WorldWideScience

Sample records for short-lived regulatory proteins

  1. Limited BRC rulemaking: Regulatory approach and experience in Texas for short-lived radioactive waste

    International Nuclear Information System (INIS)

    McBurney, Ruth E.; Pollard, Christine G.

    1992-01-01

    In 1987, the Texas Department of Health (TDH) implemented a rule to allow, under certain conditions, wastes containing limited concentrations of short- lived radionuclides (less than 300-day half-life) to be disposed of in Type I sanitary landfills. The rule was based on a technical analysis that demonstrated the degree of safety for approximately 340 m of radioactive waste generated annually in Texas and identified major restrictions and conditions for disposal. TDH's Bureau of Radiation Control staff have been able to maintain an account of licensees utilizing the rule during the past years. Several research and industrial facilities in the state have saved significantly on waste disposal expenses. Public concerns and economic impacts for licensees as well as other regulatory aspects and experiences with the rule are discussed. (author)

  2. Short-lived non-coding transcripts (SLiTs): Clues to regulatory long non-coding RNA.

    Science.gov (United States)

    Tani, Hidenori

    2017-03-22

    Whole transcriptome analyses have revealed a large number of novel long non-coding RNAs (lncRNAs). Although the importance of lncRNAs has been documented in previous reports, the biological and physiological functions of lncRNAs remain largely unknown. The role of lncRNAs seems an elusive problem. Here, I propose a clue to the identification of regulatory lncRNAs. The key point is RNA half-life. RNAs with a long half-life (t 1/2 > 4 h) contain a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short half-life (t 1/2 regulatory ncRNAs and regulatory mRNAs. This novel class of ncRNAs with a short half-life can be categorized as Short-Lived non-coding Transcripts (SLiTs). I consider that SLiTs are likely to be rich in functionally uncharacterized regulatory RNAs. This review describes recent progress in research into SLiTs.

  3. Practical applications of short-lived radioisotopes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1963-01-15

    The advantages of the use of short-lived radioisotopes in agriculture, food industry and medicine as well as some industrial uses are discussed. Methods for isotope production in small research reactors and laboratories are presented

  4. Enzymatic Mercury Detoxification: The Regulatory Protein MerR

    CERN Multimedia

    Ctortecka, B; Walsh, C T; Comess, K M

    2002-01-01

    Mercury ions and organomercurial reagents are extremely toxic due to their affinity for thiol groups. Many bacteria contain an elaborate detoxification system for a metabolic conversion of toxic Hg$^{2+}$ or organomercurials to less toxic elemental Hg$^0$. The main components of the enzymatic mercury detoxification (see Fig. 1) are the regulatory protein MerR (mercury responsive genetic switch), the organomercurial lyase MerB (cleavage of carbon mercury bonds), and the mercuric ion reductase MerA (reduction of mercuric ions). In these proteins Hg$^{2+}$ is usually coordinated by the thiol groups of cysteines. We utilize the nuclear quadrupole interaction (NQI) of ${\\rm^{199m}}$Hg detected by time differential perturbed angular correlation (TDPAC) to identify the Hg metal site geometries in these proteins in order to elucidate the molecular origin of the ultrasensitivity, selectivity and reaction mechanism of this detoxification system. The short lived TDPAC probe ${\\rm^{199m}}$Hg ($\\tau_{1/2} =$ 43 min) is su...

  5. Separation of short-lived fission products

    International Nuclear Information System (INIS)

    Tamai, Tadaharu; Ohyoshi, Emiko; Ohyoshi, Akira; Kiso, Yoshiyuki; Shinagawa, Mutsuaki.

    1976-01-01

    A rbief review is presented on the various methods of separation available for both gaseous and liquid states, for the separation of short-lived fission products formed by binary fission of neutron irradiated uranium. The means available for gaseous state are the hot atom reaction, the hydride method and on-line mass separation. For liquid state, use can be made of precipitation, ionic or atomic exchange, solvent extraction and paper electrophoresis. Particular reference is made to electrophoretic separation of ions produced by fission in aqueous solution of uranium. The principle of electrophoretic separation and the procedures for separating the element of interest from the other fission products are outlined, with reference made to the results obtained with the method by the present authors. The elements in question are alkalines, alkaline earths, rare earths, halogens, selenium and

  6. Measurements of Short-Lived Fission Isomers

    Science.gov (United States)

    Finch, Sean; Bhike, Megha; Howell, Calvin; Krishichayan, Fnu; Tornow, Werner

    2016-09-01

    Fission yields of the short lived isomers 134mTe (T1 / 2 = 162 ns) and 136mXe (T1 / 2 = 2 . 95 μs) were measured for 235U and 238U. The isomers were detected by the γ rays associated with the decay of the isomeric states using high-purity germanium detectors. Fission was induced using both monoenergetic γ rays and neutrons. At TUNL's High-Intensity Gamma-ray Source (HI γS), γ rays of 9 and 11 MeV were produced . Monoenergetic 8 MeV neutrons were produced at TUNL's tandem accelerator laboratory. Both beams were pulsed to allow for precise time-gated spectroscopy of both prompt and delayed γ rays following fission. This technique offers a non-destructive probe of special nuclear materials that is sensitive to the isotopic identity of the fissile material.

  7. Protein tyrosine phosphatases: regulatory mechanisms.

    NARCIS (Netherlands)

    den Hertog, J.; Ostman, A.; Bohmer, F.D.

    2008-01-01

    Protein-tyrosine phosphatases are tightly controlled by various mechanisms, ranging from differential expression in specific cell types to restricted subcellular localization, limited proteolysis, post-translational modifications affecting intrinsic catalytic activity, ligand binding and

  8. Radiopharmaceuticals and other compounds labelled with short-lived radionuclides

    CERN Document Server

    Welch, Michael J

    2013-01-01

    Radiopharmaceuticals and Other Compounds Labelled with Short-Lived Radionuclides covers through both review and contributed articles the potential applications and developments in labeling with short-lived radionuclides whose use is restricted to institutions with accelerators. The book discusses the current and potential use of generator-produced radionuclides as well as other short-lived radionuclides, and the problems of quality control of such labeled compounds. The book is useful to nuclear medicine physicians.

  9. Quantifying short-lived events in multistate ionic current measurements.

    Science.gov (United States)

    Balijepalli, Arvind; Ettedgui, Jessica; Cornio, Andrew T; Robertson, Joseph W F; Cheung, Kin P; Kasianowicz, John J; Vaz, Canute

    2014-02-25

    We developed a generalized technique to characterize polymer-nanopore interactions via single channel ionic current measurements. Physical interactions between analytes, such as DNA, proteins, or synthetic polymers, and a nanopore cause multiple discrete states in the current. We modeled the transitions of the current to individual states with an equivalent electrical circuit, which allowed us to describe the system response. This enabled the estimation of short-lived states that are presently not characterized by existing analysis techniques. Our approach considerably improves the range and resolution of single-molecule characterization with nanopores. For example, we characterized the residence times of synthetic polymers that are three times shorter than those estimated with existing algorithms. Because the molecule's residence time follows an exponential distribution, we recover nearly 20-fold more events per unit time that can be used for analysis. Furthermore, the measurement range was extended from 11 monomers to as few as 8. Finally, we applied this technique to recover a known sequence of single-stranded DNA from previously published ion channel recordings, identifying discrete current states with subpicoampere resolution.

  10. How Short-Lived Ikaite Affects Calcite Crystallization

    OpenAIRE

    Besselink, R; Rodriguez-Blanco, JD; Stawski, TM; Benning, LG; Tobler, DJ

    2017-01-01

    The pathways of CaCO3 crystallization are manifold, often involving one or several metastable amorphous or nanocrystalline intermediate phases. The presence of such intermediates is often overlooked, because they are short-lived and/or occur at small molar fractions. However, their occurrence does not just impact the mechanisms and pathways of formation of the final stable CaCO3 phase, but also affects their crystal size, shape, and structure. Here we document the presence of a short-lived in...

  11. Short-lived positron emitter labeled radiotracers - present status

    International Nuclear Information System (INIS)

    Fowler, J.S.; Wolf, A.P.

    1982-01-01

    The preparation of labelled compounds is important for the application of positron emission transaxial tomography (PETT) in biomedical sciences. This paper describes problems and progress in the synthesis of short-lived positron emitter ( 11 C, 18 F, 13 N) labelled tracers for PETT. Synthesis of labelled sugars, amino acids, and neurotransmitter receptors (pimozide and spiroperidol tagged with 11 C) is discussed in particular

  12. Measurement of short-lived particles at PETRA

    International Nuclear Information System (INIS)

    Saxon, D.H.

    1987-04-01

    The contribution of PETRA to the measurement of short-lived particles is reviewed with discussion of the detectors and analysis techniques. New results are presented on lifetimes of identified particles and the systematics of b-life measurement outlined. The first application of vertex-tagging to flavour separation is described. (author)

  13. Fast Resonance Raman Spectroscopy of Short-Lived Radicals

    DEFF Research Database (Denmark)

    Pagsberg, Palle Bjørn; Wilbrandt, Robert Walter; Hansen, Karina Benthin

    1976-01-01

    We report the first application of pulsed resonance Raman spectroscopy to the study of short-lived free radicals produced by pulse radiolysis. A single pulse from a flash-lamp pumped tunable dye laser is used to excite the resonance Raman spectrum of the p-terphenyl anion radical with an initial...

  14. Applications of nuclear data on short-lived fission products

    International Nuclear Information System (INIS)

    Rudstam, G.; Aagaard, P.; Aleklett, K.; Lund, E.

    1981-01-01

    The study of short-lived fission products gives information about the nuclear structure on the neutron-rich side of stability. The data are also of interest for various applications both to basic science and to nuclear technology. Some of these applications, taken up by the OSIRIS group at Studsvik, are described in the present contribution. (orig.)

  15. Soot and short-lived pollutants provide political opportunity

    Science.gov (United States)

    Victor, David G.; Zaelke, Durwood; Ramanathan, Veerabhadran

    2015-09-01

    Cutting levels of soot and other short-lived pollutants delivers tangible benefits and helps governments to build confidence that collective action on climate change is feasible. After the Paris climate meeting this December, actually reducing these pollutants will be essential to the credibility of the diplomatic process.

  16. Passive Mobile Bandwidth Classification Using Short Lived TCP Connections

    OpenAIRE

    Michelinakis, Foivos; Kreitz, Gunnar; Petrocco, Riccardo; Zhang, Boxun; Widmer, Joerg

    2015-01-01

    Consumption of multimedia content is moving from a residential environment to mobile phones. Optimizing Quality of Experience—smooth, quick, and high quality playback—is more difficult in this setting, due to the highly dynamic nature of wireless links. A key requirement for achieving this goal is estimating the available bandwidth of mobile devices. Ideally, this should be done quickly and with low overhead. One challenge is that the majority of connections on mobiles are short-lived TCP con...

  17. Short-lived radiopharmaceuticals for the diagnosis of ocular melanoma

    International Nuclear Information System (INIS)

    Packer, S.; Lambrecht, R.; Atkins, H.L.; Wolf, A.P.

    1974-01-01

    An experimental procedure has been established to evaluate radiopharmaceuticals for the specific purpose of melanoma detection by scintiscanning. By using the Greene melanoma in the hamster several labeled compounds were compared. Specifically the tumor uptake along with detailed analyses of uptake by various parts of the eye and body were determined in a hamster model. Of those short-lived radionuclides investigated 203 Pb-tris was the most promising as a non-invasive localizing agent for ocular melanoma and it should prove effective for ocular scintigraphy. (U.S.)

  18. Feasibility of short-lived radionuclide production at Fermilab

    International Nuclear Information System (INIS)

    Ten Haken, R.K.; Awschalom, M.; Rosenberg, I.

    1985-01-01

    The requirements for establishing a short-lived radionuclide production program at Fermilab are explored. Such a program would utilize beam from the linac portion of the injector much like the present Neutron Therapy Facility. It should be possible to use approximately 10 to 20 μA of 66-MeV protons for iodine-123 production. Several additional magnets would need to be acquired and a shielded target facility would need to be constructed. However, the feasibility of establishing such a program hinges upon its harmonious operation with the high energy physics program

  19. Are crab-type supernova remnants (plerions) short-lived

    International Nuclear Information System (INIS)

    Weiler, K.W.; Panagia, N.

    1978-01-01

    Arguments are given for a possible picture of the origin, maintenance, and lifetimes of the so-called Crab-like supernova remnants. It is suggested that these objects imply the existence of at least two distinct types of supernova events. A possible connection of the remnant types with the optically defined supernovae of Type I and Type II is discussed. Accepting that a pulsar is formed in at least some supernova events, the proposal is made that a rapidly rotating, rapidly slowing pulsar is necessary to create and maintain a Crab-like supernova remnant. Finally, arguments are presented that such a supernova remnant will be relatively short lived with respect to the more common shell-type of supernova remnant, perhaps surviving only 10000-20000 yr before fading into the Galactic background. The name of plerion is proposed for these filled-center supernova remnants and observational possiblities for confirming their nature are suggested. (orig.) [de

  20. Kinetic aspects of the syntheses using short-lived radionuclides

    International Nuclear Information System (INIS)

    Laangstroem, B.; Obenius, U.; Sjoeberg, S.; Bergson, G.

    1981-01-01

    In syntheses using short-lived radionuclides, such as 11 C, the reaction conditions are usually such that the concentrations of the reactants, except for the labelled reactant, can be considered constant during the reaction. Two kinetic models have been investigated - irreversible and reversible bimolecular elementary reactions. The influence of the rate constants, of the equilibrium constants, and of the ratio between the starting reactants on the yield of the labelled product has been studied. The results show that, even in cases with unfavourable equilibrium constants, high yields of the labelled products can be obtained if the rate constant for the forward reaction is large. In addition, the specific activity of the labelled product as a function of time has been studied for the irreversible bimolecular case. (author)

  1. Electron scattering off short-lived radioactive nuclei

    International Nuclear Information System (INIS)

    Wang, S.; Emoto, T.; Furukawa, Y.

    2009-01-01

    We have established a novel method which make electron scattering off short-lived radioactive nuclei come into being. This novel method was named SCRIT (Self-Confining RI ion Target). It was based on the well known "ion trapping" phenomenon in electron storage rings. Stable nucleus, 133 Cs, was used as target nucleus in the R&D experiment. The luminosity of interaction between stored electrons and Cs ions was about 1.02(0.06) × 10 26 cm -2 s -1 at beam current around 80 mA. The angular distribution of elastically scattered electrons from trapped Cs ions was measured. And an online luminosity monitor was used to monitor the change of luminosity during the experiment. (author)

  2. Organic synthesis with short-lived positron-emitting radioisotopes

    International Nuclear Information System (INIS)

    Pike, V.W.

    1988-01-01

    Chemistry with short-lived positron-emitting radioisotopes of the non-metals, principally 11 C, 13 N and 18 F, has burgeoned over the last decade. This has been almost entirely because of the emergence of positron emission tomography (PET) as a powerful non-invasive technique for investigating pathophysiology in living man. PET is essentially an external technique for the rapid serial reconstruction of the spatial distribution of any positron-emitting radioisotope that has been administered in vivo. Such a distribution is primarily governed by the chemical form in which the positron-emitting radioisotope is incorporated, and importantly for clinical research, is often perturbed by physical, biological or clinical factors. Judicious choice of the chemical form enables specific biological information to be obtained. For example, the labelling of glucose with a positron-emitting radioisotope could be expected to provide a radiopharmaceutical for the study of glucose utilisation in both health and disease. (author)

  3. Activation analysis with neutron generators using short-lived radionuclides

    International Nuclear Information System (INIS)

    Salma, I.

    1993-01-01

    The short half-life involves a number of important differences in production, transportation and measurement of radionuclides, and in counting statistics as compared with those in traditional activation analysis. Experiments were performed to investigate the analytical possibilities and prospective utilization of short-lived radionuclides produced by 14-MeV neutron irradiation. A rapid pneumatic transfer system for use with neutron generators was installed and applied for detecting radionuclides with a half-life from 300 ms to 30 s. The transport time for samples with a total mass of 1-4 g is between 130 and 160 ms for pressurized air of 0.1-0.4 MPa. 11 elements were studied by the conventional activation method using both a typical pneumatic transport system (run time 3 s) and the fast pneumatic transport facility. The effect of the cyclic activation technique on the elemental sensitivities was also investigated. (orig.)

  4. Nondispersive x-ray diagnostics of short lived plasmas

    International Nuclear Information System (INIS)

    Day, R.H.

    1983-01-01

    In this NATO Advanced Study Institute, we have discussed in detail the diagnosis of many pulse power machine properties, including their electrical behavior, grounding and shielding, and related data acquisition techniques. The purpose for many of these machines is to create high temperature/high density plasmas and, therefore, the subsequent behavior of these plasmas is of critical concern. The energy density of these plasmas is such that they will naturally radiate in the x-ray regime and thus the diagnosis of their x-ray emission is a crucial measurement of the entire system performance. In this lecture, I describe the general techniques used to perform nondispersive x-ray diagnostics of these short lived plasmas

  5. Protein kinase A regulatory subunit distribution in medulloblastoma

    International Nuclear Information System (INIS)

    Mucignat-Caretta, Carla; Denaro, Luca; Redaelli, Marco; D'Avella, Domenico; Caretta, Antonio

    2010-01-01

    Previous studies showed a differential distribution of the four regulatory subunits of cAMP-dependent protein kinases inside the brain, that changed in rodent gliomas: therefore, the distribution of these proteins inside the brain can give information on the functional state of the cells. Our goal was to examine human brain tumors to provide evidence for a differential distribution of protein kinase A in different tumors. The distribution of detergent insoluble regulatory (R1 and R2) and catalytic subunits of cAMP dependent kinases was examined in pediatric brain tumors by immunohistochemistry and fluorescent cAMP analogues binding. R2 is organized in large single dots in medulloblastomas, while it has a different appearance in other tumors. Fluorescent cAMP labelling was observed only in medulloblastoma. A different distribution of cAMP dependent protein kinases has been observed in medulloblastoma

  6. Co-suppression of sterol-regulatory element binding protein ...

    African Journals Online (AJOL)

    Administrator

    2011-06-22

    Jun 22, 2011 ... In Arabidopsis,. At5g35220 gene being sterol regulatory element-binding protein site 2, protease and metalloendopeptidase activity were required for chloroplast development and play a role in regulation of endodermal plastid size and number that are involved in ethylene-dependent gravitropism of light-.

  7. Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion.

    Science.gov (United States)

    Hovingh, Elise S; van den Broek, Bryan; Jongerius, Ilse

    2016-01-01

    The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

  8. CONSTRUCTION AND ANALYSIS OF IPBR/XYLS HYBRID REGULATORY PROTEINS

    Science.gov (United States)

    IpbR and XylS are related regulatory proteins (having 56% identity). IpbR responds to isopropylbenzene as well as to a variety of hydrophobic chemicals to activate expression of the isopropylbenzene catabolic pathway operon of pRE4 from ipbOP. XylS responds to substituted benzoic...

  9. Production of medical short-lived radionuclides in Canada

    International Nuclear Information System (INIS)

    Wiebe, L.I.

    1985-01-01

    The production of radionuclides for medical and biomedical research in Canada has been reviewed with respect to the national geographic and demographic characteristics which influence their use. The types of facilities available for the production of short-lived radionuclides have been summarized, and a tabulation of the radionuclides that are produced has been presented. In broad terms production facilities can be classified as belonging to one of two groups, nuclear reactor or charged-particle accelerators. The charged-particle accelerators produce the more neutron-deficient and (because of the resultant decay properties) the more useful radionuclides for medical application. The nuclear reactor facilities for radionuclide production range in size and capacity from the high-flux research reactors of AECL to the six SLOWPOKE reactors, five of which are located on university campuses across the country. The McMaster University reactor is used to produce curie quantities of fluorine-18 weekly. Millicurie amounts of a large number of radionuclides, most of which have half-lives ranging from 2 to 50 hr, are produced in the low-flux reactors, in support of basic medical research

  10. Contribution of short-lived nuclides to decay heat

    International Nuclear Information System (INIS)

    Katakura, Jun-ichi

    1987-01-01

    Comments are made on the calculation of decay heat, centering on evaluation of average decay energy. It is difficult to obtain sufficiently useful decay diagrams of short lived nucleides. High-energy levels are often missing in inferior decay diagrams, leading to an overestimation of the intensity of beta-rays at low-energy levels. Such an overestimation or underestimation due to the inferiority of a decay diagram is referred to as pandemonium effect. The pandemonium effect can be assessed by means of the ratio of the measured energy of the highest level of the daughter nuclide to the Q β -value of the beta-decay. When a satisfactory decay diagram cannot be obtained, the average decay energy has to be estimated by theoretical calculation. The gross theory for beta-decay proposed by Yamada and Takahashi is employed for the calculation. To carry out the calculation according to this theory, it is required to determine the value for the parameter Q 00 , the lowest energy of the daughter nuclide that meets the selection rule for beta-decay. Currently, Q 00 to be used for this purpose is estimated from data on the energy of the lowest level found in a decay diagram, even if it is inferior. Some examples of calculation of decay heat using the average beta- or gamma-ray energy are shown and compared with measurements. (author)

  11. Changing-Look AGNs or Short-Lived Radio Sources?

    Energy Technology Data Exchange (ETDEWEB)

    Wołowska, Aleksandra [Toruń Centre for Astronomy, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Toruń (Poland); Kunert-Bajraszewska, Magdalena; Mooley, Kunal [Centre for Astrophysical Surveys, University of Oxford, Oxford (United Kingdom); Hallinan, Gregg, E-mail: ola@astro.umk.pl [Cahill Center for Astronomy, California Institute of Technology, Pasadena, CA (United States)

    2017-11-17

    The evolution of extragalactic radio sources has been a fundamental problem in the study of active galactic nuclei for many years. A standard evolutionary model has been created based on observations of a wide range of radio sources. In the general scenario of the evolution, the younger and smaller Gigahertz-Peaked Spectrum (GPS) and Compact Steep Spectrum (CSS) sources become large-scale FRI and FRII objects. However, a growing number of observations of low power radio sources suggests that the model cannot explain all their properties and there are still some aspects of the evolutionary path that remain unclear. There are indications, that some sources may be short-lived objects on timescales of 10{sup 4}–10{sup 5} years. Those objects represent a new population of active galaxies. Here, we present the discovery of several radio transient sources on timescales of 5–20 yrs, largely associated with renewed AGN (Active Galactic Nucleus) activity. These changing-look AGNs possibly represent behavior typical for many active galaxies.

  12. Emission channeling lattice location experiments with short-lived isotopes

    CERN Multimedia

    Wahl, U; Ronning, C R

    2007-01-01

    Emission channeling with position-sensitive detectors is a well-established technique at ISOLDE for studying the lattice location of radioactive impurities implanted into single crystals. In the case of electron emitting isotopes, however, due to count rate and noise-related limitations of the detection systems, the technique was restricted to isotopes with half lives above 6 h and electron energies above 40 keV. Recently, major technical developments have been realized and new equipment has been acquired which has allowed these limitations to be overcome and made feasible electron emission channeling experiments with short-lived isotopes and at low electron energies.\\\\ As first application, making use of two new on-line emission channeling setups at ISOLDE, we propose to investigate the lattice location of the transition metals Ni (2.5 h) and Co (1.6 h) in semiconductors, in particular in ZnO and GaN, by means of on-line $\\beta^{-}$-emission channeling experiments. In addition, we would like to study the lat...

  13. Fast neutron activation analysis using short-lived radionuclides

    International Nuclear Information System (INIS)

    Salma, I.; Zemplen-Papp, E.

    1993-01-01

    Fast neutron activation analysis experiments were performed to investigate the analytical possibilities and prospective utilization of short-lived activation products. A rapid pneumatic transfer system for use with neutron generators has been installed and applied for detecting radionuclides with a half-life from ∼300 ms to 20 s. The transport time for samples of total mass of 1-4 g is between 130 and 160 ms for pressurized air of 0.1-0.4 MPa. The reproducibility of transport times is less than 2%. The employed method of correcting time-dependent counting losses is based on the virtual pulse generator principle. The measuring equipment consists of CAMAC modules and a special gating circuit. Typical time distributions of counting losses are presented. The same 14 elements were studied by the conventional activation method (single irradiation and single counting) by both a typical pneumatic transport system (run time 3 s) and the fast pneumatic transport facility. Furthermore, the influence of the cyclic activation technique on the elemental sensitivities was investigated. (author) 15 refs.; 5 figs.; 3 tabs

  14. Trans-acting translational regulatory RNA binding proteins.

    Science.gov (United States)

    Harvey, Robert F; Smith, Tom S; Mulroney, Thomas; Queiroz, Rayner M L; Pizzinga, Mariavittoria; Dezi, Veronica; Villenueva, Eneko; Ramakrishna, Manasa; Lilley, Kathryn S; Willis, Anne E

    2018-05-01

    The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary to provide mRNA-specific translation, and these interact with 5' and 3' untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans-acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans-acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans-acting ribosomal proteins in directing the translation of specific mRNAs. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Translation Regulation Translation > Translation Mechanisms. © 2018 Medical Research Council and University of Cambridge. WIREs RNA published by Wiley Periodicals, Inc.

  15. Short-lived radiopharmaceutical development at E.R. Squibb and Sons, Inc

    International Nuclear Information System (INIS)

    Loberg, M.D.

    1985-01-01

    This paper describes the present status and future plans of E.R. Squibb and Sons, Inc. as they relate to the development of short-lived radiopharmaceuticals. The advantages of short-lived radiopharmaceuticals are summarized as are the problems inherent in their manufacture, quality control, and distribution. The nuclear generator is advocated as the best means of distributing short-lived radiopharmaceuticals. The E.R. Squibb and Sons work with the 82 Sr → 82 Rb generator is summarized

  16. Myristoylated α subunits of guanine nucleotide-binding regulatory proteins

    International Nuclear Information System (INIS)

    Buss, J.E.; Mumby, S.M.; Casey, P.J.; Gilman, A.G.; Sefton, B.M.

    1987-01-01

    Antisera directed against specific subunits of guanine nucleotide-binding regulatory proteins (G proteins) were used to immunoprecipitate these polypeptides from metabolically labeled cells. This technique detects, in extracts of a human astrocytoma cell line, the α subunits of G/sub s/ (stimulatory) (α 45 and α 52 ), a 41-kDa subunit of G/sub i/ (inhibitory) (α 41 ), a 40-kDa protein (α 40 ), and the 36-kDa β subunit. No protein that comigrated with the α subunit of G 0 (unknown function) (α 39 ) was detected. In cells grown in the presence of [ 3 H]myristic acid, α 41 and α 40 contained 3 H label, while the β subunit did not. Chemical analysis of lipids attached covalently to purified α 41 and α 39 from bovine brain also revealed myristic acid. Similar analysis of brain G protein β and γ subunits and of G/sub t/ (Transducin) subunits (α, β, and γ) failed to reveal fatty acids. The fatty acid associated with α 41 , α 40 , and α 39 was stable to treatment with base, suggesting that the lipid is linked to the polypeptide via an amide bond. These GTP binding proteins are thus identified as members of a select group of proteins that contains myristic acid covalently attached to the peptide backbone. Myristate may play an important role in stabilizing interactions of G proteins with phospholipid or with membrane-bound proteins

  17. Protein Kinase A Regulatory Subunits in Human Adipose Tissue

    Science.gov (United States)

    Mantovani, Giovanna; Bondioni, Sara; Alberti, Luisella; Gilardini, Luisa; Invitti, Cecilia; Corbetta, Sabrina; Zappa, Marco A.; Ferrero, Stefano; Lania, Andrea G.; Bosari, Silvano; Beck-Peccoz, Paolo; Spada, Anna

    2009-01-01

    OBJECTIVE—In human adipocytes, the cAMP-dependent pathway mediates signals originating from β-adrenergic activation, thus playing a key role in the regulation of important metabolic processes, i.e., lipolysis and thermogenesis. Cyclic AMP effects are mainly mediated by protein kinase A (PKA), whose R2B regulatory isoform is the most expressed in mouse adipose tissue, where it protects against diet-induced obesity and fatty liver development. The aim of the study was to investigate possible differences in R2B expression, PKA activity, and lipolysis in adipose tissues from obese and nonobese subjects. RESEARCH DESIGN AND METHODS—The expression of the different PKA regulatory subunits was evaluated by immunohistochemistry, Western blot, and real-time PCR in subcutaneous and visceral adipose tissue samples from 20 nonobese and 67 obese patients. PKA activity and glycerol release were evaluated in total protein extract and adipocytes isolated from fresh tissue samples, respectively. RESULTS—Expression techniques showed that R2B was the most abundant regulatory protein, both at mRNA and protein level. Interestingly, R2B mRNA levels were significantly lower in both subcutaneous and visceral adipose tissues from obese than nonobese patients and negatively correlated with BMI, waist circumference, insulin levels, and homeostasis model assessment of insulin resistance. Moreover, both basal and stimulated PKA activity and glycerol release were significantly lower in visceral adipose tissue from obese patients then nonobese subjects. CONCLUSIONS—Our results first indicate that, in human adipose tissue, there are important BMI-related differences in R2B expression and PKA activation, which might be included among the multiple determinants involved in the different lipolytic response to β-adrenergic activation in obesity. PMID:19095761

  18. Harvard-MIT research program in short-lived radiopharmaceuticals. Final report

    International Nuclear Information System (INIS)

    Adelstein, S.J.

    1995-02-01

    The Harvard-MIT Research Program in Short-lived Radiopharmaceuticals was established in 1977 to foster interaction among groups working in radiopharmaceutical chemistry at Harvard Medical School, the Massachusetts Institute of Technology, and the Massachusetts General Hospital. To this was added a group at The Childrens Hospital. From these collaborations and building upon the special strengths of the participating individuals, laboratories and institutions, it was hoped that original approaches would be found for the design of new, clinically useful, radiolabeled compounds. The original thrust of this proposal included: (a) examination of the coordination chemistry of technetium as a basis for rational radiopharmaceutical design, (b) development of an ultrashort-lived radionuclide generator for the diagnosis of congenital heart disease in newborns, (c) synthesis of receptor-site-directed halopharmaceuticals, (d) improved facile labeling of complex molecules with positron-emitting radionuclides. The authors' 1986 proposal was oriented toward organs and disease, emphasizing radiolabeled agents that delineate specific functions and the distribution of receptors in brain, heart, and tumors. In 1989, they further refined their purposes and focused on two major aims: (a) synthesis and utilization of neutral technetium and rhenium complexes of high specific activity, and (b) development of new approaches to the radiolabeling of proteins, peptides, immunoglobulins, and their fragments. In 1992, the authors amended this proposal to concentrate their efforts on biologically active peptides and proteins for targeted radiodiagnosis and therapy

  19. Harvard-MIT research program in short-lived radiopharmaceuticals. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J. [Massachusetts Inst. of Tech., Cambridge, MA (United States). Office of Sponsored Programs

    1995-02-01

    The Harvard-MIT Research Program in Short-lived Radiopharmaceuticals was established in 1977 to foster interaction among groups working in radiopharmaceutical chemistry at Harvard Medical School, the Massachusetts Institute of Technology, and the Massachusetts General Hospital. To this was added a group at The Childrens Hospital. From these collaborations and building upon the special strengths of the participating individuals, laboratories and institutions, it was hoped that original approaches would be found for the design of new, clinically useful, radiolabeled compounds. The original thrust of this proposal included: (a) examination of the coordination chemistry of technetium as a basis for rational radiopharmaceutical design, (b) development of an ultrashort-lived radionuclide generator for the diagnosis of congenital heart disease in newborns, (c) synthesis of receptor-site-directed halopharmaceuticals, (d) improved facile labeling of complex molecules with positron-emitting radionuclides. The authors` 1986 proposal was oriented toward organs and disease, emphasizing radiolabeled agents that delineate specific functions and the distribution of receptors in brain, heart, and tumors. In 1989, they further refined their purposes and focused on two major aims: (a) synthesis and utilization of neutral technetium and rhenium complexes of high specific activity, and (b) development of new approaches to the radiolabeling of proteins, peptides, immunoglobulins, and their fragments. In 1992, the authors amended this proposal to concentrate their efforts on biologically active peptides and proteins for targeted radiodiagnosis and therapy.

  20. Interest of the Department of Energy in production and development of short-lived radionuclides

    International Nuclear Information System (INIS)

    Thiessen, J.W.

    1985-01-01

    The Department of Energy has developed production of potentially useful radionuclides for applications in medicine. The Department's financial commitment and the short-lived radionuclide production program, with emphasis on iodine-123, is discussed

  1. Historical review of short-lived isotope applications in New Zealand

    International Nuclear Information System (INIS)

    More, R.D.

    1986-01-01

    Production of short-lived isotopes, nitrogen 13, fluorine 18 and carbon 11 with a small Van de Graaff accelerator. Applications of these isotopes in uptake and photosynthetic translocation studies in plants, and fluorine tracing in dental studies

  2. Regional scale temperature and circulation impacts of short-lived climate pollutants reductions

    Science.gov (United States)

    Oudar, T.; Kushner, P. J.; Fyfe, J. C.; von Salzen, K.; Shrestha, R.

    2017-12-01

    The role of anthropogenic aerosols on climate is still not clearly understood. Aerosol forcing is spatially heterogeneous and their emissions are controlled by regional economic and regulatory factors. For example, it is known that black carbon is responsible for a global net warming but its regional impacts are less understood. We evaluate the regional climate impacts of anthropogenic aerosol emission changes over the recent past and near future. Specifically, we report on numerical experiments using aerosol emissions from the Evaluating the Climate and Air Quality Impacts of Short-Lived Pollutants (ECLIPSE, Stohl et al., 2015) project. These scenarios are alternative mitigation pathways for black carbon and organic aerosol over the period from 1990 to 2050. With these scenarios, we carried out three sets of simulation using the second generation Canadian Earth System Model (CanESM2): 1) A current legislation emission (CLE) scenario for black carbon and organic aerosols; 2) A mitigation (MIT) scenario for black carbon and organic aerosols, and; 3) A black carbon only mitigation scenario (MIT-BC). Five simulations were carried out for each scenario and the response analyzed in the context of a large fifty-member initial condition ensemble of simulations using historical anthropogenic aerosol forcings to 2005 as well as those forcing from the RCP8.5 scenario to 2020. Our main finding is a significant springtime cooling over the Northern midlatitudes that attributable to black carbon. Other cooling signals attributable to black carbon reductions are found in the boreal summer over Southern Europe as well as over the Northern Hemisphere midlatitudes and tropical troposphere in boreal summer and fall. All of these cooling signals are to some degree offset by simultaneous reductions in organic aerosols. As a check on the robustness, we will also report on results of five-member draws from the large ensemble over periods of comparably strong radiative forcing changes, to

  3. A conserved regulatory mechanism in bifunctional biotin protein ligases.

    Science.gov (United States)

    Wang, Jingheng; Beckett, Dorothy

    2017-08-01

    Class II bifunctional biotin protein ligases (BirA), which catalyze post-translational biotinylation and repress transcription initiation, are broadly distributed in eubacteria and archaea. However, it is unclear if these proteins all share the same molecular mechanism of transcription regulation. In Escherichia coli the corepressor biotinoyl-5'-AMP (bio-5'-AMP), which is also the intermediate in biotin transfer, promotes operator binding and resulting transcription repression by enhancing BirA dimerization. Like E. coli BirA (EcBirA), Staphylococcus aureus, and Bacillus subtilis BirA (Sa and BsBirA) repress transcription in vivo in a biotin-dependent manner. In this work, sedimentation equilibrium measurements were performed to investigate the molecular basis of this biotin-responsive transcription regulation. The results reveal that, as observed for EcBirA, Sa, and BsBirA dimerization reactions are significantly enhanced by bio-5'-AMP binding. Thus, the molecular mechanism of the Biotin Regulatory System is conserved in the biotin repressors from these three organisms. © 2017 The Protein Society.

  4. Vehicle emissions of short-lived and long-lived climate forcers: trends and tradeoffs.

    Science.gov (United States)

    Edwards, Morgan R; Klemun, Magdalena M; Kim, Hyung Chul; Wallington, Timothy J; Winkler, Sandra L; Tamor, Michael A; Trancik, Jessika E

    2017-08-24

    Evaluating technology options to mitigate the climate impacts of road transportation can be challenging, particularly when they involve a tradeoff between long-lived emissions (e.g., carbon dioxide) and short-lived emissions (e.g., methane or black carbon). Here we present trends in short- and long-lived emissions for light- and heavy-duty transport globally and in the U.S., EU, and China over the period 2000-2030, and we discuss past and future changes to vehicle technologies to reduce these emissions. We model the tradeoffs between short- and long-lived emission reductions across a range of technology options, life cycle emission intensities, and equivalency metrics. While short-lived vehicle emissions have decreased globally over the past two decades, significant reductions in CO 2 will be required by mid-century to meet climate change mitigation targets. This is true regardless of the time horizon used to compare long- and short-lived emissions. The short-lived emission intensities of some low-CO 2 technologies are higher than others, and thus their suitability for meeting climate targets depends sensitively on the evaluation time horizon. Other technologies offer low intensities of both short-lived emissions and CO 2 .

  5. Critical protein GAPDH and its regulatory mechanisms in cancer cells

    International Nuclear Information System (INIS)

    Zhang, Jin-Ying; Zhang, Fan; Hong, Chao-Qun; Giuliano, Armando E.; Cui, Xiao-Jiang; Zhou, Guang-Ji; Zhang, Guo-Jun; Cui, Yu-Kun

    2015-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), initially identified as a glycolytic enzyme and considered as a housekeeping gene, is widely used as an internal control in experiments on proteins, mRNA, and DNA. However, emerging evidence indicates that GAPDH is implicated in diverse functions independent of its role in energy metabolism; the expression status of GAPDH is also deregulated in various cancer cells. One of the most common effects of GAPDH is its inconsistent role in the determination of cancer cell fate. Furthermore, studies have described GAPDH as a regulator of cell death; other studies have suggested that GAPDH participates in tumor progression and serves as a new therapeutic target. However, related regulatory mechanisms of its numerous cellular functions and deregulated expression levels remain unclear. GAPDH is tightly regulated at transcriptional and posttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Several cancer-related factors, such as insulin, hypoxia inducible factor-1 (HIF-1), p53, nitric oxide (NO), and acetylated histone, not only modulate GAPDH gene expression but also affect protein functions via common pathways. Moreover, posttranslational modifications (PTMs) occurring in GAPDH in cancer cells result in new activities unrelated to the original glycolytic function of GAPDH. In this review, recent findings related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms and pathways involved in GAPDH regulation and its different roles in cancer cells are also described

  6. Pleiotropy constrains the evolution of protein but not regulatory sequences in a transcription regulatory network influencing complex social behaviours

    Directory of Open Access Journals (Sweden)

    Daria eMolodtsova

    2014-12-01

    Full Text Available It is increasingly apparent that genes and networks that influence complex behaviour are evolutionary conserved, which is paradoxical considering that behaviour is labile over evolutionary timescales. How does adaptive change in behaviour arise if behaviour is controlled by conserved, pleiotropic, and likely evolutionary constrained genes? Pleiotropy and connectedness are known to constrain the general rate of protein evolution, prompting some to suggest that the evolution of complex traits, including behaviour, is fuelled by regulatory sequence evolution. However, we seldom have data on the strength of selection on mutations in coding and regulatory sequences, and this hinders our ability to study how pleiotropy influences coding and regulatory sequence evolution. Here we use population genomics to estimate the strength of selection on coding and regulatory mutations for a transcriptional regulatory network that influences complex behaviour of honey bees. We found that replacement mutations in highly connected transcription factors and target genes experience significantly stronger negative selection relative to weakly connected transcription factors and targets. Adaptively evolving proteins were significantly more likely to reside at the periphery of the regulatory network, while proteins with signs of negative selection were near the core of the network. Interestingly, connectedness and network structure had minimal influence on the strength of selection on putative regulatory sequences for both transcription factors and their targets. Our study indicates that adaptive evolution of complex behaviour can arise because of positive selection on protein-coding mutations in peripheral genes, and on regulatory sequence mutations in both transcription factors and their targets throughout the network.

  7. Application of accelerator-produced short-lived radionuclides in industry

    International Nuclear Information System (INIS)

    Kupsch, H.

    1986-01-01

    Several problems such as corrosion, catalysis, wear, process optimization and diagnosis, damage analysis, arising in idustry can be solved using short-lived radioisotopes. Some examples of technological target designs which have been developed are demonstrated for the radionuclide production based on p,n; d,α; α,n; α,2n; α,p; γ,n; γ,p nuclear reactions. Applications of short-lived radionuclides in plants and processes of electrodeposition and gas concrete production are described. (author)

  8. A technique for the measurement of electron attachment to short-lived excited species

    International Nuclear Information System (INIS)

    Christophorou, L.G.; Pinnaduwage, L.A.; Bitouni, A.P.

    1990-01-01

    A technique is described for the measurement of electron attachment to short-lived (approx-lt 10 -9 s) excited species. Preliminary results are presented for photoenhanced electron attachment to short-lived electronically-excited states of triethylamine molecules produced by laser two-photon excitation. The attachment cross sections for these excited states are estimated to be >10 -11 cm 2 and are ∼10 7 larger compared to those for the unexcited (ground-state) molecules. 8 refs., 4 figs

  9. Microspheres labelled with short-lived isotopes: Development and application for tumors treatment (Experimental study)

    International Nuclear Information System (INIS)

    Drozdovsky, B.Y.; Rosiev, R.A.; Goncharova, A.Y.; Skvortsov, V.G.; Petriev, V.M.; Grigoriev, A.N.; Schischkanov, N.G.

    1997-01-01

    Analysis of the conducted studies strongly suggests the possibility of usage of the domestic protein microspheres as a vehicle for radionuclide. The neutron-activating method of RPP production enables to utilize a broad spectrum of short-living isotopes that can be delivered into the target organ and anchored there for a long time. Good treatment results were obtained in case of the experimentally induced rheumatoid arthritis in rats after intraarticular loading of 165 Dy-hMSA. Mathematical calculations show that homogeneous distribution of RPP in human articulation cavity with the square of 100 cm 2 can be achieved when the quantity of administered particles exceeds 3000. On the example of 165 Dy-hMSA energy characteristic distribution we demonstrated that the absorbed dose for damaged cells at 2mm distance from the radioactive source is 7 times less than the one for a sphere of 2mm diameter. Analysis of dosimetric data in case of intratumoral loading of 165 Dy-hMSA also point out the necessity of the absorbed dose calculation methods taking into account the distance from the source and possible heterogeneity of RPP distribution inside the tumor to be employed. The prolonged RPP detention in the target causing no essential morphological and functional changes was achieved by embolization on the level of septal and interlobular arteries and of efferent arterioles in the animal's renal. The uniformity of microsphere distribution in the organ and their accumulation in tumors depends on the number of particles being administered. Investigations carried out suggest the efficacy of radionuclide therapy application for treatment of oncological and heavy somatic diseases. They also indicate the necessity of further investigations aimed to optimize the usage of microspheres as a radionuclide carrier usage and to work out the criteria of dosimetric planning

  10. Microspheres labelled with short-lived isotopes: Development and application for tumors treatment (Experimental study)

    Energy Technology Data Exchange (ETDEWEB)

    Drozdovsky, B.Y.; Rosiev, R.A.; Goncharova, A.Y.; Skvortsov, V.G.; Petriev, V.M.; Grigoriev, A.N.; Schischkanov, N.G. [Medical Radiological Research Centre RAMS, Kaluga Region, (Russian Federation)

    1997-10-01

    Analysis of the conducted studies strongly suggests the possibility of usage of the domestic protein microspheres as a vehicle for radionuclide. The neutron-activating method of RPP production enables to utilize a broad spectrum of short-living isotopes that can be delivered into the target organ and anchored there for a long time. Good treatment results were obtained in case of the experimentally induced rheumatoid arthritis in rats after intraarticular loading of {sup 165}Dy-hMSA. Mathematical calculations show that homogeneous distribution of RPP in human articulation cavity with the square of 100 cm{sup 2} can be achieved when the quantity of administered particles exceeds 3000. On the example of {sup 165}Dy-hMSA energy characteristic distribution we demonstrated that the absorbed dose for damaged cells at 2mm distance from the radioactive source is 7 times less than the one for a sphere of 2mm diameter. Analysis of dosimetric data in case of intratumoral loading of {sup 165}Dy-hMSA also point out the necessity of the absorbed dose calculation methods taking into account the distance from the source and possible heterogeneity of RPP distribution inside the tumor to be employed. The prolonged RPP detention in the target causing no essential morphological and functional changes was achieved by embolization on the level of septal and interlobular arteries and of efferent arterioles in the animal`s renal. The uniformity of microsphere distribution in the organ and their accumulation in tumors depends on the number of particles being administered. Investigations carried out suggest the efficacy of radionuclide therapy application for treatment of oncological and heavy somatic diseases. They also indicate the necessity of further investigations aimed to optimize the usage of microspheres as a radionuclide carrier usage and to work out the criteria of dosimetric planning 25 refs.

  11. The Evolution of the Secreted Regulatory Protein Progranulin.

    Directory of Open Access Journals (Sweden)

    Roger G E Palfree

    Full Text Available Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i: the origins of metazoan progranulins (ii: the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii: the evolution of granulin module architectures of vertebrate progranulins (iv: the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl

  12. The Evolution of the Secreted Regulatory Protein Progranulin.

    Science.gov (United States)

    Palfree, Roger G E; Bennett, Hugh P J; Bateman, Andrew

    2015-01-01

    Progranulin is a secreted growth factor that is active in tumorigenesis, wound repair, and inflammation. Haploinsufficiency of the human progranulin gene, GRN, causes frontotemporal dementia. Progranulins are composed of chains of cysteine-rich granulin modules. Modules may be released from progranulin by proteolysis as 6kDa granulin polypeptides. Both intact progranulin and some of the granulin polypeptides are biologically active. The granulin module occurs in certain plant proteases and progranulins are present in early diverging metazoan clades such as the sponges, indicating their ancient evolutionary origin. There is only one Grn gene in mammalian genomes. More gene-rich Grn families occur in teleost fish with between 3 and 6 members per species including short-form Grns that have no tetrapod counterparts. Our goals are to elucidate progranulin and granulin module evolution by investigating (i): the origins of metazoan progranulins (ii): the evolutionary relationships between the single Grn of tetrapods and the multiple Grn genes of fish (iii): the evolution of granulin module architectures of vertebrate progranulins (iv): the conservation of mammalian granulin polypeptide sequences and how the conserved granulin amino acid sequences map to the known three dimensional structures of granulin modules. We report that progranulin-like proteins are present in unicellular eukaryotes that are closely related to metazoa suggesting that progranulin is among the earliest extracellular regulatory proteins still employed by multicellular animals. From the genomes of the elephant shark and coelacanth we identified contemporary representatives of a precursor for short-from Grn genes of ray-finned fish that is lost in tetrapods. In vertebrate Grns pathways of exon duplication resulted in a conserved module architecture at the amino-terminus that is frequently accompanied by an unusual pattern of tandem nearly identical module repeats near the carboxyl-terminus. Polypeptide

  13. The expression of cytoskeleton regulatory protein Mena in colorectal lesions.

    Science.gov (United States)

    Gurzu, Simona; Jung, I; Prantner, I; Ember, I; Pávai, Z; Mezei, T

    2008-01-01

    The actin regulatory proteins Ena/VASP (Enabled/Vasodilator stimulated phosphoprotein) family is involved in the control of cell motility and adhesion. They are important in the actin-dependent processes where dynamic actin reorganization it is necessary. The deregulation of actin cycle could have an important role in the cells' malignant transformation, tumor invasion or metastasis. Recently studies revealed that the human orthologue of murine Mena is modulated during the breast carcinogenesis. In our study, we tried to observe the immunohistochemical expression of mammalian Ena (Mena) in the colorectal polyps and carcinomas. We analyzed 10 adenomatous polyps (five with dysplasia) and 36 adenocarcinomas. We used the indirect immunoperoxidase staining. BD Biosciences have provided the Mena antibody. We observed that Mena was not expressed in the normal colorectal mucosa neither in polyps without dysplasia, but its expression was very high in polyps with high dysplasia. In colorectal carcinomas, Mena marked the tumoral cells in 80% of cases. In 25% of positive cases, the intensity was 3+, in 60% 2+ and in the other 15% 1+. The Mena intensity was higher in the microsatellite stable tumors (MSS) and was correlated with vascular invasion, with intensity of angiogenesis marked with CD31 and CD105 and with c-erbB-2 and p53 expression. This is the first study in the literature about Mena expression in colorectal lesions.

  14. A new integrative methodology for desertification studies based on magnetic and short-lived radioisotope measurements

    International Nuclear Information System (INIS)

    Oldfield, F.; Higgitt, S.R.; Maher, B.A.; Appleby, P.G.; Scoullos, M.

    1986-01-01

    The use of mineral magnetic measurements and short-lived radioisotope studies with 210 Pb and 137 Cs is discussed within the ecosystem watershed conceptual framework. Used in conjunction with geomorphological, sedimentological, palaeoecological and geochemical techniques, these methods can form the core of an integrated multidisciplinary study of desertification and erosion processes on all relevant temporal and spatial scales. 30 refs.; 4 figs

  15. Applications of short-lived isotopes in agricultural research in New Zealand

    International Nuclear Information System (INIS)

    McCallum, G.J.; More, R.D.; McNaughton, G.S.; Minchin, P.E.H.; Presland, M.R.; Stout, J.D.

    1981-01-01

    The use of the short-lived isotopes 11 C and 13 N in agricultural research studies in New Zealand is reviewed. The methods employed to produce these radioisotopes using a 3 MV Van de Graaff accelerator are given. Experiments on transport processes and the uptake of nutrient by plants, and the study of soil processes are described. (Auth.)

  16. Synthesis of radiopharmaceuticals containing short-lived radionuclides. Comprehensive report, March 1, 1980-February 26, 1986

    International Nuclear Information System (INIS)

    Kabalka, G.W.

    1985-09-01

    New methods for the rapid introduction of short-lived radionuclides into agents for use in diagnostic nuclear medicine are reported. Among the new syntheses reported are those for 123 I-labeled fatty acids and steroids, for 11 C-labeled alcohols, for 13 N-labeled amines, and for 15 O-labeled alcohols. 33 refs

  17. Analysing environmental and fishing effects on a short-lived species ...

    African Journals Online (AJOL)

    Short-lived species are extremely dependent on the seasonal and interannual variability of environmental conditions, and determining their stock status is often difficult. This study investigates the effects of environmental variability and fishing pressure on the stock of octopus Octopus vulgaris in Senegalese waters over a ...

  18. Disentangling the effects of CO2 and short-lived climate forcer mitigation

    NARCIS (Netherlands)

    Rogelj, J.; Schaeffer, M.; Meinshausen, M.; Shindell, D.T.; Hare, W.; Klimont, Z.; Velders, G.J.M.; Amann, M.; Schellnhuber, H.J.

    2014-01-01

    Anthropogenic global warming is driven by emissions of a wide variety of radiative forcers ranging from very short-lived climate forcers (SLCFs), like black carbon, to very long-lived, like CO2. These species are often released from common sources and are therefore intricately linked. However, for

  19. Developing role of short-lived radionuclides in nuclear medical practice. DOE symposium series; 56

    International Nuclear Information System (INIS)

    Paras, P.; Thiessen, J.W.

    1985-01-01

    The purpose was to define the developing role and state-of-the-art development of short-lived radionuclides (SLR's) in current nuclear medical practice. Special emphasis was placed on radionuclides with general-purpose labeling capabilities. The need for high-purity labeling-grade iodine-123 was emphasized in the program. Papers have been separately abstracted for the data base

  20. Synthesis of radiopharmaceuticals containing short-lived radionuclides. Progress report, March 1, 1985-February 26, 1986

    International Nuclear Information System (INIS)

    Kabalka, G.W.

    1985-09-01

    Methods for the rapid introduction of short-lived radionuclides into agents for use in diagnostic nuclear medicine are reported. Methods to synthesize radioiodinated fatty acids, lipids, and amphetamine derivatives are described. New routes for the introduction of bromine-77, chlorine-34m, and carbon-11 into agents of interest are elaborated. 46 refs

  1. Development of the k0-based cyclic neutron activation analysis for short-lived radionuclides

    NARCIS (Netherlands)

    Dung, H.M.; Blaauw, M.; Beasley, D.; Freitas, M.D.C.

    2011-01-01

    The k0-based cyclic neutron activation analysis (k0-CNAA) technique has been studied to explore the applicability at the Portuguese research reactor (RPI). In particular, for the determination of elements which form short-lived radionuclides, particularly fluorine (20F, 11.16 s half-life) and

  2. Short Lived Fission Product Yield Measurements in 235U, 238U and 239Pu

    Science.gov (United States)

    Silano, Jack; Tonchev, Anton; Tornow, Werner; Krishichayan, Fnu; Finch, Sean; Gooden, Matthew; Wilhelmy, Jerry

    2017-09-01

    Yields of short lived fission products (FPYs) with half lives of a few minutes to an hour contain a wealth of information about the fission process. Knowledge of short lived FPYs would contribute to existing data on longer lived FPY mass and charge distributions. Of particular interest are the relative yields between the ground states and isomeric states of FPYs since these isomeric ratios can be used to determine the angular momentum of the fragments. Over the past five years, a LLNL-TUNL-LANL collaboration has made precision measurements of FPYs from quasi-monoenergetic neutron induced fission of 235U, 238U and 239Pu. These efforts focused on longer lived FPYs, using a well characterized dual fission chamber and several days of neutron beam exposure. For the first time, this established technique will be applied to measuring short lived FPYs, with half lives of minutes to less than an hour. A feasibility study will be performed using irradiation times of < 1 hour, improving the sensitivity to short lived FPYs by limiting the buildup of long lived isotopes. Results from this exploratory study will be presented, and the implications for isomeric ratio measurements will be discussed. This work was performed under the auspices of US DOE by LLNL under Contract DE-AC52-07NA27344.

  3. Short-lived brain state after cued motor imagery in naive subjects

    NARCIS (Netherlands)

    Pfurtscheller, G.; Scherer, R.; Müller-Putz, G.R.; Lopes da Silva, F.H.

    2008-01-01

    Multi-channel electroencephalography recordings have shown that a visual cue, indicating right hand, left hand or foot motor imagery, can induce a short-lived brain state in the order of about 500 ms. In the present study, 10 able-bodied subjects without any motor imagery experience (naive subjects)

  4. The development of fast tantalum foil targets for short-lived isotopes

    CERN Document Server

    Bennett, J R J; Drumm, P V; Ravn, H L

    2003-01-01

    The development of fast tantalum foil targets for short-lived isotopes was discussed. It was found that the effusion was faster but the diffusion out of the foils was a limiting factor. The performance of the targets at ISOLDE with beams of **1**1Li, **1**2Be and **1**4Be was also analyzed. (Edited abstract) 13 Refs.

  5. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

    Science.gov (United States)

    Lloyd, David J.; St Jean, David J.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.; Wang, Minghan; Jordan, Steven R.; Véniant, Murielle M.; Hale, Clarence

    2013-12-01

    Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

  6. Neutron-induced cross sections of short-lived nuclei via the surrogate reaction method

    Directory of Open Access Journals (Sweden)

    Morel P.

    2011-10-01

    Full Text Available The measurement of neutron-induced cross sections of short-lived nuclei is extremely difficult due to the radioactivity of the samples. The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. This method presents the advantage that the target material can be stable or less radioactive than the material required for a neutron-induced measurement. We have successfully used the surrogate reaction method to extract neutron-induced fission cross sections of various short-lived actinides. In this work, we investigate whether this technique can be used to determine neutron-induced capture cross sections in the rare-earth region.

  7. Neutron-induced cross sections of short-lived nuclei via the surrogate reaction method

    Directory of Open Access Journals (Sweden)

    Tassan-Got L.

    2012-02-01

    Full Text Available The measurement of neutron-induced cross sections of short-lived nuclei is extremely difficult due to the radioactivity of the samples. The surrogate reaction method is an indirect way of determining cross sections for nuclear reactions that proceed through a compound nucleus. This method presents the advantage that the target material can be stable or less radioactive than the material required for a neutron-induced measurement. We have successfully used the surrogate reaction method to extract neutron-induced fission cross sections of various short-lived actinides. In this work, we investigate whether this technique can be used to determine neutron-induced capture cross sections in the rare-earth region.

  8. Determination of short-lived trace elements in environmental samples by neutron activation analysis

    International Nuclear Information System (INIS)

    Wardani, S.; Sihombing, E.; Hamzah, A.; Rochidi; Hery, P.S.; Hartaman, S.; Iman, J.

    1998-01-01

    Concentration of a short-lived trace elements in environmental samples were determined by neutron activation analysis, a counting loss often occur due to the high counting rate. A Pile-Up Rejecter (PUR) electric circuit was installed in counting a short-lived trace elements by a γ-ray spectrometer in order to correct a counting loss. The samples were irradiated for 30∼60 seconds at neutron flux of 3.5 x 10 12 n.cm -2 .s -1 , then the samples cooled for 120 second and counted for 180 second using this system. The nuclides concentration in the varieties environmental samples have a difference analysis result, was more accurate and precise, which the measured result would be 30 % more higher by PUR system than the result would be counted using a conventional γ-ray spectrometry method

  9. Use of short-lived radionuclides in the agricultural and environmental sciences

    International Nuclear Information System (INIS)

    Krohn, K.A.

    1985-01-01

    In addition to their well-known uses in physiology, biochemistry, and medicine, short-lived radioisotopes have played an important part in promoting the authors knowledge of the agricultural and environmental sciences. Numerous investigators have found that the scientific rewards justify the additional demands associated with use of short-lived radioisotopes when novel or uniquely precise results can be achieved. This is best exemplified by examining the use of 13 N. Nitrogen-13 is the longest lived radioisotope of this very important element. The 10-min half-life of 13 N has required that the agricultural or environmental test model be brought to the laboratory where the isotope is made, but this has been done successfully in numerous instances. One major incentive for this research has probably been the fact that there is no analog of the very useful 14 C tracer to study nitrogen chemistry and biology

  10. Studies on short-lived fission products at the Mainz TRIGA reactor

    International Nuclear Information System (INIS)

    Trautmann, N.

    1974-01-01

    Neutron-rich nuclei of medium mass number are produced by thermal-neutron-induced fission of heavy elements, e.g., 235 U, 239 Pu, and 249 Cf. Pulse irradiations lead to an enhancement of the ratio of short-lived activities to the accompanying longer-lived components. One approach for investigating the properties of short-lived nuclei consists in a combination of rapid chemical separations with higher-resolution gamma spectroscopy. This is demonstrated by the isolation of neutron-rich isotopes of niobium by sorption on glass and of ruthenium by solvent extraction. Other rapid separation procedures from aqueous solutions are briefly summarized and a few examples for their application in nuclear fission- and delayed neutron studies are given. Some experiments with an on-line mass separator of the ISOLDE-type, using chemical targets, are described. (U.S.)

  11. Aube storage centre for short-lived low- and intermediate-level wastes. Annual report 2009

    International Nuclear Information System (INIS)

    2010-06-01

    The National Radioactive Waste Management Agency (Andra), was established by the December 1991 Waste Act as a public body in charge of the long-term management of all radioactive waste, under the supervision of the Ministry of Ecology, Energy, Sustainable Development and the Sea (formerly the Ministry of Industry and the Ministry of Environment), and the Ministry of Research. The Andra operates two storage centers in the Aube region (France): the center for short-lived low- and intermediate-level wastes, and the center for very-low-level radioactive wastes. This document is the 2009 activity report of the center for short-lived low- and intermediate-level wastes. It presents a review of the activities of the center: presentation of the installations, safety and radiation protection, events or incidents, environmental monitoring, wastes management, public information, opinion of the Health and safety Committee (CHSCT)

  12. Aube storage center for short-lived low- and intermediate-level wastes. Annual report 2008

    International Nuclear Information System (INIS)

    2009-06-01

    The National Radioactive Waste Management Agency (Andra), was established by the December 1991 Waste Act as a public body in charge of the long-term management of all radioactive waste, under the supervision of the Ministry of Ecology, Energy, Sustainable Development and the Sea (formerly the Ministry of Industry and the Ministry of Environment), and the Ministry of Research. The Andra operates two storage centers in the Aube region (France): the center for short-lived low- and intermediate-level wastes, and the center for very-low-level radioactive wastes. This document is the 2008 activity report of the center for short-lived low- and intermediate-level wastes. It presents a review of the activities of the center: presentation of the installations, safety and radiation protection, events or incidents, environmental monitoring, wastes management, public information

  13. Aube storage center for short-lived low- and intermediate-level wastes. Annual report 2010

    International Nuclear Information System (INIS)

    2011-06-01

    The National Radioactive Waste Management Agency (Andra), was established by the December 1991 Waste Act as a public body in charge of the long-term management of all radioactive waste, under the supervision of the Ministry of Ecology, Energy, Sustainable Development and the Sea (formerly the Ministry of Industry and the Ministry of Environment), and the Ministry of Research. The Andra operates two storage centers in the Aube region (France): the center for short-lived low- and intermediate-level wastes, and the center for very-low-level radioactive wastes. This document is the 2010 activity report of the center for short-lived low- and intermediate-level wastes. It presents a review of the activities of the center: presentation of the installations, safety and radiation protection, events or incidents, environmental monitoring, wastes management, public information, recommendations of the Health and safety Committee (CHSCT)

  14. Simulation Studies of Diffusion-Release and Effusive-Flow of Short-Lived Radioactive Isotopes

    CERN Document Server

    Zhang, Yan; Kawai, Yoko

    2005-01-01

    Delay times associated with diffusion release from targets and effusive-flow transport of radioactive isotopes to ion sources are principal intensity limiters at ISOL-based radioactive ion beam facilities, and simulation studies with computer models are cost effective methods for designing targets and vapor transport systems with minimum delay times to avoid excessive decay losses of short lived ion species. A finite difference code, Diffuse II, was recently developed at the Oak Ridge National Laboratory to study diffusion-release of short-lived species from three principal target geometries. Simulation results are in close agreement with analytical solutions to Fick’s second equation. Complementary to the development of Diffuse II, the Monte-Carlo code, Effusion, was developed to address issues related to the design of fast vapor transport systems. Results, derived by using Effusion, are also found to closely agree with experimental measurements. In this presentation, the codes will be used in conc...

  15. Dynamical Detection of Topological Phase Transitions in Short-Lived Atomic Systems

    OpenAIRE

    Setiawan, F.; Sengupta, K.; Spielman, I. B.; Sau, Jay D.

    2015-01-01

    We demonstrate that dynamical probes provide direct means of detecting the topological phase transition (TPT) between conventional and topological phases, which would otherwise be difficult to access because of loss or heating processes. We propose to avoid such heating by rapidly quenching in and out of the short-lived topological phase across the transition that supports gapless excitations. Following the quench, the distribution of excitations in the final conventional phase carries signat...

  16. Extrinsic and intrinsic factors that shape the life history of the short living scallop Argopecten ventricosus

    OpenAIRE

    Guerra, Citlali

    2011-01-01

    The scallop Argopecten ventricosus is characterized by its high swimming activity, fast growth, high reproductive effort and the early age to get first sexual maturity. These traits may be the result of the adaptation to a specific environment that favors an active lifestyle and a short lifespan (2 years). This opens the question of how environmental factors modulate the way a short living marine ectotherm budget energy investments among life history traits and how this modulation impacts the...

  17. Place of the final disposal of short lived dismantling waste; Plats foer slutfoervaring av kortlivat rivningsavfall

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-01-15

    This report deals with the short-lived low and intermediate level radioactive waste, which will mainly arise from the dismantling of the Swedish nuclear power plants, but also the dismantling of other nuclear facilities. For these installations to be dismantled, there must be the capacity to receive and dispose of dismantling waste. SKB plans to expand the existing final repository for short-lived radioactive waste (SFR) in Forsmark for this purpose. The legislation requires alternatives to the chosen location. The alternate location for the disposal of decommissioning waste SKB has chosen to compare with is a location in the Simpevarp area outside Oskarshamn. There are currently Oskarshamn nuclear power plant and SKB between stock 'CLAB'. The choice of Simpevarp as alternative location is based on that it's one of the places in the country where data on the bedrock is available to an extent that allows an assessment of the prospects for long-term security, such an assessment is actually showing good potential, and that the location provide realistic opportunities to put into practice the disposal of decommissioning waste. At a comparison between the disposal of short-lived decommissioning waste in an extension of SFR with the option to build a separate repository for short-lived decommissioning waste in Simpevarp, the conclusion is that both options offer potentially good prospects for long-term security. The differences still indicated speaks to the Forsmark advantage. Similar conclusions were obtained when comparing the factors of environment, health and social aspects.

  18. Continuous administration of short-lived isotopes for evaluating dynamic parameters

    International Nuclear Information System (INIS)

    Selikson, M.

    1985-01-01

    In this paper it is shown that continuous but varying infusions (specifically, exponential infusions) of a short-lived radionuclide can be used to evaluate a wide range of dynamic parameters. The detector response to exponential infusions is derived. An example of an inert diffusible substrate for evaluating regional flow and a glucose model for evaluating regional metabolic rate are both worked out. The advantages of using exponential infusion methods are discussed

  19. Identification of short-lived neutron-rich ruthenium and rhodium isotopes in fission

    International Nuclear Information System (INIS)

    Franz, G.; Herrmann, G.

    1975-01-01

    Short-lived ruthenium and rhodium isotopes ( 107 Ru, 108 Ru, 108 Rh, 109 Ru, 109 Rh, 110 Ru, 110 Rh, 111 Ru, 111 Rh, 112 Ru, 112 Rh, 113 Ru) have been separated from fission products by a rapid chemical procedure and identified by means of γ-ray spectroscopy. Nuclides with half-lives down to 3 sec were accessible. Ruthenium isotopes up to mass number 113 have been identified. (author)

  20. Review of short-lived radionuclide activities in the United States

    International Nuclear Information System (INIS)

    Sodd, V.J.

    1985-01-01

    A review is given of the accelerator-produced short-lived radionuclides which are used in radiopharmaceuticals available commercially in the US and of the accelerator facilities devoted primarily to their production. Reactions for the efficient production of 67 Ga, 81 Rb → /sup 81m/Kr, 111 In, 201 Tl, and 123 I are given. Methods for the production of higher purity 123 I are suggested

  1. Last developments in the Belgian disposal programme for low and intermediate short-lived waste

    International Nuclear Information System (INIS)

    Boyazis, Jean-Paul

    2006-01-01

    After an historical reminder of the several phases of the Belgian program for the disposal of low and medium level short-lived waste since the creation of ONDRAF/NIRAS and the bad results obtained in the 90's by using a pure technical approach, the presentation will explain the main lines of the new methodology developed, as a consequence of the government decision of 16 January 1998 in ONDRAF/NIRAS to improve local acceptance for the disposal project. The way local partnerships were created with four nuclear municipalities under the form of a non-profit organization with a clear mission, the functioning, on a voluntary base, of the different partnerships during four to six years and the concrete results obtained until now using this very innovative method will be addressed. The last developments of the Belgian program for the disposal of low and medium level and short-lived waste will be presented, including the recent and very important decision of the Belgian government of 23 June 2006 to dispose of the low and medium active short-lived waste in a surface disposal installation on the territory of the municipality Dessel. (author)

  2. Applications of short lived nuclides in activation analysis, problems and progress

    Energy Technology Data Exchange (ETDEWEB)

    Grass, F [Atominstitut, Vienna (Austria)

    1976-07-01

    Short lived nuclides or isomeric transitions, respectively would have some advantages over long lived ones. Although we published a paper concerning a germanium-determination in iron meteorites some years ago, only few laboratories use this technique, the main reason being that the high matrix activity disturbs the measurement of energy-spectra. A multichannel analyzer in the time sequence mode enables Li-8 determination by a purely instrumental method which is therefore used more frequently. In the time sequence mode much higher counting rates up to 10 - 50 MHz are processed then by taking energy-spectra. This is the reason why activation analysis with short lived isomeric states is seldom applied when counting rate and pulse height are to be detected simultaneously. Exceptional difficulties are encountered in measurement of samples activated by a reactor pulse. Further difficulties arise from the fact that an optimal expelling time depends on the half life of the nuclide, and is more critical if the half life is short and the full width half maximum of the reactor pulse is small. Commercial Ge-Li-detectors can be used only at low counting rates, so that samples with high matrix activities cannot be measured. Modifying the electronic system enables registration of samples with high matrix activities. For short lived nuclides emitting hard beta-rays, e.g. B-12 or Li-8, a Cerenkov-detector is optimal. These problems are discussed in examples. (author)

  3. Regulatory mechanisms of skeletal muscle protein turnover during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2009-01-01

    Skeletal muscle protein turnover is a relatively slow metabolic process that is altered by various physiological stimuli such as feeding/fasting and exercise. During exercise, catabolism of amino acids contributes very little to ATP turnover in working muscle. With regards to protein turnover......, there is now consistent data from tracer studies in rodents and humans showing that global protein synthesis is blunted in working skeletal muscle. Whether there is altered skeletal muscle protein breakdown during exercise remains unclear. The blunting of protein synthesis is believed to be mediated...... downstream of changes in intracellular Ca(2+) and energy turnover. In particular, a signaling cascade involving Ca(2+)-calmodulin-eEF2 kinase-eEF2 is implicated. The possible functional significance of altered protein turnover in working skeletal muscle during exercise is discussed. Further work...

  4. Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element

    International Nuclear Information System (INIS)

    Mao, Grace; Brody, James P.

    2007-01-01

    Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16 bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16 bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014 s -1 . We conclude that (1) SPR-based assays can monitor DNA-nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase

  5. Systematic measurement of beta-decay half-lives of short-lived isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, T.; Yamamoto, H.; Kawade, K. [Nagoya Univ. (Japan); Iida, T.; Takahashi, A.; Kasugai, Y.; Ikeda, Y.

    1997-03-01

    We have measured the half-lives of short-lived isotopes for past decade and deduced the half-lives of 6 isotopes further. These results demonstrated that most of the literature values shorter than 10 min systematically deviated from our measurement ones. The cause seems to be that a large number of the previous half-life studies were performed with scintillation counters before 1970 and they had a difficulty in distinguishing the interest {gamma}-ray from the contamination and correcting for pile-up and dead-time losses. Moreover, the deviated data found to be quoted for evaluation. (author)

  6. Quantum non-locality in a two-slit interferometer for short-lived particles

    International Nuclear Information System (INIS)

    Klein, Spencer R.; Nystrand, Joakim

    2001-01-01

    We describe a new test of quantum nonlocality, using an interferometer for short-lived particles. The separation is large compared with the particle lifetimes. This interferometer is realized by vector meson production in distant heavy ion collisions. The mesons decay before waves from the two sources (ions) can overlap, so interference is only possible among the decay products. The post-decay wave function must retain amplitudes for all possible decays. The decay products are spatially separated, necessitating a non-local wave function. The interference is measurable by summing the product momenta. Alternately, the products positions could be observed, allowing new tests of the EPR paradox

  7. Short-lived cyclotron-produced radioisotopes: Medi-Physics, Inc.'s commitment

    International Nuclear Information System (INIS)

    Kramer, H.H.

    1985-01-01

    Medi-Physics, Inc., is a major US supplier of short-lived cyclotron-produced radioisotopes for radiopharmaceuticals, as well as routinely producing and distributing the greatest number of 123 I radiopharmaceuticals. The present commercial production capacity for 123 I is more than ten times the theoretical need for existing procedures and is more than adequate for the research and development of new radiopharmaceuticals. However, production capacity is only one component of many that are required to supply a radioisotope for human use. These components are summarized in this paper

  8. Rapid transfer of short-lived radioisotopes via a 2. 4 km rabbit system

    Energy Technology Data Exchange (ETDEWEB)

    Burgerjon, J J; Gelbart, Z; Lau, V; Lehnart, D; Lenz, J; Pate, B D; Ruth, T J; Sprenger, H P; van Oers, N S.C.

    1984-09-01

    A 2.4 km long pipeline between a cyclotron and a hospital is used for the rapid transfer of short-lived radiopharmaceuticals. The vials containing the pharmaceuticals are placed inside capsules (rabbits) that are blown through a tube by means of compressed air. Travel times as short as 2 min are achieved, which makes the system suitable for the transfer of /sup 15/O, which has a 2 min half-life. The construction and test results of the system are described along with a computer model, developed to explain some properties of the system. 7 references, 15 figures, 2 tables.

  9. [Hyperfine structure and isotope shift measurements of short lived elements by laser spectroscopy

    International Nuclear Information System (INIS)

    Schuessler, H.A.

    1986-01-01

    The aim of this research is to determine nuclear moments and charge distributions of short-lived isotopes produced both on-line and off-line to a nuclear facility. These measurements give detailed information on the nuclear force and are used to test current nuclear models. The small amounts of nuclei which can be produced off stability constitute the challenge in these experiments. Presently mainly neutron-rich isotopes are being studied by three ultrasensitive high-resolution laser techniques. These are collinear fast ion-beam laser spectroscopy, stored-ion laser spectroscopy and fluorescence spectroscopy. 5 figs

  10. Tantalum-178 - a short-lived nuclide for nuclear medicine: development of a potential generator system

    International Nuclear Information System (INIS)

    Neirinckx, R.D.; Jones, A.G.; Davis, M.A.; Harris, G.I.; Holman, B.L.

    1978-01-01

    We describe a chemical separation that may form the basis of a generator system for the short-lived radionuclide Ta-178 (T/sub 1/2/ = 9 min). The parent nuclide W-178 (T/sub 1/2/ = 21.7 days) is loaded on an anion-exchange column and the daughter eluted with a mixture of dilute hydrochloric acid and hydrogen peroxide. The yields of tantalum and the breakthrough of the tungsten parent as a function of the eluting conditions are discussed, and preliminary animal distribution data are presented for various treatments of the eluant solution

  11. Preparing isomerically pure beams of short-lived nuclei at JYFLTRAP

    Energy Technology Data Exchange (ETDEWEB)

    Eronen, T. [Department of Physics, University of Jyvaeskylae, P.O. Box 35 (YFL), FIN-40014 (Finland)], E-mail: tommi.eronen@jyu.fi; Elomaa, V.-V.; Hager, U.; Hakala, J.; Jokinen, A.; Kankainen, A.; Rahaman, S.; Rissanen, J.; Weber, C.; Aystoe, J. [Department of Physics, University of Jyvaeskylae, P.O. Box 35 (YFL), FIN-40014 (Finland)

    2008-10-15

    A new procedure to prepare isomerically clean samples of short-lived ions with a mass resolving power of more than 1 x 10{sup 5} has been developed at the JYFLTRAP tandem Penning trap system. The method utilises a dipolar rf-excitation of the ion motion with separated oscillatory fields in the precision trap. During a subsequent retransfer to the purification trap, the contaminants are rejected and as a consequence, the remaining bunch is isomerically cleaned. This newly-developed method is suitable for very high-resolution cleaning and is at least a factor of five faster than the methods used so far in Penning trap mass spectrometry.

  12. Changes in oxidative stress parameters in relation to age, growth and reproduction in the short-lived catarina scallop Argopecten ventricosus reared in its natural environment.

    Science.gov (United States)

    Guerra, C; Zenteno-Savín, T; Maeda-Martínez, A N; Philipp, E E R; Abele, D

    2012-08-01

    Increase in oxidative damage and decrease in cellular maintenance is often associated with aging, but, in marine ectotherms, both processes are also strongly influenced by somatic growth, maturation and reproduction. In this study, we used a single cohort of the short-lived catarina scallop Argopecten ventricosus, to investigate the effects of somatic growth, reproduction and aging on oxidative damage parameters (protein carbonyls, TBARS and lipofuscin) and cellular maintenance mechanisms (antioxidant activity and apoptosis) in scallops, caged in their natural environment. The concentrations of protein carbonyls and TBARS increased steeply during the early period of fast growth and during reproduction in one-year-old scallops. However, oxidative damage was transient, and apoptotic cell death played a pivotal role in eliminating damage in gill, mantle and muscle tissues of young scallops. Animals were able to reproduce again in the second year, but the reduced intensity of apoptosis impaired subsequent removal of damaged cells. In late survivors low antioxidant capacity and apoptotic activity together with a fast accumulation of the age pigment lipofuscin was observed. Rates of oxygen consumption and oxidative stress markers were strongly dependent on somatic growth and reproductive state but not on temperature. Compared to longer-lived bivalves, A. ventricosus seems more susceptible to oxidative stress with higher tissue-specific protein carbonyl levels and fast accumulation of lipofuscin in animals surviving the second spawning. Superoxide dismutase activity and apoptotic cell death intensity were however higher in this short-lived scallop than in longer-lived bivalves. The life strategy of this short-lived and intensely predated scallop supports rapid somatic growth and fitness as well as early maturation at young age at the cost of fast cellular degradation in second year scallops. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins Involved in a Posttranscriptional Iron Regulatory Mechanism

    Science.gov (United States)

    Figueroa-Angulo, Elisa E.; Calla-Choque, Jaeson S.; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-01-01

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

  14. Regulatory crosstalk by protein kinases on CFTR trafficking and activity

    Science.gov (United States)

    Farinha, Carlos Miguel; Swiatecka-Urban, Agnieszka; Brautigan, David; Jordan, Peter

    2016-01-01

    Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e. channel opening and closing) is regulated by protein kinases and phosphatases via phosphorylation and dephosphorylation. Here, we review recent evidence for the role of protein kinases in regulation of CFTR delivery to and retention in the plasma membrane. We review this information in a broader context of regulation of other transporters by protein kinases because the overall functional output of transporters involves the integrated control of both their number at the plasma membrane and their specific activity. While many details of the regulation of intracellular distribution of CFTR and other transporters remain to be elucidated, we hope that this review will motivate research providing new insights into how protein kinases control membrane transport to impact health and disease.

  15. Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells.

    OpenAIRE

    Jiang, M; Pandey, S; Tran, V T; Fong, H K

    1991-01-01

    The expression of GTP-binding regulatory proteins (G proteins) in retinal pigment epithelial (RPE) cells was analyzed by RNA blot hybridization and cDNA amplification. Both adult and fetal human RPE cells contain mRNA for multiple G protein alpha subunits (G alpha) including Gs alpha, Gi-1 alpha, Gi-2 alpha, Gi-3 alpha, and Gz alpha (or Gx alpha), where Gs and Gi are proteins that stimulate or inhibit adenylyl cyclase, respectively, and Gz is a protein that may mediate pertussis toxin-insensi...

  16. Short-lived radioactive nuclides in meteorites and early solar system processes

    International Nuclear Information System (INIS)

    Chaussidon, M.; Gounelle, M.

    2007-01-01

    Now extinct, short-lived radioactive nuclides, such as 7 Be (T 1/2 = 53 days), 10 Be (T 1/2 = 1.5 Ma), 26 Al (T 1/2 = 0.74 Ma), 36 Cl (T 1/2 = 0.3 Ma), 41 Ca (T 1/2 = 0.1 Ma), 53 Mn (T 1/2 = 3.7 Ma) and 60 Fe (T 1/2 = 1.5 Ma), were present in the proto-solar nebula when the various components of meteorites formed. The presence of these radioactive isotopes requires a 'last-minute' origin, either nucleosynthesis in a massive star dying close in space and time to the nascent solar system or production by local irradiation of part of the proto-solar disk by high-energy solar cosmic rays. In this review, we list: (i) the different observations indicating the existence of multiple origins for short-lived radioactive nuclides, namely 7 Be, 10 Be and 36 Cl for irradiation scenario and 60 Fe for injection scenario; (ii) the constraints that exist on their distribution (homogeneous or heterogeneous) in the accretion disk; (iii) the constraints they brought on the timescales of nebular processes (from Ca-Al-rich inclusions to chondrules) and of the accretion and differentiation of planetesimals. (authors)

  17. Behaviour of short-lived fission products within operating UO2 fuel elements

    International Nuclear Information System (INIS)

    Hastings, I.J.; Hunt, C.E.L.; Lipsett, J.J.

    1983-01-01

    We have carried out experiments using a ''sweep gas'' technique to determine the behaviour of short-lived fission products within operating, intact UO 2 fuel elements. The Zircaloy-4-clad elements were 500 mm long and contained fuel of density 10.65-10.71 Mg/m 3 . A He-2% H 2 carrier gas swept gaseous or volatile fission products out of the operating fuel element past a gamma spectrometer for measurement. In tests at linear powers of 45 and 60 kW/m to maximum burnups of 70 MW.h/kg U, the species measured directly at the spectrometer were generally the short-lived xenons and kryptons. We did not observe iodine or bromine during normal operation. However, we have deduced the behaviour of I-133 and I-135 from the decay of Xe-133 and Xe-135 during reactor shutdowns. Plots of R/B (released/born) against lambda (decay constant) or effective lambda for all isotopes observed at 45 and 60 kW/m show that a line of slope -0.5, corresponding with diffusion kinetics, is a good fit to the measured xenon and krypton data. Our inferred release of iodine fits the same line. From this we can extrapolate to an R/B for I-131 of about 5x10 -3 . The ANS 5.4 release correlation gives calculated results in good agreement with our measurements. (author)

  18. Search for short-lived particles produced on nuclei with a heavy liquid mini bubble chamber

    CERN Multimedia

    2002-01-01

    The aim of this experiment is to search for short-lived particles produced in hadronic interactions on nuclei with our high resolution heavy liquid mini bubble chamber BIBC, aiming to establish the cross-section for associated production in hadron-nucleus collisions, its $A$-dependence and an approximate value of the lifetime. The chamber will be operated at a bubble density of 290 bubbles/cm and with an apparent bubble size of 30 $\\mu$m in real space. In test runs at CERN we measured detection efficiencies which, together with simulations of $D\\bar{D}$ production and decay, lead to a sensitivity of 0.25 events/($\\mu$b/N) per day if the lifetime is of the order of $5\\times10^{-13}$s. A null result after 10 days running time would set an upper limit on the production cross section to $3 \\mu$b. \\\\ \\\\ In order to measure the momenta of charged decay products of short-lived particles, the bubble chamber will be placed 1.80 m upstream of the streamer chamber of the NA5 experiment (MPI). The geometrical acceptance ...

  19. Continuous administration of short-lived radioisotope tracers and the analogous Laplace transform

    International Nuclear Information System (INIS)

    Orr, J.S.

    1979-01-01

    Short-lived radioactive tracers are used because of the low radiation dose to patients. Another advantage finding increasing use, however, is that the equilibrium activities achieved by continuous administration to a steady state contain kinetic information. This is not the case with long-lived isotopes. The derivation of quantitative kinetic information in the form of rate constants or flows requires the formulation of a model of the system being studied. Several approaches to this have been published based on a model of single compartments with simultaneous arrival of tracer. To deal with more realistic models a method is proposed which uses the analogy between the procedure of continuous administration of short-lived tracer and the Laplace transform. This analogy permits all the theorems of Laplace transform theory to be applied to the analysis of measured activities. The basis of the analogy is explained and examples are given of its application to a number of models which represent actual physiology more realistically than single compartment models. In these applications the transformed equations representing the model, with measured values of activity inserted for each transform, are solved to derive the rate constants. This is different from the use of Laplace transforms where the constant coefficients are known and the initial value problem is solved to find the behaviour of the variables. (author)

  20. Production of exotic, short lived carbon isotopes in ISOL-type facilities

    CERN Document Server

    Franberg, Hanna; Köster, Ulli; Ammann, Markus

    2008-01-01

    The beam intensities of short-lived carbon isotopes at Isotope Separation On-Line (ISOL) facilities have been limited in the past for technical reasons. The production of radioactive ion beams of carbon isotopes is currently of high interest for fundamental nuclear physics research. To produce radioactive ions a target station consisting of a target in a container connected to an ion source via a transfer line is commonly used. The target is heated to vaporize the product for transport. Carbon in elementary form is a very reactive element and react strongly with hot metal surfaces. Due to the strong chemisorption interaction, in the target and ion source unit, the atoms undergo significant retention on their way from the target to the ion source. Due to this the short lived isotopes decays and are lost leading to low ion yields. A first approach to tackle these limitations consists of incorporating the carbon atoms into less reactive molecules and to use materials for the target housing and the transfer line ...

  1. Short-lived pollutants in the Arctic: their climate impact and possible mitigation strategies

    Directory of Open Access Journals (Sweden)

    S. Menon

    2008-03-01

    Full Text Available Several short-lived pollutants known to impact Arctic climate may be contributing to the accelerated rates of warming observed in this region relative to the global annually averaged temperature increase. Here, we present a summary of the short-lived pollutants that impact Arctic climate including methane, tropospheric ozone, and tropospheric aerosols. For each pollutant, we provide a description of the major sources and the mechanism of forcing. We also provide the first seasonally averaged forcing and corresponding temperature response estimates focused specifically on the Arctic. The calculations indicate that the forcings due to black carbon, methane, and tropospheric ozone lead to a positive surface temperature response indicating the need to reduce emissions of these species within and outside the Arctic. Additional aerosol species may also lead to surface warming if the aerosol is coincident with thin, low lying clouds. We suggest strategies for reducing the warming based on current knowledge and discuss directions for future research to address the large remaining uncertainties.

  2. Short-lived pollutants in the Arctic: their climate impact and possible mitigation strategies

    Energy Technology Data Exchange (ETDEWEB)

    Menon, Surabi; Quinn, P.K.; Bates, T.S.; Baum, E.; Doubleday, N.; Fiore, A.M.; Flanner, M.; Fridlind, A.; Garrett, T.J.; Koch, D.; Menon, S.; Shindell, D.; Stohl, A.; Warren, S.G.

    2007-09-24

    Several short-lived pollutants known to impact Arctic climate may be contributing to the accelerated rates of warming observed in this region relative to the global annually averaged temperature increase. Here, we present a summary of the short-lived pollutants that impact Arctic climate including methane, tropospheric ozone, and tropospheric aerosols. For each pollutant, we provide a description of the major sources and the mechanism of forcing. We also provide the first seasonally averaged forcing and corresponding temperature response estimates focused specifically on the Arctic. The calculations indicate that the forcings due to black carbon, methane, and tropospheric ozone lead to a positive surface temperature response indicating the need to reduce emissions of these species within and outside the Arctic. Additional aerosol species may also lead to surface warming if the aerosol is coincident with thin, low lying clouds. We suggest strategies for reducing the warming based on current knowledge and discuss directions for future research to address the large remaining uncertainties.

  3. EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions

    DEFF Research Database (Denmark)

    Luo, Yonglun; Friis, Jenny Blechingberg; Fernandes, Ana Miguel

    2015-01-01

    at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. Conclusions The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes...... involved in pathways at the RNA regulatory level with potential to mediate normal and disease-associated functions of the FUS and EWS proteins.......Background FUS (TLS) and EWS (EWSR1) belong to the FET-protein family of RNA and DNA binding proteins. FUS and EWS are structurally and functionally related and participate in transcriptional regulation and RNA processing. FUS and EWS are identified in translocation generated cancer fusion proteins...

  4. Architecture of the 99 bp DNA-six-protein regulatory complex of the lambda att site.

    Science.gov (United States)

    Sun, Xingmin; Mierke, Dale F; Biswas, Tapan; Lee, Sang Yeol; Landy, Arthur; Radman-Livaja, Marta

    2006-11-17

    The highly directional and tightly regulated recombination reaction used to site-specifically excise the bacteriophage lambda chromosome out of its E. coli host chromosome requires the binding of six sequence-specific proteins to a 99 bp segment of the phage att site. To gain structural insights into this recombination pathway, we measured 27 FRET distances between eight points on the 99 bp regulatory DNA bound with all six proteins. Triangulation of these distances using a metric matrix distance-geometry algorithm provided coordinates for these eight points. The resulting path for the protein-bound regulatory DNA, which fits well with the genetics, biochemistry, and X-ray crystal structures describing the individual proteins and their interactions with DNA, provides a new structural perspective into the molecular mechanism and regulation of the recombination reaction and illustrates a design by which different families of higher-order complexes can be assembled from different numbers and combinations of the same few proteins.

  5. Co-suppression of sterol-regulatory element binding protein ...

    African Journals Online (AJOL)

    Administrator

    2011-06-22

    Jun 22, 2011 ... protein mediates etiolation in Arabidopsis thaliana .... (A) The scheme of At5g35220 gene and pEGAD-At5g35220; .... stem length of 42-day-old plants; root length of 5-day-old seedlings grown on MS medium; fresh weight of ...

  6. Feast/famine regulatory proteins (FFRPs): Escherichia coli Lrp, AsnC and related archaeal transcription factors.

    Science.gov (United States)

    Yokoyama, Katsushi; Ishijima, Sanae A; Clowney, Lester; Koike, Hideaki; Aramaki, Hironori; Tanaka, Chikako; Makino, Kozo; Suzuki, Masashi

    2006-01-01

    Feast/famine regulatory proteins comprise a diverse family of transcription factors, which have been referred to in various individual identifications, including Escherichia coli leucine-responsive regulatory protein and asparagine synthase C gene product. A full length feast/famine regulatory protein consists of the N-terminal DNA-binding domain and the C-domain, which is involved in dimerization and further assembly, thereby producing, for example, a disc or a chromatin-like cylinder. Various ligands of the size of amino acids bind at the interface between feast/famine regulatory protein dimers, thereby altering their assembly forms. Also, the combination of feast/famine regulatory protein subunits forming the same assembly is altered. In this way, a small number of feast/famine regulatory proteins are able to regulate a large number of genes in response to various environmental changes. Because feast/famine regulatory proteins are shared by archaea and eubacteria, the genome-wide regulation by feast/famine regulatory proteins is traceable back to their common ancestor, being the prototype of highly differentiated transcription regulatory mechanisms found in organisms nowadays.

  7. Influence of endurance training on skeletal muscle mitophagy regulatory proteins in type 2 diabetic men.

    Science.gov (United States)

    Brinkmann, Christian; Przyklenk, Axel; Metten, Alexander; Schiffer, Thorsten; Bloch, Wilhelm; Brixius, Klara; Gehlert, Sebastian

    2017-11-01

    Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients. Muscle biopsies were obtained from eight overweight/obese T2DM men (61±10 years) at T1 (6 weeks pre-training), T2 (1 week pre-training), and T3 (3 to 4 days post-training). Protein contents were determined by Western blotting. The training increased mitochondrial complex II significantly (T2-T3: +29%, p = 0.037). The protein contents of mitophagy regulatory proteins (phosphorylated form of forkhead box O3A (pFOXO3A), mitochondrial E3 ubiquitin protein ligase-1 (MUL1), Bcl-2/adenovirus E1B 19-kD interacting protein-3 (BNIP3), microtubule-associated protein 1 light chain-3B (the ratio LC3B-II/LC3B-I was determined)) did not differ significantly between T1, T2, and T3. The results imply that training-induced changes in OXPHOS subunits (significant increase in complex II) are not accompanied by changes in mitophagy regulatory proteins in T2DM men. Future studies should elucidate whether acute exercise might affect mitophagic processes in T2DM patients (and whether a transient regulation of mitophagy regulatory proteins is evident) to fully clarify the role of physical activity and mitophagy for mitochondrial health in this particular patient group.

  8. Short-lived Isotopes from a Close-by AGB Star Triggering the Protosolar Nebula

    Science.gov (United States)

    Gallino, R.; Busso, M.; Wasserburg, G. J.; Straniero, O.

    The presence of short-lived isotopes in the early solar system, in particular 26Al, 41Ca, 60Fe, and 107Pd, point to a close-by and fresh nucleosynthesis source, possibly triggering the collapse of the protosolar nebula. We present the results of nucleosynthesis calculations based on an AGB polluting hypothesis. A general concordance of the predicted yields of the above radioactivities relative to 26Al can be obtained in the case of an intermediate mass AGB star with hot bottom burning in the envelope (thus producing 26Al), and mixing through a series of third dredge-up episodes a fraction of the C-rich and s-processed material from the He intershell with the extended envelope. Polution of the protosolar nebula with freshly synthesized material may derive from the efficient winds of the AGB star. In AGB stars, the s-process nucleosynthesis occurs both during the maximum phase of every thermal runaway, driven by the partial activation of the 22Ne(alpha,n)25Mg reaction, and in the interpulse phase, where the 13C nuclei are fully consumed in radiative conditions by the activation of the 13C(alpha,n)16O reaction. We have used different prescriptions for the amount of the 13C nuclei present in the intershell. A minimum amount of 13C is naturally expected in the ashes of H-shell burning. Possible formation of an extra "13C-pocket" derives from the injection of a small amount of protons from the envelope into the 12C-rich intershell during any third dredge-up episode, when the H-shell is inactivated. Prediction for other short-lived, 36Cl, 135Cs, and 205Pb, are given. General consequences for the pollution of the protosolar nebula with newly synthesized stable isotopes from the AGB winds are outlined. The origin of other detected short-lived nuclei, in particular 53Mn, 129I, and 182Hf, which cannot come from an AGB source, is analysed. The alternative trigger hypothesis by a close-by Supernova is discussed.

  9. Measurements of beta-decay half-lives of short-lived nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, T.; Tsurita, Y.; Yamamoto, H.; Kawade, K. [Nagoya Univ. (Japan); Iida, T.; Takahashi, A.; Kasugai, Y.; Ikeda, Y.

    1997-03-01

    The {beta}-decay half-lives of short-lived nuclei produced by 14 MeV neutron bombardments were measured with Ge detectors, a High-rate spectroscopy amplifier (EG and G ORTEC model 973) and a Spectrum multi-scaler (Laboratory equipment corporation SMS-48) in the multi-scaling mode. The adequate corrections for pile-up and dead-time losses were made by applying source and pulser methods. The half-lives of {sup 53}V, {sup 53g}Fe, {sup 89m}Y and {sup 162}Tb were determined with uncertainties of 0.13-0.65%. It has been shown that previous values shorter than 10 min were systematically longer than the present ones. (author)

  10. Laser generation of proton beams for the production of short-lived positron emitting radioisotopes

    International Nuclear Information System (INIS)

    Spencer, I.; Ledingham, K.W.D.; Singhal, R.P.; McCanny, T.; McKenna, P.; Clark, E.L.; Krushelnick, K.; Zepf, M.; Beg, F.N.; Tatarakis, M.; Dangor, A.E.; Norreys, P.A.; Clarke, R.J.; Allott, R.M.; Ross, I.N.

    2001-01-01

    Protons of energies up to 37 MeV have been generated when ultra-intense lasers (up to 10 20 W cm -2 ) interact with hydrogen containing solid targets. These protons can be used to induce nuclear reactions in secondary targets to produce β + -emitting nuclei of relevance to the nuclear medicine community, namely 11 C and 13 N via (p, n) and (p,α) reactions. Activities of the order of 200 kBq have been measured from a single laser pulse interacting with a thin solid target. The possibility of using ultra-intense lasers to produce commercial amounts of short-lived positron emitting sources for positron emission tomography (PET) is discussed

  11. Radioactivity of radon and its short-lived decay products in room air, 2

    International Nuclear Information System (INIS)

    Shimo, Michikuni; Katoh, Takao

    1983-01-01

    In the reactor room of the Kyoto University Research Reactor Institute, the measurements of radon (Rn) and its short-lived decay products (Rn-Dts) were carried out under ventilated and non-ventilated conditions. The indoor activities were equal to outdoor ones under ventilated condition and those activities increased till about 10 times of outdoors under non-ventilated condition. We attempted to explain these results on a basis of a simple model. The calculations were performed taking into account: (1) supply of Rn and Rn-Dts from outdoor, (2) the emanation rate of Rn from the wall materials of building, (3) the removal rate of Rn-Dts by ventilation and wall deposition, and (4) the attachment rate of unattached atom to aerosols. In addition, natural ventilation were considered during periods without artificial ventilation. (author)

  12. New three-count technique for short-lived radon decay products in air

    International Nuclear Information System (INIS)

    Tian Deyuan; Lu Zhizhao

    1998-01-01

    Up to the present, radon and its short-lived decay products in air are usually monitored by means of a detection. But radon progeny, including RaB ( 214 Pb) and RaC ( 214 Bi) which are β and γ emitters, contribute about 90% to the equilibrium equivalent radon concentration (EECRn). Therefore, this paper introduces a new three-count technique by a β detector in the light of radioactive decay law and its boundary conditions during sampling and counting times to solve the Bateman equation. β (even low level β) instruments have been fairly popularized domestically and internationally. It can be used not only as an instrument for radon and its daughters in air, but also as a monitor for β airborne activity in the environment. This new method taps further the latent power of the present instrument and realizes various uses for a unit. (author)

  13. NMR detection of short-lived β-emitter {sup 12}N implanted in water

    Energy Technology Data Exchange (ETDEWEB)

    Sugihara, T., E-mail: sugihara@vg.phys.sci.osaka-u.ac.jp; Mihara, M.; Shimaya, J.; Matsuta, K.; Fukuda, M.; Ohno, J.; Tanaka, M.; Yamaoka, S.; Watanabe, K.; Iwakiri, S.; Yanagihara, R.; Tanaka, Y.; Du, H.; Onishi, K.; Kambayashi, S.; Minamisono, T. [Osaka University, Department of Physics (Japan); Nishimura, D. [Tokyo University of Science, Department of Physics (Japan); Izumikawa, T. [Niigata University, Radioisotope Center (Japan); Ozawa, A. [University of Tsukuba, Department of Physics (Japan); Ishibashi, Y. [RIKEN Nishina Center for Accelerator-Based Science (Japan); and others

    2017-11-15

    The beta-detected nuclear magnetic resonance (β-NMR) in liquid H{sub 2}O has been observed for the first time using a short-lived β-ray emitter {sup 12}N (I{sup π} = 1{sup +},T{sub 1/2}=11 ms). A nuclear spin polarized {sup 12}N beam with an energy of about 20 MeV/nucleon was implanted into an enclosed water sample. About 50 % of implanted {sup 12}N ions maintained nuclear polarization and exhibited a β-NMR spectrum. The chemical shift of {sup 12}N in H{sub 2}O relative to {sup 12}N in Pt was deduced to be −(3.6±0.5) × 10{sup 2} ppm.

  14. Dynamical Detection of Topological Phase Transitions in Short-Lived Atomic Systems

    Science.gov (United States)

    Setiawan, F.; Sengupta, K.; Spielman, I. B.; Sau, Jay D.

    2015-11-01

    We demonstrate that dynamical probes provide direct means of detecting the topological phase transition (TPT) between conventional and topological phases, which would otherwise be difficult to access because of loss or heating processes. We propose to avoid such heating by rapidly quenching in and out of the short-lived topological phase across the transition that supports gapless excitations. Following the quench, the distribution of excitations in the final conventional phase carries signatures of the TPT. We apply this strategy to study the TPT into a Majorana-carrying topological phase predicted in one-dimensional spin-orbit-coupled Fermi gases with attractive interactions. The resulting spin-resolved momentum distribution, computed by self-consistently solving the time-dependent Bogoliubov-de Gennes equations, exhibits Kibble-Zurek scaling and Stückelberg oscillations characteristic of the TPT. We discuss parameter regimes where the TPT is experimentally accessible.

  15. Separation efficiency of the MASHA facility for short-lived mercury isotopes

    Science.gov (United States)

    Rodin, A. M.; Belozerov, A. V.; Chernysheva, E. V.; Dmitriev, S. N.; Gulyaev, A. V.; Gulyaeva, A. V.; Itkis, M. G.; Kliman, J.; Kondratiev, N. A.; Krupa, L.; Novoselov, A. S.; Oganessian, Yu. Ts.; Podshibyakin, A. V.; Salamatin, V. S.; Siváček, I.; Stepantsov, S. V.; Vanin, D. V.; Vedeneev, V. Yu.; Yukhimchuk, S. A.; Granja, C.; Pospisil, S.

    2014-06-01

    The mass-separator MASHA built to identify Super Heavy Elements by their mass-to-charge ratios is described. The results of the off- and on-line measurements of its separation efficiency are presented. In the former case four calibrated leaks of noble gases were used. In the latter the efficiency was measured via 284 MeV Ar beam and with using the hot catcher. The ECR ion source was used in both cases. The -radioactive isotopes of mercury produced in the complete fusion reaction Ar+SmHg+xn were detected at the mass-separator focal plane. The half-lives and the separation efficiency for the short-lived mercury isotopes were measured. Potentialities of the MEDIPIX detector system have been demonstrated for future use at the mass-separator MASHA.

  16. Short-lived radionuclide production capability at the Brookhaven Linac Isotope Producer

    International Nuclear Information System (INIS)

    Mausner, L.F.; Richards, P.

    1985-01-01

    The Brookhaven National Linac Isotope Producer is the first facility to demonstrate the capability of a large linear accelerator for efficient and economical production of difficult-to-make, medically useful radionuclides. The linac provides a beam of 200-MeV protons at an integrated beam current of up to 60 μA. The 200-MeV proton energy is very suitable for isotope production because the spallation process can create radionuclides unavailable at lower energy accelerators or reactors. Several medically important short-lived radionuclides are presently being prepared for on-site and off-site collaborative research programs. These are iodine-123, iron-52, manganese-52m, ruthenium-97, and the rubidium-81-krypton-81m system. The production parameters for these are summarized

  17. The short-lived African turquoise killifish: an emerging experimental model for ageing.

    Science.gov (United States)

    Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

    2016-02-01

    Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. © 2016. Published by The Company of Biologists Ltd.

  18. Production, study and use of short-lived nuclides in pure and applied nuclear research

    International Nuclear Information System (INIS)

    Bjoernstad, T.

    1986-01-01

    The thesis which is based on 17 published papers, reports on the on-line performance of the fast radiochemical separation system SISAK, technical devlopment in the preparation of sources for beta-particles and neutrons, and on important SISAK system improvements concerning liquid hold-up time. It further reports on the development of new production targets at ISOLDE for 600 MeV proton and 910 MeV 3 He-particle irradiations, on tests with a heavy ion beam of 1 GeV 12 C-particles, and on the present availability of mass-separated beams of the halogen elements through new ion source development. Some results from nuclear spectroscopic studies of nuclides in selected mass regions when using such new or improved techniques are given. Examples of techniques for practical application of short-lived nuclides in radiochemical analysis and for radiochemical production for medical purposes are presented

  19. Short-lived climate pollutant mitigation and the Sustainable Development Goals

    Science.gov (United States)

    Haines, Andy; Amann, Markus; Borgford-Parnell, Nathan; Leonard, Sunday; Kuylenstierna, Johan; Shindell, Drew

    2017-12-01

    The post-2015 development agenda is dominated by a set of Sustainable Development Goals (SDGs) that arose from the 2012 Rio+20 United Nations Conference on Sustainable Development. The 17 goals and 169 targets address diverse and intersecting aspects of human and environmental needs and challenges. Achieving the SDGs by 2030 requires implementing coordinated and concerted strategies and actions that minimize potential trade-offs and conflicts and maximize synergies to contribute to multiple SDGs. Measures to mitigate emissions of short-lived climate pollutants are an example of actions that contribute to multiple outcomes relevant to development. This Perspective highlights the interlinkages between these pollutants and the SDGs, and shows that implementing emissions reduction measures can contribute to achieving many of the SDGs.

  20. Behaviour of short-lived iodines in operating UO2 fuel elements

    International Nuclear Information System (INIS)

    Lipsett, J.J.; Hastings, I.J.; Hunt, C.E.L.

    1984-11-01

    Sweep gas experiments have been done to determine the behaviour of short-lived fission products within operating UO 2 fuel elements at linear powers of 45, 54, and 60 KW/m, and to burnups of 70, 80, and 50 MWh/kgU respectively. Although radioiodine transport was not observed directly during normal operation, equilibrium gap inventories for I-131 were deduced from the shutdown decay behaviour of the fission gases. These inventories were a strong function of fuel power and ranged from 10 GBq (0.27 Ci) to 100 GBq (2.7 Ci) over the range tested. We conclude that the iodine inventory was adsorbed onto the fuel and/or sheath surfaces with a volatile fraction of less than 10 -2 and a charcoal-filter-penetrating fraction of less than 2x10 -4

  1. Synthesis of radiopharmaceuticals containing short-lived radionuclides: Progress report, March 1, 1987-February 28, 1988

    International Nuclear Information System (INIS)

    Kabalka, G.W.

    1987-09-01

    The objective is the creation of new methods for introducing short-lived isotopes into agents for use in diagnostic nuclear medicine. Focus is on the design of new molecular architecture as opposed to the application of known reactions to the synthesis of specific radiopharmaceuticals. The new technology is utilized in nuclear medicine research at the University of Tennessee Medical Imaging Center and in collaboration with colleagues at other DOE facilities. The program provides training for students in the scientific aspects of nuclear medicine. The academic nature of the program facilitates collaborative interactions with other DOE nuclear medicine programs and helps to insure the continued availability of skilled scientists dedicated to the advancement of nuclear medicine. 70 refs., 9 figs

  2. Optimization of irradiation decay and counting times in nuclear activation analysis using short-lived nuclides

    International Nuclear Information System (INIS)

    Bjoernstad, T.

    This work describes a method and outlines a procedure for optim- ization of an activation analysis with respect to the experimental times, irradiation time, t(subi), decay time and counting time. The method is based on the 'minimum relative standard deviation criterion', and specially designed for the use on short-lived nuclides. A computer program, COMB1, is written in the BASIC language in order to make the calculations easier and faster. It is intended to be understandable, and easily applicable on a computer of modest size. Time and cost are important factors, especially for routine analysis on a service basis. In such cases one can often allow a controlled reduction in the analysis quality (through a higher relative standard deviation). The procedure outlined can therefore help find acceptable conditions by calculation of the 'best practical' (or reasonable) experimental time values, and the minimum number of accumulation cycles necessary to fulfil the requirements given. (Auth.)

  3. Simulation of radon short lived decay daughters' inhalation using the lung compartmental model

    International Nuclear Information System (INIS)

    Tomulescu, Vlad C.

    2002-01-01

    Radon and its short-lived decay daughters are the main source of radiation on natural ways for population. The radon gas, released from soil, water or construction materials is producing by radioactive decay the following solid daughters: Po-218, Bi-214, Pb-214, and Po-214, which can attach to aerosols, and consequently penetrate the organism by inhalation. The human respiratory tract can be approximated by aid of a compartment model that takes into account the different anatomical structures exposed to contamination and irradiation, as well as the respective physiological processes. This model is associated to a mathematical equation system that describes the behavior of the radioactive material inside the body. The results represent the dose equivalent on different organs and tissues, as a function of subject and the activity performed in contaminating environment. (author)

  4. Investigation of short-living fission products from the spontaneous fission of Cf-252

    International Nuclear Information System (INIS)

    Klonk, H.

    1976-01-01

    In this paper, a method of separating and measuring fission products of Cf-252 is presented. The measurement was achieved by means of γ-spectrometry and thus provides a quantitative analysis with a good separation of the fission products with respect to both atomic number Z and mass number A. The separation of the fission products from the fission source was achieved by means of solid traps. An automatic changing apparatus made it possible to keep irradiation and measuring times short, so even very short-lived fission products could be registered. The quantitative evaluation of primary fission products was made possible by correction according to Bateman equations. With that, the yields of single nuclides and the dispersion of charge can be determined. (orig./WL) [de

  5. Transport of short lived radioactive contaminants with prologed half-lives of daughters through river water

    International Nuclear Information System (INIS)

    Metwally, S.M.; Prohl, G.

    2005-01-01

    One of the main pathways for transporting contaminants to other parts in the environment, are rivers. This work is devoted for deriving and assessment the concentration of soluble radio contaminants along a river at any time after discharge, including the short-lived radionuclides in comparison with the discharge time interval, and prolonged half-life of the produced daughter nuclei. The assumed boundary conditions and deduced formulas can be applied either in case of accidental release or discharge under authority control. The formulas determining the produced daughter nuclei concentration require inequality of the parent and daughter nuclei half-lives. Because of the regional variation of river morphology, the assumed constancy of the flow velocity and dispersion coefficient requires dividing the river path into zones of similar hydrologic characteristics

  6. External tandem target system for efficient production of short-lived positron emitting radionuclides

    International Nuclear Information System (INIS)

    Koh, K.; Dwyer, J.; Finn, R.; Sheh, Y.; Sinnreich, J.; Wooten, T.

    1983-01-01

    Recent developments in radiopharmaceutical chemistry allow the incorporation of short-lived, positron-emitting radionuclides into a variety of compounds which when used with a positron emission tomograph provide a means of monitoring physiological disorders by a standard technique. To effectively meet the increased ''in-house'' clinical demands while maintaining a production schedule, a tandem target was designed and has been installed for the simultaneous ''on-line'' preparation of oxygen-15 labelled compounds such as CO 2 15 , H 2 O 15 ; and nitrogen-13 labelled compounds such as 13 NH 3 , 13 N 2 O, and 13 N 2 . The processing time required for the synthesis of the nitrogen-13 products as compared to the essentially instantaneous formation of oxygen-15 labelled compounds has provided the necessary time delay for clinical utilization. The characterisitcs of this external tandem target system as well as the automation for the dual processing are presented

  7. Compton suppression spectrometry for analysis of short-lived neutron activation products in foods

    International Nuclear Information System (INIS)

    Anderson, D.L.; Cunningham, W.C.

    2008-01-01

    Compton suppression spectrometry was used to analyze foods for elements with short-lived neutron activation products (half-lives of about 2 minutes to 1.5 days). Analysis conditions were optimized to provide quality assurance analyses for iodine in FDA's Total Diet Study. Iodine mass fractions (0.075 to 2.03 mg/kg) were measured in 19 of 42 foods analyzed, with limits of detection (LODs) ranging from 0.03 to 1.4 mg/kg, mostly depending on NaCl content. LODs were lowered by up to a factor of 2 for 16 elements. Suppression factors ranged from about 2 to 8 over the energy range 400 to 3200 keV. (author)

  8. Magnetic moment of short lived {beta}-emitter {sup 24m}Al

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, D., E-mail: daiki@vg.phys.sci.osaka-u.ac.jp; Komurasaki, J.; Matsuta, K.; Mihara, M.; Matsumiya, R. [Osaka University, Department of Physics (Japan); Momota, S. [Kochi University of Technology (Japan); Ohtsubo, T. [Niigata University, Department of Physics (Japan); Izumikawa, T. [Niigata University, RI Center (Japan); Hirano, H. [Niigata University, Department of Physics (Japan); Kitagawa, A.; Kanazawa, M.; Torikoshi, M.; Sato, S. [National Institute of Radiological Sciences (Japan); Fukuda, M.; Ishikawa, D. [Osaka University, Department of Physics (Japan); Minamisono, T. [Fukui University of Technology (Japan); Watanabe, R.; Kubo, T. [Niigata University, Department of Physics (Japan); Nojiri, Y. [Kochi University of Technology (Japan); Alonso, J. R. [Lawrence Berkeley Laboratory (United States)

    2007-11-15

    The magnetic moment of short lived {beta}-emitter {sup 24m}Al (426 keV, I{sup {pi}} = 1{sup +}, T{sub 1/2} = 131 ms) has been measured by means of {beta}-NMR technique, for the first time. From the {beta}-NMR spectrum, the magnetic moment was determined as |{mu}({sup 24m}Al)|=(2.99{+-}0.09){mu}{sub N}. Combined with the known magnetic moment of the mirror partner {sup 24m}Na, the expectation value of < S{sub z} > is obtained to be (0.08 {+-} 0.12). These values are reproduced well by the shell model calculation.

  9. Radiotracer diffusion in semiconductors and metallic compounds using short-lived isotopes

    CERN Multimedia

    Deicher, M; Kronenberg, J; Wagner, F E

    The transport of atoms in solids is of central importance for solid state physics, chemistry, metallurgy, and material sciences. Since the mobility of atoms in solids contributes to many physical phenomena the study of diffusion processes is of fundamental interest for solid state physics. Diffusion processes were frequently investigated using radioactive isotopes (radiotracers). The application of short-lived isotopes delivered at ISOLDE extends substantially the possibilities of investigating diffusion processes in solids. In particular, a new experimental set-up to be installed at ISOLDE in this year will enable the use of radioactive isotopes with half-lives down to minutes. Alternatively, in special cases diffusion processes can be investigated with help of hyperfine techniques on an atomic scale, like by perturbed $\\gamma \\gamma$-angular correlation (PAC). Here, the motion of the atom of interest becomes visible directly via characteristic changes in the measured PAC spectra.

  10. CARIBIC observations of short-lived halocarbons and carbonyl sulphide over Asia

    Science.gov (United States)

    Leedham, E.; Wisher, A.; Oram, D.; Baker, A. K.; Brenninkmeijer, C. A.

    2013-12-01

    The CARIBIC project (Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container, www.caribic-atmospheric.com) aims to investigate the spatial and temporal distribution of a wide-range of compounds, including those of marine origin/influence, via ~monthly flights to collect in situ data and whole air samples aboard a commercial Lufthansa aircraft. CARIBIC measures up to an altitude of 12 km, allowing the influence of marine compounds on the upper troposphere/lower stratosphere (UTLS) to be explored. In particular, CARIBIC is a useful tool for exploring the impact of very short lived halocarbons (e.g. CH2Br2, CHBr3), whose impact on stratospheric ozone is dependent on convective uplift to the UTLS, a process which is not yet fully quantified. As part of the suite of CARIBIC measurements, whole air samples are analysed at the University of East Anglia (UEA) via gas chromatography mass spectrometry for carbonyl sulphide (OCS) and up to 40 halocarbons (accounting for virtually 100% of organic chlorine, bromine and iodine in the UTLS). Here we present an overview of short-lived halocarbons and OCS measured by CARIBIC. We focus on two regions of particular interest. (1) measurements made in 2012 over the tropical west Pacific to link with UEA measurements made during the SHIVA campaign. (2) measurements made during a collection of flights over India in 2008. Flights over India investigated the impact of monsoon circulation on the distribution of these compounds; for example, elevated concentrations of OCS were seen in CARIBIC samples taken over India during the summer monsoon (July - September). These flights, along with a wider range of flights over Asia (from Frankfurt to Guangzhou, Manila, Bangkok and Kuala Lumpur) can provide unique information on the influence of tropical convection and monsoon circulation on halocarbon and OCS transport within this region.

  11. Evaluation of regional pulmonary function using short-lived radioactive gases

    Energy Technology Data Exchange (ETDEWEB)

    Ashitaka, Tsuyoshi [Toho Univ., Tokyo (Japan). School of Medicine

    1993-05-01

    We investigated the application of short-lived radioactive gases for the assessment of regional pulmonary function, particularly diffusing capacity, in patients with chronic obstructive lung disease and interstitial lung disease. Short-lived radioactive gases including C[sup 15]O-O, [sup 11]CO[sub 2], and [sup 11]CO were produced using a baby cyclotron for medical care. Using a [gamma] camera, breath-holding images were taken serially after inhalation of the radioactive gases. The first exponential component of time-activity curve was analyzed to obtain clearance rate, which was expressed as exponential coefficient ([lambda]). Moreover, we created a functional map which was calculated by the clearance rate of [sup 11]CO[sub 2] as a percentage. Regional clearance rates of each gas in normal volunteers revealed higher values in the lower lung field than in the upper lung field. Whole lung clearance rates ([lambda]) of each gas in patients correlated well with D[sub LCO]/V[sub A], which indicates diffusing capacity. The functional map showed decreased regional diffusion closely matched to the perfusion defects seen by [sup 99m]Tc-MAA perfusion images. However, in certain interstitial lung diseases decreased clearance of [sup 11]CO[sub 2] was observed in regions having no evidence of perfusion defects. We concluded the functional map display of [sup 11]CO[sub 2] is useful indicator of the regional diffusing capacity of both the normal and diseased lung, and that it is beneficial to analyze the pathogenic physiology of diseased lungs by making a comparison between the functional map of [sup 11]CO[sub 2] and [sup 99m]Tc-MAA perfusion images. (author).

  12. Antigen modulation of the immune response. III. Evaluation of the hypothetical short-lived memory cell

    International Nuclear Information System (INIS)

    Feldbush, T.L.; Lande, I.; Bryan, B.; O'Neill, E.

    1974-01-01

    The putative short-lived memory cells, whose existence has been suggested by the results of secondary adoptive transfer experiments, were investigated. On the basis of the following evidences we have concluded that the short-lived memory cell is probably an artifact of the adoptive transfer technique: when immune thoracic duct lymphocytes, known to consist predominantly of long-lived memory cells, were transferred to irradiated recipients and challenged at various times after transfer, approximately 80 to 90 percent of the initial response was absent by Day 14 challenge; preirradiating adoptive recipients with increasing dose of x-irradiation tended to lengthen the observed half life of memory cells; single or multiple treatments of immune donors with 0.3 mg Vinblastin before transfer resulted in neither a depression of the initial secondary response nor an alteration in the rate of decline of the memory potential; reconstitution of irradiated hosts with normal spleen cells one day before transfer of memory cells and challenge resulted in inhibition of the adoptive secondary response; and the transfer of memory cells to antigen free intermediate hosts, in which they were allowed to reside for one day or fourteen days before transfer to irradiated recipients, resulted in only a slight decline in their capacity to respond. We propose that the rapid decline of memory potential in adoptive recipients challenged at various times after transfer is due to modulating effects by the hosts as it recovers from irradiation. These effects may be the result of cell crowding or the loss of irradiation-produced stimulatory factors. The relevance of these findings to adoptive transfer systems in general and the secondary response of intact animals is discussed

  13. Muscle senescence in short-lived wild mammals, the soricine shrews Blarina brevicauda and Sorex palustris.

    Science.gov (United States)

    Hindle, Allyson G; Lawler, John M; Campbell, Kevin L; Horning, Markus

    2009-06-01

    Red-toothed (soricine) shrews are consummate predators exhibiting the highest energy turnovers and shortest life spans (ca. 18 months) of any mammal, yet virtually nothing is known regarding their physiological aging. We assessed the emerging pattern of skeletal muscle senescence (contractile/connective tissue components) in sympatric species, the semi-aquatic water shrew (WS), Sorex palustris, and the terrestrial short-tailed shrew (STS), Blarina brevicauda, to determine if muscle aging occurs in wild, short-lived mammals (H(0): shrews do not survive to an age where senescence occurs), and if so, whether these alterations are species-specific. Gracilis muscles were collected from first-year (n=17) and second-year (n=17) field-caught shrews. Consistent with typical mammalian aging, collagen content (% area) increased with age in both species (S. palustris: approximately 50%; B. brevicauda: approximately 60%). Muscle was dominated by stiffer Type I collagen, and the ratio of collagen Type I:Type III more than doubled with age. The area ratio of muscle:collagen decreased with age in both species, but was considerably lower in adult STS, suggesting species-specificity of senescence. Extracellular space was age-elevated in B. brevicauda, but was preserved in S. palustris ( approximately 50 vs. 10% elevation). Though juvenile interspecific comparisons revealed no significance, adult WS myocytes had 68% larger cross-sectional area and occurred at 28% lower fibers/area than those of adult STS. We demonstrate that age-related muscle senescence does occur in wild-caught, short-lived mammals, and we therefore reject this classic aging theory tenet. Our findings moreover illustrate that differential age adjustments in contractile/connective tissue components of muscle occur in the two species of wild-caught shrews. (c) 2009 Wiley-Liss, Inc.

  14. Muscle Senescence in Short-Lived Wild Mammals, the Soricine Shrews Blarina brevicauda and Sorex palustris

    Science.gov (United States)

    HINDLE, ALLYSON G.; LAWLER, JOHN M.; CAMPBELL, KEVIN L.; HORNING, MARKUS

    2015-01-01

    Red-toothed (soricine) shrews are consummate predators exhibiting the highest energy turnovers and shortest life spans (ca. 18 months) of any mammal, yet virtually nothing is known regarding their physiological aging. We assessed the emerging pattern of skeletal muscle senescence (contractile/connective tissue components) in sympatric species, the semi-aquatic water shrew (WS), Sorex palustris, and the terrestrial short-tailed shrew (STS), Blarina brevicauda, to determine if muscle aging occurs in wild, short-lived mammals (H0: shrews do not survive to an age where senescence occurs), and if so, whether these alterations are species-specific. Gracilis muscles were collected from first-year (n = 17) and second-year (n = 17) field-caught shrews. Consistent with typical mammalian aging, collagen content (% area) increased with age in both species (S. palustris: ~50%; B. brevicauda: ~60%). Muscle was dominated by stiffer Type I collagen, and the ratio of collagen Type I:Type III more than doubled with age. The area ratio of muscle:collagen decreased with age in both species, but was considerably lower in adult STS, suggesting species-specificity of senescence. Extracellular space was age-elevated in B. brevicauda, but was preserved in S. palustris (~50 vs. 10% elevation). Though juvenile interspecific comparisons revealed no significance, adult WS myocytes had 68% larger cross-sectional area and occurred at 28% lower fibers/area than those of adult STS. We demonstrate that age-related muscle senescence does occur in wild-caught, short-lived mammals, and we therefore reject this classic aging theory tenet. Our findings moreover illustrate that differential age adjustments in contractile/connective tissue components of muscle occur in the two species of wild-caught shrews. PMID:19296507

  15. DEMOGRAPHY OF ALPINE SHORT-LIVED PLANTS, LONGEVITY AND ONTOGENY STAGE DURATIONS

    Directory of Open Access Journals (Sweden)

    E. S. Kazantseva

    2016-01-01

    Full Text Available The aim - to evaluate lifespan (full cycle and ontogeny stage durations of nine alpine short-lived North- West Caucasus plants.Methods. For calculation we used a new method which was developed and suggested earlier by us. This method is based on a discrete ontogeny description and on the probability theory and random processes. The data on the monitoring of the marked individuals were collected during six years.Results. We found out that the lifespan of Anthyllis vulneraria is 2.6±0.3 years (hereinafter “±” is Standard error, Draba hispida – 4.5±0.3, Murbeckiella huetii – 4.6±1.1, Carum meifolium – 7.8±1.4, Eritrichium caucasicum – 9.1±1.4, Trifolium badium – 10.3±2.6, Sedum tenellum – 11±2.05, Androsace albana – 12.1±2.5, Minuartia recurva – 22.9±4.5. Also we demonstrated the matrix population models for studied plants, which show the probability of transition of individuals from one ontogeny stage to another in time interval (in our experiment – 1 year.Conclusion. Mortality of seedlings and juvenile plants, except Murbeckiella huetii, is around and more than 50%. Two years is the minimal amount of time that is necessary for full cycle of short-lived alpine plants, as it was shown for Anthyllis vulneraria, Murbeckiella huetii и Trifolium badium. A 3-12 years lifespan was calculated for other studied species. Persistence of Eritrichium caucasicum and Androsace albana populations provided by resistance of adult vegetative plants.

  16. Cell-cycle regulatory proteins in human wound healing

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Grøn, Birgitte; Dabelsteen, Erik

    2003-01-01

    Proper healing of mucosal wounds requires careful orchestration of epithelial cell migration and proliferation. To elucidate the molecular basis of the lack of cellular proliferation in the migrating 'epithelial tongue' during the re-epithelialization of oral mucosal wounds, the expression of cell......-cycle regulators critical for G(1)-phase progression and S-phase entry was here analysed immunohistochemically. Compared to normal human mucosa, epithelia migrating to cover 2- or 3-day-old wounds made either in vivo or in an organotypic cell culture all showed loss of the proliferation marker Ki67 and cyclins D(1......) and A, and reduced expression of cyclins D(3) and E, the cyclin D-dependent kinase 4 (CDK4), the MCM7 component of DNA replication origin complexes and the retinoblastoma protein pRb. Among the CDK inhibitors (CKIs), p16ink4a and p21Cip1 were moderately increased and decreased, respectively, whereas...

  17. EWS and FUS bind a subset of transcribed genes encoding proteins enriched in RNA regulatory functions.

    Science.gov (United States)

    Luo, Yonglun; Blechingberg, Jenny; Fernandes, Ana Miguel; Li, Shengting; Fryland, Tue; Børglum, Anders D; Bolund, Lars; Nielsen, Anders Lade

    2015-11-14

    FUS (TLS) and EWS (EWSR1) belong to the FET-protein family of RNA and DNA binding proteins. FUS and EWS are structurally and functionally related and participate in transcriptional regulation and RNA processing. FUS and EWS are identified in translocation generated cancer fusion proteins and involved in the human neurological diseases amyotrophic lateral sclerosis and fronto-temporal lobar degeneration. To determine the gene regulatory functions of FUS and EWS at the level of chromatin, we have performed chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes involved in pathways at the RNA regulatory level with potential to mediate normal and disease-associated functions of the FUS and EWS proteins.

  18. Variation in the local population dynamics of the short-lived Opuntia macrorhiza (Cactaceae).

    Science.gov (United States)

    Haridas, C V; Keeler, Kathleen H; Tenhumberg, Brigitte

    2015-03-01

    Spatiotemporal variation in demographic rates can have profound effects for population persistence, especially for dispersal-limited species living in fragmented landscapes. Long-term studies of plants in such habitats help with understanding the impacts of fragmentation on population persistence but such studies are rare. In this work, we reanalyzed demographic data from seven years of the short-lived cactus Opuntia macrorhiza var. macrorhiza at five plots in Boulder, Colorado. Previous work combining data from all years and all plots predicted a stable population (deterministic log lamda approximately 0). This approach assumed that all five plots were part of a single population. Since the plots were located in a suburban-agricultural interface separated by highways, grazing lands, and other barriers, and O. macrorhiza is likely dispersal limited, we analyzed the dynamics of each plot separately using stochastic matrix models assuming each plot represented a separate population. We found that the stochastic population growth rate log lamdaS varied widely between populations (log lamdaS = 0.1497, 0.0774, -0.0230, -0.2576, -0.4989). The three populations with the highest growth rates were located close together in space, while the two most isolated populations had the lowest growth rates suggesting that dispersal between populations is critical for the population viability of O. macrorhiza. With one exception, both our prospective (stochastic elasticity) and retrospective (stochastic life table response experiments) analysis suggested that means of stasis and growth, especially of smaller plants, were most important for population growth rate. This is surprising because recruitment is typically the most important vital rate in a short-lived species such as O. macrorhiza. We found that elasticity to the variance was mostly negligible, suggesting that O. macrorhiza populations are buffered against large temporal variation. Finally, single-year elasticities to means

  19. Harvard--MIT research program in short-lived radiopharmaceuticals. Progress report, September 1, 1977--April 30, 1978

    International Nuclear Information System (INIS)

    Adelstein, S.J.; Brownell, G.L.

    1978-05-01

    Progress is reported on the following studies: chemistry studies designed to achieve a more complete understanding of the fundamental chemistry of technetium in order to facilitate the design of future radiopharmaceuticals incorporating the radionuclide /sup 99m/Tc; the development of new radiopharmaceuticals intended to improve image quality and lower radiation doses by the use of short-lived radionuclides and disease-specific agents; the development of short-lived positron-emitting radionuclides which offer advantages in transverse section imaging of regional physiological processes; and studies of the toxic effects of particulate radiation

  20. Structural studies of bacterial transcriptional regulatory proteins by multidimensional heteronuclear NMR

    Energy Technology Data Exchange (ETDEWEB)

    Volkman, Brian Finley [Univ. of California, Berkeley, CA (United States)

    1995-02-01

    Nuclear magnetic resonance spectroscopy was used to elucidate detailed structural information for peptide and protein molecules. A small peptide was designed and synthesized, and its three-dimensional structure was calculated using distance information derived from two-dimensional NMR measurements. The peptide was used to induce antibodies in mice, and the cross-reactivity of the antibodies with a related protein was analyzed with enzyme-linked immunosorbent assays. Two proteins which are involved in regulation of transcription in bacteria were also studied. The ferric uptake regulation (Fur) protein is a metal-dependent repressor which controls iron uptake in bacteria. Two- and three-dimensional NMR techniques, coupled with uniform and selective isotope labeling allowed the nearly complete assignment of the resonances of the metal-binding domain of the Fur protein. NTRC is a transcriptional enhancer binding protein whose N-terminal domain is a "receiver domain" in the family of "two-component" regulatory systems. Phosphorylation of the N-terminal domain of NTRC activates the initiation of transcription of aeries encoding proteins involved in nitrogen regulation. Three- and four-dimensional NMR spectroscopy methods have been used to complete the resonance assignments and determine the solution structure of the N-terminal receiver domain of the NTRC protein. Comparison of the solution structure of the NTRC receiver domain with the crystal structures of the homologous protein CheY reveals a very similar fold, with the only significant difference being the position of helix 4 relative to the rest of the protein. The determination of the structure of the NTRC receiver domain is the first step toward understanding a mechanism of signal transduction which is common to many bacterial regulatory systems.

  1. Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma.

    Science.gov (United States)

    Pruksakorn, Dumnoensun; Teeyakasem, Pimpisa; Klangjorhor, Jeerawan; Chaiyawat, Parunya; Settakorn, Jongkolnee; Diskul-Na-Ayudthaya, Penchatr; Chokchaichamnankit, Daranee; Pothacharoen, Peraphan; Srisomsap, Chantragan

    2016-09-01

    Osteosarcoma is a common malignant bone tumor in children and adolescents. The current 5-year survival rate is ~60% and that seems to be reaching a plateau. In order to improve treatment outcomes of osteosarcoma, a better understanding of tumorigenesis and underlying molecular mechanisms is required for searching out possible new treatment targets. This study aimed to identify the potential proteins involving the pathogenesis of osteosarcoma using a proteomics approach. Proteins extracted from primary cell culture of osteosarcoma (n=7) and osteoblasts of cancellous bone (n=7) were studied. Using 2-DE based proteomics and LC-MS/MS analysis, we successfully determined seven differentially expressed protein spots. Four upregulated proteins and three downregulated proteins were observed in this study in which KH-type splicing regulatory protein (KSRP) was selected for further exploration. KSRP was significantly upregulated in osteosarcoma cells compared to osteoblasts using western blot assay. In addition, immunohistochemistry demonstrated that KSRP was also highly expressed in osteosarcoma tissue of independent cases from the experimental group. More importantly, KSRP silencing of osteosarcoma cell lines significantly decreased cell proliferation, migration ability, as well as implantation and growth ability in chick chorioallantoic membrane assay. Taken together, these findings demonstrate, that KSRP plays important roles in regulatory controls of osteosarcoma pathogenesis and serves as a potentially therapeutic target of osteosarcoma.

  2. Determination of copper in biological materials by neutron activation analysis using short-lived 66Cu

    International Nuclear Information System (INIS)

    Dybczynski, R.; Danko, B.; Kaczorowski, J.

    1989-01-01

    A method for determination of copper traces in biological materials based on neutron activation employing 65 Cu(n, γ) 66 Cu reaction and preconcentration by extraction chromatography has been devised. The 200-500 mg samples after wet digestion and evaporation were dissolved in glycine solution and after pH adjusting to ca. 4.4 were passed through the column with Lix 64N on Bio Beads SM-1 for isolation of copper traces from the matrix elements. Other cations were selectively eluted with 0.1 mol x 1 -1 (glycine-HNO 3 ) buffer, 1 mol x 1 -1 in NH 4 NO 3 (pH = 3.6). The resin bed with quantitatively retained copper was sealed in the PE bag and irradiated together with Cu standards in EWA reactor using pneumatic tube facility. The activity of the short-lived 66 Cu was measured in samples and standard by gamma-ray spectrometry with Ge(Li) detector. Good accuracy of the method was confirmed by analysis of the following certified reference materials: NBS 1571 Orchad leaves, IAEA H-4 Animal muscle, IAEA V-8 Rye flour, IAEA A-11 milk powder. The detection limit amounted to 0.34 mg/kg, for the sample weight of 500 mg. (author)

  3. Quantitative cerebral blood flow patterns with the short lived isotope 195m Au

    International Nuclear Information System (INIS)

    Lindner, P.; Nickel, O.

    1984-01-01

    A previously reported theory for quantitative cerebral blood flow measurements using intravenously injected nondiffusible radiotracers has been applied on patients after stroke and on volunteers undergoing a mental stimulation exercise. Quantitative measurements of cerebral blood flow patterns (in ml/min/100g) not only in p.a. but also in lateral views of the brain are possible by using of the short-lived (30 sec) isotope Au 195m. The energy spectrum of the eluate of the generator shows two strong photon peaks, one at 68 keV and a second at 262 keV. The 68 keV peak is suitable for perfusion studies in lateral views of the hemispheres, no 'look through' effect is seen. The 262 keV peak is good for studies in p.a. positions. The studies last less than 1 minute and can be repeated after 3 minutes. Parametric images for quantitative regional cerebral blood flow can be generated. The area of occluded vessels in the case of stroke can be made visible. Quantitative activation patterns of cerebral blood flow during mental stimulation can be generated. After optical stimulation a clear increase of blood flow was seen in the visual cortex. The results prove that not only with freely diffusible (like Xenon) but also with nondiffusible indicators like 195m Au it is possible to measure quantitatively cerebral blood flow patterns. Au 195m is very advantageous for quantitative clinical investigations of cerebrovascular disease. (Author)

  4. ''Sleeping reactor'' irradiations: Shutdown reactor determination of short-lived activation products

    International Nuclear Information System (INIS)

    Jerde, E.A.; Glasgow, D.C.

    1998-01-01

    At the High-Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory, the principal irradiation system has a thermal neutron flux (φ) of ∼ 4 x 10 14 n/cm 2 · s, permitting the detection of elements via irradiation of 60 s or less. Irradiations of 6 or 7 s are acceptable for detection of elements with half-lives of as little as 30 min. However, important elements such as Al, Mg, Ti, and V have half-lives of only a few minutes. At HFIR, these can be determined with irradiation times of ∼ 6 s, but the requirement of immediate counting leads to increased exposure to the high activity produced by irradiation in the high flux. In addition, pneumatic system timing uncertainties (about ± 0.5 s) make irradiations of 9 Be(γ,n) 8 Be, the gamma rays principally originating in the spent fuel. Upon reactor SCRAM, the flux drops to ∼ 1 x 10 10 n/cm 2 · s within 1 h. By the time the fuel elements are removed, the flux has dropped to ∼ 6 x 10 8 . Such fluxes are ideal for the determination of short-lived elements such as Al, Ti, Mg, and V. An important feature of the sleeping reactor is a flux that is not constant

  5. Short-Lived Buildings in China: Impacts on Water, Energy, and Carbon Emissions.

    Science.gov (United States)

    Cai, Wenjia; Wan, Liyang; Jiang, Yongkai; Wang, Can; Lin, Lishen

    2015-12-15

    This paper has changed the vague understanding that "the short-lived buildings have huge environmental footprints (EF)" into a concrete one. By estimating the annual floor space of buildings demolished and calibrating the average building lifetime in China, this paper compared the EF under various assumptive extended buildings' lifetime scenarios based on time-series environmental-extended input-output model. Results show that if the average buildings' lifetime in China can be extended from the current 23.2 years to their designed life expectancy, 50 years, in 2011, China can reduce 5.8 Gt of water withdrawal, 127.1 Mtce of energy consumption, and 426.0 Mt of carbon emissions, each of which is equivalent to the corresponding annual EF of Belgium, Mexico, and Italy. These findings will urge China to extend the lifetime of existing and new buildings, in order to reduce the EF from further urbanization. This paper also verifies that the lifetime of a product or the replacement rate of a sector is a very important factor that influences the cumulative EF. When making policies to reduce the EF, adjusting people's behaviors to extend the lifetime of products or reduce the replacement rate of sectors may be a very simple and cost-effective option.

  6. New use of global warming potentials to compare cumulative and short-lived climate pollutants

    Science.gov (United States)

    Allen, Myles R.; Fuglestvedt, Jan S.; Shine, Keith P.; Reisinger, Andy; Pierrehumbert, Raymond T.; Forster, Piers M.

    2016-08-01

    Parties to the United Nations Framework Convention on Climate Change (UNFCCC) have requested guidance on common greenhouse gas metrics in accounting for Nationally determined contributions (NDCs) to emission reductions. Metric choice can affect the relative emphasis placed on reductions of `cumulative climate pollutants' such as carbon dioxide versus `short-lived climate pollutants' (SLCPs), including methane and black carbon. Here we show that the widely used 100-year global warming potential (GWP100) effectively measures the relative impact of both cumulative pollutants and SLCPs on realized warming 20-40 years after the time of emission. If the overall goal of climate policy is to limit peak warming, GWP100 therefore overstates the importance of current SLCP emissions unless stringent and immediate reductions of all climate pollutants result in temperatures nearing their peak soon after mid-century, which may be necessary to limit warming to ``well below 2 °C'' (ref. ). The GWP100 can be used to approximately equate a one-off pulse emission of a cumulative pollutant and an indefinitely sustained change in the rate of emission of an SLCP. The climate implications of traditional CO2-equivalent targets are ambiguous unless contributions from cumulative pollutants and SLCPs are specified separately.

  7. Emission channeling with short-lived isotopes lattice location of impurities in semiconductors and oxides

    CERN Multimedia

    We propose to perform emission channeling lattice location experiments in a number of semiconductor and oxide systems of technological relevance: \\\\- The lattice location of the transition metal probes $^{56}$Mn ($\\textit{t}_{1/2}$=2.6 h), $^{59}$Fe (45 d), $^{61}$Co (1.6 h) and $^{65}$Ni (2.5 h) is to be investigated in materials of interest as dilute magnetic semiconductors, such as GaMnAs, GaMnN, GaFeN, AlGaN, SiC, and in a number of oxides that are candidates for “single ion ferromagnetism”, in particular SrTiO$_3$ and LiNbO$_3$.\\\\- The topic of $\\textit{p}$-type doping of nitride semiconductors shall be addressed by studying the lattice sites of the acceptor dopants Mg and Be in GaN and AlN using the short-lived probes $^{27}$Mg (9.5 min) and $^{11}$Be (13.8 s). The aim is to reach a lattice location precision around 0.05 Å in order to provide critical tests for recent theoretical models which e.g. have predicted displacements of the Mg atom from the ideal substitutional Ga and Al sites of the order...

  8. Applications of short-lived activation products in neutron activation analysis of bio-environmental specimens

    International Nuclear Information System (INIS)

    1987-03-01

    This report discusses the advantages and disadvantages, special techniques, and actual and potential applications of neutron activation analysis (NAA) utilizing short-lived neutron-induced products, with special reference to the analysis of samples of biological and environmental origin. Attention is devoted mainly to products having half-lives in roughly the range of 10 milliseconds to 60 seconds, but with some discussion of the usefulness of even shorter-lived species, and ones with half-lives as long as a few minutes. Important aspects of the analytical methodology include sample preparation, irradiation/transfer systems, activity measurements, data processing and analytical quality assurance. It is concluded that several trace elements can be determined in bio-environmental samples (as well as in samples of industrial, geochemical and other origin). In particular, this method provides analytical possibilities for several elements (e.g. B, F, Li and V) that are difficult to determine in some matrices at trace levels by any other technique. These conclusions are illustrated in an annex by results of calculations in which the applicability of the techniques to the analysis of several biological and environmental reference materials is evaluated by means of an advance computer prediction program. The report concludes with an annotated bibliography of relevant publications (including abstracts, where available) taken from the INIS database. (author)

  9. Labeling suspended aerosol particles with short-lived radionuclides for determination of particle deposition

    International Nuclear Information System (INIS)

    Smith, M.F.; Bryant, S.; Welch, S.; Digenis, G.A.

    1984-01-01

    Radiotracer techniques were developed to examine parameters that characterize pressurized aerosols designed to deliver insoluble particles suspended in the aerosol formulation. Microaggregated bovine serum albumin microspheres that were to be suspended were labeled with iodine-131 (t1/2 . 8 d). This iodination procedure (greater than 80% effective) is also applicable to iodine-123, which possesses superior characteristics for external imaging and further in vivo studies. This report shows that for pressurized aerosols containing suspended particles, each metered dose is approximately equal (not including the priming doses and the emptying doses). Increase in the delivery of the albumin particles out of the canister was best achieved by pretreating the valve assembly with a solution of 2% (w/v) bovine serum albumin in phosphate buffer. Use of a cascade impactor delineated the particle size distribution of the micropheres, with the majority of particles ranging in size from 2 to 8 microns. The data disclosed here indicate that the techniques developed with short-lived radionuclides can be used to quantitate each metered dose, characterize the particle size distribution profile of the aerosol contents, and determine the extent of deposition of the particles in the aerosol canister and all of its components

  10. High rate gamma spectroscopy system for activation analysis of short-lived isomeric transitions

    Energy Technology Data Exchange (ETDEWEB)

    Westphall, G P [Atominstitut der Oesterreichischen Hochschulen, Vienna

    1976-07-15

    A high rate spectroscopy system specially suited for measurement of short-lived isomeric transitions is described, which, as part of a fast activation analysis facility at the TRIGA Mark II reactor, provides for automatic recording and immediate evaluation of gamma spectra taken from nuclides activated at stationary or pulsed reactor power. The system consists of a commercial de-coupled Ge(Li)-detector of 70 cm/sup 3/ modified for recycling operation for input rates in excess of 500000 c/s /sup 60/Co, a time variant trapezoidal shaping section and a fast constant dead-time ADC coupled to a programmed multichannel analyzer. Novel circuits for efficient pile-up rejection and time variant base line restoration extend the concept of gated integration up to count rates of more than 200000 c/s /sup 60/Co. Time-sequenced recording of spectra is performed by a minicomputer operated as a front-end processor of a larger laboratory computer, where final data processing takes place. New concepts for very simple and cost-effective implementation of multichannel analyzers by means of general purpose small computers are described.

  11. Dissolved organic matter composition drives the marine production of brominated very short-lived substances.

    Science.gov (United States)

    Liu, Yina; Thornton, Daniel C O; Bianchi, Thomas S; Arnold, William A; Shields, Michael R; Chen, Jie; Yvon-Lewis, Shari A

    2015-03-17

    Brominated very short-lived substances (BrVSLS), such as bromoform, are important trace gases for stratospheric ozone chemistry. These naturally derived trace gases are formed via bromoperoxidase-mediated halogenation of dissolved organic matter (DOM) in seawater. Information on DOM type in relation to the observed BrVSLS concentrations in seawater, however, is scarce. We examined the sensitivity of BrVSLS production in relation to the presence of specific DOM moieties. A total of 28 model DOM compounds in artificial seawater were treated with vanadium bromoperoxidase (V-BrPO). Our results show a clear dependence of BrVSLS production on DOM type. In general, molecules that comprise a large fraction of the bulk DOM pool did not noticeably affect BrVSLS production. Only specific cell metabolites and humic acid appeared to significantly enhance BrVSLS production. Amino acids and lignin phenols suppressed enzyme-mediated BrVSLS production and may instead have formed halogenated nonvolatile molecules. Dibromomethane production was not observed in any experiments, suggesting it is not produced by the same pathway as the other BrVSLS. Our results suggest that regional differences in DOM composition may explain the observed BrVSLS concentration variability in the global ocean. Ultimately, BrVSLS production and concentrations are likely affected by DOM composition, reactivity, and cycling in the ocean.

  12. Short-Lived Electronically-Excited Diatomic Molecules Cooled via Supersonic Expansion from a Plasma Microjet

    Science.gov (United States)

    Houlahan, Thomas J., Jr.; Su, Rui; Eden, Gary

    2014-06-01

    Using a pulsed plasma microjet to generate short-lived, electronically-excited diatomic molecules, and subsequently ejecting them into vacuum to cool via supersonic expansion, we are able to monitor the cooling of molecules having radiative lifetimes as low as 16 ns. Specifically, we report on the rotational cooling of He_2 molecules in the d^3Σ_u^+, e^3Π_g, and f^3Σ_u^+ states, which have lifetimes of 25 ns, 67 ns, and 16 ns, respectively. The plasma microjet is driven with a 2.6 kV, 140 ns high-voltage pulse (risetime of 20 ns) which, when combined with a high-speed optical imaging system, allows the nonequilibrium rotational distribution for these molecular states to be monitored as they cool from 1200 K to below 250 K with spatial and temporal resolutions of below 10 μm and 10 ns, respectively. The spatial and temporal resolution afforded by this system also allows the observation of excitation transfer between the f^3Σ_u^+ state and the lower lying d^3Σ_u^+ and e^3Π_g states. The extension of this method to other electronically excited diatomics with excitation energies >5 eV will also be discussed.

  13. Sizes and shapes of short-lived nuclei via laser spectroscopy. Final report

    International Nuclear Information System (INIS)

    Lewis, D.A.

    1985-10-01

    This project, a collaboration involving Iowa State University, Argonne National Lab., and the University of Minnesota, was aimed at the determination of properties of short-lived nuclei through their atomic hyperfine structure and optical isotope shifts. The basic approach was to use a cryogenic He-jet system to thermalize, neutralize, and transport radioactive nuclei produced online into a region suitable for laser spectroscopy. The photon burst method was then used for high sensitivity with the resulting continuous atomic beam. The experiment was located on beamline of the ANL superconducting heavy-ion accelerator. The He-jet system developed would reliably transport approx.10 2 nuclei into phase space useful for high resolution laser spectroscopy. The laser system developed could accurately and reproducibly sweep small frequency ranges for periods greater than or equal to1 day and sensitivity limits less than or equal to1 atom/s were achieved. However the nuclei were not transported as free atoms precluding nuclear determinations. Attempts to obtain free atoms by eliminating turbulence and contamination were not successful. Some of the high sensitivity spectroscopy techniques developed in this work are now being applied in a search for nuclear relics of the Big Bang and in studies of the photon statistics of light scattered by a single atom. 3 refs., 4 figs

  14. Impact on short-lived climate forcers increases projected warming due to deforestation.

    Science.gov (United States)

    Scott, C E; Monks, S A; Spracklen, D V; Arnold, S R; Forster, P M; Rap, A; Äijälä, M; Artaxo, P; Carslaw, K S; Chipperfield, M P; Ehn, M; Gilardoni, S; Heikkinen, L; Kulmala, M; Petäjä, T; Reddington, C L S; Rizzo, L V; Swietlicki, E; Vignati, E; Wilson, C

    2018-01-11

    The climate impact of deforestation depends on the relative strength of several biogeochemical and biogeophysical effects. In addition to affecting the exchange of carbon dioxide (CO 2 ) and moisture with the atmosphere and surface albedo, vegetation emits biogenic volatile organic compounds (BVOCs) that alter the formation of short-lived climate forcers (SLCFs), which include aerosol, ozone and methane. Here we show that a scenario of complete global deforestation results in a net positive radiative forcing (RF; 0.12 W m -2 ) from SLCFs, with the negative RF from decreases in ozone and methane concentrations partially offsetting the positive aerosol RF. Combining RFs due to CO 2 , surface albedo and SLCFs suggests that global deforestation could cause 0.8 K warming after 100 years, with SLCFs contributing 8% of the effect. However, deforestation as projected by the RCP8.5 scenario leads to zero net RF from SLCF, primarily due to nonlinearities in the aerosol indirect effect.

  15. Context of the long-term management of low-level short-lived waste

    International Nuclear Information System (INIS)

    Hooft, E.

    2004-01-01

    Until the international moratorium of 1983, Belgium relied on sea disposal for its low-level waste. Since then, ONDRAF/NIRAS, the Belgian radioactive waste management agency, has launched studies to look for land-based solutions. These studies, which are still going on, have gone through various phases. The sometimes harsh reactions in public opinion and the recommendations of independent experts, however, progressively led ONDRAF/NIRAS to question its work methodology. On 16 January 1998 was a milestone in Belgian's nuclear waste management. On that day, the Belgian federal government opted for a final, or potentially final, solution for the long-term management of short-lived, low-level radioactive waste, a solution that also had to be progressive, flexible, and reversible. At the same time, the government entrusted new missions to ONDRAF/NIRAS in particular that of developing methods to enable the integration of final repository project proposals at a local level and restricted the number of potential sites for final disposal to the four existing nuclear sites in Belgium and to possibly interested local districts. The government's decision of 16 January 1998 forced ONDRAF/NIRAS to change its strategy. The agency set up a new work programme and worked out an innovative methodology. This new methodology aims to generate, at the level of the interested towns and villages, draft projects for a final repository supported by a wide public consensus. (author)

  16. Monitoring of processes with gamma-rays of neutron capture and short-living radionuclides

    International Nuclear Information System (INIS)

    Aripov, G.A.; Kurbanov, B.I.; Allamuratova, G.

    2004-01-01

    Element content is a fundamental parameter of a substance, on which all its properties, and also character of physical, chemical, biological, technological and ecological processes depend. Therefore monitoring of element content (in the course of technological process - on line; in natural conditions - in site; or in living organisms - in vivo) becomes necessary for investigation of aforementioned processes. This problem can be successfully solved by using the methods of prompt gamma activation analysis (PGAA) and instrumental neutron activation analysis (INAA) on short-living radionuclides. These methods don't depend on type of substance (biological, geological, technological etc.), since the content is determined by gamma radiation of nuclei, and allows to meet such a serious requirement like the necessity of achieving minimal irradiation of the object and its minimal residual activity. In this work minimal determinable concentrations of various elements are estimated (based on experimental data) by the method of PGAA using radionuclide 252 Cf - source of neutrons with the yield of the oil of 10 8 neutron/sec on the experimental device with preliminary focusing of neutrons /1/, and also data of determination of elements by their isotopes with maximum time efficiency /2,3/ by the method of INAA. (author)

  17. A high rate gamma spectroscopy system for activation analysis of short lived isomeric transitions

    Energy Technology Data Exchange (ETDEWEB)

    Westphal, G P [Atominstitut, Vienna (Austria)

    1976-07-01

    A high rate spectroscopy system specially suited for measurement of short-lived isomeric transitions is described, which, as part of a fast activation analysis facility at the TRIGA Mark II reactor, provides for automatic recording and immediate evaluation of gamma spectra taken from nuclides activated at stationary or pulsed reactor power. The system consists of a commercial DC-coupled Ge(Li)-detector of 70 cm{sup 3} modified for recycling operation for input rates in excess of 500,000 c/s Co-60, a time variant trapezoidal shaping section and a fast constant dead-time ADC coupled to a programmed multi-channel analyzer. Novel circuits for efficient pile-up rejection and time variant base line restoration extend the concept of gated integration up to count rates of more than 300,000 c/s Co-60. Time-sequenced recording of spectra is performed by a mini computer operated as a front-end processor of a larger laboratory computer, where final data processing takes place. New concepts for very simple and cost-effective implementation of multi-channel analyzers by means of general purpose small computers are described. (author)

  18. The Contribution of Serine 194 Phosphorylation to Steroidogenic Acute Regulatory Protein Function

    OpenAIRE

    Sasaki, Goro; Zubair, Mohamad; Ishii, Tomohiro; Mitsui, Toshikatsu; Hasegawa, Tomonobu; Auchus, Richard J.

    2014-01-01

    The steroidogenic acute regulatory protein (StAR) facilitates the delivery of cholesterol to the inner mitochondrial membrane, where the cholesterol side-chain cleavage enzyme catalyzes the initial step of steroid hormone biosynthesis. StAR was initially identified in adrenocortical cells as a phosphoprotein, the expression and phosphorylation of which were stimulated by corticotropin. A number of in vitro studies have implicated cAMP-dependent phosphorylation at serine 194 (S194, S195 in hum...

  19. Effects of sterol regulatory element-binding protein (SREBP in chickens

    Directory of Open Access Journals (Sweden)

    Alipour Fahimeh

    2012-02-01

    Full Text Available Abstract Sterol regulatory element binding protein- 1 and -2 (SREBP-1 and -2 are key transcription factors involved in the biosynthesis of cholesterol and fatty acids. The SREBP have mostly been studied in rodents in which lipogenesis is regulated in both liver and adipose tissue. There is, though, a paucity of information on birds, in which lipogenesis occurs essentially in the liver as in humans. Since a prelude to the investigation of the role of SREBP in lipid metabolism regulation in chicken, we review Size and Tissue expression Pattern of SREBP and role of this protein in chickens.

  20. Determination of gamma-ray exposure rate from short-lived fission products under criticality accident conditions

    International Nuclear Information System (INIS)

    Yanagisawa, Hiroshi; Ohno, Akio; Aizawa, Eijyu

    2002-01-01

    For the assessment of γ-ray doses from short-lived fission products (FPs) under criticality accident conditions, γ-ray exposure rates varying with time were experimentally determined in the Transient Experiment Critical Facility (TRACY). The data were obtained by reactivity insertion in the range of 1.50 to 2.93$. It was clarified from the experiments that the contribution of γ-ray from short-lived FPs to total exposure during the experiments was evaluated to be 15 to 17%. Hence, the contribution cannot be neglected for the assessment of γ-ray doses under criticality accident conditions. Computational analyses also indicated that γ-ray exposure rates from short-lived FPs calculated with the Monte Carlo code, MCNP4B, and photon sources based on the latest FP decay data, the JENDL FP Decay Data File 2000, well agreed with the experimental results. The exposure rates were, however, extremely underestimated when the photon sources were obtained by the ORIGEN2 code. The underestimation is due to lack of energy-dependent photon emission data for major short-lived FP nuclides in the photon database attached to the ORIGEN2 code. It was also confirmed that the underestimation arose in 1,000 or less of time lapse after an initial power burst. (author)

  1. Sizes and shapes of short-lived nuclei via laser spectroscopy. Progress report, May 1, 1980-January 31, 1981

    International Nuclear Information System (INIS)

    Lewis, D.A.

    1981-02-01

    The first stage of the program to study the sizes and shapes of short-lived nuclei through their atomic hyperfine structure is to develop a movable laser spectroscopy system. This system is now almost complete and is described in this report along with plans for measurements at Argonne National Laboratory and Brookhaven National Laboratory

  2. Non-destructive investigation of technical plants and processes and natural processes by short-lived radionuclides (radiotracer)

    International Nuclear Information System (INIS)

    Jentsch, Thorsten; Zeuner, Albert

    2009-01-01

    Short lived open radionuclides are very suitable to investigate transport and mixing processes. They do not pollute the product. After decay of the radionuclide, the product can be used without any restrictions. Examples are showed for technical processes investigation by aid of radiotracer. (orig.)

  3. Solubilization and reconstitution of the formylmethionylleucylphenylalanine receptor coupled to guanine nucleotide regulatory protein

    International Nuclear Information System (INIS)

    Williamson, K.; Dickey, B.F.; Pyun, H.Y.; Navarro, J.

    1988-01-01

    The authors describe the solubilization, resolution, and reconstitution of the formylmethionylleucylphenylalanine (fMet-Leu-Phe) receptor and guanine nucleotide regulatory proteins (G-proteins). The receptor was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Guanine nucleotides decreased the number of high-affinity binding sites and accelerated the rate of dissociation of the receptor-ligand complex, suggesting that the solubilized receptor remained coupled to endogenous G-proteins. The solubilized receptor was resolved from endogenous G-proteins by fractionation on a wheat germ agglutinin (WGA)-Sepharose 4B column. High-affinity [ 3 H]fMet-Leu-Phe binding to the WGA-purified receptor was diminished and exhibited reduced guanine nucleotide sensitivity. High-affinity [ 3 H]fMET-Leu-Phe binding and guanine nucleotide sensitivity were reconstituted upon the addition of purified brain G-proteins. Similar results were obtained when the receptor was reconstituted with brain G-proteins into phospholipid vesicles by gel filtration chromatography. In addition, they also demonstrated fMET-Leu-Phe-dependent GTP hydrolysis in the reconstituted vesicles. The results of this work indicate that coupling of the fMet-Leu-Phe receptor to G-proteins converts the receptor to a high-affinity binding state and that agonist produces activation of G-proteins. The resolution and functional reconstitution of this receptor should provide an important step toward the elucidation of the molecular mechanism of the fMet-Leu-Phe transduction system in neutrophils

  4. A proposal for assessing study quality: Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument

    Science.gov (United States)

    LaKind, Judy S.; Sobus, Jon R.; Goodman, Michael; Barr, Dana Boyd; Fürst, Peter; Albertini, Richard J.; Arbuckle, Tye E.; Schoeters, Greet; Tan, Yu-Mei; Teeguarden, Justin; Tornero-Velez, Rogelio; Weisel, Clifford P.

    2015-01-01

    The quality of exposure assessment is a major determinant of the overall quality of any environmental epidemiology study. The use of biomonitoring as a tool for assessing exposure to ubiquitous chemicals with short physiologic half-lives began relatively recently. These chemicals present several challenges, including their presence in analytical laboratories and sampling equipment, difficulty in establishing temporal order in cross-sectional studies, short- and long-term variability in exposures and biomarker concentrations, and a paucity of information on the number of measurements required for proper exposure classification. To date, the scientific community has not developed a set of systematic guidelines for designing, implementing and interpreting studies of short-lived chemicals that use biomonitoring as the exposure metric or for evaluating the quality of this type of research for WOE assessments or for peer review of grants or publications. We describe key issues that affect epidemiology studies using biomonitoring data on short-lived chemicals and propose a systematic instrument – the Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument – for evaluating the quality of research proposals and studies that incorporate biomonitoring data on short-lived chemicals. Quality criteria for three areas considered fundamental to the evaluation of epidemiology studies that include biological measurements of short-lived chemicals are described: 1) biomarker selection and measurement, 2) study design and execution, and 3) general epidemiological study design considerations. We recognize that the development of an evaluative tool such as BEES-C is neither simple nor non-controversial. We hope and anticipate that the instrument will initiate further discussion/debate on this topic. PMID:25137624

  5. Convective Transport of Very-short-lived Bromocarbons to the Stratosphere

    Science.gov (United States)

    Liang, Qing; Atlas, Elliot Leonard; Blake, Donald Ray; Dorf, Marcel; Pfeilsticker, Klaus August; Schauffler, Sue Myhre

    2014-01-01

    We use the NASA GEOS Chemistry Climate Model (GEOSCCM) to quantify the contribution of two most important brominated very short-lived substances (VSLS), bromoform (CHBr3) and dibromomethane (CH2Br2), to stratospheric bromine and its sensitivity to convection strength. Model simulations suggest that the most active transport of VSLS from the marine boundary layer through the tropopause occurs over the tropical Indian Ocean, the Western Pacific warm pool, and off the Pacific coast of Mexico. Together, convective lofting of CHBr3 and CH2Br2 and their degradation products supplies 8 ppt total bromine to the base of the Tropical Tropopause Layer (TTL, 150 hPa), similar to the amount of VSLS organic bromine available in the marine boundary layer (7.8-8.4 ppt) in the above active convective lofting regions. Of the total 8 ppt VSLS-originated bromine that enters the base of TTL at 150 hPa, half is in the form of source gas injection (SGI) and half as product gas injection (PGI). Only a small portion (Br2, together, contribute 7.7 pptv to the present-day inorganic bromine in the stratosphere. However, varying model deep convection strength between maximum and minimum convection conditions can introduce a 2.6 pptv uncertainty in the contribution of VSLS to inorganic bromine in the stratosphere (BryVSLS). Contrary to the conventional wisdom, minimum convection condition leads to a larger BryVSLS as the reduced scavenging in soluble product gases, thus a significant increase in PGI (2-3 ppt), greatly exceeds the relative minor decrease in SGI (a few 10ths ppt.

  6. A growing threat to the ozone layer from short-lived anthropogenic chlorocarbons

    Directory of Open Access Journals (Sweden)

    D. E. Oram

    2017-10-01

    Full Text Available Large and effective reductions in emissions of long-lived ozone-depleting substance (ODS are being achieved through the Montreal Protocol, the effectiveness of which can be seen in the declining atmospheric abundances of many ODSs. An important remaining uncertainty concerns the role of very short-lived substances (VSLSs which, owing to their relatively short atmospheric lifetimes (less than 6 months, are not regulated under the Montreal Protocol. Recent studies have found an unexplained increase in the global tropospheric abundance of one VSLS, dichloromethane (CH2Cl2, which has increased by around 60 % over the past decade. Here we report dramatic enhancements of several chlorine-containing VSLSs (Cl-VSLSs, including CH2Cl2 and CH2ClCH2Cl (1,2-dichloroethane, observed in surface and upper-tropospheric air in East and South East Asia. Surface observations were, on occasion, an order of magnitude higher than previously reported in the marine boundary layer, whilst upper-tropospheric data were up to 3 times higher than expected. In addition, we provide further evidence of an atmospheric transport mechanism whereby substantial amounts of industrial pollution from East Asia, including these chlorinated VSLSs, can rapidly, and regularly, be transported to tropical regions of the western Pacific and subsequently uplifted to the tropical upper troposphere. This latter region is a major provider of air entering the stratosphere, and so this mechanism, in conjunction with increasing emissions of Cl-VSLSs from East Asia, could potentially slow the expected recovery of stratospheric ozone.

  7. Development of a system for real-time measurements of metabolite transport in plants using short-lived positron-emitting radiotracers

    Science.gov (United States)

    Kiser, Matthew R.

    Over the past 200 years, the Earth's atmospheric carbon dioxide (CO 2) concentration has increased by more than 35%, and climate experts predict that CO2 levels may double by the end of this century. Understanding the mechanisms of resource management in plants is fundamental for predicting how plants will respond to the increase in atmospheric CO 2. Plant productivity sustains life on Earth and is a principal component of the planet's system that regulates atmospheric CO2 concentration. As such, one of the central goals of plant science is to understand the regulatory mechanisms of plant growth in a changing environment. Short-lived positron-emitting radiotracer techniques provide time-dependent data that are critical for developing models of metabolite transport and resource distribution in plants and their microenvironments. To better understand the effects of environmental changes on resource transport and allocation in plants, we have developed a system for real-time measurements of rnetabolite transport in plants using short-lived positron-emitting radio-tracers. This thesis project includes the design, construction, and demonstration of the capabilities of this system for performing real-time measurements of metabolite transport in plants. The short-lived radiotracer system described in this dissertation takes advantage of the combined capabilities and close proximity of two research facilities at. Duke University: the Triangle Universities Nuclear Laboratory (TUNL) and the Duke University Phytotron, which are separated by approximately 100 meters. The short-lived positron-emitting radioisotopes are generated using the 10-MV tandem Van de Graaff accelerator located in the main TUNL building, which provides the capability of producing short-lived positron-emitting isotopes such as carbon-11 (11C: 20 minute half-life), nitrogen-13 (13N; 10 minute half-life), fluorine-18 (18F; 110 minute half-life), and oxygen-15 (15O; 2 minute half-life). The radioisotopes may

  8. Production and Use of Short-Lived Radioisotopes from Reactors. Vol. II. Proceedings of a Seminar on the Practical Applications of Short-Lived Radioisotopes Produced in Small Research Reactors

    International Nuclear Information System (INIS)

    1963-01-01

    There are many radioisotope applications in which it is important that the radiation should rapidly fall to an insignificant level once the initial intense activity has served its purpose. Such applications include diagnostic tests in medicine, where it is essential to reduce the radiation dose to the patient to a minimum, non-destructive testing methods which must be applied without contaminating the material or product concerned, and repeated routine tests which are possible only if the residual activity from the previous test is negligible. All these applications call for radionuclides whose half- lives are measured in hours or even minutes. Similarly, in the new but increasingly important technique of activation analysis, whereby the quantities of elements present in a material can be determined by irradiating the material in a reactor and assaying the radionuclides produced, the latter are mainly short-lived and must be measured immediately. While the production of long-lived radionuclides can most economically be left to the large reactors at the main radioisotope centres, short-lived isotopes must be produced, or materials activation performed, in a reactor at or near the place of intended use or analysis; this, then, represents one of the most important uses for the large number of small reactors which have been installed in recent years, or will come into operation in the near future, in many parts of the world. Since in many countries the new problems of producing, separating and applying short-lived radioisotopes are being faced for the first time, the International Atomic Energy Agency believed it would be valuable to survey the state of the art by convening an international Seminar on Practical Applications of Short-lived Radioisotopes produced in Small Research Reactors at its Vienna headquarters in November, 1962. This Seminar provided an opportunity for the producers and users of short-lived radioisotopes from many countries to meet and discuss the

  9. Production and Use of Short-Lived Radioisotopes from Reactors. Vol. II. Proceedings of a Seminar on the Practical Applications of Short-Lived Radioisotopes Produced in Small Research Reactors

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1963-03-15

    There are many radioisotope applications in which it is important that the radiation should rapidly fall to an insignificant level once the initial intense activity has served its purpose. Such applications include diagnostic tests in medicine, where it is essential to reduce the radiation dose to the patient to a minimum, non-destructive testing methods which must be applied without contaminating the material or product concerned, and repeated routine tests which are possible only if the residual activity from the previous test is negligible. All these applications call for radionuclides whose half- lives are measured in hours or even minutes. Similarly, in the new but increasingly important technique of activation analysis, whereby the quantities of elements present in a material can be determined by irradiating the material in a reactor and assaying the radionuclides produced, the latter are mainly short-lived and must be measured immediately. While the production of long-lived radionuclides can most economically be left to the large reactors at the main radioisotope centres, short-lived isotopes must be produced, or materials activation performed, in a reactor at or near the place of intended use or analysis; this, then, represents one of the most important uses for the large number of small reactors which have been installed in recent years, or will come into operation in the near future, in many parts of the world. Since in many countries the new problems of producing, separating and applying short-lived radioisotopes are being faced for the first time, the International Atomic Energy Agency believed it would be valuable to survey the state of the art by convening an international Seminar on Practical Applications of Short-lived Radioisotopes produced in Small Research Reactors at its Vienna headquarters in November, 1962. This Seminar provided an opportunity for the producers and users of short-lived radioisotopes from many countries to meet and discuss the

  10. Ca2+-regulatory proteins in cardiomyocytes from the right ventricle in children with congenital heart disease

    Directory of Open Access Journals (Sweden)

    Wu Yihe

    2012-04-01

    Full Text Available Abstract Background Hypoxia and hypertrophy are the most frequent pathophysiological consequence of congenital heart disease (CHD which can induce the alteration of Ca2+-regulatory proteins and inhibit cardiac contractility. Few studies have been performed to examine Ca2+-regulatory proteins in human cardiomyocytes from the hypertrophic right ventricle with or without hypoxia. Methods Right ventricle tissues were collected from children with tetralogy of Fallot [n = 25, hypoxia and hypertrophy group (HH group], pulmonary stenosis [n = 25, hypertrophy group (H group], or small isolated ventricular septal defect [n = 25, control group (C group] during open-heart surgery. Paraffin sections of tissues were stained with 3,3′-dioctadecyloxacarbocyanine perchlorate to measure cardiomyocyte size. Expression levels of Ca2+-regulatory proteins [sarcoplasmic reticulum Ca2+-ATPase (SERCA2a, ryanodine receptor (RyR2, sodiumcalcium exchanger (NCX, sarcolipin (SLN and phospholamban (PLN] were analysed by means of real-time PCR, western blot, or immunofluorescence. Additionally, phosphorylation level of RyR and PLN and activity of protein phosphatase (PP1 were evaluated using western blot. Results Mild cardiomyocyte hypertrophy of the right ventricle in H and HH groups was confirmed by comparing cardiomyocyte size. A significant reduction of SERCA2a in mRNA (P16-phosphorylated PLN was down-regulated (PP Conclusions The decreased SERCA2a mRNA may be a biomarker of the pathological process in the early stage of cyanotic CHD with the hypertrophic right ventricle. A combination of hypoxia and hypertrophy can induce the adverse effect of PLN-Ser16 dephosphorylation. Increased PP1 could result in the decreased PLN-Ser16 and inhibition of PP1 is a potential therapeutic target for heart dysfunction in pediatrics.

  11. Dormancy and germination in short-lived lepidium perfoliatu l. (brassicaceae) seeds

    International Nuclear Information System (INIS)

    Tang, An-Jun; Tian, M.; Long, Chun-Lin

    2010-01-01

    To understand germination timing in an ecological context, the response to environmental events that effect seed dormancy is central and has to be combined with knowledge of germination responses to different ecological factors. In this study, seed dormancy, germination and seedling survival of annual short-lived clasping pepper weed Lepidium perfoliatum L. (Brassicaceae) were investigated. Three types of pre-treatments viz., various temperature dry storage, light and water stress were tested as possible dormancy and survival-affecting environmental events. Fresh mature seeds were greatly dormant. Warm (30 deg. C) dry storage more facilitated breaking dormancy, they germinated well under apt conditions (e.g. 20 deg. C and 10/20 deg. C plus periodic light, 14 h/d). For those seeds which underwent after-ripening, they could germinate at a range of constant temperatures (4, 10, 15, 20, 25, and 30 deg. C) and one alternating temperature (10/20 deg. C). Under alternating temperature regimes, the final percent germination of L. perfoliatum seeds increased from 37 deg. C to 93% when temperature altered from 4/10 deg. C to 10/20 deg. C in light, then decreased with increasing temperature. The germination pattern under constant temperature conditions was similar to that under alternating temperature and significant differences in final percent germinations and rates of germination were observed among different temperatures. Under different light treatments, final germination of showed significant differences, only with 35% of germination percentage in dark, much lower than those in red and white light (i.e. 93% and 91%, respectively). GA3 could promote the germination of non-dormant seeds in dark. When water potentials were reduced, final percent germination decreased dramatically, and few seeds germinated at -0.98 MPa (generated by PEG-8000). The changes of proline content in resultant seedlings were reverse to that of final percent germination with changing water

  12. Seasonal variation in the behaviour of a short-lived rodent.

    Science.gov (United States)

    Eccard, Jana A; Herde, Antje

    2013-11-15

    Short lived, iteroparous animals in seasonal environments experience variable social and environmental conditions over their lifetime. Animals can be divided into those with a "young-of-the-year" life history (YY, reproducing and dying in the summer of birth) and an "overwinter" life history (OW, overwintering in a subadult state before reproducing next spring).We investigated how behavioural patterns across the population were affected by season and sex, and whether variation in behaviour reflects the variation in life history patterns of each season. Applications of pace-of-life (POL) theory would suggest that long-lived OW animals are shyer in order to increase survival, and YY are bolder in order to increase reproduction. Therefore, we expected that in winter and spring samples, when only OW can be sampled, the animals should be shyer than in summer and autumn, when both OW and YY animals can be sampled.We studied common vole (Microtus arvalis) populations, which express typical, intra-annual density fluctuation. We captured a total of 492 voles at different months over 3 years and examined boldness and activity level with two standardised behavioural experiments. Behavioural variables of the two tests were correlated with each other. Boldness, measured as short latencies in both tests, was extremely high in spring compared to other seasons. Activity level was highest in spring and summer, and higher in males than in females. Being bold in laboratory tests may translate into higher risk-taking in nature by being more mobile while seeking out partners or valuable territories. Possible explanations include asset-protection, with OW animals being rather old with low residual reproductive value in spring. Therefore, OW may take higher risks during this season. Offspring born in spring encounter a lower population density and may have higher reproductive value than offspring of later cohorts. A constant connection between life history and animal personality, as

  13. Regional emission metrics for short-lived climate forcers from multiple models

    Directory of Open Access Journals (Sweden)

    B. Aamaas

    2016-06-01

    Full Text Available For short-lived climate forcers (SLCFs, the impact of emissions depends on where and when the emissions take place. Comprehensive new calculations of various emission metrics for SLCFs are presented based on radiative forcing (RF values calculated in four different (chemical-transport or coupled chemistry–climate models. We distinguish between emissions during summer (May–October and winter (November–April for emissions in Europe and East Asia, as well as from the global shipping sector and global emissions. The species included in this study are aerosols and aerosol precursors (BC, OC, SO2, NH3, as well as ozone precursors (NOx, CO, VOCs, which also influence aerosols to a lesser degree. Emission metrics for global climate responses of these emissions, as well as for CH4, have been calculated using global warming potential (GWP and global temperature change potential (GTP, based on dedicated RF simulations by four global models. The emission metrics include indirect cloud effects of aerosols and the semi-direct forcing for BC. In addition to the standard emission metrics for pulse and sustained emissions, we have also calculated a new emission metric designed for an emission profile consisting of a ramping period of 15 years followed by sustained emissions, which is more appropriate for a gradual implementation of mitigation policies.For the aerosols, the emission metric values are larger in magnitude for emissions in Europe than East Asia and for summer than winter. A variation is also observed for the ozone precursors, with largest values for emissions in East Asia and winter for CO and in Europe and summer for VOCs. In general, the variations between the emission metrics derived from different models are larger than the variations between regions and seasons, but the regional and seasonal variations for the best estimate also hold for most of the models individually. Further, the estimated climate impact of an illustrative mitigation

  14. Radon and its short-lived daughter products in the lower atmosphere

    International Nuclear Information System (INIS)

    Servant, J.

    1964-01-01

    The variations of vertical and temporal distributions of natural radioactivity with geographical location in the lower atmospheric layers are shown. The content of radon and its short lived daughters products are measured. Radon content is measured continually with a new apparatus, the sensibility of which is 0,2.10 -11 Ci m -3 i.e. the fiftieth of the mean concentration near the soil, this apparatus allowed us to show that radioactive equilibrium between radon and its daughter products is realised when the atmosphere is stable. Air observations between 0 and 100 meters above the ground point out that radon and its decay products are valuable tracers to mark the stability of the atmosphere. Under very stable nighttime conditions the radon accumulates in the former 30 meters of the air layer, at sunrise it ascends and at 9 o'clock attains 100 meters high. The removal rate of the air in the lower atmosphere is computed from the movement of this radon mass, it is equal to 90 per cent for a summer day. We have show that this radon comes from the soil in which it diffuses by brownian motion the intensity of which varies with the water content of the soil, its value for June 1958 is 6,10 -17 Ci cm -2 s -1 and for January 1959 0.2,10 -17 Ci cm -2 s - 1. During the year 1958-1959 general mean of flux for the sedimentary soil studied is equal to 3. 8 ± 1.3, 10 -17 Ci cm -2 s -1 it is identical to the world wide mean computed by H. Israel. In a hilly site in the Morvan, air movements are well marked by this radioactivity. We observed from one hand downslope and up-slope breezes having, respectively, speeds of 0.2 m s -1 and 0.7 m s -1 and from the other hand by night, in the valley and with a light wind favours the stagnation of the air near the ground, a strong increase of the radioactivity which is proportional to the one of the granitic rocks of the region. The radon flux of this soil is 74,10 -17 Ci cm -2 s -1 and the radioactivity of the air can attain 1.5,10 -8 Ci m

  15. Intracellular protein breakdown. 8

    International Nuclear Information System (INIS)

    Bohley, P.; Kirschke, H.; Langner, J.; Wiederanders, B.; Ansorge, S.

    1976-01-01

    Double-labelled proteins from rat liver cytosol ( 14 C in long-lived, 3 H in short-lived proteins after in-vivo-labelling) are used as substrates for unlabelled proteinases in vitro. Differences in the degradation rates of short-lived and long-lived proteins in vitro by different proteinases and after addition of different effectors allow conclusions concerning their importance for the in-vivo-turnover of substrate proteins. The main activity (>90%) of soluble lysosomal proteinases at pH 6.1 and pH 6.9 is caused by thiolproteinases, which degrade preferentially short-lived cytosol proteins. These proteinases are inhibited by leupeptin. Autolysis of double-labelled cell fractions shows a remarkably faster breakdown of short-lived substrate proteins only in the soluble part of lysosomes. Microsomal fractions degrade in vitro preferentially long-lived substrate proteins. (author)

  16. Evaluating the climate and air quality impacts of short-lived pollutants

    Science.gov (United States)

    Stohl, A.; Aamaas, B.; Amann, M.; Baker, L. H.; Bellouin, N.; Berntsen, T. K.; Boucher, O.; Cherian, R.; Collins, W.; Daskalakis, N.; Dusinska, M.; Eckhardt, S.; Fuglestvedt, J. S.; Harju, M.; Heyes, C.; Hodnebrog, Ø.; Hao, J.; Im, U.; Kanakidou, M.; Klimont, Z.; Kupiainen, K.; Law, K. S.; Lund, M. T.; Maas, R.; MacIntosh, C. R.; Myhre, G.; Myriokefalitakis, S.; Olivié, D.; Quaas, J.; Quennehen, B.; Raut, J.-C.; Rumbold, S. T.; Samset, B. H.; Schulz, M.; Seland, Ø.; Shine, K. P.; Skeie, R. B.; Wang, S.; Yttri, K. E.; Zhu, T.

    2015-09-01

    This paper presents a summary of the work done within the European Union's Seventh Framework Programme project ECLIPSE (Evaluating the Climate and Air Quality Impacts of Short-Lived Pollutants). ECLIPSE had a unique systematic concept for designing a realistic and effective mitigation scenario for short-lived climate pollutants (SLCPs; methane, aerosols and ozone, and their precursor species) and quantifying its climate and air quality impacts, and this paper presents the results in the context of this overarching strategy. The first step in ECLIPSE was to create a new emission inventory based on current legislation (CLE) for the recent past and until 2050. Substantial progress compared to previous work was made by including previously unaccounted types of sources such as flaring of gas associated with oil production, and wick lamps. These emission data were used for present-day reference simulations with four advanced Earth system models (ESMs) and six chemistry transport models (CTMs). The model simulations were compared with a variety of ground-based and satellite observational data sets from Asia, Europe and the Arctic. It was found that the models still underestimate the measured seasonality of aerosols in the Arctic but to a lesser extent than in previous studies. Problems likely related to the emissions were identified for northern Russia and India, in particular. To estimate the climate impacts of SLCPs, ECLIPSE followed two paths of research: the first path calculated radiative forcing (RF) values for a large matrix of SLCP species emissions, for different seasons and regions independently. Based on these RF calculations, the Global Temperature change Potential metric for a time horizon of 20 years (GTP20) was calculated for each SLCP emission type. This climate metric was then used in an integrated assessment model to identify all emission mitigation measures with a beneficial air quality and short-term (20-year) climate impact. These measures together

  17. Measurements of airborne short-lived radioactivity concentration in a PET facility at a national University hospital

    International Nuclear Information System (INIS)

    Saito, Tadashi

    2006-01-01

    National universities in Japan became under regulation of Industrial Safety and Health Law since 2004FY. One of the legal obligations is working environment measurements such as airborne radioactivity concentration in the rooms where employees handle unsealed radiation sources. Both in 2004FY and in 2005FY, measurements of airborne radioactivity concentration were carried out by two different agencies. The most prominent difference among them is the measurement for short-lived PET nuclides. In 2004FY, one agency measured the radioactivity with a Ge spectrometer at its own laboratory, whereas, in 2005FY, the other agency brought a NaI scintillation counter for gross gamma counting to the Hospital. It can be shown that detection limits for short-lived PET nuclides are in principle almost the same in both methods. It is also found that, in the actual case, gamma spectrometry with a Ge spectrometer is superior in judgement of detection of the radioactivity. (author)

  18. Pro-protein convertases control the maturation and processing of the iron-regulatory protein, RGMc/hemojuvelin

    Directory of Open Access Journals (Sweden)

    Rotwein Peter

    2008-04-01

    Full Text Available Abstract Background Repulsive guidance molecule c (RGMc or hemojuvelin, a glycosylphosphatidylinositol-linked glycoprotein expressed in liver and striated muscle, plays a central role in systemic iron balance. Inactivating mutations in the RGMc gene cause juvenile hemochromatosis (JH, a rapidly progressing iron storage disorder with severe systemic manifestations. RGMc undergoes complex biosynthetic steps leading to membrane-bound and soluble forms of the protein, including both 50 and 40 kDa single-chain species. Results We now show that pro-protein convertases (PC are responsible for conversion of 50 kDa RGMc to a 40 kDa protein with a truncated COOH-terminus. Unlike related molecules RGMa and RGMb, RGMc encodes a conserved PC recognition and cleavage site, and JH-associated RGMc frame-shift mutants undergo COOH-terminal cleavage only if this site is present. A cell-impermeable peptide PC inhibitor blocks the appearance of 40 kDa RGMc in extra-cellular fluid, as does an engineered mutation in the conserved PC recognition sequence, while the PC furin cleaves 50 kDa RGMc in vitro into a 40 kDa molecule with an intact NH2-terminus. Iron loading reduces release of RGMc from the cell membrane, and diminishes accumulation of the 40 kDa species in cell culture medium. Conclusion Our results define a role for PCs in the maturation of RGMc that may have implications for the physiological actions of this critical iron-regulatory protein.

  19. Possibilities of chemical isolation of element 106 from aqueous solutions according to the model experiments with short lived tungsten isotopes

    International Nuclear Information System (INIS)

    Szeglowski, Z.; Bruchertseifer, H.; Brudanin, V.B.

    1993-01-01

    A rapid method for continuous separation of short-lived tungsten isotopes from the lanthanides has been developed. It consists in transforming nuclear reaction products from the target by an aerosol jet to an absorber where the KCl particulates are dissolved in 0.2 M HF and percolating the product solution through three successively linked columns filled with ion exchange resins Dowex 50X8 (cationite), Dowex 1X8 (anionite) and again Dowex 50X8. 3 refs

  20. PANTHER Data from SOLVE-II Through CR-AVE: A Contrast Between Long and Short Lived Compounds.

    Science.gov (United States)

    Moore, F. L.; Dutton, G. S.; Elkins, J. W.; Hall, B. D.; Hurst, D. F.; Nance, J. D.; Thompson, T. M.

    2006-12-01

    PANTHER (PAN and other Trace Hydrohalocarbons ExpeRiment) is an airborne 6-channel gas chromatograph that measures approximately 20 important atmospheric trace gases whose changing burdens impact air quality, climate change and both stratospheric and tropospheric ozone. In this presentation we will contrast measurements of the long-lived compounds against the short-lived compounds. The long-lived compounds tend to have well-defined troposphere boundary conditions and develop spatial gradients due to stratospheric processing. These measurements have played a major role in quantifying stratospheric transport, stratosphere- troposphere exchange, and ozone loss. In contrast the short-lived species develop spatial and temporal gradients in the tropical tropopause layer (TTL), due to variations in the surface boundary layer concentrations and the coupling of this surface boundary layer to the TTL via convective processes. Deep convection acts like a "conveyor belt" between the source region in the boundary layer and the relatively stable TTL region, often bypassing the free troposphere where scavenging of these short lived species takes place. Loss rates due to reaction with OH and thermal decomposition are reduced in the cold, dry air of the TTL, resulting in longer survival times. Isolation of the TTL region from the free troposphere can last from days to over a month. Significant amounts of these short-lived compound and their byproducts can therefore be transported into the lower stratosphere (LS). Of particular interest are compounds that contain bromine, iodine, and sulfur, not only because of their intrinsic harmful effects in the atmosphere, but also because they have unique source and sink regions that can help to de- convolve transport.

  1. The ratio of long-lived to short-lived radon-222 progeny concentrations in ground-level air

    Energy Technology Data Exchange (ETDEWEB)

    Hoetzl, H.; Winkler, R. [Institut fuer Strahlenschutz, GSF-Forschungszentrum fuer Umwelt und Gesundheit, Neuherberg Oberschleissheim (Germany)

    1996-02-09

    The ratio of {sup 210}Pb air concentration to the short-lived radon ({sup 222}Rn) decay products concentration at ground level was investigated at a semi-rural location 10 km north of Munich, south Germany, for a period of 11 years (1982-1992). The average ratio from 132 monthly mean values has been found to be (7.5{+-}2.2) x 10{sup -5} (arithmetic mean{+-}S.D.). While the time series of the short-lived radon daughter concentration exhibit a distinct seasonal pattern with maxima mostly in October of each year, the course of {sup 210}Pb air concentration is characterized by high values from October through February. Consequently, high ratios of {sup 210}Pb to short-lived decay product concentration are often observed in the winter months of December-February. To study the influence of meteorological conditions on this behaviour, {sup 210}Pb and {sup 214}Pb concentrations were measured on a short-term basis with sampling intervals of 2-3 days from October 1991 to November 1992. The air concentrations obtained within those intervals were then correlated with actual meteorological parameters. On the base of this investigation the seasonal behaviour can essentially be explained by the more frequent inversion weather conditions in winter than in the summer months. At the same location, the average ratio of {sup 210}Po to {sup 210}Pb concentration in ground level air has been found to be 0.079 from 459 weakly mean values between 1976 and 1985. Hence, the corresponding average ratios of the short-lived radon daughters (EEC) to {sup 210}Pb and {sup 210}Po, were 1:7.5x10{sup -5} and 1:0.6 x 10{sup -5}, respectively.

  2. The ratio of long-lived to short-lived radon-222 progeny concentrations in ground-level air

    International Nuclear Information System (INIS)

    Hoetzl, H.; Winkler, R.

    1996-01-01

    The ratio of 210 Pb air concentration to the short-lived radon ( 222 Rn) decay products concentration at ground level was investigated at a semi-rural location 10 km north of Munich, south Germany, for a period of 11 years (1982-1992). The average ratio from 132 monthly mean values has been found to be (7.5±2.2) x 10 -5 (arithmetic mean±S.D.). While the time series of the short-lived radon daughter concentration exhibit a distinct seasonal pattern with maxima mostly in October of each year, the course of 210 Pb air concentration is characterized by high values from October through February. Consequently, high ratios of 210 Pb to short-lived decay product concentration are often observed in the winter months of December-February. To study the influence of meteorological conditions on this behaviour, 210 Pb and 214 Pb concentrations were measured on a short-term basis with sampling intervals of 2-3 days from October 1991 to November 1992. The air concentrations obtained within those intervals were then correlated with actual meteorological parameters. On the base of this investigation the seasonal behaviour can essentially be explained by the more frequent inversion weather conditions in winter than in the summer months. At the same location, the average ratio of 210 Po to 210 Pb concentration in ground level air has been found to be 0.079 from 459 weakly mean values between 1976 and 1985. Hence, the corresponding average ratios of the short-lived radon daughters (EEC) to 210 Pb and 210 Po, were 1:7.5x10 -5 and 1:0.6 x 10 -5 , respectively

  3. iTRAQ-Based Quantitative Proteomics Identifies Potential Regulatory Proteins Involved in Chicken Eggshell Brownness.

    Directory of Open Access Journals (Sweden)

    Guangqi Li

    Full Text Available Brown eggs are popular in many countries and consumers regard eggshell brownness as an important indicator of egg quality. However, the potential regulatory proteins and detailed molecular mechanisms regulating eggshell brownness have yet to be clearly defined. In the present study, we performed quantitative proteomics analysis with iTRAQ technology in the shell gland epithelium of hens laying dark and light brown eggs to investigate the candidate proteins and molecular mechanisms underlying variation in chicken eggshell brownness. The results indicated 147 differentially expressed proteins between these two groups, among which 65 and 82 proteins were significantly up-regulated in the light and dark groups, respectively. Functional analysis indicated that in the light group, the down-regulated iron-sulfur cluster assembly protein (Iba57 would decrease the synthesis of protoporphyrin IX; furthermore, the up-regulated protein solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator, member 5 (SLC25A5 and down-regulated translocator protein (TSPO would lead to increased amounts of protoporphyrin IX transported into the mitochondria matrix to form heme with iron, which is supplied by ovotransferrin protein (TF. In other words, chickens from the light group produce less protoporphyrin IX, which is mainly used for heme synthesis. Therefore, the exported protoporphyrin IX available for eggshell deposition and brownness is reduced in the light group. The current study provides valuable information to elucidate variation of chicken eggshell brownness, and demonstrates the feasibility and sensitivity of iTRAQ-based quantitative proteomics analysis in providing useful insights into the molecular mechanisms underlying brown eggshell pigmentation.

  4. Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Meisheng; Tran, V.T.; Fong, H.K.W. (Univ. of Southern California, Los Angeles (United States)); Pandey, S. (Doheny Eye Inst., Los Angeles, CA (United States))

    1991-05-01

    The expression of GTP-binding regulatory proteins (G proteins) in retinal pigment epithelial (RPE) cells was analyzed by RNA blot hybridization and cDNA amplification. Both adult and fetal human RPE cells contain mRNA for multiple G protein {alpha} subunits (G{alpha}) including G{sub s}{alpha}, G{sub i-1}{alpha}, G{sub i-2}{alpha}, G{sub i-3}{alpha}, and G{sub z}{alpha} (or G{sub x}{alpha}), where G{sub s} and G{sub i} are proteins that stimulate or inhibit adenylyl cyclase, respectively, and G{sub z} is a protein that may mediate pertussis toxin-insensitive events. Other G{alpha}-related mRNA transcripts were detected in fetal RPE cells by low-stringency hybridization to G{sub i-2}{alpha} and G{sub s}{alpha} protein-coding cDNA probes. The diversity of G proteins in RPE cells was further studied by cDNA amplification with reverse transcriptase and the polymerase chain reaction. This approach revealed that, besides the above mentioned members of the G{alpha} gene family, at least two other G{alpha} subunits are expressed in RPE cells. Human retinal cDNA clones that encode one of the additional G{alpha} subunits were isolated and characterized. The results indicate that this G{alpha} subunit belongs to a separate subfamily of G proteins that may be insensitive to inhibition by pertussis toxin.

  5. The selective phosphorylation of a guanine nucleotide-binding regulatory protein

    International Nuclear Information System (INIS)

    Carlson, K.E.

    1989-01-01

    Receptor-activated signal transduction pathways regulate the responsiveness of cells to external stimuli. These transduction pathways themselves are subject to regulation, most commonly by phosphorylation. Guanine nucleotide-binding regulatory proteins (G Proteins), as requisite signal transducing elements for many plasma membrane receptors, are considered likely targets for regulation by phosphorylation. Protein kinase C (PKC) has been shown to phosphorylate the α subunit of G i and other G proteins in solution. However, the occurrence of the phosphorylation of G 1 within intact cells in response to activation of PKC has not been rigorously demonstrated. In this thesis, the extent to which the α subunits of G i undergo phosphorylation within human platelets in response to activation of PKC was examined by means of radiolabeling and immunoprecipitation. Incubation of platelets with phorbol-12-myristate-13-acetate (PMA), a potent activator of PKC, promoted the phosphorylation of several proteins within saponin-permeabilized and intact platelets incubated with [γ 32 P]ATP and [ 32 P]H 3 PO 4 , respectively. None of the phosphoproteins, however, were precipitated by either of two antisera containing antibodies differing in specificities for epitopes within G iα -despite precipitation of a substantial fraction of the subunit itself. In contrast, other antisera, containing antibodies specific for the recently describe G zα , or antibodies for both G zα and G iα , precipitated a 40-kDa phosphoprotein

  6. Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

    International Nuclear Information System (INIS)

    Matsushita, Y.; Murakawa, T.; Shimamura, K.; Oishi, M.; Ohyama, T.; Kurita, N.

    2015-01-01

    The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA

  7. Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Y., E-mail: kurita@cs.tut.ac.jp; Murakawa, T., E-mail: kurita@cs.tut.ac.jp; Shimamura, K., E-mail: kurita@cs.tut.ac.jp; Oishi, M., E-mail: kurita@cs.tut.ac.jp; Ohyama, T., E-mail: kurita@cs.tut.ac.jp; Kurita, N., E-mail: kurita@cs.tut.ac.jp [Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580 (Japan)

    2015-02-27

    The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

  8. Multi-model evaluation of short-lived pollutant distributions over east Asia during summer 2008

    Science.gov (United States)

    Quennehen, B.; Raut, J.-C.; Law, K. S.; Daskalakis, N.; Ancellet, G.; Clerbaux, C.; Kim, S.-W.; Lund, M. T.; Myhre, G.; Olivié, D. J. L.; Safieddine, S.; Skeie, R. B.; Thomas, J. L.; Tsyro, S.; Bazureau, A.; Bellouin, N.; Hu, M.; Kanakidou, M.; Klimont, Z.; Kupiainen, K.; Myriokefalitakis, S.; Quaas, J.; Rumbold, S. T.; Schulz, M.; Cherian, R.; Shimizu, A.; Wang, J.; Yoon, S.-C.; Zhu, T.

    2016-08-01

    is too weak to explain the differences between the models. Our results rather point to an overestimation of SO2 emissions, in particular, close to the surface in Chinese urban areas. However, we also identify a clear underestimation of aerosol concentrations over northern India, suggesting that the rapid recent growth of emissions in India, as well as their spatial extension, is underestimated in emission inventories. Model deficiencies in the representation of pollution accumulation due to the Indian monsoon may also be playing a role. Comparison with vertical aerosol lidar measurements highlights a general underestimation of scattering aerosols in the boundary layer associated with overestimation in the free troposphere pointing to modelled aerosol lifetimes that are too long. This is likely linked to too strong vertical transport and/or insufficient deposition efficiency during transport or export from the boundary layer, rather than chemical processing (in the case of sulphate aerosols). Underestimation of sulphate in the boundary layer implies potentially large errors in simulated aerosol-cloud interactions, via impacts on boundary-layer clouds.This evaluation has important implications for accurate assessment of air pollutants on regional air quality and global climate based on global model calculations. Ideally, models should be run at higher resolution over source regions to better simulate urban-rural pollutant gradients and/or chemical regimes, and also to better resolve pollutant processing and loss by wet deposition as well as vertical transport. Discrepancies in vertical distributions require further quantification and improvement since these are a key factor in the determination of radiative forcing from short-lived pollutants.

  9. Multi-model evaluation of short-lived pollutant distributions over east Asia during summer 2008

    Directory of Open Access Journals (Sweden)

    B. Quennehen

    2016-08-01

    mitigation in Beijing is too weak to explain the differences between the models. Our results rather point to an overestimation of SO2 emissions, in particular, close to the surface in Chinese urban areas. However, we also identify a clear underestimation of aerosol concentrations over northern India, suggesting that the rapid recent growth of emissions in India, as well as their spatial extension, is underestimated in emission inventories. Model deficiencies in the representation of pollution accumulation due to the Indian monsoon may also be playing a role. Comparison with vertical aerosol lidar measurements highlights a general underestimation of scattering aerosols in the boundary layer associated with overestimation in the free troposphere pointing to modelled aerosol lifetimes that are too long. This is likely linked to too strong vertical transport and/or insufficient deposition efficiency during transport or export from the boundary layer, rather than chemical processing (in the case of sulphate aerosols. Underestimation of sulphate in the boundary layer implies potentially large errors in simulated aerosol–cloud interactions, via impacts on boundary-layer clouds.This evaluation has important implications for accurate assessment of air pollutants on regional air quality and global climate based on global model calculations. Ideally, models should be run at higher resolution over source regions to better simulate urban–rural pollutant gradients and/or chemical regimes, and also to better resolve pollutant processing and loss by wet deposition as well as vertical transport. Discrepancies in vertical distributions require further quantification and improvement since these are a key factor in the determination of radiative forcing from short-lived pollutants.

  10. Evolution of context dependent regulation by expansion of feast/famine regulatory proteins.

    Science.gov (United States)

    Plaisier, Christopher L; Lo, Fang-Yin; Ashworth, Justin; Brooks, Aaron N; Beer, Karlyn D; Kaur, Amardeep; Pan, Min; Reiss, David J; Facciotti, Marc T; Baliga, Nitin S

    2014-11-14

    Expansion of transcription factors is believed to have played a crucial role in evolution of all organisms by enabling them to deal with dynamic environments and colonize new environments. We investigated how the expansion of the Feast/Famine Regulatory Protein (FFRP) or Lrp-like proteins into an eight-member family in Halobacterium salinarum NRC-1 has aided in niche-adaptation of this archaeon to a complex and dynamically changing hypersaline environment. We mapped genome-wide binding locations for all eight FFRPs, investigated their preference for binding different effector molecules, and identified the contexts in which they act by analyzing transcriptional responses across 35 growth conditions that mimic different environmental and nutritional conditions this organism is likely to encounter in the wild. Integrative analysis of these data constructed an FFRP regulatory network with conditionally active states that reveal how interrelated variations in DNA-binding domains, effector-molecule preferences, and binding sites in target gene promoters have tuned the functions of each FFRP to the environments in which they act. We demonstrate how conditional regulation of similar genes by two FFRPs, AsnC (an activator) and VNG1237C (a repressor), have striking environment-specific fitness consequences for oxidative stress management and growth, respectively. This study provides a systems perspective into the evolutionary process by which gene duplication within a transcription factor family contributes to environment-specific adaptation of an organism.

  11. CCAAT/enhancer-binding proteins regulate expression of the human steroidogenic acute regulatory protein (StAR) gene.

    Science.gov (United States)

    Christenson, L K; Johnson, P F; McAllister, J M; Strauss, J F

    1999-09-10

    Two putative CCAAT/enhancer-binding protein (C/EBP) response elements were identified in the proximal promoter of the human steroidogenic acute regulatory protein (StAR) gene, which encodes a key protein-regulating steroid hormone synthesis. Expression of C/EBPalpha and -beta increased StAR promoter activity in COS-1 and HepG2 cells. Cotransfection of C/EBPalpha or -beta and steroidogenic factor 1, a transcription factor required for cAMP regulation of StAR expression, into COS-1 augmented 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP)-stimulated promoter activity. When the putative C/EBP response elements were mutated, individually or together, a pronounced decline in basal StAR promoter activity in human granulosa-lutein cells resulted, but the fold stimulation of promoter activity by 8-Br-cAMP was unaffected. Recombinant C/EBPalpha and -beta bound to the two identified sequences but not the mutated elements. Human granulosa-lutein cell nuclear extracts also bound these elements but not the mutated sequences. An antibody to C/EBPbeta, but not C/EBPalpha, supershifted the nuclear protein complex associated with the more distal element. The complex formed by nuclear extracts with the proximal element was not supershifted by either antibody. Western blot analysis revealed the presence of C/EBPalpha and C/EBPbeta in human granulosa-lutein cell nuclear extracts. C/EBPbeta levels were up-regulated 3-fold by 8-Br-cAMP treatment. Our studies demonstrate a role for C/EBPbeta as well as yet to be identified proteins, which can bind to C/EBP response elements, in the regulation of StAR gene expression and suggest a mechanism by which C/EBPbeta participates in the cAMP regulation of StAR gene transcription.

  12. Nuclear Magnetic Resonance structural studies of peptides and proteins from the vaso-regulatory System

    International Nuclear Information System (INIS)

    Sizun, Philippe

    1991-01-01

    The aim of the present work is to show how Nuclear Magnetic Resonance (NMR) allows to determine the 3D structure of peptides and proteins in solution. A comparative study of peptides involved in the vaso-regulatory System (form small hormonal peptide to the 65 amido-acid protein hirudin) has allowed to design most efficient NMR 1D and 2D strategies. It rapidly appeared that the size of the peptide plays a key role in the structuration of the molecule, smallest peptides being weakly structured owing to the lack of cooperative effects. As the molecular size increases or if conformational locks are present (disulfide bridges) the probability of stable secondary structure increases. For the protein hirudin, a combination of ail available NMR parameters deduced form dedicated experiments (chemical shifts, coupling constants, overhauser effects, accessibility of amide protons) and molecular modelling under constraints allows a clear 3D structure to be proposed for this protein in solution. Finally, a comparative study of the experimental structures and of those deduced form prediction rules has shed light on the concept of structural predisposition, the latter being of high value for a better understanding of structure-activity relationships. (author) [fr

  13. Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort.

    Directory of Open Access Journals (Sweden)

    Jane E Salmon

    2011-03-01

    Full Text Available Pregnancy in women with systemic lupus erythematosus (SLE or antiphospholipid antibodies (APL Ab--autoimmune conditions characterized by complement-mediated injury--is associated with increased risk of preeclampsia and miscarriage. Our previous studies in mice indicate that complement activation targeted to the placenta drives angiogenic imbalance and placental insufficiency.We use PROMISSE, a prospective study of 250 pregnant patients with SLE and/or APL Ab, to test the hypothesis in humans that impaired capacity to limit complement activation predisposes to preeclampsia. We sequenced genes encoding three complement regulatory proteins--membrane cofactor protein (MCP, complement factor I (CFI, and complement factor H (CFH--in 40 patients who had preeclampsia and found heterozygous mutations in seven (18%. Five of these patients had risk variants in MCP or CFI that were previously identified in atypical hemolytic uremic syndrome, a disease characterized by endothelial damage. One had a novel mutation in MCP that impairs regulation of C4b. These findings constitute, to our knowledge, the first genetic defects associated with preeclampsia in SLE and/or APL Ab. We confirmed the association of hypomorphic variants of MCP and CFI in a cohort of non-autoimmune preeclampsia patients in which five of 59 were heterozygous for mutations.The presence of risk variants in complement regulatory proteins in patients with SLE and/or APL Ab who develop preeclampsia, as well as in preeclampsia patients lacking autoimmune disease, links complement activation to disease pathogenesis and suggests new targets for treatment of this important public health problem.ClinicalTrials.gov NCT00198068.

  14. DNA-binding site of major regulatory protein alpha 4 specifically associated with promoter-regulatory domains of alpha genes of herpes simplex virus type 1.

    OpenAIRE

    Kristie, T M; Roizman, B

    1986-01-01

    Herpes simplex virus type 1 genes form at least five groups (alpha, beta 1, beta 2, gamma 1, and gamma 2) whose expression is coordinately regulated and sequentially ordered in a cascade fashion. Previous studies have shown that functional alpha 4 gene product is essential for the transition from alpha to beta protein synthesis and have suggested that alpha 4 gene expression is autoregulatory. We have previously reported that labeled DNA fragments containing promoter-regulatory domains of thr...

  15. Mitigation of Short-Lived Climate Pollutants from Residential Coal Heating and Combined Heating/Cooking Stoves: Impacts on the Cryosphere, Policy Options, and Co-benefits

    Science.gov (United States)

    Chafe, Z.; Anenberg, S.; Klimont, Z.; Kupiainen, K.; Lewis, J.; Metcalfe, J.; Pearson, P.

    2017-12-01

    Residential solid fuel combustion for cooking, heating, and other energy services contributes to indoor and outdoor air pollution, and creates impacts on the cryosphere. Solid fuel use often occurs in colder climates and at higher elevations, where a wide range of combustion emissions can reduce reflectivity of the snow- and ice-covered surfaces, causing climatic warming. Reducing short-lived climate pollutants (SLCPs), such as black carbon (BC), could have substantial climate and health co-benefits, especially in areas where emissions influence the cryosphere. A review of existing literature and emissions estimates, conducted as part of the Warsaw Summit on BC and Other Emissions from Residential Coal Heating Stoves and Combined Cooking/Heating Stoves, found little nationally-representative data on the fuels and technologies used for heating and combined cooking/heating. The GAINS model estimates that 24 million tonnes of coal equivalent were combusted by households for space heating globally in 2010, releasing 190 kilotons (kt) BC. Emissions from combined cooking/heating are virtually unknown. Policy instruments could mitigate cryosphere-relevant emissions of SLCPs from residential heating or cooking. These include indoor air quality guidelines, stove emission limits, bans on the use of specific fuels, regulatory codes that stipulate when burning can occur, stove changeout programs, and voluntary public education campaigns. These measures are being implemented in countries such as Chile (fuelwood moisture reduction campaign, energy efficiency, heating system improvements), Mongolia (stove renovation, fuel switching), Peru (improved stove programs), Poland (district heating, local fuel bans), United States (stove emission regulation) and throughout the European Community (Ecodesign Directive). Few, if any, of these regulations are likely to reduce emissions from combined cooking/heating. This research team found no global platform to create and share model

  16. Evidence for roles of the Escherichia coli Hda protein beyond regulatory inactivation of DnaA.

    Science.gov (United States)

    Baxter, Jamie C; Sutton, Mark D

    2012-08-01

    The ATP-bound form of the Escherichia coli DnaA protein binds 'DnaA boxes' present in the origin of replication (oriC) and operator sites of several genes, including dnaA, to co-ordinate their transcription with initiation of replication. The Hda protein, together with the β sliding clamp, stimulates the ATPase activity of DnaA via a process termed regulatory inactivation of DnaA (RIDA), to regulate the activity of DnaA in DNA replication. Here, we used the mutant dnaN159 strain, which expresses the β159 clamp protein, to gain insight into how the actions of Hda are co-ordinated with replication. Elevated expression of Hda impeded growth of the dnaN159 strain in a Pol II- and Pol IV-dependent manner, suggesting a role for Hda managing the actions of these Pols. In a wild-type strain, elevated levels of Hda conferred sensitivity to nitrofurazone, and suppressed the frequency of -1 frameshift mutations characteristic of Pol IV, while loss of hda conferred cold sensitivity. Using the dnaN159 strain, we identified 24 novel hda alleles, four of which supported E. coli viability despite their RIDA defect. Taken together, these findings suggest that although one or more Hda functions are essential for cell viability, RIDA may be dispensable. © 2012 Blackwell Publishing Ltd.

  17. Systematic comparison of the response properties of protein and RNA mediated gene regulatory motifs.

    Science.gov (United States)

    Iyengar, Bharat Ravi; Pillai, Beena; Venkatesh, K V; Gadgil, Chetan J

    2017-05-30

    We present a framework enabling the dissection of the effects of motif structure (feedback or feedforward), the nature of the controller (RNA or protein), and the regulation mode (transcriptional, post-transcriptional or translational) on the response to a step change in the input. We have used a common model framework for gene expression where both motif structures have an activating input and repressing regulator, with the same set of parameters, to enable a comparison of the responses. We studied the global sensitivity of the system properties, such as steady-state gain, overshoot, peak time, and peak duration, to parameters. We find that, in all motifs, overshoot correlated negatively whereas peak duration varied concavely with peak time. Differences in the other system properties were found to be mainly dependent on the nature of the controller rather than the motif structure. Protein mediated motifs showed a higher degree of adaptation i.e. a tendency to return to baseline levels; in particular, feedforward motifs exhibited perfect adaptation. RNA mediated motifs had a mild regulatory effect; they also exhibited a lower peaking tendency and mean overshoot. Protein mediated feedforward motifs showed higher overshoot and lower peak time compared to the corresponding feedback motifs.

  18. Expression of the cytoskeleton regulatory protein Mena in human gastric carcinoma and its prognostic significance.

    Science.gov (United States)

    Xu, Lihua; Tan, Huo; Liu, Ruiming; Huang, Qungai; Zhang, Nana; Li, Xi; Wang, Jiani

    2017-11-01

    The cytoskeleton regulatory protein Mena is reportedly overexpressed in breast cancer; however, data regarding its expression level and clinical significance in gastric carcinoma (GC) is limited. The aim of the present study was to investigate Mena expression levels and prognostic significance in GC. Mena mRNA expression level was determined by reverse transcription-quantitative polymerase chain reaction in 10 paired GC and adjacent normal tissues. The Mena protein expression level was analyzed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. Statistical analyses were also performed to evaluate the clinicopathological significance of Mena. The results revealed that the mRNA expression level of Mena was significantly higher in G Ct issues compared with in adjacent normal tissues from10 paired samples. In the paraffin-embedded tissue samples, the protein expression level of Mena was higher in G Ct issues compared with in adjacent normal tissues. Compared with adjacent normal tissues, Mena overexpression was observed in 52.83% (56/106) of patients. The overexpression of Mena was significantly associated with the T stage (P=0.033), tumor-node-metastasis (TNM) stage (PMena expression level was an independent prognostic factor for overall survival time. In conclusion, Mena wasoverexpressed in G C tissues and significantly associated with the T stage, TNM stage and overall survival time. Mena may therefore be suitable as a prognostic indicator for patients with GC.

  19. Centuries of thermal sea-level rise due to anthropogenic emissions of short-lived greenhouse gases.

    Science.gov (United States)

    Zickfeld, Kirsten; Solomon, Susan; Gilford, Daniel M

    2017-01-24

    Mitigation of anthropogenic greenhouse gases with short lifetimes (order of a year to decades) can contribute to limiting warming, but less attention has been paid to their impacts on longer-term sea-level rise. We show that short-lived greenhouse gases contribute to sea-level rise through thermal expansion (TSLR) over much longer time scales than their atmospheric lifetimes. For example, at least half of the TSLR due to increases in methane is expected to remain present for more than 200 y, even if anthropogenic emissions cease altogether, despite the 10-y atmospheric lifetime of this gas. Chlorofluorocarbons and hydrochlorofluorocarbons have already been phased out under the Montreal Protocol due to concerns about ozone depletion and provide an illustration of how emission reductions avoid multiple centuries of future TSLR. We examine the "world avoided" by the Montreal Protocol by showing that if these gases had instead been eliminated in 2050, additional TSLR of up to about 14 cm would be expected in the 21st century, with continuing contributions lasting more than 500 y. Emissions of the hydrofluorocarbon substitutes in the next half-century would also contribute to centuries of future TSLR. Consideration of the time scales of reversibility of TSLR due to short-lived substances provides insights into physical processes: sea-level rise is often assumed to follow air temperature, but this assumption holds only for TSLR when temperatures are increasing. We present a more complete formulation that is accurate even when atmospheric temperatures are stable or decreasing due to reductions in short-lived gases or net radiative forcing.

  20. Development of a Method to Assess the Radiation Dose due to Internal Exposure to Short-lived Radioactive Materials

    International Nuclear Information System (INIS)

    Benmaman, D.; Koch, J.; Ribak, J.

    2014-01-01

    Work with radioactive materials requires monitoring of the employees' exposure to ionizing radiation. Employees may be exposed to radiation from internal and/or external exposure. Control of external exposure is mostly conducted through personal radiation dosimeters provided to employees. Control of internal exposure can be performed by measuring the concentration of radioactive substances excreted in urine or through whole-body counting in which the entire body or target organs are scanned with a sensitive detector system (1). According to the regulations in Israel an employee that may be internally exposed must undergo an exposure control at least once every three months. The idea lying behind the control of internal exposure by urine testing is that if radioactive material has penetrated into the employee body, it can be detected even if the test is performed once every three months. A model was fitted for each element describing its dispersion in the body and its excretion therefrom (2). By means of this model, one can estimate the activity that entered the body and calculate the resulting radiation dose to which the worker was exposed. There is a problem to implement this method when it comes to short-lived radioactive materials, for which it is very likely that the material that penetrated into the body has decayed and cannot be detected by testing once every three months. As a result, workers with short-lived radioactive materials are presently not monitored for internal exposure, in contradiction to the requirements of the Safety at Work Regulations. The purpose of the study is to develop an alternative method to assess the amount of radioactive material absorbed in the body and the resulting radiation dose due to internal exposure of workers to short-lived radioactive materials

  1. Online selection of short-lived particles on many-core computer architectures in the CBM experiment at FAIR

    Energy Technology Data Exchange (ETDEWEB)

    Zyzak, Maksym

    2016-07-07

    Modern experiments in heavy ion collisions operate with huge data rates that can not be fully stored on the currently available storage devices. Therefore the data flow should be reduced by selecting those collisions that potentially carry the information of the physics interest. The future CBM experiment will have no simple criteria for selecting such collisions and requires the full online reconstruction of the collision topology including reconstruction of short-lived particles. In this work the KF Particle Finder package for online reconstruction and selection of short-lived particles is proposed and developed. It reconstructs more than 70 decays, covering signals from all the physics cases of the CBM experiment: strange particles, strange resonances, hypernuclei, low mass vector mesons, charmonium, and open-charm particles. The package is based on the Kalman filter method providing a full set of the particle parameters together with their errors including position, momentum, mass, energy, lifetime, etc. It shows a high quality of the reconstructed particles, high efficiencies, and high signal to background ratios. The KF Particle Finder is extremely fast for achieving the reconstruction speed of 1.5 ms per minimum-bias AuAu collision at 25 AGeV beam energy on single CPU core. It is fully vectorized and parallelized and shows a strong linear scalability on the many-core architectures of up to 80 cores. It also scales within the First Level Event Selection package on the many-core clusters up to 3200 cores. The developed KF Particle Finder package is a universal platform for short- lived particle reconstruction, physics analysis and online selection.

  2. Online selection of short-lived particles on many-core computer architectures in the CBM experiment at FAIR

    International Nuclear Information System (INIS)

    Zyzak, Maksym

    2016-01-01

    Modern experiments in heavy ion collisions operate with huge data rates that can not be fully stored on the currently available storage devices. Therefore the data flow should be reduced by selecting those collisions that potentially carry the information of the physics interest. The future CBM experiment will have no simple criteria for selecting such collisions and requires the full online reconstruction of the collision topology including reconstruction of short-lived particles. In this work the KF Particle Finder package for online reconstruction and selection of short-lived particles is proposed and developed. It reconstructs more than 70 decays, covering signals from all the physics cases of the CBM experiment: strange particles, strange resonances, hypernuclei, low mass vector mesons, charmonium, and open-charm particles. The package is based on the Kalman filter method providing a full set of the particle parameters together with their errors including position, momentum, mass, energy, lifetime, etc. It shows a high quality of the reconstructed particles, high efficiencies, and high signal to background ratios. The KF Particle Finder is extremely fast for achieving the reconstruction speed of 1.5 ms per minimum-bias AuAu collision at 25 AGeV beam energy on single CPU core. It is fully vectorized and parallelized and shows a strong linear scalability on the many-core architectures of up to 80 cores. It also scales within the First Level Event Selection package on the many-core clusters up to 3200 cores. The developed KF Particle Finder package is a universal platform for short- lived particle reconstruction, physics analysis and online selection.

  3. Properties of Sequence Conservation in Upstream Regulatory and Protein Coding Sequences among Paralogs in Arabidopsis thaliana

    Science.gov (United States)

    Richardson, Dale N.; Wiehe, Thomas

    Whole genome duplication (WGD) has catalyzed the formation of new species, genes with novel functions, altered expression patterns, complexified signaling pathways and has provided organisms a level of genetic robustness. We studied the long-term evolution and interrelationships of 5’ upstream regulatory sequences (URSs), protein coding sequences (CDSs) and expression correlations (EC) of duplicated gene pairs in Arabidopsis. Three distinct methods revealed significant evolutionary conservation between paralogous URSs and were highly correlated with microarray-based expression correlation of the respective gene pairs. Positional information on exact matches between sequences unveiled the contribution of micro-chromosomal rearrangements on expression divergence. A three-way rank analysis of URS similarity, CDS divergence and EC uncovered specific gene functional biases. Transcription factor activity was associated with gene pairs exhibiting conserved URSs and divergent CDSs, whereas a broad array of metabolic enzymes was found to be associated with gene pairs showing diverged URSs but conserved CDSs.

  4. Expression profiling of cell cycle regulatory proteins in oropharyngeal carcinomas using tissue microarrays.

    Science.gov (United States)

    Ribeiro, Daniel A; Nascimento, Fabio D; Fracalossi, Ana Carolina C; Gomes, Thiago S; Oshima, Celina T F; Franco, Marcello F

    2010-01-01

    The aim of this study was to investigate the expressions of cell cycle regulatory proteins such as p53, p16, p21, and Rb in squamous cell carcinoma of the oropharynx and their relation to histological differentiation, staging of disease, and prognosis. Paraffin blocks from 21 primary tumors were obtained from archives of the Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP/EPM. Immunohistochemistry was used to detect the expression of p53, p16, p21, and Rb by means of tissue microarrays. Expression of p53, p21, p16 and Rb was not correlated with the stage of disease, histopathological grading or recurrence in squamous cell carcinoma of the oropharynx. Taken together, our results suggest that p53, p16, p21 and Rb are not reliable biomarkers for prognosis of the tumor severity or recurrence in squamous cell carcinoma of the oropharynx as depicted by tissue microarrays and immunohistochemistry.

  5. Harvard-MIT research program in short-lived radiopharmaceuticals. Progress report, March 1, 1985-February 28, 1986

    International Nuclear Information System (INIS)

    1986-03-01

    The Harvard-MIT Research Program in Short-Lived Radiopharmaceuticals was established in 1977 to foster interaction among groups working at Harvard Medical School, the Massachusetts Institute of Technology and the Massachusetts General Hospital in fields related to radiopharmaceutical chemistry. From these collaborations and building upon the special, but different, strengths of the participating individuals, laboratories and institutions, it was hoped that original approaches would be found for the design of new, clinically useful, labeled compounds. We believe that examination of the record demonstrates that this has been a fruitful alliance

  6. Harvard-MIT research program in short-lived radiopharmaceuticals. Progress report, March 1, 1983-February 29, 1984

    International Nuclear Information System (INIS)

    Adelstein, S.J.; Brownell, G.L.

    1984-02-01

    This report describes research efforts towards the achievement of a clearer understanding of the solution chemistry of technetium in order to facilitate the design of future clinical agents labeled with Tc-99m, the development of new receptor binding radiopharmaceuticals for the in vivo assessment of insulin receptors and for imaging the adrenal medulla and the brain, the examination of the utility of monoclonal antibodies and liposomes in the design of radiopharmaceuticals for diagnosis and therapy, and the synthesis of short-lived positron-emitting radiopharmaceuticals for transverse imaging of regional physiological processes

  7. Large drainages from short-lived glacial lakes in the Teskey Range, Tien Shan Mountains, Central Asia

    Science.gov (United States)

    Narama, Chiyuki; Daiyrov, Mirlan; Duishonakunov, Murataly; Tadono, Takeo; Sato, Hayato; Kääb, Andreas; Ukita, Jinro; Abdrakhmatov, Kanatbek

    2018-04-01

    Four large drainages from glacial lakes occurred during 2006-2014 in the western Teskey Range, Kyrgyzstan. These floods caused extensive damage, killing people and livestock as well as destroying property and crops. Using satellite data analysis and field surveys of this area, we find that the water volume that drained at Kashkasuu glacial lake in 2006 was 194 000 m3, at western Zyndan lake in 2008 was 437 000 m3, at Jeruy lake in 2013 was 182 000 m3, and at Karateke lake in 2014 was 123 000 m3. Due to their subsurface outlet, we refer to these short-lived glacial lakes as the tunnel-type, a type that drastically grows and drains over a few months. From spring to early summer, these lakes either appear, or in some cases, significantly expand from an existing lake (but non-stationary), and then drain during summer. Our field surveys show that the short-lived lakes form when an ice tunnel through a debris landform gets blocked. The blocking is caused either by the freezing of stored water inside the tunnel during winter or by the collapse of ice and debris around the ice tunnel. The draining then occurs through an opened ice tunnel during summer. The growth-drain cycle can repeat when the ice-tunnel closure behaves like that of typical supraglacial lakes on debris-covered glaciers. We argue here that the geomorphological characteristics under which such short-lived glacial lakes appear are (i) a debris landform containing ice (ice-cored moraine complex), (ii) a depression with water supply on a debris landform as a potential lake basin, and (iii) no visible surface outflow channel from the depression, indicating the existence of an ice tunnel. Applying these characteristics, we examine 60 depressions (> 0.01 km2) in the study region and identify here 53 of them that may become short-lived glacial lakes, with 34 of these having a potential drainage exceeding 10 m3 s-1 at peak discharge.

  8. Large drainages from short-lived glacial lakes in the Teskey Range, Tien Shan Mountains, Central Asia

    Directory of Open Access Journals (Sweden)

    C. Narama

    2018-04-01

    Full Text Available Four large drainages from glacial lakes occurred during 2006–2014 in the western Teskey Range, Kyrgyzstan. These floods caused extensive damage, killing people and livestock as well as destroying property and crops. Using satellite data analysis and field surveys of this area, we find that the water volume that drained at Kashkasuu glacial lake in 2006 was 194 000  m3, at western Zyndan lake in 2008 was 437 000 m3, at Jeruy lake in 2013 was 182 000 m3, and at Karateke lake in 2014 was 123 000 m3. Due to their subsurface outlet, we refer to these short-lived glacial lakes as the tunnel-type, a type that drastically grows and drains over a few months. From spring to early summer, these lakes either appear, or in some cases, significantly expand from an existing lake (but non-stationary, and then drain during summer. Our field surveys show that the short-lived lakes form when an ice tunnel through a debris landform gets blocked. The blocking is caused either by the freezing of stored water inside the tunnel during winter or by the collapse of ice and debris around the ice tunnel. The draining then occurs through an opened ice tunnel during summer. The growth–drain cycle can repeat when the ice-tunnel closure behaves like that of typical supraglacial lakes on debris-covered glaciers. We argue here that the geomorphological characteristics under which such short-lived glacial lakes appear are (i a debris landform containing ice (ice-cored moraine complex, (ii a depression with water supply on a debris landform as a potential lake basin, and (iii no visible surface outflow channel from the depression, indicating the existence of an ice tunnel. Applying these characteristics, we examine 60 depressions (> 0.01 km2 in the study region and identify here 53 of them that may become short-lived glacial lakes, with 34 of these having a potential drainage exceeding 10 m3 s−1 at peak discharge.

  9. The low to intermediate activity and short living waste storage facility. For a controlled management of radioactive wastes

    International Nuclear Information System (INIS)

    2006-01-01

    Sited at about 50 km of Troyes (France), the Aube facility started in 1992 and has taken over the Manche facility for the surface storage of low to intermediate and short living radioactive wastes. The Aube facility (named CSFMA) is the answer to the safe management of these wastes at the industrial scale and for 50 years onward. This brochure presents the facility specifications, the wastes stored at the center, the surface storage concept, the processing and conditioning of waste packages, and the environmental monitoring performed in the vicinity of the site. (J.S.)

  10. Impact of preindustrial to present-day changes in short-lived pollutant emissions on atmospheric composition and climate forcing

    Science.gov (United States)

    Naik, Vaishali; Horowitz, Larry W.; Fiore, Arlene M.; Ginoux, Paul; Mao, Jingqiu; Aghedo, Adetutu M.; Levy, Hiram

    2013-07-01

    We describe and evaluate atmospheric chemistry in the newly developed Geophysical Fluid Dynamics Laboratory chemistry-climate model (GFDL AM3) and apply it to investigate the net impact of preindustrial (PI) to present (PD) changes in short-lived pollutant emissions (ozone precursors, sulfur dioxide, and carbonaceous aerosols) and methane concentration on atmospheric composition and climate forcing. The inclusion of online troposphere-stratosphere interactions, gas-aerosol chemistry, and aerosol-cloud interactions (including direct and indirect aerosol radiative effects) in AM3 enables a more complete representation of interactions among short-lived species, and thus their net climate impact, than was considered in previous climate assessments. The base AM3 simulation, driven with observed sea surface temperature (SST) and sea ice cover (SIC) over the period 1981-2007, generally reproduces the observed mean magnitude, spatial distribution, and seasonal cycle of tropospheric ozone and carbon monoxide. The global mean aerosol optical depth in our base simulation is within 5% of satellite measurements over the 1982-2006 time period. We conduct a pair of simulations in which only the short-lived pollutant emissions and methane concentrations are changed from PI (1860) to PD (2000) levels (i.e., SST, SIC, greenhouse gases, and ozone-depleting substances are held at PD levels). From the PI to PD, we find that changes in short-lived pollutant emissions and methane have caused the tropospheric ozone burden to increase by 39% and the global burdens of sulfate, black carbon, and organic carbon to increase by factors of 3, 2.4, and 1.4, respectively. Tropospheric hydroxyl concentration decreases by 7%, showing that increases in OH sinks (methane, carbon monoxide, nonmethane volatile organic compounds, and sulfur dioxide) dominate over sources (ozone and nitrogen oxides) in the model. Combined changes in tropospheric ozone and aerosols cause a net negative top

  11. Application of dynamic and transition magnetic fields for determination of magnetic moments of short-lived nuclear states

    International Nuclear Information System (INIS)

    Burgov, N.A.

    1986-01-01

    Problem of measuring magnetic momenta of short-living nuclear states is discussed. Different methods for measuring magnetic momenta using interionic and transient magnetic fields were considered. Possibility for determining a value g by means of measuring correlation attenuation is investigated as well as measuring magnetic momenta by means of inclined foils. At present 2 + level magnetic momenta for many odd-odd nuclei have been determined by means of the above methods. The methods are only ones for determining magnetic momenta of nuclear levels with small lifetimes up to tenth and hundredth of shares of picoseconds

  12. The multifaceted activity of the VirF regulatory protein in the Shigella lifestyle

    Directory of Open Access Journals (Sweden)

    Maria Letizia Di Martino

    2016-09-01

    Full Text Available Shigella is a highly adapted human pathogen, mainly found in the developing world and causing a severe enteric syndrome. The highly sophisticated infectious strategy of Shigella banks on the capacity to invade the intestinal epithelial barrier and cause its inflammatory destruction. The cellular pathogenesis and clinical presentation of shigellosis are the sum of the complex action of a large number of bacterial virulence factors mainly located on a large virulence plasmid (pINV. The expression of pINV genes is controlled by multiple environmental stimuli through a regulatory cascade involving proteins and sRNAs encoded by both the pINV and the chromosome. The primary regulator of the virulence phenotype is VirF, a DNA-binding protein belonging to the AraC family of transcriptional regulators. The virF gene, located on the pINV, is expressed only within the host, mainly in response to the temperature transition occurring when the bacterium transits from the outer environment to the intestinal milieu. VirF then acts as anti-H-NS protein and directly activates the icsA and virB genes, triggering the full expression of the invasion program of Shigella. In this review we will focus on the structure of VirF, on its sophisticated regulation, and on its role as major player in the path leading from the non invasive to the invasive phenotype of Shigella. We will address also the involvement of VirF in mechanisms aimed at withstanding adverse conditions inside the host, indicating that this protein is emerging as a global regulator whose action is not limited to virulence systems. Finally, we will discuss recent observations conferring VirF the potential of a novel antibacterial target for shigellosis.

  13. Corrections for the combined effects of decay and dead time in live-timed counting of short-lived radionuclides

    International Nuclear Information System (INIS)

    Fitzgerald, R.

    2016-01-01

    Studies and calibrations of short-lived radionuclides, for example "1"5O, are of particular interest in nuclear medicine. Yet counting experiments on such species are vulnerable to an error due to the combined effect of decay and dead time. Separate decay corrections and dead-time corrections do not account for this issue. Usually counting data are decay-corrected to the start time of the count period, or else instead of correcting the count rate, the mid-time of the measurement is used as the reference time. Correction factors are derived for both those methods, considering both extending and non-extending dead time. Series approximations are derived here and the accuracy of those approximations are discussed. - Highlights: • Derived combined effects of decay and dead time. • Derived for counting systems with extending or non-extending dead times. • Derived series expansions for both midpoint and decay-to-start-time methods. • Useful for counting experiments with short-lived radionuclides. • Examples given for "1"5O, used in PET scanning.

  14. Determination of k0-factors of short-lived nuclides and application of k0-NAA to selected trace elements

    International Nuclear Information System (INIS)

    Acharya, R.; Holzbecher, J.; Chatt, A.

    2012-01-01

    As part of the standardization program of k 0 -based NAA (k 0 -NAA) methods at the Dalhousie University SLOWPOKE-2 reactor (DUSR) facility, the k 0 -factors of 15 analytically important short-lived nuclides (half-life 197 Au). The elemental standards used were prepared mostly from their primary standard solutions. The samples were irradiated in both inner and outer pneumatic sites of the DUSR facility and counted using an HPGe-detector coupled to an ORTEC’s digital gamma-ray spectrometer. The k 0 -factors determined using both inner and outer irradiation sites were found to be within ±5% with respect to either recommended or literature values in most cases. The Z-score values at 95% confidence level were found to be in the range of ±0.03–1.6. The k 0 -NAA method was applied to three different NIST standard reference materials (SRMs) and concentrations of six elements, namely Ag, F, Hf, Rb, Sc, and Se were determined using their short-lived nuclides. The concentrations of these elements were also determined by relative NAA method for comparison purposes.

  15. Production cross sections of short-lived silver radionuclides from natPd(p,xn) nuclear processes

    International Nuclear Information System (INIS)

    Khandaker, Mayeen Uddin; Kim, Kwangsoo; Kim, Guinyun

    2012-01-01

    Production cross-sections of short-lived 103 Ag, 104m Ag and 104g Ag radionuclides from proton-induced reactions on natural palladium (Pd) were measured up to 41 MeV by using a stacked-foil activation technique combined with high resolution γ-ray spectrometry. The present results are compared with the available literature values as well as theoretical data calculated by the TALYS and the ALICE-IPPE computer codes. Note that production cross-sections of the 104m Ag radionuclide from nat Pd(p,xn) processes has been measured here for the first time. Physical thick target yields for the investigated radionuclides were deduced from the respective threshold energy to 41 MeV taking into account that the total energy is absorbed in the targets. Measured data of the short-lived 103 Ag radionuclide are noteworthy due to its possible applications as a precursor for the indirect production of widely used therapeutic 103 Pd radionuclide via nat Pd(p,xn) 103 Ag → 103 Pd processes. On the other hand, the investigated 104 Ag radionuclide finds importance due to its potential use as a diagnostic and positron emission tomography (PET) imaging analogue. Above all, measured data will enrich the literature database leading to various applications in science and technology.

  16. Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer.

    Science.gov (United States)

    Shafiee, Mohamad N; Mongan, Nigel; Seedhouse, Claire; Chapman, Caroline; Deen, Suha; Abu, Jafaru; Atiomo, William

    2017-05-01

    Women with polycystic ovary syndrome have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial sterol regulatory element binding protein-1 gene expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles. A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed. The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m 2 ) and controls (28.58 ± 2.62 kg/m 2 ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m 2 ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r = 0.643, p = 0.06) and waist-hip ratio (r = 0.096, p = 0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p = 0.028 and p = 0.027, respectively). Quantitative serum sterol regulatory element

  17. Distinct forms of the β subunit of GTP-binding regulatory proteins identified by molecular cloning

    International Nuclear Information System (INIS)

    Fong, H.K.W.; Amatruda, T.T. III; Birren, B.W.; Simon, M.I.

    1987-01-01

    Two distinct β subunits of guanine nucleotide-binding regulatory proteins have been identified by cDNA cloning and are referred to as β 1 and β 1 subunits. The bovine transducin β subunit (β 1 ) has been cloned previously. The author now isolated and analyzed cDNA clones that encode the β 2 subunit from bovine adrenal, bovine brain, and a human myeloid leukemia cell line, HL-60. The 340-residue M/sub r/ 37,329 Β 2 protein is 90% identical with β 1 in predicted amino acid sequence, and it is also organized as a series of repetitive homologous segments. The major mRNA that encodes the bovine β 2 subunit is 1.7 kilobases in length. It is expressed at lower levels than β 1 subunit mRNA in all tissues examined. The β 1 and β 2 messages are expressed in cloned human cell lines. Hybridization of cDNA probes to bovine DNA showed that β 1 and β 2 are encoded by separate genes. The amino acid sequences for the bovine and human β 2 subunit are identical, as are the amino acid sequences for the bovine and human β 1 subunit. This evolutionary conservation suggests that the two β subunits have different roles in the signal transduction process

  18. KH-type splicing regulatory protein is involved in esophageal squamous cell carcinoma progression.

    Science.gov (United States)

    Fujita, Yuji; Masuda, Kiyoshi; Hamada, Junichi; Shoda, Katsutoshi; Naruto, Takuya; Hamada, Satoshi; Miyakami, Yuko; Kohmoto, Tomohiro; Watanabe, Miki; Takahashi, Rizu; Tange, Shoichiro; Saito, Masako; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Tangoku, Akira; Otsuji, Eigo; Imoto, Issei

    2017-11-24

    KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein, which is involved in several post-transcriptional aspects of RNA metabolism, including microRNA (miRNA) biogenesis. It affects distinct cell functions in different tissues and can have an impact on various pathological conditions. In the present study, we investigated the oncogenic functions of KHSRP and their underlying mechanisms in the pathogenesis of esophageal squamous cell carcinoma (ESCC). KHSRP expression levels were elevated in ESCC tumors when compared with those in non-tumorous tissues by immunohistochemistry, and cytoplasmic KHSRP overexpression was found to be an independent prognosticator for worse overall survival in a cohort of 104 patients with ESCC. KHSRP knockdown inhibited growth, migration, and invasion of ESCC cells. KHSRP knockdown also inhibited the maturation of cancer-associated miRNAs, such as miR-21, miR-130b, and miR-301, and induced the expression of their target mRNAs, such as BMP6, PDCD4, and TIMP3, resulting in the inhibition of epithelial-to-mesenchymal transition. Our findings uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC.

  19. Casein kinase 1 regulates sterol regulatory element-binding protein (SREBP) to control sterol homeostasis.

    Science.gov (United States)

    Brookheart, Rita T; Lee, Chih-Yung S; Espenshade, Peter J

    2014-01-31

    Sterol homeostasis is tightly controlled by the sterol regulatory element-binding protein (SREBP) transcription factor that is highly conserved from fungi to mammals. In fission yeast, SREBP functions in an oxygen-sensing pathway to promote adaptation to decreased oxygen supply that limits oxygen-dependent sterol synthesis. Low oxygen stimulates proteolytic cleavage of the SREBP homolog Sre1, generating the active transcription factor Sre1N that drives expression of sterol biosynthetic enzymes. In addition, low oxygen increases the stability and DNA binding activity of Sre1N. To identify additional signals controlling Sre1 activity, we conducted a genetic overexpression screen. Here, we describe our isolation and characterization of the casein kinase 1 family member Hhp2 as a novel regulator of Sre1N. Deletion of Hhp2 increases Sre1N protein stability and ergosterol levels in the presence of oxygen. Hhp2-dependent Sre1N degradation by the proteasome requires Hhp2 kinase activity, and Hhp2 binds and phosphorylates Sre1N at specific residues. Our results describe a role for casein kinase 1 as a direct regulator of sterol homeostasis. Given the role of mammalian Hhp2 homologs, casein kinase 1δ and 1ε, in regulation of the circadian clock, these findings may provide a mechanism for coordinating circadian rhythm and lipid metabolism.

  20. COMK ENCODES THE COMPETENCE TRANSCRIPTION FACTOR, THE KEY REGULATORY PROTEIN FOR COMPETENCE DEVELOPMENT IN BACILLUS-SUBTILIS

    NARCIS (Netherlands)

    VANSINDEREN, D; LUTTINGER, A; KONG, LY; DUBNAU, D; VENEMA, G; HAMOEN, L

    comK is a positive autoregulatory gene occupying a central position in the com petence-signal-transduction network. All regulatory routes identified in this network converge at the level of comK expression. The ComK protein is required for the transcriptional induction of comK and the late

  1. Crystallization and quaternary structure analysis of an Lrp-like regulatory protein from the hyperthermophile Pyrococcus furiosus

    NARCIS (Netherlands)

    Sedelnikova, S.E.; Smits, S.H.J.; Leonard, P.M.; Brinkman, A.B.; Oost, van der J.; Rafferty, J.B.

    2001-01-01

    The LrpA transcriptional regulator from Pyrococcus furiosus, a member of the leucine-responsive regulatory protein (Lrp) family, has been crystallized by the hanging-drop method of vapour diffusion using ammonium sulfate as the precipitant. The crystals belong to the tetragonal system and are in

  2. The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis

    DEFF Research Database (Denmark)

    Yde, C W; Olsen, B B; Meek, D

    2008-01-01

    25 dual-specificity phosphatase family members. In somatic cells, Wee1 is downregulated by phosphorylation and ubiquitin-mediated degradation to ensure rapid activation of CDK1 at the beginning of M phase. Here, we show that downregulation of the regulatory beta-subunit of protein kinase CK2 by RNA...

  3. Epitopes of human immunodeficiency virus regulatory proteins tat, nef, and rev are expressed in normal human tissue

    NARCIS (Netherlands)

    Parmentier, H. K.; van Wichen, D. F.; Meyling, F. H.; Goudsmit, J.; Schuurman, H. J.

    1992-01-01

    The expression of regulatory proteins tat, rev, and nef of human immunodeficiency virus type-1 (HIV-1) and tat of HIV-2 was studied in frozen sections of lymph nodes from HIV-1-infected individuals, and various tissues from uninfected persons. In HIV-1-positive lymph nodes, monoclonal antibodies to

  4. Adaptation of Tri-molecular fluorescence complementation allows assaying of regulatory Csr RNA-protein interactions in bacteria.

    Science.gov (United States)

    Gelderman, Grant; Sivakumar, Anusha; Lipp, Sarah; Contreras, Lydia

    2015-02-01

    sRNAs play a significant role in controlling and regulating cellular metabolism. One of the more interesting aspects of certain sRNAs is their ability to make global changes in the cell by interacting with regulatory proteins. In this work, we demonstrate the use of an in vivo Tri-molecular Fluorescence Complementation assay to detect and visualize the central regulatory sRNA-protein interaction of the Carbon Storage Regulatory system in E. coli. The Carbon Storage Regulator consists primarily of an RNA binding protein, CsrA, that alters the activity of mRNA targets and of an sRNA, CsrB, that modulates the activity of CsrA. We describe the construction of a fluorescence complementation system that detects the interactions between CsrB and CsrA. Additionally, we demonstrate that the intensity of the fluorescence of this system is able to detect changes in the affinity of the CsrB-CsrA interaction, as caused by mutations in the protein sequence of CsrA. While previous methods have adopted this technique to study mRNA or RNA localization, this is the first attempt to use this technique to study the sRNA-protein interaction directly in bacteria. This method presents a potentially powerful tool to study complex bacterial RNA protein interactions in vivo. © 2014 Wiley Periodicals, Inc.

  5. Nitric oxide-mediated modulation of iron regulatory proteins: implication for cellular iron homeostasis.

    Science.gov (United States)

    Kim, Sangwon; Ponka, Prem

    2002-01-01

    Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) that are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO(.), a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels and a decrease in ferritin synthesis. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO(+) (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels and a dramatic increase in ferritin synthesis. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels and an increase in ferritin synthesis in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO(+)-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

  6. Changes in regulatory molecules for lymphangiogenesis in intestinal lymphangiectasia with enteric protein loss.

    Science.gov (United States)

    Hokari, Ryota; Kitagawa, Noritake; Watanabe, Chikako; Komoto, Shunsuke; Kurihara, Chie; Okada, Yoshikiyo; Kawaguchi, Atsushi; Nagao, Shigeaki; Hibi, Toshifumi; Miura, Soichiro

    2008-07-01

    Vascular endothelial growth factor receptor 3 (VEGFR3) and LYVE-1 are specifically expressed in the endothelium of the lymphatic systems. VEGF-C, D, FOXC2, Prox 1, and SOX18 are known to play central roles in lymphatic development. We investigated the expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa of idiopathic intestinal lymphangiectasia. Biopsy samples were obtained from duodenal biopsies in patients with intestinal lymphangiectasia complicated with protein-losing from white spot lesions in which lymphangiectasia was histologically confirmed. Immunohistochemical analysis for VEGFR3 and LYVE-1 was performed. mRNA expression of VEGF-C, VEGF-D, VEGFR3, and transcription factors was determined by the quantitative reverse transcription-polymerase chain reaction method. In the control mucosa, VEGFR3 was weakly expressed on the central lymphatic vessels in the lamina propria and LYVE-1 was expressed mainly on the lymphatic vessels in the submucosa. In intestinal lymphangiectasia, VEGFR3 and LYVE-1 expression levels were increased on the mucosal surface corresponding to widely dilated lymphatic vessels, while they were decreased in the deeper mucosa. mRNA expression study showed a significant increase in the expression level of VEGFR3 in lymphangiectasia, but the expression of VEGF-C and -D mRNA was significantly suppressed compared with that in controls despite the presence of lymphangiectasia. The mRNA expression levels of FOXC2 and SOX18 were also decreased, whereas Prox 1 was not altered. There is an altered expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa in these patients.

  7. Overproduction of lactimidomycin by cross-overexpression of genes encoding Streptomyces antibiotic regulatory proteins.

    Science.gov (United States)

    Zhang, Bo; Yang, Dong; Yan, Yijun; Pan, Guohui; Xiang, Wensheng; Shen, Ben

    2016-03-01

    The glutarimide-containing polyketides represent a fascinating class of natural products that exhibit a multitude of biological activities. We have recently cloned and sequenced the biosynthetic gene clusters for three members of the glutarimide-containing polyketides-iso-migrastatin (iso-MGS) from Streptomyces platensis NRRL 18993, lactimidomycin (LTM) from Streptomyces amphibiosporus ATCC 53964, and cycloheximide (CHX) from Streptomyces sp. YIM56141. Comparative analysis of the three clusters identified mgsA and chxA, from the mgs and chx gene clusters, respectively, that were predicted to encode the PimR-like Streptomyces antibiotic regulatory proteins (SARPs) but failed to reveal any regulatory gene from the ltm gene cluster. Overexpression of mgsA or chxA in S. platensis NRRL 18993, Streptomyces sp. YIM56141 or SB11024, and a recombinant strain of Streptomyces coelicolor M145 carrying the intact mgs gene cluster has no significant effect on iso-MGS or CHX production, suggesting that MgsA or ChxA regulation may not be rate-limiting for iso-MGS and CHX production in these producers. In contrast, overexpression of mgsA or chxA in S. amphibiosporus ATCC 53964 resulted in a significant increase in LTM production, with LTM titer reaching 106 mg/L, which is five-fold higher than that of the wild-type strain. These results support MgsA and ChxA as members of the SARP family of positive regulators for the iso-MGS and CHX biosynthetic machinery and demonstrate the feasibility to improve glutarimide-containing polyketide production in Streptomyces strains by exploiting common regulators.

  8. New methodology for Ozone Depletion Potentials of short-lived compounds: n-Propyl bromide as an example

    Science.gov (United States)

    Wuebbles, Donald J.; Patten, Kenneth O.; Johnson, Matthew T.; Kotamarthi, Rao

    2001-07-01

    A number of the compounds proposed as replacements for substances controlled under the Montreal Protocol have extremely short atmospheric lifetimes, on the order of days to a few months. An important example is n-propyl bromide (also referred to as 1-bromopropane, CH2BrCH2CH3 or simplified as 1-C3H7Br or nPB). This compound, useful as a solvent, has an atmospheric lifetime of less than 20 days due to its reaction with hydroxyl. Because nPB contains bromine, any amount reaching the stratosphere has the potential to affect concentrations of stratospheric ozone. The definition of Ozone Depletion Potentials (ODP) needs to be modified for such short-lived compounds to account for the location and timing of emissions. It is not adequate to treat these chemicals as if they were uniformly emitted at all latitudes and longitudes as normally done for longer-lived gases. Thus, for short-lived compounds, policymakers will need a table of ODP values instead of the single value generally provided in past studies. This study uses the MOZART2 three-dimensional chemical-transport model in combination with studies with our less computationally expensive two-dimensional model to examine potential effects of nPB on stratospheric ozone. Multiple facets of this study examine key questions regarding the amount of bromine reaching the stratosphere following emission of nPB. Our most significant findings from this study for the purposes of short-lived replacement compound ozone effects are summarized as follows. The degradation of nPB produces a significant quantity of bromoacetone which increases the amount of bromine transported to the stratosphere due to nPB. However, much of that effect is not due to bromoacetone itself, but instead to inorganic bromine which is produced from tropospheric oxidation of nPB, bromoacetone, and other degradation products and is transported above the dry and wet deposition processes of the model. The MOZART2 nPB results indicate a minimal correction of the

  9. Prompt gamma activation analysis (PGAA) and short-lived neutron activation analysis (NAA) applied to the characterization of legacy materials

    International Nuclear Information System (INIS)

    English, G.A.; Firestone, R.B.; Perry, D.L.; Reijonen, J.P.; Ka-Ngo Leung; Garabedian, G.F.; Molnar, G.L.; Revay, Zs.

    2008-01-01

    Without quality historical records that provide the composition of legacy materials, the elemental and/or chemical characterization of such materials requires a manual analytical strategy that may expose the analyst to unknown toxicological hazards. In addition, much of the existing legacy inventory also incorporates radioactivity, and, although radiological composition may be determined by various nuclear-analytical methods, most importantly, gamma-spectroscopy, current methods of chemical characterization still require direct sample manipulation, thereby presenting special problems with broad implications for both the analyst and the environment. Alternately, prompt gamma activation analysis (PGAA) provides a 'single-shot' in-situ, non-destructive method that provides a complete assay of all major entrained elemental constituents. Additionally, neutron activation analysis (NAA) using short-lived activation products complements PGAA and is especially useful when NAA activation surpasses the PGAA in elemental sensitivity. (author)

  10. Microcomputer-based systems for automatic control of sample irradiation and chemical analysis of short-lived isotopes

    International Nuclear Information System (INIS)

    Bourret, S.C.

    1974-01-01

    Two systems resulted from the need for the study of the nuclear decay of short-lived radionuclides. Automation was required for better repeatability, speed of chemical separation after irradiation and for protection from the high radiation fields of the samples. A MCS-8 computer was used as the nucleus of the automatic sample irradiation system because the control system required an extensive multiple-sequential circuit. This approach reduced the sequential problem to a computer program. The automatic chemistry control system is a mixture of a fixed and a computer-based programmable control system. The fixed control receives the irradiated liquid sample from the reactor, extracts the liquid and disposes of the used sample container. The programmable control executes the chemistry program that the user has entered through the teletype. (U.S.)

  11. Synthesis of radiopharmaceuticals containing short-lived radionuclides: Comprehensive progress report, March 1, 1986-February 28, 1989

    International Nuclear Information System (INIS)

    Kabalka, G.W.

    1988-06-01

    The primary objective of the DOE Nuclear Medicine Program at The University of Tennessee is the creation of new methods for intoducing short-lived isotopes into agents for use in PET and SPECT. A portion of our effort is directed toward the design and in vivo quantitation of boron-containing neutron therapy agents. The uniqueness of the program is its focus on the design of new chemistry (molecular architecture) and technology as opposed to the application of known reactions to the synthesis of specific radiopharmaceuticals. The following topics are outlined in this paper: new isotope incorporation reactions utilizing nitrogen 13, oxygen 15, and carbon 11; technetium-boron complexes; boron-neutron-capture

  12. Precision mass measurements of very short-lived, neutron-rich Na isotopes using a radiofrequency spectrometer

    CERN Document Server

    Lunney, M D; Doubre, H; Henry, S; Monsanglant, C; De Saint-Simon, M; Thibault, C; Toader, C F; Borcea, C; Bollen, G

    2001-01-01

    Mass measurements of high precision have been performed on sodium isotopes out to $^{30}$Na using a new technique of radiofrequency excitation of ion trajectories in a homogeneous magnetic field. This method, especially suited to very short-lived nuclides, has allowed us to significantly reduce the uncertainty in mass of the most exotic Na isotopes: a relative error of 5x10$^{-7}$ was achieved for $^{28}$Na having a half-life of only 30.5 ms and 9x10$^{-7}$ for the weakly produced $^{30}$Na. Verifying and minimizing binding energy uncertainties in this region of the nuclear chart is important for clarification of a long standing problem concerning the strength of the $N$=20 magic shell closure. These results are the fruit of the commissioning of the new experimental program Mistral.

  13. Time-separated oscillatory fields for high-precision mass measurements on short-lived Al and Ca nuclides

    CERN Document Server

    George, Simon; Blank, B.; Blaum, K.; Breitenfeldt, M.; Hager, U.; Herfurth, F.; Herlert, A.; Kellerbauer, A.; Kluge, H.J.; Kretzschmar, M.; Lunney, D.; Savreux, R.; Schwarz, Andreas S.; Schweikhard, L.; Yazidjian, C.

    2008-01-01

    High-precision Penning trap mass measurements on the stable nuclide $^{27}$Al as well as on the short-lived radionuclides $^{26}$Al and $^{38,39}$Ca have been performed by use of radio-frequency excitation with time-separated oscillatory fields, i.e. Ramsey's method, as recently introduced for the excitation of the ion motion in a Penning trap, was applied. A comparison with the conventional method of a single continuous excitation demonstrates its advantage of up to ten times shorter measurements. The new mass values of $^{26,27}$Al clarify conflicting data in this specific mass region. In addition, the resulting mass values of the superallowed $\\beta$-emitter $^{38}$Ca as well as of the groundstate of the $\\beta$-emitter $^{26}$Al$^{m}$ confirm previous measurements and corresponding theoretical corrections of the ft-values.

  14. The utilisation of short-lived radionuclides in the assessment of formulation and in vivo disposition of drugs

    International Nuclear Information System (INIS)

    Digenis, G.A.

    1982-01-01

    The utilisation of short-lived radionuclides in the assessment of drug formulations, and the in vivo distribution of drugs is discussed. Disintegration of tablets and capsules as a function of the formulation, and gastric emptying are important. The applicability of perturbed angular correlation to the study of the dissolution of water soluble substances from solid dosages in man is shown. Examples are given to illustrate how external scintigraphy can be applied to study the tissue distribution of 18 F-haloperidol, 82 Br-bromperidol, in rat and monkey. 11 C, L-andD-phenylalanine in rats, 11 C, D-leucine in mice with human colon tumours; 13 N-nitrosoureas and 13 N-nitroso-carbamates. (U.K.)

  15. Prompt gamma activation analysis (PGAA) and short-lived neutron activation analysis (NAA) applied to the characterization of legacy materials

    International Nuclear Information System (INIS)

    Firestone, Richard B; English, G.A.; Firestone, R.B.; Perry, D.L.; Reijonen, J.P.; Leung, Ka-Ngo; Garabedian, G.F.; Molnar, G.L.; Revay, Zs.

    2008-01-01

    Without quality historical records that provide the composition of legacy materials, the elemental and/or chemical characterization of such materials requires a manual analytical strategy that may expose the analyst to unknown toxicological hazards. In addition, much of the existing legacy inventory also incorporates radioactivity, and, although radiological composition may be determined by various nuclear-analytical methods, most importantly, gamma-spectroscopy, current methods of chemical characterization still require direct sample manipulation, thereby presenting special problems with broad implications for both the analyst and the environment. Alternately, prompt gamma activation analysis (PGAA) provides a 'single-shot' in-situ, non-destructive method that provides a complete assay of all major entrained elemental constituents.1-3. Additionally, neutron activation analysis (NAA) using short-lived activation products complements PGAA and is especially useful when NAA activation surpasses the PGAA in elemental sensitivity

  16. First Isochronous Time-of-Flight Mass Measurements of Short-Lived Projectile Fragments in the ESR

    International Nuclear Information System (INIS)

    Stadlmann, J.; Geissel, H.; Hausmann, M.; Nolden, F.; Radon, T.; Schatz, H.; Scheidenberger, C.; Attallah, F.; Beckert, K.; Bosch, F.; Falch, M.; Franczak, B.; Franzke, B.; Kerscher, Th.; Klepper, O.; Kluge, H.J.; Kozhuharov, C.; Loebner, K.E.G.; Muenzenberg, G.; Novikov, Yu.N.; Steck, M.; Sun, Z.; Suemmerer, K.; Weick, H.; Wollnik, H.

    2000-01-01

    A new method for precise mass measurements of short-lived hot nuclei is presented. These nuclei were produced via projectile fragmentation, separated with the FRS and injected into the storage ring ESR being operated in the isochronous mode. The revolution time of the ions is measured with a time-of-flight detector sensitive to single particles. This new method allows access to exotic nuclei with half-lives in the microsecond region. First results from this novel method obtained with measurements on neutron-deficient fragments of a chromium primary beam with half-lives down to 50 ms are reported. A precision of deltam/m ≤ 5 · 10 -6 has been achieved

  17. A phase-imaging ion-cyclotron-resonance technique for mass measurements of short-lived nuclides

    Energy Technology Data Exchange (ETDEWEB)

    Eliseev, Sergey; Blaum, Klaus; Doerr, Andreas; Eronen, Tommi; Goncharov, Mikhail; Hoecker, Martin; Ketter, Jochen; Ramirez, Enrique Minaya; Simon, Vanessa [Max-Planck Institute for Nuclear Physics (Germany); Block, Michael [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH (Germany); Chenmarev, Stanislav; Filjanin, Pavel; Nesterenko, Dmitriy; Novikov, Yuri [Petersburg Nuclear Physics Institute (Russian Federation); Droese, Christian; Schweikhard, Lutz [Institute for Physics, Ernst-Moritz-Arndt-University (Germany)

    2014-07-01

    A novel approach to mass measurements on the sub-ppb level even for short-lived nuclides with half-lives well below one second is presented. It is based on the projection of the radial ion motion in a Penning trap onto a position sensitive detector. Compared to the presently employed time-of-flight ion-cyclotron-resonance technique, the novel approach is 25-times faster and provides a 40-fold gain in resolving power. With the new technique low-lying isomeric states with excitation energy on the 10-keV level can be separated from the ground state. Moreover, the new technique possesses a substantially higher sensitivity since just two ions are sufficient to determine the ion cyclotron frequency. A measurement of the mass difference of singly charged ions of {sup 132}Xe and {sup 131}Xe with an uncertainty of 25 eV has demonstrated the great potential of the new approach.

  18. Release studies of a thin foil tantalum target for the production of short-lived radioactive nuclei

    CERN Document Server

    Bennett, J R J; Drumm, P V; Lettry, Jacques; Nilsson, T; Catherall, R; Jonsson, O C; Ravn, H L; Simon, H

    2002-01-01

    Measurements have been made at ISOLDE, of the release curves and yields of radioactive beams of lithium, sodium and beryllium from a target constructed from 2 $\\mu$m thick foils. The release curves have been analysed by fitting to a mathematical model to determine the coefficients of diffusion of the particles in the foils and effusion through the target and ionizer at several temperatures. Through a better understanding of the rate of transport of the particles, it is possible to design targets and ionizers with improved yields. This is most important for the rare, short-lived isotopes in which there is considerable interest for physics experiments. This target has demonstrated large increases in the yields of $^{11}$Li and $^{12}$Be, in agreement with the predictions of the model. (11 refs).

  19. Thyroid cancer in the Marshallese: relative risk of short-lived internal emitters and external radiation exposure

    International Nuclear Information System (INIS)

    Lessard, E.T.; Brill, A.B.; Adams, W.H.

    1985-01-01

    In a study of the comparative effects of internal versus external irradiation of the thyroid in young people, we determined that the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times less thyroid cancer than did the same dose of radiation given externally. We determined this finding for a group of 85 Marshall Islands children, who were less than 10 years of age at the time of exposure and who were accidentially exposed to internal and external thyroid radiation at an average level of 1400 rad. The external risk coefficient ranged between 2.5 and 4.9 cancers per million person-rad-years at risk, and thus, from our computations, the internal risk coefficient for the Marshallese children was estimated to range between 1.0 and 1.4 cancers per million person-rad-years at risk. In contrast, for individual more than 10 years of age at the time of exposure, the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times more thyroid cancer than did the same dose of radiation given externally. The external risk coefficients for the older age groups were reported in the literature to be in the range of 1.0 to 3.3 cancers per million person-rad-years-at risk. We computed internal risk coefficients of 3.3 to 8.1 cancers per million person-rad-years at risk for adolescent and adult groups. This higher sensitivity to cancer induction in the exposed adolescents and adults, is different from that seen in other exposed groups. 14 refs., 8 tabs

  20. Thyroid cancer in the Marshallese: relative risk of short-lived internal emitters and external radiation exposure

    International Nuclear Information System (INIS)

    Lessard, E.T.; Brill, A.B.; Adams, W.H.

    1986-01-01

    In a study of the comparative effects of internal versus external irradiation of the thyroid in young people, we determined that the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times less thyroid cancer than did the same dose of radiation given externally. The authors determined this finding for a group of 85 Marshall Islands children, who were less than 10 years of age at the time of exposure and who were accidentally exposed to internal and external thyroid radiation at an average level of 1400 rad. The external risk coefficient ranged between 2.5 and 4.9 cancers per million person-rad-years at risk, and thus, from our computations, the internal risk coefficient for the Marshallese children was estimated to range between 1.0 and 1.4 cancers per million person-rad-years at risk. In contrast, for individuals more than 10 years of age at the time of exposure, the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times more thyroid cancer than did the same dose of radiation given externally. The external risk coefficients for the older age groups were reported in the above literature to be in the range of 1.0 to 3.3 cancers per million person-rad-years-at risk. The authors computed internal risk coefficients of 3.3 to 8.1 cancers per million person-rad-years at risk for adolescent and adult groups. This higher sensitivity to cancer induction in the exposed adolescents and adults, is different from that seen in other exposed groups. The small number of cancers in the exposed population and the influence of increased levels of TSH, nonuniform irradiation of the thyroid, and thyroid cell killing at high dose make it difficult to draw firm conclusions from these studies. 14 references, 8 tables

  1. The physiological functions of iron regulatory proteins in iron homeostasis - an update

    Directory of Open Access Journals (Sweden)

    De-Liang eZhang

    2014-06-01

    Full Text Available Iron regulatory proteins (IRPs regulate the expression of genes involved in iron metabolism by binding to RNA stem-loop structures known as iron responsive elements (IREs in target mRNAs. IRP binding inhibits the translation of mRNAs that contain an IRE in the 5’untranslated region of the transcripts, and increases the stability of mRNAs that contain IREs in the 3'untranslated region of transcripts. By these mechanisms, IRPs increase cellular iron absorption and decrease storage and export of iron to maintain an optimal intracellular iron balance. There are two members of the mammalian IRP protein family, IRP1 and IRP2, and they have redundant functions as evidenced by the embryonic lethality of the mice that completely lack IRP expression (Irp1-/-/Irp2-/- mice, which contrasts with the fact that Irp1-/- and Irp2-/- mice are viable. In addition, Irp2-/- mice also display neurodegenerative symptoms and microcytic hypochromic anemia, suggesting that IRP2 function predominates in the nervous system and erythropoietic homeostasis. Though the physiological significance of IRP1 had been unclear since Irp1-/- animals were first assessed in the early 1990’s, recent studies indicate that IRP1 plays an essential function in orchestrating the balance between erythropoiesis and bodily iron homeostasis. Additionally, Irp1-/- mice develop pulmonary hypertension, and they experience sudden death when maintained on an iron-deficient diet, indicating that IRP1 has a critical role in the pulmonary and cardiovascular systems. This review summarizes recent progress that has been made in understanding the physiological roles of IRP1 and IRP2, and further discusses the implications for clinical research on patients with idiopathic polycythemia, pulmonary hypertension and neurodegeneration.

  2. Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells

    Science.gov (United States)

    Sekerková, Gabriella; Zheng, Lili; Loomis, Patricia A.; Changyaleket, Benjarat; Whitlon, Donna S.; Mugnaini, Enrico; Bartles, James R.

    2010-01-01

    Espins are associated with the parallel actin bundles of hair cell stereocilia and are the target of mutations that cause deafness and vestibular dysfunction in mice and humans. Here, we report that espins are also concentrated in the microvilli of a number of other sensory cells: vomeronasal organ sensory neurons, solitary chemoreceptor cells, taste cells and Merkel cells. Moreover, we show that hair cells and these other sensory cells contain novel espin isoforms that arise from a different transcriptional start site and differ significantly from other espin isoforms in their complement of ligand-binding activities and their effects on actin polymerization. The novel espin isoforms of sensory cells bundled actin filaments with high affinity in a Ca2+-resistant fashion, bound actin monomer via a WASP homology 2 domain, bound profilin via a single proline-rich peptide, and caused a dramatic elongation of microvillus-type parallel actin bundles in transfected epithelial cells. In addition, the novel espin isoforms of sensory cells differed from other espin isoforms in that they potently inhibited actin polymerization in vitro, did not bind the Src homology 3 domain of the adapter protein insulin receptor substrate p53 and did not bind the acidic, signaling phospholipid phosphatidylinositol 4,5- bisphosphate. Thus, the espins constitute a family of multifunctional actin cytoskeletal regulatory proteins with the potential to differentially influence the organization, dimensions, dynamics and signaling capabilities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in a variety of mechanosensory and chemosensory cells. PMID:15190118

  3. Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression

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    Andreas Bitter

    2015-01-01

    Full Text Available Background/Aims: Sterol regulatory element-binding protein (SREBP 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.

  4. Characterization of the regulatory subunit from brain cyclic AMP-dependent protein kinase II

    International Nuclear Information System (INIS)

    Stein, J.C.

    1985-01-01

    Tryptic peptides derived from the regulatory subunits of brain and heart cAMP-dependent protein kinase II were mapped by reverse phase HPLC. At 280 nm, 15 unique peptides were found only in the heart RII digest, while 5 other peptides were obtained only from brain RII. At 210 nm, 13 brain-RII specific and 15 heart-RII specific tryptic peptides were identified and resolved. Two-dimensional mapping analyses revealed that several 37 P-labeled tryptic fragments derived from the autophosphorylation and the photoaffinity labeled cAMP-binding sites of brain RII were separate and distinct from the 32 P-peptides isolated from similarly treated heart RII. The tryptic phosphopeptide containing the autophosphorylation site in brain RII was purified. The sequence and phosphorylation site is: Arg-Ala-Ser(P)-Val-Cys-Ala-Glu-Ala-Tyr-Asn-Pro-Asp-Glu-Glu-Glu-Asp-Asp-Ala-Glu. Astrocytes and neurons exhibit high levels of the brain RII enzyme, while oligodendrocytes contain the heart RII enzyme. Monoclonal antibodies to bovine cerebral cortex RII were made and characterized. The antibodies elucidated a subtle difference between membrane-associated and cytosolic RII from cerebral cortex

  5. Prognostic value of cell cycle regulatory proteins in muscle-infiltrating bladder cancer.

    Science.gov (United States)

    Galmozzi, Fabia; Rubagotti, Alessandra; Romagnoli, Andrea; Carmignani, Giorgio; Perdelli, Luisa; Gatteschi, Beatrice; Boccardo, Francesco

    2006-12-01

    The aims of this study were to investigate the expression levels of proteins involved in cell cycle regulation in specimens of bladder cancer and to correlate them with the clinicopathological characteristics, proliferative activity and survival. Eighty-two specimens obtained from patients affected by muscle-invasive bladder cancer were evaluated immunohistochemically for p53, p21 and cyclin D1 expression, as well as for the tumour proliferation index, Ki-67. The statistical analysis included Kaplan-Meier curves with log-rank test and Cox proportional hazards models. In univariate analyses, low Ki-67 proliferation index (P = 0.045) and negative p21 immunoreactivity (P = 0.04) were associated to patient's overall survival (OS), but in multivariate models p21 did not reach statistical significance. When the combinations of the variables were assessed in two separate multivariate models that included tumour stage, grading, lymph node status, vascular invasion and perineural invasion, the combined variables p21/Ki-67 or p21/cyclin D1 expression were independent predictors for OS; in particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome. Important alterations in the cell cycle regulatory pathways occur in muscle-invasive bladder cancer and the combined use of cell cycle regulators appears to provide significant prognostic information that could be used to select the patients most suitable for multimodal therapeutic approaches.

  6. Cross-phosphorylation of bacterial serine/threonine and tyrosine protein kinases on key regulatory residues

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    Lei eShi

    2014-09-01

    Full Text Available Bacteria possess protein serine/threonine and tyrosine kinases which resemble eukaryal kinases in their capacity to phosphorylate multiple substrates. We hypothesized that the analogy might extend further, and bacterial kinases may also undergo mutual phosphorylation and activation, which is currently considered as a hallmark of eukaryal kinase networks. In order to test this hypothesis, we explored the capacity of all members of four different classes of serine/threonine and tyrosine kinases present in the firmicute model organism Bacillus subtilis to phosphorylate each other in vitro and interact with each other in vivo. The interactomics data suggested a high degree of connectivity among all types of kinases, while phosphorylation assays revealed equally wide-spread cross-phosphorylation events. Our findings suggest that the Hanks-type kinases PrkC, PrkD and YabT exhibit the highest capacity to phosphorylate other B. subtilis kinases, while the BY-kinase PtkA and the two-component-like kinases RsbW and SpoIIAB show the highest propensity to be phosphorylated by other kinases. Analysis of phosphorylated residues on several selected recipient kinases suggests that most cross-phosphorylation events concern key regulatory residues. Therefore, cross-phosphorylation events are very likely to influence the capacity of recipient kinases to phosphorylate substrates downstream in the signal transduction cascade. We therefore conclude that bacterial serine/threonine and tyrosine kinases probably engage in a network-type behavior previously described only in eukaryal cells.

  7. Coordinate Regulation of Yeast Sterol Regulatory Element-binding Protein (SREBP) and Mga2 Transcription Factors.

    Science.gov (United States)

    Burr, Risa; Stewart, Emerson V; Espenshade, Peter J

    2017-03-31

    The Mga2 and Sre1 transcription factors regulate oxygen-responsive lipid homeostasis in the fission yeast Schizosaccharomyces pombe in a manner analogous to the mammalian sterol regulatory element-binding protein (SREBP)-1 and SREBP-2 transcription factors. Mga2 and SREBP-1 regulate triacylglycerol and glycerophospholipid synthesis, whereas Sre1 and SREBP-2 regulate sterol synthesis. In mammals, a shared activation mechanism allows for coordinate regulation of SREBP-1 and SREBP-2. In contrast, distinct pathways activate fission yeast Mga2 and Sre1. Therefore, it is unclear whether and how these two related pathways are coordinated to maintain lipid balance in fission yeast. Previously, we showed that Sre1 cleavage is defective in the absence of mga2 Here, we report that this defect is due to deficient unsaturated fatty acid synthesis, resulting in aberrant membrane transport. This defect is recapitulated by treatment with the fatty acid synthase inhibitor cerulenin and is rescued by addition of exogenous unsaturated fatty acids. Furthermore, sterol synthesis inhibition blocks Mga2 pathway activation. Together, these data demonstrate that Sre1 and Mga2 are each regulated by the lipid product of the other transcription factor pathway, providing a source of coordination for these two branches of lipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia.

    Science.gov (United States)

    Reich, Arno; Spering, Christopher; Gertz, Karen; Harms, Christoph; Gerhardt, Ellen; Kronenberg, Golo; Nave, Klaus A; Schwab, Markus; Tauber, Simone C; Drinkut, Anja; Harms, Kristian; Beier, Chrstioph P; Voigt, Aaron; Göbbels, Sandra; Endres, Matthias; Schulz, Jörg B

    2011-01-05

    Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.

  9. [Glucokinase and glucokinase regulatory proteins as molecular targets for novel antidiabetic drugs].

    Science.gov (United States)

    Rubtsov, P M; Igudin, E L; Tiulpakov, A N

    2015-01-01

    The impairment of glucose homeostasis leads to hyperglycemia and type-2 diabetes mellitus. Glucokinase (GK), an enzyme that catalyzes the conversion of glucose to glucose-6-phosphate in pancreatic ß-cells, liver hepatocytes, specific hypothalamic neurons, and intestine enterocytes, is a key regulator of glucose homeostasis. In hepatocytes, GK controls the glucose uptake and glycogen synthesis and inhibits the glucose synthesis via the gluconeogenesis pathway. Glucokinase regulatory protein (GKRP) synthesized in hepatocytes acts as an endogenous GK inhibitor. During fasting, GKRP binds GK, inactivates it, and transports it into the cell nucleus, thus isolating it from the hepatocyte carbohydrate metabolism. In the beginning of the 2000s, the research was mainly focused on the development and trials of the small molecule GK activators as potential antidiabetic glucose-lowering drugs. However, the use of such substances increased the risk of hypoglycemia, and clinical studies of most synthetic GK activators are currently discontinued. Allosteric inhibitors of the GK-GKRP interaction are coming as alternative agents increasing the GK activity that can substitute GKA. In this review, we discuss the recent advances and the current state of art in the development of potential antidiabetic drugs targeted to GK as a key regulator of glucose homeostasis.

  10. Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells

    International Nuclear Information System (INIS)

    Chen Haobin; Davidson, Todd; Singleton, Steven; Garrick, Michael D.; Costa, Max

    2005-01-01

    Nickel (Ni) compounds are well-established carcinogens and are known to initiate a hypoxic response in cells via the stabilization and transactivation of hypoxia-inducible factor-1 alpha (HIF-1α). This change may be the consequence of nickel's interference with the function of several Fe(II)-dependent enzymes. In this study, the effects of soluble nickel exposure on cellular iron homeostasis were investigated. Nickel treatment decreased both mitochondrial and cytosolic aconitase (c-aconitase) activity in A549 cells. Cytosolic aconitase was converted to iron-regulatory protein 1, a form critical for the regulation of cellular iron homeostasis. The increased activity of iron-regulatory protein 1 after nickel exposure stabilized and increased transferrin receptor (Tfr) mRNA and antagonized the iron-induced ferritin light chain protein synthesis. The decrease of aconitase activity after nickel treatment reflected neither direct interference with aconitase function nor obstruction of [4Fe-4S] cluster reconstitution by nickel. Exposure of A549 cells to soluble nickel decreased total cellular iron by about 40%, a decrease that likely caused the observed decrease in aconitase activity and the increase of iron-regulatory protein 1 activity. Iron treatment reversed the effect of nickel on cytosolic aconitase and iron-regulatory protein 1. To assess the mechanism for the observed effects, human embryonic kidney (HEK) cells over expressing divalent metal transporter-1 (DMT1) were compared to A549 cells expressing only endogenous transporters for inhibition of iron uptake by nickel. The inhibition data suggest that nickel can enter via DMT1 and compete with iron for entry into the cell. This disturbance of cellular iron homeostasis by nickel may have a great impact on the ability of the cell to regulate a variety of cell functions, as well as create a state of hypoxia in cells under normal oxygen tension. These effects may be very important in how nickel exerts phenotypic

  11. Stepwise catalytic mechanism via short-lived intermediate inferred from combined QM/MM MERP and PES calculations on retaining glycosyltransferase ppGalNAcT2.

    Science.gov (United States)

    Trnka, Tomáš; Kozmon, Stanislav; Tvaroška, Igor; Koča, Jaroslav

    2015-04-01

    The glycosylation of cell surface proteins plays a crucial role in a multitude of biological processes, such as cell adhesion and recognition. To understand the process of protein glycosylation, the reaction mechanisms of the participating enzymes need to be known. However, the reaction mechanism of retaining glycosyltransferases has not yet been sufficiently explained. Here we investigated the catalytic mechanism of human isoform 2 of the retaining glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different QM/MM-based approaches, namely a potential energy surface scan in two distance difference dimensions and a minimum energy reaction path optimisation using the Nudged Elastic Band method. Potential energy scan studies often suffer from inadequate sampling of reactive processes due to a predefined scan coordinate system. At the same time, path optimisation methods enable the sampling of a virtually unlimited number of dimensions, but their results cannot be unambiguously interpreted without knowledge of the potential energy surface. By combining these methods, we have been able to eliminate the most significant sources of potential errors inherent to each of these approaches. The structural model is based on the crystal structure of human isoform 2. In the QM/MM method, the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution with internal return (SNi). The optimized transition state for the reaction is 13.8 kcal/mol higher in energy than the reactant while the energy of the product complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a proton is synchronously transferred to the leaving phosphate. The presence of a short-lived metastable oxocarbenium intermediate is likely, as indicated by the reaction energy profiles obtained using high-level density functionals.

  12. Stepwise catalytic mechanism via short-lived intermediate inferred from combined QM/MM MERP and PES calculations on retaining glycosyltransferase ppGalNAcT2.

    Directory of Open Access Journals (Sweden)

    Tomáš Trnka

    2015-04-01

    Full Text Available The glycosylation of cell surface proteins plays a crucial role in a multitude of biological processes, such as cell adhesion and recognition. To understand the process of protein glycosylation, the reaction mechanisms of the participating enzymes need to be known. However, the reaction mechanism of retaining glycosyltransferases has not yet been sufficiently explained. Here we investigated the catalytic mechanism of human isoform 2 of the retaining glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different QM/MM-based approaches, namely a potential energy surface scan in two distance difference dimensions and a minimum energy reaction path optimisation using the Nudged Elastic Band method. Potential energy scan studies often suffer from inadequate sampling of reactive processes due to a predefined scan coordinate system. At the same time, path optimisation methods enable the sampling of a virtually unlimited number of dimensions, but their results cannot be unambiguously interpreted without knowledge of the potential energy surface. By combining these methods, we have been able to eliminate the most significant sources of potential errors inherent to each of these approaches. The structural model is based on the crystal structure of human isoform 2. In the QM/MM method, the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution with internal return (SNi. The optimized transition state for the reaction is 13.8 kcal/mol higher in energy than the reactant while the energy of the product complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a proton is synchronously transferred to the leaving phosphate. The presence of a short-lived metastable oxocarbenium intermediate is likely, as indicated by the reaction energy profiles obtained using high-level density functionals.

  13. The Prognostic Impact of Some Cell Cycle Regulatory Proteins in Egyptian Breast Cancer Patients

    International Nuclear Information System (INIS)

    KAMEL, A.; Mokhtar, N.; Elshaknkiry, N.; Yassin, D.; Elnahass, Y.; Zakarya, O.; Elbasmy, A.; Elmetenawy, W.

    2006-01-01

    Purpose: The particular goal of this work is to study some cell cycle regulatory proteins and their potential impact on prognosis of breast cancer; p53, cyclin D 1 and p27 are potential effectors being the major contributors to the control of the restriction (R) check point of the cell cycle. We also aimed to evaluate different techniques used to detect these cell cycle proteins. Material and Methods: Forty five breast cancer patients as well as 10 controls with non malignant pathology were assessed for cell cycle regulators each by 2 different techniques; p53 was assessed by enzyme immunoassay (EJA) and immunohistochemistry (lHC), cyclin D1 by Western Blotting (WB) and IHC and p27 by WB and me. The cut-off was calculated as the mean of the normal controls +2 SD. Patients were followed up for 4 years and their laboratory data were correlated with different clinical parameters and with other studied regulators. Results: Eighty seven percent of cases (39/45) were positive for p53 by EIA with a range from 20 to 4300, and a mean of 464±97 I pg/mg protein. By mc, 80% (24/30) of the cases showed varying degrees of positivity. Using WB, cyclin D 1 showed high expression levels above cut off values in 69% of patients (31/45) and in 67% (20/30) by me. The corresponding positive figures for p27 were 82% (37/45) and 73% (22/30) using the two techniques, respectively. No significant association was found between p53, cyclin 01 and p27 on one side and different clinical parameters as lymph node status, tumor size or presence of distant metastases on the other side. Survival was poor in patients with high p53 expression. Cyclin D1 positive cases showed comparable survival with negative cases, whereas high p27 levels favored a longer disease free survival. Conclusions: Techniques more suitable for assessment of each of these markers in our consideration were EIA for p53, WB for cyclin D1 and IHC for p27. Moreover, this study demonstrated that these markers were relevant to the

  14. Identification of high-confidence RNA regulatory elements by combinatorial classification of RNA-protein binding sites.

    Science.gov (United States)

    Li, Yang Eric; Xiao, Mu; Shi, Binbin; Yang, Yu-Cheng T; Wang, Dong; Wang, Fei; Marcia, Marco; Lu, Zhi John

    2017-09-08

    Crosslinking immunoprecipitation sequencing (CLIP-seq) technologies have enabled researchers to characterize transcriptome-wide binding sites of RNA-binding protein (RBP) with high resolution. We apply a soft-clustering method, RBPgroup, to various CLIP-seq datasets to group together RBPs that specifically bind the same RNA sites. Such combinatorial clustering of RBPs helps interpret CLIP-seq data and suggests functional RNA regulatory elements. Furthermore, we validate two RBP-RBP interactions in cell lines. Our approach links proteins and RNA motifs known to possess similar biochemical and cellular properties and can, when used in conjunction with additional experimental data, identify high-confidence RBP groups and their associated RNA regulatory elements.

  15. Role of regulatory subunits and protein kinase inhibitor (PKI) in determining nuclear localization and activity of the catalytic subunit of protein kinase A.

    Science.gov (United States)

    Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S

    1999-03-05

    Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.

  16. 182Hf-182W age dating of a 26Al-poor inclusion and implications for the origin of short-lived radioisotopes in the early Solar System

    DEFF Research Database (Denmark)

    Holst, Jesper Christian; Olsen, Mia Bjørg Stolberg; Paton, Chad

    2013-01-01

    provide a unique window into the earliest Solar System, including the origin of short-lived radioisotopes. However, their chronology is unknown. Using the 182Hf–182W chronometer, we show that a FUN CAI recording a condensation origin from a solar gas formed coevally with canonical CAIs, but with 26Al/27Al......Refractory inclusions [calcium–aluminum-rich inclusions, (CAIs)] represent the oldest Solar System solids and provide information regarding the formation of the Sun and its protoplanetary disk. CAIs contain evidence of now extinct short-lived radioisotopes (e.g., 26Al, 41Ca, and 182Hf) synthesized...... in one or multiple stars and added to the protosolar molecular cloud before or during its collapse. Understanding how and when short-lived radioisotopes were added to the Solar System is necessary to assess their validity as chronometers and constrain the birthplace of the Sun. Whereas most CAIs formed...

  17. Involvement of the iron regulatory protein from Eisenia andrei earthworms in the regulation of cellular iron homeostasis.

    Directory of Open Access Journals (Sweden)

    Petra Procházková

    Full Text Available Iron homeostasis in cells is regulated by iron regulatory proteins (IRPs that exist in different organisms. IRPs are cytosolic proteins that bind to iron-responsive elements (IREs of the 5'- or 3'-untranslated regions (UTR of mRNAs that encode many proteins involved in iron metabolism. In this study, we have cloned and described a new regulatory protein belonging to the family of IRPs from the earthworm Eisenia andrei (EaIRP. The earthworm IRE site in 5'-UTR of ferritin mRNA most likely folds into a secondary structure that differs from the conventional IRE structures of ferritin due to the absence of a typically unpaired cytosine that participates in protein binding. Prepared recombinant EaIRP and proteins from mammalian liver extracts are able to bind both mammalian and Eisenia IRE structures of ferritin mRNA, although the affinity of the rEaIRP/Eisenia IRE structure is rather low. This result suggests the possible contribution of a conventional IRE structure. When IRP is supplemented with a Fe-S cluster, it can function as a cytosolic aconitase. Cellular cytosolic and mitochondrial fractions, as well as recombinant EaIRP, exhibit aconitase activity that can be abolished by the action of oxygen radicals. The highest expression of EaIRP was detected in parts of the digestive tract. We can assume that earthworms may possess an IRE/IRP regulatory network as a potential mechanism for maintaining cellular iron homeostasis, although the aconitase function of EaIRP is most likely more relevant.

  18. Involvement of the Iron Regulatory Protein from Eisenia andrei Earthworms in the Regulation of Cellular Iron Homeostasis

    Science.gov (United States)

    Procházková, Petra; Škanta, František; Roubalová, Radka; Šilerová, Marcela; Dvořák, Jiří; Bilej, Martin

    2014-01-01

    Iron homeostasis in cells is regulated by iron regulatory proteins (IRPs) that exist in different organisms. IRPs are cytosolic proteins that bind to iron-responsive elements (IREs) of the 5′- or 3′-untranslated regions (UTR) of mRNAs that encode many proteins involved in iron metabolism. In this study, we have cloned and described a new regulatory protein belonging to the family of IRPs from the earthworm Eisenia andrei (EaIRP). The earthworm IRE site in 5′-UTR of ferritin mRNA most likely folds into a secondary structure that differs from the conventional IRE structures of ferritin due to the absence of a typically unpaired cytosine that participates in protein binding. Prepared recombinant EaIRP and proteins from mammalian liver extracts are able to bind both mammalian and Eisenia IRE structures of ferritin mRNA, although the affinity of the rEaIRP/Eisenia IRE structure is rather low. This result suggests the possible contribution of a conventional IRE structure. When IRP is supplemented with a Fe-S cluster, it can function as a cytosolic aconitase. Cellular cytosolic and mitochondrial fractions, as well as recombinant EaIRP, exhibit aconitase activity that can be abolished by the action of oxygen radicals. The highest expression of EaIRP was detected in parts of the digestive tract. We can assume that earthworms may possess an IRE/IRP regulatory network as a potential mechanism for maintaining cellular iron homeostasis, although the aconitase function of EaIRP is most likely more relevant. PMID:25279857

  19. Inhibitors Alter the Stochasticity of Regulatory Proteins to Force Cells to Switch to the Other State in the Bistable System.

    Science.gov (United States)

    Jhang, Wun-Sin; Lo, Shih-Chiang; Yeh, Chen-Chao; Shu, Che-Chi

    2017-06-30

    The cellular behaviors under the control of genetic circuits are subject to stochastic fluctuations, or noise. The stochasticity in gene regulation, far from a nuisance, has been gradually appreciated for its unusual function in cellular activities. In this work, with Chemical Master Equation (CME), we discovered that the addition of inhibitors altered the stochasticity of regulatory proteins. For a bistable system of a mutually inhibitory network, such a change of noise led to the migration of cells in the bimodal distribution. We proposed that the consumption of regulatory protein caused by the addition of inhibitor is not the only reason for pushing cells to the specific state; the change of the intracellular stochasticity is also the main cause for the redistribution. For the level of the inhibitor capable of driving 99% of cells, if there is no consumption of regulatory protein, 88% of cells were guided to the specific state. It implied that cells were pushed, by the inhibitor, to the specific state due to the change of stochasticity.

  20. A survey of selected neutron-activation reactions with short-lived products of importance to fusion reactor technology

    International Nuclear Information System (INIS)

    Ward, R.C.; Gomes, I.C.; Smith, D.L.

    1994-11-01

    The status of the cross sections for production of short-lived radioactivities in the intense high-energy neutron fields associated with D-T fusion reactors is investigated. The main concerns relative to these very radioactive isotopes are with radiation damage to sensitive components such as superconducting magnets, the decay-heat problem and the safety of personnel during operation of the facility. The present report surveys the status of nuclear data required to assess these problems. The study is limited to a few high-priority nuclear reactions which appear to be of critical concern in this context. Other reactions of lesser concern are listed but are not treated in the present work. Among the factors that were considered in defining the relevant reactions and setting priorities are: quantities of the elemental materials in a fusion reactor, isotopic abundances within elemental categories, the decay properties of the induced radioactive byproducts, the reaction cross sections, and the nature of the decay radiations. Attention has been focused on radioactive species with half lives in the range from about 1 second to 15 minutes. Available cross-section and reaction-product decay information from the literature has been compiled and included in the report. Uncertainties have been estimated by examining several sets of experimental as well as evaluated data. Comments on the general status of data for various high-priority reactions are offered. On the basis of this investigation, it has been found that the nuclear data are in reasonably good shape for some of the most important reactions but are unacceptable for others. Based on this investigation, the reactions which should be given the greatest attention are: 16 O(n,p) 16 N, 55 Mn(n,p) 55 Cr, 57 Fe(n,p) 57 Mn, 186 W(n,2n) 185m W, and 207 Pb(n,n') 207m Pb. However, the development of fusion power would benefit from an across-the-board refinement in these nuclear data so that a more accurate quantitative

  1. Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins.

    Science.gov (United States)

    Zhang, Mingce; Robinson, Tanya O; Duverger, Alexandra; Kutsch, Olaf; Heath, Sonya L; Cron, Randy Q

    2018-03-01

    During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently represent the largest subpopulation of CD4 T cell subsets, implying relative resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture system. This suppression was mediated in part via multiple inhibitory surface proteins expressed on Tregs. Antibody blockade of CTLA-4, PD-1, and GARP on Tregs resulted in increased HIV-1 DNA integration and mRNA expression in neighboring CD4 T cells. Moreover, antibody blockade of Tregs inhibitory proteins resulted in increased HIV-1 LTR transcription in co-cultured CD4 T cells. Thus, Tregs inhibit HIV-1 infection of other CD4 T cell subsets via interactions with inhibitory cell surface proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Harvard--MIT research program in short-lived radiopharmaceuticals. Progress report, September 1, 1977--April 30, 1978. [/sup 99m/Tc, positron-emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J.; Brownell, G.L.

    1978-05-01

    Progress is reported on the following studies: chemistry studies designed to achieve a more complete understanding of the fundamental chemistry of technetium in order to facilitate the design of future radiopharmaceuticals incorporating the radionuclide /sup 99m/Tc; the development of new radiopharmaceuticals intended to improve image quality and lower radiation doses by the use of short-lived radionuclides and disease-specific agents; the development of short-lived positron-emitting radionuclides which offer advantages in transverse section imaging of regional physiological processes; and studies of the toxic effects of particulate radiation.

  3. Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.

    Science.gov (United States)

    Niles, Brad J; Clegg, Michael S; Hanna, Lynn A; Chou, Susan S; Momma, Tony Y; Hong, Heeok; Keen, Carl L

    2008-02-22

    One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

  4. Short-lived long non-coding RNAs as surrogate indicators for chemical exposure and LINC00152 and MALAT1 modulate their neighboring genes.

    Directory of Open Access Journals (Sweden)

    Hidenori Tani

    Full Text Available Whole transcriptome analyses have revealed a large number of novel long non-coding RNAs (lncRNAs. Although accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression, the detailed mechanisms of action of most lncRNAs remain unclear. We previously reported that a novel class of lncRNAs with a short half-life (t1/2 < 4 h in HeLa cells, termed short-lived non-coding transcripts (SLiTs, are closely associated with physiological and pathological functions. In this study, we focused on 26 SLiTs and nuclear-enriched abundant lncRNA, MALAT1(t1/2 of 7.6 h in HeLa cells in neural stem cells (NSCs derived from human induced pluripotent stem cells, and identified four SLiTs (TUG1, GAS5, FAM222-AS1, and SNHG15 that were affected by the following typical chemical stresses (oxidative stress, heavy metal stress and protein synthesis stress. We also found the expression levels of LINC00152 (t1/2 of 2.1 h in NSCs, MALAT1 (t1/2 of 1.8 h in NSCs, and their neighboring genes were elevated proportionally to the chemical doses. Moreover, we confirmed that the overexpression of LINC00152 or MALAT1 upregulated the expressions of their neighboring genes even in the absence of chemical stress. These results reveal that LINC00152 and MALAT1 modulate their neighboring genes, and thus provide a deeper understanding of the functions of lncRNAs.

  5. RNA-seq of the aging brain in the short-lived fish N. furzeri - conserved pathways and novel genes associated with neurogenesis.

    Science.gov (United States)

    Baumgart, Mario; Groth, Marco; Priebe, Steffen; Savino, Aurora; Testa, Giovanna; Dix, Andreas; Ripa, Roberto; Spallotta, Francesco; Gaetano, Carlo; Ori, Michela; Terzibasi Tozzini, Eva; Guthke, Reinhard; Platzer, Matthias; Cellerino, Alessandro

    2014-12-01

    The brains of teleost fish show extensive adult neurogenesis and neuronal regeneration. The patterns of gene regulation during fish brain aging are unknown. The short-lived teleost fish Nothobranchius furzeri shows markers of brain aging including reduced learning performances, gliosis, and reduced adult neurogenesis. We used RNA-seq to quantify genome-wide transcript regulation and sampled five different time points to characterize whole-genome transcript regulation during brain aging of N. furzeri. Comparison with human datasets revealed conserved up-regulation of ribosome, lysosome, and complement activation and conserved down-regulation of synapse, mitochondrion, proteasome, and spliceosome. Down-regulated genes differ in their temporal profiles: neurogenesis and extracellular matrix genes showed rapid decay, synaptic and axonal genes a progressive decay. A substantial proportion of differentially expressed genes (~40%) showed inversion of their temporal profiles in the last time point: spliceosome and proteasome showed initial down-regulation and stress-response genes initial up-regulation. Extensive regulation was detected for chromatin remodelers of the DNMT and CBX families as well as members of the polycomb complex and was mirrored by an up-regulation of the H3K27me3 epigenetic mark. Network analysis showed extensive coregulation of cell cycle/DNA synthesis genes with the uncharacterized zinc-finger protein ZNF367 as central hub. In situ hybridization showed that ZNF367 is expressed in neuronal stem cell niches of both embryonic zebrafish and adult N. furzeri. Other genes down-regulated with age, not previously associated with adult neurogenesis and with similar patterns of expression are AGR2, DNMT3A, KRCP, MEX3A, SCML4, and CBX1. CBX7, on the other hand, was up-regulated with age. © 2014 The Authors. Aging cell published by the Anatomical Society and John Wiley & Sons Ltd.

  6. Short-lived radionuclides produced on the ORNL 86-inch cyclotron and High-Flux Isotope Reactor

    International Nuclear Information System (INIS)

    Lamb, E.

    1985-01-01

    The production of short-lived radionuclides at ORNL includes the preparation of target materials, irradiation on the 86-in. cyclotron and in the High Flux Isotope Reactor (HFIR), and chemical processing to recover and purify the product radionuclides. In some cases the target materials are highly enriched stable isotopes separated on the ORNL calutrons. High-purity 123 I has been produced on the 86-in. cyclotron by irradiating an enriched target of 123 Te in a proton beam. Research on calutron separations has led to a 123 Te product with lower concentrations of 124 Te and 126 Te and, consequently to lower concentrations of the unwanted radionuclides, 124 I and 126 I, in the 123 I product. The 86-in. cyclotron accelerates a beam of protons only but is unique in providing the highest available beam current of 1500 μA at 21 MeV. This beam current produces relatively large quantities of radionuclides such as 123 I and 67 Ga

  7. The investigation of properties of short-lived SF isotopes (Z > 100 at the focal plane of VASSILISSA separator

    Directory of Open Access Journals (Sweden)

    Svirikhin Alexandr

    2013-12-01

    Full Text Available For experiments aimed at the study of spontaneous fission of transfermium nuclei improvements in the focal plane detector system of recoil separator VASSILISSA have been made. A neutron detector consisting of 54 3He-filled counters has been mounted around the focal-plane detector chamber. The reaction 48Ca + 206Pb = 2n + 252No is used for tuning the separator settings and calibrating the detector system with the spontaneous fission of the 252No. The average neutron number per 252No spontaneous fission event is as large as ν̅ = 4.06 ± 0.12. The short-lived heavy isotopes 244,246Fm, produced in the complete fusion reactions 40Ar + 206,208Pb, are investigated. The average number of neutrons per spontaneous fission of 244,246Fm from the experimental data were (ν̅ = 3.3 ± 0.3 and (ν̅ = 3.55 ± 0.50, respectively. Both values are determined for the first time.

  8. Neutron-captures in Low Mass Stars and the Early Solar System Record of Short-lived Radioactivities

    Science.gov (United States)

    Busso, Maurizio; Vescovi, Diego; Trippella, Oscar; Palmerini, Sara; Cristallo, Sergio; Piersanti, Luciano

    2018-01-01

    Noticeable improvements were recently introduced in the modelling of n-capture nucleosynthesis in the advanced evolutionary stages of giant stars (Asymptotic Giant Branch, or AGB, stars). Two such improvements are closely linked together and concern the introduction of non-parameterized, physical models for extended mixing processes and the adoption of accurate reaction rates for H- and He-burning reactions, including the one for the main neutron source 13C(α,n)16O. These improvements profited of a longstanding collaboration between stellar physicists and C. Spitaleri's team and of his seminal work both as a leader in the Nuclear Astrophysics scenario and as a talent-scout in the recruitment of young researchers in the field. We present an example of the innovative results that can be obtained thanks to the novelties introduced, by estimating the contributions from a nearby AGB star to the synthesis of short-lived (t1/2 ≤ 10 Myr) radioactive nuclei which were alive in early Solar System condensates. We find that the scenario indicating an AGB star as the source of such radioactivities, discussed for many years by researchers in this field, appears now to be no longer viable, when the mentioned improvements of AGB models and nuclear parameters are considered.

  9. Transport and deposition of nano-particles. Application to the free action of short-lived radon daughters

    International Nuclear Information System (INIS)

    Malet, J.

    1997-01-01

    Short-lived radon daughters ( 218 Po, 214 Pb, 214 Bi, and 214 Po) are important contributors to the natural average annual individual dose. The models describing the evolution of these aerosol in a house depend critically on a parameter, the 218 Po deposition velocity, which, although aerosol deposition has been extensively studied, is poorly known. A numerical and experimental study is thus carried out for a simple case: deposition in a cylindrical tube under laminar flow condition. The numerical results help understanding the difference between the transport and deposition of these radionuclides and those of non radioactive aerosols. Comparison of these well environment does not give satisfactory correlation, requiring the study of phenomena that may affect deposition. The first of these is the possible variation in the e 218 Po diffusion coefficient. Furthermore, experiments coupled with numerical calculations show that this variation could be due to 218 Po neutralization. The second phenomenon concerns the effect of the surface type, which is also shown experimentally. By modelling the neutralization and using results with a piratically smooth surface, good numerical/experimental correlations are obtained. Understanding this simple case than makes possible studying a more complex case: deposition in controlled turbulent flow. Two theories are thus experimentally validated. In addition, a 218 Po deposition velocity representative of our experimental conditions is determined. Finally, we report a feasibility study of radon daughters transport and deposition in a ventilated chamber taking into account all the involved phenomena. (author)

  10. Simulation study on the measurements of diffusion coefficients in solid materials by short-lived radiotracer beams

    CERN Document Server

    Jeong, S C; Kawakami, H

    2003-01-01

    We have examined, by a computer simulation, an on-line measurement of diffusion coefficients by using a short-lived alpha particle emitter, sup 8 Li (half life of 0.84s), as a radiotracer. The energy spectra of alpha particles emitted from diffusing sup 8 Li primarily implanted in the sample of LiAl ar simulated as a measure of the diffusion of sup 8 Li in the sample. As a possible time sequence for the measurement, a time cycle of 6s, i.e. the implantation of sup 8 Li for 1.5s and subsequent diffusion for 4.5s, is supposed. The sample is primarily set on a given temperature for the measurement. The time-dependent yields of alpha particles during the time cycle reveal the possibility to measure the diffusion coefficient with an accuracy of 10% if larger than 1 x 10 sup - sup 9 cm sup 2 /s, by the comparison with the experimental spectra measured at the temperature, i.e. at a certain diffusion coefficient. (author)

  11. Impact of short-lived non-CO2 mitigation on carbon budgets for stabilizing global warming

    International Nuclear Information System (INIS)

    Rogelj, Joeri; Riahi, Keywan; Meinshausen, Malte; Schaeffer, Michiel; Knutti, Reto

    2015-01-01

    Limiting global warming to any level requires limiting the total amount of CO 2 emissions, or staying within a CO 2 budget. Here we assess how emissions from short-lived non-CO 2 species like methane, hydrofluorocarbons (HFCs), black-carbon, and sulphates influence these CO 2 budgets. Our default case, which assumes mitigation in all sectors and of all gases, results in a CO 2 budget between 2011–2100 of 340 PgC for a >66% chance of staying below 2°C, consistent with the assessment of the Fifth Assessment Report of the Intergovernmental Panel on Climate Change. Extreme variations of air-pollutant emissions from black-carbon and sulphates influence this budget by about ±5%. In the hypothetical case of no methane or HFCs mitigation—which is unlikely when CO 2 is stringently reduced—the budgets would be much smaller (40% or up to 60%, respectively). However, assuming very stringent CH 4 mitigation as a sensitivity case, CO 2 budgets could be 25% higher. A limit on cumulative CO 2 emissions remains critical for temperature targets. Even a 25% higher CO 2 budget still means peaking global emissions in the next two decades, and achieving net zero CO 2 emissions during the third quarter of the 21st century. The leverage we have to affect the CO 2 budget by targeting non-CO 2 diminishes strongly along with CO 2 mitigation, because these are partly linked through economic and technological factors. (letter)

  12. Proceedings of the specialists' meeting on 'nuclear spectroscopy and condensed matter physics using short-lived nuclei'

    International Nuclear Information System (INIS)

    Kobayashi, Yoshio; Shibata, Michihiro; Ohkubo, Yoshitaka

    2016-02-01

    The research reactor at Research Reactor Institute, Kyoto University is a very useful neutron generator, providing us neutron-rich unstable nuclei by bombarding nuclei with those neutrons. The produced unstable nuclei exhibit aspects distinct from those of stable ones. Nuclear structure studies on a variety of excited states reflecting dynamic nuclear properties are one of fascinating research subjects of physics. On the other hand, some radioactive nuclei can be used as useful probes for understanding interesting properties of condensed matters through studies of hyperfine interactions of static nuclear electromagnetic moments with extranuclear fields. Concerning these two research fields and related areas, the 2nd symposium under the title of 'Nuclear Spectroscopy and Condensed Matter Physics Using Short-lived Nuclei' was held at the Institute for two days on November 4 and 5 in 2015. We are pleased that many hot discussions were made. The talks were given on the followings: 1) Nuclear spectroscopic experiments, 2) TDPAC (time-differential perturbed angular correlation), 3) β-NMR (nuclear magnetic resonance), 4) Moessbauer spectroscopy, 5) muon, etc. This issue is the collection of 17 papers presented at the entitled meeting. The 6 of the presented papers are indexed individually. (J.P.N.)

  13. Comparison of short-lived medical isotopes activation by laser thin target induced protons and conventional cyclotron proton beams

    Science.gov (United States)

    Murray, Joseph; Dudnikova, Galina; Liu, Tung-Chang; Papadopoulos, Dennis; Sagdeev, Roald; Su, J. J.; UMD MicroPET Team

    2014-10-01

    Production diagnostic or therapeutic nuclear medicines are either by nuclear reactors or by ion accelerators. In general, diagnostic nuclear radioisotopes have a very short half-life varying from tens of minutes for PET tracers and few hours for SPECT tracers. Thus supplies of PET and SPECT radiotracers are limited by regional production facilities. For example 18F-fluorodeoxyglucose (FDG) is the most desired tracer for positron emission tomography because its 110 minutes half-life is sufficient long for transport from production facilities to nearby users. From nuclear activation to completing image taking must be done within 4 hours. Decentralized production of diagnostic radioisotopes will be idea to make high specific activity radiotracers available to researches and clinicians. 11 C, 13 N, 15 O and 18 F can be produced in the energy range from 10-20 MeV by protons. Protons of energies up to tens of MeV generated by intense laser interacting with hydrogen containing targets have been demonstrated by many groups in the past decade. We use 2D PIC code for proton acceleration, Geant4 Monte Carlo code for nuclei activation to compare the yields and specific activities of short-lived isotopes produced by cyclotron proton beams and laser driven protons.

  14. Measurement method of activation cross-sections of reactions producing short-lived nuclei with 14 MeV neutrons

    CERN Document Server

    Kawade, K; Kasugai, Y; Shibata, M; Iida, T; Takahashi, A; Fukahori, T

    2003-01-01

    We describe a method for obtaining reliable activation cross-sections in the neutron energy range between 13.4 and 14.9 MeV for the reactions producing short-lived nuclei with half-lives between 0.5 and 30 min. We noted neutron irradiation fields and measured induced activities, including (1) the contribution of scattered low-energy neutrons, (2) the fluctuation of the neutron fluence rate during the irradiation, (3) the true coincidence sum effect, (4) the random coincidence sum effect, (5) the deviation in the measuring position due to finite sample thickness, (6) the self-absorption of the gamma-ray in the sample material and (7) the interference reactions producing the same radionuclides or the ones emitting the gamma-ray with the same energy of interest. The cross-sections can be obtained within a total error of 3.6%, when good counting statistics are achieved, including an error of 3.0% for the standard cross-section of sup 2 sup 7 Al (n, alpha) sup 2 sup 4 Na. We propose here simple methods for measuri...

  15. Investigation of short-lived neutron-rich palladium and silver isotopes after fast chemical separation from fission fragments

    International Nuclear Information System (INIS)

    Bruechle, W.

    1976-01-01

    In this paper, chemical separation processes are described permitting fast and neat isolation of short-lived palladium and silver nuclides from fusion product mixtures. The process for palladium is based on the stability of palladium diethyldithiophosphate. From fission products of the reactions 238 U(n,f) and 249 Cf(nth,f), the following palladium niclides could be studied for the first time by gamma spectroscopy: 1.66 min 113 Pd, 2.45 min 114 Pd, 29 sec sup(115a)Pd, 54 sec sup(115b)Pd, 12.5 sec 116 Pd. 113 Pd could also be indentified according to the reaction 116 Cd(n,α) 113 Pd. The separation of silver is based on the fast isotopic exchange on AgCl. With this process, the following nuclides have been separated from fission product mixtures and studied by gamma spectroscopy: 70 sec sup(113m)Ag, 5.0 sec 114 Ag, 19.2 sec sup(115m)Ag, 2.65 min sup(116g)Ag, 10.5 sec sup(116m)Ag, 1.3 min sup(117g)Ag, 6.0 sec sup(117m)Ag, 4.0 sec 118 Ag. (orig./WL) [de

  16. SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.

    Science.gov (United States)

    Kirm, Benjamin; Magdevska, Vasilka; Tome, Miha; Horvat, Marinka; Karničar, Katarina; Petek, Marko; Vidmar, Robert; Baebler, Spela; Jamnik, Polona; Fujs, Štefan; Horvat, Jaka; Fonovič, Marko; Turk, Boris; Gruden, Kristina; Petković, Hrvoje; Kosec, Gregor

    2013-12-17

    Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bld

  17. Finding trans-regulatory genes and protein complexes modulating meiotic recombination hotspots of human, mouse and yeast.

    Science.gov (United States)

    Wu, Min; Kwoh, Chee-Keong; Li, Xiaoli; Zheng, Jie

    2014-09-11

    The regulatory mechanism of recombination is one of the most fundamental problems in genomics, with wide applications in genome wide association studies (GWAS), birth-defect diseases, molecular evolution, cancer research, etc. Recombination events cluster into short genomic regions called "recombination hotspots". Recently, a zinc finger protein PRDM9 was reported to regulate recombination hotspots in human and mouse genomes. In addition, a 13-mer motif contained in the binding sites of PRDM9 is found to be enriched in human hotspots. However, this 13-mer motif only covers a fraction of hotspots, indicating that PRDM9 is not the only regulator of recombination hotspots. Therefore, the challenge of discovering other regulators of recombination hotspots becomes significant. Furthermore, recombination is a complex process. Hence, multiple proteins acting as machinery, rather than individual proteins, are more likely to carry out this process in a precise and stable manner. Therefore, the extension of the prediction of individual trans-regulators to protein complexes is also highly desired. In this paper, we introduce a pipeline to identify genes and protein complexes associated with recombination hotspots. First, we prioritize proteins associated with hotspots based on their preference of binding to hotspots and coldspots. Second, using the above identified genes as seeds, we apply the Random Walk with Restart algorithm (RWR) to propagate their influences to other proteins in protein-protein interaction (PPI) networks. Hence, many proteins without DNA-binding information will also be assigned a score to implicate their roles in recombination hotspots. Third, we construct sub-PPI networks induced by top genes ranked by RWR for various species (e.g., yeast, human and mouse) and detect protein complexes in those sub-PPI networks. The GO term analysis show that our prioritizing methods and the RWR algorithm are capable of identifying novel genes associated with

  18. Partitioning of genetic variation between regulatory and coding gene segments: the predominance of software variation in genes encoding introvert proteins.

    Science.gov (United States)

    Mitchison, A

    1997-01-01

    In considering genetic variation in eukaryotes, a fundamental distinction can be made between variation in regulatory (software) and coding (hardware) gene segments. For quantitative traits the bulk of variation, particularly that near the population mean, appears to reside in regulatory segments. The main exceptions to this rule concern proteins which handle extrinsic substances, here termed extrovert proteins. The immune system includes an unusually large proportion of this exceptional category, but even so its chief source of variation may well be polymorphism in regulatory gene segments. The main evidence for this view emerges from genome scanning for quantitative trait loci (QTL), which in the case of the immune system points to a major contribution of pro-inflammatory cytokine genes. Further support comes from sequencing of major histocompatibility complex (Mhc) class II promoters, where a high level of polymorphism has been detected. These Mhc promoters appear to act, in part at least, by gating the back-signal from T cells into antigen-presenting cells. Both these forms of polymorphism are likely to be sustained by the need for flexibility in the immune response. Future work on promoter polymorphism is likely to benefit from the input from genome informatics.

  19. HOXA1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on HOXA1 targets.

    Science.gov (United States)

    De Kumar, Bony; Parker, Hugo J; Paulson, Ariel; Parrish, Mark E; Pushel, Irina; Singh, Narendra Pratap; Zhang, Ying; Slaughter, Brian D; Unruh, Jay R; Florens, Laurence; Zeitlinger, Julia; Krumlauf, Robb

    2017-09-01

    Hoxa1 has diverse functional roles in differentiation and development. We identify and characterize properties of regions bound by HOXA1 on a genome-wide basis in differentiating mouse ES cells. HOXA1-bound regions are enriched for clusters of consensus binding motifs for HOX, PBX, and MEIS, and many display co-occupancy of PBX and MEIS. PBX and MEIS are members of the TALE family and genome-wide analysis of multiple TALE members (PBX, MEIS, TGIF, PREP1, and PREP2) shows that nearly all HOXA1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins define distinct classes of HOXA1 targets, which may create functional diversity. Transgenic reporter assays in zebrafish confirm enhancer activities for many HOXA1-bound regions and the importance of HOX-PBX and TGIF motifs for their regulation. Proteomic analyses show that HOXA1 physically interacts on chromatin with PBX, MEIS, and PREP family members, but not with TGIF, suggesting that TGIF may have an independent input into HOXA1-bound regions. Therefore, TALE proteins appear to represent a wide repertoire of HOX cofactors, which may coregulate enhancers through distinct mechanisms. We also discover extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes, indicating that the specificity of HOXA1 during development may be regulated though a complex cross-regulatory network of HOXA1 and TALE proteins. This study provides new insight into a regulatory network involving combinatorial interactions between HOXA1 and TALE proteins. © 2017 De Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  20. Cyclotron production of molecules labelled with short-lived radioisotopes β+ emitters (15O, 13N, 11C) and their clinical uses

    International Nuclear Information System (INIS)

    Bougharouat, B.

    1981-01-01

    Clinical use of three short-lived radioisotopes: 15 O, 13 N and 11 C is studied on two complementary aspects. A production and purification system is realized; detection instruments in medical use are studied. The production of labelled molecules with the three radiotracers 15 O, 13 N, 11 C from the target bombardment with charged and accelerated particles was studied [fr

  1. A crossed-beam experiment on intramultiplet mixing collisions with short-lived Ne** {(2p)5(3p)} atoms

    NARCIS (Netherlands)

    Manders, M.P.I.; Ruyten, W.M.J.; van de Beucken, F..J.H.M.; Driessen, J.P.J.; Veugelers, W.J.T.; Kramer, P.H.; Vredenbregt, E.J.D.; van Hoek, W.B.M.; Sandker, G.J.; Beijerinck, H.C.W.; Verhaar, B.J.

    1988-01-01

    We describe the design, operation, and calibration of a crossed-beam experiment for the study of intramultiplet mixing collisions of short-lived electronically excited Ne{(2p)5(3p)}≡{α} atoms with ground-state atoms/molecules. The excellent performance of almost 1 kHz/Å2 (number of counts per unit

  2. Heat shock protein 70 inhibits shrinkage-induced programmed cell death via mechanisms independent of effects on cell volume-regulatory membrane transport proteins

    DEFF Research Database (Denmark)

    Nylandsted, J; Jäättelä, M; Hoffmann, E K

    2004-01-01

    Cell shrinkage is a ubiquitous feature of programmed cell death (PCD), but whether it is an obligatory signalling event in PCD is unclear. Heat shock protein 70 (Hsp70) potently counteracts PCD in many cells, by mechanisms that are incompletely understood. In the present investigation, we found...... that severe hypertonic stress greatly diminished the viability of murine fibrosarcoma cells (WEHI-902) and immortalized murine embryonic fibroblasts (iMEFs). This effect was attenuated markedly by Hsp70 over-expression. To determine whether the protective effect of Hsp70 was mediated via an effect on volume...... regulatory ion transport, we compared regulatory volume decrease (RVD) and increase (RVI) in control WEHI-902 cells and after increasing Hsp70 levels by heat shock or over-expression (WEHI-912). Hsp70 levels affected neither RVD, RVI nor the relative contributions of the Na(+)/H(+)-exchanger (NHE1) and Na...

  3. The effects of short-lived radionuclides and porosity on the early thermo-mechanical evolution of planetesimals

    Science.gov (United States)

    Lichtenberg, Tim; Golabek, Gregor J.; Gerya, Taras V.; Meyer, Michael R.

    2016-08-01

    The thermal history and internal structure of chondritic planetesimals, assembled before the giant impact phase of chaotic growth, potentially yield important implications for the final composition and evolution of terrestrial planets. These parameters critically depend on the internal balance of heating versus cooling, which is mostly determined by the presence of short-lived radionuclides (SLRs), such as 26Al and 60Fe, as well as the heat conductivity of the material. The heating by SLRs depends on their initial abundances, the formation time of the planetesimal and its size. It has been argued that the cooling history is determined by the porosity of the granular material, which undergoes dramatic changes via compaction processes and tends to decrease with time. In this study we assess the influence of these parameters on the thermo-mechanical evolution of young planetesimals with both 2D and 3D simulations. Using the code family I2ELVIS/I3ELVIS we have run numerous 2D and 3D numerical finite-difference fluid dynamic models with varying planetesimal radius, formation time and initial porosity. Our results indicate that powdery materials lowered the threshold for melting and convection in planetesimals, depending on the amount of SLRs present. A subset of planetesimals retained a powdery surface layer which lowered the thermal conductivity and hindered cooling. The effect of initial porosity was small, however, compared to those of planetesimal size and formation time, which dominated the thermo-mechanical evolution and were the primary factors for the onset of melting and differentiation. We comment on the implications of this work concerning the structure and evolution of these planetesimals, as well as their behavior as possible building blocks of terrestrial planets.

  4. Inactivation of Candida glabrata by a humid DC argon discharge afterglow: dominant contributions of short-lived aqueous active species

    International Nuclear Information System (INIS)

    Xiong, Qing; Liu, Hongbin; Xu, Le; Wang, Xia; Zhu, Qunlin; Lu, Weiping; Chen, Qiang; Zeng, Xue; Yi, Ping

    2017-01-01

    Plasma medicine applications are currently attracting significant interest all over the world. Bactericidal treatments of Candida glabrata cultured in saline suspension are performed in this study by a room-temperature reactive afterglow of a DC-driven argon discharge. Water vapor was added to the discharge to study the inactivation contributions of reactive hydrolytic species including OH and H 2 O 2 transporting along the gas flow to the treated solutions. The inactivation results indicate that the dominant roles in the bactericidal treatments are played by the short-lived aqueous active species, but not the stable species like H 2 O 2aq (aq indicates an aqueous species). Further analysis shows that the ·OH aq radicals play an important role in the inactivation process. The ·OH aq radicals in the suspension are mostly produced from the direct dissolution of the OH species in the reactive afterglow. With the increase of added water vapor content, the ·OH aq production increases and enhances the inactivation efficiency of C. glabrata . Furthermore, it is found that the ambient air diffusion shows essential effects on the bactericidal activity of the remote humid argon discharge. Higher bactericidal effects can be obtained in open-space treatments compared to in a controlled Ar + H 2 O gas atmosphere. Key active air-byproduct species are believed to be generated in the suspension during the treatments and contributing to the inactivation process. Based on chemical analysis, the peroxynitrous acid ONOOH aq is considered as the key antimicrobial air-byproduct species. These results indicate the important dependence of plasma biomedical effects on the processing environment, which finally relates to the critical contributions of the key reactive species formed therein. (paper)

  5. Study on the risk of late damage in humans after incorporation of the short-lived alpha emitter Ra-224

    International Nuclear Information System (INIS)

    Wick, R.R.; Nekolla, E.A.; Kellerer, A.M.; Goessner, W.

    2003-01-01

    An epidemiological study has been carried out at the GSF - National Research Center for Environment and Health - between 1948 and 1975, on 1460 ankylosing spondylitis (AS) patients. The aim of the study was to ascertain the late health effects suffered by these patients who had received repeated intravenous injections of the short lived α-emitter 224 Ra. These patients have been followed together with a control group of 1323 ankylosing spondylitis patients not treated with radioactive drugs and/or X-rays. Causes of death have been ascertained for 842 exposed patients and 861 controls by the end of 2002. In the exposed group there has been a total of 219 malignant diseases and 206 cases among the controls. In particular, we observed 15 cases of leukaemia in the exposure group and 8 cases of leukaemia in the control group. Further subclassification of the leukaemias demonstrated a high increase of myeloid leukaemia in the exposure group (9 cases obs. vs. 2.5 cases exp.), and out of these especially the acute myeloid leukaemias (6 cases observed vs. 1.6 expected), whereas in the control group the observed cases are within the expected range (3 myeloid leukaemias vs. 2.6 cases). Out of these 6 cases of myeloid leukaemia, 3 cases have been observed at doses comparable to those of the currently applied 224 Ra treatment with the preparation SpondylAT registered , in one case the 224 Ra-dose was the 0.6fold, in another case 1.6fold, whereas in one case the total dose could not be verified exactly. The enhanced leukaemia incidence in our exposed group is in line with results from animal experiments in mice having been injected with bone seeking α-emitters given at low dose rates. (orig.) [de

  6. Inactivation of Candida glabrata by a humid DC argon discharge afterglow: dominant contributions of short-lived aqueous active species

    Science.gov (United States)

    Xiong, Qing; Liu, Hongbin; Lu, Weiping; Chen, Qiang; Xu, Le; Wang, Xia; Zhu, Qunlin; Zeng, Xue; Yi, Ping

    2017-05-01

    Plasma medicine applications are currently attracting significant interest all over the world. Bactericidal treatments of Candida glabrata cultured in saline suspension are performed in this study by a room-temperature reactive afterglow of a DC-driven argon discharge. Water vapor was added to the discharge to study the inactivation contributions of reactive hydrolytic species including OH and H2O2 transporting along the gas flow to the treated solutions. The inactivation results indicate that the dominant roles in the bactericidal treatments are played by the short-lived aqueous active species, but not the stable species like H2O2aq (aq indicates an aqueous species). Further analysis shows that the ·OHaq radicals play an important role in the inactivation process. The ·OHaq radicals in the suspension are mostly produced from the direct dissolution of the OH species in the reactive afterglow. With the increase of added water vapor content, the ·OHaq production increases and enhances the inactivation efficiency of C. glabrata. Furthermore, it is found that the ambient air diffusion shows essential effects on the bactericidal activity of the remote humid argon discharge. Higher bactericidal effects can be obtained in open-space treatments compared to in a controlled Ar + H2O gas atmosphere. Key active air-byproduct species are believed to be generated in the suspension during the treatments and contributing to the inactivation process. Based on chemical analysis, the peroxynitrous acid ONOOHaq is considered as the key antimicrobial air-byproduct species. These results indicate the important dependence of plasma biomedical effects on the processing environment, which finally relates to the critical contributions of the key reactive species formed therein.

  7. Crystallization and preliminary X-ray diffraction analysis of iron regulatory protein 1 in complex with ferritin IRE RNA

    International Nuclear Information System (INIS)

    Selezneva, Anna I.; Cavigiolio, Giorgio; Theil, Elizabeth C.; Walden, William E.; Volz, Karl

    2006-01-01

    The iron regulatory protein IRP1 has been crystallized in a complex with ferritin IRE RNA and a complete data set has been collected to 2.8 Å resolution. Iron regulatory protein 1 (IRP1) is a bifunctional protein with activity as an RNA-binding protein or as a cytoplasmic aconitase. Interconversion of IRP1 between these mutually exclusive states is central to cellular iron regulation and is accomplished through iron-responsive assembly and disassembly of a [4Fe–4S] cluster. When in its apo form, IRP1 binds to iron responsive elements (IREs) found in mRNAs encoding proteins of iron storage and transport and either prevents translation or degradation of the bound mRNA. Excess cellular iron stimulates the assembly of a [4Fe–4S] cluster in IRP1, inhibiting its IRE-binding ability and converting it to an aconitase. The three-dimensional structure of IRP1 in its different active forms will provide details of the interconversion process and clarify the selective recognition of mRNA, Fe–S sites and catalytic activity. To this end, the apo form of IRP1 bound to a ferritin IRE was crystallized. Crystals belong to the monoclinic space group P2 1 , with unit-cell parameters a = 109.6, b = 80.9, c = 142.9 Å, β = 92.0°. Native data sets have been collected from several crystals with resolution extending to 2.8 Å and the structure has been solved by molecular replacement

  8. Structural and regulatory diversity shape HLA-C protein expression levels

    DEFF Research Database (Denmark)

    Kaur, Gurman; Gras, Stephanie; Mobbs, Jesse I

    2017-01-01

    expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules. Together with a phylogenetic analysis, these results highlight the diversity and long-term balancing selection of regulatory factors...

  9. Tumorigenic Properties of Iron Regulatory Protein 2 (IRP2) Mediated by Its Specific 73-Amino Acids Insert

    OpenAIRE

    Maffettone, Carmen; Chen, Guohua; Drozdov, Ignat; Ouzounis, Christos; Pantopoulos, Kostas

    2010-01-01

    Iron regulatory proteins, IRP1 and IRP2, bind to mRNAs harboring iron responsive elements and control their expression. IRPs may also perform additional functions. Thus, IRP1 exhibited apparent tumor suppressor properties in a tumor xenograft model. Here we examined the effects of IRP2 in a similar setting. Human H1299 lung cancer cells or clones engineered for tetracycline-inducible expression of wild type IRP2, or the deletion mutant IRP2(Delta73) (lacking a specific insert of 73 amino acid...

  10. Novel RNA-binding properties of the MTG chromatin regulatory proteins

    NARCIS (Netherlands)

    S. Rossetti (Stefano); L. van Unen (Leontine); N. Sacchi; A.T. Hoogeveen (Andre)

    2008-01-01

    textabstractBackground: The myeloid translocation gene (MTG) proteins are non-DNA-binding transcriptional regulators capable of interacting with chromatin modifying proteins. As a consequence of leukemia-associated chromosomal translocations, two of the MTG proteins, MTG8 and MTG16, are fused to the

  11. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 is Expressed inOsteoblasts and Regulated by PTH

    International Nuclear Information System (INIS)

    Sharma, Sonali; Mahalingam, Chandrika D.; Das, Varsha; Jamal, Shazia; Levi, Edi; Rishi, Arun K.; Datta, Nabanita S.

    2013-01-01

    Highlights: •CARP-1 is identified for the first time in bone cells. •PTH downregulates CARP-1 expression in differentiated osteoblasts. •PTH displaces CARP-1 from nucleus to the cytoplasm in differentiated osteoblasts. •Downregulation of CARP-1 by PTH involves PKA, PKC and P-p38 MAPK pathways. -- Abstract: Bone mass is dependent on osteoblast proliferation, differentiation and life-span of osteoblasts. Parathyroid hormone (PTH) controls osteoblast cell cycle regulatory proteins and suppresses mature osteoblasts apoptosis. Intermittent administration of PTH increases bone mass but the mechanism of action are complex and incompletely understood. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 (aka CCAR1) is a novel transducer of signaling by diverse agents including cell growth and differentiation factors. To gain further insight into the molecular mechanism, we investigated involvement of CARP-1 in PTH signaling in osteoblasts. Immunostaining studies revealed presence of CARP-1 in osteoblasts and osteocytes, while a minimal to absent levels were noted in the chondrocytes of femora from 10 to 12-week old mice. Treatment of 7-day differentiated MC3T3-E1 clone-4 (MC-4) mouse osteoblastic cells and primary calvarial osteoblasts with PTH for 30 min to 5 h followed by Western blot analysis showed 2- to 3-fold down-regulation of CARP-1 protein expression in a dose- and time-dependent manner compared to the respective vehicle treated control cells. H-89, a Protein Kinase A (PKA) inhibitor, suppressed PTH action on CARP-1 protein expression indicating PKA-dependent mechanism. PMA, a Protein Kinase C (PKC) agonist, mimicked PTH action, and the PKC inhibitor, GF109203X, partially blocked PTH-dependent downregulation of CARP-1, implying involvement of PKC. U0126, a Mitogen-Activated Protein Kinase (MAPK) Kinase (MEK) inhibitor, failed to interfere with CARP-1 suppression by PTH. In contrast, SB203580, p38 inhibitor, attenuated PTH down-regulation of CARP-1

  12. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 is Expressed inOsteoblasts and Regulated by PTH

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Sonali; Mahalingam, Chandrika D.; Das, Varsha [Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Jamal, Shazia [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Levi, Edi [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Rishi, Arun K. [Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States); VA Medical Center, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Datta, Nabanita S., E-mail: ndatta@med.wayne.edu [Department of Internal Medicine/Endocrinology, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States); Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

    2013-07-12

    Highlights: •CARP-1 is identified for the first time in bone cells. •PTH downregulates CARP-1 expression in differentiated osteoblasts. •PTH displaces CARP-1 from nucleus to the cytoplasm in differentiated osteoblasts. •Downregulation of CARP-1 by PTH involves PKA, PKC and P-p38 MAPK pathways. -- Abstract: Bone mass is dependent on osteoblast proliferation, differentiation and life-span of osteoblasts. Parathyroid hormone (PTH) controls osteoblast cell cycle regulatory proteins and suppresses mature osteoblasts apoptosis. Intermittent administration of PTH increases bone mass but the mechanism of action are complex and incompletely understood. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1 (aka CCAR1) is a novel transducer of signaling by diverse agents including cell growth and differentiation factors. To gain further insight into the molecular mechanism, we investigated involvement of CARP-1 in PTH signaling in osteoblasts. Immunostaining studies revealed presence of CARP-1 in osteoblasts and osteocytes, while a minimal to absent levels were noted in the chondrocytes of femora from 10 to 12-week old mice. Treatment of 7-day differentiated MC3T3-E1 clone-4 (MC-4) mouse osteoblastic cells and primary calvarial osteoblasts with PTH for 30 min to 5 h followed by Western blot analysis showed 2- to 3-fold down-regulation of CARP-1 protein expression in a dose- and time-dependent manner compared to the respective vehicle treated control cells. H-89, a Protein Kinase A (PKA) inhibitor, suppressed PTH action on CARP-1 protein expression indicating PKA-dependent mechanism. PMA, a Protein Kinase C (PKC) agonist, mimicked PTH action, and the PKC inhibitor, GF109203X, partially blocked PTH-dependent downregulation of CARP-1, implying involvement of PKC. U0126, a Mitogen-Activated Protein Kinase (MAPK) Kinase (MEK) inhibitor, failed to interfere with CARP-1 suppression by PTH. In contrast, SB203580, p38 inhibitor, attenuated PTH down-regulation of CARP-1

  13. The partnership experience on the disposal of low- and intermediate-level short-lived waste in Belgium

    International Nuclear Information System (INIS)

    Preter, P. de; Cool, W.; Hooft, E.; Waffelaert, A.; Blommaert, J.; Draulans, J.

    2008-01-01

    With the governmental decision of January 16, 1998, the long-term storage option for the low- and intermediate-level short-lived waste (category A waste) was abandoned and ONDRAF/NIRAS was given the mission to further examine the options of deep and surface disposal, in order to prepare a federal decision on the technical option to be developed. ONDRAF/NIRAS was also asked to develop the methods and structures of interaction with the local stakeholders, and to limit its siting activities to nuclear and candidate municipalities. This brought ONDRAF/NIRAS to the concept of local partnerships with interested municipalities, and during the pre-project phase 1998-2006 partnerships were created with the municipalities of Dessel (STOLA-Dessel, 1999), Mol (MONA, 2000) and Fleurus-Farciennes (PaLoFF, 2003). On 23 June, 2006 the Belgian Government decided that category A waste will be disposed of in a near-surface repository on the territory of the Dessel municipality. This decision implies that ONDRAF/NIRAS, in further interaction with the local stakeholders, can start the preparation of a licence application. This decision was the endpoint of the pre-project phase (1998-2006) and was based on the final reports of the partnerships of Dessel (STOLA-Dessel, now STORA) and Mol (MONA), approved by their municipality councils, and on ONDRAF/NIRAS final report, confirming the feasibility of the proposed disposal systems. As the municipality council of Fleurus did not approve the final report of the partnership PaLoFF, ONDRAF/NIRAS did not submit this report to the responsible minister. The preceding positive local decision in both Dessel (May 2005) and Mol (July 2005), and both on the partnership and municipality council level, to accept, under certain conditions, a disposal facility on their territory was the result of a 6 years long process of discussions within the partnership of all aspects of the disposal system and its integration in the municipality. During these

  14. A novel processing system of sterol regulatory element-binding protein-1c regulated by polyunsaturated fatty acid.

    Science.gov (United States)

    Nakakuki, Masanori; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Mizuguchi, Kiyoshi; Shimano, Hitoshi

    2014-05-01

    The proteolytic cascade is the key step in transactivation of sterol regulatory element-binding proteins (SREBPs), a transcriptional factor of lipid synthesis. Proteolysis of SREBP-2 is strictly regulated by sterols, but that of SREBP-1c was not strongly sterol-regulated, but inhibited by polyunsaturated fatty acids (PUFAs). In this study, the proteolytic processing of SREBP-1 and -2 was examined by transfection studies of cDNA-encoding mutants in which all the known cleavage sites were disrupted. In cultured cells, sterol-regulated SREBP-2 processing was completely eliminated by mutation of cleavage sites. In contrast, the corresponding SREBP-1c mutants as well as wild type exhibited large amounts of cleaved products in the nuclear extracts from culture cells and murine liver in vivo. The nuclear form of the mutant SREBP-1c was induced by delipidated condition and suppressed by eicosapentaenoic acid, an n-3 PUFA, but not by sterols. This novel processing mechanism was affected by neither SREBP cleavage-activating protein (SCAP) nor insulin-induced gene (Insig)-1, unlike SREBP-2, but abolished by a serine protease inhibitor. Through analysis of deletion mutant, a site-2 protease recognition sequence (DRSR) was identified to be involved in this novel processing. These findings suggest that SREBP-1c cleavage could be subjected to a novel PUFA-regulated cleavage system in addition to the sterol-regulatory SCAP/Insig system.

  15. Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells.

    Science.gov (United States)

    Haushalter, Kristofer J; Casteel, Darren E; Raffeiner, Andrea; Stefan, Eduard; Patel, Hemal H; Taylor, Susan S

    2018-03-23

    cAMP-dependent protein kinase (PKAc) is a pivotal signaling protein in eukaryotic cells. PKAc has two well-characterized regulatory subunit proteins, RI and RII (each having α and β isoforms), which keep the PKAc catalytic subunit in a catalytically inactive state until activation by cAMP. Previous reports showed that the RIα regulatory subunit is phosphorylated by cGMP-dependent protein kinase (PKG) in vitro , whereupon phosphorylated RIα no longer inhibits PKAc at normal (1:1) stoichiometric ratios. However, the significance of this phosphorylation as a mechanism for activating type I PKA holoenzymes has not been fully explored, especially in cellular systems. In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells. Analysis of a phosphomimetic substitution in RIα (S101E) showed that modification of this site increases PKAc activity in vitro and in cells, even without cAMP stimulation. Numerous techniques were used to show that although Ser 101 variants of RIα can bind PKAc, the modified linker region of the S101E mutant has a significantly reduced affinity for the PKAc active site. These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. We have thus proposed a model to explain how PKG phosphorylation of RIα creates a "sensitized intermediate" state that is in effect primed to trigger PKAc activity.

  16. Evidence for the interaction of the regulatory protein Ki-1/57 with p53 and its interacting proteins

    International Nuclear Information System (INIS)

    Nery, Flavia C.; Rui, Edmilson; Kuniyoshi, Tais M.; Kobarg, Joerg

    2006-01-01

    Ki-1/57 is a cytoplasmic and nuclear phospho-protein of 57 kDa and interacts with the adaptor protein RACK1, the transcription factor MEF2C, and the chromatin remodeling factor CHD3, suggesting that it might be involved in the regulation of transcription. Here, we describe yeast two-hybrid studies that identified a total of 11 proteins interacting with Ki-1/57, all of which interact or are functionally associated with p53 or other members of the p53 family of proteins. We further found that Ki-1/57 is able to interact with p53 itself in the yeast two-hybrid system when the interaction was tested directly. This interaction could be confirmed by pull down assays with purified proteins in vitro and by reciprocal co-immunoprecipitation assays from the human Hodgkin analogous lymphoma cell line L540. Furthermore, we found that the phosphorylation of p53 by PKC abolishes its interaction with Ki-1/57 in vitro

  17. Nuclear physics with use of KUR. Reviews of 30 years studies on short-lived nuclei and perspectives for the future

    International Nuclear Information System (INIS)

    Kawase, Yoichi

    1995-01-01

    The research works which were carried out over the past 30 years on nuclear structure study have been reviewed with emphasis on the technical developments of experimental apparatus for the studies of very short-lived isotopes produced by the Kyoto University reactor(KUR). In the first chapter, nuclear structure studies of neutron-rich nuclei with use of the on-line irradiation apparatus and the on-line isotope separator(ISOL) for fission products have been described. In the second chapter, applications of nuclear methods to solid state physics by the perturbed angular correlation(PAC) technique have been examined to investigate the local electromagnetic fields in metals and compounds through the hyperfine interactions. Perspectives for the future of related research fields are given aiming at the advanced uses of short-lived radioisotopes. (author)

  18. Contribution of the short lived radionuclides in food to the total radiation burden of man after the nuclear accident in Chernobyl

    International Nuclear Information System (INIS)

    Popovic, D.; Djuric, G.; Smelcerovic, M.; Maksimovic, B.

    1989-01-01

    The paper presents the results of the short lived radionuclides (I-131, Te(I)-132, Cs-136, Ce-141,144, Ru-103,106, Ba(La)-140, Zr-95, Mo-99, Nb-95, Sb-125) mass activities estimation in some foodstuff (milk and milk products), immediately after the nuclear accident in Chernobyl, in May 1986. The activities of the radionuclides were determined on Ge(Li) detector by standard gamma spectrometry, with the total error less than 20%. The results enabled the evaluation of the short lived radionuclides contribution in the total dose due to ingestion of milk and milk products, in the first month after the accident, compared to the contribution of I-131 and to the contribution of the main long lived radionuclides: Ce-134 and Cs-137 (author)

  19. Distinct responses of protein turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy

    NARCIS (Netherlands)

    de Theije, Chiel C.; Langen, Ramon C. J.; Lamers, Wouter H.; Schols, Annemie M. W. J.; Köhler, S. Eleonore

    2013-01-01

    The balance of muscle protein synthesis and degradation determines skeletal muscle mass. We hypothesized that hypoxia-induced muscle atrophy and alterations in the regulation of muscle protein turnover include a hypoxia-specific component, in addition to the observed effects of reduction in food

  20. Guanine nucleotide regulatory protein co-purifies with the D2-dopamine receptor

    International Nuclear Information System (INIS)

    Senogles, S.E.; Caron, M.G.

    1986-01-01

    The D 2 -dopamine receptor from bovine anterior pituitary was purified ∼1000 fold by affinity chromatography on CMOS-Sepharose. Reconstitution of the affinity-purified receptor into phospholipid vesicles revealed the presence of high and low affinity agonist sites as detected by N-n-propylnorapomorphine (NPA) competition experiments with 3 H-spiperone. High affinity agonist binding could be converted to the low affinity form by guanine nucleotides, indicating the presence of an endogenous guanine nucleotide binding protein (N protein) in the affinity-purified D 2 receptor preparations. Furthermore, this preparation contained an agonist-sensitive GTPase activity which was stimulated 2-3 fold over basal by 10 μM NPA. 35 S-GTPγS binding to these preparations revealed a stoichiometry of 0.4-0.7 mole N protein/mole receptor, suggesting the N protein may be specifically coupled with the purified D 2 -dopamine receptor and not present as a contaminant. Pertussis toxin treatment of the affinity purified receptor preparations prevented high affinity agonist binding, as well as agonist stimulation of the GTPase activity, presumably by inactivating the associated N protein. Pertussis toxin lead to the ADP-ribosylation of a protein of 39-40K on SDS-PAGE. These findings indicate that an endogenous N protein, N/sub i/ or N/sub o/, co-purifies with the D 2 -dopamine receptor which may reflect a precoupling of this receptor with an N protein within the membranes

  1. Overview of past activities for the use of short-lived radionuclides and the role of the Bureau of Radiological Health

    International Nuclear Information System (INIS)

    Paras, P.

    1985-01-01

    The Bureau of Radiological Health has developed a national program to control unnecessary medical radiation exposures to man and to assure the safe and effective use of radiation. The continuing interest and the role of the Bureau in the use of short-lived radionuclides (SLR's) are emphasized. An overview of the Bureau's SLR program, past accomplishments, and the status of production and use of iodine-123 are presented

  2. In situ detection of a heat-shock regulatory element binding protein using a soluble short synthetic enhancer sequence

    Energy Technology Data Exchange (ETDEWEB)

    Harel-Bellan, A; Brini, A T; Farrar, W L [National Cancer Institute, Frederick, MD (USA); Ferris, D K [Program Resources, Inc., Frederick, MD (USA); Robin, P [Institut Gustave Roussy, Villejuif (France)

    1989-06-12

    In various studies, enhancer binding proteins have been successfully absorbed out by competing sequences inserted into plasmids, resulting in the inhibition of the plasmid expression. Theoretically, such a result could be achieved using synthetic enhancer sequences not inserted into plasmids. In this study, a double stranded DNA sequence corresponding to the human heat shock regulatory element was chemically synthesized. By in vitro retardation assays, the synthetic sequence was shown to bind specifically a protein in extracts from the human T cell line Jurkat. When the synthetic enhancer was electroporated into Jurkat cells, not only the enhancer was shown to remain undegraded into the cells for up to 2 days, but also its was shown to bind intracellularly a protein. The binding was specific and was modulated upon heat shock. Furthermore, the binding protein was shown to be of the expected molecular weight by UV crosslinking. However, when the synthetic enhancer element was co-electroporated with an HSP 70-CAT reporter construct, the expression of the reporter plasmid was consistently enhanced in the presence of the exogenous synthetic enhancer.

  3. Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes.

    Science.gov (United States)

    Zhang, Jing; Lu, Shaohua; Zhou, Ye; Meng, Kun; Chen, Zhipeng; Cui, Yizhi; Shi, Yunfeng; Wang, Tong; He, Qing-Yu

    2017-07-01

    Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super-SILAC-based MS analysis on the exosomes secreted by three human HCC cell lines, including the non-motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified in each MS analysis with highly biological reproducibility. We justified that 469 and 443 exosomal proteins represented differentially expressed proteins (DEPs) in the 97H/Hep3B and LM3/Hep3B comparisons, respectively. These DEPs focused on sugar metabolism-centric canonical pathways per ingenuity pathway analysis, which was consistent with the gene ontology analysis on biological process enrichment. These pathways included glycolysis I, gluconeogenesis I and pentose phosphate pathways; and the DEPs enriched in these pathways could form a tightly connected network. By analyzing the relative abundance of proteins and translating mRNAs, we found significantly positive correlation between exosomes and cells. The involved exosomal proteins were again focusing on sugar metabolism. In conclusion, motile HCC cells tend to preferentially export more sugar metabolism-associated proteins via exosomes that differentiate them from non-motile HCC cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Identification of a novel Leucine-rich repeat protein and candidate PP1 regulatory subunit expressed in developing spermatids

    Directory of Open Access Journals (Sweden)

    Sperry Ann O

    2008-01-01

    . TLRR is homologous to a class of regulatory subunits for PP1, a central phosphatase in the reversible phosphorylation of proteins that is key to modulation of many intracellular processes. TLRR may serve to target this important signaling molecule near the nucleus of developing spermatids in order to control the cellular rearrangements of spermiogenesis.

  5. Selection on Coding and Regulatory Variation Maintains Individuality in Major Urinary Protein Scent Marks in Wild Mice.

    Directory of Open Access Journals (Sweden)

    Michael J Sheehan

    2016-03-01

    Full Text Available Recognition of individuals by scent is widespread across animal taxa. Though animals can often discriminate chemical blends based on many compounds, recent work shows that specific protein pheromones are necessary and sufficient for individual recognition via scent marks in mice. The genetic nature of individuality in scent marks (e.g. coding versus regulatory variation and the evolutionary processes that maintain diversity are poorly understood. The individual signatures in scent marks of house mice are the protein products of a group of highly similar paralogs in the major urinary protein (Mup gene family. Using the offspring of wild-caught mice, we examine individuality in the major urinary protein (MUP scent marks at the DNA, RNA and protein levels. We show that individuality arises through a combination of variation at amino acid coding sites and differential transcription of central Mup genes across individuals, and we identify eSNPs in promoters. There is no evidence of post-transcriptional processes influencing phenotypic diversity as transcripts accurately predict the relative abundance of proteins in urine samples. The match between transcripts and urine samples taken six months earlier also emphasizes that the proportional relationships across central MUP isoforms in urine is stable. Balancing selection maintains coding variants at moderate frequencies, though pheromone diversity appears limited by interactions with vomeronasal receptors. We find that differential transcription of the central Mup paralogs within and between individuals significantly increases the individuality of pheromone blends. Balancing selection on gene regulation allows for increased individuality via combinatorial diversity in a limited number of pheromones.

  6. Drag on a Satellite Moving across a Spherical Galaxy: Tidal and Frictional Forces in Short-lived Encounters

    Science.gov (United States)

    Colpi, Monica; Pallavicini, Andrea

    1998-07-01

    The drag force on a satellite of mass M moving with speed V in the gravitational field of a spherically symmetric background of stars is computed. During the encounter, the stars are subject to a time-dependent force that alters their equilibrium. The resulting distortion in the stellar density field acts back to produce a force FΔ that decelerates the satellite. This force is computed using a perturbative technique known as linear response theory. In this paper, we extend the formalism of linear response to derive the correct expression for the back-reaction force FΔ that applies when the stellar system is described by an equilibrium one-particle distribution function. FΔ is expressed in terms of a suitable correlation function that couples the satellite dynamics to the unperturbed dynamics of the stars. At time t, the force depends upon the whole history of the composite system. In the formalism, we account for the shift of the stellar center of mass resulting from linear momentum conservation. The self-gravity of the response is neglected since it contributes to a higher order in the perturbation. Linear response theory applies also to the case of a satellite orbiting outside the spherical galaxy. The case of a satellite moving on a straight line, at high speed relative to the stellar dispersion velocity, is explored. We find that the satellite during its passage raises (1) global tides in the stellar distribution and (2) a wake, i.e., an overdense region behind its trail. If the satellite motion is external to the galaxy, it suffers a dissipative force that is not exclusively acting along V but acquires a component along R, the position vector relative to the center of the spherical galaxy. We derive the analytical expression of the force in the impulse approximation. In penetrating short-lived encounters, the satellite moves across the stellar distribution and the transient wake excited in the density field is responsible for most of the deceleration. We

  7. Overexpression of KH-type splicing regulatory protein regulates proliferation, migration, and implantation ability of osteosarcoma

    OpenAIRE

    Pruksakorn, Dumnoensun; Teeyakasem, Pimpisa; Klangjorhor, Jeerawan; Chaiyawat, Parunya; Settakorn, Jongkolnee; Diskul-Na-Ayudthaya, Penchatr; Chokchaichamnankit, Daranee; Pothacharoen, Peraphan; Srisomsap, Chantragan

    2016-01-01

    Osteosarcoma is a common malignant bone tumor in children and adolescents. The current 5-year survival rate is ~60% and that seems to be reaching a plateau. In order to improve treatment outcomes of osteosarcoma, a better understanding of tumorigenesis and underlying molecular mechanisms is required for searching out possible new treatment targets. This study aimed to identify the potential proteins involving the pathogenesis of osteosarcoma using a proteomics approach. Proteins extracted fro...

  8. Regulatory motifs for CREB-binding protein and Nfe2l2 transcription factors in the upstream enhancer of the mitochondrial uncoupling protein 1 gene.

    Science.gov (United States)

    Rim, Jong S; Kozak, Leslie P

    2002-09-13

    Thermogenesis against cold exposure in mammals occurs in brown adipose tissue (BAT) through mitochondrial uncoupling protein (UCP1). Expression of the Ucp1 gene is unique in brown adipocytes and is regulated tightly. The 5'-flanking region of the mouse Ucp1 gene contains cis-acting elements including PPRE, TRE, and four half-site cAMP-responsive elements (CRE) with BAT-specific enhancer elements. In the course of analyzing how these half-site CREs are involved in Ucp1 expression, we found that a DNA regulatory element for NF-E2 overlaps CRE2. Electrophoretic mobility shift assay and competition assays with the CRE2 element indicates that nuclear proteins from BAT, inguinal fat, and retroperitoneal fat tissue interact with the CRE2 motif (CGTCA) in a specific manner. A supershift assay using an antibody against the CRE-binding protein (CREB) shows specific affinity to the complex from CRE2 and nuclear extract of BAT. Additionally, Western blot analysis for phospho-CREB/ATF1 shows an increase in phosphorylation of CREB/ATF1 in HIB-1B cells after norepinephrine treatment. Transient transfection assay using luciferase reporter constructs also indicates that the two half-site CREs are involved in transcriptional regulation of Ucp1 in response to norepinephrine and cAMP. We also show that a second DNA regulatory element for NF-E2 is located upstream of the CRE2 region. This element, which is found in a similar location in the 5'-flanking region of the human and rodent Ucp1 genes, shows specific binding to rat and human NF-E2 by electrophoretic mobility shift assay with nuclear extracts from brown fat. Co-transfections with an Nfe2l2 expression vector and a luciferase reporter construct of the Ucp1 enhancer region provide additional evidence that Nfe2l2 is involved in the regulation of Ucp1 by cAMP-mediated signaling.

  9. Coordination of Hepatitis C Virus Assembly by Distinct Regulatory Regions in Nonstructural Protein 5A.

    Directory of Open Access Journals (Sweden)

    Margarita Zayas

    2016-01-01

    Full Text Available Hepatitis C virus (HCV nonstructural protein (NS5A is a RNA-binding protein composed of a N-terminal membrane anchor, a structured domain I (DI and two intrinsically disordered domains (DII and DIII interacting with viral and cellular proteins. While DI and DII are essential for RNA replication, DIII is required for assembly. How these processes are orchestrated by NS5A is poorly understood. In this study, we identified a highly conserved basic cluster (BC at the N-terminus of DIII that is critical for particle assembly. We generated BC mutants and compared them with mutants that are blocked at different stages of the assembly process: a NS5A serine cluster (SC mutant blocked in NS5A-core interaction and a mutant lacking the envelope glycoproteins (ΔE1E2. We found that BC mutations did not affect core-NS5A interaction, but strongly impaired core-RNA association as well as virus particle envelopment. Moreover, BC mutations impaired RNA-NS5A interaction arguing that the BC might be required for loading of core protein with viral RNA. Interestingly, RNA-core interaction was also reduced with the ΔE1E2 mutant, suggesting that nucleocapsid formation and envelopment are coupled. These findings argue for two NS5A DIII determinants regulating assembly at distinct, but closely linked steps: (i SC-dependent recruitment of replication complexes to core protein and (ii BC-dependent RNA genome delivery to core protein, triggering encapsidation that is tightly coupled to particle envelopment. These results provide a striking example how a single viral protein exerts multiple functions to coordinate the steps from RNA replication to the assembly of infectious virus particles.

  10. Purification and binding analysis of the nitrogen fixation regulatory NifA protein from Azospirillum brasilense

    Directory of Open Access Journals (Sweden)

    L.M.P. Passaglia

    1998-11-01

    Full Text Available NifA protein activates transcription of nitrogen fixation operons by the alternative sigma54 holoenzyme form of RNA polymerase. This protein binds to a well-defined upstream activator sequence (UAS located at the -200/-100 position of nif promoters with the consensus motif TGT-N10-ACA. NifA of Azospirillum brasilense was purified in the form of a glutathione-S-transferase (GST-NifA fusion protein and proteolytic release of GST yielded inactive and partially soluble NifA. However, the purified NifA was able to induce the production of specific anti-A. brasilense NifA-antiserum that recognized NifA from A. brasilense but not from K. pneumoniae. Both GST-NifA and NifA expressed from the E. coli tac promoter are able to activate transcription from the nifHDK promoter but only in an A. brasilense background. In order to investigate the mechanism that regulates NifA binding capacity we have used E. coli total protein extracts expressing A. brasilense nifA in mobility shift assays. DNA fragments carrying the two overlapping, wild-type or mutated UAS motifs present in the nifH promoter region revealed a retarded band of related size. These data show that the binding activity present in the C-terminal domain of A. brasilense NifA protein is still functional even in the presence of oxygen.

  11. MAPA distinguishes genotype-specific variability of highly similar regulatory protein isoforms in potato tuber.

    Science.gov (United States)

    Hoehenwarter, Wolfgang; Larhlimi, Abdelhalim; Hummel, Jan; Egelhofer, Volker; Selbig, Joachim; van Dongen, Joost T; Wienkoop, Stefanie; Weckwerth, Wolfram

    2011-07-01

    Mass Accuracy Precursor Alignment is a fast and flexible method for comparative proteome analysis that allows the comparison of unprecedented numbers of shotgun proteomics analyses on a personal computer in a matter of hours. We compared 183 LC-MS analyses and more than 2 million MS/MS spectra and could define and separate the proteomic phenotypes of field grown tubers of 12 tetraploid cultivars of the crop plant Solanum tuberosum. Protein isoforms of patatin as well as other major gene families such as lipoxygenase and cysteine protease inhibitor that regulate tuber development were found to be the primary source of variability between the cultivars. This suggests that differentially expressed protein isoforms modulate genotype specific tuber development and the plant phenotype. We properly assigned the measured abundance of tryptic peptides to different protein isoforms that share extensive stretches of primary structure and thus inferred their abundance. Peptides unique to different protein isoforms were used to classify the remaining peptides assigned to the entire subset of isoforms based on a common abundance profile using multivariate statistical procedures. We identified nearly 4000 proteins which we used for quantitative functional annotation making this the most extensive study of the tuber proteome to date.

  12. Impairment of interferon regulatory factor-3 activation by hepatitis C virus core protein basic amino acid region 1.

    Science.gov (United States)

    Inoue, Kazuaki; Tsukiyama-Kohara, Kyoko; Matsuda, Chiho; Yoneyama, Mitsutoshi; Fujita, Takashi; Kuge, Shusuke; Yoshiba, Makoto; Kohara, Michinori

    2012-11-30

    Interferon regulatory factor-3 (IRF-3), a key transcriptional factor in the type I interferon system, is frequently impaired by hepatitis C virus (HCV), in order to establish persistent infection. However, the exact mechanism by which the virus establishes persistent infection has not been fully understood yet. The present study aimed to investigate the effects of various HCV proteins on IRF-3 activation, and elucidate the underlying mechanisms. To achieve this, full-length HCV and HCV subgenomic constructs corresponding to structural and each of the nonstructural proteins were transiently transfected into HepG2 cells. IFN-β induction, plaque formation, and IRF-3 dimerization were elicited by Newcastle disease virus (NDV) infection. The expressions of IRF-3 homodimer and its monomer, Ser386-phosphorylated IRF-3, and HCV core protein were detected by immunofluorescence and western blotting. IFN-β mRNA expression was quantified by real-time PCR (RT-PCR), and IRF-3 activity was measured by the levels of IRF-3 dimerization and phosphorylation, induced by NDV infection or polyriboinosinic:polyribocytidylic acid [poly(I:C)]. Switching of the expression of the complete HCV genome as well as the core proteins, E1, E2, and NS2, suppressed IFN-β mRNA levels and IRF-3 dimerization, induced by NDV infection. Our study revealed a crucial region of the HCV core protein, basic amino acid region 1 (BR1), to inhibit IRF-3 dimerization as well as its phosphorylation induced by NDV infection and poly (I:C), thus interfering with IRF-3 activation. Therefore, our study suggests that rescue of the IRF-3 pathway impairment may be an effective treatment for HCV infection. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Uncovering packaging features of co-regulated modules based on human protein interaction and transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    He Weiming

    2010-07-01

    Full Text Available Abstract Background Network co-regulated modules are believed to have the functionality of packaging multiple biological entities, and can thus be assumed to coordinate many biological functions in their network neighbouring regions. Results Here, we weighted edges of a human protein interaction network and a transcriptional regulatory network to construct an integrated network, and introduce a probabilistic model and a bipartite graph framework to exploit human co-regulated modules and uncover their specific features in packaging different biological entities (genes, protein complexes or metabolic pathways. Finally, we identified 96 human co-regulated modules based on this method, and evaluate its effectiveness by comparing it with four other methods. Conclusions Dysfunctions in co-regulated interactions often occur in the development of cancer. Therefore, we focussed on an example co-regulated module and found that it could integrate a number of cancer-related genes. This was extended to causal dysfunctions of some complexes maintained by several physically interacting proteins, thus coordinating several metabolic pathways that directly underlie cancer.

  14. pH-Regulatory Proteins as Potential Targets in Breast Cancer

    DEFF Research Database (Denmark)

    Andersen, Anne Poder

    tissues. The focus of the present PhD study is on understanding the mechanisms through which pH-regulatory transporters are regulated by the breast tumor microenvironment, and how these transporters in turn favor cancer progression. In Paper I, we summarized the recent knowledge on the dynamic...... exhibit distinct spatial organization during 3D growth of MCF-7 and MDA-MB-231 breast cancer cells. By pharmacological inhibition and stable shRNA-mediated knockdown, we addressed the specific contributions of the transporters to spheroid growth and show that the specific transporters contribute to breast...... development in the more complex in vivo setting. In Paper III, we found that chemical induction of breast cancer in NBCn1 knockout (KO) mice is delayed and tumor growth rates reduced, compared to those in wildtype (WT) mice, demonstrating a causal link between NBCn1 and breast cancer development. In Paper IV...

  15. Evolution of a G protein-coupled receptor response by mutations in regulatory network interactions

    DEFF Research Database (Denmark)

    Di Roberto, Raphaël B; Chang, Belinda; Trusina, Ala

    2016-01-01

    All cellular functions depend on the concerted action of multiple proteins organized in complex networks. To understand how selection acts on protein networks, we used the yeast mating receptor Ste2, a pheromone-activated G protein-coupled receptor, as a model system. In Saccharomyces cerevisiae......, Ste2 is a hub in a network of interactions controlling both signal transduction and signal suppression. Through laboratory evolution, we obtained 21 mutant receptors sensitive to the pheromone of a related yeast species and investigated the molecular mechanisms behind this newfound sensitivity. While...... demonstrate that a new receptor-ligand pair can evolve through network-altering mutations independently of receptor-ligand binding, and suggest a potential role for such mutations in disease....

  16. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.

    Science.gov (United States)

    Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W; Grubert, Fabian; Candille, Sophie I; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L; Tang, Hua; Ricci, Emiliano; Snyder, Michael P

    2015-11-01

    Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy--many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. © 2015 Cenik et al.; Published by Cold Spring Harbor Laboratory Press.

  17. Moonlighting microtubule-associated proteins: regulatory functions by day and pathological functions at night.

    Science.gov (United States)

    Oláh, J; Tőkési, N; Lehotzky, A; Orosz, F; Ovádi, J

    2013-11-01

    The sensing, integrating, and coordinating features of the eukaryotic cells are achieved by the complex ultrastructural arrays and multifarious functions of the cytoskeletal network. Cytoskeleton comprises fibrous protein networks of microtubules, actin, and intermediate filaments. These filamentous polymer structures are highly dynamic and undergo constant and rapid reorganization during cellular processes. The microtubular system plays a crucial role in the brain, as it is involved in an enormous number of cellular events including cell differentiation and pathological inclusion formation. These multifarious functions of microtubules can be achieved by their decoration with proteins/enzymes that exert specific effects on the dynamics and organization of the cytoskeleton and mediate distinct functions due to their moonlighting features. This mini-review focuses on two aspects of the microtubule cytoskeleton. On the one hand, we describe the heteroassociation of tubulin/microtubules with metabolic enzymes, which in addition to their catalytic activities stabilize microtubule structures via their cross-linking functions. On the other hand, we focus on the recently identified moonlighting tubulin polymerization promoting protein, TPPP/p25. TPPP/p25 is a microtubule-associated protein and it displays distinct physiological or pathological (aberrant) functions; thus it is a prototype of Neomorphic Moonlighting Proteins. The expression of TPPP/p25 is finely controlled in the human brain; this protein is indispensable for the development of projections of oligodendrocytes that are responsible for the ensheathment of axons. The nonphysiological, higher or lower TPPP/p25 level leads to distinct CNS diseases. Mechanisms contributing to the control of microtubule stability and dynamics by metabolic enzymes and TPPP/p25 will be discussed. Copyright © 2013 Wiley Periodicals, Inc.

  18. Interplay of the modified nucleotide phosphoadenosine 5'-phosphosulfate (PAPS) with global regulatory proteins in Escherichia coli: modulation of cyclic AMP (cAMP)-dependent gene expression and interaction with the HupA regulatory protein.

    Science.gov (United States)

    Longo, Francesca; Motta, Sara; Mauri, Pierluigi; Landini, Paolo; Rossi, Elio

    2016-11-25

    In the bacterium Escherichia coli, some intermediates of the sulfate assimilation and cysteine biosynthesis pathway can act as signal molecules and modulate gene expression. In addition to sensing and utilization of sulphur sources, these signaling mechanisms also impact more global cell processes, such as resistance to antimicrobial agents and biofilm formation. In a recent work, we have shown that inactivation of the cysH gene, encoding phosphoadenosine-phosphosulfate (PAPS) reductase, and the consequent increase in intracellular PAPS concentration, strongly affect production of several cell surface-associated structures, enhancing surface adhesion and cell aggregation. In order to identify the molecular mechanism relaying intracellular PAPS concentration to regulation of cell surface-associated structures, we looked for mutations able to suppress the effects of cysH inactivation. We found that mutations in the adenylate cyclase-encoding cyaA gene abolished the effects of PAPS accumulation; consistent with this result, cyclic AMP (cAMP)-dependent gene expression appears to be increased in the cysH mutant. Experiments aimed at the direct identification of proteins interacting with either CysC or CysH, i.e. the PAPS-related proteins APS kinase and PAPS reductase, allowed us to identify several regulators, namely, CspC, CspE, HNS and HupA. Protein-protein interaction between HupA and CysH was confirmed by a bacterial two hybrid system, and inactivation of the hupA gene enhanced the effects of the cysH mutation in terms of production of cell surface-associated factors. Our results indicate that PAPS can modulate different regulatory systems, providing evidence that this molecule acts as a global signal molecule in E. coli. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Identification of Novel Targets of the Human Cell Cycle Regulatory Protein Cdc34

    Science.gov (United States)

    1999-07-01

    centrifugal elutriation, with a purity of -80% as shown by micro - ethyl acetate and separated on thin-layer chromatography plates (Whatman, scopic...Spain. (2) Servicio Bioquimica, Hosp. La Paz. Madrid. ICER protein is elevated in mHR6b-/- (murine Rad6B) fibroblasts Spain. and in human cells

  20. Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Shi, T.; Niepel, M.; McDermott, J. E.; Gao, Y.; Nicora, C. D.; Chrisler, W. B.; Markillie, L. M.; Petyuk, V. A.; Smith, R. D.; Rodland, K. D.; Sorger, P. K.; Qian, W. -J.; Wiley, H. S.

    2016-07-12

    It is not known whether cancer cells generally show quantitative differences in the expression of signaling pathway proteins that could dysregulate signal transduction. To explore this issue, we first defined the primary components of the EGF-MAPK pathway in normal human mammary epithelial cells, identifying 16 core proteins and 10 feedback regulators. We then quantified their absolute abundance across a panel of normal and cancer cell lines. We found that core pathway proteins were expressed at very similar levels across all cell types. In contrast, the EGFR and transcriptionally controlled feedback regulators were expressed at highly variable levels. The absolute abundance of most core pathway proteins was between 50,000- 70,000 copies per cell, but the adaptors SOS1, SOS2, and GAB1 were found at far lower levels (2,000-5,000 per cell). MAPK signaling showed saturation in all cells between 3,000-10,000 occupied EGFR, consistent with the idea that low adaptor levels limit signaling. Our results suggest that the core MAPK pathway is essentially invariant across different cell types, with cell- specific differences in signaling likely due to variable levels of feedback regulators. The low abundance of adaptors relative to the EGFR could be responsible for previous observation of saturable signaling, endocytosis, and high affinity EGFR.

  1. Determinants of RNA binding and translational repression by the Bicaudal-C regulatory protein.

    Science.gov (United States)

    Zhang, Yan; Park, Sookhee; Blaser, Susanne; Sheets, Michael D

    2014-03-14

    Bicaudal-C (Bic-C) RNA binding proteins function as important translational repressors in multiple biological contexts within metazoans. However, their RNA binding sites are unknown. We recently demonstrated that Bic-C functions in spatially regulated translational repression of the xCR1 mRNA during Xenopus development. This repression contributes to normal development by confining the xCR1 protein, a regulator of key signaling pathways, to specific cells of the embryo. In this report, we combined biochemical approaches with in vivo mRNA reporter assays to define the minimal Bic-C target site within the xCR1 mRNA. This 32-nucleotide Bic-C target site is predicted to fold into a stem-loop secondary structure. Mutational analyses provided evidence that this stem-loop structure is important for Bic-C binding. The Bic-C target site was sufficient for Bic-C mediated repression in vivo. Thus, we describe the first RNA binding site for a Bic-C protein. This identification provides an important step toward understanding the mechanisms by which evolutionarily conserved Bic-C proteins control cellular function in metazoans.

  2. Expression of cytoskeleton regulatory protein Mena in human hepatocellular carcinoma and its prognostic significance.

    Science.gov (United States)

    Hu, Kunpeng; Wang, Jiani; Yao, Zhicheng; Liu, Bo; Lin, Yuan; Liu, Lei; Xu, Lihua

    2014-05-01

    The molecular mechanisms of the development and progression of hepatocellular carcinoma (HCC) are poorly understood. The main objective of this study was to analyze the expression of Enabled [mammalian Ena (Mena)] protein and its clinical significance in human HCC. The Mena expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction and Western blotting analysis in ten paired HCC tissues and the adjacent normal tissues. The expression of Mena protein in 81 specimens of HCC tissues was determined by immunohistochemistry. Associations of Mena expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. The result shows the expression of Mena mRNA and protein was higher in HCC than in the adjacent normal tissues in ten paired samples. Mena was mainly accumulated in the cytoplasm of tumor cells and over-expressed in 40.74% (33/81) patients by immunohistochemical staining. Over-expression of Mena was significantly associated with poor cellular differentiation (P = 0.025), advanced tumor stage (P = 0.003) and worse disease-free survival (DFS, P Mena is an independent prognostic factor for DFS in multivariate analysis (HR 2.309, 95% CI 1.104-4.828; P = 0.026). Mena is up-regulated in HCC and associated with tumor differentiation and clinical stage. Mena may be an independent prognostic marker for DFS of HCC patients.

  3. WrpA Is an Atypical Flavodoxin Family Protein under Regulatory Control of the Brucella abortus General Stress Response System.

    Science.gov (United States)

    Herrou, Julien; Czyż, Daniel M; Willett, Jonathan W; Kim, Hye-Sook; Chhor, Gekleng; Babnigg, Gyorgy; Kim, Youngchang; Crosson, Sean

    2016-04-01

    The general stress response (GSR) system of the intracellular pathogen Brucella abortus controls the transcription of approximately 100 genes in response to a range of stress cues. The core genetic regulatory components of the GSR are required for B. abortus survival under nonoptimal growth conditions in vitro and for maintenance of chronic infection in an in vivo mouse model. The functions of the majority of the genes in the GSR transcriptional regulon remain undefined. bab1_1070 is among the most highly regulated genes in this regulon: its transcription is activated 20- to 30-fold by the GSR system under oxidative conditions in vitro. We have solved crystal structures of Bab1_1070 and demonstrate that it forms a homotetrameric complex that resembles those of WrbA-type NADH:quinone oxidoreductases, which are members of the flavodoxin protein family. However, B. abortus WrbA-related protein (WrpA) does not bind flavin cofactors with a high affinity and does not function as an NADH:quinone oxidoreductase in vitro. Soaking crystals with flavin mononucleotide (FMN) revealed a likely low-affinity binding site adjacent to the canonical WrbA flavin binding site. Deletion of wrpA (ΔwrpA) does not compromise cell survival under acute oxidative stress in vitro or attenuate infection in cell-based or mouse models. However, a ΔwrpA strain does elicit increased splenomegaly in a mouse model, suggesting that WrpA modulates B. abortus interaction with its mammalian host. Despite high structural homology with canonical WrbA proteins, we propose that B. abortus WrpA represents a functionally distinct member of the diverse flavodoxin family. Brucella abortus is an etiological agent of brucellosis, which is among the most common zoonotic diseases worldwide. The general stress response (GSR) regulatory system of B. abortus controls the transcription of approximately 100 genes and is required for maintenance of chronic infection in a murine model; the majority of GSR-regulated genes

  4. Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes

    LENUS (Irish Health Repository)

    Whan, Vicki

    2010-11-23

    Abstract Background About forty human diseases are caused by repeat instability mutations. A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation is also apparent in human poly-Q encoding genes from normal individuals. As these coding sequence repeats are subject to selection in mammals, it has been suggested that normal variations in some of these typically highly conserved genes are implicated in morphological differences between species and phenotypic variations within species. At present, poly-Q encoding genes in non-human mammalian species are poorly documented, as are their functions and propensities for polymorphic variation. Results The current investigation identified 178 bovine poly-Q encoding genes (Q ≥ 5) and within this group, 26 genes with orthologs in both human and mouse that did not contain poly-Q repeats. The bovine poly-Q encoding genes typically had ubiquitous expression patterns although there was bias towards expression in epithelia, brain and testes. They were also characterised by unusually large sizes. Analysis of gene ontology terms revealed that the encoded proteins were strongly enriched for functions associated with transcriptional regulation and many contributed to physical interaction networks in the nucleus where they presumably act cooperatively in transcriptional regulatory complexes. In addition, the coding sequence CAG repeats in some bovine genes impacted mRNA splicing thereby generating unusual transcriptional diversity, which in at least one instance was tissue-specific. The poly-Q encoding genes were prioritised using multiple criteria for their likelihood of being polymorphic and then the highest ranking group was experimentally tested for polymorphic variation within a cattle diversity panel. Extensive and meiotically stable variation was identified

  5. Structural and dynamic characterization of eukaryotic gene regulatory protein domains in solution

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Andrew Loyd [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1996-05-01

    Solution NMR was primarily used to characterize structure and dynamics in two different eukaryotic protein systems: the δ-Al-ε activation domain from c-jun and the Drosophila RNA-binding protein Sex-lethal. The second system is the Drosophila Sex-lethal (Sxl) protein, an RNA-binding protein which is the ``master switch`` in sex determination. Sxl contains two adjacent RNA-binding domains (RBDs) of the RNP consensus-type. The NMR spectrum of the second RBD (Sxl-RBD2) was assigned using multidimensional heteronuclear NMR, and an intermediate-resolution family of structures was calculated from primarily NOE distance restraints. The overall fold was determined to be similar to other RBDs: a βαβ-βαβ pattern of secondary structure, with the two helices packed against a 4-stranded anti-parallel β-sheet. In addition 15N T1, T2, and 15N/1H NOE relaxation measurements were carried out to characterize the backbone dynamics of Sxl-RBD2 in solution. RNA corresponding to the polypyrimidine tract of transformer pre-mRNA was generated and titrated into 3 different Sxl-RBD protein constructs. Combining Sxl-RBD1+2 (bht RBDs) with this RNA formed a specific, high affinity protein/RNA complex that is amenable to further NMR characterization. The backbone 1H, 13C, and 15N resonances of Sxl-RBD1+2 were assigned using a triple-resonance approach, and 15N relaxation experiments were carried out to characterize the backbone dynamics of this complex. The changes in chemical shift in Sxl-RBD1+2 upon binding RNA are observed using Sxl-RBD2 as a substitute for unbound Sxl-RBD1+2. This allowed the binding interface to be qualitatively mapped for the second domain.

  6. Transcriptional analysis of the jamaicamide gene cluster from the marine cyanobacterium Lyngbya majuscula and identification of possible regulatory proteins

    Directory of Open Access Journals (Sweden)

    Dorrestein Pieter C

    2009-12-01

    Full Text Available Abstract Background The marine cyanobacterium Lyngbya majuscula is a prolific producer of bioactive secondary metabolites. Although biosynthetic gene clusters encoding several of these compounds have been identified, little is known about how these clusters of genes are transcribed or regulated, and techniques targeting genetic manipulation in Lyngbya strains have not yet been developed. We conducted transcriptional analyses of the jamaicamide gene cluster from a Jamaican strain of Lyngbya majuscula, and isolated proteins that could be involved in jamaicamide regulation. Results An unusually long untranslated leader region of approximately 840 bp is located between the jamaicamide transcription start site (TSS and gene cluster start codon. All of the intergenic regions between the pathway ORFs were transcribed into RNA in RT-PCR experiments; however, a promoter prediction program indicated the possible presence of promoters in multiple intergenic regions. Because the functionality of these promoters could not be verified in vivo, we used a reporter gene assay in E. coli to show that several of these intergenic regions, as well as the primary promoter preceding the TSS, are capable of driving β-galactosidase production. A protein pulldown assay was also used to isolate proteins that may regulate the jamaicamide pathway. Pulldown experiments using the intergenic region upstream of jamA as a DNA probe isolated two proteins that were identified by LC-MS/MS. By BLAST analysis, one of these had close sequence identity to a regulatory protein in another cyanobacterial species. Protein comparisons suggest a possible correlation between secondary metabolism regulation and light dependent complementary chromatic adaptation. Electromobility shift assays were used to evaluate binding of the recombinant proteins to the jamaicamide promoter region. Conclusion Insights into natural product regulation in cyanobacteria are of significant value to drug discovery

  7. Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium.

    Science.gov (United States)

    Rudolph, Michael C; Monks, Jenifer; Burns, Valerie; Phistry, Meridee; Marians, Russell; Foote, Monica R; Bauman, Dale E; Anderson, Steven M; Neville, Margaret C

    2010-12-01

    The lactating mammary gland synthesizes large amounts of triglyceride from fatty acids derived from the blood and from de novo lipogenesis. The latter is significantly increased at parturition and decreased when additional dietary fatty acids become available. To begin to understand the molecular regulation of de novo lipogenesis, we tested the hypothesis that the transcription factor sterol regulatory element binding factor (SREBF)-1c is a primary regulator of this system. Expression of Srebf1c mRNA and six of its known target genes increased ≥2.5-fold at parturition. However, Srebf1c-null mice showed only minor deficiencies in lipid synthesis during lactation, possibly due to compensation by Srebf1a expression. To abrogate the function of both isoforms of Srebf1, we bred mice to obtain a mammary epithelial cell-specific deletion of SREBF cleavage-activating protein (SCAP), the SREBF escort protein. These dams showed a significant lactation deficiency, and expression of mRNA for fatty acid synthase (Fasn), insulin-induced gene 1 (Insig1), mitochondrial citrate transporter (Slc25a1), and stearoyl-CoA desaturase 2 (Scd2) was reduced threefold or more; however, the mRNA levels of acetyl-CoA carboxylase-1α (Acaca) and ATP citrate lyase (Acly) were unchanged. Furthermore, a 46% fat diet significantly decreased de novo fatty acid synthesis and reduced the protein levels of ACACA, ACLY, and FASN significantly, with no change in their mRNA levels. These data lead us to conclude that two modes of regulation exist to control fatty acid synthesis in the mammary gland of the lactating mouse: the well-known SREBF1 system and a novel mechanism that acts at the posttranscriptional level in the presence of SCAP deletion and high-fat feeding to alter enzyme protein.

  8. Exploring the regulatory role of isocitrate dehydrogenase mutant protein on glioma stem cell proliferation.

    Science.gov (United States)

    Lu, H-C; Ma, J; Zhuang, Z; Qiu, F; Cheng, H-L; Shi, J-X

    2016-08-01

    Glioma is the most lethal form of cancer that originates mostly from the brain and less frequently from the spine. Glioma is characterized by abnormal regulation of glial cell differentiation. The severity of the glioma was found to be relaxed in isocitrate dehydrogenase 1 (IDH1) mutant. The present study focused on histological discrimination and regulation of cancer stem cell between IDH1 mutant and in non-IDH1 mutant glioma tissue. Histology, immunohistochemistry and Western blotting techniques are used to analyze the glioma nature and variation in glioma stem cells that differ between IDH1 mutant and in non-IDH1 mutant glioma tissue. The aggressive form of non-IDH1 mutant glioma shows abnormal cellular histological variation with prominent larger nucleus along with abnormal clustering of cells. The longer survival form of IDH1 mutant glioma has a control over glioma stem cell proliferation. Immunohistochemistry with stem cell markers, CD133 and EGFRvIII are used to demonstrate that the IDH1 mutant glioma shows limited dependence on cancer stem cells and it shows marked apoptotic signals in TUNEL assay to regulate abnormal cells. The non-IDH1 mutant glioma failed to regulate misbehaving cells and it promotes cancer stem cell proliferation. Our finding supports that the IDH1 mutant glioma has a regulatory role in glioma stem cells and their survival.

  9. Drosophila Protein Kinase CK2: Genetics, Regulatory Complexity and Emerging Roles during Development

    Directory of Open Access Journals (Sweden)

    Mohna Bandyopadhyay

    2016-12-01

    Full Text Available CK2 is a Ser/Thr protein kinase that is highly conserved amongst all eukaryotes. It is a well-known oncogenic kinase that regulates vital cell autonomous functions and animal development. Genetic studies in the fruit fly Drosophila are providing unique insights into the roles of CK2 in cell signaling, embryogenesis, organogenesis, neurogenesis, and the circadian clock, and are revealing hitherto unknown complexities in CK2 functions and regulation. Here, we review Drosophila CK2 with respect to its structure, subunit diversity, potential mechanisms of regulation, developmental abnormalities linked to mutations in the gene encoding CK2 subunits, and emerging roles in multiple aspects of eye development. We examine the Drosophila CK2 “interaction map” and the eye-specific “transcriptome” databases, which raise the prospect that this protein kinase has many additional targets in the developing eye. We discuss the possibility that CK2 functions during early retinal neurogenesis in Drosophila and mammals bear greater similarity than has been recognized, and that this conservation may extend to other developmental programs. Together, these studies underscore the immense power of the Drosophila model organism to provide new insights and avenues to further investigate developmentally relevant targets of this protein kinase.

  10. Climate response to projected changes in short-lived species under an A1B scenario from 2000-2050 in the GISS climate model

    Energy Technology Data Exchange (ETDEWEB)

    Menon, Surabi; Shindell, Drew T.; Faluvegi, Greg; Bauer, Susanne E.; Koch, Dorothy M.; Unger, Nadine; Menon, Surabi; Miller, Ron L.; Schmidt, Gavin A.; Streets, David G.

    2007-03-26

    We investigate the climate forcing from and response to projected changes in short-lived species and methane under the A1B scenario from 2000-2050 in the GISS climate model. We present a meta-analysis of new simulations of the full evolution of gas and aerosol species and other existing experiments with variations of the same model. The comparison highlights the importance of several physical processes in determining radiative forcing, especially the effect of climate change on stratosphere-troposphere exchange, heterogeneous sulfate-nitrate-dust chemistry, and changes in methane oxidation and natural emissions. However, the impact of these fairly uncertain physical effects is substantially less than the difference between alternative emission scenarios for all short-lived species. The net global mean annual average direct radiative forcing from the short-lived species is .02 W/m{sup 2} or less in our projections, as substantial positive ozone forcing is largely offset by negative aerosol direct forcing. Since aerosol reductions also lead to a reduced indirect effect, the global mean surface temperature warms by {approx}0.07 C by 2030 and {approx}0.13 C by 2050, adding 19% and 17%, respectively, to the warming induced by long-lived greenhouse gases. Regional direct forcings are large, up to 3.8 W/m{sup 2}. The ensemble-mean climate response shows little regional correlation with the spatial pattern of the forcing, however, suggesting that oceanic and atmospheric mixing generally overwhelms the effect of even large localized forcings. Exceptions are the polar regions, where ozone and aerosols may induce substantial seasonal climate changes.

  11. 182Hf-182W age dating of a 26Al-poor inclusion and implications for the origin of short-lived radioisotopes in the early Solar System.

    Science.gov (United States)

    Holst, Jesper C; Olsen, Mia B; Paton, Chad; Nagashima, Kazuhide; Schiller, Martin; Wielandt, Daniel; Larsen, Kirsten K; Connelly, James N; Jørgensen, Jes K; Krot, Alexander N; Nordlund, Ake; Bizzarro, Martin

    2013-05-28

    Refractory inclusions [calcium-aluminum-rich inclusions, (CAIs)] represent the oldest Solar System solids and provide information regarding the formation of the Sun and its protoplanetary disk. CAIs contain evidence of now extinct short-lived radioisotopes (e.g., (26)Al, (41)Ca, and (182)Hf) synthesized in one or multiple stars and added to the protosolar molecular cloud before or during its collapse. Understanding how and when short-lived radioisotopes were added to the Solar System is necessary to assess their validity as chronometers and constrain the birthplace of the Sun. Whereas most CAIs formed with the canonical abundance of (26)Al corresponding to (26)Al/(27)Al of ∼5 × 10(-5), rare CAIs with fractionation and unidentified nuclear isotope effects (FUN CAIs) record nucleosynthetic isotopic heterogeneity and (26)Al/(27)Al of Solar System, including the origin of short-lived radioisotopes. However, their chronology is unknown. Using the (182)Hf-(182)W chronometer, we show that a FUN CAI recording a condensation origin from a solar gas formed coevally with canonical CAIs, but with (26)Al/(27)Al of ∼3 × 10(-6). The decoupling between (182)Hf and (26)Al requires distinct stellar origins: steady-state galactic stellar nucleosynthesis for (182)Hf and late-stage contamination of the protosolar molecular cloud by a massive star(s) for (26)Al. Admixing of stellar-derived (26)Al to the protoplanetary disk occurred during the epoch of CAI formation and, therefore, the (26)Al-(26)Mg systematics of CAIs cannot be used to define their formation interval. In contrast, our results support (182)Hf homogeneity and chronological significance of the (182)Hf-(182)W clock.

  12. Freshly induced short-lived gamma-ray activity as a measure of fission rates in lightly re-irradiated spent fuel

    Energy Technology Data Exchange (ETDEWEB)

    Kroehnert, H., E-mail: hanna.kroehnert@psi.c [Paul Scherrer Institut (PSI), OPRA-E07, CH-5232 Villigen (Switzerland); Perret, G., E-mail: gregory.perret@psi.c [Paul Scherrer Institut (PSI), OPRA-E07, CH-5232 Villigen (Switzerland); Murphy, M.F., E-mail: mike.murphy@psi.c [Paul Scherrer Institut (PSI), OPRA-E07, CH-5232 Villigen (Switzerland); Chawla, R., E-mail: rakesh.chawla@epfl.c [Paul Scherrer Institut (PSI), OPRA-E07, CH-5232 Villigen (Switzerland); Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne (Switzerland)

    2010-12-01

    A new measurement technique has been developed to determine fission rates in burnt fuel, following re-irradiation in a zero-power research reactor. The development has been made in the frame of the LIFE-PROTEUS program at the Paul Scherrer Institute, which aims at characterizing the interfaces between fresh and highly burnt fuel assemblies in modern LWRs. To discriminate against the high intrinsic gamma-ray activity of the burnt fuel, the proposed measurement technique uses high-energy gamma-rays, above 2000 keV, emitted by short-lived fission products freshly produced in the fuel. To demonstrate the feasibility of this technique, a fresh UO{sub 2} sample and a 36 GWd/t burnt UO{sub 2} sample were irradiated in the PROTEUS reactor and their gamma-ray activities were recorded directly after irradiation. For both fresh and the burnt fuel samples, relative fission rates were derived for different core positions, based on the short-lived {sup 142}La (2542 keV), {sup 89}Rb (2570 keV), {sup 138}Cs (2640 keV) and {sup 95}Y (3576 keV) gamma-ray lines. Uncertainties on the inter-position fission rate ratios were mainly due to the uncertainties on the net-area of the gamma-ray peaks and were about 1-3% for the fresh sample, and 3-6% for the burnt one. Thus, for the first time, it has been shown that the short-lived gamma-ray activity, induced in burnt fuel by irradiation in a zero-power reactor, can be used as a quantitative measure of the fission rate. For both fresh and burnt fuel, the measured results agreed, within the uncertainties, with Monte Carlo (MCNPX) predictions.

  13. Regulatory proteins (inhibitors or activators) affect estimates of Msub(r) of enzymes and receptors by radiation inactivation

    International Nuclear Information System (INIS)

    Potier, M.; Giroux, S.

    1985-01-01

    The radiation-inactivation method allows the determination of the Msub(r) of enzymes and receptors by monitoring the decay of biological activity as a function of absorbed dose. The presence of regulatory or effector proteins (inhibitors or activators) associated with an enzyme or receptor, or released in the preparation after tissue homogenization, may affect the decay of biological activity. How the activity is affected, however, will depend on the type of inhibition (competitive or non-competitive), the inhibitor or activator concentration, the dissociation constant of the enzyme-effector system, and the effector Msub(r) relative to that of the enzyme. Since little is known on how effector proteins influence radiation inactivation of enzymes and receptors, we have considered a theoretical model in an effort to provide a framework for the interpretation of experimentally obtained data. Our model predicts that competitive and non-competitive inhibitors of enzymes could be distinguished by analysing irradiated samples with various substrate concentrations. Inhibitors will decrease whereas activators will increase the apparent target size of enzymes or receptors. (author)

  14. Regulation of steroid 5-{alpha} reductase type 2 (Srd5a2) by sterol regulatory element binding proteins and statin

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Young-Kyo [Department of Molecular Biology and Biochemistry, 3244 McGaugh Hall, University of California, UC Irvine, Irvine, CA 92697-3900 (United States); Zhu, Bing [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0144 (United States); Jeon, Tae-Il [Department of Molecular Biology and Biochemistry, 3244 McGaugh Hall, University of California, UC Irvine, Irvine, CA 92697-3900 (United States); Osborne, Timothy F., E-mail: tfosborn@uci.edu [Department of Molecular Biology and Biochemistry, 3244 McGaugh Hall, University of California, UC Irvine, Irvine, CA 92697-3900 (United States)

    2009-11-01

    In this study, we show that sterol regulatory element binding proteins (SREBPs) regulate expression of Srd5a2, an enzyme that catalyzes the irreversible conversion of testosterone to dihydroxytestosterone in the male reproductive tract and is highly expressed in androgen-sensitive tissues such as the prostate and skin. We show that Srd5a2 is induced in livers and prostate from mice fed a chow diet supplemented with lovastatin plus ezitimibe (L/E), which increases the activity of nuclear SREBP-2. The three fold increase in Srd5a2 mRNA mediated by L/E treatment was accompanied by the induction of SREBP-2 binding to the Srd5a2 promoter detected by a ChIP-chip assay in liver. We identified a SREBP-2 responsive region within the first 300 upstream bases of the mouse Srd5a2 promoter by co-transfection assays which contain a site that bound SREBP-2 in vitro by an EMSA. Srd5a2 protein was also induced in cells over-expressing SREBP-2 in culture. The induction of Srd5a2 through SREBP-2 provides a mechanistic explanation for why even though statin therapy is effective in reducing cholesterol levels in treating hypercholesterolemia it does not compromise androgen production in clinical studies.

  15. Protein Arginine Methyltransferase 5 Inhibition Upregulates Foxp3+ Regulatory T Cells Frequency and Function during the Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Yingxia Zheng

    2017-05-01

    Full Text Available Ulcerative colitis (UC pathogenesis is related to imbalance of immune responses, and the equilibrium between inflammatory T cells and Foxp3+ regulatory T cells (Tregs plays an important role in the intestinal homeostasis. Protein arginine methyltransferases (PRMTs regulate chromatin remodeling and gene expression. Here, we investigated whether inhibition of PRMTs affects colitis pathogenesis in mice and inflammatory bowel disease patients and further explored the underlying mechanisms. In this study, we found that protein arginine N-methyltransferase inhibitor 1 (AMI-1 treatments increased Tregs frequency, function, and reduced colitis incidence. Adoptive transfer of AMI-1-treated Tregs could reduce the colitis incidence. Colitis was associated with increased local PRMT5 expression, which was inhibited by AMI-1 treatment. Additionally, PRMT5 knockdown T cells produced a better response to TGFβ and promoted Tregs differentiation through decreased DNA methyltransferase 1 (DNMT1 expression. PRMT5 also enhanced H3K27me3 and DNMT1 binding to Foxp3 promoter, which restricted Tregs differentiation. Furthermore, PRMT5 knockdown led to decreased Foxp3 promoter methylation during Tregs induction. PRMT5 expression had a negative relationship with Tregs in UC patients, knockdown of PRMT5 expression increased Tregs frequency and decreased TNFα, IL-6, and IL-13 levels. Our study outlines a novel regulation of PRMT5 on Tregs development and function. Strategies to decrease PRMT5 expression might have therapeutic potential to control UC.

  16. Regulation of steroid 5-α reductase type 2 (Srd5a2) by sterol regulatory element binding proteins and statin

    International Nuclear Information System (INIS)

    Seo, Young-Kyo; Zhu, Bing; Jeon, Tae-Il; Osborne, Timothy F.

    2009-01-01

    In this study, we show that sterol regulatory element binding proteins (SREBPs) regulate expression of Srd5a2, an enzyme that catalyzes the irreversible conversion of testosterone to dihydroxytestosterone in the male reproductive tract and is highly expressed in androgen-sensitive tissues such as the prostate and skin. We show that Srd5a2 is induced in livers and prostate from mice fed a chow diet supplemented with lovastatin plus ezitimibe (L/E), which increases the activity of nuclear SREBP-2. The three fold increase in Srd5a2 mRNA mediated by L/E treatment was accompanied by the induction of SREBP-2 binding to the Srd5a2 promoter detected by a ChIP-chip assay in liver. We identified a SREBP-2 responsive region within the first 300 upstream bases of the mouse Srd5a2 promoter by co-transfection assays which contain a site that bound SREBP-2 in vitro by an EMSA. Srd5a2 protein was also induced in cells over-expressing SREBP-2 in culture. The induction of Srd5a2 through SREBP-2 provides a mechanistic explanation for why even though statin therapy is effective in reducing cholesterol levels in treating hypercholesterolemia it does not compromise androgen production in clinical studies.

  17. Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells.

    Science.gov (United States)

    Kim, You-Mie; Song, Insun; Seo, Yong-Hak; Yoon, Gyesoon

    2013-12-01

    Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 µM) of deferoxamine (DFO) and H2O2. In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3α (GSK3α) and β corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3α and β also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.

  18. Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR.

    Science.gov (United States)

    Lee, Soon Goo; Krishnan, Hari B; Jez, Joseph M

    2014-04-29

    The symbiosis between rhizobial microbes and host plants involves the coordinated expression of multiple genes, which leads to nodule formation and nitrogen fixation. As part of the transcriptional machinery for nodulation and symbiosis across a range of Rhizobium, NolR serves as a global regulatory protein. Here, we present the X-ray crystal structures of NolR in the unliganded form and complexed with two different 22-base pair (bp) double-stranded operator sequences (oligos AT and AA). Structural and biochemical analysis of NolR reveals protein-DNA interactions with an asymmetric operator site and defines a mechanism for conformational switching of a key residue (Gln56) to accommodate variation in target DNA sequences from diverse rhizobial genes for nodulation and symbiosis. This conformational switching alters the energetic contributions to DNA binding without changes in affinity for the target sequence. Two possible models for the role of NolR in the regulation of different nodulation and symbiosis genes are proposed. To our knowledge, these studies provide the first structural insight on the regulation of genes involved in the agriculturally and ecologically important symbiosis of microbes and plants that leads to nodule formation and nitrogen fixation.

  19. A general dead-time correction method based on live-time stamping. Application to the measurement of short-lived radionuclides.

    Science.gov (United States)

    Chauvenet, B; Bobin, C; Bouchard, J

    2017-12-01

    Dead-time correction formulae are established in the general case of superimposed non-homogeneous Poisson processes. Based on the same principles as conventional live-timed counting, this method exploits the additional information made available using digital signal processing systems, and especially the possibility to store the time stamps of live-time intervals. No approximation needs to be made to obtain those formulae. Estimates of the variances of corrected rates are also presented. This method is applied to the activity measurement of short-lived radionuclides. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Measurement of formation cross sections producing short-lived nuclei by 14 MeV neutrons. Pr, Ba, Ce, Sm, W, Sn, Hf

    International Nuclear Information System (INIS)

    Murahira, S.; Satoh, Y.; Honda, N.; Shibata, M.; Yamamoto, H.; Kawade, K.; Takahashi, A.; Iida, T.

    1996-01-01

    Thirteen neutron activation cross sections for (n,2n), (n,p), (n,np) and (n,α) reactions producing short-lived nuclei with half-lives between 56 s and 24 min were measured in the energy range from 13.4 MeV to 14.9 MeV for Pr, Ba, Ce, Sm, W, Sn and Hf. The cross sections of 179 Hf(n,np) 178m Lu and 180 Hf(n,p) 180 Lu were measured for the first time. (author)

  1. Antioxidant and regulatory role of mitochondrial uncoupling protein UCP2 in pancreatic beta-cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Olejár, Tomáš; Smolková, Katarína; Ježek, Jan; Dlasková, Andrea; Plecitá-Hlavatá, Lydie; Zelenka, Jaroslav; Špaček, Tomáš; Engstová, Hana; Reguera Pajuelo, David; Jabůrek, Martin

    2014-01-01

    Roč. 63, Suppl.1 (2014), S73-S91 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GAP305/12/1247; GA ČR(CZ) GPP304/10/P204; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : mitochondria * uncoupling protein UCP2 * pancreatic beta-cells * reactive oxygen species * glucose-stimulated insulin secretion Subject RIV: EA - Cell Biology Impact factor: 1.293, year: 2014

  2. Altered expression of the cell cycle regulatory protein cyclin D1 in the rat dentate gyrus after adrenalectomy-induced granular cell lass

    NARCIS (Netherlands)

    Postigo, JA; Van der Werf, YD; Korf, J; Krugers, HJ

    1998-01-01

    The loss of dentate gyrus (DG) granular cells after removal of the rat adrenal glands (ADX) is mediated by a process that is apoptotic in nature. The present study was initiated to compare changes in the immunocytochemical distribution of the cell-cycle regulatory protein cyclin D1, which has been

  3. Sterol regulatory element binding protein 2 overexpression is associated with reduced adipogenesis and ectopic fat accumulation in transgenic spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Trnovská, J.; Kazdová, L.; Pravenec, Michal

    2014-01-01

    Roč. 63, č. 5 (2014), s. 587-590 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH12061 Institutional support: RVO:67985823 Keywords : sterol regulatory element binding protein 2 * transgenic * spontaneously hypertensive rat * lipid metabolism Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

  4. A widespread amino acid polymorphism at codon 905 of the glycogen-associated regulatory subunit of protein phosphatase-1 is associated with insulin resistance and hypersecretion of insulin

    DEFF Research Database (Denmark)

    Hansen, L; Hansen, T; Vestergaard, H

    1995-01-01

    The regulatory G-subunit of the glycogen-associated form of protein phosphatase 1 (PP1) plays a crucial part in muscle tissue glycogen synthesis and breakdown. As impaired insulin stimulated glycogen synthesis in peripheral tissues is considered to be a pathogenic factor in subsets of non-insulin...

  5. A novel Snf2 protein maintains trans-generational regulatory states established by paramutation in maize.

    Directory of Open Access Journals (Sweden)

    Christopher J Hale

    2007-10-01

    Full Text Available Paramutations represent heritable epigenetic alterations that cause departures from Mendelian inheritance. While the mechanism responsible is largely unknown, recent results in both mouse and maize suggest paramutations are correlated with RNA molecules capable of affecting changes in gene expression patterns. In maize, multiple required to maintain repression (rmr loci stabilize these paramutant states. Here we show rmr1 encodes a novel Snf2 protein that affects both small RNA accumulation and cytosine methylation of a proximal transposon fragment at the Pl1-Rhoades allele. However, these cytosine methylation differences do not define the various epigenetic states associated with paramutations. Pedigree analyses also show RMR1 does not mediate the allelic interactions that typically establish paramutations. Strikingly, our mutant analyses show that Pl1-Rhoades RNA transcript levels are altered independently of transcription rates, implicating a post-transcriptional level of RMR1 action. These results suggest the RNA component of maize paramutation maintains small heterochromatic-like domains that can affect, via the activity of a Snf2 protein, the stability of nascent transcripts from adjacent genes by way of a cotranscriptional repression process. These findings highlight a mechanism by which alleles of endogenous loci can acquire novel expression patterns that are meiotically transmissible.

  6. Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis.

    Science.gov (United States)

    Reinecke, James B; Katafiasz, Dawn; Naslavsky, Naava; Caplan, Steve

    2015-01-01

    During interphase, recycling endosomes mediate the transport of internalized cargo back to the plasma membrane. However, in mitotic cells, recycling endosomes are essential for the completion of cytokinesis, the last phase of mitosis that promotes the physical separation the two daughter cells. Despite recent advances, our understanding of the molecular determinants that regulate recycling endosome dynamics during cytokinesis remains incomplete. We have previously demonstrated that Molecule Interacting with CasL Like-1 (MICAL-L1) and C-terminal Eps15 Homology Domain protein 1 (EHD1) coordinately regulate receptor transport from tubular recycling endosomes during interphase. However, their potential roles in controlling cytokinesis had not been addressed. In this study, we show that MICAL-L1 and EHD1 regulate mitosis. Depletion of either protein resulted in increased numbers of bi-nucleated cells. We provide evidence that bi-nucleation in MICAL-L1- and EHD1-depleted cells is a consequence of impaired recycling endosome transport during late cytokinesis. However, depletion of MICAL-L1, but not EHD1, resulted in aberrant chromosome alignment and lagging chromosomes, suggesting an EHD1-independent function for MICAL-L1 earlier in mitosis. Moreover, we provide evidence that MICAL-L1 and EHD1 differentially influence microtubule dynamics during early and late mitosis. Collectively, our new data suggest several unanticipated roles for MICAL-L1 and EHD1 during the cell cycle. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Perilipin-mediated lipid droplet formation in adipocytes promotes sterol regulatory element-binding protein-1 processing and triacylglyceride accumulation.

    Directory of Open Access Journals (Sweden)

    Yu Takahashi

    Full Text Available Sterol regulatory element-binding protein-1 (SREBP-1 has been thought to be a critical factor that assists adipogenesis. During adipogenesis SREBP-1 stimulates lipogenic gene expression, and peroxisome proliferator-activated receptor γ (PPARγ enhances perilipin (plin gene expression, resulting in generating lipid droplets (LDs to store triacylglycerol (TAG in adipocytes. Plin coats adipocyte LDs and protects them from lipolysis. Here we show in white adipose tissue (WAT of plin-/- mice that nuclear active SREBP-1 and its target gene expression, but not nuclear SREBP-2, significantly decreased on attenuated LD formation. When plin-/- mouse embryonic fibroblasts (MEFs differentiated into adipocytes, attenuated LDs were formed and nuclear SREBP-1 decreased, but enforced plin expression restored them to their original state. Since LDs are largely derived from the endoplasmic reticulum (ER, alterations in the ER cholesterol content were investigated during adipogenesis of 3T3-L1 cells. The ER cholesterol greatly reduced in differentiated adipocytes. The ER cholesterol level in plin-/- WAT was significantly higher than that of wild-type mice, suggesting that increased LD formation caused a change in ER environment along with a decrease in cholesterol. When GFP-SREBP-1 fusion proteins were exogenously expressed in 3T3-L1 cells, a mutant protein lacking the S1P cleavage site was poorly processed during adipogenesis, providing evidence of the increased canonical pathway for SREBP processing in which SREBP-1 is activated by two cleavage enzymes in the Golgi. Therefore, LD biogenesis may create the ER microenvironment favorable for SREBP-1 activation. We describe the novel interplay between LD formation and SREBP-1 activation through a positive feedback loop.

  8. Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression

    International Nuclear Information System (INIS)

    Myllymaeki, S.A.; Karjalainen, M.; Haavisto, T.E.; Toppari, J.; Paranko, J.

    2005-01-01

    Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening

  9. The function of the RNA-binding protein TEL1 in moss reveals ancient regulatory mechanisms of shoot development.

    Science.gov (United States)

    Vivancos, Julien; Spinner, Lara; Mazubert, Christelle; Charlot, Florence; Paquet, Nicolas; Thareau, Vincent; Dron, Michel; Nogué, Fabien; Charon, Céline

    2012-03-01

    The shoot represents the basic body plan in land plants. It consists of a repeated structure composed of stems and leaves. Whereas vascular plants generate a shoot in their diploid phase, non-vascular plants such as mosses form a shoot (called the gametophore) in their haploid generation. The evolution of regulatory mechanisms or genetic networks used in the development of these two kinds of shoots is unclear. TERMINAL EAR1-like genes have been involved in diploid shoot development in vascular plants. Here, we show that disruption of PpTEL1 from the moss Physcomitrella patens, causes reduced protonema growth and gametophore initiation, as well as defects in gametophore development. Leafy shoots formed on ΔTEL1 mutants exhibit shorter stems with more leaves per shoot, suggesting an accelerated leaf initiation (shortened plastochron), a phenotype shared with the Poaceae vascular plants TE1 and PLA2/LHD2 mutants. Moreover, the positive correlation between plastochron length and leaf size observed in ΔTEL1 mutants suggests a conserved compensatory mechanism correlating leaf growth and leaf initiation rate that would minimize overall changes in plant biomass. The RNA-binding protein encoded by PpTEL1 contains two N-terminus RNA-recognition motifs, and a third C-terminus non-canonical RRM, specific to TEL proteins. Removal of the PpTEL1 C-terminus (including this third RRM) or only 16-18 amino acids within it seriously impairs PpTEL1 function, suggesting a critical role for this third RRM. These results show a conserved function of the RNA-binding PpTEL1 protein in the regulation of shoot development, from early ancestors to vascular plants, that depends on the third TEL-specific RRM.

  10. Multiple regulatory roles of the mouse transmembrane adaptor protein NTAL in gene transcription and mast cell physiology.

    Directory of Open Access Journals (Sweden)

    Iva Polakovicova

    Full Text Available Non-T cell activation linker (NTAL; also called LAB or LAT2 is a transmembrane adaptor protein that is expressed in a subset of hematopoietic cells, including mast cells. There are conflicting reports on the role of NTAL in the high affinity immunoglobulin E receptor (FcεRI signaling. Studies carried out on mast cells derived from mice with NTAL knock out (KO and wild type mice suggested that NTAL is a negative regulator of FcεRI signaling, while experiments with RNAi-mediated NTAL knockdown (KD in human mast cells and rat basophilic leukemia cells suggested its positive regulatory role. To determine whether different methodologies of NTAL ablation (KO vs KD have different physiological consequences, we compared under well defined conditions FcεRI-mediated signaling events in mouse bone marrow-derived mast cells (BMMCs with NTAL KO or KD. BMMCs with both NTAL KO and KD exhibited enhanced degranulation, calcium mobilization, chemotaxis, tyrosine phosphorylation of LAT and ERK, and depolymerization of filamentous actin. These data provide clear evidence that NTAL is a negative regulator of FcεRI activation events in murine BMMCs, independently of possible compensatory developmental alterations. To gain further insight into the role of NTAL in mast cells, we examined the transcriptome profiles of resting and antigen-activated NTAL KO, NTAL KD, and corresponding control BMMCs. Through this analysis we identified several genes that were differentially regulated in nonactivated and antigen-activated NTAL-deficient cells, when compared to the corresponding control cells. Some of the genes seem to be involved in regulation of cholesterol-dependent events in antigen-mediated chemotaxis. The combined data indicate multiple regulatory roles of NTAL in gene expression and mast cell physiology.

  11. The Endocytic Recycling Regulatory Protein EHD1 Is Required for Ocular Lens Development

    Science.gov (United States)

    Arya, Priyanka; Rainey, Mark A.; Bhattacharyya, Sohinee; Mohapatra, Bhopal; George, Manju; Kuracha, Murali R; Storck, Matthew D.; Band, Vimla; Govindarajan, Venkatesh; Band, Hamid

    2015-01-01

    The C-terminal Eps15 homology domain-containing (EHD) proteins play a key role in endocytic recycling, a fundamental cellular process that ensures the return of endocytosed membrane components and receptors back to the cell surface. To define the in vivo biological functions of EHD1, we have generated Ehd1 knockout mice and previously reported a requirement of EHD1 for spermatogenesis. Here, we show that approximately 56% of the Ehd1-null mice displayed gross ocular abnormalities, including anophthalmia, aphakia, microphthalmia and congenital cataracts. Histological characterization of ocular abnormalities showed pleiotropic defects that include a smaller or absent lens, persistence of lens stalk and hyaloid vasculature, and deformed optic cups. To test whether these profound ocular defects resulted from the loss of EHD1 in the lens or in non-lenticular tissues, we deleted the Ehd1 gene selectively in the presumptive lens ectoderm using Le-Cre. Conditional Ehd1 deletion in the lens resulted in developmental defects that included thin epithelial layers, small lenses and absence of corneal endothelium. Ehd1 deletion in the lens also resulted in reduced lens epithelial proliferation, survival and expression of junctional proteins E-cadherin and ZO-1. Finally, Le-Cre-mediated deletion of Ehd1 in the lens led to defects in corneal endothelial differentiation. Taken together, these data reveal a unique role for EHD1 in early lens development and suggest a previously unknown link between the endocytic recycling pathway and regulation of key developmental processes including proliferation, differentiation and morphogenesis. PMID:26455409

  12. Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Zhonghua; Qiao, Ling; Zhou, Yan [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada); Babiuk, Lorne A. [University of Alberta, Edmonton, Alberta (Canada); Liu, Qiang, E-mail: qiang.liu@usask.ca [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada)

    2010-11-19

    Research highlights: {yields} A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone. {yields} HCV-3a NS5A increases mature SREBP-1c protein level. {yields} HCV-3a NS5A activates SREBP-1c transcription. {yields} Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation. {yields} Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A. -- Abstract: Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that the nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.

  13. Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1

    International Nuclear Information System (INIS)

    Xiang, Zhonghua; Qiao, Ling; Zhou, Yan; Babiuk, Lorne A.; Liu, Qiang

    2010-01-01

    Research highlights: → A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone. → HCV-3a NS5A increases mature SREBP-1c protein level. → HCV-3a NS5A activates SREBP-1c transcription. → Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation. → Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A. -- Abstract: Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that the nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.

  14. Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian, E-mail: jianzhou@scut.edu.cn

    2016-07-30

    Graphical abstract: Preferential adsorption of Vpr13-33 on graphene accompanied by early conformational change from α-helix to β-sheet structures was observed by molecular simulations. This work presents the molecular mechanism of graphene-induced peptide conformational alteration and sheds light on developing graphene-based materials to inhibit HIV. - Highlights: • Graphene induced early structural transition of Vpr13-33 is studied by MD simulations. • Both π-π stacking and hydrophobic interactions orchestrate the peptide adsorption. • Vpr has an increased propensity of β-sheet content on graphene surface. • To develop graphene-based materials to inhibit HIV is possible. - Abstract: The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of

  15. Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

    International Nuclear Information System (INIS)

    Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian

    2016-01-01

    Graphical abstract: Preferential adsorption of Vpr13-33 on graphene accompanied by early conformational change from α-helix to β-sheet structures was observed by molecular simulations. This work presents the molecular mechanism of graphene-induced peptide conformational alteration and sheds light on developing graphene-based materials to inhibit HIV. - Highlights: • Graphene induced early structural transition of Vpr13-33 is studied by MD simulations. • Both π-π stacking and hydrophobic interactions orchestrate the peptide adsorption. • Vpr has an increased propensity of β-sheet content on graphene surface. • To develop graphene-based materials to inhibit HIV is possible. - Abstract: The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of

  16. Absence of residual structure in the intrinsically disordered regulatory protein CP12 in its reduced state

    Energy Technology Data Exchange (ETDEWEB)

    Launay, Hélène; Barré, Patrick [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France); Puppo, Carine [Aix-Marseille Université, Centre National de la Recherche Scientifique, UMR 7281, Laboratoire de Bioénergétique et Ingénierie des Protéines, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 20 (France); Manneville, Stéphanie [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France); Gontero, Brigitte [Aix-Marseille Université, Centre National de la Recherche Scientifique, UMR 7281, Laboratoire de Bioénergétique et Ingénierie des Protéines, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 20 (France); Receveur-Bréchot, Véronique, E-mail: veronique.brechot@inserm.fr [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France)

    2016-08-12

    The redox switch protein CP12 is a key player of the regulation of the Benson–Calvin cycle. Its oxidation state is controlled by the formation/dissociation of two intramolecular disulphide bridges during the day/night cycle. CP12 was known to be globally intrinsically disordered on a large scale in its reduced state, while being partly ordered in the oxidised state. By combining Nuclear Magnetic Resonance and Small Angle X-ray Scattering experiments, we showed that, contrary to secondary structure or disorder predictions, reduced CP12 is fully disordered, with no transient or local residual structure likely to be precursor of the structures identified in the oxidised active state and/or in the bound state with GAPDH or PRK. These results highlight the diversity of the mechanisms of regulation of conditionally disordered redox switches, and question the stability of oxidised CP12 scaffold. - Highlights: • CP12 is predicted to form two helices in its N-terminal sequence. • Reduced CP12 is disordered as a random coil according to SAXS. • Limited or no transient structures are observed in reduced CP12 by NMR.

  17. Whole Genome Shotgun Sequencing Shows Selection on Leptospira Regulatory Proteins during in vitro Culture Attenuation

    Science.gov (United States)

    Lehmann, Jason S.; Corey, Victoria C.; Ricaldi, Jessica N.; Vinetz, Joseph M.; Winzeler, Elizabeth A.; Matthias, Michael A.

    2016-01-01

    Leptospirosis is the most common zoonotic disease worldwide with an estimated 500,000 severe cases reported annually, and case fatality rates of 12–25%, due primarily to acute kidney and lung injuries. Despite its prevalence, the molecular mechanisms underlying leptospirosis pathogenesis remain poorly understood. To identify virulence-related genes in Leptospira interrogans, we delineated cumulative genome changes that occurred during serial in vitro passage of a highly virulent strain of L. interrogans serovar Lai into a nearly avirulent isogenic derivative. Comparison of protein coding and computationally predicted noncoding RNA (ncRNA) genes between these two polyclonal strains identified 15 nonsynonymous single nucleotide variant (nsSNV) alleles that increased in frequency and 19 that decreased, whereas no changes in allelic frequency were observed among the ncRNA genes. Some of the nsSNV alleles were in six genes shown previously to be transcriptionally upregulated during exposure to in vivo-like conditions. Five of these nsSNVs were in evolutionarily conserved positions in genes related to signal transduction and metabolism. Frequency changes of minor nsSNV alleles identified in this study likely contributed to the loss of virulence during serial in vitro culture. The identification of new virulence-associated genes should spur additional experimental inquiry into their potential role in Leptospira pathogenesis. PMID:26711524

  18. Absence of residual structure in the intrinsically disordered regulatory protein CP12 in its reduced state

    International Nuclear Information System (INIS)

    Launay, Hélène; Barré, Patrick; Puppo, Carine; Manneville, Stéphanie; Gontero, Brigitte; Receveur-Bréchot, Véronique

    2016-01-01

    The redox switch protein CP12 is a key player of the regulation of the Benson–Calvin cycle. Its oxidation state is controlled by the formation/dissociation of two intramolecular disulphide bridges during the day/night cycle. CP12 was known to be globally intrinsically disordered on a large scale in its reduced state, while being partly ordered in the oxidised state. By combining Nuclear Magnetic Resonance and Small Angle X-ray Scattering experiments, we showed that, contrary to secondary structure or disorder predictions, reduced CP12 is fully disordered, with no transient or local residual structure likely to be precursor of the structures identified in the oxidised active state and/or in the bound state with GAPDH or PRK. These results highlight the diversity of the mechanisms of regulation of conditionally disordered redox switches, and question the stability of oxidised CP12 scaffold. - Highlights: • CP12 is predicted to form two helices in its N-terminal sequence. • Reduced CP12 is disordered as a random coil according to SAXS. • Limited or no transient structures are observed in reduced CP12 by NMR.

  19. MAR binding protein SMAR1 favors IL-10 mediated regulatory T cell function in acute colitis

    International Nuclear Information System (INIS)

    Mirlekar, Bhalchandra; Patil, Sachin; Bopanna, Ramanamurthy; Chattopadhyay, Samit

    2015-01-01

    T reg cells are not only crucial for controlling immune responses to autoantigens but also prevent those directed towards commensal pathogens. Control of effector immune responses by T reg cells depend on their capacity to accumulate at inflammatory site and accordingly accommodate to inflammatory environment. Till date, the factors associated with maintaining these aspects of T reg phenotype is not understood properly. Here we have shown that a known nuclear matrix binding protein SMAR1 is selectively expressed more in colonic T reg cells and is required for their ability to accumulate at inflammatory site and to sustain high levels of Foxp3 and IL-10 expression during acute colitis. Elimination of anti-inflammatory subsets revealed a protective role for IL-10 producing T reg cells in SMAR1 −/− mice. Moreover, a combined action of Foxp3 and SMAR1 restricts effector cytokine production and enhance the production of IL-10 by colonic T reg cells that controls acute colitis. This data highlights a critical role of SMAR1 in maintaining T reg physiology during inflammatory disorders. - Highlights: • SMAR1 is essential to sustain high level of Foxp3 and IL-10 in T reg cells. • SMAR1 −/− T reg cells produce pro-inflammatory cytokine IL-17 leads to inflammation. • IL-10 administration can control the inflammation in SMAR1 −/− mice. • Both Foxp3 and SMAR1 maintain T reg phenotype that controls colitis

  20. Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types

    Science.gov (United States)

    Jereb, Saša; Hwang, Hun-Way; Van Otterloo, Eric; Govek, Eve-Ellen; Fak, John J; Yuan, Yuan; Hatten, Mary E

    2018-01-01

    Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the principal types of mouse cerebellar neurons, the Purkinje and granule cells, as well as between proliferating and differentiated granule cells. Transcripts that differed in APA in these comparisons were enriched in key neuronal functions and many differed in coding sequence in addition to 3’UTR length. We characterize Memo1, a transcript that shifted from expressing a short 3’UTR isoform to a longer one during granule cell differentiation. We show that Memo1 regulates granule cell precursor proliferation and that its long 3’UTR isoform is targeted by miR-124, contributing to its downregulation during development. Our findings provide insight into roles for APA in specific cell types and establish a platform for further functional studies. PMID:29578408

  1. MAR binding protein SMAR1 favors IL-10 mediated regulatory T cell function in acute colitis

    Energy Technology Data Exchange (ETDEWEB)

    Mirlekar, Bhalchandra; Patil, Sachin [Chromatin and Disease Biology Laboratory, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Bopanna, Ramanamurthy [Experimental Animal Facility, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India); Chattopadhyay, Samit, E-mail: samit@nccs.res.in [Chromatin and Disease Biology Laboratory, National Centre for Cell Science, Ganeshkhind, Pune 411007 (India)

    2015-08-21

    T{sub reg} cells are not only crucial for controlling immune responses to autoantigens but also prevent those directed towards commensal pathogens. Control of effector immune responses by T{sub reg} cells depend on their capacity to accumulate at inflammatory site and accordingly accommodate to inflammatory environment. Till date, the factors associated with maintaining these aspects of T{sub reg} phenotype is not understood properly. Here we have shown that a known nuclear matrix binding protein SMAR1 is selectively expressed more in colonic T{sub reg} cells and is required for their ability to accumulate at inflammatory site and to sustain high levels of Foxp3 and IL-10 expression during acute colitis. Elimination of anti-inflammatory subsets revealed a protective role for IL-10 producing T{sub reg} cells in SMAR1{sup −/−} mice. Moreover, a combined action of Foxp3 and SMAR1 restricts effector cytokine production and enhance the production of IL-10 by colonic T{sub reg} cells that controls acute colitis. This data highlights a critical role of SMAR1 in maintaining T{sub reg} physiology during inflammatory disorders. - Highlights: • SMAR1 is essential to sustain high level of Foxp3 and IL-10 in T{sub reg} cells. • SMAR1{sup −/−} T{sub reg} cells produce pro-inflammatory cytokine IL-17 leads to inflammation. • IL-10 administration can control the inflammation in SMAR1{sup −/−} mice. • Both Foxp3 and SMAR1 maintain T{sub reg} phenotype that controls colitis.

  2. The HTLV-1 Tax protein binding domain of cyclin-dependent kinase 4 (CDK4 includes the regulatory PSTAIRE helix

    Directory of Open Access Journals (Sweden)

    Grassmann Ralph

    2005-09-01

    Full Text Available Abstract Background The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1 is leukemogenic in transgenic mice and induces permanent T-cell growth in vitro. It is found in active CDK holoenzyme complexes from adult T-cell leukemia-derived cultures and stimulates the G1- to-S phase transition by activating the cyclin-dependent kinase (CDK CDK4. The Tax protein directly and specifically interacts with CDK4 and cyclin D2 and binding is required for enhanced CDK4 kinase activity. The protein-protein contact between Tax and the components of the cyclin D/CDK complexes increases the association of CDK4 and its positive regulatory subunit cyclin D and renders the complex resistant to p21CIP inhibition. Tax mutants affecting the N-terminus cannot bind cyclin D and CDK4. Results To analyze, whether the N-terminus of Tax is capable of CDK4-binding, in vitro binding -, pull down -, and mammalian two-hybrid analyses were performed. These experiments revealed that a segment of 40 amino acids is sufficient to interact with CDK4 and cyclin D2. To define a Tax-binding domain and analyze how Tax influences the kinase activity, a series of CDK4 deletion mutants was tested. Different assays revealed two regions which upon deletion consistently result in reduced binding activity. These were isolated and subjected to mammalian two-hybrid analysis to test their potential to interact with the Tax N-terminus. These experiments concurrently revealed binding at the N- and C-terminus of CDK4. The N-terminal segment contains the PSTAIRE helix, which is known to control the access of substrate to the active cleft of CDK4 and thus the kinase activity. Conclusion Since the N- and C-terminus of CDK4 are neighboring in the predicted three-dimensional protein structure, it is conceivable that they comprise a single binding domain, which interacts with the Tax N-terminus.

  3. Induction of tumor cell death through targeting tubulin and evoking dysregulation of cell cycle regulatory proteins by multifunctional cinnamaldehydes.

    Directory of Open Access Journals (Sweden)

    Amrita A Nagle

    Full Text Available Multifunctional trans-cinnamaldehyde (CA and its analogs display anti-cancer properties, with 2-benzoyloxycinnamaldehyde (BCA and 5-fluoro-2-hydroxycinnamaldehyde (FHCA being identified as the ortho-substituted analogs that possess potent anti-tumor activities. In this study, BCA, FHCA and a novel analog 5-fluoro-2-benzoyloxycinnamaldehyde (FBCA, were demonstrated to decrease growth and colony formation of human colon-derived HCT 116 and mammary-derived MCF-7 carcinoma cells under non-adhesive conditions. The 2-benzoyloxy and 5-fluoro substituents rendered FBCA more potent than BCA and equipotent to FHCA. The cellular events by which these cinnamaldehydes caused G(2/M phase arrest and halted proliferation of HCT 116 cells were thereby investigated. Lack of significant accumulation of mitosis marker phospho-histone H3 in cinnamaldehyde-treated cells indicated that the analogs arrested cells in G(2 phase. G(2 arrest was brought about partly by cinnamaldehyde-mediated depletion of cell cycle proteins involved in regulating G(2 to M transition and spindle assembly, namely cdk1, cdc25C, mad2, cdc20 and survivin. Cyclin B1 levels were found to be increased, which in the absence of active cdk1, would fail to drive cells into M phase. Concentrations of cinnamaldehydes that brought about dysregulation of levels of cell cycle proteins also caused tubulin aggregation, as evident from immunodetection of dose-dependent tubulin accumulation in the insoluble cell lysate fractions. In a cell-free system, reduced biotin-conjugated iodoacetamide (BIAM labeling of tubulin protein pretreated with cinnamaldehydes was indicative of drug interaction with the sulfhydryl groups in tubulin. In conclusion, cinnamaldehydes treatment at proapoptotic concentrations caused tubulin aggregation and dysegulation of cell cycle regulatory proteins cdk1 and cdc25C that contributed at least in part to arresting cells at G(2 phase, resulting in apoptotic cell death characterized by

  4. Induction of tumor cell death through targeting tubulin and evoking dysregulation of cell cycle regulatory proteins by multifunctional cinnamaldehydes.

    Science.gov (United States)

    Nagle, Amrita A; Gan, Fei-Fei; Jones, Gavin; So, Choon-Leng; Wells, Geoffrey; Chew, Eng-Hui

    2012-01-01

    Multifunctional trans-cinnamaldehyde (CA) and its analogs display anti-cancer properties, with 2-benzoyloxycinnamaldehyde (BCA) and 5-fluoro-2-hydroxycinnamaldehyde (FHCA) being identified as the ortho-substituted analogs that possess potent anti-tumor activities. In this study, BCA, FHCA and a novel analog 5-fluoro-2-benzoyloxycinnamaldehyde (FBCA), were demonstrated to decrease growth and colony formation of human colon-derived HCT 116 and mammary-derived MCF-7 carcinoma cells under non-adhesive conditions. The 2-benzoyloxy and 5-fluoro substituents rendered FBCA more potent than BCA and equipotent to FHCA. The cellular events by which these cinnamaldehydes caused G(2)/M phase arrest and halted proliferation of HCT 116 cells were thereby investigated. Lack of significant accumulation of mitosis marker phospho-histone H3 in cinnamaldehyde-treated cells indicated that the analogs arrested cells in G(2) phase. G(2) arrest was brought about partly by cinnamaldehyde-mediated depletion of cell cycle proteins involved in regulating G(2) to M transition and spindle assembly, namely cdk1, cdc25C, mad2, cdc20 and survivin. Cyclin B1 levels were found to be increased, which in the absence of active cdk1, would fail to drive cells into M phase. Concentrations of cinnamaldehydes that brought about dysregulation of levels of cell cycle proteins also caused tubulin aggregation, as evident from immunodetection of dose-dependent tubulin accumulation in the insoluble cell lysate fractions. In a cell-free system, reduced biotin-conjugated iodoacetamide (BIAM) labeling of tubulin protein pretreated with cinnamaldehydes was indicative of drug interaction with the sulfhydryl groups in tubulin. In conclusion, cinnamaldehydes treatment at proapoptotic concentrations caused tubulin aggregation and dysegulation of cell cycle regulatory proteins cdk1 and cdc25C that contributed at least in part to arresting cells at G(2) phase, resulting in apoptotic cell death characterized by emergence

  5. Glucokinase regulatory protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Pablo Perez-Martinez

    Full Text Available Glucokinase Regulatory Protein (GCKR plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS risk.To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP and n-3 PUFA in MetS subjects.Homeostasis model assessment of insulin resistance (HOMA-IR, HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019, C-peptide (P = 0.004, HOMA-IR (P = 0.008 and CRP (P = 0.032 as compared with subjects carrying the minor T-allele (Leu446. In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.ClinicalTrials.gov NCT00429195.

  6. Identification of Rbd2 as a candidate protease for sterol regulatory element binding protein (SREBP) cleavage in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinsil; Ha, Hye-Jeong [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Kim, Sujin [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113 (Korea, Republic of); Choi, Ah-Reum [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Lee, Sook-Jeong [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Hoe, Kwang-Lae, E-mail: kwanghoe@cnu.ac.kr [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Kim, Dong-Uk, E-mail: kimdongu@kribb.re.kr [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of)

    2015-12-25

    Lipid homeostasis in mammalian cells is regulated by sterol regulatory element-binding protein (SREBP) transcription factors that are activated through sequential cleavage by Golgi Site-1 and Site-2 proteases. Fission yeast SREBP, Sre1, engages a different mechanism involving the Golgi Dsc E3 ligase complex, but it is not clearly understood exactly how Sre1 is proteolytically cleaved and activated. In this study, we screened the Schizosaccharomyces pombe non-essential haploid deletion collection to identify missing components of the Sre1 cleavage machinery. Our screen identified an additional component of the SREBP pathway required for Sre1 proteolysis named rhomboid protein 2 (Rbd2). We show that an rbd2 deletion mutant fails to grow under hypoxic and hypoxia-mimetic conditions due to lack of Sre1 activity and that this growth phenotype is rescued by Sre1N, a cleaved active form of Sre1. We found that the growth inhibition phenotype under low oxygen conditions is specific to the strain with deletion of rbd2, not any other fission yeast rhomboid-encoding genes. Our study also identified conserved residues of Rbd2 that are required for Sre1 proteolytic cleavage. All together, our results suggest that Rbd2 is a functional SREBP protease with conserved residues required for Sre1 cleavage and provide an important piece of the puzzle to understand the mechanisms for Sre1 activation and the regulation of various biological and pathological processes involving SREBPs. - Highlights: • An rbd2-deleted yeast strain shows defects in growth in response to low oxygen levels. • rbd2-deficient cells fail to generate cleaved Sre1 (Sre1N) under hypoxic conditions. • Expression of Sre1N rescues the rbd2 deletion mutant growth phenotype. • Rbd2 contains conserved residues potentially critical for catalytic activity. • Mutation of the conserved Rbd2 catalytic residues leads to defects in Sre1 cleavage.

  7. Protein Kinase A Regulatory Subunit Isoforms Regulate Growth and Differentiation in Mucor circinelloides: Essential Role of PKAR4

    Science.gov (United States)

    Ocampo, J.; McCormack, B.; Navarro, E.; Moreno, S.; Garre, V.

    2012-01-01

    The protein kinase A (PKA) signaling pathway plays a role in regulating growth and differentiation in the dimorphic fungus Mucor circinelloides. PKA holoenzyme is comprised of two catalytic (C) and two regulatory (R) subunits. In M. circinelloides, four genes encode the PKAR1, PKAR2, PKAR3, and PKAR4 isoforms of R subunits. We have constructed null mutants and demonstrate that each isoform has a different role in growth and differentiation. The most striking finding is that pkaR4 is an essential gene, because only heterokaryons were obtained in knockout experiments. Heterokaryons with low levels of wild-type nuclei showed an impediment in the emission of the germ tube, suggesting a pivotal role of this gene in germ tube emergence. The remaining null strains showed different alterations in germ tube emergence, sporulation, and volume of the mother cell. The pkaR2 null mutant showed an accelerated germ tube emission and was the only mutant that germinated under anaerobic conditions when glycine was used as a nitrogen source, suggesting that pkaR2 participates in germ tube emergence by repressing it. From the measurement of the mRNA and protein levels of each isoform in the wild-type and knockout strains, it can be concluded that the expression of each subunit has its own mechanism of differential regulation. The PKAR1 and PKAR2 isoforms are posttranslationally modified by ubiquitylation, suggesting another regulation point in the specificity of the signal transduction. The results indicate that each R isoform has a different role in M. circinelloides physiology, controlling the dimorphism and contributing to the specificity of cyclic AMP (cAMP)-PKA pathway. PMID:22635921

  8. Characterization of novel StAR (steroidogenic acute regulatory protein mutations causing non-classic lipoid adrenal hyperplasia.

    Directory of Open Access Journals (Sweden)

    Christa E Flück

    Full Text Available CONTEXT: Steroidogenic acute regulatory protein (StAR is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH. OBJECTIVE: StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. DESIGN: To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. SETTING: Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. PATIENTS: Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. RESULTS: StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30% and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. CONCLUSIONS: StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

  9. A Model of Yeast Cell-Cycle Regulation Based on a Standard Component Modeling Strategy for Protein Regulatory Networks.

    Directory of Open Access Journals (Sweden)

    Teeraphan Laomettachit

    Full Text Available To understand the molecular mechanisms that regulate cell cycle progression in eukaryotes, a variety of mathematical modeling approaches have been employed, ranging from Boolean networks and differential equations to stochastic simulations. Each approach has its own characteristic strengths and weaknesses. In this paper, we propose a "standard component" modeling strategy that combines advantageous features of Boolean networks, differential equations and stochastic simulations in a framework that acknowledges the typical sorts of reactions found in protein regulatory networks. Applying this strategy to a comprehensive mechanism of the budding yeast cell cycle, we illustrate the potential value of standard component modeling. The deterministic version of our model reproduces the phenotypic properties of wild-type cells and of 125 mutant strains. The stochastic version of our model reproduces the cell-to-cell variability of wild-type cells and the partial viability of the CLB2-dbΔ clb5Δ mutant strain. Our simulations show that mathematical modeling with "standard components" can capture in quantitative detail many essential properties of cell cycle control in budding yeast.

  10. Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action

    International Nuclear Information System (INIS)

    Zhang, Haimou; Qin, Gangjian; Liang, Gang; Li, Jinan; Chiu, Isaac; Barrington, Robert A.; Liu, Dongxu

    2007-01-01

    Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-κB activation and nuclear translocation in an IκBα-dependent manner. The inhibitory effects were associated with reduction of inhibitor IκB kinase activity and stabilization of the NF-κB inhibitor IκB. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations

  11. Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia.

    Science.gov (United States)

    Li, J N; Mahmoud, M A; Han, W F; Ripple, M; Pizer, E S

    2000-11-25

    Endogenous fatty acid synthesis has been observed in certain rapidly proliferating normal and neoplastic tissues. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of lipogenic genes including fatty acid synthase (FAS), the major biosynthetic enzyme for fatty acid synthesis. We have previously shown that SREBP-1, FAS, and Ki-67, a proliferation marker, colocalized in the crypts of the fetal gastrointestinal tract epithelium. This study sought to determine whether SREBP-1 participates in the regulation of proliferation-associated fatty acid synthesis in colorectal neoplasia. An immunohistochemical analysis of SREBP-1, FAS, and Ki-67 expression in 25 primary human colorectal carcinoma specimens showed colocalization in 22 of these. To elucidate a functional linkage between SREBP-1 activation and proliferation-associated FA synthesis, SREBP-1 and FAS content were assayed during the adaptive response of cultured HCT116 colon carcinoma cells to pharmacological inhibition of FA synthesis. Cerulenin and TOFA each inhibited the endogenous synthesis of fatty acids in a dose-dependent manner and each induced increases in both precursor and mature forms of SREBP-1. Subsequently, both the transcriptional activity of the FAS promoter in a luciferase reporter gene construct and the FAS expression increased. These results demonstrate that tumor cells recognize and respond to a deficiency in endogenous fatty acid synthesis by upregulating both SREBP-1 and FAS expression and support the model that SREBP-1 participates in the transcriptional regulation of lipogenic genes in colorectal neoplasia. Copyright 2000 Academic Press.

  12. Association of pro-inflammatory cytokines and iron regulatory protein 2 (IRP2 with Leishmania burden in canine visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Paulo Ricardo Porfírio do Nascimento

    Full Text Available Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2 were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.

  13. p75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3.

    Science.gov (United States)

    Pham, Dan Duc; Do, Hai Thi; Bruelle, Céline; Kukkonen, Jyrki P; Eriksson, Ove; Mogollón, Isabel; Korhonen, Laura T; Arumäe, Urmas; Lindholm, Dan

    2016-05-13

    Nerve growth factor (NGF) influences the survival and differentiation of a specific population of neurons during development, but its role in non-neuronal cells has been less studied. We observed here that NGF and its pro-form, pro-NGF, are elevated in fatty livers from leptin-deficient mice compared with controls, concomitant with an increase in low density lipoprotein receptors (LDLRs). Stimulation of mouse primary hepatocytes with NGF or pro-NGF increased LDLR expression through the p75 neurotrophin receptor (p75NTR). Studies using Huh7 human hepatocyte cells showed that the neurotrophins activate the sterol regulatory element-binding protein-2 (SREBP2) that regulates genes involved in lipid metabolism. The mechanisms for this were related to stimulation of p38 mitogen-activated protein kinase (p38 MAPK) and activation of caspase-3 and SREBP2 cleavage following NGF and pro-NGF stimulations. Cell fractionation experiments showed that caspase-3 activity was increased particularly in the membrane fraction that harbors SREBP2 and caspase-2. Experiments showed further that caspase-2 interacts with pro-caspase-3 and that p38 MAPK reduced this interaction and caused caspase-3 activation. Because of the increased caspase-3 activity, the cells did not undergo cell death following p75NTR stimulation, possibly due to concomitant activation of nuclear factor-κB (NF-κB) pathway by the neurotrophins. These results identify a novel signaling pathway triggered by ligand-activated p75NTR that via p38 MAPK and caspase-3 mediate the activation of SREBP2. This pathway may regulate LDLRs and lipid uptake particularly after injury or during tissue inflammation accompanied by an increased production of growth factors, including NGF and pro-NGF. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Detection of 210Po on filter papers 16 years after use for the collection of short-lived radon progeny in a room

    International Nuclear Information System (INIS)

    Abu-Jarad, F.; Fazal-ur-Rehman

    2003-01-01

    Radon gas was allowed to accumulate in its radium source and then injected into a 36 m 3 test room, resulting in an initial radon concentration of 15 kBq m -3 . Filter papers were used to collect the short-lived radon progeny and thus to measure the Potential Alpha Energy Concentration (PAEC) in-situ in the year 1984 at different times and conditions according to the experimental design. The radon progeny collected on the filter papers were studied as a function of aerosol particle concentration ranging from 10 2 -10 5 particles cm -3 in three different experiments. The highest aerosol particle concentration was generated by indoor cigarette smoking. Those filters were stored after the experiment, and were used after 16 years to study the activity of the radon long-lived alpha emitter progeny, 210 Po (T 1/2 =138 days). This isotope is separated from the short-lived progeny by 210 Pb beta emitter with 22.3 years half-life. After 16 years' storage of these filters, each filter paper was sandwiched and wrapped between two CR-39 nuclear track detectors, to put the detectors in contact with the surfaces of different filters, for 337 days. Correlation between the PAEC measured using filter papers in the year 1984 and the activity of long-lived alpha emitter 210 Po on the same filter papers measured in the year 2000 were studied. The results of the 210 Po activity showed a very good correlation of 0.92 with the PAEC 16 years ago. The results also depict that the PAEC and 210 Po activity in indoor air increased with the increase of aerosol particle concentration, which shows the attachment of short-lived radon progeny with the aerosol particles. The experiment proves that indoor cigarette smoking is a major source of aerosol particles carrying radon progeny and, thus, indoor cigarette smoking is an additional source of internal radiation hazard to the occupants whether smoker or non-smoker

  15. Detection of {sup 210}Po on filter papers 16 years after use for the collection of short-lived radon progeny in a room

    Energy Technology Data Exchange (ETDEWEB)

    Abu-Jarad, F. E-mail: falah.abujarad@aramco.com; Fazal-ur-Rehman

    2003-07-01

    Radon gas was allowed to accumulate in its radium source and then injected into a 36 m{sup 3} test room, resulting in an initial radon concentration of 15 kBq m{sup -3}. Filter papers were used to collect the short-lived radon progeny and thus to measure the Potential Alpha Energy Concentration (PAEC) in-situ in the year 1984 at different times and conditions according to the experimental design. The radon progeny collected on the filter papers were studied as a function of aerosol particle concentration ranging from 10{sup 2}-10{sup 5} particles cm{sup -3} in three different experiments. The highest aerosol particle concentration was generated by indoor cigarette smoking. Those filters were stored after the experiment, and were used after 16 years to study the activity of the radon long-lived alpha emitter progeny, {sup 210}Po (T{sub 1/2}=138 days). This isotope is separated from the short-lived progeny by {sup 210}Pb beta emitter with 22.3 years half-life. After 16 years' storage of these filters, each filter paper was sandwiched and wrapped between two CR-39 nuclear track detectors, to put the detectors in contact with the surfaces of different filters, for 337 days. Correlation between the PAEC measured using filter papers in the year 1984 and the activity of long-lived alpha emitter {sup 210}Po on the same filter papers measured in the year 2000 were studied. The results of the {sup 210}Po activity showed a very good correlation of 0.92 with the PAEC 16 years ago. The results also depict that the PAEC and {sup 210}Po activity in indoor air increased with the increase of aerosol particle concentration, which shows the attachment of short-lived radon progeny with the aerosol particles. The experiment proves that indoor cigarette smoking is a major source of aerosol particles carrying radon progeny and, thus, indoor cigarette smoking is an additional source of internal radiation hazard to the occupants whether smoker or non-smoker.

  16. WrpA Is an Atypical Flavodoxin Family Protein under Regulatory Control of the Brucella abortus General Stress Response System

    Energy Technology Data Exchange (ETDEWEB)

    Herrou, Julien; Czyż, Daniel M.; Willett, Jonathan W.; Kim, Hye-Sook; Chhor, Gekleng; Babnigg, Gyorgy; Kim, Youngchang; Crosson, Sean; Stock, A. M.

    2016-02-08

    ABSTRACT

    The general stress response (GSR) system of the intracellular pathogenBrucella abortuscontrols the transcription of approximately 100 genes in response to a range of stress cues. The core genetic regulatory components of the GSR are required forB. abortussurvival under nonoptimal growth conditionsin vitroand for maintenance of chronic infection in anin vivomouse model. The functions of the majority of the genes in the GSR transcriptional regulon remain undefined.bab1_1070is among the most highly regulated genes in this regulon: its transcription is activated 20- to 30-fold by the GSR system under oxidative conditionsin vitro. We have solved crystal structures of Bab1_1070 and demonstrate that it forms a homotetrameric complex that resembles those of WrbA-type NADH:quinone oxidoreductases, which are members of the flavodoxin protein family. However,B. abortusWrbA-relatedprotein (WrpA) does not bind flavin cofactors with a high affinity and does not function as an NADH:quinone oxidoreductasein vitro. Soaking crystals with flavin mononucleotide (FMN) revealed a likely low-affinity binding site adjacent to the canonical WrbA flavin binding site. Deletion ofwrpAwrpA) does not compromise cell survival under acute oxidative stressin vitroor attenuate infection in cell-based or mouse models. However, a ΔwrpAstrain does elicit increased splenomegaly in a mouse model, suggesting that WrpA modulatesB. abortusinteraction with its mammalian host. Despite

  17. Study of short-lived fission products with the aid of an isotope separator connected to reactor R2-0

    International Nuclear Information System (INIS)

    Rudstam, G.

    1976-01-01

    This report constitutes a final report on project 74-3289 together with a preliminary report for project 75-3332. These projects have been included in the budget years 1974/75 and 1975/76 as a contribution to the operating costs of reactor R2-0 at Studsvik. The reactor was used for experimental studies on short-lived fission products with OSIRIS isotope-separator equipment. The scientific programme is very broad. It comprises, in the first place, characterisation of fission products (a study of their excitation levels, measurement of decay properties such as half-life and emission of delayed neutrons, determination of neutron energy spectrum, determination of total decay energy, etc.). An important application of this field of research is the determination of decay heat in nuclear fuel. The programme thus comprises research of a fundamental character and applied research. (H.E.G.)

  18. Design a 10 kJ IS Mather Type Plasma Focus for Solid Target Activation to Produce Short-Lived Radioisotopes 12C(d,n)13N

    Science.gov (United States)

    Sadat Kiai, S. M.; Adlparvar, S.; Sheibani, S.; Elahi, M.; Safarien, A.; Farhangi, S.; Zirak, A. R.; Alhooie, S.; Mortazavi, B. N.; Khalaj, M. M.; Khanchi, A. R.; Dabirzadeh, A. A.; Kashani, A.; Zahedi, F.

    2010-10-01

    A 10 kJ (15 kV, 88 μF) IS (Iranian Sun) Mather type plasma focus device has been studied to determine the activity of a compound exogenous carbon solid target through 12C(d,n)13N nuclear reaction. The produced 13N is a short-lived radioisotope with a half-life of 9.97 min and threshold energy of 0.28 MeV. The results indicate that energetic deuterons impinging on the solid target can produce yield of = 6.7 × 10-5 with an activity of A = 6.8 × 104 Bq for one plasma focus shut and A ν = 4 × 105 Bq for 6 shut per mint when the projectile maximum deuterons energy is E max = 3 MeV.

  19. Detailed description of a new management system for solid, short-lived low and intermediate level radioactive waste at Ignalina NPP

    International Nuclear Information System (INIS)

    2002-01-01

    The objective is to modify and extend the existing system at the Ignalina Nuclear Power Plant (INPP) for handling of Very Low Level Waste (VLLW), short lived Low and Intermediate Level Waste (LLW-SL and ILW-SL). The ultimate aim is to reduce the risks and the influence on the personnel and the environment. According to the request from INPP, the modified system is based on the existence of an incineration plant. This system description describes treatment of non-combustible VLLW, LLW-SL and ILW-SL at a new waste handling facility (WHF) located in the future buildings 159/2 and 159/3 at the INPP. The new WHF is also handling Exempt Waste (EW), Reusable Material (RM) and Free Release Goods (FRG). The buildings 159/2 and 159/3 are future extensions of the existing building 159. (author)

  20. Studies of short-lived radicals in the. gamma. -irradiated aqueous solution of uridine-5'-monophosphate by the spin-trapping method and the liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Kominami, S [Hiroshima Univ. (Japan); Rokushika, S; Hatano, H

    1976-12-01

    An aerated aqueous solution of uridine-5'-monophosphate was ..gamma..-irradiated with 2-methyl-2-nitrosopropane as a spin-trapping reagent. Liquid chromatography was applied to separate the stable nitroxide radicals in the irradiated solution. The radicals were detected by U.V. and e.s.r. spectrometry. The e.s.r. detection showed four peaks in the chromatogram. The orcinol method for detection of the residual sugar moieties was applied before and after reduction of the base to determine the existence of the 5,6-double bond for the molecules in each fraction. From the combined results of the e.s.r. and orcinol methods, the short-lived radicals which were trapped by 2-methyl-2-nitrosopropane were identified as radicals of N-1 and C-6 positions of the base moiety and t-butyl radicals which was the radiolytic product of the trapping reagent.

  1. Surface disposal of low-level and medium-level short-lived waste. How safe is the disposal facility in Dessel in the long term?

    International Nuclear Information System (INIS)

    2014-01-01

    A disposal facility for the disposal of low-level and medium-level short-lived waste is planned to be built on a site located in the community of Dessel (Belgium). The facility will consist of 34 modules, corresponding to a storage volume capacity of approximately 70,000 m3. The disposal concept includes waste containers that are encapsulated in a concrete box which is filled with mortar. Approximately 900 of these blocks, or monoliths, fit inside each module. The article discusses the Research and Development programme that has been conducted at the Belgian Nuclear Research Center SCK-CEN in conjunction with the development of this facility. Main emphasis is on the models that have been developed for predicting the long-term containment of the disposal facility.

  2. Formation of short-lived positron emitters in reactions of protons of energies up to 200 MeV with the target elements carbon, nitrogen and oxygen

    CERN Document Server

    Kettern, K; Qaim, S M; Shubin, Yu N; Steyn, G F; Van der Walt, T N; 10.1016/j.apradiso.2004.02.007

    2004-01-01

    Excitation functions were measured by the stacked-foil technique for proton induced reactions on carbon, nitrogen and oxygen leading to the formation of the short-lived positron emitters /sup 11/C (T/sub 1 /2/=20.38 min) and /sup 13/N (T/sub 1/2/=9.96 min). The energy region covered extended up to 200 MeV. The product activity was measured non-destructively via gamma -ray spectrometry. A careful decay curve analysis of the positron annihilation radiation was invariably performed. The experimental results were compared with theoretical data obtained using the modified hybrid nuclear model code ALICE-IPPE for intermediate energies. The agreement was found to be generally satisfactory. The data are of importance in proton therapy.

  3. Fractional release of short-lived noble gases and iodine from HTGR fuel compact containing a fraction of coated fuel particles with through-coating defects

    International Nuclear Information System (INIS)

    Ogawa, Toru; Fukuda, Kosaku; Kobayashi, Fumiaki; Kikuchi, Teruo; Tobita, Tsutomu; Kashimura, Satoru; Kikuchi, Hironobu; Yamamoto, Katsumune.

    1986-10-01

    Fractional release (R/B) data of short-lived noble gases and iodine from sweep-gas irradiated HTGR fuel compacts were analyzed. Empirical formulas to predict R/B of 88 Kr as a function of temperature and fraction through-coating defects, and to calculate ratios of R/B's of other shortlived gases to that of 88 Kr were proposed. A method to predict R/B of iodine was also proposed. As for 131 I, a fission product of major safety concern, (R/B) I 131 ≅ (R/B) Xe 133 was predicted. Applying those methods, R/B from OGL-1 fuel element (5th and 6th) was predicted to show a good agreement with observation. (author)

  4. Unattached fraction of short-lived Rn decay products in indoor and outdoor environments: An improved single-screen method and results

    International Nuclear Information System (INIS)

    Reineking, A.; Porstendoerfer, J.

    1990-01-01

    The unattached fraction fp of potential alpha energy of short-lived Rn decay products was measured under realistic, natural conditions in different dwellings and in the open atmosphere by a single-screen technique. An improved data evaluation method was developed where the measured activities of 218 Po (RaA) and 214 Pb (RaB) were corrected by the screen-attached activities of 214 Bi ( 214 Po) [RaC (RaC')]. This method is based on the experimental observation that the 214 Bi ( 214 Po) unattached activities are negligible under realistic living conditions and that the size distributions of the aerosol-attached activities of all short-lived Rn daughters are identical. In closed rooms without additional aerosol sources, a mean unattached fraction fp of the potential alpha energy of 0.096 was obtained at a mean aerosol particle concentration of 6100 cm-3 and at a mean equilibrium factor F of 0.30. This mean fp value is about three times higher than the value used in the literature for the radiation exposure calculation of the human public. In closed rooms with additional aerosol sources (cigarette smoke, heating systems, aerosols from a burning candle), the aerosol particle concentrations ranged up to 10(6) cm-3 and the attachment rates, X, increased up to 1000 h-1. The fp values sometimes decreased below the detection limit of 0.005, and the F values increased to as high as 0.77. In the ambient atmosphere in the vicinity of Goettingen, a mean unattached fraction fp of 0.02 and a mean aerosol particle concentration of 3.4 x 10(4) cm-3 were measured at 1 m above the ground. The mean equilibrium factor F was determined to be 0.7.A

  5. Investigation concerning the relative formation rate and half-life time of short-lived nuclides with a fast conveyor tube system

    International Nuclear Information System (INIS)

    Kreiner, H.J.

    1976-01-01

    Since the installation of the 'Ultrafast Rabbit System' at the FRN in end of 1974, some research was started concerning the possibility of neutron activation analysis of short-lived nuclides (0.02 1/2 < 1 s) and measurements of short-lived fission products of U-235 and Pu-239. One of the results of the investigations is a more exact gamma-energy determination of the 0.8 s Cl-38m with 671.33 keV. In NAA it was possible to reach a sensitivity for lead and boron near 2 μg per sample respectively 10 ppm. In measurements of light fission products 0.1 - 8s after a pulse irradiation some differences of the relative formation rate and half-life in the region of A approximately 100 were found in comparison to literature. For example a strong build-up could be seen measuring the gamma-energy of 276.1 keV that belongs to Nb-101. Therefore we suppose the existence of an isomeric state of Nb-101. In comparison to our own results of yield ratio of the Pu- and U-fission products a good agreement with known data was found. Furthermore the measuring method gives the possibility of coordination of unknown gamma-lines to nuclides using the rate of formation, the half-life, the yield ratio between U and Pu and the build-up factor. That could be verified in some cases, e.g. Nb-103 and Sr-96. (author)

  6. Low interannual precipitation has a greater negative effect than seedling herbivory on the population dynamics of a short-lived shrub, Schiedea obovata.

    Science.gov (United States)

    Bialic-Murphy, Lalasia; Gaoue, Orou G

    2018-01-01

    Climate projections forecast more extreme interannual climate variability over time, with an increase in the severity and duration of extreme drought and rainfall events. Based on bioclimatic envelope models, it is projected that changing precipitation patterns will drastically alter the spatial distributions and density of plants and be a primary driver of biodiversity loss. However, many other underlying mechanisms can impact plant vital rates (i.e., survival, growth, and reproduction) and population dynamics. In this study, we developed a size-dependent integral projection model (IPM) to evaluate how interannual precipitation and mollusk herbivory influence the dynamics of a Hawaii endemic short-lived shrub, Schiedea obovata (Caryophyllaceae). Assessing how wet season precipitation effects population dynamics it critical, as it is the timeframe when most of the foliar growth occurs, plants flower and fruit, and seedlings establish. Temporal variation in wet season precipitation had a greater effect than mollusk herbivory on S . obovata population growth rate λ, and the impact of interannual precipitation on vital rates shifted across plant ontogeny. Furthermore, wet season precipitation influenced multiple vital rates in contrasting ways and the effect of precipitation on the survival of larger vegetative and reproductively mature individuals contributed the most to variation in the population growth rate. Among all combination of wet season precipitation and herbivory intensities, the only scenario that led to a growing population was when high wet precipitation was associated with low herbivory. Our study highlights the importance of evaluating how abiotic factors and plant-consumer interactions influence an organism across its life cycle to fully understand the underpinning mechanisms that structure its spatial and temporal distribution and abundance. Our results also illustrate that for short-lived species, like S. obovata , seedling herbivory can have

  7. Tests to determine the release of short-lived fission products from UO2 fuel operating at linear powers of 45 and 60 kW/m

    International Nuclear Information System (INIS)

    Hastings, I.J.; Hunt, C.E.L.; Lipsett, J.J.; MacDonald, R.D.

    1985-09-01

    Experiments have been carried out using a 'sweep gas' technique to determine the behaviour of short-lived fission products within operating, intact UO 2 fuel elements. The Zircaloy-4-clad elements were 600 mm long and contained fuel of density 10.65 - 10.71 Mg/m 3 . A He-2% H 2 carrier gas swept gaseous or volatile fission products out of the operating fuel element past a gamma spectrometer for measurement. We outline our loop model and give full details of calculational procedures. In tests at linear powers of 45 (FIO-122) and 60 kW/m (FIO-124) to a maximum burnup of 80 MW.h/kg U, the species measured directly at the spectrometer during normal operation were generally the short-lived xenons and kryptons. Iodines were not observed during normal operation. The behaviour of I-133 and I-135 was deduced from the decay of Xe-133 and Xe-135 during reactor shutdowns. Plots of R/B (released/born) against λ (decay constant) or effective λ for all isotopes observed at 45 and 60 kW/m show that a line of slope -0.5, corresponding with diffusion kinetics, is a good fit to the measured xenon and krypton data. The inferred release of iodine fits the same line. From this we can extrapolate to an R/B for I-131 of about 5 x 10 -4 at 45 kW/m, and 3 x 10 -3 at 60 kW/m. Both tests were terminated by defects. Under defect conditions, R/B dependence on λ was about 0.6. I-131 release under defect conditions was 5 Ci and 60 mCi for FIO-122 and FI0-124, respectively. 22 refs

  8. Platelet cytosolic 44-kDa protein is a substrate of cholera toxin-induced ADP-ribosylation and is not recognized by antisera against the α subunit of the stimulatory guanine nucleotide-binding regulatory protein

    International Nuclear Information System (INIS)

    Molina Y Vedia, L.M.; Reep, B.R.; Lapetina, E.G.

    1988-01-01

    ADP-ribosylation induced by cholera toxin and pertussis toxin was studied in particulate and cytosolic fractions of human platelets. Platelets were disrupted by a cycle of freezing and thawing in the presence of a hyposmotic buffer containing protease inhibitors. In both fractions, the A subunit of cholera toxin ADP-ribosylates two proteins with molecular masses of 42 and 44 kDa, whereas pertussis toxin ADP-ribosylates a 41-kDa polypeptide. Two antisera against the α subunit of the stimulatory guanine nucleotide-binding regulatory protein recognize only the 42-kDa polypeptide. Cholera toxin-induced ADP-ribosylation of the 42- and 44-kDa proteins is reduced by pretreatment of platelets with iloprost, a prostacyclin analog. The 44-kDa protein, which is substrate of cholera toxin, could be extracted completely from the membrane and recovered in the cytosolic fraction when the cells were disrupted by Dounce homogenization and the pellet was extensively washed. A 44-kDa protein can also be labeled with 8-azidoguanosine 5'-[α- 32 P]triphosphate in the cytosol and membranes. These finding indicate that cholera and pertussis toxins produced covalent modifications of proteins present in particulate and cytosolic platelet fractions. Moreover, the 44-kDa protein might be an α subunit of a guanine nucleotide-binding regulatory protein that is not recognized by available antisera

  9. High concentrations of protein test substances may have non-toxic effects on Daphnia magna: implications for regulatory study designs and ecological risk assessments for GM crops.

    Science.gov (United States)

    Raybould, Alan; Burns, Andrea; Hamer, Mick

    2014-01-01

    Laboratory testing for possible adverse effects of insecticidal proteins on non-target organisms (NTOs) is an important part of many ecological risk assessments for regulatory decision-making about the cultivation of insect-resistant genetically modified (IRGM) crops. To increase confidence in the risk assessments, regulatory guidelines for effects testing specify that representative surrogate species for NTOs are exposed to concentrations of insecticidal proteins that are in excess of worst-case predicted exposures in the field. High concentrations in effects tests are achieved by using protein test substances produced in microbes, such as Escherichia coli. In a study that exposed Daphnia magna to a single high concentration of a microbial test substance containing Vip3Aa20, the insecticidal protein in MIR162 maize, small reductions in growth were observed. These effects were surprising as many other studies strongly suggest that the activity of Vip3Aa20 is limited to Lepidoptera. A plausible explanation for the effect on growth is that high concentrations of test substance have a non-toxic effect on Daphnia, perhaps by reducing its feeding rate. A follow-up study tested that hypothesis by exposing D. magna to several concentrations of Vip3Aa20, and a high concentration of a non-toxic protein, bovine serum albumin (BSA). Vip3Aa20 and BSA had sporadic effects on the reproduction and growth of D. magna. The pattern of the effects suggests that they result from non-toxic effects of high concentrations of protein, and not from toxicity. The implications of these results for regulatory NTO effects testing and ERA of IRGM crops are discussed.

  10. The adeno-associated virus major regulatory protein Rep78-c-Jun-DNA motif complex modulates AP-1 activity

    International Nuclear Information System (INIS)

    Prasad, C. Krishna; Meyers, Craig; Zhan Dejin; You Hong; Chiriva-Internati, Maurizio; Mehta, Jawahar L.; Liu Yong; Hermonat, Paul L.

    2003-01-01

    Multiple epidemiologic studies show that adeno-associated virus (AAV) is negatively associated with cervical cancer (CX CA), a cancer which is positively associated with human papillomavirus (HPV) infection. Mechanisms for this correlation may be by Rep78's (AAV's major regulatory protein) ability to bind the HPV-16 p97 promoter DNA and inhibit transcription, to bind and interfere with the functions of the E7 oncoprotein of HPV-16, and to bind a variety of HPV-important cellular transcription factors such as Sp1 and TBP. c-Jun is another important cellular factor intimately linked to the HPV life cycle, as well as keratinocyte differentiation and skin development. Skin is the natural host tissue for both HPV and AAV. In this article it is demonstrated that Rep78 directly interacts with c-Jun, both in vitro and in vivo, as analyzed by Western blot, yeast two-hybrid cDNA, and electrophoretic mobility shift-supershift assay (EMSA supershift). Addition of anti-Rep78 antibodies inhibited the EMSA supershift. Investigating the biological implications of this interaction, Rep78 inhibited the c-Jun-dependent c-jun promoter in transient and stable chloramphenicol acetyl-transferase (CAT) assays. Rep78 also inhibited c-Jun-augmented c-jun promoter as well as the HPV-16 p97 promoter activity (also c-Jun regulated) in in vitro transcription assays in T47D nuclear extracts. Finally, the Rep78-c-Jun interaction mapped to the amino-half of Rep78. The ability of Rep78 to interact with c-Jun and down-regulate AP-1-dependent transcription suggests one more mechanism by which AAV may modulate the HPV life cycle and the carcinogenesis process

  11. Detection of Signal Regulatory Protein α in Saimiri sciureus (Squirrel Monkey) by Anti-Human Monoclonal Antibody

    Science.gov (United States)

    de Souza, Hugo Amorim dos Santos; Costa-Correa, Edmar Henrique; Bianco-Junior, Cesare; Andrade, Márcia Cristina Ribeiro; Lima-Junior, Josué da Costa; Pratt-Riccio, Lilian Rose; Daniel-Ribeiro, Cláudio Tadeu; Totino, Paulo Renato Rivas

    2017-01-01

    Non-human primates (NHP) are suitable models for studying different aspects of the human system, including pathogenesis and protective immunity to many diseases. However, the lack of specific immunological reagents for neo-tropical monkeys, such as Saimiri sciureus, is still a major factor limiting studies in these models. An alternative strategy to circumvent this obstacle has been the selection of immunological reagents directed to humans, which present cross-reactivity with NHP molecules. In this context and considering the key role of inhibitory immunoreceptors—such as the signal regulatory protein α (SIRPα)—in the regulation of immune responses, in the present study, we attempted to evaluate the ability of anti-human SIRPα monoclonal antibodies to recognize SIRPα in antigen-presenting S. sciureus peripheral blood mononuclear cells (PBMC). As shown by flow cytometry analysis, the profile of anti-SIRPα staining as well as the levels of SIRPα-positive cells in PBMC from S. sciureus were similar to those observed in human PBMC. Furthermore, using anti-SIRPα monoclonal antibody, it was possible to detect a decrease of the SIRPα levels on surface of S. sciureus cells after in vitro stimulation with lipopolysaccharides. Finally, using computed-based analysis, we observed a high degree of conservation of SIRPα across six species of primates and the presence of shared epitopes in the extracellular domain between humans and Saimiri genus that could be targeted by antibodies. In conclusion, we have identified a commercially available anti-human monoclonal antibody that is able to detect SIRPα of S. sciureus monkeys and that, therefore, can facilitate the study of the immunomodulatory role of SIRPα when S. sciureus is used as a model. PMID:29312325

  12. Detection of Signal Regulatory Protein α in Saimiri sciureus (Squirrel Monkey by Anti-Human Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Hugo Amorim dos Santos de Souza

    2017-12-01

    Full Text Available Non-human primates (NHP are suitable models for studying different aspects of the human system, including pathogenesis and protective immunity to many diseases. However, the lack of specific immunological reagents for neo-tropical monkeys, such as Saimiri sciureus, is still a major factor limiting studies in these models. An alternative strategy to circumvent this obstacle has been the selection of immunological reagents directed to humans, which present cross-reactivity with NHP molecules. In this context and considering the key role of inhibitory immunoreceptors—such as the signal regulatory protein α (SIRPα—in the regulation of immune responses, in the present study, we attempted to evaluate the ability of anti-human SIRPα monoclonal antibodies to recognize SIRPα in antigen-presenting S. sciureus peripheral blood mononuclear cells (PBMC. As shown by flow cytometry analysis, the profile of anti-SIRPα staining as well as the levels of SIRPα-positive cells in PBMC from S. sciureus were similar to those observed in human PBMC. Furthermore, using anti-SIRPα monoclonal antibody, it was possible to detect a decrease of the SIRPα levels on surface of S. sciureus cells after in vitro stimulation with lipopolysaccharides. Finally, using computed-based analysis, we observed a high degree of conservation of SIRPα across six species of primates and the presence of shared epitopes in the extracellular domain between humans and Saimiri genus that could be targeted by antibodies. In conclusion, we have identified a commercially available anti-human monoclonal antibody that is able to detect SIRPα of S. sciureus monkeys and that, therefore, can facilitate the study of the immunomodulatory role of SIRPα when S. sciureus is used as a model.

  13. Tumorigenic properties of iron regulatory protein 2 (IRP2) mediated by its specific 73-amino acids insert.

    Science.gov (United States)

    Maffettone, Carmen; Chen, Guohua; Drozdov, Ignat; Ouzounis, Christos; Pantopoulos, Kostas

    2010-04-13

    Iron regulatory proteins, IRP1 and IRP2, bind to mRNAs harboring iron responsive elements and control their expression. IRPs may also perform additional functions. Thus, IRP1 exhibited apparent tumor suppressor properties in a tumor xenograft model. Here we examined the effects of IRP2 in a similar setting. Human H1299 lung cancer cells or clones engineered for tetracycline-inducible expression of wild type IRP2, or the deletion mutant IRP2(Delta73) (lacking a specific insert of 73 amino acids), were injected subcutaneously into nude mice. The induction of IRP2 profoundly stimulated the growth of tumor xenografts, and this response was blunted by addition of tetracycline in the drinking water of the animals, to turnoff the IRP2 transgene. Interestingly, IRP2(Delta73) failed to promote tumor growth above control levels. As expected, xenografts expressing the IRP2 transgene exhibited high levels of transferrin receptor 1 (TfR1); however, the expression of other known IRP targets was not affected. Moreover, these xenografts manifested increased c-MYC levels and ERK1/2 phosphorylation. A microarray analysis identified distinct gene expression patterns between control and tumors containing IRP2 or IRP1 transgenes. By contrast, gene expression profiles of control and IRP2(Delta73)-related tumors were more similar, consistently with their growth phenotype. Collectively, these data demonstrate an apparent pro-oncogenic activity of IRP2 that depends on its specific 73 amino acids insert, and provide further evidence for a link between IRPs and cancer biology.

  14. Tumorigenic properties of iron regulatory protein 2 (IRP2 mediated by its specific 73-amino acids insert.

    Directory of Open Access Journals (Sweden)

    Carmen Maffettone

    2010-04-01

    Full Text Available Iron regulatory proteins, IRP1 and IRP2, bind to mRNAs harboring iron responsive elements and control their expression. IRPs may also perform additional functions. Thus, IRP1 exhibited apparent tumor suppressor properties in a tumor xenograft model. Here we examined the effects of IRP2 in a similar setting. Human H1299 lung cancer cells or clones engineered for tetracycline-inducible expression of wild type IRP2, or the deletion mutant IRP2(Delta73 (lacking a specific insert of 73 amino acids, were injected subcutaneously into nude mice. The induction of IRP2 profoundly stimulated the growth of tumor xenografts, and this response was blunted by addition of tetracycline in the drinking water of the animals, to turnoff the IRP2 transgene. Interestingly, IRP2(Delta73 failed to promote tumor growth above control levels. As expected, xenografts expressing the IRP2 transgene exhibited high levels of transferrin receptor 1 (TfR1; however, the expression of other known IRP targets was not affected. Moreover, these xenografts manifested increased c-MYC levels and ERK1/2 phosphorylation. A microarray analysis identified distinct gene expression patterns between control and tumors containing IRP2 or IRP1 transgenes. By contrast, gene expression profiles of control and IRP2(Delta73-related tumors were more similar, consistently with their growth phenotype. Collectively, these data demonstrate an apparent pro-oncogenic activity of IRP2 that depends on its specific 73 amino acids insert, and provide further evidence for a link between IRPs and cancer biology.

  15. Sterol regulatory element-binding proteins are regulators of the rat thyroid peroxidase gene in thyroid cells.

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    Christine Rauer

    Full Text Available Sterol regulatory element-binding proteins (SREBPs-1c and -2, which were initially discovered as master transcriptional regulators of lipid biosynthesis and uptake, were recently identified as novel transcriptional regulators of the sodium-iodide symporter gene in the thyroid, which is essential for thyroid hormone synthesis. Based on this observation that SREBPs play a role for thyroid hormone synthesis, we hypothesized that another gene involved in thyroid hormone synthesis, the thyroid peroxidase (TPO gene, is also a target of SREBP-1c and -2. Thyroid epithelial cells treated with 25-hydroxycholesterol, which is known to inhibit SREBP activation, had about 50% decreased mRNA levels of TPO. Similarly, the mRNA level of TPO was reduced by about 50% in response to siRNA mediated knockdown of both, SREBP-1 and SREBP-2. Reporter gene assays revealed that overexpression of active SREBP-1c and -2 causes a strong transcriptional activation of the rat TPO gene, which was localized to an approximately 80 bp region in the intron 1 of the rat TPO gene. In vitro- and in vivo-binding of both, SREBP-1c and SREBP-2, to this region in the rat TPO gene could be demonstrated using gel-shift assays and chromatin immunoprecipitation. Mutation analysis of the 80 bp region of rat TPO intron 1 revealed two isolated and two overlapping SREBP-binding elements from which one, the overlapping SRE+609/InvSRE+614, was shown to be functional in reporter gene assays. In connection with recent findings that the rat NIS gene is also a SREBP target gene in the thyroid, the present findings suggest that SREBPs may be possible novel targets for pharmacological modulation of thyroid hormone synthesis.

  16. Interaction of the regulatory subunit of the cAMP-dependent protein kinase with PATZ1 (ZNF278)

    International Nuclear Information System (INIS)

    Yang, Weng-Lang; Ravatn, Roald; Kudoh, Kazuya; Alabanza, Leah; Chin, Khew-Voon

    2010-01-01

    The effects of cAMP in cell are predominantly mediated by the cAMP-dependent protein kinase (PKA), which is composed of two genetically distinct subunits, catalytic (C) and regulatory (R), forming a tetrameric holoenzyme R 2 C 2 . The only known function for the R subunit is that of inhibiting the activity of the C subunit kinase. It has been shown that overexpression of RIα, but not the C subunit kinase, is associated with neoplastic transformation. In addition, it has also been demonstrated that mutation in the RIα, but not the C subunit is associated with increased resistance to the DNA-damaging anticancer drug cisplatin, thus suggesting that the RIα subunit of PKA may have functions independent of the kinase. We show here that the RIα subunit interacts with a BTB/POZ domain zinc-finger transcription factor, PATZ1 (ZNF278), and co-expression with RIα results in its sequestration in the cytoplasm. The cytoplasmic/nuclear translocation is inducible by cAMP. C-terminus deletion abolishes PATZ1 interaction with RIα and results in its localization in the nucleus. PATZ1 transactivates the cMyc promoter and the presence of cAMP and co-expression with RIα modulates its transactivation. Moreover, PATZ1 is aberrantly expressed in cancer. Taken together, our results showed a potentially novel mechanism of cAMP signaling mediated through the interaction of RIα with PATZ1 that is independent of the kinase activity of PKA, and the aberrant expression of PATZ1 in cancer point to its role in cell growth regulation.

  17. Interaction of the regulatory subunit of the cAMP-dependent protein kinase with PATZ1 (ZNF278)

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Weng-Lang [Long Island Jewish Medical Center, North Shore University Hospital, Manhasset, NY 11030 (United States); Ravatn, Roald [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Kudoh, Kazuya [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama (Japan); Alabanza, Leah [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, University of Toledo, College of Medicine, Toledo, OH 43614 (United States)

    2010-01-15

    The effects of cAMP in cell are predominantly mediated by the cAMP-dependent protein kinase (PKA), which is composed of two genetically distinct subunits, catalytic (C) and regulatory (R), forming a tetrameric holoenzyme R{sub 2}C{sub 2}. The only known function for the R subunit is that of inhibiting the activity of the C subunit kinase. It has been shown that overexpression of RI{alpha}, but not the C subunit kinase, is associated with neoplastic transformation. In addition, it has also been demonstrated that mutation in the RI{alpha}, but not the C subunit is associated with increased resistance to the DNA-damaging anticancer drug cisplatin, thus suggesting that the RI{alpha} subunit of PKA may have functions independent of the kinase. We show here that the RI{alpha} subunit interacts with a BTB/POZ domain zinc-finger transcription factor, PATZ1 (ZNF278), and co-expression with RI{alpha} results in its sequestration in the cytoplasm. The cytoplasmic/nuclear translocation is inducible by cAMP. C-terminus deletion abolishes PATZ1 interaction with RI{alpha} and results in its localization in the nucleus. PATZ1 transactivates the cMyc promoter and the presence of cAMP and co-expression with RI{alpha} modulates its transactivation. Moreover, PATZ1 is aberrantly expressed in cancer. Taken together, our results showed a potentially novel mechanism of cAMP signaling mediated through the interaction of RI{alpha} with PATZ1 that is independent of the kinase activity of PKA, and the aberrant expression of PATZ1 in cancer point to its role in cell growth regulation.

  18. Comprehensive behavioral analysis of voltage-gated calcium channel beta-anchoring and -regulatory protein knockout mice

    Science.gov (United States)

    Nakao, Akito; Miki, Takafumi; Shoji, Hirotaka; Nishi, Miyuki; Takeshima, Hiroshi; Miyakawa, Tsuyoshi; Mori, Yasuo

    2015-01-01

    Calcium (Ca2+) influx through voltage-gated Ca2+ channels (VGCCs) induces numerous intracellular events such as neuronal excitability, neurotransmitter release, synaptic plasticity, and gene regulation. It has been shown that genes related to Ca2+ signaling, such as the CACNA1C, CACNB2, and CACNA1I genes that encode VGCC subunits, are associated with schizophrenia and other psychiatric disorders. Recently, VGCC beta-anchoring and -regulatory protein (BARP) was identified as a novel regulator of VGCC activity via the interaction of VGCC β subunits. To examine the role of the BARP in higher brain functions, we generated BARP knockout (KO) mice and conducted a comprehensive battery of behavioral tests. BARP KO mice exhibited greatly reduced locomotor activity, as evidenced by decreased vertical activity, stereotypic counts in the open field test, and activity level in the home cage, and longer latency to complete a session in spontaneous T-maze alteration test, which reached “study-wide significance.” Acoustic startle response was also reduced in the mutants. Interestingly, they showed multiple behavioral phenotypes that are seemingly opposite to those seen in the mouse models of schizophrenia and its related disorders, including increased working memory, flexibility, prepulse inhibition, and social interaction, and decreased locomotor activity, though many of these phenotypes are statistically weak and require further replications. These results demonstrate that BARP is involved in the regulation of locomotor activity and, possibly, emotionality. The possibility was also suggested that BARP KO mice may serve as a unique tool for investigating the pathogenesis/pathophysiology of schizophrenia and related disorders. Further evaluation of the molecular and physiological phenotypes of the mutant mice would provide new insights into the role of BARP in higher brain functions. PMID:26136667

  19. Identification of a phosphorylation-dependent nuclear localization motif in interferon regulatory factor 2 binding protein 2.

    Directory of Open Access Journals (Sweden)

    Allen C T Teng

    Full Text Available Interferon regulatory factor 2 binding protein 2 (IRF2BP2 is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known.Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS to an evolutionarily conserved sequence (354ARKRKPSP(361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360. Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C(2C(12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C(2C(12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2.Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status

  20. DnaA protein DNA-binding domain binds to Hda protein to promote inter-AAA+ domain interaction involved in regulatory inactivation of DnaA.

    Science.gov (United States)

    Keyamura, Kenji; Katayama, Tsutomu

    2011-08-19

    Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis.

  1. DnaA Protein DNA-binding Domain Binds to Hda Protein to Promote Inter-AAA+ Domain Interaction Involved in Regulatory Inactivation of DnaA*

    Science.gov (United States)

    Keyamura, Kenji; Katayama, Tsutomu

    2011-01-01

    Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis. PMID:21708944

  2. α -Actinin TvACTN3 of Trichomonas vaginalis is an RNA-binding protein that could participate in its posttranscriptional iron regulatory mechanism.

    Science.gov (United States)

    Calla-Choque, Jaeson Santos; Figueroa-Angulo, Elisa Elvira; Ávila-González, Leticia; Arroyo, Rossana

    2014-01-01

    Trichomonas vaginalis is a sexually transmitted flagellated protist parasite responsible for trichomoniasis. This parasite is dependent on high levels of iron, favoring its growth and multiplication. Iron also differentially regulates some trichomonad virulence properties by unknown mechanisms. However, there is evidence to support the existence of gene regulatory mechanisms at the transcriptional and posttranscriptional levels that are mediated by iron concentration in T. vaginalis. Thus, the goal of this study was to identify an RNA-binding protein in T. vaginalis that interacts with the tvcp4 RNA stem-loop structure, which may participate in a posttranscriptional iron regulatory mechanism mediated by RNA-protein interactions. We performed RNA electrophoretic mobility shift assay (REMSA) and supershift, UV cross-linking, Northwestern blot, and western blot (WB) assays using cytoplasmic protein extracts from T. vaginalis with the tvcp4 RNA hairpin structure as a probe. We identified a 135-kDa protein isolated by the UV cross-linking assays as α-actinin 3 (TvACTN3) by MALDI-TOF-MS that was confirmed by LS-MS/MS and de novo sequencing. TvACTN3 is a cytoplasmic protein that specifically binds to hairpin RNA structures from trichomonads and humans when the parasites are grown under iron-depleted conditions. Thus, TvACTN3 could participate in the regulation of gene expression by iron in T. vaginalis through a parallel posttranscriptional mechanism similar to that of the IRE/IRP system.

  3. A Novel, In-solution Separation of Endogenous Cardiac Sarcomeric Proteins and Identification of Distinct Charged Variants of Regulatory Light Chain*

    Science.gov (United States)

    Scruggs, Sarah B.; Reisdorph, Rick; Armstrong, Mike L.; Warren, Chad M.; Reisdorph, Nichole; Solaro, R. John; Buttrick, Peter M.

    2010-01-01

    The molecular conformation of the cardiac myosin motor is modulated by intermolecular interactions among the heavy chain, the light chains, myosin binding protein-C, and titin and is governed by post-translational modifications (PTMs). In-gel digestion followed by LC/MS/MS has classically been applied to identify cardiac sarcomeric PTMs; however, this approach is limited by protein size, pI, and difficulties in peptide extraction. We report a solution-based work flow for global separation of endogenous cardiac sarcomeric proteins with a focus on the regulatory light chain (RLC) in which specific sites of phosphorylation have been unclear. Subcellular fractionation followed by OFFGEL electrophoresis resulted in isolation of endogenous charge variants of sarcomeric proteins, including regulatory and essential light chains, myosin heavy chain, and myosin-binding protein-C of the thick filament. Further purification of RLC using reverse-phase HPLC separation and UV detection enriched for RLC PTMs at the intact protein level and provided a stoichiometric and quantitative assessment of endogenous RLC charge variants. Digestion and subsequent LC/MS/MS unequivocally identified that the endogenous charge variants of cardiac RLC focused in unique OFFGEL electrophoresis fractions were unphosphorylated (78.8%), singly phosphorylated (18.1%), and doubly phosphorylated (3.1%) RLC. The novel aspects of this study are that 1) milligram amounts of endogenous cardiac sarcomeric subproteome were focused with resolution comparable with two-dimensional electrophoresis, 2) separation and quantification of post-translationally modified variants were achieved at the intact protein level, 3) separation of intact high molecular weight thick filament proteins was achieved in solution, and 4) endogenous charge variants of RLC were separated; a novel doubly phosphorylated form was identified in mouse, and singly phosphorylated, singly deamidated, and deamidated/phosphorylated forms were

  4. Short Lived Climate Pollutants cause a Long Lived Effect on Sea-level Rise: Analyzing climate metrics for sea-level rise

    Science.gov (United States)

    Sterner, E.; Johansson, D. J.

    2013-12-01

    Climate change depends on the increase of several different atmospheric pollutants. While long term global warming will be determined mainly by carbon dioxide, warming in the next few decades will depend to a large extent on short lived climate pollutants (SLCP). Reducing emissions of SLCPs could contribute to lower the global mean surface temperature by 0.5 °C already by 2050 (Shindell et al. 2012). Furthermore, the warming effect of one of the most potent SLCPs, black carbon (BC), may have been underestimated in the past. Bond et al. (2013) presents a new best estimate of the total BC radiative forcing (RF) of 1.1 W/m2 (90 % uncertainty bounds of 0.17 to 2.1 W/m2) since the beginning of the industrial era. BC is however never emitted alone and cooling aerosols from the same sources offset a majority of this RF. In the wake of calls for mitigation of SLCPs it is important to study other aspects of the climate effect of SLCPs. One key impact of climate change is sea-level rise (SLR). In a recent study, the effect of SLCP mitigation scenarios on SLR is examined. Hu et al (2013) find a substantial effect on SLR from mitigating SLCPs sharply, reducing SLR by 22-42% by 2100. We choose a different approach focusing on emission pulses and analyse a metric based on sea level rise so as to further enlighten the SLR consequences of SLCPs. We want in particular to understand the time dynamics of SLR impacts caused by SLCPs compared to other greenhouse gases. The most commonly used physical based metrics are GWP and GTP. We propose and evaluate an additional metric: The global sea-level rise potential (GSP). The GSP is defined as the sea level rise after a time horizon caused by an emissions pulse of a forcer to the sea level rise after a time horizon caused by an emissions pulse of a CO2. GSP is evaluated and compared to GWP and GTP using a set of climate forcers chosen to cover the whole scale of atmospheric perturbation life times (BC, CH4, N2O, CO2 and SF6). The study

  5. Cloning, overexpression, purification and preliminary X-ray analysis of a feast/famine regulatory protein (Rv2779c) from Mycobacterium tuberculosis H37Rv.

    Science.gov (United States)

    Dey, Abhishek; Ramachandran, Ravishankar

    2014-01-01

    Rv2779c from Mycobacterium tuberculosis is a feast/famine regulatory protein. This class of proteins are also known as the leucine-responsive regulatory protein/asparagine synthase C family (Lrp/AsnC) of transcriptional regulators and are known to be involved in various metabolic processes in bacteria and fungi. They contain a RAM (regulator of amino-acid metabolism) domain that is rarely found in humans and acts as the oligomerization domain. Since the oligomeric status is often linked to the particular functional role in these proteins, binding of ligands to the domain can elicit specific functional responses. Full-length Rv2779c corresponding to a molecular mass of 19.8 kDa and 179 residues was cloned and purified to homogeneity following transformation into Escherichia coli C41 (DE3) cells. Crystals were grown by vapour diffusion using the hanging-drop method. Diffraction data extending to 2.8 Å resolution were collected from a single crystal that belonged to space group P2(1)2(1)2, with unit-cell parameters a = 99.6, b = 146.0, c = 49.9 Å. Matthews coefficient (VM) calculations suggest that four molecules are present in the asymmetric unit, corresponding to a solvent content of ∼46%. Molecular-replacement calculations using the crystal structure of a homologue, Rv3291c, as the search model gave an unambiguous solution corresponding to four subunits in the asymmetric unit.

  6. IN-SITU RADIONUCLIDE TRANSPORT NEAR THE NOPAL I URANIUM DEPOSIT AT PENA BLANCA, MEXICO: CONSTRAINTS FROM SHORT-LIVED DECAY-SERIES RADIONUCLIDES

    International Nuclear Information System (INIS)

    Luo, S.; Ku, T.L.; Todd, V.; Murrell, M.; Pineda, J. Alfredo Rodriguez; Dinsmoor, J.; Mitchell, A.

    2005-01-01

    For nuclear waste management, an important mechanism by which radioactive waste components are isolated from returning to the human environment, the biosphere, is by the geological barrier in which the effectiveness of the barrier is characterized by in-situ retardation factor, i.e., the transport rate of a radionuclide relative to that of groundwater. As part of natural analog studies of the Yucca Mountain Project of the U. S. Department of Energy, we propose such characterization by using naturally-occurring decay-series radioisotopes as an analog. We collected large-volume (>1000 liters) groundwater samples from three wells (PB, Pozos, and PB4, respectively) near the Nopal I Uranium Ore site at Pena Blanca, Mexico, by using an in-situ Mn-cartridge filtration technique for analysis of short-lived decay-series radionuclides. Results show that the activities of short-lived radioisotopes ( 228 Ra, 224 Ra and 223 Ra) and activity ratios of 224 Ra/ 228 Ra and 224 Ra/ 223 Ra are higher at PB and Pozos than at PB4. In contrast, the 210 Po activity is much lower at PB and Pozos than at PB4. The high Ra activities and activities ratios at PB and Pozos are attributable to the high alpha-recoil input from the aquifer rocks, while the high 210 Po activity at PB4 is due to the enhanced colloidal transport. Based on a uranium-series transport model, we estimate that the in-situ retardation factor of Ra is (0.43 ± 0.02) x 10 3 at PB, (1.68 ± 0.08) x 10 3 at Pozos, and (1.19 ± 0.08) x 10 3 at PB4 and that the mean fracture width in the aquifer rocks is about 0.23 (micro)m at PB, 0.37 (micro)m at Posos, and 4.0 (micro)m at PB4, respectively. The large fracture width at PB4 as derived from the model provides an additional evidence to the inference from the Po measurements that particle-reactive radionuclides are transported mainly as colloidal forms through the large fractures in rocks. Our model also suggests that in addition to alpha recoil, decay of 226 Ra from the adsorbed

  7. IN-SITU RADIONUCLIDE TRANSPORT NEAR THE NOPAL I URANIUM DEPOSIT AT PENA BLANCA, MEXICO: CONSTRAINTS FROM SHORT-LIVED DECAY-SERIES RADIONUCLIDES

    Energy Technology Data Exchange (ETDEWEB)

    S. Luo; T.L. Ku; V. Todd; M. Murrell; J. Alfredo Rodriguez Pineda; J. Dinsmoor; A. Mitchell

    2005-07-11

    For nuclear waste management, an important mechanism by which radioactive waste components are isolated from returning to the human environment, the biosphere, is by the geological barrier in which the effectiveness of the barrier is characterized by in-situ retardation factor, i.e., the transport rate of a radionuclide relative to that of groundwater. As part of natural analog studies of the Yucca Mountain Project of the U. S. Department of Energy, we propose such characterization by using naturally-occurring decay-series radioisotopes as an analog. We collected large-volume (>1000 liters) groundwater samples from three wells (PB, Pozos, and PB4, respectively) near the Nopal I Uranium Ore site at Pena Blanca, Mexico, by using an in-situ Mn-cartridge filtration technique for analysis of short-lived decay-series radionuclides. Results show that the activities of short-lived radioisotopes ({sup 228}Ra, {sup 224}Ra and {sup 223}Ra) and activity ratios of {sup 224}Ra/{sup 228}Ra and {sup 224}Ra/{sup 223}Ra are higher at PB and Pozos than at PB4. In contrast, the {sup 210}Po activity is much lower at PB and Pozos than at PB4. The high Ra activities and activities ratios at PB and Pozos are attributable to the high alpha-recoil input from the aquifer rocks, while the high {sup 210}Po activity at PB4 is due to the enhanced colloidal transport. Based on a uranium-series transport model, we estimate that the in-situ retardation factor of Ra is (0.43 {+-} 0.02) x 10{sup 3} at PB, (1.68 {+-} 0.08) x 10{sup 3} at Pozos, and (1.19 {+-} 0.08) x 10{sup 3} at PB4 and that the mean fracture width in the aquifer rocks is about 0.23 {micro}m at PB, 0.37 {micro}m at Posos, and 4.0 {micro}m at PB4, respectively. The large fracture width at PB4 as derived from the model provides an additional evidence to the inference from the Po measurements that particle-reactive radionuclides are transported mainly as colloidal forms through the large fractures in rocks. Our model also suggests that

  8. Increased Concentrations of Short-Lived Decay-Series Radionuclides in Groundwaters Underneath the Nopal I Uranium Deposit at Pena Blanca, Mexico

    Science.gov (United States)

    Luo, S.; Ku, T.; Todd, V.; Murrell, M. T.; Dinsmoor, J. C.

    2007-05-01

    The Nopal I uranium ore deposit at Pena Blanca, Mexico, located at > 200 meters above the groundwater table, provides an ideal natural analog for quantifying the effectiveness of geological barrier for isolation of radioactive waste nuclides from reaching the human environments through ground water transport. To fulfill such natural analog studies, three wells (PB1, PB2, and PB3 respectively) were drilled at the site from the land surface down to the saturated groundwater zone and ground waters were collected from each of these wells through large- volume sampling/in-situ Mn-filter filtration for analyses of short-lived uranium/thorium-series radionuclides. Our measurements from PB1 show that the groundwater standing in the hole has much lower 222Rn activity than the freshly pumped groundwater. From this change in 222Rn activity, we estimate the residence time of groundwater in PB1 to be about 20 days. Our measurements also show that the activities of short-lived radioisotopes of Th (234Th), Ra (228Ra, 224Ra, 223Ra), Rn (222Rn), Pb (210Pb), and Po (210Po) in PB1, PB2, and PB3 are all significantly higher than those from the other wells near the Nopal I site. These high activities provide evidence for the enrichment of long-lived U and Ra isotopes in the groundwater as well as in the associated adsorbed phases on the fractured aquifer rocks underneath the ore deposit. Such enrichment suggests a rapid dissolution of U and Ra isotopes from the uranium ore deposit in the vadose zone and the subsequent migration to the groundwater underneath. A reactive transport model can be established to characterize the in-situ transport of radionuclides at the site. The observed change of 222Rn activity at PB1 also suggests that the measured high radioactivityies in ground waters from the site isare not an artifact of drilling operations. However, further studies are needed to assess if or to what extent the radionuclide migration is affected by the previous mining activities at

  9. Daily and seasonal variation of short-lived radon decay product concentrations in ground-level air at Munich-Neuherberg - a long-term study

    International Nuclear Information System (INIS)

    Winkler, R.

    2001-09-01

    Daily and seasonal variation of the equilibrium equivalent radon concentration (EEC Rn-222 ) and of the concentration of the short-lived radon decay product 214 Pb in ground-level air was investigated at Munich-Neuherberg from 1982 to 2000, and from 1989 to 2000, respectively. For this, the EEC was measured continuously with an alpha/beta aerosol monitor at 2.5 m above ground, and 214 Pb was determined by online gamma spectrometry at about 12 m above ground. The resulting time series were analysed statistically. For the respective periods, the measurements yielded a long-term average concentration of 7.8 Bq m -3 (geometric mean: 6.1 Bq m -3 ) for the EEC, and 6.0 Bq m -3 (geom. mean: 5.0 Bq m -3 ) for 214 Pb. In these periods, daily averages ranged from 0.6 to 49 Bq m -3 (EEC), and from 0.6 to 43 Bq m -3 ( 214 Pb). Monthly mean concentrations varied between 3.0 Bq m -3 in March 1988 and 20 Bq m -3 in October 1985 (EEC), and from 3.4 Bq m -3 in April 1992 to 11 Bq m -3 in October 1995 ( 214 Pb), respectively. The annual average concentrations were from 5.9 Bq m -3 in 1999 to 10.6 Bq m -3 in 1985 (EEC), and from 5.3 Bq m -3 in 1999 to 6.8 Bq m -3 in 1991 ( 214 Pb). From the long-term average equilibrium equivalent radon concentration (EEC), an average annual effective dose of 0.13 mSv due to the short-lived radon progeny outdoors was estimated. The time series showed distinct daily and seasonal variations. The variations from day to day are mainly caused by the actual weather conditions (wind, rain, etc.), i.e. the short-term turbulent conditions. The seasonal pattern is characterised by an autumn to winter maximum and an early summer minimum, and reflects the prevailing turbulent conditions at the respective seasons. As known, at Munich-Neuherberg during autumn and winter months (October/November to February) inversion weather conditions frequently occur, while the other months are characterised by more turbulent conditions. (orig.)

  10. Sterol regulatory element-binding proteins are regulators of the sodium/iodide symporter in mammary epithelial cells.

    Science.gov (United States)

    Wen, G; Pachner, L I; Gessner, D K; Eder, K; Ringseis, R

    2016-11-01

    The sodium/iodide symporter (NIS), which is essential for iodide concentration in the thyroid, is reported to be transcriptionally regulated by sterol regulatory element-binding proteins (SREBP) in rat FRTL-5 thyrocytes. The SREBP are strongly activated after parturition and throughout lactation in the mammary gland of cattle and are important for mammary epithelial cell synthesis of milk lipids. In this study, we tested the hypothesis that the NIS gene is regulated also by SREBP in mammary epithelial cells, in which NIS is functionally expressed during lactation. Regulation of NIS expression and iodide uptake was investigated by means of inhibition, silencing, and overexpression of SREBP and by reporter gene and DNA-binding assays. As a mammary epithelial cell model, the human MCF-7 cell line, a breast adenocarcinoma cell line, which shows inducible expression of NIS by all-trans retinoic acid (ATRA), and unlike bovine mammary epithelial cells, is widely used to investigate the regulation of mammary gland NIS and NIS-specific iodide uptake, was used. Inhibition of SREBP maturation by treatment with 25-hydroxycholesterol (5 µM) for 48h reduced ATRA (1 µM)-induced mRNA concentration of NIS and iodide uptake in MCF-7 cells by approximately 20%. Knockdown of SREBP-1c and SREBP-2 by RNA interference decreased the mRNA and protein concentration of NIS by 30 to 50% 48h after initiating knockdown, whereas overexpression of nuclear SREBP (nSREBP)-1c and nSREBP-2 increased the expression of NIS in MCF-7 cells by 45 to 60%, respectively, 48h after initiating overexpression. Reporter gene experiments with varying length of NIS promoter reporter constructs revealed that the NIS 5'-flanking region is activated by nSREBP-1c and nSREBP-2 approximately 1.5- and 4.5-fold, respectively, and activation involves a SREBP-binding motif (SRE) at -38 relative to the transcription start site of the NIS gene. Gel shift assays using oligonucleotides spanning either the wild-type or the

  11. AGE-DEPENDENT INHALATION DOSE DUE TO EXPOSURE OF SHORT LIVED PROGENY OF RADON AND THORON FOR DIFFERENT AGE GROUPS IN JAMMU & KASHMIR, HIMALAYAS.

    Science.gov (United States)

    Sharma, Sumit; Kumar, Ajay; Mehra, Rohit

    2018-05-16

    Dosimetric approach is used in this study for the assessment of doses due to inhalation of short lived radon/thoron progeny to the inhabitants of Udhampur district of Jammu & Kashmir. This paper also presents the activity concentrations and unattached fraction of radon and thoron progeny. The observed annual concentration of attached and unattached 222Rn and 220Rn progeny has been found to vary from 8 to 32 and 0.09 to 14 Bq/m3, 0.75 to 3.16 and 0.01 to 1.13 Bq/m3, respectively. The inhalation doses from radon progeny to different body organs of different age groups have been calculated by using the age dependent biokinetic model. The attachment rate of 222Rn and indoor aerosol concentration of 222Rn and 220Rn have been estimated and their relation between them has also been studied. The dose conversion factor for mouth and nasal breathing to different exposure conditions has been obtained from Porstendorfer model.

  12. Studies on the separation of rare earth elements and the nuclear decay properties of short lived rare-earth nuclides in U-235 fission products

    International Nuclear Information System (INIS)

    Ohyoshi, Akira; Ohyoshi, Emiko.

    1980-01-01

    The effect of a complex-forming agent, with which rare earths consecutively form the complexes, on the separation of a pair of adjacent rare earths by electromigration has been investigated. The relation between the separation factor for two complexes and the ligand-ion concentration was examined in the separation of La-Ce and Ce-Pr pairs with nitrilotriacetic acid. Rare earths were able to be isolated rapidly at the optimum ligand-ion concentration in lower one, and this method was applied to study the nuclear decay properties of the short lived isotopes of La, Ce, Pr, Nd and Yt formed in the fission of U-235. This method permits the direct measurement of the decay of La-144 without the interference from the radiation of other fission products. The gamma-ray spectrum of La-144 was measured with a high resolution Ge(Li) detector, and the gamma-transition was observed. From the decay plots of two strong photopeaks, the half-life of La-144 was determined. In the case of Ce fraction, the photopeaks assigned to respective isotopes were observed. In the studies on the decay properties of Pr-148 and Pr-149, the decay plot of the strong photopeak showed good linearity, and the accurate half-life of Pr-148 was determined. Similarly, the half-life of Pr-149 was longer than the previously reported value. (Kako, I.)

  13. 4-Amino-3H-pyrimidin-2-one ('isocytosine') is a short-lived non-radical intermediate formed in the pulse radiolysis of cytosine in aqueous solution

    International Nuclear Information System (INIS)

    Nien Schuchmann, Man; Naumov, Sergej; Schuchmann, Heinz-Peter; Sonntag, Justus von; Sonntag, Clemens von

    2005-01-01

    In the pulse radiolysis of 2'-deoxycytidine (dCyd) in N 2 O-saturated solutions containing 0.5M tertiary butanol to completely scavenge the water radicals, a short-lived intermediate (λmax=287nm) is observed by UV spectroscopy which is attributed to dCydH + , generated in the reaction of dCyd with H + formed during the pulse. By reacting with OH - , which is formed in the pulse in amounts matching that of H + , this intermediate disappears in the μs time range without a change of the spectrum. Similarly, cytosine (Cyt) gives rise to CytH + which, in contrast, in part transforms into another species (λmax=286nm) which can be assigned to isocytosine 1, 4-amino-3H-pyrimidin-2-one, a tautomer of Cyt which is formed by two routes (i) deprotonation of CytH + at N(1) by OH - and (ii) deprotonation of Cyt and reprotonation of the Cyt anion by water at N(3). Compared to Cyt, 1 is richer in Gibbs' free enthalpy by 14kJmol -1 . Its presence in low equilibrium concentrations has also been observed by conventional UV spectroscopy, making use of the increase of its equilibrium concentration with increasing temperature. From these data, an absorption coefficient of 3.3x10 4 dm 3 mol -1 cm -1 at 286nm has been calculated. Supporting quantum chemical calculations are also reported

  14. FORMATION OF THE SHORT-LIVED RADIONUCLIDE 36Cl IN THE PROTOPLANETARY DISK DURING LATE-STAGE IRRADIATION OF A VOLATILE-RICH RESERVOIR

    International Nuclear Information System (INIS)

    Jacobsen, Benjamin; Yin Qingzhu; Matzel, Jennifer; Hutcheon, Ian D.; Ramon, Erick C.; Weber, Peter K.; Krot, Alexander N.; Nagashima, Kazuhide; Ishii, Hope A.; Ciesla, Fred J.

    2011-01-01

    Short-lived radionuclides (SLRs) in the early solar system provide fundamental insight into protoplanetary disk evolution. We measured the 36 Cl- 36 S-isotope abundance in wadalite ( 36 Cl (τ 1/2 ∼ 3 x 10 5 yr) in the early solar system. Its presence, initial abundance, and the noticeable decoupling from 26 Al raise serious questions about the origin of SLRs. The inferred initial 36 Cl abundance for wadalite, corresponding to a 36 Cl/ 35 Cl ratio of (1.81 ± 0.13) x 10 -5 , is the highest 36 Cl abundance ever reported in any early solar system material. The high level of 36 Cl in wadalite and the absence of 26 Al ( 26 Al/ 27 Al ≤ 3.9 x 10 -6 ) in co-existing grossular (1) unequivocally support the production of 36 Cl by late-stage solar energetic particle irradiation in the protoplanetary disk and (2) indicates that the production of 36 Cl, recorded by wadalite, is unrelated to the origin of 26 Al and other SLRs ( 10 Be, 53 Mn) recorded by primary minerals of CAIs and chondrules. We infer that 36 Cl was largely produced by irradiation of a volatile-rich reservoir in an optically thin protoplanetary disk adjacent to the region in which the CV chondrite parent asteroid accreted while the Sun was a weak T Tauri star. Subsequently, 36 Cl accreted into the Allende CV chondrite together with condensed water ices.

  15. Transport of short-lived climate forcers/pollutants (SLCF/P) to the Himalayas during the South Asian summer monsoon onset

    International Nuclear Information System (INIS)

    Cristofanelli, P; Putero, D; Landi, T C; Marinoni, A; Duchi, R; Calzolari, F; Bonasoni, P; Adhikary, B; Stocchi, P; Verza, G; Vuillermoz, E; Laj, P; Kang, S; Ming, J

    2014-01-01

    Over the course of six years (2006–2011), equivalent black carbon (eqBC), coarse aerosol mass (PM 1–10 ), and surface ozone (O 3 ), observed during the monsoon onset period at the Nepal Climate Observatory–Pyramid WMO/GAW Global Station (NCO-P, 5079 m a.s.l.), were analyzed to investigate events characterized by a significant increase in these short-lived climate forcers/pollutants (SLCF/P). These events occurred during periods characterized by low (or nearly absent) rain precipitation in the central Himalayas, and they appeared to be related to weakening stages (or ‘breaking’) of the South Asian summer monsoon system. As revealed by the combined analysis of atmospheric circulation, air-mass three-dimensional back trajectories, and satellite measurements of atmospheric aerosol loading, surface open fire, and tropospheric NO x , the large amount of SLCF/P reaching the NCO-P appeared to be related to natural (mineral dust) and anthropogenic emissions occurring within the PBL of central Pakistan (i.e., Thar Desert), the Northwestern Indo-Gangetic plain, and the Himalayan foothills. The systematic occurrence of these events appeared to represent the most important source of SLCF/P inputs into the central Himalayas during the summer monsoon onset period, with possible important implications for the regional climate and for hydrological cycles. (letter)

  16. Design and development of a computer-based continuous monitor for the determination of the short-lived decay products of radon and thoron

    Energy Technology Data Exchange (ETDEWEB)

    Bigu, J [Department of Energy, Mines and Resources, Elliot Lake, Ontario (Canada). Elliot Lake Lab.; Raz, R; Golden, K; Dominguez, P [Alpha-NUCLEAR, Toronto, Ontario (Canada)

    1984-08-15

    A portable, rugged, monitor has been designed and built for measuring the short-lived decay products of radon and thoron. The monitor is computer-based and employs a continuous filter strip which can be advanced at programmable time intervals to allow unattended continuous operation with automatic sampling, analysis and recording of radiation levels. Radionuclide analysis is carried out by two silicon diffused-junction alpha-detectors and electronic circuitry with multichannel spectral analysis capabilities. Standard gross ..cap alpha..-count methods and ..cap alpha..-spectroscopy methods can easily be implemented. The built-in computer performs a variety of operations via a specially designed interface module, including control and data recording functions, and computations, program storage and display functions. Programs and data are stored in the built-in casette tape drive and the computer integrated CRT display and keyboard allow simple, prompted menu-type operation of standard software. Graphical presentation of ..cap alpha..-spectra can be shown on the computer CRT and printed when required on the computer built-in thermal printer. In addition, to implementing the specially developed radionuclide analysis software, the operator can interact and modify existing software, and program new ones, through BASIC language programming, or employ the computer in a totally unrelated, general purpose model. Although the monitor is ideally suited for environmental radon (thoron) daughter monitoring, it could also be used in the determination of other airborne radionuclides provided adequate analytical procedures are developed or included in the already existing computer software.

  17. Half-life and mass measurement of the short-lived {sup 215}Po isotope (1.78 ms) at the FRS ion catcher

    Energy Technology Data Exchange (ETDEWEB)

    Rink, Ann-Kathrin; Bergmann, Julian; Ebert, Jens; Hornung, Christine; Miskun, Ivan; Reiter, Moritz P. [Justus-Liebig Universitaet Giessen (Germany); Ayet San Andres, Samuel; Dickel, Timo; Plass, Wolfgang R.; Scheidenberger, Christoph [Justus-Liebig Universitaet Giessen (Germany); GSI, Darmstadt (Germany); Geissel, Hans; Purushothaman, Sivaji [GSI, Darmstadt (Germany)

    2016-07-01

    At the Low-Energy Branch (LEB) of the Super-FRS at FAIR, precision experiments with exotic nuclei will be performed using ion traps and lasers. The nuclei will be produced at relativistic energies, slowed down, thermalised in a cryogenic stopping cell (CSC) and made available to various experiments. The thermalisation is a challenging task because of the large energy straggling of the nuclei after production, which requires a stopping cell with large areal densities. Also, the process needs to be performed on a millisecond time scale in order to give access to short-lived nuclides. This method has already been successfully applied at the FRS Ion Catcher at GSI using a prototype CSC. Recently the potential of the method has been demonstrated by the mass and half-life measurement of the {sup 215}Po nuclide with a half-life of 1.78 ms only. The multiple-reflection time-of-flight mass spectrometer at the FRS Ion Catcher has been used to determine the mass to a sub-ppm accuracy and to provide a mass-selected beam for alpha spectroscopy. Furthermore, experiments have been performed with the prototype CSC in order to test novel concepts to be used with the final version of the CSC for the LEB.

  18. Tropospheric ozone and its precursors from the urban to the global scale from air quality to short-lived climate forcer

    Science.gov (United States)

    Monks, P. S.; Archibald, A. T.; Colette, A.; Cooper, O.; Coyle, M.; Derwent, R.; Fowler, D.; Granier, C.; Law, K. S.; Mills, G. E.; Stevenson, D. S.; Tarasova, O.; Thouret, V.; von Schneidemesser, E.; Sommariva, R.; Wild, O.; Williams, M. L.

    2015-08-01

    Ozone holds a certain fascination in atmospheric science. It is ubiquitous in the atmosphere, central to tropospheric oxidation chemistry, yet harmful to human and ecosystem health as well as being an important greenhouse gas. It is not emitted into the atmosphere but is a byproduct of the very oxidation chemistry it largely initiates. Much effort is focused on the reduction of surface levels of ozone owing to its health and vegetation impacts, but recent efforts to achieve reductions in exposure at a country scale have proved difficult to achieve owing to increases in background ozone at the zonal hemispheric scale. There is also a growing realisation that the role of ozone as a short-lived climate pollutant could be important in integrated air quality climate change mitigation. This review examines current understanding of the processes regulating tropospheric ozone at global to local scales from both measurements and models. It takes the view that knowledge across the scales is important for dealing with air quality and climate change in a synergistic manner. The review shows that there remain a number of clear challenges for ozone such as explaining surface trends, incorporating new chemical understanding, ozone-climate coupling, and a better assessment of impacts. There is a clear and present need to treat ozone across the range of scales, a transboundary issue, but with an emphasis on the hemispheric scales. New observational opportunities are offered both by satellites and small sensors that bridge the scales.

  19. Triggering Collapse of the Presolar Dense Cloud Core and Injecting Short-lived Radioisotopes with a Shock Wave. V. Nonisothermal Collapse Regime

    Energy Technology Data Exchange (ETDEWEB)

    Boss, Alan P., E-mail: aboss@carnegiescience.edu [Department of Terrestrial Magnetism, Carnegie Institution for Science, 5241 Broad Branch Road, NW, Washington, DC 20015-1305 (United States)

    2017-08-01

    Recent meteoritical analyses support an initial abundance of the short-lived radioisotope (SLRI) {sup 60}Fe that may be high enough to require nucleosynthesis in a core-collapse supernova, followed by rapid incorporation into primitive meteoritical components, rather than a scenario where such isotopes were inherited from a well-mixed region of a giant molecular cloud polluted by a variety of supernovae remnants and massive star winds. This paper continues to explore the former scenario, by calculating three-dimensional, adaptive mesh refinement, hydrodynamical code (FLASH 2.5) models of the self-gravitational, dynamical collapse of a molecular cloud core that has been struck by a thin shock front with a speed of 40 km s{sup −1}, leading to the injection of shock front matter into the collapsing cloud through the formation of Rayleigh–Taylor fingers at the shock–cloud intersection. These models extend the previous work into the nonisothermal collapse regime using a polytropic approximation to represent compressional heating in the optically thick protostar. The models show that the injection efficiencies of shock front materials are enhanced compared to previous models, which were not carried into the nonisothermal regime, and so did not reach such high densities. The new models, combined with the recent estimates of initial {sup 60}Fe abundances, imply that the supernova triggering and injection scenario remains a plausible explanation for the origin of the SLRIs involved in the formation of our solar system.

  20. 'Sleeping reactor' irradiations. The use of a shut-down reactor for the determination of elements with short-lived activation products

    International Nuclear Information System (INIS)

    Jerde, E.A.; Oak Ridge National Laboratory, TN; Glasgow, D.C.

    1999-01-01

    Neutron activation analysis utilizing the High Flux Isotope Reactor (HFIR) immediately following SCRAM is a workable solution to obtaining data for ultra-short lived species, principally Al, Ti, Mg, and V. Neutrons are produced in the HFIR core within the beryllium reflector due to gamma-ray bombardment from the spent fuel elements. This neutron flux is not constant, varying by over two orders of magnitude during the first 24 hours. The problems associated with irradiation in a changing neutron flux are removed through the use of a specially tailored activation equation. This activation equation is applicable to any irradiation at HFIR in the firs 24 hours after SCRAM since the fuel elements are identical from cycle to cycle, and the gamma-emitting nuclides responsible for the neutrons reach saturation during the fuel cycle. Reference material tests demonstrate that this method is successful, and detection limit estimates reveal that it should be applicable to materials of widely ranging mass and composition. (author)

  1. The origin and disappearance of the late Pleistocene-early Holocene short-lived coastal wetlands along the Carmel coast, Israel

    Science.gov (United States)

    Sivan, Dorit; Greenbaum, Noam; Cohen-Seffer, Ronit; Sisma-Ventura, Guy; Almogi-Labin, Ahuva

    The formation of short-lived backswamps along the Carmel coast of Israel coincides with the rapid global sea-level rise during the late Pleistocene-early Holocene transition. The current study shows that the wetland phenomena originated around 10,000 yr ago and dried up shortly before the local Pre-Pottery Neolithic humans settled on the wetland dark clay sediments 9430 cal yr BP. Palaeontological and stable-isotope data were used in this study to elucidate previously published sedimentological reconstruction obtained from a core drilled into the western trough of the Carmel coastal plain. The water body contained typical brackish calcareous fauna, with variable numerical abundance and low species richness of ostracods and foraminifera. The δ 18O and δ 13C of the ostracod Cyprideis torosa show close similarity to the present Pleistocene coastal aquifer isotopic values. This study therefore concludes that the wetlands were shallow-water bodies fed by groundwater, with no evidence of sea-water mixing. It seems that they developed as the result of high groundwater levels, transportation of sediments landward, and deposition of sand bars at the paleo-river mouths. It is still not fully understood why these wetlands deteriorated abruptly and disappeared within less than 1000 yr.

  2. Design and Performance Assessment of a Conceptual Cover Cap of Near Surface Repository for Short Lived Low and Intermediate Level Radioactive Waste

    Energy Technology Data Exchange (ETDEWEB)

    Asaba, Ruth; Kim, Changlak [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

    2014-05-15

    The safety of the overall waste disposal system is determined by the performance of its individual components: waste form, waste container, engineered barrier and the host environment. The design of the cover cap helps in preventing percolation of water, and in retarding radionuclide migration from the disposal facility to the biosphere. The cover of a disposal facility is usually a combination of materials such as sand, gravel, concrete, clay and soil conditioned for vegetation growth. The cover system will be designed using models such as EPA's Hydrological Evaluation of Land fill Performance (HELP) code. This paper describes a conceptual design for a cover cap for a land fill as a preferred disposal facility for low and short lived intermediate radioactive waste in Uganda. Majority of the waste is generated from disused sealed and unsealed radioactive sources arising from medical, industrial applications, and research. Radioactive waste management has raised a lot of concern in both developed and developing countries. Each country has a responsibility to come up with a solution to prevent contamination of the environment and humans from radioactive waste. It is important to have thicker soil layers in cap designs so as to support vegetation growth since some activities such as erosion and settlements are expected. Help simulations in this study will assist to demonstrate that it is possible to design a cover cap which can contain radioactive waste packages for hundreds of years provided the proper institutional and performance monitoring schemes are implemented.

  3. Leadership emergence over time in short-lived groups: Integrating expectations states theory with temporal person-perception and self-serving bias.

    Science.gov (United States)

    Kalish, Yuval; Luria, Gil

    2016-10-01

    Research into leadership emergence typically focuses on the attributes of the emergent leader. By considering also the attributes of perceivers and the passage of time, we develop a more complete theory of leadership emergence in short-lived groups. Using expectation states theory as an overarching theoretical framework, and integrating it with the surface- and deep-level diversity literature and with theories of self-serving biases, we examine the predictors of leadership emergence in short timeframes. We conduct a field study in a military assessment boot camp (a pilot study, n = 60; and a main study, n = 89). We use cross-sectional and longitudinal exponential random graph models to analyze data on participants' abilities and on their perceptions of who, in their respective groups, were "leaders." We find that the criteria by which people perceive leadership in others change over time, from easily noticeable attributes to covert leadership-relevant attributes, and that people also rely on leadership-relevant attributes that they possess at high levels to inform their perceptions of leadership in others. The integration of expectation states theory, attribute salience over time and theories of self-serving bias is needed for a full understanding of leadership emergence in groups, because perceivers' own abilities are instrumental in shaping their perceptions of emergent leadership over time. Theoretical and practical implications are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  4. Design and development of a computer-based continuous monitor for the determination of the short-lived decay products of radon and thoron

    International Nuclear Information System (INIS)

    Bigu, J.

    1984-01-01

    A portable, rugged, monitor has been designed and built for measuring the short-lived decay products of radon and thoron. The monitor is computer-based and employs a continuous filter strip which can be advanced at programmable time intervals to allow unattended continuous operatin with automatic sampling, analysis and recording of radiation levels. Radionuclide analysis is carried out by two silicon diffused-junction alpha-detectors and electronic circuitry with multichannel spectral analysis capabilities. Standard gross α-count methods and α-spectroscopy methods can easily be implemented. The built-in computer performs a variety of operations via a specially designed interface module, including control and data recording functions, and computations, program storage and display functions. Programs and data are stored in the built-in casette tape drive and the computer integrated CRT display and keyboard allow simple, prompted menu-type operation of standard software. Graphical presentation of α-spectra can be shown on the computer CRT and printed when required on the computer built-in thermal printer. In addition, to implementing the specially developed radionuclide analysis software, the operator can interact and modify existing software, and program new ones, through BASIC language programming, or employ the computer in a totally unrelated, general purpose model. Although the monitor is ideally suited for environmental radon (thoron) daughter monitoring, it could also be used in the determination of other airborne radionuclides provided adequate analytical procedures are developed or included in the already existing computer software. (orig.)

  5. Climate impacts of short-lived climate forcers versus CO2 from biodiesel: a case of the EU on-road sector.

    Science.gov (United States)

    Lund, Marianne T; Berntsen, Terje K; Fuglestvedt, Jan S

    2014-12-16

    Biofuels are proposed to play an important role in several mitigation strategies to meet future CO2 emission targets for the transport sector but remain controversial due to significant uncertainties in net impacts on environment, society, and climate. A switch to biofuels can also affect short-lived climate forcers (SLCFs), which provide significant contributions to the net climate impact of transportation. We quantify the radiative forcing (RF) and global-mean temperature response over time to EU on-road fossil diesel SLCFs and the impact of 20% (B20) and 100% (B100) replacement of fossil diesel by biodiesel. SLCFs are compared to impacts of on-road CO2 using different approaches from existing literature to account for biodiesel CO2. Given the best estimates for changes in emissions when replacing fossil diesel with biodiesel, the net positive RF from EU on-road fossil diesel SLCFs of 3.4 mW/m(2) is reduced by 15% and 80% in B20 and B100, respectively. Over time the warming of SLCFs is likely small compared to biodiesel CO2 impacts. However, SLCFs may be relatively more important for the total warming than in the fossil fuel case if biodiesel from feedstock with very short rotation periods and low land-use-change impacts replaces a high fraction of fossil diesel.

  6. Nitrosylation of Nitric-Oxide-Sensing Regulatory Proteins Containing [4Fe-4S] Clusters Gives Rise to Multiple Iron-Nitrosyl Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Serrano, Pauline N. [Department of Chemistry, University of California, Davis CA 95616 USA; Wang, Hongxin [Department of Chemistry, University of California, Davis CA 95616 USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley CA 94720 USA; Crack, Jason C. [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Prior, Christopher [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Hutchings, Matthew I. [School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ UK; Thomson, Andrew J. [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Kamali, Saeed [University of Tennessee Space Institute, Tullahome TN 37388-9700 USA; Yoda, Yoshitaka [Research and Utilization Division, SPring-8/JASRI, 1-1-1 Kouto, Sayo Hyogo 679-5198 Japan; Zhao, Jiyong [Advanced Photon Source, Argonne National Laboratory, Argonne IL 60439 USA; Hu, Michael Y. [Advanced Photon Source, Argonne National Laboratory, Argonne IL 60439 USA; Alp, Ercan E. [Advanced Photon Source, Argonne National Laboratory, Argonne IL 60439 USA; Oganesyan, Vasily S. [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Le Brun, Nick E. [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Cramer, Stephen P. [Department of Chemistry, University of California, Davis CA 95616 USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley CA 94720 USA

    2016-10-25

    The reaction of protein-bound iron–sulfur (Fe-S) clusters with nitric oxide (NO) plays key roles in NO-mediated toxicity and signaling. Elucidation of the mechanism of the reaction of NO with DNA regulatory proteins that contain Fe-S clusters has been hampered by a lack of information about the nature of the iron-nitrosyl products formed. Herein, we report nuclear resonance vibrational spectroscopy (NRVS) and density functional theory (DFT) calculations that identify NO reaction products in WhiD and NsrR, regulatory proteins that use a [4Fe-4S] cluster to sense NO. This work reveals that nitrosylation yields multiple products structurally related to Roussin's Red Ester (RRE, [Fe2(NO)4(Cys)2]) and Roussin's Black Salt (RBS, [Fe4(NO)7S3]. In the latter case, the absence of 32S/34S shifts in the Fe-S region of the NRVS spectra suggest that a new species, Roussin's Black Ester (RBE), may be formed, in which one or more of the sulfide ligands is replaced by Cys thiolates.

  7. Fusobacterium nucleatum binding to complement regulatory protein CD46 modulates the expression and secretion of cytokines and matrix metalloproteinases by oral epithelial cells.

    Science.gov (United States)

    Mahtout, Hayette; Chandad, Fatiha; Rojo, Jose M; Grenier, Daniel

    2011-02-01

    Periodontitis is a chronic inflammatory disease that results in the destruction of the supporting tissues of the teeth. Gingival epithelial cells are an important mechanical barrier and participate in the host inflammatory response to periodontopathogens. The aim of the present study is to investigate the capacity of Fusobacterium nucleatum to bind to the complement regulatory protein CD46 expressed by oral epithelial cells and to determine the impact of the binding on the gene expression and protein secretion of interleukin (IL)-6, IL-8, and matrix metalloproteinase (MMP)-9 by oral epithelial cells. Binding of recombinant human CD46 to the surface of F. nucleatum was demonstrated by immunologic assays. After stimulation of oral epithelial cells with F. nucleatum, gene expression was determined by real-time polymerase chain reaction analysis while protein secretion was monitored by enzyme-linked immunosorbent assays. Heat and protease treatments of bacterial cells reduced CD46 binding. F. nucleatum-bound CD46 mediated the cleavage of C3b in the presence of factor I. Stimulating oral epithelial cells with F. nucleatum at a multiplicity of infection of 50 resulted in a significant upregulation of the gene expression and protein secretion of IL-6, IL-8, and MMP-9 by oral epithelial cells. However, pretreating the epithelial cells with an anti-CD46 polyclonal antibody attenuated the production of IL-6, IL-8, and MMP-9 in response to F. nucleatum. Such an inhibitory effect was not observed with non-specific antibodies. The present study demonstrates that F. nucleatum can bind the complement regulatory protein CD46. The interaction of F. nucleatum with epithelial cell surface CD46 may contribute to increasing the levels of proinflammatory mediators and MMPs in periodontal sites and consequently modulate tissue destruction.

  8. Dual regulatory roles of the extended N terminus for activation of the tomato MI-1.2 resistance protein

    NARCIS (Netherlands)

    Lukasik-Shreepaathy, E.; Slootweg, E.; Richter, H.; Goverse, A.; Cornelissen, B.J.C.; Takken, F.L.W.

    2012-01-01

    Plant resistance (R) proteins mediate race-specific immunity and initiate host defenses that are often accompanied by a localized cell-death response. Most R proteins belong to the nucleotide binding-leucine-rich repeat (NB-LRR) protein family, as they carry a central NB-ARC domain fused to an LRR

  9. Sterols regulate 3β-hydroxysterol Δ24-reductase (DHCR24) via dual sterol regulatory elements: cooperative induction of key enzymes in lipid synthesis by Sterol Regulatory Element Binding Proteins.

    Science.gov (United States)

    Zerenturk, Eser J; Sharpe, Laura J; Brown, Andrew J

    2012-10-01

    3β-Hydroxysterol Δ24-reductase (DHCR24) catalyzes a final step in cholesterol synthesis, and has been ascribed diverse functions, such as being anti-apoptotic and anti-inflammatory. How this enzyme is regulated transcriptionally by sterols is currently unclear. Some studies have suggested that its expression is regulated by Sterol Regulatory Element Binding Proteins (SREBPs) while another suggests it is through the Liver X Receptor (LXR). However, these transcription factors have opposing effects on cellular sterol levels, so it is likely that one predominates. Here we establish that sterol regulation of DHCR24 occurs predominantly through SREBP-2, and identify the particular region of the DHCR24 promoter to which SREBP-2 binds. We demonstrate that sterol regulation is mediated by two sterol regulatory elements (SREs) in the promoter of the gene, assisted by two nearby NF-Y binding sites. Moreover, we present evidence that the dual SREs work cooperatively to regulate DHCR24 expression by comparison to two known SREBP target genes, the LDL receptor with one SRE, and farnesyl-diphosphate farnesyltransferase 1, with two SREs. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. The dengue vector Aedes aegypti contains a functional high mobility group box 1 (HMGB1 protein with a unique regulatory C-terminus.

    Directory of Open Access Journals (Sweden)

    Fabio Schneider Ribeiro

    Full Text Available The mosquito Aedes aegypti can spread the dengue, chikungunya and yellow fever viruses. Thus, the search for key molecules involved in the mosquito survival represents today a promising vector control strategy. High Mobility Group Box (HMGB proteins are essential nuclear factors that maintain the high-order structure of chromatin, keeping eukaryotic cells viable. Outside the nucleus, secreted HMGB proteins could alert the innate immune system to foreign antigens and trigger the initiation of host defenses. In this work, we cloned and functionally characterized the HMGB1 protein from Aedes aegypti (AaHMGB1. The AaHMGB1 protein typically consists of two HMG-box DNA binding domains and an acidic C-terminus. Interestingly, AaHMGB1 contains a unique alanine/glutamine-rich (AQ-rich C-terminal region that seems to be exclusive of dipteran HMGB proteins. AaHMGB1 is localized to the cell nucleus, mainly associated with heterochromatin. Circular dichroism analyses of AaHMGB1 or the C-terminal truncated proteins revealed α-helical structures. We showed that AaHMGB1 can effectively bind and change the topology of DNA, and that the AQ-rich and the C-terminal acidic regions can modulate its ability to promote DNA supercoiling, as well as its preference to bind supercoiled DNA. AaHMGB1 is phosphorylated by PKA and PKC, but not by CK2. Importantly, phosphorylation of AaHMGB1 by PKA or PKC completely abolishes its DNA bending activity. Thus, our study shows that a functional HMGB1 protein occurs in Aedes aegypt and we provide the first description of a HMGB1 protein containing an AQ-rich regulatory C-terminus.

  11. The E1A proteins of all six human adenovirus subgroups target the p300/CBP acetyltransferases and the SAGA transcriptional regulatory complex

    International Nuclear Information System (INIS)

    Shuen, Michael; Avvakumov, Nikita; Torchia, Joe; Mymryk, Joe S.

    2003-01-01

    The N-terminal/conserved region 1 (CR1) portion of the human adenovirus (Ad) 5 E1A protein was previously shown to inhibit growth in the simple eukaryote Saccharomyces cerevisiae. We now demonstrate that the corresponding regions of the E1A proteins of Ad3,-4,-9,-12, and -40, which represent the remaining five Ad subgroups, also inhibit yeast growth. These results suggest that the E1A proteins of all six human Ad subgroups share a common cellular target(s) conserved in yeast. Growth inhibition induced by either full-length or the N-terminal/CR1 portion of Ad5 E1A was relieved by coexpression of the E1A binding portions of the mammalian p300, CBP, and pCAF acetyltransferases. Similarly, growth inhibition by the N-terminal/CR1 portions of the other Ad E1A proteins was suppressed by expression of the same regions of CBP or pCAF known to bind Ad5 E1A. The physical interaction of each of the different Ad E1A proteins with CBP, p300, and pCAF was confirmed in vitro. Furthermore, deletion of the gene encoding yGcn5, the yeast homolog of pCAF and a subunit of the SAGA transcriptional regulatory complex, restored growth in yeast expressing each of the different Ad E1A proteins. This indicates that the SAGA complex is a conserved target of all Ad E1A proteins. Our results demonstrate for the first time that the p300, CBP, and pCAF acetyltransferases are common targets for the E1A proteins of all six human Ad subgroups, highlighting the importance of these interactions for E1A function

  12. Ultrastructural and biochemical evidence for the presence of mature steroidogenic acute regulatory protein (StAR) in the cytoplasm of human luteal cells.

    Science.gov (United States)

    Sierralta, Walter D; Kohen, Paulina; Castro, Olga; Muñoz, Alex; Strauss, Jerome F; Devoto, Luigi

    2005-10-20

    The distribution of the steroidogenic acute regulatory protein (StAR) inside thecal and granulosa-lutein cells of human corpus luteum (CL) was assessed by immunoelectron microscopy. We found greater levels of StAR immunolabeling in steroidogenic cells from early- and mid-than in late luteal phase CL and lower levels in cells from women treated with a GnRH antagonist in the mid-luteal phase. Immunoelectron microscopy revealed significant levels of StAR antigen in the mitochondria and in the cytoplasm of luteal cells. The 30 kDa mature StAR protein was present in both mitochondria and cytosol (post-mitochondrial) fractions from homogenates of CL at different ages, whereas cytochrome c and mitochondrial HSP70 were detected only in the mitochondrial fraction. Therefore, we hypothesized that either appreciable processing of StAR 37 kDa pre-protein occurs outside the mitochondria, or mature StAR protein is selectively released into the cytoplasm after mitochondrial processing. The presence of mature StAR in the cytoplasm is consonant with the notion that StAR acts on the outer mitochondrial membrane to effect sterol import, and that StAR may interact with other cytoplasmic proteins involved in cholesterol metabolism, including hormone sensitive lipase.

  13. Public participation in decision-making processes: ONDRAF/NIRAS' approach to the disposal of low-level and short-lived radioactive waste

    International Nuclear Information System (INIS)

    Hooft, E.

    2000-01-01

    January 16, 1998, is a milestone in the nuclear waste management in Belgium. On that day, the Belgian government effectively opted for a definitive or potentially definitive solution for the Iona term management of low-level, short-lived radioactive waste. The government also wanted this solution to be implemented in a progressive, flexible, and reversible manner. it was thereby definitively abandoning the prolonged interim storage option, in favour of either surface disposal or deep geological disposal. At the same time, the government entrusted new missions to ONDRAFINIRAS, aimed at enabling it to make, around 2001-2002, the necessary technical and economic choice between surface disposal and deep geological disposal. ONDRAFNIRAS had to develop, in particular, methods, including the management and dialogue strictures, necessary to integrate a repository project at the local level. Furthermore, it had to restrict from then on its investigations to the four already existing nuclear zones in Belgium namely those of Doel, Fleurus, Mol-Dessel, and Tihange, and to the local towns or villages having shown an interest in a preliminary field study. Early in 1998, ONDRAFNIRAS set up a new work programme and developed an entirely new work methodology. As we understood that the best way to take involved into account the interests of all parties, is to involve them in the decision making on the project, we developed the idea of the local partnerships. Any party that could be directly affected by a collective decision, must have a say in it. Another innovative aspect of this new methodology is that of integration: an integration at the local level which is meant to enable the development of draft repository projects creating new perspectives for the regions concerned. Extending over four to five years, ONDRAFINIRAS's new work programme assumes the active participation of all the interested local representatives. Because it has understood that any party that could be directly

  14. TRIGGERING COLLAPSE OF THE PRESOLAR DENSE CLOUD CORE AND INJECTING SHORT-LIVED RADIOISOTOPES WITH A SHOCK WAVE. II. VARIED SHOCK WAVE AND CLOUD CORE PARAMETERS

    Energy Technology Data Exchange (ETDEWEB)

    Boss, Alan P.; Keiser, Sandra A., E-mail: boss@dtm.ciw.edu, E-mail: keiser@dtm.ciw.edu [Department of Terrestrial Magnetism, Carnegie Institution, 5241 Broad Branch Road, NW, Washington, DC 20015-1305 (United States)

    2013-06-10

    A variety of stellar sources have been proposed for the origin of the short-lived radioisotopes that existed at the time of the formation of the earliest solar system solids, including Type II supernovae (SNe), asymptotic giant branch (AGB) and super-AGB stars, and Wolf-Rayet star winds. Our previous adaptive mesh hydrodynamics models with the FLASH2.5 code have shown which combinations of shock wave parameters are able to simultaneously trigger the gravitational collapse of a target dense cloud core and inject significant amounts of shock wave gas and dust, showing that thin SN shocks may be uniquely suited for the task. However, recent meteoritical studies have weakened the case for a direct SN injection to the presolar cloud, motivating us to re-examine a wider range of shock wave and cloud core parameters, including rotation, in order to better estimate the injection efficiencies for a variety of stellar sources. We find that SN shocks remain as the most promising stellar source, though planetary nebulae resulting from AGB star evolution cannot be conclusively ruled out. Wolf-Rayet (WR) star winds, however, are likely to lead to cloud core shredding, rather than to collapse. Injection efficiencies can be increased when the cloud is rotating about an axis aligned with the direction of the shock wave, by as much as a factor of {approx}10. The amount of gas and dust accreted from the post-shock wind can exceed that injected from the shock wave, with implications for the isotopic abundances expected for a SN source.

  15. Impact on short-lived climate forcers (SLCFs) from a realistic land-use change scenario via changes in biogenic emissions.

    Science.gov (United States)

    Scott, C E; Monks, S A; Spracklen, D V; Arnold, S R; Forster, P M; Rap, A; Carslaw, K S; Chipperfield, M P; Reddington, C L S; Wilson, C

    2017-08-24

    More than one quarter of natural forests have been cleared by humans to make way for other land-uses, with changes to forest cover projected to continue. The climate impact of land-use change (LUC) is dependent upon the relative strength of several biogeophysical and biogeochemical effects. In addition to affecting the surface albedo and exchanging carbon dioxide (CO 2 ) and moisture with the atmosphere, vegetation emits biogenic volatile organic compounds (BVOCs), altering the formation of short-lived climate forcers (SLCFs) including aerosol, ozone (O 3 ) and methane (CH 4 ). Once emitted, BVOCs are rapidly oxidised by O 3 , and the hydroxyl (OH) and nitrate (NO 3 ) radicals. These oxidation reactions yield secondary organic products which are implicated in the formation and growth of aerosol particles and are estimated to have a negative radiative effect on the climate (i.e. a cooling). These reactions also deplete OH, increasing the atmospheric lifetime of CH 4 , and directly affect concentrations of O 3 ; the latter two being greenhouse gases which impose a positive radiative effect (i.e. a warming) on the climate. Our previous work assessing idealised deforestation scenarios found a positive radiative effect due to changes in SLCFs; however, since the radiative effects associated with changes to SLCFs result from a combination of non-linear processes it may not be appropriate to scale radiative effects from complete deforestation scenarios according to the deforestation extent. Here we combine a land-surface model, a chemical transport model, a global aerosol model, and a radiative transfer model to assess the net radiative effect of changes in SLCFs due to historical LUC between the years 1850 and 2000.

  16. Contributions of short-lived radioiodines to thyroid doses received by evacuees from the Chernobyl area estimated using early in vivo activity measurements

    International Nuclear Information System (INIS)

    Balonov, M.; Kaidanovsky, G.; Zvonova, I.; Kovtun, A.; Bouville, A.; Luckyanov, L.; Voilleque, P.

    2003-01-01

    A series of in-vivo gamma spectrometric measurements of 65 people, evacuated from Pripyat 1.5 days after the Chernobyl Nuclear Power Plant Unit 4 explosion was performed in St. Petersburg, Russia, as early as 30 April 1986. The historical spectra and interviews were recently processed and the results used for thyroid dose estimation. Activities of 131 I in thyroid and 132 Te in lungs were determined easily; for estimation of 132 I and 133 I activities in thyroid, sophisticated methods of spectra processing were developed. According to thyroid measurement data, the mean ratio of 133 I/ 131 I activities (at the time of the accident) inhaled by residents of Pripyat was 2.0. The mean ratio of thyroid dose from 133 I inhalation to that caused by 131 I amounts to 0.3, which confirms accuracy of dose estimates based on the evolution of the Chernobyl accident. The mean ratio of 132 I activity in thyroid to that of 132 Te in lungs was assessed from the human measurement data to be 0.2, which is in reasonable agreement with the metabolic properties of these radionuclides. The mean ratio of thyroid dose from 132 I originating from 132 Te deposited in lungs to the dose caused by 131 I was 0.13 ± 0.02 for Pripyat residents who did not take KI pills and 0.9 ± 0.1 for persons who took KI pills. Thus, the contribution of short-lived radioiodines to total thyroid dose of Pripyat residents, which was on average 30% for persons who did not apply stable iodine prophylaxis, and about 50% for persons who took KI pills on 26-27 April, should be accounted for in the assessment of thyroid health effects. (author)

  17. Preliminary Results of IS Plasma Focus as a Breeder of Short-Lived Radioisotopes 12C(d,n)13N

    Science.gov (United States)

    Sadat Kiai, S. M.; Elahi, M.; Adlparvar, S.; Shahhoseini, E.; Sheibani, S.; Ranjber akivaj, H.; Alhooie, S.; Safarien, A.; Farhangi, S.; Aghaei, N.; Amini, S.; Khalaj, M. M.; Zirak, A. R.; Dabirzadeh, A. A.; Soleimani, J.; Torkzadeh, F.; Mousazadeh, M. M.; Moradi, K.; Abdollahzadeh, M.; Talaei, A.; Zaeem, A. A.; Moslehi, A.; Kashani, A.; Babazadeh, A. R.; Bagiyan, F.; Ardestani, M.; Roozbahani, A.; Pourbeigi, H.; Tajik Ahmadi, H.; Ahmadifaghih, M. A.; Mahlooji, M. S.; Mortazavi, B. N.; Zahedi, F.

    2011-04-01

    Modified IS (Iranian Sun) plasma focus (10 kJ,15 kV, 94 μF, 0.1 Hz) has been used to produce the short-lived radioisotope 13N (half-life of 9.97 min) through 12C(d,n)13N nuclear reaction. The filling gas was 1.5-3 torr of hydrogen (60%) deuterium (40%) mixture. The target was solid nuclear grade graphite with 5 mm thick, 9 cm width and 13 in length. The activations of the exogenous target on average of 20 shots (only one-third acceptable) through 10-13 kV produced the 511 keV gamma rays. Another peak found at the 570 keV gamma of which both was measured by a NaI portable gamma spectrometer calibrated by a 137Cs 0.25 μCi sealed reference source with its single line at 661.65 keV and 22Na 0.1 μCi at 511 keV. To measure the gamma rays, the graphite target converts to three different phases; solid graphite, powder graphite, and powder graphite in water solution. The later phase approximately has a doubled activity with respect to the solid graphite target up to 0.5 μCi of 511 keV and 1.1 μCi of 570 keV gamma lines were produced. This increment in activity was perhaps due to structural transformation of graphite powder to nano-particles characteristic in liquid water.

  18. Time-series variations of the short-lived Ra in coastal waters: implying input of SGD to the coastal zone of Da-Chia River, Taichung, Taiwan

    Science.gov (United States)

    Hsu, Feng-Hsin; Su, Chih-Chieh; Lin, In-Tain; Huh, Chih-An

    2015-04-01

    Submarine groundwater discharge (SGD) has been recognized as an important pathway for materials exchanging between land and sea. Input of SGD carries the associated nutrients, trace metals, and inorganic carbon that may makes great impacts on ecosystem in the coastal zone. Due to the variability of SGD magnitude, it is difficult to estimate the flux of those associated materials around the world. Even in the same area, SGD magnitude also varies in response to tide fluctuation and seasonal change on hydraulic gradient. Thus, long-term investigation is in need. In Taiwan, the SGD study is rare and the intrusion of seawater in the coastal aquifer is emphasized in previous studies. According to the information from Hydrogeological Data Bank (Central Geological Survey, MOEA), some areas still show potentiality of SGD. Here, we report the preliminary investigation result of SGD at Gaomei Wildlife Conservation Area which located at the south of the Da-Chia River mouth. This study area is characterized by a great tidal rang and a shallow aquifer with high groundwater recharge rate. Time-series measurement of the short-lived Ra in surface water was done in both dry and wet seasons at a tidal flat site and shows different trends of excess Ra-224 between dry and wet seasons. High excess Ra-224 activities (>20 dpm/100L) occurred at high tide in dry season but at low tide in wet season. The plot of salinity versus excess Ra-224, showing non-conservative curve, suggests that high excess Ra-224 activities derive from desorption in dry season but from SGD input in wet season.

  19. The prolactin response to an acute stressor in relation to parental care and corticosterone in a short-lived bird, the Eurasian hoopoe.

    Science.gov (United States)

    Schmid, Baptiste; Chastel, Olivier; Jenni, Lukas

    2011-10-01

    Prolactin plays an important role in mediating parental care in birds, but little is known about changes in prolactin levels when animals disrupt their reproductive behaviour during emergency life-history stages. We investigated the variation of prolactin levels with breeding stage, sex, body condition and as a response to a standardized acute stressor in a small short-lived bird, the Eurasian hoopoe Upupa epops under natural field conditions. We found higher baseline levels of prolactin in females during the brooding phase than in their mates which feed them and their chicks at this stage. Moreover, this is the first report of a differential prolactin stress-response between sexes with contrasting parental care within a breeding phase. Capture, handling and restraint induced a clear decrease of prolactin levels which was less pronounced in females at the very early stage of brooding compared to females in later stages. In contrast, the prolactin stress response in males remained nearly constant over the breeding stages and was stronger than in females. Baseline levels of prolactin, but not handling-induced levels, were positively correlated with body condition. We found a weak relationship between the decrease in prolactin due to acute handling stress and handling-induced levels of corticosterone. Taken together, both baseline and stress response levels of prolactin were related to the amount of parental care, although we found no relationship with reproductive success. It appears that the response to an acute stressor in prolactin levels is finely tuned to parental duties and investment. Hence, prolactin appears to be involved in mediating the trade-off between current reproduction versus self-maintenance and future reproduction. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Activation of an immune-regulatory macrophage response and inhibition of lung inflammation in a mouse model of COPD using heat-shock protein alpha B-crystallin-loaded PLGA microparticles

    NARCIS (Netherlands)

    van Noort, J.M.; Bsibsi, M.; Nacken, P.J.; Gerritsen, W.H.; Amor, S.; Holtman, I.R.; Boddeke, E.; van Ark, I.; Leusink-Muis, T.; Folkerts, G.; Hennink, W.E.; Amidi, M.

    2013-01-01

    As an extracellular protein, the small heat-shock protein alpha B-crystallin (HSPB5) has anti-inflammatory effects in several mouse models of inflammation. Here, we show that these effects are associated with the ability of HSPB5 to activate an immune-regulatory response in macrophages via

  1. Activation of an immune-regulatory macrophage response and inhibition of lung inflammation in a mouse model of COPD using heat-shock protein alpha B-crystallin-loaded PLGA microparticles

    NARCIS (Netherlands)

    van Noort, Johannes M.; Bsibsi, Malika; Nacken, Peter J.; Gerritsen, Wouter H.; Amor, Sandra; Holtman, Inge R.; Boddeke, Erik; van Ark, Ingrid; Leusink-Muis, Thea; Folkerts, Gert; Hennink, Wim E.; Amidi, Maryam

    As an extracellular protein, the small heat-shock protein alpha B-crystallin (HSPB5) has anti-inflammatory effects in several mouse models of inflammation. Here, we show that these effects are associated with the ability of HSPB5 to activate an immune-regulatory response in macrophages via

  2. PipY, a Member of the Conserved COG0325 Family of PLP-Binding Proteins, Expands the Cyanobacterial Nitrogen Regulatory Network

    Directory of Open Access Journals (Sweden)

    José I. Labella

    2017-07-01

    Full Text Available Synechococcus elongatus PCC 7942 is a paradigmatic model organism for nitrogen regulation in cyanobacteria. Expression of genes involved in nitrogen assimilation is positively regulated by the 2-oxoglutarate receptor and global transcriptional regulator NtcA. Maximal activation requires the subsequent binding of the co-activator PipX. PII, a protein found in all three domains of life as an integrator of signals of the nitrogen and carbon balance, binds to PipX to counteract NtcA activity at low 2-oxoglutarate levels. PII-PipX complexes can also bind to the transcriptional regulator PlmA, whose regulon remains unknown. Here we expand the nitrogen regulatory network to PipY, encoded by the bicistronic operon pipXY in S. elongatus. Work with PipY, the cyanobacterial member of the widespread family of COG0325 proteins, confirms the conserved roles in vitamin B6 and amino/keto acid homeostasis and reveals new PLP-related phenotypes, including sensitivity to antibiotics targeting essential PLP-holoenzymes or synthetic lethality with cysK. In addition, the related phenotypes of pipY and pipX mutants are consistent with genetic interactions in the contexts of survival to PLP-targeting antibiotics and transcriptional regulation. We also showed that PipY overexpression increased the length of S. elongatus cells. Taken together, our results support a universal regulatory role for COG0325 proteins, paving the way to a better understanding of these proteins and of their connections with other biological processes.

  3. Regulatory-associated protein of TOR (RAPTOR) alters the hormonal and metabolic composition of Arabidopsis seeds, controlling seed morphology, viability and germination potential.

    Science.gov (United States)

    Salem, Mohamed A; Li, Yan; Wiszniewski, Andrew; Giavalisco, Patrick

    2017-11-01

    Target of Rapamycin (TOR) is a positive regulator of growth and development in all eukaryotes, which positively regulates anabolic processes like protein synthesis, while repressing catabolic processes, including autophagy. To better understand TOR function we decided to analyze its role in seed development and germination. We therefore performed a detailed phenotypic analysis using mutants of the REGULATORY-ASSOCIATED PROTEIN OF TOR 1B (RAPTOR1B), a conserved TOR interactor, acting as a scaffold protein, which recruits substrates for the TOR kinase. Our results show that raptor1b plants produced seeds that were delayed in germination and less resistant to stresses, leading to decreased viability. These physiological phenotypes were accompanied by morphological changes including decreased seed-coat pigmentation and reduced production of seed-coat mucilage. A detailed molecular analysis revealed that many of these morphological changes were associated with significant changes of the metabolic content of raptor1b seeds, including elevated levels of free amino acids, as well as reduced levels of protective secondary metabolites and storage proteins. Most of these observed changes were accompanied by significantly altered phytohormone levels in the raptor1b seeds, with increases in abscisic acid, auxin and jasmonic acid, which are known to inhibit germination. Delayed germination and seedling growth, observed in the raptor1b seeds, could be partially restored by the exogenous supply of gibberellic acid, indicating that TOR is at the center of a regulatory hub controlling seed metabolism, maturation and germination. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  4. Continuous monitoring α-activity on aerosol filters by the pseudo-coincidence-technique. Explicitly taking into account the short lived Po-218 activity; Kontinuierliche Ueberwachung der α-Aktivitaet eines Aerosolfilters mit der Pseudokoinzidenzmesstechnik. Explizite Beruecksichtigung der kurzlebigen Po-218 Aktivitaetsbeitraaege

    Energy Technology Data Exchange (ETDEWEB)

    Kraut, W.; Schwarz, W. [Duale Hochschule Baden-Wuerttemberg (DHBW), Karlsruhe (Germany). Studiengang Sicherheitswesen; Kraut, B. [Berthold Technologies GmbH und Co.KG, Bad Wildbad (Germany)

    2015-07-01

    Pseudo-coincidence-technique is applied to continuous monitoring of α-activity on aerosolfilters by proportional counters. Filter activity can markedly increase or decrease by changing air conditions especially by the amount of short lived Po-218 activity. Conditions of constant proportions of activity concentrations for the short lived species for operating this technique are seldom fulfilled. The dynamic behavior of artificial (long lived) and natural (short lived) activity is mathematically modelled and the measured moving count rates are analyzed under this model by a multivariate regression analysis for activity concentrations of artificial resp. short lived activity. Results are compared to standard recommendations of DIN ISO 11929.

  5. [Regulatory effect and mechanism of RNA binding motif protein 38 on the expression of progesterone receptor in human breast cancer ZR-75-1 cells].

    Science.gov (United States)

    Lou, P P; Li, C L; Xia, T S; Shi, L; Wu, J; Zhou, X J; Wang, Y; Ding, Q

    2016-06-23

    To investigate the regulatory mechanism of RNA binding motif protein 38 (RNPC1) on the expression of progesterone receptor (PR) in breast cancer cell line ZR-75-1. Lentiviral vector was used to induce overexpression of RNPC1 in ZR-75-1 cells. qRT-PCR and Western blot were used to assess the regulatory effect of RNPC1 on PR expression. Actinomycin was used to detect the regulatory mechanism involved. Immunohistochemical (IHC) staining was used to determine the protein expression of RNPC1 and PR in 80 breast cancer tissues. IHC staining showed that the expression of RNPC1 was significantly higher in the PR positive breast cancer tissues than that in the PR negative breast cancer tissues (P<0.05). The qRT-PCR results showed that overexpression of RNPC1 in ZR-75-1 cells significantly upregulated the mRNA level of PR (1.764±0.028 vs. 1.001±0.037, P<0.01), whereas knockdown of RNPC1 did the opposite (0.579± 0.007 vs. 1.000±0.002, P<0.01). The Western blot results also showed that overexpression of RNPC1 up-regulated PR levels, while knockdown of RNPC1 resulted in down-regulation of PR levels in the ZR-75-1 cells.The actinomycin assay showed that overexpression of RNPC1 increased the mRNA stability of PR. The half-life of PR mRNA was increased from 4.0 h to 6.5 h. Knockdown of RNPC1 decreased the mRNA stability of PR and the half-life of PR transcript was decreased from 4.1 h to 3.0 h. RNPC1 plays a crucial role in regulating the expression of PR in breast cancer ZR-75-1 cells.

  6. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  7. The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus.

    Science.gov (United States)

    Danger, Jessica L; Makthal, Nishanth; Kumaraswami, Muthiah; Sumby, Paul

    2015-12-01

    The group A Streptococcus (GAS; Streptococcus pyogenes) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to the prtF1 and prtF2 mRNAs within their 5' untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and the prtF1 and prtF2 mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection. More than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small

  8. Identification of a cis-regulatory region of a gene in Arabidopsis thaliana whose induction by dehydration is mediated by abscisic acid and requires protein synthesis.

    Science.gov (United States)

    Iwasaki, T; Yamaguchi-Shinozaki, K; Shinozaki, K

    1995-05-20

    In Arabidopsis thaliana, the induction of a dehydration-responsive gene, rd22, is mediated by abscisic acid (ABA) but the gene does not include any sequence corresponding to the consensus ABA-responsive element (ABRE), RYACGTGGYR, in its promoter region. The cis-regulatory region of the rd22 promoter was identified by monitoring the expression of beta-glucuronidase (GUS) activity in leaves of transgenic tobacco plants transformed with chimeric gene fusions constructed between 5'-deleted promoters of rd22 and the coding region of the GUS reporter gene. A 67-bp nucleotide fragment corresponding to positions -207 to -141 of the rd22 promoter conferred responsiveness to dehydration and ABA on a non-responsive promoter. The 67-bp fragment contains the sequences of the recognition sites for some transcription factors, such as MYC, MYB, and GT-1. The fact that accumulation of rd22 mRNA requires protein synthesis raises the possibility that the expression of rd22 might be regulated by one of these trans-acting protein factors whose de novo synthesis is induced by dehydration or ABA. Although the structure of the RD22 protein is very similar to that of a non-storage seed protein, USP, of Vicia faba, the expression of the GUS gene driven by the rd22 promoter in non-stressed transgenic Arabidopsis plants was found mainly in flowers and bolted stems rather than in seeds.

  9. Metal ion interaction of an oligopeptide fragment representing the regulatory metal binding site of a CueR protein

    DEFF Research Database (Denmark)

    Jancsó, Attila; Szokolai, Hajnalka; Roszahegyi, Livia

    2013-01-01

    Metalloregulatory proteins of the MerR family are transcriptional activators that sense/control the concentration of various metal ions inside bacteria.1 The Cu+ efflux regulator CueR, similarly to other MerR proteins, possesses a short multiple Cys-containing metal binding loop close to the C...... of cognate metal ions.2 Nevertheless, it is an interesting question whether the same sequence, when removed from the protein, shows a flexibility to adopt different coordination environments and may efficiently bind metal ions having preferences for larger coordination numbers....

  10. ChIPBase v2.0: decoding transcriptional regulatory networks of non-coding RNAs and protein-coding genes from ChIP-seq data.

    Science.gov (United States)

    Zhou, Ke-Ren; Liu, Shun; Sun, Wen-Ju; Zheng, Ling-Ling; Zhou, Hui; Yang, Jian-Hua; Qu, Liang-Hu

    2017-01-04

    The abnormal transcriptional regulation of non-coding RNAs (ncRNAs) and protein-coding genes (PCGs) is contributed to various biological processes and linked with human diseases, but the underlying mechanisms remain elusive. In this study, we developed ChIPBase v2.0 (http://rna.sysu.edu.cn/chipbase/) to explore the transcriptional regulatory networks of ncRNAs and PCGs. ChIPBase v2.0 has been expanded with ∼10 200 curated ChIP-seq datasets, which represent about 20 times expansion when comparing to the previous released version. We identified thousands of binding motif matrices and their binding sites from ChIP-seq data of DNA-binding proteins and predicted millions of transcriptional regulatory relationships between transcription factors (TFs) and genes. We constructed 'Regulator' module to predict hundreds of TFs and histone modifications that were involved in or affected transcription of ncRNAs and PCGs. Moreover, we built a web-based tool, Co-Expression, to explore the co-expression patterns between DNA-binding proteins and various types of genes by integrating the gene expression profiles of ∼10 000 tumor samples and ∼9100 normal tissues and cell lines. ChIPBase also provides a ChIP-Function tool and a genome browser to predict functions of diverse genes and visualize various ChIP-seq data. This study will greatly expand our understanding of the transcriptional regulations of ncRNAs and PCGs. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle.

    Science.gov (United States)

    Kanzaki, Keita; Watanabe, Daiki; Kuratani, Mai; Yamada, Takashi; Matsunaga, Satoshi; Wada, Masanobu

    2017-02-01

    The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca 2+ -regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3. Tetanic force was markedly reduced at REC0 and remained reduced at REC3. CI treatment ameliorated the ECC-induced force decline but only at REC3. No evidence was found for proteolysis of dihydropyridine receptor (DHPR), junctophilin (JP)1, JP2, ryanodine receptor (RyR), sarcoplasmic reticulum Ca 2+ -ATPase (SERCA)1a, or junctional face protein-45 at REC0. At REC3, ECC resulted in decreases in DHPR, JP1, JP2, RyR, and SERCA1a. CI treatment prevented the decreases in DHPR, JP1, and JP2, whereas it had little effect on RyR and SERCA1a. These findings suggest that DHPR, JP1, and JP2, but not RyR and SERCA1a, undergo calpain-dependent proteolysis in in vivo muscles subjected to ECC and that impaired function of DHPR and/or JP might cause prolonged force deficits with ECC. NEW & NOTEWORTHY Calpain-dependent proteolysis is one of the contributing factors to muscle damage that occurs with eccentric contraction (ECC). It is unclear, however, whether calpains account for proteolysis of Ca 2+ -regulatory proteins in in vivo muscles subjected to ECC. Here, we provide evidence that dihydropyridine receptor and junctophilin, but not ryanodine receptor and sarcoplasmic reticulum Ca 2+ -ATPase, undergo calpain-dependent proteolysis. Copyright © 2017 the American Physiological Society.

  12. IBT-based quantitative proteomics identifies potential regulatory proteins involved in pigmentation of purple sea cucumber, Apostichopus japonicus.

    Science.gov (United States)

    Xing, Lili; Sun, Lina; Liu, Shilin; Li, Xiaoni; Zhang, Libin; Yang, Hongsheng

    2017-09-01

    Sea cucumbers are an important economic species and exhibit high yield value among aquaculture animals. Purple sea cucumbers are very rare and beautiful and have stable hereditary patterns. In this study, isobaric tags (IBT) were first used to reveal the molecular mechanism of pigmentation in the body wall of the purple sea cucumber. We analyzed the proteomes of purple sea cucumber in early pigmentation stage (Pa), mid pigmentation stage (Pb) and late pigmentation stage (Pc), resulting in the identification of 5580 proteins, including 1099 differentially expressed proteins in Pb: Pa and 339 differentially expressed proteins in Pc: Pb. GO and KEGG analyses revealed possible differentially expressed proteins, including"melanogenesis", "melanosome", "melanoma", "pigment-biosynthetic process", "Epidermis development", "Ras-signaling pathway", "Wnt-signaling pathway", "response to UV light", and "tyrosine metabolism", involved in pigment synthesis and regulation in purple sea cucumbers. The large number of differentially expressed proteins identified here should be highly useful in further elucidating the mechanisms underlying pigmentation in sea cucumbers. Furthermore, these results may also provide the base for further identification of proteins involved in resistance mechanisms against melanoma, albinism, UV damage, and other diseases in sea cucumbers. Copyright © 2017. Published by Elsevier Inc.

  13. Expression of Genes Involved in Bacteriocin Production and Self-Resistance in Lactobacillus brevis 174A Is Mediated by Two Regulatory Proteins.

    Science.gov (United States)

    Noda, Masafumi; Miyauchi, Rumi; Danshiitsoodol, Narandalai; Matoba, Yasuyuki; Kumagai, Takanori; Sugiyama, Masanori

    2018-04-01

    We have previously shown that the lactic acid bacterium Lactobacillus brevis 174A, isolated from Citrus iyo fruit, produces a bacteriocin designated brevicin 174A, which is comprised of two antibacterial polypeptides (designated brevicins 174A-β and 174A-γ). We have also found a gene cluster, composed of eight open reading frames (ORFs), that contains genes for the biosynthesis of brevicin 174A, self-resistance to its own bacteriocin, and two transcriptional regulatory proteins. Some lactic acid bacterial strains have a system to start the production of bacteriocin at an adequate stage of growth. Generally, the system consists of a membrane-bound histidine protein kinase (HPK) that senses a specific environmental stimulus and a corresponding response regulator (RR) that mediates the cellular response. We have previously shown that although the HPK- and RR-encoding genes are not found on the brevicin 174A biosynthetic gene cluster in the 174A strain, two putative regulatory genes, designated breD and breG , are in the gene cluster. In the present study, we demonstrate that the expression of brevicin 174A production and self-resistance is positively controlled by two transcriptional regulatory proteins, designated BreD and BreG. BreD is expressed together with BreE as the self-resistance determinant of L. brevis 174A. DNase I footprinting analysis and a promoter assay demonstrated that BreD binds to the breED promoter as a positive autoregulator. The present study also demonstrates that BreG, carrying a transmembrane domain, binds to the common promoter of breB and breC , encoding brevicins 174A-β and 174A-γ, respectively, for positive regulation. IMPORTANCE The problem of the appearance of bacteria that are resistant to practical antibiotics and the increasing demand for safe foods have increased interest in replacing conventional antibiotics with bacteriocin produced by the lactic acid bacteria. This antibacterial substance can inhibit the growth of pathogenic

  14. Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32

    Directory of Open Access Journals (Sweden)

    Sugiyama Hideaki

    2011-05-01

    Full Text Available Abstract Background Elevated numbers of regulatory T cells (Tregs have been implicated in certain cancers. Depletion of Tregs has been shown to increase anti-tumor immunity. Tregs also play a critical role in the suppression of autoimmune responses. The study of Tregs has been hampered by a lack of adequate surface markers. Leucine Rich Repeat Containing 32 (LRRC32, also known as Glycoprotein A Repetitions Predominant (GARP, has been postulated as a novel surface marker of activated Tregs. However, there is limited information regarding the processing of LRRC32 or the regulatory phenotype and functional activity of Tregs expressing LRRC32. Results Using naturally-occurring freshly isolated Tregs, we demonstrate that low levels of LRRC32 are present intracellularly prior to activation and that freshly isolated LRRC32+ Tregs are distinct from LRRC32- Tregs with respect to the expression of surface CD62L. Using LRRC32 transfectants of HEK cells, we demonstrate that the N-terminus of LRRC32 is cleaved prior to expression of the protein at the cell surface. Furthermore, we demonstrate using a construct containing a deleted putative signal peptide region that the presence of a signal peptide region is critical to cell surface expression of LRRC32. Finally, mixed lymphocyte assays demonstrate that LRRC32+ Tregs are more potent suppressors than LRRC32- Tregs. Conclusions A cleaved signal peptide site in LRRC32 is necessary for surface localization of native LRRC32 following activation of naturally-occurring freshly-isolated regulatory T cells. LRRC32 expression appears to alter the surface expression of activation markers of T cells such as CD62L. LRRC32 surface expression may be useful as a marker that selects for more potent Treg populations. In summary, understanding the processing and expression of LRRC32 may provide insight into the mechanism of action of Tregs and the refinement of immunotherapeutic strategies aimed at targeting these cells.

  15. Lysosomal-associated Transmembrane Protein 4B (LAPTM4B) Decreases Transforming Growth Factor β1 (TGF-β1) Production in Human Regulatory T Cells.

    Science.gov (United States)

    Huygens, Caroline; Liénart, Stéphanie; Dedobbeleer, Olivier; Stockis, Julie; Gauthy, Emilie; Coulie, Pierre G; Lucas, Sophie

    2015-08-14

    Production of active TGF-β1 is one mechanism by which human regulatory T cells (Tregs) suppress immune responses. This production is regulated by glycoprotein A repetitions predominant (GARP), a transmembrane protein present on stimulated Tregs but not on other T lymphocytes (Th and CTLs). GARP forms disulfide bonds with proTGF-β1, favors its cleavage into latent inactive TGF-β1, induces the secretion and surface presentation of GARP·latent TGF-β1 complexes, and is required for activation of the cytokine in Tregs. We explored whether additional Treg-specific protein(s) associated with GARP·TGF-β1 complexes regulate TGF-β1 production in Tregs. We searched for such proteins by yeast two-hybrid assay, using GARP as a bait to screen a human Treg cDNA library. We identified lysosomal-associated transmembrane protein 4B (LAPTM4B), which interacts with GARP in mammalian cells and is expressed at higher levels in Tregs than in Th cells. LAPTM4B decreases cleavage of proTGF-β1, secretion of soluble latent TGF-β1, and surface presentation of GARP·TGF-β1 complexes by Tregs but does not contribute to TGF-β1 activation. Therefore, LAPTM4B binds to GARP and is a negative regulator of TGF-β1 production in human Tregs. It may play a role in the control of immune responses by decreasing Treg immunosuppression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Revisiting interaction specificity reveals neuronal and adipocyte Munc18 membrane fusion regulatory proteins differ in their binding interactions with partner SNARE Syntaxins.

    Directory of Open Access Journals (Sweden)

    Michelle P Christie

    Full Text Available The efficient delivery of cellular cargo relies on the fusion of cargo-carrying vesicles with the correct membrane at the correct time. These spatiotemporal fusion events occur when SNARE proteins on the vesicle interact with cognate SNARE proteins on the target membrane. Regulatory Munc18 proteins are thought to contribute to SNARE interaction specificity through interaction with the SNARE protein Syntaxin. Neuronal Munc18a interacts with Syntaxin1 but not Syntaxin4, and adipocyte Munc18c interacts with Syntaxin4 but not Syntaxin1. Here we show that this accepted view of specificity needs revision. We find that Munc18c interacts with both Syntaxin4 and Syntaxin1, and appears to bind "non-cognate" Syntaxin1 a little more tightly than Syntaxin4. Munc18a binds Syntaxin1 and Syntaxin4, though it interacts with its cognate Syntaxin1 much more tightly. We also observed that when bound to non-cognate Munc18c, Syntaxin1 captures its neuronal SNARE partners SNAP25 and VAMP2, and Munc18c can bind to pre-formed neuronal SNARE ternary complex. These findings reveal that Munc18a and Munc18c bind Syntaxins differently. Munc18c relies principally on the Syntaxin N-peptide interaction for binding Syntaxin4 or Syntaxin1, whereas Munc18a can bind Syntaxin1 tightly whether or not the Syntaxin1 N-peptide is present. We conclude that Munc18a and Munc18c differ in their binding interactions with Syntaxins: Munc18a has two tight binding modes/sites for Syntaxins as defined previously but Munc18c has just one that requires the N-peptide. These results indicate that the interactions between Munc18 and Syntaxin proteins, and the consequences for in vivo function, are more complex than can be accounted for by binding specificity alone.

  17. Evolution of hepatic glucose metabolism: liver-specific glucokinase deficiency explained by parallel loss of the gene for glucokinase regulatory protein (GCKR.

    Directory of Open Access Journals (Sweden)

    Zhao Yang Wang

    Full Text Available Glucokinase (GCK plays an important role in the regulation of carbohydrate metabolism. In the liver, phosphorylation of glucose to glucose-6-phosphate by GCK is the first step for both glycolysis and glycogen synthesis. However, some vertebrate species are deficient in GCK activity in the liver, despite containing GCK genes that appear to be compatible with function in their genomes. Glucokinase regulatory protein (GCKR is the most important post-transcriptional regulator of GCK in the liver; it participates in the modulation of GCK activity and location depending upon changes in glucose levels. In experimental models, loss of GCKR has been shown to associate with reduced hepatic GCK protein levels and activity.GCKR genes and GCKR-like sequences were identified in the genomes of all vertebrate species with available genome sequences. The coding sequences of GCKR and GCKR-like genes were identified and aligned; base changes likely to disrupt coding potential or splicing were also identified.GCKR genes could not be found in the genomes of 9 vertebrate species, including all birds. In addition, in multiple mammalian genomes, whereas GCKR-like gene sequences could be identified, these genes could not predict a functional protein. Vertebrate species that were previously reported to be deficient in hepatic GCK activity were found to have deleted (birds and lizard or mutated (mammals GCKR genes. Our results suggest that mutation of the GCKR gene leads to hepatic GCK deficiency due to the loss of the stabilizing effect of GCKR.

  18. In silico analysis, mapping of regulatory elements and corresponding dna-protein interaction in polyphenol oxidase gene promoter from different rice varieties

    International Nuclear Information System (INIS)

    Mahmood, T.; Rehman, M.; Aziz, E.

    2015-01-01

    Polyphenol oxidase (PPO) is an important enzyme that has positive impact regarding plant resistance against different biotic and abiotic stresses. In the present study PPO promoter from six different rice varieties was amplified and then analyzed for cis- and trans-acting elements. The study revealed a total of 79 different cis-acting regulatory elements including 11 elements restricted to only one or other variety. Among six varieties Pakhal-Basmati had highest number (5) of these elements, whereas C-622 and Rachna-Basmati have no such sequences. Rachna-Basmati, IR-36-Basmati and Kashmir- Basmati had 1, 2 and 3 unique elements, respectively. Different elementsrelated to pathogen, salt and water stresses were found, which may be helpful in controlling PPO activity according to changing environment. Moreover, HADDOCK was used to understand molecular mechanism of PPO regulation and it was found that DNA-protein interactions are stabilized by many potential hydrogen bonds. Adenine and arginine were the most reactive residues in DNA and proteins respectively.Structural comparison of different protein-DNA complexes show that even a highly conserved transcriptional factor can adopt different conformations when they contact a different DNA binding sequence, however their stable interactions depend on the number of hydrogen bonds formed and distance. (author)

  19. Identification and characterization of PhbF: a DNA binding protein with regulatory role in the PHB metabolism of Herbaspirillum seropedicae SmR1.

    Science.gov (United States)

    Kadowaki, Marco A S; Müller-Santos, Marcelo; Rego, Fabiane G M; Souza, Emanuel M; Yates, Marshall G; Monteiro, Rose A; Pedrosa, Fabio O; Chubatsu, Leda S; Steffens, Maria B R

    2011-10-14

    Herbaspirillum seropedicae SmR1 is a nitrogen fixing endophyte associated with important agricultural crops. It produces polyhydroxybutyrate (PHB) which is stored intracellularly as granules. However, PHB metabolism and regulatory control is not yet well studied in this organism. In this work we describe the characterization of the PhbF protein from H. seropedicae SmR1 which was purified and characterized after expression in E. coli. The purified PhbF protein was able to bind to eleven putative promoters of genes involved in PHB metabolism in H. seropedicae SmR1. In silico analyses indicated a probable DNA-binding sequence which was shown to be protected in DNA footprinting assays using purified PhbF. Analyses using lacZ fusions showed that PhbF can act as a repressor protein controlling the expression of PHB metabolism-related genes. Our results indicate that H. seropedicae SmR1 PhbF regulates expression of phb-related genes by acting as a transcriptional repressor. The knowledge of the PHB metabolism of this plant-associated bacterium may contribute to the understanding of the plant-colonizing process and the organism's resistance and survival in planta.

  20. Identification and characterization of PhbF: A DNA binding protein with regulatory role in the PHB metabolism of Herbaspirillum seropedicae SmR1

    Directory of Open Access Journals (Sweden)

    Pedrosa Fabio O

    2011-10-01

    Full Text Available Abstract Background Herbaspirillum seropedicae SmR1 is a nitrogen fixing endophyte associated with important agricultural crops. It produces polyhydroxybutyrate (PHB which is stored intracellularly as granules. However, PHB metabolism and regulatory control is not yet well studied in this organism. Results In this work we describe the characterization of the PhbF protein from H. seropedicae SmR1 which was purified and characterized after expression in E. coli. The purified PhbF protein was able to bind to eleven putative promoters of genes involved in PHB metabolism in H. seropedicae SmR1. In silico analyses indicated a probable DNA-binding sequence which was shown to be protected in DNA footprinting assays using purified PhbF. Analyses using lacZ fusions showed that PhbF can act as a repressor protein controlling the expression of PHB metabolism-related genes. Conclusions Our results indicate that H. seropedicae SmR1 PhbF regulates expression of phb-related genes by acting as a transcriptional repressor. The knowledge of the PHB metabolism of this plant-associated bacterium may contribute to the understanding of the plant-colonizing process and the organism's resistance and survival in planta.

  1. Rho family GTP binding proteins are involved in the regulatory volume decrease process in NIH3T3 mouse fibroblasts

    DEFF Research Database (Denmark)

    Pedersen, Stine F; Beisner, Kristine H; Willumsen, Berthe M

    2002-01-01

    The role of Rho GTPases in the regulatory volume decrease (RVD) process following osmotic cell swelling is controversial and has so far only been investigated for the swelling-activated Cl- efflux. We investigated the involvement of RhoA in the RVD process in NIH3T3 mouse fibroblasts, using wild......-type cells and three clones expressing constitutively active RhoA (RhoAV14). RhoAV14 expression resulted in an up to fourfold increase in the rate of RVD, measured by large-angle light scattering. The increase in RVD rate correlated with RhoAV14 expression. RVD in wild-type cells was unaffected by the Rho...

  2. Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-β pathways in a dihydrotestosterone-induced mouse model.

    Science.gov (United States)

    Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Mavlonov, Gafurjon Turdalievich; Yi, Tae-Hoo

    2014-01-01

    This study was conducted to test whether ginsenoside F2 can reduce hair loss by influencing sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and the transforming growth factor beta (TGF-β) pathway of apoptosis in dihydrotestosterone (DHT)-treated hair cells and in a DHT-induced hair loss model in mice. Results for ginsenoside F2 were compared with finasteride. DHT inhibits proliferation of hair cells and induces androgenetic alopecia and was shown to activate an apoptosis signal pathway both in vitro and in vivo. The cell-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the proliferation rates of DHT-treated human hair dermal papilla cells (HHDPCs) and HaCaTs increased by 48% in the ginsenoside F2-treated group and by 12% in the finasteride-treated group. Western blot analysis showed that ginsenoside F2 decreased expression of TGF-β2 related factors involved in hair loss. The present study suggested a hair loss related pathway by changing SCAP related apoptosis pathway, which has been known to control cholesterol metabolism. SCAP, sterol regulatory element-binding protein (SREBP) and caspase-12 expression in the ginsenoside F2-treated group were decreased compared to the DHT and finasteride-treated group. C57BL/6 mice were also prepared by injection with DHT and then treated with ginsenoside F2 or finasteride. Hair growth rate, density, thickness measurements and tissue histotological analysis in these groups suggested that ginsenoside F2 suppressed hair cell apoptosis and premature entry to catagen more effectively than finasteride. Our results indicated that ginsenoside F2 decreased the expression of TGF-β2 and SCAP proteins, which have been suggested to be involved in apoptosis and entry into catagen. This study provides evidence those factors in the SCAP pathway could be targets for hair loss prevention drugs.

  3. A multi-model intercomparison of halogenated very short-lived substances (TransCom-VSLS): linking oceanic emissions and tropospheric transport for a reconciled estimate of the stratospheric source gas injection of bromine

    OpenAIRE

    Hossaini, R.; Patra, P. K.; Leeson, A. A.; Krysztofiak, G.; Abraham, N. L.; Andrews, S. J.; Archibald, A. T.; Aschmann, J.; Atlas, E. L.; Belikov, D. A.; Bonisch, H.; Carpenter, L. J.; Dhomse, S.; Dorf, M.; Engel, A.

    2016-01-01

    The first concerted multi-model intercomparison of halogenated very short-lived substances (VSLS) has been performed, within the framework of the ongoing Atmospheric Tracer Transport Model Intercomparison Project (TransCom). Eleven global models or model variants participated (nine chemical transport models and two chemistry–climate models) by simulating the major natural bromine VSLS, bromoform (CHBr3) and dibromomethane (CH2Br2), over a 20-year period (1993–2012). Except f...

  4. Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle

    Directory of Open Access Journals (Sweden)

    A. Manimaran

    2016-01-01

    Full Text Available Among the various systemic reactions against infection or injury, the acute phase response is the cascade of reaction and mostly coordinated by cytokines-mediated acute phase proteins (APPs production. Since APPs are sensitive innate immune molecules, they are useful for early detection of inflammation in bovines and believed to be better discriminators than routine hematological parameters. Therefore, the possibility of using APPs as a diagnostic and prognostic marker of inflammation in major bovine health disorders including postpartum uterine infection has been explored by many workers. In this review, we discussed specifically importance of postpartum uterine infection, the role of energy balance in uterine infections and potential of APPs as a predictor of postpartum uterine infections during the transition period and its regulatory mechanism in dairy cattle.

  5. 14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif

    DEFF Research Database (Denmark)

    Andersen, Sofie Dabros; Keijzers, Guido; Rampakakis, Emmanouil

    2012-01-01

    Human exonuclease 1 (hEXO1) acts directly in diverse DNA processing events, including replication, mismatch repair (MMR), and double strand break repair (DSBR), and it was also recently described to function as damage sensor and apoptosis inducer following DNA damage. In contrast, 14-3-3 proteins...... are specifically induced by replication inhibition leading to protein ubiquitination and degradation. We demonstrate direct and robust interaction between hEXO1 and six of the seven 14-3-3 isoforms in vitro, suggestive of a novel protein interaction network between DNA repair and cell cycle control. Binding...... and most likely a second unidentified binding motif. 14-3-3 associations do not appear to directly influence hEXO1 in vitro nuclease activity or in vitro DNA replication initiation. Moreover, specific phosphorylation variants, including hEXO1 S746A, are efficiently imported to the nucleus; to associate...

  6. Effects of light and the regulatory B-subunit composition of protein phosphatase 2A on the susceptibility of Arabidopsis thaliana to aphid (Myzus persicae) infestation.

    Science.gov (United States)

    Rasool, Brwa; Karpinska, Barbara; Konert, Grzegorz; Durian, Guido; Denessiouk, Konstantin; Kangasjärvi, Saijaliisa; Foyer, Christine H

    2014-01-01

    The interactions between biotic and abiotic stress signaling pathways are complex and poorly understood but protein kinase/phosphatase cascades are potentially important components. Aphid fecundity and susceptibility to Pseudomonas syringae infection were determined in the low light-grown Arabidopsis thaliana wild type and in mutant lines defective in either the protein phosphatase (PP)2A regulatory subunit B'γ (gamma; pp2a-b'γ) or B'ζ (zeta; pp2a-b'ζ1-1 and pp2a-b'ζ 1-2) and in gamma zeta double mutants (pp2a-b'γζ) lacking both subunits. All the mutants except for pp2a-b'ζ 1-1 had significantly lower leaf areas than the wild type. Susceptibility to P. syringae was similar in all genotypes. In contrast, aphid fecundity was significantly decreased in the pp2a-b'γ mutant relative to the wild type but not in the pp2a-b'γζ double mutant. A high light pre-treatment, which led to a significant increase in rosette growth in all mutant lines but not in the wild type, led to a significant decrease in aphid fecundity in all genotypes. The high light pre-treatment abolished the differences in aphid resistance observed in the pp2a-b'γ mutant relative to the wild type. The light and CO2 response curves for photosynthesis were changed in response to the high light pre-treatment, but the high light effects were similar in all genotypes. These data demonstrate that a pre-exposure to high light and the composition of B-subunits on the trimeric PP2A holoenzymes are important in regulating plant resistance to aphids. The functional specificity for the individual regulatory B-subunits may therefore limit aphid colonization, depending on the prevailing abiotic stress environment.

  7. Effects of light and the regulatory Beta subunit composition of protein phosphatase 2A on the susceptibility of Arabidopsis thaliana to aphid (Myzus persicae infestation

    Directory of Open Access Journals (Sweden)

    Brwa eRasool

    2014-08-01

    Full Text Available The interactions between biotic and abiotic stress signalling pathways are complex and poorly understood but protein kinase/phosphatase cascades are potentially important components. Aphid fecundity and susceptibility to Pseudomonas syringae infection were determined in the low light-grown Arabidopsis thaliana wild type and in mutant lines defective in either the protein phosphatase (PP2A regulatory subunit B’γ (gamma; pp2a-b’γ or B’ζ (zeta; pp2a-b’ζ1-1 and pp2a-b’ζ1-2 and in gamma zeta double mutants (pp2a-b’γζ lacking both subunits. All the mutants except for pp2a-b’ζ1-1 had significantly lower leaf areas than the wild type. Susceptibility to P. syringae was similar in all genotypes. In contrast, aphid fecundity was significantly decreased in the pp2a-b’γ mutant relative to the wild type but not in the pp2a-b’γζ double mutant. A high light pre-treatment, which led to a significant increase in rosette growth in all mutant lines but not in the wild type, led to a significant decrease in aphid fecundity in all genotypes. The high light pre-treatment abolished the differences in aphid resistance observed in the pp2a-b’γ mutant relative to the wild type. The light and CO2 response curves for photosynthesis were changed in response to the high light pre-treatment, but the high light effects were similar in all genotypes. These data demonstrate that a pre-exposure to high light and the composition of subunits on the trimeric PP2A holoenzymes are important in regulating plant resistance to aphids. The functional specificity for the individual regulatory B-subunits may therefore limit aphid colonisation, depending on the prevailing abiotic stress environment.

  8. The Yersinia enterocolitica type three secretion chaperone SycO is integrated into the Yop regulatory network and binds to the Yop secretion protein YscM1

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    Heesemann Jürgen

    2007-07-01

    Full Text Available Abstract Background Pathogenic yersiniae (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica share a virulence plasmid encoding a type three secretion system (T3SS. This T3SS comprises more than 40 constituents. Among these are the transport substrates called Yops (Yersinia outer proteins, the specific Yop chaperones (Sycs, and the Ysc (Yop secretion proteins which form the transport machinery. The effectors YopO and YopP are encoded on an operon together with SycO, the chaperone of YopO. The characterization of SycO is the focus of this study. Results We have established the large-scale production of recombinant SycO in its outright form. We confirm that Y. enterocolitica SycO forms homodimers which is typical for Syc chaperones. SycO overproduction in Y. enterocolitica decreases secretion of Yops into the culture supernatant suggesting a regulatory role of SycO in type III secretion. We demonstrate that in vitro SycO interacts with YscM1, a negative regulator of Yop expression in Y. enterocolitica. However, the SycO overproduction phenotype was not mediated by YscM1, YscM2, YopO or YopP as revealed by analysis of isogenic deletion mutants. Conclusion We present evidence that SycO is integrated into the regulatory network of the Yersinia T3SS. Our picture of the Yersinia T3SS interactome is supplemented by identification of the SycO/YscM1 interaction. Further, our results suggest that at least one additional interaction partner of SycO has to be identified.

  9. Regulatory mechanisms for 3'-end alternative splicing and polyadenylation of the Glial Fibrillary Acidic Protein, GFAP, transcript

    DEFF Research Database (Denmark)

    Blechingberg, Jenny; Lykke-Andersen, Søren; Jensen, Torben Heick

    2007-01-01

    (PTB) protein enhanced both exon 7a polyadenylation and exon 7a splicing. Finally, increasing transcription by the VP16 trans-activator did not affect the frequency of use of the exon 7a polyadenylation signal whereas the exon 7a splicing frequency was decreased. Our data suggest a model...

  10. Dissecting the expression relationships between RNA-binding proteins and their cognate targets in eukaryotic post-transcriptional regulatory networks

    Science.gov (United States)

    Nishtala, Sneha; Neelamraju, Yaseswini; Janga, Sarath Chandra

    2016-05-01

    RNA-binding proteins (RBPs) are pivotal in orchestrating several steps in the metabolism of RNA in eukaryotes thereby controlling an extensive network of RBP-RNA interactions. Here, we employed CLIP (cross-linking immunoprecipitation)-seq datasets for 60 human RBPs and RIP-ChIP (RNP immunoprecipitation-microarray) data for 69 yeast RBPs to construct a network of genome-wide RBP- target RNA interactions for each RBP. We show in humans that majority (~78%) of the RBPs are strongly associated with their target transcripts at transcript level while ~95% of the studied RBPs were also found to be strongly associated with expression levels of target transcripts when protein expression levels of RBPs were employed. At transcript level, RBP - RNA interaction data for the yeast genome, exhibited a strong association for 63% of the RBPs, confirming the association to be conserved across large phylogenetic distances. Analysis to uncover the features contributing to these associations revealed the number of target transcripts and length of the selected protein-coding transcript of an RBP at the transcript level while intensity of the CLIP signal, number of RNA-Binding domains, location of the binding site on the transcript, to be significant at the protein level. Our analysis will contribute to improved modelling and prediction of post-transcriptional networks.

  11. A regulatory effect of INMAP on centromere proteins: antisense INMAP induces CENP-B variation and centromeric halo.

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    Tan Tan

    Full Text Available CENP-B is a highly conserved protein that facilitates the assembly of specific centromere structures both in interphase nuclei and on mitotic chromosomes. INMAP is a conserved protein that localizes at nucleus in interphase cells and at mitotic apparatus in mitotic cells. Our previous results showed that INMAP over-expression leads to spindle defects, mitotic arrest and formation of polycentrosomal and multinuclear cells, indicating that INMAP may modulate the function of (a key protein(s in mitotic apparatus. In this study, we demonstrate that INMAP interacts with CENP-B and promotes cleavage of the N-terminal DNA binding domain from CENP-B. The cleaved CENP-B cannot associate with centromeres and thus lose its centromere-related functions. Consistent with these results, CENP-B in INMAP knockdown cells becomes more diffused around kinetochores. Although INMAP knockdown cells do not exhibit gross defects in mitotic spindle formation, these cells go through mitosis, especially prophase and metaphase, with different relative timing, indicating subtle abnormality. These results identify INMAP as a model regulator of CENP-B and support the notion that INMAP regulates mitosis through modulating CENP-B-mediated centromere organization.

  12. PuF, an antimetastatic and developmental signaling protein, interacts with the Alzheimer’s amyloid-β precursor protein via a tissue-specific proximal regulatory element (PRE

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    Lahiri Debomoy K

    2013-01-01

    Full Text Available Abstract Background Alzheimer’s disease (AD is intimately tied to amyloid-β (Aβ peptide. Extraneuronal brain plaques consisting primarily of Aβ aggregates are a hallmark of AD. Intraneuronal Aβ subunits are strongly implicated in disease progression. Protein sequence mutations of the Aβ precursor protein (APP account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or “proximal regulatory element” (PRE, at −76/−47, from the +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay (EMSA and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. Results EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 (AP2, nm23 nucleoside diphosphate kinase/metastatic inhibitory protein (PuF, and specificity protein 1 (SP1. These sites crossed a known single nucleotide polymorphism (SNP. EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. Conclusions We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also

  13. Oxygen isotopic and geochemical evidence for a short-lived, high-temperature hydrothermal event in the Chegem caldera, Caucasus Mountains, Russia

    Science.gov (United States)

    Gazis, C.; Taylor, H.P.; Hon, K.; Tsvetkov, A.

    1996-01-01

    Within the 2.8 Ma Chegem ash-flow caldera (11 ?? 15 km), a single cooling unit of rhyolitic to dacitic welded tuff more than 2 km thick is exposed in deep valleys incised during recent rapid uplift of the Caucasus Mountains. The intracaldera tuff is mineralogically fresh and unaltered, and is overlain by andesite lavas and cut by a resurgent granodiorite intrusion. Major- and trace-element compositions for a 1405-m stratigraphic section of intracaldera tuff display trends of upwardly increasing Na2O, CaO, Al2O3, total Fe, MgO, TiO2, Sr and Zr and decreasing SiO2, K2O and Rb. This mafic-upward zoning (from 76.1 to 69.9% SiO2) reflects an inverted view of the upper part of the source magma chamber. Oxygen isotope studies of 35 samples from this 1405-m section define a striking profile with "normal" igneous ??18O values (+7.0 to +8.5) in the lower 600 m of tuff, much lower ??18O values (-4.0 to +4.3) in a 700-m zone above that and a shift to high ??18O values (+4.4 to -10.9) in the upper 100 m of caldera-fill exposure. Data from two other partial stratigraphic sections indicate that these oxygen isotope systematics are probably a caldera-wide phenomenon. Quartz and feldspar phenocrysts everywhere have "normal" igneous ??18O values of about +8.5 and +7.5, respectively, whereas groundmass and glass ??18O values range from -7.7 to +12.3. Consequently, the ??18O values of coexisting feldspar, groundmass and glass form a steep array in a plot of ??feldspar vs. ??groundmass/glass. Such pronounced disequilibrium between coexisting feldspar and groundmass or glass has never before been observed on this scale. It requires a hydrothermal event involving large amounts of low-18O H2O at sufficiently high temperatures and short enough time (tens of years or less) that glass exchanges thoroughly but feldspar does not. The most likely process responsible for the O depletions at Chegem is a very high temperature (500-600??C), short-lived, vigorous meteoric-hydrothermal event that was

  14. Delivery of halogenated very short-lived substances from the west Indian Ocean to the stratosphere during the Asian summer monsoon

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    A. Fiehn

    2017-06-01

    Full Text Available Halogenated very short-lived substances (VSLSs are naturally produced in the ocean and emitted to the atmosphere. When transported to the stratosphere, these compounds can have a significant influence on the ozone layer and climate. During a research cruise on RV Sonne in the subtropical and tropical west Indian Ocean in July and August 2014, we measured the VSLSs, methyl iodide (CH3I and for the first time bromoform (CHBr3 and dibromomethane (CH2Br2, in surface seawater and the marine atmosphere to derive their emission strengths. Using the Lagrangian particle dispersion model FLEXPART with ERA-Interim meteorological fields, we calculated the direct contribution of observed VSLS emissions to the stratospheric halogen burden during the Asian summer monsoon. Furthermore, we compare the in situ calculations with the interannual variability of transport from a larger area of the west Indian Ocean surface to the stratosphere for July 2000–2015. We found that the west Indian Ocean is a strong source for CHBr3 (910 pmol m−2 h−1, very strong source for CH2Br2 (930 pmol m−2 h−1, and an average source for CH3I (460 pmol m−2 h−1. The atmospheric transport from the tropical west Indian Ocean surface to the stratosphere experiences two main pathways. On very short timescales, especially relevant for the shortest-lived compound CH3I (3.5 days lifetime, convection above the Indian Ocean lifts oceanic air masses and VSLSs towards the tropopause. On a longer timescale, the Asian summer monsoon circulation transports oceanic VSLSs towards India and the Bay of Bengal, where they are lifted with the monsoon convection and reach stratospheric levels in the southeastern part of the Asian monsoon anticyclone. This transport pathway is more important for the longer-lived brominated compounds (17 and 150 days lifetime for CHBr3 and CH2Br2. The entrainment of CHBr3 and CH3I from the west Indian Ocean to the stratosphere during the

  15. The Scl1 protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H, and inhibits the alternative pathway of complement.

    Science.gov (United States)

    Caswell, Clayton C; Han, Runlin; Hovis, Kelley M; Ciborowski, Pawel; Keene, Douglas R; Marconi, Richard T; Lukomski, Slawomir

    2008-02-01

    Non-specific activation of the complement system is regulated by the plasma glycoprotein factor H (FH). Bacteria can avoid complement-mediated opsonization and phagocytosis through acquiring FH to the cell surface. Here, we characterize an interaction between the streptococcal collagen-like protein Scl1.6 of M6-type group A Streptococcus (GAS) and FH. Using affinity chromatography with immobilized recombinant Scl1.6 protein, we co-eluted human plasma proteins with molecular weight of 155 kDa, 43 kDa and 38 kDa. Mass spectrometry identified the 155 kDa band as FH and two other bands as isoforms of the FH-related protein-1. The identities of all three bands were confirmed by Western immunoblotting with specific antibodies. Structure-function relation studies determined that the globular domain of the Scl1.6 variant specifically binds FH while fused to collagenous tails of various lengths. This binding is not restricted to Scl1.6 as the phylogenetically linked Scl1.55 variant also binds FH. Functional analyses demonstrated the cofactor activity of the rScl1.6-bound FH for factor I-mediated cleavage of C3b. Finally, purified FH bound to the Scl1.6 protein present in the cell wall material obtained from M6-type GAS. In conclusion, we have identified a functional interaction between Scl1 and plasma FH, which may contribute to GAS evasion of complement-mediated opsonization and phagocytosis.

  16. The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice.

    Science.gov (United States)

    Kesby, James P; Markou, Athina; Semenova, Svetlana

    2016-10-01

    Depression and psychostimulant abuse are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced dysfunction of dopamine and serotonin systems in corticolimbic brain areas may result in impaired reward function, thus, contributing to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+, TAT- control) show neuropathology resembling brain abnormalities in HIV+ humans. We evaluated brain reward function in response to TAT expression, nicotine and methamphetamine administration in TAT+ and TAT- mice using the intracranial self-stimulation procedure. We evaluated the brain dopamine and serotonin systems with high-performance liquid chromatography. The effects of TAT expression on delay-dependent working memory in TAT+ and TAT- mice using the operant delayed nonmatch-to-position task were also assessed. During doxycycline administration, reward thresholds were elevated by 20% in TAT+ mice compared with TAT- mice. After the termination of doxycycline treatment, thresholds of TAT+ mice remained significantly higher than those of TAT- mice and this was associated with changes in mesolimbic serotonin and dopamine levels. TAT+ mice showed a greater methamphetamine-induced threshold lowering compared with TAT- mice. TAT expression did not alter delay-dependent working memory. These results indicate that TAT expression in mice leads to reward deficits, a core symptom of depression, and a greater sensitivity to methamphetamine-induced reward enhancement. Our findings suggest that the TAT protein may contribute to increased depressive-like symptoms and continued methamphetamine use in HIV-positive individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The Hepatitis C Virus-induced NLRP3 Inflammasome Activates the Sterol Regulatory Element-binding Protein (SREBP) and Regulates Lipid Metabolism.

    Science.gov (United States)

    McRae, Steven; Iqbal, Jawed; Sarkar-Dutta, Mehuli; Lane, Samantha; Nagaraj, Abhiram; Ali, Naushad; Waris, Gulam

    2016-02-12

    Hepatitis C virus (HCV) relies on host lipids and lipid droplets for replication and morphogenesis. The accumulation of lipid droplets in infected hepatocytes manifests as hepatosteatosis, a common pathology observed in chronic hepatitis C patients. One way by which HCV promotes the accumulation of intracellular lipids is through enhancing de novo lipogenesis by activating the sterol regulatory element-binding proteins (SREBPs). In general, activation of SREBPs occurs during cholesterol depletion. Interestingly, during HCV infection, the activation of SREBPs occurs under normal cholesterol levels, but the underlying mechanisms are still elusive. Our previous study has demonstrated the activation of the inflammasome complex in HCV-infected human hepatoma cells. In this study, we elucidate the potential link between chronic hepatitis C-associated inflammation and alteration of lipid homeostasis in infected cells. Our results reveal that the HCV-activated NLRP3 inflammasome is required for the up-regulation of lipogenic genes such as 3-hydroxy-3-methylglutaryl-coenzyme A synthase, fatty acid synthase, and stearoyl-CoA desaturase. Using pharmacological inhibitors and siRNA against the inflammasome components (NLRP3, apoptosis-associated speck-like protein containing a CARD, and caspase-1), we further show that the activation of the NLRP3 inflammasome plays a critical role in lipid droplet formation. NLRP3 inflammasome activation in HCV-infected cells enables caspase-1-mediated degradation of insulin-induced gene proteins. This subsequently leads to the transport of the SREBP cleavage-activating protein·SREBP complex from the endoplasmic reticulum to the Golgi, followed by proteolytic activation of SREBPs by S1P and S2P in the Golgi. Typically, inflammasome activation leads to viral clearance. Paradoxically, here we demonstrate how HCV exploits the NLRP3 inflammasome to activate SREBPs and host lipid metabolism, leading to liver disease pathogenesis associated with

  18. Iron Starvation Conditions Upregulate Ehrlichia ruminantium Type IV Secretion System, tr1 Transcription Factor and map1 Genes Family through the Master Regulatory Protein ErxR

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    Amal Moumène

    2018-01-01

    Full Text Available Ehrlichia ruminantium is an obligatory intracellular bacterium that causes heartwater, a fatal disease in ruminants. Due to its intracellular nature, E. ruminantium requires a set of specific virulence factors, such as the type IV secretion system (T4SS, and outer membrane proteins (Map proteins in order to avoid and subvert the host's immune response. Several studies have been conducted to understand the regulation of the T4SS or outer membrane proteins, in Ehrlichia, but no integrated approach has been used to understand the regulation of Ehrlichia pathogenicity determinants in response to environmental cues. Iron is known to be a key nutrient for bacterial growth both in the environment and within hosts. In this study, we experimentally demonstrated the regulation of virB, map1, and tr1 genes by the newly identified master regulator ErxR (for Ehrlichia ruminantium expression regulator. We also analyzed the effect of iron depletion on the expression of erxR gene, tr1 transcription factor, T4SS and map1 genes clusters in E. ruminantium. We show that exposure of E. ruminantium to iron starvation induces erxR and subsequently tr1, virB, and map1 genes. Our results reveal tight co-regulation of T4SS and map1 genes via the ErxR regulatory protein at the transcriptional level, and, for the first time link map genes to the virulence function sensu stricto, thereby advancing our understanding of Ehrlichia's infection process. These results suggest that Ehrlichia is able to sense changes in iron concentrations in the environment and to regulate the expression of virulence factors accordingly.

  19. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    International Nuclear Information System (INIS)

    Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja; Park, Jin Wook; Park, Yeong-Min; Lee, Sang Eun

    2011-01-01

    Highlights: → Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. → Induction of CD4 + CD25 + Foxp3 + T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. → C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4 + CD25 + Foxp3 + regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfe