica network connectivity after irradiation with alpha particles and gold ions is deduced from the structural changes observations. NMR spectra revealed a partial conversion of BO 4 to BO 3 units but also a formation of AlO 5 and AlO 6 species after irradiation with Kr ions. The relationships between the mechanical and structural changes are also discussed. - Highlights: • Mechanical and structural properties of two borosilicate glass compositions irradiated with alpha particles and heavy ions were investigated. • Both kinds of particles induced a decrease of the hardness, reduced Young's modulus and density. • Electronic and nuclear interactions are responsible for the changes observed. • The evolution of the mechanical properties under irradiation is linked to the changes occured in the

  16. Nuclear magnetic resonance of D(-)-{alpha}-amino-benzyl penicillin; Ressonancia magnetica nuclear da D(-)-{alpha}-amino-benzil penicilina

    Energy Technology Data Exchange (ETDEWEB)

    Aguiar, Monica R.M.P.; Gemal, Andre L.; San Gil, Rosane A.S. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Quimica; Menezes, Sonia M.C. [PETROBRAS, Rio de Janeiro, RJ (Brazil). Centro de Pesquisas

    1995-12-31

    The development of new drugs from penicillins has induced the study of this substances by nuclear magnetic resonance. Several samples of D(-)-{alpha}-amino-benzyl penicillin were analysed using {sup 13} C NMR techniques in aqueous solution and solid state. Spectral data of this compounds were shown and the results were presented and analysed 7 figs., 4 tabs.

  17. Calculation of nuclear radius using alpha decay

    International Nuclear Information System (INIS)

    Castro, R.B. de.

    1988-01-01

    Using a Quantum Theory approach for the Alpha-Decay process, a formula is deduced for determination of the nuclear radius of the s-state, that is, a nuclear model with a spherical shell. The hypothesis that it is possible to individualize the alpha particle and the daughter nucleus at the moment of the alpha particle emission is considered. In considered in these conditions, the treatment of a two body problem considered as point particles, repelling each other by Coulomb's Law. Using the new values of the fundamental physical constants, experimentally determinated, by substitution of their numerical values in the proposed, new values of nuclear radii are obtained. These values are compared with those found in the literature. (author) [pt

  18. Neutron-induced alpha radiography

    International Nuclear Information System (INIS)

    Pereira, Marco Antonio Stanojev

    2008-01-01

    A new radiography technique to inspect thin samples was developed. Low energy alpha particles, generated by a boron based screen under thermal neutron irradiation, are used as penetrating radiation. The solid state nuclear track detector CR-39 has been used to register the image. The interaction of the α - particles with the CR-39 gives rise to damages which under an adequate chemical etching became tracks the basic units forming the image. A digital system was developed for data acquisition and data analysis as well as for image processing. The irradiation and etching conditions to obtain the best radiography are 1,3 hours and 25 minutes at 70 deg C respectively. For such conditions samples having 10 μm in thickness can be inspected with a spatial resolution of 32 μm. The use of the digital system has reduced the time spent for data acquisition and data analysis and has improved the radiography image visualization. Furthermore, by using the digital system, it was possible to study several new parameters regarding the tracks which are very important to understand and study the image formation theory in solid state nuclear track detectors, the one used in this thesis. Some radiography images are also shown which demonstrate the potential of the proposed radiography technique. When compared with the other radiography techniques already in use to inspect thin samples, the present one developed in the present paper allows a smaller time to obtain the image, it is not necessary to handle liquid radioactive substances, the detector is insensitive to β, γ, X-ray and visible light. (author)

  19. Diesel exhaust particles induce the over expression of tumor necrosis factor-alpha (TNF-alpha) gene in alvelor machrophage and failed to induce apoptosis through activation of nuclear factor-kappaB (NF-kappaB)

    Science.gov (United States)

    Exposure to particulate matter (PM2.5-10), including diesel exhaust particles (DEP) has been reported to induce lung injury and exacerbation of asthma and chronic obstructive pulmonary disease. Alveolar macrophages play a major role in the lung's response to inhaled particles and...

  20. Alpha-decay within Feshbach theory of nuclear reactions

    International Nuclear Information System (INIS)

    Sandulescu, A.; Silisteanu, I.; Wunsch, R.

    1977-01-01

    In the frame of Feshbach theory of nuclear reactions the alpha-decay widths are determined by the alpha-daughter nucleus optical potential and by the formation factors. It is shown that the calculated absolute values of the alpha widths for Po light isotopes are in good agreement with experimental data, if the real part of the optical potential with the parameters fitted by the low energy α-scattering is used

  1. Ligands specify estrogen receptor alpha nuclear localization and degradation

    Directory of Open Access Journals (Sweden)

    Caze-Subra Stéphanie

    2010-12-01

    Full Text Available Abstract Background The estrogen receptor alpha (ERα is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate. Results A MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα. Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2, and pure antagonists (selective estrogen regulator disruptor; SERD, ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM, 4-hydroxytamoxifen (OHT or RU39,411, diffuse nuclear staining persisted. Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels of ESR1 were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus. Conclusions Our results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on

  2. Flavonoids-induced accumulation of hypoxia-inducible factor (HIF)-1alpha/2alpha is mediated through chelation of iron.

    Science.gov (United States)

    Park, Sung-Soo; Bae, Insoo; Lee, Yong J

    2008-04-15

    Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the regulatory subunit of the heterodimeric transcription factor HIF-1 that is the key regulator of cellular response to low oxygen tension. Under normoxic conditions, HIF-1alpha is continuously degraded by the ubiquitin-proteasome pathway through pVHL (von Hippel-Lindau tumor suppressor protein). Under hypoxic conditions, HIF-1alpha is stabilized and induces the transcription of HIF-1 target genes. Quercetin, a flavonoid with anti-oxidant, anti-inflammatory, and kinase modulating properties, has been found to induce HIF-1alpha accumulation and VEGF secretion in normoxia. In this study, the molecular mechanisms of quercetin-mediated HIF-1alpha accumulation were investigated. Previous studies have shown that, in addition to being induced by hypoxia, HIF-1alpha can be induced through the phosphatidylinositol 3-kinase (PI3K)/Akt and p53 signaling pathways. But our study revealed, through p53 mutant-type as well as p53 null cell lines, that neither the PI3K/Akt nor the p53 signaling pathway is required for quercetin-induced HIF-1alpha accumulation. And we observed that HIF-1alpha accumulated by quercetin is not ubiquitinated and the interaction of HIF-1alpha with pVHL is reduced, compared with HIF-1alpha accumulated by the proteasome inhibitor MG132. The use of quercetin's analogues showed that only quercetin and galangin induce HIF-1/2alpha accumulation and this effect is completely reversed by additional iron ions. This is because quercetin and galangin are able to chelate cellular iron ions that are cofactors of HIF-1/2alpha proline hydroxylase (PHD). These data suggest that quercetin inhibits the ubiquitination of HIF-1/2alpha in normoxia by hindering PHD through chelating iron ions.

  3. Induced nuclear beta decay

    International Nuclear Information System (INIS)

    Reiss, H.R.

    1986-01-01

    Certain nuclear beta decay transitions normally inhibited by angular momentum or parity considerations can be induced to occur by the application of an electromagnetic field. Such decays can be useful in the controlled production of power, and in fission waste disposal

  4. High Nuclear Hypoxia-Inducible Factor 1 Alpha Expression Is a Predictor of Distant Recurrence in Patients With Resected Pancreatic Adenocarcinoma

    International Nuclear Information System (INIS)

    Colbert, Lauren E.; Fisher, Sarah B.; Balci, Serdar; Saka, Burcu; Chen, Zhengjia; Kim, Sungjin; El-Rayes, Bassel F.; Adsay, N. Volkan; Maithel, Shishir K.; Landry, Jerome C.

    2015-01-01

    Purpose: To evaluate nuclear hypoxia-inducible factor 1α (HIF-1α) expression as a prognostic factor for distant recurrence (DR) and local recurrence (LR) after pancreatic adenocarcinoma resection. Methods and Materials: Tissue specimens were collected from 98 patients with pancreatic adenocarcinoma who underwent resection without neoadjuvant therapy between January 2000 and December 2011. Local recurrence was defined as radiographic or pathologic evidence of progressive disease in the pancreas, pancreatic bed, or associated nodal regions. Distant recurrence was defined as radiographically or pathologically confirmed recurrent disease in other sites. Immunohistochemical staining was performed and scored by an independent pathologist blinded to patient outcomes. High HIF-1α overall expression score was defined as high percentage and intensity staining and thus score >1.33. Univariate analysis was performed for HIF-1α score with LR alone and with DR. Multivariate logistic regression was used to determine predictors of LR and DR. Results: Median follow-up time for all patients was 16.3 months. Eight patients (8%) demonstrated isolated LR, 26 patients (26.5%) had isolated DR, and 13 patients had both LR and DR. Fifty-three patients (54%) had high HIF-1α expression, and 45 patients (46%) had low HIF-1α expression. High HIF-1α expression was significantly associated with DR (P=.03), and low HIF-1α expression was significantly associated with isolated LR (P=.03). On multivariate logistic regression analysis, high HIF-1α was the only significant predictor of DR (odds ratio 2.46 [95% confidence interval 1.06-5.72]; P=.03). In patients with a known recurrence, an HIF-1α score ≥2.5 demonstrated a specificity of 100% for DR. Conclusions: High HIF-1α expression is a significant predictor of distant failure versus isolated local failure in patients undergoing resection of pancreatic adenocarcinoma. Expression of HIF-1α may have utility in determining candidates for

  5. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xia, E-mail: zhongxia1977@126.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Li, Xiaonan; Liu, Fuli; Tan, Hui [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Shang, Deya, E-mail: wenhuashenghuo1@163.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

  6. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, Allan Randrup

    2000-01-01

    with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...

  7. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis.

    Science.gov (United States)

    Lee, Dae-Hee; Lee, Yong J

    2008-10-01

    Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF-1alpha accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX-1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia-induced secretion of VEGF. Suppression of HIF-1alpha accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O(2)) in the presence of 100 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. (c) 2008 Wiley-Liss, Inc.

  8. Alpha-contaminated waste from reprocessing of nuclear fuel

    International Nuclear Information System (INIS)

    Sumner, W.

    1982-01-01

    The anticipated alpha-waste production rates from the Barnwell Nuclear Fuel Reprocessing plant is discussed. The estimated alpha-waste production rate from the 1500 metric ton/year plant is about 85,000 ft 3 /year at the 10 nCi/g limit. Most of this waste is estimated to come from the separation facility, and the major waste sources were cladding, which was 27%, and low-level contact-handled general process trash, which was estimated at 32% of the total. It was estimated that 45% of the waste was combustible and 72% of the waste was compactible. These characteristics could have a significant impact on the final volumes as disposed. Changing the alpha-waste limit from 10 nCi/g to 100 nCi/g was estimated to reduce the amount of alpha waste produced by about 20%. Again, the uncertainty in this value obviously has to be substantial. One has to recognize that these estimates were just that; they were not based on any operating experience. The total plutonium losses to waste, including the high-level waste, was estimated to be 1.5%. The cladding waste was estimated to be contaminated with alpha emitters to the extent of 10 4 to 10 5 nCi/g

  9. Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

    Science.gov (United States)

    Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

    2009-11-01

    To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

  10. Excitation functions of alpha particles induced nuclear reactions on natural titanium in the energy range of 10.4–50.2 MeV

    International Nuclear Information System (INIS)

    Usman, Ahmed Rufai; Khandaker, Mayeen Uddin; Haba, Hiromitsu; Otuka, Naohiko; Murakami, Masashi

    2017-01-01

    Highlights: • Detailed presentation of new results on experimental cross-sections of "n"a"tTi(α,x) processes. • Calculations of thick target yields for scandium and other radionuclides via the "n"a"tTi(α,x) production route. • Comparison with TENDL-2015 library. • Detailed review of previous experimental data. - Abstract: We studied the excitation functions of residual radionuclide productions from α particles bombardment on natural titanium in the energy range of 10.4–50.2 MeV. A well-established stacked-foil activation technique combined with HPGe γ-ray spectrometry was used to measure the excitation functions for the "5"1","4"9","4"8Cr, "4"8V, "4"3K, and "4"3","4"4"m","4"4"g","4"6"g"+"m","4"7","4"8Sc radionuclides. The thick target yields for all assessed radionuclides were also calculated. The obtained experimental data were compared with the earlier experimental ones and also with the evaluated data in the TENDL-2015 library. A reasonable agreement was found between this work and some of the previous ones, while a partial agreement was found with the evaluated data. The present results would further enrich the experimental database and facilitate the understanding of existing discrepancies among the previous measurements. The results would also help to enhance the prediction capability of the nuclear reaction model codes.

  11. Excitation functions of alpha particles induced nuclear reactions on natural titanium in the energy range of 10.4–50.2 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Usman, Ahmed Rufai [Department of Physics, University of Malaya, 50603 Kuala Lumpur (Malaysia); Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan); Department of Physics, Umaru Musa Yar' adua University, Katsina (Nigeria); Khandaker, Mayeen Uddin, E-mail: mu_khandaker@um.edu.my [Department of Physics, University of Malaya, 50603 Kuala Lumpur (Malaysia); Haba, Hiromitsu [Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan); Otuka, Naohiko [Nuclear Data Section, Division of Physical and Chemical Sciences, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, A-1400 Vienna (Austria); Murakami, Masashi [Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan)

    2017-05-15

    Highlights: • Detailed presentation of new results on experimental cross-sections of {sup nat}Ti(α,x) processes. • Calculations of thick target yields for scandium and other radionuclides via the {sup nat}Ti(α,x) production route. • Comparison with TENDL-2015 library. • Detailed review of previous experimental data. - Abstract: We studied the excitation functions of residual radionuclide productions from α particles bombardment on natural titanium in the energy range of 10.4–50.2 MeV. A well-established stacked-foil activation technique combined with HPGe γ-ray spectrometry was used to measure the excitation functions for the {sup 51,49,48}Cr, {sup 48}V, {sup 43}K, and {sup 43,44m,44g,46g+m,47,48}Sc radionuclides. The thick target yields for all assessed radionuclides were also calculated. The obtained experimental data were compared with the earlier experimental ones and also with the evaluated data in the TENDL-2015 library. A reasonable agreement was found between this work and some of the previous ones, while a partial agreement was found with the evaluated data. The present results would further enrich the experimental database and facilitate the understanding of existing discrepancies among the previous measurements. The results would also help to enhance the prediction capability of the nuclear reaction model codes.

  12. Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors.

    Science.gov (United States)

    Kelley, Joshua B; Talley, Ashley M; Spencer, Adam; Gioeli, Daniel; Paschal, Bryce M

    2010-08-11

    Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin alpha and importin beta. NLS cargo is recognized by importin alpha, which is bound by importin beta. Importin beta mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin beta triggers disassembly of the complex. To date, six importin alpha family members, encoded by separate genes, have been described in humans. We sequenced and characterized a seventh member of the importin alpha family of transport factors, karyopherin alpha 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin beta (IBB) is divergent, and shows stronger binding to importin beta than the IBB domains from of other importin alpha family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. KPNA7 is a novel importin alpha family member in humans that belongs to the importin alpha2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin alpha family. These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation.

  13. TIF1alpha: a possible link between KRAB zinc finger proteins and nuclear receptors

    DEFF Research Database (Denmark)

    Le Douarin, B; You, J; Nielsen, Anders Lade

    1998-01-01

    Ligand-induced gene activation by nuclear receptors (NRs) is thought to be mediated by transcriptional intermediary factors (TIFs), that interact with their ligand-dependent AF-2 activating domain. Included in the group of the putative AF-2 TIFs identified so far is TIF1alpha, a member of a new...... family of proteins which contains an N-terminal RBCC (RING finger-B boxes-coiled coil) motif and a C-terminal bromodomain preceded by a PHD finger. In addition to these conserved domains present in a number of transcriptional regulatory proteins, TIF1alpha was found to contain several protein......-protein interaction sites. Of these, one specifically interacts with NRs bound to their agonistic ligand and not with NR mutants that are defective in the AF-2 activity. Immediately adjacent to this 'NR box', TIF1alpha contains an interaction site for members of the chromatin organization modifier (chromo) family, HP...

  14. Laser induced nuclear reactions

    International Nuclear Information System (INIS)

    Ledingham, Ken; McCanny, Tom; Graham, Paul; Fang Xiao; Singhal, Ravi; Magill, Joe; Creswell, Alan; Sanderson, David; Allott, Ric; Neely, David; Norreys, Peter; Santala, Marko; Zepf, Matthew; Watts, Ian; Clark, Eugene; Krushelnick, Karl; Tatarakis, Michael; Dangor, Bucker; Machecek, Antonin; Wark, Justin

    1998-01-01

    Dramatic improvements in laser technology since 1984 have revolutionised high power laser technology. Application of chirped-pulse amplification techniques has resulted in laser intensities in excess of 10 19 W/cm 2 . In the mid to late eighties, C. K. Rhodes and K. Boyer discussed the possibility of shining laser light of this intensity onto solid surfaces and to cause nuclear transitions. In particular, irradiation of a uranium target could induce electro- and photofission in the focal region of the laser. In this paper it is shown that μCi of 62 Cu can be generated via the (γ,n) reaction by a laser with an intensity of about 10 19 Wcm -2

  15. Evidence for a Field-induced Quantum Spin Liquid in $\\alpha$-RuCl$_3$

    OpenAIRE

    Baek, S. -H.; Do, S. -H.; Choi, K. -Y.; Kwon, Y. S.; Wolter, A. U. B.; Nishimoto, S.; Brink, Jeroen van den; Büchner, B.

    2017-01-01

    We report a $^{35}$Cl nuclear magnetic resonance study in the honeycomb lattice, $\\alpha$-RuCl$_3$, a material that has been suggested to potentially realize a Kitaev quantum spin liquid (QSL) ground state. Our results provide direct evidence that $\\alpha$-RuCl$_3$ exhibits a magnetic field-induced QSL. For fields larger than $\\sim 10$ T a spin-gap opens up while resonance lines remain sharp, evidencing that spins are quantum disordered and locally fluctuating. The spin gap increases linearly...

  16. Chromosomal aberrations induced by alpha particles

    International Nuclear Information System (INIS)

    Guerrero C, C.; Brena V, M.

    2005-01-01

    The chromosomal aberrations produced by the ionizing radiation are commonly used when it is necessary to establish the exposure dose of an individual, it is a study that is used like complement of the traditional physical systems and its application is only in cases in that there is doubt about what indicates the conventional dosimetry. The biological dosimetry is based on the frequency of aberrations in the chromosomes of the lymphocytes of the individual in study and the dose is calculated taking like reference to the dose-response curves previously generated In vitro. A case of apparent over-exposure to alpha particles to which is practiced analysis of chromosomal aberrations to settle down if in fact there was exposure and as much as possible, to determine the presumed dose is presented. (Author)

  17. Induced-Fission Imaging of Nuclear Material

    International Nuclear Information System (INIS)

    Hausladen, Paul; Blackston, Matthew A.; Mullens, James Allen; McConchie, Seth M.; Mihalczo, John T.; Bingham, Philip R.; Ericson, Milton Nance; Fabris, Lorenzo

    2010-01-01

    This paper presents initial results from development of the induced-fission imaging technique, which can be used for the purpose of measuring or verifying the distribution of fissionable material in an unopened container. The technique is based on stimulating fissions in nuclear material with 14 MeV neutrons from an associated-particle deuterium-tritium (D-T) generator and counting the subsequent induced fast fission neutrons with an array of fast organic scintillation detectors. For each source neutron incident on the container, the neutron creation time and initial trajectory are known from detection of the associated alpha particle of the d + t → α + n reaction. Many induced fissions will lie along (or near) the interrogating neutron path, allowing an image of the spatial distribution of prompt induced fissions, and thereby fissionable material, to be constructed. A variety of induced-fission imaging measurements have been performed at Oak Ridge National Laboratory with a portable, low-dose D-T generator, including single-view radiographic measurements and three-dimensional tomographic measurements. Results from these measurements will be presented along with the neutron transmission images that have been performed simultaneously. This new capability may have applications to a number of areas in which there may be a need to confirm the presence or configuration of nuclear materials, such as nuclear material control and accountability, quality assurance, treaty confirmation, or homeland security applications.

  18. Modifications of the optical properties for DAM-ADC nuclear track detector exposed to alpha particles

    Science.gov (United States)

    Rammah, Y. S.; Awad, E. M.

    2018-05-01

    Modifications of the optical properties of diallyl maleate-allyl diglycol carbonate (DAM-ADC) nuclear detector induced by alpha particles are described. DAM-ADC samples were irradiated perpendicularly by thin 241Am disk source that emits alpha particles with 5.48 MeV. The optical absorption has been measured using the ultraviolet-visible (UV-1100) spectroscopy. It was found that DAM-ADC polymer shows substantial modifications in its optical characteristics upon irradiated with alpha particles with different energies. The optical energy band gap (Egap) for the detector was calculated for the direct and the indirect allowed transitions in K-space using two approaches (Tauc's model and absorption spectrum fitting (ASF) method). Urbach's energy (Ea), number of carbon atoms per conjugated length (N), number of carbon atoms per cluster (M), and refractive index (n) for the present samples were determined. Results reveal that the values of energy gap in direct transition are greater than those of indirect, before and after irradiation. (Egap), (Ea), (N), (M), and (n) of the present samples are changed significantly with irradiation time and value of alpha energy. Results reflect the possibility of using DAM-ADC polymer track detectors to estimate alpha particle energies using the variation of the absorbance.

  19. HNF4alpha dysfunction as a molecular rational for cyclosporine induced hypertension.

    Science.gov (United States)

    Niehof, Monika; Borlak, Jürgen

    2011-01-27

    Induction of tolerance against grafted organs is achieved by the immunosuppressive agent cyclosporine, a prominent member of the calcineurin inhibitors. Unfortunately, its lifetime use is associated with hypertension and nephrotoxicity. Several mechanism for cyclosporine induced hypertension have been proposed, i.e. activation of the sympathetic nervous system, endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in prostaglandin and nitric oxide, altered cytosolic calcium translocation, and activation of the renin-angiotensin system (RAS). In this regard the molecular basis for undue RAS activation and an increased signaling of the vasoactive oligopeptide angiotensin II (AngII) remain elusive. Notably, angiotensinogen (AGT) is the precursor of AngII and transcriptional regulation of AGT is controlled by the hepatic nuclear factor HNF4alpha. To better understand the molecular events associated with cyclosporine induced hypertension, we investigated the effect of cyclosporine on HNF4alpha expression and activity and searched for novel HNF4alpha target genes among members of the RAS cascade. Using bioinformatic algorithm and EMSA bandshift assays we identified angiotensin II receptor type 1 (AGTR1), angiotensin I converting enzyme (ACE), and angiotensin I converting enzyme 2 (ACE2) as genes targeted by HNF4alpha. Notably, cyclosporine represses HNF4alpha gene and protein expression and its DNA-binding activity at consensus sequences to AGT, AGTR1, ACE, and ACE2. Consequently, the gene expression of AGT, AGTR1, and ACE2 was significantly reduced as evidenced by quantitative real-time RT-PCR. While RAS is composed of a sophisticated interplay between multiple factors we propose a decrease of ACE2 to enforce AngII signaling via AGTR1 to ultimately result in vasoconstriction and hypertension. Taken collectively we demonstrate cyclosporine to repress HNF4alpha activity through calcineurin inhibitor mediated inhibition of nuclear

  20. HNF4alpha dysfunction as a molecular rational for cyclosporine induced hypertension.

    Directory of Open Access Journals (Sweden)

    Monika Niehof

    Full Text Available Induction of tolerance against grafted organs is achieved by the immunosuppressive agent cyclosporine, a prominent member of the calcineurin inhibitors. Unfortunately, its lifetime use is associated with hypertension and nephrotoxicity. Several mechanism for cyclosporine induced hypertension have been proposed, i.e. activation of the sympathetic nervous system, endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in prostaglandin and nitric oxide, altered cytosolic calcium translocation, and activation of the renin-angiotensin system (RAS. In this regard the molecular basis for undue RAS activation and an increased signaling of the vasoactive oligopeptide angiotensin II (AngII remain elusive. Notably, angiotensinogen (AGT is the precursor of AngII and transcriptional regulation of AGT is controlled by the hepatic nuclear factor HNF4alpha. To better understand the molecular events associated with cyclosporine induced hypertension, we investigated the effect of cyclosporine on HNF4alpha expression and activity and searched for novel HNF4alpha target genes among members of the RAS cascade. Using bioinformatic algorithm and EMSA bandshift assays we identified angiotensin II receptor type 1 (AGTR1, angiotensin I converting enzyme (ACE, and angiotensin I converting enzyme 2 (ACE2 as genes targeted by HNF4alpha. Notably, cyclosporine represses HNF4alpha gene and protein expression and its DNA-binding activity at consensus sequences to AGT, AGTR1, ACE, and ACE2. Consequently, the gene expression of AGT, AGTR1, and ACE2 was significantly reduced as evidenced by quantitative real-time RT-PCR. While RAS is composed of a sophisticated interplay between multiple factors we propose a decrease of ACE2 to enforce AngII signaling via AGTR1 to ultimately result in vasoconstriction and hypertension. Taken collectively we demonstrate cyclosporine to repress HNF4alpha activity through calcineurin inhibitor mediated inhibition

  1. Determination of alpha dose rate profile at the HLW nuclear glass/water interface

    Energy Technology Data Exchange (ETDEWEB)

    Mougnaud, S., E-mail: sarah.mougnaud@cea.fr [CEA Marcoule, DEN/DTCD/SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Tribet, M.; Rolland, S. [CEA Marcoule, DEN/DTCD/SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Renault, J.-P. [CEA Saclay, NIMBE UMR 3685 CEA/CNRS, 91191 Gif-sur-Yvette cedex (France); Jégou, C. [CEA Marcoule, DEN/DTCD/SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France)

    2015-07-15

    Highlights: • The nuclear glass/water interface is studied. • The way the energy of alpha particles is deposited is modeled using MCNPX code. • A model giving dose rate profiles at the interface using intrinsic data is proposed. • Bulk dose rate is a majoring estimation in alteration layer and in surrounding water. • Dose rate is high in small cracks; in larger ones irradiated volume is negligible. - Abstract: Alpha irradiation and radiolysis can affect the alteration behavior of High Level Waste (HLW) nuclear glasses. In this study, the way the energy of alpha particles, emitted by a typical HLW glass, is deposited in water at the glass/water interface is investigated, with the aim of better characterizing the dose deposition at the glass/water interface during water-induced leaching mechanisms. A simplified chemical composition was considered for the nuclear glass under study, wherein the dose rate is about 140 Gy/h. The MCNPX calculation code was used to calculate alpha dose rate and alpha particle flux profiles at the glass/water interface in different systems: a single glass grain in water, a glass powder in water and a water-filled ideal crack in a glass package. Dose rate decreases within glass and in water as distance to the center of the grain increases. A general model has been proposed to fit a dose rate profile in water and in glass from values for dose rate in glass bulk, alpha range in water and linear energy transfer considerations. The glass powder simulation showed that there was systematic overlapping of radiation fields for neighboring glass grains, but the water dose rate always remained lower than the bulk value. Finally, for typical ideal cracks in a glass matrix, an overlapping of irradiation fields was observed while the crack aperture was lower than twice the alpha range in water. This led to significant values for the alpha dose rate within the crack volume, as long as the aperture remained lower than 60 μm.

  2. Spontaneous local alpha oscillations predict motion-induced blindness.

    Science.gov (United States)

    Händel, Barbara F; Jensen, Ole

    2014-11-01

    Bistable visual illusions are well suited for exploring the neuronal states of the brain underlying changes in perception. In this study, we investigated oscillatory activity associated with 'motion-induced blindness' (MIB), which denotes the perceptual disappearance of salient target stimuli when a moving pattern is superimposed on them (Bonneh et al., ). We applied an MIB paradigm in which illusory target disappearances would occur independently in the left and right hemifields. Both illusory and real target disappearance were followed by an alpha lateralization with weaker contralateral than ipsilateral alpha activity (~10 Hz). However, only the illusion showed early alpha lateralization in the opposite direction, which preceded the alpha effect present for both conditions and coincided with the estimated onset of the illusion. The duration of the illusory disappearance was further predicted by the magnitude of this early lateralization when considered over subjects. In the gamma band (60-80 Hz), we found an increase in activity contralateral relative to ipsilateral only after a real disappearance. Whereas early alpha activity was predictive of onset and length of the illusory percept, gamma activity showed no modulation in relation to the illusion. Our study demonstrates that the spontaneous changes in visual alpha activity have perceptual consequences. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Alpha-Driven MHD and MHD-Induced Alpha Loss in TFTR DT Experiments

    Science.gov (United States)

    Chang, Zuoyang

    1996-11-01

    Theoretical calculation and numerical simulation indicate that there can be interesting interactions between alpha particles and MHD activity which can adversely affect the performance of a tokamak reactor (e.g., ITER). These interactions include alpha-driven MHD, like the toroidicity-induced-Alfven-eigenmode (TAE) and MHD induced alpha particle losses or redistribution. Both phenomena have been observed in recent TFTR DT experiments. Weak alpha-driven TAE activity was observed in a NBI-heated DT experiment characterized by high q0 ( >= 2) and low core magnetic shear. The TAE mode appears at ~30-100 ms after the neutral beam turning off approximately as predicted by theory. The mode has an amplitude measured by magnetic coils at the edge tildeB_p ~1 mG, frequency ~150-190 kHz and toroidal mode number ~2-3. It lasts only ~ 30-70 ms and has been seen only in DT discharges with fusion power level about 1.5-2.0 MW. Numerical calculation using NOVA-K code shows that this type of plasma has a big TAE gap. The calculated TAE frequency and mode number are close to the observation. (2) KBM-induced alpha particle loss^1. In some high-β, high fusion power DT experiments, enhanced alpha particle losses were observed to be correlated to the high frequency MHD modes with f ~100-200 kHz (the TAE frequency would be two-times higher) and n ~5-10. These modes are localized around the peak plasma pressure gradient and have ballooning characteristics. Alpha loss increases by 30-100% during the modes. Particle orbit simulations show the added loss results from wave-particle resonance. Linear instability analysis indicates that the plasma is unstable to the kinetic MHD ballooning modes (KBM) driven primarily by strong local pressure gradients. ----------------- ^1Z. Chang, et al, Phys. Rev. Lett. 76 (1996) 1071. In collaberation with R. Nazikian, G.-Y. Fu, S. Batha, R. Budny, L. Chen, D. Darrow, E. Fredrickson, R. Majeski, D. Mansfield, K. McGuire, G. Rewoldt, G. Taylor, R. White, K

  4. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

    Science.gov (United States)

    Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

    2007-09-01

    Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

  5. Protection against cyanide-induced convulsions with alpha-ketoglutarate.

    Science.gov (United States)

    Yamamoto, H

    1990-04-30

    Protection against convulsions induced by cyanide was observed after treatment with alpha-ketoglutarate, either alone or in combination with sodium thiosulfate, a classical antagonist for cyanide intoxication. However, sodium thiosulfate alone did not protect against cyanide (30 mg/kg)-induced convulsions. gamma-Aminobutyric acid (GABA) levels in brain were decreased by 31% in KCN-treated mice exhibiting convulsions. The combined administration of alpha-ketoglutarate and sodium thiosulfate completely abolished the decrease of GABA levels induced by cyanide. Furthermore, sodium thiosulfate alone also completely abolished the decrease of GABA levels. These results suggest that the depletion of brain GABA levels may not directly contribute to the development of convulsions induced by cyanide. On the other hand, cyanide increased calcium levels by 32% in brain crude mitochondrial fractions in mice with convulsions. The increased calcium levels were completely abolished by the combined administration of alpha-ketoglutarate and sodium thiosulfate, but not affected by sodium thiosulfate alone. These findings support the hypothesis proposed by Johnson et al. (Toxicol. Appl. Pharmacol., 84 (1986) 464) and Robinson et al. (Toxicology, 35 (1985) 59) that calcium may play an important role in mediating cyanide neurotoxicity.

  6. Inhibition of HIF-1{alpha} activity by BP-1 ameliorates adjuvant induced arthritis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, J. [Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago (United States); Thippegowda, P.B., E-mail: btprabha@uic.edu [Department of Pharmacology, (M/C 868), College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612 (United States); Kanum, S.A. [Department of Chemistry, Yuvaraj' s College, University of Mysore, Mysore (India)

    2009-09-18

    Rheumatoid arthritis (RA) is a chronic inflammatory, angiogenic disease. Inflamed synovitis is a hallmark of RA which is hypoxic in nature. Vascular endothelial growth factor (VEGF), one of the key regulators of angiogenesis, is overexpressed in the pathogenesis of RA. VEGF expression is regulated by hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), a master regulator of homeostasis which plays a pivotal role in hypoxia-induced angiogenesis. In this study we show that synthetic benzophenone analogue, 2-benzoyl-phenoxy acetamide (BP-1) can act as a novel anti-arthritic agent in an experimental adjuvant induced arthritis (AIA) rat model by targeting VEGF and HIF-1{alpha}. BP-1 administered hypoxic endothelial cells and arthritic animals clearly showed down regulation of VEGF expression. Further, BP-1 inhibits nuclear translocation of HIF-1{alpha}, which in turn suppresses transcription of the VEGF gene. These results suggest a further possible clinical application of the BP-1 derivative as an anti-arthritic agent in association with conventional chemotherapeutic agents.

  7. The T alpha 2 nuclear protein binding site from the human T cell receptor alpha enhancer functions as both a T cell-specific transcriptional activator and repressor

    OpenAIRE

    1990-01-01

    T cell-specific expression of the human T cell receptor alpha (TCR- alpha) gene is regulated by the interaction of variable region promoter elements with a transcriptional enhancer that is located 4.5 kb 3' of the TCR-alpha constant region (C alpha) gene segment. The minimal TCR- alpha enhancer is composed of two nuclear protein binding sites, T alpha 1 and T alpha 2, that are both required for the T cell-specific activity of the enhancer. The T alpha 1 binding site contains a consensus cAMP ...

  8. Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

    Science.gov (United States)

    Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

    2004-01-16

    Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

  9. Nuclear EMP induced chaos

    Energy Technology Data Exchange (ETDEWEB)

    Dance, B

    1983-08-01

    In the event of nuclear war, the availability of first class communications facilities and of reliable electricity supplies would be of absolutely vital importance to any of the population surviving the first onslaught not only for their own welfare, but also for the preservation of their nation's retaliation deterrent capability. However, it is to be expected that a single nuclear explosion of adequate size on the outside of the atmosphere would generate a pulse of sufficient intensity to damage communications equipment (including telephones, radio transmitters and receivers) and to interrupt main supplies. The situation caused by electromagnetic pulses (EMP) is discussed.

  10. Alpha particle induced soft errors in NMOS RAMs: a review

    International Nuclear Information System (INIS)

    Carter, P.M.; Wilkins, B.R.

    1987-01-01

    The paper aims to explain the alpha particle induced soft error phenomenon using the NMOS dynamic random access memory (RAM) as a model. It discusses some of the many techniques experimented with by manufacturers to overcome the problem, and gives a review of the literature covering most aspects of soft errors in dynamic RAMs. Finally, the soft error performance of current dynamic RAM and static RAM products from several manufacturers are compared. (author)

  11. Alpha particles induce expression of immunogenic markers on tumour cells

    International Nuclear Information System (INIS)

    Gorin, J.B.; Gouard, S.; Cherel, M.; Davodeau, F.; Gaschet, J.; Morgenstern, A.; Bruchertseifer, F.

    2013-01-01

    The full text of the publication follows. Radioimmunotherapy (RIT) is an approach aiming at targeting the radioelements to tumours, usually through the use of antibodies specific for tumour antigens. The radiations emitted by the radioelements then induce direct killing of the targeted cells as well as indirect killing through bystander effect. Interestingly, it has been shown that ionizing radiations, in some settings of external radiotherapy, can foster an immune response directed against tumour cells. Our research team is dedicated to the development of alpha RIT, i.e RIT using alpha particle emitters, we therefore decided to study the effects of such particles on tumour cells in regards to their immunogenicity. First, we studied the effects of bismuth 213, an alpha emitter, on cellular death and autophagy in six different tumour cell lines. Then, we measured the expression of 'danger' signals and MHC molecules at the cell surface to determine whether irradiation with 213 Bi could cause the tumour cells to be recognized by the immune system. Finally a co-culture of dendritic cells with irradiated tumour cells was performed to test whether it would induce dendritic cells to mature. No apoptosis was detected within 48 hours after irradiation in any cell line, however half of them exhibited signs of autophagy. No increase in membrane expression of 'danger' signals was observed after treatment with 213 Bi, but we showed an increase in expression of MHC class I and II for some cell lines. Moreover, the co-culture experiment indicated that the immunogenicity of a human adenocarcinoma cell line (LS 174T) was enhanced in vitro after irradiation with alpha rays. These preliminary data suggest that alpha particles could be of interest in raising an immune response associated to RIT. (authors)

  12. Measurement and analysis of $\\alpha$ particle induced reactions on yttrium

    CERN Document Server

    Singh, N L; Chintalapudi, S N

    2000-01-01

    Excitation functions for /sup 89/Y[( alpha ,3n); ( alpha ,4n); ( alpha , p3n); ( alpha , alpha n); ( alpha , alpha 2n)] reactions were measured up to 50 MeV using stacked foil activation technique and HPGe gamma ray spectroscopy method. The experimental data were compared with calculations considering equilibrium as well as preequilibrium reactions according to the hybrid model of Blann (ALICE/90). For ( alpha , xnyp) type of reactions, the precompound contributions are described by the model. There seems to be indications of direct inelastic scattering effects in ( alpha , alpha xn) type of reactions. To the best of our knowledge, the excitation functions for ( alpha ,4n), ( alpha , p3n), ( alpha , alpha n) and ( alpha , alpha 2n) reactions were measured for the first time. (23 refs).

  13. Measurement and analysis of alpha particle induced reactions on yttrium

    Energy Technology Data Exchange (ETDEWEB)

    Singh, N.L.; Gadkari, M.S. [Baroda Univ. (India). Dept. of Physics; Chintalapudi, S.N. [IUC-DAEF Calcutta Centre, Calcutta (India)

    2000-05-01

    Excitation functions for {sup 89}Y[({alpha},3n);({alpha},4n);({alpha},p3n);({alpha},{alpha}n);({alpha},{alpha}2n)] reactions were measured up to 50 MeV using stacked foil activation technique and HPGe gamma ray spectroscopy method. The experimental data were compared with calculations considering equilibrium as well as preequilibrium reactions according to the hybrid model of Blann (ALICE/90). For ({alpha},xnyp) type of reactions, the precompound contributions are described by the model. There seems to be indications of direct inelastic scattering effects in ({alpha},{alpha}xn) type of reactions. To the best of our knowledge, the excitation functions for ({alpha},4n), ({alpha},p3n), ({alpha},{alpha}n) and ({alpha},{alpha}2n) reactions were measured for the first time. (orig.)

  14. Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Weiping, E-mail: weiping.qin@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States); Cardozo, Christopher, E-mail: Chris.Cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States)

    2010-12-17

    Research highlights: {yields} In rat gastrocnemius muscle, dexamethasone reduced PGC-1{alpha} cellular and nuclear levels without altering mRNA levels for this factor. {yields} Dexamethasone reduced phosphorylating of p38 MAPK, which stabilizes PGC-1{alpha} and promotes its nuclear entry. {yields} Co-administration of testosterone with dexamethasone increased cellular and nuclear levels of PGC-1{alpha} protein without changing its mRNA levels. {yields} Co-administration of testosterone restored p38 MAPK levels to those of controls. -- Abstract: Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and reduced protein synthesis, associated with increased expression of two muscle-specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein synthesis, REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC-1{alpha} has been shown to attenuate many forms of muscle atrophy and to repress FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced muscle atrophy can be prevented by testosterone, which blocks up-regulation by dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle atrophy was used to further characterize effects of testosterone to abrogate adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to determine how these agents affect PGC-1{alpha}, and its upstream activators, p38 MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and nuclear protein. Dexamethasone reduced total and nuclear PGC-1{alpha} protein levels in the gastrocnemius; co-administration of testosterone with dexamethasone increased total and nuclear PGC-1{alpha} levels above those present in untreated controls. Testosterone blocked dexamethasone-induced decreases in activity of p38 MAPK in the gastrocnemius

  15. {alpha}-particle induced reactions on yttrium and terbium

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, S.; Kumar, B.B. [School of Studies in Physics, Vikram University, Ujjain-456010 (India); Rashid, M.H. [Variable Energy Cyclotron Center, 1/AF, Bidhan Nagar, Calcutta (India); Chintalapudi, S.N. [Inter-University Consortium for DAE Facilities, 3/LB, Bidhan Nagar, Calcutta (India)

    1997-05-01

    The stacked foil activation technique has been employed for the investigation of {alpha}-particle induced reactions on the target elements yttrium and terbium up to 50 MeV. Six excitation functions for the ({alpha},xn) type of reactions were studied using high-resolution HPGe {gamma}-ray spectroscopy. A comparison with Blann{close_quote}s geometric dependent hybrid model has been made using the initial exciton number n{sub 0}=4(4p0h) and n{sub 0}=5(5p0h). A broad general agreement is observed between the experimental results and theoretical predictions with an initial exciton number n{sub 0}=4(4p0h). {copyright} {ital 1997} {ital The American Physical Society}

  16. Nuclear EMP induced chaos

    International Nuclear Information System (INIS)

    Dance, B.

    1983-01-01

    It is anticipated that a single nuclear explosion, of adequate size, on the outside of the atmosphere would generate a pulse of sufficient intensity to damage communications equipment (including telephones, radio transmitters and receivers), and to disrupt main power supplies. This damage could be done by a very intense, short duration electro-magnetic pulse (EMP). The article discusses the generation and history of EMP, the test facilities that are needed for EMP test, and techniques that can be used to harden equipment against EMP. It is also important to protect extensive systems against EMP. The article points out that fibre-optics are very useful, because they are EMP resistant and a single fibre can also carry a very high data rate

  17. Nuclear rich alpha cellulosic waste management experiments by acid digestion

    International Nuclear Information System (INIS)

    Arnal; Cousinou; Desille; Maigret.

    1985-03-01

    At Cadarache, where the French plutonium fuel fabrication plant is located, the strategy used for the management of rich alpha waste (superior to accepted level for storage) consist in incinerating the wastes, crushed and washed by cryogenic crushing and soda-nitric solutions. Although all ''technological'' wastes could be processed this way, the cellulosic are sorted and treated separately by the sulfuric acid digestion process. This process has definite advantages, particularly since it is specific to cellulosis, which dissolves easily at low temperature, i-e under the boiling point of H 2 SO 4 . Except for this aspect, of great importance for the gaz treatment operations and the resistance of material to corrosion, the process is identical to the one given in the literature: dehydration of cellulosis by H 2 SO 4 72% and carbon oxydation by HNO 3 13N. The apparatus used hold in a small volume (10 m 3 ); the gloves-box in which the dissolver and the filtration treatments (insoluble Pu sulfate for one part, and reaction gas for the other) are placed is in stainless steel coated with corrosion proof paint; the equipments are made of glass (dissolver) teflon (flanges) PVDF (pipes) hastelloy (pompes). A general balance is given for the recuperated nuclear materials, as well as for the mass and volumes of input and output cellulosic wastes

  18. First Results of Using a UVTron Flame Sensor to Detect Alpha-Induced Air Fluorescence in the UVC Wavelength Range

    Directory of Open Access Journals (Sweden)

    Anita J. Crompton

    2017-11-01

    Full Text Available In this work, a robust stand-off alpha detection method using the secondary effects of alpha radiation has been sought. Alpha particles ionise the surrounding atmosphere as they travel. Fluorescence photons produced as a consequence of this can be used to detect the source of the alpha emissions. This paper details experiments carried out to detect this fluorescence, with the focus on photons in the ultraviolet C (UVC wavelength range (180–280 nm. A detector, UVTron R9533 (Hamamatsu, 325-6, Sunayama-cho, Naka-ku, Hamamatsu City, Shizuoka Pref., 430-8587, Japan, designed to detect the UVC emissions from flames for fire alarm purposes, was tested in various gas atmospheres with a 210Po alpha source to determine if this could provide an avenue for stand-off alpha detection. The results of the experiments show that this detector is capable of detecting alpha-induced air fluorescence in normal indoor lighting conditions, as the interference from daylight and artificial lighting is less influential on this detection system which operates below the UVA and UVB wavelength ranges (280–315 nm and 315–380 nm respectively. Assuming a standard 1 r 2 drop off in signal, the limit of detection in this configuration can be calculated to be approximately 240 mm, well beyond the range of alpha-particles in air, which indicates that this approach could have potential for stand-off alpha detection. The gas atmospheres tested produced an increase in the detector count, with xenon having the greatest effect with a measured 52% increase in the detector response in comparison to the detector response in an air atmosphere. This type of alpha detection system could be operated at a distance, where it would potentially provide a more cost effective, safer, and faster solution in comparison with traditional alpha detection methods to detect and characterise alpha contamination in nuclear decommissioning and security applications.

  19. Investigation of activation cross section data of alpha particle induced nuclear reaction on molybdenum up to 40 MeV: Review of production routes of medically relevant {sup 97,103}Ru

    Energy Technology Data Exchange (ETDEWEB)

    Tárkányi, F. [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Hermanne, A., E-mail: aherman@vub.ac.be [Cyclotron Laboratory, Vrije Universiteit Brussel, Brussels (Belgium); Ditrói, F.; Takács, S. [Institute of Nuclear Research of the Hungarian Academy of Sciences, Debrecen (Hungary); Ignatyuk, A. [Institute of Physics and Power Engineering (IPPE), Obninsk (Russian Federation)

    2017-05-15

    The main goals of this investigations were to expand and consolidate reliable activation cross-section data for the {sup nat}Mo(α,x) reactions in connection with production of medically relevant {sup 97,103}Ru and the use of the {sup nat}Mo(α,x){sup 97}Ru reaction for monitoring beam parameters. The excitation functions for formation of the gamma-emitting radionuclides {sup 94}Ru, {sup 95}Ru, {sup 97}Ru, {sup 103}Ru, {sup 93m}Tc, {sup 93g}Tc(m+), {sup 94m}Tc, {sup 94g}Tc, {sup 95m}Tc, {sup 95g}Tc, {sup 96g}Tc(m+), {sup 99m}Tc, {sup 93m}Mo, {sup 99}Mo(cum), {sup 90}Nb(m+) and {sup 88}Zr were measured up to 40 MeV alpha-particle energy by using the stacked foil technique and activation method. Data of our earlier similar experiments were re-evaluated and resulted in corrections on the reported results. Our experimental data were compared with critically analyzed literature data and with the results of model calculations, obtained by using the ALICE-IPPE, EMPIRE 3.1 (Rivoli) and TALYS codes (TENDL-2011 and TENDL-2015 on-line libraries). Nuclear data for different production routes of {sup 97}Ru and {sup 103}Ru are compiled and reviewed.

  20. A history of nuclear transmutations by natural alpha particles

    International Nuclear Information System (INIS)

    Leone, Matteo

    2005-01-01

    A systematic account of the use of alpha particles up to the 1930s for promoting the disintegration of atoms is here provided. As will be shown, a number of different radium family alpha sources were used in the experiments that led to the discoveries of the proton (Rutherford E 1919 Phil. Mag. 37 581-7) and neutron (Chadwick J 1932 Nature 129 312). The reasons leading to the employment of a particular alpha particle source, as well as the relationship between these sources and the available methods of recording, will be closely addressed

  1. Alpha decay studies on Po isotopes using different versions of nuclear potentials

    Energy Technology Data Exchange (ETDEWEB)

    Santhosh, K.P.; Sukumaran, Indu [Kannur University, School of Pure and Applied Physics, Payyanur, Kerala (India)

    2017-12-15

    The alpha decays from {sup 186-224}Po isotopes have been studied using 25 different versions of nuclear potentials so as to select a suitable nuclear potential for alpha decay studies. The computed standard deviation of the calculated half-lives in comparison with the experimental data suggested that proximity 2003-I is the apt form of nuclear potential for alpha decay studies as it possesses the least standard deviation, σ = 0.620. Among the different proximity potentials, proximity 1966 (σ = 0.630) and proximity 1977 (σ = 0.636), are also found to work well in alpha decay studies with low deviation. Among other versions of nuclear potentials (other than proximity potentials), Bass 1980 is suggested to be a significant form of nuclear potential because of its good predictive power. However, while the other forms of potentials are able to reproduce the experimental data to some extent, these potentials cannot be considered as apposite potentials for alpha decay studies in their present form. Since the experimental correlation of the models is noticed to be satisfying, the alpha decay half-lives of certain Po isotopes that are not detected experimentally yet have been predicted. (orig.)

  2. Alpha decay and nuclear deformation: the case for favoured alpha transitions of even-even emitters

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, F. [Universidade Estadual de Santa Cruz, Ilheus, BA (Brazil). Dept. de Ciencias Exatas e Tecnologicas; Rodriguez, O.; Guzman, F. [Instituto Superior de Ciencias y Tecnologia Nucleares (ISCTN), La Habana (Cuba); Goncalves, M. [Instituto de Radioprotecao e Dosimetria IRD/CNEN, Rio de Janeiro, RJ (Brazil); Duarte, S.B.; Tavares, O.A.P. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil). E-mail: sbd@cbpf.br

    2000-02-01

    Alpha-decay half-life for ground-state transitions of 174 even-even alpha emitters has been calculated from a simple, Gamow-like model in which the quadrupole deformation of the product nucleus (assumed to have an ellipsoidal shape) is taken into account. The assumption made is that before tunneling through a purely Coulomb potential barrier the two-body system oscillates isotropically, thus giving rise to an equivalent, average polar direction {theta} (referred to the symmetry axis of the ellipsoid) for alpha emission. It is shown that the experimental half-life data are much better reproduced by the present description than in the spherical-shaped approximation for the daughter nucleus. (author)

  3. Alpha decay and nuclear deformation: the case for favoured alpha transitions of even-even emitters

    International Nuclear Information System (INIS)

    Garcia, F.; Goncalves, M.; Duarte, S.B.; Tavares, O.A.P.

    2000-02-01

    Alpha-decay half-life for ground-state transitions of 174 even-even alpha emitters has been calculated from a simple, Gamow-like model in which the quadrupole deformation of the product nucleus (assumed to have an ellipsoidal shape) is taken into account. The assumption made is that before tunneling through a purely Coulomb potential barrier the two-body system oscillates isotropically, thus giving rise to an equivalent, average polar direction θ (referred to the symmetry axis of the ellipsoid) for alpha emission. It is shown that the experimental half-life data are much better reproduced by the present description than in the spherical-shaped approximation for the daughter nucleus. (author)

  4. Preliminary study on the analysis of alpha emitters at working places in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hanna; Kim, Jeong In; Lee, Byoungil [Korea Hydro and Nuclear Power Co., Seoul (Korea, Republic of); Yoon, Suk Won [Korea Institute of Radiological and Medical Sciences National Radiation Emergency Medical Center, Seoul (Korea, Republic of)

    2012-10-15

    Over sea nuclear power plants have been reported cases of internal contamination by alpha nuclides. In many cases, stations encountered significant alpha contamination when aged/legacy equipment was disturbed or handled. Under normal operating conditions, transuranic radionuclides are contained within the fuel rods and therefore are not a contributor to radioactive contamination within a facility. However, transuranic radionuclides result from the presence of tramp-uranium contamination on the exterior of fuel elements. Fuel failures may develop during operating cycles due to a variety of causes, ranging from manufacturing defects to mechanical or abrasive damage. In case of domestic nuclear power plants, the pressure tube replacements in Wolsong Unit 1 and steam generator replacements in Kori Unit 1 were done. Due to deterioration of equipment in accordance with the long-term operation, the domestic nuclear power plants are expected to improve the facilities and the probability of internal exposure from alpha emitters is increasing. The domestic nuclear power plants are only keeping alpha radionuclides of the effluent from the exterior under constant surveillance. The representative areas of CV are just carried out continuous alpha monitoring in during a unit outage. So far, there is no other case with alpha nuclides analysis. As the domestic nuclear power plants are expected to improve the facilities, it is the time to take proactive measures to deal with internal contamination by alpha emitting radioactive elements. In this paper, the possible risk of internal exposure is based on preliminary experiments on the analysis of alpha emitting radioactive elements at working places in nuclear power plants.

  5. Radiation induced structural changes in alpha-copper-zinc alloys

    International Nuclear Information System (INIS)

    Schuele, W.; Gieb, M.

    1991-01-01

    During irradiation of alpha-copper-zinc alloys with high energy electrons and protons a decrease of the electrical resistivity due to an increase of the degree of short range order is observed through radiation enhanced diffusion followed by an increase of the electrical resistivity through the formation of radiation induced interstitial clusters. The initial formation rate of interstitial clusters increases about linearly with the displacement rate for electron and proton irradiation. The largest initial formation rate is found between 60 and 130 0 C becoming negligibly small above 158 0 C and decreases drastically below 60 0 C. The dynamic steady state interstitial cluster concentration increases with decreasing irradiation temperature in the investigated temperature range between 158 and 40 0 C. Above 158 0 C the formation rate of interstitial clusters is negligibly small. Thus the transition temperature for radiation induced interstitial cluster formation is 158 0 C, depending mainly on the migration activation energy of vacancies. The radiation induced interstitial clusters are precipitates in those alloys in which the diffusion rate of the undersized component atoms via an interstitialcy diffusion mechanism is larger than that of the other atoms

  6. Alpha-driven magnetohydrodynamics (MHD) and MHD-induced alpha loss in the Tokamak Fusion Test Reactor

    International Nuclear Information System (INIS)

    Chang, Z.; Nazikian, R.; Fu, G.Y.

    1997-02-01

    Alpha-driven toroidal Alfven eigenmodes (TAEs) are observed as predicted by theory in the post neutral beam phase in high central q (safety factor) deuterium-tritium (D-T) plasmas in the Tokamak Fusion Test Reactor (TFTR). The mode location, poloidal structure and the importance of q profile for TAE instability are discussed. So far no alpha particle loss due to these modes was detected due to the small mode amplitude. However, alpha loss induced by kinetic ballooning modes (KBMs) was observed in high confinement D-T discharges. Particle orbit simulation demonstrates that the wave-particle resonant interaction can explain the observed correlation between the increase in alpha loss and appearance of multiple high-n (n ≥ 6, n is the toroidal mode number) modes

  7. Influence of Magnolol on the bystander effect induced by alpha-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wong, T.P.W.; Law, Y.L. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Tse, A.K.W.; Fong, W.F. [Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road, Kowloon Tong (Hong Kong); Yu, K.N. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)], E-mail: peter.yu@cityu.edu.hk

    2010-04-15

    In this work, the influence of Magnolol on the bystander effect in alpha-particle irradiated Chinese hamster ovary (CHO) cells was examined. The bystander effect was studied through medium transfer experiments. Cytokinesis-block micronucleus (CBMN) assay was performed to quantify the chromosome damage induced by alpha-particle irradiation. Our results showed that the alpha-particle induced micronuclei (MN) frequencies were suppressed with the presence of Magnolol.

  8. Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

    Science.gov (United States)

    Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

    2018-01-20

    The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

  9. Alpha self irradiation effects in nuclear borosilicate glass

    International Nuclear Information System (INIS)

    Peuget, S.; Roudil, D.; Deschanels, X.; Jegou, C.; Broudic, V.; Bart, J.M.

    2004-01-01

    The properties of actinide glasses are studied in the context of high-level waste management programs. Reprocessing high burnup fuels in particular will increase the minor actinide content in the glass package, resulting in higher cumulative alpha decay doses in the glass, and raising the question of the glass matrix behavior and especially its containment properties. The effect of alpha self-irradiation on the glass behavior is evaluated by doping the glass with a short-lived actinide ( 244 Cm) to reach in several years the alpha dose received by the future glass packages over several thousand years. 'R7T7' borosilicate glasses were doped with 3 different curium contents (0.04, 0.4 and 1.2 wt% 244 CmO 2 ). The density and mechanical properties of the curium-doped glasses were characterized up to 2. 10 18 α/g, revealing only a slight evolution of the macroscopic behavior of R7T7 glass in this range. The leaching behavior of curium-doped glass was also studied by Soxhlet tests. The results do not show any significant evolution of the initial alteration rate with the alpha dose. (authors)

  10. Enhanced diffusion under alpha self-irradiation in spent nuclear fuel: Theoretical approaches

    International Nuclear Information System (INIS)

    Ferry, Cecile; Lovera, Patrick; Poinssot, Christophe; Garcia, Philippe

    2005-01-01

    Various theoretical approaches have been developed in order to estimate the enhanced diffusion coefficient of fission products under alpha self-irradiation in spent nuclear fuel. These simplified models calculate the effects of alpha particles and recoil atoms on mobility of uranium atoms in UO 2 . They lead to a diffusion coefficient which is proportional to the volume alpha activity with a proportionality factor of about 10 -44 (m 5 ). However, the same models applied for fission lead to a radiation-enhanced diffusion coefficient which is approximately two orders of magnitude lower than values reported in literature for U and Pu. Other models are based on an extrapolation of radiation-enhanced diffusion measured either in reactors or under heavy ion bombardment. These models lead to a proportionality factor between the alpha self-irradiation enhanced diffusion coefficient and the volume alpha activity of 2 x 10 -41 (m 5 )

  11. Application of solid state nuclear track detectors in measurement of natural alpha- radioactivity in environment

    Energy Technology Data Exchange (ETDEWEB)

    Maged, A F; El-Behay, A Z; Borham, E [National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo (Egypt)

    1997-12-31

    The use of solid state nuclear track detectors (SSNTDs) is one of the most convenient techniques to assess the average radiation levels of alpha activities in the environment. This technique has been used to assess radon gas and its daughters in buildings. Exposed SSNTD films are chemically etched in an alkali solution and alpha tracks are evaluated by using the image analyzer system. The detailed procedure for this study and the etched films for conversion of alpha track density to radon concentration in Bq m{sup -}3 are given and discussed in the text.1 fig., 3 tabs.

  12. Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.

    Science.gov (United States)

    Taie, Satoshi; Ono, Junichiro; Iwanaga, Yasuyuki; Tomita, Shuhei; Asaga, Takehiko; Chujo, Kosuke; Ueki, Masaaki

    2009-08-01

    Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.

  13. alpha-Amanitin induced apoptosis in primary cultured dog hepatocytes.

    Directory of Open Access Journals (Sweden)

    Adam Szelag

    2010-06-01

    Full Text Available Amatoxin poisoning is caused by mushroom species belonging to the genera Amanita, Galerina and Lepiota with the majority of lethal mushroom exposures attributable to Amanita phalloides. High mortality rate in intoxications with these mushrooms is principally a result of the acute liver failure following significant hepatocyte damage due to hepatocellular uptake of amatoxins. A wide variety of amatoxins have been isolated; however, alpha-amanitin (alpha-AMA appears to be the primary toxin. Studies in vitro and in vivo suggest that alpha-AMA does not only cause hepatocyte necrosis, but also may lead to apoptotic cell death. The objective of this study was to evaluate the complex hepatocyte apoptosis in alpha-AMA cytotoxicity. All experiments were performed on primary cultured canine hepatocytes. The cells were incubated for 12 h with alpha-AMA at a final concentration of 1, 5, 10 and 20 microM. Viability test (MTT assay, apoptosis evaluation (TUNEL reaction, detection of DNA laddering and electron microscopy were performed at 6 and 12 h of exposure to alpha-AMA. There was a clear correlation between hepatocyte viability, concentration of alpha-AMA and time of exposure to this toxin. The decline in cultured dog hepatocyte viability during the exposure to alpha-AMA is most likely preceded by enhanced cellular apoptosis. Our results demonstrate that apoptosis might contribute to pathogenesis of the severe liver injury in the course of amanitin intoxication, particularly during the early phase of poisoning.

  14. Neutron induced alpha production from carbon between 18 and 22 MeV

    International Nuclear Information System (INIS)

    Stevens, A.P.

    1976-10-01

    Cross sections for neutron induced alpha production in carbon were measured at seventeen energies between 18 and 22 MeV, using a deuterated anthracene crystal as both target and detector. Pulse shape discrimination was employed to separate the alphas and elastically scattered deuterons from the other reaction products. Published (n,d) elastic scattering data were used as a standard to obtain the alpha production cross sections. Comparison with available measurements shows good agreement

  15. Averaged currents induced by alpha particles in an InSb compound semiconductor detector

    International Nuclear Information System (INIS)

    Kanno, Ikuo; Hishiki, Shigeomi; Kogetsu, Yoshitaka; Nakamura, Tatsuya; Katagiri, Masaki

    2008-01-01

    Very fast pulses due to alpha particle incidence were observed by an undoped-type InSb Schottky detector. This InSb detector was operated without applying bias voltage and its depletion layer thickness was less than the range of alpha particles. The averaged current induced by alpha particles was analyzed as a function of operating temperature and was shown to be proportional to the Hall mobility of InSb. (author)

  16. Radioactive alpha wastes processing at the nuclear center of Mol

    International Nuclear Information System (INIS)

    Voorde, N. van de

    1978-01-01

    This process is based on calcination at very high temperature (1500 0 C) of wastes, mainly burnable, with selected non-burnable wastes, such as glass, metal, sludge, ion echanger, etc. Incineration wastes melt at this temperature and an insoluble granitic mass is obtained. This operation is performed in a special oven equipped with a gas purification device installed in a place like alpha bearing wastes treatment working spot where the staff can work in an air-supplied suit. Two incineration units are planned, the first one with a capacity of 150 kg/hr in view to treat a large amount of wastes with a low plutonium content (max. 10 mg/l), the second smaller with a capacity of 10 kg/hr, specially designed to process wastes with a high Pu content. This project for the first unit, at least is now tested with beta gamma wastes processing. Alpha bearing wastes pocessing will start at the end of 1978, we are now building the second unit [fr

  17. Development of alpha spectroscopy method with solid state nuclear track detector using aluminium thin films

    Energy Technology Data Exchange (ETDEWEB)

    Dwaikat, N., E-mail: ndwaikat@kfupm.edu.sa [King Fahd University of Petroleum and Minerals, College of Sciences, Department of Physics, Dhahran 31261 (Saudi Arabia)

    2015-10-15

    This work presents the development of alpha spectroscopy method with Solid-state nuclear track detectors using aluminum thin films. The resolution of this method is high, and it is able to discriminate between alpha particles at different incident energy. It can measure the exact number of alpha particles at specific energy without needing a calibration of alpha track diameter versus alpha energy. This method was tested by using Cf-252 alpha standard source at energies 5.11 MeV, 3.86 MeV and 2.7 MeV, which produced by the variation of detector -standard source distance. On front side, two detectors were covered with two Aluminum thin films and the third detector was kept uncovered. The thickness of Aluminum thin films was selected carefully (using SRIM 2013) such that one of the films will block the lower two alpha particles (3.86 MeV and 2.7 MeV) and the alpha particles at higher energy (5.11 MeV) can penetrate the film and reach the detectors surface. The second thin film will block alpha particles at lower energy of 2.7 MeV and allow alpha particles at higher two energies (5.11 MeV and 3.86 MeV) to penetrate and produce tracks. For uncovered detector, alpha particles at three different energies can produce tracks on it. For quality assurance and accuracy, the detectors were mounted on thick enough copper substrates to block exposure from the backside. The tracks on the first detector are due to alpha particles at energy of 5.11 MeV. The difference between the tracks number on the first detector and the tracks number on the second detector is due to alpha particles at energy of 3.8 MeV. Finally, by subtracting the tracks number on the second detector from the tracks number on the third detector (uncovered), we can find the tracks number due to alpha particles at energy 2.7 MeV. After knowing the efficiency calibration factor, we can exactly calculate the activity of standard source. (Author)

  18. Development of alpha spectroscopy method with solid state nuclear track detector using aluminium thin films

    International Nuclear Information System (INIS)

    Dwaikat, N.

    2015-10-01

    This work presents the development of alpha spectroscopy method with Solid-state nuclear track detectors using aluminum thin films. The resolution of this method is high, and it is able to discriminate between alpha particles at different incident energy. It can measure the exact number of alpha particles at specific energy without needing a calibration of alpha track diameter versus alpha energy. This method was tested by using Cf-252 alpha standard source at energies 5.11 MeV, 3.86 MeV and 2.7 MeV, which produced by the variation of detector -standard source distance. On front side, two detectors were covered with two Aluminum thin films and the third detector was kept uncovered. The thickness of Aluminum thin films was selected carefully (using SRIM 2013) such that one of the films will block the lower two alpha particles (3.86 MeV and 2.7 MeV) and the alpha particles at higher energy (5.11 MeV) can penetrate the film and reach the detectors surface. The second thin film will block alpha particles at lower energy of 2.7 MeV and allow alpha particles at higher two energies (5.11 MeV and 3.86 MeV) to penetrate and produce tracks. For uncovered detector, alpha particles at three different energies can produce tracks on it. For quality assurance and accuracy, the detectors were mounted on thick enough copper substrates to block exposure from the backside. The tracks on the first detector are due to alpha particles at energy of 5.11 MeV. The difference between the tracks number on the first detector and the tracks number on the second detector is due to alpha particles at energy of 3.8 MeV. Finally, by subtracting the tracks number on the second detector from the tracks number on the third detector (uncovered), we can find the tracks number due to alpha particles at energy 2.7 MeV. After knowing the efficiency calibration factor, we can exactly calculate the activity of standard source. (Author)

  19. alpha(7) Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Christensen, Ditte Z; Hansen, Henrik H

    2009-01-01

    in a modified Y-maze test. Polymorphisms in the alpha(7) nicotinic acetylcholine receptor (nAChR) gene have been linked to schizophrenia. Here we demonstrate that acute administration of the selective alpha(7) nAChR partial agonist SSR180711 dose-dependently reversed the behavioral impairment induced by PCP...

  20. A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth

    DEFF Research Database (Denmark)

    Greenberger, Lee M; Horak, Ivan D; Filpula, David

    2008-01-01

    Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in angiogenesis, survival, metastasis, drug resistance, and glucose metabolism. Elevated expression of the alpha-subunit of HIF-1 (HIF-1alpha), which occurs in response to hypoxia or activation of growth facto...

  1. Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages.

    Science.gov (United States)

    Nadra, Imad; Boccaccini, Aldo R; Philippidis, Pandelis; Whelan, Linda C; McCarthy, Geraldine M; Haskard, Dorian O; Landis, R Clive

    2008-01-01

    Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.

  2. alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

    Science.gov (United States)

    de Fiebre, Nancyellen C; de Fiebre, Christopher M

    2005-01-03

    The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

  3. Quantitative immuno-electron microscopic analysis of depolarization-induced expression of PGC-1alpha in cultured rat visual cortical neurons.

    Science.gov (United States)

    Meng, Hui; Liang, Huan Ling; Wong-Riley, Margaret

    2007-10-17

    Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC- 1alpha) is a coactivator of nuclear receptors and other transcription factors that regulate several metabolic processes, including mitochondrial biogenesis, energy homeostasis, respiration, and gluconeogenesis. PGC-1alpha plays a vital role in stimulating genes that are important to oxidative metabolism and other mitochondrial functions in brown adipose tissue and skeleton muscles, but the significance of PGC-1alpha in the brain remains elusive. The goal of our present study was to determine by means of quantitative immuno-electron microscopy the expression of PGC-1alpha in cultured rat visual cortical neurons under normal conditions as well as after depolarizing stimulation for varying periods of time. Our results showed that: (a) PGC-1alpha was normally located in both the nucleus and the cytoplasm. In the nucleus, PGC-1alpha was associated mainly with euchromatin rather than heterochromatin, consistent with active involvement in transcription. In the cytoplasm, it was associated mainly with free ribosomes. (b) Neuronal depolarization by KCl for 0.5 h induced a significant increase in PGC-1alpha labeling density in both the nucleus and the cytoplasm (Pneuronal activity by synthesizing more proteins in the cytoplasm and translocating them to the nucleus for gene activation. PGC-1alpha level in neurons is, therefore, tightly regulated by neuronal activity.

  4. Registration of alpha particles in Makrofol-E nuclear track detectors

    Energy Technology Data Exchange (ETDEWEB)

    Rammah, Y.S. [Physics Department, Faculty of Science, Menoufia University, Shebin El-Koom (Egypt); Abdalla, Ayman M., E-mail: aymanabdalla62@hotmail.com [Physics Department, Faculty of Sciences and Arts, Najran University, P. O. Box. 11001, Najran (Saudi Arabia); Promising Centre for Sensors and Electronic Devices, Faculty of Arts and Sciences, Najran University (Saudi Arabia); Ashraf, O., E-mail: osama.ashraf@edu.asu.edu.eg [Physics Department, Faculty of Education, Ain Shams University, Cairo 11575 (Egypt); Ashry, A.H. [Physics Department, Faculty of Education, Ain Shams University, Cairo 11575 (Egypt)

    2016-06-15

    Highlights: • Makrofol-E detectors have been irradiated with alpha particles and fission fragments. • Fast detection of alpha particles in Makrofol-E detectors. • Bulk etching rate was calculated from fission track diameters. - Abstract: Fast detection of alpha particles in the range from 1 to 5 MeV in Makrofol-E polycarbonate nuclear track detectors (PCTDs) using a new chemical etchant was investigated. {sup 252}Cf and {sup 241}Am-thin open sources were used for irradiating Makrofol-E detectors with fission fragments and alpha particles in air at normal pressure and temperature (NPT). A chain of experimental work has been carried out using new etchants to register alpha particle in short time in Makrofol-E polycarbonate detectors. The etching efficiency were exhibited a clear dependence on the amount of methanol in the etching solution and etching time. The optimized chemical condition obtained at this stage of development for 200 μm Makrofol-E detectors are (8 ml of 10 N NaOH + 2 ml CH{sub 3}OH) etching solutions at 60 °C for 3 h. In this study; it is possible to observe energy detection windows for Makrofol-E detectors according to applied etching duration. Makrofol-E introduced the characteristic Bragg peak, which indicates the advantages of this detector as alpha spectrometer. Consequently, the suggested new etchant can be developed for heavy ions detection and monitoring radon levels and its daughters.

  5. Nuclear Track Detector Characterization via Alpha-Spectrometry for Radioprotection Use

    Energy Technology Data Exchange (ETDEWEB)

    Morelli, D.; Imme, G.; Catalano, R. [Dipartimento di Fisica e Astronomia, Universita degli Studi di Catania, via S. Sofia, 64- 95123 Catania (Italy); Istituto Nazionale di Fisica Nucleare - Sezione di Catania, via S. Sofia, 64- 95123 Catania (Italy); Aranzulla, M. [Istituto Nazionale Geofisica e Vulcanologia - Sezione di Catania, piazza Roma, 2- 95127 Catania (Italy); Tazzer, A. L. Rosselli; Mangano, G. [Dipartimento di Fisica e Astronomia, Universita degli Studi di Catania, via S. Sofia, 64- 95123 Catania (Italy)

    2011-12-13

    Solid Nuclear Track Detectors (SNTDs), CR-39 type, are usually adopted to monitor radon gas concentrations. In order to characterize the detectors according to track geometrical parameters, detectors were irradiated inside a vacuum chamber by alpha particles at twelve energy values, obtained by different Mylar foils in front of a {sup 241}Am source. The alpha energy values were verified using a Si detector. After the exposure to the alpha particles, the detectors were chemically etched to enlarge the tracks, which were then analyzed by means of a semiautomatic system composed of an optical microscope equipped with a CCD camera connected to a personal computer to store images. A suitable routine analyzed the track parameters: major and minor axis length and mean grey level, allowing us to differentiate tracks according to the incident alpha energy and then to individuate the discrimination factors for radon alpha tracks. The combined use of geometrical and optical parameters allows one to overcome the ambiguity in the alpha energy determination due to the non-monotonicity of each parameter versus energy. After track parameter determination, a calibration procedure was performed by means of a radon chamber. The calibration was verified through an inter-comparing survey.

  6. Alpha-Methyldopa-Induced Autoimmune Hemolytic Anemia in the Third Trimester of Pregnancy

    Directory of Open Access Journals (Sweden)

    Charalampos Grigoriadis

    2013-01-01

    Full Text Available Alpha-methyldopa has been demonstrated to be safe for use during pregnancy and is now used to treat gestational hypertension. In pregnancy, alpha-methyldopa-induced autoimmune hemolytic anemia does not have typical features and the severity of symptoms ranges from mild fatigue to dyspnea, respiratory failure, and death if left untreated. A case of alpha-methyldopa-induced autoimmune hemolytic anemia in a 36-year-old gravida 2, para 1 woman at 37+6 weeks of gestation is reported herein along with the differential diagnostic procedure and the potential risks to the mother and the fetus.

  7. Dynamical chaos and induced nuclear fission

    Energy Technology Data Exchange (ETDEWEB)

    Bolotin, Yu L; Krivoshej, I V

    1985-01-01

    It is shown that the exponential instability of trajectories, which arises at negative curvature of the potential energy surface, leads to diffusion of the image point through the barrier and determines real time delays in induced nuclear fission.

  8. Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats.

    Science.gov (United States)

    Khamphaya, Tanaporn; Chansela, Piyachat; Piyachaturawat, Pawinee; Suksamrarn, Apichart; Nathanson, Michael H; Weerachayaphorn, Jittima

    2016-10-15

    Cholestasis is a cardinal manifestation of liver diseases but effective therapeutic approaches are limited. Therefore, alternative therapy for treating and preventing cholestatic liver diseases is necessary. Andrographolide, a promising anticancer drug derived from the medicinal plant Andrographis paniculata, has diverse pharmacological properties and multi-spectrum therapeutic applications. However, it is unknown whether andrographolide has a hepatoprotective effect on intrahepatic cholestasis. The aims of this study were to investigate the protective effect and possible mechanisms of andrographolide in a rat model of acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT). Andrographolide was administered intragastrically for four consecutive days, with a single intraperitoneal injection of ANIT on the second day. Liver injury was evaluated biochemically and histologically together with hepatic gene and protein expression analysis. Rats pretreated with andrographolide prior to ANIT injection demonstrated lower levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, as well as bilirubin and bile acids as compared to rats treated with ANIT alone. Andrographolide also decreased the incidence and extent of periductular fibrosis and bile duct proliferation. Analysis of protein expression in livers from andrographolide-treated cholestatic rats revealed markedly decreased expression of alpha-smooth muscle actin and nuclear factor kappa-B (NF-κB). In conclusion, andrographolide has a potent protective property against ANIT-induced cholestatic liver injury. The mechanisms that underlie this protective effect are mediated through down-regulation of NF-κB expression and inhibition of hepatic stellate cell activation. These findings suggest that andrographolide could be a promising therapeutic option in prevention and slowing down the progression of cholestatic liver diseases. Copyright

  9. Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions

    DEFF Research Database (Denmark)

    Lundby, Carsten; Gassmann, Max; Pilegaard, Henriette

    2005-01-01

    and 2 (HIFs) are clearly related heterodimeric transcription factors that consist of an oxygen-depended alpha-subunit and a constitutive beta-subunit. With hypoxic exposure, HIF-1alpha and HIF-2alpha protein are stabilized. Upon heterodimerization, HIFs induce the transcription of a variety of genes......Regular exercise induces a variety of adaptive responses that enhance the oxidative and metabolic capacity of human skeletal muscle. Although the physiological adjustments of regular exercise have been known for decades, the underlying mechanisms are still unclear. The hypoxia inducible factors 1...... including erythropoietin (EPO), transferrin and its receptor, as well as vascular endothelial growth factor (VEGF) and its receptor. Considering that several of these genes are also induced with exercise, we tested the hypothesis that the mRNA level of HIF-1alpha and HIF-2alpha subunits increases...

  10. Alpha lipoic acid attenuates high-fructose-induced pancreatic toxicity.

    Science.gov (United States)

    Topsakal, Senay; Ozmen, Ozlem; Cankara, Fatma Nihan; Yesilot, Sukriye; Bayram, Dilek; Genç Özdamar, Nilüfer; Kayan, Sümeyra

    2016-01-01

    Chronic consumption of high-fructose corn syrup (HFCS) causes several problems such as insulin resistance. The goal of the study was to investigate pancreatic damage induced by chronic HFCS consumption and the protective effects of alpha lipoic acid (ALA) on pancreatic cells. Wistar Albino, 4-month-old, female rats weighing 250-300 g were randomly distributed into three groups, each containing eight rats. The study included an HFCS group, an HFCS + ALA-administered group and a control group (CON). The prepared 30% solution of HFCS (F30) (24% fructose, 28% dextrose) was added to the drinking water for 10 weeks. ALA treatment was begun 4 weeks after the first HFCS administration (100 mg/kg/oral, last 6 weeks). Rats were anaesthetised and euthanised by cervical dislocation 24 h after the last ALA administration. Blood samples for biochemical tests (amylase, lipase, malondialdehyde (MDA) and catalase (CAT)) and tissue samples for histopathological and immunohistochemical examinations (caspase-3, insulin and glucagon) were collected. Comparing the control and HFCS groups, serum glucose (150.92 ± 39.77 and 236.50 ± 18.28, respectively, p < 0.05), amylase (2165.00 ± 150.76 and 3027.66 ± 729.19, respectively, p < 0.01), lipase (5.58 ± 2.22 and 11.51 ± 2.74, respectively, p < 0.01) and pancreatic tissue MDA (0.0167 ± 0.004 and 0.0193 ± 0.006, respectively, p < 0.05) levels were increased, whereas tissue CAT (0.0924 ± 0.029 and 0.0359 ± 0.023, respectively, p < 0.05) activity decreased in the HFCS group significantly. Histopathological examination revealed degenerative and necrotic changes in Langerhans islet cells and slight inflammatory cell infiltration in pancreatic tissue in the HFCS group. Immunohistochemically there was a significant decrease in insulin (2.85 ± 0.37 and 0.87 ± 0.64, respectively, p < 0.001) and glucagon (2.71 ± 0.48 and 1.00 ± 0.75, respectively, p < 0.001) secreting cell scores, whereas a

  11. Molecular mechanisms underlying mancozeb-induced inhibition of TNF-alpha production

    International Nuclear Information System (INIS)

    Corsini, Emanuela; Viviani, Barbara; Birindelli, Sarah; Gilardi, Federica; Torri, Anna; Codeca, Ilaria; Lucchi, Laura; Bartesaghi, Stefano; Galli, Corrado L.; Marinovich, Marina; Colosio, Claudio

    2006-01-01

    Mancozeb, a polymeric complex of manganese ethylenebisdithiocarbamate with zinc salt, is widely used in agriculture as fungicide. Literature data indicate that ethylenebisdithiocarbamates (EBDTCs) may have immunomodulatory effects in humans. We have recently found in agricultural workers occupationally exposed to the fungicide mancozeb a statistically significant decrease in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF) production in leukocytes. TNF is an essential proinflammatory cytokine whose production is normally stimulated during an infection. The purpose of this work was to establish an in vitro model reflecting in vivo data and to characterize the molecular mechanism of action of mancozeb. The human promyelocytic cell line THP-1 was used as in vitro model to study the effects of mancozeb and its main metabolite ethylenthiourea (ETU) on LPS-induced TNF release. Mancozeb, but not ETU, at non-cytotoxic concentrations (1-100 μg/ml), induced a dose- and time-dependent inhibition of LPS-induced TNF release, reflecting in vivo data. The modulatory effect observed was not limited to mancozeb but also other EBDTCs, namely zineb and ziram, showed similar inhibitory effects. Mancozeb must be added before or simultaneously to LPS in order to observe the effect, indicating that it acts on early events triggered by LPS. It is known that nuclear factor-κB (NF-κB) tightly regulates TNF transcription. We could demonstrate that mancozeb, modulating LPS-induced reactive oxygen species generation, prevented IκB degradation and NF-κB nuclear translocation, which in turn resulted in decreased TNF production. To further understand the mechanism of the effect of mancozeb on TNF transcription, THP-1 cells were transfected with NF-κB promoter-luciferase construct, and the effect of mancozeb on luciferase activity was measured. Cells transfected with promoter constructs containing κB site showed decreased LPS-induced luciferase activity relative to control

  12. Alpha-induced instabilities in tandem thermal barriers

    Energy Technology Data Exchange (ETDEWEB)

    Kammash, T.; Galbraith, D.L.

    1987-01-01

    A major premise in the operation of Tandem Mirror reactors is that the fusion reactions take place in the central cell only. The alpha particles generated by the Deuterium-Tritium (DT) fusions, along with other ions, will however pass from the central cell to the thermal barriers and return to the central cell as a result of reflection by the potential hills that exist by the plugs' side of these barriers. This streaming motion gives rise to electrostatic and electomagnetic instabilities which could detract from the barrier's function as a thermal insulator. The number density and streaming velocity of these passing particles are dictated by the electrostatic potential variation and the magnetic field structure in these regions. It is shown that, in the absence of alphas, barriers with deep potential depression are less susceptible to electrostatic instabilities while particularly vulnerable to unstable electromagnetic modes. In the presence of alphas, especially the fast alphas whose mean energy is significantly larger than the barrier potentials they see, (which is twice as high as that seen by the ions) both types of modes become unstable.

  13. Optimization in the nuclear fuel cycle II: Concentration of alpha emitters in the air

    International Nuclear Information System (INIS)

    Pereira, W.S.; Silva, A.X.; Lopes, J.M.; Carmo, A.S.; Mello, C.R.; Fernandes, T.S.; Kelecom, A.

    2017-01-01

    Optimization is one of the bases of radioprotection and aims to move doses away from the dose limit that is the borderline of acceptable radiological risk. The work aims to use the monitoring of the concentration of alpha emitters in the air as a tool of the optimization process. We analyzed 27 sampling points of airborne alpha concentration in a nuclear fuel cycle facility. The monthly averages were considered statistically different, the highest in the month of February and the lowest in the month of August. All other months were found to have identical mean activity concentration values. Regarding the sampling points, the points with the highest averages were points 12, 15 and 9. These points were indicated for the beginning of the optimization process. Analysis of the production of the facility should be performed to verify possible correlations between production and concentration of alpha emitters in the air

  14. Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression

    International Nuclear Information System (INIS)

    Simiantonaki, Nektaria; Taxeidis, Marios; Jayasinghe, Caren; Kurzik-Dumke, Ursula; Kirkpatrick, Charles James

    2008-01-01

    Hypoxia-inducible factor 1 alpha (HIF-1α) is involved in processes promoting carcinogenesis of many tumors. However, its role in the development of colorectal cancer is unknown. To investigate the significance of HIF-1α during colorectal carcinogenesis and progression we examined its expression in precursor lesions constituting the conventional and serrated pathways, as well as in non-metastatic and metastatic adenocarcinomas. Immunohistochemistry and Western blot is used to analyse HIF-1α expression in normal colonic mucosa, hyperplastic polyps (HPP), sessile serrated adenomas (SSA), low-grade (TA-LGD) and high-grade (TA-HGD) traditional adenomas as well as in non-metastatic and metastatic colorectal adenocarcinomas. Eight colorectal carcinoma cell lines are tested for their HIF-1α inducibility after lipopolysaccharide (LPS) stimulation using western blot and immunocytochemistry. In normal mucosa, HPP and TA-LGD HIF-1α was not expressed. In contast, perinuclear protein accumulation and nuclear expression of HIF-1α were shown in half of the examined SSA and TA-HGD. In all investigated colorectal carcinomas a significant nuclear HIF-1α overexpression compared to the premalignant lesions was observed but a significant correlation with the metastatic status was not found. Nuclear HIF-1α expression was strongly accumulated in perinecrotic regions. In these cases HIF-1α activation was seen in viable cohesive tumor epithelia surrounding necrosis and in dissociated tumor cells, which subsequently die. Enhanced distribution of HIF-1α was also seen in periiflammatory regions. In additional in vitro studies, treatment of diverse colorectal carcinoma cell lines with the potent pro-inflammatory factor lipopolysaccharide (LPS) led to HIF-1α expression and nuclear translocation. We conclude that HIF-1α expression occurs in early stages of colorectal carcinogenesis and achieves a maximum in the invasive stage independent of the metastatic status. Perinecrotic

  15. Laser induced nuclear orientation effects

    International Nuclear Information System (INIS)

    Burns, M.; Pappas, P.; Feld, M.S.; Murnick, D.E.

    1977-01-01

    Resonant laser radiation can orient metastable nuclei, resulting in spatially anisotropic emission of β or γ radiation. This technique can be used to obtain isomer shifts and nuclear moments and can lead to isomer separation. (Auth.)

  16. Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line

    International Nuclear Information System (INIS)

    Choi, Hyun-Jeung; Kim, Tae Yong; Ruiz-Llorente, Sergio; Jeon, Min Ji; Han, Ji Min; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

    2012-01-01

    Introduction: Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells. Methods: Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay. Results: Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells. Conclusions: ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.

  17. Preliminary Results of Nuclear Fluorescence Imaging of Alpha and Beta Emitting Sources

    International Nuclear Information System (INIS)

    Feener, Jessica S.; Charlton, William S.

    2013-06-01

    The preliminary results from a series of nuclear fluorescence imaging experiments using a variety of radioactive sources and shielding are given. These experiments were done as part of a proof of concept to determine if nuclear fluorescence imaging could be used as a safeguards measurements tool or for nuclear warhead verification for nuclear arms control treaties such as the New Strategic Arms Reduction Treaty and the Fissile Material Cut-Off Treaty. An off-the-shelf Princeton Instruments charged coupled device camera system was used to image the emission of fluorescence photons from the de-excitation of nitrogen molecules in air that have been excited by ionizing radiation. The fluorescence emissions are primarily in the near ultraviolet range; between the wavelengths of 300 and 400 nm. Fluorescent imaging techniques are currently being investigated in a number of applications. A French research team has successfully demonstrated this concept for remote imaging of alpha contamination. It has also been shown that the phenomenon can be seen through translucent materials and that alpha radiation can be seen in the presence of large gamma backgrounds. Additionally, fluorescence telescopes and satellites utilize the de-excitation of nitrogen molecules to observe cosmic ray showers in the atmosphere. In cosmic ray shower detection, electrons are the main contributor to the excitation of the of nitrogen molecules in air. The experiments presented in this paper were designed to determine if the imaging system could observe beta emitting sources, differentiate between beta emitters and alpha emitting materials such as uranium oxide and uranium metal, and to further investigate the phenomenon through translucent and non-translucent materials. The initial results show that differentiation can be made between beta and alpha emitting sources and that the device can observe the phenomenon through very thin non-transparent material. Additionally, information is given on the

  18. Chromosomal aberrations induced by alpha particles; Aberraciones cromosomicas inducidas por particulas {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero C, C.; Brena V, M. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: cgc@nuclear.inin.mx

    2005-07-01

    The chromosomal aberrations produced by the ionizing radiation are commonly used when it is necessary to establish the exposure dose of an individual, it is a study that is used like complement of the traditional physical systems and its application is only in cases in that there is doubt about what indicates the conventional dosimetry. The biological dosimetry is based on the frequency of aberrations in the chromosomes of the lymphocytes of the individual in study and the dose is calculated taking like reference to the dose-response curves previously generated In vitro. A case of apparent over-exposure to alpha particles to which is practiced analysis of chromosomal aberrations to settle down if in fact there was exposure and as much as possible, to determine the presumed dose is presented. (Author)

  19. Generation of an induced pluripotent stem cell (iPSC line from a patient with maturity-onset diabetes of the young type 3 (MODY3 carrying a hepatocyte nuclear factor 1-alpha (HNF1A mutation

    Directory of Open Access Journals (Sweden)

    Frank Griscelli

    2018-05-01

    Full Text Available Heterozygous non-synonymous (p.S142F mutation in HNF1A leads to maturity-onset diabetes of the young (MODY type 3, which is a subtype of dominant inherited young-onset non-autoimmune diabetes due to the defect of insulin secretion from pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs from a patient with HNF1A p.S142F mutation. Cells from this patient, which were reprogrammed by non-integrative viral transduction had normal karyotype, harboured the HNF1A p.S142F mutation, expressed pluripotency hallmarks.

  20. Nuclear alpha spectrin: Critical roles in DNA interstrand cross-link repair and genomic stability

    OpenAIRE

    Lambert, Muriel W

    2016-01-01

    Non-erythroid alpha spectrin (?IISp) is a structural protein which we have shown is present in the nucleus of human cells. It interacts with a number of nuclear proteins such as actin, lamin, emerin, chromatin remodeling factors, and DNA repair proteins. ?IISp?s interaction with DNA repair proteins has been extensively studied. We have demonstrated that nuclear ?IISp is critical in DNA interstrand cross-link (ICL) repair in S phase, in both genomic (non-telomeric) and telomeric DNA, and in ma...

  1. The applicability of ALPHA/PHOENIX/ANC nuclear design code system on Korean standard PWR's

    International Nuclear Information System (INIS)

    Lee, Kookjong; Choi, Kie-Yong; Lee, Hae-Chan; Roh, Eun-Rae

    1996-01-01

    For the Korean Standard Nuclear Power Plant (KSNPP) designed based on Combustion Engineering (CE) System 80, the Westinghouse nuclear design code system ALPHA/PHOENIX/ANC was applied to the follow-up design of initial and reload core of KSNPP. The follow-up design results of Yonggwang Unit 3 Cycle 1, 2 and Yonggwang Unit 4 Cycle 1 have shown good agreements with the measured data. The assemblywise power distributions have shown less than 2% average differences and critical boron concentrations have shown less than 20 ppm differences. All the low power physics test parameters are in good agreement. Consequently, APA design code system can be applied to KNSPP cores. (author)

  2. IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes

    DEFF Research Database (Denmark)

    Falkencrone, Sidsel; Poulsen, Lars K.; Bindslev-Jensen, Carsten

    2013-01-01

    IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have...

  3. Laser-induced nuclear fusion

    International Nuclear Information System (INIS)

    Jablon, Claude

    1977-01-01

    Research programs on laser-induced thermonuclear fusion in the United States, in Europe and in USSR are reviewed. The principle of the fusion reactions induced is explained, together with the theoretical effects of the following phenomena: power and type of laser beams, shape and size of the solid target, shock waves, and laser-hydrodynamics coupling problems [fr

  4. Alpha7 nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells.

    Science.gov (United States)

    Li, Y; King, M A; Grimes, J; Smith, N; de Fiebre, C M; Meyer, E M

    1999-01-16

    Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific alpha7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 microM) found previously to protect against apoptotic and necrotic cell loss. The alpha7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of alpha7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity. Copyright 1999 Elsevier Science B.V.

  5. Pre-equilibrium decay process in alpha particle induced reactions on thulium and tantalum

    Energy Technology Data Exchange (ETDEWEB)

    Mohan, Rao, A.V.; Chintalapudi, S.N. (Inter Univ. Consortium for Dept. of atomic Energy Facilities, Calcutta (India))

    1994-01-01

    Alpha particle induced reactions on the target elements Thulium and Tantalum were investigated upto 60 MeV using stacked foil activation technique and Ge(Li) gamma ray spectroscopy method. Excitation functions for six reactions of [sup 169]Tm([alpha],xn); x=1-4 and [sup 181]Ta([alpha],xn); x=2,4 were studied. The experimental results were compared with the updated version of Hybrid model (ALICE/90) using initial exciton configuration n[sub 0]=4(4pOh). A general agreement was found for all the reactions with this option. (author).

  6. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection.

    NARCIS (Netherlands)

    Pearson, E.R.; Pruhova, S.; Tack, C.J.J.; Johansen, A.; Castleden, H.A.; Lumb, P.J.; Wierzbicki, A.S.; Clark, P.M.; Lebl, J.; Pedersen, O.; Ellard, S.; Hansen, T.; Hattersley, A.T.

    2005-01-01

    AIMS/HYPOTHESIS: Heterozygous mutations in the gene of the transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) are considered a rare cause of MODY with only 14 mutations reported to date. The description of the phenotype is limited to single families. We investigated the genetics and

  7. Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

    Science.gov (United States)

    Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

    2009-01-01

    Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

  8. Prediction of lung cells oncogenic transformation for induced radon progeny alpha particles using sugarscape cellular automata.

    Science.gov (United States)

    Baradaran, Samaneh; Maleknasr, Niaz; Setayeshi, Saeed; Akbari, Mohammad Esmaeil

    2014-01-01

    Alpha particle irradiation from radon progeny is one of the major natural sources of effective dose in the public population. Oncogenic transformation is a biological effectiveness of radon progeny alpha particle hits. The biological effects which has caused by exposure to radon, were the main result of a complex series of physical, chemical, biological and physiological interactions. The cellular and molecular mechanisms for radon-induced carcinogenesis have not been clear yet. Various biological models, including cultured cells and animals, have been found useful for studying the carcinogenesis effects of radon progeny alpha particles. In this paper, sugars cape cellular automata have been presented for computational study of complex biological effect of radon progeny alpha particles in lung bronchial airways. The model has included mechanism of DNA damage, which has been induced alpha particles hits, and then formation of transformation in the lung cells. Biomarkers were an objective measure or evaluation of normal or abnormal biological processes. In the model, the metabolism rate of infected cell has been induced alpha particles traversals, as a biomarker, has been followed to reach oncogenic transformation. The model results have successfully validated in comparison with "in vitro oncogenic transformation data" for C3H 10T1/2 cells. This model has provided an opportunity to study the cellular and molecular changes, at the various stages in radiation carcinogenesis, involving human cells. It has become well known that simulation could be used to investigate complex biomedical systems, in situations where traditional methodologies were difficult or too costly to employ.

  9. Specific outcomes of the research on the radiation stability of the French nuclear glass towards alpha decay accumulation

    Science.gov (United States)

    Peuget, S.; Delaye, J.-M.; Jégou, C.

    2014-01-01

    This paper presents an overview of the main results of the French research on the long-term behavior of SON68 nuclear glass towards alpha decay accumulation. The effect of the radiation damage induced by alpha decay and also helium build-up were investigated by examining glass specimens, doped with a short-lived actinide 244Cm, irradiated by light and heavy ions. Additionally, atomistic simulations by molecular dynamics have provided further information on the atomic-scale effects of the macroscopic phenomena observed. These studies have shown that some macroscopic properties vary with the accumulation of alpha decay, but then stabilize after integrated doses of the order of 4 × 1018 α g-1. For example, the glass density diminishes by about 0.6%, its Young's modulus by about 15%, and its hardness by about 30%, while its fracture toughness increases by around 50%. The SEM and TEM characterization showed that the glass is still homogeneous. No phase separation, crystallization or bubbles formation was noticed up to an alpha decay dose corresponding to several thousand years of disposal of nuclear glass canister. Moreover the initial alteration rate of the glass is not significantly affected by the glass damage induced by alpha decays or heavy ions irradiations. The comparison of the macroscopic evolutions of the Cm doped glass with those obtained for glasses irradiated with light or heavy ions (from either experimental and molecular dynamic studies) suggests that the macroscopic evolutions are induced by the nuclear interactions induced by the recoil nuclei of alpha decay. The analysis of the behavior of the glass structure subjected to ballistic effects with various spectroscopic studies, together with the results of atomistic modeling by molecular dynamics, have identified some slight changes in the local order around some cations. Moreover a modification of the medium-range order has also been demonstrated through changes in the bond angles between network

  10. Specific outcomes of the research on the radiation stability of the French nuclear glass towards alpha decay accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Peuget, S., E-mail: sylvain.peuget@cea.fr; Delaye, J.-M.; Jégou, C.

    2014-01-15

    This paper presents an overview of the main results of the French research on the long-term behavior of SON68 nuclear glass towards alpha decay accumulation. The effect of the radiation damage induced by alpha decay and also helium build-up were investigated by examining glass specimens, doped with a short-lived actinide {sup 244}Cm, irradiated by light and heavy ions. Additionally, atomistic simulations by molecular dynamics have provided further information on the atomic-scale effects of the macroscopic phenomena observed. These studies have shown that some macroscopic properties vary with the accumulation of alpha decay, but then stabilize after integrated doses of the order of 4 × 10{sup 18} α g{sup −1}. For example, the glass density diminishes by about 0.6%, its Young’s modulus by about 15%, and its hardness by about 30%, while its fracture toughness increases by around 50%. The SEM and TEM characterization showed that the glass is still homogeneous. No phase separation, crystallization or bubbles formation was noticed up to an alpha decay dose corresponding to several thousand years of disposal of nuclear glass canister. Moreover the initial alteration rate of the glass is not significantly affected by the glass damage induced by alpha decays or heavy ions irradiations. The comparison of the macroscopic evolutions of the Cm doped glass with those obtained for glasses irradiated with light or heavy ions (from either experimental and molecular dynamic studies) suggests that the macroscopic evolutions are induced by the nuclear interactions induced by the recoil nuclei of alpha decay. The analysis of the behavior of the glass structure subjected to ballistic effects with various spectroscopic studies, together with the results of atomistic modeling by molecular dynamics, have identified some slight changes in the local order around some cations. Moreover a modification of the medium-range order has also been demonstrated through changes in the bond angles

  11. Alpha Stable Distribution Based Morphological Filter for Bearing and Gear Fault Diagnosis in Nuclear Power Plant

    Directory of Open Access Journals (Sweden)

    Xinghui Zhang

    2015-01-01

    Full Text Available Gear and bearing play an important role as key components of rotating machinery power transmission systems in nuclear power plants. Their state conditions are very important for safety and normal operation of entire nuclear power plant. Vibration based condition monitoring is more complicated for the gear and bearing of planetary gearbox than those of fixed-axis gearbox. Many theoretical and engineering challenges in planetary gearbox fault diagnosis have not yet been resolved which are of great importance for nuclear power plants. A detailed vibration condition monitoring review of planetary gearbox used in nuclear power plants is conducted in this paper. A new fault diagnosis method of planetary gearbox gears is proposed. Bearing fault data, bearing simulation data, and gear fault data are used to test the new method. Signals preprocessed using dilation-erosion gradient filter and fast Fourier transform for fault information extraction. The length of structuring element (SE of dilation-erosion gradient filter is optimized by alpha stable distribution. Method experimental verification confirmed that parameter alpha is superior compared to kurtosis since it can reflect the form of entire signal and it cannot be influenced by noise similar to impulse.

  12. Possible inducement of skin basaloma by external alpha radiation

    International Nuclear Information System (INIS)

    Sevcova, M.; Sevc, J.; Thomas, J.

    1975-01-01

    A comparison was made of the latest data on the thickness of the epidermis and the resulting estimate of dose rates to its basal layer with the results of several years of clinical observation in uranium miners exposed over a long term to alpha radiation from a 222 Rn daughter product deposit on the skin. It was found that the average dose equivalent in the basal layer of the epidermis from deposited 222 Rn daughter products was within the region of tens of rem/year even under good hygienic conditions in the uranium mine, and accumulated doses may after several years of exposure reach several thousands rems. In the narrow selection of workers where statistical comparison was possible it appeared that the frequency of observed skin carcinomas, mainly basal carcinomas of the face, neck and hands, is significantly higher in miners working in underground mines as against expected incidence. (B.S.)

  13. Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}.

    Science.gov (United States)

    Hertz, Rachel; Kalderon, Bella; Byk, Tamara; Berman, Ina; Za'tara, Ghadeer; Mayer, Raphael; Bar-Tana, Jacob

    2005-07-01

    Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not the respective free acids, and to catalyze the hydrolysis of bound fatty acyl-CoAs. The free acid pocket, previously reported in the x-ray structure of HNF-4alpha E-domain, entraps fatty acids but excludes acyl-CoAs. The acyl-CoA and free acid sites are distinctive and noncongruent. Free fatty acid products of HNF-4alpha thioesterase may exchange with free acids entrapped in the fatty acid pocket of HNF-4alpha. Cross-talk between the acyl-CoA and free fatty acid binding sites is abrogated by high affinity, nonhydrolyzable acyl-CoA ligands of HNF-4alpha that inhibit its thioesterase activity. Hence, HNF-4alpha transcriptional activity is controlled by its two interrelated acyl ligands and two binding sites interphased in tandem by the thioesterase activity. The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors.

  14. FcepsilonRI-alpha siRNA inhibits the antigen-induced activation of mast cells.

    Science.gov (United States)

    Safaralizadeh, Reza; Soheili, Zahra-Soheila; Deezagi, Abdolkhaleg; Pourpak, Zahra; Samiei, Shahram; Moin, Mostafa

    2009-12-01

    FcepsilonRI, The high affinity receptor for IgE plays a critical role in triggering the allergic reactions. It is responsible for inducing mast cell degranulation and deliberation of allergy mediators when it is aggregated by allergen and IgE complexes. FcepsilonRI on the mast cells consists of three subunits; alpha chain directly binds IgE, beta chain and dimmer of gamma chains together mediate intracellular signaling. Cross-linking of IgE-bound FcepsilonRI on the surface of mast cells and basophils by the multivalent antigen induces release of chemical mediators. The present in vitro study was designed to investigate the effect of synthetic FcepsilonRI-alpha siRNA on the antigen-induced activation of MC/9 cells. MC/9 cells which are murine mast cells were transfected by FcepsilonRI-alpha siRNA and negative control siRNA. After 6 h, anti-DNP (Dinitrophenyl) IgE was used for the cells sensitization. Then the cells were challenged with Dinitrophenyl-Human Serum Albumin (DNP-HSA) for mast cell degranulation induction before collection of supernatants. The amount of mRNA and protein expression was measured by Real Time PCR and western blot analysis, respectively. Determination of the expression rate of FcepsilonRI-alpha on cell surface was achieved by flow cytometry. ELISA and spectrophotometry methods were used subsequently for measuring the effects of FcepsilonRI-alpha siRNA on antigen-induced histamine and beta-hexosaminidase release. FcepsilonRI-alpha siRNA treated cells showed significant decrease in FcepsilonRI-alpha mRNA and protein expression in comparison to control cells. FcepsilonRI-mediated mast cell release of beta-hexosaminidase and histamine were also inhibited. In this study it was shown that FcepsilonRI-alpha siRNA could suppress FcepsilonRI-alpha expression and inhibited degranulation and histamine release in antigen-stimulated MC/9 cells. In conclusion, knock-down of FcepsilonRI-alpha by siRNA could be a promising method for inhibition of the mast

  15. Trans-generational effects induced by alpha and gamma ionizing radiations at Daphnia magna

    International Nuclear Information System (INIS)

    Parisot, Florian

    2015-01-01

    Anthropogenic activities related to the nuclear industry contribute to continuous discharges of radionuclides into terrestrial and aquatic ecosystems. Over the past decades, the ecological risk of ionizing radiation has become a growing public, regulatory and scientific concern for ecosystems protection. Until recently, only few studies focus on exposure situations at low doses of irradiation, although these situations are representative of realistic environmental conditions. Understanding how ionizing radiation affects species over several generations and at various levels of biological organization is a major research goal in radioecology. The aim of this PhD was to bring new knowledge on the effects of ionizing radiation during a multi-generational expose of the aquatic invertebrate, Daphnia magna. A two-step strategy was implemented. First, an external gamma radiation at environmentally relevant dose rates was performed on D. magna over three successive generations (F0, F1 and F2). The objective of this experiment was to examine whether low dose rates of radiation induced increasing effects on survival, growth and reproduction of daphnids over generations and to test a possible accumulation and transmission of DNA alterations from adults to offspring. Results showed an accumulation and a transmission of DNA alterations over generations, together with an increase in effect severity on growth and reproduction from generation F0 to generation F2. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in generation F1. Second, data from the external gamma irradiation and those from an earlier study of internal alpha contamination were analyzed with DEBtox models (Dynamic Energy Budget applied to toxicology), to identify and compare the causes of the trans-generational increase in effect severity between the two types of radiation. In each case, two distinct metabolic modes of action were necessary to explain effects on

  16. Interaction of alpha radiation with thermally-induced defects in silicon

    International Nuclear Information System (INIS)

    Ali, Akbar; Majid, Abdul

    2008-01-01

    The interaction of radiation-induced defects created by energetic alpha particles and thermally-induced defects in silicon has been studied using a Deep Level Transient Spectroscopy (DLTS) technique. Two thermally-induced defects at energy positions E c -0.48 eV and E c -0.25 eV and three radiation-induced defects E2, E3 and E5 have been observed. The concentration of both of the thermally-induced defects has been observed to increase on irradiation. It has been noted that production rates of the radiation-induced defects are suppressed in the presence of thermally-induced defects. A significant difference in annealing characteristics of thermally-induced defects in the presence of radiation-induced defects has been observed compared to the characteristics measured in pre-irradiated samples

  17. Alpha Particles Induce Autophagy in Multiple Myeloma Cells.

    Science.gov (United States)

    Gorin, Jean-Baptiste; Gouard, Sébastien; Ménager, Jérémie; Morgenstern, Alfred; Bruchertseifer, Frank; Faivre-Chauvet, Alain; Guilloux, Yannick; Chérel, Michel; Davodeau, François; Gaschet, Joëlle

    2015-01-01

    Radiation emitted by the radionuclides in radioimmunotherapy (RIT) approaches induce direct killing of the targeted cells as well as indirect killing through the bystander effect. Our research group is dedicated to the development of α-RIT, i.e., RIT using α-particles especially for the treatment of multiple myeloma (MM). γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by (213)Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of (213)Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation. Murine 5T33 and human LP-1 MM cell lines were used to study the effects of such α-particles. We first examined the effects of (213)Bi on proliferation rate, double-strand DNA breaks, cell cycle, and cell death. Then, we investigated autophagy after (213)Bi irradiation. Finally, a coculture of dendritic cells (DCs) with irradiated tumor cells or their culture media was performed to test whether it would induce DC activation. We showed that (213)Bi induces DNA double-strand breaks, cell cycle arrest, and autophagy in both cell lines, but we detected only slight levels of early apoptosis within the 120 h following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented (213)Bi-induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s); however, no increase in membrane or extracellular expression of danger-associated molecular patterns was observed after irradiation. This study demonstrates that (213)Bi induces mainly necrosis in MM cells, low levels of apoptosis, and autophagy that might be involved in tumor cell death.

  18. Alpha-particles induce autophagy in multiple myeloma cells

    Directory of Open Access Journals (Sweden)

    Joelle Marcelle Gaschet

    2015-10-01

    Full Text Available Objectives: Radiations emitted by the radionuclides in radioimmunotherapy (RIT approaches induce direct killing of the targeted cells as well as indirect killing through bystander effect. Our research group is dedicated to the development of α-RIT, i.e RIT using α-particles especially for the treatment of multiple myeloma (MM. γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by 213Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of 213Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation.Methods: Murine 5T33 and human LP-1 multiple myeloma (MM cell lines were used to study the effects of such α-particles. We first examined the effects of 213Bi on proliferation rate, double strand DNA breaks, cell cycle and cell death. Then, we investigated autophagy after 213Bi irradiation. Finally, a co-culture of dendritic cells (DC with irradiated tumour cells or their culture media was performed to test whether it would induce DC activation.Results: We showed that 213Bi induces DNA double strand breaks, cell cycle arrest and autophagy in both cell lines but we detected only slight levels of early apoptosis within the 120 hours following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented 213Bi induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s, however no increase in membrane or extracellular expression of danger associated molecular patterns (DAMPs was observed after irradiation.Conclusion: This study demonstrates that 213Bi induces mainly necrosis in MM cells, low levels of apoptosis and also autophagy that might be involved in tumor cell death.

  19. Release of alpha emitters into the environment by Nuclear Industries of Brazil in Resende, RJ

    International Nuclear Information System (INIS)

    Pereira, Wagner S.; Kelecom, Alphonse; Santos, Rodney; Santos, Maisa F.M.; Torres, Vinicius R.M.; Rodrigues, Jéssica J.S.; Universidade Veiga de Almeida; Universidade Federal Fluminense

    2017-01-01

    The Nuclear Industries of Brazil operates in the field of nuclear energy and has a monopoly on mining and manufacturing the nuclear fuel element in Brazil. The Nuclear Fuel Factory is also responsible for the reconversion process, the manufacture of the pellets and the assembly of the fuel element. Once there is a possibility of particulate material generation during the reconversion processes and the manufacture of pellets, a method of collective protection of the worker was established, which includes a system of air exhaustion of the factory area, with the capacity to renew the indoor air six times per hour. As a control measure, there is a system of automatic detection of the release of radionuclides in the chimney that monitors and calculates the released values. Through the dose calculation model established by the National Commission for Nuclear Energy the release limit is fixed at 1.2∙ 10"7Bq.y"-"1 of alpha emitters by FCN. The present work aims to evaluate the alpha radionuclides released by FCN, in terms of total release (Bq) and Activity Concentration (AC, mBq∙m"-"3). In 2016 it was released 4.14∙10"6Bq.y"-"1, which means an average of 3.45∙10"5Bq.month"-"1. The largest mean for AC was 4.03 mBq∙m"-"3. The release data was almost an order of magnitude lower than the annual release limit, proving the suitability of the atmospheric effluents to the licensing requirements. The largest magnitudes of the two variables (AC and release) were observed in August while the smallest ones, in January. (author)

  20. Release of alpha emitters into the environment by Nuclear Industries of Brazil in Resende, RJ

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Wagner S.; Kelecom, Alphonse; Santos, Rodney; Santos, Maisa F.M.; Torres, Vinicius R.M.; Rodrigues, Jéssica J.S., E-mail: comap@inb.gov.br, E-mail: pereiraws@gmail.com, E-mail: lararapls@hotmail.com [Indústrias Nucleares do Brasil (COMAP.N/FCN/INB), Resende RJ (Brazil). Fábrica de Combustível Nuclear. Coordenação de Meio Ambiente e Proteção Radiológica Ambiental; Universidade Veiga de Almeida (UVA), Rio de Janeiro, RJ (Brazil); Universidade Federal Fluminense (LARARA-PLS/UFF), Niterói, RJ (Brazil). Laboratório de Radiobiologia e Radiometria

    2017-07-01

    The Nuclear Industries of Brazil operates in the field of nuclear energy and has a monopoly on mining and manufacturing the nuclear fuel element in Brazil. The Nuclear Fuel Factory is also responsible for the reconversion process, the manufacture of the pellets and the assembly of the fuel element. Once there is a possibility of particulate material generation during the reconversion processes and the manufacture of pellets, a method of collective protection of the worker was established, which includes a system of air exhaustion of the factory area, with the capacity to renew the indoor air six times per hour. As a control measure, there is a system of automatic detection of the release of radionuclides in the chimney that monitors and calculates the released values. Through the dose calculation model established by the National Commission for Nuclear Energy the release limit is fixed at 1.2∙ 10{sup 7}Bq.y{sup -1} of alpha emitters by FCN. The present work aims to evaluate the alpha radionuclides released by FCN, in terms of total release (Bq) and Activity Concentration (AC, mBq∙m{sup -3}). In 2016 it was released 4.14∙10{sup 6}Bq.y{sup -1}, which means an average of 3.45∙10{sup 5}Bq.month{sup -1}. The largest mean for AC was 4.03 mBq∙m{sup -3}. The release data was almost an order of magnitude lower than the annual release limit, proving the suitability of the atmospheric effluents to the licensing requirements. The largest magnitudes of the two variables (AC and release) were observed in August while the smallest ones, in January. (author)

  1. Alpha-fetoprotein is a predictor of outcome in acetaminophen-induced liver injury

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2005-01-01

    An increase in alpha-fetoprotein (AFP) following hepatic necrosis is considered indicative of hepatic regeneration. This study evaluated the prognostic value of serial AFP measurements in patients with severe acetaminophen-induced liver injury. Prospectively, serial measurements of AFP were...

  2. Effect of hypoxia-inducible factor 1-alpha (HIF-1α) on proliferation ...

    African Journals Online (AJOL)

    Jane

    2011-07-25

    Jul 25, 2011 ... Full Length Research Paper. Effect of hypoxia-inducible factor 1-alpha ... 1Department of Neurosurgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025,. China. 2Department of Neurosurgery, Chaoyang Hospital, Huainan, Anhui, China. 3Department of Neurosurgery ...

  3. Drug-Induced Endoplasmic Reticulum and Oxidative Stress Responses Independently Sensitize Toward TNF alpha-Mediated Hepatotoxicity

    NARCIS (Netherlands)

    Fredriksson, Lisa; Wink, Steven; Herpers, Bram; Benedetti, Giulia; Hadi, Mackenzie; de Bont, Hans; Groothuis, Geny; Luijten, Mirjam; Danen, Erik; de Graauw, Marjo; Meerman, John; van de Water, Bob

    Drug-induced liver injury (DILI) is an important clinical problem. Here, we used a genomics approach to in detail investigate the hypothesis that critical drug-induced toxicity pathways act in synergy with the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha) to cause cell death of

  4. Expression of hypoxia-induced factor-1 alpha in early-stage and in metastatic oral squamous cell carcinoma.

    Science.gov (United States)

    Ribeiro, Maisa; Teixeira, Sarah R; Azevedo, Monarko N; Fraga, Ailton C; Gontijo, Antônio Pm; Vêncio, Eneida F

    2017-04-01

    To investigate hypoxia-induced factor-1 alpha expression in distinct oral squamous cell carcinoma subtypes and topographies and correlate with clinicopathological data. Hypoxia-induced factor-1 alpha expression was assessed by immunohistochemistry in 93 cases of OSCC. Clinical and histopathological data were reviewed from medical records. Hypoxia-induced factor-1 alpha status was distinct according to tumor location, subtype and topography affect. In superficial oral squamous cell carcinomas, most tumor cells overexpressed hypoxia-induced factor-1 alpha, whereas hypoxia-induced factor-1 alpha was restricted to the intratumoral region in conventional squamous cell carcinomas. All basaloid squamous cell carcinomas exhibited downregulation of hypoxia-induced factor-1 alpha. Interestingly, metastatic lymph nodes (91.7%, p = 0.001) and the intratumoral regions of corresponding primary tumors (58.3%, p = 0.142) showed hypoxia-induced factor-1 alpha-positive tumor cells. Overall survival was poor in patients with metastatic lymph nodes. Hypoxia-induced factor-1 alpha has distinct expression patterns in different oral squamous cell carcinoma subtypes and topographies, suggesting that low oxygen tension promotes the growth pattern of superficial and conventional squamous cell carcinoma, but not basaloid squamous cell carcinoma. Indeed, a hypoxic environment may facilitate regional metastasis, making it a useful diagnostic and prognostic marker in primary tumors.

  5. 17-AAG induces cytoplasmic alpha-synuclein aggregate clearance by induction of autophagy.

    Science.gov (United States)

    Riedel, Michael; Goldbaum, Olaf; Schwarz, Lisa; Schmitt, Sebastian; Richter-Landsberg, Christiane

    2010-01-18

    The accumulation and aggregation of alpha-synuclein in nerve cells and glia are characteristic features of a number of neurodegenerative diseases termed synucleinopathies. alpha-Synuclein is a highly soluble protein which in a nucleation dependent process is capable of self-aggregation. The causes underlying aggregate formation are not yet understood, impairment of the proteolytic degradation systems might be involved. In the present study the possible aggregate clearing effects of the geldanamycin analogue 17-AAG (17-(Allylamino)-17-demethoxygeldanamycin) was investigated. Towards this, an oligodendroglial cell line (OLN-93 cells), stably expressing human alpha-synuclein (A53T mutation) was used. In these cells small punctate aggregates, not staining with thioflavine S, representing prefibrillary aggregates, occur characteristically. Our data demonstrate that 17-AAG attenuated the formation of alpha-synuclein aggregates by stimulating macroautophagy. By blocking the lysosomal compartment with NH(4)Cl the aggregate clearing effects of 17-AAG were abolished and alpha-synuclein deposits were enlarged. Analysis of LC3-II immunoreactivity, which is an indicator of autophagosome formation, further revealed that 17-AAG led to the recruitment of LC3-II and to the formation of LC3 positive puncta. This effect was also observed in cultured oligodendrocytes derived from the brains of newborn rats. Inhibition of macroautophagy by 3-methyladenine prevented 17-AAG induced occurrence of LC3 positive puncta as well as the removal of alpha-synuclein aggregates in OLN-A53T cells. Our data demonstrate for the first time that 17-AAG not only causes the upregulation of heat shock proteins, but also is an effective inducer of the autophagic pathway by which alpha-synuclein can be removed. Hence geldanamycin derivatives may provide a means to modulate autophagy in neural cells, thereby ameliorating pathogenic aggregate formation and protecting the cells during disease and aging.

  6. Photoluminescence detection of alpha particle using DAM-ADC nuclear detector

    Energy Technology Data Exchange (ETDEWEB)

    Abdalla, Ayman M., E-mail: aymanabdalla62@hotmail.com [Department of Physics, College of Science and Arts, Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box: 1988, Najran 11001 (Saudi Arabia); Harraz, Farid A., E-mail: fharraz68@yahoo.com [Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box: 1988, Najran 11001 (Saudi Arabia); Nanostructured Materials and Nanotechnology Division, Central Metallurgical Research and Development Institute (CMRDI), P.O. Box: 87 Helwan, Cairo 11421 (Egypt); Ali, Atif M. [Department of Physics, Faculty of Science, King Khalid University, Abha (Saudi Arabia); Al-Sayari, S.A. [Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box: 1988, Najran 11001 (Saudi Arabia); College of Science and Arts-Sharoura, Najran University (Saudi Arabia); Al-Hajry, A. [Department of Physics, College of Science and Arts, Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box: 1988, Najran 11001 (Saudi Arabia)

    2016-09-11

    The photoluminescence (PL) and UV–vis spectral analysis of DAM-ADC (diallyl maleate: DAM, polyallyl diglycol carbonate: ADC) nuclear detector are demonstrated for the first time. The DAM-ADC surfaces were exposed to thin {sup 241}Am disk source that emits alpha particles with activity 333 kBq. It is found that the track density of the irradiated samples remarkably influences the PL characteristics of the DAM-ADC detector. The spectral peak heights and the integrated intensities under the peaks exhibit linear correlations with correlation coefficient R{sup 2}=0.9636 and 0.9806, respectively for different alpha particle fluences ranging from 8.16–40.82×10{sup 7} particles/cm{sup 2}. Additionally, a correlation coefficient R{sup 2}=0.9734 was achieved for the UV–vis spectral analysis. The linear fitting functions, along with the corresponding fitting parameters were evaluated in each case. Both the PL and the UV–vis data of the irradiated DAM-ADC samples showed considerable spectral differences, and hence they would be used to offer sensitive approaches for alpha particle detection.

  7. The role of hepatocyte nuclear factor 4 alpha in development and progression of liver diseases

    Directory of Open Access Journals (Sweden)

    YANG Jinlian

    2016-02-01

    Full Text Available Hepatocyte nuclear factor 4 alpha (HNF4α, a member of the nuclear receptor superfamily, has a high expression level in mature hepatocytes. HNF4α can regulate hepatocyte-specific gene expression at a transcriptional level, promote hepatocyte development and differentiation, participate in establishment and maintenance of hepatocyte polarity, and enhance the synthetic, metabolic, and detoxifying functions of the liver. Through inhibiting the activation of hepatic stellate cells, reversing epithelial-mesenchymal transition, and inhibiting the proliferation, invasion, and metastasis of hepatoma cells, HNF4α may be involved in the development and progression of various liver diseases including liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. This paper elaborates on the biological functions of HNF4α, and summarizes and analyzes the research advances in the mechanisms of action of HNF4α in the pathological process of liver diseases, in order to provide references for further investigation of the potential targeted therapies for liver diseases.

  8. Induced isospin mixing in direct nuclear reactions

    International Nuclear Information System (INIS)

    Lenske, H.

    1979-07-01

    The effect of charge-dependent interactions on nuclear reactions is investigated. First, a survey is given on the most important results concerning the charge dependence of the nucleon-nucleon interaction. The isospin symmetry and invariance principles are discussed. Violations of the isospin symmetry occuring in direct nuclear reactions are analysed using the soupled channel theory, the folding model and microscopic descriptions. Finally, induced isospin mixing in isospin-forbidden direct reactions is considered using the example of the inelastic scattering of deuterons on 12 C. (KBE)

  9. alpha-Adrenoceptor and opioid receptor modulation of clonidine-induced antinociception.

    Science.gov (United States)

    Sierralta, F; Naquira, D; Pinardi, G; Miranda, H F

    1996-10-01

    1. The antinociceptive action of clonidine (Clon) and the interactions with alpha 1, alpha 2 adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test). 2. Clon produced a dose-dependent antinociceptive action and the ED50 for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg-1 vs 300 ng kg-1). The parallelism of the dose-response curves indicates activation of a common receptor subtype. 3. Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon-induced activity. These results suggest that alpha 1- and alpha 2-adrenoceptors, either located at the pre- and/or post-synaptic level, are involved in the control of spinal antinociception. 4. Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (microgram kg-1 range) and a lower antinociceptive effect at higher doses (mg kg-1 range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential mu opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P. 5. The results obtained in the present work suggest the involvement of alpha 1-, alpha 2-adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level.

  10. Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S

    1991-04-01

    A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

  11. Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-alpha and translocating PKC-delta.

    Science.gov (United States)

    Zhang, Xian-Ming; Chen, Jia; Xia, Yu-Gui; Xu, Qiang

    2005-03-01

    In our previous study, quercetin was found to induce apoptosis of murine melanoma B16-BL6 cells. The cellular and molecular mechanism of quercetin-induced apoptosis was investigated in the present study. Nuclear morphology was determined by fluorescence microscopy. DNA fragmentation was analyzed by electrophoresis and quantified by the diphenylamine method. The transmembrane potential of mitochondria was measured by flow cytometry. Bcl-2, Bcl-X(L), PKC-alpha, PKC-beta, and PKC-delta were detected by Western blotting. Caspase activity was determined spectrophotometrically. Quercetin induced the condensation of nuclei of B16-BL6 cells in a dose-dependent pattern as visualized by Hoechst 33258 and propidium iodide dying. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, significantly enhanced apoptosis induced by quercetin, while doxorubicin, a PKC inhibitor, markedly decreased it. Both PMA and doxorubicin showed a consistent effect on the fragmentation of nuclear DNA caused by various dosages of quercetin. Quercetin dose-dependently led to loss of the mitochondrial membrane potential, which was also significantly reinforced or antagonized by PMA and doxorubicin, respectively. Moreover, PMA showed reinforcement, while doxorubicin showed significant antagonization, of the quercetin-mediated decrease in the expression of Bcl-2. Quercetin promoted caspase-3 activity in a dose-dependent manner, which was also regulated by PMA and doxorubicin with a pattern similar to that seen in their effect on apoptosis, mitochondrial membrane potential and Bcl-2 expression, but none of these were directly affected by PMA and doxorubicin. Free fatty acid and chlorpromazine, a PKC activator and inhibitor, respectively, did not interfere with these effects of quercetin. B16-BL6 cells expressed PKC-alpha, PKC-beta, and PKC-delta. Quercetin dose-dependently inhibited the expression of PKC-alpha but not that of PKC-beta and PKC-delta. Doxorubicin almost completely blocked the effect of

  12. Mapping of nuclear import signal and importin {alpha}3 binding regions of 52K protein of bovine adenovirus-3

    Energy Technology Data Exchange (ETDEWEB)

    Paterson, Carolyn P.; Ayalew, Lisanework E. [Vaccine and Infectious Disease Organization-International Vaccine Center (VIDO-InterVac), University of Saskatchewan, Saskatoon, SK S7N 5E3 Canada (Canada); Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK S7N 5E3 S7N 5B4 Canada (Canada); Tikoo, Suresh K., E-mail: suresh.tik@usask.ca [Vaccine and Infectious Disease Organization-International Vaccine Center (VIDO-InterVac), University of Saskatchewan, Saskatoon, SK S7N 5E3 Canada (Canada); Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK S7N 5E3 S7N 5B4 Canada (Canada); School of Public Health, University of Saskatchewan, Saskatoon, SK S7N 5E5 Canada (Canada)

    2012-10-10

    The L1 region of bovine adenovirus (BAdV)-3 encodes a non-structural protein designated 52K. Anti-52K serum detected a protein of 40 kDa, which localized to the nucleus but not to the nucleolus in BAdV-3-infected or transfected cells. Analysis of mutant 52K proteins suggested that three basic residues ({sup 105}RKR{sup 107}) of the identified domain (amino acids {sup 102}GMPRKRVLT{sup 110}) are essential for nuclear localization of 52K. The nuclear import of a GST-52K fusion protein utilizes the classical importin {alpha}/{beta}-dependent nuclear transport pathway. The 52K protein is preferentially bound to the cellular nuclear import receptor importin {alpha}3. Although deletion of amino acid 102-110 is sufficient to abrogate the nuclear localization of 52K, amino acid 90-133 are required for interaction with importin-{alpha}3 and localizing a cytoplasmic protein to the nucleus. These results suggest that 52K contains a bipartite NLS, which preferentially utilize an importin {alpha}3 nuclear import receptor-mediated pathway to transport 52K to the nucleus.

  13. Alpha band cortico-muscular coherence occurs in healthy individuals during mechanically-induced tremor.

    Directory of Open Access Journals (Sweden)

    Francesco Budini

    Full Text Available The present work aimed at investigating the effects of mechanically amplified tremor on cortico-muscular coherence (CMC in the alpha band. The study of CMC in this specific band is of particular interest because this coherence is usually absent in healthy individuals and it is an aberrant feature in patients affected by pathological tremors; understanding its mechanisms is therefore important. Thirteen healthy volunteers (23±4 years performed elbow flexor sustained contractions both against a spring load and in isometric conditions at 20% of maximal voluntary isometric contraction (MVC. Spring stiffness was selected to induce instability in the stretch reflex servo loop. 64 EEG channels, surface EMG from the biceps brachii muscle and force were simultaneously recorded. Contractions against the spring resulted in greater fluctuations of the force signal and EMG amplitude compared to isometric conditions (p<.05. During isometric contractions CMC was systematically found in the beta band and sporadically observed in the alpha band. However, during the contractions against the spring load, CMC in the alpha band was observed in 12 out of 13 volunteers. Partial directed coherence (PDC revealed an increased information flow in the EMG to EEG direction in the alpha band (p<.05. Therefore, coherence in the alpha band between the sensory-motor cortex and the biceps brachii muscle can be systematically induced in healthy individuals by mechanically amplifying tremor. The increased information flow in the EMG to EEG direction may reflect enhanced afferent activity from the muscle spindles. These results may contribute to the understanding of the presence of alpha band CMC in tremor related pathologies by suggesting that the origin of this phenomenon may not only be at cortical level but may also be affected by spinal circuit loops.

  14. Integral excitation functions for proton and alpha induced reactions on target elements 22 <= Z <= 28

    International Nuclear Information System (INIS)

    Brinkmann, G.

    1979-01-01

    In the framework of a systematic study which is also important for certain cosmological questions a series of integral excitation functions of p- and α-induced nuclear reactions on target elements 22 [de

  15. PGC-1alpha mediates exercise-induced skeletal muscle VEGF expression in mice

    DEFF Research Database (Denmark)

    Leick, Lotte; Hellsten, Ylva; Fentz, Joachim

    2009-01-01

    The aim of the present study was to test the hypothesis that PGC-1alpha is required for exercise-induced VEGF expression in both young and old mice and that AMPK activation leads to increased VEGF expression through a PGC-1alpha-dependent mechanism. Whole body PGC-1alpha knockout (KO......) and littermate wild-type (WT) mice were submitted to either 1) 5 wk of exercise training, 2) lifelong (from 2 to 13 mo of age) exercise training in activity wheel, 3) a single exercise bout, or 4) 4 wk of daily subcutaneous AICAR or saline injections. In skeletal muscle of PGC-1alpha KO mice, VEGF protein...... expression was approximately 60-80% lower and the capillary-to-fiber ratio approximately 20% lower than in WT. Basal VEGF mRNA expression was similar in WT and PGC-1alpha KO mice, but acute exercise and AICAR treatment increased the VEGF mRNA content in WT mice only. Exercise training of young mice increased...

  16. Estradiol-induced estrogen receptor-alpha trafficking.

    Science.gov (United States)

    Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

    2009-12-02

    Estradiol has rapid actions in the CNS that are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca(2+)](i)) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERalpha has an extracellular portion. In addition to the full-length ERalpha [apparent molecular weight (MW), 66 kDa], surface biotinylation labeled an ERalpha-immunoreactive protein (MW, approximately 52 kDa) identified by both COOH- and NH(2)-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 and 52 kDa ERalpha. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24-48 h reduced ERalpha levels, suggesting receptor downregulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERalpha-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERalpha trafficking to and from the membrane. Estradiol-induced [Ca(2+)](i) flux was also significantly increased at the time of peak ERalpha activation/internalization. These results demonstrate that ERalpha is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERalpha are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERalpha to augment and then terminate membrane-initiated signaling.

  17. Prolactin, TNF alpha and nitric oxide expression in nitroso-N-methylurea-induced-mammary tumours

    Directory of Open Access Journals (Sweden)

    Vegh Irene

    2007-11-01

    Full Text Available Abstract Background The N-Nitrosomethylurea breast cancer model induced in rats is used for the study of carcinogenesis in mammary cancer, prostate, pancreas, etc. This model is very similar to human neoplastic disease. Methods The present experimental study was designed to assess whether metoclopramide administration has any effect on development of MNU-induced tumours, and evaluate the treatment of goserelin acetate on PRL, TNF alpha and NO expression. NMU was administered to female Wistar rats on 2 occasions (5 mg/100 g body w/rat. PRL and TNF alpha were performed by immune-assay. Nitric Oxide by semi automated-assay and ploidy analyses by flow cytometry. Results The administration of metoclopramide made the induction time shorter and increased the incidence and average of tumours per rat. Tumours development was inhibited by a goserelin chronic administration. The ploidy of adenocarcinoma was polyploid-aneuploid type (average S = 60%. It was higher basal PRL plasma levels in rats with NMU induced tumours than in basal controls without tumour (p Conclusion The increase of blood PRL levels in NMU-induced rats may be an indicator of a poor prognosis of mammary cancer evolution. The metoclopramide administration accelerates tumour growth. However goserelin administration achieves regression in tumour development associated to inhibition PRL, TNF alpha and NO expression.

  18. Vibration induced hearing loss in guinea pig cochlea: expression of TNF-alpha and VEGF.

    Science.gov (United States)

    Zou, Jing; Pyykkö, Ilmari; Sutinen, Päivi; Toppila, Esko

    2005-04-01

    Transcranial vibration was applied for seven animals at a frequency of 250 Hz for 15 min, and five animals were used as normal controls to investigate cellular and molecular mechanism linked to vibration-induced hearing loss in animal model. Compound action potential (CAP) thresholds were measured by round window niche electrode. The expression of tumour necrosis factor alpha (TNF-alpha) and its receptors (TNF R1, TNF R2), vascular endothelium growth factor (VEGF) and its receptors (VEGF R1, VEGF R2) were analysed by immunohistochemistry. Transcranial vibration caused expression of TNF-alpha, TNF R1 and TNF R2 in the cochlea and the expression of TNF R2 was stronger than that of TNF R1. Vibration also induced VEGF and VEGF R2 expression in the cochlea. The average immediate hearing loss was 62 dB and after three days still 48 dB. It is concluded that transcranial vibration as during temporal bone drilling produces cochlear shear stress that is connected with up-regulation of TNF-alpha and its receptors. Also VEGF and VEGF R2 are up-regulated. These responses may be linked to both the damage and repair process of the cochlea.

  19. Alpha Radiolysis of Nuclear Solvent Extraction Ligands Used for An(III) and Ln(III) Separations

    Energy Technology Data Exchange (ETDEWEB)

    Mezyk, Stephen P. [California State Univ. (CalState), Long Beach, CA (United States); Mincher, Bruce J. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Nilsson, Mikael [Univ. of California, Irvine, CA (United States)

    2016-08-01

    This document is the final report for the Nuclear Energy Universities Program (NEUP) grant 10-910 (DE-AC07-05ID14517) “Alpha Radiolysis of Nuclear Solvent Extraction Ligands used for An(III) and Ln(III) Separations”. The goal of this work was to obtain a quantitative understanding of the impacts of both low Linear Energy Transfer (LET, gamma-rays) and high LET (alpha particles) radiation chemistry occurring in future large-scale separations processes. This quantitative understanding of the major radiation effects on diluents and ligands is essential for optimal process implementation, and could result in significant cost savings in the future.

  20. Crystal structure of importin-{alpha} complexed with a classic nuclear localization sequence obtained by oriented peptide library screening

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, A.A.S.; Fontes, M.R.M. [UNESP, Universidade Estadual Paulista, Botucatu, SP (Brazil); Yang, S.N.Y. [University of Melbourne, Melbourne (Australia); Harris, J.M. [Queensland University of Technology, Brisbane (Australia); Jans, D.A. [Monash University, Clayton (Australia); Kobe, B. [University of Queensland, Brisbane, QU (Australia)

    2012-07-01

    Full text: Importin-{alpha} (Imp{alpha}) plays a role in the classical nuclear import pathway, binding to cargo proteins with activities in the nucleus. Different Imp{alpha} paralogs responsible for specific cargos can be found in a single organism. The cargos contain nuclear localization sequences (NLSs), which are characterized by one or two clusters of basic amino acids (monopartite and bipartite NLSs, respectively). In this work we present the crystal structure of Imp{alpha} from M. musculus (residues 70-529, lacking the auto inhibitory domain) bound to a NLS peptide (pepTM). The peptide corresponds to the optimal sequence obtained by an oriented peptide library experiment designed to probe the specificity of the major NLS binding site. The peptide library used five degenerate positions and identified the sequence KKKRR as the optimal sequence for binding to this site for mouse Imp{alpha} (70-529). The protein was obtained using an E. coli expression system and purified by affinity chromatography followed by an ion exchange chromatography. A single crystal of Imp{alpha} -pepTM complex was grown by the hanging drop method. The data were collected using the Synchrotron Radiation Source LNLS, Brazil and processed to 2.3. Molecular replacement techniques were used to determine the crystal structure. Electron density corresponding to the peptide was present in both major and minor binding sites The peptide is bound to Imp{alpha} similar as the simian virus 40 (SV40) large tumour (T)-antigen NLS. Binding assays confirmed that the peptide bound to Imp{alpha} with low nM affinities. This is the first time that structural information has been linked to an oriented peptide library screening approach for importin-{alpha}; the results will contribute to understanding of the sequence determinants of classical NLSs, and may help identify as yet unidentified classical NLSs in novel proteins. (author)

  1. Nuclear fission induced by heavy ions

    International Nuclear Information System (INIS)

    Newton, J.O.

    1988-09-01

    Because the accelerators of the 50's and 60's mostly provided beams of light ions, well suited for studying individual quantum states of low angular momentum or reactions involving the transfer of one or two nucleons, the study of fission, being an example of large-scale collective motion, has until recently been outside of the mainstream of nuclear research. This situation has changed in recent years, due to the new generation of accelerators capable of producing beams of heavy ions with energies high enough to overcome the Coulomb barriers of all stable nuclei. These have made possible the study of new examples of large-scale collective motions, involving major rearrangements of nuclear matter, such as deep-inelastic collisions and heavy-ion fusion. Perhaps the most exciting development in the past few years is the discovery that dissipative effects (nuclear viscosity) play an important role in fission induced by heavy ions, contrary to earlier assumptions that the viscosity involved in fission was very weak and played only a minor role. This review will be mainly concerned with developments in heavy-ion induced fission during the last few years and have an emphasis on the very recent results on dissipative effects. Since heavy-ion bombardment usually results in compound systems with high excitation energies and angular momenta, shell effects might be expected to be small, and the subject of low energy fission, where they are important, will not be addressed. 285 refs., 58 figs

  2. Interferin with thyroid scintigraphy: the effects of interferon alpha induced thyroid gland autoimmunity and dysfunction upon thyroid scintigraphy in patients with the hepatitis C virus

    International Nuclear Information System (INIS)

    Rome, S.P.; Karamoskos, P.; Schlicht, S.M.

    2003-01-01

    Full text: The incidence of hepatitis C virus (HCV) infection is increasing. Interferon alpha therapy is often used to treat patients who are HCV positive. Thyroid gland autoimmunity and dysfunction has been reported to occur with variable frequency during INF-alpha therapy in patients with the HCV. This study reviews the scintigraphic findings of thyroid scans in such patients in order to assess for the effects on thyroid scintigraphy. To our knowledge, there has been no comprehensive study of this important occurrence to date. There were a number of patients with the HCV being treated at our institution between 23/09/1996 and 09/08/2000. Some of them received INF-alpha therapy, certain were subsequently diagnosed with thyroid gland autoimmunity and/or dysfunction. Eight were imaged with thyroid scintigraphy and reviewed. The scintigraphic findings in the 8 patients fell into two broad categories; 4 demonstrated changes of Graves' disease, and 3 changes of thyroiditis (1 of these was sub-acute). One hypothyroid patient with anti-thyroglobulin antibodies had normal thyroid scintigraphy. Six patients were found to have antithyroid antibodies. One patient with thyroiditis tested negative to antithyroid antibodies. One patient was not tested for antithyroid antibodies. Interferon alpha induced thyroid gland autoimmunity and/or dysfunction can markedly affect the thyroid scintigraphic findings of patients with the hepatitis C virus. This hitherto undescribed occurrence on thyroid scintigraphy has important practical implications of which Nuclear Medicine Specialists need to be aware in order to correctly interpret thyroid scintigraphy studies in such patients. The clinical presentation and effects on imaging appearances are varied. The Nuclear Medicine Specialist can play a central role in establishing the causal link. Awareness of this occurrence enables the Nuclear Medicine Specialist to add value to the referral. This occurrence will become an increasingly common

  3. Partial deficiency of HIF-1 alpha stimulates pathological cardiac changes in streptozotocin-induced diabetic mice

    Czech Academy of Sciences Publication Activity Database

    Bohuslavová, Romana; Kolář, František; Sedmera, David; Škvorová, Lada; Papoušek, František; Neckář, Jan; Pavlínková, Gabriela

    2014-01-01

    Roč. 14, Feb 6 (2014) ISSN 1472-6823 R&D Projects: GA ČR GA301/09/0117; GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:68378271 Keywords : Echocardiographic parameters * Hypoxia inducible factor 1 alpha * Diabetic cardiomyopathy Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.710, year: 2014

  4. Reactivity determination in accelerator driven nuclear reactors by statistics from neutron detectors (Feynman-Alpha Method)

    International Nuclear Information System (INIS)

    Ceder, M.

    2002-03-01

    The Feynman-alpha method is used in traditional nuclear reactors to determine the subcritical reactivity of a system. The method is based on the measurement of the mean number and the variance of detector counts for different measurement times. The measurement is performed while a steady-state neutron flux is maintained in the reactor by an external neutron source, as a rule a radioactive source. From a plot of the variance-to-mean ratio as a function of measurement time ('gate length'), the reactivity can be determined by fitting the measured curve to the analytical solution. A new situation arises in the planned accelerator driven systems (ADS). An ADS will be run in a subcritical mode, and the steady flux will be maintained by an accelerator based source. Such a source has statistical properties that are different from those of a steady radioactive source. As one example, in a currently running European Community project for ADS research, the MUSE project, the source will be a periodically pulsed neutron generator. The theory of Feynman-alpha method needs to be extended to such nonstationary sources. There are two ways of performing and evaluating such pulsed source experiments. One is to synchronise the detector time gate start with the beginning of an incoming pulse. The Feynman-alpha method has been elaborated for such a case recently. The other method can be called stochastic pulsing. It means that there is no synchronisation between the detector time gate start and the source pulsing, i.e. the start of each measurement is chosen at a random time. The analytical solution to the Feynman-alpha formula from this latter method is the subject of this report. We have obtained an analytical Feynman-alpha formula for the case of stochastic pulsing by two different methods. One is completely based on the use of the symbolic algebra code Mathematica, whereas the other is based on complex function techniques. Closed form solutions could be obtained by both methods

  5. Reactivity determination in accelerator driven nuclear reactors by statistics from neutron detectors (Feynman-Alpha Method)

    Energy Technology Data Exchange (ETDEWEB)

    Ceder, M

    2002-03-01

    The Feynman-alpha method is used in traditional nuclear reactors to determine the subcritical reactivity of a system. The method is based on the measurement of the mean number and the variance of detector counts for different measurement times. The measurement is performed while a steady-state neutron flux is maintained in the reactor by an external neutron source, as a rule a radioactive source. From a plot of the variance-to-mean ratio as a function of measurement time ('gate length'), the reactivity can be determined by fitting the measured curve to the analytical solution. A new situation arises in the planned accelerator driven systems (ADS). An ADS will be run in a subcritical mode, and the steady flux will be maintained by an accelerator based source. Such a source has statistical properties that are different from those of a steady radioactive source. As one example, in a currently running European Community project for ADS research, the MUSE project, the source will be a periodically pulsed neutron generator. The theory of Feynman-alpha method needs to be extended to such nonstationary sources. There are two ways of performing and evaluating such pulsed source experiments. One is to synchronise the detector time gate start with the beginning of an incoming pulse. The Feynman-alpha method has been elaborated for such a case recently. The other method can be called stochastic pulsing. It means that there is no synchronisation between the detector time gate start and the source pulsing, i.e. the start of each measurement is chosen at a random time. The analytical solution to the Feynman-alpha formula from this latter method is the subject of this report. We have obtained an analytical Feynman-alpha formula for the case of stochastic pulsing by two different methods. One is completely based on the use of the symbolic algebra code Mathematica, whereas the other is based on complex function techniques. Closed form solutions could be obtained by both methods

  6. Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-alpha in monocyte-derived macrophages.

    Science.gov (United States)

    Kim, Sung-Jo

    2010-06-01

    In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in differentiated THP-1 cells, a human monocytic cell line. LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-alpha and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Leptin enhanced P. intermedia LPS-induced TNF-alpha production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-alpha expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-alpha production was not mediated by the leptin receptor. The ability of leptin to enhance P. intermedia LPS-induced TNF-alpha production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

  7. Synthetic. cap alpha. subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, D.J.; Griesmann, G.E.; Huang, Z.; Lennon, V.A.

    1986-03-05

    A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) ..cap alpha.. subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 ..mu..g of peptide (T ..cap alpha.. 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR ..cap alpha.. subunit. Peptide H ..cap alpha.. 125-147 differs from T ..cap alpha.. 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodies to Torpedo AChR bound /sup 125/I-labelled H..cap alpha.. 125-147 antibody bound H..cap alpha.. 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither H..cap alpha.. 125-147 nor T ..cap alpha.. 125-147. Rats immunized with H ..cap alpha.. 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR ..cap alpha.. subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man.

  8. Vinculin but not alpha-actinin is a target of PKC phosphorylation during junctional assembly induced by calcium

    DEFF Research Database (Denmark)

    Perez-Moreno, M; Avila, A; Islas, S

    1998-01-01

    and alpha-actinin, two actin binding proteins of the adherent junctions. We found that during the junctional sealing induced by Ca2+, both proteins move towards the cell periphery and, while there is a significant increase in the phosphorylation of vinculin, alpha-actinin remains unchanged. The increased...

  9. Lactobacillus casei secreting alpha-MSH induces the therapeutic effect on DSS-induced acute colitis in Balb/c Mice.

    Science.gov (United States)

    Yoon, Sun-Woo; Lee, Chul-Ho; Kim, Jeong-Yoon; Kim, Jie-Youn; Sung, Moon-Hee; Poo, Haryoung

    2008-12-01

    The neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-alpha-MSH on the colitis, L. casei or L. casei-alpha-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-alpha-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45+/-0. 2 g; L. casei-alpha- MSH: 18.2+/-0.12 g), colitis score (DSS alone: 3.6+/-0.4; L. casei-alpha-MSH: 1.4+/-0.6), MPO activity (DSS alone: 42.7+/-4.5 U/g; L. casei-alpha-MSH: 10.25+/-0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappaB activation. The alpha-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

  10. Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.

    Science.gov (United States)

    Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

    2006-10-01

    Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.

  11. [Alpha interferon induced hyperthyroidism: a case report and review of the literature].

    Science.gov (United States)

    Maiga, I; Valdes-Socin, H; Thiry, A; Delwaide, J; Sidibe, A T; Beckers, A

    2015-01-01

    Treatment with alpha interferon in hepatitis C triggers a thyroid autoimmunity in a variable percentage of cases (2-8%). This complication raises some questions about its screening, the possibility to continue anti-viral therapy and thyroid treatment. Alpha interferon has an immunomodulatory effect on the thyroid, but also an inhibitory effect on thyroid hormone synthesis. This explains the occurrence of cases of thyroid dysfunction, which often remain undetected because of their latency. Factors predicting thyroid dysfunction with interferon use are: female sex, history of thyroid disease and previous autoimmunity. Several clinical aspects are encountered including hypothyroidism (the most frequent depending on the series) and hyperthyroidism related to Graves' disease. For their detection, a cooperation between general practionners, gastroenterologists and endocrinologists is mandatory thyroid function tests are requested before, during and after treatment,with alpha interferon. Therapeutic aspects of thyroid disorders range from simple monitoring to symptomatic treatment, such as thyroxine prescription in the presence of hypothyroidism. Antithyroid drugs radioactive iodine or thyroid surgery are used in cases of severe or persistent Graves' disease induced by alpha interferon.

  12. Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lukas, R.J.; Bennett, E.L.

    1979-01-01

    The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

  13. PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Leick, Lotte; Wojtaszewski, Jørgen F P; Johansen, Sune T.

    2008-01-01

    The aim of the present study was to test the hypothesis that peroxisome proliferator activated receptor-gamma coactivator (PGC) 1alpha is required for exercise-induced adaptive gene responses in skeletal muscle. Whole body PGC-1alpha knockout (KO) and littermate wild-type (WT) mice performed....... Resting muscles of the PGC-1alpha KO mice had lower ( approximately 20%) cytochrome c (cyt c), cytochrome oxidase (COX) I, and aminolevulinate synthase (ALAS) 1 mRNA and protein levels than WT, but similar levels of AMP-activated protein kinase (AMPK) alpha1, AMPKalpha2, and hexokinase (HK) II compared...

  14. Photon hormesis deactivates alpha-particle induced bystander effects between zebrafish embryos

    International Nuclear Information System (INIS)

    Ng, C.Y.P.; Cheng, S.H.; Yu, K.N.

    2017-01-01

    In the present work, we studied the effects of low-dose X-ray photons on the alpha-particle induced bystander effects between embryos of the zebrafish, Danio rerio. The effects on the naive whole embryos were studied through quantification of apoptotic signals (amounts of cells undergoing apoptosis) at 24 h post fertilization (hpf) using vital dye acridine orange staining, followed by counting the stained cells under a fluorescent microscope. We report data showing that embryos at 5 hpf subjected to a 4.4 mGy alpha-particle irradiation could release a stress signal into the medium, which could induce bystander effect in partnered naive embryos sharing the same medium. We also report that the bystander effect was deactivated when the irradiated embryos were subjected to a concomitant irradiation of 10 or 14 mGy of X-rays, but no such deactivation was achieved if the concomitant X-ray dose dropped to 2.5 or 5 mGy. In the present study, the significant drop in the amount of apoptotic signals on the embryos having received 4.4 mGy alpha particles together X-rays irradiation from 2.5 or 5 mGy to 10 or 14 mGy, together with the deactivation of RIBE with concomitant irradiation of 10 or 14 mGy of X-rays supported the participation of photon hormesis with an onset dose between 5 and 10 mGy, which might lead to removal of aberrant cells through early apoptosis or induction of high-fidelity DNA repair. As we found that photons and alpha particles could have opposite biological effects when these were simultaneously irradiated onto living organisms, these ionizing radiations could be viewed as two different environmental stressors, and the resultant effects could be regarded as multiple stressor effects. The present work presented the first study on a multiple stressor effect which occurred on bystander organisms. In other words, this was a non-targeted multiple stressor effect. The photon hormesis could also explain some failed attempts to observe neutron-induced bystander

  15. New features of nuclear excitation by {alpha} particles scattering; Nouveaux aspects de l'excitation nucleaire par diffusion de particules {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Saudinos, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1962-07-01

    Inelastic scattering of medium energy a particles by nuclei is known to excite preferentially levels of collective character. We have studied the scattering of isotopically enriched targets of Ca, Fe, Ni, Cu, Zn. In part I, we discuss the theoretical features of the interaction. In part II, we describe the experimental procedure. Results are presented and analysed in part III. {alpha} particles scattering by Ca{sup 40} is showed to excite preferentially odd parity levels. In odd nuclei we have observed multiplets due to the coupling of the odd nucleon with the even-even core vibrations. For even-even nuclei, a few levels are excited with lower cross-sections between the well-known first 2{sup +} and 3{sup -} states. Some could be members of the two phonon quadrupole excitation and involve a double nuclear excitation process. (author) [French] On sait que la diffusion inelastique des particules alpha de moyenne energie excite preferentiellement des niveaux de caractere collectif. Nous avons etudie la diffusion des particules alpha de 44 MeV du cyclotron de Saclay par des isotopes separes de Ca, Fe, Ni, Cu, Zn. Dans la premiere partie nous exposons les theories de cette interaction. Dans la seconde nous decrivons le systeme experimental. Les resultats sont donnes dans la troisieme partie. Nous montrons que les niveaux excites preferentiellement pour {sup 40}Ca par diffusion ({alpha},{alpha}') sont de parite negative. Dans les noyaux pair-impair nous avons observe des multiplets dus au couplage du nucleon celibataire avec les vibrations du coeur pair-pair. Pour les noyaux pair-pair nous avons pu etudier entre le premier niveau 2{sup +} et le niveau 3{sup -} deja bien connus certains etats plus faiblement excites. Il semble qu'ils sont dus a une excitation quadrupolaire a deux phonons et impliquent un processus de double excitation nucleaire. (auteur)

  16. Analyses of human exposures to alpha-emitting radionuclides from nuclear fuel cycles

    International Nuclear Information System (INIS)

    Cuddihy, R.G.; McClellan, R.O.; Griffith, W.C.; Hoover, M.D.

    1977-01-01

    Human populations may potentially be exposed to alpha-emitting radionuclides released to the environment from a variety of activities associated with nuclear fuel cycles. Generally, the most important exposure pathway is by way of inhalation. This can occur soon after release of these substances or after they have been deposited on ground surfaces and resuspended with soil particles. Estimating the potential magnitude of these exposures is usually done through the use of mathematical models accounting for the dispersion of the released material through the environment and its uptake by people living near the nuclear facilities. Studies described in this paper suggest that these exposures can probably be estimated within a factor of 10 based upon our previous experience with measured human organ levels of other trace metals taken up from the environment. It should also be noted that variability among individuals within the population may result in a few percent accumulating more than 10 times the geometric mean of the internal organ radionuclide burdens

  17. Relative workload determines exercise-induced increases in PGC-1alpha mRNA

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai Baastrup; Lundby, Carsten; Leick, Lotte

    2010-01-01

    INTRODUCTION:: The hypothesis that brief intermittent exercise induced increases in human skeletal muscle metabolic mRNA is dependent on relative workload was investigated. METHODS:: Trained (n=10) and untrained (n=8) subjects performed exhaustive intermittent cycling exercise (4x4 min @ 85% of VO2...... peak, interspersed by 3 min). Trained subjects also performed the intermittent exercise at the same absolute workload as untrained, corresponding to 70% of VO2 peak (n=6). RESULTS:: Exercise at 85% of VO2 peak elevated (P... and untrained, respectively. PGC-1alpha mRNA expression was increased (Pelevated (3.1+/-0.7 mM) and PGC-1alpha mRNA content was less (P

  18. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

    DEFF Research Database (Denmark)

    Lyckesvärd, Madeleine Nordén; Delle, Ulla; Kahu, Helena

    2014-01-01

    Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same...... mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation...... and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ((60)Co) and alpha particles from (211)At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity...

  19. Estrogen increases smooth muscle expression of alpha2C-adrenoceptors and cold-induced constriction of cutaneous arteries.

    Science.gov (United States)

    Eid, A H; Maiti, K; Mitra, S; Chotani, M A; Flavahan, S; Bailey, S R; Thompson-Torgerson, C S; Flavahan, N A

    2007-09-01

    Raynaud's phenomenon, which is characterized by intense cold-induced constriction of cutaneous arteries, is more common in women compared with men. Cold-induced constriction is mediated in part by enhanced activity of alpha(2C)-adrenoceptors (alpha(2C)-ARs) located on vascular smooth muscle cells (VSMs). Experiments were therefore performed to determine whether 17beta-estradiol regulates alpha(2C)-AR expression and function in cutaneous VSMs. 17beta-Estradiol (0.01-10 nmol/l) increased expression of the alpha(2C)-AR protein and the activity of the alpha(2C)-AR gene promoter in human cultured dermal VSMs, which was assessed following transient transfection of the cells with a promoter-reporter construct. The effect of 17beta-estradiol was associated with increased accumulation of cAMP and activation of the cAMP-responsive Rap2 GTP-binding protein. Transient transfection of VSMs with a dominant-negative mutant of Rap2 inhibited the 17beta-estradiol-induced activation of the alpha(2C)-AR gene promoter, whereas a constitutively active mutant of Rap2 increased alpha(2C)-AR promoter activity. The effects of 17beta-estradiol were inhibited by the estrogen receptor (ER) antagonist, ICI-182780 (1 micromol/l), and were mimicked by a cell-impermeable form of the hormone (estrogen:BSA) or by the selective ER-alpha receptor agonist 4,4',4'''-(4-propyl-[(1)H]-pyrazole-1,3,5-triyl)tris-phenol (PPT; 10 nmol/l) or the selective ER-beta receptor agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; 10 nmol/l). Therefore, 17beta-estradiol increased expression of alpha(2C)-ARs by interacting with cell surface receptors to cause a cAMP/Rap2-dependent increase in alpha(2C)-AR transcription. In mouse tail arteries, 17beta-estradiol (10 nmol/l) increased alpha(2C)-AR expression and selectively increased the cold-induced amplification of alpha(2)-AR constriction, which is mediated by alpha(2C)-ARs. An estrogen-dependent increase in expression of cold-sensitive alpha(2C)-ARs may contribute

  20. Retinal neuroprotection by hypoxic preconditioning is independent of hypoxia-inducible factor-1 alpha expression in photoreceptors.

    Science.gov (United States)

    Thiersch, Markus; Lange, Christina; Joly, Sandrine; Heynen, Severin; Le, Yun Zheng; Samardzija, Marijana; Grimm, Christian

    2009-06-01

    Hypoxic preconditioning stabilizes hypoxia-inducible factor (HIF) 1 alpha in the retina and protects photoreceptors against light-induced cell death. HIF-1 alpha is one of the major transcription factors responding to low oxygen tension and can differentially regulate a large number of target genes. To analyse whether photoreceptor-specific expression of HIF-1 alpha is essential to protect photoreceptors by hypoxic preconditioning, we knocked down expression of HIF-1 alpha specifically in photoreceptor cells, using the cyclization recombinase (Cre)-lox system. The Cre-mediated knockdown caused a 20-fold reduced expression of Hif-1 alpha in the photoreceptor cell layer. In the total retina, RNA expression was reduced by 65%, and hypoxic preconditioning led to only a small increase in HIF-1 alpha protein levels. Accordingly, HIF-1 target gene expression after hypoxia was significantly diminished. Retinas of Hif-1 alpha knockdown animals did not show any pathological alterations, and tolerated hypoxic exposure in a comparable way to wild-type retinas. Importantly, the strong neuroprotective effect of hypoxic preconditioning against light-induced photoreceptor degeneration persisted in knockdown mice, suggesting that hypoxia-mediated survival of light exposure does not depend on an autocrine action of HIF-1 alpha in photoreceptor cells. Hypoxia-mediated stabilization of HIF-2 alpha and phosphorylation of signal transducer and activator of transcription 3 (STAT 3) were not affected in the retinas of Hif-1 alpha knockdown mice. Thus, these factors are candidates for regulating the resistance of photoreceptors to light damage after hypoxic preconditioning, along with several potentially neuroprotective genes that were similarly induced in hypoxic knockdown and control mice.

  1. Biological stress responses induced by alpha radiation exposure in Lemna minor

    Energy Technology Data Exchange (ETDEWEB)

    Van Hoeck, A.; Horemans, N.; Van Hees, M.; Nauts, R. [Belgian Nuclear Research Centre SCK-CEN (Belgium); Knapen, D.; Blust, R. [University of Antwerp (Belgium)

    2014-07-01

    experiments Steinberg medium was selected for further dose-response experiments to analyse additional end-points like DNA-damage and enzymes involved in detoxification of reactive oxygen species. Finally, these results enable comparison of alpha radiation-induced effects at different levels of biological complexity from metabolic pathways to morphological growth effects. This research was supported by the Fund for Scientific Research (FWO-Vlaanderen, G.A040.11N) Document available in abstract form only. (authors)

  2. Ketamine increases the frequency of electroencephalographic bicoherence peak on the alpha spindle area induced with propofol.

    Science.gov (United States)

    Hayashi, K; Tsuda, N; Sawa, T; Hagihira, S

    2007-09-01

    The reticular and thalamocortical system is known to play a prominent role in spindle wave activity, and the spindle wave is related to the sedative effects of anaesthetics. Recently, bispectral analysis of the EEG has been developed as a better method to indicate nonlinear regulation including the thalamocortical system linking to the cortical area. In the present study, in order to explore the interference of ketamine with the nonlinear regulation of the sub-cortical system, we examined the effect of ketamine on spindle alpha waves through the bispectral analysis. The study included 21 patients. Anaesthesia was induced and maintained using a propofol-TCI system (target-controlled infusion, with target concentration 3.5 microg ml(-1)). An A-2000 BIS monitor was used and the raw EEG signals were collected via an RS232 interface on a personal computer. Bicoherence, the normalized bispectrum, and power spectrum were analysed before and after i.v. administration of 1 mg kg(-1) racemic ketamine. Propofol caused alpha peaks in both power and bicoherence spectra, with average frequencies of 10.6 (SD 0.9) Hz and 10.7 (1.0) Hz, respectively. The addition of ketamine significantly shifted each peak to frequencies of 14.4 (1.4) Hz and 13.6 (1.5) Hz, respectively [P < 0.05, mean (SD)]. Ketamine shifted the alpha peaks of bicoherence induced by propofol to higher frequencies. This suggests that ketamine changes the alpha spindle rhythms through the modulation of the nonlinear sub-cortical reverberating network.

  3. The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation.

    Science.gov (United States)

    Matos, Rita; Serrão, Paula; Rodriguez, Larissa; Birder, Lori Ann; Cruz, Francisco; Charrua, Ana

    2017-08-01

    Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.

  4. Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Han Wei; Zhu Lingyan; Jiang Erkang; Wang Jun; Chen Shaopeng; Bao Linzhi; Zhao Ye; Xu An; Yu Zengliang [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)], E-mail: ljw@ipp.ac.cn

    2007-11-01

    Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of {gamma}-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process (<1 h post irradiation), and the generation of micronuclei (MN), a sensitive marker for relative long process of RIBE. Our results showed that in the absence of irradiation, NaCl at elevated concentration such as 8.0, 9.0 and 10.0 g/L did not significantly increase the frequency of {gamma}-H2AX foci-positive cells and the number of foci per positive cell comparing with that NaCl at a normal concentration (6.8 g/L). However, with 0.2 cGy {alpha}-particle irradiation, the induced fraction of {gamma}-H2AX foci-positive cells and the number of induced {gamma}-H2AX foci per positive cell were significantly increased in both irradiated and adjacent non-irradiated regions. Similarly, the induction of MN by 0.2 cGy {alpha}-particle irradiation also increased with the elevated NaCl concentrations. With N{sup G}-methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effectively inhibited both in 0.2 cGy {alpha}-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose {alpha}-particle irradiation and nitric oxide generated by irradiation was also very important in this process.

  5. [Cellular adhesion signal transduction network of tumor necrosis factor-alpha induced hepatocellular carcinoma cells].

    Science.gov (United States)

    Zheng, Yongchang; Du, Shunda; Xu, Haifeng; Xu, Yiyao; Zhao, Haitao; Chi, Tianyi; Lu, Xin; Sang, Xinting; Mao, Yilei

    2014-11-18

    To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools. Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network. In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α. EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

  6. Mechanisms of alpha emitter production in 12C induced reactions at 1 GeV

    International Nuclear Information System (INIS)

    Dufour, J.P.; Delagrange, H.; Del Moral, R.

    1982-01-01

    We present cross sections, mean projected recoil ranges and angular distributions of radioactive alpha emitters produced in 12 C-induced reactions at 1 GeV on targets ranging from Gd to Pb. We use a new technique of on-line electrostatic collection. The wide spectrum of produced isotopes corresponds to nuclei close to the target up to nuclei with as much as 60 nucleons less than the target. The intranuclear cascade calculations can reproduce the main features of nuclei having lost up

  7. Pre-equilibrium decay process in alpha particle induced reactions on thulium and tantalum

    International Nuclear Information System (INIS)

    Mohan, Rao, A.V.; Chintalapudi, S.N.

    1994-01-01

    Alpha particle induced reactions on the target elements Thulium and Tantalum were investigated upto 60 MeV using stacked foil activation technique and Ge(Li) gamma ray spectroscopy method. Excitation functions for six reactions of 169 Tm(α,xn); x=1-4 and 181 Ta(α,xn); x=2,4 were studied. The experimental results were compared with the updated version of Hybrid model (ALICE/90) using initial exciton configuration n 0 =4(4pOh). A general agreement was found for all the reactions with this option. (author)

  8. Influence of catechins on bystander responses in CHO cells induced by alpha-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Law, Y.L.; Wong, T.P.W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)], E-mail: peter.yu@cityu.edu.hk

    2010-04-15

    In this work, we studied alpha-particle induced and medium-mediated bystander effects in Chinese hamster ovary (CHO) cells through micronucleus (MN) assay. We showed that signal transduction from irradiated cells to bystander cells occur within a short time after irradiation. We then studied the effects of ROS (reactive oxygen species)-scavenging catechins in the medium before irradiation. We observed decreases in the percentage of bystander cells with MN formation and thus proved the protection effect of catechins on bystander cells from radiation.

  9. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans

    DEFF Research Database (Denmark)

    Starkie, Rebecca; Ostrowski, Sisse Rye; Jauffred, Sune

    2003-01-01

    and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli...... exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced...

  10. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

    Energy Technology Data Exchange (ETDEWEB)

    Lyckesvärd, Madeleine Nordén, E-mail: madeleine.lyckesvard@oncology.gu.se [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden); Delle, Ulla; Kahu, Helena [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden); Lindegren, Sture [Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg (Sweden); Jensen, Holger [The PET and Cyclotron Unit Copenhagen University Hospital, Rigshospitalet (Denmark); Bäck, Tom [Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg (Sweden); Swanpalmer, John [Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg (Sweden); Elmroth, Kecke [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden)

    2014-07-15

    Highlights: • We study DNA damage response to low-LET photons and high-LET alpha particles. • Cycling primary thyrocytes are more sensitive to radiation than stationary cells. • Influence of radiation quality varies due to cell cycle status of normal cells. • High-LET radiation gives rise to a sustained DNA damage response. - Abstract: Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ({sup 211}At), concentrated in the thyroid by the same mechanism as {sup 131}I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ({sup 60}Co) and alpha particles from {sup 211}At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of γH2AX decreased during the first 24 h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to {sup 211}At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1 Gy {sup 211}At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative

  11. Staurosporine, but not Ro 31-8220, induces interleukin 2 production and synergizes with interleukin 1alpha in EL4 thymoma cells.

    Science.gov (United States)

    Mahon, T M; Matthews, J S; O'Neill, L A

    1997-07-01

    Protein kinase C (PKC) has been implicated in interleukin 1 (IL1) signal transduction in a number of cellular systems, either as a key event in IL1 action or as a negative regulator. Here we have examined the effects of two PKC inhibitors, staurosporine and the more selective agent Ro 31-8220, on IL1 responses in the murine thymoma line EL4.NOB-1. A 1 h pulse of staurosporine was found to strongly potentiate the induction of IL2 by IL1alpha in these cells. In contrast, neither a pulse nor prolonged incubation with Ro 31-8220 affected the response to IL1alpha. Both agents blocked the response to PMA, however. A 1 h pulse of staurosporine was also found to induce IL2 production on its own, activate the transcription factor nuclear factor kappaB (NFkappaB) and increase the expression of a NFkappaB-linked reporter gene. It synergized with IL1alpha in all of these responses. Ro 31-8220 was again without effect, although both staurosporine and Ro 31-8220 blocked the activation of NFkappaB by PMA. Finally, staurosporine caused the translocation of PKC-alpha and -epsilon, and to a lesser extent PKC-beta, but not PKC-θ or -zeta, from the cytosol to the membrane, although a similar effect was observed with Ro 31-8220. The results suggest that PKC is not involved in IL1alpha signalling in EL4 cells. Furthermore, the potentiating effect of staurosporine on IL1alpha action does not involve PKC inhibition, and is likely to be at the level of NFkappaB activation.

  12. A new scanning system for alpha decay events as calibration sources for range-energy relation in nuclear emulsion

    Science.gov (United States)

    Yoshida, J.; Kinbara, S.; Mishina, A.; Nakazawa, K.; Soe, M. K.; Theint, A. M. M.; Tint, K. T.

    2017-03-01

    A new scanning system named "Vertex picker" has been developed to rapid collect alpha decay events, which are calibration sources for the range-energy relation in nuclear emulsion. A computer-controlled optical microscope scans emulsion layers exhaustively, and a high-speed and high-resolution camera takes their micrographs. A dedicated image processing picks out vertex-like shapes. Practical operations of alpha decay search were demonstrated by emulsion sheets of the KEK-PS E373 experiment. Alpha decays of nearly 28 events were detected in eye-check work on a PC monitor per hour. This yield is nearly 20 times more effective than that by the conventional eye-scan method. The speed and quality is acceptable for the coming new experiment, J-PARC E07.

  13. A new scanning system for alpha decay events as calibration sources for range-energy relation in nuclear emulsion

    International Nuclear Information System (INIS)

    Yoshida, J.; Kinbara, S.; Mishina, A.; Nakazawa, K.; Soe, M.K.; Theint, A.M.M.; Tint, K.T.

    2017-01-01

    A new scanning system named “Vertex picker” has been developed to rapid collect alpha decay events, which are calibration sources for the range-energy relation in nuclear emulsion. A computer-controlled optical microscope scans emulsion layers exhaustively, and a high-speed and high-resolution camera takes their micrographs. A dedicated image processing picks out vertex-like shapes. Practical operations of alpha decay search were demonstrated by emulsion sheets of the KEK-PS E373 experiment. Alpha decays of nearly 28 events were detected in eye-check work on a PC monitor per hour. This yield is nearly 20 times more effective than that by the conventional eye-scan method. The speed and quality is acceptable for the coming new experiment, J-PARC E07.

  14. A simple alpha spectrometric method for the measurement of transuranics in water samples from the nuclear power plant

    International Nuclear Information System (INIS)

    Chourasiya, G.; Verma, P.C.; Sebastian, Letha

    1997-01-01

    A simple one step method is described for the simultaneous determination of all the alpha-emitting transuranic nuclides in the primary circuit of the nuclear power plant. The method exploits the intrinsic chemical characteristics of the system and obviates the use of external chemicals. At the pH of the system (8-10) hydroxides of the actinides are coprecipitated with Fe(III) present as corrosion product. This precipitate is collected on a 25 mm membrane filter with 0.1 m pore in a form suitable for alpha spectrometry without need for electrodeposition. The alpha spectrum is comparable to that obtained with electrodeposition. The method gives consistently higher yield (>90%) and does not need use of tracers for the quantitative determinations. (author). 3 refs., 1 fig., 1 tab

  15. PGC-1{alpha} is required for AICAR induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Leick, Lotte; Fentz, Joachim; Biensø, Rasmus S

    2010-01-01

    We tested the hypothesis that repeated activation of AMPK induces mitochondrial and glucose membrane transporter gene/protein expression via a peroxisome proliferator activated receptor Upsilon co-activator (PGC)-1alpha dependent mechanism. Whole body PGC-1alpha knockout (KO) and littermate wild...... GLUT4, cytochrome c oxidase (COX)I and cytochrome (cyt) c protein expression ~10-40% relative to saline in white muscles of the WT mice, but not of the PGC-1alpha KO mice. In line, GLUT4 and cyt c mRNA content increased 30-60% 4h after a single AICAR injection relative to saline only in WT mice. One...... and PGC-1alpha KO mice. In conclusion, we here provide genetic evidence for a major role of PGC-1alpha in AMPK mediated regulation of mitochondrial and glucose membrane transport protein expression in skeletal muscle....

  16. Laser-induced nuclear physics and applications

    International Nuclear Information System (INIS)

    Ledingham, K.W.D.; Singhal, R.P.; McKenna, P.; Spencer, I.

    2002-01-01

    With a 1 ps pulse laser at 1 μm wavelength, He gas is ionised at about 3.10 14 W.cm -2 . As the intensity increases, the inert gases become multiple ionised and between 10 18 and 10 19 W.cm -2 photon induced nuclear reactions are energetically possible. Close to 10 21 W.cm -2 pion production can take place. At the very high intensities of 10 28 W.cm -2 , it can be shown that electron-positron pairs can be created from the vacuum. The authors review the applications of high intensity focused laser beams in particle acceleration, laser-induced fission and laser production of protons and neutrons. Exciting new phenomena are expected at intensities higher than 10 22 W.cm -2 , -) the oscillating electric field can affect directly the protons in exactly the same way as the electrons in the plasma, -) fusion reactions by direct laser acceleration of ions. (A.C.)

  17. [Effects of intermittent hypoxic exposure on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha and erythropoietin levels].

    Science.gov (United States)

    Zhang, Cheng-yan; Zhang, Ji-xin; Lü, Xiao-tao; Li, Bao-yu

    2009-10-01

    To investigate the effects of intermittent hypoxic exposure and normoxic convalescence on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha (HIF-1alpha) and erythropoietin (EPO) levels. Rat models of intermittent hypoxic exposure were established, combined with the clinical research on volunteers experiencing the intermittent plateau work. Blood samples for red blood cell (RBC) counts, hemoglobin (Hb) and hematocrit (HCT) were collected, serum HIF-1alpha and EPO levels were measured using enzyme linked immunosorbent assay. RBC counts, Hb concentration and HCT were significantly higher than the normoxic group (P hypoxic exposure can enhance serum hypoxia inducible factor-1 alpha and erythropointin levels and the generation of red blood cells, which leads to an increase in hemoglobin concentration and hematocrit. The results have changed with the hypoxic exposure period prolonged. Normoxic convalescence after intermittent hypoxic exposure can make the related indexes reduced, and contribute to the organism recovery.

  18. Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling.

    Directory of Open Access Journals (Sweden)

    Bénédicte Mugnier

    Full Text Available Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR-induced immunological synapse (IS formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of alpha beta T cells, together with defects in cell activation and cytokine production following TCR triggering. The mutant T cells further displayed excessive accumulation yet reduced dynamics of F-actin and the WASP-Arp2/3 machinery at the IS, correlating with extended cell-cell contact. Cell signaling was also affected with the basal activation of the stress kinases sAPK/JNK1/2; and deficits in TCR-induced Ca2+ influx and phosphorylation and degradation of the inhibitor of NF-kappaB (I kappa B. Coronin-1A therefore links cytoskeleton plasticity with the functioning of discrete TCR signaling components. This function may be required to adjust TCR responses to selecting ligands accounting in part for the homeostasis defect that impacts alpha beta T cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages.

  19. Hypoxia inducible factor 1-alpha (HIF-1 alpha is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.

    Directory of Open Access Journals (Sweden)

    Elisa Conde

    Full Text Available Acute tubular necrosis (ATN caused by ischemia/reperfusion (I/R during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α, using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.

  20. Swelling induced by alpha decay in monazite and zirconolite ceramics: A XRD and TEM comparative study

    Science.gov (United States)

    Deschanels, X.; Seydoux-Guillaume, A. M.; Magnin, V.; Mesbah, A.; Tribet, M.; Moloney, M. P.; Serruys, Y.; Peuget, S.

    2014-05-01

    Zirconolite and monazite matrices are potential ceramics for the containment of actinides (Np, Cm, Am, Pu) which are produced over the reprocessing of spent nuclear fuel. Actinides decay mainly through the emission of alpha particles, which in turn causes most ceramics to undergo structural and textural changes (amorphization and/or swelling). In order to study the effects of alpha decays on the above mentioned ceramics two parallel approaches were set up. The first involved the use of an external irradiation source, Au, which allowed the deposited recoil energy to be simulated. The second was based on short-lived actinide doping with 238Pu, (i.e. an internal source), via the incorporation of plutonium oxide into both the monazite and zirconolite structures during synthesis. In both types of irradiation experiments, the zirconolite samples became amorphous at room temperature with damage close to 0.3 dpa; corresponding to a critical dose of 4 × 1018 α g-1 (i.e. ∼1.3 × 1021 keV cm-3). Both zirconolite samples also showed the same degree of macroscopic swelling at saturation (∼6%), with ballistic processes being the predominant damaging effect. In the case of the monazite however, the macroscopic swelling and amorphization were dependent on the nature of the irradiation. Externally, (Au), irradiated samples became amorphous while also demonstrating a saturation swelling of up to 8%. In contrast to this, the swelling of the 238Pu doped samples was much smaller at ∼1%. Also, unlike the externally (Au) irradiated monazite these 238Pu doped samples remained crystalline up to 7.5 × 1018 α g-1 (0.8 dpa). XRD, TEM and swelling measurements were used to fully characterize and interpret this behavior. The low swelling and the conservation of the crystalline state of 238Pu doped monazite samples indicates that alpha annealing took place within this material.

  1. Investigation of double strand breaks induced by alpha particle irradiation using C.N.B.G. microbeam in human keratinocytes

    International Nuclear Information System (INIS)

    Pouthier, Th.

    2006-12-01

    To understand the mechanisms of interaction of ionizing radiation with living tissues exposed to low and protracted doses remains a major issue for risk evaluation. The response cannot be found in epidemiological studies because the only available data concern accidental exposures to high doses of radiation. The natural exposure represents the main source of exposure in the daily life, just before the medical sources (radiology, radiotherapy). In addition, this kind of exposure is very difficult to reproduce in vitro by irradiating cell lines. The method per preference is based on random irradiation of cell populations. The mean number of particles having traversed cells is then calculated on the basis of Poisson statistics. In addition to inevitable multiple impacts, the numerous potential intracellular targets (nuclei, cytoplasm), the indirect effects induced by the impact of particles on neighbouring cells or simply the extracellular targets, constitute phenomena that make more complex the interpretation of experimental data. A charged particle microbeam was developed at C.E.N.B.G. to perform the targeted irradiation of individual cells with a targeting precision of a few microns. It is possible to deliver a counted number of alpha particles down to the ultimate dose of one alpha per cell, to target predetermined cells and then to observe the response of the neighbouring cells. This facility has been validated during this work on human keratinocyte cells expressing a recombinant nuclear fluorescent protein (histone H2B-GFP). The combination of ion micro-beams with confocal microscopy and numeric quantitative analysis allowed the measurement of DNA double strand breaks via the phosphorylation of the histone H2A.X in individual cells. The mechanisms of DNA reparation and apoptosis induction were also in the scope of those studies. The experimental results obtained during this thesis validate the methodology we have developed by demonstrating the targeting

  2. Minocycline treatment ameliorates interferon-alpha-induced neurogenic defects and depression-like behaviors in mice

    Directory of Open Access Journals (Sweden)

    Lian-Shun eZheng

    2015-01-01

    Full Text Available Interferon-alpha (IFN-α is a proinflammatory cytokine that is widely used for the treatment of chronic viral hepatitis and malignancy, because of its immune-activating, antiviral, and antiproliferative properties. However, long-term IFN-α treatment frequently causes depression, which limits its clinical utility. The precise molecular and cellular mechanisms of IFN-α-induced depression are not currently understood. Neural stem cells (NSCs in the hippocampus continuously generate new neurons, and some evidence suggests that decreased neurogenesis plays a role in the neuropathology of depression. We previously reported that IFN-α treatment suppressed hippocampal neurogenesis and induced depression-like behaviors via its receptors in the brain in adult mice. However, it is unclear how systemic IFN-α administration induces IFN-α signaling in the hippocampus. In this study, we analyzed the role of microglia, immune cells in the brain, in mediating the IFN-α-induced neurogenic defects and depressive behaviors. In vitro studies demonstrated that IFN-α treatment induced the secretion of endogenous IFN-α from microglia, which suppressed NSC proliferation. In vivo treatment of adult mice with IFN-α for five weeks increased the production of proinflammatory cytokines, including IFN-α, and reduced neurogenesis in the hippocampus. Both effects were prevented by simultaneous treatment with minocycline, an inhibitor of microglial activation. Furthermore, minocycline treatment significantly suppressed IFN-α-induced depressive behaviors in mice. These results suggest that microglial activation plays a critical role in the development of IFN-α-induced depression, and that minocycline is a promising drug for the treatment of IFN-α-induced depression in patients, especially those who are low responders to conventional antidepressant treatments.

  3. Nuclear fission and neutron-induced fission cross-sections

    CERN Document Server

    James, G D; Michaudon, A; Michaudon, A; Cierjacks, S W; Chrien, R E

    2013-01-01

    Nuclear Fission and Neutron-Induced Fission Cross-Sections is the first volume in a series on Neutron Physics and Nuclear Data in Science and Technology. This volume serves the purpose of providing a thorough description of the many facets of neutron physics in different fields of nuclear applications. This book also attempts to bridge the communication gap between experts involved in the experimental and theoretical studies of nuclear properties and those involved in the technological applications of nuclear data. This publication will be invaluable to those interested in studying nuclear fis

  4. Neutron-induced alpha radiography; Radiografia com particulas alfa induzida por neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Marco Antonio Stanojev

    2008-07-01

    A new radiography technique to inspect thin samples was developed. Low energy alpha particles, generated by a boron based screen under thermal neutron irradiation, are used as penetrating radiation. The solid state nuclear track detector CR-39 has been used to register the image. The interaction of the {alpha} - particles with the CR-39 gives rise to damages which under an adequate chemical etching became tracks the basic units forming the image. A digital system was developed for data acquisition and data analysis as well as for image processing. The irradiation and etching conditions to obtain the best radiography are 1,3 hours and 25 minutes at 70 deg C respectively. For such conditions samples having 10 {mu}m in thickness can be inspected with a spatial resolution of 32 {mu}m. The use of the digital system has reduced the time spent for data acquisition and data analysis and has improved the radiography image visualization. Furthermore, by using the digital system, it was possible to study several new parameters regarding the tracks which are very important to understand and study the image formation theory in solid state nuclear track detectors, the one used in this thesis. Some radiography images are also shown which demonstrate the potential of the proposed radiography technique. When compared with the other radiography techniques already in use to inspect thin samples, the present one developed in the present paper allows a smaller time to obtain the image, it is not necessary to handle liquid radioactive substances, the detector is insensitive to {beta}, {gamma}, X-ray and visible light. (author)

  5. Pharmacological dose of alpha-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

    Science.gov (United States)

    The effect of pharmacological dose of alpha-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha-tocopherol, n = 11) group. Animals received corn oil (C) or alpha-tocopherol dissolved in corn oil (250 mg alpha-tocopherol/[...

  6. Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline.

    Science.gov (United States)

    Porter, M H; Hrupka, B J; Altreuther, G; Arnold, M; Langhans, W

    2000-12-01

    Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-alpha production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 microg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 microg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-alpha production by more than 95% and IL-1beta production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-alpha production was reduced by approximately 90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-alpha (150 ug/kg body wt). The results suggest that suppression of TNF-alpha production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection.

  7. Nuclear transitions induced by atomic excitations

    International Nuclear Information System (INIS)

    Dyer, P.; Bounds, J.A.; Haight, R.C.; Luk, T.S.

    1988-01-01

    In the two-step pumping scheme for a gamma-ray laser, an essential step is that of exciting the nucleus from a long-lived storage isomer to a nearby short- lived state that then decays to the upper lasing level. An experiment is in progress to induce this transfer by first exciting the atomic electrons with UV photons. The incident photons couple well to the electrons, which then couple via a virtual photon to the nucleus. As a test case, excitation of the 235 U nucleus is being sought, using a high- brightness UV laser. The excited nuclear state, having a 26- minute half-life, decays by internal conversion, resulting in emission of an atomic electron. A pulsed infrared laser produces an atomic beam of 235 U which is then bombarded by the UV laser beam. Ions are collected, and conversion electrons are detected by a channel electron multiplier. In preliminary experiments, an upper limit of 7 x 10 -5 has been obtained for the probability of exciting a 235 U atom in the UV beam for one picosecond at an intensity of about 10 15 W/cm 2 . Experiments with higher sensitivities and at higher UV beam intensities are underway

  8. The Alpha-Melanocyte Stimulating Hormone Induces Conversion of Effector T Cells into Treg Cells

    Directory of Open Access Journals (Sweden)

    Andrew W. Taylor

    2011-01-01

    Full Text Available The neuropeptide alpha-melanocyte stimulating hormone (α-MSH has an important role in modulating immunity and homeostasis. The production of IFN-γ by effector T cells is suppressed by α-MSH, while TGF-β production is promoted in the same cells. Such α-MSH-treated T cells have immune regulatory activity and suppress hypersensitivity, autoimmune diseases, and graft rejection. Previous characterizations of the α-MSH-induced Treg cells showed that the cells are CD4+ T cells expressing the same levels of CD25 as effector T cells. Therefore, we further analyzed the α-MSH-induced Treg cells for expression of effector and regulatory T-cell markers. Also, we examined the potential for α-MSH-induced Treg cells to be from the effector T-cell population. We found that the α-MSH-induced Treg cells are CD25+  CD4+ T cells that share similar surface markers as effector T cells, except that they express on their surface LAP. Also, the α-MSH treatment augments FoxP3 message in the effector T cells, and α-MSH induction of regulatory activity was limited to the effector CD25+ T-cell population. Therefore, α-MSH converts effector T cells into Treg cells, which suppress immunity targeting specific antigens and tissues.

  9. Atomic force microscopic neutron-induced alpha-autoradiography for boron imaging in detailed cellular histology

    International Nuclear Information System (INIS)

    Amemiya, K.; Takahashi, H.; Fujita, K.; Nakazawa, M.; Yanagie, H.; Eriguchi, M.; Nakagawa, Y.; Sakurai, Y.

    2006-01-01

    The information on subcellular microdistribution of 10 B compounds a cell is significant to evaluate the efficacy of boron neutron capture therapy (BNCT) because the damage brought by the released alpha/lithium particles is highly localized along their path, and radiation sensitivity is quite different among each cell organelles. In neutron-induced alpha-autoradiography (NIAR) technique, 10 B can be measured as tracks for the energetic charged particles from 10 B(n, alpha) 7 Li reactions in solid state track detectors. To perform the NIAR at intracellular structure level for research of 10 B uptake and/or microdosimetry in BNCT, we have developed high-resolution NIAR method with an atomic force microscope (AFM). AFM has been used for analyses of biological specimens such as proteins, DNAs and surface of living cells have, however, intracellular detailed histology of cells has been hardly resolved with AFM since flat surface of sectioned tissue has quite less topographical contrast among each organelle. In our new sample preparation method using UV processing, materials that absorb UV in a semi-thin section are selectively eroded and vaporized by UV exposure, and then fine relief for cellular organelles such as mitochondria, endoplasmic reticulum, filament structure and so on reveals on flat surface of the section, which can be observed with an AFM. The imaging resolution was comparable to TEM imaging of cells. This new method provides fast and cost-effective observation of histological sections with an AFM. Combining this method with NIAR technique, intracellular boron mapping would be possible. (author)

  10. Performance of alpha spectrometry in the analysis of uranium isotopes in environmental and nuclear materials

    International Nuclear Information System (INIS)

    Carvalho, F.P.; Oliveira, J.M.

    2009-01-01

    The accuracy of alpha spectrometry in the determination of uranium isotopes at various concentrations levels and with various isotope ratios was tested in a round robin international intercomparison exercise. Results of isotope activity/mass and isotope mass ratios obtained by alpha spectrometry were accurate in a wide range of uranium masses and in isotopic ratios typical of depleted, natural, and low enriched uranium samples. Determinations by alpha spectrometry compared very satisfactorily in accuracy with those by mass spectrometry. For example, determination of U isotopes in natural uranium by alpha spectrometry agreed with mass spectrometry determinations at within ±1%. However, the 236 U isotope, particularly if present in activities much lower than 235 U, might not be determined accurately due to overlap in the alpha particle energies of these two uranium isotopes. (author)

  11. Quantitative surface analysis using deuteron-induced nuclear reactions

    International Nuclear Information System (INIS)

    Afarideh, Hossein

    1991-01-01

    The nuclear reaction analysis (NRA) technique consists of looking at the energies of the reaction products which uniquely define the particular elements present in the sample and it analysis the yield/energy distribution to reveal depth profiles. A summary of the basic features of the nuclear reaction analysis technique is given, in particular emphasis is placed on quantitative light element determination using (d,p) and (d,alpha) reactions. The experimental apparatus is also described. Finally a set of (d,p) spectra for the elements Z=3 to Z=17 using 2 MeV incident deutrons is included together with example of more applications of the (d,alpha) spectra. (author)

  12. MicroRNA-195 induced apoptosis in hypoxic chondrocytes by targeting hypoxia-inducible factor 1 alpha.

    Science.gov (United States)

    Bai, R; Zhao, A-Q; Zhao, Z-Q; Liu, W-L; Jian, D-M

    2015-02-01

    The chondrocytes, the resident cells of cartilage, are maintained and take effects in the whole life upon chronic hypoxic exposure, which hypoxia-inducible factor 1 alpha (HIF-1α) play pivotal roles in response to. Dysregulation of some microRNA (miRNAs) have also been identified to be involved in hypoxia-related physiologic and pathophysiologic responses in some tissues or cell lines. However, the mechanism of miRNAs reponse to hypoxia remain largely unknown in chondrocytes, including the microRNA-195 (miR-195). AIM To investigate the effects of microRNAs (miRNAs) and hypoxia-inducible factor 1 alpha (HIF-1α) on chondrocytes in physiologic environment. We compared the expression of miR-195 and HIF-1α mRNA on hypoxia with that on normoxia in ATDC 5 cells by qRT-PCR. Further experiments was performed to confirmed the relationships of miR-195 and HIF-1α by bioinformatics analysis and dual reporter gene assay. we also assessed the effect of miR-195 on apoptosis in hypoxic ATDC 5 cells by transfect with miR-195 mimics. It was found the downregulated miR-195 and upregulated HIF-1α were present in hypoxic ATDC 5 cells. miR-195 negatively regulated HIF-1α by targeting its 3'-untranslated region. Moreover, the founding indicated miR-195 greatly increased apoptosis and downregulated HIF-1α mRNA occurred simultaneously in hypoxic chondrocytes. We concluded that miR-195 induced apoptosis in hypoxic chondrocytes by directly targeting HIF-1α.

  13. SCALP: Scintillating ionization chamber for ALPha particle production in neutron induced reactions

    Science.gov (United States)

    Galhaut, B.; Durand, D.; Lecolley, F. R.; Ledoux, X.; Lehaut, G.; Manduci, L.; Mary, P.

    2017-09-01

    The SCALP collaboration has the ambition to build a scintillating ionization chamber in order to study and measure the cross section of the α-particle production in neutron induced reactions. More specifically on 16O and 19F targets. Using the deposited energy (ionization) and the time of flight measurement (scintillation) with a great accuracy, all the nuclear reaction taking part on this project will be identify.

  14. Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors.

    Science.gov (United States)

    Melis, Miriam; Pillolla, Giuliano; Luchicchi, Antonio; Muntoni, Anna Lisa; Yasar, Sevil; Goldberg, Steven R; Pistis, Marco

    2008-12-17

    Nicotine stimulates the activity of mesolimbic dopamine neurons, which is believed to mediate the rewarding and addictive properties of tobacco use. Accumulating evidence suggests that the endocannabinoid system might play a major role in neuronal mechanisms underlying the rewarding properties of drugs of abuse, including nicotine. Here, we investigated the modulation of nicotine effects by the endocannabinoid system on dopamine neurons in the ventral tegmental area with electrophysiological techniques in vivo and in vitro. We discovered that pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme that catabolizes fatty acid ethanolamides, among which the endocannabinoid anandamide (AEA) is the best known, suppressed nicotine-induced excitation of dopamine cells. Importantly, this effect was mimicked by the administration of the FAAH substrates oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), but not methanandamide, the hydrolysis resistant analog of AEA. OEA and PEA are naturally occurring lipid signaling molecules structurally related to AEA, but devoid of affinity for cannabinoid receptors. They blocked the effects of nicotine by activation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor transcription factor involved in several aspects of lipid metabolism and energy balance. Activation of PPAR-alpha triggered a nongenomic stimulation of tyrosine kinases, which might lead to phosphorylation and negative regulation of neuronal nicotinic acetylcholine receptors. These data indicate for the first time that the anorexic lipids OEA and PEA possess neuromodulatory properties as endogenous ligands of PPAR-alpha in the brain and provide a potential new target for the treatment of nicotine addiction.

  15. alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.

    Science.gov (United States)

    Tomasetti, M; Strafella, E; Staffolani, S; Santarelli, L; Neuzil, J; Guerrieri, R

    2010-04-13

    A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death. The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected. These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.

  16. Excitation functions for alpha-particle-induced reactions with natural antimony

    Energy Technology Data Exchange (ETDEWEB)

    Singh, N. L.; Shah, D. J.; Mukherjee, S.; Chintalapudi, S. N. [Vadodara, M. S. Univ. of Baroda (India). Fac. of Science. Dept. of Physics

    1997-07-01

    Stacked-foil activation technique and {gamma} - rays spectroscopy were used for the determination of the excitation functions of the {sup 121}Sb [({alpha}, n); ({alpha}, 2n); ({alpha},4 n); ({alpha}, p3n); ({alpha}, {alpha}n)]; and Sb [({alpha}, 3n); ({alpha}, 4n); ({alpha}, {alpha}3n)] reactions. The excitation functions for the production of {sup 124}I, {sup 123}I, {sup 121}I, {sup 121}Te and {sup 120}Sb were reported up to 50 MeV. The reactions {sup 121} Sb ({alpha}, {alpha}n) + {sup 123} Sb ({alpha}, {alpha}3n) are measured for the first time. Since natural antimony used as the target has two odd mass stable isotopes of abundances 57.3 % ({sup 121}Sb), their activation in some cases gives the same product nucleus through different reaction channels but with very different Q-values. In such cases, the individual reaction cross-sections are separated with the help of theoretical cross-sections. The experimental cross-sections were compared with the predictions based on hybrid model of Blann. The high-energy part of the excitation functions are dominated by the pre-equilibrium reaction mechanism and the initial exciton number n{sub 0} = 4 (4 p 0 h) gives fairly good agreement with presently measured results.

  17. Determination of alpha effectiveness in ESR dating using nuclear accelerator techniques: methods and energy dependence

    International Nuclear Information System (INIS)

    Lyons, R.G.

    1988-01-01

    An important parameter in calculating the environmental dose rate for electron spin resonance (ESR) age estimates is the relative effectiveness of alpha and gamma radiation. A small research accelerator is used as a source of alpha particles of various pre-selected energies, corresponding to those found in the environment, to determine the effectiveness of alpha radiation of different energies. Preparation of sample targets is discussed, including the use of absolute ethanol, thorough etching and deposition by centrifuge. Preliminary results show that the alpha/gamma effectiveness ratio, k, depends on the energy of the incident alpha and must therefore be expressed in terms of a reference energy. The effectiveness of an alpha particle in causing ESR damage is found to vary linearly with its range or path length, not with its energy, a fact which must be considered when calculating effective dose-rates from environmental radionuclide concentrations. Failure to do so may lead to serious systematic errors in the effective alpha contribution to environmental dose-rates and consequently in age estimates. (author)

  18. Analysis and Quantitation of NF-[kappa]B Nuclear Translocation in Tumor Necrosis Factor Alpha (TNF-[alpha]) Activated Vascular Endothelial Cells

    Science.gov (United States)

    Fuseler, John W.; Merrill, Dana M.; Rogers, Jennifer A.; Grisham, Matthew B.; Wolf, Robert E.

    2006-07-01

    Nuclear factor kappa B (NF-[kappa]B) is a heterodimeric transcription factor typically composed of p50 and p65 subunits and is a pleiotropic regulator of various inflammatory and immune responses. In quiescent cells, p50/p65 dimers are sequestered in the cytoplasm bound to its inhibitors, the I-[kappa]Bs, which prevent entry into the nucleus. Following cellular stimulation, the I-[kappa]Bs are rapidly degraded, activating NF-[kappa]B. The active form of NF-[kappa]B rapidly translocates into the nucleus, binding to consensus sequences in the promoter/enhancer region of various genes, promoting their transcription. In human vascular endothelial cells activated with tumor necrosis factor-alpha, the activation and translocation of NF-[kappa]B is rapid, reaching maximal nuclear localization by 30 min. In this study, the appearance of NF-[kappa]B (p65 subunit, p65-NF-[kappa]B) in the nucleus visualized by immunofluorescence and quantified by morphometric image analysis (integrated optical density, IOD) is compared to the appearance of activated p65-NF-[kappa]B protein in the nucleus determined biochemically. The appearance of p65-NF-[kappa]B in the nucleus measured by fluorescence image analysis and biochemically express a linear correlation (R2 = 0.9477). These data suggest that localization and relative protein concentrations of NF-[kappa]B can be reliably determined from IOD measurements of the immunofluorescent labeled protein.

  19. A hormone pulse induces transient changes in the subcellular distribution and leads to a lysosomal accumulation of the estradiol receptor alpha in target tissues.

    Science.gov (United States)

    Qualmann, B; Kessels, M M; Thole, H H; Sierralta, W D

    2000-06-01

    An intrauterine pulse-stimulation with estradiol induced changes in the subcellular localization of estrogen receptor alpha in porcine endometrium, as detected with F(ab') fragments of various anti-receptor antibodies covalently linked to nanogold. The low-sterically hindered immunoreagents--recognizing different epitopes within the hormone binding domain--allowed for an efficient immunolabeling of estradiol receptor alpha, detecting it both in the cytoplasm and the nucleus of nonstimulated epithelium cells. In the cytoplasm, the receptor often seemed to be associated with actin filaments and the endoplasmatic reticulum. After the stimulation with estradiol, a predominantly nuclear localization and a labeling of nucleoli was observed. Our immunoelectron microscopy study demonstrates a localization of the receptor in cytoplasmic organelles that increased after the hormone pulse. These organelles exhibited the morphological properties of lysosomes and relocated to the perinuclear area. In analogous cytoplasmic organelles, the presence of cathepsin D was detected via indirect immunogold labeling, justifying their classification as lysosomes. Quantitative examinations revealed that not only the number of lysosomes in the proximity of the nucleus but also their immunostaining for estradiol receptor alpha increased significantly after the hormone pulse. Thus, estradiol induces both the rapid shift of receptor into the nucleus, a slower perinuclear accumulation of lysosomes and an increase of lysosomal ERalpha-immunoreactivity. These results suggest a role for lysosomes in the degradation of receptor shuttling out of the nucleus. This could serve as termination of the estradiol receptor alpha-dependent activation of target cells. This hypothesis is strengthened by the fact that the receptor content in uterine tissue declined drastically few hours after the hormone pulse.

  20. Laser induced nuclear orientation: intersection of laser and nuclear spectroscopy

    International Nuclear Information System (INIS)

    Burns, M.; Pappas, P.; Field, M.S.

    1978-01-01

    The application of lasers to the study of hyperfine structure is reviewed with emphasis placed on the ability of the laser beam to align the nuclei in a sample. This aligning effect is especially useful if the nuclei are unstable as then the angular distribution of the subsequent nuclear radiation may be effected and information will by given about the nuclear parameters. (B.R.H.)

  1. Alpha 7 nicotinic acetylcholine receptor-mediated protection against ethanol-induced neurotoxicity.

    Science.gov (United States)

    de Fiebre, NancyEllen C; de Fiebre, Christopher M

    2003-11-01

    The alpha(7)-selective nicotinic partial agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB) was examined for its ability to modulate ethanol-induced neurotoxicity in primary cultures of rat neurons. Primary cultures of hippocampal neurons were established from Long-Evans, embryonic day (E)-18 rat fetuses and maintained for 7 days. Ethanol (0-150 mM), DMXB (0-56 microM), or both were subsequently co-applied to cultures. Ethanol was added two additional times to the cultures to compensate for evaporation. After 5 days, neuronal viability was assessed with the MTT cell proliferation assay. Results demonstrated that ethanol reduces neuronal viability in a concentration-dependent fashion and that DMXB protects against this ethanol-induced neurotoxicity, also in a concentration-dependent fashion. These results support the suggestion that nicotinic partial agonists may be useful in treating binge drinking-induced neurotoxicity and may provide clues as to why heavy drinkers are usually smokers.

  2. Acetyl-CoA carboxylase-alpha inhibitor TOFA induces human cancer cell apoptosis.

    Science.gov (United States)

    Wang, Chun; Xu, Canxin; Sun, Mingwei; Luo, Dixian; Liao, Duan-Fang; Cao, Deliang

    2009-07-31

    Acetyl-CoA carboxylase-alpha (ACCA) is a rate-limiting enzyme in long chain fatty acid synthesis, playing a critical role in cellular energy storage and lipid synthesis. ACCA is upregulated in multiple types of human cancers and small interfering RNA-mediated ACCA silencing in human breast and prostate cancer cells results in oxidative stress and apoptosis. This study reports for the first time that TOFA (5-tetradecyloxy-2-furoic acid), an allosteric inhibitor of ACCA, is cytotoxic to lung cancer cells NCI-H460 and colon carcinoma cells HCT-8 and HCT-15, with an IC(50) at approximately 5.0, 5.0, and 4.5 microg/ml, respectively. TOFA at 1.0-20.0 microg/ml effectively blocked fatty acid synthesis and induced cell death in a dose-dependent manner. The cell death was characterized with PARP cleavage, DNA fragmentation, and annexin-V staining, all of which are the features of the apoptosis. Supplementing simultaneously the cells with palmitic acids (100 microM), the end-products of the fatty acid synthesis pathway, prevented the apoptosis induced by TOFA. Taken together, these data suggest that TOFA is a potent cytotoxic agent to lung and colon cancer cells, inducing apoptosis through disturbing their fatty acid synthesis.

  3. Gapless Spin Excitations in the Field-Induced Quantum Spin Liquid Phase of alpha-RuCl3

    OpenAIRE

    Zheng, Jiacheng; Ran, Kejing; Li, Tianrun; Wang, Jinghui; Wang, Pengshuai; Liu, Bin; Liu, Zhengxin; Normand, B.; Wen, Jinsheng; Yu, Weiqiang

    2017-01-01

    $\\alpha$-RuCl$_3$ is a leading candidate material for theobservation of physics related to the Kitaev quantum spin liquid (QSL). By combined susceptibility, specific-heat, and nuclear-magnetic-resonance measurements, we demonstrate that $\\alpha$-RuCl$_3$ undergoes a quantum phase transition to a QSL in a magnetic field of 7.5 T applied in the $ab$ plane. We show further that this high-field QSL phase has gapless spin excitations over a field range up to 16 T. This highly unconventional result...

  4. The role of hypoxia inducible factor-1 alpha in bypassing oncogene-induced senescence.

    Directory of Open Access Journals (Sweden)

    Mehtap Kilic Eren

    Full Text Available Oncogene induced senescence (OIS is a sustained anti-proliferative response acutely induced in primary cells via activation of mitogenic oncogenes such as Ras/BRAF. This mechanism acts as an initial barrier preventing normal cells transformation into malignant cell. Besides oncogenic activation and DNA damage response (DDR, senescence is modulated by a plethora of other factors, and one of the most important one is oxygen tension of the tissue. The aim of this study was to determine the impact of hypoxia on RasV12-induced senescence in human diploid fibroblasts (HDFs. We showed here that hypoxia prevents execution of oncogene induced senescence (OIS, through a strong down-regulation of senescence hallmarks, such as SA- β-galactosidase, H3K9me3, HP1γ, p53, p21CIP1 and p16INK4a in association with induction of hypoxia inducible factor-1α (HIF-1α. In addition, hypoxia also decreased marks of H-RasV12-induced DDR in both cell lines through down-regulation of ATM/ATR, Chk1 and Chk2 phosphorylation as well as decreased γ-H2AX positivity. Utilizing shRNA system targeting HIF-1α we show that HIF-1α is directly involved in down regulation of p53 and its target p21CIP1 but not p16INK4a. In line with this finding we found that knock down of HIF-1α leads to a strong induction of apoptotic response, but not restoration of senescence in Ras expressing HDFs in hypoxia. This indicates that HIF-1α is an important player in early steps of tumorigenesis, leading to suppression of senescence through its negative regulation of p53 and p21CIP1. In our work we describe a mechanism through which hypoxia and specifically HIF-1α preclude cells from maintaining senescence-driven anti proliferative response. These findings indicate the possible mechanism through which hypoxic environment helps premalignant cells to evade impingement of cellular failsafe pathways.

  5. Development of a chromosomally integrated metabolite-inducible Leu3p-alpha-IPM "off-on" gene switch.

    Directory of Open Access Journals (Sweden)

    Maria Poulou

    2010-08-01

    Full Text Available Present technology uses mostly chimeric proteins as regulators and hormones or antibiotics as signals to induce spatial and temporal gene expression.Here, we show that a chromosomally integrated yeast 'Leu3p-alpha-IotaRhoMu' system constitutes a ligand-inducible regulatory "off-on" genetic switch with an extensively dynamic action area. We find that Leu3p acts as an active transcriptional repressor in the absence and as an activator in the presence of alpha-isopropylmalate (alpha-IotaRhoMu in primary fibroblasts isolated from double transgenic mouse embryos bearing ubiquitously expressing Leu3p and a Leu3p regulated GFP reporter. In the absence of the branched amino acid biosynthetic pathway in animals, metabolically stable alpha-IPM presents an EC(50 equal to 0.8837 mM and fast "OFF-ON" kinetics (t(50ON = 43 min, t(50OFF = 2.18 h, it enters the cells via passive diffusion, while it is non-toxic to mammalian cells and to fertilized mouse eggs cultured ex vivo.Our results demonstrate that the 'Leu3p-alpha-IotaRhoMu' constitutes a simpler and safer system for inducible gene expression in biomedical applications.

  6. Studying effects of Magnolol on alpha-particle induced bystander effects using PADC-film based dishes

    International Nuclear Information System (INIS)

    Wong, T.P.W.; Tse, A.K.W.; Fong, W.F.; Yu, K.N.

    2009-01-01

    Radiation-induced bystander effect refers to the biological response found in cells (called bystander cells) which are not irradiated directly by ionizing radiation but are next to cells irradiated directly by ionizing radiation. In the present paper, the effects of Magnolol, an extract from the bark of Magnolia officinalis which is used as a traditional Chinese medicine, were studied on alpha-particle induced bystander effects. In our experiments, Chinese hamster ovary (CHO) cells were cultured in PADC-film based dishes and were irradiated with low fluences of alpha particles passing through the PADC films. The precise number of cells traversed or missed by alpha particles could be determined by studying the alpha-particle tracks developed on the PADC films upon subsequent chemical etching. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay was employed to analyze the biological response of bystander cells in terms of DNA strand breaks. With the pretreatment of Magnolol, the DNA strand breaks in bystander cells were reduced, which showed that the alpha-particle induced bystander effects were suppressed with the presence of Magnolol. Since Magnolol is an antioxidant which can scavenge reactive oxygen species (ROS), our results give support to that ROS play a role in the bystander signal transmission in our experiments.

  7. Studying effects of Magnolol on alpha-particle induced bystander effects using PADC-film based dishes

    Energy Technology Data Exchange (ETDEWEB)

    Wong, T.P.W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Tse, A.K.W.; Fong, W.F. [Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.h [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2009-10-15

    Radiation-induced bystander effect refers to the biological response found in cells (called bystander cells) which are not irradiated directly by ionizing radiation but are next to cells irradiated directly by ionizing radiation. In the present paper, the effects of Magnolol, an extract from the bark of Magnolia officinalis which is used as a traditional Chinese medicine, were studied on alpha-particle induced bystander effects. In our experiments, Chinese hamster ovary (CHO) cells were cultured in PADC-film based dishes and were irradiated with low fluences of alpha particles passing through the PADC films. The precise number of cells traversed or missed by alpha particles could be determined by studying the alpha-particle tracks developed on the PADC films upon subsequent chemical etching. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay was employed to analyze the biological response of bystander cells in terms of DNA strand breaks. With the pretreatment of Magnolol, the DNA strand breaks in bystander cells were reduced, which showed that the alpha-particle induced bystander effects were suppressed with the presence of Magnolol. Since Magnolol is an antioxidant which can scavenge reactive oxygen species (ROS), our results give support to that ROS play a role in the bystander signal transmission in our experiments.

  8. Xanthophylls and alpha-tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells.

    Science.gov (United States)

    Chitchumroonchokchai, Chureeporn; Bomser, Joshua A; Glamm, Jayme E; Failla, Mark L

    2004-12-01

    Epidemiological studies suggest that consumption of vegetables rich in the xanthophylls lutein (LUT) and zeaxanthin (ZEA) reduces the risk for developing age-related cataract, a leading cause of vision loss. Although LUT and ZEA are the only dietary carotenoids present in the lens, direct evidence for their photoprotective effect in this organ is not available. The present study examined the effects of xanthophylls and alpha-tocopherol (alpha-TC) on lipid peroxidation and the mitogen-activated stress signaling pathways in human lens epithelial (HLE) cells following ultraviolet B light (UVB) irradiation. When presented with LUT, ZEA, astaxanthin (AST), and alpha-TC as methyl-beta-cyclodextrin complexes, HLE cells accumulated the lipophiles in a concentration- and time-dependent manner with uptake of LUT exceeding that of ZEA and AST. Pretreatment of cultures with either 2 micromol/L xanthophyll or 10 micromol/L alpha-TC for 4 h before exposure to 300 J/m(2) UVB radiation decreased lipid peroxidation by 47-57% compared with UVB-treated control HLE cells. Pretreatment with the xanthophylls and alpha-TC also inhibited UVB-induced activation of c-JUN NH(2)-terminal kinase (JNK) and p38 by 50-60 and 25-32%, respectively. There was substantial inhibition of UVB-induced JNK and p38 activation for cells containing xanthophylls/mg, respectively, whereas >2.3 nmol alpha-TC/mg protein was required to significantly decrease UVB-induced stress signaling. These data suggest that xanthophylls are more potent than alpha-TC for protecting human lens epithelial cells against UVB insult.

  9. Determination of alpha activity produced by Indian tea samples using solid state nuclear track detection technique

    International Nuclear Information System (INIS)

    Azam, Ameer; Naqvi, A.H.; Srivastava, D.S.

    2001-01-01

    India has first place in the world in the production, consumption and export of tea. The average production of tea in India is about 780 million kg annually. Indian population uses tea as a favourite beverage specially with the breakfast. Tea leaves are perennial plants and they have extension root system spread over deeper layers in the soil. Soil contains uranium as trace element. Hence, uranium is transferred to the leaves as a result of uptake from the soil over the years. Since many of the decay products of uranium are alpha emitters hence tea is a source of alpha radioactivity and can cause damaging effects. Therefore, data on alpha activity of tea samples will be useful in estimating these harmful effects at least qualitatively. In the present study the alpha activity produced by thirteen samples of tea available in the local market was measured

  10. Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers.

    Directory of Open Access Journals (Sweden)

    Judit Váradi

    Full Text Available Alpha-melanocyte-stimulating hormone (α-MSH is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines.

  11. Charged particle-induced nuclear fission reactions

    Indian Academy of Sciences (India)

    The nuclear fission phenomenon continues to be an enigma, even after nearly 75 years of its discovery. Considerable progress has been made towards understanding the fission process. Both light projectiles and heavy ions have been employed to investigate nuclear fission. An extensive database of the properties of ...

  12. Expression of hypoxia-inducible factor 1 alpha and its downstream targets in fibroepithelial tumors of the breast

    NARCIS (Netherlands)

    Kuijper, Arno; Groep, P. van der; Wall, E. van der; Diest, P.J. van

    2005-01-01

    INTRODUCTION Hypoxia-inducible factor 1 (HIF-1) alpha and its downstream targets carbonic anhydrase IX (CAIX) and vascular endothelial growth factor (VEGF) are key factors in the survival of proliferating tumor cells in a hypoxic microenvironment. We studied the expression and prognostic relevance

  13. Suppressor of cytokine signalling-3 inhibits Tumor necrosis factor-alpha induced apoptosis and signalling in beta cells

    DEFF Research Database (Denmark)

    Bruun, Christine; Heding, Peter E; Rønn, Sif G

    2009-01-01

    Tumor necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine involved in the pathogenesis of several diseases including type 1 diabetes mellitus (T1DM). TNFalpha in combination with interleukin-1-beta (IL-1beta) and/or interferon-gamma (IFNgamma) induces specific destruction...

  14. Interleukin-4 inhibits both paracrine and autocrine tumor necrosis factor-alpha-induced proliferation of B chronic lymphocytic leukemia cells

    NARCIS (Netherlands)

    van Kooten, C.; Rensink, I.; Aarden, L.; van Oers, R.

    1992-01-01

    The proliferative response of purified malignant B cells from 26 patients with chronic lymphocytic leukemia (CLL) was investigated in vitro. In the majority of these patients, a proliferative response could be induced by the combination of tumor necrosis factor (TNF)-alpha and PMA. The concentration

  15. Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

    Directory of Open Access Journals (Sweden)

    Alireza Abed

    2017-11-01

    Full Text Available Objective(s: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

  16. MutY DNA Glycosylase Protects Cells From Tumor Necrosis Factor Alpha-Induced Necroptosis.

    Science.gov (United States)

    Tran, An Hue Vy; Han, Se Hee; Kim, Joon; Grasso, Francesca; Kim, In San; Han, Ye Sun

    2017-07-01

    Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival. After investigating the role of MYH interacts with various proteins following TNF-α stimulation, here, we focus on MYH and TRADD interaction functions in necroptosis and its effects to related proteins. We report that the level of the MYH and TRADD complex was also reduced during necroptosis induced by TNF-α and zVAD-fmk. In particular, we also found that MYH is a biologically important necrosis suppressor. Under combined TNF-α and zVAD-fmk treatment, MYH-deficient cells were induced to enter the necroptosis pathway but primary mouse embryonic fibroblasts (MEFs) were not. Necroptosis in the absence of MYH proceeds via the inactivation of caspase-8, followed by an increase in the formation of the kinase receptor- interacting protein 1 (RIP1)-RIP3 complex. Our results suggested that MYH, which interacts with TRADD, inhibits TNF-α necroptotic signaling. Therefore, MYH inactivation is essential for necroptosis via the downregulation of caspase-8. J. Cell. Biochem. 118: 1827-1838, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Aphidicolin-induced nuclear elongation in tobacco BY-2 cells.

    Science.gov (United States)

    Yasuhara, Hiroki; Kitamoto, Kazuki

    2014-05-01

    Plant nuclei are known to differentiate into various shapes within a single plant. However, little is known about the mechanisms of nuclear morphogenesis. We found that nuclei of tobacco BY-2 cells were highly elongated on long-term treatment with 5 mg l⁻¹ aphidicolin, an inhibitor of DNA polymerase α. In aphidicolin-treated cells, the nuclear length was correlated with the cell length. During culture in the presence of aphidicolin, the nuclei were elongated in parallel with cell elongation. Nuclear elongation was inhibited by the inhibition of cell elongation with 2,6-dichlorobenzonitrile, a cellulose synthesis inhibitor. However, cell elongation induced in the auxin-depleted medium in the absence of aphidicolin did not cause nuclear elongation, indicating that cell elongation alone is not sufficient for nuclear elongation. Treatment with either latrunculin B or propyzamide inhibited the aphidicolin-induced nuclear elongation, indicating that both actin filaments and microtubules (MTs) are required for nuclear elongation. Observations using BY-YTHCLR2 cells, in which actin filaments, MTs and nuclei were simultaneously visualized, revealed that the longitudinally arranged MT bundles associated with the nucleus play an important role in nuclear elongation, and that actin filaments affect the formation of these MT bundles. In aphidicolin-treated cells, the nuclear DNA contents of the elongated nuclei exceeded 4C, and the nuclear length was highly correlated with the nuclear DNA content. In cells treated with 50 mg l⁻¹ aphidicolin, cells were elongated and nucleus-associated longitudinal MT bundles were formed, but the nuclear DNA contents did not exceed 4C and the nuclei did not elongate. These results indicate that an increase in the nuclear DNA content above 4C is also required for nuclear elongation.

  18. Early detection of doxorubicin-induced cariotoxocity and its prevention by alpha-tocopherol

    International Nuclear Information System (INIS)

    Ajmal, K.; Khan, B.T.

    2014-01-01

    To detect doxorubicin-induced myocardial injury by quantitative estimation of cardiospecific protein, Cardiac Troponin I (cTnI) at early stage and to evaluate the cardioprotective effects of Tocopherol. Study Design: Labbased randomized controlled in-vivo study in rabbits. Place and Duration of Study: Department of Pharmacology in collaboration with Pathology department, Army Medical College Rawalpindi, Pakistan from Jan 2012 to Dec 2012. Material and Methods: Eighteen healthy male adult rabbits were used. Cardiotoxicity was induced by single intravenous injection of 12 mg /kg of doxorubicin in a group of rabbits, control group was treated with normal saline only and the rabbits of third group were pretreated with Tocopherol 200 mg/kg of body weight for ten days before injection of doxorubicin 12mg/kg. Results: Doxorubicin produced severe cardiotoxicity confirmed by markedly raised serum levels of cTnI, CK-MB, LDH and grade 3 necrosis of the heart issue in rabbits. The pre-treatment with Tocopherol resulted in improved serum levels of cTnI and the histological picture of heart tissue. Conclusions: The quantitative cTnI estimation for detection of cardiotoxicity at subclinical level can lead to significant economic impact in management of cancer patients because the troponin-negative subjects can be excluded from long term cardiac monitoring programs, which require high cost imaging techniques. Furthermore, the outcome of most potent and widely used doxorubicin chemotherapy can be made successful with the concurrent use of alpha-Tocopherol. (author)

  19. Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mushfiquddin Khan

    2017-01-01

    Full Text Available Mild traumatic brain injury (TBI, also called concussion, initiates sequelae leading to motor deficits, cognitive impairments and subtly compromised neurobehaviors. While the acute phase of TBI is associated with neuroinflammation and nitroxidative burst, the chronic phase shows a lack of stimulation of the neurorepair process and regeneration. The deficiency of nitric oxide (NO, the consequent disturbed NO metabolome, and imbalanced mechanisms of S-nitrosylation are implicated in blocking the mechanisms of neurorepair processes and functional recovery in the both phases. Hypoxia inducible factor-1 alpha (HIF-1α, a master regulator of hypoxia/ischemia, stimulates the process of neurorepair and thus aids in functional recovery after brain trauma. The activity of HIF-1α is regulated by NO via the mechanism of S-nitrosylation of HIF-1α. S-nitrosylation is dynamically regulated by NO metabolites such as S-nitrosoglutathione (GSNO and peroxynitrite. GSNO stabilizes, and peroxynitrite destabilizes HIF-1α. Exogenously administered GSNO was found not only to stabilize HIF-1α and to induce HIF-1α-dependent genes but also to stimulate the regeneration process and to aid in functional recovery in TBI animals.

  20. Calculated /alpha/-induced thick target neutron yields and spectra, with comparison to measured data

    International Nuclear Information System (INIS)

    Wilson, W.B.; Bozoian, M.; Perry, R.T.

    1988-01-01

    One component of the neutron source associated with the decay of actinide nuclides in many environments is due to the interaction of decay /alpha/ particles in (/alpha/,n) reactions on low Z nuclides. Measurements of (/alpha/,n) thick target neutron yields and associated neutron spectra have been made for only a few combinations of /alpha/ energy and target nuclide or mixtures of actinide and target nuclides. Calculations of thick target neutron yields and spectra with the SOURCES code require /alpha/-energy-dependent cross sections for (/alpha/,n) reactions, as well as branching fractions leading to the energetically possible levels of the product nuclides. A library of these data has been accumulated for target nuclides of Z /le/ 15 using that available from measurements and from recent GNASH code calculations. SOURCES, assuming neutrons to be emitted isotopically in the center-of-mass system, uses libraries of /alpha/ stopping cross sections, (/alpha/,n) reaction cross reactions, product nuclide level branching fractions, and actinide decay /alpha/ spectra to calculate thick target (/alpha/,n) yields and neutron spectra for homogeneous combinations of nuclides. The code also calculates the thick target yield and angle intergrated neutron spectrum produced by /alpha/-particle beams on targets of homogeneous mixtures of nuclides. Illustrative calculated results are given and comparisons are made with measured thick target yields and spectra. 50 refs., 1 fig., 2 tabs

  1. Influence of Alpha Tocopherol on Heat Stress-Induced Changes in the Reproductive Function of Swiss Albino Mice

    International Nuclear Information System (INIS)

    AlEnazi, Maher M.

    2007-01-01

    The present study was carried out to investigate the influence of vitamin E (alpha-tocopherol) on heat stress-induced changes in the reproduction of Swiss albino mice. The evaluated parameters include: the estrous cycle, fertility, post-implantation losses of fetuses and estimation of progesterone levels in the serum. Eight groups of experimental mice (10 each) were used. Groups 1-4 (24 degree C) consisted of a control and alpha-tocopherol (100, 200 and 400 mg/kg) treated groups. Groups 5-8 (42 degree C) consisted of a positive control and alpha-tocopherol (100, 200 and 400 mg/kg) treated group. Heat-stress reduced significantly (p > 0.001) the number of fetuses and corpora lutea. There was also a significant decrease in the mean weights of fetuses (p > 0.001) and placenta (p > 0.01) in the heat-stress group with a decrease in their serum progesterone levels (p > 0.01). Heat-stress groups treated with high doses of alpha-tocopherol 200 and 400 mg/kg, showed protection against heat-stress related abnormalities. The results showed that alpha-tocopherol plays a role in protection against hyperthermia induced changes in the estrous cycle length, infertility, post-implantation losses and depletion in the serum level of progesterone. (author)

  2. Different signaling pathways induced by alpha-CD3 monoclonal antibody versus alloantigen on the basis of differential ornithine sensitivity.

    Science.gov (United States)

    Mehrotra nee Tandon, P; Lind, D S; Bear, H D; Susskind, B M

    1992-08-01

    Previously we reported that 10 mM ornithine (Orn) selectively inhibits the development of CD8+ CTL in MLC. Herein we show that induction by alpha-CD3 mAb of CD8+ killer cells which manifest antibody-redirected cytotoxicity (ARC) of FcR+ targets is not Orn sensitive. Orn resistance was independent of activation kinetics or alpha-CD3 mAb concentration. alpha-CD3 mAb added to the cytotoxicity assay did not reveal a cytolytic potential in CTL from an Orn-treated MLC when the target cells bore both the inducing alloantigen and FcR. Addition of alpha-CD3 mAb to MLC failed to overcome Orn inhibition of CTL and yet induced ARC activity in the same culture. Expression of mRNA for pore-forming proteins (PFP) and granzyme B was inhibited by Orn in CTL but not in ARC killer cells. Our results demonstrate differences in the T cell activation process stimulated by alloantigen or alpha-CD3 mAb.

  3. Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma

    OpenAIRE

    Cai, Shao-hang; Lu, Shi-xun; Liu, Li-li; Zhang, Chris Zhiyi; Yun, Jing-ping

    2017-01-01

    Background: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. Methods: A total of 615 HCC specimens were obtained to construct tissue microarrays and pe...

  4. Alpha Particles and X Rays Interact in Inducing DNA Damage in U2OS Cells.

    Science.gov (United States)

    Sollazzo, Alice; Brzozowska, Beata; Cheng, Lei; Lundholm, Lovisa; Haghdoost, Siamak; Scherthan, Harry; Wojcik, Andrzej

    2017-10-01

    Survivors of the atomic bombings of Hiroshima and Nagasaki are monitored for health effects within the Life Span Study (LSS). The LSS results represent the most important source of data about cancer effects from ionizing radiation exposure, which forms the foundation for the radiation protection system. One uncertainty connected to deriving universal risk factors from these results is related to the problem of mixed radiation qualities. The A-bomb explosions generated a mixed beam of the sparsely ionizing gamma radiation and densely ionizing neutrons. However, until now the possible interaction of the two radiation types of inducing biological effects has not been taken into consideration. The existence of such interaction would suggest that the application of risk factors derived from the LSS to predict cancer effects after pure gamma-ray irradiation (such as in the Fukushima prefecture) leads to an overestimation of risk. To analyze the possible interaction of radiation types, a mixed-beam exposure facility was constructed where cells can be exposed to sparsely ionizing X rays and densely ionizing alpha particles. U2OS cells were used, which are stably transfected with a plasmid coding for the DNA repair gene 53BP1 coupled to a gene coding for the green fluorescent protein (GFP). The induction and repair of DNA damage, which are known to be related to cancer induction, were analyzed. The results suggest that alpha particles and X rays interact, leading to cellular and possibly cancer effects, which cannot be accurately predicted based on assuming simple additivity of the individual mixed-beam components.

  5. Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice: a comparative study using anti-TNFalpha, anti-IL-1alpha/beta and IL-1Ra.

    NARCIS (Netherlands)

    Joosten, L.A.B.; Helsen, M.M.A.; Loo, F.A.J. van de; Berg, W.B. van den

    2008-01-01

    OBJECTIVE: To examine the role of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), and IL-1 beta in collagen-induced arthritis (CIA), immediately after onset and during the phase of established arthritis. METHODS: Male DBA/1 mice with collagen-induced arthritis were treated

  6. Effects of dietary [alpha]-tocopherol and [beta]-carotene on lipid peroxidation induced by methyl mercuric chloride in mice

    Energy Technology Data Exchange (ETDEWEB)

    Raun Andersen, H; Andersen, O [Department of Environmental Medicine, University of Odense, Odense (Denmark)

    1993-01-01

    Exposure of male CBA mice to methyl mercuric chloride, CH[sub 3]HgCl, (10-40 mg/l in drinking water) for 2 weeks resulted in dose-related Hg deposition and enhanced lipid peroxidation in liver, kidney and brain. Mice were fed well-defined semisynthetic diets containing different levels of [alpha]-tocopherol (10, 100 or 1000 mg/kg) or [beta]-carotene (1000, 10,000 or 100,000 IU/kg) for four weeks, two groups on each diet. The concentration of [alpha]-tocopherol and [beta]-carotene used corresponded to deficient, normal and high levels. During the last two weeks, one group on each diet was given 40 mg CH[sub 3]HgCl/l of drinking water. High dietary [alpha]-tocopherol protected against CH[sub 3]HgCl induced hepatic lipid peroxidation, whereas the [alpha]-tocopherol deficient diet further enhanced CH[sub 3]HgCl induced hepatic lipid peroxidation. Similar, though statistically non-significant effects occurred in the kidneys, [alpha]-tocopherol did not protect against CH[sub 3]HgCl induced lipid peroxidation in the brain. Excess dietary [beta]-carotene further enhanced CH[sub 3]HgCl induced lipid peroxidation in liver, kidney and brain. CH[sub 3]HgCl significantly decreased the activity of total glutathione peroxidase (T-GSH-Px) and Se-dependent glutathione peroxidase (Se-GSH-Px) in the kidneys in all dietary groups. High dietary [alpha]-tocopherol enhanced the activity of Se-GSH-Px in liver and kidney compared to the activity in mice fed the normal level of [alpha]-tocopherol. This occurred in mice exposed to CH[sub 3]-HgCl as well as in unexposed mice, and the difference between CH[sub 3]HgCl exposed and unexposed mice was not diminished. High dietary [alpha]-tocopherol increased the activity of both Se-GSH-Px and T-GSH-Px in the brain of CH[sub 3]HgCl-exposed mice. The dietary level of [beta]-carotene did not affect the activity of the two enzymes in the organs investigated. (au) (43 refs.).

  7. Enhancement of alpha particles-induced cell transformation by oxygen free radicals and tumor necrosis factor released from phagocytes

    International Nuclear Information System (INIS)

    Gong Yifen; Guo Renfeng; Zhu Maoxiang; Shou Jiang; Ge Guixiu; Yang Zhihua; Hieber, L.; Peters, K.; Schippel, C.

    1997-01-01

    To illustrate the role of several endogenous factors released from phagocytes under chronic inflammation in radiation-induced cancer. C 3 T 10 T 1/2 and SHE cells were used as targets, and 238 Pu alpha source was used in alpha irradiation. The enhancement of TF in alpha particles-induced cell transformation by PMA-stimulated human blood and zymosan-stimulated U-937 cells was studied using formation of transformed foci. Transformation frequency (TF) of C 3 H 10 T 1/2 cells exposed to alpha particles of 0.5 Gy increased 2.1 and 2.8 fold by PMA-and PMA-stimulated neutrophils, respectively. TF of irradiated SHE cells at a dose of 0.5 Gy increased 12 fold by the addition of the supernatant of macrophage-like U-937 cell line. It was shown that TF of irradiated SHE cells at above dose increased 8 fold by the supernatant treated with anti-TNF-α could be subcultured continuously in vitro. The cells at 40 th passage and two lines of monoclone cells have the ability to develop malignant tumors in nude mice. The overdose of free radicals and TNF-α released from neutrophils and macrophages have played an important role in low dose radiation-induced cancer

  8. Study on cytotoxicities induced by alpha particle irradiation combined with NNK treatment

    International Nuclear Information System (INIS)

    Li Ping; Yang Zhihua; Pan Xiujie; Cao Zhenshan; Mi Na; Chen Zhongmin; Liu Gang; Wei Han; Li Huiyin; Zhu Maoxiang

    2006-01-01

    Objective: To investigate cytotoxicities of alpha-particle irradiation combined with NNK treatment. Methods: Exponentially growing immortalized human bronchial epithelial cells were divided into normal control group (NC), alpha particle irradiation group (α), NNK administration group (NNK), NNK administration (100 μg/ml) followed by alpha particle irradiation group (NNK + α), and alphaparticle irradiation followed by NNK administration (100 μg/ml) group (α + NNK). Cell survival fractions were measured by cloning rate of low-density plating cell. Ethidium bromide and 2', 7'-dichlorofluorescein, fluorescent products of the membrane-permeable dyes hydroethine and 2', 7'-dichloroflurescindiacetate were used to monitor the inarticulate reactive oxygen species (ROS) . Damage to membrane permeability was evaluated through testing LDH activity in medium. Results: In the groups exposed to both alpha particles and NNK, the survival rates were significantly lower than that of the groups administrated with the same dose of alpha particles or NNK alone. The levels of intracellular ROS and the activity of LDH in medium were significantly higher than that of the groups administrated with the same dose of alpha particles or NNK alone. Subtracted the NNK effect, the survival rates of the groups received both alpha particle irradiation and NNK treatment were significantly lower than that of alpha particle irradiated only group. However, the intracellular ROS level and the activity of LDH in medium were significantly higher than that of alpha-particle irradiated only group. In addition, the survival rates of the cells in groups exposed to alpha particle irradiation followed by NNK administration were significantly lower than that of cells treated with NNK administration followed by alpha particle irradiation. Conclusions: Alpha particle irradiation and NNK administration had synergisticity in cytotoxicity, and furthermore different schedules of the administration resulted in

  9. In vivo administration of interferon alpha and interleukin 2 induces proliferation of lymphoid cells in the organs of mice

    International Nuclear Information System (INIS)

    Puri, R.K.; Travis, W.D.; Rosenberg, S.A.

    1990-01-01

    We have previously shown that interleukin 2 (IL-2) synergizes with interferon alpha (IFN-alpha) in mediating the regression of established pulmonary and hepatic metastases and the reduction of intradermal tumor in various murine tumor models. To understand the mechanism of synergy, we have examined lymphoid cell proliferation in various organs of mice in response to IL-2 and IFN-alpha administration. We have utilized a technique for labeling newly synthesized DNA in vivo with 5-[125I]iodo-2'-deoxyuridine to examine proliferation of endogenous cells in response to IL-2 and IL-2 plus IFN-alpha. A proliferation index was calculated by dividing cpm in the tissues treated with cytokines by cpm obtained in corresponding tissues of control mice. After 4 days of IL-2 administration, a significant uptake of 5-[125I]iodo-2'-deoxyuridine was observed in the lungs, liver, kidneys, and spleen (proliferation index of 13, 10.3, 3.6, and 3.2, respectively). IFN-alpha alone mediated very little incorporation of radiolabel but when administered in combination with IL-2 a reduction of IL-2-induced proliferation was seen on day 4. For example 19,272 +/- 4,556 cpm (mean +/- SE) were obtained in the liver of IL-2-treated mice, compared to 8,103 +/- 2,111 cpm in livers of IL-2 plus IFN-alpha-treated mice (P less than 0.05). Similar inhibition of IL-2-induced proliferation was observed in the lungs, kidneys, and spleen. In contrast, on days 7 or 8, higher uptake of radiolabel was obtained in IFN-alpha plus IL-2-treated lungs, liver, and kidneys, compared to organs of mice treated with IL-2 alone or IFN-alpha alone. A proliferation index of 30.5, 9.8, and 10 was obtained in the lungs, liver, and kidneys of IL-2- plus IFN-alpha-treated animals, compared to 9.6, 3.6, and 5.5 in the corresponding organs of IL-2-treated mice

  10. Antigen-specific tolerance of human alpha1-antitrypsin induced by helper-dependent adenovirus.

    Science.gov (United States)

    Cerullo, V; McCormack, W; Seiler, M; Mane, V; Cela, R; Clarke, C; Rodgers, J R; Lee, B

    2007-12-01

    As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body. Some studies suggest that immunity to serum proteins can be avoided in some mouse strains by using tissue-specific promoters. Here we show that expression of human alpha1-antitrypsin (AAT) was nonimmunogenic in the immune-responsive strain C3H/HeJ, when expressed from helper-dependent (HD) vectors using ubiquitous as well as tissue-specific promoters. Coadministration of less immunogenic HD vectors with an immunogenic first-generation vector failed to immunize, suggesting immune suppression rather than immune stealth. Indeed, mice primed with HD vectors were tolerant to immune challenge with hAAT emulsified in complete Freund's adjuvant. Such animals developed high-titer antibodies to coemulsified human serum albumin, showing that tolerance was antigen specific. AAT-specific T cell responses were depressed in tolerized animals, suggesting that tolerance affects both T and B cells. These results are consistent with models of high-dose tolerance of B cells and certain other suppressive mechanisms, and suggest that a high level of expression from HD vectors can be sufficient to induce specific immune tolerance to serum proteins.

  11. Production of interleukin-1alpha by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1alpha released upon ovarian steroids withdrawal.

    Science.gov (United States)

    Pretto, Chrystel M; Gaide Chevronnay, Héloïse P; Cornet, Patricia B; Galant, Christine; Delvaux, Denis; Courtoy, Pierre J; Marbaix, Etienne; Henriet, Patrick

    2008-10-01

    Endometrial breakdown during menstruation and dysfunctional bleeding is triggered by the abrupt expression of matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal cells via epithelium-derived IL-1alpha is repressed by ovarian steroids. However, the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha expression and bioactivity remains unknown. Variations of endometrial IL-1alpha mRNA and protein along the menstrual cycle and during dysfunctional bleeding were determined using RT-PCR, in situ hybridization, and immunolabeling. The mechanism of EP control was analyzed using culture of explants, laser capture microdissection, and purified cells. Data were compared with expression changes of IL-1beta and IL-1 receptor antagonist. IL-1alpha is synthesized by epithelial cells throughout the cycle but E and/or P prevents its release. In contrast, endometrial stromal cells produce IL-1alpha only at menses and during irregular bleeding in areas of tissue breakdown. Stromal expression of IL-1alpha, like that of MMP-1, is repressed by P (alone or with E) but triggered by epithelium-derived IL-1alpha released upon EP withdrawal. Our experiments in cultured endometrium suggest that IL-1alpha released by epithelial cells triggers the production of IL-1alpha by stromal cells in a paracrine amplification loop to induce MMP-1 expression during menstruation and dysfunctional bleeding. All three steps of this amplification cascade are repressed by EP.

  12. Therapeutic potential of alpha-ketoglutarate against acetaminophen-induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Lalita Mehra

    2016-01-01

    Full Text Available Objective: Alpha-ketoglutarate (α-KG is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP induced toxicity in rats. Materials and Methods: Animals were divided into three groups of six animals each. Group I (Vehicle control: Normal Saline, Group II (APAP: A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + α-KG: APAP as in Group II with α-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP with oxidative stress markers including malondialdehyde (MDA, reduced glutathione (GSH, superoxide dismutase (SOD, catalase (CAT, and histopathology were analyzed. Results: The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of α-KG showed a significant (P < 0.05 reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of α-KG. Conclusion: These results indicate the possible therapeutic potential of α-KG in protecting liver damage by APAP in rats.

  13. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oishi, Katsutaka, E-mail: k-ooishi@aist.go.jp [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Uchida, Daisuke [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki (Japan); Ohkura, Naoki [Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa (Japan); Horie, Shuichi [Department of Clinical Biochemistry, Kagawa Nutrition University, Sakado, Saitama (Japan)

    2010-10-15

    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR{alpha

  14. alpha2 adrenoceptors are involved in the regulation of the gripping-induced immobility episodes in taiep rats.

    Science.gov (United States)

    Eguibar, José R; Cortés, Ma Del Carmen; Valencia, Jaime; Arias-Montaño, José A

    2006-10-01

    In 1989 Holmgren et al. (Holmgren et al. 1989 Lab Anim Sci 39:226-228) described a new mutant rat that developed a progressive motor disturbance during its lifespan. The syndrome is characterized by a tremor in the hind limbs followed by ataxia, episodes of tonic immobility, epilepsy, and paralysis. The acronym of these symptoms (taiep) became the name of this autosomic, recessive mutant rat. The taiep rats are neurological mutant animals with a hypomyelination, followed by a progressive demyelination process. At 7-8 months of age, taiep rats develop immobility episodes (IEs) characterized by a cortical desynchronization, associated with the theta rhythm in the hippocampus and changes of the nucal electromyogram (EMG), whose pattern is like rapid-eye-movement (REM) sleep. These rats also show an altered sleep pattern with an equal REM sleep distribution. This study analyzed therole of alpha(2) adrenoceptors in the expression of gripping-induced IEs in 8-month-old male taiep rats. The alpha(2) adrenoceptor agonists clonidine and xylacine increased the frequency of gripping-induced IEs whereas the alpha(2) antagonists yohimbine and idazoxandecreased or prevented such episodes. These findings correlate with the pharmacological observations in narcoleptic dogs and humans in which alpha(2) adrenergic mechanisms are involved in the modulation of cataplexy. Unexpectedly, the repetitive administration of clonidine resulted in jumping behavior, indicative of phasic activation of extensor musculature. Taken together, our results show that alpha(2) adrenoceptors are involved in the modulation in gripping-induced IEs and after the administration of several doses of clonidine produced phasic motor activation.

  15. Stress-induced decrease of uterine blood flow in sheep is mediated by alpha 1-adrenergic receptors.

    Science.gov (United States)

    Dreiling, Michelle; Bischoff, Sabine; Schiffner, Rene; Rupprecht, Sven; Kiehntopf, Michael; Schubert, Harald; Witte, Otto W; Nathanielsz, Peter W; Schwab, Matthias; Rakers, Florian

    2016-09-01

    Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates. UBF, blood pressure (BP), heart rate (HR), stress hormones, and blood gases were determined before and during this isolation challenge. Twenty-four hours later, experiments were repeated during alpha 1-adrenergic receptor blockage induced by a continuous intravenous infusion of urapidil. In both experiments, ewes reacted to isolation with an increase in serum norepinephrine, cortisol, BP, and HR as typical signs of activation of sympatho-adrenal and the hypothalamic-pituitary-adrenal axis. Stress-induced UBF decrease was prevented by alpha 1-adrenergic receptor blockage. We conclude that UBF decrease induced by maternal stress in sheep is mediated by alpha 1-adrenergic receptors. Future studies investigating prevention strategies of impact of prenatal maternal stress on fetal health should consider selective blockage of alpha 1-receptors to interrupt maternal-fetal stress transfer mediated by utero-placental malperfusion.

  16. Study on cellular genotoxicities induced by alpha particles irradiation in combination with NNK treatment

    International Nuclear Information System (INIS)

    Li Ping; Yang Zhihua; Pan Xiujie; Cao Zhenshan; Mi Na; Chen Zhongmin; Liu Gang; Wei Han; Li Huiying; Zhu Maoxiang

    2006-01-01

    Objective: To investigate cellular genotoxicities of aplha particles irradiation in combination with NNK treatment. Methods: Exponentially growing immortalized human bronchial epithelial cells were divided into the normal control group (NC), alpha particles irradiation (α), NNK administration group (NNK), NNK administration (100 μg/ml) followed by alpha particles irradiation group (NNK + α), and alpha particles irradiation followed by NNK administration (100 μg/ml) group (μ + NNK). DNA damage were detected by single cell gel electrophoresis (SCGE); multinuclear cell assay was used to detect the frequency of the HPRT gene mutation; cell micronucleus frequency were detected by cytogenetic methods. Results: In the group exposed to both alpha particles irradiation and NNK, DNA damage, HPRT gene mutation frequency, and cell micronucleus frequency were significantly higher than those in the same dose groups irradiated with alpha particles or NNK administration alone. Subtracted the NNK effect, DNA damage, HPRT gene mutation frequency and cell micronucleus frequency in the group irradiated by alpha particles in combination with NNK administration were significantly higher than those of alpha particles irradiation alone. Conclusion: The genotoxicity of alpha particles irradiation in combination with NNK administration had synergistic effect. (authors)

  17. Specific Genetic Immunotherapy Induced by Recombinant Vaccine Alpha-Fetoprotein-Heat Shock Protein 70 Complex

    Science.gov (United States)

    Wang, Xiaoping; Lin, Huanping; Wang, Qiaoxia

    Purposes: To construct a recombinant vaccine alpha-fetoprotein (AFP)-heat shock protein (HSP70) complex, and study its ability to induce specific CTL response and its protective effect against AFP-producing tumor. Material/Methods: A recombinant vaccine was constructed by conjugating mouse alpha-fetoprotein to heat shock protein 70. By way of intracutaneous injection, mice were primed and boosted with recombinant vaccine mAFP/HSP70, whereas single mAFP or HSP70 injection as controls. The ELISPOT and ELISA were used to measure the frequency of cells producing the cytokine IFN-γ in splenocytes and the level of anti-AFP antibody of serum from immunized mice respectively. In vivo tumor challenge were carried out to assess the immune effect of the recombinant vaccine. Results: By recombinant mAFP/HSP70 vaccine immunization, the results of ELISPOT and ELISA showed that the number of splenic cells producing IFN-γ and the level of anti-AFP antibody of serum were significantly higher in mAFP/HSP70 group than those in mAFP and HSP70 groups (108.50±11.70 IFN-γ spots/106 cells vs 41.60±10.40 IFN-γ spots/106 cells, 7.32±3.14 IFN-γ spots/106 cells, P<0.01; 156.32±10.42 μg/mL vs 66.52±7.35 μg/mL, 5.73±2.89 μg/mL, P<0.01). The tumor volume in mAFP/HSP70 group was significantly smaller than that in mAFP and HSP70 groups (42.44±7.14 mm3 vs 392.23±12.46 mm3, 838.63±13.84 mm3, P<0.01). Conclusions: The study further confirmed the function of heat shock protein 70's immune adjuvant. Sequential immunization with recombinant mAFP/HSP70 vaccine could generate effective antitumor immunity on AFP-producing tumor. The recombined mAFP/HSP70 vaccine may be suitable for serving as an immunotherapy for hepatocellular carcinoma.

  18. Ultra-high-resolution alpha spectrometry for nuclear forensics and safeguards applications

    International Nuclear Information System (INIS)

    Bacrania, Minesh K.; Croce, Mark; Bond, Evelyn; Dry, Donald; Moody, W. Allen; Lamont, Stephen; Rabin, Michael; Rim, Jung; Smith, Audrey; Beall, James; Bennett, Douglas; Kotsubo, Vincent; Horansky, Robert; Hilton, Gene; Schmidt, Daniel; Ullom, Joel; Cantor, Robin

    2010-01-01

    We will present our work on the development of ultra-high-resolution detectors for alpha particle spectrometry. These detectors, based on superconducting transition-edge sensors, offer energy resolution that is five to ten times better than conventional silicon detectors. Using these microcalorimeter detectors, the isotopic composition of mixed-actinide samples can be determined rapidly without the need for actinide separation chemistry to isolate each element, or mass spectrometry to separate isotopic signatures that can not be resolved using traditional alpha spectrometry (e.g. Pu-239/Pu-240, or Pu-238/Am-241). This paper will cover the detector and measurement system, actinide source preparation, and the quantitative isotopic analysis of a number of forensics- and safeguards-relevant radioactive sources.

  19. Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bernardino, Liliana; Xapelli, Sara; Silva, Ana P

    2005-01-01

    The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects...... of mouse recombinant TNF-alpha (10 ng/ml) enhanced excitotoxicity when the cultures were simultaneously exposed to AMPA and to this cytokine. Decreasing the concentration of TNF-alpha to 1 ng/ml resulted in neuroprotection against AMPA-induced neuronal death independently on the application protocol....... By using TNF-alpha receptor (TNFR) knock-out mice, we demonstrated that the potentiation of AMPA-induced toxicity by TNF-alpha involves TNF receptor-1, whereas the neuroprotective effect is mediated by TNF receptor-2. AMPA exposure was associated with activation and proliferation of microglia as assessed...

  20. Stability of zinc stearate under alpha irradiation in the manufacturing process of SFR nuclear fuels

    Science.gov (United States)

    Gracia, J.; Vermeulen, J.; Baux, D.; Sauvage, T.; Venault, L.; Audubert, F.; Colin, X.

    2018-03-01

    The manufacture of new fuels for sodium-cooled fast reactors (SFRs) will involve powders derived from recycling existing fuels in order to keep on producing electricity while saving natural resources and reducing the amount of waste produced by spent MOX fuels. Using recycled plutonium in this way will significantly increase the amount of 238Pu, a high energy alpha emitter, in the powders. The process of shaping powders by pressing requires the use of a solid lubricant, zinc stearate, to produce pellets with no defects compliant with the standards. The purpose of this study is to determine the impact of alpha radiolysis on this additive and its lubrication properties. Experiments were conducted on samples in contact with PuO2, as well as under external helium ion beam irradiation, in order to define the kinetics of radiolytic gas generation. The yield results relating to the formation of these gases (G0) show that the alpha radiation of plutonium can be simulated using external helium ion beam irradiation. The isotopic composition of plutonium has little impact on the yield. However, an increased yield was globally observed with increasing the mean linear energy transfer (LET). A radiolytic degradation process is proposed.

  1. Induced γ emission for nuclear isomer long-lived

    International Nuclear Information System (INIS)

    Yang Tianli; Hao Fanhua

    2007-06-01

    It is pointed that the induced 7 emission for long lived isomer 178m2 Hf by low energy X rays has been a topic subject in the nuclear field recently. The background and development status are described. A principle for T ray transitions induced by X rays and the theoretical about magnificent induced emission have been related. In addition, the possible method of 178m2 Hf produce has been introduced also. Although the argument has existed for the experimental results of induced 7 emission, it can push forward in solving energy crisis and in future military field after controlling effectively the releasing of high excited energy for isomer. (authors)

  2. DNA damage-induced inflammation and nuclear architecture.

    Science.gov (United States)

    Stratigi, Kalliopi; Chatzidoukaki, Ourania; Garinis, George A

    2017-07-01

    Nuclear architecture and the chromatin state affect most-if not all- DNA-dependent transactions, including the ability of cells to sense DNA lesions and restore damaged DNA back to its native form. Recent evidence points to functional links between DNA damage sensors, DNA repair mechanisms and the innate immune responses. The latter raises the question of how such seemingly disparate processes operate within the intrinsically complex nuclear landscape and the chromatin environment. Here, we discuss how DNA damage-induced immune responses operate within chromatin and the distinct sub-nuclear compartments highlighting their relevance to chronic inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Protective Role of Alpha Lipoic Acid Against Disorders Induced by Gamma Radiation

    International Nuclear Information System (INIS)

    Abd El Azeem, Kh.N.M.

    2011-01-01

    Ionizing radiation interacts with living cells, causing a variety of biochemical changes depending on exposed and absorbed doses, duration of exposure, interval after exposure and susceptibility of tissues to ionizing radiation. So, it may increase the oxidative stress and damage of body organs. Alpha-lipoic acid (ALA-also known as thioctic acid) appears to be readily absorbed from an oral dose and converts easily to its reduced form, dihydro lipoic acid (DHLA), in many tissues of the body. ALA can neutralize free radicals in both fatty and watery regions of cells. The present study has been designed to evaluate the possible efficiency of ALA as antioxidant and radio-protector against radiation induced oxidative stress in different organs (liver, kidney and heart) in rats through estimation of the activity of markers of serum liver, kidney and heart function, in addition to the histopathological differentiation of these organs by light and electron microscope. Five equal groups were conducted for the study: control, ALA (30 mg/kg body wt), irradiated (each rat was exposed to 6 Gy as a fractionated dose of gamma (γ) radiation), irradiated plus ALA (each rat received ALA for 9 days simultaneously during exposure) and ALA plus irradiation plus ALA groups (each rat received ALA for a week pre-exposure plus 9 days during exposure). Radiation doses were fractionated dose levels of 2 Gy each 3 days to reach accumulative dose of 6 Gy. After 3 days of each exposure rats were sacrificed, except, those left for recovery test one month after last exposure. The results revealed that whole body γ-irradiation of rats induces oxidative stress in liver, kidney and heart obviously manifested by significant elevation in alanine and aspartate transaminase ( ALT and AST), alkaline phosphatase (ALP), urea, creatinine and creatine kinase (CK-MB). ALA treated-irradiated rats showed lower significantly values indicating remarkable improvement in all measured parameters and

  4. Inhibition of polymerases-alpha and -beta completely blocks DNA repair induced by UV irradiation in cultured mouse neuronal cells

    International Nuclear Information System (INIS)

    Licastro, F.; Sarafian, T.; Verity, A.M.; Walford, R.L.

    1985-01-01

    The effects of hydroxyurea, aphidicolin and dideoxythymidine on UV-induced DNA repair of mouse neuronal granular cells were studied. Aphidicolin, which is considered a specific inhibitor of polymerase-alpha, decreased spontaneous DNA synthesis by 93% and totally suppressed DNA repair. Dideoxythymidine, an inhibitor of polymerase-beta, was more potent in decreasing scheduled DNA synthesis than aphidicolin, and also completely blocked the UV-induced DNA repair. Hydroxyurea, a specific inhibitor of ribonucleotide reductase, inhibited scheduled DNA synthesis, but unscheduled DNA synthesis after UV irradiation was always well detectable. Our data suggest that in neuronal cells from 5 to 10 days old mice both polymerases-alpha and -beta are required for both DNA synthesis and repair. These two enzymes may act jointly in filling up the gaps along the DNA molecule and elongating the DNA chain

  5. Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration

    International Nuclear Information System (INIS)

    Panduro, A.; Shalaby, F.; Weiner, F.R.; Biempica, L.; Zern, M.A.; Shafritz, D.A.

    1986-01-01

    During liver regeneration induced by CCl 4 administration to rats, changes in the relative transcription rates of albumin and alpha-fetoprotein genes have been measured in conjunction with other liver-specific and general cellular function genes. Within 24 h following CCl 4 administration, albumin gene transcription decreases by 85%, whereas alpha-fetoprotein transcription increases from undetectable levels to 50% of that observed for albumin. These changes precede maximal [ 3 H]thymidine incorporation into DNA which peaks at 48 h. Other genes related to liver-specific functions, such as ligandin, alpha 1-antitrypsin, and cytochrome P-450's, as well as general cellular genes pro alpha 1- and pro alpha 2-collagen, beta-actin, and alpha-tubulin, respond in kinetic patterns often distinct from each other and from albumin and alpha-fetoprotein. Changes in the steady-state levels of albumin and alpha-fetoprotein mRNA correlate with changes in transcription, but there is a lag in alpha-fetoprotein mRNA accumulation, which peaks at 72 h following CCl 4 administration. These studies indicate that reciprocal changes in albumin and alpha-fetoprotein gene transcription occur during CCl 4 -induced liver regeneration, leading to changes in the level of these specific mRNAs. These changes precede DNA synthesis and would appear to represent an alteration in differentiated function of hepatocytes in conjunction with the liver regenerative process

  6. Nuclear proliferomics: A new field of study to identify signatures of nuclear materials as demonstrated on alpha-UO3.

    Science.gov (United States)

    Schwerdt, Ian J; Brenkmann, Alexandria; Martinson, Sean; Albrecht, Brent D; Heffernan, Sean; Klosterman, Michael R; Kirkham, Trenton; Tasdizen, Tolga; McDonald Iv, Luther W

    2018-08-15

    The use of a limited set of signatures in nuclear forensics and nuclear safeguards may reduce the discriminating power for identifying unknown nuclear materials, or for verifying processing at existing facilities. Nuclear proliferomics is a proposed new field of study that advocates for the acquisition of large databases of nuclear material properties from a variety of analytical techniques. As demonstrated on a common uranium trioxide polymorph, α-UO 3 , in this paper, nuclear proliferomics increases the ability to improve confidence in identifying the processing history of nuclear materials. Specifically, α-UO 3 was investigated from the calcination of unwashed uranyl peroxide at 350, 400, 450, 500, and 550 °C in air. Scanning electron microscopy (SEM) images were acquired of the surface morphology, and distinct qualitative differences are presented between unwashed and washed uranyl peroxide, as well as the calcination products from the unwashed uranyl peroxide at the investigated temperatures. Differential scanning calorimetry (DSC), UV-Vis spectrophotometry, powder X-ray diffraction (p-XRD), and thermogravimetric analysis-mass spectrometry (TGA-MS) were used to understand the source of these morphological differences as a function of calcination temperature. Additionally, the SEM images were manually segmented using Morphological Analysis for MAterials (MAMA) software to identify quantifiable differences in morphology for three different surface features present on the unwashed uranyl peroxide calcination products. No single quantifiable signature was sufficient to discern all calcination temperatures with a high degree of confidence; therefore, advanced statistical analysis was performed to allow the combination of a number of quantitative signatures, with their associated uncertainties, to allow for complete discernment by calcination history. Furthermore, machine learning was applied to the acquired SEM images to demonstrate automated discernment with

  7. Salivary alpha-amylase: More than an enzyme Investigating confounders of stress-induced and basal amylase activity

    OpenAIRE

    Strahler, Jana

    2010-01-01

    Summary: Salivary alpha-amylase: More than an enzyme - Investigating confounders of stress-induced and basal amylase activity (Dipl.-Psych. Jana Strahler) The hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are two of the major systems playing a role in the adaptation of organisms to developmental changes that threaten homeostasis. The HPA system involves the secretion of glucocorticoids, including cortisol, into the circulatory system. Numerous studies hav...

  8. Uniform decrease of alpha-global field power induced by intermittent photic stimulation of healthy subjects

    Directory of Open Access Journals (Sweden)

    Rau R.

    2002-01-01

    Full Text Available Nineteen-channel EEGs were recorded from the scalp surface of 30 healthy subjects (16 males and 14 females, mean age: 34 years, SD: 11.7 years at rest and under trains of intermittent photic stimulation (IPS at rates of 5, 10 and 20 Hz. Digitalized data were submitted to spectral analysis with fast fourier transformation providing the basis for the computation of global field power (GFP. For quantification, GFP values in the frequency ranges of 5, 10 and 20 Hz at rest were divided by the corresponding data obtained under IPS. All subjects showed a photic driving effect at each rate of stimulation. GFP data were normally distributed, whereas ratios from photic driving effect data showed no uniform behavior due to high interindividual variability. Suppression of alpha-power after IPS with 10 Hz was observed in about 70% of the volunteers. In contrast, ratios of alpha-power were unequivocal in all subjects: IPS at 20 Hz always led to a suppression of alpha-power. Dividing alpha-GFP with 20-Hz IPS by alpha-GFP at rest (R = alpha-GFP IPS/alpha-GFPrest thus resulted in ratios lower than 1. We conclude that ratios from GFP data with 20-Hz IPS may provide a suitable paradigm for further investigations.

  9. INDUCED NUCLEAR ACTIVITY IN GALAXY PAIRS

    OpenAIRE

    F. J. Hernández-Ibarra; D. Dultzin; Y. Krongold; A. Del Olmo; J. Perea

    2011-01-01

    Analizamos espectros del núcleo de 893 galaxias entre pares de galaxias y galaxias aisladas de la muestra SLOAN (DR7). Estos pares pueden ser divididos en tres grupos: S+S, E+E y E+S de acuerdo con el catálago de pares aislados de galaxias de Karachentsev (KPG). También analizamos dos muestras de galaxias aisladas: el catálogo de galaxias aisladas de Karachentseva (CIG) y la muestra de galaxias aisladas en el hemisferio norte de Varela. Estudiamos la incidencia de la actividad nuclear en cada...

  10. The tumor necrosis factor-alpha-induced protein 8 family in immune homeostasis and inflammatory cancer diseases.

    Science.gov (United States)

    Luan, Y Y; Yao, Y M; Sheng, Z Y

    2013-01-01

    Within the immune system homeostasis is maintained by a myriad of mechanisms that include the regulation of immune cell activation and programmed cell death. The breakdown of immune homeostasis may lead to fatal inflammatory diseases. We set out to identify genes of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) family that has a functional role in the process of immune homeostasis. Tumor necrosis factor-alpha-induced protein 8 (TNFAIP8), which functions as an oncogenic molecule, is also associated with enhanced cell survival and inhibition of apoptosis. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) governs immune homeostasis in both the innate and adaptive immune system and prevents hyper-responsiveness by negatively regulating signaling via T cell receptors and Toll-like receptors (TLRs). There also exist two highly homologous but uncharacterized proteins, TIPE1 and TIPE3. This review is an attempt to provide a summary of TNFAIP8 family associated with immune homeostasis and inflammatory cancer diseases.

  11. Evolution of etched nuclear track profiles of alpha particles in CR-39 by atomic force microscopy

    International Nuclear Information System (INIS)

    Félix-Bautista, R.; Hernández-Hernández, C.; Zendejas-Leal, B.E.; Fragoso, R.; Golzarri, J.I.; Vázquez-López, C.; Espinosa, G.

    2013-01-01

    A series of atomic force microscopy (AFM) images of etched nuclear tracks has been obtained and used to calculate the nuclear track registration sensitivity parameter V(x) = Vt(x)/Vb. Due to the AFM limitations the samples were irradiated normally to the surface, and with energies attenuated in order to include the Bragg peak region in the AFM piezo-scanner z movement range. The simulation of the track profile evolution was then obtained. The different stages of etched nuclear track profiles were rendered. - Highlights: ► Using AFM we reach that Bragg peak region of etched tracks in CR-39. ► The etched track sensitivity V was calculated by data obtained by AFM. ► The evolucion of etched nuclear tracks was simulated by data achieved by AFM

  12. Nuclear and Membrane Actions of Estrogen Receptor Alpha: Contribution to the Regulation of Energy and Glucose Homeostasis.

    Science.gov (United States)

    Guillaume, Maeva; Montagner, Alexandra; Fontaine, Coralie; Lenfant, Françoise; Arnal, Jean-François; Gourdy, Pierre

    2017-01-01

    Estrogen receptor alpha (ERα) has been demonstrated to play a key role in reproduction but also to exert numerous functions in nonreproductive tissues. Accordingly, ERα is now recognized as a key regulator of energy homeostasis and glucose metabolism and mediates the protective effects of estrogens against obesity and type 2 diabetes. This chapter attempts to summarize our current understanding of the mechanisms of ERα activation and their involvement in the modulation of energy balance and glucose metabolism. We first focus on the experimental studies that constitute the basis of the understanding of ERα as a nuclear receptor and more specifically on the key roles played by its two activation functions (AFs). We depict the consequences of the selective inactivation of these AFs in mouse models, which further underline the prominent role of nuclear ERα in the prevention of obesity and diabetes, as on the reproductive tract and the vascular system. Besides these nuclear actions, a fraction of ERα is associated with the plasma membrane and activates nonnuclear signaling from this site. Such rapid effects, called membrane-initiated steroid signals (MISS), have been characterized in a variety of cell lines and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS as well as the generation of mice expressing an ERα protein impeded for membrane localization has just begun to unravel the physiological role of MISS in vivo and their contribution to ERα-mediated metabolic protection. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators.

  13. Development of an image analysis screen for estrogen receptor alpha (ERα) ligands through measurement of nuclear translocation dynamics.

    Science.gov (United States)

    Dull, Angie; Goncharova, Ekaterina; Hager, Gordon; McMahon, James B

    2010-11-01

    We have developed a robust high-content assay to screen for novel estrogen receptor alpha (ERα) agonists and antagonists by quantitation of cytoplasmic to nuclear translocation of an estrogen receptor chimera in 384-well plates. The screen utilizes a green fluorescent protein tagged-glucocorticoid/estrogen receptor (GFP-GRER) chimera which consisted of the N-terminus of the glucocorticoid receptor fused to the human ER ligand binding domain. The GFP-GRER exhibited cytoplasmic localization in the absence of ERα ligands, and translocated to the nucleus in response to stimulation with ERα agonists or antagonists. The BD Pathway 435 imaging system was used for image acquisition, analysis of translocation dynamics, and cytotoxicity measurements. The assay was validated with known ERα agonists and antagonists, and the Library of Pharmacologically Active Compounds (LOPAC 1280). Additionally, screening of crude natural product extracts demonstrated the robustness of the assay, and the ability to quantitate the effects of toxicity on nuclear translocation dynamics. The GFP-GRER nuclear translocation assay was very robust, with z' values >0.7, CVs screening of natural product extracts. This assay has been developed for future primary screening of synthetic, pure natural products, and natural product extracts libraries available at the National Cancer Institute at Frederick. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  15. Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection

    DEFF Research Database (Denmark)

    Stylianou, E; Aukrust, P; Bendtzen, K

    2000-01-01

    -infected patients had raised levels of both IP-10 and IFN-alpha compared with healthy controls (n = 19), with particularly high levels in advanced disease. HAART induced a marked decrease in levels of both IFN-alpha, neopterin and IP-10, though not to normal concentrations. In contrast, IFN-gamma levels were low...

  16. Intermitted pharmacologic pretreatment by xenon, isoflurane, nitrous oxide, and the opioid morphine prevents tumor necrosis factor alpha-induced adhesion molecule expression in human umbilical vein endothelial cells

    NARCIS (Netherlands)

    Weber, Nina C.; Kandler, Jennis; Schlack, Wolfgang; Grueber, Yvonne; Frädorf, Jan; Preckel, Benedikt

    2008-01-01

    BACKGROUND: The barrier properties of the endothelium are of critical importance during pathophysiologic processes. These barrier properties depend on an intact cytoskeleton and are regulated by cell adhesion molecules. Tumor necrosis factor alpha (TNF-alpha) is known to induce cell adhesion

  17. Coordination chemistry of the 212Pb/212Bi nuclear transformation: Alpha-emitting radiopharmaceuticals

    International Nuclear Information System (INIS)

    Parks, N.J.; Harris, W.R.; Keen, C.L.; Cooper, S.R.

    1992-07-01

    Subdivisions of this project are: (a) the synthesis of prototypical thiolate and dithiocarbamate based hexacoordinate complexes, (b) radiochemical engineering for generation of no-carrier-added lead and bismuth radioelements, (c) the first isolation of bismuth-binding proteins from in vivo studies with cyclotron produced 205/206 Bi tracer, and (d) initial development of transport mechanisms for the intracellular radiobiological study of alpha emitting bismuth, and (e) the initiation of chemical equilibrium studies and biochemical pathways with cyclotron-produced, no-carrier-added, 203 Pb (T 1/2 = 51 hr)

  18. Coordination chemistry of the sup 212 Pb/ sup 212 Bi nuclear transformation: Alpha-emitting radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Parks, N.J.; Harris, W.R.; Keen, C.L.; Cooper, S.R.

    1992-07-01

    Subdivisions of this project are: (a) the synthesis of prototypical thiolate and dithiocarbamate based hexacoordinate complexes, (b) radiochemical engineering for generation of no-carrier-added lead and bismuth radioelements, (c) the first isolation of bismuth-binding proteins from in vivo studies with cyclotron produced {sup 205/206}Bi tracer, and (d) initial development of transport mechanisms for the intracellular radiobiological study of alpha emitting bismuth, and (e) the initiation of chemical equilibrium studies and biochemical pathways with cyclotron-produced, no-carrier-added, {sup 203}Pb (T{sub 1/2} = 51 hr).

  19. Method and apparatus for induced nuclear beta decay

    International Nuclear Information System (INIS)

    Reiss, H.

    1986-01-01

    This invention relates to a method and apparatus for inducing beta decay transition that are normally inhibited by angular momentum or parity considerations. According to one aspect of this invention a method of inducing nuclear beta decay transition comprises providing a medium which includes atomic nuclei that have forbidden beta decay transition in which the initial and final nuclear states do not have the same intrinsic parity or have total angular momenta which differ by more than one quantum unit of angular momentum, and applying to the medium an electromagnetic field which has an intensity sufficient to provide the angular momentum or intrinsic parity necessary to overcome the forbiddenness of the beta decay transition of the atomic nuclei, thereby to induce the beta decay transitions. According to another aspect of this invention an apparatus for inducing beta decay transition comprises a medium which includes atomic nuclei that have forbidden beta decay transitions in which the initial and final nuclear states do not have the same intrinsic parity or have total angular momenta which differ by more than one quantum unit of angular momentum, field producing means for producing an electromagnetic field in the medium and means for energising the field producing means to establish the field at an intensity sufficient to provide the angular momentum or intrinsic parity necessary to overcome the forbiddenness of the beta decay transitions of the atomic nuclei. The energy released in these induced nuclear transition is useful for the controlled production of power. The induced beta dacay transitions are also useful to reduce the halflives of long-lived fission product wastes from conventional nuclear fission power plants

  20. Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

    Science.gov (United States)

    Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

    2006-10-01

    Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

  1. Alpha clustering in nuclei

    International Nuclear Information System (INIS)

    Hodgson, P.E.

    1990-01-01

    The effects of nucleon clustering in nuclei are described, with reference to both nuclear structure and nuclear reactions, and the advantages of using the cluster formalism to describe a range of phenomena are discussed. It is shown that bound and scattering alpha-particle states can be described in a unified way using an energy-dependent alpha-nucleus potential. (author)

  2. Note: Real time optical sensing of alpha-radiation emitting radioactive aerosols based on solid state nuclear track detector

    International Nuclear Information System (INIS)

    Kulkarni, A.; Bak, M. S.; Ha, S.; Joshirao, P.; Manchanda, V.; Kim, T.

    2015-01-01

    A sensitive radioactive aerosols sensor has been designed and developed. Its design guidance is based on the need for a low operational cost and reliable measurements to provide daily aerosol monitoring. The exposure of diethylene-glycol bis (allylcarbonate) to radiation causes modification of its physico-chemical properties like surface roughness and reflectance. In the present study, optical sensor based on the reflectance measurement has been developed with an aim to monitor real time presence of alpha radioactive aerosols emitted from thorium nitrate hydrate. The results shows that the fabricated sensor can detect 0.0157 kBq to 0.1572 kBq of radio activity by radioactive aerosols generated from (Th(NO 3 ) 4 ⋅ 5H 2 O) at 0.1 ml/min flow rate. The proposed instrument will be helpful to monitor radioactive aerosols in/around a nuclear facility, building construction sites, mines, and granite polishing factories

  3. Note: Real time optical sensing of alpha-radiation emitting radioactive aerosols based on solid state nuclear track detector

    Science.gov (United States)

    Kulkarni, A.; Ha, S.; Joshirao, P.; Manchanda, V.; Bak, M. S.; Kim, T.

    2015-06-01

    A sensitive radioactive aerosols sensor has been designed and developed. Its design guidance is based on the need for a low operational cost and reliable measurements to provide daily aerosol monitoring. The exposure of diethylene-glycol bis (allylcarbonate) to radiation causes modification of its physico-chemical properties like surface roughness and reflectance. In the present study, optical sensor based on the reflectance measurement has been developed with an aim to monitor real time presence of alpha radioactive aerosols emitted from thorium nitrate hydrate. The results shows that the fabricated sensor can detect 0.0157 kBq to 0.1572 kBq of radio activity by radioactive aerosols generated from (Th(NO3)4 ṡ 5H2O) at 0.1 ml/min flow rate. The proposed instrument will be helpful to monitor radioactive aerosols in/around a nuclear facility, building construction sites, mines, and granite polishing factories.

  4. Note: Real time optical sensing of alpha-radiation emitting radioactive aerosols based on solid state nuclear track detector

    Energy Technology Data Exchange (ETDEWEB)

    Kulkarni, A.; Bak, M. S., E-mail: tkim@skku.edu, E-mail: moonsoo@skku.edu [School of Mechanical Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Ha, S. [SKKU Advanced Institute of Nano Technology (SAINT), Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Joshirao, P.; Manchanda, V. [Department of Energy Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Kim, T., E-mail: tkim@skku.edu, E-mail: moonsoo@skku.edu [School of Mechanical Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); SKKU Advanced Institute of Nano Technology (SAINT), Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

    2015-06-15

    A sensitive radioactive aerosols sensor has been designed and developed. Its design guidance is based on the need for a low operational cost and reliable measurements to provide daily aerosol monitoring. The exposure of diethylene-glycol bis (allylcarbonate) to radiation causes modification of its physico-chemical properties like surface roughness and reflectance. In the present study, optical sensor based on the reflectance measurement has been developed with an aim to monitor real time presence of alpha radioactive aerosols emitted from thorium nitrate hydrate. The results shows that the fabricated sensor can detect 0.0157 kBq to 0.1572 kBq of radio activity by radioactive aerosols generated from (Th(NO{sub 3}){sub 4} ⋅ 5H{sub 2}O) at 0.1 ml/min flow rate. The proposed instrument will be helpful to monitor radioactive aerosols in/around a nuclear facility, building construction sites, mines, and granite polishing factories.

  5. Electrochemically induced nuclear fusion of deuterium

    International Nuclear Information System (INIS)

    Jorne, J.

    1990-01-01

    In this paper cold fusion of deuterium by electrolysis of heavy water onto a palladium (or titanium) cathode is reported. Contrary to the assumption of Fleishmann and Pons that electrochemically compressed D + exists inside the palladium cathode, the observations of Jones et al. can be partially explained by the simultaneous presence of deuteride D - and the highly mobile positive deuterium ion D + . The opposite charges reduce the intranuclear distance and enhance the tunneling fusion rate. Furthermore, alloying of lithium with palladium can stabilize a negatively charged deuteride ion due to the salinelike character of lithium deuteride. The enormous pressure (or fugacity), achieved by the applied electrochemical potential (10 30 atm), is a virtual pressure that would have existed in equilibrium with palladium deuteride (PdD x ). It is speculated that nuclear fusion occurs at the surface, and the PdD x serves as a reservoir for the supply of deuteride ions

  6. Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1{alpha}, suppress amyloid {beta}-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Raman, Dayanidhi; Milatovic, Snjezana-Zaja [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Milatovic, Dejan [Department of Pediatrics/Pediatric Toxicology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Splittgerber, Ryan [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Fan, Guo-Huang [Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37221 (United States); Richmond, Ann, E-mail: ann.richmond@vanderbilt.edu [VA Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States)

    2011-11-15

    Alzheimer's disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-{beta} (A{beta}). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1{alpha} (SDF-1{alpha}), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress A{beta}-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1{alpha} significantly protected neurons from A{beta}-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1{alpha}. Intra-cerebroventricular (ICV) injection of A{beta} led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The A{beta}-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes, were significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1{alpha}. Additionally, MIP-2 or SDF-1{alpha} was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against A{beta} neurotoxicity in CXCR2-/- mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration. -- Research highlights: Black-Right-Pointing-Pointer Neuroprotective ability of the chemokines MIP2 and CXCL12 against A{beta} toxicity. Black-Right-Pointing-Pointer MIP

  7. Functional defect of truncated hepatocyte nuclear factor-1{alpha} (G554fsX556) associated with maturity-onset diabetes of the young

    Energy Technology Data Exchange (ETDEWEB)

    Kooptiwut, Suwattanee, E-mail: S_kooptiwut@hotmail.com [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Sujjitjoon, Jatuporn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Plengvidhya, Nattachet [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapapron [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Semprasert, Namoiy [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Furuta, Hiroto; Nanjo, Kishio [The First Department, Wakayama Medical University (Japan); Banchuin, Napatawn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai [Division of Medical Molecular Biology, Medicine Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Bangkok (Thailand)

    2009-05-22

    A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1{alpha} (HNF-1{alpha}) encoding a truncated HNF-1{alpha} (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1{alpha} proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1{alpha} could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1{alpha} on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1{alpha} (G554fsX556) on the transactivation of its target-gene promoters would account for the {beta}-cell dysfunction associated with the pathogenesis of MODY.

  8. Laser-induced time-resolved spectrofluorometry and thermal lensing: applications in the nuclear industry

    International Nuclear Information System (INIS)

    Decambox, P.; Delorme, N.; Mauchien, P.; Moulin, C.

    1989-01-01

    Sensitive spectroscopic methods for the determination of actinides and lanthanides in various media are required in the nuclear industry. Laser-Induced Time-Resolved Spectrofluorometry (LITRS) for several actinides and lanthanides at very low levels and thermal lensing (TL) for oxidation state characterization allow these determinations. The set-up of LITRS is presented. Spectra, limit of detections and lifetimes obtained for U, Cm, Am, Eu, Gd, Tb, Dy, Ce, Sm, Tm are shown. Detection limit as low as 5.10 -12 M can be achieved. Examples of matrices encountered for the determination of uranium are given as well as comparison with mass spectrometry and alpha counting. The set-up of TL and performances obtained on plutonium as well as future developments are presented

  9. Optically induced dynamic nuclear spin polarisation in diamond

    International Nuclear Information System (INIS)

    Scheuer, Jochen; Naydenov, Boris; Jelezko, Fedor; Schwartz, Ilai; Chen, Qiong; Plenio, Martin B; Schulze-Sünninghausen, David; Luy, Burkhard; Carl, Patrick; Höfer, Peter; Retzker, Alexander; Sumiya, Hitoshi; Isoya, Junichi

    2016-01-01

    The sensitivity of magnetic resonance imaging (MRI) depends strongly on nuclear spin polarisation and, motivated by this observation, dynamical nuclear spin polarisation has recently been applied to enhance MRI protocols (Kurhanewicz et al 2011 Neoplasia 13 81). Nuclear spins associated with the 13 C carbon isotope (nuclear spin I = 1/2) in diamond possess uniquely long spin lattice relaxation times (Reynhardt and High 2011 Prog. Nucl. Magn. Reson. Spectrosc. 38 37). If they are present in diamond nanocrystals, especially when strongly polarised, they form a promising contrast agent for MRI. Current schemes for achieving nuclear polarisation, however, require cryogenic temperatures. Here we demonstrate an efficient scheme that realises optically induced 13 C nuclear spin hyperpolarisation in diamond at room temperature and low ambient magnetic field. Optical pumping of a nitrogen-vacancy centre creates a continuously renewable electron spin polarisation which can be transferred to surrounding 13 C nuclear spins. Importantly for future applications we also realise polarisation protocols that are robust against an unknown misalignment between magnetic field and crystal axis. (paper)

  10. Probability of bystander effect induced by alpha-particles emitted by radon progeny using the analytical model of tracheobronchial tree

    International Nuclear Information System (INIS)

    Jovanovic, B.; Nikezic, D.

    2010-01-01

    Radiation-induced biological bystander effects have become a phenomenon associated with the interaction of radiation with cells. There is a need to include the influence of biological effects in the dosimetry of the human lung. With this aim, the purpose of this work is to calculate the probability of bystander effect induced by alpha-particle radiation on sensitive cells of the human lung. Probability was calculated by applying the analytical model cylinder bifurcation, which was created to simulate the geometry of the human lung with the geometric distribution of cell nuclei in the airway wall of the tracheobronchial tree. This analytical model of the human tracheobronchial tree represents the extension of the ICRP 66 model, and follows it as much as possible. Reported probabilities are calculated for various targets and alpha-particle energies. Probability of bystander effect has been calculated for alpha particles with 6 and 7.69 MeV energies, which are emitted in the 222 Rn chain. The application of these results may enhance current dose risk estimation approaches in the sense of the inclusion of the influence of the biological effects. (authors)

  11. Thorium: one of the analytical techniques in neutronic activation and alpha spectrometry of the CDTN (Brazilian Nuclear Technology Development Center) in the last three decades

    International Nuclear Information System (INIS)

    Menezes, M.A.B.C.; Sabino, C.V.S.

    1994-01-01

    For long years, the CDTN (Brazilian Nuclear Technology Development Center ) has applied several analytical techniques in the thorium determination. This work is about the evolution of the neutronic activation in the thorium 232 analysis from the 1960's to now. The importance of the analysis request and alpha spectrometry for the thorium 228 and thorium 232 determination is emphasized. (J.A.M.M.)

  12. Nuclear structure approach to the calculation of the imaginary alpha-nucleus optical potential

    International Nuclear Information System (INIS)

    Dermawan, H.; Osterfeld, F.; Madsen, V.A.

    1981-01-01

    A microscopic calculation of the second-order imaginary optical potential for 40 (Ca(α,α) is made for incident energies of 31 and 100 MeV using RPA transition densities for intermediate excited states. The projectile is treated as an elementary particle, and the alpha-nucleon interaction is normalized by fitting 3 - inelastic cross sections with a folded M3Y potential. The use of an optical Green's function for the intermediate propagator is found to be important. Equivalent local potentials are obtained and used to calculate elastic scattering cross sections. Agreement with low-angle experimental data is fair at 31 MeV, but at 100 MeV the calculated cross sections indicate much too little absorption. 9 figures, 1 table

  13. The maximum entropy determination of nuclear densities of calcium isotopes from elastic scattering of alpha particles

    International Nuclear Information System (INIS)

    Engel, Y.M.; Friedman, E.; Levine, R.D.

    1982-01-01

    Radial moments of the real part of the optical potential for elastic scattering of 104 MeV α particles are used as constraints, in determining the nuclear density of maximal entropy. The potential is related to the density by the folding model. (orig.)

  14. Alpha radiation-induced alterations of the proliferation kinetics, chromatin structure and gene expression in mammalian cells

    International Nuclear Information System (INIS)

    Hieber, L.

    1983-01-01

    Exponentially growing mammalian cells were exposed to 3.4 MeV alpha particles. The chromatin of cells arrested in G2 by alpha irradiation was severely damaged, though all cells were still capable to condensate their chromatin after fusion with mitotic cells. In addition to the common types of aberrations (breaks, gaps, dicentrics and exchanges) cells were found possessing one or more chromosomes with long stretches of undercondensed chromatin. Repair of these lesions was indicated by site specific unscheduled DNA synthesis and by the observation that condensation of these regions improved during G2 arrest. Furthermore, during G2 arrest the synthesis of two cellular proteins was stimulated. This was studied by two-dimensional gel electrophoresis of 35 S-methionine labeled cellular proteins. All these findings provided evidence that radiation-induced G2 arrest is caused by chromatin damage, which prevents regular chromosome condensation for mitosis. (orig./MG) [de

  15. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    Energy Technology Data Exchange (ETDEWEB)

    Nintasen, Rungrat [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Riches, Kirsten; Mughal, Romana S. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa [Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Turner, Neil A. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Porter, Karen E., E-mail: medkep@leeds.ac.uk [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

  16. Nitric oxide mediated DNA double strand breaks induced in proliferating bystander cells after {alpha}-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Han Wei [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Chen Shaopeng [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)

    2010-02-03

    Low-dose {alpha}-particle exposures comprise 55% of the environmental dose to the human population and have been shown to induce bystander responses. Previous studies showed that bystander effect could induce stimulated cell growth or genotoxicity, such as excessive DNA double strand breaks (DSBs), micronuclei (MN), mutation and decreased cell viability, in the bystander cell population. In the present study, the stimulated cell growth, detected with flow cytometry (FCM), and the increased MN and DSB, detected with p53 binding protein 1 (53BP1) immunofluorescence, were observed simultaneously in the bystander cell population, which were co-cultured with cells irradiated by low-dose {alpha}-particles (1-10 cGy) in a mixed system. Further studies indicated that nitric oxide (NO) and transforming growth factor {beta}1 (TGF-{beta}1) played very important roles in mediating cell proliferation and inducing MN and DSB in the bystander population through treatments with NO scavenger and TGF-{beta}1 antibody. Low-concentrations of NO, generated by spermidine, were proved to induce cell proliferation, DSB and MN simultaneously. The proliferation or shortened cell cycle in bystander cells gave them insufficient time to repair DSBs. The increased cell division might increase the probability of carcinogenesis in bystander cells since cell proliferation increased the probability of mutation from the mis-repaired or un-repaired DSBs.

  17. Nuclear dynamics in heavy ion induced fusion-fission reactions

    International Nuclear Information System (INIS)

    Kapoor, S.S.

    1992-01-01

    Heavy ion induced fission and fission-like reactions evolve through a complex nuclear dynamics encountered in the medium energy nucleus-nucleus collisions. In the recent years, measurements of the fragment-neutron and fragment-charged particle angular correlations in heavy ion induced fusion-fission reactions, have provided new information on the dynamical times of nuclear deformations of the initial dinuclear complex to the fission saddle point and the scission point. From the studies of fragment angular distributions in heavy ion induced fission it has been possible to infer the relaxation times of the dinuclear complex in the K-degree of freedom and our recent measurements on the entrance channel dependence of fragment anisotropies have provided an experimental signature of the presence of fissions before K-equilibration. This paper reviews recent experimental and theoretical status of the above studies with particular regard to the questions relating to dynamical times, nuclear dissipation and the effect of nuclear dissipation on the K-distributions at the fission saddle in completely equilibrated compound nucleus. (author). 19 refs., 9 figs

  18. Activation cross-section data for -particle-induced nuclear reactions ...

    Indian Academy of Sciences (India)

    B M ALI

    2018-02-20

    particle-induced nuclear reactions on natural vanadium up to 20 MeV. It should be mentioned that this study represents a part of (a supplement) systematical study of charged particles-induced nuclear reactions. Earlier studies were.

  19. Tamoxifen induces the expression of maspin through estrogen receptor-alpha.

    Science.gov (United States)

    Liu, Zesheng; Shi, Heidi Y; Nawaz, Zafar; Zhang, Ming

    2004-06-08

    Maspin (mammary serine protease inhibitor) is a tumor suppressor gene that plays an important role in inhibiting tumor growth, invasion and metastasis. Maspin expression is down regulated at transcription level in primary and metastatic breast tumor cells. Previous studies on hormonal regulation of maspin prompt us to test whether an estrogen antagonist tamoxifen (TAM) can exert its anti-tumor function by up regulating maspin gene expression. For this purpose, we first tested whether maspin promoter could be activated in normal and several breast tumor cells. We then carried out a series of promoter analysis in which estrogen receptors and TAM were reconstituted in an in vitro cell culture system. Here we report our new finding that tumor suppresser gene maspin is one of the TAM target genes. TAM induces a maspin/luciferase reporter in cell culture and this induction requires the presence of (estrogen receptor alpha) ERalpha but not estrogen receptor-beta (ERbeta). Maspin promoter deletion and mutation analysis showed that the cis element(s) within a region between -90and+87 bp but not the HRE site (-272 bp) was involved in TAM induction of maspin expression. TAM bound ERalpha may directly control maspin gene expression through the interaction with cofactor (s). Analysis using several ERalpha mutants showed that the N-terminal A/B motif (AF-1) was critical for maspin basal level transcription activation. An ERalpha mutant with point mutations at DNA binding domain abolished estrogen induction of an ERE-luciferase reporter but was still active in activating maspin promoter by TAM. LBD-AF2 domain was required for ERalpha-dependent TAM induction. Deletion of LBD-AF2 or a point mutation in the ERalpha LBD-AF2 region (LBDmtL539A) completely abolished the activation of maspin promoter, suggesting that TAM induction of maspin involves the recruitment of cofactor(s) by ERalpha to the maspin promoter region. This finding indicates that one of the pathways for cancer

  20. Pur-Alpha Induces JCV Gene Expression and Viral Replication by Suppressing SRSF1 in Glial Cells.

    Directory of Open Access Journals (Sweden)

    Ilker Kudret Sariyer

    Full Text Available PML is a rare and fatal demyelinating disease of the CNS caused by the human polyomavirus, JC virus (JCV, which occurs in AIDS patients and those on immunosuppressive monoclonal antibody therapies (mAbs. We sought to identify mechanisms that could stimulate reactivation of JCV in a cell culture model system and targeted pathways which could affect early gene transcription and JCV T-antigen production, which are key steps of the viral life cycle for blocking reactivation of JCV. Two important regulatory partners we have previously identified for T-antigen include Pur-alpha and SRSF1 (SF2/ASF. SRSF1, an alternative splicing factor, is a potential regulator of JCV whose overexpression in glial cells strongly suppresses viral gene expression and replication. Pur-alpha has been most extensively characterized as a sequence-specific DNA- and RNA-binding protein which directs both viral gene transcription and mRNA translation, and is a potent inducer of the JCV early promoter through binding to T-antigen.Pur-alpha and SRSF1 both act directly as transcriptional regulators of the JCV promoter and here we have observed that Pur-alpha is capable of ameliorating SRSF1-mediated suppression of JCV gene expression and viral replication. Interestingly, Pur-alpha exerted its effect by suppressing SRSF1 at both the protein and mRNA levels in glial cells suggesting this effect can occur independent of T-antigen. Pur-alpha and SRSF1 were both localized to oligodendrocyte inclusion bodies by immunohistochemistry in brain sections from patients with HIV-1 associated PML. Interestingly, inclusion bodies were typically positive for either Pur-alpha or SRSF1, though some cells appeared to be positive for both proteins.Taken together, these results indicate the presence of an antagonistic interaction between these two proteins in regulating of JCV gene expression and viral replication and suggests that they play an important role during viral reactivation leading to

  1. Alpha-particle irradiation induced defects in SiO2 films of Si-SiO2 structures

    International Nuclear Information System (INIS)

    Koman, B.P.; Gal'chynskyy, O.V.; Kovalyuk, R.O.; Shkol'nyy, A.K.

    1996-01-01

    The aim of the work was to investigate alpha-particle irradiation induced defects in Si-SiO 2 structures by means of the thermostimulated discharge currents (TSDC) analysis. The object of investigation were (p-Si)-SiO 2 structures formed by a combined oxidation of the industrial p-Si wafers in dry and wet oxygen at temperature of 1150 C. The TSD currents were investigated in the temperature range between 90 and 500 K under linear heating rate. Pu 238 isotopes were the source of alpha-particles with an energy of 4-5 MeV and a density of 5.10 7 s -1 cm -2 . The TSD current curves show two peculiar maxima at about 370 and 480 K. Alpha-particle irradiation doesn't affect the general shape of the TSDC curves but leads to a shift of the maximum at 370 K and reduces the total electret charge which is accumulated in the Si-SiO 2 structures during polarization. The energy distribution function of the defects which are involved in SiO 2 polarization has been calculated. It showes that defects with activation energies of about 0.8 and 1.0 eV take part in forming the electret state, and these activation energies have certain energy distributions. It has been found that the TSDC maximum at 370 K has space charge nature and is caused by migration of hydrogen ions. In irradiated samples hydrogen and natrium ions localize on deeper trapping centres induced by alpha-particle irradiation. (orig.)

  2. RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest.

    Science.gov (United States)

    Yu, W; Sanders, B G; Kline, K

    1997-01-01

    RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.

  3. Effects of alpha decays on nuclear waste glasses, simulation through atomistic models

    International Nuclear Information System (INIS)

    Ghaleb, D.; Delaye, J.M.

    1997-01-01

    In a simplified (SiO 2 , B 2 O 3 , Na 2 O 3 , Al 2 O 3 , ZrO 2 ) nuclear glass we have simulated, by Molecular Dynamics simulations, the effects of displacement cascades created by the slowing-down of the recoil nucleus. The methodology employed to construct and validate the used Molecular Dynamics model representing the basis matrix of the 'light-water' French nuclear glass (R77) and the manner which are simulated atomic displacements are described. Although the energies given to recoil nucleus were relatively low (≤ 1/10 of actual energies) the study has yielded a number of interesting results. Notably we have: - identified the main mechanisms responsible for the depolymerization of the network; - observed, at the atomic level, the kinetic of the structure evolution; - detailed the behavior and displacement mechanisms of every atomic species during the cascade sequences; - made a link with the experimentation through the calculation of some physical properties. (authors)

  4. Large field-induced gap of Kitaev-Heisenberg paramagnons in $\\alpha$-RuCl$_{3}$

    OpenAIRE

    Hentrich, Richard; Wolter, Anja U. B.; Zotos, Xenophon; Brenig, Wolfram; Nowak, Domenic; Isaeva, Anna; Doert, Thomas; Banerjee, Arnab; Lampen-Kelley, Paula; Mandrus, David G.; Nagler, Stephen E.; Sears, Jennifer; Kim, Young-June; Büchner, Bernd; Hess, Christian

    2017-01-01

    The honeycomb Kitaev-Heisenberg model is a source of a quantum spin liquid with Majorana fermions and gauge flux excitations as fractional quasiparticles. In the quest of finding a pertinent material, $\\alpha$-RuCl$_{3}$ recently emerged as a prime candidate. Here we unveil highly unusual low-temperature heat conductivity $\\kappa$ of $\\alpha$-RuCl$_{3}$: beyond a magnetic field of $B_c\\approx$ 7.5 T, $\\kappa$ increases by about one order of magnitude, resulting in a large magnetic field depen...

  5. Trim24 (Tif1 alpha): an essential 'brake' for retinoic acid-induced transcription to prevent liver cancer.

    Science.gov (United States)

    Khetchoumian, Konstantin; Teletin, Marius; Tisserand, Johan; Herquel, Benjamin; Ouararhni, Khalid; Losson, Régine

    2008-12-01

    Retinoic acid (RA), the active derivative of vitamin A, is an important signaling molecule that controls various developmental processes and influence the proliferation and differentiation of a variety of cell types. RA exerts its biological functions primarily through binding to and activating nuclear RA receptors (RARs, which include the RAR alpha, beta and gamma isotypes RARA, RARB and RARC). Aberrant expression or impaired function of these nuclear receptors has been linked to diverse types of cancer. RARs are RA-dependent transcription factors that regulate gene expression through the recruitment of different co-regulators (co-activators and co-repressors). TRIM24 (formerly known as TIF1 alpha) was among the first co-regulators identified as interacting with RARs in a ligand-dependent fashion, and it was recently shown to function in mice as a potent liver-specific tumor suppressor by attenuating Rara-mediated transcription. The fact that Trim24(-/-), but not Trim24(-/-)Rara(+/-), mutant mice are highly predisposed to the development of hepatocellular carcinoma (HCC) has significant implications in cancer research. This result, along with the observation that in response to pharmacological inhibition of the RA signaling, hepatocytes lacking Trim24 loose their ability to proliferate, strongly implicates Rara as a proto-oncogene in hepatocytes and demonstrates that overactivated RA signaling is deleterious to liver homeostasis.

  6. High-Frequency Gravitational Wave Induced Nuclear Fusion

    International Nuclear Information System (INIS)

    Fontana, Giorgio; Baker, Robert M. L. Jr.

    2007-01-01

    Nuclear fusion is a process in which nuclei, having a total initial mass, combine to produce a single nucleus, having a final mass less than the total initial mass. Below a given atomic number the process is exothermic; that is, since the final mass is less than the combined initial mass and the mass deficit is converted into energy by the nuclear fusion. On Earth nuclear fusion does not happen spontaneously because electrostatic barriers prevent the phenomenon. To induce controlled, industrial scale, nuclear fusion, only a few methods have been discovered that look promising, but net positive energy production is not yet possible because of low overall efficiency of the systems. In this paper we propose that an intense burst of High Frequency Gravitational Waves (HFGWs) could be focused or beamed to a target mass composed of appropriate fuel or target material to efficiently rearrange the atomic or nuclear structure of the target material with consequent nuclear fusion. Provided that efficient generation of HFGW can be technically achieved, the proposed fusion reactor could become a viable solution for the energy needs of mankind and alternatively a process for beaming energy to produce a source of fusion energy remotely - even inside solid materials

  7. Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl succinate in mesothelioma cells

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Dong, L.F.; Wang, X.F.; Zingg, J.M.

    2006-01-01

    Roč. 343, č. 4 (2006), s. 1113-1117 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514 Keywords : apoptosis * tocopherol-associated protein * alpha-tocopheryl succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.855, year: 2006

  8. rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

    Science.gov (United States)

    Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

    2013-01-01

    Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

  9. Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

    Science.gov (United States)

    Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

    1997-01-01

    We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

  10. Study of the antioxidant effect of {alpha}-tocopherol on low-density lipoprotein peroxidation induced at low and high {gamma}-radiation dose rates

    Energy Technology Data Exchange (ETDEWEB)

    Khalil, Abdelouahed [Research Centre on Aging and Department of Medicine, University of Sherbrooke, Sherbrooke, QC, J1H 4C4 (Canada)]. E-mail: abdelouahed.khalil@usherbrooke.ca; Milochevitch, Christelle [Research Centre on Aging and Department of Medicine, University of Sherbrooke, Sherbrooke, QC, J1H 4C4 (Canada)

    2005-02-01

    It is well known that vitamin E ({alpha}-tocopherol, {alpha}-toc) is a very efficient lipid soluble antioxidant and several studies showed its beneficial action in the prevention and reduction of atherosclerosis. However, some in vitro studies suggest a prooxidant role of vitamin E, which could occur under given circumstances. This study was thus designed to investigate the antioxidant vs. prooxidant effect of vitamin E with regards to LDL peroxidation induced under different oxidative stress conditions. LDL was enriched with {alpha}-tocopherol and different {alpha}-toc/LDL ratios were studied (8.0{+-}2.5, 14.3{+-}3.0, 33.3{+-}3.7, 42.7{+-}3.5 and 48.2{+-}4.5 molecules of {alpha}-toc/LDL particle). Enriched and control LDL were oxidized by action of {sup {center_dot}}OH and O{sub 2}{sup {center_dot}}{sup -} free radicals produced by {gamma}-radiolysis at different dose rates. Susceptibility of LDL to oxidation was examined by the measure of conjugated diene and TBARS formation as well as LDL endogenous {alpha}-toc disappearance. Increasing LDL {alpha}-toc concentration reduced the LDL susceptibility to oxidation and their oxidizability. {alpha}-toc disappearance rates were comprised between 43 and 8.3x10{sup -10} M s{sup -1} and decreased with the radiation dose rate. Our results support an antioxidant role for {alpha}-tocopherol at high and low oxidative stress conditions.

  11. Differential modulation of a radiation-induced bystander effect in glioblastoma cells by pifithrin-alpha and wortmannin

    Energy Technology Data Exchange (ETDEWEB)

    Shao Chunlin, E-mail: clshao@shmu.edu.c [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Zhang Jianghong [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Prise, Kevin M. [Centre for Cancer Research and Cell Biology, Queen' s University Belfast, Lisburn Road, Belfast BT9 7AB (United Kingdom)

    2010-03-15

    The implication of radiation-induced bystander effect (RIBE) for both radiation protection and radiotherapy has attracted significant attention, but a key question is how to modulate the RIBE. The present study found that, when a fraction of glioblastoma cells in T98G population were individually targeted with precise helium particles through their nucleus, micronucleus (MN) were induced and its yield increased non-linearly with radiation dose. After co-culturing with irradiated cells, additional MN could be induced in the non-irradiated bystander cells and its yield was independent of irradiation dose, giving direct evidence of a RIBE. Further results showed that the RIBE could be eliminated by pifithrin-alpha (p53 inhibitor) but enhanced by wortmannin (PI3K inhibitor). Moreover, it was found that nitric oxide (NO) contributed to this RIBE, and the levels of NO of both irradiated cells and bystander cells could be extensively diminished by pifithrin-alpha but insignificantly reduced by wortmannin. Our results indicate that RIBE can be modulated by p53 and PI3K through a NO-dependent and NO-independent pathway, respectively.

  12. Angular distribution measurements of {sup 6}Li(p,{alpha}){sup 3}He reaction at 140 keV proton energy using nuclear track detectors

    Energy Technology Data Exchange (ETDEWEB)

    Al-Jarallah, M.I. E-mail: mibrahim@kfupm.edu.sa; Naqvi, A.A.; Abu-Jarad, F.A.; Fazal-ur-Rehman; Durrani, S.M.A.; Kidwai, S

    2001-06-01

    Angular distributions of a {sup 6}Li(p,{alpha}) {sup 3}He reaction were measured at six angles for 140 keV proton energy using nuclear track detectors (NTDs). The measurements were carried out over 60 deg. -160 deg. lab. angles in 20 deg. increments using a scattering chamber of 80 deg. beam line of the 350 kV accelerator. A semiconductor silicon surface barrier (SSB) detector was placed at +160 deg. and was used as a monitor. The results have shown that the CR-39 detector has excellent capabilities to distinguish 1.4-2.7 MeV {alpha}+ {sup 3}He particles from the {sup 6}Li(p,{alpha}) {sup 3}He reaction and 8-9.4 MeV {alpha}-particles from the {sup 7}Li(p,{alpha}) {sup 4}He reaction through their track diameters. However, it was not possible to distinguish between the 2.3 MeV {sup 3}He ions and the 1.7 MeV {sup 4}He ions from the {sup 6}Li(p,{alpha}) {sup 3}He reaction from their track diameter measurements, but it was possible to differentiate between the two, from the darker contrast of the {sup 3}He particles caused by its deeper tracks as compared to those of {sup 4}He.

  13. Molecular evidence for the existence of lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel/NF-kB pathways in disk abalone (Haliotis discus discus).

    Science.gov (United States)

    De Zoysa, Mahanama; Nikapitiya, Chamilani; Oh, Chulhong; Whang, Ilson; Lee, Jae-Seong; Jung, Sung-Ju; Choi, Cheol Young; Lee, Jehee

    2010-01-01

    The lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel family nuclear factor kappaB (Rel/NF-kB) are two important transcription factors which play major roles in the regulating inflammatory cytokine, apoptosis and immune related genes. Here, we report the discovery of disk abalone LITAF (AbLITAF) and Rel/NF-kB (AbRel/NF-kB) homologues and their immune responses. Full-length cDNA of AbLITAF consists of 441 bp open reading frame (ORF) that translates into putative peptide of 147 aa. Analysis of AbLITAF sequence showed it has characteristic LITAF (Zn(+2)) binding domain with two CXXC motifs. Phylogenetic analysis results further revealed that AbLITAF is a member of LITAF family. AbRel/NF-kB is 584 aa protein that contains several characteristic motifs including Rel homology domain (RHD), Rel protein signature, DNA binding motif, nuclear localization signal (NLS) and transcription factor immunoglobulin - like fold (TIG) similar to their invertebrate and vertebrate counterparts. Tissue specific analysis results showed that both AbLITAF and AbRel/NF-kB mRNA was expressed ubiquitously in all selected tissues in constitutive manner. However, constitutive expression of AbLITAF was higher than AbRel/NF-kB in all tissues except mantle. Upon immune challenge by bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Lysteria monocytogenes) and viral hemoragic septicemia virus (VHSV), AbLITAF showed the significant up-regulation in gills while AbRel/NF-kB transcription was not change significantly. Based on transcriptional response against immune challenge, we could suggest that regulation of TNF-alpha expression may have occurred mainly by LITAF activation rather than NF-kB in disk abalone. The cumulative data from other molluscs and our data with reference to TNF-alpha, LITAF and Rel/NF-kB from disk abalone provide strong evidence that LITAF and NF-kB are independent pathways likely to occur throughout the Phylum mollusca. 2010 Elsevier Ltd. All rights reserved.

  14. 17-AAG, a Hsp90 inhibitor, attenuates the hypoxia-induced expression of SDF-1alpha and ILK in mouse RPE cells.

    Science.gov (United States)

    Wang, Ye Qing; Zhang, Xiao Mei; Wang, Xiao Dan; Wang, Bin Jie; Wang, Wei

    2010-03-01

    The aim of this study was to investigate the changes of SDF-1alpha and ILK expression in mouse retinal pigment epithelium (RPE) cells in response to hypoxia, and the effect of 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a heat shock protein 90 (Hsp90) inhibitor, on the hypoxia-induced expression of SDF-1alpha and ILK. RPE cells were cultured with 200 micromol/L cobalt chloride (CoCl(2)) for different times (1, 3, 6, 12, 24, 72 h) to imitate chemical hypoxia. Pretreatment of 17-AAG was 1 h prior to hypoxic insult. Cellular viability after 17-AAG treatment was assessed by MTT assay, and the changes of SDF-1alpha and ILK expression were examined by RT-PCR and Western blot. Up-regulation of SDF-1alpha and ILK expression in response to hypoxia was observed. One hour pretreatment of 17-AAG could remarkably decreased the hypoxia-induced SDF-1alpha and ILK expression in vitro. Our results indicated that SDF-1alpha and ILK involved in the hypoxic response of RPE cells, and 1 h pretreatment of 17-AAG had an inhibitive effect on the hypoxia-induced SDF-1alpha and ILK expression.

  15. Prediction for the high-level alpha-active waste to be generated by nuclear power stations in the Member States of the European Communities

    International Nuclear Information System (INIS)

    Schmidt, E.

    1977-04-01

    Starting with a forecast for the nuclear power generating capacity to be installed in the Member States of the European Communities before the end of this century, a prediction is made of the annual production of high-level alpha-active waste from reprocessing plants and the corresponding accumulation up to the year 2000. The isotopic composition of the alpha-active waste from individual reactor types was calculated and an estimation of the influence of recycling plutonium through light water reactors on the produced quantity of higher actinides is made

  16. Results of solid state nuclear track detector technique application in radon detection, by alpha particles tracks, for uranium prospecting in Caetite (BA-Brazil)

    International Nuclear Information System (INIS)

    Moraes, M.A.P.V. de; Khouri, M.T.F.C.

    1988-11-01

    The solid state nuclear track detector technique has been used in radon detection, by alpha particles tracks for uranium prospecting on the ground in Caetite city (Bahia-Brazil). The sensitive film to alpha particles used were CA 8015 exposed during 15 days and the results of three anomalies of this region are showed in a form of maps, made with the density of tracks obtained, and were compared with scintillation counter measurements. The technique showed to be simple and an effective auxiliary for the prospection of uranium ore bodies. The initial uranium exploration costs can be reduced by using this technique. (author) [pt

  17. Nuclear densities of 1fsub(7/2) nuclei from elastic alpha-particle scattering

    International Nuclear Information System (INIS)

    Friedman, E.; Gils, H.J.; Rebel, H.

    1983-12-01

    The elastic scattering of 104 MeV α particles by sup(40,42,43,44,48)Ca, 50 Ti, 51 V, 52 Cr has been analyzed by phenomenological and semimicroscopic optical potentials in order to get information on isotopic and isotonic differences of the α particle optical potentials and of nuclear matter densities. The phenomenological optical potentials based on a Fourier-Bessel description of the real part reveal different behaviour in size and shape for the isotonic chain as compared to the isotopic chain. Odd-even effects are also indicated to be different for isotones and isotopes. The semi-microscopic analyses use a single-folding model with a density-dependent effective αN-interaction including a realistic local density approximation. The calculated potentials are fully consistent with the phenomenological ones. Isopotic and isotonic differences of the nuclear matter densities obtained from the folding model in general show a similar behavior as the optical potential differences. The results on matter densities are compared to other investigations. (orig.) [de

  18. The limits of the nuclear chart set by fission and alpha decay

    Directory of Open Access Journals (Sweden)

    Möller Peter

    2016-01-01

    Full Text Available I will review how our picture of heavy-element nuclear structure has evolved through remarkably simple ideas and related models. It is well known that the Bethe-Weizsäcker semi-empirical mass model had an important role in unraveling radioactive decay and element transmutation in the heavy-element region in the 1930s. A remarkable aspect is that this model could immediately after the discovery of fission be generalized to explain this phenomenon through the consideration of deformation of a charged liquid drop. Bethe and Bacher already raised the possibility that shell structure (by them calculated in terms of a single-particle oscillator potential could give rise to noticeable deviations between results of the macroscopic mass model and experiment but limited data prevented firm conclusions. In the 1950s the single-particle models took a realistic form and also included deformation. The possibility of the existence of a relatively stable “island” of superheavy elements was raised already then. But it was not until the work by Strutinsky in the mid 1960s that a quantitative model for the nuclear potential-energy emerged in the form of the macroscopic-microscopic model. Although new elements have been discovered at an almost steady pace since 1940, theory indicates that we are close to the end of this era: repulsive Coulomb effects will set the limit of observable elements to near Z = 120.

  19. Designing experimental setup and procedures for studying alpha-particle-induced adaptive response in zebrafish embryos in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Choi, V.W.Y.; Lam, R.K.K.; Chong, E.Y.W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Cheng, S.H. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.h [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2010-03-15

    The present work was devoted to designing the experimental setup and the associated procedures for alpha-particle-induced adaptive response in zebrafish embryos in vivo. Thin PADC films with a thickness of 16 mum were fabricated and employed as support substrates for holding dechorionated zebrafish embryos for alpha-particle irradiation from the bottom through the films. Embryos were collected within 15 min when the light photoperiod began, which were then incubated and dechorionated at 4 h post fertilization (hpf). They were then irradiated at 5 hpf by alpha particles using a planar {sup 241}Am source with an activity of 0.1151 muCi for 24 s (priming dose), and subsequently at 10 hpf using the same source for 240 s (challenging dose). The levels of apoptosis in irradiated zebrafish embryos at 24 hpf were quantified through staining with the vital dye acridine orange, followed by counting the stained cells under a florescent microscope. The results revealed the presence of the adaptive response in zebrafish embryos in vivo, and demonstrated the feasibility of the adopted experimental setup and procedures.

  20. Polarized nuclear target based on parahydrogen induced polarization

    OpenAIRE

    Budker, D.; Ledbetter, M. P.; Appelt, S.; Bouchard, L. S.; Wojtsekhowski, B.

    2012-01-01

    We discuss a novel concept of a polarized nuclear target for accelerator fixed-target scattering experiments, which is based on parahydrogen induced polarization (PHIP). One may be able to reach a 33% free-proton polarization in the ethane molecule. The potential advantages of such a target include operation at zero magnetic field, fast ($\\sim$100 Hz) polarization reversal, and operation with large intensity of an electron beam.

  1. Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.

    Directory of Open Access Journals (Sweden)

    Mathieu Darsigny

    Full Text Available BACKGROUND: Hnf4alpha, an epithelial specific transcriptional regulator, is decreased in inflammatory bowel disease and protects against chemically-induced colitis in mice. However, the precise role of this factor in maintaining normal inflammatory homeostasis of the intestine remains unclear. The aim of this study was to evaluate the sole role of epithelial Hnf4alpha in the maintenance of gut inflammatory homeostasis in mice. METHODOLOGY/PRINCIPAL FINDINGS: We show here that specific epithelial deletion of Hnf4alpha in mice causes spontaneous chronic intestinal inflammation leading to focal areas of crypt dropout, increased cytokines and chemokines secretion, immune cell infiltrates and crypt hyperplasia. A gene profiling analysis in diseased Hnf4alpha null colon confirms profound genetic changes in cell death and proliferative behaviour related to cancer. Among the genes involved in the immune protection through epithelial barrier function, we identify the ion transporter claudin-15 to be down-modulated early in the colon of Hnf4alpha mutants. This coincides with a significant decrease of mucosal ion transport but not of barrier permeability in young animals prior to the manifestation of the disease. We confirm that claudin-15 is a direct Hnf4alpha gene target in the intestinal epithelial context and is down-modulated in mouse experimental colitis and inflammatory bowel disease. CONCLUSION: Our results highlight the critical role of Hnf4alpha to maintain intestinal inflammatory homeostasis during mouse adult life and uncover a novel function for Hnf4alpha in the regulation of claudin-15 expression. This establishes Hnf4alpha as a mediator of ion epithelial transport, an important process for the maintenance of gut inflammatory homeostasis.

  2. Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

    Science.gov (United States)

    Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

    1989-06-01

    Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

  3. Investigations of nuclear structure and nuclear reactions induced by complex projectiles

    International Nuclear Information System (INIS)

    Sarantites, D.G.

    1993-01-01

    This is a progress report on activities of the Washington University group in nuclear reaction studies for the period Sept 1, 1992 to Aug 31, 1993. This group has a research program which touches five areas of nuclear physics: nuclear structure studies at high spin; studies at the interface between structure and reactions; production and study of hot nuclei; reaction mechanism studies; development and use of novel techniques and instrumentation in the above areas of research. Specific activities of the group include in part: superdeformation in 82 Sr; structure of and identical bands in 182 Hg and 178 Pt; a highly deformed band in 136 Pm; particle decay of the 164 Yb compound nucleus; fusion reactions; proton evaporation; two-proton decay of 12 O; modeling and theoretical studies; excited 16 O disassembly into four alpha particles; 209 Bi + 136 Xe collisions at 28.2 MeV/amu; and development work on 4π solid angle gamma detectors, and x-ray detectors

  4. Human LT-alpha-mediated resistance to autoimmune diabetes is induced in NOD, but not NOD-scid, mice and abrogated by IL-12.

    Science.gov (United States)

    Miyaguchi, S; Satoh, J; Takahashi, K; Sakata, Y; Nakazawa, T; Miyazaki, J; Toyota, T

    2001-01-01

    Systemic administration of human lymphotoxin-alpha (hLT-alpha) made NOD mice resistant not only to spontaneous autoimmune type 1 diabetes mellitus but also to cyclophosphamide (CY)-induced diabetes and diabetes transfer by diabetic NOD spleen cells (triple resistance). In this study we analyzed the mechanisms of hLT-alpha-induced resistance, focusing on (1) hLT-alpha-induced resistance in the pancreatic beta cell, (2) CY-resistant suppressor cells, (3) suppression of induction or function of effector cells for beta cell destruction, or (4) others. To examine the first possibility in vitro, a NOD-derived beta cell line (MIN6N) was pretreated with hLT-alpha and then mixed with diabetic NOD spleen cells and MIN6N cell viability was measured. Treatment with hLT-alpha did not protect MIN6N cells but rather enhanced cytotoxicity. Next NOD-scid mice were pretreated with hLT-alpha and then transferred with diabetic NOD spleen. All the recipients developed diabetes. These results excluded the first possibility. The second possibility was also excluded by a cotransfer experiment, in which diabetic NOD spleen cells were cotransferred to NOD-scid mice with nontreated or hLT-alpha-treated nondiabetic NOD spleens. There was no significant difference in diabetes incidence between the two groups. To observe the third possibility, spleen cells of hLT-alpha-treated triple-resistant NOD mice were transferred to NOD-scid mice. Diabetes developed in the recipients, although the onset of diabetes was slightly delayed. Finally, hLT-alpha-treated triple-resistant NOD mice developed diabetes 1 week after daily IL-12 treatment. In summary, hLT-alpha administration made NOD mice resistant to effector cells for beta cell destruction. This resistance was induced in NOD, but not in NOD-scid, mice, indicating that lymphocytes were obligatory for the resistance. However, it was not mediated by transferable suppressor cells. Because effector cells were present in hLT-alpha-treated NOD spleen and

  5. The far and distal enhancers in the CYP3A4 gene co-ordinate the proximal promoter in responding similarly to the pregnane X receptor but differentially to hepatocyte nuclear factor-4alpha.

    Science.gov (United States)

    Liu, Fu-Jun; Song, Xiulong; Yang, Dongfang; Deng, Ruitang; Yan, Bingfang

    2008-01-01

    CYP3A4 (cytochrome P450 3A4) is involved in the metabolism of more than 50% of drugs and other xenobiotics. The expression of CYP3A4 is induced by many structurally dissimilar compounds. The PXR (pregnane X receptor) is recognized as a key regulator for the induction, and the PXR-directed transactivation of the CYP3A4 gene is achieved through a co-ordinated mechanism of the distal module with the proximal promoter. Recently, a far module was found to support constitutive expression of CYP3A4. The far module, like the distal module, is structurally clustered by a PXR response element (F-ER6) and elements recognized by HNF-4alpha (hepatocyte nuclear receptor-4alpha). We hypothesized that the far module supports PXR transactivation of the CYP3A4 gene. Consistent with the hypothesis, fusion of the far module to the proximal promoter of CYP3A4 markedly increased rifampicin-induced reporter activity. The increase was synergistically enhanced when both the far and distal modules were fused to the proximal promoter. The increase, however, was significantly reduced when the F-ER6 was disrupted. Chromatin immunoprecipitation detected the presence of PXR in the far module. Interestingly, HNF-4alpha increased the activity of the distal-proximal fused promoter, but decreased the activity of the far-proximal fused promoter. Given the fact that induction of CYP3A4 represents an important detoxification mechanism, the functional redundancy and synergistic interaction in supporting PXR transactivation suggest that the far and distal modules ensure the induction of CYP3A4 during chemical insults. The difference in responding to HNF-4alpha suggests that the magnitude of the induction is under control through various transcriptional networks.

  6. Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-kappaB activation.

    Science.gov (United States)

    Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

    2010-05-01

    Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear factor (NF)-kappaB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-alpha level and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS.

  7. Particularisation of Alpha Contamination using CR-39 Track Detectors

    International Nuclear Information System (INIS)

    Zakia, M.F.; El-Shaer, Y.H.

    2008-01-01

    Solid-state nuclear track detectors have found wide use in various domains of science and technology, e.g. in environmental experiments. The measurement of alpha activity on sources in an environment, such as air is not easy because of short penetration range of the alpha particles. Furthermore, the measurement of alpha activity by most gas ionization detectors suffers from the high background induced by the accompanying gamma radiation. Solid State Nuclear Track Detectors (SSNTDs) have been used successfully as detecting devices as passive system to detect the alpha contamination different surfaces. This work presents the response of CR-39 (for two types) to alpha particles from two sources, 238 Pu with energy 5 MeV and 241 Am with energy 5.4 MeV. The methods of etching and counting are investigated, along with the achievable linearity, efficiency and reproducibility. The sensitivity to low activity and energy resolution are studied

  8. Determination of Neptunium, Americium and Curium in Spent Nuclear Fuel Samples by Alpha Spectrometry Using 239Np and 243Am as a Spike and a Tracer

    International Nuclear Information System (INIS)

    Jeo, Kih-Soo; Song, Byung-Chul; Kim, Young-Bok; Han, Sun-Ho; Jeon, Young-Shin; Jung, Euo-Chang; Jee, Kwang-Yong

    2007-01-01

    Determination of actinide elements and fission products in spent nuclear fuels is of importance for a burnup determination and source term evaluation. Especially, the amounts of uranium and plutonium isotopes are used for the evaluation of a burnup credit in spent nuclear fuels. Additionally, other actinides such as Np, Am and Cm in spent nuclear fuel samples is also required for the purposes mentioned above. In this study, 237 Np, 241 Am and 244 Cm were determined by an alpha spectrometry for the source term data for high burnup spent nuclear fuels ranging from 37 to 62.9 GWD/MtU as a burnup. Generally, mass spectrometry has been known as the most powerful method for isotope determinations such as high concentrations of uranium and plutonium. However, in the case of minor actinides such as Np, Am and Cm, alpha spectrometry would be recommended instead. Determination of the transuranic elements in spent nuclear fuel samples is different from that for environmental samples because the amount of each nuclide in the spent fuel samples is higher and the relative ratios between each nuclide are also different from those for environmental samples. So, it is important to select an appropriate tracer and an optimum sample size depending on the nuclides and analytical method. In this study 237 Np was determined by an isotope dilution alpha(gamma) spectrometry using 239 Np as a spike, and 241 Am and curium isotopes were determined by alpha spectrometry using 243 Am as a tracer. The content of each nuclide was compared with that by the Origen-2 code

  9. Nuclear magnetic resonance in pulse radiolysis. Chemically induced dynamic nuclear polarization

    International Nuclear Information System (INIS)

    Trifunac, A.D.; Johnson, K.W.; Lowers, R.H.

    1976-01-01

    Nuclear magnetic resonance and chemically induced dynamic nuclear polarization (CIDNP) were applied to the study of pulse radiolysis. Samples were irradiated with a 3-MeV electron beam from the Argonne Van de Graaff accelerator in an EPR magnet (approximately 4000 G) which had axial holes for beam access. A fast flow system transferred the irradiated solution to the rotating 5-mm NMR sample tube. The NMR spectra of mixtures of sodium acetate and methanol were presented to demonstrate the features of the CIDNP in pulse radiolysis

  10. Alpha band oscillations correlate with illusory self-location induced by virtual reality.

    Science.gov (United States)

    Lenggenhager, Bigna; Halje, Pär; Blanke, Olaf

    2011-05-01

    Neuroscience of the self has focused on high-level mechanisms related to language, memory or imagery of the self. However, recent evidence suggests that low-level mechanisms such as multisensory and sensorimotor integration may play a fundamental role in self-related processing. Here we used virtual reality technology and visuo-tactile conflict to study such low-level mechanisms and manipulate where participants experienced their self to be localized (self-location). Frequency analysis and electrical neuroimaging of co-recorded high-resolution electroencephalography revealed body-specific alpha band power modulations in bilateral sensorimotor cortices. Furthermore, alpha power in the medial prefrontal cortex (mPFC) was correlated with the degree of experimentally manipulated self-location. We argue that these alpha oscillations in sensorimotor cortex and mPFC reflect self-location as manipulated through multisensory conflict. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  11. Interaction of a gibberellin-induced factor with the upstream region of an alpha-amylase gene in rice aleurone tissue.

    OpenAIRE

    Ou-Lee, T M; Turgeon, R; Wu, R

    1988-01-01

    The interaction between the DNA sequences of an alpha-amylase (EC 3.2.1.1) gene and a tissue-specific factor induced in rice (Oryza sativa L.) aleurone tissue by gibberellin was studied. DNA mobility-shift during electrophoresis indicated that a 500-base-pair sequence (HS500) of a rice alpha-amylase genomic clone (OSamy-a) specifically interacted with a factor from gibberellin-induced rice aleurone tissue. The amount of complex formed between the HS500 DNA fragment and the gibberellin-induced...

  12. The use of alpha-methyl-D-glucoside, a synthetic analogue of maltose, as inducer of amylase by Aspergillus sp in solid-state and submerged fermentations

    Directory of Open Access Journals (Sweden)

    Fabiana G. Moreira

    2001-03-01

    Full Text Available The use of a methyl-D-glucoside (alphaMG, a synthetic analogue of maltose, as carbon source and inducer of amylase synthesis to several species of Aspergillus was studied in submerged and solid-state fermentations. Among a group of ten species, A. tamarii, A. fumigatus and A. flavus were able to produce biomass and high specific amylolytic activity in submerged cultures containing alphaMG as the only carbon source. In solid state fermentation, the enrichment of basal wheat bran or corn cob medium with alphaMG increased up to 3 times the production of amylases. In both submerged and solid state fermentations, alphaMG was more effective inducer of amylases than maltose and starch.

  13. Some characteristics of the CR-39 solid state nuclear - Track Detector for register of protons and low energy alpha particles

    International Nuclear Information System (INIS)

    Fonseca, E.S. da.

    1983-01-01

    Experimental results related to registration properties of the CR-39 Solid State Nuclear Track Detector for charged particles are presented and discussed. The existence of an inverse proportion between the induction time and the temperature as well as normal concentration of solutions, is showed by the study of CR-39 chemical etching characteristics in NaOH and KOH solutions, comprising varied concentration and temperature. The bulk-etch rate and activation energy of the process were obtained. The critical energy and critical energy-loss rate of CR-39 track-detectors for registration of protons were experimentally determined. Samples were exposed to 24 Mev proton beams in the IEN/CNEN Cyclotron (CV-28), using scattering chamber with a tantalum thin target and aluminium absorbers in contact with the samples, in order to provide the required fluctuation in the scattered beam energy. From the mean track-diameter plotted against incident proton energy the critical energy was obtained. From the calculated energy-loss rate vs. energy curve, the critical energy loss rate were evaluated. The CR-39 response for low energy alpha particles (E = 7h) under the conditions of 6.25 N NaOH at 70 0 C. It is shown that successive chemical etchings do not produce the same track geometry as obtained by means of a continous revelation with the same total etching time. (Author) [pt

  14. A Polymorphism in Hepatocyte Nuclear Factor 1 Alpha, rs7310409, Is Associated with Left Main Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Rui Liu

    2014-01-01

    Full Text Available Coronary artery disease is the leading cause of mortality and morbidity in the world. Left main coronary artery disease (LMCAD is a particularly severe phenotypic form of CAD and has a genetic basis. We hypothesized that some inflammation- and hyperhomocysteinemia-related gene polymorphisms may contribute to LMCAD susceptibility in a Chinese population. We studied the association between polymorphisms in the genes hepatocyte nuclear factor 1 alpha (HNF1A; rs7310409, G/A, C-reactive protein (rs1800947 and rs3093059 T/C, methylenetetrahydrofolate reductase (rs1801133, C/T, and methylenetetrahydrofolate dehydrogenase (rs1076991, A/G in 402 LMCAD and 804 more peripheral CAD patients in a Chinese population. Genotyping was performed using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. When the HNF1A rs7310409 GG homozygote genotype was used as the reference group, both the individual, GA and AA, and combined GA/AA genotypes were associated with an increased risk of LMCAD. This single nucleotide polymorphism (rs7310409 is strongly associated with plasma CRP levels. In conclusion, the present study provides evidence that the HNF1A rs7310409 G/A functional polymorphism may contribute to the risk of LMCAD.

  15. The effect of alpha incident- and poloidal-angle distributions on blister-induced first-wall erosion

    International Nuclear Information System (INIS)

    Fenske, G.; Hively, L.; Miley, G.

    1979-01-01

    The incident velocity distribution of high-energy alpha particles bombarding the first wall of an axisymmetric tokamak is evaluated as a function of poloidal angle (theta). The resulting helium concentration profile as a function of the poloidal angle and the implant depth is calculated for a typical Experimental Power Reactor (EPR) design. The critical helium concentration for blistering is first exceeded at theta approx. 55 0 . Peak concentrations are reduced somewhat through continuous D-T sputtering which, dependent on theta, reduces the blister skin thicknesses. The blistering-induced impurity level is found to increase drastically (< approx. 50%), relative to sputtering-induced impurities, at periodic intervals corresponding to approx. 4000 hours operation when each generation of blister begins to exfoliate. (orig.)

  16. Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts.

    Science.gov (United States)

    Rapisarda, Annamaria; Zalek, Jessica; Hollingshead, Melinda; Braunschweig, Till; Uranchimeg, Badarch; Bonomi, Carrie A; Borgel, Suzanne D; Carter, John P; Hewitt, Stephen M; Shoemaker, Robert H; Melillo, Giovanni

    2004-10-01

    We have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-inducible factor (HIF)-1alpha protein accumulation by a DNA damage-independent mechanism. Here, we report that daily administration of topotecan inhibits HIF-1alpha protein expression in U251-HRE glioblastoma xenografts. Concomitant with HIF-1alpha inhibition, topotecan caused a significant tumor growth inhibition associated with a marked decrease of angiogenesis and expression of HIF-1 target genes in tumor tissue. These results provide a compelling rationale for testing topotecan in clinical trials to target HIF-1 in cancer patients.

  17. General applicability of chicken egg yolk antibodies: the performance of IgY immunoglobulins raised against the hypoxia-inducible factor 1alpha

    OpenAIRE

    Camenisch, G; Tini, M; Chilov, D; Kvietikova, I; Srinivas, V; Caro, J; Spielmann, P; Wenger, R H; Gassmann, M

    1999-01-01

    Avian embryos and neonates acquire passive immunity by transferring maternal immunoglobulins from serum to egg yolk. Despite being a convenient source of antibodies, egg yolk immunoglobulins (IgY) from immunized hens have so far received scant attention in research. Here we report the generation and rapid isolation of IgY from the egg yolk of hens immunized against the alpha subunit of the human hypoxia-inducible factor 1 (HIF-1alpha). Anti-HIF-1alpha IgY antibodies were affinity purified and...

  18. NEW APPROACHES TO CONFINED ALPHA DIAGNOSTICS

    Energy Technology Data Exchange (ETDEWEB)

    FISHER,R.K

    2004-04-01

    Three new approaches to obtain information on the confined fast alphas in International Thermonuclear Experimental Reactor (ITER) are proposed. The first technique measures the energetic charge exchange (CX) neutrals that result from the alpha collision-induced knock-on fuel ion tails undergoing electron capture on the MeV D neutral beams planned for heating and current drive. The second technique measures the energetic knock-on neutron tail due to alphas using the lengths of the proton recoil tracks produced by neutron collisions in nuclear emulsions. The range of the 14 to 20 MeV recoil protons increases by {approx}140 microns per MeV. The third approach would measure the CX helium neutrals resulting from confined alphas capturing two electrons in the ablation cloud surrounding a dense gas jet that has been proposed for disruption mitigation in ITER.

  19. NEW APPROACHES TO CONFINED ALPHA DIAGNOSTICS

    International Nuclear Information System (INIS)

    FISHER, R.K.

    2004-01-01

    Three new approaches to obtain information on the confined fast alphas in International Thermonuclear Experimental Reactor (ITER) are proposed. The first technique measures the energetic charge exchange (CX) neutrals that result from the alpha collision-induced knock-on fuel ion tails undergoing electron capture on the MeV D neutral beams planned for heating and current drive. The second technique measures the energetic knock-on neutron tail due to alphas using the lengths of the proton recoil tracks produced by neutron collisions in nuclear emulsions. The range of the 14 to 20 MeV recoil protons increases by ∼140 microns per MeV. The third approach would measure the CX helium neutrals resulting from confined alphas capturing two electrons in the ablation cloud surrounding a dense gas jet that has been proposed for disruption mitigation in ITER

  20. Experimentally nonylphenol-polluted diet induces the expression of silent genes VTG and ER{alpha} in the liver of male lizard Podarcis sicula

    Energy Technology Data Exchange (ETDEWEB)

    Verderame, Mariailaria; Prisco, Marina; Andreuccetti, Piero [Department of Biological Sciences, Evolutionary and Comparative Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy); Aniello, Francesco [Department of Biological Sciences, Genetic and Molecular Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy); Limatola, Ermelinda, E-mail: limatola@unina.it [Department of Biological Sciences, Evolutionary and Comparative Biology Division, University Federico II of Naples, Via Mezzocannone 8, 80134 Naples (Italy)

    2011-05-15

    Endocrine Disruptor Chemicals (EDCs) with estrogen-like properties i.e nonylphenol (NP) induce vitellogenin (VTG) synthesis in males of aquatic and semi-aquatic specie. In the oviparous species VTG is a female-specific oestrogen dependent protein. Males are unable to synthesize VTG except after E{sub 2} treatment. This study aimed to verify if NP, administered via food and water, is able to induce the expression of VTG even in males of vertebrates with a terrestrial habitat such as the lizard Podarcis. By means of ICC, ISH, W/B and ELISA we demonstrated that NP induces the presence of VTG in the plasma and its expression in the liver. VTG, undetectable in untreated males, reaches the value of 4.34 {mu}g/{mu}l in the experimental ones. Expression analysis and ISH in the liver showed that an NP-polluted diet also elicits the expression of ER{alpha} in the liver which is known to be related to VTG synthesis in Podarcis. - Highlights: > Nonylphenol (NP) polluted diet induces VTG synthesis in a terrestrial vertebrate. > VTG and ER{alpha} genes are unexpressed in the liver of untreated male lizards Podarcis. > In the liver cells of NP-treated males the expression of both VTG and ER{alpha} occurs. > In treated males VTG synthesis is coupled with ER{alpha} expression as in breeding females. - NP-polluted diet induces the expression of ER{alpha} and VTG in the liver.

  1. Parvovirus induced alterations in nuclear architecture and dynamics.

    Directory of Open Access Journals (Sweden)

    Teemu O Ihalainen

    2009-06-01

    Full Text Available The nucleus of interphase eukaryotic cell is a highly compartmentalized structure containing the three-dimensional network of chromatin and numerous proteinaceous subcompartments. DNA viruses induce profound changes in the intranuclear structures of their host cells. We are applying a combination of confocal imaging including photobleaching microscopy and computational methods to analyze the modifications of nuclear architecture and dynamics in parvovirus infected cells. Upon canine parvovirus infection, expansion of the viral replication compartment is accompanied by chromatin marginalization to the vicinity of the nuclear membrane. Dextran microinjection and fluorescence recovery after photobleaching (FRAP studies revealed the homogeneity of this compartment. Markedly, in spite of increase in viral DNA content of the nucleus, a significant increase in the protein mobility was observed in infected compared to non-infected cells. Moreover, analysis of the dynamics of photoactivable capsid protein demonstrated rapid intranuclear dynamics of viral capsids. Finally, quantitative FRAP and cellular modelling were used to determine the duration of viral genome replication. Altogether, our findings indicate that parvoviruses modify the nuclear structure and dynamics extensively. Intranuclear crowding of viral components leads to enlargement of the interchromosomal domain and to chromatin marginalization via depletion attraction. In conclusion, parvoviruses provide a useful model system for understanding the mechanisms of virus-induced intranuclear modifications.

  2. Laser-induced nuclear orientation and gamma anisotropy in sodium

    International Nuclear Information System (INIS)

    Pappas, P.G.

    1980-12-01

    The use of laser optical pumping to induce nuclear orientation in several isotopes and one isomer of atomic sodium vapor is described. Essentially complete nuclear polarization, P > 90%, has been achieved in stable 23 Na when pumping with modest laser intensities (I approx. = 10 mW/cm 2 ). The volume of the sample cell was approximately 10 cc, and was filled with a sodium density of about 10'' atoms/cc. Complete coverage of the Doppler distribution was accomplished with the use of trace amounts (less than or equal to 1 torr) of argon buffer gas to induce velocity changing collisions. A theoretical model which accurately predicts the amount of polarization is developed. The orientation of nuclei which are unstable to gamma decay can manifest itself in anisotropic gamma ray emission. This anisotropy can be used to measure isotope and isomer shifts, from which nuclear properties can be derived. Gamma anisotropy was observed in two systems, 22 Na and /sup 24m/Na. From the observed anisotropy in /sup 24m/Na, a negative sign for the g factor is determined. Values are derived for the magnetic moment, μ = 2.56 +- 0.64 nm, and the isomer shift, deltaν/sub 24m/ = 288 +- 191 MHz (D1 line). A model is described which relates various laser and fubber gas parameters to the observed gamma anisotropy lineshape. This model facilitates the extraction of physical parameters from knowledge of the laser frequency at which the anisotropy is a maximum

  3. Inducible alpha-synuclein overexpression affects human Neural Stem Cells behavior

    OpenAIRE

    Conti, Luciano; Zasso, Jacopo; Cutarelli, Alessandro; Ahmed, Mastad

    2018-01-01

    Converging evidence suggest that levels of alpha-Synuclein (aSyn) expression play a critical role in Parkinson's disease (PD). Several mutations of the SNCA gene, encoding for aSyn have been associated to either the familial or the sporadic forms of PD. Nonetheless, the mechanism underlying wild type aSyn-mediated neurotoxicity in neuronal cells as well as its specific driving role in PD pathogenesis has yet to be fully clarified. In this view, the development of proper in vitro cellular syst...

  4. Mechanistic and kinetic insights into the thermally induced rearrangement of alpha-pinene.

    Science.gov (United States)

    Stolle, Achim; Ondruschka, Bernd; Findeisen, Matthias

    2008-11-07

    The thermal rearrangement of alpha-pinene (1) is interesting from mechanistic as well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal network of these hydrocarbons. Kinetic analysis of the major reaction steps allows for a deeper insight in the reaction mechanism. Thus it was possible to explain the racemization of 1, the formation of racemic limonene (4), and the absence of the primary pyrolysis product 2 in the reaction mixture resulting from thermal rearrangement of 1. Results supported the conclusion that the reactions starting with 1 involve biradical transition states.

  5. DNA Methylation at a Bovine Alpha Satellite I Repeat CpG Site during Development following Fertilization and Somatic Cell Nuclear Transfer

    OpenAIRE

    Couldrey, Christine; Wells, David N.

    2013-01-01

    Incomplete epigenetic reprogramming is postulated to contribute to the low developmental success following somatic cell nuclear transfer (SCNT). Here, we describe the epigenetic reprogramming of DNA methylation at an alpha satellite I CpG site (αsatI-5) during development of cattle generated either by artificial insemination (AI) or in vitro fertilization (IVF) and SCNT. Quantitative methylation analysis identified that SCNT donor cells were highly methylated at αsatI-5 and resulting SCNT bla...

  6. Nuclear level density variation with angular momentum induced shape transition

    International Nuclear Information System (INIS)

    Aggarwal, Mamta

    2016-01-01

    Variation of Nuclear level density (NLD) with the excitation energy and angular momentum in particular has been a topic of interest in the recent past and there have been continuous efforts in this direction on the theoretical and experimental fronts but a conclusive trend in the variation of nuclear level density parameter with angular momentum has not been achieved so far. A comprehensive investigation of N=68 isotones around the compound nucleus 119 Sb from neutron rich 112 Ru (Z=44) to neutron deficient 127 Pr (Z= 59) nuclei is presented to understand the angular momentum induced variations in inverse level density parameter and the possible influence of deformation and structural transitions on the variations on NLd

  7. Nuclear fission and neutron-induced fission cross-sections

    Energy Technology Data Exchange (ETDEWEB)

    James, G.D.; Lynn, J.E.; Michaudon, A.; Rowlands, J.; de Saussure, G.

    1981-01-01

    A general presentation of current knowledge of the fission process is given with emphasis on the low energy fission of actinide nuclei and neutron induced fission. The need for and the required accuracy of fission cross section data in nuclear energy programs are discussed. A summary is given of the steps involved in fission cross section measurement and the range of available techniques. Methods of fission detection are described with emphasis on energy dependent changed and detector efficiency. Examples of cross section measurements are given and data reduction is discussed. The calculation of fission cross sections is discussed and relevant nuclear theory including the formation and decay of compound nuclei and energy level density is introduced. A description of a practical computation of fission cross sections is given.

  8. Nuclear suppression in p-A collisions from induced radiation

    International Nuclear Information System (INIS)

    Arleo, F.; Kolevatov, R.; Peigne, S.; Sami, T.

    2016-01-01

    The current status of coherent energy loss is reviewed, both in theory and in its phenomenological applications to p-A collisions. The induced energy loss is not bounded in general, but only in the specific situation where the energetic parton is suddenly accelerated (as in deep inelastic scattering) in the nuclear medium. In the situation where the parton is asymptotic, i.e. 'prepared' at t = -∞ and 'tagged' at t = +∞ after crossing a nuclear medium of thickness L (a situation relevant to forward hadron production in p-A collisions), ΔE appears to be proportional to E. Both situations are detailed in the article

  9. Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Hui-Hsuan [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Chou, Fen-Pi [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Wang, Chau-Jong [Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Hsuan, Shu-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China); Wang, Cheng-Kun [E-Chyun Dermatology Clinic, No.70, Sec. 3, Jhonghua E. Rd., East District, Tainan, Taiwan (China); Chen, Jing-Hsien [Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China)

    2011-02-01

    Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to inhibit non-small cell lung cancer (NSCLC) A549 cell migration and invasion via down-regulation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Here we demonstrated that Andro inhibited the expression of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in A549 cells. HIF-1{alpha} plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1{alpha} was correlated with a rapid ubiquitin-dependent degradation of HIF-1{alpha}, and was accompanied by increased expressions of hydroxyl-HIF-1{alpha} and prolyl hydroxylase (PHD2), and a later decrease of vascular endothelial growth factor (VEGF) upon the treatment of Andro. The Andro-inhibited VEGF expression appeared to be a consequence of HIF-1{alpha} inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGF{beta}1/PHD2/HIF-1{alpha} pathway, as demonstrated by the transfection of TGF{beta}1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1{alpha} transduced VEGF expression in A549 cells and other NSCLC cell lines. In conclusion, these results highlighted the potential effects of Andro, which may be developed as a chemotherapeutic or an anti-angiogenesis agent for NSCLC in the future.

  10. A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians

    DEFF Research Database (Denmark)

    Anuradha, Shekher; Radha, Venkatesan; Deepa, Raj

    2005-01-01

    Among Europeans, mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown....... The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1alpha gene in different types of diabetes in Asian Indians....

  11. Infection of Human Fallopian Tube Epithelial Cells with Neisseria gonorrhoeae Protects Cells from Tumor Necrosis Factor Alpha-Induced Apoptosis

    Science.gov (United States)

    Morales, Priscilla; Reyes, Paz; Vargas, Macarena; Rios, Miguel; Imarai, Mónica; Cardenas, Hugo; Croxatto, Horacio; Orihuela, Pedro; Vargas, Renato; Fuhrer, Juan; Heckels, John E.; Christodoulides, Myron; Velasquez, Luis

    2006-01-01

    Following infection with Neisseria gonorrhoeae, bacteria may ascend into the Fallopian tubes (FT) and induce salpingitis, a major cause of infertility. In the FT, interactions between mucosal epithelial cells and gonococci are pivotal events in the pathogen's infection cycle and the inflammatory response. In the current study, primary FT epithelial cells were infected in vitro with different multiplicities of infection (MOI) of Pil+ Opa+ gonococci. Bacteria showed a dose-dependent association with cells and induced the secretion of tumor necrosis factor alpha (TNF-α). A significant finding was that gonococcal infection (MOI = 1) induced apoptosis in approximately 30% of cells, whereas increasing numbers of bacteria (MOI = 10 to 100) did not induce apoptosis. Apoptosis was observed in only 11% of cells with associated bacteria, whereas >84% of cells with no adherent bacteria were apoptotic. TNF-α was a key contributor to apoptosis, since (i) culture supernatants from cells infected with gonococci (MOI = 1) induced apoptosis in naïve cultures, suggesting that a soluble factor was responsible; (ii) gonococcal infection-induced apoptosis was inhibited with anti-TNF-α antibodies; and (iii) the addition of exogenous TNF-α induced apoptosis, which was inhibited by the presence of increasing numbers of bacteria (MOI = 10 to 100). These data suggest that TNF-α-mediated apoptosis of FT epithelial cells is likely a primary host defense mechanism to prevent pathogen colonization. However, epithelial cell-associated gonococci have evolved a mechanism to protect the cells from undergoing TNF-α-mediated apoptosis, and this modulation of the host innate response may contribute to establishment of infection. Understanding the antiapoptotic mechanisms used by Neisseria gonorrhoeae will inform the pathogenesis of salpingitis and could suggest new intervention strategies for prevention and treatment of the disease. PMID:16714596

  12. 5-Hydroxytryptamine 1A/7 and 4alpha receptors differentially prevent opioid-induced inhibition of brain stem cardiorespiratory function.

    Science.gov (United States)

    Wang, Xin; Dergacheva, Olga; Kamendi, Harriet; Gorini, Christopher; Mendelowitz, David

    2007-08-01

    Opioids evoke respiratory depression, bradycardia, and reduced respiratory sinus arrhythmia, whereas serotonin (5-HT) agonists stimulate respiration and cardiorespiratory interactions. This study tested whether serotonin agonists can prevent the inhibitory effects of opioids on cardiorespiratory function. Spontaneous and rhythmic inspiratory-related activity and gamma-aminobutyric acid (GABA) neurotransmission to premotor parasympathetic cardioinhibitory neurons in the nucleus ambiguus were recorded simultaneously in an in vitro thick slice preparation. The mu-opioid agonist fentanyl inhibited respiratory frequency. The 5-hydroxytryptamine 1A/7 receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin increased respiratory frequency by itself and also prevented the fentanyl-induced respiratory depression. The 5-hydroxytryptamine 4alpha agonist BIMU-8 did not by itself change inspiratory activity but prevented the mu-opioid-mediated respiratory depression. Both spontaneous and inspiratory-evoked GABAergic neurotransmission to cardiac vagal neurons were inhibited by fentanyl. 8-Hydroxy-2-(di-n-propylamino)tetralin inhibited spontaneous but not inspiratory-evoked GABAergic activity to parasympathetic cardiac neurons. However, 8-hydroxy-2-(di-n-propylamino)tetralin differentially altered the opioid-mediated depression of inspiratory-evoked GABAergic activity but did not change the opioid-induced reduction in spontaneous GABAergic neurotransmission. In contrast, BIMU-8 did not alter GABAergic neurotransmission to cardiac vagal neurons by itself but prevented the fentanyl depression of both spontaneous and inspiratory-elicited GABAergic neurotransmission to cardiac vagal neurons. In the presence of tetrodotoxin, the inhibition of GABAergic inhibitory postsynaptic currents with fentanyl is prevented by coapplication of BIMU-8, indicating that BIMU-8 acts at presynaptic GABAergic terminals to prevent fentanyl-induced depression. These results suggest that activation of 5

  13. Tumor necrosis factor-alpha-independent downregulation of hepatic cholesterol 7alpha-hydroxylase gene in mice treated with lead nitrate.

    Science.gov (United States)

    Kojima, Misaki; Sekikawa, Kenji; Nemoto, Kiyomitsu; Degawa, Masakuni

    2005-10-01

    We previously reported that lead nitrate (LN), an inducer of hepatic tumor necrosis factor-alpha (TNF-alpha), downregulated gene expression of cholesterol 7alpha-hydroxylase. Herein, to clarify the role of TNF-alpha in LN-induced downregulation of cholesterol 7alpha-hydroxylase, effects of LN on gene expression of hepatic cholesterol 7alpha-hydroxylase (Cyp7a1) in TNF-alpha-knockout (KO) and TNF-alpha-wild-type (WT) mice were comparatively examined. Gene expression of hepatic Cyp7a1 in both WT and KO mice decreased to less than 5% of the corresponding controls at 6-12 h after treatment with LN (100 mumol/kg body weight, iv). Levels of hepatic TNF-alpha protein in either WT or KO mice were below the detection limit, although expression levels of the TNF-alpha gene markedly increased at 6 h in WT mice by LN treatment, but not in KO mice. In contrast, in both WT and KO mice, levels of hepatic IL-1beta protein, which is known to be a suppressor of the cholesterol 7alpha-hydroxylase gene in hamsters, were significantly increased 3-6 h after LN treatment. Furthermore, LN-induced downregulation of the Cyp7a1 gene did not necessarily result from altered gene expression of hepatic transcription factors, including positive regulators (liver X receptor alpha, retinoid X receptor alpha, fetoprotein transcription factor, and hepatocyte nuclear factor 4alpha) and a negative regulator small heterodimer partner responsible for expression of the Cyp7a1 gene. The present findings indicated that LN-induced downregulation of the Cyp7a1 gene in mice did not necessarily occur through a TNF-alpha-dependent pathway and might occur mainly through an IL-1beta-dependent pathway.

  14. K-shell X-ray production cross sections of Ni induced by protons, alpha-particles, and He{sup +}

    Energy Technology Data Exchange (ETDEWEB)

    Bertol, A.P.L. [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Hinrichs, R. [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Geociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Vasconcellos, M.A.Z., E-mail: marcos@if.ufrgs.br [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2015-11-15

    The proton, alpha-particle, and He{sup +} induced X-ray emissions of Ni were measured on mono-elemental thin films in order to obtain the K-shell X-ray production cross section in the energy range of 0.7–2.0 MeV for protons, 4.0–6.5 MeV for alpha-particles, and 3.0–4.0 MeV for He{sup +}. The proton-induced X-ray production cross section for Ni agreed well with the theoretical values, endorsing the quality of the measurements. The X-ray production cross section induced with alpha-particles is in good agreement with ECPSSR theory in the complete range of energies, while for He{sup +} that quantity is systematically below. K{sub β}/K{sub α} ratios were evaluated and compared with experimental and theoretical values.

  15. Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT

    Directory of Open Access Journals (Sweden)

    Mejía Salvador

    2006-02-01

    Full Text Available Abstract Background The biochemical bases for hormone dependence in breast cancer have been recognized as an important element in tumor resistance, proliferation and metastasis. On this respect, dexamethasone (Dex dependent protection against TNF-alpha-mediated cell death in the MCF-7 cell line has been demonstrated to be a useful model for the study of this type of cancer. Recently, cytoplasmic signaling induced by steroid receptors has been described, such as the activation of the PI3K/Akt and NF-kappaB pathways. We evaluated their possible participation in the Dex-dependent protection against TNF-alpha-mediated cell death. Results Cellular cultures of the MCF-7 cell line were exposed to either, TNF-alpha or TNF-alpha and Dex, and cell viability was evaluated. Next, negative dominants of PI3K and IkappaB-alpha, designed to block the PI3K/Akt and NF-kappaB pathways, respectively, were transfected and selection and evaluation of several clones overexpressing the mutants were examined. Also, correlation with inhibitor of apoptosis proteins (IAPs expression was examined. Independent inhibition of these two pathways allowed us to test their participation in Dex-dependent protection against TNF-alpha-cytotoxicity in MCF-7 cells. Expression of the PI3K dominant negative mutant did not alter the protection conferred by Dex against TNF-alpha mediated cell death. Contrariwise, clones expressing the IkappaB-alpha dominant negative mutant lost the Dex-conferred protection against TNF-alpha. In these clones degradation of c-IAP was accelerated, while that of XIAP was remained unaffected. Conclusion NF-kappaB, but not PI3K/Akt activation, is required for the Dex protective effect against TNF-alpha-mediated cell death, and correlates with lack of degradation of the anti-apoptotic protein c-IAP1.

  16. Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT.

    Science.gov (United States)

    Machuca, Catalina; Mendoza-Milla, Criselda; Córdova, Emilio; Mejía, Salvador; Covarrubias, Luis; Ventura, José; Zentella, Alejandro

    2006-02-21

    The biochemical bases for hormone dependence in breast cancer have been recognized as an important element in tumor resistance, proliferation and metastasis. On this respect, dexamethasone (Dex) dependent protection against TNF-alpha-mediated cell death in the MCF-7 cell line has been demonstrated to be a useful model for the study of this type of cancer. Recently, cytoplasmic signaling induced by steroid receptors has been described, such as the activation of the PI3K/Akt and NF-kappaB pathways. We evaluated their possible participation in the Dex-dependent protection against TNF-alpha-mediated cell death. Cellular cultures of the MCF-7 cell line were exposed to either, TNF-alpha or TNF-alpha and Dex, and cell viability was evaluated. Next, negative dominants of PI3K and IkappaB-alpha, designed to block the PI3K/Akt and NF-kappaB pathways, respectively, were transfected and selection and evaluation of several clones overexpressing the mutants were examined. Also, correlation with inhibitor of apoptosis proteins (IAPs) expression was examined. Independent inhibition of these two pathways allowed us to test their participation in Dex-dependent protection against TNF-alpha-cytotoxicity in MCF-7 cells. Expression of the PI3K dominant negative mutant did not alter the protection conferred by Dex against TNF-alpha mediated cell death. Contrariwise, clones expressing the IkappaB-alpha dominant negative mutant lost the Dex-conferred protection against TNF-alpha. In these clones degradation of c-IAP was accelerated, while that of XIAP was remained unaffected. NF-kappaB, but not PI3K/Akt activation, is required for the Dex protective effect against TNF-alpha-mediated cell death, and correlates with lack of degradation of the anti-apoptotic protein c-IAP1.

  17. 1-4 Strangeness Production in Antiproton Induced Nuclear Reactions.

    Institute of Scientific and Technical Information of China (English)

    Feng; Zhaoqing[1

    2014-01-01

    More localized energy deposition is able to be produced in antiproton-nucleus collisions in comparison withheavy-ion collisions due to annihilation reactions. Searching for the cold quark-gluon plasma (QGP) with antiprotonbeamshas been considered as a hot topic both in experiments and in theretical calculations over the past severaldecades. Strangeness production and hypernucleus formation in antiproton-induced nuclear reactions are importancein exploring the hyperon (antihyperon)-nucleon (HN) potential and the antinucleon-nucleon interaction, whichhave been hot topics in the forthcoming experiments at PANDA in Germany.

  18. Radiation-induced invagination of the nuclear envelope

    International Nuclear Information System (INIS)

    Szekely, J.G.; Copps, T.P.; Morash, B.D.

    1980-01-01

    Using electron microscopy, we have measured radiation-induced invagination of the nuclear envelope of Chinese hamster V-79 and mouse L cells to produce a quantifiable radiation endpoint on a membrane system. In the dose ranges measured (800 to 3000 rad in L cells and 1270 to 5700 rad in V-79 cells), the amount of invagination increased with dose and continued to develop in intact cells for up to 72 hr after the original population was irradiated. Small vacuoles, which sometimes appeared in the nuclei of L cells, were also more numerous in irradiated cells and increased with dose and incubation time in a similar fashion to invagination development

  19. Alpha-induced reaction cross section measurements on 151Eu for the astrophysical γ-process

    International Nuclear Information System (INIS)

    Gyuerky, Gy.; Elekes, Z.; Farkas, J.; Fueloep, Zs.; Halasz, Z.; Kiss, G.G.; Somorjai, E.; Szuecs, T.; Gueraya, R.T.; Oezkana, N.

    2010-01-01

    Compete text of publication follows. The astrophysical γ-process is the main production mechanism of the p-isotopes, the heavy, proton-rich nuclei not produced by neutron capture reactions in the astrophysical sand r-processes. The γ-process is a poorly known process of nucleosynthesis, the models are not able to reproduce well the p-isotope abundances observed in nature. Experimental data on nuclear reactions involved in γ-process reaction networks are clearly needed to provide input for a more reliable γ-process network calculation. As a continuation of our systematic study of reactions relevant for the γ-process, the cross sections of the 151 Eu(α, γ) 155 Tb and 151 Eu(α,n) 154 Tb reactions have been measured. These reactions have been chosen because α-induced cross section data in the region of heavy p-isotopes are almost completely missing although the calculations show a strong influence of these cross section on the resulting abundances. Since the reaction products of both reactions are radioactive, the cross sections have been measured using the activation technique. The targets have been prepared by evaporating Eu 2 O 3 enriched to 99.2% in 151 Eu onto thin Al foils. The target thicknesses have been measured by weighing and Rutherford Backscattering Spectroscopy. The targets have been irradiated by typically 1-2 μA intensity α-beams from the cyclotron of ATOMKI. The investigated energy range between 12 and 17 MeV was covered with 0.5 MeV steps. This energy range is somewhat higher than the astrophysically relevant one, but the cross section at astrophysical energies is so low that the measurements are not possible there. The γ- activity of the reaction products has been measured by a shielded HPGe detector. The absolute efficiency of the detector was measured with several calibration sources. Since 154 Tb has two long lived isomeric states, partial cross sections of the 151 Eu(α,n) 154 Tb reaction leading to the ground and isomeric states

  20. Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha gene and the relationship to beta-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitus

    DEFF Research Database (Denmark)

    Lauenborg, J; Damm, P; Ek, J

    2004-01-01

    In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to beta-cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene has been associated with decreased serum insulin and C-peptide r...

  1. Statins and PPAR{alpha} agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Timothy E [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States); Zhang, Xiaohua [Department of Biometrics Research, Merck Research Laboratories, West Point, PA 19486 (United States); Shi, Shu [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States); Umbenhauer, Diane R [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States)

    2005-11-01

    Statins and fibrates (weak PPAR{alpha} agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPAR{alpha} agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPAR{alpha} compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPAR{gamma} agonist Rosiglitazone caused little or no cell death at up to 10 {mu}M and the PPAR{delta} ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPAR{alpha} agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPAR{alpha} agonism mediates in part the toxicity response to PPAR{alpha} compounds. Furthermore, PPAR{alpha} agonists and statins cause myotoxicity through distinct and independent pathways.

  2. Yes-associated protein/TEA domain family member and hepatocyte nuclear factor 4-alpha (HNF4α) repress reciprocally to regulate hepatocarcinogenesis in rats and mice.

    Science.gov (United States)

    Cai, Wang-Yu; Lin, Ling-Yun; Hao, Han; Zhang, Sai-Man; Ma, Fei; Hong, Xin-Xin; Zhang, Hui; Liu, Qing-Feng; Ye, Guo-Dong; Sun, Guang-Bin; Liu, Yun-Jia; Li, Sheng-Nan; Xie, Yuan-Yuan; Cai, Jian-Chun; Li, Bo-An

    2017-04-01

    Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between Yes-associated protein/TEA domain family member (YAP-TEAD) and hepatocyte nuclear factor 4-alpha (HNF4α) in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells by a ubiquitin proteasome pathway. By contrast, HNF4α was found to directly associate with TEAD4 to compete with YAP1 for binding to TEAD4, thus inhibiting the transcriptional activity of YAP-TEAD and expression of their target genes. Moreover, overexpression of HNF4α was found to significantly compromise YAP-TEAD-induced HCC cell proliferation and stem cell expansion. Finally, we documented the regulatory mechanism between YAP-TEAD and HNF4α in rat and mouse tumor models, which confirmed our in vitro results. There is a double-negative feedback mechanism that controls TEAD-YAP and HNF4α expression in vitro and in vivo, thereby regulating cellular proliferation and differentiation. Given that YAP acts as a dominant oncogene in HCC and plays a crucial role in stem cell homeostasis and tissue regeneration, manipulating the interaction between YAP, TEADs, and HNF4α may provide a new approach for HCC treatment and regenerative medicine. (Hepatology 2017;65:1206-1221). © 2016 by the American Association for the Study of Liver Diseases.

  3. miR-19a promotes colitis-associated colorectal cancer by regulating tumor necrosis factor alpha-induced protein 3-NF-κB feedback loops.

    Science.gov (United States)

    Wang, T; Xu, X; Xu, Q; Ren, J; Shen, S; Fan, C; Hou, Y

    2017-06-08

    Chronic inflammation is believed to have a crucial role in colon cancer development. MicroRNA (miRNA) deregulation is common in human colorectal cancers, but little is known regarding whether miRNA drives tumor progression by regulating inflammation. Here, we showed that miR-19a can promote colitis and colitis-associated colon cancer (CAC) development using a CAC mouse model and an acute colitis mouse model. Tumor necrosis factor-α (TNF-α) stimulation can increase miR-19a expression, and upregulated miR-19a can in turn activate nuclear factor (NF)-κB signaling and TNF-α production by targeting TNF alpha-induced protein 3 (TNFAIP3). miR-19a inhibition can also alleviate CAC in vivo. Moreover, the regulatory effects of miR-19a on TNFAIP3 and NF-κB signaling were confirmed using tumor samples from patients with colon cancer. These new findings demonstrate that miR-19a has a direct role in upregulating NF-κB signaling and that miR-19a has roles in inflammation and CAC.

  4. Hepatocyte nuclear factor 4 alpha is a key factor related to depression and physiological homeostasis in the mouse brain.

    Directory of Open Access Journals (Sweden)

    Kyosuke Yamanishi

    Full Text Available Major depressive disorder (MDD is a common psychiatric disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities. MDD is associated with not only psychological and sociocultural problems, but also pervasive physical dysfunctions such as metabolic, neurobiological and immunological abnormalities. Nevertheless, the mechanisms underlying the interactions between these factors have yet to be determined in detail. The aim of the present study was to identify the molecular mechanisms responsible for the interactions between MDD and dysregulation of physiological homeostasis, including immunological function as well as lipid metabolism, coagulation, and hormonal activity in the brain. We generated depression-like behavior in mice using chronic mild stress (CMS as a model of depression. We compared the gene expression profiles in the prefrontal cortex (PFC of CMS and control mice using microarrays. We subsequently categorized genes using two web-based bioinformatics applications: Ingenuity Pathway Analysis and The Database for Annotation, Visualization, and Integrated Discovery. We then confirmed significant group-differences by analyzing mRNA and protein expression levels not only in the PFC, but also in the thalamus and hippocampus. These web tools revealed that hepatocyte nuclear factor 4 alpha (Hnf4a may exert direct effects on various genes specifically associated with amine synthesis, such as genes involved in serotonin metabolism and related immunological functions. Moreover, these genes may influence lipid metabolism, coagulation, and hormonal activity. We also confirmed the significant effects of Hnf4a on both mRNA and protein expression levels in the brain. These results suggest that Hnf4a may have a critical influence on physiological homeostasis under depressive states, and may be associated with the mechanisms responsible for the interactions between MDD and the dysregulation of

  5. Some characteristics of the CR-39 solid state nuclear-track detector for protons and low energy alpha particles

    International Nuclear Information System (INIS)

    Fonseca, E.S. da.

    1983-01-01

    Experimental results related to certain registration properties of the CR-39 solid state nuclear-track detector for charged particles are presented and discussed. The determination of the CR-39 chemical etching in NaOH and KOH solutions, comprising concentration (2-10N) and temperature effects (50-90 0 C), showed the existence of an inverse proportion between the induction time and the temperature as well as the normal concentration of the solutions. The critical energy and the critical energy-loss rate of CR-39 track detectors for registration of protons were experimentally determined. A number of samples was exposed to 24MeV proton beams in the IEN-CNEN Cyclotron (CV-28), using a scattering chamber with a tantalum thin target and aluminium absorbers in contact with the samples in order to provide the required fluctuation in the scattered beam energy. From the mean track-diameter plotted against incident proton energy for 16h and 24h chemical etching (6.25 NaOH, 70 0 C), and considering 1.5 μm as the minimum observable track-diameter, the values (21.0 + - 1.5) MeV and (22.5 + - 1.5) MeV were deduced, respectively, for the critical energy. From the calculated energy-loss rate versus energy curve, the critical energy-loss rate was evaluated as 24 + - 2 MeV.cm 2 /g. Finally, the CR-39 response for low energy alpha particles (E [pt

  6. Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    Cai, Shao-Hang; Lu, Shi-Xun; Liu, Li-Li; Zhang, Chris Zhiyi; Yun, Jing-Ping

    2017-10-01

    Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry. The relationship between P2-HNF4α and clinical features of HCC patients were analysed. Kaplan-Meier analysis was conducted to assess the prognostic value of P2-HNF4α. The results showed that the expression of P2-HNF4α in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4α expression was negatively correlated with P2-HNF4α expression ( p  = 0.023). High P2-HNF4α expression was significantly associated with poor differentiation of HCC ( p = 0.002) and vascular invasion ( p = 0.017). Kaplan-Meier analysis showed that P2-HNF4α expression was closely correlated with overall survival in the training group ( p = 0.01), validation group ( p = 0.034), and overall group of patients with HCC ( p P2-HNF4α, different from P1-HNF4α, is markedly upregulated and serves as an oncogene-associated protein in HCC. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.

  7. Endothelial monocyte activating polypeptide-II modulates endothelial cell responses by degrading hypoxia-inducible factor-1alpha through interaction with PSMA7, a component of the proteasome

    Energy Technology Data Exchange (ETDEWEB)

    Tandle, Anita T. [Tumor Angiogenesis Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 (United States); Calvani, Maura; Uranchimeg, Badarch [DTP-Tumor Hypoxia Laboratory, SAIC Frederick, Inc., National Cancer Institute, Frederick, Maryland 21702 (United States); Zahavi, David [Tumor Angiogenesis Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 (United States); Melillo, Giovanni [DTP-Tumor Hypoxia Laboratory, SAIC Frederick, Inc., National Cancer Institute, Frederick, Maryland 21702 (United States); Libutti, Steven K., E-mail: slibutti@montefiore.org [Department of Surgery, Montefiore-Einstein Center for Cancer Care, Albert Einstein College of Medicine, Greene Medical Arts Pavilion, 4th Floor 3400, Bainbridge Avenue, Bronx, New York 10467 (United States)

    2009-07-01

    The majority of human tumors are angiogenesis dependent. Understanding the specific mechanisms that contribute to angiogenesis may offer the best approach to develop therapies to inhibit angiogenesis in cancer. Endothelial monocyte activating polypeptide-II (EMAP-II) is an anti-angiogenic cytokine with potent effects on endothelial cells (ECs). It inhibits EC proliferation and cord formation, and it suppresses primary and metastatic tumor growth in-vivo. However, very little is known about the molecular mechanisms behind the anti-angiogenic activity of EMAP-II. In the present study, we explored the molecular mechanism behind the anti-angiogenic activity exerted by this protein on ECs. Our results demonstrate that EMAP-II binds to the cell surface {alpha}5{beta}1 integrin receptor. The cell surface binding of EMAP-II results in its internalization into the cytoplasmic compartment where it interacts with its cytoplasmic partner PSMA7, a component of the proteasome degradation pathway. This interaction increases hypoxia-inducible factor 1-alpha (HIF-1{alpha}) degradation under hypoxic conditions. The degradation results in the inhibition of HIF-1{alpha} mediated transcriptional activity as well as HIF-1{alpha} mediated angiogenic sprouting of ECs. HIF-1{alpha} plays a critical role in angiogenesis by activating a variety of angiogenic growth factors. Our results suggest that one of the major anti-angiogenic functions of EMAP-II is exerted through its inhibition of the HIF-1{alpha} activities.

  8. Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

    Science.gov (United States)

    Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

    2010-01-01

    Although Interferon-alpha (IFN-alpha, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuropsychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT(1A) receptor- and 5-HT(1B) receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT(1A) receptor- and 5-HT(1B) receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-alpha-induced increase of the immobility time in the forced swimming test; (2) 5-HT(1A) receptor- and 5-HT(1B) receptor ligands alone or in combination had no effects on IFN-alpha-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT(1A) receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT(1A) receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-alpha-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT(1B) receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT(1B/1D) receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-alpha-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-alpha-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to

  9. Thermally Induced Alpha-Helix to Beta-Sheet Transition in Regenerated Silk Fibers and Films

    Energy Technology Data Exchange (ETDEWEB)

    Drummy,L.; Phillips, D.; Stone, M.; Farmer, B.; Naik, R.

    2005-01-01

    The structure of thin films cast from regenerated solutions of Bombyx mori cocoon silk in hexafluoroisopropyl alcohol (HFIP) was studied by synchrotron X-ray diffraction during heating. A solid-state conformational transition from an alpha-helical structure to the well-known beta-sheet silk II structure occurred at a temperature of approximately 140 degrees C. The transition appeared to be homogeneous, as both phases do not coexist within the resolution of the current study. Modulated differential scanning calorimetry (DSC) of the films showed an endothermic melting peak followed by an exothermic crystallization peak, both occurring near 140 degrees C. Oriented fibers were also produced that displayed this helical molecular conformation. Subsequent heating above the structural transition temperature produced oriented beta-sheet fibers very similar in structure to B. mori cocoon fibers. Heat treatment of silk films at temperatures well below their degradation temperature offers a controllable route to materials with well-defined structures and mechanical behavior.

  10. Oxytocin induces prostaglandin F2 alpha release in pregnant cows: influence of gestational age and oxytocin receptor concentrations.

    Science.gov (United States)

    Fuchs, A R; Rollyson, M K; Meyer, M; Fields, M J; Minix, J M; Randel, R D

    1996-03-01

    Brahman cows with known breeding dates received i.v. injections of either 10 or 100 IU oxytocin (OT) on Days 50, 150, 250, or 280 of gestation (n = 6 for each stage). Concentrations of the prostaglandin (PG) F2 alpha metabolite, 13,14-dihydro-15-keto-prostaglandin (PGFM), and OT were measured in samples of peripheral plasma collected at 15-min intervals for 1 h before and 1 h after treatment and then at 30-min intervals for 3 h. Plasma progesterone was measured daily for 14 days after OT injections on Days 50 and 250 of gestation. The increase in plasma OT after injection was dose-dependent (p = 0.001) but not affected by stage of gestation. Plasma PGFM increased after OT in a dose- and stage-dependent manner (p = 0.0001). At Day 280, the increase in plasma PGFM after 100 IU OT was sevenfold greater than at Day 50. Plasma progesterone declined significantly during the 7th to 12th days postinjection and returned to normal pregnancy values by the 14th day (4.4 +/- 0.3 ng/ml) except in two cows treated on Day 50 of gestation that later aborted. In these, plasma progesterone was significantly lower, 2.6 +/- 0.1 ng/ml. In a second experiment, the concentration of OT receptors was determined in endometrium collected from purebred Angus or Hereford cows slaughtered on Days 50, 150, 250, and 280 of gestation (n = 3 or 4 at each stage). Endometrial concentrations of OT receptor changed as a function of gestational age, increasing sixfold from Day 50 to Day 280, which was parallel to the increase by OT of plasma PGFM. Thus, endometrial OT receptors are functionally coupled to PGF2 alpha release during pregnancy, and their concentration determines the magnitude of OT-induced PGF2 alpha release during gestation. Consequently, endogenous OT is a factor in the regulation of PGF2 alpha release from the bovine uterus during pregnancy and parturition.

  11. Expression and function of hypoxia inducible factor-1 alpha in human melanoma under non-hypoxic conditions

    Directory of Open Access Journals (Sweden)

    Joshi Sandeep S

    2009-11-01

    Full Text Available Abstract Background Hypoxia inducible factor-1 alpha (HIF-1α protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP, vertical growth phase (VGP and metastatic (MET melanomas. Results HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part of the oxygen-dependent regulation domain in WM1366 and WM9 melanoma cells. Over-expression of HIF-1α and its splice variant in the RGP cell line SbCl2 resulted in a small increase in soft agar colony formation and a large increase in matrigel invasion relative to control transfected cells. Knockdown of HIF-1α expression by siRNA in the MET WM9 melanoma cell line resulted in a large decrease in both soft agar colony formation and matrigel invasion relative to cells treated with non-specific siRNA. There is a high level of ERK1/2 phosphorylation in WM9 cells, indicating an activated Ras-Raf-MEK-ERK1/2 MAPK pathway. Treatment of WM9 cells with 30 μM U0126 MEK inhibitor, decreased ERK1/2 phosphorylation and resulted in a decrease in HIF-1α expression. However, a 24 h treatment with 10 μM U0126 totally eliminated Erk1/2 phosphorylation, but did not change HIF-1alpha levels. Furthermore, siRNA knockdown of MEK siRNA did not change HIF-1alpha levels. Conclusion We speculate that metabolic products of U0126 decrease HIF-1alpha expression through "off target" effects. Overall our data suggest that increased HIF-1α expression under normoxic conditions contributes to some of the malignant phenotypes exhibited by human melanoma cells. The expanded role of HIF-1α in melanoma biology increases

  12. Comparison of bone tumors induced by beta-emitting or alpha-emitting radionuclides: Schemes of pathogenesis

    International Nuclear Information System (INIS)

    Gillett, N.A.; Muggenburg, B.A.; Pool, R.R.; Hahn, F.F.

    1988-01-01

    Life-span studies in Beagle dogs have documented the occurrence of bone tumors following exposure to bone-seeking alpha- or beta-emitting radionuclides administered by different routes of exposure. Bone tumors from dogs in four different life-span studies were analyzed according to tumor phenotype, tumor location, radiographic appearance, incidence of metastasis, and association with radiation osteodystrophy. Marked differences in these parameters were observed that did not correlate with differences in radionuclide type, route of exposure, or duration of radionuclide uptake. Radiation osteodystrophy, which is postulated to be a preneoplastic lesion, was not a significant component in one of the studies. Analysis of the data from these four studies suggests that at least two different mechanisms of bone tumor pathogenesis occur for radiation-induced bone tumors. (author)

  13. Ultraviolet B irradiation of skin induces mast cell degranulation and release of tumour necrosis factor-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, L.J. [University of Queensland, Brisbane, QLD (Australia). Dept. of Dentistry, Immunopathology Unit

    1995-06-01

    In the `sunburn` response in skin, dermal blood vessels are activated and traffic of dendritic Langerhans` cells altered. While these changes have been attributed to the cytokine TNF-{alpha}, the source of this acutely released TNF has not been identified. This report demonstrates that the `sunburn` response, both in vivo and in vitro, is accompanied by rapid degranulation of cutaneous mast cells, with consequential release of intracellular stores of TNF. Epidermal keratinocytes were only minor contributors to local TNF production. Expression of the TNF-inducible CD62E (E-selectin/ELAM-1) and CD54 adhesion molecules on cutaneous endothelium occurred 2 hours following mast cell degranulation, and this event was sensitive to blockade of mast cells with disodium cromoglycate. These results indicate that TNF release in skin in the acute sunburn response can largely be attributed to mast cells. 47 refs., 5 tabs., 2 figs.

  14. Generalised pustular psoriasis induced by cyclosporin a withdrawal responding to the tumour necrosis factor alpha inhibitor etanercept.

    Science.gov (United States)

    Kamarashev, J; Lor, P; Forster, A; Heinzerling, L; Burg, G; Nestle, F O

    2002-01-01

    We report a 50-year-old male patient with a 15-year history of psoriasis including mutilating psoriatic arthritis, in whom the withdrawal of cyclosporin A induced a generalised pustular exacerbation and a aggravation of the joint condition. Two weekly injections of 25 mg of the tumour necrosis factor alpha inhibitor etanercept led to a rapid improvement of his psoriatic arthritis, as well as regression of the pustular eruption, while residual erythema was still present. The clinical response was reflected by an increase in circulating interleukin (IL) 10 and a decrease in IL-6 and IL-8 serum levels during treatment. We conclude that etanercept may be a safe and effective therapy not only in severe psoriatic arthritis, but also in cases of pustular rebound after withdrawal of immunosuppressive agents. Copyright 2002 S. Karger AG, Basel

  15. Chrysophanic Acid Suppresses Adipogenesis and Induces Thermogenesis by Activating AMP-activated Protein Kinase Alpha in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Hara Lim

    2016-12-01

    Full Text Available Chrysophanic acid (CA is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Though several studies have indicated numerous features of CA, no study has yet reported the effect of CA on obesity. In this study, we tried to identify the anti-obesity effects of CA. By using 3T3-L1 adipocytes and primary cultured brown adipocytes as in vitro models, high-fat diet (HFD-induced obese mice, and zebrafish as in vivo models, we determined the anti-obesity effects of CA. CA reduced weight gain in HFD-induced obese mice. They also decreased lipid accumulation and the expressions of adipogenesis factors including peroxisome proliferator-activated receptor gamma (PPARγ and CCAAT/enhancer-binding protein alpha (C/EBPα in 3T3-L1 adipocytes. In addition, uncoupling protein 1 (UCP1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α, the brown fat specific thermogenic genes, were up-regulated in brown adipocytes by CA treatment. Furthermore, when co-treated with Compound C, the AMP-activated protein kinase (AMPK inhibitor, CA was able to restore the activation of AMPKα in both types of adipocytes, indicating the multi-controlling effect of CA was partially via the AMPKα pathway. Given all together, these results indicate that CA can ameliorate obesity by controlling the adipogenic and thermogenic pathway at the same time. On these bases we suggest the new potential of CA as an anti-obese pharmacotherapy.

  16. The efficacy of intravitreal interferon alpha-2b for the treatment of experimental endotoxin-induced uveitis

    Directory of Open Access Journals (Sweden)

    Mehrdad Afarid

    2016-01-01

    Full Text Available Purpose: To study the efficacy of intravitreal interferon alpha-2b for endotoxin-induced uveitis. Materials and Methods: A total of 36 rabbits were randomly allocated to one of the three groups: (1 received interferon plus balanced-salt solution; (2 received lipopolysaccharide (LPS plus interferon; and (3 received LPS plus balanced-salt solution. Intraocular inflammation was evaluated by slit-lamp biomicroscopy (standardization of uveitis nomenclature grading, binocular indirect ophthalmoscopy (BIO score, and histopathology. Results: Group 2 showed significantly lower mean (±standard deviation anterior chamber reaction than Group 3 (3.1 ± 0.9 vs. 3.8 ± 0.4 on day 1 postinjection, lower vitreous cells on days 1 through 7 (day 1: 3.1 ± 0.9 vs. 3.8 ± 0.4; day 3: 2.1 ± 1.6 vs. 3.8 ± 0.4; day 7: 1.9 ± 1.3 vs. 3.6 ± 0.7, and lower BIO score on days 1-7 (day 1: 3.3 ± 1.2 vs. 4.4 ± 0.7; day 3: 3.0 ± 1.4 vs. 4.3 ± 0.9; day 7: 2.4 ± 1.4 vs. 3.7 ± 1.2. The protein content of anterior and vitreous aspirates was lower in Group 2 than 3 (1618.5 ± 411.4 vs. 2567.3 ± 330.8 and 2157.0 ± 283.3 vs. 3204.6 ± 259.5, respectively. Conclusion: Intravitreal interferon alpha-2b was effective in controlling endotoxin-induced uveitis.

  17. The efficacy of intravitreal interferon alpha-2b for the treatment of experimental endotoxin-induced uveitis.

    Science.gov (United States)

    Afarid, Mehrdad; Lashkarizadeh, Hamid; Ashraf, Mohammad J; Nowroozzadeh, Mohammad Hossein; Shafiee, Sayed M

    2016-05-01

    To study the efficacy of intravitreal interferon alpha-2b for endotoxin-induced uveitis. A total of 36 rabbits were randomly allocated to one of the three groups: (1) received interferon plus balanced-salt solution; (2) received lipopolysaccharide (LPS) plus interferon; and (3) received LPS plus balanced-salt solution. Intraocular inflammation was evaluated by slit-lamp biomicroscopy (standardization of uveitis nomenclature grading), binocular indirect ophthalmoscopy (BIO) score, and histopathology. Group 2 showed significantly lower mean (±standard deviation) anterior chamber reaction than Group 3 (3.1 ± 0.9 vs. 3.8 ± 0.4) on day 1 postinjection, lower vitreous cells on days 1 through 7 (day 1: 3.1 ± 0.9 vs. 3.8 ± 0.4; day 3: 2.1 ± 1.6 vs. 3.8 ± 0.4; day 7: 1.9 ± 1.3 vs. 3.6 ± 0.7), and lower BIO score on days 1-7 (day 1: 3.3 ± 1.2 vs. 4.4 ± 0.7; day 3: 3.0 ± 1.4 vs. 4.3 ± 0.9; day 7: 2.4 ± 1.4 vs. 3.7 ± 1.2). The protein content of anterior and vitreous aspirates was lower in Group 2 than 3 (1618.5 ± 411.4 vs. 2567.3 ± 330.8 and 2157.0 ± 283.3 vs. 3204.6 ± 259.5, respectively). Intravitreal interferon alpha-2b was effective in controlling endotoxin-induced uveitis.

  18. Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

    Science.gov (United States)

    Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

    1996-08-01

    The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

  19. Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha.

    Science.gov (United States)

    Wu, Shan; Ren, Jun

    2006-02-13

    Diabetes mellitus leads to thiamine deficiency and multiple organ damage including diabetic neuropathy. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cerebral oxidative stress. Adult male FVB mice were made diabetic with a single injection of STZ (200 mg/kg, i.p.). Fourteen days later, control and diabetic (fasting blood glucose >13.9 mM) mice received benfotiamine (100 mg/kg/day, i.p.) for 14 days. Oxidative stress and protein damage were evaluated by glutathione/glutathione disulfide (GSH/GSSG) assay and protein carbonyl formation, respectively. Pro-oxidative or pro-inflammatory factors including advanced glycation end-product (AGE), tissue factor and tumor necrosis factor-alpha (TNF-alpha) were evaluated by immunoblot analysis. Four weeks STZ treatment led to hyperglycemia, enhanced cerebral oxidative stress (reduced GSH/GSSG ratio), elevated TNF-alpha and AGE levels without changes in protein carbonyl or tissue factor. Benfotiamine alleviated diabetes-induced cerebral oxidative stress without affecting levels of AGE, protein carbonyl, tissue factor and TNF-alpha. Collectively, our results indicated benfotiamine may antagonize diabetes-induced cerebral oxidative stress through a mechanism unrelated to AGE, tissue factor and TNF-alpha.

  20. Hypoxia-induced cytotoxic drug resistance in osteosarcoma is independent of HIF-1Alpha.

    Directory of Open Access Journals (Sweden)

    Jennifer Adamski

    Full Text Available Survival rates from childhood cancer have improved dramatically in the last 40 years, such that over 80% of children are now cured. However in certain subgroups, including metastatic osteosarcoma, survival has remained stubbornly poor, despite dose intensive multi-agent chemotherapy regimens, and new therapeutic approaches are needed. Hypoxia is common in adult solid tumours and is associated with treatment resistance and poorer outcome. Hypoxia induces chemotherapy resistance in paediatric tumours including neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma, in vitro, and this drug resistance is dependent on the oxygen-regulated transcription factor hypoxia inducible factor-1 (HIF-1. In this study the effects of hypoxia on the response of the osteosarcoma cell lines 791T, HOS and U2OS to the clinically relevant cytotoxics cisplatin, doxorubicin and etoposide were evaluated. Significant hypoxia-induced resistance to all three agents was seen in all three cell lines and hypoxia significantly reduced drug-induced apoptosis. Hypoxia also attenuated drug-induced activation of p53 in the p53 wild-type U2OS osteosarcoma cells. Drug resistance was not induced by HIF-1α stabilisation in normoxia by cobalt chloride nor reversed by the suppression of HIF-1α in hypoxia by shRNAi, siRNA, dominant negative HIF or inhibition with the small molecule NSC-134754, strongly suggesting that hypoxia-induced drug resistance in osteosarcoma cells is independent of HIF-1α. Inhibition of the phosphoinositide 3-kinase (PI3K pathway using the inhibitor PI-103 did not reverse hypoxia-induced drug resistance, suggesting the hypoxic activation of Akt in osteosarcoma cells does not play a significant role in hypoxia-induced drug resistance. Targeting hypoxia is an exciting prospect to improve current anti-cancer therapy and combat drug resistance. Significant hypoxia-induced drug resistance in osteosarcoma cells highlights the potential importance of hypoxia as a target

  1. Protective Efficacy of Alpha-lipoic Acid against AflatoxinB1-induced Oxidative Damage in the Liver

    Directory of Open Access Journals (Sweden)

    Y. Li

    2014-06-01

    Full Text Available Alpha-lipoic acid (α-LA is not only involved in energy metabolism, but is also a powerful antioxidant that can protect against hepatic oxidative stress induced by some drugs, toxins, or under various physiological and pathophysiological conditions. Here, we investigated the effect of α-LA against liver oxidative damage in broilers exposed to aflatoxin B1 (AFB1. Birds were randomly divided into four groups and assigned different diets: basal diet, 300 mg/kg α-LA supplementation in basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1, for 3 weeks. The results revealed that the addition of 300 mg/kg α-LA protected against the liver function damage of broilers induced by chronic low dose of AFB1 as estimated by a significant (p<0.05 change in levels of plasma total protein, albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. The histopathological analysis also showed that liver tissues were injured in the AFB1 diet, but this effect was alleviated by the addition of 300 mg/kg α-LA. Additionally, AFB1 induced a profound elevation of oxidative stress in birds, as indicated by an increase in malondialdehyde level, a decrease in glutathione peroxidase activity and a depletion of the glutathione content in the liver. All of these negative effects were inhibited by treatment with α-LA. Our results suggest that the inhibition of AFB1-induced excess production of lipid peroxides and the maintenance of intracellular antioxidant status may play important roles in the protective effects of α-LA against AFB1-induced oxidative damage in the liver.

  2. Optimization in the nuclear fuel cycle II: Concentration of alpha emitters in the air; Otimização no ciclo do combustível nuclear II: concentração de alfa emissores no ar

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, W.S., E-mail: pereiras@gmail.com [Universidade Veiga de Ameida (UVA), Rio de Janeiro, RJ (Brazil); Silva, A.X.; Lopes, J.M.; Carmo, A.S.; Mello, C.R.; Fernandes, T.S., E-mail: lararapls@hotmail.com, E-mail: Ademir@nuclear.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Kelecom, A. [Universidade Federal Fluminense (UFF), Niterói, RJ (Brazil)

    2017-07-01

    Optimization is one of the bases of radioprotection and aims to move doses away from the dose limit that is the borderline of acceptable radiological risk. The work aims to use the monitoring of the concentration of alpha emitters in the air as a tool of the optimization process. We analyzed 27 sampling points of airborne alpha concentration in a nuclear fuel cycle facility. The monthly averages were considered statistically different, the highest in the month of February and the lowest in the month of August. All other months were found to have identical mean activity concentration values. Regarding the sampling points, the points with the highest averages were points 12, 15 and 9. These points were indicated for the beginning of the optimization process. Analysis of the production of the facility should be performed to verify possible correlations between production and concentration of alpha emitters in the air.

  3. Solid state nuclear track detectors in the measurement of alpha to fission branching ratios of heavy actinides

    International Nuclear Information System (INIS)

    Pandey, A.K.; Sharma, R.C.; Padalkar, S.K.; Kalsi, P.C.; Iyer, R.H.

    1992-01-01

    A sequential etching procedure for revelation of alpha and fission tracks in CR-39 was developed and optimized. Using this technique alpha and fission tracks can be differentiated unambiguously because of significant differences in their sizes and etching times. This registration and revelation procedure for alpha and fission tracks may be used for the studies of half lives, alpha to fission branching ratios and identification of radionuclides based on their decay schemes. It has the added advantage that both alpha decay and fission events can be studied using one detector and hence uncertainties related to efficiency, registration geometry, registration times, amount of radionuclides etc can be eliminated or minimized. The effects of neutron, gamma and alpha radiations on the alpha and fission fragment tracks registration and revelation properties of CR-39 detectors [CR-39, CR-39 (DOP)] were also studied. The IR spectra were also studied to find out the nature of chemical changes produced by these radiations on CR-39. (author). 32 refs., 7 figs., 4 tabs

  4. Experimental study and nuclear model calculations of {sup 3}He-induced nuclear reactions on zinc

    Energy Technology Data Exchange (ETDEWEB)

    Al-Abyad, M.; Mohamed, Gehan Y. [Nuclear Research Centre, Atomic Energy Authority, Physics Department (Cyclotron Facility), Cairo (Egypt); Ditroi, F.; Takacs, S.; Tarkanyi, F. [Hungarian Academy of Sciences (ATOMKI), Institute for Nuclear Research, Debrecen (Hungary)

    2017-05-15

    Excitation functions of {sup 3}He-induced nuclear reactions on natural zinc were measured using the standard stacked-foil technique and high-resolution gamma-ray spectrometry. From their threshold energies up to 27 MeV, the cross-sections for {sup nat}Zn ({sup 3}He,xn) {sup 69}Ge, {sup nat}Zn({sup 3}He,xnp) {sup 66,67,68}Ga, and {sup nat}Zn({sup 3}He,x){sup 62,65}Zn reactions were measured. The nuclear model codes TALYS-1.6, EMPIRE-3.2 and ALICE-IPPE were used to describe the formation of these products. The present data were compared with the theoretical results and with the available experimental data. Integral yields for some important radioisotopes were determined. (orig.)

  5. Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity.

    Science.gov (United States)

    Juarez, Esther; Tufiño, Cecilia; Querejeta, Enrique; Bracho-Valdes, Ismael; Bobadilla-Lugo, Rosa A

    2017-11-01

    To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α 1 adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD 2 hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.

  6. Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis.

    Directory of Open Access Journals (Sweden)

    David Freeman

    Full Text Available α-synuclein dysregulation is a critical aspect of Parkinson's disease pathology. Recent studies have observed that α-synuclein aggregates are cytotoxic to cells in culture and that this toxicity can be spread between cells. However, the molecular mechanisms governing this cytotoxicity and spread are poorly characterized. Recent studies of viruses and bacteria, which achieve their cytoplasmic entry by rupturing intracellular vesicles, have utilized the redistribution of galectin proteins as a tool to measure vesicle rupture by these organisms. Using this approach, we demonstrate that α-synuclein aggregates can induce the rupture of lysosomes following their endocytosis in neuronal cell lines. This rupture can be induced by the addition of α-synuclein aggregates directly into cells as well as by cell-to-cell transfer of α-synuclein. We also observe that lysosomal rupture by α-synuclein induces a cathepsin B dependent increase in reactive oxygen species (ROS in target cells. Finally, we observe that α-synuclein aggregates can induce inflammasome activation in THP-1 cells. Lysosomal rupture is known to induce mitochondrial dysfunction and inflammation, both of which are well established aspects of Parkinson's disease, thus connecting these aspects of Parkinson's disease to the propagation of α-synuclein pathology in cells.

  7. Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk

    Directory of Open Access Journals (Sweden)

    Ma L

    2018-02-01

    Full Text Available Ling Ma,1 Yong Jiang,2 Yanan Dong,2 Jun Gao,2 Bin Du,2 Dianwei Liu2 1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Background: Subarachnoid hemorrhage (SAH can induce apoptosis in many regions of the brain including the cortex and hippocampus. However, few studies have focused on apoptosis in the hypothalamus after SAH. Although some antiapoptotic strategies have been developed for SAH, such as anti-tumor necrosis factor-alpha (TNF-α antibody, the molecular mechanisms underlying this condition have yet to be elucidated. Therefore, the purpose of this study was to evaluate whether SAH could induce apoptosis in the hypothalamus and identify the potential molecular mechanisms underlying the actions of anti-TNF-α antibody, as a therapeutic regimen, upon apoptosis. Materials and methods: SAH was induced in a rat model. Thirty minutes prior to SAH, anti-TNF-α antibody or U0126, an extracellular signal-regulated kinase (Erk inhibitor, was microinjected into the left lateral cerebral ventricle. In addition, phorbol-12-myristate-13-acetate was injected intraperitoneally immediately after the anti-TNF-α antibody microinjection. Then, real-time polymerase chain reaction, Western blotting and immunohistochemistry were used to detect the expression of caspase-3, bax, bcl-2, phosphorylated Erk (p-Erk and Erk. Finally, anxiety-like behavior was identified by using open field. Results: Levels of caspase-3, bax and bcl-2, all showed a temporary rise after SAH in the hypothalamus, indicating the induction of apoptosis in this brain region. Interestingly, we found that the microinjection of anti-TNF-α antibody could selectively block the elevated levels of bax, suggesting the potential role of anti-TNF-α antibody in the inhibition of SAH-induced

  8. Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

    Science.gov (United States)

    Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

    2009-02-11

    Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

  9. Alpha-particles induce preneoplastic transformation of rat tracheal epithelial cells in culture

    International Nuclear Information System (INIS)

    Thomassen, D.G.; Seiler, F.A.; Shyr, L.-J.; Griffith, W.C.

    1990-01-01

    To characterize the potential role of high-l.e.t. radiation in respiratory carcinogenesis, the cytotoxic and transforming potency of 5.5 MeV α-particles from electroplated sources of 238 Pu were determined using primary cultures of rat tracheal epithelial cells. RBE for cell killing by α-particles versus X-rays varied with dose, and ranged between 4 and 1.5 for α doses in the range 0.2-4 Gy. At equally toxic doses (relative survival 0.18-0.2), all three agents induced similar frequencies of preneoplastic transformation. For preneoplastic transformation induced by doses of α- and X-radiations giving 80 per cent toxicity, an α RBE of 2.4 was derived. The similar RBEs for cell killing and for preneoplastic transformation suggest an association between the type or degree of radiation-induced damage responsible for both cell killing and cell transformation. (author)

  10. Radiative nonrecoil nuclear finite size corrections of order $\\alpha(Z \\alpha)^5$ to the Lamb shift in light muonic atoms

    OpenAIRE

    Faustov, R. N.; Martynenko, A. P.; Martynenko, F. A.; Sorokin, V. V.

    2017-01-01

    On the basis of quasipotential method in quantum electrodynamics we calculate nuclear finite size radiative corrections of order α(Zα)5 to the Lamb shift in muonic hydrogen and helium. To construct the interaction potential of particles, which gives the necessary contributions to the energy spectrum, we use the method of projection operators to states with a definite spin. Separate analytic expressions for the contributions of the muon self-energy, the muon vertex operator and the amplitude...

  11. Inducible alpha-synuclein expression affects human Neural Stem Cell behavior.

    Science.gov (United States)

    Zasso, Jacopo; Mastad, Ahmed; Cutarelli, Alessandro; Conti, Luciano

    2018-04-19

    Converging evidence suggest that levels of alpha-Synuclein (aSyn) expression play a critical role in Parkinson's disease (PD). Several mutations of the SNCA gene, encoding for aSyn have been associated to either the familial or the sporadic forms of PD. Nonetheless, the mechanism underlying wild type aSyn-mediated neurotoxicity in neuronal cells as well as its specific driving role in PD pathogenesis has yet to be fully clarified. In this view, the development of proper in vitro cellular systems is a crucial step. Here we present a novel human Tet-on hNSC cell line, in which aSyn timing and level of expression can be tightly experimentally tuned. Induction of aSyn in self-renewing hNSCs leads to progressive formation of aSyn aggregates and impairs their proliferation and cell survival. Furthermore, aSyn induction during the neuronal differentiation process results in reduced neuronal differentiation and increased number astrocytes and undifferentiated cells in culture. Finally, acute aSyn induction in hNSC-derived dopaminergic neuronal cultures results in cell toxicity. This novel conditional in vitro cell model system may be a valuable tool for dissecting of aSyn pathogenic effects in hNSCs and neurons and in developing new potential therapeutic strategies.

  12. Standoff alpha radiation detection for hot cell imaging and crime scene investigation

    Science.gov (United States)

    Kerst, Thomas; Sand, Johan; Ihantola, Sakari; Peräjärvi, Kari; Nicholl, Adrian; Hrnecek, Erich; Toivonen, Harri; Toivonen, Juha

    2018-02-01

    This paper presents the remote detection of alpha contamination in a nuclear facility. Alpha-active material in a shielded nuclear radiation containment chamber has been localized by optical means. Furthermore, sources of radiation danger have been identified in a staged crime scene setting. For this purpose, an electron-multiplying charge-coupled device camera was used to capture photons generated by alpha-induced air scintillation (radioluminescence). The detected radioluminescence was superimposed with a regular photograph to reveal the origin of the light and thereby the alpha radioactive material. The experimental results show that standoff detection of alpha contamination is a viable tool in radiation threat detection. Furthermore, the radioluminescence spectrum in the air is spectrally analyzed. Possibilities of camera-based alpha threat detection under various background lighting conditions are discussed.

  13. Neutrino induced decoherence and variation in nuclear decay rates

    International Nuclear Information System (INIS)

    Singleton, Douglas; Inan, Nader; Chiao, Raymond Y.

    2015-01-01

    Recent work has proposed that the interaction between ordinary matter and a stochastic gravitational background can lead to the decoherence of large aggregates of ordinary matter. In this work we point out that these arguments can be carried over to a stochastic neutrino background but with the Planck scale of the gravitational decoherence replaced by the weak scale. This implies that it might be possible to observe such neutrino induced decoherence on a small, microscopic system rather than a macroscopic system as is the case for gravitationally induced decoherence. In particular we suggest that neutrino decoherence could be linked with observed variations in the decay rates of certain nuclei. Finally we point out that this proposed neutrino induced decoherence can be considered the complement of the Mikheev–Smirnov–Wolfenstein (MSW) effect. - Highlights: • Review of decoherence arguments for matter moving in a stochastic gravitational background. • Application of these decoherence arguments to neutrinos and the weak interaction scale. • Suggestions of a connection between neutrino decoherence and variable nuclear decay rates. • Connection of neutron decoherence as the inverse of the MSW effect

  14. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Raymond; Matthews, Jason, E-mail: jason.matthews@utoronto.ca

    2013-07-15

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  15. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Lo, Raymond; Matthews, Jason

    2013-01-01

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  16. Measurement of gross alpha - activity in some thermal water sources in Yugoslavia by SSNTDs. [Solid state nuclear track detectors

    Energy Technology Data Exchange (ETDEWEB)

    Benderac, R.; Ristic, D. (Inst. of Security, Belgrade (Yugoslavia)); Antanasijevic, R.; Vukovic, J. (Belgrade Univ. (Yugoslavia))

    1991-01-01

    The possible application of the CN-BDH (type 1) nitrocellulose detector synthesized in laboratory conditions, and also the CR-39 detector, to the measurement of the gross alpha-activity of geothermal and mineral water has been investigated. (author).

  17. Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Wojtaszewski, Jørgen; Viollet, Benoit

    2005-01-01

    We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body a2- and a1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmi...

  18. Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis

    DEFF Research Database (Denmark)

    Ben-Othman, Nouha; Vieira, Andhira; Courtney, Monica

    2017-01-01

    , these neo-generated β-like cells are functional and can repeatedly reverse chemically induced diabetes in vivo. Similarly, the treatment of transplanted human islets with GABA results in a loss of α cells and a concomitant increase in β-like cell counts, suggestive of α-to-β-like cell conversion processes...

  19. Alpha-lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice

    Science.gov (United States)

    Abstract: Hypothermia is a key symptom of sepsis and the mechanism(s) leading to hypothermia during sepsis is largely unknown. To investigate a potential mechanism and find an effective treatment for hypothermia in sepsis, we induced hypothermia in mice by lipopolysaccharide (LP...

  20. Kinetics of the urea-induced dissociation of human plasma alpha-2-macroglobulin as measured by small-angle neutron scattering

    DEFF Research Database (Denmark)

    Sjöberg, B.; Pap, S.; Järnberg, S.-E.

    1991-01-01

    The kinetics of the urea-induced dissociation of human plasma alpha-2-macroglobulin into two half-molecular fragments was investigated at 21.0-degrees-C by using small-angle neutron scattering. The relative change in molecular mass that occurs upon dissociation was monitored by recording the forw...

  1. Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon

    Science.gov (United States)

    Akiyama, Hisashi; Ramirez, Nora-Guadalupe Pina; Gibson, Gregory; Kline, Christopher; Watkins, Simon; Ambrose, Zandrea

    2017-01-01

    ABSTRACT A hallmark of human immunodeficiency virus type 1 (HIV-1) infection in vivo is chronic immune activation concomitant with type I interferon (IFN) production. Although type I IFN induces an antiviral state in many cell types, HIV-1 can replicate in vivo via mechanisms that have remained unclear. We have recently identified a type I IFN-inducible protein, CD169, as the HIV-1 attachment factor on dendritic cells (DCs) that can mediate robust infection of CD4+ T cells in trans. Since CD169 expression on macrophages is also induced by type I IFN, we hypothesized that type I IFN-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells in cis and CD4+ T cells in trans and thus offset antiviral effects of type I IFN. In support of this hypothesis, infection of HIV-1 or murine leukemia virus Env (MLV-Env)-pseudotyped HIV-1 particles was enhanced in IFN-α-treated THP-1 monocytoid cells, and this enhancement was primarily dependent on CD169-mediated enhancement at the virus entry step, a phenomenon phenocopied in HIV-1 infections of IFN-α-treated primary monocyte-derived macrophages (MDMs). Furthermore, expression of CD169, a marker of type I IFN-induced immune activation in vivo, was enhanced in lymph nodes from pigtailed macaques infected with simian immunodeficiency virus (SIV) carrying HIV-1 reverse transcriptase (RT-SHIV), compared to uninfected macaques, and interestingly, there was extensive colocalization of p27gag and CD169, suggesting productive infection of CD169+ myeloid cells in vivo. While cell-free HIV-1 infection of IFN-α-treated CD4+ T cells was robustly decreased, initiation of infection in trans via coculture with CD169+ IFN-α-treated DCs restored infection, suggesting that HIV-1 exploits CD169 in cis and in trans to attenuate a type I IFN-induced antiviral state. IMPORTANCE HIV-1 infection in humans causes immune activation characterized by elevated levels of proinflammatory cytokines, including type I interferons (IFN

  2. Excitation function of alpha-particle-induced reactions on {sup nat}Ni from threshold to 44 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Uddin, M.S. [Atomic Energy Research Establishment, Tandem Accelerator Facilities, Institute of Nuclear Science and Technology, Savar, Dhaka (Bangladesh); Kim, K.S.; Nadeem, M.; Kim, G.N. [Kyungpook National University, Department of Physics, Buk-gu, Daegu (Korea, Republic of); Sudar, S. [Debrecen University, Institute of Experimental Physics, Debrecen (Hungary)

    2017-05-15

    Excitation functions of the {sup nat}Ni(α,x){sup 62,63,65}Zn, {sup nat}Ni(α,x){sup 56,57}Ni and {sup nat}Ni(α,x){sup 56,57,58m+g}Co reactions were measured from the respective thresholds to 44MeV using the stacked-foil activation technique. The tests for the beam characterization are described. The radioactivity was measured using HPGe γ-ray detectors. Theoretical calculations on α-particles-induced reactions on {sup nat}Ni were performed using the nuclear model code TALYS-1.8. A few results are new, the others strengthen the database. Our experimental data were compared with results of nuclear model calculations and described the reaction mechanism. (orig.)

  3. [Characteristics of sublingual vein and expressions of vascular endothelial growth factor and hypoxia-inducible factor 1alpha proteins in sublingual tissues of Beagle dogs with portal hypertension].

    Science.gov (United States)

    Li, Bai-yu; Wang, Li-na; Yue, Xiao-qiang; Li, Bai

    2009-05-01

    To observe sublingual vein characteristics and the expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) proteins in sublingual tissues of Beagle dogs with cirrhotic portal hypertension. Twelve Beagle dogs were randomly divided into normal control group and cirrhotic portal hypertension group. There were 6 dogs in each group. A canine model of cirrhosis portal hypertension was established by injecting dimethylnitrosamine (DMN) into portal vein once a week for 7 weeks. The characteristics of sublingual vein were observed. Portal venous pressure was measured by using bioelectric recording techniques. The expressions of VEGF and HIF-1alpha proteins in sublingual vein were detected by immunohistochemical method. The shape and color of sublingual vein in beagle dogs in the cirrhotic portal hypertension group changed obviously as compared with the normal control group. Immunohistochemical results showed that there were almost no expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the normal control group; however, the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in the cirrhotic portal hypertension group significantly increased. Changes of portal pressure may lead to the formation of the abnormal sublingual vein by increasing the expressions of VEGF and HIF-1alpha proteins in sublingual tissues in Beagle dogs with portal hypertension.

  4. Kinetics of amorphization induced by swift heavy ions in {alpha}-quartz

    Energy Technology Data Exchange (ETDEWEB)

    Pena-Rodriguez, O., E-mail: ovidio.pena@uam.es [Centro de Micro-Analisis de Materiales, Universidad Autonoma de Madrid (CMAM-UAM), Cantoblanco, E-28049 Madrid (Spain); Instituto de Optica, Consejo Superior de Investigaciones Cientificas (IO-CSIC), C/Serrano 121, E-28006 Madrid (Spain); Manzano-Santamaria, J. [Centro de Micro-Analisis de Materiales, Universidad Autonoma de Madrid (CMAM-UAM), Cantoblanco, E-28049 Madrid (Spain); Euratom/CIEMAT Fusion Association, Madrid (Spain); Rivera, A. [Instituto de Fusion Nuclear, Universidad Politecnica de Madrid, C/ Jose Gutierrez Abascal 2, E-28006 Madrid (Spain); Garcia, G. [Laboratory of Synchrotron Light (CELLS-ALBA), 08290 Cerdanyola del Valles, Barcelona (Spain); Olivares, J. [Centro de Micro-Analisis de Materiales, Universidad Autonoma de Madrid (CMAM-UAM), Cantoblanco, E-28049 Madrid (Spain); Instituto de Optica, Consejo Superior de Investigaciones Cientificas (IO-CSIC), C/Serrano 121, E-28006 Madrid (Spain); Agullo-Lopez, F. [Centro de Micro-Analisis de Materiales, Universidad Autonoma de Madrid (CMAM-UAM), Cantoblanco, E-28049 Madrid (Spain); Departamento de Fisica de Materiales, Universidad Autonoma de Madrid (UAM), Cantoblanco, E-28049 Madrid (Spain)

    2012-11-15

    The kinetics of amorphization in crystalline SiO{sub 2} ({alpha}-quartz) under irradiation with swift heavy ions (O{sup +1} at 4 MeV, O{sup +4} at 13 MeV, F{sup +2} at 5 MeV, F{sup +4} at 15 MeV, Cl{sup +3} at 10 MeV, Cl{sup +4} at 20 MeV, Br{sup +5} at 15 and 25 MeV and Br{sup +8} at 40 MeV) has been analyzed in this work with an Avrami-type law and also with a recently developed cumulative approach (track-overlap model). This latter model assumes a track morphology consisting of an amorphous core (area {sigma}) and a surrounding defective halo (area h), both being axially symmetric. The parameters of the two approaches which provide the best fit to the experimental data have been obtained as a function of the electronic stopping power S{sub e}. The extrapolation of the {sigma}(S{sub e}) dependence yields a threshold value for amorphization, S{sub th} Almost-Equal-To 2.1 keV/nm; a second threshold is also observed around 4.1 keV/nm. We believe that this double-threshold effect could be related to the appearance of discontinuous tracks in the region between 2.1 and 4.1 keV/nm. For stopping power values around or below the lower threshold, where the ratio h/{sigma} is large, the track-overlap model provides a much better fit than the Avrami function. Therefore, the data show that a right modeling of the amorphization kinetics needs to take into account the contribution of the defective track halo. Finally, a short comparative discussion with the kinetic laws obtained for elastic collision damage is given.

  5. ER Alpha Rapid Signaling Is Required for Estrogen Induced Proliferation and Migration of Vascular Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs, which likely underlies its ability to accelerate re-endothelialization and reduce adverse remodeling after vascular injury. In previous studies, we have shown that the protective effects of E2 (the active endogenous form of estrogen in vascular injury require the estrogen receptor alpha (ERα. ERα transduces the effects of estrogen via a classical DNA binding, "genomic" signaling pathway and via a more recently-described "rapid" signaling pathway that is mediated by a subset of ERα localized to the cell membrane. However, which of these pathways mediates the effects of estrogen on endothelial cells is poorly understood. Here we identify a triple point mutant version of ERα (KRR ERα that is specifically defective in rapid signaling, but is competent to regulate transcription through the "genomic" pathway. We find that in ECs expressing wild type ERα, E2 regulates many genes involved in cell migration and proliferation, promotes EC migration and proliferation, and also blocks the adhesion of monocytes to ECs. ECs expressing KRR mutant ERα, however, lack all of these responses. These observations establish KRR ERα as a novel tool that could greatly facilitate future studies into the vascular and non-vascular functions of ERα rapid signaling. Further, they support that rapid signaling through ERα is essential for many of the transcriptional and physiological responses of ECs to E2, and that ERα rapid signaling in ECs, in vivo, may be critical for the vasculoprotective and anti-inflammatory effects of estrogen.

  6. Differential effects of alpha-adrenoceptor blockade on essential, physiological and isoprenaline-induced tremor: evidence for a central origin of essential tremor.

    OpenAIRE

    Abila, B; Wilson, J F; Marshall, R W; Richens, A

    1985-01-01

    Intravenous thymoxamine reduced the power of essential tremor but increased that of physiological and isoprenaline-induced tremor. These findings indicate that essential and physiological tremor have dissimilar pathophysiological mechanisms. They also suggest that central adrenergic mechanisms are involved in the pathophysiology of essential tremor and that isoprenaline-induced tremor is not a good model of essential tremor. Furthermore, alpha-adrenoceptor blockers may be a useful therapy for...

  7. Expression of transforming growth factor alpha and epidermal growth factor receptor in rat lung neoplasms induced by plutonium-239

    International Nuclear Information System (INIS)

    Stegelmeier, B.L.; Gillett, N.A.; Hahn, F.F.; Kelly, G.; Rebar, A.H.

    1994-01-01

    Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239 PuO 2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-α) and epidermal growth factor receptor (EGFR). Expression of TGF-α protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-α. Many neoplasms expressing TGF-α also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-α were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation. 44 refs., 4 figs., 1 tab

  8. Alpha-ketoglutarate enhances freeze-thaw tolerance and prevents carbohydrate-induced cell death of the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Bayliak, Maria M; Hrynkiv, Olha V; Knyhynytska, Roksolana V; Lushchak, Volodymyr I

    2018-01-01

    Stress resistance and fermentative capability are important quality characteristics of baker's yeast. In the present study, we examined protective effects of exogenous alpha-ketoglutarate (AKG), an intermediate of the tricarboxylic acid cycle and amino acid metabolism, against freeze-thaw and carbohydrate-induced stresses in the yeast Saccharomyces cerevisiae. Growth on AKG-supplemented medium prevented a loss of viability and improved fermentative capacity of yeast cells after freeze-thaw treatment. The cells grown in the presence of AKG had higher levels of amino acids (e.g., proline), higher metabolic activity and total antioxidant capacity, and higher activities of catalase, NADP-dependent glutamate dehydrogenase and glutamine synthase compared to control ones. Both synthesis of amino acids and enhancement of antioxidant system capacity could be involved in AKG-improved freeze-thaw tolerance in S. cerevisiae. Cell viability dramatically decreased under incubation of stationary-phase yeast cells in 2% glucose or fructose solutions (in the absence of the other nutrients) as compared with incubation in distilled water or in 10 mM AKG solution. The decrease in cell viability was accompanied by acidification of the medium, and decrease in cellular respiration, aconitase activity, and levels of total protein and free amino acids. The supplementation with 10 mM AKG effectively prevented carbohydrate-induced yeast death. Protective mechanisms of AKG could be associated with the intensification of respiration and prevention of decreasing protein level as well as with direct antioxidant AKG action.

  9. Prophylactic effect of four prescriptions of traditional Chinese medicine on alpha-naphthylisothiocyanate and carbon tetrachloride induced toxicity in rats.

    Science.gov (United States)

    Lin, K J; Chen, J C; Tsauer, W; Lin, C C; Lin, J G; Tsai, C C

    2001-12-01

    To study the prophylactic effects of four Chinese traditional prescriptions against experimental liver injury. Liver toxins, alpha-naphthylisothiocyanate (ANIT), and carbon tetrachloride (CCl4) were used to induce acute liver injury. Simo Yin(SMY), Guizhi Fuling Wan (GFW), Xieqing Wan (XQW), and Sini San (SNS) were fed (500 mg/kg, in saline, po) to the rats before toxin administration. All the animals were killed 48 h after toxin insulted. Serum index of liver function and hepatic lipid peroxidation (LPO) were estimated. Histopathological observation was conducted simultaneously. The rats treated with ANIT exhibited elevations of serum total bilirubin (TBI), alkaline phosphatase (ALP), glutamate-oxalate- transaminase (GOT), glutamate-pyruvate-transaminase (GPT), as well as cholestasis and parenchyma necrosis. In rats, challenged with ANIT, receiving the pre-treatment of prescriptions of SMY, XQW, and SNS, the biochemical and morphological parameters of liver injury were significantly reduced. The increased LPO level in liver tissue, associated with the provoked serum GOT and GPT levels were the salient features observed in CCl4-insulting rats. Pre-treatment of four prescriptions showed a remarkable protective effect, and also was effective in counteracting the free radical toxicity by bringing about a significant decrease in peroxidative level. These recipes ameliorate liver damage induced by both ANIT and CCl4 despite the differences in their mechanisms of injury. Therefore they may be able to exert hepatoprotective effects through more than one mechanism of action because they contained a mixture of anti-hepatotoxic ingredients with mutual reinforcement and assistance.

  10. Interferon-alpha-induced destructive thyroiditis followed by Graves' disease in a patient with chronic hepatitis C: a case report.

    Science.gov (United States)

    Kim, Bu Kyung; Choi, Young Sik; Park, Yo Han; Lee, Sang Uk

    2011-12-01

    Interferon-induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon-alpha (IFN-α) therapy. But, destructive thyroiditis followed by Graves' disease associated with IFN-α therapy is very rarely reported. Herein, we report a rare case of pegylated IFN-α (pegIFN-α) induced destructive thyroiditis followed by Graves' disease in a patient with HCV infection. A 31-yr-old woman suffered from chronic active hepatitis C and was treated with pegIFN-α and ribavirin for 12 months. Results of a thyroid function test and autoantibody levels were normal before IFN-α therapy was initiated. Destructive thyrotoxicosis appeared seven months after the initiation of IFN-α therapy, followed by Graves' thyrotoxicosis two months after the cessation of therapy. The diagnoses of destructive thyroiditis and Graves' disease were confirmed by the presence of TSH receptor antibodies in addition to Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer increased gradually during IFN-α therapy and remained weakly positive after IFN-α therapy was discontinued.

  11. Contribution to the study of the effects of {alpha}-irradiation in nuclear glasses; Contribution a l'etude des effets de l'irradiation {alpha} sur les verres nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, A

    2001-07-01

    The main topic of this work is to characterise the effects of {alpha}-disintegration in nuclear waste glasses. Experimental and numerical approaches have been considered. The structure of the French nuclear waste glass (R7T7) has been simulated using four- and six-oxides simplified glasses which contain the main elements of the R7T7 glass: SiO{sub 2}, B{sub 2}O{sub 3}, Na{sub 2}O, ZrO{sub 2}, Al{sub 2}O{sub 3} and CaO. Four- and six-oxides glasses have been irradiated with 1 MeV-He{sup +} (ionisation) and 2.1 MeV-Kr{sup 3+} (ionisation and atomic collisions) ions in order to reproduce the effects of the {alpha}-particle and of the recoil nucleus emitted during {alpha}-disintegration of actinides, and also to differentiate electronic and ballistic effects. Irradiated glasses have been characterised using several techniques, which have been adapted to the peculiarities of our samples (isolated material, small irradiated depth). The results point out the salient role of sodium in the observed modifications: depth concentration profiles obtained with RBS show an accumulation of sodium at the irradiated surface. We found a apparent acceleration of sodium release in leaching experiments which confirm that point. Modifications observed in Raman spectra of irradiated glasses show an increase of the polymerisation (increase of Q{sub 3}/Q{sub 2} ratio) due to sodium migration. In simplified glasses we have found that the modifications of mechanical properties by external irradiations reproduce the modifications observed in actinide doped nuclear glass (decrease of hardness and increase of fracture toughness). At the same time, we performed Molecular Dynamics simulations of a six-oxides glass. We have shown that the surface modifies the glass structure down to a depth of 10 Angstrom: modification of depth concentration profiles, decrease of the atomic coordination number (A1, B and Si). During cascades, we found that atomic displacements are easier near the surface. This

  12. Detecting special nuclear material using muon-induced neutron emission

    Energy Technology Data Exchange (ETDEWEB)

    Guardincerri, Elena; Bacon, Jeffrey; Borozdin, Konstantin; Matthew Durham, J.; Fabritius II, Joseph [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Hecht, Adam [University of New Mexico, Albuquerque, NM 87131 (United States); Milner, Edward C. [Southern Methodist University, Dallas, TX 75205 (United States); Miyadera, Haruo; Morris, Christopher L. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Perry, John [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); University of New Mexico, Albuquerque, NM 87131 (United States); Poulson, Daniel [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

    2015-07-21

    The penetrating ability of cosmic ray muons makes them an attractive probe for imaging dense materials. Here, we describe experimental results from a new technique that uses neutrons generated by cosmic-ray muons to identify the presence of special nuclear material (SNM). Neutrons emitted from SNM are used to tag muon-induced fission events in actinides and laminography is used to form images of the stopping material. This technique allows the imaging of SNM-bearing objects tagged using muon tracking detectors located above or to the side of the objects, and may have potential applications in warhead verification scenarios. During the experiment described here we did not attempt to distinguish the type or grade of the SNM.

  13. Investigation of Activation Cross-Sections of Alpha-Induced Nuclear Reactions on Natural Silver

    International Nuclear Information System (INIS)

    Shahid, Muhammad; Kim, Kwangsoo; Naik, Haladhara; Zaman, Muhammad; Kang, Sinchul; Huh, Changgi; Kim, Guinyun

    2015-01-01

    The purpose was to study the production route of some radioisotopes applicable in medicine and industry. The measured results were compared with literature data and theoretical values. The nat Ag(α,x) reaction has already been studied for different energy ranges. However, the literature data needed new data set to increase the reliability of the reported results. The current experimental work will be helpful to make the literature data more reliable and to modify the theoretical models. The literature data needed new data set to increase the reliability of the reported results. The current experimental work is helpful to make the literature data more reliable and to modify the theoretical models

  14. Alpha-Tocopherol Counteracts the Cytotoxicity Induced by Ochratoxin A in Primary Porcine Fibroblasts

    DEFF Research Database (Denmark)

    Fusi, Elenora; Rebucci, Raffaella; Pecorini, Chiara

    2010-01-01

    The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in counteracting its toxicity....... Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM α-tocopherol significantly (P tocopherol...

  15. Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

    International Nuclear Information System (INIS)

    Han Wei; Zhu Lingyan; Jiang Erkang; Wang Jun; Chen Shaopeng; Bao Linzhi; Zhao Ye; Xu An; Yu Zengliang; Wu Lijun

    2007-01-01

    Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of γ-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process ( G -methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effectively inhibited both in 0.2 cGy α-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose α-particle irradiation and nitric oxide generated by irradiation was also very important in this process

  16. Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human beta-defensin 2 in middle ear epithelial cells

    Directory of Open Access Journals (Sweden)

    Park Raekil

    2006-01-01

    Full Text Available Abstract Background We recently showed that beta-defensins have antimicrobial activity against nontypeable Haemophilus influenzae (NTHi and that interleukin 1 alpha (IL-1 alpha up-regulates the transcription of beta-defensin 2 (DEFB4 according to new nomenclature of the Human Genome Organization in human middle ear epithelial cells via a Src-dependent Raf-MEK1/2-ERK signaling pathway. Based on these observations, we investigated if human middle ear epithelial cells could release IL-1 alpha upon exposure to a lysate of NTHi and if this cytokine could have a synergistic effect on beta-defensin 2 up-regulation by the bacterial components. Methods The studies described herein were carried out using epithelial cell lines as well as a murine model of acute otitis media (OM. Human cytokine macroarray analysis was performed to detect the released cytokines in response to NTHi exposure. Real time quantitative PCR was done to compare the induction of IL-1 alpha or beta-defensin 2 mRNAs and to identify the signaling pathways involved. Direct activation of the beta-defensin 2 promoter was monitored using a beta-defensin 2 promoter-Luciferase construct. An IL-1 alpha blocking antibody was used to demonstrate the direct involvement of this cytokine on DEFB4 induction. Results Middle ear epithelial cells released IL-1 alpha when stimulated by NTHi components and this cytokine acted in an autocrine/paracrine synergistic manner with NTHi to up-regulate beta-defensin 2. This synergistic effect of IL-1 alpha on NTHi-induced beta-defensin 2 up-regulation appeared to be mediated by the p38 MAP kinase pathway. Conclusion We demonstrate that IL-1 alpha is secreted by middle ear epithelial cells upon exposure to NTHi components and that it can synergistically act with certain of these molecules to up-regulate beta-defensin 2 via the p38 MAP kinase pathway.

  17. Gamma radiation induced changes in nuclear waste glass containing Eu

    Science.gov (United States)

    Mohapatra, M.; Kadam, R. M.; Mishra, R. K.; Kaushik, C. P.; Tomar, B. S.; Godbole, S. V.

    2011-10-01

    Gamma radiation induced changes were investigated in sodium-barium borosilicate glasses containing Eu. The glass composition was similar to that of nuclear waste glasses used for vitrifying Trombay research reactor nuclear waste at Bhabha Atomic Research Centre, India. Photoluminescence (PL) and electron paramagnetic resonance (EPR) techniques were used to study the speciation of the rare earth (RE) ion in the matrix before and after gamma irradiation. Judd-Ofelt ( J- O) analyses of the emission spectra were done before and after irradiation. The spin counting technique was employed to quantify the number of defect centres formed in the glass at the highest gamma dose studied. PL data suggested the stabilisation of the trivalent RE ion in the borosilicate glass matrix both before and after irradiation. It was also observed that, the RE ion distributes itself in two different environments in the irradiated glass. From the EPR data it was observed that, boron oxygen hole centre based radicals are the predominant defect centres produced in the glass after irradiation along with small amount of E’ centres. From the spin counting studies the concentration of defect centres in the glass was calculated to be 350 ppm at 900 kGy. This indicated the fact that bulk of the glass remained unaffected after gamma irradiation up to 900 kGy.

  18. Laser induced breakdown spectroscopy for applications in nuclear industry

    International Nuclear Information System (INIS)

    Suri, B.M.

    2010-01-01

    There are several analytical techniques employing laser spectroscopy - each with its own distinctive potential. Laser Induced Breakdown Spectroscopy (LIBS) is one such technique which is attractive in view of its relative compactness and simplicity (in configuration), remote and online analysis (with no sample handling requirement) and high spatial resolution allowing compositional map or homogeneity analysis. In this technique, a high power pulsed (mostly nanosecond) laser is employed to irradiate the sample causing spark emission, characteristics of the sample composition, which is collected using suitable optics and analysed spectroscopically. Remote and online capability is derived from long distance delivery of laser beams and collection of emitted light by fibres or conventional optics. Since laser can be focused sharply on the target, it can facilitate compositional mapping. Beam Technology Development Group at BARC had initiated work on LIBS of nuclear materials several years ago. Recently the challenge of online monitoring of radioactive waste vitrification plant in a hot cell has been taken up. The theoretical and experimental work done by the group related to instrument development, plasma characterization, quantitative compositional analysis of ternary alloys and uranium vitrified glass samples (comprising more than dozen elements) are described. The future plans for setting up online glass homogeneity monitoring facility are also described. This should fulfill an important demand for optimization of vitrification process. Various other demands of nuclear industry are also reviewed

  19. A peptide derived from alpha-fetoprotein inhibits the proliferation induced by estradiol in mammary tumor cells in culture.

    Science.gov (United States)

    Sierralta, Walter D; Epuñan, Maria J; Reyes, José M; Valladares, Luis E; Andersen, Thomas T; Bennett, James A; Jacobson, Herbert I; Pino, Ana M

    2008-01-01

    This study was aimed to obtain additional information on the activity of a cyclized 9-amino acid peptide (cP) containing the active site of alpha fetoprotein, which inhibits the estrogen-stimulated proliferation of tumor cells in culture and of xenografts in immunodeficient mice. Breast cancer cells cultured in the presence of 2 nM estradiol were exposed to cP for different periods and their proliferation, estradiol binding parameters, clustering tendency and expression of E-cadherin and p21Cip1 were analyzed by biochemical and cell biology methods. The proliferation of MCF7 cells was significantly decreased by the addition of 2 microg/ml cP to the medium. cP did not increase cell death rate nor alter the number of binding sites for estradiol nor the endogenous aromatase activity of MCF7 cells. cP also decreased the proliferation of estrogen-dependent ZR75-1 cells but had no effect on estrogen-independent MDA-MB-231 cells. An increased nuclear p21Cip1 expression detected after cP treatment suggests that cP slows MCF7 cell proliferation via this regulator. We propose that cP could represent a novel breast cancer therapeutic agent whose mechanism of action is different from that of tamoxifen or of inhibitors of aromatase.

  20. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    LENUS (Irish Health Repository)

    Gupta, Sanjeev

    2010-01-01

    Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha\\/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  1. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    Directory of Open Access Journals (Sweden)

    Sanjeev Gupta

    2010-07-01

    Full Text Available Endoplasmic reticulum (ER stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR. Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  2. Cow's milk increases the activities of human nuclear receptors peroxisome proliferator-activated receptors alpha and delta and retinoid X receptor alpha involved in the regulation of energy homeostasis, obesity, and inflammation.

    Science.gov (United States)

    Suhara, W; Koide, H; Okuzawa, T; Hayashi, D; Hashimoto, T; Kojo, H

    2009-09-01

    The nuclear peroxisome proliferator-activated receptors (PPAR) have been shown to play crucial roles in regulating energy homeostasis including lipid and carbohydrate metabolism, inflammatory responses, and cell proliferation, differentiation, and survival. Because PPAR agonists have the potential to prevent or ameliorate diseases such as hyperlipidemia, diabetes, atherosclerosis, and obesity, we have explored new natural agonists for PPAR. For this purpose, cow's milk was tested for agonistic activity toward human PPAR subtypes using a reporter gene assay. Milk increased human PPARalpha activity in a dose-dependent manner with a 3.2-fold increase at 0.5% (vol/vol). It also enhanced human PPARdelta activity in a dose-dependent manner with an 11.5-fold increase at 0.5%. However, it only slightly affected human PPARgamma activity. Ice cream, butter, and yogurt also increased the activities of PPARalpha and PPARdelta, whereas vegetable cream affected activity of PPARdelta but not PPARalpha. Skim milk enhanced the activity of PPAR to a lesser degree than regular milk. Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta. Both milk and fresh cream were shown by quantitative real-time PCR to increase the quantity of mRNA for uncoupling protein 2 (UCP2), an energy expenditure gene, in a dose-dependent manner. The increase in UCP2 mRNA was found to be reduced by treatment with PPARdelta-short interfering (si)RNA. This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha. The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.

  3. PGC-1alpha in exercise- and exercise training-induced metabolic adaptations

    DEFF Research Database (Denmark)

    Jørgensen, Stine Ringholm

    and interferes with the exercise-induced adaptive response in human skeletal muscle. Study II demonstrates that mouse liver glucose-6-phosphatase (G6Pase) mRNA content increased in recovery from acute exercise in both wildtype (WT) and PGC-1α knockout (KO) mice, while phosphoenolpyruvate carboxykinase (PEPCK......) and pyruvate carboxylase mRNA content did not change in either genotype. Exercise training increased PEPCK protein content in both WT and PGC-1α KO mice. In addition, the mRNA and protein content of cytochrome (Cyt) c and cytochrome c oxidase (COX) subunit I increased in response to acute exercise and exercise...

  4. Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury.

    Science.gov (United States)

    Proper, Steven P; Saini, Yogesh; Greenwood, Krista K; Bramble, Lori A; Downing, Nathaniel J; Harkema, Jack R; Lapres, John J

    2014-02-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2α(Δ/Δ)) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2α(Δ/Δ) mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2α(Δ/Δ) and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung.

  5. Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

    Directory of Open Access Journals (Sweden)

    Gunduz Feyza

    2012-08-01

    Full Text Available Abstract Background Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC patients. The mechanism of response to interferon-alpha (IFN-α therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV replication and IFN-α antiviral response in a cell culture model. Methods Sub-genomic replicon (S3-GFP and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. Results FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. Conclusion These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN

  6. Different effects of ursodeoxycholic acid on intrahepatic cholestasis in acute and recovery stages induced by alpha-naphthylisothiocyanate in mice.

    Science.gov (United States)

    Zhang, Linlin; Su, Huizong; Li, Yue; Fan, Yujuan; Wang, Qian; Jiang, Jian; Hu, Yiyang; Chen, Gaofeng; Tan, Bo; Qiu, Furong

    2018-03-01

    The aim of this study was to determine the effect of ursodeoxycholic acid (UDCA) on the alpha-naphthylisothiocyanate (ANIT)-induced acute and recovery stage of cholestasis model mice. In the acute stage of model mice, pretreatment with UDCA (25, 50, and 100 mg·kg -1 , ig) for 12 days prior to ANIT administration (50 mg·kg -1 , ig) resulted in the dramatic increase in serum biochemistry, with aggrevation of bile infarcts and hepatocyte necrosis. The elevation of beta-muricholic acid (β-MCA), cholic acid (CA), and taurocholic acid (TCA) in serum and liver, and reduction of these bile acids (BAs) in bile was observed. In contrast, in the recovery stage of model mice, treatment with UDCA (25, 50, and 100 mg·kg -1 , ig) for 7 days after ANIT administration (50 mg·kg -1 , ig) resulted in the significant decrease in levels of serum alanine aminotransferase (ALT) and total bile acid (TBA). Liver injury was attenuated, and the levels of TBA, CA, TCA, and β-MCA in the liver were significantly decreased. Additionally, UDCA can upregulate expression of BSEP, but it cannot upregulate expression of AE2. UDCA, which induced BSEP to increase bile acid-dependent bile flow, aggravated cholestasis and liver injury when the bile duct was obstructed in the acute stage of injury in model mice. In contrast, UDCA alleviated cholestasis and liver injury induced by ANIT when the obstruction was improved in the recovery stage. Copyright © 2018. Published by Elsevier Inc.

  7. The use of alpha-methyl-D-glucoside, a synthetic analogue of maltose, as inducer of amylase by Aspergillus sp in solid-state and submerged fermentations

    OpenAIRE

    Moreira, Fabiana G.; Lenartovicz, Veridiana; Souza, Cristina G.M. de; Ramos, Edivan P.; Peralta, Rosane M.

    2001-01-01

    The use of a methyl-D-glucoside (alphaMG), a synthetic analogue of maltose, as carbon source and inducer of amylase synthesis to several species of Aspergillus was studied in submerged and solid-state fermentations. Among a group of ten species, A. tamarii, A. fumigatus and A. flavus were able to produce biomass and high specific amylolytic activity in submerged cultures containing alphaMG as the only carbon source. In solid state fermentation, the enrichment of basal wheat bran or corn cob m...

  8. Detection of stable isotopes with a (n,. cap alpha. ) nuclear reaction: application to the measurement of unidirectional fluxes of borate in a plant

    Energy Technology Data Exchange (ETDEWEB)

    Duval, Y; Thellier, M; Heurteaux, C; Wissocq, J C [Centre National de la Recherche Scientifique, Mont-Saint-Aignan (France). Lab. ' ' Echanges cellulaires' '

    1980-01-01

    The unidirectional influx of borate has been studied in Lemna minor plants with the aid of purified boron isotopes, /sup 10/B and /sup 11/B. Isotope /sup 10/B was detected specifically by nuclear reaction /sup 10/B(n, ..cap alpha..)/sup 7/Li in the presence of ''homogeneous'' detectors. Despite technical difficulties in performing the /sup 10/B-estimations in the plant samples themselves, the results obtained here were consistent with those of efflux experiments, published previously, where the /sup 10/B-measurements were performed in the external solution. Kinetic parameters of borate transports in Lemna minor have been calculated.

  9. Flow induced vibrational excitation of nuclear reactor structures

    International Nuclear Information System (INIS)

    Gibert, R.J.

    1979-01-01

    The pressure fluctuations generated by disturbed flows, encountered in nuclear reactors induce vibrations in the structures. In order to make forecastings for these vibrational levels, it is necessary to know the characteristics of the random pressure fluctuations induced in the walls by the main flow peculiarities of the circuits. This knowledge is essentially provided by experimentation which shows that most of the energy from these fluctuations is in the low frequency area. It is also necessary to determine the transfer functions of the fluid-structure coupled system. Given the frequency range of the excitations, a calculation of the characteristics of the first eigenmodes is generally sufficient. This calculation is carried out by finite element codes, the modal dampings being assessed separately. In this paper, emphasis is placed mainly on the analysis of the sources of excitation due to flow peculiarities. Some examples will also be given of assessments of vibrations in real structures (pipes, reactor internals, etc.) and of comparisons with the experimental results obtained on models or on a site [fr

  10. Role of PGC-1{alpha} in exercise and fasting induced adaptations in mouse liver

    DEFF Research Database (Denmark)

    Haase, Tobias Nørresø; Jørgensen, Stine Ringholm; Leick, Lotte

    2011-01-01

    The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)-¿ coactivator (PGC)-1a plays a role in regulation of several metabolic pathways. By use of whole body PGC-1a knockout (KO) mice we investigated the role of PGC-1a in fasting, acute exercise and exercise training ind...... role in regulation of Cyt c and COXI expression in the liver in response to a single exercise bout and prolonged exercise training, which implies that exercise training induced improvements in oxidative capacity of the liver is regulated by PGC-1a.......The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)-¿ coactivator (PGC)-1a plays a role in regulation of several metabolic pathways. By use of whole body PGC-1a knockout (KO) mice we investigated the role of PGC-1a in fasting, acute exercise and exercise training...... induced regulation of key proteins in gluconeogenesis and metabolism in the liver. In both wild type (WT) and PGC-1a KO mice liver, the mRNA content of the gluconeogenic proteins glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was upregulated during fasting. Pyruvate...

  11. Unilateral vestibular deafferentation-induced changes in calcium signaling-related molecules in the rat vestibular nuclear complex.

    Science.gov (United States)

    Masumura, Chisako; Horii, Arata; Mitani, Kenji; Kitahara, Tadashi; Uno, Atsuhiko; Kubo, Takeshi

    2007-03-23

    Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage-gated Ca(2+) channels (VGCC) and intracellular Ca(2+) signaling. Indeed, our previous microarray analysis showed an up-regulation of some calcium signaling-related genes such as the alpha2 subunit of L-type calcium channels, calcineurin, and plasma membrane Ca(2+) ATPase 1 (PMCA1) in the ipsilateral vestibular nuclear complex (VNC) following unilateral vestibular deafferentation (UVD). To further elucidate the role of calcium signaling-related molecules in vestibular compensation, we used a quantitative real-time polymerase chain reaction (PCR) method to confirm the microarray results and investigated changes in expression of these molecules at various stages of compensation (6 h to 2 weeks after UVD). We also investigated the changes in gene expression during Bechterew's phenomenon and the effects of a calcineurin inhibitor on vestibular compensation. Real-time PCR showed that genes for the alpha2 subunit of VGCC, PMCA2, and calcineurin were transiently up-regulated 6 h after UVD in ipsilateral VNC. A subsequent UVD, which induced Bechterew's phenomenon, reproduced a complete mirror image of the changes in gene expressions of PMCA2 and calcineurin seen in the initial UVD, while the alpha2 subunit of VGCC gene had a trend to increase in VNC ipsilateral to the second lesion. Pre-treatment by FK506, a calcineurin inhibitor, decelerated the vestibular compensation in a dose-dependent manner. Although it is still uncertain whether these changes in gene expression are causally related to the molecular mechanisms of vestibular compensation, this observation suggests that after increasing the Ca(2+) influx into the ipsilateral VNC neurons via up-regulated VGCC, calcineurin may be involved in their synaptic plasticity. Conversely, an up-regulation of PMCA2, a brain-specific Ca(2+) pump, would increase an efflux of Ca

  12. IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM.

    Science.gov (United States)

    Henness, Sheridan; van Thoor, Eveline; Ge, Qi; Armour, Carol L; Hughes, J Margaret; Ammit, Alaina J

    2006-06-01

    Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells. Here, we perform an in vitro study to show that although IL-17A did not induce secretion of the CXC chemokine IL-8 from ASM cells, IL-17A significantly potentiates TNF-alpha-induced IL-8 protein secretion and gene expression in a concentration- and time-dependent manner (P ASM cells, acting via a p38 MAPK-dependent posttranscriptional pathway to augment TNF-alpha-induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells.

  13. Modeling of SQS propagation induced by alpha ray in gas counters

    International Nuclear Information System (INIS)

    Nohtomi, A.; Narita, K.; Sakae, T.; Uozumi, Y.; Matoba, M.

    1995-01-01

    With reference to optical images of the self-quenching streamer (SQS), the authors have already proposed a possible mechanism of SQSs induced by α-rays. To check the validity of the mechanism, they have been designing a model for the computer simulation of the SQS propagation based on the newly proposed mechanism. In the present modeling, in order to calculate the growth of the discharge, a set of continuity equations for electrons and ions is numerically solved in a two-dimensional space. An electron supply process from the α-ray ionization track is assumed to be the dominant process for the streamer development instead of the conventional electron-supply process which is based on the photoionization in the gas media. The streamer propagation is simulated under the concept of two-region model. A first comparison between computed and experimental results shows a good agreement

  14. Boron-Proton Nuclear-Fusion Enhancement Induced in Boron-Doped Silicon Targets by Low-Contrast Pulsed Laser

    Directory of Open Access Journals (Sweden)

    A. Picciotto

    2014-08-01

    Full Text Available We show that a spatially well-defined layer of boron dopants in a hydrogen-enriched silicon target allows the production of a high yield of alpha particles of around 10^{9} per steradian using a nanosecond, low-contrast laser pulse with a nominal intensity of approximately 3×10^{16}  W cm^{−2}. This result can be ascribed to the nature of the long laser-pulse interaction with the target and with the expanding plasma, as well as to the optimal target geometry and composition. The possibility of an impact on future applications such as nuclear fusion without production of neutron-induced radioactivity and compact ion accelerators is anticipated.

  15. The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance.

    Science.gov (United States)

    Pincelli, A I; Brunani, A; Scacchi, M; Dubini, A; Borsotti, R; Tibaldi, A; Pasqualinotto, L; Maestri, E; Cavagnini, F

    2001-01-01

    The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA. We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. These data indicate

  16. Diffuse glomerular nodular lesions in diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha, an inheritant diabetic gene in humans.

    Directory of Open Access Journals (Sweden)

    Satoshi Hara

    Full Text Available Glomerular nodular lesions, known as Kimmelstiel-Wilson nodules, are a pathological hallmark of progressive human diabetic nephropathy. We have induced severe diabetes in pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha (HNF1α P291fsinsC, a maturity-onset diabetes of the young type-3 (MODY3 gene in humans. In this model, glomerular pathology revealed that formation of diffuse glomerular nodules commenced as young as 1 month of age and increased in size and incidence until the age of 10 months, the end of the study period. Immunohistochemistry showed that the nodules consisted of various collagen types (I, III, IV, V and VI with advanced glycation end-product (AGE and Nε-carboxymethyl-lysine (CML deposition, similar to those in human diabetic nodules, except for collagen type I. Transforming growth factor-beta (TGF-β was also expressed exclusively in the nodules. The ultrastructure of the nodules comprised predominant interstitial-type collagen deposition arising from the mesangial matrices. Curiously, these nodules were found predominantly in the deep cortex. However, diabetic pigs failed to show any of the features characteristic of human diabetic nephropathy; e.g., proteinuria, glomerular basement membrane thickening, exudative lesions, mesangiolysis, tubular atrophy, interstitial fibrosis, and vascular hyalinosis. The pigs showed only Armanni-Ebstein lesions, a characteristic tubular manifestation in human diabetes. RT-PCR analysis showed that glomeruli in wild-type pigs did not express endogenous HNF1α and HNF1β, indicating that mutant HNF1α did not directly contribute to glomerular nodular formation in diabetic pigs. In conclusion, pigs harboring the dominant-negative mutant human MODY3 gene showed reproducible and distinct glomerular nodules, possibly due to AGE- and CML-based collagen accumulation. Although the pathology differed in several respects from that of human glomerular nodular lesions, the

  17. Alpha-chymotrypcin ameliorates neuroinflammation and apoptosis characterizing Alzheimer's disease-induced in ovarictomized rats.

    Science.gov (United States)

    El Dayem, Samiha M Abd; Ahmed, Hanaa H; Metwally, Fateheya; Foda, Fatma M Aly; Shalby, Aziza B; Zaazaa, Asmaa M A

    2013-07-01

    Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Very little is known about the causes of AD, except that its end stages involve extensive neuronal loss and the appearance of distinctive neuropathological features. This study was under taken to investigate the role of α-chymotrypcin (α-ch) in management of AD-induced in ovariectomized rats. Sixty female Sprague Dawley rats were divided into four groups n=15, (1) normal control group (con), (2) group underwent surgery to remove ovaries (ovx control group), (3) ovx group received aluminum chloride in a dose of 17 mg/kg daily for 2 months to induce AD (AD group), (4) AD group treated with α-chymotrypcin (α-ch) at dose (8.1 unit/rat/day) which is equivalent to the recommended human dose (α-ch-treated group) for three months. At the end of the experimental period, rats were sacrificed; brain samples were obtained for different biochemical analyses and histopathological examination. The biochemical analyses included determination of tumor necrosis factor-α (TNF- α), IL-18, monocyte chemo attractant protein-1 MCP-1, FAS, B-cell lymphoma 2 (Bcl2). In comparison with normal control group, the ovx control group recorded significant increase in the brain levels of TNF-α, IL-18, MCP-1 and FAS. On the other hand, the brain level of Bcl2 was significantly decreased. Also, AD group showed a significant increase in TNF-α, IL-18, MCP-1 and FAS levels in brain tissue. In contrast, significant decrease in brain Bcl2 level was detected in AD group as compared to the ovx control group. However, the treatment of AD group with α-chymotrypcin caused an improvement in the most studied biochemical parameters as indicated by decreased brain levels of TNF-α, IL-18, MCP-1 and FAS accompanied with significant increase in the level of Bcl2 compared to AD group. Histopathological investigation of brain tissue of ovx rats administered with aluminum (AD group) showed AD plaques. While, AD group treated with

  18. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue

    Directory of Open Access Journals (Sweden)

    Liu Suling

    2008-07-01

    Full Text Available Abstract Background Conjugated linoleic acid (CLA, a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues. Methods The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction. Results The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E2 stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA

  19. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue

    International Nuclear Information System (INIS)

    Wang, Li-Shu; Huang, Yi-Wen; Liu, Suling; Yan, Pearlly; Lin, Young C

    2008-01-01

    Conjugated linoleic acid (CLA), a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues. The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction. The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E 2 ) stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam) and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA-MB-231 cells. These data, therefore, demonstrate that

  20. The measurement and modeling of alpha-particle-induced charge collection in dynamic memories

    International Nuclear Information System (INIS)

    Oldiges, P.J.

    1989-01-01

    This thesis addresses the problem of α-particle-induced charge collection in high-density dynamic random access memories. A novel technique for the measurement of charge collection in high-density memory cells and bit lines due to α-particle strikes was developed. The technique involves D.C. tests on simple test structures with an α-particle source on the device package as a lid. The advantages of this new measurement technique are: the method allows for in-situ measurements of charge collection on both MOS capacitors and bit lines found in present-day memories; the on-chip measurement technique minimizes errors due to external probes loading the device under test; the measurements can be controlled by a personal computer, with the data being able to be reduced on the same machine. Results obtained using this new measurement technique show that the charge collection is found to depend upon test-structure size and the configuration of its neighbors. Results of two-dimensional simulations of charge flow along the surface of an MOS capacitor from current injection due to an α-particle strike indicate that a spatial potential variation of 0.5V may occur between the point of current injection and capacitor edge for a 1M dRAM capacitor

  1. The histone deacetylase inhibitor, Vorinostat, represses hypoxia inducible factor 1 alpha expression through translational inhibition.

    Directory of Open Access Journals (Sweden)

    Darren M Hutt

    Full Text Available Hypoxia inducible factor 1α (HIF-1α is a master regulator of tumor angiogenesis being one of the major targets for cancer therapy. Previous studies have shown that Histone Deacetylase Inhibitors (HDACi block tumor angiogenesis through the inhibition of HIF-1α expression. As such, Vorinostat (Suberoylanilide Hydroxamic Acid/SAHA and Romidepsin, two HDACis, were recently approved by the Food and Drug Administration (FDA for the treatment of cutaneous T cell lymphoma. Although HDACis have been shown to affect HIF-1α expression by modulating its interactions with the Hsp70/Hsp90 chaperone axis or its acetylation status, the molecular mechanisms by which HDACis inhibit HIF-1α expression need to be further characterized. Here, we report that the FDA-approved HDACi Vorinostat/SAHA inhibits HIF-1α expression in liver cancer-derived cell lines, by a new mechanism independent of p53, prolyl-hydroxylases, autophagy and proteasome degradation. We found that SAHA or silencing of HDAC9 mechanism of action is due to inhibition of HIF-1α translation, which in turn, is mediated by the eukaryotic translation initiation factor--eIF3G. We also highlighted that HIF-1α translation is dramatically inhibited when SAHA is combined with eIF3H silencing. Taken together, we show that HDAC activity regulates HIF-1α translation, with HDACis such as SAHA representing a potential novel approach for the treatment of hepatocellular carcinoma.

  2. Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: Successful treatment with repeated TIPS and interferon alpha

    Directory of Open Access Journals (Sweden)

    Akoum Riad

    2009-01-01

    Full Text Available Polycythemia vera (PV is a common cause of Budd-Chiari syndrome (BCS and portal vein thrombosis (PVT. The postpartum period is a precipitating cofactor. An additional heparin-induced thrombocytopenia/thrombosis (HIT/T leads to a life-threatening condition in which transjugular intrahepatic portosystemic shunting (TIPS seems to be the only life-saving procedure. We describe the case of a subacute BCS and PVT in the late postpartum period. The diagnosis was established using CT scan, MRI, and Doppler ultrasonography of abdominal vessels and the laboratory findings were compatible with PV. After a successful creation of TIPS, a HIT/T worsened the hemorrhagic and thrombotic picture. TIPS procedure was successfully repeated and heparin was replaced with Fondaparinux and then vitamin K antagonist. The treatment with interferon alpha-2A, started after the normalization of liver functions, resulted in a complete remission within 6 months. The JAK2 V617F mutation clone remained undetectable after 2 years′ follow-up.

  3. Polymorphisms in the hypoxia-inducible factor 1 alpha gene in Mexican patients with preeclampsia: A case-control study

    Directory of Open Access Journals (Sweden)

    Nava-Salazar Sonia

    2011-03-01

    Full Text Available Abstract Background Although the etiology of preeclampsia is still unclear, recent work suggests that changes in circulating angiogenic factors play a key role in its pathogenesis. In the trophoblast of women with preeclampsia, hypoxia-inducible factor 1 alpha (HIF-1α is over-expressed, and induces the expression of non-angiogenic factors and inhibitors of trophoblast differentiation. This observation prompted the study of HIF-1α and its relation to preeclampsia. It has been described that the C1772T (P582S and G1790A (A588T polymorphisms of the HIF1A gene have significantly greater transcriptional activity, correlated with an increased expression of their proteins, than the wild-type sequence. In this work, we studied whether either or both HIF1A variants contribute to preeclampsia susceptibility. Results Genomic DNA was isolated from 150 preeclamptic and 105 healthy pregnant women. Exon 12 of the HIF1A gene was amplified by PCR, and the genotypes of HIF1A were determined by DNA sequencing. In preeclamptic women and controls, the frequencies of the T allele for C1772T were 4.3 vs. 4.8%, and the frequencies of the A allele for G1790A were 0.0 vs. 0.5%, respectively. No significant differences were found between groups. Conclusion The frequency of the C1772T and G1790A polymorphisms of the HIF1A gene is very low, and neither polymorphism is associated with the development of preeclampsia in the Mexican population.

  4. A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia.

    Science.gov (United States)

    Kim, Eosu; Park, Dong-Wha; Choi, Song-Hee; Kim, Jae-Jin; Cho, Hyun-Sang

    2008-04-01

    Weight gain and other metabolic disturbances have now become discouraging, major side effects of atypical antipsychotic drugs (AAPDs). The novel strategies required to counteract these serious consequences, however, should avoid modulating the activities of the neurotransmitter receptors involved because those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate-activated protein kinase is an enzyme that plays a pivotal role in energy homeostasis. We hypothesized that alpha-lipoic acid (ALA), which is known to modulate adenosine monophosphate-activated protein kinase activity in the hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain. We describe the case series of a 12-week ALA trial in schizophrenia patients treated with AAPDs. Two of 7 enrolled subjects were dropped from the study because of noncompliance and demand for new medication to treat depressive symptoms, respectively. The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080). Three subjects reported increased energy subjectively. The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg Depression Rating Scale did not vary significantly during the study. These preliminary data suggest the possibility that ALA can ameliorate the adverse metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended study is warranted.

  5. Alpha-Adrenoceptor Antagonists Improve Memory by Activating -methyl-D-Aspartate-Induced Ion Currents in the Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Chang Hee Kim

    2015-12-01

    Full Text Available Purpose: Alpha1 (α1-adrenoceptor antagonists are widely used to treat lower urinary tract symptoms. These drugs not only act on peripheral tissues, but also cross the blood-brain barrier and affect the central nervous system. Therefore, α1-adrenoceptor antagonists may enhance brain functions. In the present study, we investigated the effects of tamsulosin, an α1-adrenoceptor antagonist, on short-term memory, as well as spatial learning and memory, in rats. Methods: The step-down avoidance test was used to evaluate short-term memory, and an eight-arm radial maze test was used to evaluate spatial learning and memory. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining was performed in order to evaluate the effect of tamsulosin on apoptosis in the hippocampal dentate gyrus. Patch clamp recordings were used to evaluate the effect of tamsulosin on ionotropic glutamate receptors, such as N-methyl-D-aspartate (NMDA, amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, and kainate receptors, in hippocampal CA1 neurons. Results: Tamsulosin treatment improved short-term memory, as well as spatial learning and memory, without altering apoptosis. The amplitudes of NMDA-induced ion currents were dose-dependently increased by tamsulosin. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin. Conclusions: Tamsulosin enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus without initiating apoptosis. The present study suggests the possibility of using tamsulosin to enhance memory under normal conditions, in addition to its use in treating overactive bladder.

  6. Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis.

    Science.gov (United States)

    Wang, Xiaoyu; Zhang, Yiting; Lin, Haiyingjie; Liu, Yan; Tan, Yi; Lin, Jie; Gao, Fenze; Lin, Shaoqiang

    2017-01-22

    Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin. We found that the expression of ST3Gal3 has reverse correlation with the dosage of cisplatin used in both SKOV3 and HO8910PM cells, and high dose of cisplatin could down-regulate ST3Gal3 expression. We then examined the functional effects of ST3Gal3 knockdown in cancer cell lines using FACS analysis. The number of apoptotic cells was much higher in cells if ST3Gal3 expression was knocked down by siRNA and/or by treating cells with higher dosage of cisplatin in comparison to control cells. Interestingly, in HO8910PM cells with ST3Gal3 knockdown, the levels of caspase 8 and caspase 3 proteins increased, which was more obvious in cells treated with both ST3Gal3 knockdown and cisplatin, suggesting that ST3Gal3 knockdown synergistically enhanced cisplatin-induced apoptosis in ovarian cancer cells. Taken together, these results uncover an alternative mechanism of cisplatin-resistance through ST3Gal3 and open a window for effective prevention of chemoresistance and relapse of ovarian cancer by targeting ST3Gal3. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. High sensitivity boron quantification in bulk silicon using the {sup 11}B(p,{alpha}{sub 0}){sup 8}Be nuclear reaction

    Energy Technology Data Exchange (ETDEWEB)

    Moro, Marcos V.; Silva, Tiago F. da; Added, Nemitala; Rizutto, Marcia A.; Tabacniks, Manfredo H. [Instituto de Fisica da Universidade de Sao Paulo, C.P. 66318, 05315-970 Sao Paulo, SP (Brazil); Neira, John B.; Neto, Joao B. F. [Institute of Research Tecnology, Cidade Universitaria, SP, 05508-091 (Brazil)

    2013-05-06

    There is a great need to quantify sub-ppm levels of boron in bulk silicon. There are several methods to analyze B in Si: Nuclear Reaction Analysis using the {sup 11}B(p,{alpha}{sub 0}){sup 8}Be reaction exhibits a quantification limit of some hundreds ppm of B in Si. Heavy Ion Elastic Recoil Detection Analysis offers a detection limit of 5 to 10 at. ppm. Secondary Ion Mass Spectrometry is the method of choice of the semiconductor industry for the analysis of B in Si. This work verifies the use of NRA to quantify B in Si, and the corresponding detection limits. Proton beam with 1.6 up to 2.6 MeV was used to obtain the cross-section of the {sup 11}B(p,{alpha}{sub 0}){sup 8}Be nuclear reaction at 170 Degree-Sign scattering angle. The results show good agreementwith literature indicating that the quantification of boron in silicon can be achieved at 100 ppm level (high sensitivity) at LAMFI-IFUSP with about 16% uncertainty. Increasing the detection solid angle and the collected beam charge, can reduce the detection limit to less than 100 ppm meeting present technological needs.

  8. Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, Masashi [Kyoto University, Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto (Japan); Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kudo, Takashi; Konishi, Hiroaki; Miyano, Azusa; Ono, Masahiro; Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kuge, Yuji [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Mukai, Takahiro [Kyushu University, Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Fukuoka (Japan); Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Masahiro [Kyoto University, Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto (Japan)

    2010-08-15

    Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-{sup 123}I-iodobenzoyl)norbiotinamide ({sup 123}I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and {sup 123}I-IBB for rapid imaging of HIF-1-active tumours. Tumour-implanted mice were pretargeted with POS. After 24 h, {sup 125}I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between {sup 125}I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of {sup 125}I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1{alpha} immunohistochemistry. {sup 125}I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from {sup 125}I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of {sup 125}I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of {sup 125}I-IBB was heterogeneous and was significantly correlated with HIF-1{alpha}-positive regions (R=0.58, p<0.0001). POS pretargeting with {sup 123}I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours. (orig.)

  9. STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-{alpha}2b peptide

    Energy Technology Data Exchange (ETDEWEB)

    Blank, Viviana C.; Pena, Clara [Institute of Biochemistry and Biophysics (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956-C1113AAD Buenos Aires (Argentina); Roguin, Leonor P., E-mail: rvroguin@qb.ffyb.uba.ar [Institute of Biochemistry and Biophysics (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956-C1113AAD Buenos Aires (Argentina)

    2010-02-15

    In the search of mimetic peptides of the interferon-{alpha}2b molecule (IFN-{alpha}2b), we have previously designed and synthesized a chimeric cyclic peptide of the IFN-{alpha}2b that inhibits WISH cell proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-{alpha}2b stimulus. JNK and p44/42 pathways were not activated by the peptide in WISH cells. We also showed that STAT1 and STAT3 downregulation by RNA interference decreased the antiproliferative activity and the amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.

  10. Prognostic role of hypoxia-inducible factor-1 alpha expression in osteosarcoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Ren HY

    2016-03-01

    Full Text Available Hai-Yong Ren,1 Yin-Hua Zhang,1,2 Heng-Yuan Li,1 Tao Xie,1 Ling-Ling Sun,1 Ting Zhu,1 Sheng-Dong Wang,1 Zhao-Ming Ye1 1Department of Orthopaedics, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 2The First Department of Orthopaedics, Hospital of Zhejiang General Corps of Armed Police Forces, Jiaxing, People’s Republic of China Background: Hypoxia-inducible factor-1α (HIF-1α plays an important role in tumor progression and metastasis. A number of studies have investigated the association of HIF-1α with prognosis and clinicopathological characteristics of osteosarcoma but yielded inconsistent results.  Method: Systematic computerized searches were performed in PubMed, Embase, and Web of Science databases for relevant original articles. The pooled hazard ratios (HRs and odds ratios (ORs with corresponding confidence intervals (CIs were calculated to assess the prognostic value of HIF-1α expression. The standard mean difference was used to analyze the continuous variable.  Results: Finally, nine studies comprising 486 patients were subjected to final analysis. Protein expression level of HIF-1α was found to be significantly related to overall survival (HR =3.0; 95% CI: 1.46–6.15, disease-free survival (HR =2.23; 95% CI: 1.26–3.92, pathologic grade (OR =21.33; 95% CI: 4.60–98.88, tumor stage (OR =10.29; 95% CI: 3.55–29.82, chemotherapy response (OR =9.68; 95% CI: 1.87–50.18, metastasis (OR =5.06; 95% CI: 2.87–8.92, and microvessel density (standard mean difference =2.83; 95% CI: 2.28–3.39.  Conclusion: This meta-analysis revealed that overexpression of HIF-1α is a predictive factor of poor outcomes for osteosarcoma. HIF-1α appeared to play an important role in prognostic evaluation and may be a potential target in antitumoral therapy. Keywords: HIF-1α, osteosarcoma, prognosis, meta-analysis

  11. {alpha}-Tocopherol impact on oxy-radical induced free radical decomposition of DMSO: Spin trapping EPR and theoretical studies

    Energy Technology Data Exchange (ETDEWEB)

    Jerzykiewicz, Maria, E-mail: Mariaj@wchuwr.pl [Faculty of Chemistry, Wroclaw University, 14 F. Joliot-Curie St., 50-383 Wroclaw (Poland); Cwielag-Piasecka, Irmina; Witwicki, Maciej; Jezierski, Adam [Faculty of Chemistry, Wroclaw University, 14 F. Joliot-Curie St., 50-383 Wroclaw (Poland)

    2011-05-26

    Graphical abstract: {alpha}-Tocopherol inhibits the oxidation of {center_dot}CH{sub 3} to {center_dot}OCH{sub 3}. Display Omitted Highlights: {yields} {alpha}-Tocopherol does not inhibit the oxidation of DMSO to {center_dot}CH{sub 3}. {yields} {alpha}-Tocopherol inhibits the oxidation of {center_dot}CH{sub 3} to {center_dot}OCH{sub 3}. {yields} {alpha}-Tocopherol does not inhibit the oxidation of PBN. {yields} The structures of observed spin adducts were theoretically confirmed. - Abstract: EPR spin trapping and theoretical methods such as density functional theory (DFT) as well as combined DFT and quadratic configuration interaction approach (DFT/QCISD) were used to identify the radicals produced in the reaction of oxy-radicals and dimethyl sulfoxide (DMSO) in the presence and absence of {alpha}-tocopherol. Additionally, the mixtures of {alpha}-tocopherol with linolenic acid and glyceryl trilinoleate as well as bioglycerols (glycerol fractions from biodiesel production) were tested. {alpha}-Tocopherol inhibited oxidation of the main decomposition product of DMSO, {center_dot}CH{sub 3} to {center_dot}OCH{sub 3} but did not prevent the transformation process of N-t-butyl-{alpha}-phenylnitrone (PBN) into 2-methyl-2-nitrosopropane (MNP). Theoretical investigations confirmed the structures of proposed spin adducts and allowed to correlate the EPR parameters observed in the experiment with the spin adducts electronic structure.

  12. TNF alpha induces ABCA1 through NF-kappa B in macrophages and in phagocytes ingesting apoptotic cells

    NARCIS (Netherlands)

    Gerbod-Giannone, Marie-Christine; Li, Yankun; Holleboom, Adriaan; Han, Seongah; Hsu, Li-Chung; Tabas, Ira; Tall, Alan R.

    2006-01-01

    Recent evidence suggests that tumor necrosis factor alpha (TNF alpha) signaling in vascular cells can have antiatherogenic consequences, but the mechanisms are poorly understood. TNFa is released by free cholesterol loaded apoptotic macrophages, and the clearance of these cells by phagocytic

  13. Influence of some exo nucleases in response to the induced genetic damage in Escherichia coli by alpha radiation

    International Nuclear Information System (INIS)

    Aguilar M, M.

    2005-01-01

    Within the strategies with those that E. coli counts to overcome to the genetic damage there is the SOS response, a group of genes that participate in repair and/or tolerance that it confers to the bacteria major opportunities of surviving. These genes are repressed and its only are expressed when it happens genetic damage. So that this system is activated it is necessary that DNA of a band exists and in this sense the double ruptures (RDB) its are not able to induce this response unless there is a previous processing. In stumps with defects in certain genes that have to do with repair of RDB (as recO, recJ and xonA) the activity of SOS is smaller than in a wild stump what suggests that these participate in the previous processes to the activation of the response. The ionizing radiation produce among other many lesions, RDB in greater or smaller proportion, depending on the ionization capacity. A parameter to evaluate this capacity is the lineal energy transfer (LET), defined as the average energy given by unit of distance travelled. In general the LET of the corpuscular radiations is a lot but high that of the electromagnetic one, for what produces bigger quantity of ionizations inside a restricted zone and it increases by this way the probability that RDB has been generated. This work has for object to infer the participation of xonA and recJ in this response and to evaluate the damage produced by ionizing radiation of different LET (alpha particles of different energies) in a stump with all the functional repair mechanisms. Its were considered two parameters: the survival and the activity of SOS evaluated by means of the chromo test. The results indicate that the activity of these exo nucleases is necessary for the repair of RDB as well as for the processing of lesions foresaw to the activation of SOS. As for the treatment with alphas of different energies is observed that so much the survival like the activity of SOS vary as the LET of the radiation changes

  14. Nuclear Fusion Effects Induced in Intense Laser-Generated Plasmas

    Directory of Open Access Journals (Sweden)

    Lorenzo Torrisi

    2013-01-01

    Full Text Available Deutered polyethylene (CD2n thin and thick targets were irradiated in high vacuum by infrared laser pulses at 1015W/cm2 intensity. The high laser energy transferred to the polymer generates plasma, expanding in vacuum at supersonic velocity, accelerating hydrogen and carbon ions. Deuterium ions at kinetic energies above 4 MeV have been measured by using ion collectors and SiC detectors in time-of-flight configuration. At these energies the deuterium–deuterium collisions may induce over threshold fusion effects, in agreement with the high D-D cross-section valuesaround 3 MeV energy. At the first instants of the plasma generation, during which high temperature, density and ionacceleration occur, the D-D fusions occur as confirmed by the detection of mono-energetic protonsand neutrons with a kinetic energy of 3.0 MeV and 2.5 MeV, respectively, produced by the nuclear reaction. The number of fusion events depends strongly on the experimental set-up, i.e. on the laser parameters (intensity, wavelength, focal spot dimension, target conditions (thickness, chemical composition, absorption coefficient, presence of secondary targets and used geometry (incidence angle, laser spot, secondary target positions.A number of D-D fusion events of the order of 106÷7 per laser shot has been measured.

  15. Knockdown of hypoxia-inducible factor-1 alpha reduces proliferation, induces apoptosis and attenuates the aggressive phenotype of retinoblastoma WERI-Rb-1 cells under hypoxic conditions.

    Science.gov (United States)

    Xia, Tian; Cheng, Hao; Zhu, Yu

    2014-01-01

    Hypoxia-inducible factor-1 alpha (HIF-1α) plays a critical role in tumor cell adaption to hypoxia by inducing the transcription of numerous genes. The role of HIF-1α in malignant retinoblastoma remains unclear. We analyzed the role of HIF-1α in WERI-Rb-1 retinoblastoma cells under hypoxic conditions. CoCl2 (125 mmol/L) was added to the culture media to mimic hypoxia. HIF-1α was silenced using siRNA. Gene and protein expression were measured by semi-quantitative RT-PCR and Western blotting. Cell cycle and apoptosis were analyzed by flow cytometry. Cell proliferation, adhesion and invasion were assayed using MTT, Transwell invasion, and cell adhesion assays respectively. Hypoxia significantly upregulated HIF-1α protein expression and the HIF-1α target genes VEGF, GLUT1, and Survivin mRNA. HIF-1α mRNA expression was not affected by hypoxia. Transfection of the siRNA expression plasmid pRNAT-CMV3.2/Neo-HIF-1α silenced HIF-1α by approximately 80% in hypoxic WERI-Rb-1 cells. The knockdown of HIF-1α under hypoxic conditions downregulated VEGF, GLUT1, and Survivin mRNA. It also inhibited proliferation, promoted apoptosis, induced the G0/G1 phase cell cycle arrest, and reduced the adhesion and invasion of WERI-Rb-1 cells. HIF-1α plays a major role in the survival and aggressive phenotype of retinoblastoma cells under hypoxic conditions. Targeting HIF-1α may be a promising therapeutic strategy for human malignant retinoblastoma.

  16. C-terminal cleavage of DeltaNp63alpha is associated with TSA-induced apoptosis in immortalized corneal epithelial cells.

    Science.gov (United States)

    Robertson, Danielle M; Ho, Su-Inn; Cavanagh, H Dwight

    2010-08-01

    In the central human corneal epithelium, loss of DeltaNp63 occurs in all surface epithelial cells preparing to undergo desquamation, suggesting a potential role for DeltaNp63 isoforms in mediating surface cell apoptotic shedding. In this study, the authors investigated a role for DeltaNp63 isoforms in caspase-mediated apoptosis in a telomerase-immortalized corneal epithelial cell line. For in vitro studies, hTCEpi cells were cultured in KGM-2 serum-free culture media containing 0.15 mM calcium. To assess dynamic protein interactions among individual DeltaNp63 isoforms, DeltaNp63-EGFP expression plasmids were transiently expressed in hTCEpi cells and evaluated by FRAP. Trichostatin-A (TSA; 3.31 muM) was used to induce cell death as measured by caspase activity. Cleavage and loss of endogenous DeltaNp63alpha, DeltaNp63-EGFP expression plasmids, and p53 were assessed after treatment with TSA and siRNA. Transient expression of DeltaNp63-EGFP alpha and beta isoforms resulted in the formation of a smaller isoform similar in size to DeltaNp63gamma-EGFP. FRAP demonstrated that DeltaNp63alpha-EGFP has greater immobile fraction than beta or gamma. TSA induced caspase-mediated apoptotic pathways; caspase induction was accompanied by a decrease in endogenous DeltaNp63alpha and p53. TSA upregulated DeltaNp63-EGFP plasmid expression; this was accompanied by a selective increase in cleavage of DeltaNp63alpha-EGFP. siRNA knockdown of DeltaNp63alpha correlated with a reduction in p53 independently of TSA. DeltaNp63alpha is the dominant active isoform in corneal epithelial cell nuclei. Loss of DeltaNp63alpha occurs during apoptotic signaling by cleavage at the C terminus. The corresponding loss of p53 suggests that a significant relationship appears to exist between these two regulatory proteins.

  17. Adrenergic stimulation promotes T-wave alternans and arrhythmia inducibility in a TNF-alpha genetic mouse model of congestive heart failure.

    Science.gov (United States)

    Shusterman, Vladimir; McTiernan, Charles F; Goldberg, Anna; Saba, Samir; Salama, Guy; London, Barry

    2010-02-01

    T-wave alternans (TWA) is a proarrhythmic repolarization instability that is common in congestive heart failure (CHF). Although transgenic mice are commonly used to study the mechanisms of arrhythmogenesis in CHF, little is known about the dynamics of TWA in these species. We hypothesized that TWA is present in a TNF-alpha model of CHF and can be further promoted by adrenergic stimulation. We studied 16 TNF-alpha mice and 12 FVB controls using 1) in vivo intracardiac electrophysiological testing and 2) ambulatory telemetry during 30 min before and after an intraperitoneal injection of isoproterenol. TWA was examined using both linear and nonlinear filtering applied in the time domain. In addition, changes in the mean amplitude of the T wave and area under the T wave were computed. During intracardiac electrophysiological testing, none of the animals had TWA or inducible arrhythmias before the injection of isoproterenol. After the injection, sustained TWA and inducible ventricular tachyarrhythmias were observed in TNF-alpha mice but not in FVB mice. In ambulatory telemetry, before the isoproterenol injection, the cardiac cycle length (CL) was longer in TNF-alpha mice than in FVB mice (98 +/- 9 and 88 +/- 3 ms, P = 0.04). After the injection of isoproterenol, the CL became 8% and 6% shorter in TNF-alpha and FVB mice (P mice, the magnitude of TWA was 1.5-2 times greater than in FVB mice both before and after the isoproterenol injection. The magnitude of TWA increased significantly after the isoproterenol injection compared with the baseline in TNF-alpha mice (P = 0.003) but not in FVB mice. The mean amplitude of the T wave and area under the T wave increased 60% and 80% in FVB mice (P = 0.006 and 0.009) but not in TNF-alpha mice. In conclusion, TWA is present in a TNF-alpha model of CHF and can be further promoted by adrenergic stimulation, along with the enhanced susceptibility for ventricular arrhythmias.

  18. Anti-obesogenic effects of WY14643 (PPAR-alpha agonist): Hepatic mitochondrial enhancement and suppressed lipogenic pathway in diet-induced obese mice.

    Science.gov (United States)

    Veiga, Flavia Maria Silva; Graus-Nunes, Francielle; Rachid, Tamiris Lima; Barreto, Aline Barcellos; Mandarim-de-Lacerda, Carlos Alberto; Souza-Mello, Vanessa

    2017-09-01

    Non-alcoholic fatty liver disease (NAFLD) presents with growing prevalence worldwide, though its pharmacological treatment remains to be established. This study aimed to evaluate the effects of a PPAR-alpha agonist on liver tissue structure, ultrastructure, and metabolism, focusing on gene and protein expression of de novo lipogenesis and gluconeogenesis pathways, in diet-induced obese mice. Male C57BL/6 mice (three months old) received a control diet (C, 10% of lipids, n = 10) or a high-fat diet (HFD, 50% of lipids, n = 10) for ten weeks. These groups were subdivided to receive the treatment (n = 5 per group): C, C-alpha (PPAR-alpha agonist, 2.5 mg/kg/day mixed in the control diet), HFD and HFD-alpha group (PPAR-alpha agonist, 2.5 mg/kg/day mixed in the HFD). The effects were compared with biometrical, biochemical, molecular biology and transmission electron microscopy (TEM) analyses. HFD showed greater body mass (BM) and insulinemia than C, both of which were tackled by the treatment in the HFD-alpha group. Increased hepatic protein expression of glucose-6-phosphatase, CHREBP and gene expression of PEPCK in HFD points to increased gluconeogenesis. Treatment rescued these parameters in the HFD-alpha group, eliciting a reduced hepatic glucose output, confirmed by the smaller GLUT2 expression in HFD-alpha than in HFD. Conversely, favored de novo lipogenesis was found in the HFD group by the increased expression of PPAR-gamma, and its target gene SREBP-1, FAS and GK when compared to C. The treatment yielded a marked reduction in the expression of all lipogenic factors. TEM analyses showed a greater numerical density of mitochondria per area of tissue in treated than in untreated groups, suggesting an increase in beta-oxidation and the consequent NAFLD control. PPAR-alpha activation reduced BM and treated insulin resistance (IR) and NAFLD by increasing the number of mitochondria and reducing hepatic gluconeogenesis and de novo lipogenesis protein and gene

  19. Renin-angiotensin system inhibition ameliorates CCl4-induced liver fibrosis in mice through the inactivation of nuclear transcription factor kappa B.

    Science.gov (United States)

    Saber, Sameh; Mahmoud, Amr A A; Helal, Noha S; El-Ahwany, Eman; Abdelghany, Rasha H

    2018-06-01

    Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl 4 -induced liver fibrosis. Mice were treated with silymarin (30 mg·kg -1 ), perindopril (1 mg·kg -1 ), fosinopril (2 mg·kg -1 ), or losartan (10 mg·kg -1 ). The administration of RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline. These effects found to be mediated via inactivation of nuclear transcription factor kappa B (NFκB) pathway by the inhibition of NFκB p65 phosphorylation at the Ser536 residue and phosphorylation-induced degradation of nuclear factor kappa-B inhibitor alpha (NFκBia) subsequently inhibited NFκB-induced TNF-α and TGF-β1, leading to lower levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). We concluded that the tissue affinity of the angiotensin converting enzyme inhibitors (ACEIs) has no impact on its antifibrotic activity and that interfering the RAS either through the inhibition of ACE or the blockade of AT1R has the same therapeutic benefit. These results suggest RAS inhibitors as promising candidates for further clinical trials in the management of hepatic fibrosis.

  20. Nuclear IL-33 is a transcriptional regulator of NF-{kappa}B p65 and induces endothelial cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yeon-Sook; Park, Jeong Ae; Kim, Jihye; Rho, Seung-Sik; Park, Hyojin [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Young-Myeong [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon (Korea, Republic of); Kwon, Young-Guen, E-mail: ygkwon@yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer IL-33 as nuclear factor regulated expression of ICAM-1 and VCAM-1. Black-Right-Pointing-Pointer Nuclear IL-33 increased the transcription of NF-{kappa}B p65 by binding to the p65 promoter. Black-Right-Pointing-Pointer Nuclear IL-33 controls NF-{kappa}B-dependent inflammatory responses. -- Abstract: Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-{kappa}B complex and is involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-{alpha}-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-{kappa}B pathway; NF-{kappa}B p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-{kappa}B p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-{kappa}B p65.

  1. Calibration of sources for alpha spectroscopy systems

    International Nuclear Information System (INIS)

    Freitas, I.S.M.; Goncalez, O.L.

    1992-01-01

    This paper describes the calibration methodology for measuring the total alpha activity of plane and thin sources with the Alpha Spectrometer for Silicon Detector in the Nuclear Measures and Dosimetry laboratory at IEAv/CTA. (author)

  2. Ubiquitination is absolutely required for the degradation of hypoxia-inducible factor - 1 alpha protein in hypoxic conditions

    International Nuclear Information System (INIS)

    Wang, Ronghai; Zhang, Ping; Li, Jinhang; Guan, Hongzai; Shi, Guangjun

    2016-01-01

    The hypoxia-inducible factor (HIF) is recognized as the master regulator of hypoxia response. HIF-α subunits expression are tightly regulated. In this study, our data show that ts20 cells still expressed detectable E1 protein even at 39.5° C for 12 h, and complete depletion of E1 protein expression at 39.5° C by siRNA enhanced HIF-1α and P53 protein expression. Further inhibition of E1 at 39.5 °C by siRNA, or E1 inhibitor Ube1-41 completely blocked HIF-1α degradation. Moreover, immunoprecipitations of co-transfection of HA-ubiquitin and FLAG–HIF–1α plasmids directly confirmed the involvement of ubiquitin in the hypoxic degradation of HIF-1α. Additionally, hypoxic HIF-1 α degradation is independent of HAF, RACK1, sumoylation or nuclear/cytoplasmic localization. Taken together, our data suggest that constitutive HIF-1α protein degradation in hypoxia is absolutely ubiquitination-dependent, and unidentified E3 ligase may exist for this degradation pathway. - Highlights: • HIF-1α protein is constitutively degraded in hypoxic conditions. • Requirement of ubiquitination for HIF-1α degradation in hypoxia. • Hypoxic HIF-1α degradation is independent of HAF, RACK1, sumoylation or nuclear/cytoplasmic localization.

  3. Ubiquitination is absolutely required for the degradation of hypoxia-inducible factor - 1 alpha protein in hypoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ronghai [Department of Urology, Linzi District People' s Hospital, Zibo, 255400 (China); Zhang, Ping, E-mail: zpskx001@163.com [Department of Gynecology, Qingdao Municipal Hospital, Qingdao, 266011 (China); Li, Jinhang [Department of Gynecology, Qingdao Municipal Hospital, Qingdao, 266011 (China); Guan, Hongzai [Laboratory Department, School of Medicine, Qingdao University, Qingdao, 266071 (China); Shi, Guangjun, E-mail: qdmhshigj@yahoo.com [Department of Hepatobiliary Surgery, Qingdao Municipal Hospital, Qingdao, 266071 (China)

    2016-01-29

    The hypoxia-inducible factor (HIF) is recognized as the master regulator of hypoxia response. HIF-α subunits expression are tightly regulated. In this study, our data show that ts20 cells still expressed detectable E1 protein even at 39.5° C for 12 h, and complete depletion of E1 protein expression at 39.5° C by siRNA enhanced HIF-1α and P53 protein expression. Further inhibition of E1 at 39.5 °C by siRNA, or E1 inhibitor Ube1-41 completely blocked HIF-1α degradation. Moreover, immunoprecipitations of co-transfection of HA-ubiquitin and FLAG–HIF–1α plasmids directly confirmed the involvement of ubiquitin in the hypoxic degradation of HIF-1α. Additionally, hypoxic HIF-1 α degradation is independent of HAF, RACK1, sumoylation or nuclear/cytoplasmic localization. Taken together, our data suggest that constitutive HIF-1α protein degradation in hypoxia is absolutely ubiquitination-dependent, and unidentified E3 ligase may exist for this degradation pathway. - Highlights: • HIF-1α protein is constitutively degraded in hypoxic conditions. • Requirement of ubiquitination for HIF-1α degradation in hypoxia. • Hypoxic HIF-1α degradation is independent of HAF, RACK1, sumoylation or nuclear/cytoplasmic localization.

  4. Supernatants from Staphylococcus epidermidis grown in the presence of different antibiotics induce differential release of tumor necrosis factor alpha from human monocytes.

    OpenAIRE

    Mattsson, E; Van Dijk, H; Verhoef, J; Norrby, R; Rollof, J

    1996-01-01

    Bacterial products from gram-positive bacteria, such as peptidoglycan, teichoic acid, and toxins, activate mononuclear cells to produce tumor necrosis factor alpha (TNF). The present study evaluated the release of soluble cell wall components from Staphylococcus epidermidis capable of inducing TNF after exposure of the bacteria to various antibiotics. A clinical S. epidermidis isolate (694) was incubated with either penicillin, oxacillin, vancomycin, or clindamycin at five times the MIC. Supe...

  5. Light charged particle production in fast neutron-induced reactions on carbon (En=40 to 75 MeV) (II). Tritons and alpha particles

    International Nuclear Information System (INIS)

    Dufauquez, C.; Slypen, I.; Benck, S.; Meulders, J.P.; Corcalciuc, V.

    2000-01-01

    Double-differential cross sections for fast neutron-induced triton and alpha-particle production on carbon are reported at six incident neutron energies between 40 and 75 MeV. Angular distributions were measured at laboratory angles between 20 deg. and 160 deg. . Energy-differential, angle-differential and total cross sections are also reported. Experimental cross sections are compared to existing experimental data and to theoretical model calculations

  6. Prm3p is a pheromone-induced peripheral nuclear envelope protein required for yeast nuclear fusion.

    Science.gov (United States)

    Shen, Shu; Tobery, Cynthia E; Rose, Mark D

    2009-05-01

    Nuclear membrane fusion is the last step in the mating pathway of the yeast Saccharomyces cerevisiae. We adapted a bioinformatics approach to identify putative pheromone-induced membrane proteins potentially required for nuclear membrane fusion. One protein, Prm3p, was found to be required for nuclear membrane fusion; disruption of PRM3 caused a strong bilateral defect, in which nuclear congression was completed but fusion did not occur. Prm3p was localized to the nuclear envelope in pheromone-responding cells, with significant colocalization with the spindle pole body in zygotes. A previous report, using a truncated protein, claimed that Prm3p is localized to the inner nuclear envelope. Based on biochemistry, immunoelectron microscopy and live cell microscopy, we find that functional Prm3p is a peripheral membrane protein exposed on the cytoplasmic face of the outer nuclear envelope. In support of this, mutations in a putative nuclear localization sequence had no effect on full-length protein function or localization. In contrast, point mutations and deletions in the highly conserved hydrophobic carboxy-terminal domain disrupted both protein function and localization. Genetic analysis, colocalization, and biochemical experiments indicate that Prm3p interacts directly with Kar5p, suggesting that nuclear membrane fusion is mediated by a protein complex.

  7. The small-molecule TNF-alpha modulator, UTL-5g, reduces side effects induced by cisplatin and enhances the therapeutic effect of cisplatin in vivo.

    Science.gov (United States)

    Shaw, JiaJiu; Chen, Ben; Huang, Wen-Hsin; Lee, An-Rong; Media, Joseph; Valeriote, Frederick A

    2011-01-01

    We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by cisplatin treatment. The levels of both aspartate transaminase (AST) and alanine transaminase (ALT) in these animals were also reduced by UTL-5g. Pretreatment of UTL-5g did not significantly affect the number of white blood cells (WBC) under current experimental conditions, yet it markedly increased blood platelet counts by more than threefold. Therapeutic assessment in SCID mice inoculated with human HCT-15 tumor cells showed that UTL-5g did not attenuate the anti-tumor effect of cisplatin but increased the therapeutic efficacy of cisplatin. The LD50 of UTL-5g was determined to be > 2,000 mg/kg by an acute toxicity study. In summary, our studies showed that 1) UTL-5g significantly reduces nephrotoxicity and hepatotoxicity induced by cisplatin in mice, presumably by lowering the levels of TNF-alpha, 2) UTL-5g markedly increased blood platelet counts in mice and 3) UTL-5g treatment increased the therapeutic efficacy of cisplatin against HCT-15 cells inoculated in SCID mice.

  8. The Effect of Nigella Sativa Extract on Alpha-ketoglutarate Activity and Histopathologic Changes on Rat Liver Induced by Monosodium Glutamate

    Directory of Open Access Journals (Sweden)

    Ala Sh Emhemed Eshami

    2015-09-01

    Full Text Available Monosodium glutamate (MSG is a commonly used food additive and found in most soups, fish, and processed meat. The use of MSG in food is growing. However, the fear of consuming MSG has increased in the last few years due to the adverse reactions and toxicity in the liver. Nigella sativa (NS is used as traditional medicine for the treatment of many diseases. It has been extensively investigated in recent years due to its notable pharmacological properties such as inhibit oxidative stress. The present study was undertaken to investigate the effect of different doses of Nigella Sativa on alpha KGDH activity and liver histology of MSG-induced rats. The animals (n=30 were grouped into A (control, B (treated with MSG 1g/kg.bw , C (treated with MSG 1g/kg.bw and NS 0.1 g/kg.bw, D (treated with MSG 1g/kg.bw and NS 0.2 g/kg.bw, E (treated with MSG 1g/kg.bw and NS 0.4 g/kg.bw and F (given a daily NS extract 0.2 g/kg.bw. Alpha KGDH activity was investigated using ELISA method and liver histopathology by light microscope. The MSG treatment increased Alpha KGDH activity and disturbed liver architecture, hemorrhage in the central veins, areas of necrosis, vacuolation and increased inflammatory cells infiltration. The condition was normalized by treatment NS on dose 0.2 and 0.4 g/kg.bw. The findings showed that the administration of MSG increases alpha KGDH and induces damage in liver tissue. Nigella sativa extract can reduce alpha KGDH and prevent liver damage caused by MSG.

  9. [Genetic cloning and expression of hypoxia inducible factor 1 alpha in high altitude hypoxic adaptation species Tibetan antelope (Pantholops hodgsonii)].

    Science.gov (United States)

    Liu, Fang; Wuren, Tana; Ma, Lan; Yang, Ying-Zhong; Ge, Ri-Li

    2011-12-25

    In order to investigate the role of the hypoxia inducible factor 1 alpha (HIF-1α) in the adaptation mechanism to high altitude hypoxia, the cloning of the HIF-1α gene cDNA of Tibetan antelope (Pantholops hodgsonii), using RT-PCR and RACE, was applied, and the comparative analysis of the tissue-specific expressions of HIF-1α among Tibetan antelope, Tibetan sheep and plain sheep was performed using real-time PCR and Western blot. The sequence analysis indicated that the cDNA sequences acquired by cloning from the HIF-1α gene of Tibetan antelope comprised a 2 471-bp open reading frame (ORF) and a 1 911-bp 3'UTR. The similarity between its coding sequence, predicted amino acid sequence and HIF-1α of other mammals exceeded 87%, in which the similarity with cow was up to more than 98%, which showed that this sequence was the cDNA of HIF-1α of Tibetan antelope. The results of real-time PCR and Western blot showed that expressions of HIF-1α mRNA and protein appeared in Tibetan antelope's lung, cardiac muscle and skeletal muscle, with the highest expression in lung. HIF-1α mRNA and protein had obvious differential expression in these tissues. Further research showed that Tibetan antelope and Tibetan sheep possessed higher expressions of HIF-1α protein in the three tissues above-mentioned compared with plain sheep, and the expressions of HIF-1α mRNA and protein in Tibetan antelope's lung, cardiac muscle and skeletal muscle were higher than those of Tibetan sheep. It illustrates that the hypoxic HIF-1α-specific expression is one of the molecular bases of high altitude hypoxia adaptation in Tibetan antelope.

  10. Psychomotor retardation and vulnerability to interferon alpha induced major depressive disorder: Prospective study of a chronic hepatitis C cohort.

    Science.gov (United States)

    Whale, Richard; Fialho, Renata; Rolt, Michael; Eccles, Jessica; Pereira, Marco; Keller, Majella; File, Alexandra; Haq, Inam; Tibble, Jeremy

    2015-12-01

    Major depressive disorder (MDD) is a common consequence of interferon alpha (IFNα) treatment and important supporting evidence of a role of inflammation in the aetiology of depression. This study aimed to expand the knowledge of baseline clinical vulnerability characteristics to IFNα induced MDD, particularly exploring sub-threshold depressive symptoms. A prospective cohort of chronic HCV patients undergoing treatment with pegylated-IFNα and ribavirin was studied. MDD was assessed using the Structured Clinical Interview for DSM-IV (SCID-I). Depressive symptoms and severity were assessed at baseline and monthly with the Hamilton Depression Rating Scale (HAMD). Subjects with MDD or taking antidepressant treatment at baseline were excluded. 278 patients were assessed for this cohort with a final study sample of 190. 94.2% had contracted HCV through intravenous drug use. During six months IFNα treatment, 53.2% of patients transitioned to DSM-IV threshold MDD. In the multivariate logistic analysis, independent factors significantly associated with development of MDD were younger age (OR 0.96, 95% CI 0.93-1.00, p=0.028), past history of MDD (OR 3.82, 95% CI 1.63-8.92, p=0.002), baseline HAMD items psychomotor retardation (OR 15.21, 95% CI 1.33-173.41, p=0.032) and somatic symptoms (general) (OR 2.96, 95% CI 1.44-6.08, p=0.003), and HCV genotype 2 (OR 2.27, 95% CI 1.07-4.78, p=0.032). During IFNα treatment, the rate of transition to MDD was high in this cohort. Psychomotor retardation and somatic symptoms may represent a greater inflamed state pre-treatment. This iatrogenic model of MDD may offer important insights into wider depression aetiology. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model.

    Directory of Open Access Journals (Sweden)

    Clément Guillou

    Full Text Available To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1 or its immunodominant peptide (pEP1 to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way.Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight. Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP and anti-CII (total IgG and IgG1/IgG2a isotypes antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation.Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group.Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift.

  12. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model

    Science.gov (United States)

    Guillou, Clément; Derambure, Céline; Fréret, Manuel; Verdet, Mathieu; Avenel, Gilles; Golinski, Marie-Laure; Sabourin, Jean-Christophe; Loarer, François Le; Adriouch, Sahil; Boyer, Olivier; Lequerré, Thierry; Vittecoq, Olivier

    2015-01-01

    Objective To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way. Methods Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation. Results Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group. Conclusions Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift. PMID:26302382

  13. Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Tsukasaki, Masayuki [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Suzuki, Dai [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Aizawa, Ryo [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Miyazono, Agasa [Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Miyamoto, Yoichi; Suzawa, Tetsuo; Takami, Masamichi; Yoshimura, Kentaro [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Morimura, Naoko [Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan); Yamamoto, Matsuo [Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Kamijo, Ryutaro [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan)

    2011-07-15

    Highlights: {yields} TNF-{alpha} inhibits POEM gene expression. {yields} Inhibition of POEM gene expression is caused by NF-{kappa}B activation by TNF-{alpha}. {yields} Over-expression of POEM recovers inhibition of osteoblast differentiation by TNF-{alpha}. -- Abstract: POEM, also known as nephronectin, is an extracellular matrix protein considered to be a positive regulator of osteoblast differentiation. In the present study, we found that tumor necrosis factor-{alpha} (TNF-{alpha}), a key regulator of bone matrix properties and composition that also inhibits terminal osteoblast differentiation, strongly inhibited POEM expression in the mouse osteoblastic cell line MC3T3-E1. TNF-{alpha}-induced down-regulation of POEM gene expression occurred in both time- and dose-dependent manners through the nuclear factor kappa B (NF-{kappa}B) pathway. In addition, expressions of marker genes in differentiated osteoblasts were down-regulated by TNF-{alpha} in a manner consistent with our findings for POEM, while over-expression of POEM recovered TNF-{alpha}-induced inhibition of osteoblast differentiation. These results suggest that TNF-{alpha} inhibits POEM expression through the NF-{kappa}B signaling pathway and down-regulation of POEM influences the inhibition of osteoblast differentiation by TNF-{alpha}.

  14. TNF-alpha-induced apoptosis is prevented by erythropoietin treatment on SH-SY5Y cells

    International Nuclear Information System (INIS)

    Pregi, Nicolas; Wenker, Shirley; Vittori, Daniela; Leiros, Claudia Perez; Nesse, Alcira

    2009-01-01

    The growth factor erythropoietin (Epo) has shown neuronal protective action in addition to its well known proerythroid activity. Furthermore, Epo has dealt with cellular inflammation by inhibiting the expression of several proinflammatory cytokines, such as IL-1 and TNF-α. The action of TNF can have both apoptotic and antiapoptotic consequences due to altered balance between different cell signalling pathways. This work has focused on the apoptotic effects of this cytokine and the potential protective action of Epo. The model we used was neuroblastoma SH-SY5Y cells cultured in the presence of 25 ng/ml TNF-α or pretreated with 25 U/ml Epo for 12 h before the addition of TNF-α. Apoptosis was evaluated by differential cell count after Hoechst staining, analysis of DNA ladder pattern, and measurement of caspase activity. Despite its ability to induce NF-κB nuclear translocation, TNF-α induced cell death, which was found to be associated to upregulation of TNF Receptor 1 expression. On the other hand, cells activated by Epo became resistant to cell death. Prevention of death receptor upregulation and caspase activation may explain this antiapoptotic effect of Epo, which may be also favoured by the induction of a higher expression of protective factors, such as Bcl-2 and NF-κB, through mechanisms involving Jak/STAT and PI3K signalling pathways

  15. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    International Nuclear Information System (INIS)

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-01-01

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface

  16. Chymosin-induced hydrolysis of caseins: Influence of degree of phosphorylation of alpha-s1-casein and genetic variants of beta-casein

    NARCIS (Netherlands)

    Bijl, E.; Valenberg, van H.J.F.; Sikkes, S.; Jumelet, S.; Sala, G.; Olieman, K.; Hooijdonk, van A.C.M.; Huppertz, T.

    2014-01-01

    The objective of this study was to investigate the impact of natural variations in aS1-casein and b-casein composition of milk on chymosin-induced hydrolysis of these caseins in milk gels and in sodium caseinate solutions. At 50% casein degradation, 15% more of aS1-casein with eight phosphate groups

  17. Relative efficiency of the radiothermoluminescence induced by 238Pu alpha-particles in LiF:Mg, Al2O3 and CaSO4:Dy

    International Nuclear Information System (INIS)

    Vicy, Masok.

    1978-01-01

    This work represents a comparative study of the radiothermoluminescence (R.T.L.) induced by 60 Co gamma rays and 238 Pu alpha-particles in three R.T.L. materials: lithium fluoride, alumina and dysprosium activated calcium sulphate. The T.L. glow curves induced by the two radiations are very similar. However, for the same absorbed dose, different sensitivity is seen to each form of irradiation. Measurements of the relative R.T.L. efficiency, epsilon, were made in the linear zone (dose [fr

  18. MYC-induced nuclear antigen (MINA) and preeclampsia.

    Science.gov (United States)

    Martinez-Fierro, Margarita L; Reyes-Oliva, Edwin A; Cabral-Pacheco, Griselda A; Garza-Veloz, Idalia; Aceves-Medina, Maria C; Luevano, Martha; Barbosa-Cisneros, Olga Y; Galvan-Valencia, Marisol; Yahuaca-Mendoza, Patricia; Delgado-Enciso, Ivan; Zamudio-Osuna, Michelle; Rodriguez-Sanchez, Iram P; Vazquez-Castro, Rosbel; Guerrero-Saucedo, Marycruz

    2016-05-01

    Inadequate trophoblast invasion and the subsequent inflammatory response have been implicated in preeclampsia (PE) pathogenesis. Because MYC-induced nuclear antigen (MINA) gene expression is involved in cell proliferation and differentiation, inflammatory response modulation, and the unpaired regulation of which is associated with human diseases, we sought to investigate the connection between MINA and PE. The aim of this study was to evaluate the possible relationship between the MINA rs4857304 variant and susceptibility to PE development as well as to estimate placental MINA gene expression and its association with PE. About 242 pregnant women (126 PE cases and 116 controls) were included. MINA genotyping and gene expression were evaluated by quantitative real-time polymerase chain reaction using TaqMan probes. The G/G genotype of the MINA rs4857304 variant was associated with severe PE (p = 0.027, OR = 1.8, 95% CI = 1.8-3.2). Carriers of one G allele of the MINA rs4857304 variant exhibited a 1.7-fold increased risk of severe PE (p = 0.029, 95% CI = 1.1-3.0). MINA was underexpressed in preeclamptic placentas and MINA expression differed between the mild and severe PE groups. Differences in the expression levels of MINA were found among women with the T/T genotype of the rs4857304 polymorphism and carriers of at least one G allele (p = 0.024). PE and its severity are associated with the underexpression of placental MINA, and the G/G genotype of the MINA rs4857304 variant may modify the risk of severe PE among the PE cases evaluated.

  19. Evaluation of Cucurbita maxima extract against scopolamine-induced amnesia in rats: implication of tumour necrosis factor alpha.

    Science.gov (United States)

    Jawaid, Talha; Shakya, Ashok K; Siddiqui, Hefazat Hussain; Kamal, Mehnaz

    2014-01-01

    Cucurbita maxima (CM) seed oil is commonly used in Indian folk medicine to treat various ailments. We have investigated the effect of CM seed oil on memory impairment induced by scopolamine in rats. Male adult Wistar rats were administered scopolamine 1 mg/kg body weight, i.p. or 1.25 mg/kg body weight, s.c. to induce memory impairment. The nootropic agent piracetam 100 mg/kg body weight, i.p. and CM seed oil 100 and 200 mg/kg body weight, p.o. were administered daily for five consecutive days. The memory function was evaluated in the Morris water maze (MWM) test, the social recognition test (SRT), the elevated plus maze (EPM) test, and the pole climbing test (PCT). Acetylcholinesterase (AChE) activity and oxidative stress parameters were estimated in the cortex, hippocampus, and cerebellum of the brains after completion of the behavioural studies. The effects of scopolamine on the levels of the tumour necrosis factor alpha (TNF-α) transcript were also investigated. Scopolamine caused memory impairment in all the behavioural paradigms along with a significant increase in the AChE activity and oxidative stress in the brain. Scopolamine also caused a significant increase in the expression of TNF-α in the hippocampus. CM seed oil exhibited antiamnesic activity as indicated by a significant reduction in the latency time in the MWM test and decreased social interaction during trial 2 in the SRT. Further, treatment with CM seed oil significantly decreased the AChE activity and malondialdehyde levels and increased the glutathione level in brain regions. CM seed oil also significantly decreased the expression of TNF-α in the hippocampus. The effect of CM seed oil on behavioural and biochemical parameters was comparable to that observed in rats treated with piracetam. These results indicate that CM seed oil may exert antiamnesic activity which may be attributed to the inhibition of AChE and inflammation as well as its antioxidant activity in the brain.

  20. Protective Effects of Alpha-Lipoic Acid on Oleic Acid-Induced Acute Lung Injury in Rats

    Directory of Open Access Journals (Sweden)

    Funda Gülcü Bulmuş

    2013-09-01

    Full Text Available Background: Oxidative stress is believed to be an important factor in the pathogenesis of acute lung injury (ALI. Aims: The aim of this study was to investigate the possible protective role of alpha-lipoic acid (α-LA on oleic acid (OA-induced ALI in rats. Study Design: Animal experiment. Methods: A total of thirty-five rats were divided into five groups in the study. Group 1 served as a control group. Rats in Group 2 (α-LA were administered α-LA intraperitoneally at a dose of 100 mg/kg body weight (BW. Rats in Group 3 (OA were administered OA intravenously at a dose of 100 mg/kg BW. In Group 4 (pre-OA-α-LA, α-LA was given 15 minutes prior to OA infusion, and in Group 5 (post-OA-α-LA, α-LA was given two hours after OA infusion. Four hours after the OA infusion, rats were decapitated. Blood samples were collected to measure serum levels of malondialdehyde (MDA and glutathione (GSH, and the levels of activity for superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GSH-Px. Lung tissue samples were taken for histopathological examination. Results: Exposure to OA resulted in increases in serum MDA levels (p<0.001, as well as histopathological lesions in lung tissue, and decreases in CAT (p<0.05, GSH-Px (p<0.05 activities and GSH (p<0.05 levels. On the other hand, MDA levels were decreased significantly (p<0.001, while CAT (p<0.05, GSH-Px (p<0.01 activities and GSH (p<0.05 levels were increased significantly in the pre-OA-α-LA group compared with the OA group. Conclusion: α-LA was found to lessen oxidative stress and to have positive effects on antioxidants in cases of OA-induced ALI. In conclusion, α-LA appears to have protective effects against ALI and potential for the prevention of ALI.

  1. A study of the scintillation induced by alpha particles and gamma rays in liquid xenon in an electric field

    International Nuclear Information System (INIS)

    Dawson, J.V.; Howard, A.S.; Akimov, D.; Araujo, H.; Bewick, A.; Davidge, D.C.R.; Jones, W.G.; Joshi, M.; Lebedenko, V.N.; Liubarsky, I.; Quenby, J.J.; Rochester, G.; Shaul, D.; Sumner, T.J.; Walker, R.J.

    2005-01-01

    Scintillation produced in liquid xenon by alpha particles and gamma rays has been studied as a function of applied electric field. For back scattered gamma rays with energy of about 200keV, the number of scintillation photons was found to decrease by 64±2% with increasing field strength. Consequently, the pulse shape discrimination power between alpha particles and gamma rays is found to reduce with increasing field, but remaining non-zero at higher fields

  2. EMPIRE-II 2.18, Comprehensive Nuclear Model Code, Nucleons, Ions Induced Cross-Sections

    International Nuclear Information System (INIS)

    Herman, Michal Wladyslaw; Panini, Gian Carlo

    2003-01-01

    1 - Description of program or function: EMPIRE-II is a flexible code for calculation of nuclear reactions in the frame of combined optical, Multi-step Direct (TUL), Multi-step Compound (NVWY) and statistical (Hauser-Feshbach) models. Incident particle can be a nucleon or any nucleus(Heavy Ion). Isomer ratios, residue production cross sections and emission spectra for neutrons, protons, alpha-particles, gamma-rays, and one type of Light Ion can be calculated. The energy range starts just above the resonance region for neutron induced reactions and extends up to several hundreds of MeV for the Heavy Ion induced reactions. IAEA1169/06: This version corrects an error in the Absoft compile procedure. 2 - Method of solution: For projectiles with A<5 EMPIRE calculates fusion cross section using spherical optical model transmission coefficients. In the case of Heavy Ion induced reactions the fusion cross section can be determined using various approaches including simplified coupled channels method (code CCFUS). Pre-equilibrium emission is treated in terms of quantum-mechanical theories (TUL-MSD and NVWY-MSC). MSC contribution to the gamma emission is taken into account. These calculations are followed by statistical decay with arbitrary number of subsequent particle emissions. Gamma-ray competition is considered in detail for every decaying compound nucleus. Different options for level densities are available including dynamical approach with collective effects taken into account. EMPIRE contains following third party codes converted into subroutines: - SCAT2 by O. Bersillon, - ORION and TRISTAN by H. Lenske and H. Wolter, - CCFUS by C.H. Dasso and S. Landowne, - BARMOM by A. Sierk. 3 - Restrictions on the complexity of the problem: The code can be easily adjusted to the problem by changing dimensions in the dimensions.h file. The actual limits are set by the available memory. In the current formulation up to 4 ejectiles plus gamma are allowed. This limit can be relaxed

  3. Diclofenac inhibits tumor necrosis factor-α-induced nuclear factor-κB activation causing synergistic hepatocyte apoptosis.

    Science.gov (United States)

    Fredriksson, Lisa; Herpers, Bram; Benedetti, Giulia; Matadin, Quraisha; Puigvert, Jordi C; de Bont, Hans; Dragovic, Sanja; Vermeulen, Nico P E; Commandeur, Jan N M; Danen, Erik; de Graauw, Marjo; van de Water, Bob

    2011-06-01

    Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF-α). HepG2 cells were treated with diclofenac followed by TNF-α challenge and subsequent evaluation of necrosis and apoptosis. Diclofenac caused a mild apoptosis of HepG2 cells, which was strongly potentiated by TNF-α. A focused apoptosis machinery short interference RNA (siRNA) library screen identified that this TNF-α-mediated enhancement involved activation of caspase-3 through a caspase-8/Bid/APAF1 pathway. Diclofenac itself induced sustained activation of c-Jun N-terminal kinase (JNK) and inhibition of JNK decreased both diclofenac and diclofenac/TNF-α-induced apoptosis. Live cell imaging of GFPp65/RelA showed that diclofenac dampened the TNF-α-mediated nuclear factor kappaB (NF-κB) translocation oscillation in association with reduced NF-κB transcriptional activity. This was associated with inhibition by diclofenac of the TNF-α-induced phosphorylation of the inhibitor of NF-κB alpha (IκBα). Finally, inhibition of IκB kinase β (IKKβ) with BMS-345541 as well as stable lentiviral short hairpin RNA (shRNA)-based knockdown of p65/RelA sensitized hepatocytes towards diclofenac/TNF-α-induced cytotoxicity. Together, our data suggest a model whereby diclofenac-mediated stress signaling suppresses TNF-α-induced survival signaling routes and sensitizes cells to apoptosis. Copyright © 2011 American Association for the Study of Liver Diseases.

  4. Vitamin E analogue, D-alpha tocopherol succinate, enhances x-ray induced growth delay of human adenocarcinoma cancer cell line

    International Nuclear Information System (INIS)

    Jaworska, A.; Ottesen, T.E.

    2003-01-01

    The purpose of this study was to assess the effects of d-alpha Tocopherol succinate (alpha-TS) in modifying radiation-induced viability reduction and apoptosis occurrence in the model for normal and cancer cells. Our hypothesis was that alpha-TS enhances the growth-inhibitory effect of x-irradiation in cancer cells and that the effect is more pronounced in these cells than in normal cells. Murine NIH 3T3 Swiss albino embryonic cells and HT29 human Caucasian colon adenocarcinoma cells were used in the experiments. Alpha-TS was added to the cultures 1 h prior to irradiation with doses of 2 or 5Gy of x-ray. After irradiation cells were incubated for 73 h. Trypan blue exclusion viability test and estimation of apoptosis and necrosis were made. Apoptotic and necrotic cells were counted in fluorescence microscope using fluorescence dyes: propidium iodide and Hoechst 33342. For experiments with the dose of 5 Gy at least five series of experiments were performed. At lower doses (up to approximately 25μM/ml) treatment with alpha-TS alone enhanced growth of both cell lines. At higher doses treatment with alpha-TS alone delayed the growth of the cell cultures, accompanied by 20-25% necrosis. At the concentrations higher than 25μM/mL alpha-TS alone caused growth delay of both cell cultures, being much more pronounced for the cancer cell line HT29. At the concentrations of 50 μM/mL, responsible for about 30-60% of growth delay, there was observed a synergy effect for x-rays and alpha-TS for both cell lines. The effect was more pronounced for HT29 cells (DMF=0.48 for HT29 versus DMF=0.73 for NIH 3T3). These results may confirm the views of the literature reports suggesting that use of vitamin E t