Scalar pseudo-Nambu-Goldstone boson in nuclei and dense nuclear matter

NASA Astrophysics Data System (ADS)

Lee, Hyun Kyu; Paeng, Won-Gi; Rho, Mannque

2015-12-01

The notion that the scalar listed as f0(500 ) in the particle data booklet is a pseudo-Nambu-Goldstone (NG) boson of spontaneously broken scale symmetry, explicitly broken by a small departure from an infrared fixed point, is explored in nuclear dynamics. This notion—which puts the scalar (which we shall identify as the "dilaton") on the same footing as the pseudoscalar pseudo-NG bosons, i.e., octet π , while providing a simple explanation for the Δ I =1 /2 rule for kaon decay—generalizes the standard chiral perturbation theory (χ PT ) to "scale chiral perturbation theory," denoted χPT σ , with one infrared mass scale for both symmetries, with the σ figuring as a chiral singlet NG mode in the nonstrange sector. Applied to nuclear dynamics, it is seen to provide answers to various hitherto unclarified nuclear phenomena, such as the success of one-boson-exchange potentials, the large cancellation of a strongly attractive scalar potential by a strongly repulsive vector potential in relativistic mean-field theory of nuclear systems and in-medium QCD sum rules, the interplay of the dilaton and the vector meson ω in dense Skyrmion matter, the Bogomol'nyi-Prasad-Sommerfeld Skyrmion structure of nuclei accounting for small binding energies of medium-heavy nuclei, and the suppression of hyperon degrees of freedom in compact-star matter.

Early Universe synthesis of asymmetric dark matter nuggets

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

Gresham, Moira I.; Lou, Hou Keong; Zurek, Kathryn M.

We compute the mass function of bound states of asymmetric dark matter - nuggets - synthesized in the early Universe. We apply our results for the nugget density and binding energy computed from a nuclear model to obtain analytic estimates of the typical nugget size exiting synthesis. We numerically solve the Boltzmann equation for synthesis including two-to-two fusion reactions, estimating the impact of bottlenecks on the mass function exiting synthesis. These results provide the basis for studying the late Universe cosmology of nuggets in a future companion paper.

Early Universe synthesis of asymmetric dark matter nuggets

DOE PAGES

Gresham, Moira I.; Lou, Hou Keong; Zurek, Kathryn M.

2018-02-12

We compute the mass function of bound states of asymmetric dark matter - nuggets - synthesized in the early Universe. We apply our results for the nugget density and binding energy computed from a nuclear model to obtain analytic estimates of the typical nugget size exiting synthesis. We numerically solve the Boltzmann equation for synthesis including two-to-two fusion reactions, estimating the impact of bottlenecks on the mass function exiting synthesis. These results provide the basis for studying the late Universe cosmology of nuggets in a future companion paper.

Role of nuclear factor-kappa B activation in the adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture.

PubMed

Dagher, Zeina; Garçon, Guillaume; Billet, Sylvain; Verdin, Anthony; Ledoux, Frédéric; Courcot, Dominique; Aboukais, Antoine; Shirali, Pirouz

2007-01-01

To contribute to improving knowledge on the adverse health effects induced by particulate matter (PM) air pollution, an extensive investigation was undertaken of the underlying mechanisms of action activated by PM(2.5) air pollution collected in Dunkerque, a strongly industrialized French seaside city. Their chemical and physical characteristics have been previously determined, and earlier in vitro short-term studies have shown them to cause dose-dependent and time-dependent oxidative damage, gene expression and protein secretion of inflammatory mediators, and apoptotic events in human lung epithelial cells (L132) in culture. Hence, this work studied the activation of nuclear factor-kappa B (NF-kappaB)/inhibitory kappa B (IkappaB) by Dunkerque city PM(2.5) in these target cells, by determination of phosphorylated p65 and phosphorylated IkappaBalpha protein levels in cytoplasmic extracts, and p65 and p50 DNA binding in nuclear extracts. In PM-exposed L132 cells, there were concentration- and/or time-dependent increases in nuclear p65 and cytoplasmic IkB-alpha phosphorylation, and nuclear p65 and p50 DNA binding. Taken together, these results showed that Dunkerque city PM(2.5) were involved in the activation of the NF-kappaB/IkappaB complex, notably through the occurrence of oxidative stress conditions, and, therefore, in the gene expression and protein secretion of inflammatory mediators in target L132 cells. Hence, these findings suggested that the activation of the NF-kappaB/IkappaB complex preceded cytotoxicity in Dunkerque city PM-exposed L132 cells. (c) 2007 John Wiley & Sons, Ltd.

The many facets of the (non-relativistic) Nuclear Equation of State

NASA Astrophysics Data System (ADS)

Giuliani, G.; Zheng, H.; Bonasera, A.

2014-05-01

A nucleus is a quantum many body system made of strongly interacting Fermions, protons and neutrons (nucleons). This produces a rich Nuclear Equation of State whose knowledge is crucial to our understanding of the composition and evolution of celestial objects. The nuclear equation of state displays many different features; first neutrons and protons might be treated as identical particles or nucleons, but when the differences between protons and neutrons are spelled out, we can have completely different scenarios, just by changing slightly their interactions. At zero temperature and for neutron rich matter, a quantum liquid-gas phase transition at low densities or a quark-gluon plasma at high densities might occur. Furthermore, the large binding energy of the α particle, a Boson, might also open the possibility of studying a system made of a mixture of Bosons and Fermions, which adds to the open problems of the nuclear equation of state.

The Nuclear Symmetry Energy and the Mass-Radius Relation of Neutron Stars

NASA Astrophysics Data System (ADS)

Lattimer, James

2017-01-01

The assumptions that i) neutron stars have hadronic crusts, ii) the equation of state is causal, iii) GR is the correct theory of gravity, and iv) their largest observed mass is 2 solar masses, when coupled with recent results from nuclear experiment and theoretical studies of neutron matter, generate powerful constraints on their structure. These include restriction of the radii of typical neutron stars to the range 11-13 km, as well as significant correlations among their masses, compactnesses, moments of inertia, binding energies, and tidal deformabilities. In addition, properties of quark matter, including the location and magnitude of the quark-hadron phase transition, can also be limited. The implications of recent and forthcoming experiments, such as those pertaining to the neutron skin thickness and astrophysical measurements of various structural properties is discussed. For the latter, emphasis is placed on pulsar timing, X-ray observations, supernova neutrino detections, and gravitational waves from mergers involving neutron stars. Supported in part by the US DOE grant DE-AC02-87ER40317.

Double-stranded telomeric DNA binding proteins: Diversity matters.

PubMed

Červenák, Filip; Juríková, Katarína; Sepšiová, Regina; Neboháčová, Martina; Nosek, Jozef; Tomáška, L'ubomír

2017-01-01

Telomeric sequences constitute only a small fraction of the whole genome yet they are crucial for ensuring genomic stability. This function is in large part mediated by protein complexes recruited to telomeric sequences by specific telomere-binding proteins (TBPs). Although the principal tasks of nuclear telomeres are the same in all eukaryotes, TBPs in various taxa exhibit a surprising diversity indicating their distinct evolutionary origin. This diversity is especially pronounced in ascomycetous yeasts where they must have co-evolved with rapidly diversifying sequences of telomeric repeats. In this article we (i) provide a historical overview of the discoveries leading to the current list of TBPs binding to double-stranded (ds) regions of telomeres, (ii) describe examples of dsTBPs highlighting their diversity in even closely related species, and (iii) speculate about possible evolutionary trajectories leading to a long list of various dsTBPs fulfilling the same general role(s) in their own unique ways.

Equation of State for Isospin Asymmetric Nuclear Matter Using Lane Potential

NASA Astrophysics Data System (ADS)

Basu, D. N.; Chowdhury, P. Roy; Samanta, C.

2006-10-01

A mean field calculation for obtaining the equation of state (EOS) for symmetric nuclear matter from a density dependent M3Y interaction supplemented by a zero-range potential is described. The energy per nucleon is minimized to obtain the ground state of symmetric nuclear matter. The saturation energy per nucleon used for nuclear matter calculations is determined from the co-efficient of the volume term of Bethe--Weizsäcker mass formula which is evaluated by fitting the recent experimental and estimated atomic mass excesses from Audi--Wapstra--Thibault atomic mass table by minimizing the mean square deviation. The constants of density dependence of the effective interaction are obtained by reproducing the saturation energy per nucleon and the saturation density of spin and isospin symmetric cold infinite nuclear matter. The EOS of symmetric nuclear matter, thus obtained, provide reasonably good estimate of nuclear incompressibility. Once the constants of density dependence are determined, EOS for asymmetric nuclear matter is calculated by adding to the isoscalar part, the isovector component of the M3Y interaction that do not contribute to the EOS of symmetric nuclear matter. These EOS are then used to calculate the pressure, the energy density and the velocity of sound in symmetric as well as isospin asymmetric nuclear matter.

Using new hetero-spectral two-dimensional correlation analyses and synchrotron-radiation-based spectromicroscopy to characterize binding of Cu to soil dissolved organic matter.

PubMed

Sun, Fusheng; Li, Yaqing; Wang, Xiang; Chi, Zhilai; Yu, Guanghui

2017-04-01

Understanding the binding characteristics of copper (Cu) to different functional groups in soil dissolved organic matter (DOM) is important to explore Cu toxicity, bioavailability and ultimate fate in the environment. However, the methods used to explore such binding characteristics are still limited. Here, two-dimensional correlation spectroscopy (2DCOS) integrated with Fourier transform infrared (FTIR), 29 Si nuclear magnetic resonance (NMR), 27 Al NMR, and synchrotron-radiation-based FTIR spectromicroscopy were used to explore the binding characteristics of Cu to soil DOM as part of a long-term (23 years) fertilization experiment. Compared with no fertilization and inorganic fertilization (NPK), long-term pig manure fertilization (M) treatment significantly increased the concentration of total and bioavailable Cu in soils. Furthermore, hetero-spectral 2DCOS analyses demonstrated that the binding characteristics of Cu onto functional groups in soil DOM were modified by fertilization regimes. In the NPK treatment, Cu was bound to aliphatic C, whereas in the manure treatment SiO groups had higher affinity toward Cu than aliphatic C. Also, the sequence of binding of functional groups to Cu was modified by the fertilization treatments. Moreover, synchrotron-radiation-based FTIR spectromicroscopy showed that Cu, clay minerals and sesquioxides, and C functional groups were heterogeneously distributed at the micro-scale. Specifically, clay-OH as well as mineral elements had a distribution pattern similar to Cu, but certain (but not all) C forms showed a distribution pattern inconsistent with that of Cu. The combination of synchrotron radiation spectromicroscopy and 2DCOS is a useful tool in exploring the interactions among heavy metals, minerals and organic components in soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mass predictions of atomic nuclei in the infinite nuclear matter model

NASA Astrophysics Data System (ADS)

Nayak, R. C.; Satpathy, L.

2012-07-01

We present here the mass excesses, binding energies, one- and two-neutron, one- and two-proton and α-particle separation energies of 6727 nuclei in the ranges 4≤Z≤120 and 8≤A≤303 calculated in the infinite nuclear matter model. Compared to our predictions of 1999 mass table, the present ones are obtained using larger data base of 2003 mass table of Wapstra and Audi and resorting to higher accuracy in the solutions of the η-differential equations of the INM model. The local energy η's supposed to carry signature of the characteristic properties of nuclei are found to possess the predictive capability. In fact η-systematics reveal new magic numbers in the drip-line regions giving rise to new islands of stability supported by relativistic mean field theoretic calculations. This is a manifestation of a new phenomenon where shell-effect overcomes the instability due to repulsive components of the nucleon-nucleon force broadening the stability peninsula. The two-neutron separation energy-systematics derived from the present mass predictions reveal a general new feature for the existence of islands of inversion in the exotic neutron-rich regions of nuclear landscape, apart from supporting the presently known islands around 31Na and 62Ti. The five global parameters representing the properties of infinite nuclear matter, the surface, the Coulomb and the pairing terms are retained as per our 1999 mass table. The root-mean-square deviation of the present mass-fit to 2198 known masses is 342 keV, while the mean deviation is 1.3 keV, reminiscent of no left-over systematic effects. This is a substantive improvement over our 1999 mass table having rms deviation of 401 keV and mean deviation of 9 keV for 1884 data nuclei.

A nuclear magnetic resonance study of the dynamics of organofluorine interactions with a dissolved humic acid.

PubMed

Longstaffe, James G; Courtier-Murias, Denis; Simpson, Andre J

2016-02-01

A quantitative understanding of the dynamics of the interactions between organofluorine compounds and humic acids will contribute to an improved understanding of the role that Natural Organic Matter plays as a mediator in the fate, transport and distribution of these contaminants in the environment. Here, Nuclear Magnetic Resonance (NMR) spectroscopy-based diffusion measurements are used to estimate the association dynamics between dissolved humic acid and selected organofluorine compounds: pentafluoroaniline, pentafluorophenol, potassium perfluorooctane sulfonate, and perfluorooctanoic acid. Under the conditions used here, the strength of the association with humic acid increases linearly as temperature decreases for all compounds except for perfluorooctanoic acid, which exhibits divergent behavior with a non-linear decrease in the extent of interaction as temperature decreases. A general interaction mechanism controlled largely by desolvation effects is suggested for all compounds examined here except for perfluorooctanoic acid, which exhibits a specific mode of interaction consistent with a proteinaceous binding site. Reverse Heteronuclear Saturation Transfer Difference NMR is used to confirm the identity and nature of the humic acid binding sites. Copyright © 2015 Elsevier Ltd. All rights reserved.

Variational Theory of Hot Dense Matter

ERIC Educational Resources Information Center

Mukherjee, Abhishek

2009-01-01

We develop a variational theory of hot nuclear matter in neutron stars and supernovae. It can also be used to study charged, hot nuclear matter which may be produced in heavy-ion collisions. This theory is a generalization of the variational theory of cold nuclear and neutron star matter based on realistic models of nuclear forces and pair…

Early Universe synthesis of asymmetric dark matter nuggets

NASA Astrophysics Data System (ADS)

Gresham, Moira I.; Lou, Hou Keong; Zurek, Kathryn M.

2018-02-01

We compute the mass function of bound states of asymmetric dark matter—nuggets—synthesized in the early Universe. We apply our results for the nugget density and binding energy computed from a nuclear model to obtain analytic estimates of the typical nugget size exiting synthesis. We numerically solve the Boltzmann equation for synthesis including two-to-two fusion reactions, estimating the impact of bottlenecks on the mass function exiting synthesis. These results provide the basis for studying the late Universe cosmology of nuggets in a future companion paper.

Systematic structure of the neutron drip-line {sup 22}C nucleus

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

Ismail, Atef; Cheong, Lee Yen; Yahya, Noorhana

2014-10-24

In the present work we systematically discuss the nuclear structure of the the heaviest particle-bound carbon isotope, {sup 22}C. The ground state wave function of the carbon isotope is calculated using the {sup 20}C core plus two-valence neutron based on a phenomenological mean-field MF potential. We apply the deduced wave function to provide the nuclear matter density which is necessary in the calculations of the total reaction cross section. Calculations show that there is a reasonable good description of the experimental binding energy BE and root-mean square RMS radius. The exotic structure and configuration of the ground state carbon isotopemore » is explained and a consistent explanation on the two-neutron halo (Borromean) nucleus is given.« less

Nuclear dipole polarizability from mean-field modeling constrained by chiral effective field theory

NASA Astrophysics Data System (ADS)

Zhang, Zhen; Lim, Yeunhwan; Holt, Jeremy W.; Ko, Che Ming

2018-02-01

We construct a new Skyrme interaction Skχm* by fitting the equation of state and nucleon effective masses in asymmetric nuclear matter from chiral two- and three-body forces as well as the binding energies of finite nuclei. Employing this interaction to study the electric dipole polarizabilities of 48Ca, 68Ni, 120Sn, and 208Pb in the random-phase approximation, we find that the theoretical predictions are in good agreement with experimentally measured values without additional fine tuning of the Skyrme interaction, thus confirming the usefulness of the new Skyrme interaction in studying the properties of nuclei. We further use this interaction to study the neutron skin thicknesses of 48Ca and 208Pb, and they are found to be consistent with the experimental data.

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

DOE PAGES

McDermott, Samuel D.

2018-06-01

Here, we suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than v n~(10 –(2–3)) n, where n=1, 2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be σ~0.1–1 barn, moderately larger than for standard model deuteron fusion, indicating a dark nuclear scale Λ~O(100 MeV). Darkmore » fusion firmly predicts constant σv below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometers per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.« less

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

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

McDermott, Samuel D.

2017-11-02

We suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than v^n ~ [10^{-(2-3)}]^n, where n=1,2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be sigma ~ 0.1-1 barn, moderately larger than for Standard Model deuteron fusion, indicating a dark nuclear scale Lambda ~ O(100 MeV).more » Dark fusion firmly predicts constant sigma v below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometer per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.« less

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

NASA Astrophysics Data System (ADS)

McDermott, Samuel D.

2018-06-01

We suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than vn˜(10-(2 -3 ))n , where n =1 , 2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be σ˜0.1 - 1 barn, moderately larger than for standard model deuteron fusion, indicating a dark nuclear scale Λ ˜O (100 MeV ) . Dark fusion firmly predicts constant σ v below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometers per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.

Is Self-Interacting Dark Matter Undergoing Dark Fusion?

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

McDermott, Samuel D.

Here, we suggest that two-to-two dark matter fusion may be the relaxation process that resolves the small-scale structure problems of the cold collisionless dark matter paradigm. In order for the fusion cross section to scale correctly across many decades of astrophysical masses from dwarf galaxies to galaxy clusters, we require the fractional binding energy released to be greater than v n~(10 –(2–3)) n, where n=1, 2 depends on local dark sector chemistry. The size of the dark-sector interaction cross sections must be σ~0.1–1 barn, moderately larger than for standard model deuteron fusion, indicating a dark nuclear scale Λ~O(100 MeV). Darkmore » fusion firmly predicts constant σv below the characteristic velocities of galaxy clusters. Observations of the inner structure of galaxy groups with velocity dispersion of several hundred kilometers per second, of which a handful have been identified, could differentiate dark fusion from a dark photon model.« less

Adrenocortical nuclear progesterone-binding protein: Identification by photoaffinity labeling and evidence for deoxyribonucleic acid binding and stimulation by adrenocorticotropin

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

Demura, T.; Driscoll, W.J.; Lee, Y.C.

1991-01-01

Nuclei of the guinea pig adrenal cortex contain a protein that specifically binds progesterone and that, biochemically, is clearly distinct from the classical progesterone receptor. The adrenocortical nuclear progesterone-binding protein has now been purified more than 2000-fold by steroid-affinity chromatography with a 75% yield. The purified protein preparation demonstrated three major bands on sodium dodecyl sulfate-polyacrylamide gel of 79K, 74K, and 50K. To determine which of the three might represent the progesterone-binding protein, steroid photoaffinity labeling was performed which resulted in the specific and exclusive labeling of a 50K band. Thus, the adrenocortical nuclear progesterone-binding protein appears to be distinctmore » from the classical progesterone receptor not only biochemically, but also on the basis of molecular size. To test whether the adrenocortical nuclear progesterone-binding protein can be hormonally stimulated, guinea pigs were treated with ACTH. The chronic administration of ACTH caused a 4- to 6-fold increase in the specific progesterone binding capacity without a change in the binding affinity. There appeared to be no significant difference in nuclear progesterone binding between the zona fasciculata and zona reticularis. This finding suggests a mediating role for the progesterone-binding protein in ACTH action. In addition, the nuclear progesterone-binding protein bound to nonspecific DNA sequences, further suggesting a possible transcriptional regulatory role.« less

Molecular dynamics for dense matter

NASA Astrophysics Data System (ADS)

Maruyama, Toshiki; Watanabe, Gentaro; Chiba, Satoshi

2012-08-01

We review a molecular dynamics method for nucleon many-body systems called quantum molecular dynamics (QMD), and our studies using this method. These studies address the structure and the dynamics of nuclear matter relevant to neutron star crusts, supernova cores, and heavy-ion collisions. A key advantage of QMD is that we can study dynamical processes of nucleon many-body systems without any assumptions about the nuclear structure. First, we focus on the inhomogeneous structures of low-density nuclear matter consisting not only of spherical nuclei but also of nuclear "pasta", i.e., rod-like and slab-like nuclei. We show that pasta phases can appear in the ground and equilibrium states of nuclear matter without assuming nuclear shape. Next, we show our simulation of compression of nuclear matter which corresponds to the collapsing stage of supernovae. With the increase in density, a crystalline solid of spherical nuclei changes to a triangular lattice of rods by connecting neighboring nuclei. Finally, we discuss fragment formation in expanding nuclear matter. Our results suggest that a generally accepted scenario based on the liquid-gas phase transition is not plausible at lower temperatures.

Emission and transport of cesium-137 from boreal biomass burning in the summer of 2010

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

Strode, S.; Ott, Lesley E.; Pawson, Steven

2012-05-09

While atmospheric concentrations of cesium-137 have decreased since the nuclear testing era, resuspension of Cs-137 during biomass burning provides an ongoing emission source. The summer of 2010 was an intense biomass burning season in western Russia, with high levels of particulate matter impacting air quality and visibility. A radionuclide monitoring station in western Russia shows enhanced airborne Cs-137 concentrations during the wildfire period. Since Cs-137 binds to aerosols, satellite observations of aerosols and fire occurrences can provide a global-scale context for Cs-137 emissions and transport during biomass burning events.

Examining the possibility to observe neutron dark decay in nuclei

NASA Astrophysics Data System (ADS)

Pfützner, M.; Riisager, K.

2018-04-01

As proposed recently by Fornal and Grinstein, neutrons can undergo a dark matter decay mode which has not yet been observed. Such a decay could explain the existing discrepancy between two different methods of neutron lifetime measurements. If such neutron decay is possible, then it should occur also in nuclei with sufficiently low neutron binding energy. We examine a few nuclear candidates for the dark neutron decay and we consider the possibilities of their experimental identification. In more detail we discuss the case of 11Be which appears as the most promising nucleus for the observation of neutron dark decay.

Quarkonium-nucleus bound states from lattice QCD

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

Beane, S.  R.; Chang, E.; Cohen, S.  D.

2015-06-11

Quarkonium-nucleus systems are composed of two interacting hadronic states without common valence quarks, which interact primarily through multi-gluon exchanges, realizing a color van der Waals force. We present lattice QCD calculations of the interactions of strange and charm quarkonia with light nuclei. Both the strangeonium-nucleus and charmonium-nucleus systems are found to be relatively deeply bound when the masses of the three light quarks are set equal to that of the physical strange quark. Extrapolation of these results to the physical light-quark masses suggests that the binding energy of charmonium to nuclear matter is B < 40 MeV.

New relativistic effective interaction for finite nuclei, infinite nuclear matter, and neutron stars

NASA Astrophysics Data System (ADS)

Kumar, Bharat; Patra, S. K.; Agrawal, B. K.

2018-04-01

We carry out the study of finite nuclei, infinite nuclear matter, and neutron star properties with the newly developed relativistic force, the Institute of Physics Bhubaneswar-I (IOPB-I). Using this force, we calculate the binding energies, charge radii, and neutron-skin thickness for some selected nuclei. From the ground-state properties of superheavy nuclei (Z =120 ), it is noticed that considerable shell gaps appear at neutron numbers N =172 , 184, and 198, manifesting the magicity at these numbers. The low-density behavior of the equation of state for pure neutron matter is compatible with other microscopic models. Along with the nuclear symmetry energy, its slope and curvature parameters at the saturation density are consistent with those extracted from various experimental data. We calculate the neutron star properties with the equation of state composed of nucleons and leptons in β -equilibrium, which are in good agreement with the x-ray observations by Steiner [Astrophys. J. 722, 33 (2010), 10.1088/0004-637X/722/1/33] and Nättilä [Astron. Astrophys. 591, A25 (2016), 10.1051/0004-6361/201527416]. Based on the recent observation of GW170817 with a quasi-universal relation, Rezzolla et al. [Astrophys. J. Lett. 852, L25 (2018), 10.3847/2041-8213/aaa401] have set a limit for the maximum mass that can be supported against gravity by a nonrotating neutron star in the range 2.01 ±0.04 ≲M (M⊙)≲2.16 ±0.03 . We find that the maximum mass of the neutron star for the IOPB-I parametrization is 2.15 M⊙ . The radius and tidal deformability of a canonical neutron star of mass 1.4 M⊙ are 13.2 km and 3.9 ×1036g cm2s2 , respectively.

Mass predictions of atomic nuclei in the infinite nuclear matter model

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

Nayak, R.C., E-mail: rcnayak00@yahoo.com; Satpathy, L., E-mail: satpathy@iopb.res.in

We present here the mass excesses, binding energies, one- and two-neutron, one- and two-proton and {alpha}-particle separation energies of 6727 nuclei in the ranges 4{<=}Z{<=}120 and 8{<=}A{<=}303 calculated in the infinite nuclear matter model. Compared to our predictions of 1999 mass table, the present ones are obtained using larger data base of 2003 mass table of Wapstra and Audi and resorting to higher accuracy in the solutions of the {eta}-differential equations of the INM model. The local energy {eta}'s supposed to carry signature of the characteristic properties of nuclei are found to possess the predictive capability. In fact {eta}-systematics revealmore » new magic numbers in the drip-line regions giving rise to new islands of stability supported by relativistic mean field theoretic calculations. This is a manifestation of a new phenomenon where shell-effect overcomes the instability due to repulsive components of the nucleon-nucleon force broadening the stability peninsula. The two-neutron separation energy-systematics derived from the present mass predictions reveal a general new feature for the existence of islands of inversion in the exotic neutron-rich regions of nuclear landscape, apart from supporting the presently known islands around {sup 31}Na and {sup 62}Ti. The five global parameters representing the properties of infinite nuclear matter, the surface, the Coulomb and the pairing terms are retained as per our 1999 mass table. The root-mean-square deviation of the present mass-fit to 2198 known masses is 342 keV, while the mean deviation is 1.3 keV, reminiscent of no left-over systematic effects. This is a substantive improvement over our 1999 mass table having rms deviation of 401 keV and mean deviation of 9 keV for 1884 data nuclei.« less

Structure of cold nuclear matter at subnuclear densities by quantum molecular dynamics

NASA Astrophysics Data System (ADS)

Watanabe, Gentaro; Sato, Katsuhiko; Yasuoka, Kenji; Ebisuzaki, Toshikazu

2003-09-01

Structure of cold nuclear matter at subnuclear densities for the proton fraction x=0.5, 0.3, and 0.1 is investigated by quantum molecular dynamics (QMD) simulations. We demonstrate that the phases with slablike and rodlike nuclei, etc. can be formed dynamically from hot uniform nuclear matter without any assumptions on nuclear shape, and also systematically analyze the structure of cold matter using two-point correlation functions and Minkowski functionals. In our simulations, we also observe intermediate phases, which have complicated nuclear shapes. It has been found out that these phases can be characterized as those with negative Euler characteristic. Our result implies the existence of these kinds of phases in addition to the simple “pasta” phases in neutron star crusts and supernova inner cores. In addition, we investigate the properties of the effective QMD interaction used in the present work to examine the validity of our results. The resultant energy per nucleon ɛn of the pure neutron matter, the proton chemical μ(0)p in pure neutron matter and the nuclear surface tension Esurf are generally reasonable in comparison with other nuclear interactions.

Can tonne-scale direct detection experiments discover nuclear dark matter?

NASA Astrophysics Data System (ADS)

Butcher, Alistair; Kirk, Russell; Monroe, Jocelyn; West, Stephen M.

2017-10-01

Models of nuclear dark matter propose that the dark sector contains large composite states consisting of dark nucleons in analogy to Standard Model nuclei. We examine the direct detection phenomenology of a particular class of nuclear dark matter model at the current generation of tonne-scale liquid noble experiments, in particular DEAP-3600 and XENON1T. In our chosen nuclear dark matter scenario distinctive features arise in the recoil energy spectra due to the non-point-like nature of the composite dark matter state. We calculate the number of events required to distinguish these spectra from those of a standard point-like WIMP state with a decaying exponential recoil spectrum. In the most favourable regions of nuclear dark matter parameter space, we find that a few tens of events are needed to distinguish nuclear dark matter from WIMPs at the 3 σ level in a single experiment. Given the total exposure time of DEAP-3600 and XENON1T we find that at best a 2 σ distinction is possible by these experiments individually, while 3 σ sensitivity is reached for a range of parameters by the combination of the two experiments. We show that future upgrades of these experiments have potential to distinguish a large range of nuclear dark matter models from that of a WIMP at greater than 3 σ.

Can tonne-scale direct detection experiments discover nuclear dark matter?

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

Butcher, Alistair; Kirk, Russell; Monroe, Jocelyn

Models of nuclear dark matter propose that the dark sector contains large composite states consisting of dark nucleons in analogy to Standard Model nuclei. We examine the direct detection phenomenology of a particular class of nuclear dark matter model at the current generation of tonne-scale liquid noble experiments, in particular DEAP-3600 and XENON1T. In our chosen nuclear dark matter scenario distinctive features arise in the recoil energy spectra due to the non-point-like nature of the composite dark matter state. We calculate the number of events required to distinguish these spectra from those of a standard point-like WIMP state with amore » decaying exponential recoil spectrum. In the most favourable regions of nuclear dark matter parameter space, we find that a few tens of events are needed to distinguish nuclear dark matter from WIMPs at the 3 σ level in a single experiment. Given the total exposure time of DEAP-3600 and XENON1T we find that at best a 2 σ distinction is possible by these experiments individually, while 3 σ sensitivity is reached for a range of parameters by the combination of the two experiments. We show that future upgrades of these experiments have potential to distinguish a large range of nuclear dark matter models from that of a WIMP at greater than 3 σ .« less

Constraining the surface properties of effective Skyrme interactions

NASA Astrophysics Data System (ADS)

Jodon, R.; Bender, M.; Bennaceur, K.; Meyer, J.

2016-08-01

Background: Deformation energy surfaces map how the total binding energy of a nuclear system depends on the geometrical properties of intrinsic configurations, thereby providing a powerful tool to interpret nuclear spectroscopy and large-amplitude collective-motion phenomena such as fission. The global behavior of the deformation energy is known to be directly connected to the surface properties of the effective interaction used for its calculation. Purpose: The precise control of surface properties during the parameter adjustment of an effective interaction is key to obtain a reliable and predictive description of nuclear properties. The most relevant indicator is the surface-energy coefficient asurf. There are several possibilities for its definition and estimation, which are not fully equivalent and require a computational effort that can differ by orders of magnitude. The purpose of this study is threefold: first, to identify a scheme for the determination of asurf that offers the best compromise between robustness, precision, and numerical efficiency; second, to analyze the correlation between values for asurf and the characteristic energies of the fission barrier of 240Pu; and third, to lay out an efficient and robust procedure for how the deformation properties of the Skyrme energy density functional (EDF) can be constrained during the parameter fit. Methods: There are several frequently used possibilities to define and calculate the surface energy coefficient asurf of effective interactions built for the purpose of self-consistent mean-field calculations. The most direct access is provided by the model system of semi-infinite nuclear matter, but asurf can also be extracted from the systematics of binding energies of finite nuclei. Calculations can be carried out either self-consistently [Hartree-Fock (HF)], which incorporates quantal shell effects, or in one of the semiclassical extended Thomas-Fermi (ETF) or modified Thomas-Fermi (MTF) approximations. The latter is of particular interest because it provides asurf as a numerical integral without the need to solve self-consistent equations. Results for semi-infinite nuclear matter obtained with the HF, ETF, and MTF methods will be compared with one another and with asurf, as deduced from ETF calculations of very heavy fictitious nuclei. Results: The surface energy coefficient of 76 parametrizations of the Skyrme EDF have been calculated. Values obtained with the HF, ETF, and MTF methods are not identical, but differ by fairly constant systematic offsets. By contrast, extracting asurf from the binding energy of semi-infinite matter or of very large nuclei within the same method gives the same result within the numerical uncertainties. Conclusions: Despite having some drawbacks compared to the other methods studied here, the MTF approach provides sufficiently precise values for asurf such that it can be used as a very robust constraint on surface properties during a parameter fit at negligible additional cost. While the excitation energy of superdeformed states and the height of fission barriers is obviously strongly correlated to asurf, the presence of shell effects prevents a one-to-one correspondence between them. As in addition the value of asurf providing realistic fission barriers depends on the choices made for corrections for spurious motion, its "best value" (within a given scheme to calculate it) depends on the fit protocol. Through the construction of a series of eight parametrizations SLy5s1-SLy5s8 of the standard Skyrme EDF with systematically varied asurf value, it is shown how to arrive at a fit with realistic deformation properties.

Memory binding and white matter integrity in familial Alzheimer’s disease

PubMed Central

Saarimäki, Heini; Bastin, Mark E.; Londoño, Ana C.; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

2015-01-01

Binding information in short-term and long-term memory are functions sensitive to Alzheimer’s disease. They have been found to be affected in patients who meet criteria for familial Alzheimer’s disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer’s disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer’s disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer’s disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer’s disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer’s disease. PMID:25762465

Memory binding and white matter integrity in familial Alzheimer's disease.

PubMed

Parra, Mario A; Saarimäki, Heini; Bastin, Mark E; Londoño, Ana C; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

2015-05-01

Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer's disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

75 FR 10833 - In the Matter of Entergy Nuclear Operations; Vermont Yankee Nuclear Power Station; Demand for...

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2010-03-09

... NUCLEAR REGULATORY COMMISSION [Docket No. 05000271; License No. DPR-28; EA-10-034; NRC-2010-0089] In the Matter of Entergy Nuclear Operations; Vermont Yankee Nuclear Power Station; Demand for.... The license authorizes the operation of the Vermont Yankee Nuclear Power Station (Vermont Yankee) in...

Argonne Physics Division

Science.gov Websites

, nuclear structure and reaction research, nuclear theory, medium energy nuclear research and accelerator structure of baryonic matter in the universe - the matter that makes up stars, planets and human life itself

JAB1 regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cells

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

Nishimoto, Arata, E-mail: anishimo@yamaguchi-u.ac.jp; Kugimiya, Naruji; Hosoyama, Toru

2013-08-30

Highlights: •JAB1 interacted with unphosphorylated STAT3 in the nucleus. •JAB1 knockdown tended to increase nuclear STAT3 expression. •JAB1 knockdown significantly decreased unphosphorylated STAT3 DNA-binding activity. •JAB1 knockdown significantly decreased MDR1, NANOG, and VEGF expressions. •Nuclear JAB1, but not nuclear STAT3, correlated with STAT3 DNA-binding activity. -- Abstract: Recent studies have revealed that unphosphorylated STAT3 forms a dimer, translocates to the nucleus, binds to the STAT3 binding site, and activates the transcription of STAT3 target genes, thereby playing an important role in oncogenesis in addition to phosphorylated STAT3. Among signaling steps of unphosphorylated STAT3, nuclear translocation and target DNA-binding are themore » critical steps for its activation. Therefore, elucidating the regulatory mechanism of these signaling steps of unphosphorylated STAT3 is a potential step in the discovery of a novel cancer drug. However, the mechanism of unphosphorylated STAT3 binding to the promoter of target genes remains unclear. In this study, we focused on Jun activation domain-binding protein 1 (JAB1) as a candidate protein that regulates unphosphorylated STAT3 DNA-binding activity. Initially, we observed that both unphosphorylated STAT3 and JAB1 existed in the nucleus of human colon cancer cell line COLO205 at the basal state (no cytokine stimulation). On the other hand, phosphorylated STAT3 did not exist in the nucleus of COLO205 cells at the basal state. Immunoprecipitation using nuclear extract of COLO205 cells revealed that JAB1 interacted with unphosphorylated STAT3. To investigate the effect of JAB1 on unphosphorylated STAT3 activity, RNAi studies were performed. Although JAB1 knockdown tended to increase nuclear STAT3 expression, it significantly decreased unphosphorylated STAT3 DNA-binding activity. Subsequently, JAB1 knockdown significantly decreased the expression levels of MDR1, NANOG, and VEGF, which are STAT3 target genes. Furthermore, the expression level of nuclear JAB1, but not nuclear STAT3, correlated with unphosphorylated STAT3 DNA-binding activity between COLO205 and LoVo cells. Taken together, these results suggest that nuclear JAB1 positively regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cell line COLO205.« less

Nuclear structure of bound states of asymmetric dark matter

NASA Astrophysics Data System (ADS)

Gresham, Moira I.; Lou, Hou Keong; Zurek, Kathryn M.

2017-11-01

Models of asymmetric dark matter (ADM) with a sufficiently attractive and long-range force give rise to stable bound objects, analogous to nuclei in the Standard Model, called nuggets. We study the properties of these nuggets and compute their profiles and binding energies. Our approach, applicable to both elementary and composite fermionic ADM, utilizes relativistic mean field theory, and allows a more systematic computation of nugget properties, over a wider range of sizes and force mediator masses, compared to previous literature. We identify three separate regimes of nugget property behavior corresponding to (1) nonrelativistic and (2) relativistic constituents in a Coulomb-like limit, and (3) saturation in an anti-Coulomb limit when the nuggets are large compared to the force range. We provide analytical descriptions for nuggets in each regime. Through numerical calculations, we are able to confirm our analytic descriptions and also obtain smooth transitions for the nugget profiles between all three regimes. We also find that over a wide range of parameter space, the binding energy in the saturation limit is an O (1 ) fraction of the constituent's mass, significantly larger than expectations in the nonrelativistic case. In a companion paper, we apply our results to the synthesis of ADM nuggets in the early Universe.

Cross-linking of surface Ig receptors on murine B lymphocytes stimulates the expression of nuclear tetradecanoyl phorbol acetate-response element-binding proteins

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

Chiles, T.C.; Liu, J.L.; Rothstein, T.L.

1991-03-15

Cross-linking of sIg on primary B lymphocytes leads to increased nuclear DNA-binding activity specific for the tetradecanoyl phorbol acetate-response element (TRE), as judged by gel mobility shift assays. Stimulation of B cells to enter S phase of the cell cycle by treatment with the combination of phorbol ester plus calcium ionophore also stimulated nuclear TRE-binding activity within 2 h, with maximal expression at 4 h; however, phorbol ester and calcium ionophore were not as effective in stimulating binding activity when examined separately. Stimulated nuclear expression of TRE-binding activity appears to require protein synthesis. Fos- and Jun/AP-1-related proteins participate directly inmore » the identified nucleoprotein complex, as shown by the ability of c-fos- and c-jun-specific antisera to either alter or completely abolish electrophoretic migration of the complex in native gels. Further, UV photo-cross-linking studies identified two major TRE-binding protein species, whose sizes correspond to TRE-binding proteins derived from HeLa cell nuclear extracts. The results suggest that in primary B cells nuclear TRE-binding activity represents a downstream signaling event that occurs subsequent to changes in protein kinase C activity and intracellular Ca2+ but that can be triggered physiologically through sIg.« less

Influence of flow constraints on the properties of the critical endpoint of symmetric nuclear matter

NASA Astrophysics Data System (ADS)

Ivanytskyi, A. I.; Bugaev, K. A.; Sagun, V. V.; Bravina, L. V.; Zabrodin, E. E.

2018-06-01

We propose a novel family of equations of state for symmetric nuclear matter based on the induced surface tension concept for the hard-core repulsion. It is shown that having only four adjustable parameters the suggested equations of state can, simultaneously, reproduce not only the main properties of the nuclear matter ground state, but the proton flow constraint up its maximal particle number densities. Varying the model parameters we carefully examine the range of values of incompressibility constant of normal nuclear matter and its critical temperature, which are consistent with the proton flow constraint. This analysis allows us to show that the physically most justified value of nuclear matter critical temperature is 15.5-18 MeV, the incompressibility constant is 270-315 MeV and the hard-core radius of nucleons is less than 0.4 fm.

Kaon Condensation and the Non-Uniform Nuclear Matter

NASA Astrophysics Data System (ADS)

Maruyama, Toshiki; Tatsumi, Toshitaka; Voskresensky, Dmitri N.; Tanigawa, Tomonori; Chiba, Satoshi

2004-04-01

Non-uniform structures of nuclear matter are studied in a wide density-range. Using the density functional theory with a relativistic mean-field model, we examine non-uniform structures at sub-nuclear densities (nuclear "pastas") and at high densities, where kaon condensate is expected. We try to give a unified view about the change of the matter structure as density increases, carefully taking into account the Coulomb screening effects from the viewpoint of first-order phase transition.

Data on natural organic substances in dissolved, colloidal, suspended-silt and -clay, and bed-sediment phases in the Mississippi River and some of its tributaries, 1987-90

USGS Publications Warehouse

Leenheer, J.A.; Noyes, T.I.; Brown, P.A.

1994-01-01

The Mississippi River and some of its tributaries were sampled for natural organic substances dissolved in water and in suspended and bed sediments during seven sampling cruises from 1987-90. The sampling cruises were made during different seasons, in the free-flowing reaches of the river from St. Louis, Missouri, to New Orleans, Louisiana. The first three cruises were made during low-water conditions, and the last four cruises during high-water conditions. The purpose for sampling and characterizing natural organic substances in the various phases in the river was to provide an understanding of how these substances facilitate contaminant transport and transformations in the Mississippi River. Significant conclusions of this study were: (1) Natural organic substances appear to stabilize ' certain colloids against aggregation; therefore, these colloids remain in suspension and can act as transport agents that are not affected by sedimentation. Bacteria were found to be a significant fraction of organic colloids. (2) A new class of organic contaminants (polyethylene glycols) derived from nonionic surfactant residues was discovered dissolved with natural organic substances in water. These polyethylene glycols have the potential to affect both organic and inorganic contaminant transport in water. (3) The entire dissolved organic-matter component under varying hydrologic and seasonal conditions was characterized. (4) A method was developed to characterize organic matter in sediment by solid-state, 13C-nuclear magnetic resonance spectrometry. (5) The organic matter in suspended sediments was characterized by a variety of spectral and nonspectral methods. The protein component (significant in trace-metal binding) and lipid component (significant in organic-contaminant binding) were found to be major constituents in natural organic matter in suspended sediment. (6) Pools are reservoirs acting as traps of sedimentary organic matter of allochthonous origin and export material of autochthonous nitrogen. (7) A major portion of the mass of organic colloids in transport consisted of bacterial cells.

Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of Peroxisome Proliferator-activated Receptor α in a Ligand-selective Manner*

PubMed Central

Hughes, Maria L. R.; Liu, Bonan; Halls, Michelle L.; Wagstaff, Kylie M.; Patil, Rahul; Velkov, Tony; Jans, David A.; Bunnett, Nigel W.; Scanlon, Martin J.; Porter, Christopher J. H.

2015-01-01

Nuclear hormone receptors (NHRs) regulate the expression of proteins that control aspects of reproduction, development and metabolism, and are major therapeutic targets. However, NHRs are ubiquitous and participate in multiple physiological processes. Drugs that act at NHRs are therefore commonly restricted by toxicity, often at nontarget organs. For endogenous NHR ligands, intracellular lipid-binding proteins, including the fatty acid-binding proteins (FABPs), can chaperone ligands to the nucleus and promote NHR activation. Drugs also bind FABPs, raising the possibility that FABPs similarly regulate drug activity at the NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid-binding proteins that are highly expressed in tissues involved in lipid metabolism, including the liver and intestine) to influence drug-mediated activation of the lipid regulator peroxisome proliferator-activated receptor (PPAR) α. We show by quantitative fluorescence imaging and gene reporter assays that drug binding to FABP1 and FABP2 promotes nuclear localization and PPARα activation in a drug- and FABP-dependent manner. We further show that nuclear accumulation of FABP1 and FABP2 is dependent on the presence of PPARα. Nuclear accumulation of FABP on drug binding is driven largely by reduced nuclear egress rather than an increased rate of nuclear entry. Importin binding assays indicate that nuclear access occurs via an importin-independent mechanism. Together, the data suggest that specific drug-FABP complexes can interact with PPARα to effect nuclear accumulation of FABP and NHR activation. Because FABPs are expressed in a regionally selective manner, this may provide a means to tailor the patterns of NHR drug activation in a tissue-specific manner. PMID:25847235

Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of Peroxisome Proliferator-activated Receptor α in a Ligand-selective Manner.

PubMed

Hughes, Maria L R; Liu, Bonan; Halls, Michelle L; Wagstaff, Kylie M; Patil, Rahul; Velkov, Tony; Jans, David A; Bunnett, Nigel W; Scanlon, Martin J; Porter, Christopher J H

2015-05-29

Nuclear hormone receptors (NHRs) regulate the expression of proteins that control aspects of reproduction, development and metabolism, and are major therapeutic targets. However, NHRs are ubiquitous and participate in multiple physiological processes. Drugs that act at NHRs are therefore commonly restricted by toxicity, often at nontarget organs. For endogenous NHR ligands, intracellular lipid-binding proteins, including the fatty acid-binding proteins (FABPs), can chaperone ligands to the nucleus and promote NHR activation. Drugs also bind FABPs, raising the possibility that FABPs similarly regulate drug activity at the NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid-binding proteins that are highly expressed in tissues involved in lipid metabolism, including the liver and intestine) to influence drug-mediated activation of the lipid regulator peroxisome proliferator-activated receptor (PPAR) α. We show by quantitative fluorescence imaging and gene reporter assays that drug binding to FABP1 and FABP2 promotes nuclear localization and PPARα activation in a drug- and FABP-dependent manner. We further show that nuclear accumulation of FABP1 and FABP2 is dependent on the presence of PPARα. Nuclear accumulation of FABP on drug binding is driven largely by reduced nuclear egress rather than an increased rate of nuclear entry. Importin binding assays indicate that nuclear access occurs via an importin-independent mechanism. Together, the data suggest that specific drug-FABP complexes can interact with PPARα to effect nuclear accumulation of FABP and NHR activation. Because FABPs are expressed in a regionally selective manner, this may provide a means to tailor the patterns of NHR drug activation in a tissue-specific manner. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Sequence and characterization of cytoplasmic nuclear protein import factor p97

PubMed Central

1995-01-01

Nuclear location sequence-mediated binding of karyophilic proteins to the nuclear pore complexes is one of the earliest steps in nuclear protein import. We previously identified two cytosolic proteins that reconstitute this step in a permeabilized cell assay: the 54/56-kD NLS receptor and p97. A monoclonal antibody to p97 localizes the protein to the cytoplasm and the nuclear envelope. p97 is extracted from nuclear envelopes under the same conditions as the O-glycosylated nucleoporins indicating a tight association with the pore complex. The antibody inhibits import in a permeabilized cell assay but does not affect binding of karyophiles to the nuclear pore complex. Immunodepletion of p97 renders the cytosol inactive for import and identifies at least three other cytosolic proteins that interact with p97. cDNA cloning of p97 shows that it is a unique protein containing 23 cysteine residues. Recombinant p97 binds zinc and a bound metal ion is required for the nuclear envelope binding activity of the protein. PMID:7615630

10 CFR 820.8 - Evidentiary matters.

Code of Federal Regulations, 2011 CFR

2011-01-01

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10 CFR 820.8 - Evidentiary matters.

Code of Federal Regulations, 2013 CFR

2013-01-01

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Code of Federal Regulations, 2012 CFR

2012-01-01

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Code of Federal Regulations, 2010 CFR

2010-01-01

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2014-01-01

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The limits of the nuclear landscape explored by the relativistic continuum Hartree-Bogoliubov theory

NASA Astrophysics Data System (ADS)

Xia, X. W.; Lim, Y.; Zhao, P. W.; Liang, H. Z.; Qu, X. Y.; Chen, Y.; Liu, H.; Zhang, L. F.; Zhang, S. Q.; Kim, Y.; Meng, J.

2018-05-01

The ground-state properties of nuclei with 8 ⩽ Z ⩽ 120 from the proton drip line to the neutron drip line have been investigated using the spherical relativistic continuum Hartree-Bogoliubov (RCHB) theory with the relativistic density functional PC-PK1. With the effects of the continuum included, there are totally 9035 nuclei predicted to be bound, which largely extends the existing nuclear landscapes predicted with other methods. The calculated binding energies, separation energies, neutron and proton Fermi surfaces, root-mean-square (rms) radii of neutron, proton, matter, and charge distributions, ground-state spins and parities are tabulated. The extension of the nuclear landscape obtained with RCHB is discussed in detail, in particular for the neutron-rich side, in comparison with the relativistic mean field calculations without pairing correlations and also other predicted landscapes. It is found that the coupling between the bound states and the continuum due to the pairing correlations plays an essential role in extending the nuclear landscape. The systematics of the separation energies, radii, densities, potentials and pairing energies of the RCHB calculations are also discussed. In addition, the α-decay energies and proton emitters based on the RCHB calculations are investigated.

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

Eberhard, Jeremy; Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

We previously discovered that nuclear import of high risk HPV16 E7 is mediated by a cNLS located within the zinc-binding domain via a pathway that is independent of karyopherins/importins (Angeline et al., 2003; Knapp et al., 2009). In this study we continued our characterization of the cNLS and nuclear import pathway of HPV16 E7. We find that an intact zinc-binding domain is essential for the cNLS function in mediating nuclear import of HPV16 E7. Mutagenesis of cysteine residues to alanine in each of the two CysXXCys motifs involved in zinc-binding changes the nuclear localization of the EGFP-16E7 and 2xEGFP-16E7 mutants.more » We further discover that a patch of hydrophobic residues, {sub 65}LRLCV{sub 69}, within the zinc-binding domain of HPV16 E7 mediates its nuclear import via hydrophobic interactions with the FG domain of the central channel nucleoporin Nup62. - Highlights: • An intact zinc-binding domain is essential for the nuclear localization of HPV16 E7. • Identification of a hydrophobic patch that is critical for the nuclear import of HPV16 E7. • HPV16 E7 interacts via its zinc-binding domain with the FG domain of Nup62.« less

Holographic Quark Matter and Neutron Stars.

PubMed

Hoyos, Carlos; Jokela, Niko; Rodríguez Fernández, David; Vuorinen, Aleksi

2016-07-15

We use a top-down holographic model for strongly interacting quark matter to study the properties of neutron stars. When the corresponding equation of state (EOS) is matched with state-of-the-art results for dense nuclear matter, we consistently observe a first-order phase transition at densities between 2 and 7 times the nuclear saturation density. Solving the Tolman-Oppenheimer-Volkov equations with the resulting hybrid EOSs, we find maximal stellar masses in excess of two solar masses, albeit somewhat smaller than those obtained with simple extrapolations of the nuclear matter EOSs. Our calculation predicts that no quark matter exists inside neutron stars.

78 FR 66965 - In the Matter of Exelon Generation Company, LLC; Dresden Nuclear Power Station Confirmatory Order...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-07

...; NRC-2013-0245] In the Matter of Exelon Generation Company, LLC; Dresden Nuclear Power Station... licenses authorize the operation of the Dresden Nuclear Power Station (Dresden Station) in accordance with... actions described below will be taken at Dresden Nuclear Power Station and other nuclear plants in Exelon...

Near-threshold J/ψ-meson photoproduction on nuclei

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

Paryev, E. Ya.; Kiselev, Yu. T., E-mail: yurikis@itep.ru

On the basis of the first-collision model that relies on the nuclear spectral function and which includes incoherent processes involving charmonium production in proton–nucleon collisions, the photoproduction of J/ψ mesons on nuclei is considered at energies close to the threshold for their production on a nucleon. The absorption of final J/ψ mesons, their formation length, and the binding and Fermi motion of target nucleons are taken into account in this model along with the effect of the nuclear potential on these processes. The A dependences of the absolute and relative charmonium yields are calculated together with absolute and relative excitationmore » functions under various assumptions on the magnitude of the cross section for J/ψN absorption, the J/ψ-meson formation length, and their inmedium modification. It is shown that, at energies above the threshold, these features are virtually independent of the formation length and the change in the J/ψ-meson mass in nuclear matter but are rather highly sensitive to the cross section for J/ψN interaction. The calculations performed in the present study can be used to determine the unknown cross section for J/ψ-meson absorption in nuclei from a comparison of their results with data expected from experiments in the Hall C of the CEBAF (USA) facility upgraded to the energy of 12 GeV. It is also shown that the absolute and relative excitation functions for J/ψ mesons in photon–nucleus reactions at subthreshold energies are sensitive to the change in the meson mass and, hence, carry information about the properties of charmonium in nuclear matter.« less

Compact Stars with Sequential QCD Phase Transitions.

PubMed

Alford, Mark; Sedrakian, Armen

2017-10-20

Compact stars may contain quark matter in their interiors at densities exceeding several times the nuclear saturation density. We explore models of such compact stars where there are two first-order phase transitions: the first from nuclear matter to a quark-matter phase, followed at a higher density by another first-order transition to a different quark-matter phase [e.g., from the two-flavor color-superconducting (2SC) to the color-flavor-locked (CFL) phase]. We show that this can give rise to two separate branches of hybrid stars, separated from each other and from the nuclear branch by instability regions, and, therefore, to a new family of compact stars, denser than the ordinary hybrid stars. In a range of parameters, one may obtain twin hybrid stars (hybrid stars with the same masses but different radii) and even triplets where three stars, with inner cores of nuclear matter, 2SC matter, and CFL matter, respectively, all have the same mass but different radii.

Insight on AV-45 binding in white and grey matter from histogram analysis: a study on early Alzheimer's disease patients and healthy subjects

PubMed Central

Nemmi, Federico; Saint-Aubert, Laure; Adel, Djilali; Salabert, Anne-Sophie; Pariente, Jérémie; Barbeau, Emmanuel; Payoux, Pierre; Péran, Patrice

2014-01-01

Purpose AV-45 amyloid biomarker is known to show uptake in white matter in patients with Alzheimer’s disease (AD) but also in healthy population. This binding; thought to be of a non-specific lipophilic nature has not yet been investigated. The aim of this study was to determine the differential pattern of AV-45 binding in healthy and pathological populations in white matter. Methods We recruited 24 patients presenting with AD at early stage and 17 matched, healthy subjects. We used an optimized PET-MRI registration method and an approach based on intensity histogram using several indexes. We compared the results of the intensity histogram analyses with a more canonical approach based on target-to-cerebellum Standard Uptake Value (SUVr) in white and grey matters using MANOVA and discriminant analyses. A cluster analysis on white and grey matter histograms was also performed. Results White matter histogram analysis revealed significant differences between AD and healthy subjects, which were not revealed by SUVr analysis. However, white matter histograms was not decisive to discriminate groups, and indexes based on grey matter only showed better discriminative power than SUVr. The cluster analysis divided our sample in two clusters, showing different uptakes in grey but also in white matter. Conclusion These results demonstrate that AV-45 binding in white matter conveys subtle information not detectable using SUVr approach. Although it is not better than standard SUVr to discriminate AD patients from healthy subjects, this information could reveal white matter modifications. PMID:24573658

Nuclear cartography: patterns in binding energies and subatomic structure

NASA Astrophysics Data System (ADS)

Simpson, E. C.; Shelley, M.

2017-11-01

Nuclear masses and binding energies are some of the first nuclear properties met in high school physics, and can be used to introduce radioactive decays, fusion, and fission. With relatively little extension, they can also illustrate fundamental concepts in nuclear physics, such as shell structure and pairing, and to discuss how the elements around us were formed in stars. One way of visualising these nuclear properties is through the nuclide chart, which maps all nuclides as a function of their proton and neutron numbers. Here we use the nuclide chart to illustrate various aspects of nuclear physics, and present 3D visualisations of it produced as part of the binding blocks project.

Nuclear Cartography: Patterns in Binding Energies and Subatomic Structure

ERIC Educational Resources Information Center

Simpson, E. C.; Shelley, M.

2017-01-01

Nuclear masses and binding energies are some of the first nuclear properties met in high school physics, and can be used to introduce radioactive decays, fusion, and fission. With relatively little extension, they can also illustrate fundamental concepts in nuclear physics, such as shell structure and pairing, and to discuss how the elements…

Ground-state properties of neutron-rich Mg isotopes

NASA Astrophysics Data System (ADS)

Watanabe, S.; Minomo, K.; Shimada, M.; Tagami, S.; Kimura, M.; Takechi, M.; Fukuda, M.; Nishimura, D.; Suzuki, T.; Matsumoto, T.; Shimizu, Y. R.; Yahiro, M.

2014-04-01

We analyze recently measured total reaction cross sections for 24-38Mg isotopes incident on 12C targets at 240 MeV/nucleon by using the folding model and antisymmetrized molecular dynamics (AMD). The folding model well reproduces the measured reaction cross sections, when the projectile densities are evaluated by the deformed Woods-Saxon (def-WS) model with AMD deformation. Matter radii of 24-38Mg are then deduced from the measured reaction cross sections by fine tuning the parameters of the def-WS model. The deduced matter radii are largely enhanced by nuclear deformation. Fully microscopic AMD calculations with no free parameter well reproduce the deduced matter radii for 24-36Mg, but still considerably underestimate them for 37,38Mg. The large matter radii suggest that 37,38Mg are candidates for deformed halo nucleus. AMD also reproduces other existing measured ground-state properties (spin parity, total binding energy, and one-neutron separation energy) of Mg isotopes. Neutron-number (N) dependence of deformation parameter is predicted by AMD. Large deformation is seen from 31Mg with N =19 to a drip-line nucleus 40Mg with N =28, indicating that both the N =20 and 28 magicities disappear. N dependence of neutron skin thickness is also predicted by AMD.

Crystal structure of importin-α3 bound to the nuclear localization signal of Ran-binding protein 3.

PubMed

Koyama, Masako; Matsuura, Yoshiyuki

2017-09-23

Ran-binding protein 3 (RanBP3) is a primarily nuclear Ran-binding protein that functions as an accessory factor in the Ran GTPase system. RanBP3 associates with Ran-specific nucleotide exchange factor RCC1 and enhances its catalytic activity towards Ran. RanBP3 also promotes CRM1-mediated nuclear export as well as CRM1-independent nuclear export of β-catenin, Smad2, and Smad3. Nuclear import of RanBP3 is dependent on the nuclear import adaptor protein importin-α and, RanBP3 is imported more efficiently by importin-α3 than by other members of the importin-α family. Protein kinase signaling pathways control nucleocytoplasmic transport through phosphorylation of RanBP3 at Ser58, immediately C-terminal to the nuclear localization signal (NLS) in the N-terminal region of RanBP3. Here we report the crystal structure of human importin-α3 bound to an N-terminal fragment of human RanBP3 containing the NLS sequence that is necessary and sufficient for nuclear import. The structure reveals that RanBP3 binds to importin-α3 residues that are strictly conserved in all seven isoforms of human importin-α at the major NLS-binding site, indicating that the region of importin-α outside the NLS-binding site, possibly the autoinhibotory importin-β1-binding domain, may be the key determinant for the preferential binding of RanBP3 to importin-α3. Computational docking simulation indicates that phosphorylation of RanBP3 at Ser58 could potentially stabilize the association of RanBP3 with importin-α through interactions between the phosphate moiety of phospho-Ser58 of RanBP3 and a cluster of basic residues (Arg96 and Lys97 in importin-α3) on armadillo repeat 1 of importin-α. Copyright © 2017 Elsevier Inc. All rights reserved.

Recent advances in the detection of specific natural organic compounds as carriers for radionuclides in soil and water environments, with examples of radioiodine and plutonium

DOE PAGES

Santschi, P. H.; Xu, C.; Zhang, S.; ...

2017-03-09

Among the key environmental factors influencing the fate and transport of radionuclides in the environment is natural organic matter (NOM). While this has been known for decades, there still remains great uncertainty in predicting NOM-radionuclide interactions because of lack of understanding of radionuclide interactions with the specific organic moieties within NOM. Furthermore, radionuclide-NOM studies conducted using modelled organic compounds or elevated radionuclide concentrations provide compromised information related to true environmental conditions. Thus, sensitive techniques are required not only for the detection of radionuclides, and their different species, at ambient and/or far-field concentrations, but also for potential trace organic compounds thatmore » are chemically binding these radionuclides. GC-MS and AMS techniques developed in our lab are reviewed in this paper that aim to assess how two radionuclides, iodine and plutonium, form strong bonds with NOM by entirely different mechanisms; iodine tends to bind to aromatic functionalities, whereas plutonium binds to N-containing hydroxamate siderophores at ambient concentrations. While low-level measurements are a prerequisite for assessing iodine and plutonium migration at nuclear waste sites and as environmental tracers, it is necessary to determine their in-situ speciation, which ultimately controls their mobility and transport in natural environments. Finally and more importantly, advanced molecular-level instrumentation (e.g., nuclear magnetic resonance (NMR) and Fourier-transform ion cyclotron resonance coupled with electrospray ionization (ESI-FTICRMS) were applied to resolve either directly or indirectly the molecular environments in which the radionuclides are associated with the NOM.« less

Recent advances in the detection of specific natural organic compounds as carriers for radionuclides in soil and water environments, with examples of radioiodine and plutonium

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

Santschi, P. H.; Xu, C.; Zhang, S.

Among the key environmental factors influencing the fate and transport of radionuclides in the environment is natural organic matter (NOM). While this has been known for decades, there still remains great uncertainty in predicting NOM-radionuclide interactions because of lack of understanding of radionuclide interactions with the specific organic moieties within NOM. Furthermore, radionuclide-NOM studies conducted using modelled organic compounds or elevated radionuclide concentrations provide compromised information related to true environmental conditions. Thus, sensitive techniques are required not only for the detection of radionuclides, and their different species, at ambient and/or far-field concentrations, but also for potential trace organic compounds thatmore » are chemically binding these radionuclides. GC-MS and AMS techniques developed in our lab are reviewed in this paper that aim to assess how two radionuclides, iodine and plutonium, form strong bonds with NOM by entirely different mechanisms; iodine tends to bind to aromatic functionalities, whereas plutonium binds to N-containing hydroxamate siderophores at ambient concentrations. While low-level measurements are a prerequisite for assessing iodine and plutonium migration at nuclear waste sites and as environmental tracers, it is necessary to determine their in-situ speciation, which ultimately controls their mobility and transport in natural environments. Finally and more importantly, advanced molecular-level instrumentation (e.g., nuclear magnetic resonance (NMR) and Fourier-transform ion cyclotron resonance coupled with electrospray ionization (ESI-FTICRMS) were applied to resolve either directly or indirectly the molecular environments in which the radionuclides are associated with the NOM.« less

76 FR 77023 - In the Matter of Florida Power Corporation, et al., Crystal River Unit 3 Nuclear Generating Plant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

... the Nuclear Regulatory Commission (NRC, the Commission) consent to the proposed indirect transfer of... transfer action, FPC shall inform the Director of the Office of Nuclear Reactor Regulation in writing of... NUCLEAR REGULATORY COMMISSION [NRC-2011-0281; License No. DPR-72; Docket No. 50-302] In the Matter...

Interpretation of the Raji cell assay in sera containing anti-nuclear antibodies and immune complexes.

PubMed Central

Horsfall, A C; Venables, P J; Mumford, P A; Maini, R N

1981-01-01

The Raji cell assay is regarded as a test for the detection and quantitation of immune complexes. It is frequently positive in sera from patients with SLE. We have demonstrated a relationship between Raji cell binding and antibodies to DNA and soluble cellular antigens. In five sera containing high titres of antibodies of known single specificity, most of the Raji cell binding occurred in the 7S IgG fraction where the majority of anti-nuclear antibody was also found. When each of these sera was incubated with its specific antigen, Raji cell binding increased. Subsequent fractionation showed that this binding was in the high molecular weight fraction (greater than 200,000 daltons) and that Raji cell binding and antibody activity were abolished in the 7S fraction. These data confirm that Raji cell bind immune complexes but also indicate that 7S anti-nuclear antibodies may interact directly with Raji cells by an unknown mechanism. Therefore, in sera of patients with anti-nuclear antibodies, binding to Raji cells does not necessarily imply the presence of immune complexes alone. PMID:6975676

Equation of state of dense nuclear matter and neutron star structure from nuclear chiral interactions

NASA Astrophysics Data System (ADS)

Bombaci, Ignazio; Logoteta, Domenico

2018-02-01

Aims: We report a new microscopic equation of state (EOS) of dense symmetric nuclear matter, pure neutron matter, and asymmetric and β-stable nuclear matter at zero temperature using recent realistic two-body and three-body nuclear interactions derived in the framework of chiral perturbation theory (ChPT) and including the Δ(1232) isobar intermediate state. This EOS is provided in tabular form and in parametrized form ready for use in numerical general relativity simulations of binary neutron star merging. Here we use our new EOS for β-stable nuclear matter to compute various structural properties of non-rotating neutron stars. Methods: The EOS is derived using the Brueckner-Bethe-Goldstone quantum many-body theory in the Brueckner-Hartree-Fock approximation. Neutron star properties are next computed solving numerically the Tolman-Oppenheimer-Volkov structure equations. Results: Our EOS models are able to reproduce the empirical saturation point of symmetric nuclear matter, the symmetry energy Esym, and its slope parameter L at the empirical saturation density n0. In addition, our EOS models are compatible with experimental data from collisions between heavy nuclei at energies ranging from a few tens of MeV up to several hundreds of MeV per nucleon. These experiments provide a selective test for constraining the nuclear EOS up to 4n0. Our EOS models are consistent with present measured neutron star masses and particularly with the mass M = 2.01 ± 0.04 M⊙ of the neutron stars in PSR J0348+0432.

Unmatter Plasma revisited

NASA Astrophysics Data System (ADS)

Smarandache, Florentin

2017-10-01

Unmmatter Plasma is a novel form of plasma, exclusively made of matter and its antimatter counterpart. The electron-positron beam plasma was generated in the laboratory in the beginning of 2015. This experimental fact shows that unmatter, a new form of matter that is formed by matter and antimatter bind together (mathematically predicted since 2004) really exists. That is the electron-positron plasma experiment of 2015 is the experimentum crucis verifying the mathematically predicted unmatter. Unmatter is formed by combinations of matter and antimatter that bind together, or by long-range mixture of matter and antimatter forming a weakly-coupled phase. Binding and bound state means that the interaction is sufficiently strong to tie together the particles of a system, therefore hindering them from becoming free. For example, a usual liquid is a bound state of molecules, while a gas is an un-bounded where the molecules can move freely in successive collisions.

Nuclear equation of state for core-collapse supernova simulations with realistic nuclear forces

NASA Astrophysics Data System (ADS)

Togashi, H.; Nakazato, K.; Takehara, Y.; Yamamuro, S.; Suzuki, H.; Takano, M.

2017-05-01

A new table of the nuclear equation of state (EOS) based on realistic nuclear potentials is constructed for core-collapse supernova numerical simulations. Adopting the EOS of uniform nuclear matter constructed by two of the present authors with the cluster variational method starting from the Argonne v18 and Urbana IX nuclear potentials, the Thomas-Fermi calculation is performed to obtain the minimized free energy of a Wigner-Seitz cell in non-uniform nuclear matter. As a preparation for the Thomas-Fermi calculation, the EOS of uniform nuclear matter is modified so as to remove the effects of deuteron cluster formation in uniform matter at low densities. Mixing of alpha particles is also taken into account following the procedure used by Shen et al. (1998, 2011). The critical densities with respect to the phase transition from non-uniform to uniform phase with the present EOS are slightly higher than those with the Shen EOS at small proton fractions. The critical temperature with respect to the liquid-gas phase transition decreases with the proton fraction in a more gradual manner than in the Shen EOS. Furthermore, the mass and proton numbers of nuclides appearing in non-uniform nuclear matter with small proton fractions are larger than those of the Shen EOS. These results are consequences of the fact that the density derivative coefficient of the symmetry energy of our EOS is smaller than that of the Shen EOS.

Rydberg phases of Hydrogen and low energy nuclear reactions

NASA Astrophysics Data System (ADS)

Olafsson, Sveinn; Holmlid, Leif

2016-03-01

For over the last 26 years the science of cold fusion/LENR has been researched around the world with slow pace of progress. Modest quantity of excess heat and signatures of nuclear transmutation and helium production have been confirmed in experiments and theoretical work has only resulted in a large flora of inadequate theoretical scenarios. Here we review current state of research in Rydberg matter of Hydrogen that is showing strong signature of nuclear processes. In the presentation experimental behavior of Rydberg matter of hydrogen is described. An extensive collaboration effort of surface physics, catalysis, atomic physics, solid state physics, nuclear physics and quantum information is need to tackle the surprising experimental results that have so far been obtained. Rydberg matter of Hydrogen is the only known state of matter that is able to bring huge collection of protons to so short distances and for so long time that tunneling becomes a reasonable process for making low energy nuclear reactions. Nuclear quantum entanglement can also become realistic process at theses conditions.

Retinoblastoma-binding Protein 4-regulated Classical Nuclear Transport Is Involved in Cellular Senescence*

PubMed Central

Tsujii, Akira; Miyamoto, Yoichi; Moriyama, Tetsuji; Tsuchiya, Yuko; Obuse, Chikashi; Mizuguchi, Kenji; Oka, Masahiro; Yoneda, Yoshihiro

2015-01-01

Nucleocytoplasmic trafficking is a fundamental cellular process in eukaryotic cells. Here, we demonstrated that retinoblastoma-binding protein 4 (RBBP4) functions as a novel regulatory factor to increase the efficiency of importin α/β-mediated nuclear import. RBBP4 accelerates the release of importin β1 from importin α via competitive binding to the importin β-binding domain of importin α in the presence of RanGTP. Therefore, it facilitates importin α/β-mediated nuclear import. We showed that the importin α/β pathway is down-regulated in replicative senescent cells, concomitant with a decrease in RBBP4 level. Knockdown of RBBP4 caused both suppression of nuclear transport and induction of cellular senescence. This is the first report to identify a factor that competes with importin β1 to bind to importin α, and it demonstrates that the loss of this factor can trigger cellular senescence. PMID:26491019

75 FR 74750 - In the Matter of Toshiba America Nuclear Energy Corporation and All Other Persons Who Seek or...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-01

... NUCLEAR REGULATORY COMMISSION [EA-10-152; Project No. 52-0001; NRC-2010-0368] In the Matter of Toshiba America Nuclear Energy Corporation and All Other Persons Who Seek or Obtain Access to Safeguards... protect SGI (73 FR 63546). The NRC is issuing this Order to Toshiba America Nuclear Energy Corporation...

Binding blocks: building the Universe one nucleus at a time

NASA Astrophysics Data System (ADS)

Diget, C. Aa; Pastore, A.; Leech, K.; Haylett, T.; Lock, S.; Sanders, T.; Shelley, M.; Willett, H. V.; Keegans, J.; Sinclair, L.; Simpson, E. C.; Binding Blocks Collaboration

2017-03-01

We present a new teaching and outreach activity based around the construction of a three-dimensional chart of isotopes using \\text{LEG}{{\\text{O}}\\circledR} bricks5. The activity, binding blocks, demonstrates nuclear and astrophysical processes through a seven-meter chart of all nuclear isotopes, built from over 26 000 \\text{LEG}{{\\text{O}}\\circledR} bricks. It integrates A-Level and GCSE curricula across areas of nuclear physics, astrophysics, and chemistry, including: nuclear decays (through the colours in the chart); nuclear binding energy (through tower heights); production of chemical elements in the cosmos; fusion processes in stars and fusion energy on Earth; as well as links to medical physics, particularly diagnostics and radiotherapy.

Many-particle theory of nuclear system with application to neutron-star matter and other systems

NASA Technical Reports Server (NTRS)

Yang, C. H.

1978-01-01

General problems in nuclear-many-body theory were considered. Superfluid states of neutron star matter and other strongly interacting many-fermion systems were analyzed by using the soft-core potential of Reid. The pion condensation in neutron star matter was also treated.

Automodification of PARP-1 mediates its tight binding to the nuclear matrix

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

Zaalishvili, Giorgi, E-mail: giozaal@gmail.com; Margiani, Dina; Kutalia, Ketevan

2010-02-26

Poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme that catalyzes the NAD{sup +}-dependent addition of ADP-ribose polymers on a variety of nuclear proteins, has been shown to be associated with the nuclear matrix. As yet, the properties and conditions of this association are unclear. Here, we show the existence of two PARP-1 pools associated with the nuclear matrix of rat liver and the ability of PARP-1 automodification to facilitate its binding to the nuclear matrix.

Atomic Mass and Nuclear Binding Energy for I-131 (Iodine)

NASA Astrophysics Data System (ADS)

Sukhoruchkin, S. I.; Soroko, Z. N.

This document is part of the Supplement containing the complete sets of data of Subvolume A `Nuclei with Z = 1 - 54' of Volume 22 `Nuclear Binding Energies and Atomic Masses' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms'. It provides atomic mass, mass excess, nuclear binding energy, nucleon separation energies, Q-values, and nucleon residual interaction parameters for atomic nuclei of the isotope I-131 (Iodine, atomic number Z = 53, mass number A = 131).

Atomic Mass and Nuclear Binding Energy for F-22 (Fluorine)

NASA Astrophysics Data System (ADS)

Sukhoruchkin, S. I.; Soroko, Z. N.

This document is part of the Supplement containing the complete sets of data of Subvolume A `Nuclei with Z = 1 - 54' of Volume 22 `Nuclear Binding Energies and Atomic Masses' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms'. It provides atomic mass, mass excess, nuclear binding energy, nucleon separation energies, Q-values, and nucleon residual interaction parameters for atomic nuclei of the isotope F-22 (Fluorine, atomic number Z = 9, mass number A = 22).

Quark matter droplets in neutron stars

NASA Technical Reports Server (NTRS)

Heiselberg, H.; Pethick, C. J.; Staubo, E. F.

1993-01-01

We show that, for physically reasonable bulk and surface properties, the lowest energy state of dense matter consists of quark matter coexisting with nuclear matter in the presence of an essentially uniform background of electrons. We estimate the size and nature of spatial structure in this phase, and show that at the lowest densities the quark matter forms droplets embedded in nuclear matter, whereas at higher densities it can exhibit a variety of different topologies. A finite fraction of the interior of neutron stars could consist of matter in this new phase, which would provide new mechanisms for glitches and cooling.

Separation of β-amyloid binding and white matter uptake of 18F-flutemetamol using spectral analysis

PubMed Central

Heurling, Kerstin; Buckley, Christopher; Vandenberghe, Rik; Laere, Koen Van; Lubberink, Mark

2015-01-01

The kinetic components of the β-amyloid ligand 18F-flutemetamol binding in grey and white matter were investigated through spectral analysis, and a method developed for creation of parametric images separating grey and white matter uptake. Tracer uptake in grey and white matter and cerebellar cortex was analyzed through spectral analysis in six subjects, with (n=4) or without (n=2) apparent β-amyloid deposition, having undergone dynamic 18F-flutemetamol scanning with arterial blood sampling. The spectra were divided into three components: slow, intermediate and fast basis function rates. The contribution of each of the components to total volume of distribution (VT) was assessed for different tissue types. The slow component dominated in white matter (average 90%), had a higher contribution to grey matter VT in subjects with β-amyloid deposition (average 44%) than without (average 6%) and was absent in cerebellar cortex, attributing the slow component of 18F-flutemetamol uptake in grey matter to β-amyloid binding. Parametric images of voxel-based spectral analysis were created for VT, the slow component and images segmented based on the slow component contribution; confirming that grey matter and white matter uptake can be discriminated on voxel-level using a threshold for the contribution from the slow component to VT. PMID:26550542

The limits of the nuclear landscape explored by the relativistic continuum Hartree–Bogoliubov theory

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

Xia, X. W.; Lim, Y.; Zhao, P. W.

The ground-state properties of nuclei with 8more » $$\\leqslant$$ Z $$\\leqslant$$ 120 from the proton drip line to the neutron drip line have been investigated using the relativistic continuum Hartree-Bogoliubov (RCHB) theory with the relativistic density functional PC-PK1. With the effects of the continuum included, there are totally 9035 nuclei predicted to be bound, which largely extends the existing nuclear landscapes predicted with other methods. The calculated binding energies, separation energies, neutron and proton Fermi surfaces, root-mean-square (rms) radii of neutron, proton, matter, and charge distributions, ground-state spins and parities are tabulated. The extension of the nuclear landscape obtained with RCHB is discussed in detail, in particular for the neutron-rich side, in comparison with the relativistic mean field calculations without pairing correlations and also other predicted landscapes. Here, it is found that the coupling between the bound states and the continuum due to the pairing correlations plays an essential role in extending the nuclear landscape. The systematics of the separation energies, radii, densities, potentials and pairing energies of the RCHB calculations are also discussed. In addition, the α-decay energies and proton emitters based on the RCHB calculations are investigated.« less

The limits of the nuclear landscape explored by the relativistic continuum Hartree–Bogoliubov theory

DOE PAGES

Xia, X. W.; Lim, Y.; Zhao, P. W.; ...

2017-11-01

The ground-state properties of nuclei with 8more » $$\\leqslant$$ Z $$\\leqslant$$ 120 from the proton drip line to the neutron drip line have been investigated using the relativistic continuum Hartree-Bogoliubov (RCHB) theory with the relativistic density functional PC-PK1. With the effects of the continuum included, there are totally 9035 nuclei predicted to be bound, which largely extends the existing nuclear landscapes predicted with other methods. The calculated binding energies, separation energies, neutron and proton Fermi surfaces, root-mean-square (rms) radii of neutron, proton, matter, and charge distributions, ground-state spins and parities are tabulated. The extension of the nuclear landscape obtained with RCHB is discussed in detail, in particular for the neutron-rich side, in comparison with the relativistic mean field calculations without pairing correlations and also other predicted landscapes. Here, it is found that the coupling between the bound states and the continuum due to the pairing correlations plays an essential role in extending the nuclear landscape. The systematics of the separation energies, radii, densities, potentials and pairing energies of the RCHB calculations are also discussed. In addition, the α-decay energies and proton emitters based on the RCHB calculations are investigated.« less

MNDA binds NPM/B23 and the NPM-MLF1 chimera generated by the t(3;5) associated with myelodysplastic syndrome and acute myeloid leukemia.

PubMed

Xie, J; Briggs, J A; Morris, S W; Olson, M O; Kinney, M C; Briggs, R C

1997-10-01

The myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed specifically in developing cells of the human myelomonocytic lineage, including the end-stage monocytes/macrophages and granulocytes. Nuclear localization, lineage- and stage-specific expression, association with chromatin, and regulation by interferon alpha indicate that this protein is involved in regulating gene expression uniquely associated with the differentiation process and/or function of the monocyte/macrophage. MNDA does not bind specific DNA sequences, but rather a set of nuclear proteins that includes nucleolin (C23). Both in vitro binding assays and co-immunoprecipitation were used to demonstrate that MNDA also binds protein B23 (nucleophosmin/NPM). Three reciprocal chromosome translocations found in certain cases of leukemia/lymphoma involve fusions with the NPM/B23 gene, t(5;17) NPM-RARalpha, t(2;5) NPM-ALK, and the t(3;5) NPM-MLF1. In the current study, MNDA was not able to bind the NPM-ALK chimera originating from the t(2;5) and containing residues 1-117 of NPM. However, MNDA did bind the NPM-MLF1 product of the t(3;5) that contains the N-terminal 175 residues of NPM. The additional 58 amino acids (amino acids 117-175) of the NPM sequence that are contained in the product of the NPM-MLF1 fusion gene relative to the product of the NPM-ALK fusion appear responsible for MNDA binding. This additional NPM sequence contains a nuclear localization signal and clusters of acidic residues believed to bind nuclear localization signals of other proteins. Whereas NPM and nucleolin are primarily localized within the nucleolus, MNDA is distributed throughout the nucleus including the nucleolus, suggesting that additional interactions define overall MNDA localization.

Protein Cofactors Are Essential for High-Affinity DNA Binding by the Nuclear Factor κB RelA Subunit.

PubMed

Mulero, Maria Carmen; Shahabi, Shandy; Ko, Myung Soo; Schiffer, Jamie M; Huang, De-Bin; Wang, Vivien Ya-Fan; Amaro, Rommie E; Huxford, Tom; Ghosh, Gourisankar

2018-05-22

Transcription activator proteins typically contain two functional domains: a DNA binding domain (DBD) that binds to DNA with sequence specificity and an activation domain (AD) whose established function is to recruit RNA polymerase. In this report, we show that purified recombinant nuclear factor κB (NF-κB) RelA dimers bind specific κB DNA sites with an affinity significantly lower than that of the same dimers from nuclear extracts of activated cells, suggesting that additional nuclear cofactors might facilitate DNA binding by the RelA dimers. Additionally, recombinant RelA binds DNA with relatively low affinity at a physiological salt concentration in vitro. The addition of p53 or RPS3 (ribosomal protein S3) increases RelA:DNA binding affinity 2- to >50-fold depending on the protein and ionic conditions. These cofactor proteins do not form stable ternary complexes, suggesting that they stabilize the RelA:DNA complex through dynamic interactions. Surprisingly, the RelA-DBD alone fails to bind DNA under the same solution conditions even in the presence of cofactors, suggesting an important role of the RelA-AD in DNA binding. Reduced RelA:DNA binding at a physiological ionic strength suggests that multiple cofactors might be acting simultaneously to mitigate the electrolyte effect and stabilize the RelA:DNA complex in vivo. Overall, our observations suggest that the RelA-AD and multiple cofactor proteins function cooperatively to prime the RelA-DBD and stabilize the RelA:DNA complex in cells. Our study provides a mechanism for nuclear cofactor proteins in NF-κB-dependent gene regulation.

Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding

PubMed Central

Vuković, Lidija D.; Jevtić, Predrag; Zhang, Zhaojie; Stohr, Bradley A.; Levy, Daniel L.

2016-01-01

ABSTRACT Altered nuclear size is associated with many cancers, and determining whether cancer-associated changes in nuclear size contribute to carcinogenesis necessitates an understanding of mechanisms of nuclear size regulation. Although nuclear import rates generally positively correlate with nuclear size, NTF2 levels negatively affect nuclear size, despite the role of NTF2 (also known as NUTF2) in nuclear recycling of the import factor Ran. We show that binding of Ran to NTF2 is required for NTF2 to inhibit nuclear expansion and import of large cargo molecules in Xenopus laevis egg and embryo extracts, consistent with our observation that NTF2 reduces the diameter of the nuclear pore complex (NPC) in a Ran-binding-dependent manner. Furthermore, we demonstrate that ectopic NTF2 expression in Xenopus embryos and mammalian tissue culture cells alters nuclear size. Finally, we show that increases in nuclear size during melanoma progression correlate with reduced NTF2 expression, and increasing NTF2 levels in melanoma cells is sufficient to reduce nuclear size. These results show a conserved capacity for NTF2 to impact on nuclear size, and we propose that NTF2 might be a new cancer biomarker. PMID:26823604

IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs

PubMed Central

Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L

2017-01-01

Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation. PMID:28990926

IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.

PubMed

Zhou, Hao; Bulek, Katarzyna; Li, Xiao; Herjan, Tomasz; Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L; Li, Xiaoxia

2017-10-09

Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation.

Myosin-1C uses a novel phosphoinositide-dependent pathway for nuclear localization.

PubMed

Nevzorov, Ilja; Sidorenko, Ekaterina; Wang, Weihuan; Zhao, Hongxia; Vartiainen, Maria K

2018-02-01

Accurate control of macromolecule transport between nucleus and cytoplasm underlines several essential biological processes, including gene expression. According to the canonical model, nuclear import of soluble proteins is based on nuclear localization signals and transport factors. We challenge this view by showing that nuclear localization of the actin-dependent motor protein Myosin-1C (Myo1C) resembles the diffusion-retention mechanism utilized by inner nuclear membrane proteins. We show that Myo1C constantly shuttles in and out of the nucleus and that its nuclear localization does not require soluble factors, but is dependent on phosphoinositide binding. Nuclear import of Myo1C is preceded by its interaction with the endoplasmic reticulum, and phosphoinositide binding is specifically required for nuclear import, but not nuclear retention, of Myo1C. Our results therefore demonstrate, for the first time, that membrane association and binding to nuclear partners is sufficient to drive nuclear localization of also soluble proteins, opening new perspectives to evolution of cellular protein sorting mechanisms. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

77 FR 11168 - In the Matter of Exelon Corporation; Constellation Energy Group, Inc.; Nine Mile Nuclear Station...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0193; Docket Nos. 50-220 and 50-410; License Nos. DPR-63 and NPF-69] In the Matter of Exelon Corporation; Constellation Energy Group, Inc.; Nine Mile Nuclear Station, LLC; Nine Mile Point Nuclear Station, Units 1 and 2; Order Approving Application Regarding Proposed Corporate Merger and Indirect Transfer o...

77 FR 11169 - In the Matter of Exelon Corporation; Constellation Energy Group, Inc.; R.E. Ginna Nuclear Power...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0192; Docket Nos. 50-244 and 72-67; License No. DPR-18; Docket No. 72-67; General License] In the Matter of Exelon Corporation; Constellation Energy Group, Inc.; R.E. Ginna Nuclear Power Plant, LLC; R.E. Ginna Nuclear Power Plant; R.E. Ginna Independent Spent Fuel Storage Installation; Order Approving...

78 FR 28245 - In the Matter of Southern Nuclear Operating Company, Farley Nuclear Plant, Units 1 and 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-14

... recent public examples, including those documented in EA-12-240 and EA-12-230, and the impacts when there... and EA-12-230, and the impacts when there is a loss of integrity and trustworthiness. f. By the later...-8; EA-12-145] In the Matter of Southern Nuclear Operating Company, Farley Nuclear Plant, Units 1 and...

Agricultural aspects of radiocontamination induced by the Fukushima nuclear accident — A survey of studies by the Univ. of Tokyo Agricultural Dept. (2011–2016)

PubMed Central

NAKANISHI, Tomoko M.

2018-01-01

Immediately after the Fukushima nuclear power plant accident, a team of 40–50 researchers at the Graduate School of Agricultural and Life Sciences at the University of Tokyo began to analyze the behavior of radioactive materials in the fallout regions. The fallout has remained in situ and become strongly adsorbed within the soil over time. 137Cs was found to bind strongly to the fine clay, weathered biotite, and organic matter in the soil; therefore, it has not mobilized from mountainous regions, even after heavy rainfall. In farmland, the quantity of 137Cs in the soil absorbed by crop plants was small. The downward migration of 137Cs in soil is now estimated at 1–2 mm/year. The intake of 137Cs by trees occurred through the bark and not from the roots. This report summarizes the findings of research across a wide variety of agricultural specialties. PMID:29321444

Agricultural aspects of radiocontamination induced by the Fukushima nuclear accident - A survey of studies by the Univ. of Tokyo Agricultural Dept. (2011-2016).

PubMed

Nakanishi, Tomoko M

2018-01-01

Immediately after the Fukushima nuclear power plant accident, a team of 40-50 researchers at the Graduate School of Agricultural and Life Sciences at the University of Tokyo began to analyze the behavior of radioactive materials in the fallout regions. The fallout has remained in situ and become strongly adsorbed within the soil over time. 137 Cs was found to bind strongly to the fine clay, weathered biotite, and organic matter in the soil; therefore, it has not mobilized from mountainous regions, even after heavy rainfall. In farmland, the quantity of 137 Cs in the soil absorbed by crop plants was small. The downward migration of 137 Cs in soil is now estimated at 1-2 mm/year. The intake of 137 Cs by trees occurred through the bark and not from the roots. This report summarizes the findings of research across a wide variety of agricultural specialties.

Basic Equations Interrelate Atomic and Nuclear Properties to Patterns at the Size Scales of the Cosmos, Extended Clusters of Galaxies, Galaxies, and Nebulae

NASA Astrophysics Data System (ADS)

Allen, Rob

2016-09-01

Structures within molecules and nuclei have relationships to astronomical patterns. The COBE cosmic scale plots, and large scale surveys of galaxy clusters have patterns also repeating and well known at atomic scales. The Induction, Strong Force, and Nuclear Binding Energy Periods within the Big Bang are revealed to have played roles in the formation of these large scale distributions. Equations related to the enormous patterns also model chemical bonds and likely nucleus and nucleon substructures. ratios of the forces that include gravity are accurately calculated from the distributions and shapes. In addition, particle masses and a great many physical constants can be derived with precision and accuracy from astrophysical shapes. A few very basic numbers can do modelling from nucleon internals to molecules to super novae, and up to the Visible Universe. Equations are also provided along with possible structural configurations for some Cold Dark Matter and Dark Energy.

Quark Matter and Nuclear Collisions a Brief History of Strong Interaction Thermodynamics

NASA Astrophysics Data System (ADS)

Satz, Helmut

2012-08-01

The past 50 years have seen the emergence of a new field of research in physics, the study of matter at extreme temperatures and densities. The theory of strong interactions, quantum chromodynamics (QCD), predicts that in this limit, matter will become a plasma of deconfined quarks and gluons — the medium which made up the early universe in the first 10 microseconds after the Big Bang. High energy nuclear collisions are expected to produce short-lived bubbles of such a medium in the laboratory. I survey the merger of statistical QCD and nuclear collision studies for the analysis of strongly interacting matter in theory and experiment.

Photons in dense nuclear matter: Random-phase approximation

NASA Astrophysics Data System (ADS)

Stetina, Stephan; Rrapaj, Ermal; Reddy, Sanjay

2018-04-01

We present a comprehensive and pedagogic discussion of the properties of photons in cold and dense nuclear matter based on the resummed one-loop photon self-energy. Correlations among electrons, muons, protons, and neutrons in β equilibrium that arise as a result of electromagnetic and strong interactions are consistently taken into account within the random phase approximation. Screening effects, damping, and collective excitations are systematically studied in a fully relativistic setup. Our study is relevant to the linear response theory of dense nuclear matter, calculations of transport properties of cold dense matter, and investigations of the production and propagation of hypothetical vector bosons such as the dark photons.

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

Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

We have previously discovered and characterized the nuclear import pathways for the E7 oncoproteins of mucosal alpha genus HPVs, type 16 and 11. Here we investigated the nuclear import of cutaneous beta genus HPV8 E7 protein using confocal microscopy after transfections of HeLa cells with EGFP-8E7 and mutant plasmids and nuclear import assays in digitonin-permeabilized HeLa cells. We determined that HPV8 E7 contains a nuclear localization signal (NLS) within its zinc-binding domain that mediates its nuclear import. Furthermore, we discovered that a mostly hydrophobic patch {sub 65}LRLFV{sub 69} within the zinc-binding domain is essential for the nuclear import and localizationmore » of HPV8 E7 via hydrophobic interactions with the FG nucleoporins Nup62 and Nup153. Substitution of the hydrophobic residues within the {sub 65}LRLFV{sub 69} patch to alanines, and not R66A mutation, disrupt the interactions between the 8E7 zinc-binding domain and Nup62 and Nup153 and consequently inhibit nuclear import of HPV8 E7. - Highlights: • HPV8 E7 has a cNLS within its zinc-binding domain that mediates its nuclear import. • Discovery of a hydrophobic patch that is critical for the nuclear import of HPV8 E7. • HPV8 E7 nuclear import is mediated by hydrophobic interactions with FG-Nups, Nup62 and Nup153.« less

CONSTANTS FOR MERCURY BINDING BY DISSOLVED ORGANIC MATTER ISOLATES FROM THE FLORIDA EVERGLADES. (R827653)

EPA Science Inventory

Dissolved organic matter (DOM) has been implicated as an important complexing agent for Hg that can affect its mobility and bioavailability in aquatic ecosystems. However, binding constants for natural Hg-DOM complexes are not well known. We employed a competitive ligand appro...

Functional Activity of the Fanconi Anemia Protein FAA Requires FAC Binding and Nuclear Localization

PubMed Central

Näf, Dieter; Kupfer, Gary M.; Suliman, Ahmed; Lambert, Kathleen; D’Andrea, Alan D.

1998-01-01

Fanconi anemia (FA) is an autosomal recessive disease characterized by genomic instability, cancer susceptibility, and cellular hypersensitivity to DNA-cross-linking agents. Eight complementation groups of FA (FA-A through FA-H) have been identified. Two FA genes, corresponding to complementation groups FA-A and FA-C, have been cloned, but the functions of the encoded FAA and FAC proteins remain unknown. We have recently demonstrated that FAA and FAC interact to form a nuclear complex. In this study, we have analyzed a series of mutant forms of the FAA protein with respect to functional activity, FAC binding, and nuclear localization. Mutation or deletion of the amino-terminal nuclear localization signal (NLS) of FAA results in loss of functional activity, loss of FAC binding, and cytoplasmic retention of FAA. Replacement of the NLS sequence with a heterologous NLS sequence, derived from the simian virus 40 T antigen, results in nuclear localization but does not rescue functional activity or FAC binding. Nuclear localization of the FAA protein is therefore necessary but not sufficient for FAA function. Mutant forms of FAA which fail to bind to FAC also fail to promote the nuclear accumulation of FAC. In addition, wild-type FAC promotes the accumulation of wild-type FAA in the nucleus. Our results suggest that FAA and FAC perform a concerted function in the cell nucleus, required for the maintenance of chromosomal stability. PMID:9742112

Efficient and dynamic nuclear localization of green fluorescent protein via RNA binding

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

Kitamura, Akira; Nakayama, Yusaku; Kinjo, Masataka, E-mail: kinjo@sci.hokudai.ac.jp

2015-07-31

Classical nuclear localization signal (NLS) sequences have been used for artificial localization of green fluorescent protein (GFP) in the nucleus as a positioning marker or for measurement of the nuclear-cytoplasmic shuttling rate in living cells. However, the detailed mechanism of nuclear retention of GFP-NLS remains unclear. Here, we show that a candidate mechanism for the strong nuclear retention of GFP-NLS is via the RNA-binding ability of the NLS sequence. GFP tagged with a classical NLS derived from Simian virus 40 (GFP-NLS{sup SV40}) localized not only in the nucleoplasm, but also to the nucleolus, the nuclear subdomain in which ribosome biogenesismore » takes place. GFP-NLS{sup SV40} in the nucleolus was mobile, and intriguingly, the diffusion coefficient, which indicates the speed of diffusing molecules, was 1.5-fold slower than in the nucleoplasm. Fluorescence correlation spectroscopy (FCS) analysis showed that GFP-NLS{sup SV40} formed oligomers via RNA binding, the estimated molecular weight of which was larger than the limit for passive nuclear export into the cytoplasm. These findings suggest that the nuclear localization of GFP-NLS{sup SV40} likely results from oligomerization mediated via RNA binding. The analytical technique used here can be applied for elucidating the details of other nuclear localization mechanisms, including those of several types of nuclear proteins. In addition, GFP-NLS{sup SV40} can be used as an excellent marker for studying both the nucleoplasm and nucleolus in living cells. - Highlights: • Nuclear localization signal-tagged GFP (GFP-NLS) showed clear nuclear localization. • The GFP-NLS dynamically localized not only in the nucleoplasm, but also to the nucleolus. • The nuclear localization of GFP-NLS results from transient oligomerization mediated via RNA binding. • Our NLS-tagging procedure is ideal for use in artificial sequestration of proteins in the nucleus.« less

Structural Basis for Activation of Fatty Acid-binding Protein 4

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

Gillilan,R.; Ayers, S.; Noy, N.

2007-01-01

Fatty acid-binding protein 4 (FABP4) delivers ligands from the cytosol to the nuclear receptor PPAR{gamma} in the nucleus, thereby enhancing the transcriptional activity of the receptor. Notably, FABP4 binds multiple ligands with a similar affinity but its nuclear translocation is activated only by specific compounds. To gain insight into the structural features that underlie the ligand-specificity in activation of the nuclear import of FABP4, we solved the crystal structures of the protein complexed with two compounds that induce its nuclear translocation, and compared these to the apo-protein and to FABP4 structures bound to non-activating ligands. Examination of these structures indicatesmore » that activation coincides with closure of a portal loop phenylalanine side-chain, contraction of the binding pocket, a subtle shift in a helical domain containing the nuclear localization signal of the protein, and a resultant change in oligomeric state that exposes the nuclear localization signal to the solution. Comparisons of backbone displacements induced by activating ligands with a measure of mobility derived from translation, libration, screw (TLS) refinement, and with a composite of slowest normal modes of the apo state suggest that the helical motion associated with the activation of the protein is part of the repertoire of the equilibrium motions of the apo-protein, i.e. that ligand binding does not induce the activated configuration but serves to stabilize it. Nuclear import of FABP4 can thus be understood in terms of the pre-existing equilibrium hypothesis of ligand binding.« less

Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal

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

Nakada, Ryohei; Hirano, Hidemi; Structural Biology Research Center, Graduate School of Science, Nagoya University

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is expressed in every EBV-positive tumor and is essential for the maintenance, replication, and transcription of the EBV genome in the nucleus of host cells. EBNA1 is a serine phosphoprotein, and it has been shown that phosphorylation of S385 in the nuclear localization signal (NLS) of EBNA1 increases the binding affinity to the nuclear import adaptor importin-α1 as well as importin-α5, and stimulates nuclear import of EBNA1. To gain insights into how phosphorylation of the EBNA1 NLS regulates nuclear import, we have determined the crystal structures of two peptide complexes of importin-α1: onemore » with S385-phosphorylated EBNA1 NLS peptide, determined at 2.0 Å resolution, and one with non-phosphorylated EBNA1 NLS peptide, determined at 2.2 Å resolution. The structures show that EBNA1 NLS binds to the major and minor NLS-binding sites of importin-α1, and indicate that the binding affinity of the EBNA1 NLS to the minor NLS-binding site could be enhanced by phosphorylation of S385 through electrostatic interaction between the phosphate group of phospho-S385 and K392 of importin-α1 (corresponding to R395 of importin-α5) on armadillo repeat 8. - Highlights: • Nuclear import of EBNA1 can be regulated by phosphorylation of NLS. • Crystal structures of importin-α1 bound to the NLS peptides of EBNA1 are solved. • Structures provide insights into how phosphorylation can regulate nuclear import.« less

A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K.

PubMed

García-Santisteban, Iraia; Arregi, Igor; Alonso-Mariño, Marián; Urbaneja, María A; Garcia-Vallejo, Juan J; Bañuelos, Sonia; Rodríguez, Jose A

2016-12-01

The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclear export has not yet been evaluated in a cellular setting. Here, we describe SRV100, a cellular reporter to interrogate CRM1 nuclear export activity. Using this novel tool, we provide evidence further validating the model of NES binding and release by CRM1. Furthermore, using both SRV100-based cellular assays and in vitro biochemical analyses, we investigate the functional consequences of a recurrent cancer-related mutation, which targets a residue near CRM1 NES-binding cleft. Our data indicate that this mutation does not necessarily abrogate the nuclear export activity of CRM1, but may increase its affinity for NES sequences bearing a more negatively charged C-terminal end.

77 FR 63893 - In the Matter of Timothy M. Goold; IA-12-014; Confirmatory Order (Effective Immediately)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-17

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0242] In the Matter of Timothy M. Goold; IA-12-014... the U.S. Nuclear Regulatory Commission (NRC or Commission's) Materials License No. 21-16560-01 which authorized, at the time, specific activities involving byproduct, source, and/or special nuclear material...

Quantum Monte Carlo methods for nuclear physics

DOE PAGES

Carlson, J.; Gandolfi, S.; Pederiva, F.; ...

2015-09-09

Quantum Monte Carlo methods have proved valuable to study the structure and reactions of light nuclei and nucleonic matter starting from realistic nuclear interactions and currents. These ab-initio calculations reproduce many low-lying states, moments, and transitions in light nuclei, and simultaneously predict many properties of light nuclei and neutron matter over a rather wide range of energy and momenta. The nuclear interactions and currents are reviewed along with a description of the continuum quantum Monte Carlo methods used in nuclear physics. These methods are similar to those used in condensed matter and electronic structure but naturally include spin-isospin, tensor, spin-orbit,more » and three-body interactions. A variety of results are presented, including the low-lying spectra of light nuclei, nuclear form factors, and transition matrix elements. Low-energy scattering techniques, studies of the electroweak response of nuclei relevant in electron and neutrino scattering, and the properties of dense nucleonic matter as found in neutron stars are also described. Furthermore, a coherent picture of nuclear structure and dynamics emerges based upon rather simple but realistic interactions and currents.« less

Quantum Monte Carlo methods for nuclear physics

DOE PAGES

Carlson, Joseph A.; Gandolfi, Stefano; Pederiva, Francesco; ...

2014-10-19

Quantum Monte Carlo methods have proved very valuable to study the structure and reactions of light nuclei and nucleonic matter starting from realistic nuclear interactions and currents. These ab-initio calculations reproduce many low-lying states, moments and transitions in light nuclei, and simultaneously predict many properties of light nuclei and neutron matter over a rather wide range of energy and momenta. We review the nuclear interactions and currents, and describe the continuum Quantum Monte Carlo methods used in nuclear physics. These methods are similar to those used in condensed matter and electronic structure but naturally include spin-isospin, tensor, spin-orbit, and three-bodymore » interactions. We present a variety of results including the low-lying spectra of light nuclei, nuclear form factors, and transition matrix elements. We also describe low-energy scattering techniques, studies of the electroweak response of nuclei relevant in electron and neutrino scattering, and the properties of dense nucleonic matter as found in neutron stars. A coherent picture of nuclear structure and dynamics emerges based upon rather simple but realistic interactions and currents.« less

Toward an Experimental Quantum Chemistry: Exploring a New Energy Partitioning.

PubMed

Rahm, Martin; Hoffmann, Roald

2015-08-19

Following the work of L. C. Allen, this work begins by relating the central chemical concept of electronegativity with the average binding energy of electrons in a system. The average electron binding energy, χ̅, is in principle accessible from experiment, through photoelectron and X-ray spectroscopy. It can also be estimated theoretically. χ̅ has a rigorous and understandable connection to the total energy. That connection defines a new kind of energy decomposition scheme. The changing total energy in a reaction has three primary contributions to it: the average electron binding energy, the nuclear-nuclear repulsion, and multielectron interactions. This partitioning allows one to gain insight into the predominant factors behind a particular energetic preference. We can conclude whether an energy change in a transformation is favored or resisted by collective changes to the binding energy of electrons, the movement of nuclei, or multielectron interactions. For example, in the classical formation of H2 from atoms, orbital interactions dominate nearly canceling nuclear-nuclear repulsion and two-electron interactions. While in electron attachment to an H atom, the multielectron interactions drive the reaction. Looking at the balance of average electron binding energy, multielectron, and nuclear-nuclear contributions one can judge when more traditional electronegativity arguments can be justifiably invoked in the rationalization of a particular chemical event.

Form factors for dark matter capture by the Sun in effective theories

NASA Astrophysics Data System (ADS)

Catena, Riccardo; Schwabe, Bodo

2015-04-01

In the effective theory of isoscalar and isovector dark matter-nucleon interactions mediated by a heavy spin-1 or spin-0 particle, 8 isotope-dependent nuclear response functions can be generated in the dark matter scattering by nuclei. We compute the 8 nuclear response functions for the 16 most abundant elements in the Sun, i.e. H, 3He, 4He, 12C, 14N, 16O, 20Ne, 23Na, 24Mg, 27Al, 28Si, 32S, 40Ar, 40Ca, 56Fe, and 59Ni, through numerical shell model calculations. We use our response functions to compute the rate of dark matter capture by the Sun for all isoscalar and isovector dark matter-nucleon effective interactions, including several operators previously considered for dark matter direct detection only. We study in detail the dependence of the capture rate on specific dark matter-nucleon interaction operators, and on the different elements in the Sun. We find that a so far neglected momentum dependent dark matter coupling to the nuclear vector charge gives a larger contribution to the capture rate than the constant spin-dependent interaction commonly included in dark matter searches at neutrino telescopes. Our investigation lays the foundations for model independent analyses of dark matter induced neutrino signals from the Sun. The nuclear response functions obtained in this study are listed in analytic form in an appendix, ready to be used in other projects.

Study of nuclear matter in hard proton-nuclei and nuclei-nuclei collisions at the U70 accelerator (FLUKTON project proposal)

NASA Astrophysics Data System (ADS)

Antonov, N. N.; Baldin, A. A.; Viktorov, V. A.; Gapienko, V. A.; Gapienko, G. S.; Gres, V. N.; Ilyushin, M. A.; Korotkov, V. A.; Mysnik, A. I.; Prudkoglyad, A. F.; Pryanikov, D. S.; Semak, A. A.; Stavinsky, A. V.; Terekhov, V. I.; Uglekov, V. Ya.; Ukhanov, M. N.; Chuiko, B. V.; Shimansky, S. S.

2017-11-01

A two-arm spectrometer FLUKTON for investigations in the field of relativistic nuclear physics at U70 energies is proposed to be constructed on base of the existing detector SPIN (IHEP, Protvino). The main objective is to obtain new data on clusters of cold superdense nuclear matter. Interaction of a high intensity proton beam with nuclear targets and an ion beam with liquid hydrogen and nuclear targets will be studied.

Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals.

PubMed

Fung, Ho Yee Joyce; Fu, Szu-Chin; Chook, Yuh Min

2017-03-10

Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs.

Insight into nuclear body formation of phytochromes through stochastic modelling and experiment.

PubMed

Grima, Ramon; Sonntag, Sebastian; Venezia, Filippo; Kircher, Stefan; Smith, Robert W; Fleck, Christian

2018-05-01

Spatial relocalization of proteins is crucial for the correct functioning of living cells. An interesting example of spatial ordering is the light-induced clustering of plant photoreceptor proteins. Upon irradiation by white or red light, the red light-active phytochrome, phytochrome B, enters the nucleus and accumulates in large nuclear bodies. The underlying physical process of nuclear body formation remains unclear, but phytochrome B is thought to coagulate via a simple protein-protein binding process. We measure, for the first time, the distribution of the number of phytochrome B-containing nuclear bodies as well as their volume distribution. We show that the experimental data cannot be explained by a stochastic model of nuclear body formation via simple protein-protein binding processes using physically meaningful parameter values. Rather modelling suggests that the data is consistent with a two step process: a fast nucleation step leading to macroparticles followed by a subsequent slow step in which the macroparticles bind to form the nuclear body. An alternative explanation for the observed nuclear body distribution is that the phytochromes bind to a so far unknown molecular structure. We believe it is likely this result holds more generally for other nuclear body-forming plant photoreceptors and proteins. Creative Commons Attribution license.

Probing nuclear matter with jet conversions

NASA Astrophysics Data System (ADS)

Liu, W.; Fries, R. J.

2008-05-01

We discuss the flavor of leading jet partons as a valuable probe of nuclear matter. We point out that the coupling of jets to nuclear matter naturally leads to an alteration of jet chemistry even at high transverse momentum pT. In particular, quantum chromodynamics (QCD) jets coupling to a chemically equilibrated quark gluon plasma in nuclear collisions will lead to hadron ratios at high transverse momentum pT that can differ significantly from their counterparts in p+p collisions. Flavor measurements could complement energy loss as a way to study interactions of hard QCD jets with nuclear matter. Roughly speaking they probe the inverse mean free path 1/λ while energy loss probes the average squared momentum transfer μ2/λ. We present some estimates for the rate of jet conversions in a consistent Fokker-Planck framework and their impact on future high-pT identified hadron measurements at RHIC and LHC. We also suggest some novel observables to test flavor effects.

Functional relationship between CABIT, SAM and 14-3-3 binding domains of GAREM1 that play a role in its subcellular localization

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

Nishino, Tasuku; Matsunaga, Ryota; Konishi, Hiroaki, E-mail: hkonishi@pu-hiroshima.ac.jp

2015-08-21

GAREM1 (Grb2-associated regulator of Erk/MAPK1) is an adaptor protein that is involved in the epidermal growth factor (EGF) pathway. The nuclear localization of GAREM1 depends on the nuclear localization sequence (NLS), which is located at the N-terminal CABIT (cysteine-containing, all in Themis) domain. Here, we identified 14-3-3ε as a GAREM-binding protein, and its binding site is closely located to the NLS. This 14-3-3 binding site was of the atypical type and independent of GAREM phosphorylation. Moreover, the binding of 14-3-3 had an effect on the nuclear localization of GAREM1. Unexpectedly, we observed that the CABIT domain had intramolecular association withmore » the C-terminal SAM (sterile alpha motif) domain. This association might be inhibited by binding of 14-3-3 at the CABIT domain. Our results demonstrate that the mechanism underlying the nuclear localization of GAREM1 depends on its NLS in the CABIT domain, which is controlled by the binding of 14-3-3 and the C-terminal SAM domain. We suggest that the interplay between 14-3-3, SAM domain and CABIT domain might be responsible for the distribution of GAREM1 in mammalian cells. - Highlights: • 14-3-3ε regulated the nuclear localization of GAREM1 as its binding partner. • The atypical 14-3-3 binding site of GAREM1 is located near the NLS in CABIT domain. • The CABIT domain had intramolecular association with the SAM domain in GAREM1. • Subcellular localization of GAREM1 is affected with its CABIT-SAM interaction.« less

An N-terminal nuclear localization sequence but not the calmodulin-binding domain mediates nuclear localization of nucleomorphin, a protein that regulates nuclear number in Dictyostelium

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

Myre, Michael A.; O'Day, Danton H.

2005-06-24

Nucleomorphin is a novel nuclear calmodulin (CaM)-binding protein (CaMBP) containing an extensive DEED (glu/asp repeat) domain that regulates nuclear number. GFP-constructs of the 38 kDa NumA1 isoform localize as intranuclear patches adjacent to the inner nuclear membrane. The translocation of CaMBPs into nuclei has previously been shown by others to be mediated by both classic nuclear localization sequences (NLSs) and CaM-binding domains (CaMBDs). Here we show that NumA1 possesses a CaMBD ({sup 171}EDVSRFIKGKLLQKQQKIYKDLERF{sup 195}) containing both calcium-dependent-binding motifs and an IQ-like motif for calcium-independent binding. GFP-constructs containing only NumA1 residues 1-129, lacking the DEED and CaMBDs, still localized as patchesmore » at the internal periphery of nuclei thus ruling out a direct role for the CaMBD in nuclear import. These constructs contained the amino acid residues {sup 48}KKSYQDPEIIAHSRPRK{sup 64} that include both a putative bipartite and classical NLS. GFP-bipartite NLS constructs localized uniformly within nuclei but not as patches. As with previous work, removal of the DEED domain resulted in highly multinucleate cells. However as shown here, multinuclearity only occurred when the NLS was present allowing the protein to enter nuclei. Site-directed mutation analysis in which the NLS was changed to {sup 48}EF{sup 49} abolished the stability of the GFP fusion at the protein but not RNA level preventing subcellular analyses. Cells transfected with the {sup 48}EF{sup 49} construct exhibited slowed growth when compared to parental AX3 cells and other GFP-NumA1 deletion mutants. In addition to identifying an NLS that is sufficient for nuclear translocation of nucleomorphin and ruling out CaM-binding in this event, this work shows that the nuclear localization of NumA1 is crucial to its ability to regulate nuclear number in Dictyostelium.« less

Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms.

PubMed Central

Zhao, Xiangshan; Gan, Lixia; Pan, Haiyun; Kan, Donghui; Majeski, Michael; Adam, Stephen A; Unterman, Terry G

2004-01-01

FOXO1, a Forkhead transcription factor, is an important target of insulin and growth factor action. Phosphorylation of Thr-24, Ser-256 and Ser-319 promotes nuclear exclusion of FOXO1, yet the mechanisms regulating nuclear/cytoplasmic shuttling of FOXO1 are poorly understood. Previous studies have identified an NLS (nuclear localization signal) in the C-terminal basic region of the DBD (DNA-binding domain), and a leucine-rich, leptomycin-B sensitive NES (nuclear export signal) located further downstream. Here, we find that other elements in the DBD also contribute to nuclear localization, and that multiple mechanisms contribute to nuclear exclusion of FOXO1. Phosphorylation of Ser-319 and a cluster of nearby residues (Ser-322, Ser-325 and Ser-329) functions co-operatively with the nearby NES to promote nuclear exclusion. The N-terminal region of FOXO1 (amino acids 1-149) also is sufficient to promote nuclear exclusion, and does so through multiple mechanisms. Amino acids 1-50 are sufficient to promote nuclear exclusion of green fluorescent protein fusion proteins, and the phosphorylation of Thr-24 is required for this effect. A leucine-rich, leptomycin B-sensitive export signal is also present nearby. Phosphorylated FOXO1 binds 14-3-3 proteins, and co-precipitation studies with tagged proteins indicate that 14-3-3 binding involves co-operative interactions with both Thr-24 and Ser-256. Ser-256 is located in the C-terminal region of the DBD, where 14-3-3 proteins may interfere both with DNA-binding and with nuclear-localization functions. Together, these studies demonstrate that multiple elements contribute to nuclear/cytoplasmic shuttling of FOXO1, and that phosphorylation and 14-3-3 binding regulate the cellular distribution and function of FOXO1 through multiple mechanisms. The presence of these redundant mechanisms supports the concept that the regulation of FOXO1 function plays a critical role in insulin and growth factor action. PMID:14664696

Myeloid leukemia factor 1 associates with a novel heterogeneous nuclear ribonucleoprotein U-like molecule.

PubMed

Winteringham, Louise N; Endersby, Raelene; Kobelke, Simon; McCulloch, Ross K; Williams, James H; Stillitano, Justin; Cornwall, Scott M; Ingley, Evan; Klinken, S Peter

2006-12-15

Myeloid leukemia factor 1 (MLF1) is an oncoprotein associated with hemopoietic lineage commitment and acute myeloid leukemia. Here we show that Mlf1 associated with a novel binding partner, Mlf1-associated nuclear protein (Manp), a new heterogeneous nuclear ribonucleoprotein (hnRNP) family member, related to hnRNP-U. Manp localized exclusively in the nucleus and could redirect Mlf1 from the cytoplasm into the nucleus. The nuclear content of Mlf1 was also regulated by 14-3-3 binding to a canonical 14-3-3 binding motif within the N terminus of Mlf1. Significantly Mlf1 contains a functional nuclear export signal and localized primarily to the nuclei of hemopoietic cells. Mlf1 was capable of binding DNA, and microarray analysis revealed that it affected the expression of several genes, including transcription factors. In summary, this study reveals that Mlf1 translocates between nucleus and cytoplasm, associates with a novel hnRNP, and influences gene expression.

Minimal color-flavor-locked-nuclear interface

NASA Astrophysics Data System (ADS)

Alford, Mark; Rajagopal, Krishna; Reddy, Sanjay; Wilczek, Frank

2001-10-01

At nuclear matter density, electrically neutral strongly interacting matter in weak equilibrium is made of neutrons, protons, and electrons. At sufficiently high density, such matter is made of up, down, and strange quarks in the color-flavor-locked (CFL) phase, with no electrons. As a function of increasing density (or, perhaps, increasing depth in a compact star) other phases may intervene between these two phases, which are guaranteed to be present. The simplest possibility, however, is a single first order phase transition between CFL and nuclear matter. Such a transition, in space, could take place either through a mixed phase region or at a single sharp interface with electron-free CFL and electron-rich nuclear matter in stable contact. Here we construct a model for such an interface. It is characterized by a region of separated charge, similar to an inversion layer at a metal-insulator boundary. On the CFL side, the charged boundary layer is dominated by a condensate of negative kaons. We then consider the energetics of the mixed phase alternative. We find that the mixed phase will occur only if the nuclear-CFL surface tension is significantly smaller than dimensional analysis would indicate.

Nuclear magnetic biosignatures in the carbonaceous matter of ancient cherts: comparison with carbonaceous meteorites.

PubMed

Gourier, Didier; Delpoux, Olivier; Binet, Laurent; Vezin, Hervé

2013-10-01

The search for organic biosignatures is motivated by the hope of understanding the conditions of emergence of life on Earth and the perspective of finding traces of extinct life in martian sediments. Paramagnetic radicals, which exist naturally in amorphous carbonaceous matter fossilized in Precambrian cherts, were used as local structural probes and studied by electron paramagnetic resonance (EPR) spectroscopy. The nuclear magnetic resonance transitions of elements inside and around these radicals were detected by monitoring the nuclear modulations of electron spin echo in pulsed EPR. We found that the carbonaceous matter of fossilized microorganisms with age up to 3.5 billion years gives specific nuclear magnetic signatures of hydrogen (¹H), carbon (¹³C), and phosphorus (³¹P) nuclei. We observed that these potential biosignatures of extinct life are found neither in the carbonaceous matter of carbonaceous meteorites (4.56 billion years), the most ancient objects of the Solar System, nor in any carbonaceous matter resulting from carbonization of organic and bioorganic precursors. These results indicate that these nuclear signatures are sensitive to thermal episodes and can be used for Archean cherts with metamorphism not higher than the greenschist facies.

Symmetry Parameter Constraints from a Lower Bound on Neutron-matter Energy

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

Tews, Ingo; Lattimer, James M.; Ohnishi, Akira

We propose the existence of a lower bound on the energy of pure neutron matter (PNM) on the basis of unitary-gas considerations. We discuss its justification from experimental studies of cold atoms as well as from theoretical studies of neutron matter. We demonstrate that this bound results in limits to the density-dependent symmetry energy, which is the difference between the energies of symmetric nuclear matter and PNM. In particular, this bound leads to a lower limit to the volume symmetry energy parameter S {sub 0}. In addition, for assumed values of S {sub 0} above this minimum, this bound impliesmore » both upper and lower limits to the symmetry energy slope parameter L , which describes the lowest-order density dependence of the symmetry energy. A lower bound on neutron-matter incompressibility is also obtained. These bounds are found to be consistent with both recent calculations of the energies of PNM and constraints from nuclear experiments. Our results are significant because several equations of state that are currently used in astrophysical simulations of supernovae and neutron star mergers, as well as in nuclear physics simulations of heavy-ion collisions, have symmetry energy parameters that violate these bounds. Furthermore, below the nuclear saturation density, the bound on neutron-matter energies leads to a lower limit to the density-dependent symmetry energy, which leads to upper limits to the nuclear surface symmetry parameter and the neutron-star crust–core boundary. We also obtain a lower limit to the neutron-skin thicknesses of neutron-rich nuclei. Above the nuclear saturation density, the bound on neutron-matter energies also leads to an upper limit to the symmetry energy, with implications for neutron-star cooling via the direct Urca process.« less

Symmetry Parameter Constraints from a Lower Bound on Neutron-matter Energy

NASA Astrophysics Data System (ADS)

Tews, Ingo; Lattimer, James M.; Ohnishi, Akira; Kolomeitsev, Evgeni E.

2017-10-01

We propose the existence of a lower bound on the energy of pure neutron matter (PNM) on the basis of unitary-gas considerations. We discuss its justification from experimental studies of cold atoms as well as from theoretical studies of neutron matter. We demonstrate that this bound results in limits to the density-dependent symmetry energy, which is the difference between the energies of symmetric nuclear matter and PNM. In particular, this bound leads to a lower limit to the volume symmetry energy parameter S 0. In addition, for assumed values of S 0 above this minimum, this bound implies both upper and lower limits to the symmetry energy slope parameter L ,which describes the lowest-order density dependence of the symmetry energy. A lower bound on neutron-matter incompressibility is also obtained. These bounds are found to be consistent with both recent calculations of the energies of PNM and constraints from nuclear experiments. Our results are significant because several equations of state that are currently used in astrophysical simulations of supernovae and neutron star mergers, as well as in nuclear physics simulations of heavy-ion collisions, have symmetry energy parameters that violate these bounds. Furthermore, below the nuclear saturation density, the bound on neutron-matter energies leads to a lower limit to the density-dependent symmetry energy, which leads to upper limits to the nuclear surface symmetry parameter and the neutron-star crust-core boundary. We also obtain a lower limit to the neutron-skin thicknesses of neutron-rich nuclei. Above the nuclear saturation density, the bound on neutron-matter energies also leads to an upper limit to the symmetry energy, with implications for neutron-star cooling via the direct Urca process.

The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

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

Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong

2015-11-30

Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibitsmore » constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.« less

70-kDa Heat Shock Cognate Protein hsc70 Mediates Calmodulin-dependent Nuclear Import of the Sex-determining Factor SRY*

PubMed Central

Kaur, Gurpreet; Lieu, Kim G.; Jans, David A.

2013-01-01

We recently showed that the developmentally important family of SOX (SRY (sex determining region on the Y chromosome)-related high mobility group (HMG) box) proteins require the calcium-binding protein calmodulin (CaM) for optimal nuclear accumulation, with clinical mutations in SRY that specifically impair nuclear accumulation via this pathway resulting in XY sex reversal. However, the mechanism by which CaM facilitates nuclear accumulation is unknown. Here, we show, for the first time, that the 70-kDa heat shock cognate protein hsc70 plays a key role in CaM-dependent nuclear import of SRY. Using a reconstituted nuclear import assay, we show that antibodies to hsc70 significantly reduce nuclear accumulation of wild type SRY and mutant derivatives thereof that retain CaM-dependent nuclear import, with an increased rate of nuclear accumulation upon addition of both CaM and hsc70, in contrast to an SRY mutant derivative with impaired CaM binding. siRNA knockdown of hsc70 in intact cells showed similar results, indicating clear dependence upon hsc70 for CaM-dependent nuclear import. Analysis using the technique of fluorescence recovery after photobleaching indicated that hsc70 is required for the maximal rate of SRY nuclear import in living cells but has no impact upon SRY nuclear retention/nuclear dynamics. Finally, we demonstrate direct binding of hsc70 to the SRY·CaM complex, with immunoprecipitation experiments from cell extracts showing association of hsc70 with wild type SRY, but not with a mutant derivative with impaired CaM binding, dependent on Ca2+. Our novel findings strongly implicate hsc70 in CaM-dependent nuclear import of SRY. PMID:23235156

Equation of state for nucleonic matter and its quark mass dependence from the nuclear force in lattice QCD.

PubMed

Inoue, Takashi; Aoki, Sinya; Doi, Takumi; Hatsuda, Tetsuo; Ikeda, Yoichi; Ishii, Noriyoshi; Murano, Keiko; Nemura, Hidekatsu; Sasaki, Kenji

2013-09-13

Quark mass dependence of the equation of state (EOS) for nucleonic matter is investigated, on the basis of the Brueckner-Hartree-Fock method with the nucleon-nucleon interaction extracted from lattice QCD simulations. We observe saturation of nuclear matter at the lightest available quark mass corresponding to the pseudoscalar meson mass ≃469  MeV. Mass-radius relation of the neutron stars is also studied with the EOS for neutron-star matter from the same nuclear force in lattice QCD. We observe that the EOS becomes stiffer and thus the maximum mass of neutron star increases as the quark mass decreases toward the physical point.

Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding.

PubMed

Vuković, Lidija D; Jevtić, Predrag; Zhang, Zhaojie; Stohr, Bradley A; Levy, Daniel L

2016-03-15

Altered nuclear size is associated with many cancers, and determining whether cancer-associated changes in nuclear size contribute to carcinogenesis necessitates an understanding of mechanisms of nuclear size regulation. Although nuclear import rates generally positively correlate with nuclear size, NTF2 levels negatively affect nuclear size, despite the role of NTF2 (also known as NUTF2) in nuclear recycling of the import factor Ran. We show that binding of Ran to NTF2 is required for NTF2 to inhibit nuclear expansion and import of large cargo molecules in Xenopus laevis egg and embryo extracts, consistent with our observation that NTF2 reduces the diameter of the nuclear pore complex (NPC) in a Ran-binding-dependent manner. Furthermore, we demonstrate that ectopic NTF2 expression in Xenopus embryos and mammalian tissue culture cells alters nuclear size. Finally, we show that increases in nuclear size during melanoma progression correlate with reduced NTF2 expression, and increasing NTF2 levels in melanoma cells is sufficient to reduce nuclear size. These results show a conserved capacity for NTF2 to impact on nuclear size, and we propose that NTF2 might be a new cancer biomarker. © 2016. Published by The Company of Biologists Ltd.

78 FR 16894 - In the Matter of Luminant Generation Company LLC, Comanche Peak Nuclear Power Plant, Units 1 and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0310; Docket Nos.: 50-445 and 50-446; License Nos.: NPF-87 and NPF-89] In the Matter of Luminant Generation Company LLC, Comanche Peak Nuclear Power Plant, Units 1 and 2; Order Approving the Proposed Internal Restructuring and Indirect Transfer of License...

Properties of Localized Protons in Neutron Star Matter at Finite Temperatures

NASA Astrophysics Data System (ADS)

Szmaglinski, A.; Kubis, S.; Wójcik, W.

2014-02-01

We study properties of the proton component of neutron star matter for realistic nuclear models. Vanishing of the nuclear symmetry energy implies proton-neutron separation in dense nuclear matter. Protons which form admixture tend to be localized in potential wells. Here, we extend the description of proton localization to finite temperatures. It appears that the protons are still localized at temperatures typical for hot neutron stars. That fact has important astrophysical consequences. Moreover, the temperature inclusion leads to unexpected results for the behavior of the proton localized state.

Atomic Mass and Nuclear Binding Energy for U-287 (Uranium)

NASA Astrophysics Data System (ADS)

Sukhoruchkin, S. I.; Soroko, Z. N.

This document is part of the Supplement containing the complete sets of data of Subvolume B `Nuclei with Z = 55 - 100' of Volume 22 `Nuclear Binding Energies and Atomic Masses' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms', and additionally including data for nuclei with Z = 101 - 130. It provides atomic mass, mass excess, nuclear binding energy, nucleon separation energies, Q-values, and nucleon residual interaction parameters for atomic nuclei of the isotope U-287 (Uranium, atomic number Z = 92, mass number A = 287).

Atomic Mass and Nuclear Binding Energy for Ac-212 (Actinium)

NASA Astrophysics Data System (ADS)

Sukhoruchkin, S. I.; Soroko, Z. N.

This document is part of the Supplement containing the complete sets of data of Subvolume B `Nuclei with Z = 55 - 100' of Volume 22 `Nuclear Binding Energies and Atomic Masses' of Landolt-Börnstein - Group I `Elementary Particles, Nuclei and Atoms', and additionally including data for nuclei with Z = 101 - 130. It provides atomic mass, mass excess, nuclear binding energy, nucleon separation energies, Q-values, and nucleon residual interaction parameters for atomic nuclei of the isotope Ac-212 (Actinium, atomic number Z = 89, mass number A = 212).

A chimeric protein composed of NuMA fused to the DNA binding domain of LANA is sufficient for the ori-P-dependent DNA replication

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

Ohsaki, Eriko; Ueda, Keiji, E-mail: kueda@virus.me

The Kaposi's sarcoma-associated herpesvirus (KSHV) genome is stably maintained in KSHV-infected PEL cell lines during cell division. We previously showed that accumulation of LANA in the nuclear matrix fraction could be important for the latent DNA replication, and that the functional significance of LANA should be its recruitment of ori-P to the nuclear matrix. Here, we investigated whether the forced localization of the LANA-DNA binding domain (DBD) to the nuclear matrix facilitated ori-P-containing plasmid replication. We demonstrated that chimeric proteins constructed by fusion of LANA DBD with the nuclear mitotic apparatus protein (NuMA), which is one of the components ofmore » the nuclear matrix, could bind with ori-P and enhance replication of an ori-P-containing plasmid, compared with that in the presence of DBD alone. These results further suggested that the ori-P recruitment to the nuclear matrix through the binding with DBD is important for latent viral DNA replication. - Highlights: •KSHV replication in latency depends on LANA localization to the nuclear matrix. •LANA DBD was fused with NuMA, a nuclear matrix protein, at the N- and C-terminus. •NuMA-DBD was in the nuclear matrix and supported the ori-P dependent replication. •LANA in the nuclear matrix should be important for the KSHV replication in latency.« less

Equation of state of asymmetric nuclear matter using re-projected nucleon–nucleon potentials

NASA Astrophysics Data System (ADS)

Asadi Aghbolaghi, Z.; Bigdeli, M.

2018-06-01

In this paper, we have calculated the equation of state of asymmetric nuclear matter using the lowest order constrained variational approach and Argonne family potentials with and without three-nucleon interaction (TNI) contribution. In particular, we have used the AV18 potential and the re-projected potentials, AV8‧, and AV6‧. We have also calculated the saturation properties of symmetric nuclear matter, and the nuclear symmetry energy using AV18+TNI, AV8‧+TNI and AV6‧+TNI potentials. The inclusion of TNI has modified the agreement with experiment. We have also made a comparison between our results and those of other many-body calculations.

Nuclear ``pasta'' structures in low-density nuclear matter and properties of the neutron-star crust

NASA Astrophysics Data System (ADS)

Okamoto, Minoru; Maruyama, Toshiki; Yabana, Kazuhiro; Tatsumi, Toshitaka

2013-08-01

In the neutron-star crust, nonuniform structure of nuclear matter—called the “pasta” structure—is expected. From recent studies of giant flares in magnetars, these structures might be related to some observables and physical quantities of the neutron-star crust. To investigate the above quantities, we numerically explore the pasta structure with a fully three-dimensional geometry and study the properties of low-density nuclear matter, based on the relativistic mean-field model and the Thomas-Fermi approximation. We observe typical pasta structures for fixed proton number fraction and two of them for cold catalyzed matter. We also discuss the crystalline configuration of “pasta.”

Predictions for cold nuclear matter effects in p+Pb collisions at √{sNN } = 8.16 TeV

NASA Astrophysics Data System (ADS)

Albacete, Javier L.; Arleo, François; Barnaföldi, Gergely G.; Bíró, Gábor; d'Enterria, David; Ducloué, Bertrand; Eskola, Kari J.; Ferreiro, Elena G.; Gyulassy, Miklos; Harangozó, Szilvester Miklós; Helenius, Ilkka; Kang, Zhong-Bo; Kotko, Piotr; Kulagin, Sergey A.; Kutak, Krzysztof; Lansberg, Jean Philippe; Lappi, Tuomas; Lévai, Péter; Lin, Zi-Wei; Ma, Guoyang; Ma, Yan-Qing; Mäntysaari, Heikki; Paukkunen, Hannu; Papp, Gábor; Petti, Roberto; Rezaeian, Amir H.; Ru, Peng; Sapeta, Sebastian; Schenke, Björn; Schlichting, Sören; Shao, Hua-Sheng; Tribedy, Prithwish; Venugopalan, Raju; Vitev, Ivan; Vogt, Ramona; Wang, Enke; Wang, Xin-Nian; Xing, Hongxi; Xu, Rong; Zhang, Ben-Wei; Zhang, Hong-Fei; Zhang, Wei-Ning

2018-04-01

Predictions for cold nuclear matter effects on charged hadrons, identified light hadrons, quarkonium and heavy flavor hadrons, Drell-Yan dileptons, jets, photons, gauge bosons and top quark pairs produced in p+Pb collisions at √{sNN } = 8.16 TeV are compiled and, where possible, compared to each other. Predictions of the normalized ratios of p+Pb to p + p cross sections are also presented for most of the observables, providing new insights into the expected role of cold nuclear matter effects. In particular, the role of nuclear parton distribution functions on particle production can now be probed over a wider range of phase space than ever before.

BEC-BCS crossover and the liquid-gas phase transition in hot and dense nuclear matter

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

Jin Meng; Urban, Michael; Schuck, Peter

2010-08-15

The effect of nucleon-nucleon correlations in symmetric nuclear matter at finite temperature is studied beyond BCS theory. Starting from a Hartree-Fock description of nuclear matter with the Gogny effective interaction, we add correlations corresponding to the formation of preformed pairs and scattering states above the superfluid critical temperature within the in-medium T-matrix approach, which is analogous to the Nozieres-Schmitt-Rink theory. We calculate the critical temperature for a BEC superfluid of deuterons, of a BCS superfluid of nucleons, and in the crossover between these limits. The effect of the correlations on thermodynamic properties (equation of state, energy, entropy) and the liquid-gasmore » phase transition is discussed. Our results show that nucleon-nucleon correlations beyond BCS play an important role for the properties of nuclear matter, especially in the low-density region.« less

Rapid heating of matter using high power lasers

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

Bang, Woosuk

2016-04-08

This slide presentation describes motivation (uniform and rapid heating of a target, opportunity to study warm dense matter, study of nuclear fusion reactions), rapid heating of matter with intense laser-driven ion beams, visualization of the expanding warm dense gold and diamond, and nuclear fusion experiments using high power lasers (direct heating of deuterium spheres (radius ~ 10nm) with an intense laser pulse.

Pasta nucleosynthesis: Molecular dynamics simulations of nuclear statistical equilibrium

NASA Astrophysics Data System (ADS)

Caplan, M. E.; Schneider, A. S.; Horowitz, C. J.; Berry, D. K.

2015-06-01

Background: Exotic nonspherical nuclear pasta shapes are expected in nuclear matter at just below saturation density because of competition between short-range nuclear attraction and long-range Coulomb repulsion. Purpose: We explore the impact nuclear pasta may have on nucleosynthesis during neutron star mergers when cold dense nuclear matter is ejected and decompressed. Methods: We use a hybrid CPU/GPU molecular dynamics (MD) code to perform decompression simulations of cold dense matter with 51 200 and 409 600 nucleons from 0.080 fm-3 down to 0.00125 fm-3 . Simulations are run for proton fractions YP= 0.05, 0.10, 0.20, 0.30, and 0.40 at temperatures T = 0.5, 0.75, and 1.0 MeV. The final composition of each simulation is obtained using a cluster algorithm and compared to a constant density run. Results: Size of nuclei in the final state of decompression runs are in good agreement with nuclear statistical equilibrium (NSE) models for temperatures of 1 MeV while constant density runs produce nuclei smaller than the ones obtained with NSE. Our MD simulations produces unphysical results with large rod-like nuclei in the final state of T =0.5 MeV runs. Conclusions: Our MD model is valid at higher densities than simple nuclear statistical equilibrium models and may help determine the initial temperatures and proton fractions of matter ejected in mergers.

76 FR 11522 - In the Matter of Progress Energy Florida, Inc. (Combined License Application, Levy County Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 52-029-COL, 52-030-COL] In the Matter of Progress Energy Florida, Inc. (Combined License Application, Levy County Nuclear Power Plant, Units 1 and 2... of 10 CFR 2.347 and 2.348 in their communications with Mr. Dehmel. It is so ordered. Dated at...

Annual Historical Review FY88

DTIC Science & Technology

1990-06-01

Army Executive Agent for RDA vi LTG Fred Hissong, Jr. DCG for Materiel Readiness Executive Director for Chemical and Nuclear Matters Executive Director...Chemical & Equal Employment To 31 March 1988 Nuclear Matters To 1 March 1988 To 1 January 1988 xv MG Thomas W. Kelly Mr. Edward Korte MG Eugene B. Leedy DCS...13 Chemical/ Nuclear ......................................... 14 Hazardous And Toxic Materials ............................... 14 International

PRIC320, a transcription coactivator, isolated from peroxisome proliferator-binding protein complex.

PubMed

Surapureddi, Sailesh; Viswakarma, Navin; Yu, Songtao; Guo, Dongsheng; Rao, M Sambasiva; Reddy, Janardan K

2006-05-05

Ciprofibrate, a potent peroxisome proliferator, induces pleiotropic responses in liver by activating peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear receptor. Transcriptional regulation by liganded nuclear receptors involves the participation of coregulators that form multiprotein complexes possibly to achieve cell and gene specific transcription. SDS-PAGE and matrix-assisted laser desorption/ionization reflection time-of-flight mass spectrometric analyses of ciprofibrate-binding proteins from liver nuclear extracts obtained using ciprofibrate-Sepharose affinity matrix resulted in the identification of a new high molecular weight nuclear receptor coactivator, which we designated PRIC320. The full-length human cDNA encoding this protein has an open-reading frame that codes for a 320kDa protein containing 2882 amino acids. PRIC320 contains five LXXLL signature motifs that mediate interaction with nuclear receptors. PRIC320 binds avidly to nuclear receptors PPARalpha, CAR, ERalpha, and RXR, but only minimally with PPARgamma. PRIC320 also interacts with transcription cofactors CBP, PRIP, and PBP. Immunoprecipitation-immunoblotting as well as cellular localization studies confirmed the interaction between PPARalpha and PRIC320. PRIC320 acts as a transcription coactivator by stimulating PPARalpha-mediated transcription. We conclude that ciprofibrate, a PPARalpha ligand, binds a multiprotein complex and PRIC320 cloned from this complex functions as a nuclear receptor coactivator.

Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

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

Patterson, Edward I.; EH Graham Centre for Agricultural Innovation; Dombrovski, Andrew K.

2013-09-06

Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediatemore » nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.« less

A Distinct and Parallel Pathway for the Nuclear Import of an mRNA-binding Protein

PubMed Central

Pemberton, Lucy F.; Rosenblum, Jonathan S.; Blobel, Günter

1997-01-01

Three independent pathways of nuclear import have so far been identified in yeast, each mediated by cognate nuclear transport factors, or karyopherins. Here we have characterized a new pathway to the nucleus, mediated by Mtr10p, a protein first identified in a screen for strains defective in polyadenylated RNA export. Mtr10p is shown to be responsible for the nuclear import of the shuttling mRNA-binding protein Npl3p. A complex of Mtr10p and Npl3p was detected in cytosol, and deletion of Mtr10p was shown to lead to the mislocalization of nuclear Npl3p to the cytoplasm, correlating with a block in import. Mtr10p bound peptide repeat-containing nucleoporins and Ran, suggesting that this import pathway involves a docking step at the nuclear pore complex and is Ran dependent. This pathway of Npl3p import is distinct and does not appear to overlap with another known import pathway for an mRNA-binding protein. Thus, at least two parallel pathways function in the import of mRNA-binding proteins, suggesting the need for the coordination of these pathways. PMID:9412460

Strongly Interacting Multi-component Fermions: From Ultracold Atomic Fermi Gas to Asymmetric Nuclear Matter in Neutron Stars

NASA Astrophysics Data System (ADS)

Tajima, Hiroyuki; Hatsuda, Tetsuo; Ohashi, Yoji

2018-03-01

We investigate an asymmetric nuclear matter consisting of protons and neutrons with spin degrees of freedom (σ = ↑, ↓). By generalizing the Nozières and Schmitt-Rink theory for two-component Fermi gases to the four-component case, we analyze the critical temperature T c of the superfluid phase transition. Although the pure neutron matter exhibits the dineutron condensation in the low-density region, the superfluid instability toward the deuteron condensation is found to take place as the proton fraction increases. We clarify the mechanism of the competition between the deuteron condensation and dineutron condensation. Our results would serve for understanding the properties of asymmetric nuclear matter realized in the interior of neutron stars.

East Europe Report, Scientific Affairs, No. 776.

DTIC Science & Technology

1983-05-11

Washington, D.C. 20402. Correspondence pertaining to matters other than procurement may be addressed to Joint Publications Research Service, 1000...the beginning of neutrons physics--the science of the properties of the neutron and its interactions-with the nucleus and matter . The science has...media, the magnetic properties of matter and phase transitions; in the physics of nuclear reactors and nuclear technology; in developing and applying

Microscopic calculations of nuclear and neutron matter, symmetry energy and neutron stars

DOE PAGES

Gandolfi, S.

2015-02-01

We present Quantum Monte Carlo calculations of the equation of state of neutron matter. The equation of state is directly related to the symmetry energy and determines the mass and radius of neutron stars, providing then a connection between terrestrial experiments and astronomical observations. As a result, we also show preliminary results of the equation of state of nuclear matter.

77 FR 134 - In the Matter of Yankee Atomic Electric Company; Northeast Utilities; NSTAR (Yankee Nuclear Power...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-03

... Matter of Yankee Atomic Electric Company; Northeast Utilities; NSTAR (Yankee Nuclear Power Station); Order Approving Application Regarding Proposed Merger I Yankee Atomic Electric Company (Yankee Atomic or... (together, the [[Page 135

LEM4/ANKLE-2 deficiency impairs post-mitotic re-localization of BAF, LAP2α and LaminA to the nucleus, causes nuclear envelope instability in telophase and leads to hyperploidy in HeLa cells.

PubMed

Snyers, Luc; Erhart, Renate; Laffer, Sylvia; Pusch, Oliver; Weipoltshammer, Klara; Schöfer, Christian

2018-01-01

The human LEM-domain protein family is involved in fundamental aspects of nuclear biology. The LEM-domain interacts with the barrier-to-autointegration factor (BAF), which itself binds DNA. LEM-domain proteins LAP2, emerin and MAN1 are proteins of the inner nuclear membrane; they have important functions: maintaining the integrity of the nuclear lamina and regulating gene expression at the nuclear periphery. LEM4/ANKLE-2 has been proposed to participate in nuclear envelope reassembly after mitosis and to mediate dephosphorylation of BAF through binding to phosphatase PP2A. Here, we used CRISPR/Cas9 to create several cell lines deficient in LEM4/ANKLE-2. By using time-lapse video microscopy, we show that absence of this protein severely compromises the post mitotic re-association of the nuclear proteins BAF, LAP2α and LaminA to chromosomes. These defects give rise to a strong mechanical instability of the nuclear envelope in telophase and to a chromosomal instability leading to increased number of hyperploid cells. Reintroducing LEM4/ANKLE-2 in the cells by transfection could efficiently restore the telophase association of BAF and LAP2α to the chromosomes. This rescue phenotype was abolished for N- or C-terminally truncated mutants that had lost the capacity to bind PP2A. We demonstrate also that, in addition to binding to PP2A, LEM4/ANKLE-2 binds BAF through its LEM-domain, providing further evidence for a generic function of this domain as a principal interactor of BAF. Copyright © 2017 Elsevier GmbH. All rights reserved.

Importin α5 negatively regulates importin β1-mediated nuclear import of Newcastle disease virus matrix protein and viral replication and pathogenicity in chicken fibroblasts.

PubMed

Duan, Zhiqiang; Xu, Haixu; Ji, Xinqin; Zhao, Jiafu; Xu, Houqiang; Hu, Yan; Deng, Shanshan; Hu, Shunlin; Liu, Xiufan

2018-12-31

The matrix (M) protein of Newcastle disease virus (NDV) is demonstrated to localize in the nucleus via intrinsic nuclear localization signal (NLS), but cellular proteins involved in the nuclear import of NDV M protein and the role of M's nuclear localization in the replication and pathogenicity of NDV remain unclear. In this study, importin β1 was screened to interact with NDV M protein by yeast two-hybrid screening. This interaction was subsequently confirmed by co-immunoprecipitation and pull-down assays. In vitro binding studies indicated that the NLS region of M protein and the amino acids 336-433 of importin β1 that belonged to the RanGTP binding region were important for binding. Importantly, a recombinant virus with M/NLS mutation resulted in a pathotype change of NDV and attenuated viral replication and pathogenicity in chicken fibroblasts and SPF chickens. In agreement with the binding data, nuclear import of NDV M protein in digitonin-permeabilized HeLa cells required both importin β1 and RanGTP. Interestingly, importin α5 was verified to interact with M protein through binding importin β1. However, importin β1 or importin α5 depletion by siRNA resulted in different results, which showed the obviously cytoplasmic or nuclear accumulation of M protein and the remarkably decreased or increased replication ability and pathogenicity of NDV in chicken fibroblasts, respectively. Our findings therefore demonstrate for the first time the nuclear import mechanism of NDV M protein and the negative regulation role of importin α5 in importin β1-mediated nuclear import of M protein and the replication and pathogenicity of a paramyxovirus.

Predictions for cold nuclear matter effects in p+Pb collisions at s N N = 8.16 TeV

DOE PAGES

Albacete, Javier L.; Arleo, Francois; Barnafoldi, Gergely G.; ...

2018-02-07

In this study, predictions for cold nuclear matter effects on charged hadrons, identified light hadrons, quarkonium and heavy flavor hadrons, Drell-Yan dileptons, jets, photons, gauge bosons and top quark pairs produced in p+Pb collisions at √sNN = 8.16 TeV are compiled and, where possible, compared to each other. Predictions of the normalized ratios of p+Pb to p + p cross sections are also presented for most of the observables, providing new insights into the expected role of cold nuclear matter effects. In particular, the role of nuclear parton distribution functions on particle production can now be probed over a widermore » range of phase space than ever before.« less

Predictions for cold nuclear matter effects in p+Pb collisions at s N N = 8.16 TeV

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

Albacete, Javier L.; Arleo, Francois; Barnafoldi, Gergely G.

In this study, predictions for cold nuclear matter effects on charged hadrons, identified light hadrons, quarkonium and heavy flavor hadrons, Drell-Yan dileptons, jets, photons, gauge bosons and top quark pairs produced in p+Pb collisions at √sNN = 8.16 TeV are compiled and, where possible, compared to each other. Predictions of the normalized ratios of p+Pb to p + p cross sections are also presented for most of the observables, providing new insights into the expected role of cold nuclear matter effects. In particular, the role of nuclear parton distribution functions on particle production can now be probed over a widermore » range of phase space than ever before.« less

Dark Coulomb binding of heavy neutrinos of fourth family

NASA Astrophysics Data System (ADS)

Belotsky, K. M.; Esipova, E. A.; Khlopov, M. Yu.; Laletin, M. N.

2015-11-01

Direct dark matter searches put severe constraints on the weakly interacting massive particles (WIMPs). These constraints cause serious troubles for the model of stable neutrino of fourth generation with mass around 50GeV. Though the calculations of primordial abundance of these particles make them in the charge symmetric case a sparse subdominant component of the modern dark matter, their presence in the universe would exceed the current upper limits by several orders of the magnitude. However, if quarks and leptons of fourth generation possess their own Coulomb-like y-interaction, recombination of pairs of heavy neutrinos and antineutrinos and their annihilation in the “neutrinium” atoms can play important role in their cosmological evolution, reducing their modern abundance far below the experimental upper limits. The model of stable fourth generation assumes that the dominant part of dark matter is explained by excessive Ū antiquarks, forming (ŪŪŪ)-- charged clusters, bound with primordial helium in nuclear-interacting O-helium (OHe) dark atoms. The y charge conservation implies generation of the same excess of fourth generation neutrinos, potentially dangerous WIMP component of this scenario. We show that due to y-interaction recombination of fourth neutrinos with OHe hides these WIMPs from direct WIMP searches, leaving the negligible fraction of free neutrinos, what makes their existence compatible with the experimental constraints.

Importin α-importin β complex mediated nuclear translocation of insulin-like growth factor binding protein-5.

PubMed

Sun, Min; Long, Juan; Yi, Yuxin; Xia, Wei

2017-10-28

Insulin-like growth factor-binding protein (IGFBP)-5 is a secreted protein that binds to IGFs and modulates IGF actions, as well as regulates cell proliferation, migration, and apoptosis independent of IGF. Proper cellular localization is critical for the effective function of most signaling molecules. In previous studies, we have shown that the nuclear IGFBP-5 comes from ER-cytosol retro-translocation. In this study, we further investigated the pathway mediating IGFBP-5 nuclear import after it retro-translocation. Importin-α5 was identified as an IGFBP-5-interacting protein with a yeast two-hybrid system, and its interaction with IGFBP-5 was further confirmed by GST pull down and co-immunoprecipitation. Binding affinity of IGFBP-5 and importins were determined by surface plasmon resonance (IGFBP-5/importin-β: K D =2.44e-7, IGFBP-5/importin-α5: K D =3.4e-7). Blocking the importin-α5/importin-β nuclear import pathway using SiRNA or dominant negative impotin-β dramatically inhibited IGFBP-5-EGFP nuclear import, though importin-α5 overexpress does not affect IGFBP-5 nuclear import. Furthermore, nuclear IGFBP-5 was quantified using luciferase report assay. When deleted the IGFBP-5 nuclear localization sequence (NLS), IGFBP-5 ΔNLS loss the ability to translocate into the nucleus and accumulation of IGFBP-5 ΔNLS was visualized in the cytosol. Altogether, our findings provide a substantially evidence showed that the IGFBP-5 nuclear import is mediated by importin-α/importin-β complex, and NLS is critical domain in IGFBP-5 nuclear translocation.

Nuclear astrophysics and electron beams

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

Schwenk, A.

Electron beams provide important probes and constraints for nuclear astrophysics. This is especially exciting at energies within the regime of chiral effective field theory (EFT), which provides a systematic expansion for nuclear forces and electroweak operators based on quantum chromodynamics. This talk discusses some recent highlights and future directions based on chiral EFT, including nuclear structure and reactions for astrophysics, the neutron skin and constraints for the properties of neutron-rich matter in neutron stars and core-collapse supernovae, and the dark matter response of nuclei.

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

Catena, Riccardo; Schwabe, Bodo, E-mail: riccardo.catena@theorie.physik.uni-goettingen.de, E-mail: bodo.schwabe@theorie.physik.uni-goettingen.de

In the effective theory of isoscalar and isovector dark matter-nucleon interactions mediated by a heavy spin-1 or spin-0 particle, 8 isotope-dependent nuclear response functions can be generated in the dark matter scattering by nuclei. We compute the 8 nuclear response functions for the 16 most abundant elements in the Sun, i.e. H, {sup 3}He, {sup 4}He, {sup 12}C, {sup 14}N, {sup 16}O, {sup 20}Ne, {sup 23}Na, {sup 24}Mg, {sup 27}Al, {sup 28}Si, {sup 32}S, {sup 40}Ar, {sup 40}Ca, {sup 56}Fe, and {sup 59}Ni, through numerical shell model calculations. We use our response functions to compute the rate of dark mattermore » capture by the Sun for all isoscalar and isovector dark matter-nucleon effective interactions, including several operators previously considered for dark matter direct detection only. We study in detail the dependence of the capture rate on specific dark matter-nucleon interaction operators, and on the different elements in the Sun. We find that a so far neglected momentum dependent dark matter coupling to the nuclear vector charge gives a larger contribution to the capture rate than the constant spin-dependent interaction commonly included in dark matter searches at neutrino telescopes. Our investigation lays the foundations for model independent analyses of dark matter induced neutrino signals from the Sun. The nuclear response functions obtained in this study are listed in analytic form in an appendix, ready to be used in other projects.« less

Form factors for dark matter capture by the Sun in effective theories

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

Catena, Riccardo; Schwabe, Bodo

2015-04-24

In the effective theory of isoscalar and isovector dark matter-nucleon interactions mediated by a heavy spin-1 or spin-0 particle, 8 isotope-dependent nuclear response functions can be generated in the dark matter scattering by nuclei. We compute the 8 nuclear response functions for the 16 most abundant elements in the Sun, i.e. H, {sup 3}He, {sup 4}He, {sup 12}C, {sup 14}N, {sup 16}O, {sup 20}Ne, {sup 23}Na, {sup 24}Mg, {sup 27}Al, {sup 28}Si, {sup 32}S, {sup 40}Ar, {sup 40}Ca, {sup 56}Fe, and {sup 59}Ni, through numerical shell model calculations. We use our response functions to compute the rate of dark mattermore » capture by the Sun for all isoscalar and isovector dark matter-nucleon effective interactions, including several operators previously considered for dark matter direct detection only. We study in detail the dependence of the capture rate on specific dark matter-nucleon interaction operators, and on the different elements in the Sun. We find that a so far neglected momentum dependent dark matter coupling to the nuclear vector charge gives a larger contribution to the capture rate than the constant spin-dependent interaction commonly included in dark matter searches at neutrino telescopes. Our investigation lays the foundations for model independent analyses of dark matter induced neutrino signals from the Sun. The nuclear response functions obtained in this study are listed in analytic form in an appendix, ready to be used in other projects.« less

A Role for the NF-kb/Rel Transcription Factors in Human Breast Cancer

DTIC Science & Technology

1998-07-01

binding proteins present in a series of nuclear extracts from cell lines and from breast tumor tissues as well as normal mammary epithelium. Finally, we...RelA is nuclear in several examples. Our recent data on nuclear extracts of breast tumors shows that there is a significant increase in NF-KB binding...Figure 2 in the appendix). Additionally, immunoblotting of nuclear extracts versus adjacent tissue controls showed that NF-KB p50, p52 and c-Rel were

78 FR 29158 - In the Matter of Zion Solutions, LLC; Zion Nuclear Power Station, Units 1 and 2; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0096; Docket Nos. 50-295 and 50-304; License Nos. DPR-39 and DPR-48] In the Matter of Zion Solutions, LLC; Zion Nuclear Power Station, Units 1 and 2; Order Approving Indirect Transfer of Control of Facility Operating Licenses I. ZionSolutions, LLC (ZS) is the...

Variational calculation of ground-state energy of iron atoms and condensed matter in strong magnetic fields. [at neutron star surfaces

NASA Technical Reports Server (NTRS)

Flowers, E. G.; Ruderman, M. A.; Lee, J.-F.; Sutherland, P. G.; Hillebrandt, W.; Mueller, E.

1977-01-01

Variational calculations of the binding energies of iron atoms and condensed matter in strong magnetic fields (greater than 10 to the 12th gauss). These calculations include the electron exchange energy. The cohesive energy of the condensed matter, which is the difference between these two binding energies, is of interest in pulsar theories and in the description of the surfaces of neutron stars. It is found that the cohesive energy ranges from 2.6 keV to 8.0 keV.

Discrimination between NL1- and NL2-Mediated Nuclear Localization of the Glucocorticoid Receptor

PubMed Central

Savory, Joanne G. A.; Hsu, Brian; Laquian, Ian R.; Giffin, Ward; Reich, Terry; Haché, Robert J. G.; Lefebvre, Yvonne A.

1999-01-01

Glucocorticoid receptor (GR) cycles between a free liganded form that is localized to the nucleus and a heat shock protein (hsp)-immunophilin-complexed, unliganded form that is usually localized to the cytoplasm but that can also be nuclear. In addition, rapid nucleocytoplasmic exchange or shuttling of the receptor underlies its localization. Nuclear import of liganded GR is mediated through a well-characterized sequence, NL1, adjacent to the receptor DNA binding domain and a second, uncharacterized motif, NL2, that overlaps with the ligand binding domain. In this study we report that rapid nuclear import (half-life [t1/2] of 4 to 6 min) of agonist- and antagonist-treated GR and the localization of unliganded, hsp-associated GRs to the nucleus in G0 are mediated through NL1 and correlate with the binding of GR to pendulin/importin α. By contrast, NL2-mediated nuclear transfer of GR occurred more slowly (t1/2 = 45 min to 1 h), was agonist specific, and appeared to be independent of binding to importin α. Together, these results suggest that NL2 mediates the nuclear import of GR through an alternative nuclear import pathway. Nuclear export of GR was inhibited by leptomycin B, suggesting that the transfer of GR to the cytoplasm is mediated through the CRM1-dependent pathway. Inhibition of GR nuclear export by leptomycin B enhanced the nuclear localization of both unliganded, wild-type GR and hormone-treated NL1− GR. These results highlight that the subcellular localization of both liganded and unliganded GRs is determined, at least in part, by a flexible equilibrium between the rates of nuclear import and export. PMID:9891038

A Highly Organized Structure Mediating Nuclear Localization of a Myb2 Transcription Factor in the Protozoan Parasite Trichomonas vaginalis ▿ †

PubMed Central

Chu, Chien-Hsin; Chang, Lung-Chun; Hsu, Hong-Ming; Wei, Shu-Yi; Liu, Hsing-Wei; Lee, Yu; Kuo, Chung-Chi; Indra, Dharmu; Chen, Chinpan; Ong, Shiou-Jeng; Tai, Jung-Hsiang

2011-01-01

Nuclear proteins usually contain specific peptide sequences, referred to as nuclear localization signals (NLSs), for nuclear import. These signals remain unexplored in the protozoan pathogen, Trichomonas vaginalis. The nuclear import of a Myb2 transcription factor was studied here using immunodetection of a hemagglutinin-tagged Myb2 overexpressed in the parasite. The tagged Myb2 was localized to the nucleus as punctate signals. With mutations of its polybasic sequences, 48KKQK51 and 61KR62, Myb2 was localized to the nucleus, but the signal was diffusive. When fused to a C-terminal non-nuclear protein, the Myb2 sequence spanning amino acid (aa) residues 48 to 143, which is embedded within the R2R3 DNA-binding domain (aa 40 to 156), was essential and sufficient for efficient nuclear import of a bacterial tetracycline repressor (TetR), and yet the transport efficiency was reduced with an additional fusion of a firefly luciferase to TetR, while classical NLSs from the simian virus 40 T-antigen had no function in this assay system. Myb2 nuclear import and DNA-binding activity were substantially perturbed with mutation of a conserved isoleucine (I74) in helix 2 to proline that altered secondary structure and ternary folding of the R2R3 domain. Disruption of DNA-binding activity alone by point mutation of a lysine residue, K51, preceding the structural domain had little effect on Myb2 nuclear localization, suggesting that nuclear translocation of Myb2, which requires an ordered structural domain, is independent of its DNA binding activity. These findings provide useful information for testing whether myriad Mybs in the parasite use a common module to regulate nuclear import. PMID:22021237

Age-related decline in oligodendrogenesis retards white matter repair in mice.

PubMed

Miyamoto, Nobukazu; Pham, Loc-Duyen D; Hayakawa, Kazuhide; Matsuzaki, Toshinori; Seo, Ji Hae; Magnain, Caroline; Ayata, Cenk; Kim, Kyu-Won; Boas, David; Lo, Eng H; Arai, Ken

2013-09-01

Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask whether, compared with young brains, white matter regions in older brains may be more vulnerable in part because of decreased rates of compensatory oligodendrogenesis after injury. A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month-old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells to sublethal 7-day CoCl2 treatment to induce chemical hypoxic stress. Baseline myelin density in the corpus callosum was similar in 2-month and 8-month-old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in cyclic AMP response element-binding protein signaling may be involved because activating cyclic AMP response element-binding protein with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of oligodendrocyte precursor cells, alleviated myelin loss, and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of oligodendrocyte precursor cells. An age-related decline in cyclic AMP response element-binding protein-mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate cyclic AMP response element-binding protein signaling provide a potential therapeutic approach for treating white matter injury in aging brains.

Influence of water chemistry and natural organic matter on active and passive uptake of inorganic mercury by gills of rainbow trout (Oncorhynchus mykiss).

PubMed

Klinck, Joel; Dunbar, Michael; Brown, Stephanie; Nichols, Joel; Winter, Anna; Hughes, Christopher; Playle, Richard C

2005-03-25

To distinguish physiologically regulated uptake from passive uptake of inorganic Hg in fish, rainbow trout (Oncorhynchus mykiss) were exposed to inorganic Hg (0.5, 1, or 2 microM total Hg) in ion-poor water with various treatments. Addition of ions to the water (mM concentrations of Ca, K, Cl) did not consistently alter Hg accumulation by trout gills, although there was a trend to higher Hg accumulation at higher ion concentrations. The apical Ca channel blockers Verapamil and lanthanum also did not consistently affect Hg accumulation by trout gills. Pre-treatment of trout with the Na channel blocker Phenamil decreased Hg uptake by about half. These results suggest a combination of physiologically regulated and passive uptake of Hg by trout gills. Strong complexing agents of Hg (EDTA, NTA, ethylenediamine, cysteine) decreased Hg-binding by trout gills in a dose-dependent manner. From these data, a conditional equilibrium binding constant for Hg to the gills was estimated as logK(Hg-gill) = 18.0, representing very strong binding of Hg to the gills. This value is a first step in creating a biotic ligand model (BLM) for inorganic Hg and fish. Natural organic matter (2-10 mg C/L) also decreased Hg-binding by trout gills, although mM concentrations of Na, K, and Cl interfered with this effect. At low concentrations of these ions, natural organic matter samples isolated from various sources bound Hg to similar degrees, as judged by Hg accumulation by trout gills. A conditional binding constant to natural organic matter (NOM) was estimated as logK(Hg-NOM) = 18.0 with about 0.5 micromol binding sites per mg C, representing strong binding of Hg to NOM.

Three flavor Nambu-Jona-Lasinio model with Polyakov loop and competition with nuclear matter

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

Ciminale, M.; Ippolito, N. D.; Nardulli, G.

2008-03-01

We study the phase diagram of the three flavor Polyakov-Nambu-Jona-Lasinio (PNJL) model and, in particular, the interplay between chiral symmetry restoration and deconfinement crossover. We compute chiral condensates, quark densities, and the Polyakov loop at several values of temperature and chemical potential. Moreover we investigate on the role of the Polyakov loop dynamics in the transition from nuclear matter to quark matter.

The search for axion-like dark matter using magnetic resonance

NASA Astrophysics Data System (ADS)

Sushkov, Alexander; Casper Collaboration

2016-05-01

The nature of dark matter is one of the most important open problems in modern physics, and it is necessary to develop techniques to search for a wide class of dark-matter candidates. Axions, originally introduced to resolve the strong CP problem in quantum chromodynamics (QCD), and axion-like particles (ALPs) are strongly motivated dark matter candidates. Nuclear spins interacting with axion-like background dark matter experience an energy shift, oscillating at the frequency equal to the axion Compton frequency. The Cosmic Axion Spin Precession Experiments (CASPEr) use precision magnetometry and nuclear magnetic resonance techniques to search for the effects of this interaction. The experimental signature is precession of the nuclear spins under the condition of magnetic resonance: when the bias magnetic field is tuned such that the nuclear spin sublevel splitting is equal to the axion Compton frequency. These experiments have the potential to detect axion-like dark matter in a wide mass range (10-12 eV to 10-6 eV, scanned by changing the bias magnetic field from approximately 1 gauss to 20 tesla) and with coupling strengths many orders of magnitude beyond the current astrophysical and laboratory limits, and all the way down to those corresponding to the QCD axion. Supported by the Heising-Simons Foundation.

Yeast Ran-Binding Protein 1 (Yrb1) Shuttles between the Nucleus and Cytoplasm and Is Exported from the Nucleus via a CRM1 (XPO1)-Dependent Pathway

PubMed Central

Künzler, Markus; Gerstberger, Thomas; Stutz, Françoise; Bischoff, F. Ralf; Hurt, Ed

2000-01-01

The RanGTP-binding protein RanBP1, which is located in the cytoplasm, has been implicated in release of nuclear export complexes from the cytoplasmic side of the nuclear pore complex. Here we show that Yrb1 (the yeast homolog of RanBP1) shuttles between the nucleus and the cytoplasm. Nuclear import of Yrb1 is a facilitated process that requires a short basic sequence within the Ran-binding domain (RBD). By contrast, nuclear export of Yrb1 requires an intact RBD, which forms a ternary complex with the Xpo1 (Crm1) NES receptor in the presence of RanGTP. Nuclear export of Yrb1, however, is insensitive towards leptomycin B, suggesting a novel type of substrate recognition between Yrb1 and Xpo1. Taken together, these data suggest that ongoing nuclear import and export is an important feature of Yrb1 function in vivo. PMID:10825193

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

Nishino, Tomonori G.; Department of Biotechnology, University of Tokyo, Bunkyo-ku, Tokyo 113-8657; Miyazaki, Masaya

Class IIa histone deacetylases (HDACs) form complexes with a class of transcriptional repressors in the nucleus. While screening for compounds that could block the association of HDAC4 with the BTB domain-containing transcriptional repressor Bach2, we discovered that phorbol 12-myristate 13-acetate (PMA) induced the cytoplasmic retention of HDAC4 mutants lacking a nuclear export signal (NES). Although PMA treatment and PKD overexpression has been proposed to facilitate the nuclear export of class IIa HDACs by creating 14-3-3 binding sites containing phosphoserines, our experiments using HDAC mutants demonstrated that PMA greatly reduces nuclear import. PMA treatment repressed the NLS activity in a mannermore » dependent on 14-3-3 binding. These results suggest that nuclear HDAC4 is not tethered in the nucleus, but instead shuttles between the nucleus and the cytoplasm. Phosphorylation-induced 14-3-3 binding biases the balance of nucleo-cytoplasmic shuttling toward the cytoplasm by inhibiting nuclear import.« less

Interaction of acute-phase-inducible and liver-enriched nuclear factors with the promoter region of the mouse alpha sub 1 -acid glycoprotein gene-1

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

Alam, T.; Papaconstantinou, J.

1992-02-25

The synthesis and secretion of several acute-phase proteins increases markedly following physiological stress. {alpha}{sub 1}-Acid glycoprotein (AGP), a major acute-phase reactant made by the liver, is strongly induced by inflammatory agents such as lipopolysaccharide (LPS). Nuclear run-on assay showed a 17-fold increase in the rate of AGP transcription 4 h following LPS injection. DNase I footprinting assays revealed multiple protein binding domains in the mouse AGP-1 promoter region. Region B ({minus}104 to {minus}91) is protected by a liver-enriched transcription factor that is heat labile and in limiting quantity. An adjacent region, C ({minus}125 to {minus}104), is well-protected by nuclear extractsmore » from hepatocytes. Electrophoretic mobility shift assays indicated that only one DNA-protein complex can form with an oligonucleotide corresponding to region B. However, nuclear proteins from untreated mouse liver can form three strong complexes (C1, C2, and C3) and a weak one (C4) with oligonucleotide C. An acute-phase-inducible DNA-binding protein (AP-DBP) forms complex 4. A dramatic increase (over 11-fold) in AP-DBP binding activity is seen with nuclear proteins from LPS-stimulated animals. Interestingly, AP-DBP, a heat-stable factor, can form heterodimers with the transcription factor CCAAT/enhancer binding protein (C/EBP). Furthermore, purified C/EBP also binds avidly to region C. The studies indicate that several liver-enriched nuclear factors can interact with AGP-1 promoter and that AP-DBP binds to the AGP-1 promoter with high affinity only during the acute-phase induction.« less

Evidence that Poly(A) Binding Protein C1 Binds Nuclear Pre-mRNA Poly(A) Tails

PubMed Central

Hosoda, Nao; Lejeune, Fabrice; Maquat, Lynne E.

2006-01-01

In mammalian cells, poly(A) binding protein C1 (PABP C1) has well-known roles in mRNA translation and decay in the cytoplasm. However, PABPC1 also shuttles in and out of the nucleus, and its nuclear function is unknown. Here, we show that PABPC1, like the major nuclear poly(A) binding protein PABPN1, associates with nuclear pre-mRNAs that are polyadenylated and intron containing. PABPC1 does not bind nonpolyadenylated histone mRNA, indicating that the interaction of PABPC1 with pre-mRNA requires a poly(A) tail. Consistent with this conclusion, UV cross-linking results obtained using intact cells reveal that PABPC1 binds directly to pre-mRNA poly(A) tails in vivo. We also show that PABPC1 immunopurifies with poly(A) polymerase, suggesting that PABPC1 is acquired by polyadenylated transcripts during poly(A) tail synthesis. Our findings demonstrate that PABPC1 associates with polyadenylated transcripts earlier in mammalian mRNA biogenesis than previously thought and offer insights into the mechanism by which PABPC1 is recruited to newly synthesized poly(A). Our results are discussed in the context of pre-mRNA processing and stability and mRNA trafficking and the pioneer round of translation. PMID:16581783

Library Binding Manual. Revised Edition.

ERIC Educational Resources Information Center

Lakhanpal, S. K.

This procedural manual is designed to be used in bindery sections in public, university and special libraries. It briefly discusses these general matters: administrative control; selection of a binder; when and what to bind; conventional binding; routines; missing issues; schedule for shipments; temporary binding; rare books, maps and newspapers;…

Nuclear matter from effective quark-quark interaction.

PubMed

Baldo, M; Fukukawa, K

2014-12-12

We study neutron matter and symmetric nuclear matter with the quark-meson model for the two-nucleon interaction. The Bethe-Bruckner-Goldstone many-body theory is used to describe the correlations up to the three hole-line approximation with no extra parameters. At variance with other nonrelativistic realistic interactions, the three hole-line contribution turns out to be non-negligible and to have a substantial saturation effect. The saturation point of nuclear matter, the compressibility, the symmetry energy, and its slope are within the phenomenological constraints. Since the interaction also reproduces fairly well the properties of the three-nucleon system, these results indicate that the explicit introduction of the quark degrees of freedom within the considered constituent quark model is expected to reduce the role of three-body forces.

Nuclear localization of the DNA repair scaffold XRCC1: Uncovering the functional role of a bipartite NLS

DOE PAGES

Kirby, Thomas W.; Gassman, Natalie R.; Smith, Cassandra E.; ...

2015-08-25

We have characterized the nuclear localization signal (NLS) of XRCC1 structurally using X-ray crystallography and functionally using fluorescence imaging. Crystallography and binding studies confirm the bipartite nature of the XRCC1 NLS interaction with Importin α (Impα) in which the major and minor binding motifs are separated by >20 residues, and resolve previous inconsistent determinations. Binding studies of peptides corresponding to the bipartite NLS, as well as its major and minor binding motifs, to both wild-type and mutated forms of Impα reveal pronounced cooperative binding behavior that is generated by the proximity effect of the tethered major and minor motifs ofmore » the NLS. The cooperativity stems from the increased local concentration of the second motif near its cognate binding site that is a consequence of the stepwise binding behavior of the bipartite NLS. We predict that the stepwise dissociation of the NLS from Impα facilitates unloading by providing a partially complexed intermediate that is available for competitive binding by Nup50 or the Importin β binding domain. This behavior gives a basis for meeting the intrinsically conflicting high affinity and high flux requirements of an efficient nuclear transport system.« less

Tensor Fermi liquid parameters in nuclear matter from chiral effective field theory

NASA Astrophysics Data System (ADS)

Holt, J. W.; Kaiser, N.; Whitehead, T. R.

2018-05-01

We compute from chiral two- and three-body forces the complete quasiparticle interaction in symmetric nuclear matter up to twice nuclear matter saturation density. Second-order perturbative contributions that account for Pauli blocking and medium polarization are included, allowing for an exploration of the full set of central and noncentral operator structures permitted by symmetries and the long-wavelength limit. At the Hartree-Fock level, the next-to-next-to-leading order three-nucleon force contributes to all noncentral interactions, and their strengths grow approximately linearly with the nucleon density up to that of saturated nuclear matter. Three-body forces are shown to enhance the already strong proton-neutron effective tensor interaction, while the corresponding like-particle tensor force remains small. We also find a large isovector cross-vector interaction but small center-of-mass tensor interactions in the isoscalar and isovector channels. The convergence of the expansion of the noncentral quasiparticle interaction in Landau parameters and Legendre polynomials is studied in detail.

Quark-Meson-Coupling (QMC) model for finite nuclei, nuclear matter and beyond

NASA Astrophysics Data System (ADS)

Guichon, P. A. M.; Stone, J. R.; Thomas, A. W.

2018-05-01

The Quark-Meson-Coupling model, which self-consistently relates the dynamics of the internal quark structure of a hadron to the relativistic mean fields arising in nuclear matter, provides a natural explanation to many open questions in low energy nuclear physics, including the origin of many-body nuclear forces and their saturation, the spin-orbit interaction and properties of hadronic matter at a wide range of densities up to those occurring in the cores of neutron stars. Here we focus on four aspects of the model (i) a full comprehensive survey of the theory, including the latest developments, (ii) extensive application of the model to ground state properties of finite nuclei and hypernuclei, with a discussion of similarities and differences between the QMC and Skyrme energy density functionals, (iii) equilibrium conditions and composition of hadronic matter in cold and warm neutron stars and their comparison with the outcome of relativistic mean-field theories and, (iv) tests of the fundamental idea that hadron structure changes in-medium.

Examination of N*(1535 ) as a probe to observe the partial restoration of chiral symmetry in nuclear matter

NASA Astrophysics Data System (ADS)

Suenaga, Daiki

2018-04-01

I investigate modifications of mass and decay width of N*(1535 ) in nuclear matter in a chiral symmetric way. The nucleon and N*(1535 ) are introduced by a parity doublet model, and nuclear matter is constructed by one-loop diagrams of the nucleon and N*(1535 ) . The decay width of N*(1535 ) is studied with respect to chiral symmetry. My calculations show that the partial width of ΓN*→N π is slightly broadened by a collisional broadening and that of ΓN*→N η is drastically suppressed at density. As a result, the total decay width Γtot gets small at density. These modifications, especially the drastic narrowing of partial width of ΓN*→N η, together with the drop in mass of N*(1535 ) , provide experiments for observing the partial restoration of chiral symmetry in nuclear matter by means of N*(1535 ) resonance with useful information.

Nuclear Matter Effects on ϕ Production in Cu+Au Collisions at √{s}NN = 200 GeV with the PHENIX Muon Arms at RHIC

NASA Astrophysics Data System (ADS)

Jezghani, Margaret; Phenix Collaboration

2015-10-01

A major objective in the field of high-energy nuclear physics is to quantify and characterize the quark-gluon plasma formed in relativistic heavy-ion collisions. The ϕ meson is an excellent probe for studying this hot and dense state of nuclear matter due to its very short lifetime, and the absence of strong interactions between muons and the surrounding hot hadronic matter makes the ϕ to dimuon decay channel particularly interesting. Since the ϕ meson is composed of a strange and antistrange quark, its nuclear modification in heavy-ion collisions may provide insight on strangeness enhancement in-medium. Additionally, the rapidity dependence of ϕ production in asymmetric heavy-ion collisions provides a unique means to study the entanglement of hot and cold nuclear matter effects. In this talk, we present the measurement of ϕ meson production and nuclear modification in asymmetric Cu+Au heavy-ion collisions at √{s}NN = 200 GeV at both forward (Cu-going direction) and backward (Au-going direction) rapidities. This material is based upon work supported by the U.S. Department of Energy (DOE), Office of Science, Office of Workforce Development for Teachers and Scientists, Office of Science Graduate Student Research (SCGSR) award program.

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

Bozorgnia, Nassim; Gelmini, Graciela B.; Gondolo, Paolo, E-mail: n.bozorgnia@uva.nl, E-mail: gelmini@physics.ucla.edu, E-mail: paolo@physics.utah.edu

Directional dark matter detection attempts to measure the direction of motion of nuclei recoiling after having interacted with dark matter particles in the halo of our Galaxy. Due to Earth's motion with respect to the Galaxy, the dark matter flux is concentrated around a preferential direction. An anisotropy in the recoil direction rate is expected as an unmistakable signature of dark matter. The average nuclear recoil direction is expected to coincide with the average direction of dark matter particles arriving to Earth. Here we point out that for a particular type of dark matter, inelastic exothermic dark matter, the meanmore » recoil direction as well as a secondary feature, a ring of maximum recoil rate around the mean recoil direction, could instead be opposite to the average dark matter arrival direction. Thus, the detection of an average nuclear recoil direction opposite to the usually expected direction would constitute a spectacular experimental confirmation of this type of dark matter.« less

Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors.

PubMed

Milles, Sigrid; Mercadante, Davide; Aramburu, Iker Valle; Jensen, Malene Ringkjøbing; Banterle, Niccolò; Koehler, Christine; Tyagi, Swati; Clarke, Jane; Shammas, Sarah L; Blackledge, Martin; Gräter, Frauke; Lemke, Edward A

2015-10-22

The mechanisms by which intrinsically disordered proteins engage in rapid and highly selective binding is a subject of considerable interest and represents a central paradigm to nuclear pore complex (NPC) function, where nuclear transport receptors (NTRs) move through the NPC by binding disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Combining single-molecule fluorescence, molecular simulations, and nuclear magnetic resonance, we show that a rapidly fluctuating FG-Nup populates an ensemble of conformations that are prone to bind NTRs with near diffusion-limited on rates, as shown by stopped-flow kinetic measurements. This is achieved using multiple, minimalistic, low-affinity binding motifs that are in rapid exchange when engaging with the NTR, allowing the FG-Nup to maintain an unexpectedly high plasticity in its bound state. We propose that these exceptional physical characteristics enable a rapid and specific transport mechanism in the physiological context, a notion supported by single molecule in-cell assays on intact NPCs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Plasticity of an Ultrafast Interaction between Nucleoporins and Nuclear Transport Receptors

PubMed Central

Milles, Sigrid; Mercadante, Davide; Aramburu, Iker Valle; Jensen, Malene Ringkjøbing; Banterle, Niccolò; Koehler, Christine; Tyagi, Swati; Clarke, Jane; Shammas, Sarah L.; Blackledge, Martin; Gräter, Frauke; Lemke, Edward A.

2015-01-01

Summary The mechanisms by which intrinsically disordered proteins engage in rapid and highly selective binding is a subject of considerable interest and represents a central paradigm to nuclear pore complex (NPC) function, where nuclear transport receptors (NTRs) move through the NPC by binding disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Combining single-molecule fluorescence, molecular simulations, and nuclear magnetic resonance, we show that a rapidly fluctuating FG-Nup populates an ensemble of conformations that are prone to bind NTRs with near diffusion-limited on rates, as shown by stopped-flow kinetic measurements. This is achieved using multiple, minimalistic, low-affinity binding motifs that are in rapid exchange when engaging with the NTR, allowing the FG-Nup to maintain an unexpectedly high plasticity in its bound state. We propose that these exceptional physical characteristics enable a rapid and specific transport mechanism in the physiological context, a notion supported by single molecule in-cell assays on intact NPCs. PMID:26456112

Properties of ΣQ*, ΞQ* and ΩQ* heavy baryons in cold nuclear matter

NASA Astrophysics Data System (ADS)

Azizi, K.; Er, N.

2018-02-01

The in-medium properties of the heavy spin-3/2 ΣQ*, ΞQ* and ΩQ* baryons with Q being b or c quark are investigated. The shifts in some spectroscopic parameters of these particles due to the saturated cold nuclear matter are calculated. The variations of those parameters with respect to the changes in the density of the cold nuclear medium are studied, as well. It is observed that the parameters of ΣQ* baryons are considerably affected by the nuclear matter compared to the ΞQ* and ΩQ* particles that roughly do not see the medium. The results obtained may be used in analyses of the data to be provided by the in-medium experiments like PANDA.

Probing Sub-GeV Dark Matter with Conventional Detectors.

PubMed

Kouvaris, Chris; Pradler, Josef

2017-01-20

The direct detection of dark matter particles with mass below the GeV scale is hampered by soft nuclear recoil energies and finite detector thresholds. For a given maximum relative velocity, the kinematics of elastic dark matter nucleus scattering sets a principal limit on detectability. Here, we propose to bypass the kinematic limitations by considering the inelastic channel of photon emission from bremsstrahlung in the nuclear recoil. Our proposed method allows us to set the first limits on dark matter below 500 MeV in the plane of dark matter mass and cross section with nucleons. In situations where a dark-matter-electron coupling is suppressed, bremsstrahlung may constitute the only path to probe low-mass dark matter awaiting new detector technologies with lowered recoil energy thresholds.

Actin, actin-binding proteins, and actin-related proteins in the nucleus.

PubMed

Kristó, Ildikó; Bajusz, Izabella; Bajusz, Csaba; Borkúti, Péter; Vilmos, Péter

2016-04-01

Extensive research in the past decade has significantly broadened our view about the role actin plays in the life of the cell and added novel aspects to actin research. One of these new aspects is the discovery of the existence of nuclear actin which became evident only recently. Nuclear activities including transcriptional activation in the case of all three RNA polymerases, editing and nuclear export of mRNAs, and chromatin remodeling all depend on actin. It also became clear that there is a fine-tuned equilibrium between cytoplasmic and nuclear actin pools and that this balance is ensured by an export-import system dedicated to actin. After over half a century of research on conventional actin and its organizing partners in the cytoplasm, it was also an unexpected finding that the nucleus contains more than 30 actin-binding proteins and new classes of actin-related proteins which are not able to form filaments but had evolved nuclear-specific functions. The actin-binding and actin-related proteins in the nucleus have been linked to RNA transcription and processing, nuclear transport, and chromatin remodeling. In this paper, we attempt to provide an overview of the wide range of information that is now available about actin, actin-binding, and actin-related proteins in the nucleus.

Copper(II) binding by dissolved organic matter: Importance of the copper-to-dissolved organic matter ratio and implications for the Biotic Ligand Model

USGS Publications Warehouse

Craven, Alison M.; Aiken, George R.; Ryan, Joseph N.

2012-01-01

The ratio of copper to dissolved organic matter (DOM) is known to affect the strength of copper binding by DOM, but previous methods to determine the Cu2+–DOM binding strength have generally not measured binding constants over the same Cu:DOM ratios. In this study, we used a competitive ligand exchange–solid-phase extraction (CLE-SPE) method to determine conditional stability constants for Cu2+–DOM binding at pH 6.6 and 0.01 M ionic strength over a range of Cu:DOM ratios that bridge the detection windows of copper-ion-selective electrode and voltammetry measurements. As the Cu:DOM ratio increased from 0.0005 to 0.1 mg of Cu/mg of DOM, the measured conditional binding constant (cKCuDOM) decreased from 1011.5 to 105.6 M–1. A comparison of the binding constants measured by CLE-SPE with those measured by copper-ion-selective electrode and voltammetry demonstrates that the Cu:DOM ratio is an important factor controlling Cu2+–DOM binding strength even for DOM isolates of different types and different sources and for whole water samples. The results were modeled with Visual MINTEQ and compared to results from the biotic ligand model (BLM). The BLM was found to over-estimate Cu2+ at low total copper concentrations and under-estimate Cu2+ at high total copper concentrations.

Characterization of the Binding of a Potent Synthetic Androgen, Methyltrienolone, to Human Tissues

PubMed Central

Menon, Mani; Tananis, Catherine E.; Hicks, L. Louise; Hawkins, Edward F.; McLoughlin, Martin G.; Walsh, Patrick C.

1978-01-01

The potent synthetic androgen methytrienolone (R 1881), which does not bind to serum proteins, was utilized to characterize binding to receptors in human androgen responsive tissues. Cytosol extracts prepared from hypertrophic prostates (BPH) were utilized as the source of receptor for the initial studies. High affinity binding was detected in the cytosol of 29 of 30 samples of BPH (average number of binding sites, 45.8±4.7 fmol/mg of protein; dissociation constant, 0.9±0.2 nM). This binding had the characteristics of a receptor: heat lability, precipitability by 0-33% ammonium sulfate and by protamine sulfate, and 8S sedimentation coefficient. High affinity binding was also detected in cytosol prepared from seminal vesicle, epididymis, and genital skin but not in non-genital skin or muscle. However, similar binding was demonstrated in the cytosol of human uterus. The steroid specificities of binding to the cytosol of male tissues of accessory reproduction and of uterus were similar in that progestational agents were more effective competitors than natural androgens. Binding specificities in cytosol prepared from genital skin were distinctly different and were similar to those of ventral prostate from the castrated rat in that dihydrotestosterone was much more potent than progestins in competition. Thus binding of R 1881 to the cytosol of prostate, epididymis, and seminal vesicle has some characteristics of binding to a progesterone receptor. When the nuclear extract from BPH was analyzed, high affinity binding was demonstrated that conformed to the specificities of binding to an androgen receptor. Here dihydrotestosterone was a more potent competitor than progestational agents. Similar patterns of binding were detected in the crude nuclear extracts from seminal vesicle, epididymis, and genital skin but not in uterus, muscle, or non-genital skin. We conclude that the androgen receptor is not demonstrable in the cytosol of prostate, epididymis, or seminal vesicle of non-castrated men but can be measured in the cytosol of genital skin and the nuclear extracts of androgen responsive tissues. Because steroid hormones exert their major influence within the nucleus of target tissues, the measurement of nuclear receptor may provide valuable insight into the regulation of growth of target tissues. PMID:73547

Energy-range relations for hadrons in nuclear matter

NASA Technical Reports Server (NTRS)

Strugalski, Z.

1985-01-01

Range-energy relations for hadrons in nuclear matter exist similarly to the range-energy relations for charged particles in materials. When hadrons of GeV kinetic energies collide with atomic nuclei massive enough, events occur in which incident hadron is stopped completely inside the target nucleus without causing particle production - without pion production in particular. The stoppings are always accompanied by intensive emission of nucleons with kinetic energy from about 20 up to about 400 MeV. It was shown experimentally that the mean number of the emitted nucleons is a measure of the mean path in nuclear matter in nucleons on which the incident hadrons are stopped.

Nuclear matter compressibility from isoscalar giant monopole resonance

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

Shlomo, S.; Youngblood, D.H.

1993-02-01

We examine the status of the nuclear matter compressibility [ital K][sub nm] obtained from experimental data of the strength distribution of the giant monopole resonance in nuclei and employing a least-squares fit to a semiempirical expansion of the nucleus compressibility [ital K][sub [ital A

Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the Pacific oyster and in silico binding to environmental chemicals

PubMed Central

Vogeler, Susanne; Galloway, Tamara S.; Isupov, Michail

2017-01-01

Disruption of nuclear receptors, a transcription factor superfamily regulating gene expression in animals, is one proposed mechanism through which pollution causes effects in aquatic invertebrates. Environmental pollutants have the ability to interfere with the receptor’s functions through direct binding and inducing incorrect signals. Limited knowledge of invertebrate endocrinology and molecular regulatory mechanisms, however, impede the understanding of endocrine disruptive effects in many aquatic invertebrate species. Here, we isolated three nuclear receptors of the Pacific oyster, Crassostrea gigas: two isoforms of the retinoid X receptor, CgRXR-1 and CgRXR-2, a retinoic acid receptor ortholog CgRAR, and a peroxisome proliferator-activated receptor ortholog CgPPAR. Computer modelling of the receptors based on 3D crystal structures of human proteins was used to predict each receptor’s ability to bind to different ligands in silico. CgRXR showed high potential to bind and be activated by 9-cis retinoic acid and the organotin tributyltin (TBT). Computer modelling of CgRAR revealed six residues in the ligand binding domain, which prevent the successful interaction with natural and synthetic retinoid ligands. This supports an existing theory of loss of retinoid binding in molluscan RARs. Modelling of CgPPAR was less reliable due to high discrepancies in sequence to its human ortholog. Yet, there are suggestions of binding to TBT, but not to rosiglitazone. The effect of potential receptor ligands on early oyster development was assessed after 24h of chemical exposure. TBT oxide (0.2μg/l), all-trans retinoic acid (ATRA) (0.06 mg/L) and perfluorooctanoic acid (20 mg/L) showed high effects on development (>74% abnormal developed D-shelled larvae), while rosiglitazone (40 mg/L) showed no effect. The results are discussed in relation to a putative direct (TBT) disruption effect on nuclear receptors. The inability of direct binding of ATRA to CgRAR suggests either a disruptive effect through a pathway excluding nuclear receptors or an indirect interaction. Our findings provide valuable information on potential mechanisms of molluscan nuclear receptors and the effects of environmental pollution on aquatic invertebrates. PMID:28426724

Electron-ion collider: The next QCD frontier: Understanding the glue that binds us all

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

Accardi, A.; Albacete, J. L.; Anselmino, M.

This White Paper presents the science case of an Electron-Ion Collider (EIC), focused on the structure and interactions of gluon-dominated matter, with the intent to articulate it to the broader nuclear science community. It was commissioned by the managements of Brookhaven National Laboratory (BNL) and Thomas Jefferson National Accelerator Facility (JLab) with the objective of presenting a summary of scientific opportunities and goals of the EIC as a follow-up to the 2007 NSAC Long Range plan. This document is a culmination of a community-wide effort in nuclear science following a series of workshops on EIC physics over the past decadesmore » and, in particular, the focused ten-week program on “Gluons and quark sea at high energies” at the Institute for Nuclear Theory in Fall 2010. It contains a brief description of a few golden physics measurements along with accelerator and detector concepts required to achieve them. It has been benefited profoundly from inputs by the users’ communities of BNL and JLab. Furthermore, this White Paper offers the promise to propel the QCD science program in the US, established with the CEBAF accelerator at JLab and the RHIC collider at BNL, to the next QCD frontier.« less

Electron-ion collider: The next QCD frontier: Understanding the glue that binds us all

DOE PAGES

Accardi, A.; Albacete, J. L.; Anselmino, M.; ...

2016-09-08

This White Paper presents the science case of an Electron-Ion Collider (EIC), focused on the structure and interactions of gluon-dominated matter, with the intent to articulate it to the broader nuclear science community. It was commissioned by the managements of Brookhaven National Laboratory (BNL) and Thomas Jefferson National Accelerator Facility (JLab) with the objective of presenting a summary of scientific opportunities and goals of the EIC as a follow-up to the 2007 NSAC Long Range plan. This document is a culmination of a community-wide effort in nuclear science following a series of workshops on EIC physics over the past decadesmore » and, in particular, the focused ten-week program on “Gluons and quark sea at high energies” at the Institute for Nuclear Theory in Fall 2010. It contains a brief description of a few golden physics measurements along with accelerator and detector concepts required to achieve them. It has been benefited profoundly from inputs by the users’ communities of BNL and JLab. Furthermore, this White Paper offers the promise to propel the QCD science program in the US, established with the CEBAF accelerator at JLab and the RHIC collider at BNL, to the next QCD frontier.« less

From the crust to the core of neutron stars on a microscopic basis

NASA Astrophysics Data System (ADS)

Baldo, M.; Burgio, G. F.; Centelles, M.; Sharma, B. K.; Viñas, X.

2014-09-01

Within a microscopic approach the structure of Neutron Stars is usually studied by modelling the homogeneous nuclear matter of the core by a suitable Equation of State, based on a many-body theory, and the crust by a functional based on a more phenomenological approach. We present the first calculation of Neutron Star overall structure by adopting for the core an Equation of State derived from the Brueckner-Hartree-Fock theory and for the crust, including the pasta phase, an Energy Density Functional based on the same Equation of State, and which is able to describe accurately the binding energy of nuclei throughout the mass table. Comparison with other approaches is discussed. The relevance of the crust Equation of State for the Neutron Star radius is particularly emphasised.

Massive GGAAs in genomic repetitive sequences serve as a nuclear reservoir of NF-κB.

PubMed

Wu, Jian; Wang, Qiao; Dai, Wei; Wang, Wei; Yue, Ming; Wang, Jinke

2018-04-13

Nuclear factor κB (NF-κB) is a DNA-binding transcription factor. Characterizing its genomic binding sites is crucial for understanding its gene regulatory function and mechanism in cells. This study characterized the binding sites of NF-κB RelA/p65 in the tumor neurosis factor-α (TNFα) stimulated HeLa cells by a precise chromatin immunoprecipitation-sequencing (ChIP-seq). The results revealed that NF-κB binds nontraditional motifs (nt-motifs) containing conserved GGAA quadruplet. Moreover, nt-motifs mainly distribute in the peaks nearby centromeres that contain a larger number of repetitive elements such as satellite, simple repeats and short interspersed nuclear elements (SINEs). This intracellular binding pattern was then confirmed by the in vitro detection, indicating that NF-κB dimers can bind the nontraditional κB (nt-κB) sites with low affinity. However, this binding hardly activates transcription. This study thus deduced that NF-κB binding nt-motifs may realize functions other than gene regulation as NF-κB binding traditional motifs (t-motifs). To testify the deduction, many ChIP-seq data of other cell lines were then analyzed. The results indicate that NF-κB binding nt-motifs is also widely present in other cells. The ChIP-seq data analysis also revealed that nt-motifs more widely distribute in the peaks with low-fold enrichment. Importantly, it was also found that NF-κB binding nt-motifs is mainly present in the resting cells, whereas NF-κB binding t-motifs is mainly present in the stimulated cells. Astonishingly, no known function was enriched by the gene annotation of nt-motif peaks. Based on these results, this study proposed that the nt-κB sites that extensively distribute in larger numbers of repeat elements function as a nuclear reservoir of NF-κB. The nuclear NF-κB proteins stored at nt-κB sites in the resting cells may be recruited to the t-κB sites for regulating its target genes upon stimulation. Copyright © 2018 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Profiles of embryonic nuclear protein binding to the proximal promoter region of the soybean β-conglycinin α subunit gene.

PubMed

Yoshino, M; Tsutsumi, K; Kanazawa, A

2015-01-01

β-Conglycinin, a major component of seed storage protein in soybean, comprises three subunits: α, α' and β. The expression of genes for these subunits is strictly controlled during embryogenesis. The proximal promoter region up to 245 bp upstream of the transcription start site of the α subunit gene sufficiently confers spatial and temporal control of transcription in embryos. Here, the binding profile of nuclear proteins in the proximal promoter region of the α subunit gene was analysed. DNase I footprinting analysis indicated binding of proteins to the RY element and DNA regions including box I, a region conserved in cognate gene promoters. An electrophoretic mobility shift assay (EMSA) using different portions of box I as a probe revealed that multiple portions of box I bind to nuclear proteins. In addition, an EMSA using nuclear proteins extracted from embryos at different developmental stages indicated that the levels of major DNA-protein complexes on box I increased during embryo maturation. These results are consistent with the notion that box I is important for the transcriptional control of seed storage protein genes. Furthermore, the present data suggest that nuclear proteins bind to novel motifs in box I including 5'-TCAATT-3' rather than to predicted cis-regulatory elements. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Low Energy Nuclear Reactions: 2007 Update

NASA Astrophysics Data System (ADS)

Krivit, Steven B.

2007-03-01

This paper presents an overview of low energy nuclear reactions, a subset of the field of condensed matter nuclear science. Condensed matter nuclear science studies nuclear effects in and/or on condensed matter, including low energy nuclear reactions, an entirely new branch of science that gained widespread attention and notoriety beginning in 1989 with the announcement of a previously unrecognized source of energy by Martin Fleischmann and Stanley Pons that came to be known as cold fusion. Two branches of LENR are recognized. The first includes a set of reactions like those observed by Fleischmann and Pons that use palladium and deuterium and yield excess heat and helium-4. Numerous mechanisms have been proposed to explain these reactions, however there is no consensus for, or general acceptance of, any of the theories. The claim of fusion is still considered speculative and, as such, is not an ideal term for this work. The other branch is a wide assortment of nuclear reactions that may occur with either hydrogen or deuterium. Anomalous nuclear transmutations are reported that involve light as well as heavy elements. The significant questions that face this field of research are: 1) Are LENRs a genuine nuclear reaction? 2) If so, is there a release of excess energy? 3) If there is, is the energy release cost-effective?

Iron-Inducible Nuclear Translocation of a Myb3 Transcription Factor in the Protozoan Parasite Trichomonas vaginalis

PubMed Central

Hsu, Hong-Ming; Lee, Yu; Indra, Dharmu; Wei, Shu-Yi; Liu, Hsing-Wei; Chang, Lung-Chun; Chen, Chinpan; Ong, Shiou-Jeng

2012-01-01

In Trichomonas vaginalis, a novel nuclear localization signal spanning the folded R2R3 DNA-binding domain of a Myb2 protein was previously identified. To study whether a similar signal is used for nuclear translocation by other Myb proteins, nuclear translocation of Myb3 was examined in this report. When overexpressed, hemagglutinin-tagged Myb3 was localized to nuclei of transfected cells, with a cellular distribution similar to that of endogenous Myb3. Fusion to a bacterial tetracycline repressor, R2R3, of Myb3 that spans amino acids (aa) 48 to 156 was insufficient for nuclear translocation of the fusion protein, unless its C terminus was extended to aa 167. The conserved isoleucine in helix 2 of R2R3, which is important for Myb2's structural integrity in maintaining DNA-binding activity and nuclear translocation, was also vital for the former activity of Myb3, but less crucial for the latter. Sequential nuclear influx and efflux of Myb3, which require further extension of the nuclear localization signal to aa 180, were immediately induced after iron repletion. Sequence elements that regulate nuclear translocation with cytoplasmic retention, nuclear influx, and nuclear efflux were identified within the C-terminal tail. These results suggest that the R2R3 DNA-binding domain also serves as a common module for the nuclear translocation of both Myb2 and Myb3, but there are intrinsic differences between the two nuclear localization signals. PMID:23042127

Transport Properties in Nuclear Pasta

NASA Astrophysics Data System (ADS)

Caplan, Matthew; Horowitz, Charles; Berry, Donald; da Silva Schneider, Andre

2016-09-01

At the base of the inner crust of neutron stars, where matter is near the nuclear saturation density, nuclear matter arranges itself into exotic shapes such as cylinders and slabs, called `nuclear pasta.' Lepton scattering from these structures may govern the transport properties of the inner crust; electron scattering from protons in the pasta determines the thermal and electrical conductivity, as well as the shear viscosity of the inner crust. These properties may vary in pasta structures which form at various densities, temperatures, and proton fractions. In this talk, we report on our calculations of lepton transport in nuclear pasta and the implication for neutron star observables.

Physics division annual report 2006.

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

Glover, J.; Physics

2008-02-28

This report highlights the activities of the Physics Division of Argonne National Laboratory in 2006. The Division's programs include the operation as a national user facility of ATLAS, the Argonne Tandem Linear Accelerator System, research in nuclear structure and reactions, nuclear astrophysics, nuclear theory, investigations in medium-energy nuclear physics as well as research and development in accelerator technology. The mission of nuclear physics is to understand the origin, evolution and structure of baryonic matter in the universe--the core of matter, the fuel of stars, and the basic constituent of life itself. The Division's research focuses on innovative new ways tomore » address this mission.« less

75 FR 70042 - In the Matter of All Power Reactor Licensees and Research Reactor Licensees Who Transport Spent...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

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Tracer Kinetic Analysis of (S)-¹⁸F-THK5117 as a PET Tracer for Assessing Tau Pathology.

PubMed

Jonasson, My; Wall, Anders; Chiotis, Konstantinos; Saint-Aubert, Laure; Wilking, Helena; Sprycha, Margareta; Borg, Beatrice; Thibblin, Alf; Eriksson, Jonas; Sörensen, Jens; Antoni, Gunnar; Nordberg, Agneta; Lubberink, Mark

2016-04-01

Because a correlation between tau pathology and the clinical symptoms of Alzheimer disease (AD) has been hypothesized, there is increasing interest in developing PET tracers that bind specifically to tau protein. The aim of this study was to evaluate tracer kinetic models for quantitative analysis and generation of parametric images for the novel tau ligand (S)-(18)F-THK5117. Nine subjects (5 with AD, 4 with mild cognitive impairment) received a 90-min dynamic (S)-(18)F-THK5117 PET scan. Arterial blood was sampled for measurement of blood radioactivity and metabolite analysis. Volume-of-interest (VOI)-based analysis was performed using plasma-input models; single-tissue and 2-tissue (2TCM) compartment models and plasma-input Logan and reference tissue models; and simplified reference tissue model (SRTM), reference Logan, and SUV ratio (SUVr). Cerebellum gray matter was used as the reference region. Voxel-level analysis was performed using basis function implementations of SRTM, reference Logan, and SUVr. Regionally averaged voxel values were compared with VOI-based values from the optimal reference tissue model, and simulations were made to assess accuracy and precision. In addition to 90 min, initial 40- and 60-min data were analyzed. Plasma-input Logan distribution volume ratio (DVR)-1 values agreed well with 2TCM DVR-1 values (R(2)= 0.99, slope = 0.96). SRTM binding potential (BP(ND)) and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 (R(2)= 1.00, slope ≈ 1.00) whereas SUVr(70-90)-1 values correlated less well and overestimated binding. Agreement between parametric methods and SRTM was best for reference Logan (R(2)= 0.99, slope = 1.03). SUVr(70-90)-1 values were almost 3 times higher than BP(ND) values in white matter and 1.5 times higher in gray matter. Simulations showed poorer accuracy and precision for SUVr(70-90)-1 values than for the other reference methods. SRTM BP(ND) and reference Logan DVR-1 values were not affected by a shorter scan duration of 60 min. SRTM BP(ND) and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 values. VOI-based data analyses indicated robust results for scan durations of 60 min. Reference Logan generated quantitative (S)-(18)F-THK5117 DVR-1 parametric images with the greatest accuracy and precision and with a much lower white-matter signal than seen with SUVr(70-90)-1 images. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The neutrino opacity of neutron rich matter

NASA Astrophysics Data System (ADS)

Alcain, P. N.; Dorso, C. O.

2017-05-01

The study of neutron rich matter, present in neutron star, proto-neutron stars and core-collapse supernovae, can lead to further understanding of the behavior of nuclear matter in highly asymmetric nuclei. Heterogeneous structures are expected to exist in these systems, often referred to as nuclear pasta. We have carried out a systematic study of neutrino opacity for different thermodynamic conditions in order to assess the impact that the structure has on it. We studied the dynamics of the neutrino opacity of the heterogeneous matter at different thermodynamic conditions with semiclassical molecular dynamics model already used to study nuclear multifragmentation. For different densities, proton fractions and temperature, we calculate the very long range opacity and the cluster distribution. The neutrino opacity is of crucial importance for the evolution of the core-collapse supernovae and the neutrino scattering.

49 CFR 1109.3 - Confidentiality in ADR Matters

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Confidentiality in ADR Matters 1109.3 Section 1109... PROCEEDINGS AND THOSE IN WHICH THE BOARD IS A PARTY § 1109.3 Confidentiality in ADR Matters In all ADR matters... provisions of that Act (5 U.S.C. 574) shall bind the Board and all parties and neutrals in those ADR matters...

49 CFR 1109.3 - Confidentiality in ADR Matters

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Confidentiality in ADR Matters 1109.3 Section 1109... PROCEEDINGS AND THOSE IN WHICH THE BOARD IS A PARTY § 1109.3 Confidentiality in ADR Matters In all ADR matters... provisions of that Act (5 U.S.C. 574) shall bind the Board and all parties and neutrals in those ADR matters...

49 CFR 1109.3 - Confidentiality in ADR Matters

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Confidentiality in ADR Matters 1109.3 Section 1109... PROCEEDINGS AND THOSE IN WHICH THE BOARD IS A PARTY § 1109.3 Confidentiality in ADR Matters In all ADR matters... provisions of that Act (5 U.S.C. 574) shall bind the Board and all parties and neutrals in those ADR matters...

The VirD2 pilot protein of Agrobacterium-transferred DNA interacts with the TATA box-binding protein and a nuclear protein kinase in plants

PubMed Central

Bakó, László; Umeda, Masaaki; Tiburcio, Antonio F.; Schell, Jeff; Koncz, Csaba

2003-01-01

The bacterial virulence protein VirD2 plays an important role in nuclear import and chromosomal integration of Agrobacterium-transferred DNA in fungal, plant, animal, and human cells. Here we show that in nuclei of alfalfa cells, VirD2 interacts with and is phosphorylated by CAK2Ms, a conserved plant ortholog of cyclin-dependent kinase-activating kinases. CAK2Ms binds to and phosphorylates the C-terminal regulatory domain of RNA polymerase II largest subunit, which can recruit the TATA box-binding protein. VirD2 is found in tight association with the TATA box-binding protein in vivo. These results indicate that recognition of VirD2 is mediated by widely conserved nuclear factors in eukaryotes. PMID:12900506

Molecular simulations of polycation-DNA binding exploring the effect of peptide chemistry and sequence in nuclear localization sequence based polycations.

PubMed

Elder, Robert M; Jayaraman, Arthi

2013-10-10

Gene therapy relies on the delivery of DNA into cells, and polycations are one class of vectors enabling efficient DNA delivery. Nuclear localization sequences (NLS), cationic oligopeptides that target molecules for nuclear entry, can be incorporated into polycations to improve their gene delivery efficiency. We use simulations to study the effect of peptide chemistry and sequence on the DNA-binding behavior of NLS-grafted polycations by systematically mutating the residues in the grafts, which are based on the SV40 NLS (peptide sequence PKKKRKV). Replacing arginine (R) with lysine (K) reduces binding strength by eliminating arginine-DNA interactions, but placing R in a less hindered location (e.g., farther from the grafting point to the polycation backbone) has surprisingly little effect on polycation-DNA binding strength. Changing the positions of the hydrophobic proline (P) and valine (V) residues relative to the polycation backbone changes hydrophobic aggregation within the polycation and, consequently, changes the conformational entropy loss that occurs upon polycation-DNA binding. Since conformational entropy loss affects the free energy of binding, the positions of P and V in the grafts affect DNA binding affinity. The insight from this work guides synthesis of polycations with tailored DNA binding affinity and, in turn, efficient DNA delivery.

Molecular environment of stable iodine and radioiodine (129I) in natural organic matter: Evidence inferred from NMR and binding experiments at environmentally relevant concentrations

NASA Astrophysics Data System (ADS)

Xu, Chen; Zhong, Junyan; Hatcher, Patrick G.; Zhang, Saijin; Li, Hsiu-Ping; Ho, Yi-Fang; Schwehr, Kathleen A.; Kaplan, Daniel I.; Roberts, Kimberly A.; Brinkmeyer, Robin; Yeager, Chris M.; Santschi, Peter H.

2012-11-01

129I is a major by-product of nuclear fission and had become one of the major radiation risk drivers at Department of Energy (DOE) sites. 129I is present at elevated levels in the surface soils of the Savannah River Site (SRS) F-Area and was found to be bound predominantly to soil organic matter (SOM). Naturally bound 127I and 129I to sequentially extracted humic acids (HAs), fulvic acids (FAs) and a water extractable colloid (WEC) were measured in a 129I-contaminated wetland surface soil located on the SRS. WEC is a predominantly colloidal organic fraction obtained from soil re-suspension experiments to mimic the fraction that may be released during groundwater exfiltration, storm water or surface runoff events. For the first time, NMR techniques were applied to infer the molecular environment of naturally occurring stable iodine and radioiodine binding to SOM. Iodine uptake partitioning coefficients (Kd) by these SOM samples at ambient iodine concentrations were also measured and related to quantitative structural analyses by 13C DPMAS NMR and solution state 1H NMR on the eight humic acid fractions. By assessing the molecular environment of iodine, it was found that it was closely associated with the aromatic regions containing esterified products of phenolic and formic acids or other aliphatic carboxylic acids, amide functionalities, quinone-like structures activated by electron-donating groups (e.g., NH2), or a hemicellulose-lignin-like complex with phenyl-glycosidic linkages. However, FAs and WEC contained much greater concentrations of 127I or 129I than HAs. The contrasting radioiodine contents among the three different types of SOM (HAs, FAs and WEC) suggest that the iodine binding environment cannot be explained solely by the difference in the amount of their reactive binding sites. Instead, indirect evidence indicates that the macro-molecular conformation, such as the hydrophobic aliphatic periphery hindering the active aromatic cores and the hydrophilic polysaccharides favoring the access by hydrophilic iodine species, also influences iodine-SOM interactions.

Evolution of the nuclear receptor gene superfamily.

PubMed Central

Laudet, V; Hänni, C; Coll, J; Catzeflis, F; Stéhelin, D

1992-01-01

Nuclear receptor genes represent a large family of genes encoding receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. This family also contains genes encoding putative receptors for unknown ligands. Nuclear receptor gene products are composed of several domains important for transcriptional activation, DNA binding (C domain), hormone binding and dimerization (E domain). It is not known whether these genes have evolved through gene duplication from a common ancestor or if their different domains came from different independent sources. To test these possibilities we have constructed and compared the phylogenetic trees derived from two different domains of 30 nuclear receptor genes. The tree built from the DNA binding C domain clearly shows a common progeny of all nuclear receptors, which can be grouped into three subfamilies: (i) thyroid hormone and retinoic acid receptors, (ii) orphan receptors and (iii) steroid hormone receptors. The tree constructed from the central part of the E domain which is implicated in transcriptional regulation and dimerization shows the same distribution in three subfamilies but two groups of receptors are in a different position from that in the C domain tree: (i) the Drosophila knirps family genes have acquired very different E domains during evolution, and (ii) the vitamin D and ecdysone receptors, as well as the FTZ-F1 and the NGF1B genes, seem to have DNA binding and hormone binding domains belonging to different classes. These data suggest a complex evolutionary history for nuclear receptor genes in which gene duplication events and swapping between domains of different origins took place. PMID:1312460

Dark Matter Detection Using Helium Evaporation and Field Ionization

NASA Astrophysics Data System (ADS)

Maris, Humphrey J.; Seidel, George M.; Stein, Derek

2017-11-01

We describe a method for dark matter detection based on the evaporation of helium atoms from a cold surface and their subsequent detection using field ionization. When a dark matter particle scatters off a nucleus of the target material, elementary excitations (phonons or rotons) are produced. Excitations which have an energy greater than the binding energy of helium to the surface can result in the evaporation of helium atoms. We propose to detect these atoms by ionizing them in a strong electric field. Because the binding energy of helium to surfaces can be below 1 meV, this detection scheme opens up new possibilities for the detection of dark matter particles in a mass range down to 1 MeV /c2 .

Dark Matter Detection Using Helium Evaporation and Field Ionization.

PubMed

Maris, Humphrey J; Seidel, George M; Stein, Derek

2017-11-03

We describe a method for dark matter detection based on the evaporation of helium atoms from a cold surface and their subsequent detection using field ionization. When a dark matter particle scatters off a nucleus of the target material, elementary excitations (phonons or rotons) are produced. Excitations which have an energy greater than the binding energy of helium to the surface can result in the evaporation of helium atoms. We propose to detect these atoms by ionizing them in a strong electric field. Because the binding energy of helium to surfaces can be below 1 meV, this detection scheme opens up new possibilities for the detection of dark matter particles in a mass range down to 1  MeV/c^{2}.

Coherent photon scattering background in sub- GeV / c 2 direct dark matter searches

DOE PAGES

Robinson, Alan E.

2017-01-18

Here, proposed dark matter detectors with eV-scale sensitivities will detect a large background of atomic (nuclear) recoils from coherent photon scattering of MeV-scale photons. This background climbs steeply below ~10 eV, far exceeding the declining rate of low-energy Compton recoils. The upcoming generation of dark matter detectors will not be limited by this background, but further development of eV-scale and sub-eV detectors will require strategies, including the use of low nuclear mass target materials, to maximize dark matter sensitivity while minimizing the coherent photon scattering background.

The Exploration of Hot Nuclear Matter

NASA Astrophysics Data System (ADS)

Jacak, Barbara V.; Müller, Berndt

2012-07-01

When nuclear matter is heated beyond 2 trillion degrees, it becomes a strongly coupled plasma of quarks and gluons. Experiments using highly energetic collisions between heavy nuclei have revealed that this new state of matter is a nearly ideal, highly opaque liquid. A description based on string theory and black holes in five dimensions has made the quark-gluon plasma an archetypical strongly coupled quantum system. Open questions about the structure and theory of the quark-gluon plasma are under active investigation. Many of the insights are also relevant to ultracold fermionic atoms and strongly correlated condensed matter.

Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

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

Vognsen, Tina, E-mail: tv@farma.ku.dk; Kristensen, Ole, E-mail: ok@farma.ku.dk

2012-03-30

Highlights: Black-Right-Pointing-Pointer The crystal structure of the NTF2-like domain of Rasputin protein is presented. Black-Right-Pointing-Pointer Differences to known ligand binding sites of nuclear transport factor 2 are discussed. Black-Right-Pointing-Pointer A new ligand binding site for the Rasputin and G3BP proteins is proposed. -- Abstract: The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7 A resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a {beta}-sheet and three {alpha}-helices forming a cone-like shape. However, known binding sites formore » RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site.« less

75 FR 57532 - In the Matter of: Stone & Webster Construction, Inc.; Confirmatory Order (Effective Immediately)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... to working in the nuclear industry for workers coming in without nuclear experience; New Hire... employees in its Nuclear Services (i.e., construction) and Nuclear Maintenance Divisions working at nuclear... (i.e., construction) and Nuclear Maintenance Divisions working at nuclear facilities addressing: (a...

Generalized Resistance to Thyroid Hormone Associated with a Mutation in the Ligand-Binding Domain of the Human Thyroid Hormone Receptor β

NASA Astrophysics Data System (ADS)

Sakurai, Akihiro; Takeda, Kyoko; Ain, Kenneth; Ceccarelli, Paola; Nakai, Akira; Seino, Susumu; Bell, Graeme I.; Refetoff, Samuel; Degroot, Leslie J.

1989-11-01

The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine --> cytosine replacement in the codon for amino acid 340 resulted in a glycine --> arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor β gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor β gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.

Four nucleocytoplasmic-shuttling proteins and p53 interact specifically with the YB-NLS and are involved in anticancer reagent-induced nuclear localization of YB-1

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

Tanaka, Toru; Ohashi, Sachiyo; Kobayashi, Shunsuke

In cancer cells, anticancer reagents often trigger nuclear accumulation of YB-1, which participates in the progression of cancer malignancy. YB-1 has a non-canonical nuclear localization signal (YB-NLS). Here we found that four nucleocytoplasmic-shuttling RNA-binding proteins and p53 interact specifically with the YB-NLS and co-accumulate with YB-1 in the nucleus of actinomycin D-treated cells. To elucidate the roles of these YB-NLS-binding proteins, we performed a dominant-negative experiment in which a large excess of YB-NLS interacts with the YB-NLS-binding proteins, and showed inhibitory effects on actinomycin D-induced nuclear transport of endogenous YB-1 and subsequent MDR1 gene expression. Furthermore, the YB-NLS-expressing cells weremore » also found to show increased drug sensitivity. Our results suggest that these YB-NLS-associating proteins are key factors for nuclear translocation/accumulation of YB-1 in cancer cells. - Highlights: • Four nucleocytoplasmic-shuttling proteins and p53 associate with YB-NLS. • They showed nuclear co-accumulation with YB-1 in actinomycin D-treated cells. • Overexpression of YB-NLS was carried out to take YB-NLS-binding proteins from YB-1. • YB-NLS inhibited actinomycin D-induced nuclear localization of endogenous YB-1. • YB-NLS suppressed actinomycin D-induced expression of MDR1.« less

Karyopherin α 3 and karyopherin α 4 proteins mediate the nuclear import of methyl-CpG binding protein 2.

PubMed

Baker, Steven Andrew; Lombardi, Laura Marie; Zoghbi, Huda Yahya

2015-09-11

Methyl-CpG binding protein 2 (MeCP2) is a nuclear protein with important roles in regulating chromatin structure and gene expression, and mutations in MECP2 cause Rett syndrome (RTT). Within the MeCP2 protein sequence, the nuclear localization signal (NLS) is reported to reside between amino acids 255-271, and certain RTT-causing mutations overlap with the MeCP2 NLS, suggesting that they may alter nuclear localization. One such mutation, R270X, is predicted to interfere with the localization of MeCP2, but recent in vivo studies have demonstrated that this mutant remains entirely nuclear. To clarify the mechanism of MeCP2 nuclear import, we isolated proteins that interact with the NLS and identified karyopherin α 3 (KPNA3 or Kap-α3) and karyopherin α 4 (KPNA4 or Kap-α4) as key binding partners of MeCP2. MeCP2-R270X did not interact with KPNA4, consistent with a requirement for an intact NLS in this interaction. However, this mutant retains binding to KPNA3, accounting for the normal localization of MeCP2-R270X to the nucleus. These data provide a mechanism for MeCP2 nuclear import and have implications for the design of therapeutics aimed at modulating the function of MeCP2 in RTT patients. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

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

Onder, Zeynep; Chang, Vivian; Moroianu, Junona, E-mail: moroianu@bc.edu

2015-01-01

We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7more » interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.« less

Covariant density functional theory: predictive power and first attempts of a microscopic derivation

NASA Astrophysics Data System (ADS)

Ring, Peter

2018-05-01

We discuss systematic global investigations with modern covariant density functionals. The number of their phenomenological parameters can be reduced considerable by using microscopic input from ab-initio calculations in nuclear matter. The size of the tensor force is still an open problem. Therefore we use the first full relativistic Brueckner-Hartree-Fock calculations in finite nuclear systems in order to study properties of such functionals, which cannot be obtained from nuclear matter calculations.

Nuclear Physics of neutron stars

NASA Astrophysics Data System (ADS)

Piekarewicz, Jorge

2015-04-01

One of the overarching questions posed by the recent community report entitled ``Nuclear Physics: Exploring the Heart of Matter'' asks How Does Subatomic Matter Organize Itself and What Phenomena Emerge? With their enormous dynamic range in both density and neutron-proton asymmetry, neutron stars provide ideal laboratories to answer this critical challenge. Indeed, a neutron star is a gold mine for the study of physical phenomena that cut across a variety of disciplines, from particle physics to general relativity. In this presentation--targeted at non-experts--I will focus on the essential role that nuclear physics plays in constraining the dynamics, structure, and composition of neutron stars. In particular, I will discuss some of the many exotic states of matter that are speculated to exist in a neutron star and the impact of nuclear-physics experiments on elucidating their fascinating nature. This material is based upon work supported by the U.S. Department of Energy Office of Science, Office of Nuclear Physics under Award Number DE-FD05-92ER40750.

75 FR 80697 - Nuclear Decommissioning Funds

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... Nuclear Decommissioning Funds AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Final regulations... decommissioning nuclear power plants. These final regulations affect taxpayers that own an interest in a nuclear... preamble. 1. Definitional Matters A. Definition of Nuclear Decommissioning Costs One commentator on the...

NXT1, a Novel Influenza A NP Binding Protein, Promotes the Nuclear Export of NP via a CRM1-Dependent Pathway.

PubMed

Chutiwitoonchai, Nopporn; Aida, Yoko

2016-07-28

Influenza remains a serious worldwide public health problem. After infection, viral genomic RNA is replicated in the nucleus and packed into viral ribonucleoprotein, which will then be exported to the cytoplasm via a cellular chromosome region maintenance 1 (CRM1)-dependent pathway for further assembly and budding. However, the nuclear export mechanism of influenza virus remains controversial. Here, we identify cellular nuclear transport factor 2 (NTF2)-like export protein 1 (NXT1) as a novel binding partner of nucleoprotein (NP) that stimulates NP-mediated nuclear export via the CRM1-dependent pathway. NXT1-knockdown cells exhibit decreased viral replication kinetics and nuclear accumulated viral RNA and NP. By contrast, NXT1 overexpression promotes nuclear export of NP in a CRM1-dependent manner. Pull-down assays suggest the formation of an NXT1, NP, and CRM1 complex, and demonstrate that NXT1 binds to the C-terminal region of NP. These findings reveal a distinct mechanism for nuclear export of the influenza virus and identify the NXT1/NP interaction as a potential target for antiviral drug development.

Detection of a nuclear, EBNA-type antigen in apparently EBNA-negative Herpesvirus papio (HVP)-transformed lymphoid lines by the acid-fixed nuclear binding technique.

PubMed

Ohno, S; Luka, J; Falk, L; Klein, G

1977-12-15

In agreement with the findings of previous authors, we could not detect a virally determined nuclear antigen in Herpesvirus papio (HVP)-transformed baboon lymphoid lines by anticomplementary staining in situ, as for EBNA. However, by means of our recently developed acid-fixed nuclear binding technique an EBNA-like antigen could be readily demonstrated, after extraction from both producer and non-producer lines. We propose to designate the antigen as HUPNA. It can be detected by a human anti-EBNA antibody, suggesting cross-reactivity, if not identity, between EBNA and HUPNA. HVP-DNA carrying non-producer lines, negative for in situ ACIF stainability but capable of yielding HUPNA by the nuclear binding technique, can be superinfected with EBV, with brilliant EBNA expression as the result, suggesting that the defective in situ staining is a property associated with the baboon HVP, rather than the baboon lymphoid cell per se.

Skyrme interaction to second order in nuclear matter

NASA Astrophysics Data System (ADS)

Kaiser, N.

2015-09-01

Based on the phenomenological Skyrme interaction various density-dependent nuclear matter quantities are calculated up to second order in many-body perturbation theory. The spin-orbit term as well as two tensor terms contribute at second order to the energy per particle. The simultaneous calculation of the isotropic Fermi-liquid parameters provides a rigorous check through the validity of the Landau relations. It is found that published results for these second order contributions are incorrect in most cases. In particular, interference terms between s-wave and p-wave components of the interaction can contribute only to (isospin or spin) asymmetry energies. Even with nine adjustable parameters, one does not obtain a good description of the empirical nuclear matter saturation curve in the low density region 0\\lt ρ \\lt 2{ρ }0. The reason for this feature is the too strong density-dependence {ρ }8/3 of several second-order contributions. The inclusion of the density-dependent term \\frac{1}{6}{t}3{ρ }1/6 is therefore indispensable for a realistic description of nuclear matter in the Skyrme framework.

On the way to a microscopic derivation of covariant density functionals in nuclei

NASA Astrophysics Data System (ADS)

Ring, Peter

2018-02-01

Several methods are discussed to derive covariant density functionals from the microscopic input of bare nuclear forces. In a first step there are semi-microscopic functionals, which are fitted to ab-initio calculations of nuclear matter and depend in addition on very few phenomenological parameters. They are able to describe nuclear properties with the same precision as fully phenomenological functionals. In a second step we present first relativistic Brueckner-Hartree-Fock calculations in finite nuclei in order to study properties of such functionals, which cannot be obtained from nuclear matter calculations.

Perturbation theory of nuclear matter with a microscopic effective interaction

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

Benhar, Omar; Lovato, Alessandro

Here, an updated and improved version of the effective interaction based on the Argonne-Urbana nuclear Hamiltonian, derived using the formalism of correlated basis functions and the cluster expansion technique, is employed to obtain a number of properties of cold nuclear matter at arbitrary neutron excess within the formalism of many-body perturbation theory. The numerical results, including the ground-state energy per nucleon, the symmetry energy, the pressure, the compressibility, and the single-particle spectrum, are discussed in the context of the available empirical information, obtained from measured nuclear properties and heavy-ion collisions.

Perturbation theory of nuclear matter with a microscopic effective interaction

DOE PAGES

Benhar, Omar; Lovato, Alessandro

2017-11-01

Here, an updated and improved version of the effective interaction based on the Argonne-Urbana nuclear Hamiltonian, derived using the formalism of correlated basis functions and the cluster expansion technique, is employed to obtain a number of properties of cold nuclear matter at arbitrary neutron excess within the formalism of many-body perturbation theory. The numerical results, including the ground-state energy per nucleon, the symmetry energy, the pressure, the compressibility, and the single-particle spectrum, are discussed in the context of the available empirical information, obtained from measured nuclear properties and heavy-ion collisions.

Binding Blocks: Building the Universe One Nucleus at a Time

ERIC Educational Resources Information Center

Diget, C. Aa.; Pastore, A.; Leech, K.; Haylett, T.; Lock, S.; Sanders, T.; Shelley, M.; Willett, H. V.; Keegans, J.; Sinclair, L.; Simpson, E. C.

2017-01-01

We present a new teaching and outreach activity based around the construction of a three-dimensional chart of isotopes using LEGO® bricks. The activity, "binding blocks", demonstrates nuclear and astrophysical processes through a seven-meter chart of all nuclear isotopes, built from over 26000 LEGO® bricks. It integrates A-Level and GCSE…

Evidence against the nuclear in situ binding of arsenicals-oxidative stress theory of arsenic carcinogenesis

EPA Science Inventory

A large amount of evidence suggests that arsenicals act via oxidative stress in causing cancer in humans and experimental animals. It is possible that arsenicals could bind in situ close to nuclear DNA followed by Haber-Weiss type oxidative DNA damage. Therefore, we tested this...

IDA Gamma-Ray Laser Annual Summary Report (1985). Investigation of the Feasibility of Developing a Laser Using Nuclear Transitions. Revised.

DTIC Science & Technology

1986-06-01

beams of coherent radiation whose short wavelengths would permit greater penetration of matter than is possible with current laser sources. With that...nuclear linewidth. It is claimed that the time required for any narrowing is at least as long as the inverse of the linewidth achieved, no matter what...with the re- quired narrow line can be prepared is a different matter . The point is that the previous uncertainty principle does not forbid the

α-Catenin is an inhibitor of transcription

PubMed Central

Daugherty, Rebecca L.; Serebryannyy, Leonid; Yemelyanov, Alex; Flozak, Annette S.; Yu, Hui-Jun; Kosak, Steven T.; deLanerolle, Primal; Gottardi, Cara J.

2014-01-01

α-Catenin (α-cat) is an actin-binding protein required for cell–cell cohesion. Although this adhesive function for α-cat is well appreciated, cells contain a substantial amount of nonjunctional α-cat that may be used for other functions. We show that α-cat is a nuclear protein that can interact with β-catenin (β-cat) and T-cell factor (TCF) and that the nuclear accumulation of α-cat depends on β-cat. Using overexpression, knockdown, and chromatin immunoprecipitation approaches, we show that α-cat attenuates Wnt/β-cat–responsive genes in a manner that is downstream of β-cat/TCF loading on promoters. Both β-cat– and actin-binding domains of α-cat are required to inhibit Wnt signaling. A nuclear-targeted form of α-cat induces the formation of nuclear filamentous actin, whereas cells lacking α-cat show altered nuclear actin properties. Formation of nuclear actin filaments correlates with reduced RNA synthesis and altered chromatin organization. Conversely, nuclear extracts made from cells lacking α-cat show enhanced general transcription in vitro, an activity that can be partially rescued by restoring the C-terminal actin-binding region of α-cat. These data demonstrate that α-cat may limit gene expression by affecting nuclear actin organization. PMID:24706864

New Mechanisms of Mercury Binding to Peat

NASA Astrophysics Data System (ADS)

Nagy, K. L.; Manceau, A.; Gasper, J. D.; Ryan, J. N.; Aiken, G. R.

2007-12-01

Mercury can be immobilized in the aquatic environment by binding to peat, a solid form of natural organic matter. Binding mechanisms can vary in strength and reversibility, and therefore will control concentrations of bioreactive mercury, may explain rates of mercury methylation, and are important for designing approaches to improve water quality using natural wetlands or engineered phytoremediation schemes. In addition, strong binding between mercury and peat is likely to result in the fixation of mercury that ultimately resides in coal. The mechanisms by which aqueous mercury at low concentrations reacts with both dissolved and solid natural organic matter remain incompletely understood, despite recent efforts. We have identified three distinct binding mechanisms of divalent cationic mercury to solid peats from the Florida Everglades using EXAFS spectroscopic data (FAME beamline, European Synchrotron Radiation Facility (ESRF)) obtained on experimental samples as compared to relevant references including mercury-bearing solids and mercury bound to various organic molecules. The proportions of the three molecular configurations vary with Hg concentration, and two new configurations that involve sulfur ligands occur at Hg concentrations up to about 4000 ppm. The binding mechanism at the lowest experimental Hg concentration (60-80 ppm) elucidates published reports on the inhibition of metacinnabar formation in the presence of Hg-bearing solutions and dissolved natural organic matter, and also, the differences in extent of mercury methylation in distinct areas of the Florida Everglades.

Stability of Matter-Antimatter Molecules

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

Wong, Cheuk-Yin; Lee, Teck-Ghee

2011-01-01

We examine the stability of matter-antimatter molecules by reducing the four-body problem into a simpler two-body problem with residual interactions. We find that matter-antimatter molecules with constituents (m{sub 1}{sup +}, m{sub 2}{sup -}, {bar m}{sub 2}{sup +}, {bar m}{sub 1}{sup -}) possess bound states if their constituent mass ratio m{sub 1}/m{sub 2} is greater than about 4. This stability condition suggests that the binding of matter-antimatter molecules is a rather common phenomenon. We evaluate the binding energies and eigenstates of matter-antimatter molecules ({mu}{sup +}e{sup 0})-(e{sup +}{mu}{sup -}), ({pi}{sup +}e{sup -})-(e{sup +}{pi}{sup -}), (K{sup +}e{sup -})-(e{sup +}K{sup -}), (pe{sup -})-(e{sup +}{barmore » p}), (p{mu}{sup -})-({mu}{sup +}{bar p}), and (K{sup +}{mu}{sup -})-({mu}{sup +}K{sup -}), which satisfy the stability condition. We estimate the molecular annihilation lifetimes in their s states.« less

A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies.

PubMed

Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

2016-04-08

The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior - a key element for the transport selectivity of the NPC - was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface.

Mean-field study of hot β -stable protoneutron star matter: Impact of the symmetry energy and nucleon effective mass

NASA Astrophysics Data System (ADS)

Tan, Ngo Hai; Loan, Doan Thi; Khoa, Dao T.; Margueron, Jerome

2016-03-01

A consistent Hartree-Fock study of the equation of state (EOS) of asymmetric nuclear matter at finite temperature has been performed using realistic choices of the effective, density-dependent nucleon-nucleon (NN ) interaction, which were successfully used in different nuclear structure and reaction studies. Given the importance of the nuclear symmetry energy in the neutron star formation, EOSs associated with different behaviors of the symmetry energy were used to study hot asymmetric nuclear matter. The slope of the symmetry energy and nucleon effective mass with increasing baryon density was found to affect the thermal properties of nuclear matter significantly. Different density-dependent NN interactions were further used to study the EOS of hot protoneutron star (PNS) matter of the n p e μ ν composition in β equilibrium. The hydrostatic configurations of PNS in terms of the maximal gravitational mass Mmax and radius, central density, pressure, and temperature at the total entropy per baryon S /A =1 ,2 , and 4 have been determined in both the neutrino-free and neutrino-trapped scenarios. The obtained results show consistently a strong impact of the symmetry energy and nucleon effective mass on thermal properties and composition of hot PNS matter. Mmax values obtained for the (neutrino-free) β -stable PNS at S /A =4 were used to assess time tBH of the collapse of a 40 M⊙ protoneutron progenitor to a black hole, based on a correlation between tBH and Mmax found from the hydrodynamic simulation by Hempel et al. [Astrophys. J. 748, 70 (2012), 10.1088/0004-637X/748/1/70].

Characterization of particulate matter binding peptides screened from phage display.

PubMed

Liang Alvin, Aw Wei; Tanaka, Masayoshi; Okochi, Mina

2017-05-01

Particulate matter (PM), especially particulates with diameters of less than 2.5 μm, can penetrate the alveolar region and increase the risk of respiratory diseases. This has stimulated research efforts to develop detection methods so that counter measures can be taken. In this study, four PM binding peptides were obtained by phage display and binding characteristics of these peptides were investigated using the peptide array. The strongest binding peptide, WQDFGAVRSTRS, displayed a binding property, measured in terms of spot intensity, 11.4 times higher than that of the negative control, AAAAA. Inductively coupled plasma mass spectrometry (ICPMS) analysis of the transition metal compounds in the PM bound to the peptide spots was performed, and two peptides showed higher binding towards Cu and Zn compounds in PM. These results suggest that the screened peptides could serve as an indicator of transition metal compounds, which are related to adverse health effects, contained in PM. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

Pack, Chan-Gi, E-mail: changipack@amc.seoul.kr; Ahn, Sang-Gun

The cellular response to stress is primarily controlled in cells via transcriptional activation by heat shock factor 1 (HSF1). HSF1 is well-known to form homotrimers for activation upon heat shock and subsequently bind to target DNAs, such as heat-shock elements, by forming stress granules. A previous study demonstrated that nuclear HSF1 and HSF2 molecules in live cells interacted with target DNAs on the stress granules. However, the process underlying the binding interactions of HSF family in cells upon heat shock remains unclear. This study demonstrate for the first time that the interaction kinetics among nuclear HSF1, HSF2, and HSF4 uponmore » heat shock can be detected directly in live cells using dual color fluorescence cross-correlation spectroscopy (FCCS). FCCS analyses indicated that the binding between HSFs was dramatically changed by heat shock. Interestingly, the recovery kinetics of interaction between HSF1 molecules after heat shock could be represented by changes in the relative interaction amplitude and mobility. - Highlights: • The binding interactions among nuclear HSFs were successfully detected. • The binding kinetics between HSF1s during recovery was quantified. • HSF2 and HSF4 strongly formed hetero-complex, even before heat shock. • Nuclear HSF2 and HSF4 bound to HSF1 only after heat shock.« less

Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid-Activated Receptor

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

Kruse, Schoen W; Suino-Powell, Kelly; Zhou, X Edward

2010-01-12

The chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and II) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis, neuronal development, organogenesis, cell fate determination, and metabolic homeostasis. Although the biological functions of COUP-TFs have been studied extensively, little is known of their structural features or aspects of ligand regulation. Here we report the ligand-free 1.48 {angstrom} crystal structure of the human COUP-TFII ligand-binding domain. The structure reveals an autorepressed conformation of the receptor, where helix {alpha}10 is bent into the ligand-binding pocket and the activation function-2 helix is folded into the cofactor binding site,more » thus preventing the recruitment of coactivators. In contrast, in multiple cell lines, COUP-TFII exhibits constitutive transcriptional activity, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, and ligand binding, substantially reduce the COUP-TFII transcriptional activity. Importantly, retinoid acids are able to promote COUP-TFII to recruit coactivators and activate a COUP-TF reporter construct. Although the concentration needed is higher than the physiological levels of retinoic acids, these findings demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation.« less

Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology

PubMed Central

Chew, Li-Jin; DeBoy, Cynthia A

2015-01-01

White matter disease afflicts both developing and mature central nervous systems. Both cell intrinsic and extrinsic dysregulation result in profound changes in cell survival, axonal metabolism and functional performance. Experimental models of developmental white matter (WM) injury and demyelination have not only delineated mechanisms of signaling and inflammation, but have also paved the way for the discovery of pharmacological approaches to intervention. These reagents have been shown to enhance protection of the mature oligodendrocyte cell, accelerate progenitor cell recruitment and/or differentiation, or attenuate pathological stimuli arising from the inflammatory response to injury. Here we highlight reports of studies in the CNS in which compounds, namely peptides, hormones, and small molecule agonists/antagonists, have been used in experimental animal models of demyelination and neonatal brain injury that affect aspects of excitotoxicity, oligodendrocyte development and survival, and progenitor cell function, and which have been demonstrated to attenuate damage and improve WM protection in experimental models of injury. The molecular targets of these agents include growth factor and neurotransmitter receptors, morphogens and their signaling components, nuclear receptors, as well as the processes of iron transport and actin binding. By surveying the current evidence in non-immune targets of both the immature and mature WM, we aim to better understand pharmacological approaches modulating endogenous oligodendroglia that show potential for success in the contexts of developmental and adult WM pathology. PMID:26116759

Structure of a Yeast Dyn2-Nup159 Complex and Molecular Basis for Dynein Light Chain-Nuclear Pore Interaction*

PubMed Central

Romes, Erin M.; Tripathy, Ashutosh; Slep, Kevin C.

2012-01-01

The nuclear pore complex gates nucleocytoplasmic transport through a massive, eight-fold symmetric channel capped by a nucleoplasmic basket and structurally unique, cytoplasmic fibrils whose tentacles bind and regulate asymmetric traffic. The conserved Nup82 complex, composed of Nsp1, Nup82, and Nup159, forms the unique cytoplasmic fibrils that regulate mRNA nuclear export. Although the nuclear pore complex plays a fundamental, conserved role in nuclear trafficking, structural information about the cytoplasmic fibrils is limited. Here, we investigate the structural and biochemical interactions between Saccharomyces cerevisiae Nup159 and the nucleoporin, Dyn2. We find that Dyn2 is predominantly a homodimer and binds arrayed sites on Nup159, promoting the Nup159 parallel homodimerization. We present the first structure of Dyn2, determined at 1.85 Å resolution, complexed with a Nup159 target peptide. Dyn2 resembles homologous metazoan dynein light chains, forming homodimeric composite substrate binding sites that engage two independent 10-residue target motifs, imparting a β-strand structure to each peptide via antiparallel extension of the Dyn2 core β-sandwich. Dyn2 recognizes a highly conserved QT motif while allowing sequence plasticity in the flanking residues of the peptide. Isothermal titration calorimetric analysis of the comparative binding of Dyn2 to two Nup159 target sites shows similar affinities (18 and 13 μm), but divergent thermal binding modes. Dyn2 homodimers are arrayed in the crystal lattice, likely mimicking the arrayed architecture of Dyn2 on the Nup159 multivalent binding sites. Crystallographic interdimer interactions potentially reflect a cooperative basis for Dyn2-Nup159 complex formation. Our data highlight the determinants that mediate oligomerization of the Nup82 complex and promote a directed, elongated cytoplasmic fibril architecture. PMID:22411995

Towards a Conceptual Diagnostic Survey in Nuclear Physics

ERIC Educational Resources Information Center

Kohnle, Antje; Mclean, Stewart; Aliotta, Marialuisa

2011-01-01

Understanding students' prior beliefs in nuclear physics is a first step towards improving nuclear physics instruction. This paper describes the development of a diagnostic survey in nuclear physics covering the areas of radioactive decay, binding energy, properties of the nuclear force and nuclear reactions, that was administered to students at…

A New Family of Nuclear Receptor Coregulators That Integrate Nuclear Receptor Signaling through CREB-Binding Protein

PubMed Central

Mahajan, Muktar A.; Samuels, Herbert H.

2000-01-01

We describe the cloning and characterization of a new family of nuclear receptor coregulators (NRCs) which modulate the function of nuclear hormone receptors in a ligand-dependent manner. NRCs are expressed as alternatively spliced isoforms which may exhibit different intrinsic activities and receptor specificities. The NRCs are organized into several modular structures and contain a single functional LXXLL motif which associates with members of the steroid hormone and thyroid hormone/retinoid receptor subfamilies with high affinity. Human NRC (hNRC) harbors a potent N-terminal activation domain (AD1), which is as active as the herpesvirus VP16 activation domain, and a second activation domain (AD2) which overlaps with the receptor-interacting LXXLL region. The C-terminal region of hNRC appears to function as an inhibitory domain which influences the overall transcriptional activity of the protein. Our results suggest that NRC binds to liganded receptors as a dimer and this association leads to a structural change in NRC resulting in activation. hNRC binds CREB-binding protein (CBP) with high affinity in vivo, suggesting that hNRC may be an important functional component of a CBP complex involved in mediating the transcriptional effects of nuclear hormone receptors. PMID:10866662

Gadd45a Is an RNA Binding Protein and Is Localized in Nuclear Speckles

PubMed Central

Sytnikova, Yuliya A.; Kubarenko, Andriy V.; Schäfer, Andrea; Weber, Alexander N. R.; Niehrs, Christof

2011-01-01

Background The Gadd45 proteins play important roles in growth control, maintenance of genomic stability, DNA repair, and apoptosis. Recently, Gadd45 proteins have also been implicated in epigenetic gene regulation by promoting active DNA demethylation. Gadd45 proteins have sequence homology with the L7Ae/L30e/S12e RNA binding superfamily of ribosomal proteins, which raises the question if they may interact directly with nucleic acids. Principal Findings Here we show that Gadd45a binds RNA but not single- or double stranded DNA or methylated DNA in vitro. Sucrose density gradient centrifugation experiments demonstrate that Gadd45a is present in high molecular weight particles, which are RNase sensitive. Gadd45a displays RNase-sensitive colocalization in nuclear speckles with the RNA helicase p68 and the RNA binding protein SC35. A K45A point mutation defective in RNA binding was still active in DNA demethylation. This suggests that RNA binding is not absolutely essential for demethylation of an artificial substrate. A point mutation at G39 impared RNA binding, nuclear speckle localization and DNA demethylation, emphasizing its relevance for Gadd45a function. Significance The results implicate RNA in Gadd45a function and suggest that Gadd45a is associated with a ribonucleoprotein particle. PMID:21249130

Imaging chromatin nanostructure with binding-activated localization microscopy based on DNA structure fluctuations

PubMed Central

Szczurek, Aleksander; Klewes, Ludger; Xing, Jun; Gourram, Amine; Birk, Udo; Knecht, Hans; Dobrucki, Jurek W.; Mai, Sabine

2017-01-01

Abstract Advanced light microscopy is an important tool for nanostructure analysis of chromatin. In this report we present a general concept for Single Molecule localization Microscopy (SMLM) super-resolved imaging of DNA-binding dyes based on modifying the properties of DNA and the dye. By careful adjustment of the chemical environment leading to local, reversible DNA melting and hybridization control over the fluorescence signal of the DNA-binding dye molecules can be introduced. We postulate a transient binding as the basis for our variation of binding-activated localization microscopy (BALM). We demonstrate that several intercalating and minor-groove binding DNA dyes can be used to register (optically isolate) only a few DNA-binding dye signals at a time. To highlight this DNA structure fluctuation-assisted BALM (fBALM), we applied it to measure, for the first time, nanoscale differences in nuclear architecture in model ischemia with an anticipated structural resolution of approximately 50 nm. Our data suggest that this approach may open an avenue for the enhanced microscopic analysis of chromatin nano-architecture and hence the microscopic analysis of nuclear structure aberrations occurring in various pathological conditions. It may also become possible to analyse nuclear nanostructure differences in different cell types, stages of development or environmental stress conditions. PMID:28082388

The identification of FANCD2 DNA binding domains reveals nuclear localization sequences.

PubMed

Niraj, Joshi; Caron, Marie-Christine; Drapeau, Karine; Bérubé, Stéphanie; Guitton-Sert, Laure; Coulombe, Yan; Couturier, Anthony M; Masson, Jean-Yves

2017-08-21

Fanconi anemia (FA) is a recessive genetic disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. The FA pathway consists of at least 21 FANC genes (FANCA-FANCV), and the encoded protein products interact in a common cellular pathway to gain resistance against DNA interstrand crosslinks. After DNA damage, FANCD2 is monoubiquitinated and accumulates on chromatin. FANCD2 plays a central role in the FA pathway, using yet unidentified DNA binding regions. By using synthetic peptide mapping and DNA binding screen by electromobility shift assays, we found that FANCD2 bears two major DNA binding domains predominantly consisting of evolutionary conserved lysine residues. Furthermore, one domain at the N-terminus of FANCD2 bears also nuclear localization sequences for the protein. Mutations in the bifunctional DNA binding/NLS domain lead to a reduction in FANCD2 monoubiquitination and increase in mitomycin C sensitivity. Such phenotypes are not fully rescued by fusion with an heterologous NLS, which enable separation of DNA binding and nuclear import functions within this domain that are necessary for FANCD2 functions. Collectively, our results enlighten the importance of DNA binding and NLS residues in FANCD2 to activate an efficient FA pathway. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Retinoid Pathway and Cancer Therapeutics

PubMed Central

Bushue, Nathan; Wan, Yu-Jui Yvonne

2010-01-01

The retinoids are a class of compounds that are structurally related to vitamin A. Retinoic acid, which is the active metabolite of retinol, regulates a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids exert their effects through a variety of binding proteins including cellular retinol binding protein (CRBP), retinol-binding proteins (RBP), cellular retinoic acid-binding protein (CRABP), and nuclear receptors i.e. retinoic acid receptor (RAR) and retinoid × receptor (RXR). Because of the pleiotropic effects of retinoids, understanding the function of these binding proteins and nuclear receptors assists us in developing compounds that have specific effects. This review summarizes our current understanding of how retinoids are processed and act with the emphasis on the application of retinoids in cancer treatment and prevention. PMID:20654663

78 FR 68102 - Atomic Safety and Licensing Board; In the Matter of Nuclear Innovation North America LLC (South...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

...] Atomic Safety and Licensing Board; In the Matter of Nuclear Innovation North America LLC (South Texas... Administrative Judges: Michael M. Gibson, Chairman, Dr. Gary S. Arnold, Dr. Randall J. Charbeneau. The Atomic... follows: Mail: Administrative Judge Michael M. Gibson, Atomic Safety and Licensing Board Panel, Mail Stop...

76 FR 44623 - Atomic Safety and Licensing Board; In the Matter of Nuclear Innovation North America LLC (South...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

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The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex.

PubMed

Garcia-Higuera, I; Kuang, Y; Denham, J; D'Andrea, A D

2000-11-01

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with 8 complementation groups. Four of the FA genes have been cloned, and at least 3 of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a multisubunit protein complex. The FANCG protein binds directly to the amino terminal nuclear localization sequence (NLS) of FANCA, suggesting that FANCG plays a role in regulating FANCA nuclear accumulation. In the current study the functional consequences of FANCG/FANCA binding were examined. Correction of an FA-G cell line with the FANCG complementary DNA (cDNA) resulted in FANCA/FANCG binding, prolongation of the cellular half-life of FANCA, and an increase in the nuclear accumulation of the FA protein complex. Similar results were obtained upon correction of an FA-A cell line, with a reciprocal increase in the half-life of FANCG. Patient-derived mutant forms of FANCA, containing an intact NLS sequence but point mutations in the carboxy-terminal leucine zipper region, bound FANCG in the cytoplasm. The mutant forms failed to translocate to the nucleus of transduced cells, thereby suggesting a model of coordinated binding and nuclear translocation. These results demonstrate that the FANCA/FANCG interaction is required to maintain the cellular levels of both proteins. Moreover, at least one function of FANCG and FANCA is to regulate the nuclear accumulation of the FA protein complex. Failure to accumulate the nuclear FA protein complex results in the characteristic spectrum of clinical and cellular abnormalities observed in FA.

Identification of a maize nucleic acid-binding protein (NBP) belonging to a family of nuclear-encoded chloroplast proteins.

PubMed Central

Cook, W B; Walker, J C

1992-01-01

A cDNA encoding a nuclear-encoded chloroplast nucleic acid-binding protein (NBP) has been isolated from maize. Identified as an in vitro DNA-binding activity, NBP belongs to a family of nuclear-encoded chloroplast proteins which share a common domain structure and are thought to be involved in posttranscriptional regulation of chloroplast gene expression. NBP contains an N-terminal chloroplast transit peptide, a highly acidic domain and a pair of ribonucleoprotein consensus sequence domains. NBP is expressed in a light-dependent, organ-specific manner which is consistent with its involvement in chloroplast biogenesis. The relationship of NBP to the other members of this protein family and their possible regulatory functions are discussed. Images PMID:1346929

Dynamics of Galectin-3 in the Nucleus and Cytoplasm

PubMed Central

Haudek, Kevin C.; Spronk, Kimberly J.; Voss, Patricia G.; Patterson, Ronald J.; Wang, John L.; Arnoys, Eric J.

2009-01-01

This review summarizes selected studies on galectin-3 (Gal3) as an example of the dynamic behavior of a carbohydrate-binding protein in the cytoplasm and nucleus of cells. Within the 15-member galectin family of proteins, Gal3 (Mr ~30,000) is the sole representative of the chimera subclass in which a proline- and glycine-rich NH2-terminal domain is fused onto a COOH-terminal carbohydrate recognition domain responsible for binding galactose-containing glycoconjugates. The protein shuttles between the cytoplasm and nucleus on the basis of targeting signals that are recognized by importin(s) for nuclear localization and exportin-1 (CRM1) for nuclear export. Depending on the cell type, specific experimental conditions in vitro, or tissue location, Gal3 has been reported to be exclusively cytoplasmic, predominantly nuclear, or distributed between the two compartments. The nuclear versus cytoplasmic distribution of the protein must reflect, then, some balance between nuclear import and export, as well as mechanisms of cytoplasmic anchorage or binding to a nuclear component. Indeed, a number of ligands have been reported for Gal3 in the cytoplasm and in the nucleus. Most of the ligands appear to bind Gal3, however, through protein-protein interactions rather than through protein-carbohydrate recognition. In the cytoplasm, for example, Gal3 interacts with the apoptosis repressor Bcl-2 and this interaction may be involved in Gal3’s anti-apoptotic activity. In the nucleus, Gal3 is a required pre-mRNA splicing factor; the protein is incorporated into spliceosomes via its association with the U1 small nuclear ribonucleoprotein (snRNP) complex. Although the majority of these interactions occur via the carbohydrate recognition domain of Gal3 and saccharide ligands such as lactose can perturb some of these interactions, the significance of the protein’s carbohydrate-binding activity, per se, remains a challenge for future investigations. PMID:19616076

Cyclosporin A and FK-506 both affect DNA binding of regulatory nuclear proteins to the human interleukin-2 promoter.

PubMed

Baumann, G; Geisse, S; Sullivan, M

1991-03-01

The structurally unrelated immunosuppressive drugs cyclosporin A (Sandimmun) and FK-506 both interfere with the process of T-cell proliferation by blocking the transcription of the T-cell growth factor interleukin-2 (IL-2). Here we demonstrate that the transcriptional activation of this gene requires the binding of regulatory nuclear proteins to a promoter element with sequence similarity to the consensus binding site for NF-kappa B-related transcription factors. We present evidence that the binding by regulatory nuclear proteins to the kappa B element of the IL-2 promoter is affected negatively by cyclosporin A and FK-506 at concentrations paralleling their immunosuppressive activity in vivo. The decrease in DNA-protein complex formation induced by the immunosuppressive drugs correlates with a decrease in IL-2 production. FK-506 is 10 to 100 times more potent than cyclosporin A in its ability to inhibit sequence-specific DNA binding and IL-2 production. Our findings suggest that the actions of both drugs converge at the level of DNA-protein interaction.

Mercury(II) sorption to two Florida Everglades peat--Evidence for strong and weak binding and competition by dissolved organic matter released from the peat

USGS Publications Warehouse

Drexel, R. Todd; Haitzer, Markus; Ryan, Joseph N.; Aiken, George R.; Nagy, Kathryn L.

2002-01-01

The binding of mercury(II) to two peats from Florida Everglades sites with different rates of mercury methylation was measured at pH 6.0 and 0.01 M ionic strength. The mercury(II) sorption isotherms, measured over a total mercury(II) range of 10-7.4 to 10-3.7 M, showed the competition for mercury(II) between the peat and dissolved organic matter released from the peat and the existence of strong and weak binding sites for mercury(II). Binding was portrayed by a model accounting for strong and weak sites on both the peat and the released DOM. The conditional binding constants (for which the ligand concentration was set as the concentration of reduced sulfur in the organic matter as measured by X-ray absorption near-edge structure spectroscopy) determined for the strong sites on the two peats were similar (Kpeat,s = 1021.8±0.1and 1022.0±0.1 M-1), but less than those determined for the DOM strong sites (Kdom,s = 1022.8±0.1and 1023.2±0.1 M-1), resulting in mercury(II) binding by the DOM at low mercury(II) concentrations. The magnitude of the strong site binding constant is indicative of mercury(II) interaction with organic thiol functional groups. The conditional binding constants determined for the weak peat sites (Kpeat,w = 1011.5±0.1 and 1011.8±0.1 M-1) and weak DOM sites (Kdom,w = 108.7±3.0 and 107.3±4.5 M-1) were indicative of mercury(II) interaction with carboxyl and phenol functional groups.

Nuclear matter parameters and optical model analysis of proton elastic scattering on the doubly magic nucleus 40Ca

NASA Astrophysics Data System (ADS)

Khalaf, A. M.; Khalifa, M. M.; Solieman, A. H. M.; Comsan, M. N. H.

2018-01-01

Owing to its doubly magic nature having equal numbers of protons and neutrons, the 40Ca nuclear scattering can be successfully described by the optical model that assumes a spherical nuclear potential. Therefore, optical model analysis was employed to calculate the elastic scattering cross section for p +40Ca interaction at energies from 9 to 22 MeV as well as the polarization at energies from 10 to 18.2 MeV. New optical model parameters (OMPs) were proposed based on the best fitting to experimental data. It is found that the best fit OMPs depend on the energy by smooth relationships. The results were compared with other OMPs sets regarding their chi square values (χ2). The obtained OMP's set was used to calculate the volume integral of the potentials and the root mean square (rms) value of nuclear matter radius of 40Ca. In addition, 40Ca bulk nuclear matter properties were discussed utilizing both the obtained rms radius and the Thomas-Fermi rms radius calculated using spherical Hartree-Fock formalism employing Skyrme type nucleon-nucleon force. The nuclear scattering SCAT2000 FORTRAN code was used for the optical model analysis.

Nuclear-Recoil Energy Scale in CDMS II Silicon Dark-Matter Detectors

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

Agnese, R.; et al.

The Cryogenic Dark Matter Search (CDMS II) experiment aims to detect dark matter particles that elastically scatter from nuclei in semiconductor detectors. The resulting nuclear-recoil energy depositions are detected by ionization and phonon sensors. Neutrons produce a similar spectrum of low-energy nuclear recoils in such detectors, while most other backgrounds produce electron recoils. The absolute energy scale for nuclear recoils is necessary to interpret results correctly. The energy scale can be determined in CDMS II silicon detectors using neutrons incident from a broad-spectrummore » $$^{252}$$Cf source, taking advantage of a prominent resonance in the neutron elastic scattering cross section of silicon at a recoil (neutron) energy near 20 (182) keV. Results indicate that the phonon collection efficiency for nuclear recoils is $$4.8^{+0.7}_{-0.9}$$% lower than for electron recoils of the same energy. Comparisons of the ionization signals for nuclear recoils to those measured previously by other groups at higher electric fields indicate that the ionization collection efficiency for CDMS II silicon detectors operated at $$\\sim$$4 V/cm is consistent with 100% for nuclear recoils below 20 keV and gradually decreases for larger energies to $$\\sim$$75% at 100 keV. The impact of these measurements on previously published CDMS II silicon results is small.« less

Nuclear binding of progesterone in hen oviduct. Binding to multiple sites in vitro.

PubMed Central

Pikler, G M; Webster, R A; Spelsberg, T C

1976-01-01

Steroid hormones, including progesterone, are known to bind with high affinity (Kd approximately 1x10(-10)M) to receptor proteins once they enter target cells. This complex (the progesterone-receptor) then undergoes a temperature-and/or salt-dependent activation which allows it to migrate to the cell nucleus and to bind to the deoxyribonucleoproteins. The present studies demonstrate that binding the hormone-receptor complex in vitro to isolated nuclei from the oviducts of laying hens required the same conditions as do other studies of bbinding in vitro reported previously, e.g. the hormone must be complexed to intact and activated receptor. The assay of the nuclear binding by using multiple concentrations of progesterone receptor reveals the presence of more than one class of binding site in the oviduct nuclei. The affinity of each of these classes of binding sites range from Kd approximately 1x10(-9)-1x10(-8)M. Assays using free steroid (not complexed with receptor) show no binding to these sites. The binding to each of the classes of sites, displays a differential stability to increasing ionic concentrations, suggesting primarily an ionic-type interaction for all classes. Only the highest-affinity class of binding site is capable of binding progesterone receptor under physioligical-saline conditions. This class represent 6000-10000 sites per cell nucleus and resembles the sites detected in vivo (Spelsberg, 1976, Biochem. J. 156, 391-398) which cause maximal transcriptional response when saturated with the progesterone receptor. The multiple binding sites for the progesterone receptor either are not present or are found in limited numbers in the nuclei of non-target organs. Differences in extent of binding to the nuclear material between a target tissue (oviduct) and other tissues (spleen or erythrocyte) are markedly dependent on the ionic conditions, and are probably due to binding to different classes of sites in the nuclei. PMID:182147

Influence of structural variation on nuclear localization of DNA-binding polyamide-fluorophore conjugates.

PubMed

Edelson, Benjamin S; Best, Timothy P; Olenyuk, Bogdan; Nickols, Nicholas G; Doss, Raymond M; Foister, Shane; Heckel, Alexander; Dervan, Peter B

2004-01-01

A pivotal step forward in chemical approaches to controlling gene expression is the development of sequence-specific DNA-binding molecules that can enter live cells and traffic to nuclei unaided. DNA-binding polyamides are a class of programmable, sequence-specific small molecules that have been shown to influence a wide variety of protein-DNA interactions. We have synthesized over 100 polyamide-fluorophore conjugates and assayed their nuclear uptake profiles in 13 mammalian cell lines. The compiled dataset, comprising 1300 entries, establishes a benchmark for the nuclear localization of polyamide-dye conjugates. Compounds in this series were chosen to provide systematic variation in several structural variables, including dye composition and placement, molecular weight, charge, ordering of the aromatic and aliphatic amino-acid building blocks and overall shape. Nuclear uptake does not appear to be correlated with polyamide molecular weight or with the number of imidazole residues, although the positions of imidazole residues affect nuclear access properties significantly. Generally negative determinants for nuclear access include the presence of a beta-Ala-tail residue and the lack of a cationic alkyl amine moiety, whereas the presence of an acetylated 2,4-diaminobutyric acid-turn is a positive factor for nuclear localization. We discuss implications of these data on the design of polyamide-dye conjugates for use in biological systems.

Structural basis for nuclear import complex dissociation by RanGTP.

PubMed

Lee, Soo Jae; Matsuura, Yoshiyuki; Liu, Sai Man; Stewart, Murray

2005-06-02

Nuclear protein import is mediated mainly by the transport factor importin-beta that binds cytoplasmic cargo, most often via the importin-alpha adaptor, and then transports it through nuclear pore complexes. This active transport is driven by disassembly of the import complex by nuclear RanGTP. The switch I and II loops of Ran change conformation with nucleotide state, and regulate its interactions with nuclear trafficking components. Importin-beta consists of 19 HEAT repeats that are based on a pair of antiparallel alpha-helices (referred to as the A- and B-helices). The HEAT repeats stack to yield two C-shaped arches, linked together to form a helicoidal molecule that has considerable conformational flexibility. Here we present the structure of full-length yeast importin-beta (Kap95p or karyopherin-beta) complexed with RanGTP, which provides a basis for understanding the crucial cargo-release step of nuclear import. We identify a key interaction site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95p. This interaction produces a change in helicoidal pitch that locks Kap95p in a conformation that cannot bind importin-alpha or cargo. We suggest an allosteric mechanism for nuclear import complex disassembly by RanGTP.

Numerical simulations of relativistic heavy-ion reactions

NASA Astrophysics Data System (ADS)

Daffin, Frank Cecil

Bulk quantities of nuclear matter exist only in the compact bodies of the universe. There the crushing gravitational forces overcome the Coulomb repulsion in massive stellar collapses. Nuclear matter is subjected to high pressures and temperatures as shock waves propagate and burn their way through stellar cores. The bulk properties of nuclear matter are important parameters in the evolution of these collapses, some of which lead to nucleosynthesis. The nucleus is rich in physical phenomena. Above the Coulomb barrier, complex interactions lead to the distortion of, and as collision energies increase, the destruction of the nuclear volume. Of critical importance to the understanding of these events is an understanding of the aggregate microscopic processes which govern them. In an effort to understand relativistic heavy-ion reactions, the Boltzmann-Uehling-Uhlenbeck (Ueh33) (BUU) transport equation is used as the framework for a numerical model. In the years since its introduction, the numerical model has been instrumental in providing a coherent, microscopic, physical description of these complex, highly non-linear events. This treatise describes the background leading to the creation of our numerical model of the BUU transport equation, details of its numerical implementation, its application to the study of relativistic heavy-ion collisions, and some of the experimental observables used to compare calculated results to empirical results. The formalism evolves the one-body Wigner phase-space distribution of nucleons in time under the influence of a single-particle nuclear mean field interaction and a collision source term. This is essentially the familiar Boltzmann transport equation whose source term has been modified to address the Pauli exclusion principle. Two elements of the model allow extrapolation from the study of nuclear collisions to bulk quantities of nuclear matter: the modification of nucleon scattering cross sections in nuclear matter, and the compressibility of nuclear matter. Both are primarily subject to the short- range portion of the inter-nucleon potential, and do not show strong finite-size effects. To that end, several useful observables are introduced and their behavior, as BUU model parameters are changed, explored. The average, directed, in-plane, transverse momentum distribution in rapidity is the oldest of the observables presented in this work. Its slope at mid- rapidity is called the flow of the event, and well characterizes the interplay of repulsive and attractive elements of the dynamics of the events. The BUU model has been quite successful in its role of illuminating the physics of intermediate energy heavy-ion collisions. Though current numerical implementations suffer from some shortcomings they have nonetheless served the community well.

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

Robinson, Alan E.

Here, proposed dark matter detectors with eV-scale sensitivities will detect a large background of atomic (nuclear) recoils from coherent photon scattering of MeV-scale photons. This background climbs steeply below ~10 eV, far exceeding the declining rate of low-energy Compton recoils. The upcoming generation of dark matter detectors will not be limited by this background, but further development of eV-scale and sub-eV detectors will require strategies, including the use of low nuclear mass target materials, to maximize dark matter sensitivity while minimizing the coherent photon scattering background.

The XENON100 Dark Matter Experiment: Design, Construction, Calibration and 2010 Search Results with Improved Measurement of the Scintillation Response of Liquid Xenon to Low-Energy Nuclear Recoils

NASA Astrophysics Data System (ADS)

Plante, Guillaume

An impressive array of astrophysical observations suggest that 83% of the matter in the universe is in a form of non-luminous, cold, collisionless, non-baryonic dark matter. Several extensions of the Standard Model of particle physics aimed at solving the hierarchy problem predict stable weakly interacting massive particles (WIMPs) that could naturally have the right cosmological relic abundance today to compose most of the dark matter if their interactions with normal matter are on the order of a weak scale cross section. These candidates also have the added benefit that their properties and interaction rates can be computed in a well defined particle physics model. A considerable experimental effort is currently under way to uncover the nature of dark matter. One method of detecting WIMP dark matter is to look for its interactions in terrestrial detectors where it is expected to scatter off nuclei. In 2007, the XENON10 experiment took the lead over the most sensitive direct detection dark matter search in operation, the CDMS II experiment, by probing spin-independent WIMP-nucleon interaction cross sections down to sigmachi N ˜ 5 x 10-44 cm 2 at 30 GeV/c2. Liquefied noble gas detectors are now among the technologies at the forefront of direct detection experiments. Liquid xenon (LXe), in particular, is a well suited target for WIMP direct detection. It is easily scalable to larger target masses, allows discrimination between nuclear recoils and electronic recoils, and has an excellent stopping power to shield against external backgrounds. A particle losing energy in LXe creates both ionization electrons and scintillation light. In a dual-phase LXe time projection chamber (TPC) the ionization electrons are drifted and extracted into the gas phase where they are accelerated to amplify the charge signal into a proportional scintillation signal. These two signals allow the three-dimensional localization of events with millimeter precision and the ability to fiducialize the target volume, yielding an inner core with a very low background. Additionally, the ratio of ionization and scintillation can be used to discriminate between nuclear recoils, from neutrons or WIMPs, and electronic recoils, from gamma or beta backgrounds. In these detectors, the energy scale is based on the scintillation signal of nuclear recoils and consequently the precise knowledge of the scintillation efficiency of nuclear recoils in LXe is of prime importance. Inspired by the success of the XENON10 experiment, the XENON collaboration designed and built a new, ten times larger, with a one hundred times lower background, LXe TPC to search for dark matter. It is currently the most sensitive direct detection experiment in operation. In order to shed light on the response of LXe to low energy nuclear recoils a new single phase detector designed specifically for the measurement of the scintillation efficiency of nuclear recoils was also built. In 2011, the XENON100 dark matter results from 100 live days set the most stringent limit on the spin-independent WIMP-nucleon interaction cross section over a wide range of masses, down to sigma chi N ˜ 7 x 10-45 cm2 at 50 GeV/c2, almost an order of magnitude improvement over XENON10 in less than four years. This thesis describes the research conducted in the context of the XENON100 dark matter search experiment. I describe the initial simulation results and ideas that influenced the design of the XENON100 detector, the construction and assembly steps that lead into its concrete realization, the detector and its subsystems, a subset of the calibration results of the detector, and finally dark matter exclusion limits. I also describe in detail the new improved measurement of the important quantity for the interpretation of results from LXe dark matter searches, the scintillation efficiency of low-energy nuclear recoils in LXe.

SPiRIT-TPC with GET readout electronics for the study of density dependent symmetry energy of high dense matter with Heavy RI collisions

NASA Astrophysics Data System (ADS)

Isobe, Tadaaki; SPiRIT Collaboration

2014-09-01

The nuclear Equation of State (EoS) is a fundamental property of nuclear matter that describes the relationships between the parameters for a nuclear system, such as energy, density and temperature. An international collaboration, named SPiRIT, to study the nuclear EoS has been formed recently. One of the main devices of experimental setup is a Time Projection Chamber (TPC) which will be installed into the SAMURAI dipole magnet at RIKEN-RIBF. The TPC can measure charged pions, protons and light ions simultaneously in heavy RI collisions, and those will be used as probes to study the asymmetric dense nuclear matter. In addition to the status of the SPiRIT project, testing of SPiRIT-TPC with GET electronics will be presented in this talk. GET, general electronics for TPC, is a project for the development of novel electronics for TPC supported by NSF and ANR. This work is supported in part by the Japan Grant-in-Aide award and the US DOE grant DE-SC0004835 and JUSEIPEN.

[The concept of nuclear physics].

PubMed

Ducassou, D

1995-03-15

Understanding of the biological effects of radioactivity on living matter requires some basic notions of nuclear physics. The interreactions between living matter and ionising rays, emitted by natural or artificial radioelements, are responsible for such effects. These radioelements are characterised by the period, the nature and the energy of the rays they emit; they constitute the source of radiation whose effects generally depend on their activity.

Properties of nuclear matter from macroscopic-microscopic mass formulas

NASA Astrophysics Data System (ADS)

Wang, Ning; Liu, Min; Ou, Li; Zhang, Yingxun

2015-12-01

Based on the standard Skyrme energy density functionals together with the extended Thomas-Fermi approach, the properties of symmetric and asymmetric nuclear matter represented in two macroscopic-microscopic mass formulas: Lublin-Strasbourg nuclear drop energy (LSD) formula and Weizsäcker-Skyrme (WS*) formula, are extracted through matching the energy per particle of finite nuclei. For LSD and WS*, the obtained incompressibility coefficients of symmetric nuclear matter are K∞ = 230 ± 11 MeV and 235 ± 11 MeV, respectively. The slope parameter of symmetry energy at saturation density is L = 41.6 ± 7.6 MeV for LSD and 51.5 ± 9.6 MeV for WS*, respectively, which is compatible with the liquid-drop analysis of Lattimer and Lim [4]. The density dependence of the mean-field isoscalar and isovector effective mass, and the neutron-proton effective masses splitting for neutron matter are simultaneously investigated. The results are generally consistent with those from the Skyrme Hartree-Fock-Bogoliubov calculations and nucleon optical potentials, and the standard deviations are large and increase rapidly with density. A better constraint for the effective mass is helpful to reduce uncertainties of the depth of the mean-field potential.

Phytochrome regulates GTP-binding protein activity in the envelope of pea nuclei

NASA Technical Reports Server (NTRS)

Clark, G. B.; Memon, A. R.; Thompson, G. A. Jr; Roux, S. J.

1993-01-01

Three GTP-binding proteins with apparent molecular masses of 27, 28 and 30 kDa have been detected in isolated nuclei of etiolated pea plumules. After LDS-PAGE and transfer to nitrocellulose these proteins bind [32P]GTP in the presence of excess ATP, suggesting that they are monomeric G proteins. When nuclei are disrupted, three proteins co-purify with the nuclear envelope fraction and are highly enriched in this fraction. The level of [32P]GTP-binding for all three protein bands is significantly increased when harvested pea plumules are irradiated by red light, and this effect is reversed by far-red light. The results indicate that GTP-binding activity associated with the nuclear envelope of plant cells is photoreversibly regulated by the pigment phytochrome.

76 FR 11764 - Sunshine Act Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-03

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD Sunshine Act Notice AGENCY: Defense Nuclear Facilities... Defense Nuclear Facilities Safety Board's public hearing and meeting described below. Interested persons... the matters to be considered. TIME AND DATE OF MEETING: 9 a.m., March 31, 2011. PLACE: Defense Nuclear...

CacyBP/SIP nuclear translocation regulates p27Kip1 stability in gastric cancer cells

PubMed Central

Niu, Ying-Lin; Li, Ya-Jun; Wang, Jing-Bo; Lu, Yuan-Yuan; Liu, Zhen-Xiong; Feng, Shan-Shan; Hu, Jian-Guo; Zhai, Hui-Hong

2016-01-01

AIM: To investigate the mechanism of calcyclin binding protein/Siah-1 interacting protein (CacyBP/SIP) nuclear translocation in promoting the proliferation of gastric cancer (GC) cells. METHODS: The effect of CacyBP/SIP nuclear translocation on cell cycle was investigated by cell cycle analysis. Western blot analysis was used to assess the change in expression of cell cycle regulatory proteins and proteasome-mediated degradation of p27Kip1. Co-immunoprecipitation (co-IP) analysis was performed to examine the binding of CacyBP/SIP with Skp1. A CacyBP/SIP truncation mutant which lacked the Skp1 binding site was constructed and fused to a fluorescent protein. Subsequently, the effect on Skp1 binding with the fusion protein was examined by co-IP, while localization of fluorescent fusion protein observed by confocal laser microscopy, and change in p27Kip1 protein expression assessed by Western blot analysis. RESULTS: CacyBP/SIP nuclear translocation induced by gastrin promoted progression of GC cells from G1 phase. However, while CacyBP/SIP nuclear translocation was inhibited using siRNA to suppress CacyBP/SIP expression, cell cycle was clearly inhibited. CacyBP/SIP nuclear translocation significantly decreased the level of cell cycle inhibitor p27Kip1, increased Cyclin E protein expression whereas the levels of Skp1, Skp2, and CDK2 were not affected. Upon inhibition of CacyBP/SIP nuclear translocation, there were no changes in protein levels of p27Kip1 and Cyclin E, while p27Kip1 decrease could be prevented by the proteasome inhibitor MG132. Moreover, CacyBP/SIP was found to bind to Skp1 by immunoprecipitation, an event that was abolished by mutant CacyBP/SIP, which also failed to stimulate p27Kip1 degradation, even though the mutant could still translocate into the nucleus. CONCLUSION: CacyBP/SIP nuclear translocation contributes to the proliferation of GC cells, and CacyBP/SIP exerts this effect, at least in part, by stimulating ubiquitin-mediated degradation of p27Kip1. PMID:27099442

Nuclear Physics Research at ELI-NP

NASA Astrophysics Data System (ADS)

Zamfir, N. V.

2018-05-01

The new research facility Extreme Light Infrastructure - Nuclear Physics (ELI-NP) is under construction in Romania, on the Magurele Physics campus. Valued more than 300 Meuros the center will be operational in 2019. The research center will use a high brilliance Gamma Beam and a High-power Laser beam, with unprecedented characteristics worldwide, to investigate the interaction of very intense radiation with matter with specific focus on nuclear phenomena and their applications. The energetic particle beams and radiation produced by the 2x10 PW laser beam interacting with matter will be studied. The precisely tunable energy and excellent bandwidth of the gamma-ray beam will allow for new experimental approaches regarding nuclear astrophysics, nuclear resonance fluorescence, and applications. The experimental equipment is presented, together with the main directions of the research envisioned with special emphasizes on nuclear physics studies.

Ran-binding protein 5 (RanBP5) is related to the nuclear transport factor importin-beta but interacts differently with RanBP1.

PubMed Central

Deane, R; Schäfer, W; Zimmermann, H P; Mueller, L; Görlich, D; Prehn, S; Ponstingl, H; Bischoff, F R

1997-01-01

We report the identification and characterization of a novel 124-kDa Ran binding protein, RanBP5. This protein is related to importin-beta, the key mediator of nuclear localization signal (NLS)-dependent nuclear transport. RanBP5 was identified by two independent methods: it was isolated from HeLa cells by using its interaction with RanGTP in an overlay assay to monitor enrichment, and it was also found by the yeast two-hybrid selection method with RanBP1 as bait. RanBP5 binds to RanBP1 as part of a trimeric RanBP1-Ran-RanBP5 complex. Like importin-beta, RanBP5 strongly binds the GTP-bound form of Ran, stabilizing it against both intrinsic and RanGAP1-induced GTP hydrolysis and also against nucleotide exchange. The GAP resistance of the RanBP5-RanGTP complex can be relieved by RanBP1, which might reflect an in vivo role for RanBP1. RanBP5 is a predominantly cytoplasmic protein that can bind to nuclear pore complexes. We propose that RanBP5 is a mediator of a nucleocytoplasmic transport pathway that is distinct from the importin-alpha-dependent import of proteins with a classical NLS. PMID:9271386

Charmonium interaction in nuclear matter at FAIR

NASA Astrophysics Data System (ADS)

Pratim Bhaduri, Partha; Deveaux, Michael; Toia, Alberica

2018-05-01

We have studied the dissociation of J/ψ mesons in low energy proton-nucleus (p + A) collisions in the energy range of the future SIS100 accelerator at Facility for Anti-proton and Ion Research (FAIR). According to the results of our calculations, various scenarios of J/ψ absorption in nuclear matter show very distinct suppression patterns in the kinematic regime to be probed at FAIR. This suggests that the SIS100 energies are particularly suited to shed light on the issue of interaction of J/ψ resonance in nuclear medium.

Small collision systems: Theory overview on cold nuclear matter effects

NASA Astrophysics Data System (ADS)

Armesto, Néstor

2018-02-01

Many observables measured at the Relativistic Heavy Ion Collider and the Large Hadron Collider show a smooth transition between proton-proton and protonnucleus collisions (small systems), and nucleus-nucleus collisions (large systems), when represented versus some variable like the multiplicity in the event. In this contribution I review some of the physics mechanisms, named cold nuclear matter effects, that may lead to a collective-like behaviour in small systems beyond the macroscopic description provided by relativistic hydrodynamics. I focus on the nuclear modification of parton densities, single inclusive particle production and correlations.

Measurement of the ionization produced by sub-keV silicon nuclear recoils in a CCD dark matter detector

DOE PAGES

Chavarria, A. E.; Collar, J. I.; Peña, J. R.; ...

2016-10-15

We report a measurement of the ionization efficiency of silicon nuclei recoiling with sub-keV kinetic energy in the bulk silicon of a charge-coupled device (CCD). Nuclear recoils are produced by low-energy neutrons (<24 keV) from a 124Sb– 9Be photoneutron source, and their ionization signal is measured down to 60 eV electron equivalent. This energy range, previously unexplored, is relevant for the detection of low-mass dark matter particles. The measured efficiency is found to deviate from the extrapolation to low energies of the Lindhard model. Furthermore, this measurement also demonstrates the sensitivity to nuclear recoils of CCDs employed by DAMIC, amore » dark matter direct detection experiment located in the SNOLAB underground laboratory.« less

Scattering and stopping of hadrons in nuclear matter

NASA Technical Reports Server (NTRS)

Strugalski, Z.

1985-01-01

It was observed, in the 180 litre xenon bubble chamber, that when hadrons with kinetic energy higher than the pion production threshold fall on a layer of nuclear matter - on an atomic nucleus in other words - in many cases they can pass through it without causing particles production but they are deflected through some deflection angles; if the energy is lower than a few GeV and the nuclear matter layer is thick enough, the hadrons can be stopped in it. The amount of the deflection at a given incident hadron energy varies with the way the hadron strikes the atomic nucleus; the probability of the occurrence of stopping depends on the incident hadron identity and energy, and on the way the hadron passed through the nucleus, as well.

NEWSdm: Nuclear Emulsions for WIMP Search with directional measurement

NASA Astrophysics Data System (ADS)

Di Crescenzo, A.

2017-12-01

Direct Dark Matter searches are nowadays one of the most exciting research topics. Several experimental efforts are concentrated on the development, construction, and operation of detectors looking for the scattering of target nuclei with Weakly Interactive Massive Particles (WIMPs). The measurement of the direction of WIMP-induced nuclear recoils is a challenging strategy to extend dark matter searches beyond the neutrino floor and provide an unambiguous signature of the detection of Galactic dark matter. Current directional experiments are based on the use of gas TPC whose sensitivity is strongly limited by the small achievable detector mass. We present an innovative directional experiment based on the use of a solid target made by newly developed nuclear emulsions and read-out systems reaching a position resolution of the order of 10 nm.

Is Dark Matter Similar to the Force?

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

Bernstein, Adam; Vranas, Pavlos

When Obi Wan Kenobi explained the Force to Luke Skywalker, he said, "It's an energy field created by all living things. It surrounds us and penetrates us; it binds the galaxy together." The same thing could be said of the invisible, elusive, yet ubiquitous dark matter. Explore the similarities and differences between dark matter and the Force and find out why LLNL studies dark matter.

Evolution of Structure in Nuclei: Meditation by Sub-Shell Modifications and Relation to Binding Energies

NASA Astrophysics Data System (ADS)

Casten, R. F.; Cakirli, R. B.

2009-03-01

Understanding the development of configuration mixing, coherence, collectivity, and deformation in nuclei is one of the crucial challenges in nuclear structure physics, and one which has become all the more important with the advent of next generation facilities for the study of exotic nuclei. We will discuss recent work on phase/shape transitional behavior in nuclei, and the role of changes in sub-shell structure in mediating such transitional regions. We will also discuss a newly found, much deeper, link between nuclear structure and nuclear binding energies.

Nuclear localisation of 53BP1 is regulated by phosphorylation of the nuclear localisation signal.

PubMed

von Morgen, Patrick; Lidak, Tomas; Horejsi, Zuzana; Macurek, Libor

2018-06-01

Repair of damaged DNA is essential for maintaining genomic stability. TP53-binding protein 1 (53BP1) plays an important role in repair of the DNA double-strand breaks. Nuclear localisation of 53BP1 depends on importin β and nucleoporin 153, but the type and location of 53BP1 nuclear localisation signal (NLS) have yet to be determined. Here, we show that nuclear import of 53BP1 depends on two basic regions, namely 1667-KRK-1669 and 1681-KRGRK-1685, which are both needed for importin binding. Lysine 1667 is essential for interaction with importin and its substitution to arginine reduced nuclear localisation of 53BP1. Furthermore, we have found that CDK1-dependent phosphorylation of 53BP1 at S1678 impairs importin binding during mitosis. Phosphorylation-mimicking mutant S1678D showed reduced nuclear localisation, suggesting that phosphorylation of the NLS interferes with nuclear import of the 53BP1 CONCLUSIONS: We show that 53BP1 contains a classical bipartite NLS 1666-GKRKLITSEEERSPAKRGRKS-1686, which enables the importin-mediated nuclear transport of 53BP1. Additionally, we found that posttranslational modification within the NLS region can regulate 53BP1 nuclear import. Our results indicate that integrity of the NLS is important for 53BP1 nuclear localisation. Precise mapping of the NLS will facilitate further studies on the effect of posttranslational modifications and somatic mutations on the nuclear localisation 53BP1 and DNA repair. © 2018 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Solution Structure and Molecular Interactions of Lamin B Receptor Tudor Domain*

PubMed Central

Liokatis, Stamatis; Edlich, Christian; Soupsana, Katerina; Giannios, Ioannis; Panagiotidou, Parthena; Tripsianes, Konstantinos; Sattler, Michael; Georgatos, Spyros D.; Politou, Anastasia S.

2012-01-01

Lamin B receptor (LBR) is a polytopic protein of the nuclear envelope thought to connect the inner nuclear membrane with the underlying nuclear lamina and peripheral heterochromatin. To better understand the function of this protein, we have examined in detail its nucleoplasmic region, which is predicted to harbor a Tudor domain (LBR-TD). Structural analysis by multidimensional NMR spectroscopy establishes that LBR-TD indeed adopts a classical β-barrel Tudor fold in solution, which, however, features an incomplete aromatic cage. Removal of LBR-TD renders LBR more mobile at the plane of the nuclear envelope, but the isolated module does not bind to nuclear lamins, heterochromatin proteins (MeCP2), and nucleosomes, nor does it associate with methylated Arg/Lys residues through its aromatic cage. Instead, LBR-TD exhibits tight and stoichiometric binding to the “histone-fold” region of unassembled, free histone H3, suggesting an interesting role in histone assembly. Consistent with such a role, robust binding to native nucleosomes is observed when LBR-TD is extended toward its carboxyl terminus, to include an area rich in Ser-Arg residues. The Ser-Arg region, alone or in combination with LBR-TD, binds both unassembled and assembled H3/H4 histones, suggesting that the TD/RS interface may operate as a “histone chaperone-like platform.” PMID:22052904

Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.

PubMed

Yanai, Mako; Sakai, Madoka; Makino, Akiko; Tomonaga, Keizo

2017-07-11

Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear. We examined the subcellular localization, viral polymerase activity, and P-binding ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV) harboring an NES mutation of N. BoDV-N with four alanine-substitutions in the leucine and isoleucine residues of the NES impaired its cytoplasmic localization and abolished polymerase activity and P-binding ability. Although an alanine-substitution at position 131 markedly enhanced viral polymerase activity as determined by a minigenome assay, rBoDV harboring this mutation showed expression of viral RNAs and proteins relative to that of wild-type rBoDV. Our results demonstrate that BoDV-N NES has a dual function in BoDV replication, i.e., nuclear export of N and an interaction with P, affecting viral polymerase activity in the nucleus.

Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration

PubMed Central

Bernis, Cyril; Swift-Taylor, Beth; Nord, Matthew; Carmona, Sarah; Chook, Yuh Min; Forbes, Douglass J.

2014-01-01

The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin β for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin β, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107–160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin β and transportin “global positioning system”or “GPS” pathways that are mechanistically parallel. PMID:24478460

Storage and Bioavailability of Molybdenum in Soils Increased by Organic Matter Complexation

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

Wichard, T.; Mishra, B; Myneni, S

2009-01-01

The micronutrient molybdenum is a necessary component of the nitrogen-fixing enzyme nitrogenase1, 2. Molybdenum is very rare in soils, and is usually present in a highly soluble form, making it susceptible to leaching3, 4. However, it is generally thought that molybdenum attaches to mineral surfaces in acidic soils; this would prevent its escape into the groundwater, but would also impede uptake by microbes3. Here we use X-ray spectroscopy to examine the chemical speciation of molybdenum in soil samples from forests in Arizona and New Jersey. We show that in the leaf litter layer, most of the molybdenum forms strong complexesmore » with plant-derived tannins and tannin-like compounds; molybdenum binds to these organic ligands across a wide pH range. In deeper soils, molybdenum binds to both iron oxides and natural organic matter. We suggest that the molybdenum bound to organic matter can be captured by small complexing agents that are released by nitrogen-fixing bacteria; the molybdenum can then be incorporated into nitrogenase. We conclude that the binding of molybdenum to natural organic matter helps prevent leaching of molybdenum, and is thus a critical step in securing new nitrogen in terrestrial ecosystems.« less

The chiral quark condensate and pion decay constant in nuclear matter at next-to-leading order

NASA Astrophysics Data System (ADS)

Lacour, A.; Oller, J. A.; Meißner, U.-G.

2010-12-01

Making use of the recently developed chiral power counting for the physics of nuclear matter (Oller et al 2010 J. Phys. G: Nucl. Part. Phys. 37 015106, Lacour et al Ann. Phys. at press), we evaluate the in-medium chiral quark condensate up to next-to-leading order for both symmetric nuclear matter and neutron matter. Our calculation includes the full in-medium iteration of the leading order local and one-pion exchange nucleon-nucleon interactions. Interestingly, we find a cancellation between the contributions stemming from the quark mass dependence of the nucleon mass appearing in the in-medium nucleon-nucleon interactions. Only the contributions originating from the explicit quark mass dependence of the pion mass survive. This cancellation is the reason of previous observations concerning the dominant role of the long-range pion contributions and the suppression of short-range nucleon-nucleon interactions. We find that the linear density contribution to the in-medium chiral quark condensate is only slightly modified for pure neutron matter by the nucleon-nucleon interactions. For symmetric nuclear matter, the in-medium corrections are larger, although smaller compared to other approaches due to the full iteration of the lowest order nucleon-nucleon tree-level amplitudes. Our calculation satisfies the Hellmann-Feynman theorem to the order worked out. Also we address the problem of calculating the leading in-medium corrections to the pion decay constant. We find that there are no extra in-medium corrections that violate the Gell-Mann-Oakes-Renner relation up to next-to-leading order.

The effects of dexamethasone on rat brain cortical nuclear factor kappa B (NF-{kappa}B) in endotoxic shock

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

Wang Zhi; Kang Jinsong; Li Yang

2006-08-01

To explore the molecular mechanism of brain tissue injury induced by lipopolysaccharide (LPS), we studied the effects of endotoxic shock on rat brain cortex NF-{kappa}B and the effects of dexamethasone on these changes. Rats were randomly divided into LPS, LPS + dexamethasone, and control groups. The DNA-binding activity of NF-{kappa}B was observed using electrophoretic mobility shift assay (EMSA). Protein expression in nuclear extracts was studied using Western blots, and nuclear translocation was observed using immunohistochemistry. These indices were assayed at 1 h and 4 h after intravenous injection of LPS (4 mg.kg{sup -1}). EMSA showed significantly increased NF-{kappa}B DNA-binding activitymore » in nuclear extracts from the LPS group at both 1 h and 4 h after LPS injection, compared with the control group (P < 0.01). For the LPS group, the NF-{kappa}B DNA-binding activity was greater at 1 h than at 4 h (P < 0.05). The expression of p65 and p50 protein in the nuclear extracts was also increased, as compared with the control group. However, the expression of p65 and p50 protein from cytosolic extracts did not show any significant change. Dexamethasone down-regulated not only NF-{kappa}B DNA-binding activity but also the expression of p65 protein in the nuclear extracts. From these data, we have concluded that NF-{kappa}B activation and nuclear translocation of NF-{kappa}B play a key role in the molecular mechanism of brain tissue injury in endotoxic shock. Dexamethasone may alleviate brain injury by inhibiting NF-{kappa}B activation.« less

LINC Complexes Form by Binding of Three KASH Peptides to Domain Interfaces of Trimeric SUN Proteins

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

Sosa, Brian A.; Rothballer, Andrea; Kutay, Ulrike

Linker of nucleoskeleton and cytoskeleton (LINC) complexes span the nuclear envelope and are composed of KASH and SUN proteins residing in the outer and inner nuclear membrane, respectively. LINC formation relies on direct binding of KASH and SUN in the perinuclear space. Thereby, molecular tethers are formed that can transmit forces for chromosome movements, nuclear migration, and anchorage. We present crystal structures of the human SUN2-KASH1/2 complex, the core of the LINC complex. The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. The peptides bind in three deep and expansivemore » grooves formed between adjacent SUN domains, effectively acting as molecular glue. In addition, a disulfide between conserved cysteines on SUN and KASH covalently links both proteins. The structure provides the basis of LINC complex formation and suggests a model for how LINC complexes might arrange into higher-order clusters to enhance force-coupling.« less

RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators

PubMed Central

Redfern, Andrew D.; Colley, Shane M.; Beveridge, Dianne J.; Ikeda, Naoya; Epis, Michael R.; Li, Xia; Foulds, Charles E.; Stuart, Lisa M.; Barker, Andrew; Russell, Victoria J.; Ramsay, Kerry; Kobelke, Simon J.; Li, Xiaotao; Hatchell, Esme C.; Payne, Christine; Giles, Keith M.; Messineo, Adriana; Gatignol, Anne; Lanz, Rainer B.; O’Malley, Bert W.; Leedman, Peter J.

2013-01-01

The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. There is increasing evidence for important functional interactions between the miRNA and nuclear receptor (NR) signaling networks, with recent data showing that estrogen, acting through the estrogen receptor, can modulate initial aspects of nuclear miRNA processing. Here, we show that the cytoplasmic RISC proteins PACT, TRBP, and Dicer are steroid receptor RNA activator (SRA) binding NR coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression. Furthermore, each of the RISC proteins, together with Argonaute 2, associates with SRA and specific pre-microRNAs in both the nucleus and cytoplasm, providing evidence for links between NR-mediated transcription and some of the factors involved in miRNA processing. PMID:23550157

A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies

PubMed Central

Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

2016-01-01

The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior – a key element for the transport selectivity of the NPC – was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface. DOI: http://dx.doi.org/10.7554/eLife.14119.001 PMID:27058170

RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators.

PubMed

Redfern, Andrew D; Colley, Shane M; Beveridge, Dianne J; Ikeda, Naoya; Epis, Michael R; Li, Xia; Foulds, Charles E; Stuart, Lisa M; Barker, Andrew; Russell, Victoria J; Ramsay, Kerry; Kobelke, Simon J; Li, Xiaotao; Hatchell, Esme C; Payne, Christine; Giles, Keith M; Messineo, Adriana; Gatignol, Anne; Lanz, Rainer B; O'Malley, Bert W; Leedman, Peter J

2013-04-16

The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. There is increasing evidence for important functional interactions between the miRNA and nuclear receptor (NR) signaling networks, with recent data showing that estrogen, acting through the estrogen receptor, can modulate initial aspects of nuclear miRNA processing. Here, we show that the cytoplasmic RISC proteins PACT, TRBP, and Dicer are steroid receptor RNA activator (SRA) binding NR coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression. Furthermore, each of the RISC proteins, together with Argonaute 2, associates with SRA and specific pre-microRNAs in both the nucleus and cytoplasm, providing evidence for links between NR-mediated transcription and some of the factors involved in miRNA processing.

Reflections on the theory of "silver bullet" octreotide tracers: implications for ligand-receptor interactions in the age of peptides, heterodimers, receptor mosaics, truncated receptors, and multifractal analysis

PubMed Central

2011-01-01

The classical attitude of Nuclear Medicine practitioners on matters of peptide-receptor interactions has maintained an intrinsic monogamic character since many years. New advances in the field of biochemistry and even in clinical Nuclear Medicine have challenged this type of thinking, which prompted me to work on this review. The central issue of this paper will be the use of somatostatin analogs, i.e., octreotide, in clinical imaging procedures as well as in relation to neuroendocirne tumors. Newly described characteristics of G-protein coupled receptors such as the formation of receptor mosaics will be discussed. A small section will enumerate the regulatory processes found in the cell membrane. Possible new interpretations, other than tumor detection, based on imaging procedures with somatostatin analogs will be presented. The readers will be taken to situations such as inflammation, nociception, mechanosensing, chemosensing, fibrosis, taste, and vascularity where somatostatin is involved. Thyroid-associated orbitopathy will be used as a model for the development of multi-agent therapeutics. The final graphical summary depicts the multifactorial properties of ligand binding. PMID:22214590

A verotoxin 1 B subunit-lambda CRO chimeric protein specifically binds both DNA and globotriaosylceramide (Gb(3)) to effect nuclear targeting of exogenous DNA in Gb(3) positive cells.

PubMed

Facchini, L M; Lingwood, C A

2001-09-10

Inefficient nuclear incorporation of foreign DNA remains a critical roadblock in the development of effective nonviral gene delivery systems. DNA delivered by traditional protocols remains within endosomal/lysosomal vesicles, or is rapidly degraded in the cytoplasm. Verotoxin I (VT), an AB(5) subunit toxin produced by enterohaemorrhagic Escherichia coli, binds to the cell surface glycolipid, globotriaosylceramide (Gb(3)) and is internalized into preendosomes. VT is then retrograde transported to the Golgi, endoplasmic reticulum (ER), and nucleus of highly VT-sensitive cells. We have utilized this nuclear targeting of VT to design a unique delivery system which transports exogenous DNA via vesicular traffic to the nucleus. The nontoxic VT binding subunit (VTB) was fused to the lambda Cro DNA-binding repressor, generating a 14-kDa VTB-Cro chimera. VTB-Cro binds specifically via the Cro domain to a 25-bp DNA fragment containing the consensus Cro operator. VTB-Cro demonstrates simultaneous specific binding to Gb(3). Treatment of Vero cells with fluorescent-labeled Cro operator DNA in the presence of VTB-Cro, results in DNA internalization to the Golgi, ER, and nucleus, whereas fluorescent DNA alone is incorporated poorly and randomly within the cytoplasm. VTB-Cro mediated nuclear DNA transport is prevented by brefeldin A, consistent with Golgi/ER intracellular routing. Pretreatment with filipin had no effect, indicating that caveoli are not involved. This novel VTB-Cro shuttle protein may find practical applications in the fields of intracellular targeting, gene delivery, and gene therapy. Copyright 2001 Academic Press.

Role of nuclear charge change and nuclear recoil on shaking processes and their possible implication on physical processes

NASA Astrophysics Data System (ADS)

Sharma, Prashant

2017-12-01

The probable role of the sudden nuclear charge change and nuclear recoil in the shaking processes during the neutron- or heavy-ion-induced nuclear reactions and weakly interacting massive particle-nucleus scattering has been investigated in the present work. Using hydrogenic wavefunctions, general analytical expressions of survival, shakeup/shakedown, and shakeoff probability have been derived for various subshells of hydrogen-like atomic systems. These expressions are employed to calculate the shaking, shakeup/shakedown, and shakeoff probabilities in some important cases of interest in the nuclear astrophysics and the dark matter search experiments. The results underline that the shaking processes are one of the probable channels of electronic transitions during the weakly interacting massive particle-nucleus scattering, which can be used to probe the dark matter in the sub-GeV regime. Further, it is found that the shaking processes initiating due to nuclear charge change and nuclear recoil during the nuclear reactions may influence the electronic configuration of the participating atomic systems and thus may affect the nuclear reaction measurements at astrophysically relevant energies.

The Gpn3 Q279* cancer-associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting.

PubMed

Barbosa-Camacho, Angel A; Méndez-Hernández, Lucía E; Lara-Chacón, Bárbara; Peña-Gómez, Sonia G; Romero, Violeta; González-González, Rogelio; Guerra-Moreno, José A; Robledo-Rivera, Angélica Y; Sánchez-Olea, Roberto; Calera, Mónica R

2017-11-01

Gpn3 is required for RNA polymerase II (RNAPII) nuclear targeting. Here, we investigated the effect of a cancer-associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi-resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity were markedly decreased in cells expressing only Gpn3R Q279*. Wild-type Gpn3R localized to the cytoplasm but a fraction of Gpn3R Q279* entered the cell nucleus and inhibited Gpn1-EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*-expressing cells required a PDZ-binding motif generated by the Q279* mutation. We conclude that an acquired PDZ-binding motif in Gpn3 Q279* caused Gpn3 nuclear entry, and inhibited Gpn1 nuclear export and Gpn3-mediated RNAPII nuclear targeting. © 2017 Federation of European Biochemical Societies.

Auxiliary-field quantum Monte Carlo simulations of neutron matter in chiral effective field theory.

PubMed

Wlazłowski, G; Holt, J W; Moroz, S; Bulgac, A; Roche, K J

2014-10-31

We present variational Monte Carlo calculations of the neutron matter equation of state using chiral nuclear forces. The ground-state wave function of neutron matter, containing nonperturbative many-body correlations, is obtained from auxiliary-field quantum Monte Carlo simulations of up to about 340 neutrons interacting on a 10(3) discretized lattice. The evolution Hamiltonian is chosen to be attractive and spin independent in order to avoid the fermion sign problem and is constructed to best reproduce broad features of the chiral nuclear force. This is facilitated by choosing a lattice spacing of 1.5 fm, corresponding to a momentum-space cutoff of Λ=414  MeV/c, a resolution scale at which strongly repulsive features of nuclear two-body forces are suppressed. Differences between the evolution potential and the full chiral nuclear interaction (Entem and Machleidt Λ=414  MeV [L. Coraggio et al., Phys. Rev. C 87, 014322 (2013).

Surface properties for α-cluster nuclear matter

NASA Astrophysics Data System (ADS)

Castro, J. J.; Soto, J. R.; Yépez, E.

2013-03-01

We introduce a new microscopic model for α-cluster matter, which simulates the properties of ordinary nuclear matter and α-clustering in a curved surface of a large but finite nucleus. The model is based on a nested icosahedral fullerene-like multiple-shell structure, where each vertex is occupied by a microscopic α-particle. The novel aspect of this model is that it allows a consistent description of nuclear surface properties from microscopic parameters to be made without using the leptodermous expansion. In particular, we show that the calculated surface energy is in excellent agreement with the corresponding coefficient of the Bethe-Weizäcker semi-empirical mass formula. We discuss the properties of the surface α-cluster state, which resembles an ultra cold bosonic quantum gas trapped in an optical lattice. By comparing the surface and interior states we are able to estimate the α preformation probability. Possible extensions of this model to study nuclear dynamics through surface vibrations and departures from approximate sphericity are mentioned.

Nuclear pasta phases within the quark-meson coupling model

NASA Astrophysics Data System (ADS)

Grams, Guilherme; Santos, Alexandre M.; Panda, Prafulla K.; Providência, Constança; Menezes, Débora P.

2017-05-01

In this work, the low-density regions of nuclear and neutron star matter are studied. The search for the existence of nuclear pasta phases in this region is performed within the context of the quark-meson coupling (QMC) model, which incorporates quark degrees of freedom. Fixed proton fractions are considered, as well as nuclear matter in β equilibrium at zero temperature. We discuss the recent attempts to better understand the surface energy in the coexistence phases regime and we present results that show the existence of the pasta phases subject to some choices of the surface energy coefficient. We also analyze the influence of the nuclear pasta on some neutron star properties. The equation of state containing the pasta phase will be part of a complete grid for future use in supernova simulations.

The pure estrogen receptor antagonist ICI 182,780 promotes a novel interaction of estrogen receptor-alpha with the 3',5'-cyclic adenosine monophosphate response element-binding protein-binding protein/p300 coactivators.

PubMed

Jaber, Basem M; Gao, Tong; Huang, Luping; Karmakar, Sudipan; Smith, Carolyn L

2006-11-01

Estrogen receptor-alpha (ERalpha) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Abundant evidence demonstrates that ERalpha agonists promote, whereas antagonists inhibit, receptor binding to coactivators. In this report we demonstrate that binding of the ICI 182,780 (ICI) pure antiestrogen to ERalpha promotes its interaction with the cAMP response element-binding protein-binding protein (CBP)/p300 but not the p160 family of coactivators, demonstrating the specificity of this interaction. Amino acid mutations within the coactivator binding surface of the ERalpha ligand-binding domain revealed that CBP binds to this region of the ICI-liganded receptor. The carboxy-terminal cysteine-histidine rich domain 3 of CBP, rather than its amino-terminal nuclear interacting domain, shown previously to mediate agonist-dependent interactions of CBP with nuclear receptors, is required for binding to ICI-liganded ERalpha. Chromatin immunoprecipitation assays revealed that ICI but not the partial agonist/antagonist 4-hydroxytamoxifen is able to recruit CBP to the pS2 promoter, and this distinguishes ICI from this class of antiestrogens. Chromatin immunoprecipitation assays for pS2 and cytochrome P450 1B1 promoter regions revealed that ICI-dependent recruitment of CBP, but not receptor, to ERalpha targets is gene specific. ICI treatment did not recruit the steroid receptor coactivator 1 to the pS2 promoter, and it failed to induce the expression of this gene. Taken together, these data indicate that recruitment of the CBP coactivator/cointegrator without steroid receptor coactivator 1 to ERalpha is insufficient to promote transcription of ERalpha target genes.

Proposed entanglement of X-ray nuclear polaritons as a potential method for probing matter at the subatomic scale.

PubMed

Liao, Wen-Te; Pálffy, Adriana

2014-02-07

A setup for generating the special superposition of a simultaneously forward- and backward-propagating collective excitation in a nuclear sample is studied. We show that by actively manipulating the scattering channels of single x-ray quanta with the help of a normal incidence x-ray mirror, a nuclear polariton which propagates in two opposite directions can be generated. The two counterpropagating polariton branches are entangled by a single x-ray photon. The quantum nature of the nuclear excitation entanglement gives rise to a subangstrom-wavelength standing wave excitation pattern that can be used as a flexible tool to probe matter dynamically on the subatomic scale.

Does CTCF mediate between nuclear organization and gene expression?

PubMed

Ohlsson, Rolf; Lobanenkov, Victor; Klenova, Elena

2010-01-01

The multifunctional zinc-finger protein CCCTC-binding factor (CTCF) is a very strong candidate for the role of coordinating the expression level of coding sequences with their three-dimensional position in the nucleus, apparently responding to a "code" in the DNA itself. Dynamic interactions between chromatin fibers in the context of nuclear architecture have been implicated in various aspects of genome functions. However, the molecular basis of these interactions still remains elusive and is a subject of intense debate. Here we discuss the nature of CTCF-DNA interactions, the CTCF-binding specificity to its binding sites and the relationship between CTCF and chromatin, and we examine data linking CTCF with gene regulation in the three-dimensional nuclear space. We discuss why these features render CTCF a very strong candidate for the role and propose a unifying model, the "CTCF code," explaining the mechanistic basis of how the information encrypted in DNA may be interpreted by CTCF into diverse nuclear functions.

Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization

PubMed Central

Roux, Kyle J.; Crisp, Melissa L.; Liu, Qian; Kim, Daein; Kozlov, Serguei; Stewart, Colin L.; Burke, Brian

2009-01-01

Nucleocytoplasmic coupling is mediated by outer nuclear membrane (ONM) nesprin proteins and inner nuclear membrane Sun proteins. Interactions spanning the perinuclear space create nesprin–Sun complexes connecting the cytoskeleton to nuclear components. A search for proteins displaying a conserved C-terminal sequence present in nesprins 1–3 identified nesprin 4 (Nesp4), a new member of this family. Nesp4 is a kinesin-1-binding protein that displays Sun-dependent localization to the ONM. Expression of Nesp4 is associated with dramatic changes in cellular organization involving relocation of the centrosome and Golgi apparatus relative to the nucleus. These effects can be accounted for entirely by Nesp4's kinesin-binding function. The implication is that Nesp4 may contribute to microtubule-dependent nuclear positioning. PMID:19164528

Nesprin 4 is an outer nuclear membrane protein that can induce kinesin-mediated cell polarization.

PubMed

Roux, Kyle J; Crisp, Melissa L; Liu, Qian; Kim, Daein; Kozlov, Serguei; Stewart, Colin L; Burke, Brian

2009-02-17

Nucleocytoplasmic coupling is mediated by outer nuclear membrane (ONM) nesprin proteins and inner nuclear membrane Sun proteins. Interactions spanning the perinuclear space create nesprin-Sun complexes connecting the cytoskeleton to nuclear components. A search for proteins displaying a conserved C-terminal sequence present in nesprins 1-3 identified nesprin 4 (Nesp4), a new member of this family. Nesp4 is a kinesin-1-binding protein that displays Sun-dependent localization to the ONM. Expression of Nesp4 is associated with dramatic changes in cellular organization involving relocation of the centrosome and Golgi apparatus relative to the nucleus. These effects can be accounted for entirely by Nesp4's kinesin-binding function. The implication is that Nesp4 may contribute to microtubule-dependent nuclear positioning.

Role of ANC-1 in tethering nuclei to the actin cytoskeleton.

PubMed

Starr, Daniel A; Han, Min

2002-10-11

Mutations in anc-1 (nuclear anchorage defective) disrupt the positioning of nuclei and mitochondria in Caenorhabditis elegans. ANC-1 is shown to consist of mostly coiled regions with a nuclear envelope localization domain (called the KASH domain) and an actin-binding domain; this structure was conserved with the Drosophila protein Msp-300 and the mammalian Syne proteins. Antibodies against ANC-1 localized cytoplasmically and were enriched at the nuclear periphery in an UNC-84-dependent manner. Overexpression of the KASH domain or the actin-binding domain caused a dominant negative anchorage defect. Thus, ANC-1 may connect nuclei to the cytoskeleton by interacting with UNC-84 at the nuclear envelope and with actin in the cytoplasm.

10 CFR 4.44 - Resolution of matters.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Resolution of matters. 4.44 Section 4.44 Energy NUCLEAR... matters. (a) If an investigation pursuant to § 4.43 indicates a failure to comply with this subpart, the responsible NRC official will so inform the recipient and the matter will be resolved by voluntary means...

10 CFR 4.44 - Resolution of matters.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Resolution of matters. 4.44 Section 4.44 Energy NUCLEAR... matters. (a) If an investigation pursuant to § 4.43 indicates a failure to comply with this subpart, the responsible NRC official will so inform the recipient and the matter will be resolved by voluntary means...

10 CFR 4.44 - Resolution of matters.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Resolution of matters. 4.44 Section 4.44 Energy NUCLEAR... matters. (a) If an investigation pursuant to § 4.43 indicates a failure to comply with this subpart, the responsible NRC official will so inform the recipient and the matter will be resolved by voluntary means...

10 CFR 4.44 - Resolution of matters.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Resolution of matters. 4.44 Section 4.44 Energy NUCLEAR... matters. (a) If an investigation pursuant to § 4.43 indicates a failure to comply with this subpart, the responsible NRC official will so inform the recipient and the matter will be resolved by voluntary means...

10 CFR 4.44 - Resolution of matters.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Resolution of matters. 4.44 Section 4.44 Energy NUCLEAR... matters. (a) If an investigation pursuant to § 4.43 indicates a failure to comply with this subpart, the responsible NRC official will so inform the recipient and the matter will be resolved by voluntary means...

Intrinsic neutron background of nuclear emulsions for directional Dark Matter searches

NASA Astrophysics Data System (ADS)

Alexandrov, A.; Asada, T.; Buonaura, A.; Consiglio, L.; D'Ambrosio, N.; De Lellis, G.; Di Crescenzo, A.; Di Marco, N.; Di Vacri, M. L.; Furuya, S.; Galati, G.; Gentile, V.; Katsuragawa, T.; Laubenstein, M.; Lauria, A.; Loverre, P. F.; Machii, S.; Monacelli, P.; Montesi, M. C.; Naka, T.; Pupilli, F.; Rosa, G.; Sato, O.; Strolin, P.; Tioukov, V.; Umemoto, A.; Yoshimoto, M.

2016-07-01

Recent developments of the nuclear emulsion technology led to the production of films with nanometric silver halide grains suitable to track low energy nuclear recoils with submicrometric length. This improvement opens the way to a directional Dark Matter detection, thus providing an innovative and complementary approach to the on-going WIMP searches. An important background source for these searches is represented by neutron-induced nuclear recoils that can mimic the WIMP signal. In this paper we provide an estimation of the contribution to this background from the intrinsic radioactive contamination of nuclear emulsions. We also report the neutron-induced background as a function of the read-out threshold, by using a GEANT4 simulation of the nuclear emulsion, showing that it amounts to about 0.06 per year per kilogram, fully compatible with the design of a 10 kg × year exposure.

Toxic metals (Ni2+, Pb2+, Hg2+) binding affinity of dissolved organic matter (DOM) derived from different ages municipal landfill leachate

NASA Astrophysics Data System (ADS)

Rikta, S. Y.; Tareq, Shafi M.; Uddin, M. Khabir

2018-03-01

Solid waste production is rapidly increasing in Bangladesh and landfill leachate is the consequence of the decomposition of this waste. These leachates contain heavy metals and significant amount of dissolved organic matter (DOM). DOM is known to have considerable role in heavy metals speciation. Hence, it is important to characterize DOM/leachate and evaluate toxic metals binding affinity of DOM. The objectives of this study were to characterize the DOM in landfill leachate through physico-chemical and optical analyses and to investigate the toxic metals (Ni2+, Pb2+ and Hg2+) binding affinity of three different ages (fresh sample L-1, young sample L-2 and mature sample L-3) DOM samples. Results suggested that leachate is a potential pollutant which contained very high organic pollutant load. Conditional stability constant (Log K) and percentages of fluorophores that correspond to metal binding (% f) values indicated that young DOM sample (L-2) had the highest binding affinity to all the three metals ions. In general, DOM samples showed the following order affinity to the metal ions; Ni2+ binding affinity: L-2 > L-3 > L-1, Pb2+ binding affinity: L-2 > L-3 > L-1 and Hg2+ binding affinity: L-2 > L-1 > L-3.

Self-Organization of Metal Nanoparticles in Light: Electrodynamics-Molecular Dynamics Simulations and Optical Binding Experiments.

PubMed

McCormack, Patrick; Han, Fei; Yan, Zijie

2018-02-01

Light-driven self-organization of metal nanoparticles (NPs) can lead to unique optical matter systems, yet simulation of such self-organization (i.e., optical binding) is a complex computational problem that increases nonlinearly with system size. Here we show that a combined electrodynamics-molecular dynamics simulation technique can simulate the trajectories and predict stable configurations of silver NPs in optical fields. The simulated dynamic equilibrium of a two-NP system matches the probability density of oscillations for two optically bound NPs obtained experimentally. The predicted stable configurations for up to eight NPs are further compared to experimental observations of silver NP clusters formed by optical binding in a Bessel beam. All configurations are confirmed to form in real systems, including pentagonal clusters with five-fold symmetry. Our combined simulations and experiments have revealed a diverse optical matter system formed by anisotropic optical binding interactions, providing a new strategy to discover artificial materials.

The insulin and islet amyloid polypeptide genes contain similar cell-specific promoter elements that bind identical beta-cell nuclear complexes.

PubMed Central

German, M S; Moss, L G; Wang, J; Rutter, W J

1992-01-01

The pancreatic beta cell makes several unique gene products, including insulin, islet amyloid polypeptide (IAPP), and beta-cell-specific glucokinase (beta GK). The functions of isolated portions of the insulin, IAPP, and beta GK promoters were studied by using transient expression and DNA binding assays. A short portion (-247 to -197 bp) of the rat insulin I gene, the FF minienhancer, contains three interacting transcriptional regulatory elements. The FF minienhancer binds at least two nuclear complexes with limited tissue distribution. Sequences similar to that of the FF minienhancer are present in the 5' flanking DNA of the human IAPP and rat beta GK genes and also the rat insulin II and mouse insulin I and II genes. Similar minienhancer constructs from the insulin and IAPP genes function as cell-specific transcriptional regulatory elements and compete for binding of the same nuclear factors, while the beta GK construct competes for protein binding but functions poorly as a minienhancer. These observations suggest that the patterns of expression of the beta-cell-specific genes result in part from sharing the same transcriptional regulators. Images PMID:1549125

Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

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

Wada, Takeyoshi; Asahi, Toru; Research Organization for Nano & Life Innovation, Waseda University #03C309, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480

2016-08-26

The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as amore » thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. - Highlights: • We found that CRBN is a nucleocytoplasmic shutting protein and identified the key domain for nucleocytoplasmic shuttling. • CRBN associates with the transcription factor Ikaros via the N-terminal domain. • CRBN modulates Ikaros-mediated transcriptional regulation and its downstream target, enkephalin.« less

Mammalian Peptidylglycine α-Amidating Monooxygenase mRNA Expression Can Be Modulated by the La Autoantigen

PubMed Central

Brenet, Fabienne; Dussault, Nadège; Borch, Jonas; Ferracci, Géraldine; Delfino, Christine; Roepstorff, Peter; Miquelis, Raymond; Ouafik, L'Houcine

2005-01-01

Peptidylglycine α-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the COOH-terminal α-amidation of peptidylglycine substrates, yielding amidated products. We have previously reported a putative regulatory RNA binding protein (PAM mRNA-BP) that binds specifically to the 3′ untranslated region (UTR) of PAM-mRNA. Here, the PAM mRNA-BP was isolated and revealed to be La protein using affinity purification onto a 3′ UTR PAM RNA, followed by tandem mass spectrometry identification. We determined that the core binding sequence is approximately 15-nucleotides (nt) long and is located 471 nt downstream of the stop codon. Moreover, we identified the La autoantigen as a protein that specifically binds the 3′ UTR of PAM mRNA in vivo and in vitro. Furthermore, La protein overexpression caused a nuclear retention of PAM mRNAs and resulted in the down-regulation of endogenous PAM activity. Most interestingly, the nuclear retention of PAM mRNA is lost upon expressing the La proteins that lack a conserved nuclear retention element, suggesting a direct association between PAM mRNA and La protein in vivo. Reporter assays using a chimeric mRNA that combined luciferase and the 3′ UTR of PAM mRNA demonstrated a decrease of the reporter activity due to an increase in the nuclear localization of reporter mRNAs, while the deletion of the 15-nt La binding site led to their clear-cut cytoplasmic relocalization. The results suggest an important role for the La protein in the modulation of PAM expression, possibly by mechanisms that involve a nuclear retention and perhaps a processing of pre-PAM mRNA molecules. PMID:16107699

Specific repression of β-globin promoter activity by nuclear ferritin

PubMed Central

Broyles, Robert H.; Belegu, Visar; DeWitt, Christina R.; Shah, Sandeep N.; Stewart, Charles A.; Pye, Quentin N.; Floyd, Robert A.

2001-01-01

Developmental hemoglobin switching involves sequential globin gene activations and repressions that are incompletely understood. Earlier observations, described herein, led us to hypothesize that nuclear ferritin is a repressor of the adult β-globin gene in embryonic erythroid cells. Our data show that a ferritin-family protein in K562 cell nuclear extracts binds specifically to a highly conserved CAGTGC motif in the β-globin promoter at −153 to −148 bp from the cap site, and mutation of the CAGTGC motif reduces binding 20-fold in competition gel-shift assays. Purified human ferritin that is enriched in ferritin-H chains also binds the CAGTGC promoter segment. Expression clones of ferritin-H markedly repress β-globin promoter-driven reporter gene expression in cotransfected CV-1 cells in which the β-promoter has been stimulated with the transcription activator erythroid Krüppel-like factor (EKLF). We have constructed chloramphenicol acetyltransferase reporter plasmids containing either a wild-type or mutant β-globin promoter for the −150 CAGTGC motif and have compared the constructs for susceptibility to repression by ferritin-H in cotransfection assays. We find that stimulation by cotransfected EKLF is retained with the mutant promoter, whereas repression by ferritin-H is lost. Thus, mutation of the −150 CAGTGC motif not only markedly reduces in vitro binding of nuclear ferritin but also abrogates the ability of expressed ferritin-H to repress this promoter in our cell transfection assay, providing a strong link between DNA binding and function, and strong support for our proposal that nuclear ferritin-H is a repressor of the human β-globin gene. Such a repressor could be helpful in treating sickle cell and other genetic diseases. PMID:11481480

Chiral effective theory of dark matter direct detection

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

Bishara, Fady; Brod, Joachim; Grinstein, Benjamin

2017-02-01

We present the effective field theory for dark matter interactions with the visible sector that is valid at scales of O(1 GeV). Starting with an effective theory describing the interactions of fermionic and scalar dark matter with quarks, gluons and photons via higher dimension operators that would arise from dimension-five and dimension-six operators above electroweak scale, we perform a nonperturbative matching onto a heavy baryon chiral perturbation theory that describes dark matter interactions with light mesons and nucleons. This is then used to obtain the coefficients of the nuclear response functions using a chiral effective theory description of nuclear forces.more » Our results consistently keep the leading contributions in chiral counting for each of the initial Wilson coefficients.« less

Nuclear scaffold attachment stimulates, but is not essential for ARS activity in Saccharomyces cerevisiae: analysis of the Drosophila ftz SAR.

PubMed Central

Amati, B; Pick, L; Laroche, T; Gasser, S M

1990-01-01

Nuclei isolated from eukaryotic cells can be depleted of histones and most soluble nuclear proteins to isolate a structural framework called the nuclear scaffold. This structure maintains specific interactions with genomic DNA at sites known as scaffold attached regions (SARs), which are thought to be the bases of DNA loops. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, genomic ARS elements are recovered as SARs. In addition, SARs from Drosophila melanogaster bind to yeast nuclear scaffolds in vitro and a subclass of these promotes autonomous replication of plasmids in yeast. In the present report, we present fine mapping studies of the Drosophila ftz SAR, which has both SAR and ARS activities in yeast. The data establish a close relationship between the sequences involved in ARS activity and scaffold binding: ARS elements that can bind the nuclear scaffold in vitro promote more efficient plasmid replication in vivo, but scaffold association is not a strict prerequisite for ARS function. Efficient interaction with nuclear scaffolds from both yeast and Drosophila requires a minimal length of SAR DNA that contains reiteration of a narrow minor groove structure of the double helix. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2123454

Autosomal recessive mutations in nuclear transport factor KPNA7 are associated with infantile spasms and cerebellar malformation.

PubMed

Paciorkowski, Alex R; Weisenberg, Judy; Kelley, Joshua B; Spencer, Adam; Tuttle, Emily; Ghoneim, Dalia; Thio, Liu Lin; Christian, Susan L; Dobyns, William B; Paschal, Bryce M

2014-05-01

Nuclear import receptors of the KPNA family recognize the nuclear localization signal in proteins and together with importin-β mediate translocation into the nucleus. Accordingly, KPNA family members have a highly conserved architecture with domains that contact the nuclear localization signal and bind to importin-β. Here, we describe autosomal recessive mutations in KPNA7 found by whole exome sequencing in a sibling pair with severe developmental disability, infantile spasms, subsequent intractable epilepsy consistent with Lennox-Gastaut syndrome, partial agenesis of the corpus callosum, and cerebellar vermis hypoplasia. The mutations mapped to exon 7 in KPNA7 result in two amino-acid substitutions, Pro339Ala and Glu344Gln. On the basis of the crystal structure of the paralog KPNA2 bound to a bipartite nuclear localization signal from the retinoblastoma protein, the amino-acid substitutions in the affected subjects were predicted to occur within the seventh armadillo repeat that forms one of the two nuclear localization signal-binding sites in KPNA family members. Glu344 is conserved in all seven KPNA proteins, and we found that the Glu354Gln mutation in KPNA2 is sufficient to reduce binding to the retinoblastoma nuclear localization signal to approximately one-half that of wild-type protein. Our data show that compound heterozygous mutations in KPNA7 are associated with a human neurodevelopmental disease, and provide the first example of a human disease associated with mutation of a nuclear transport receptor.

Autosomal recessive mutations in nuclear transport factor KPNA7 are associated with infantile spasms and cerebellar malformation

PubMed Central

Paciorkowski, Alex R; Weisenberg, Judy; Kelley, Joshua B; Spencer, Adam; Tuttle, Emily; Ghoneim, Dalia; Thio, Liu Lin; Christian, Susan L; Dobyns, William B; Paschal, Bryce M

2014-01-01

Nuclear import receptors of the KPNA family recognize the nuclear localization signal in proteins and together with importin-β mediate translocation into the nucleus. Accordingly, KPNA family members have a highly conserved architecture with domains that contact the nuclear localization signal and bind to importin-β. Here, we describe autosomal recessive mutations in KPNA7 found by whole exome sequencing in a sibling pair with severe developmental disability, infantile spasms, subsequent intractable epilepsy consistent with Lennox–Gastaut syndrome, partial agenesis of the corpus callosum, and cerebellar vermis hypoplasia. The mutations mapped to exon 7 in KPNA7 result in two amino-acid substitutions, Pro339Ala and Glu344Gln. On the basis of the crystal structure of the paralog KPNA2 bound to a bipartite nuclear localization signal from the retinoblastoma protein, the amino-acid substitutions in the affected subjects were predicted to occur within the seventh armadillo repeat that forms one of the two nuclear localization signal-binding sites in KPNA family members. Glu344 is conserved in all seven KPNA proteins, and we found that the Glu354Gln mutation in KPNA2 is sufficient to reduce binding to the retinoblastoma nuclear localization signal to approximately one-half that of wild-type protein. Our data show that compound heterozygous mutations in KPNA7 are associated with a human neurodevelopmental disease, and provide the first example of a human disease associated with mutation of a nuclear transport receptor. PMID:24045845

Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

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

Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha

2014-07-18

Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated thatmore » TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.« less

Embryonic subcellular distribution of 13-cis- and all-trans-retinoic acid indicates differential cytosolic/nuclear localization.

PubMed

Rühl, R; Plum, C; Elmazar, M M; Nau, H

2001-09-01

Isotretinoin (13-cis-retinoic acid [13CRA], Accutane) is used for the treatment of dermatological diseases. Isotretinoin is, however, teratogenic in animals and humans. The mechanism of action of its teratogenicity is still not clearly identified. It has little or no binding properties to cytosolic retinoid-binding proteins or nuclear retinoid receptors (RAR, RXR). One hypothesis is that the teratogenicity of 2 approximately equipotent teratogenic doses of 13CRA and all-trans-retinoic acids (ATRA) could mainly be correlated to ATRA in the nuclei, where the retinoic acid receptors (RARs) are located. To test this hypothesis, female mice at gestational day 11 were treated with approximately equipotent teratogenic doses of 13-cis-retinoic acid (100 mg/kg orally) or all-trans-retinoic acid (10 mg/kg orally) and sacrificed 1 h and 4 h after administration. Embryos were homogenized and centrifuged into 4 fractions, and the purity of the fractions was tested by quantification of marker constituents for various cell compartments. We analyzed, by RP-HPLC, nuclear, mitochondrial, microsomal, and cytosolic fractions, as well as embryo homogenate and maternal plasma. After treatment with 13-cis-retinoic acid, this substance was mainly located in the nuclear fraction of the embryo (approximately 82%), whereas all-trans-retinoic acid, after ATRA treatment, was mainly located in the cytosolic supernatant (approximately 64%). The binding to cellular retinoid-binding protein (CRABP) may limit the access of ATRA to the nucleus, in contrast to 13CRA, which does not bind to CRABP. The concentration of ATRA in the nuclear fraction was similar after administration of either 13CRA or ATRA. The teratogenic activity of 13-cis-retinoic acid could therefore be explained by its access to the nucleus and its possible conversion to all-trans-retinoic acids, which will interact with the nuclear retinoid receptors.

High-affinity binding of (/sup 3/H)estradiol-17 beta by an estrogen receptor in the liver of the turtle

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

Ho, S.M.; Fehrer, S.; Yu, M.

1988-06-01

Specific (3H)estradiol-17 beta ((3H)E2) binding activity (EBA) with characteristics of an estrogen receptor (ER) was demonstrated in cytosols and nuclear extracts of the female turtle, Chrysemys picta. Three different receptor assays (dextran-coated charcoal assay, hydroxylapatite batch procedure, and DNA-cellulose chromatography) were evaluated in terms of their applicability in analyzing large numbers of samples. For the measurement of cytosolic EBA, the hydroxylapatite batch procedure was found to be the most reliable assay. On the other hand, the dextran-coated charcoal assay was found to be the most appropriate method for the measurement of nuclear EBA. Turtle hepatic EBA binds (3H)E2 with highmore » affinity (cytosolic, 17.4 +/- 2.8 X 10(9) M-1; nuclear, 17.7 +/- 1.9 X 10(9) M-1), limited capacity (cytosolic, 133.7 +/- 4.6 fmol/g tissue; nuclear, 81.1 +/- 9.0 fmol/g tissue), and strict steroid specificity. The EBA bound natural estrogens (E2, estrone, estriol) as well as the nonsteroidal estrogen, diethylstilbestrol, but exhibited little affinity for androgens, progesterone, or corticosterone. The turtle hepatic EBA resembled mammalian and avian ERs in terms of binding characteristics; however, unlike mammalian and avian ERs it was shown to be heat-labile. Incubation at 30 degrees caused rapid loss of (3H)E2 binding activity in both cytosolic and nuclear fractions. The exchange between (3H)E2 and the endogenously bound estrogen was slow at 4 and 15 degrees, but the exchange process was facilitated in the presence of the chaotropic salt, NaSCN. Establishment of quantitation methods for both cytosolic and nuclear forms of EBA will enable future investigation of the mechanism and regulation of estrogen action in the liver of this turtle species.« less

Ammonoxidised lignins as slow nitrogen-releasing soil amendments and CO₂-binding matrix.

PubMed

Liebner, Falk; Pour, Georg; de la Rosa Arranz, José Maria; Hilscher, André; Rosenau, Thomas; Knicker, Heike

2011-09-05

Nitrogen (N) is a major nutrient element controlling the cycling of organic matter in the biosphere. Its availability in soils is closely related to biological productivity. In order to reduce the negative environmental impact, associated with the application of mineral N-fertilizers, the use of ammonoxidised technical lignins is suggested. They can act as potential slow N-release fertilisers which concomitantly may increase C sequestration of soils by its potential to bind CO₂. The idea of our study was to combine an improved chemical characterisation of ammonoxidised ligneous matter as well as their CO₂-binding potential, with laboratory pot experiments, performed to enable an evaluation of their behaviour and stability during the biochemical reworking occurring in active soils.

Cold-nuclear-matter effects on heavy-quark production at forward and backward rapidity in d + Au collisions at √sNN = 200  GeV.

PubMed

Adare, A; Aidala, C; Ajitanand, N N; Akiba, Y; Akimoto, R; Al-Bataineh, H; Al-Ta'ani, H; Alexander, J; Andrews, K R; Angerami, A; Aoki, K; Apadula, N; Appelt, E; Aramaki, Y; Armendariz, R; Aschenauer, E C; Atomssa, E T; Averbeck, R; Awes, T C; Azmoun, B; Babintsev, V; Bai, M; Baksay, G; Baksay, L; Bannier, B; Barish, K N; Bassalleck, B; Basye, A T; Bathe, S; Baublis, V; Baumann, C; Bazilevsky, A; Belikov, S; Belmont, R; Ben-Benjamin, J; Bennett, R; Bhom, J H; Blau, D S; Bok, J S; Boyle, K; Brooks, M L; Broxmeyer, D; Buesching, H; Bumazhnov, V; Bunce, G; Butsyk, S; Campbell, S; Caringi, A; Castera, P; Chen, C-H; Chi, C Y; Chiu, M; Choi, I J; Choi, J B; Choudhury, R K; Christiansen, P; Chujo, T; Chung, P; Chvala, O; Cianciolo, V; Citron, Z; Cole, B A; Conesa Del Valle, Z; Connors, M; Csanád, M; Csörgő, T; Dahms, T; Dairaku, S; Danchev, I; Das, K; Datta, A; David, G; Dayananda, M K; Denisov, A; Deshpande, A; Desmond, E J; Dharmawardane, K V; Dietzsch, O; Dion, A; Donadelli, M; Drapier, O; Drees, A; Drees, K A; Durham, J M; Durum, A; Dutta, D; D'Orazio, L; Edwards, S; Efremenko, Y V; Ellinghaus, F; Engelmore, T; Enokizono, A; En'yo, H; Esumi, S; Fadem, B; Fields, D E; Finger, M; Finger, M; Fleuret, F; Fokin, S L; Fraenkel, Z; Frantz, J E; Franz, A; Frawley, A D; Fujiwara, K; Fukao, Y; Fusayasu, T; Gal, C; Garishvili, I; Glenn, A; Gong, H; Gong, X; Gonin, M; Goto, Y; Granier de Cassagnac, R; Grau, N; Greene, S V; Grim, G; Grosse Perdekamp, M; Gunji, T; Guo, L; Gustafsson, H-Å; Haggerty, J S; Hahn, K I; Hamagaki, H; Hamblen, J; Han, R; Hanks, J; Harper, C; Hashimoto, K; Haslum, E; Hayano, R; He, X; Heffner, M; Hemmick, T K; Hester, T; Hill, J C; Hohlmann, M; Hollis, R S; Holzmann, W; Homma, K; Hong, B; Horaguchi, T; Hori, Y; Hornback, D; Huang, S; Ichihara, T; Ichimiya, R; Iinuma, H; Ikeda, Y; Imai, K; Inaba, M; Iordanova, A; Isenhower, D; Ishihara, M; Issah, M; Ivanischev, D; Iwanaga, Y; Jacak, B V; Jia, J; Jiang, X; Jin, J; John, D; Johnson, B M; Jones, T; Joo, K S; Jouan, D; Jumper, D S; Kajihara, F; Kamin, J; Kaneti, S; Kang, B H; Kang, J H; Kang, J S; Kapustinsky, J; Karatsu, K; Kasai, M; Kawall, D; Kawashima, M; Kazantsev, A V; Kempel, T; Khanzadeev, A; Kijima, K M; Kikuchi, J; Kim, A; Kim, B I; Kim, D J; Kim, E-J; Kim, Y-J; Kim, Y K; Kinney, E; Kiss, A; Kistenev, E; Kleinjan, D; Kline, P; Kochenda, L; Komkov, B; Konno, M; Koster, J; Kotov, D; Král, A; Kravitz, A; Kunde, G J; Kurita, K; Kurosawa, M; Kwon, Y; Kyle, G S; Lacey, R; Lai, Y S; Lajoie, J G; Lebedev, A; Lee, D M; Lee, J; Lee, K B; Lee, K S; Lee, S H; Lee, S R; Leitch, M J; Leite, M A L; Li, X; Lichtenwalner, P; Liebing, P; Lim, S H; Linden Levy, L A; Liška, T; Liu, H; Liu, M X; Love, B; Lynch, D; Maguire, C F; Makdisi, Y I; Malik, M D; Manion, A; Manko, V I; Mannel, E; Mao, Y; Masui, H; Matathias, F; McCumber, M; McGaughey, P L; McGlinchey, D; McKinney, C; Means, N; Mendoza, M; Meredith, B; Miake, Y; Mibe, T; Mignerey, A C; Miki, K; Milov, A; Mitchell, J T; Miyachi, Y; Mohanty, A K; Moon, H J; Morino, Y; Morreale, A; Morrison, D P; Motschwiller, S; Moukhanova, T V; Murakami, T; Murata, J; Nagamiya, S; Nagle, J L; Naglis, M; Nagy, M I; Nakagawa, I; Nakamiya, Y; Nakamura, K R; Nakamura, T; Nakano, K; Nam, S; Newby, J; Nguyen, M; Nihashi, M; Nouicer, R; Nyanin, A S; Oakley, C; O'Brien, E; Oda, S X; Ogilvie, C A; Oka, M; Okada, K; Onuki, Y; Oskarsson, A; Ouchida, M; Ozawa, K; Pak, R; Pantuev, V; Papavassiliou, V; Park, B H; Park, I H; Park, S K; Park, W J; Pate, S F; Patel, L; Pei, H; Peng, J-C; Pereira, H; Peressounko, D Yu; Petti, R; Pinkenburg, C; Pisani, R P; Proissl, M; Purschke, M L; Qu, H; Rak, J; Ravinovich, I; Read, K F; Rembeczki, S; Reygers, K; Riabov, V; Riabov, Y; Richardson, E; Roach, D; Roche, G; Rolnick, S D; Rosati, M; Rosen, C A; Rosendahl, S S E; Ružička, P; Sahlmueller, B; Saito, N; Sakaguchi, T; Sakashita, K; Samsonov, V; Sano, S; Sarsour, M; Sato, T; Savastio, M; Sawada, S; Sedgwick, K; Seele, J; Seidl, R; Seto, R; Sharma, D; Shein, I; Shibata, T-A; Shigaki, K; Shim, H H; Shimomura, M; Shoji, K; Shukla, P; Sickles, A; Silva, C L; Silvermyr, D; Silvestre, C; Sim, K S; Singh, B K; Singh, C P; Singh, V; Slunečka, M; Sodre, T; Soltz, R A; Sondheim, W E; Sorensen, S P; Sourikova, I V; Stankus, P W; Stenlund, E; Stoll, S P; Sugitate, T; Sukhanov, A; Sun, J; Sziklai, J; Takagui, E M; Takahara, A; Taketani, A; Tanabe, R; Tanaka, Y; Taneja, S; Tanida, K; Tannenbaum, M J; Tarafdar, S; Taranenko, A; Tennant, E; Themann, H; Thomas, D; Thomas, T L; Togawa, M; Toia, A; Tomášek, L; Tomášek, M; Torii, H; Towell, R S; Tserruya, I; Tsuchimoto, Y; Utsunomiya, K; Vale, C; Valle, H; van Hecke, H W; Vazquez-Zambrano, E; Veicht, A; Velkovska, J; Vértesi, R; Virius, M; Vossen, A; Vrba, V; Vznuzdaev, E; Wang, X R; Watanabe, D; Watanabe, K; Watanabe, Y; Watanabe, Y S; Wei, F; Wei, R; Wessels, J; White, S N; Winter, D; Woody, C L; Wright, R M; Wysocki, M; Yamaguchi, Y L; Yamaura, K; Yang, R; Yanovich, A; Ying, J; Yokkaichi, S; Yoo, J S; You, Z; Young, G R; Younus, I; Yushmanov, I E; Zajc, W A; Zelenski, A; Zhou, S

2014-06-27

The PHENIX experiment has measured open heavy-flavor production via semileptonic decay over the transverse momentum range 1 < p(T) < 6  GeV/c at forward and backward rapidity (1.4 < |y| < 2.0) in d+Au and p + p collisions at √sNN = 200  GeV. In central d+Au collisions, relative to the yield in p + p collisions scaled by the number of binary nucleon-nucleon collisions, a suppression is observed at forward rapidity (in the d-going direction) and an enhancement at backward rapidity (in the Au-going direction). Predictions using nuclear-modified-parton-distribution functions, even with additional nuclear-p(T) broadening, cannot simultaneously reproduce the data at both rapidity ranges, which implies that these models are incomplete and suggests the possible importance of final-state interactions in the asymmetric d + Au collision system. These results can be used to probe cold-nuclear-matter effects, which may significantly affect heavy-quark production, in addition to helping constrain the magnitude of charmonia-breakup effects in nuclear matter.

Measurement of Quark Energy Loss in Cold Nuclear Matter at Fermilab E906/SeaQuest

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

Lin, Po-Ju

Parton energy loss is a process within QCD that draws considerable interest. The measurement of parton energy loss can provide valuable information for other hard-scattering processes in nuclei, and also serves as an important tool for exploring the properties of the quark-gluon plasma (QGP). Quantifying the energy loss in cold nuclear matter will help to set a baseline relative to energy loss in the QGP. With the Drell-Yan process, the energy loss of incoming quarks in cold nuclear matter can be ideally investigated since the final state interaction is expected to be minimal. E906/SeaQuest is a fixed-target experiment using themore » 120 GeV proton beam from the Fermilab Main Injector and has been collecting data from p+p, p+d, p+C, p+Fe, and p+W collisions. Within the E906 kinematic coverage of Drell-Yan production via the dimuon channel, the quark energy loss can be measured in a regime where other nuclear effects are expected to be small. In this thesis, the study of quark ener gy loss from different cold nuclear targets is presented.« less

Twist-averaged boundary conditions for nuclear pasta Hartree-Fock calculations

DOE PAGES

Schuetrumpf, B.; Nazarewicz, W.

2015-10-21

Nuclear pasta phases, present in the inner crust of neutron stars, are associated with nucleonic matter at subsaturation densities arranged in regular shapes. Those complex phases, residing in a layer which is approximately 100-m thick, impact many features of neutron stars. Theoretical quantum-mechanical simulations of nuclear pasta are usually carried out in finite three-dimensional boxes assuming periodic boundary conditions. The resulting solutions are affected by spurious finite-size effects. To remove spurious finite-size effects, it is convenient to employ twist-averaged boundary conditions (TABC) used in condensed matter, nuclear matter, and lattice quantum chromodynamics applications. In this work, we study the effectivenessmore » of TABC in the context of pasta phase simulations within nuclear density functional theory. We demonstrated that by applying TABC reliable results can be obtained from calculations performed in relatively small volumes. By studying various contributions to the total energy, we gain insights into pasta phases in mid-density range. Future applications will include the TABC extension of the adaptive multiresolution 3D Hartree-Fock solver and Hartree-Fock-Bogoliubov TABC applications to superfluid pasta phases and complex nucleonic topologies as in fission.« less

Further Insights into Metal-DOM Interaction: Consideration of Both Fluorescent and Non-Fluorescent Substances

PubMed Central

Xu, Huacheng; Zhong, Jicheng; Yu, Guanghui; Wu, Jun; Jiang, Helong; Yang, Liuyan

2014-01-01

Information on metal binding with fluorescent substances has been widely studied. By contrast, information on metal binding with non-fluorescent substances remains lacking despite the dominance of these substances in aquatic systems. In this study, the metal binding properties of both fluorescent and non-fluorescent substances were investigated by using metal titration combined with two-dimensional correlation spectroscopy (2D–COS) analysis. The organic matters in the eutrophic algae-rich lake, including natural organic matters (NOM) and algae-induced extracellular polymeric substances (EPS), both contained fluorescent and non-fluorescent substances. The peaks in the one-dimensional spectra strongly overlapped, while 2D–COS can decompose the overlapped peaks and thus enhanced the spectral resolution. Moreover, 2D FTIR COS demonstrated that the binding susceptibility of organic ligands in both NOM and algal EPS matrices followed the order: 3400>1380>1650 cm−1, indicative the significant contribution of non-fluorescent ligands in metal binding. The modified Stern-Volmer equation also revealed a substantial metal binding potential for the non-fluorescent substances (logKM: 3.57∼4.92). As for the effects of organic ligands on metal binding, EPS was characterized with higher binding ability than NOM for both fluorescent and non-fluorescent ligands. Algae-induced EPS and the non-fluorescent substances in eutrophic algae-rich lakes should not be overlooked because of their high metal binding potential. PMID:25380246

Activation of protein kinase C induces nuclear translocation of RFX1 and down-regulates c-myc via an intron 1 X box in undifferentiated leukemia HL-60 cells.

PubMed

Chen, L; Smith, L; Johnson, M R; Wang, K; Diasio, R B; Smith, J B

2000-10-13

Treatment of human promyelocytic leukemia cells (HL-60) with phorbol 12-myristate 13-acetate (PMA) is known to decrease c-myc mRNA by blocking transcription elongation at sites near the first exon/intron border. Treatment of HL-60 cells with either PMA or bryostatin 1, which acutely activates protein kinase C (PKC), decreased the levels of myc mRNA and Myc protein. The inhibition of Myc synthesis accounted for the drop in Myc protein, because PMA treatment had no effect on Myc turnover. Treatment with PMA or bryostatin 1 increased nuclear protein binding to MIE1, a c-myc intron 1 element that defines an RFX1-binding X box. RFX1 antiserum supershifted MIE1-protein complexes. Increased MIE1 binding was independent of protein synthesis and abolished by a selective PKC inhibitor, which also prevented the effect of PMA on myc mRNA and protein levels and Myc synthesis. PMA treatment increased RFX1 in the nuclear fraction and decreased it in the cytosol without affecting total RFX1. Transfection of HL-60 cells with myc reporter gene constructs showed that the RFX1-binding X box was required for the down-regulation of reporter gene expression by PMA. These findings suggest that nuclear translocation and binding of RFX1 to the X box cause the down-regulation of myc expression, which follows acute PKC activation in undifferentiated HL-60 cells.

Distinct functional domains in nesprin-1{alpha} and nesprin-2{beta} bind directly to emerin and both interactions are disrupted in X-linked Emery-Dreifuss muscular dystrophy

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

Wheeler, Matthew A.; Davies, John D.; Zhang Qiuping

2007-08-01

Emerin and specific isoforms of nesprin-1 and -2 are nuclear membrane proteins which are binding partners in multi-protein complexes spanning the nuclear envelope. We report here the characterisation of the residues both in emerin and in nesprin-1{alpha} and -2{beta} which are involved in their interaction and show that emerin requires nesprin-1 or -2 to retain it at the nuclear membrane. Using several protein-protein interaction methods, we show that residues 368 to 627 of nesprin-1{alpha} and residues 126 to 219 of nesprin-2{beta}, which show high homology to one another, both mediate binding to emerin residues 140-176. This region has previously beenmore » implicated in binding to F-actin, {beta}-catenin and lamin A/C suggesting that it is critical for emerin function. Confirmation that these protein domains interact in vivo was shown using GFP-dominant negative assays. Exogenous expression of either of these nesprin fragments in mouse myoblast C2C12 cells displaced endogenous emerin from the nuclear envelope and reduced the targeting of newly synthesised emerin. Furthermore, we are the first to report that emerin mutations which give rise to X-linked Emery-Dreifuss muscular dystrophy, disrupt binding to both nesprin-1{alpha} and -2{beta} isoforms, further indicating a role of nesprins in the pathology of Emery-Dreifuss muscular dystrophy.« less

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver.

PubMed

Whitton, Holly; Singh, Larry N; Patrick, Marissa A; Price, Andrew J; Osorio, Fernando G; López-Otín, Carlos; Bochkis, Irina M

2018-06-01

Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1-associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors. We also show that Foxa2 binds more sites in Zmpste24 mutant mice, a progeroid laminopathy model, similar to increased Foxa2 occupancy in old livers. Aged and Zmpste24-deficient livers share several features, including nuclear lamina abnormalities, increased Foxa2 binding, de-repression of PPAR- and LXR-dependent gene expression, and fatty liver. In old livers, additional Foxa2 binding is correlated to loss of lamin B1 and heterochromatin (H3K9me3 occupancy) at these loci. Our observations suggest that changes at the nuclear lamina are linked to altered Foxa2 binding, enabling opening of chromatin and de-repression of genes encoding lipid synthesis and storage targets that contribute to etiology of hepatic steatosis. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses

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

Lloyd, Richard E., E-mail: rlloyd@bcm.edu

Plus strand RNA viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. Most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular RNA-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building RNA replication complexes. In the course of infectious cycles many nuclear-cytoplasmic shuttling proteins of mostly nuclear distribution are detained in the cytoplasm by viruses and re-purposed for their own gain. Many mammalian viruses hijack a common group of the same factors. This review summarizesmore » recent gains in our knowledge of how cytoplasmic RNA viruses use these co-opted host nuclear factors in new functional roles supporting virus translation and virus RNA replication and common themes employed between different virus groups. - Highlights: • Nuclear shuttling host proteins are commonly hijacked by RNA viruses to support replication. • A limited group of ubiquitous RNA binding proteins are commonly hijacked by a broad range of viruses. • Key virus proteins alter roles of RNA binding proteins in different stages of virus replication.« less

Nuclear binding energy using semi empirical mass formula

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

Ankita,, E-mail: ankitagoyal@gmail.com; Suthar, B.

2016-05-06

In the present communication, semi empirical mass formula using the liquid drop model has been presented. Nuclear binding energies are calculated using semi empirical mass formula with various constants given by different researchers. We also compare these calculated values with experimental data and comparative study for finding suitable constants is added using the error plot. The study is extended to find the more suitable constant to reduce the error.

Specifying peripheral heterochromatin during nuclear lamina reassembly

PubMed Central

Poleshko, Andrey; Katz, Richard A

2014-01-01

A conserved organizational feature of eukaryotic nuclei is the peripheral heterochromatin compartment, which provides a protected area for epigenetically silent genes and gene-poor DNA. In metazoan cells this compartment is associated with the nuclear lamina, the protein meshwork at the inner edge of the nucleus. Heterochromatin-nuclear lamina interactions promote epigenetic gene silencing, which may drive many normal and diseased biological processes. We recently obtained evidence that a previously unstudied human protein, PRR14, participates in the tethering of heterochromatin to the inner nuclear periphery. PRR14 associates with the nuclear lamina and attaches to heterochromatin through its binding partner, heterochromatin protein 1 (HP1). After disassembly early in mitosis, PRR14 reassembles in two steps, first binding to anaphase chromosomes through HP1, followed by association with the nuclear lamina in telophase. PRR14 may thereby play a role in specifying HP1-bound heterochromatin for reattachment to the nuclear lamina at mitotic exit. Here we review the relevant literature, summarize our initial work, and provide additional comments and findings. PMID:24637393

Specifying peripheral heterochromatin during nuclear lamina reassembly.

PubMed

Poleshko, Andrey; Katz, Richard A

2014-01-01

A conserved organizational feature of eukaryotic nuclei is the peripheral heterochromatin compartment, which provides a protected area for epigenetically silent genes and gene-poor DNA. In metazoan cells this compartment is associated with the nuclear lamina, the protein meshwork at the inner edge of the nucleus. Heterochromatin-nuclear lamina interactions promote epigenetic gene silencing, which may drive many normal and diseased biological processes. We recently obtained evidence that a previously unstudied human protein, PRR14, participates in the tethering of heterochromatin to the inner nuclear periphery. PRR14 associates with the nuclear lamina and attaches to heterochromatin through its binding partner, heterochromatin protein 1 (HP1). After disassembly early in mitosis, PRR14 reassembles in two steps, first binding to anaphase chromosomes through HP1, followed by association with the nuclear lamina in telophase. PRR14 may thereby play a role in specifying HP1-bound heterochromatin for reattachment to the nuclear lamina at mitotic exit. Here we review the relevant literature, summarize our initial work, and provide additional comments and findings.

Neuronal differentiation modulates the dystrophin Dp71d binding to the nuclear matrix

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

Rodriguez-Munoz, Rafael; Villarreal-Silva, Marcela; Gonzalez-Ramirez, Ricardo

The function of dystrophin Dp71 in neuronal cells remains unknown. To approach this issue, we have selected the PC12 neuronal cell line. These cells express both a Dp71f cytoplasmic variant and a Dp71d nuclear isoform. In this study, we demonstrated by electron and confocal microscopy analyses of in situ nuclear matrices and Western blotting evaluation of cell extracts that Dp71d associates with the nuclear matrix. Interestingly, this binding is modulated during NGF-induced neuronal differentiation of PC12 cells with a twofold increment in the differentiated cells, compared to control cells. Also, distribution of Dp71d along the periphery of the nuclear matrixmore » observed in the undifferentiated cells is replaced by intense fluorescent foci localized in Center of the nucleoskeletal structure. In summary, we revealed that Dp71d is a dynamic component of nuclear matrix that might participate in the nuclear modeling occurring during neuronal differentiation.« less

Quantification of transcription factor-DNA binding affinity in a living cell

PubMed Central

Belikov, Sergey; Berg, Otto G.; Wrange, Örjan

2016-01-01

The apparent dissociation constant (Kd) for specific binding of glucocorticoid receptor (GR) and androgen receptor (AR) to DNA was determined in vivo in Xenopus oocytes. The total nuclear receptor concentration was quantified as specifically retained [3H]-hormone in manually isolated oocyte nuclei. DNA was introduced by nuclear microinjection of single stranded phagemid DNA, chromatin is then formed during second strand synthesis. The fraction of DNA sites occupied by the expressed receptor was determined by dimethylsulphate in vivo footprinting and used for calculation of the receptor-DNA binding affinity. The forkhead transcription factor FoxA1 enhanced the DNA binding by GR with an apparent Kd of ∼1 μM and dramatically stimulated DNA binding by AR with an apparent Kd of ∼0.13 μM at a composite androgen responsive DNA element containing one FoxA1 binding site and one palindromic hormone receptor binding site known to bind one receptor homodimer. FoxA1 exerted a weak constitutive- and strongly cooperative DNA binding together with AR but had a less prominent effect with GR, the difference reflecting the licensing function of FoxA1 at this androgen responsive DNA element. PMID:26657626

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

Hirano, Hidemi; Matsuura, Yoshiyuki, E-mail: matsuura.yoshiyuki@d.mbox.nagoya-u.ac.jp

Highlights: {yields} MAL has a bipartite NLS that binds to Imp{alpha} in an extended conformation. {yields} Mutational analyses verified the functional significance of MAL-Imp{alpha} interactions. {yields} Induced folding and NLS-masking by G-actins inhibit nuclear import of MAL. -- Abstract: The coordination of cytoskeletal actin dynamics with gene expression reprogramming is emerging as a crucial mechanism to control diverse cellular processes, including cell migration, differentiation and neuronal circuit assembly. The actin-binding transcriptional coactivator MAL (also known as MRTF-A/MKL1/BSAC) senses G-actin concentration and transduces Rho GTPase signals to serum response factor (SRF). MAL rapidly shuttles between the cytoplasm and the nucleus inmore » unstimulated cells but Rho-induced depletion of G-actin leads to MAL nuclear accumulation and activation of transcription of SRF:MAL-target genes. Although the molecular and structural basis of actin-regulated nucleocytoplasmic shuttling of MAL is not understood fully, it is proposed that nuclear import of MAL is mediated by importin {alpha}/{beta} heterodimer, and that G-actin competes with importin {alpha}/{beta} for the binding to MAL. Here we present structural, biochemical and cell biological evidence that MAL has a classical bipartite nuclear localization signal (NLS) in the N-terminal 'RPEL' domain containing Arg-Pro-X-X-X-Glu-Leu (RPEL) motifs. The NLS residues of MAL adopt an extended conformation and bind along the surface groove of importin-{alpha}, interacting with the major- and minor-NLS binding sites. We also present a crystal structure of wild-type MAL RPEL domain in complex with five G-actins. Comparison of the importin-{alpha}- and actin-complexes revealed that the binding of G-actins to MAL is associated with folding of NLS residues into a helical conformation that is inappropriate for importin-{alpha} recognition.« less

10 CFR 76.72 - Miscellaneous procedural matters.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Miscellaneous procedural matters. 76.72 Section 76.72 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.72 Miscellaneous procedural matters. (a) The filing of any petitions for review or any responses...

10 CFR 76.72 - Miscellaneous procedural matters.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Miscellaneous procedural matters. 76.72 Section 76.72 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.72 Miscellaneous procedural matters. (a) The filing of any petitions for review or any responses...

10 CFR 76.72 - Miscellaneous procedural matters.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Miscellaneous procedural matters. 76.72 Section 76.72 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.72 Miscellaneous procedural matters. (a) The filing of any petitions for review or any responses...

10 CFR 76.72 - Miscellaneous procedural matters.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Miscellaneous procedural matters. 76.72 Section 76.72 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.72 Miscellaneous procedural matters. (a) The filing of any petitions for review or any responses...

10 CFR 76.72 - Miscellaneous procedural matters.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Miscellaneous procedural matters. 76.72 Section 76.72 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Certification § 76.72 Miscellaneous procedural matters. (a) The filing of any petitions for review or any responses...

Limits on Momentum-Dependent Asymmetric Dark Matter with CRESST-II.

PubMed

Angloher, G; Bento, A; Bucci, C; Canonica, L; Defay, X; Erb, A; Feilitzsch, F V; Ferreiro Iachellini, N; Gorla, P; Gütlein, A; Hauff, D; Jochum, J; Kiefer, M; Kluck, H; Kraus, H; Lanfranchi, J-C; Loebell, J; Münster, A; Pagliarone, C; Petricca, F; Potzel, W; Pröbst, F; Reindl, F; Schäffner, K; Schieck, J; Schönert, S; Seidel, W; Stodolsky, L; Strandhagen, C; Strauss, R; Tanzke, A; Trinh Thi, H H; Türkoğlu, C; Uffinger, M; Ulrich, A; Usherov, I; Wawoczny, S; Willers, M; Wüstrich, M; Zöller, A

2016-07-08

The usual assumption in direct dark matter searches is to consider only the spin-dependent or spin-independent scattering of dark matter particles. However, especially in models with light dark matter particles O(GeV/c^{2}), operators which carry additional powers of the momentum transfer q^{2} can become dominant. One such model based on asymmetric dark matter has been invoked to overcome discrepancies in helioseismology and an indication was found for a particle with a preferred mass of 3  GeV/c^{2} and a cross section of 10^{-37}  cm^{2}. Recent data from the CRESST-II experiment, which uses cryogenic detectors based on CaWO_{4} to search for nuclear recoils induced by dark matter particles, are used to constrain these momentum-dependent models. The low energy threshold of 307 eV for nuclear recoils of the detector used, allows us to rule out the proposed best fit value above.

From hadrons to quarks in neutron stars: a review.

PubMed

Baym, Gordon; Hatsuda, Tetsuo; Kojo, Toru; Powell, Philip D; Song, Yifan; Takatsuka, Tatsuyuki

2018-05-01

In recent years our understanding of neutron stars has advanced remarkably, thanks to research converging from many directions. The importance of understanding neutron star behavior and structure has been underlined by the recent direct detection of gravitational radiation from merging neutron stars. The clean identification of several heavy neutron stars, of order two solar masses, challenges our current understanding of how dense matter can be sufficiently stiff to support such a mass against gravitational collapse. Programs underway to determine simultaneously the mass and radius of neutron stars will continue to constrain and inform theories of neutron star interiors. At the same time, an emerging understanding in quantum chromodynamics (QCD) of how nuclear matter can evolve into deconfined quark matter at high baryon densities is leading to advances in understanding the equation of state of the matter under the extreme conditions in neutron star interiors. We review here the equation of state of matter in neutron stars from the solid crust through the liquid nuclear matter interior to the quark regime at higher densities. We focus in detail on the question of how quark matter appears in neutron stars, and how it affects the equation of state. After discussing the crust and liquid nuclear matter in the core we briefly review aspects of microscopic quark physics relevant to neutron stars, and quark models of dense matter based on the Nambu-Jona-Lasinio framework, in which gluonic processes are replaced by effective quark interactions. We turn then to describing equations of state useful for interpretation of both electromagnetic and gravitational observations, reviewing the emerging picture of hadron-quark continuity in which hadronic matter turns relatively smoothly, with at most only a weak first order transition, into quark matter with increasing density. We review construction of unified equations of state that interpolate between the reasonably well understood nuclear matter regime at low densities and the quark matter regime at higher densities. The utility of such interpolations is driven by the present inability to calculate the dense matter equation of state in QCD from first principles. As we review, the parameters of effective quark models-which have direct relevance to the more general structure of the QCD phase diagram of dense and hot matter-are constrained by neutron star mass and radii measurements, in particular favoring large repulsive density-density and attractive diquark pairing interactions. We describe the structure of neutron stars constructed from the unified equations of states with crossover. Lastly we present the current equations of state-called 'QHC18' for quark-hadron crossover-in a parametrized form practical for neutron star modeling.

Nuclear Import of β-Dystroglycan Is Facilitated by Ezrin-Mediated Cytoskeleton Reorganization

PubMed Central

Vásquez-Limeta, Alejandra; Wagstaff, Kylie M.; Ortega, Arturo; Crouch, Dorothy H.; Jans, David A.; Cisneros, Bulmaro

2014-01-01

The β-dystroglycan (β-DG) protein has the ability to target to multiple sites in eukaryotic cells, being a member of diverse protein assemblies including the transmembranal dystrophin-associated complex, and a nuclear envelope-localised complex that contains emerin and lamins A/C and B1. We noted that the importin α2/β1-recognised nuclear localization signal (NLS) of β-DG is also a binding site for the cytoskeletal-interacting protein ezrin, and set out to determine whether ezrin binding might modulate β-DG nuclear translocation for the first time. Unexpectedly, we found that ezrin enhances rather than inhibits β-DG nuclear translocation in C2C12 myoblasts. Both overexpression of a phosphomimetic activated ezrin variant (Ez-T567D) and activation of endogenous ezrin through stimulation of the Rho pathway resulted in both formation of actin-rich surface protrusions and significantly increased nuclear translocation of β-DG as shown by quantitative microscopy and subcellular fractionation/Western analysis. In contrast, overexpression of a nonphosphorylatable inactive ezrin variant (Ez-T567A) or inhibition of Rho signaling, decreased nuclear translocation of β-DG concomitant with a lack of cell surface protrusions. Further, a role for the actin cytoskeleton in ezrin enhancement of β-DG nuclear translocation was implicated by the observation that an ezrin variant lacking its actin-binding domain failed to enhance nuclear translocation of β-DG, while disruption of the actin cytoskeleton led to a reduction in β-DG nuclear localization. Finally, we show that ezrin-mediated cytoskeletal reorganization enhances nuclear translocation of the cytoplasmic but not the transmembranal fraction of β-DG. This is the first study showing that cytoskeleton reorganization can modulate nuclear translocation of β-DG, with the implication that β-DG can respond to cytoskeleton-driven changes in cell morphology by translocating from the cytoplasm to the nucleus to orchestrate nuclear processes in response to the functional requirements of the cell. PMID:24599031

Nuclear pasta in hot dense matter and its implications for neutrino scattering

NASA Astrophysics Data System (ADS)

Roggero, Alessandro; Margueron, Jérôme; Roberts, Luke F.; Reddy, Sanjay

2018-04-01

The abundance of large clusters of nucleons in neutron-rich matter at subnuclear density is found to be greatly reduced by finite-temperature effects when matter is close to β equilibrium, compared to the case where the electron fraction is fixed at Ye>0.1 , as often considered in the literature. Large nuclei and exotic nonspherical nuclear configurations called pasta, favored in the vicinity of the transition to uniform matter at T =0 , dissolve at a relatively low temperature Tu as protons leak out of nuclei and pasta. For matter at β equilibrium with a negligible neutrino chemical potential we find that Tuβ≃4 ±1 MeV for realistic equations of state. This is lower than the maximum temperature Tmaxβ≃9 ±1 MeV at which nuclei can coexist with a gas of nucleons and can be explained by a change in the nature of the transition to uniform matter called retrograde condensation. An important new finding is that coherent neutrino scattering from nuclei and pasta makes a modest contribution to the opacity under the conditions encountered in supernovas and neutron star mergers. This is because large nuclear clusters dissolve at most relevant temperatures, and at lower temperatures, when clusters are present, Coulomb correlations between them suppress coherent neutrino scattering off individual clusters. Implications for neutrino signals from galactic supernovas are briefly discussed.

Computational identification of post-translational modification-based nuclear import regulations by characterizing nuclear localization signal-import receptor interaction.

PubMed

Lin, Jhih-Rong; Liu, Zhonghao; Hu, Jianjun

2014-10-01

The binding affinity between a nuclear localization signal (NLS) and its import receptor is closely related to corresponding nuclear import activity. PTM-based modulation of the NLS binding affinity to the import receptor is one of the most understood mechanisms to regulate nuclear import of proteins. However, identification of such regulation mechanisms is challenging due to the difficulty of assessing the impact of PTM on corresponding nuclear import activities. In this study we proposed NIpredict, an effective algorithm to predict nuclear import activity given its NLS, in which molecular interaction energy components (MIECs) were used to characterize the NLS-import receptor interaction, and the support vector regression machine (SVR) was used to learn the relationship between the characterized NLS-import receptor interaction and the corresponding nuclear import activity. Our experiments showed that nuclear import activity change due to NLS change could be accurately predicted by the NIpredict algorithm. Based on NIpredict, we developed a systematic framework to identify potential PTM-based nuclear import regulations for human and yeast nuclear proteins. Application of this approach has identified the potential nuclear import regulation mechanisms by phosphorylation of two nuclear proteins including SF1 and ORC6. © 2014 Wiley Periodicals, Inc.

Non-canonical modulators of nuclear receptors.

PubMed

Tice, Colin M; Zheng, Ya-Jun

2016-09-01

Like G protein-coupled receptors (GPCRs) and protein kinases, nuclear receptors (NRs) are a rich source of pharmaceutical targets. Over 80 NR-targeting drugs have been approved for 18 NRs. The focus of drug discovery in NRs has hitherto been on identifying ligands that bind to the canonical ligand binding pockets of the C-terminal ligand binding domains (LBDs). Due to the development of drug resistance and selectivity concerns, there has been considerable interest in exploring other, non-canonical ligand binding sites. Unfortunately, the potencies of compounds binding at other sites have generally not been sufficient for clinical development. However, the situation has changed dramatically over the last 3years, as compounds with sufficient potency have been reported for several NR targets. Here we review recent developments in this area from a medicinal chemistry point of view in the hope of stimulating further interest in this area of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Onset of η-nuclear binding in a pionless EFT approach

NASA Astrophysics Data System (ADS)

Barnea, N.; Bazak, B.; Friedman, E.; Gal, A.

2017-08-01

ηNNN and ηNNNN bound states are explored in stochastic variational method (SVM) calculations within a pionless effective field theory (EFT) approach at leading order. The theoretical input consists of regulated NN and NNN contact terms, and a regulated energy dependent ηN contact term derived from coupled-channel models of the N* (1535) nucleon resonance. A self consistency procedure is applied to deal with the energy dependence of the ηN subthreshold input, resulting in a weak dependence of the calculated η-nuclear binding energies on the EFT regulator. It is found, in terms of the ηN scattering length aηN, that the onset of binding η 3He requires a minimal value of ReaηN close to 1 fm, yielding then a few MeV η binding in η 4He. The onset of binding η 4He requires a lower value of ReaηN, but exceeding 0.7 fm.

Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation-response (TAR) element of human immunodeficiency virus.

PubMed Central

Marciniak, R A; Garcia-Blanco, M A; Sharp, P A

1990-01-01

Human immunodeficiency virus type 1 RNAs contain a sequence, trans-activation-response (TAR) element, which is required for tat protein-mediated trans-activation of viral gene expression. We have identified a nuclear protein from extracts of HeLa cells that binds to the TAR element RNA in a sequence-specific manner. The binding of this 68-kDa polypeptide was detected by UV cross-linking proteins to TAR element RNA transcribed in vitro. Competition experiments were performed by using a partially purified preparation of the protein to quantify the relative binding affinities of TAR element RNA mutants. The binding affinity of the TAR mutants paralleled the reported ability of those mutants to support tat trans-activation in vivo. We propose that this cellular protein moderates TAR activity in vivo. Images PMID:2333305

Identification of an allosteric binding site for RORγt inhibition

PubMed Central

Scheepstra, Marcel; Leysen, Seppe; van Almen, Geert C.; Miller, J. Richard; Piesvaux, Jennifer; Kutilek, Victoria; van Eenennaam, Hans; Zhang, Hongjun; Barr, Kenneth; Nagpal, Sunil; Soisson, Stephen M.; Kornienko, Maria; Wiley, Kristen; Elsen, Nathaniel; Sharma, Sujata; Correll, Craig C.; Trotter, B. Wesley; van der Stelt, Mario; Oubrie, Arthur; Ottmann, Christian; Parthasarathy, Gopal; Brunsveld, Luc

2015-01-01

RORγt is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases. We report the discovery of a novel allosteric binding site on the nuclear receptor RORγt. Co-crystallization of the ligand binding domain (LBD) of RORγt with a series of small-molecule antagonists demonstrates occupancy of a previously unreported allosteric binding pocket. Binding at this non-canonical site induces an unprecedented conformational reorientation of helix 12 in the RORγt LBD, which blocks cofactor binding. The functional consequence of this allosteric ligand-mediated conformation is inhibition of function as evidenced by both biochemical and cellular studies. RORγt function is thus antagonized in a manner molecularly distinct from that of previously described orthosteric RORγt ligands. This brings forward an approach to target RORγt for the treatment of Th17-mediated autoimmune diseases. The elucidation of an unprecedented modality of pharmacological antagonism establishes a mechanism for modulation of nuclear receptors. PMID:26640126

The PDZ-binding motif of Yes-associated protein is required for its co-activation of TEAD-mediated CTGF transcription and oncogenic cell transforming activity

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

Shimomura, Tadanori; Miyamura, Norio; Hata, Shoji

2014-01-17

Highlights: •Loss of the PDZ-binding motif inhibits constitutively active YAP (5SA)-induced oncogenic cell transformation. •The PDZ-binding motif of YAP promotes its nuclear localization in cultured cells and mouse liver. •Loss of the PDZ-binding motif inhibits YAP (5SA)-induced CTGF transcription in cultured cells and mouse liver. -- Abstract: YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces oncogenic transformation. The C-terminus of YAP contains amore » highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the oncogenic transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription.« less

Neutron-proton effective mass splitting in neutron-rich matter and its impacts on nuclear reactions

NASA Astrophysics Data System (ADS)

Li, Bao-An; Chen, Lie-Wen

2015-04-01

The neutron-proton effective mass splitting in neutron-rich nucleonic matter reflects the spacetime nonlocality of the isovector nuclear interaction. It affects the neutron/proton ratio during the earlier evolution of the Universe, cooling of proto-neutron stars, structure of rare isotopes and dynamics of heavy-ion collisions. While there is still no consensus on whether the neutron-proton effective mass splitting is negative, zero or positive and how it depends on the density as well as the isospin-asymmetry of the medium, significant progress has been made in recent years in addressing these issues. There are different kinds of nucleon effective masses. In this mini-review, we focus on the total effective masses often used in the non-relativistic description of nuclear dynamics. We first recall the connections among the neutron-proton effective mass splitting, the momentum dependence of the isovector potential and the density dependence of the symmetry energy. We then make a few observations about the progress in calculating the neutron-proton effective mass splitting using various nuclear many-body theories and its effects on the isospin-dependence of in-medium nucleon-nucleon cross-sections. Perhaps, our most reliable knowledge so far about the neutron-proton effective mass splitting at saturation density of nuclear matter comes from optical model analyses of huge sets of nucleon-nucleus scattering data accumulated over the last five decades. The momentum dependence of the symmetry potential from these analyses provide a useful boundary condition at saturation density for calibrating nuclear many-body calculations. Several observables in heavy-ion collisions have been identified as sensitive probes of the neutron-proton effective mass splitting in dense neutron-rich matter based on transport model simulations. We review these observables and comment on the latest experimental findings.

Corrigendum to “Suppression of Υ production in d+Au and Au+Au collisions at √ SNN = 200 GeV" [Phys. Lett. B 735 (2014) 127-137

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

Adamczyk, L.

We report measurements of Υ meson production in p + p, d + Au, and Au+Au collisions using the STAR detector at RHIC. We compare the Υ yield to the measured cross section in p + p collisions in order to quantify any modifications of the yield in cold nuclear matter using d + Au data and in hot nuclear matter using Au+Au data separated into three centrality classes. Our p + p measurement is based on three times the statistics of our previous result. We obtain a nuclear modification factor for Upsilon (1S + 2S + 3S) in themore » rapidity range |y| < 1 in d + Au collisions of R dAu = 0.79 ± 0.24(stat.) ± 0.03(syst.) ± 0.10(p + p syst.). A comparison with models including shadowing and initial state parton energy loss indicates the presence of additional cold-nuclear matter suppression. Similarly, in the top 10% most-central Au + Au collisions, we measure a nuclear modification factor of R AA = 0.49 ±0.1(stat.) ±0.02(syst.) ±0.06(p + p syst.), which is a larger suppression factor than that seen in cold nuclear matter. Our results are consistent with complete suppression of excited-state Upsilon mesons in Au + Au collisions. The additional suppression in Au + Au is consistent with the level expected in model calculations that include the presence of a hot, deconfined Quark–Gluon Plasma. However, understanding the suppression seen in d + Au is still needed before any definitive statements about the nature of the suppression in Au + Au can be made.« less

Suppression of Υ production in d + Au + and Au + Au collisions at √ sNN =200 GeV

DOE PAGES

None

2014-07-01

We report measurements of Upsilon meson production in p + p, d +Au, and Au+Au collisions using the STAR detector at RHIC. We compare the Upsilon yield to the measured cross section in p + p collisions in order to quantify any modifications of the yield in cold nuclear matter using d +Au data and in hot nuclear matter using Au+Au data separated into three centrality classes. Our p +p measurement is based on three times the statistics of our previous result. We obtain a nuclear modification factor for Upsilon (1S + 2S + 3S) in the rapidity range |y|more » < 1 in d + Au collisions of R dAu = 0.79 ± 0.24(stat.) ± 0.03(syst.) ± 0.10(p + p syst.). A comparison with models including shadowing and initial state part on energy loss indicates the presence of additional cold-nuclear matter suppression. Similarly, in the top 10% most-central Au + Au collisions, we measure a nuclear modification factor of R AA = 0.49 ±0.1(stat.) ±0.02(syst.) ±0.06(p + p syst.), which is a larger suppression factor than that seen in cold nuclear matter. Our results are consistent with complete suppression of excited-state Upsilon mesons in Au + Au collisions. The additional suppression in Au + Au is consistent with the level expected in model calculations that include the presence of a hot, deconfined Quark–Gluon Plasma. However, understanding the suppression seen in d + Au is still needed before any definitive statements about the nature of the suppression in Au + Au can be made.« less

Corrigendum to “Suppression of Υ production in d+Au and Au+Au collisions at √ SNN = 200 GeV" [Phys. Lett. B 735 (2014) 127-137

DOE PAGES

Adamczyk, L.

2015-04-01

We report measurements of Υ meson production in p + p, d + Au, and Au+Au collisions using the STAR detector at RHIC. We compare the Υ yield to the measured cross section in p + p collisions in order to quantify any modifications of the yield in cold nuclear matter using d + Au data and in hot nuclear matter using Au+Au data separated into three centrality classes. Our p + p measurement is based on three times the statistics of our previous result. We obtain a nuclear modification factor for Upsilon (1S + 2S + 3S) in themore » rapidity range |y| < 1 in d + Au collisions of R dAu = 0.79 ± 0.24(stat.) ± 0.03(syst.) ± 0.10(p + p syst.). A comparison with models including shadowing and initial state parton energy loss indicates the presence of additional cold-nuclear matter suppression. Similarly, in the top 10% most-central Au + Au collisions, we measure a nuclear modification factor of R AA = 0.49 ±0.1(stat.) ±0.02(syst.) ±0.06(p + p syst.), which is a larger suppression factor than that seen in cold nuclear matter. Our results are consistent with complete suppression of excited-state Upsilon mesons in Au + Au collisions. The additional suppression in Au + Au is consistent with the level expected in model calculations that include the presence of a hot, deconfined Quark–Gluon Plasma. However, understanding the suppression seen in d + Au is still needed before any definitive statements about the nature of the suppression in Au + Au can be made.« less

Implications of effluent organic matter and its hydrophilic fraction on zinc(II) complexation in rivers under strong urban pressure: aromaticity as an inaccurate indicator of DOM-metal binding.

PubMed

Louis, Yoann; Pernet-Coudrier, Benoît; Varrault, Gilles

2014-08-15

The zinc binding characteristics of dissolved organic matter (DOM) fractions from the Seine River Basin were studied after being separated and extracted according to their polarity: hydrophobic, transphilic, and hydrophilic. The applied experimental methodology was based on a determination of labile zinc species by means of differential pulse anodic stripping voltammetry (DPASV) at increasing concentrations of total zinc on a logarithmic scale and at fixed levels of: pH, ionic strength, and temperature. Fitting the DOM fractions with two discrete classes of ligands successfully allowed determining the conditional zinc binding constants (Ki) as well as total ligand density (LiT). The binding constants obtained for each DOM fraction were then compared and discussed with respect to the hydrophobic/hydrophilic nature and sample origin. Results highlighted a strong complexation of zinc to the effluent organic matter and especially the most hydrophilic fraction, which also displayed a very low specific UV absorbance. Although the biotic ligand model takes into account the quality of DOM through UV absorbance in the predictions of metal bioavailability and toxicity, this correction is not efficient for urban waters. Copyright © 2014 Elsevier B.V. All rights reserved.

Establishment of Korean Nuclear Ombudsman System Importing Compensation and Insurance Concept for Residents

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

Hyun Seok Ko; Yong Min Kim; Young Wook Lee

2006-07-01

In Korea, the nuclear power generation is grown technically well. Already, 20 nuclear reactors are operated, and approximate they supply the 40% of whole the consumption of electric power. This is the driving force of Korean industrial development. Besides, Korean Standard Nuclear Power Plant that was developed by Korean self-technique with nuclear plant technique independence, Ul-Chin 6 has started the commercial operation. Advanced Korean Standard Nuclear Power Plant, new Gori 1, 2 constructions are commenced. But, past days Korean situation is that intention of residents is neglected in the decision making process of nuclear power plant construction and operation. Inmore » existing decision making process, it is regarded as the role of public opinion is secondary, and the problem of decision making process is that public is persuaded and believed. So, in decision making process, the public opinion is considered restrictively, there is not the actual public participation. Therefore the dissatisfaction of public is increased continuously, and in Korea, bad recognition about nuclear power is getting full. The method of public participation for complement of this problem is public hearing or ombudsman system. The public hearing is ensuring public participation before decision of a case, and ombudsman is the system that elevates the public satisfaction through continuous feedback of public requirement to occur in deciding and performing the matters. In Korean situation, that present 20 nuclear reactors are operated and also the place of radioactive waste repository has been decided, not only the introduction of public hearing to decide the coming matter but also the operation of ombudsman system to continuously correct and collect the public requirements about the matter to already decided and operated is necessary. In Korea, administration type ombudsman is operated now. But, it has operated without basic element at the aspect of organization, function and phase. So it is not established a firm phase as right relief body to be believed by public with lack of independence, authority and specialty. Therefore the establishment of organization that can be the role as special ombudsman organization about sensitive and special matter like nuclear matter is necessary. Definite establishment element of ombudsman system is to introduce of congress type ombudsman element, to be permanent standing system ombudsman, to limit jurisdiction extent and have strong authority, to be able to access easily, to be composed of legal and nuclear specialist. One of important requirements of resident is compensation. So, based on the resident compensation theory about aversion equipment, ombudsman system should be established introducing the insurance theory through risk management as functional background for appropriate compensation. (authors)« less

Phosphorylation of a conserved serine in the deoxyribonucleic acid binding domain of nuclear receptors alters intracellular localization.

PubMed

Sun, Kai; Montana, Vedrana; Chellappa, Karthikeyani; Brelivet, Yann; Moras, Dino; Maeda, Yutaka; Parpura, Vladimir; Paschal, Bryce M; Sladek, Frances M

2007-06-01

Nuclear receptors (NRs) are a superfamily of transcription factors whose genomic functions are known to be activated by lipophilic ligands, but little is known about how to deactivate them or how to turn on their nongenomic functions. One obvious mechanism is to alter the nuclear localization of the receptors. Here, we show that protein kinase C (PKC) phosphorylates a highly conserved serine (Ser) between the two zinc fingers of the DNA binding domain of orphan receptor hepatocyte nuclear factor 4alpha (HNF4alpha). This Ser (S78) is adjacent to several positively charged residues (Arg or Lys), which we show here are involved in nuclear localization of HNF4alpha and are conserved in nearly all other NRs, along with the Ser/threonine (Thr). A phosphomimetic mutant of HNF4alpha (S78D) reduced DNA binding, transactivation ability, and protein stability. It also impaired nuclear localization, an effect that was greatly enhanced in the MODY1 mutant Q268X. Treatment of the hepatocellular carcinoma cell line HepG2 with PKC activator phorbol 12-myristate 13-acetate also resulted in increased cytoplasmic localization of HNF4alpha as well as decreased endogenous HNF4alpha protein levels in a proteasome-dependent fashion. We also show that PKC phosphorylates the DNA binding domain of other NRs (retinoic acid receptor alpha, retinoid X receptor alpha, and thyroid hormone receptor beta) and that phosphomimetic mutants of the same Ser/Thr result in cytoplasmic localization of retinoid X receptor alpha and peroxisome proliferator-activated receptor alpha. Thus, phosphorylation of this conserved Ser between the two zinc fingers may be a common mechanism for regulating the function of NRs.

Nuclear IL-33 is a transcriptional regulator of NF-{kappa}B p65 and induces endothelial cell activation

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

Choi, Yeon-Sook; Park, Jeong Ae; Kim, Jihye

2012-05-04

Highlights: Black-Right-Pointing-Pointer IL-33 as nuclear factor regulated expression of ICAM-1 and VCAM-1. Black-Right-Pointing-Pointer Nuclear IL-33 increased the transcription of NF-{kappa}B p65 by binding to the p65 promoter. Black-Right-Pointing-Pointer Nuclear IL-33 controls NF-{kappa}B-dependent inflammatory responses. -- Abstract: Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-{kappa}B complex and ismore » involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-{alpha}-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-{kappa}B pathway; NF-{kappa}B p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-{kappa}B p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-{kappa}B p65.« less

Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

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

Di Nunzio, Francesca, E-mail: francesca.di-nunzio@pasteur.fr; Fricke, Thomas; Miccio, Annarita

The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants formore » the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites.« less

Phase transitions in core-collapse supernova matter at sub-saturation densities

NASA Astrophysics Data System (ADS)

Pais, Helena; Newton, William G.; Stone, Jirina R.

2014-12-01

Phase transitions in hot, dense matter in the collapsing cores of massive stars have an important impact on the core-collapse supernova mechanism as they absorb heat, disrupt homology, and so weaken the developing shock. We perform a three-dimensional, finite temperature Skyrme-Hartree-Fock (SHF) study of inhomogeneous nuclear matter to determine the critical density and temperature for the phase transition between the pasta phase and homogeneous matter and its properties. We employ four different parametrizations of the Skyrme nuclear energy-density functional, SkM*, SLy4, NRAPR, and SQMC700, which span a range of saturation-density symmetry energy behaviors constrained by a variety of nuclear experimental probes. For each of these interactions we calculate free energy, pressure, entropy, and chemical potentials in the range of particle number densities where the nuclear pasta phases are expected to exist, 0.02-0.12 fm-3, temperatures 2-8 MeV, and a proton fraction of 0.3. We find unambiguous evidence for a first-order phase transition to uniform matter, unsoftened by the presence of the pasta phases. No conclusive signs of a first-order phase transition between the pasta phases is observed, and it is argued that the thermodynamic quantities vary continuously right up to the first-order phase transition to uniform matter. We compare our results with thermodynamic spinodals calculated using the same Skyrme parametrizations, finding that the effect of short-range Coulomb correlations and quantum shell effects included in our model leads to the pasta phases existing at densities up to 0.01 fm-3 above the spinodal boundaries, thus increasing the transition density to uniform matter by the same amount. The transition density is otherwise shown to be insensitive to the symmetry energy at saturation density within the range constrained by the concordance of a variety of experimental constraints, and can be taken to be a well determined quantity.

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

Lee, Sungsoo, E-mail: sungsoo.lee@utsouthwestern.edu; Wang, Ping-Yuan; Jeong, Yangsik

Oxysterol binding protein related protein 1S (ORP1S) is a member of a family of sterol transport proteins. Here we present evidence that ORP1S translocates from the cytoplasm to the nucleus in response to sterol binding. The sterols that best promote nuclear import of ORP1S also activate the liver X receptor (LXR) transcription factors and we show that ORP1S binds to LXRs, promotes binding of LXRs to LXR response elements (LXREs) and specifically enhances LXR-dependent transcription via the ME.1 and ME.2 enhancer elements of the apoE gene. We propose that ORP1S is a cytoplasmic sterol sensor, which transports sterols to themore » nucleus and promotes LXR-dependent gene transcription through select enhancer elements. -- Highlights: Black-Right-Pointing-Pointer ORP1S translocates to the nucleus in response to sterol binding. Black-Right-Pointing-Pointer The sterols that best promote nuclear import of ORP1S are LXR agonists. Black-Right-Pointing-Pointer ORP1S binds to LXRs, enhances binding of LXRs to LXREs and promotes LXR-dependent transcription of apoE.« less

Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway.

PubMed

Onder, Zeynep; Chang, Vivian; Moroianu, Junona

2015-01-01

We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP-8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76IRTFQELLF84, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. Copyright © 2014 Elsevier Inc. All rights reserved.

RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

PubMed

Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

2011-01-05

The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

Strategies to regulate transcription factor-mediated gene positioning and interchromosomal clustering at the nuclear periphery.

PubMed

Randise-Hinchliff, Carlo; Coukos, Robert; Sood, Varun; Sumner, Michael Chas; Zdraljevic, Stefan; Meldi Sholl, Lauren; Garvey Brickner, Donna; Ahmed, Sara; Watchmaker, Lauren; Brickner, Jason H

2016-03-14

In budding yeast, targeting of active genes to the nuclear pore complex (NPC) and interchromosomal clustering is mediated by transcription factor (TF) binding sites in the gene promoters. For example, the binding sites for the TFs Put3, Ste12, and Gcn4 are necessary and sufficient to promote positioning at the nuclear periphery and interchromosomal clustering. However, in all three cases, gene positioning and interchromosomal clustering are regulated. Under uninducing conditions, local recruitment of the Rpd3(L) histone deacetylase by transcriptional repressors blocks Put3 DNA binding. This is a general function of yeast repressors: 16 of 21 repressors blocked Put3-mediated subnuclear positioning; 11 of these required Rpd3. In contrast, Ste12-mediated gene positioning is regulated independently of DNA binding by mitogen-activated protein kinase phosphorylation of the Dig2 inhibitor, and Gcn4-dependent targeting is up-regulated by increasing Gcn4 protein levels. These different regulatory strategies provide either qualitative switch-like control or quantitative control of gene positioning over different time scales. © 2016 Randise-Hinchliff et al.

Protein Binding Capacity of Different Forages Tannin

NASA Astrophysics Data System (ADS)

Yusiati, L. M.; Kurniawati, A.; Hanim, C.; Anas, M. A.

2018-02-01

Eight forages of tannin sources(Leucaena leucocephala, Arachis hypogaea, Mimosa pudica, Morus alba L, Swietenia mahagoni, Manihot esculenta, Gliricidia sepium, and Bauhinia purpurea)were evaluated their tannin content and protein binding capacity. The protein binding capacity of tannin were determined using precipitation of bovine serum albumin (BSA). Swietenia mahagonihas higest total tannin level and condensed tannin (CT) compared with other forages (P<0.01). The Leucaena leucocephala has highest hydrolysable tannin (HT) level (P<0.01). The total and condensed tannin content of Swietenia mahagoni were 11.928±0.04 mg/100 mg and 9.241±0.02mg/100mg dry matter (DM) of leaves. The hydrolysable tannin content of Leucaena leucocephala was 5.338±0.03 mg/100 mg DM of leaves. Binding capacity was highest in Swietenia mahagoni and Leucaena leucocephala compared to the other forages (P<0.01). The optimum binding of BSA to tannin in Leucaena leucocephala and Swietenia mahagoniwere1.181±0.44 and 1.217±0.60mg/mg dry matter of leaves. The present study reports that Swietenia mahagoni has highest of tannin content and Leucaena leucocephala and Swietenia mahagoni capacity of protein binding.

Calibration, event reconstruction, data analysis, and limit calculation for the LUX dark matter experiment

NASA Astrophysics Data System (ADS)

Akerib, D. S.; Alsum, S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Beltrame, P.; Bernard, E. P.; Bernstein, A.; Biesiadzinski, T. P.; Boulton, E. M.; Brás, P.; Byram, D.; Cahn, S. B.; Carmona-Benitez, M. C.; Chan, C.; Currie, A.; Cutter, J. E.; Davison, T. J. R.; Dobi, A.; Dobson, J. E. Y.; Druszkiewicz, E.; Edwards, B. N.; Faham, C. H.; Fallon, S. R.; Fan, A.; Fiorucci, S.; Gaitskell, R. J.; Gehman, V. M.; Genovesi, J.; Ghag, C.; Gilchriese, M. G. D.; Hall, C. R.; Hanhardt, M.; Haselschwardt, S. J.; Hertel, S. A.; Hogan, D. P.; Horn, M.; Huang, D. Q.; Ignarra, C. M.; Jacobsen, R. G.; Ji, W.; Kamdin, K.; Kazkaz, K.; Khaitan, D.; Knoche, R.; Larsen, N. A.; Lee, C.; Lenardo, B. G.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Manalaysay, A.; Mannino, R. L.; Marzioni, M. F.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J. A.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H. N.; Neves, F.; O'Sullivan, K.; Oliver-Mallory, K. C.; Palladino, K. J.; Pease, E. K.; Reichhart, L.; Rhyne, C.; Shaw, S.; Shutt, T. A.; Silva, C.; Solmaz, M.; Solovov, V. N.; Sorensen, P.; Sumner, T. J.; Szydagis, M.; Taylor, D. J.; Taylor, W. C.; Tennyson, B. P.; Terman, P. A.; Tiedt, D. R.; To, W. H.; Tripathi, M.; Tvrznikova, L.; Uvarov, S.; Velan, V.; Verbus, J. R.; Webb, R. C.; White, J. T.; Whitis, T. J.; Witherell, M. S.; Wolfs, F. L. H.; Xu, J.; Yazdani, K.; Young, S. K.; Zhang, C.; LUX Collaboration

2018-05-01

The LUX experiment has performed searches for dark-matter particles scattering elastically on xenon nuclei, leading to stringent upper limits on the nuclear scattering cross sections for dark matter. Here, for results derived from 1.4 ×104 kg days of target exposure in 2013, details of the calibration, event-reconstruction, modeling, and statistical tests that underlie the results are presented. Detector performance is characterized, including measured efficiencies, stability of response, position resolution, and discrimination between electron- and nuclear-recoil populations. Models are developed for the drift field, optical properties, background populations, the electron- and nuclear-recoil responses, and the absolute rate of low-energy background events. Innovations in the analysis include in situ measurement of the photomultipliers' response to xenon scintillation photons, verification of fiducial mass with a low-energy internal calibration source, and new empirical models for low-energy signal yield based on large-sample, in situ calibrations.

Readout technologies for directional WIMP Dark Matter detection

NASA Astrophysics Data System (ADS)

Battat, J. B. R.; Irastorza, I. G.; Aleksandrov, A.; Asada, T.; Baracchini, E.; Billard, J.; Bosson, G.; Bourrion, O.; Bouvier, J.; Buonaura, A.; Burdge, K.; Cebrián, S.; Colas, P.; Consiglio, L.; Dafni, T.; D'Ambrosio, N.; Deaconu, C.; De Lellis, G.; Descombes, T.; Di Crescenzo, A.; Di Marco, N.; Druitt, G.; Eggleston, R.; Ferrer-Ribas, E.; Fusayasu, T.; Galán, J.; Galati, G.; García, J. A.; Garza, J. G.; Gentile, V.; Garcia-Sciveres, M.; Giomataris, Y.; Guerrero, N.; Guillaudin, O.; Guler, A. M.; Harton, J.; Hashimoto, T.; Hedges, M. T.; Iguaz, F. J.; Ikeda, T.; Jaegle, I.; Kadyk, J. A.; Katsuragawa, T.; Komura, S.; Kubo, H.; Kuge, K.; Lamblin, J.; Lauria, A.; Lee, E. R.; Lewis, P.; Leyton, M.; Loomba, D.; Lopez, J. P.; Luzón, G.; Mayet, F.; Mirallas, H.; Miuchi, K.; Mizumoto, T.; Mizumura, Y.; Monacelli, P.; Monroe, J.; Montesi, M. C.; Naka, T.; Nakamura, K.; Nishimura, H.; Ochi, A.; Papevangelou, T.; Parker, J. D.; Phan, N. S.; Pupilli, F.; Richer, J. P.; Riffard, Q.; Rosa, G.; Santos, D.; Sawano, T.; Sekiya, H.; Seong, I. S.; Snowden-Ifft, D. P.; Spooner, N. J. C.; Sugiyama, A.; Taishaku, R.; Takada, A.; Takeda, A.; Tanaka, M.; Tanimori, T.; Thorpe, T. N.; Tioukov, V.; Tomita, H.; Umemoto, A.; Vahsen, S. E.; Yamaguchi, Y.; Yoshimoto, M.; Zayas, E.

2016-11-01

The measurement of the direction of WIMP-induced nuclear recoils is a compelling but technologically challenging strategy to provide an unambiguous signature of the detection of Galactic dark matter. Most directional detectors aim to reconstruct the dark-matter-induced nuclear recoil tracks, either in gas or solid targets. The main challenge with directional detection is the need for high spatial resolution over large volumes, which puts strong requirements on the readout technologies. In this paper we review the various detector readout technologies used by directional detectors. In particular, we summarize the challenges, advantages and drawbacks of each approach, and discuss future prospects for these technologies.

Structural determinants of nuclear export signal orientation in binding to exportin CRM1

DOE PAGES

Fung, Ho Yee Joyce; Fu, Szu -Chin; Brautigam, Chad A.; ...

2015-09-08

The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). A comparison of minus and plus NESs identified structural and sequencemore » determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.« less

77 FR 14007 - Sunshine Act Meeting Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-08

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD Sunshine Act Meeting Notice Federal Register CITATION OF... THE MEETING: The Defense Nuclear Facilities Safety Board (Board) is expanding the matters to be.../ resolution of safety and technical issues across the defense nuclear facilities complex. Since this panel...

Insights into the binding interactions of autochthonous dissolved organic matter released from Microcystis aeruginosa with pyrene using spectroscopy.

PubMed

Yang, Chenghu; Liu, Yangzhi; Zhu, Yaxian; Zhang, Yong

2016-03-15

The autochthonous dissolved organic matter (DOM) released by Microcystis aeruginosa (M. aeruginosa-DOM) during its growth period was characterized by spectroscopy. Furthermore, the relationships between the M. aeruginosa-DOM spectroscopic descriptors and the pyrene binding coefficient (KDOC) values were explored. The results showed that the spectroscopic characteristics of the M. aeruginosa-DOM and the binding properties of pyrene were dynamically changed along with the algae growth. Pearson correlation analysis demonstrated that a higher pyrene KDOC value was observed for the M. aeruginosa-DOM that has a higher humification index (HIX) value, a lower biological index (BIX) value and a lower absorption ratio (E2/E3). The presence of protein-like and long-wavelength-excited humic-like components may impose negative and positive effects on binding of pyrene by the M. aeruginosa-DOM, respectively. Principal component analysis (PCA) further supported that the binding affinity of pyrene may be primarily influenced by the humification degree of the M. aeruginosa-DOM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional Conservation of the Transportin Nuclear Import Pathway in Divergent Organisms

PubMed Central

Siomi, Mikiko C.; Fromont, Micheline; Rain, Jean-Christophe; Wan, Lili; Wang, Fan; Legrain, Pierre; Dreyfuss, Gideon

1998-01-01

Human transportin1 (hTRN1) is the nuclear import receptor for a group of pre-mRNA/mRNA-binding proteins (heterogeneous nuclear ribonucleoproteins [hnRNP]) represented by hnRNP A1, which shuttle continuously between the nucleus and the cytoplasm. hTRN1 interacts with the M9 region of hnRNP A1, a 38-amino-acid domain rich in Gly, Ser, and Asn, and mediates the nuclear import of M9-bearing proteins in vitro. Saccharomyces cerevisiae transportin (yTRN; also known as YBR017c or Kap104p) has been identified and cloned. To understanding the nuclear import mediated by yTRN, we searched with a yeast two-hybrid system for proteins that interact with it. In an exhaustive screen of the S. cerevisiae genome, the most frequently selected open reading frame was the nuclear mRNA-binding protein, Nab2p. We delineated a ca.-50-amino-acid region in Nab2p, termed NAB35, which specifically binds yTRN and is similar to the M9 motif. NAB35 also interacts with hTRN1 and functions as a nuclear localization signal in mammalian cells. Interestingly, yTRN can also mediate the import of NAB35-bearing proteins into mammalian nuclei in vitro. We also report on additional substrates for TRN as well as sequences of Drosophila melanogaster, Xenopus laevis, and Schizosaccharomyces pombe TRNs. Together, these findings demonstrate that both the M9 signal and the nuclear import machinery utilized by the transportin pathway are conserved in evolution. PMID:9632798

Regulation of Nuclear Import and Export of Negative Cofactor 2*S⃞

PubMed Central

Kahle, Joerg; Piaia, Elisa; Neimanis, Sonja; Meisterernst, Michael; Doenecke, Detlef

2009-01-01

The negative cofactor 2 (NC2) is a protein complex composed of two subunits, NC2α and NC2β, and plays a key role in transcription regulation. Here we investigate whether each subunit contains a nuclear localization signal (NLS) that permits individual crossing of the nuclear membrane or whether nuclear import of NC2α and NC2β depends on heterodimerization. Our results from in vitro binding studies and transfection experiments in cultured cells show that each subunit contains a classical NLS (cNLS) that is recognized by the importin α/β heterodimer. Regardless of the individual cNLSs the two NC2 subunits are translocated as a preassembled complex as co-transfection experiments with wild-type and cNLS-deficient NC2 subunits demonstrate. Ran-dependent binding of the nuclear export receptor Crm1/exportin 1 confirmed the presence of a leucine-rich nuclear export signal (NES) in NC2β. In contrast, NC2α does not exhibit a NES. Our results from interspecies heterokaryon assays suggest that heterodimerization with NC2α masks the NES in NC2β, which prevents nuclear export of the NC2 complex. A mutation in either one of the two cNLSs decreases the extent of importin α/β-mediated nuclear import of the NC2 complex. In addition, the NC2 complex can enter the nucleus via a second pathway, facilitated by importin 13. Because importin 13 binds exclusively to the NC2 complex but not to the individual subunits this alternative import pathway depends on sequence elements distributed among the two subunits. PMID:19204005

From hadrons to quarks in neutron stars: a review

NASA Astrophysics Data System (ADS)

Baym, Gordon; Hatsuda, Tetsuo; Kojo, Toru; Powell, Philip D.; Song, Yifan; Takatsuka, Tatsuyuki

2018-05-01

In recent years our understanding of neutron stars has advanced remarkably, thanks to research converging from many directions. The importance of understanding neutron star behavior and structure has been underlined by the recent direct detection of gravitational radiation from merging neutron stars. The clean identification of several heavy neutron stars, of order two solar masses, challenges our current understanding of how dense matter can be sufficiently stiff to support such a mass against gravitational collapse. Programs underway to determine simultaneously the mass and radius of neutron stars will continue to constrain and inform theories of neutron star interiors. At the same time, an emerging understanding in quantum chromodynamics (QCD) of how nuclear matter can evolve into deconfined quark matter at high baryon densities is leading to advances in understanding the equation of state of the matter under the extreme conditions in neutron star interiors. We review here the equation of state of matter in neutron stars from the solid crust through the liquid nuclear matter interior to the quark regime at higher densities. We focus in detail on the question of how quark matter appears in neutron stars, and how it affects the equation of state. After discussing the crust and liquid nuclear matter in the core we briefly review aspects of microscopic quark physics relevant to neutron stars, and quark models of dense matter based on the Nambu–Jona–Lasinio framework, in which gluonic processes are replaced by effective quark interactions. We turn then to describing equations of state useful for interpretation of both electromagnetic and gravitational observations, reviewing the emerging picture of hadron-quark continuity in which hadronic matter turns relatively smoothly, with at most only a weak first order transition, into quark matter with increasing density. We review construction of unified equations of state that interpolate between the reasonably well understood nuclear matter regime at low densities and the quark matter regime at higher densities. The utility of such interpolations is driven by the present inability to calculate the dense matter equation of state in QCD from first principles. As we review, the parameters of effective quark models—which have direct relevance to the more general structure of the QCD phase diagram of dense and hot matter—are constrained by neutron star mass and radii measurements, in particular favoring large repulsive density-density and attractive diquark pairing interactions. We describe the structure of neutron stars constructed from the unified equations of states with crossover. Lastly we present the current equations of state—called ‘QHC18’ for quark-hadron crossover—in a parametrized form practical for neutron star modeling.

Nucleon effective E-mass in neutron-rich matter from the Migdal–Luttinger jump

DOE PAGES

Cai, Bao-Jun; Li, Bao-An

2016-03-25

The well-known Migdal-Luttinger theorem states that the jump of the single-nucleon momentum distribution at the Fermi surface is equal to the inverse of the nucleon effective E-mass. Recent experiments studying short-range correlations (SRC) in nuclei using electron-nucleus scatterings at the Jefferson National Laboratory (JLAB) together with model calculations constrained significantly the Migdal-Luttinger jump at saturation density of nuclear matter. We show that the corresponding nucleon effective E-mass is consequently constrained to M-0(*,E)/M approximate to 2.22 +/- 0.35 in symmetric nuclear matter (SNM) and the E-mass of neutrons is smaller than that of protons in neutron-rich matter. Moreover, the average depletionmore » of the nucleon Fermi sea increases (decreases) approximately linearly with the isospin asymmetry delta according to kappa(p/n) approximate to 0.21 +/- 0.06 +/- (0.19 +/- 0.08)delta for protons (neutrons). These results will help improve our knowledge about the space-time non-locality of the single-nucleon potential in neutron-rich nucleonic matter Useful in both nuclear physics and astrophysics. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP(3).« less

Cd-binding to model membranes

NASA Astrophysics Data System (ADS)

Geszner, R.; Saibene, S.; Butz, T.; Lerf, A.

1990-08-01

The binding of Cd2+ to the model membranes Di-myristoyl L-α-phosphatidic acid (DMPA) and Di-myristoyl L-α-phosphatidylcholine (DMPC) was studied by time differential perturbed angular correlation (TDPAC) on111mCd, via its nuclear quadrupole interaction. Whereas Cd2+ does not bind to the neutral DMPC, it binds to charged DMPA up to a 0.8∶1 Cd/lipid ratio.

Evaluation of the Effect of Fingolimod Treatment on Microglial Activation Using Serial PET Imaging in Multiple Sclerosis.

PubMed

Sucksdorff, Marcus; Rissanen, Eero; Tuisku, Jouni; Nuutinen, Salla; Paavilainen, Teemu; Rokka, Johanna; Rinne, Juha; Airas, Laura

2017-10-01

Traditionally, multiple sclerosis (MS) has been considered a white matter disease with focal inflammatory lesions. It is, however, becoming clear that significant pathology, such as microglial activation, also takes place outside the plaque areas, that is, in areas of normal-appearing white matter (NAWM) and gray matter (GM). Microglial activation can be detected in vivo using 18-kDa translocator protein (TSPO)-binding radioligands and PET. It is unknown whether fingolimod affects microglial activation in MS. The aim of this study was to investigate whether serial PET can be used to evaluate the effect of fingolimod treatment on microglial activation. Methods: Ten relapsing-remitting MS patients were studied using the TSPO radioligand 11 C-( R )-PK11195. Imaging was performed at baseline and after 8 and 24 wk of fingolimod treatment. Eight healthy individuals were imaged for comparison. Microglial activation was evaluated as distribution volume ratio of 11 C-( R )-PK11195. Results: The patients had MS for an average of 7.9 ± 4.3 y (mean ± SD), their total relapses averaged 4 ± 2.4, and their Expanded Disability Status Scale was 2.7 ± 0.5. The patients were switched to fingolimod because of safety reasons or therapy escalation. The mean washout period before the initiation of fingolimod was 2.3 ± 1.1 mo. The patients were clinically stable on fingolimod. At baseline, microglial activation was significantly higher in the combined NAWM and GM areas of MS patients than in healthy controls ( P = 0.021). 11 C-( R )-PK11195 binding was reduced (-12.31%) within the combined T2 lesion area after 6 mo of fingolimod treatment ( P = 0.040) but not in the areas of NAWM or GM. Conclusion: Fingolimod treatment reduced microglial/macrophage activation at the site of focal inflammatory lesions, presumably by preventing leukocyte trafficking from the periphery. It did not affect the widespread, diffuse microglial activation in the NAWM and GM. The study opens new vistas for designing future therapeutic studies in MS that use the evaluation of microglial activation as an imaging outcome measure. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Nuclear IGF-1R interacts with regulatory regions of chromatin to promote RNA polymerase II recruitment and gene expression associated with advanced tumor stage.

PubMed

Aleksic, Tamara; Gray, Nicki E; Wu, Xiaoning; Rieunier, Guillaume; Osher, Eliot; Mills, Jack; Verrill, Clare; Bryant, Richard J; Han, Cheng; Hutchinson, Kathryn; Lambert, Adam; Kumar, Rajeev; Hamdy, Freddie C; Weyer-Czernilofsky, Ulrike; Sanderson, Michael; Bogenrieder, Thomas; Taylor, Stephen; Macaulay, Valentine M

2018-05-07

Internalization of ligand-activated type 1 IGF receptor (IGF-1R) is followed by recycling to the plasma membrane, degradation or nuclear translocation. Nuclear IGF-1R reportedly associates with clinical response to IGF-1R inhibitory drugs, yet its role in the nucleus is poorly characterized. Here we investigated the significance of nuclear IGF-1R in clinical cancers and cell line models. In prostate cancers, IGF-1R was predominantly membrane-localized in benign glands, while malignant epithelium contained prominent internalized (nuclear/cytoplasmic) IGF-1R, and nuclear IGF-1R associated significantly with advanced tumor stage. Using ChIP-seq to assess global chromatin occupancy, we identified IGF-1R binding sites at or near transcription start sites of genes including JUN and FAM21, most sites coinciding with occupancy by RNA polymerase II (RNAPol2) and histone marks of active enhancers/promoters. IGF-1R was inducibly recruited to chromatin, directly binding DNA and interacting with RNAPol2 to upregulate expression of JUN and FAM21, shown to mediate tumor cell survival and IGF-induced migration. IGF-1 also enriched RNAPol2 on promoters containing IGF-1R binding sites. These functions were inhibited by IGF-1/2 neutralizing antibody xentuzumab (BI 836845), or by blocking receptor internalization. We detected nuclear IGF-1R on JUN and FAM21 promoters in fresh prostate cancers that contained abundant nuclear IGF-1R, with evidence of correlation between nuclear IGF-1R content and JUN expression in malignant prostatic epithelium. Taken together, these data reveal previously unrecognized molecular mechanisms through which IGFs promote tumorigenesis, with implications for therapeutic evaluation of anti-IGF drugs. Copyright ©2018, American Association for Cancer Research.

Nuclear poly(A)-binding protein aggregates misplace a pre-mRNA outside of SC35 speckle causing its abnormal splicing

PubMed Central

Klein, Pierre; Oloko, Martine; Roth, Fanny; Montel, Valérie; Malerba, Alberto; Jarmin, Susan; Gidaro, Teresa; Popplewell, Linda; Perie, Sophie; Lacau St Guily, Jean; de la Grange, Pierre; Antoniou, Michael N.; Dickson, George; Butler-Browne, Gillian; Bastide, Bruno; Mouly, Vincent; Trollet, Capucine

2016-01-01

A short abnormal polyalanine expansion in the polyadenylate-binding protein nuclear-1 (PABPN1) protein causes oculopharyngeal muscular dystrophy (OPMD). Mutated PABPN1 proteins accumulate as insoluble intranuclear aggregates in muscles of OPMD patients. While the roles of PABPN1 in nuclear polyadenylation and regulation of alternative poly(A) site choice have been established, the molecular mechanisms which trigger pathological defects in OPMD and the role of aggregates remain to be determined. Using exon array, for the first time we have identified several splicing defects in OPMD. In particular, we have demonstrated a defect in the splicing regulation of the muscle-specific Troponin T3 (TNNT3) mutually exclusive exons 16 and 17 in OPMD samples compared to controls. This splicing defect is directly linked to the SC35 (SRSF2) splicing factor and to the presence of nuclear aggregates. As reported here, PABPN1 aggregates are able to trap TNNT3 pre-mRNA, driving it outside nuclear speckles, leading to an altered SC35-mediated splicing. This results in a decreased calcium sensitivity of muscle fibers, which could in turn plays a role in muscle pathology. We thus report a novel mechanism of alternative splicing deregulation that may play a role in various other diseases with nuclear inclusions or foci containing an RNA binding protein. PMID:27507886

Studies of nuclei under the extreme conditions of density, temperature, isospin asymmetry and the phase diagram of hadronic matter

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

Mekjian, Aram

2016-10-18

The main emphasis of the entire project is on issues having to do with medium energy and ultra-relativistic energy and heavy ion collisions. A major goal of both theory and experiment is to study properties of hot dense nuclear matter under various extreme conditions and to map out the phase diagram in density or chemical potential and temperature. My studies in medium energy nuclear collisions focused on the liquid-gas phase transition and cluster yields from such transitions. Here I developed both the statistical model of nuclear multi-fragmentation and also a mean field theory.

Phase diagram of dilute cosmic matter

NASA Astrophysics Data System (ADS)

Iwata, Yoritaka

2011-10-01

Enhancement of nuclear pasta formation due to multi-nucleus simultaneous collision is presented based on time-dependent density functional calculations with periodic boundary condition. This calculation corresponds to the situation with density lower than the known low-density existence limit of the nuclear pasta phase. In order to evaluate the contribution from three-nucleus simultaneous collisions inside the cosmic matter, the possibility of multi-nucleus simultaneous collisions is examined by a systematic Monte-Carlo calculation, and the mean free path of a nucleus is obtained. Consequently the low-density existence limit of the nuclear pasta phase is formed to be lower than believed up to now.

Cluster formation in nuclear reactions from mean-field inhomogeneities

NASA Astrophysics Data System (ADS)

Napolitani, Paolo; Colonna, Maria; Mancini-Terracciano, Carlo

2018-05-01

Perturbing fluids of neutrons and protons (nuclear matter) may lead, as the most catastrophic effect, to the rearrangement of the fluid into clusters of nucleons. A similar process may occur in a single atomic nucleus undergoing a violent perturbation, like in heavy-ion collisions tracked in particle accelerators at around 30 to 50 MeV per nucleon: in this conditions, after the initial collision shock, the nucleus expands and then clusterises into several smaller nuclear fragments. Microscopically, when violent perturbation are applied to nuclear matter, a process of clusterisation arises from the combination of several fluctuation modes of large-amplitude where neutrons and protons may oscillate in phase or out of phase. The imposed perturbation leads to conditions of instability, the wavelengths which are the most amplified have sizes comparable to small atomic nuclei. We found that these conditions, explored in heavy-ion collisions, correspond to the splitting of a nucleus into fragments ranging from Oxygen to Neon in a time interval shorter than one zeptosecond (10 ‑ 21s). From the out-of-phase oscillations of neutrons and protons another property arises, the smaller fragments belonging to a more volatile phase get more neutron enriched: in the heavy-ion collision case this process, called distillation, reflects in the isotopic distributions of the fragments. The resulting dynamical description of heavy-ion collisions is an improvement with respect to more usual statistical approaches, based on the equilibrium assumption. It allows in fact to characterise also the very fast early stages of the collision process which are out of equilibrium. Such dynamical description is the core of the Boltzmann-Langevin One Body (BLOB) model, which in its latest development unifies in a common approach the description of fluctuations in nuclear matter, and a predictive description of the disintegration of nuclei into nuclear fragments. After a theoretical introduction, a few practical examples will be illustrated. This paper resumes the extended analysis of fluctuations in nuclear matter of ref. [2] and briefly reviews applications to heavy-ion collisions.

Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.

PubMed

Kobayashi, Masakazu; Retra, Kim; Figaroa, Francis; Hollander, Johan G; Ab, Eiso; Heetebrij, Robert J; Irth, Hubertus; Siegal, Gregg

2010-09-01

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ligands with affinity weaker than 1 mM K(D) is limited. Similarly, they find that SPR detection is most suited to ligands that bind with K(D) better than 1 mM. However, the good correlation between SPR and potency in a bioassay makes this a good method for hit validation and characterization studies.

CORE-COLLAPSE SUPERNOVA EQUATIONS OF STATE BASED ON NEUTRON STAR OBSERVATIONS

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

Steiner, A. W.; Hempel, M.; Fischer, T.

2013-09-01

Many of the currently available equations of state for core-collapse supernova simulations give large neutron star radii and do not provide large enough neutron star masses, both of which are inconsistent with some recent neutron star observations. In addition, one of the critical uncertainties in the nucleon-nucleon interaction, the nuclear symmetry energy, is not fully explored by the currently available equations of state. In this article, we construct two new equations of state which match recent neutron star observations and provide more flexibility in studying the dependence on nuclear matter properties. The equations of state are also provided in tabularmore » form, covering a wide range in density, temperature, and asymmetry, suitable for astrophysical simulations. These new equations of state are implemented into our spherically symmetric core-collapse supernova model, which is based on general relativistic radiation hydrodynamics with three-flavor Boltzmann neutrino transport. The results are compared with commonly used equations of state in supernova simulations of 11.2 and 40 M{sub Sun} progenitors. We consider only equations of state which are fitted to nuclear binding energies and other experimental and observational constraints. We find that central densities at bounce are weakly correlated with L and that there is a moderate influence of the symmetry energy on the evolution of the electron fraction. The new models also obey the previously observed correlation between the time to black hole formation and the maximum mass of an s = 4 neutron star.« less

Genome-wide identification of nuclear receptor (NR) superfamily genes in the copepod Tigriopus japonicus.

PubMed

Hwang, Dae-Sik; Lee, Bo-Young; Kim, Hui-Su; Lee, Min Chul; Kyung, Do-Hyun; Om, Ae-Son; Rhee, Jae-Sung; Lee, Jae-Seong

2014-11-18

Nuclear receptors (NRs) are a large superfamily of proteins defined by a DNA-binding domain (DBD) and a ligand-binding domain (LBD). They function as transcriptional regulators to control expression of genes involved in development, homeostasis, and metabolism. The number of NRs differs from species to species, because of gene duplications and/or lineage-specific gene losses during metazoan evolution. Many NRs in arthropods interact with the ecdysteroid hormone and are involved in ecdysone-mediated signaling in arthropods. The nuclear receptor superfamily complement has been reported in several arthropods, including crustaceans, but not in copepods. We identified the entire NR repertoire of the copepod Tigriopus japonicus, which is an important marine model species for ecotoxicology and environmental genomics. Using whole genome and transcriptome sequences, we identified a total of 31 nuclear receptors in the genome of T. japonicus. Nomenclature of the nuclear receptors was determined based on the sequence similarities of the DNA-binding domain (DBD) and ligand-binding domain (LBD). The 7 subfamilies of NRs separate into five major clades (subfamilies NR1, NR2, NR3, NR4, and NR5/6). Although the repertoire of NR members in, T. japonicus was similar to that reported for other arthropods, there was an expansion of the NR1 subfamily in Tigriopus japonicus. The twelve unique nuclear receptors identified in T. japonicus are members of NR1L. This expansion may be a unique lineage-specific feature of crustaceans. Interestingly, E78 and HR83, which are present in other arthropods, were absent from the genomes of T. japonicus and two congeneric copepod species (T. japonicus and Tigriopus californicus), suggesting copepod lineage-specific gene loss. We identified all NR receptors present in the copepod, T. japonicus. Knowledge of the copepod nuclear receptor repertoire will contribute to a better understanding of copepod- and crustacean-specific NR evolution.

Catalysis of partial chiral symmetry restoration by Δ matter

NASA Astrophysics Data System (ADS)

Takeda, Yusuke; Kim, Youngman; Harada, Masayasu

2018-06-01

We study the phase structure of dense hadronic matter including Δ (1232 ) as well as N (939 ) based on the parity partner structure, where the baryons have their chiral partners with a certain amount of chiral invariant masses. We show that, in symmetric matter, Δ enters into matter in the density region of about one to four times normal nuclear matter density, ρB˜1 -4 ρ0 . The onset density of Δ matter depends on the chiral invariant mass of Δ ,mΔ 0 : As mΔ 0 increases, the onset density becomes bigger. The stable Δ -nucleon matter is realized for ρB≳1.5 ρ0 , i.e., the phase transition from nuclear matter to Δ -nucleon matter is of first order for small mΔ 0, and it is of second order for large mΔ 0. We find that, associated with the phase transition, the chiral condensate changes very rapidly; i.e., the chiral symmetry restoration is accelerated by Δ matter. As a result of the accelerations, there appear N*(1535 ) and Δ (1700 ) , which are the chiral partners to N (939 ) and Δ (1232 ) , in high-density matter, signaling the partial chiral symmetry restoration. Furthermore, we find that complete chiral symmetry restoration itself is delayed by Δ matter. We also calculate the effective masses, pressure, and symmetry energy to study how the transition to Δ matter affects such physical quantities. We observe that the physical quantities change drastically at the transition density.

A study of intrinsic statistical variation for low-energy nuclear recoils in liquid xenon detector for dark matter searches

NASA Astrophysics Data System (ADS)

Wang, Lu; Wei, Wenzhao; Mei, Dongming; Cubed Collaboration

2015-10-01

Noble liquid xenon experiments, such as XENON100, LUX, XENON 1-Ton, and LZ are large dark matter experiments directly searches for weakly interacting massive particles (WIMPs). One of the most important features is to discriminate nuclear recoils from electronic recoils. Detector response is generally calibrated with different radioactive sources including 83mKr, tritiated methane, 241AmBe, 252Cf, and DD-neutrons. The electronic recoil and nuclear recoil bands have been determined by these calibrations. However, the width of nuclear recoil band needs to be fully understood. We derive a theoretical model to understand the correlation of the width of nuclear recoil band and intrinsic statistical variation. In addition, we conduct experiments to validate the theoretical model. In this paper, we present the study of intrinsic statistical variation contributing to the width of nuclear recoil band. DE-FG02-10ER46709 and the state of South Dakota.

Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

PubMed

Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

2016-12-01

We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

The Heart of Matter: A Nuclear Chemistry Module. Teacher's Guide.

ERIC Educational Resources Information Center

Viola, Vic; Hearle, Robert

This teacher's guide is designed to provide science teachers with the necessary guidance and suggestions for teaching nuclear chemistry. In this book, the fundamental concepts of nuclear science and the applications of nuclear energy are discussed. The material in this book can be integrated with the other modules in a sequence that helps students…

The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

PubMed

Booth, David S; Cheng, Yifan; Frankel, Alan D

2014-12-08

The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

Phosphatidic acid interacts with a MYB transcription factor and regulates its nuclear localization and function in Arabidopsis.

PubMed

Yao, Hongyan; Wang, Geliang; Guo, Liang; Wang, Xuemin

2013-12-01

Phosphatidic acid (PA) has emerged as a class of cellular mediators involved in various cellular and physiological processes, but little is known about its mechanism of action. Here we show that PA interacts with werewolf (WER), a R2R3 MYB transcription factor involved in root hair formation. The PA-interacting region is confined to the end of the R2 subdomain. The ablation of the PA binding motif has no effect on WER binding to DNA, but abolishes its nuclear localization and its function in regulating epidermal cell fate. Inhibition of PA production by phospholipase Dζ also suppresses WER's nuclear localization, root hair formation, and elongation. These results suggest a role for PA in promoting protein nuclear localization.

Phosphatidic Acid Interacts with a MYB Transcription Factor and Regulates Its Nuclear Localization and Function in Arabidopsis[C][W

PubMed Central

Yao, Hongyan; Wang, Geliang; Guo, Liang; Wang, Xuemin

2013-01-01

Phosphatidic acid (PA) has emerged as a class of cellular mediators involved in various cellular and physiological processes, but little is known about its mechanism of action. Here we show that PA interacts with WEREWOLF (WER), a R2R3 MYB transcription factor involved in root hair formation. The PA-interacting region is confined to the end of the R2 subdomain. The ablation of the PA binding motif has no effect on WER binding to DNA, but abolishes its nuclear localization and its function in regulating epidermal cell fate. Inhibition of PA production by phospholipase Dζ also suppresses WER’s nuclear localization, root hair formation, and elongation. These results suggest a role for PA in promoting protein nuclear localization. PMID:24368785

Exact solution of equations for proton localization in neutron star matter

NASA Astrophysics Data System (ADS)

Kubis, Sebastian; Wójcik, Włodzimierz

2015-11-01

The rigorous treatment of proton localization phenomenon in asymmetric nuclear matter is presented. The solution of proton wave function and neutron background distribution is found by the use of the extended Thomas-Fermi approach. The minimum of energy is obtained in the Wigner-Seitz approximation of a spherically symmetric cell. The analysis of four different nuclear models suggests that the proton localization is likely to take place in the interior of a neutron star.

Two-level convolution formula for nuclear structure function

NASA Astrophysics Data System (ADS)

Ma, Boqiang

1990-05-01

A two-level convolution formula for the nuclear structure function is derived in considering the nucleus as a composite system of baryon-mesons which are also composite systems of quark-gluons again. The results show that the European Muon Colaboration effect can not be explained by the nuclear effects as nucleon Fermi motion and nuclear binding contributions.

Equation of state for dense nucleonic matter from metamodeling. I. Foundational aspects

NASA Astrophysics Data System (ADS)

Margueron, Jérôme; Hoffmann Casali, Rudiney; Gulminelli, Francesca

2018-02-01

Metamodeling for the nucleonic equation of state (EOS), inspired from a Taylor expansion around the saturation density of symmetric nuclear matter, is proposed and parameterized in terms of the empirical parameters. The present knowledge of nuclear empirical parameters is first reviewed in order to estimate their average values and associated uncertainties, and thus defining the parameter space of the metamodeling. They are divided into isoscalar and isovector types, and ordered according to their power in the density expansion. The goodness of the metamodeling is analyzed against the predictions of the original models. In addition, since no correlation among the empirical parameters is assumed a priori, all arbitrary density dependences can be explored, which might not be accessible in existing functionals. Spurious correlations due to the assumed functional form are also removed. This meta-EOS allows direct relations between the uncertainties on the empirical parameters and the density dependence of the nuclear equation of state and its derivatives, and the mapping between the two can be done with standard Bayesian techniques. A sensitivity analysis shows that the more influential empirical parameters are the isovector parameters Lsym and Ksym, and that laboratory constraints at supersaturation densities are essential to reduce the present uncertainties. The present metamodeling for the EOS for nuclear matter is proposed for further applications in neutron stars and supernova matter.

The hrp23 Protein in the Balbiani Ring Pre-mRNP Particles Is Released Just before or at the Binding of the Particles to the Nuclear Pore Complex

PubMed Central

Sun, Xin; Alzhanova-Ericsson, Alla T.; Visa, Neus; Aissouni, Youssef; Zhao, Jian; Daneholt, Bertil

1998-01-01

Balbiani ring (BR) pre-mRNP particles reside in the nuclei of salivary glands of the dipteran Chironomus tentans and carry the message for giant-sized salivary proteins. In the present study, we identify and characterize a new protein component in the BR ribonucleoprotein (RNP) particles, designated hrp23. The protein with a molecular mass of 20 kD has a single RNA-binding domain and a glycine-arginine-serine–rich auxiliary domain. As shown by immunoelectron microscopy, the hrp23 protein is added to the BR transcript concomitant with transcription, is still present in the BR particles in the nucleoplasm, but is absent from the BR particles that are bound to the nuclear pore complex or are translocating through the central channel of the complex. Thus, hrp23 is released just before or at the binding of the particles to the nuclear pore complex. It is noted that hrp23 behaves differently from two other BR RNP proteins earlier studied: hrp36 and hrp45. These proteins both reach the nuclear pore complex, and hrp36 even accompanies the RNA into the cytoplasm. It is concluded that each BR RNA-binding protein seems to have a specific flow pattern, probably related to the particular role of the protein in gene expression. PMID:9732280

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs.

PubMed

Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D; Pelletier, Jerry; Ferraiuolo, Maria A; Sonenberg, Nahum

2008-07-01

Eukaryotic initiation factor (eIF) 4E, the mRNA 5'-cap-binding protein, mediates the association of eIF4F with the mRNA 5'-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (approximately 30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras-expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization.

Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs

PubMed Central

Rong, Liwei; Livingstone, Mark; Sukarieh, Rami; Petroulakis, Emmanuel; Gingras, Anne-Claude; Crosby, Katherine; Smith, Bradley; Polakiewicz, Roberto D.; Pelletier, Jerry; Ferraiuolo, Maria A.; Sonenberg, Nahum

2008-01-01

Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (∼30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras–expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization. PMID:18515545

Identification and characterization of a nuclear localization signal of TRIM28 that overlaps with the HP1 box

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

Moriyama, Tetsuji; Sangel, Percival; Yamaguchi, Hiroki

2015-07-03

Tripartite motif-containing 28 (TRIM28) is a transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (HP1). Here, we report identification of a nuclear localization signal (NLS) within the 462-494 amino acid region of TRIM28 that overlaps with its HP1 binding site, HP1 box. GST-pulldown experiments revealed the interaction of the arginine-rich TRIM28 NLS with various importin α subtypes (α1, α2 and α4). In vitro transport assay demonstrated that nuclear localization of GFP-TRIM28 NLS is mediated by importin αs, in conjunction with importin β1 and Ran. Further, we demonstrated that HP1 and importin αs compete for binding to TRIM28. Together,more » our findings suggest that importin α has an essential role in the nuclear delivery and preferential HP1 interaction of TRIM28. - Highlights: • TRIM28 contains an NLS within the 462-494 amino acid region. • The nuclear import of TRIM28 is mediated by importin α/importin β1. • TRIM28 NLS overlaps with HP1 Box. • HP1 and importin α compete for binding to TRIM28.« less

DNA-histone complexes as ligands amplify cell penetration and nuclear targeting of anti-DNA antibodies via energy-independent mechanisms.

PubMed

Zannikou, Markella; Bellou, Sofia; Eliades, Petros; Hatzioannou, Aikaterini; Mantzaris, Michael D; Carayanniotis, George; Avrameas, Stratis; Lymberi, Peggy

2016-01-01

We have generated three monoclonal cell-penetrating antibodies (CPAbs) from a non-immunized lupus-prone (NZB × NZW)F1 mouse that exhibited high anti-DNA serum titres. These CPAbs are polyreactive because they bind to DNA and other cellular components, and localize mainly in the nucleus of HeLa cells, albeit with a distinct nuclear labelling profile. Herein, we have examined whether DNA-histone complexes (DHC) binding to CPAbs, before cell entry, could modify the cell penetration of CPAbs or their nuclear staining properties. By applying confocal microscopy and image analysis, we found that extracellular binding of purified CPAbs to DHC significantly enhanced their subsequent cell-entry, both in terms of percentages of positively labelled cells and fluorescence intensity (internalized CPAb amount), whereas there was a variable effect on their nuclear staining profile. Internalization of CPAbs, either alone or bound to DHC, remained unaltered after the addition of endocytosis-specific inhibitors at 37° or assay performance at 4°, suggesting the involvement of energy-independent mechanisms in the internalization process. These findings assign to CPAbs a more complex pathogenetic role in systemic lupus erythematosus where both CPAbs and nuclear components are abundant. © 2015 John Wiley & Sons Ltd.

Toxic PRn poly-dipeptides encoded by the C9orf72 repeat expansion block nuclear import and export.

PubMed

Shi, Kevin Y; Mori, Eiichiro; Nizami, Zehra F; Lin, Yi; Kato, Masato; Xiang, Siheng; Wu, Leeju C; Ding, Ming; Yu, Yonghao; Gall, Joseph G; McKnight, Steven L

2017-02-14

The toxic proline:arginine (PR n ) poly-dipeptide encoded by the (GGGGCC) n repeat expansion in the C9orf72 form of heritable amyotrophic lateral sclerosis (ALS) binds to the central channel of the nuclear pore and inhibits the movement of macromolecules into and out of the nucleus. The PR n poly-dipeptide binds to polymeric forms of the phenylalanine:glycine (FG) repeat domain, which is shared by several proteins of the nuclear pore complex, including those in the central channel. A method of chemical footprinting was used to characterize labile, cross-β polymers formed from the FG domain of the Nup54 protein. Mutations within the footprinted region of Nup54 polymers blocked both polymerization and binding by the PR n poly-dipeptide. The aliphatic alcohol 1,6-hexanediol melted FG domain polymers in vitro and reversed PR n -mediated enhancement of the nuclear pore permeability barrier. These data suggest that toxicity of the PR n poly-dipeptide results in part from its ability to lock the FG repeats of nuclear pore proteins in the polymerized state. Our study offers a mechanistic interpretation of PR n poly-dipeptide toxicity in the context of a prominent form of ALS.

Nucleon effective masses in neutron-rich matter

NASA Astrophysics Data System (ADS)

Li, Bao-An; Cai, Bao-Jun; Chen, Lie-Wen; Xu, Jun

2018-03-01

Various kinds of isovector nucleon effective masses are used in the literature to characterize the momentum/energy dependence of the nucleon symmetry potential or self-energy due to the space/time non-locality of the underlying isovector strong interaction in neutron-rich nucleonic matter. The multifaceted studies on nucleon isovector effective masses are multi-disciplinary in nature. Besides structures, masses and low-lying excited states of nuclei as well as nuclear reactions, studies of the isospin dependence of short-range correlations in nuclei from scatterings of high-energy electrons and protons on heavy nuclei also help understand nucleon effective masses especially the so-called E-mass in neutron-rich matter. A thorough understanding of all kinds of nucleon effective masses has multiple impacts on many interesting issues in both nuclear physics and astrophysics. Indeed, essentially all microscopic many-body theories and phenomenological models with various nuclear forces available in the literature have been used to calculate single-nucleon potentials and the associated nucleon effective masses in neutron-rich matter. There are also fundamental principles connecting different aspects and impacts of isovector strong interactions. In particular, the Hugenholtz-Van Hove theorem connects analytically nuclear symmetry energy with both isoscalar and isovector nucleon effective masses as well as their own momentum dependences. It also reveals how the isospin-quartic term in the equation of state of neutron-rich matter depends on the high-order momentum-derivatives of both isoscalar and isovector nucleon potentials. The Migdal-Luttinger theorem facilitates the extraction of nucleon E-mass and its isospin dependence from experimentally constrained single-nucleon momentum distributions. The momentum/energy dependence of the symmetry potential and the corresponding neutron-proton effective mass splitting also affect transport properties and the liquid-gas phase transition in neutron-rich matter. Moreover, they influence the dynamics and isospin-sensitive observables of heavy-ion collisions through both the Vlasov term and the collision integrals of the Boltzmann-Uehling-Uhlenbeck transport equation. We review here some of the significant progresses made in recent years by the nuclear physics community in resolving some of the hotly debated and longstanding issues regarding nucleon effective masses especially in dense neutron-rich matter. We also point out some of the remaining key issues requiring further investigations in the era of high precision experiments using advanced rare isotope beams.

Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes.

PubMed

Murata, H; Hattori, T; Maeda, H; Takashiba, S; Takigawa, M; Kido, J; Nagata, T

2015-08-01

Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. We identified TDP-43 as one of the novel TNF-α factors and found that it bound to the LPS-responsive element in the TNF-α promoter to increase TNF-α expression. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Equation of State Effects on Binary Neutron Star and Neutron Star-Black Hole Merger Ejecta

NASA Astrophysics Data System (ADS)

Rizzo, Monica; Pankow, Chris; Kalogera, Vassiliki; Coughlin, Scott; Chase, Eve; Imperato, Sam

2018-01-01

Binary neutron stars (BNSs) and neutron star-black hole (NSBH) binaries are not only potential sources of gravitational waves (GWs), but also are thought to generate phenomena such as kilonova, which have proven to be difficult to catch with electromagnetic (EM) instruments. Kilonovae are believed to arise from the radioactive decay of nuclear matter ejected from NSBH and BNS mergers. As they spiral toward each other, neutron stars (NSs), composed of highly dense nuclear matter, are torn apart by their companion's gravity and eject matter. The amount of matter they eject depends sensitively on the composition of NSs, which is described by a nuclear equation of state (EOS). Using fit formulas for ejected mass from Kawaguchi et. al. (2016) and T. Dietrich and M. Ujevic (2016), for NSBH and BNS respectively, we calculate the amount of mass ejected given the initial parameters (masses, black hole spin, etc.) of NSBH and BNS systems. We then predict the distribution of ejected matter for populations of NSBH and BNS mergers, assuming a different EOS for each population. Using formulas derived from The Kilonova Handbook (Metzger, 2016), we can use the calculated ejected mass to generate light curves which, along with GW detections, can be used to place constraints on an EOS for NSs when GW detections are made. We find that the amount of ejected matter observed is distinct for most EOSs, though to draw any solid conclusions about NS composition, joint GW wave and EM counterpart detections are necessary.

Nuclear pasta in hot dense matter and its implications for neutrino scattering

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

Roggero, Alessandro; Margueron, Jerome; Roberts, Luke F.

The abundance of large clusters of nucleons in neutron-rich matter at subnuclear density is found to be greatly reduced by finite-temperature effects when matter is close to β equilibrium, compared to the case where the electron fraction is fixed at Y e > 0.1 , as often considered in the literature. Large nuclei and exotic nonspherical nuclear configurations called pasta, favored in the vicinity of the transition to uniform matter at T = 0 , dissolve at a relatively low temperature T u as protons leak out of nuclei and pasta. For matter at β-equilibrium with a negligible neutrino chemical potential we find that Tmore » $$β\\atop{u}$$ ≃ 4 ± 1 MeV for realistic equations of state. This is lower than the maximum temperature T$$β\\atop{max}$$ ≃ 9 ± 1 MeV at which nuclei can coexist with a gas of nucleons and can be explained by a change in the nature of the transition to uniform matter called retrograde condensation. An important new finding is that coherent neutrino scattering from nuclei and pasta makes a modest contribution to the opacity under the conditions encountered in supernovas and neutron star mergers. This is because large nuclear clusters dissolve at most relevant temperatures, and at lower temperatures, when clusters are present, Coulomb correlations between them suppress coherent neutrino scattering off individual clusters. Lastly, implications for neutrino signals from galactic supernovas are briefly discussed.« less

Nuclear pasta in hot dense matter and its implications for neutrino scattering

DOE PAGES

Roggero, Alessandro; Margueron, Jerome; Roberts, Luke F.; ...

2018-04-16

The abundance of large clusters of nucleons in neutron-rich matter at subnuclear density is found to be greatly reduced by finite-temperature effects when matter is close to β equilibrium, compared to the case where the electron fraction is fixed at Y e > 0.1 , as often considered in the literature. Large nuclei and exotic nonspherical nuclear configurations called pasta, favored in the vicinity of the transition to uniform matter at T = 0 , dissolve at a relatively low temperature T u as protons leak out of nuclei and pasta. For matter at β-equilibrium with a negligible neutrino chemical potential we find that Tmore » $$β\\atop{u}$$ ≃ 4 ± 1 MeV for realistic equations of state. This is lower than the maximum temperature T$$β\\atop{max}$$ ≃ 9 ± 1 MeV at which nuclei can coexist with a gas of nucleons and can be explained by a change in the nature of the transition to uniform matter called retrograde condensation. An important new finding is that coherent neutrino scattering from nuclei and pasta makes a modest contribution to the opacity under the conditions encountered in supernovas and neutron star mergers. This is because large nuclear clusters dissolve at most relevant temperatures, and at lower temperatures, when clusters are present, Coulomb correlations between them suppress coherent neutrino scattering off individual clusters. Lastly, implications for neutrino signals from galactic supernovas are briefly discussed.« less

Density dependence of the nuclear energy-density functional

NASA Astrophysics Data System (ADS)

Papakonstantinou, Panagiota; Park, Tae-Sun; Lim, Yeunhwan; Hyun, Chang Ho

2018-01-01

Background: The explicit density dependence in the coupling coefficients entering the nonrelativistic nuclear energy-density functional (EDF) is understood to encode effects of three-nucleon forces and dynamical correlations. The necessity for the density-dependent coupling coefficients to assume the form of a preferably small fractional power of the density ρ is empirical and the power is often chosen arbitrarily. Consequently, precision-oriented parametrizations risk overfitting in the regime of saturation and extrapolations in dilute or dense matter may lose predictive power. Purpose: Beginning with the observation that the Fermi momentum kF, i.e., the cubic root of the density, is a key variable in the description of Fermi systems, we first wish to examine if a power hierarchy in a kF expansion can be inferred from the properties of homogeneous matter in a domain of densities, which is relevant for nuclear structure and neutron stars. For subsequent applications we want to determine a functional that is of good quality but not overtrained. Method: For the EDF, we fit systematically polynomial and other functions of ρ1 /3 to existing microscopic, variational calculations of the energy of symmetric and pure neutron matter (pseudodata) and analyze the behavior of the fits. We select a form and a set of parameters, which we found robust, and examine the parameters' naturalness and the quality of resulting extrapolations. Results: A statistical analysis confirms that low-order terms such as ρ1 /3 and ρ2 /3 are the most relevant ones in the nuclear EDF beyond lowest order. It also hints at a different power hierarchy for symmetric vs. pure neutron matter, supporting the need for more than one density-dependent term in nonrelativistic EDFs. The functional we propose easily accommodates known or adopted properties of nuclear matter near saturation. More importantly, upon extrapolation to dilute or asymmetric matter, it reproduces a range of existing microscopic results, to which it has not been fitted. It also predicts a neutron-star mass-radius relation consistent with observations. The coefficients display naturalness. Conclusions: Having been already determined for homogeneous matter, a functional of the present form can be mapped onto extended Skyrme-type functionals in a straightforward manner, as we outline here, for applications to finite nuclei. At the same time, the statistical analysis can be extended to higher orders and for different microscopic (ab initio) calculations with sufficient pseudodata points and for polarized matter.

The gammaPE complex contains both SATB1 and HOXB2 and has positive and negative roles in human gamma-globin gene regulation.

PubMed

Case, S S; Huber, P; Lloyd, J A

1999-11-01

A large nuclear protein complex, termed gammaPE (for gamma-globin promoter and enhancer binding factor), binds to five sites located 5' and 3' of the human y-globin gene. Two proteins, SATB1 (special A-T-rich binding protein 1) and HOXB2, can bind to yPE binding sites. SATB1 binds to nuclear matrix-attachment sites, and HOXB2 is a homeodomain protein important in neural development that is also expressed during erythropoiesis. The present work showed that antisera directed against either SATB1 or HOXB2 reacted specifically with the entire gammaPE complex in electrophoretic mobility shift assays (EMSAs), suggesting that the two proteins can bind to the gammaPE binding site simultaneously. When SATB1 or HOXB2 was expressed in vitro, they could bind independently to gammaPE binding sites in EMSA. Interestingly, the proteins expressed in vitro competed effectively with each other for the gammaPE binding site, suggesting that this may occur under certain conditions in vivo. Transient cotransfections of a HOXB2 cDNA and a y-globin-luciferase reporter gene construct into cells expressing SATB1 suggested that SATB1 has a positive and HOXB2 a negative regulatory effect on transcription. Taking into account their potentially opposing effects and binding activities, SATB1 and HOXB2 may modulate the amount of gamma-globin mRNA expressed during development and differentiation.

75 FR 5357 - In the Matter of Entergy Nuclear Operations, Inc., et al.; Order Extending the Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-02

...). Pilgrim is a boiling water nuclear reactor that is owned by Entergy Nuclear and operated by ENO. The... Generating Unit No. 1 (IP1). IP1 is a pressurized water nuclear reactor that is owned by ENIP2 and maintained... nuclear reactors that are owned by ENIP2 and ENIP3, respectively, and operated by ENO. The facilities are...

Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.

PubMed

Hong, Huixiao; Branham, William S; Ng, Hui Wen; Moland, Carrie L; Dial, Stacey L; Fang, Hong; Perkins, Roger; Sheehan, Daniel; Tong, Weida

2015-02-01

One endocrine disruption mechanism is through binding to nuclear receptors such as the androgen receptor (AR) and estrogen receptor (ER) in target cells. The concentration of a chemical in serum is important for its entry into the target cells to bind the receptors, which is regulated by the serum proteins. Human sex hormone-binding globulin (SHBG) is the major transport protein in serum that can bind androgens and estrogens and thus change a chemical's availability to enter the target cells. Sequestration of an androgen or estrogen in the serum can alter the chemical elicited AR- and ER-mediated responses. To better understand the chemical-induced endocrine activity, we developed a competitive binding assay using human pregnancy plasma and measured the binding to the human SHBG for 125 structurally diverse chemicals, most of which were known to bind AR and ER. Eighty seven chemicals were able to bind the human SHBG in the assay, whereas 38 chemicals were nonbinders. Binding data for human SHBG are compared with that for rat α-fetoprotein, ER and AR. Knowing the binding profiles between serum and nuclear receptors will improve assessment of a chemical's potential for endocrine disruption. The SHBG binding data reported here represent the largest data set of structurally diverse chemicals tested for human SHBG binding. Utilization of the SHBG binding data with AR and ER binding data could enable better evaluation of endocrine disrupting potential of chemicals through AR- and ER-mediated responses since sequestration in serum could be considered. Published by Oxford University Press on behalf of the Society of Toxicology 2014. This work is written by US Government employees and is in the public domain in the US.

Plasma, The Fourth State of Matter

ERIC Educational Resources Information Center

Zandy, Hassan F.

1970-01-01

Discusses plasma as a source of energy through nuclear fission processes, as well as the difficulties encountered in such a process. States that 99 percent of the matter in the universe is plasma, and only 1 percent is the common three states of matter. Describes the fundamental properties of plasma, plasma "pinch, and plasma oscillations. (RR)

Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer.

PubMed

Gessner, C; Woischwill, C; Schumacher, A; Liebers, U; Kuhn, H; Stiehl, P; Jürchott, K; Royer, H D; Witt, C; Wolff, G

2004-01-01

The human Y-box binding protein, YB-1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB-1 has been associated with chemoresistance and poor prognosis of tumour patients. Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB-1 and p53, in order to evaluate the prognostic role of nuclear expression of YB-1. Cytoplasmic YB-1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB-1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB-1. Patients with nuclear YB-1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB-1 and wildtype p53 (median survival 15 months). This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y-box binding protien seems to be an independent prognostic marker.

Symmetry Energy and Its Components in Finite Nuclei

NASA Astrophysics Data System (ADS)

Antonov, A. N.; Gaidarov, M. K.; Kadrev, D. N.; Sarriguren, P.; Moya de Guerra, E.

2018-05-01

We derive the volume and surface components of the nuclear symmetry energy (NSE) and their ratio within the coherent density fluctuation model. The estimations use the results of the model for the NSE in finite nuclei based on the Brueckner and Skyrme energy-density functionals for nuclear matter. The obtained values of the volume and surface contributions to the NSE and their ratio for the Ni, Sn, and Pb isotopic chains are compared with estimations of other approaches which have used available experimental data on binding energies, neutron-skin thicknesses, and excitation energies to isobaric analog states (IAS). Apart from the density dependence investigated in our previous works, we study also the temperature dependence of the symmetry energy in finite nuclei in the framework of the local density approximation combining it with the self-consistent Skyrme-HFB method using the cylindrical transformed deformed harmonic-oscillator basis. The results for the thermal evolution of the NSE in the interval T = 0–4 MeV show that its values decrease with temperature. The investigations of the T-dependence of the neutron and proton root-mean-square radii and the corresponding neutron skin thickness point out that the effect of temperature leads mainly to a substantial increase of the neutron radii and skins, especially in nuclei which are more rich of neutrons.

Equations of state for real gases on the nuclear scale

NASA Astrophysics Data System (ADS)

Vovchenko, Volodymyr

2017-07-01

The formalism to augment the classical models of the equation of state for real gases with quantum statistical effects is presented. It allows an arbitrary excluded volume procedure to model repulsive interactions, and an arbitrary density-dependent mean field to model attractive interactions. Variations on the excluded volume mechanism include van der Waals (VDW) and Carnahan-Starling models, while the mean fields are based on VDW, Redlich-Kwong-Soave, Peng-Robinson, and Clausius equations of state. The VDW parameters of the nucleon-nucleon interaction are fitted in each model to the properties of the ground state of nuclear matter, and the following range of values is obtained: a =330 -430 MeV fm3 and b =2.5 -4.4 fm3 . In the context of the excluded volume approach, the fits to the nuclear ground state disfavor the values of the effective hard-core radius of a nucleon significantly smaller than 0.5 fm , at least for the nuclear matter region of the phase diagram. Modifications to the standard VDW repulsion and attraction terms allow one to improve significantly the value of the nuclear incompressibility factor K0, bringing it closer to empirical estimates. The generalization to include the baryon-baryon interactions into the hadron resonance gas model is performed. The behavior of the baryon-related lattice QCD observables at zero chemical potential is shown to be strongly correlated to the nuclear matter properties: an improved description of the nuclear incompressibility also yields an improved description of the lattice data at μ =0 .

Copper speciation and binding by organic matter in copper-contaminated streamwater

USGS Publications Warehouse

Breault, R.F.; Colman, J.A.; Aiken, G.R.; McKnight, D.

1996-01-01

Fulvic acid binding sites (1.3-70 ??M) and EDTA (0.0017-0.18 ??M) accounted for organically bound Cu in seven stream samples measured by potentiometric titration. Cu was 84-99% organically bound in filtrates with 200 nM total Cu. Binding of Cu by EDTA was limited by competition from other trace metals. Water hardness was inversely related to properties of dissolved organic carbon (DOC) that enhance fulvic acid binding: DOC concentration, percentage of DOC that is fulvic acid, and binding sites per fulvic acid carbon. Dissolved trace metals, stabilized by organic binding, occurred at increased concentration in soft water as compared to hard water.

77 FR 6598 - In the Matter of Entergy Nuclear Operations, Inc., Palisades Nuclear Plant, 27780 Blue Star...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-08

... through Entergy Nuclear Management Manual EN-OP-115, Revision 9, ``Conduct of Operations.'' Specifically... underlying the apparent violation. These actions included: (a) Operations management conducted a briefing for... the timely notification of events; (b) Management conducted a comprehensive assessment during the week...

Radioactive cesium concentrations in coastal suspended matter after the Fukushima nuclear accident.

PubMed

Kubo, Atsushi; Tanabe, Kai; Suzuki, Genta; Ito, Yukari; Ishimaru, Takashi; Kasamatsu-Takasawa, Nobue; Tsumune, Daisuke; Mizuno, Takuji; Watanabe, Yutaka W; Arakawa, Hisayuki; Kanda, Jota

2018-06-01

Radioactive cesium concentrations in the suspended matter of the coastal waters around the Fukushima Daiichi Nuclear Power Plant (FDNPP) were investigated between January 2014 and August 2015. The concentrations of radioactive cesium in the suspended matter were two orders higher in magnitude than those determined in the sediment. In addition, we discovered highly radioactive Cs particles in the suspended matter using autoradiography. The geometrical average radioactivity of particles was estimated to be 0.6 Bq at maximum and 0.2 Bq on average. The contribution ratio of highly radioactive Cs particles to each sample ranged from 13 to 54%, and was 36% on average. A major part of the radioactive Cs concentration in the suspended matter around the FDNPP was strongly influenced by the highly radioactive particles. The subsequent resuspension of highly radioactive Cs particles has been suggested as a possible reason for the delay in radioactive Cs depuration from benthic biota. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nuclear actions of insulin-like growth factor binding protein-3.

PubMed

Baxter, Robert C

2015-09-10

In addition to its actions outside the cell, cellular uptake and nuclear import of insulin-like growth factor binding protein-3 (IGFBP-3) has been recognized for almost two decades, but knowledge of its nuclear actions has been slow to emerge. IGFBP-3 has a functional nuclear localization signal and interacts with the nuclear transport protein importin-β. Within the nucleus IGFBP-3 appears to have a role in transcriptional regulation. It can bind to the nuclear receptor, retinoid X receptor-α and several of its dimerization partners, including retinoic acid receptor, vitamin D receptor (VDR), and peroxisome proliferator-activated receptor-γ (PPARγ). These interactions modulate the functions of these receptors, for example inhibiting VDR-dependent transcription in osteoblasts and PPARγ-dependent transcription in adipocytes. Nuclear IGFBP-3 can be detected by immunohistochemistry in cancer and other tissues, and its presence in the nucleus has been shown in many cell culture studies to be necessary for its pro-apoptotic effect, which may also involve interaction with the nuclear receptor Nur77, and export from the nucleus. IGFBP-3 is p53-inducible and in response to DNA damage, forms a complex with the epidermal growth factor receptor (EGFR), translocating to the nucleus to interact with DNA-dependent protein kinase. Inhibition of EGFR kinase activity or downregulation of IGFBP-3 can inhibit DNA double strand-break repair by nonhomologous end joining. IGFBP-3 thus has the ability to influence many cell functions through its interactions with intranuclear pathways, but the importance of these interactions in vivo, and their potential to be targeted for therapeutic benefit, require further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

Improved Dual-Luciferase Reporter Assays for Nuclear Receptors

PubMed Central

Paguio, Aileen; Stecha, Pete; Wood, Keith V; Fan, Frank

2010-01-01

Nuclear receptors play important roles in many cellular functions through control of gene transcription. It is also a large target class for drug discovery. Luciferase reporter assays are frequently used to study nuclear receptor function because of their wide dynamic range, low endogenous activity, and ease of use. Recent improvements of luciferase genes and vectors have further enhanced their utilities. Here we applied these improvements to two reporter formats for studying nuclear receptors. The first assay contains a Murine Mammary Tumor Virus promoter upstream of a destabilized luciferase. The presence of response elements for nuclear hormone receptor in this promoter allows the studies of endogenous and/or exogenous full length receptors. The second assay contains a ligand binding domain (LBD) of a nuclear receptor fused to the GAL4 DNA binding domain (DBD) on one vector and multiple Gal4 Upstream Activator Sequences (UAS) upstream of luciferase reporter on another vector. We showed that codon optimization of luciferase reporter genes increased expression levels in conjunction with the incorporation of protein destabilizing sequences into luciferase led to a larger assay dynamic range in both formats. The optimum number of UAS to generate the best response was determined. The expression vector for nuclear receptor LBD/GAL4 DBD fusion also constitutively expresses a Renilla luciferase-neoR fusion protein, which provides selection capability (G418 resistance, neoR) as well as an internal control (Renilla luciferase). This dual-luciferase format allowed detecting compound cytotoxicity or off-target change in expression during drug screening, therefore improved data quality. These luciferase reporter assays provided better research and drug discovery tools for studying the functions of full length nuclear receptors and ligand binding domains. PMID:21687560

Exclusive nuclear location of estrogen receptors in Squalus testis.

PubMed Central

Callard, G V; Mak, P

1985-01-01

An estrogen (E)-binding molecule having both occupied and unoccupied sites is restricted to nuclear subfractions in the testis of the spiny dogfish (Squalus acanthias). We investigated the hypothesis that a species characterized by high body-fluid osmolarity (1010 mosM) has an estrogen receptor (ER) that binds to chromatin with high affinity and consequently resists redistribution during tissue processing. Although the steroid binding and sedimentation properties of the Squalus nuclear ER conformed to those of classical ER, its elution maximum from DNA-cellulose was unusually high (0.55 M NaCl). A tendency to adhere tightly to cell nuclei was reflected in the high salt concentration (0.43 M KCl) required to extract 50% of the receptors from the nuclear compartment during homogenization and in the stability of the nuclear ER population in the presence of high concentrations of a nonionic solute (urea) or increased buffer volume. Mixing and redistribution experiments showed that nuclear ER could be quantitatively and qualitatively measured in cytosolic extracts, ruling out the possibility that soluble receptors were being masked. Although Squalus oviduct ER was similar to that of testis, ER in the testis and liver of a related elasmobranch (Potamotrygon) that maintains osmotic equilibrium at 300 mosM more closely resembled mammalian ER in its elution maximum from DNA-cellulose (0.22 M NaCl) and cytosolic/nuclear ratios in low-salt buffers. We conclude that Squalus testis has a single ER pool located exclusively in the nuclear compartment. These observations support a revised concept of steroid action and further indicate that the chromatin affinity of the hormone-ER complex is an important factor in determining subfractional distribution during tissue processing. PMID:3856265

Neutrino Opacity in High Density Nuclear Matter

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

Santos, Sergio M. dos; Razeira, Moises; Vasconcellos, Cesar A.Z.

2004-12-02

We estimate the contribution of the nucleon weak magnetism on the neutrino absorption mean free path inside high density nuclear matter. In the mean field approach, three different ingredients are taken into account: (a) a relativistic generalization of the approach developed by Sanjay et al.; (b) the inclusion of the nucleon weak-magnetism (c) and the pseudo-scalar interaction involving the nucleons. Our main result shows that the neutrino absorption mean free path is three times the corresponding result obtained by those authors.

Colloquium: Toward living matter with colloidal particles

NASA Astrophysics Data System (ADS)

Zeravcic, Zorana; Manoharan, Vinothan N.; Brenner, Michael P.

2017-07-01

A fundamental unsolved problem is to understand the differences between inanimate matter and living matter. Although this question might be framed as philosophical, there are many fundamental and practical reasons to pursue the development of synthetic materials with the properties of living ones. There are three fundamental properties of living materials that we seek to reproduce: The ability to spontaneously assemble complex structures, the ability to self-replicate, and the ability to perform complex and coordinated reactions that enable transformations impossible to realize if a single structure acted alone. The conditions that are required for a synthetic material to have these properties are currently unknown. This Colloquium examines whether these phenomena could emerge by programming interactions between colloidal particles, an approach that bootstraps off of recent advances in DNA nanotechnology and in the mathematics of sphere packings. The argument is made that the essential properties of living matter could emerge from colloidal interactions that are specific—so that each particle can be programmed to bind or not bind to any other particle—and also time dependent—so that the binding strength between two particles could increase or decrease in time at a controlled rate. There is a small regime of interaction parameters that gives rise to colloidal particles with lifelike properties, including self-assembly, self-replication, and metabolism. The parameter range for these phenomena can be identified using a combinatorial search over the set of known sphere packings.

The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone.

PubMed

Tambyrajah, Winston S; Doran, Elena; Wood, Jeffrey D; McGivan, John D

2004-11-15

Functional analysis of the pig cytochrome P4502E1 (CYP2E1) promoter identified two major activating elements. One corresponded to the hepatic nuclear factor 1 (HNF-1) consensus binding sequence at nucleotides -128/-98 and the other was located in the region -292/-266. The binding of proteins in pig liver nuclear extracts to a synthetic double-stranded oligonucleotide corresponding to this more distal activating sequence was studied by electrophoretic mobility shift assay. The minimum protein binding sequence was identified as TGTTCTGACCTCTGGG. Gel super-shift assays identified the protein binding to this site as chick ovalbumin upstream promoter transcription factor 1 (COUP-TF1). Androstenone inhibited promoter activity in transfection experiments only with constructs which included the COUP-TF1 binding site. Androstenone inhibited COUP-TF1 binding to synthetic oligonucleotides but did not affect HNF-1 binding. The results offer an explanation for the inhibition of CYP2E1 protein expression by androstenone in isolated pig hepatocytes and may be relevant to the low expression of hepatic CYP2E1 in those pigs which accumulate high levels of androstenone in vivo.

Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.

PubMed

Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

2017-07-01

An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. Copyright © 2017 Elsevier Inc. All rights reserved.

PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3.

PubMed

Jeanne, Marion; Lallemand-Breitenbach, Valérie; Ferhi, Omar; Koken, Marcel; Le Bras, Morgane; Duffort, Stéphanie; Peres, Laurent; Berthier, Caroline; Soilihi, Hassane; Raught, Brian; de Thé, Hugues

2010-07-13

As(2)O(3) cures acute promyelocytic leukemia (APL) by initiating PML/RARA oncoprotein degradation, through sumoylation of its PML moiety. However, how As(2)O(3) initiates PML sumoylation has remained largely unexplained. As(2)O(3) binds vicinal cysteines and increases reactive oxygen species (ROS) production. We demonstrate that upon As(2)O(3) exposure, PML undergoes ROS-initiated intermolecular disulfide formation and binds arsenic directly. Disulfide-linked PML or PML/RARA multimers form nuclear matrix-associated nuclear bodies (NBs), become sumoylated and are degraded. Hematopoietic progenitors transformed by an As(2)O(3)-binding PML/RARA mutant exhibit defective As(2)O(3) response. Conversely, nonarsenical oxidants elicit PML/RARA multimerization, NB-association, degradation, and leukemia response in vivo, but do not affect PLZF/RARA-driven APLs. Thus, PML oxidation regulates NB-biogenesis, while oxidation-enforced PML/RARA multimerization and direct arsenic-binding cooperate to enforce APL's exquisite As(2)O(3) sensitivity. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Characterization of neurons in the cortical white matter in human temporal lobe epilepsy.

PubMed

Richter, Zsófia; Janszky, József; Sétáló, György; Horváth, Réka; Horváth, Zsolt; Dóczi, Tamás; Seress, László; Ábrahám, Hajnalka

2016-10-01

The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. Neurons were identified with immunohistochemistry using antibodies against NeuN, calcium-binding proteins, transcription factor Tbr1 and neurofilaments. We found significantly higher density of neurons in the archi- and neocortical white matter of patients with temporal lobe epilepsy than in that of controls. Based on their morphology and neurochemical content, both excitatory and inhibitory cells were present among these neurons. A subset of neurons in the white matter was Tbr-1-immunoreactive and these neurons coexpressed NeuN and neurofilament marker SMI311R. No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Unifying Theory of Low-Energy Nuclear Reaction and Transmutation Processes in Deuterated/hydrogenated Metals, Acoustic Cavitation, Glow Discharge, and Deuteron Beam Experiments

NASA Astrophysics Data System (ADS)

Kim, Yeong E.; Zubarev, Alexander L.

The most basic theoretical challenge for understanding low-energy nuclear reaction (LENR) and transmutation reaction (LETR) in condensed matters is to find mechanisms by which the large Coulomb barrier between fusing nuclei can be overcome. A unifying theory of LENR and LETR has been developed to provide possible mechanisms for the LENR and LETR processes in matters based on high-density nano-scale and micro-scale quantum plasmas. It is shown that recently developed theoretical models based on Bose-Einstein Fusion (BEF) mechanism and Quantum Plasma Nuclear Fusion (QPNF) mechanism are applicable to the results of many different types of LENR and LETR experiments.

Effects of charge symmetry on heavy ion reaction mechanisms

NASA Astrophysics Data System (ADS)

Colonna, M.; di Toro, M.; Fabbri, G.; Maccarone, S.

1998-03-01

We suggest several possibilities to study the properties of the symmetry term in the nuclear equation of state from radioactive beam experiments. Collision simulations with a stochastic transport approach, where asymmetry effects are suitably introduced, are presented. The dynamical response of an interacting highly asymmetric nuclear matter can be studied, taking advantage of the neutron skin structure. The main reaction mechanisms, from fusion to deep inelastic and fragmentation, appear quite sensitive to the form of the symmetry term of the effective force used, opening some new appealing experimental perspectives. Finally new features of fragment production are presented, due to the onset of chemical plus mechanical instabilities in dilute asymmetric nuclear matter.

Studying Cold Nuclear Matter with the MPC-EX of PHENIX

NASA Astrophysics Data System (ADS)

Grau, Nathan; Phenix Collaboration

2017-09-01

Highly asymmetric collision systems, such as d+Au, provide a unique environment to study cold nuclear matter. Potential measurements range from pinning down the modification of the nuclear wave function, i.e. saturation, to studying final state interactions, i.e. energy loss. The PHENIX experiment has enhanced the muon piston calorimeter (MPC) with a silicon-tungsten preshower, the MPC-EX. With its fine segmentation the MPC-EX extends the photon detection capability at 3 < | η | < 3.8. In this talk we review the current status of the detector, its calibration, and its identification capabilities using the 2016 d+Au dataset. We also discuss the specific physics observables the MPC-EX can measure.

Structural basis for corepressor assembly by the orphan nuclear receptor TLX

PubMed Central

Zhou, X. Edward; He, Yuanzheng; Searose-Xu, Kelvin; Zhang, Chun-Li; Tsai, Chih-Cheng; Melcher, Karsten

2015-01-01

The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX–Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression. PMID:25691470

Loss of ISWI Function in Drosophila Nuclear Bodies Drives Cytoplasmic Redistribution of Drosophila TDP-43

PubMed Central

Bonaccorso, Rosa; Li Greci, Lorenzo; Romano, Giulia; Sollazzo, Martina; Ingrassia, Antonia Maria Rita; Feiguin, Fabian; Corona, Davide F. V.; Onorati, Maria Cristina

2018-01-01

Over the past decade, evidence has identified a link between protein aggregation, RNA biology, and a subset of degenerative diseases. An important feature of these disorders is the cytoplasmic or nuclear aggregation of RNA-binding proteins (RBPs). Redistribution of RBPs, such as the human TAR DNA-binding 43 protein (TDP-43) from the nucleus to cytoplasmic inclusions is a pathological feature of several diseases. Indeed, sporadic and familial forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration share as hallmarks ubiquitin-positive inclusions. Recently, the wide spectrum of neurodegenerative diseases characterized by RBPs functions’ alteration and loss was collectively named proteinopathies. Here, we show that TBPH (TAR DNA-binding protein-43 homolog), the Drosophila ortholog of human TDP-43 TAR DNA-binding protein-43, interacts with the arcRNA hsrω and with hsrω-associated hnRNPs. Additionally, we found that the loss of the omega speckles remodeler ISWI (Imitation SWI) changes the TBPH sub-cellular localization to drive a TBPH cytoplasmic accumulation. Our results, hence, identify TBPH as a new component of omega speckles and highlight a role of chromatin remodelers in hnRNPs nuclear compartmentalization. PMID:29617352

Structural basis for corepressor assembly by the orphan nuclear receptor TLX

DOE PAGES

Zhi, Xiaoyong; Zhou, X. Edward; He, Yuanzheng; ...

2015-02-15

The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conservedmore » ALXXLXXY motif of the Atro box. Mutations that weaken the TLX–Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression.« less

Chitosan Nanoparticles for Nuclear Targeting: The Effect of Nanoparticle Size and Nuclear Localization Sequence Density.

PubMed

Tammam, Salma N; Azzazy, Hassan M E; Breitinger, Hans G; Lamprecht, Alf

2015-12-07

Many recently discovered therapeutic proteins exert their main function in the nucleus, thus requiring both efficient uptake and correct intracellular targeting. Chitosan nanoparticles (NPs) have attracted interest as protein delivery vehicles due to their biocompatibility and ability to escape the endosomes offering high potential for nuclear delivery. Molecular entry into the nucleus occurs through the nuclear pore complexes, the efficiency of which is dependent on NP size and the presence of nuclear localization sequence (NLS). Chitosan nanoparticles of different sizes (S-NPs ≈ 25 nm; L-NP ≈ 150 nm) were formulated, and they were modified with different densities of the octapeptide NLS CPKKKRKV (S-NPs, 0.25, 0.5, 2.0 NLS/nm(2); L-NPs, 0.6, 0.9, 2 NLS/nm(2)). Unmodified and NLS-tagged NPs were evaluated for their protein loading capacity, extent of cell association, cell uptake, cell surface binding, and finally nuclear delivery efficiency in L929 fibroblasts. To avoid errors generated with cell fractionation and nuclear isolation protocols, nuclear delivery was assessed in intact cells utilizing Förster resonance energy transfer (FRET) fluorometry and microscopy. Although L-NPs showed ≈10-fold increase in protein loading per NP when compared to S-NPs, due to higher cell association and uptake S-NPs showed superior protein delivery. NLS exerts a size and density dependent effect on nanoparticle uptake and surface binding, with a general reduction in NP cell surface binding and an increase in cell uptake with the increase in NLS density (up to 8.4-fold increase in uptake of High-NLS-L-NPs (2 NLS/nm(2)) compared to unmodified L-NPs). However, for nuclear delivery, unmodified S-NPs show higher nuclear localization rates when compared to NLS modified NPs (up to 5-fold by FRET microscopy). For L-NPs an intermediate NLS density (0.9 NLS/nm(2)) seems to provide highest nuclear localization (3.7-fold increase in nuclear delivery compared to High-NLS-L-NPs). Results indicate that a higher NLS density does not result in maximum protein nuclear localization and that a universal optimal density for NPs of different sizes does not exist.

Particle Physics Primer: Explaining the Standard Model of Matter.

ERIC Educational Resources Information Center

Vondracek, Mark

2002-01-01

Describes the Standard Model, a basic model of the universe that describes electromagnetic force, weak nuclear force radioactivity, and the strong nuclear force responsible for holding particles within the nucleus together. (YDS)

The Production and Study of Antiprotons and Cold Antihydrogen

DTIC Science & Technology

2010-11-10

techniques required to produce and store atoms made entirely of anti- matter . Anti- matter provides high-density energy storage that far outstrips even nuclear...materials. Potential applications for anti- matter include rocketry and explosives. In the last grant period, a new positron accumulator was developed...encounter with ordinary matter will cause them to turn all their mass into energy as they annihilate. The scientific goal, which gives this program a

Quartetting in Nuclear Matter and α Particle Condensation in Nuclear Systems

NASA Astrophysics Data System (ADS)

Röpke, G.; Schuck, P.; Horiuchi, H.; Tohsaki, A.; Funaki, Y.; Yamada, T.

2008-02-01

Alternatively to pairing, four-particle correlations may become of importance for the formation of quantum condensates in nuclear matter. With increasing density, four-particle correlations are suppressed because of Pauli blocking. Signatures of α-like clusters are expected to occur in low-density nuclear systems. The famous Hoyle state (02+ at 7.654 MeV in 12C) is identified as being an almost ideal condensate of three α-particles, hold together only by the Coulomb barrier. It, therefore, has a 8Be-α structure of low density. Transition probability and inelastic form factor together with position and other physical quantities are correctly reproduced without any adjustable parameter from our two parameter wave function of α-particle condensate type. The possibility of the existence of α-particle condensed states in heavier nα nuclei is also discussed.

Specific nuclear localizing sequence directs two myosin isoforms to the cell nucleus in calmodulin-sensitive manner.

PubMed

Dzijak, Rastislav; Yildirim, Sukriye; Kahle, Michal; Novák, Petr; Hnilicová, Jarmila; Venit, Tomáš; Hozák, Pavel

2012-01-01

Nuclear myosin I (NM1) was the first molecular motor identified in the cell nucleus. Together with nuclear actin, they participate in crucial nuclear events such as transcription, chromatin movements, and chromatin remodeling. NM1 is an isoform of myosin 1c (Myo1c) that was identified earlier and is known to act in the cytoplasm. NM1 differs from the "cytoplasmic" myosin 1c only by additional 16 amino acids at the N-terminus of the molecule. This amino acid stretch was therefore suggested to direct NM1 into the nucleus. We investigated the mechanism of nuclear import of NM1 in detail. Using over-expressed GFP chimeras encoding for truncated NM1 mutants, we identified a specific sequence that is necessary for its import to the nucleus. This novel nuclear localization sequence is placed within calmodulin-binding motif of NM1, thus it is present also in the Myo1c. We confirmed the presence of both isoforms in the nucleus by transfection of tagged NM1 and Myo1c constructs into cultured cells, and also by showing the presence of the endogenous Myo1c in purified nuclei of cells derived from knock-out mice lacking NM1. Using pull-down and co-immunoprecipitation assays we identified importin beta, importin 5 and importin 7 as nuclear transport receptors that bind NM1. Since the NLS sequence of NM1 lies within the region that also binds calmodulin we tested the influence of calmodulin on the localization of NM1. The presence of elevated levels of calmodulin interfered with nuclear localization of tagged NM1. We have shown that the novel specific NLS brings to the cell nucleus not only the "nuclear" isoform of myosin I (NM1 protein) but also its "cytoplasmic" isoform (Myo1c protein). This opens a new field for exploring functions of this molecular motor in nuclear processes, and for exploring the signals between cytoplasm and the nucleus.

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

Meissner, Torsten B.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215; Li, Amy

Highlights: Black-Right-Pointing-Pointer NLRC5 requires an intact NLS for its function as MHC class I transactivator. Black-Right-Pointing-Pointer Nuclear presence of NLRC5 is required for MHC class I induction. Black-Right-Pointing-Pointer Nucleotide-binding controls nuclear import and transactivation activity of NLRC5. -- Abstract: Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. A member of the NLR (nucleotide-binding domain, leucine-rich repeat) protein family, NLRC5, has recently been identified as a transcriptional regulator of MHC class I and related genes. While a 'master regulator' of MHC class II genes, CIITA, has long been known,more » NLRC5 specifically associates with and transactivates the proximal promoters of MHC class I genes. In this study, we analyzed the molecular requirements of NLRC5 nuclear import and transactivation activity. We show that NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. In addition, we find that the nucleotide-binding domain (NBD) of NLRC5 is critical not only for nuclear translocation but also for the transactivation of MHC class I genes. Changing the cellular localization of NLRC5 is likely to immediately impact MHC class I expression as well as MHC class I-mediated antigen presentation. NLRC5 may thus provide a promising target for the modulation of MHC class I antigen presentation, especially in the setting of transplant medicine.« less

Close but Distinct Regions of Human Herpesvirus 8 Latency-Associated Nuclear Antigen 1 Are Responsible for Nuclear Targeting and Binding to Human Mitotic Chromosomes

PubMed Central

Piolot, Tristan; Tramier, Marc; Coppey, Maité; Nicolas, Jean-Claude; Marechal, Vincent

2001-01-01

Human herpesvirus 8 is associated with all forms of Kaposi's sarcoma, AIDS-associated body cavity-based lymphomas, and some forms of multicentric Castleman's disease. Herpesvirus 8, like other gammaherpesviruses, can establish a latent infection in which viral genomes are stably maintained as multiple episomes. The latent nuclear antigen (LANA or LNAI) may play an essential role in the stable maintenance of latent episomes, notably by interacting concomitantly with the viral genomes and the metaphase chromosomes, thus ensuring an efficient transmission of the neoduplicated episomes to the daughter cells. To identify the regions responsible for its nuclear and subnuclear localization in interphase and mitotic cells, LNAI and various truncated forms were fused to a variant of green fluorescent protein. This enabled their localization and chromosome binding activity to be studied by low-light-level fluorescence microscopy in living HeLa cells. The results demonstrate that nuclear localization of LNAI is due to a unique signal, which maps between amino acids 24 and 30. Interestingly, this nuclear localization signal closely resembles those identified in EBNA1 from Epstein-Barr virus and herpesvirus papio. A region encompassing amino acids 5 to 22 was further proved to mediate the specific interaction of LNA1 with chromatin during interphase and the chromosomes during mitosis. The presence of putative phosphorylation sites in the chromosome binding sites of LNA1 and EBNA1 suggests that their activity may be regulated by specific cellular kinases. PMID:11264383

Berberine binds RXRα to suppress β-catenin signaling in colon cancer cells.

PubMed

Ruan, H; Zhan, Y Y; Hou, J; Xu, B; Chen, B; Tian, Y; Wu, D; Zhao, Y; Zhang, Y; Chen, X; Mi, P; Zhang, L; Zhang, S; Wang, X; Cao, H; Zhang, W; Wang, H; Li, H; Su, Y; Zhang, X K; Hu, T

2017-12-14

Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating β-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits β-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα. Berberine binding promotes RXRα interaction with nuclear β-catenin, leading to c-Cbl mediated degradation of β-catenin, and consequently inhibits the proliferation of colon cancer cells. Furthermore, berberine suppresses the growth of human colon carcinoma xenograft in nude mice in an RXRα-dependent manner. Together, our study not only identifies RXRα as a direct protein target for berberine but also dissects their binding mode and validates that berberine indeed suppresses β-catenin signaling and cell growth in colon cancer via binding RXRα, which provide new strategies for the design of new RXRα-based antitumor agents and drug combinations.

Berberine binds RXRα to suppress β-catenin signaling in colon cancer cells

PubMed Central

Ruan, H; Zhan, Y Y; Hou, J; Xu, B; Chen, B; Tian, Y; Wu, D; Zhao, Y; Zhang, Y; Chen, X; Mi, P; Zhang, L; Zhang, S; Wang, X; Cao, H; Zhang, W; Wang, H; Li, H; Su, Y; Zhang, X K; Hu, T

2017-01-01

Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating β-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits β-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα. Berberine binding promotes RXRα interaction with nuclear β-catenin, leading to c-Cbl mediated degradation of β-catenin, and consequently inhibits the proliferation of colon cancer cells. Furthermore, berberine suppresses the growth of human colon carcinoma xenograft in nude mice in an RXRα-dependent manner. Together, our study not only identifies RXRα as a direct protein target for berberine but also dissects their binding mode and validates that berberine indeed suppresses β-catenin signaling and cell growth in colon cancer via binding RXRα, which provide new strategies for the design of new RXRα-based antitumor agents and drug combinations. PMID:28846104

Chromatin as active matter

NASA Astrophysics Data System (ADS)

Agrawal, Ankit; Ganai, Nirmalendu; Sengupta, Surajit; Menon, Gautam I.

2017-01-01

Active matter models describe a number of biophysical phenomena at the cell and tissue scale. Such models explore the macroscopic consequences of driving specific soft condensed matter systems of biological relevance out of equilibrium through ‘active’ processes. Here, we describe how active matter models can be used to study the large-scale properties of chromosomes contained within the nuclei of human cells in interphase. We show that polymer models for chromosomes that incorporate inhomogeneous activity reproduce many general, yet little understood, features of large-scale nuclear architecture. These include: (i) the spatial separation of gene-rich, low-density euchromatin, predominantly found towards the centre of the nucleus, vis a vis. gene-poor, denser heterochromatin, typically enriched in proximity to the nuclear periphery, (ii) the differential positioning of individual gene-rich and gene-poor chromosomes, (iii) the formation of chromosome territories, as well as (iv), the weak size-dependence of the positions of individual chromosome centres-of-mass relative to the nuclear centre that is seen in some cell types. Such structuring is induced purely by the combination of activity and confinement and is absent in thermal equilibrium. We systematically explore active matter models for chromosomes, discussing how our model can be generalized to study variations in chromosome positioning across different cell types. The approach and model we outline here represent a preliminary attempt towards a quantitative, first-principles description of the large-scale architecture of the cell nucleus.

The Molecular Chaperone TRiC/CCT Binds to the Trp-Asp 40 (WD40) Repeat Protein WDR68 and Promotes Its Folding, Protein Kinase DYRK1A Binding, and Nuclear Accumulation*

PubMed Central

Miyata, Yoshihiko; Shibata, Takeshi; Aoshima, Masato; Tsubata, Takuichi; Nishida, Eisuke

2014-01-01

Trp-Asp (WD) repeat protein 68 (WDR68) is an evolutionarily conserved WD40 repeat protein that binds to several proteins, including dual specificity tyrosine phosphorylation-regulated protein kinase (DYRK1A), MAPK/ERK kinase kinase 1 (MEKK1), and Cullin4-damage-specific DNA-binding protein 1 (CUL4-DDB1). WDR68 affects multiple and diverse physiological functions, such as controlling anthocyanin synthesis in plants, tissue growth in insects, and craniofacial development in vertebrates. However, the biochemical basis and the regulatory mechanism of WDR68 activity remain largely unknown. To better understand the cellular function of WDR68, here we have isolated and identified cellular WDR68 binding partners using a phosphoproteomic approach. More than 200 cellular proteins with wide varieties of biochemical functions were identified as WDR68-binding protein candidates. Eight T-complex protein 1 (TCP1) subunits comprising the molecular chaperone TCP1 ring complex/chaperonin-containing TCP1 (TRiC/CCT) were identified as major WDR68-binding proteins, and phosphorylation sites in both WDR68 and TRiC/CCT were identified. Co-immunoprecipitation experiments confirmed the binding between TRiC/CCT and WDR68. Computer-aided structural analysis suggested that WDR68 forms a seven-bladed β-propeller ring. Experiments with a series of deletion mutants in combination with the structural modeling showed that three of the seven β-propeller blades of WDR68 are essential and sufficient for TRiC/CCT binding. Knockdown of cellular TRiC/CCT by siRNA caused an abnormal WDR68 structure and led to reduction of its DYRK1A-binding activity. Concomitantly, nuclear accumulation of WDR68 was suppressed by the knockdown of TRiC/CCT, and WDR68 formed cellular aggregates when overexpressed in the TRiC/CCT-deficient cells. Altogether, our results demonstrate that the molecular chaperone TRiC/CCT is essential for correct protein folding, DYRK1A binding, and nuclear accumulation of WDR68. PMID:25342745

Paxillin associates with poly(A)-binding protein 1 at the dense endoplasmic reticulum and the leading edge of migrating cells.

PubMed

Woods, Alison J; Roberts, Marnie S; Choudhary, Jyoti; Barry, Simon T; Mazaki, Yuichi; Sabe, Hisataka; Morley, Simon J; Critchley, David R; Norman, Jim C

2002-02-22

Using mass spectrometry we have identified proteins which co-immunoprecipitate with paxillin, an adaptor protein implicated in the integrin-mediated signaling pathways of cell motility. A major component of paxillin immunoprecipitates was poly(A)-binding protein 1, a 70-kDa mRNA-binding protein. Poly(A)-binding protein 1 associated with both the alpha and beta isoforms of paxillin, and this was unaffected by RNase treatment consistent with a protein-protein interaction. The NH(2)-terminal region of paxillin (residues 54-313) associated directly with poly(A)-binding protein 1 in cell lysates, and with His-poly(A)-binding protein 1 immobilized in microtiter wells. Binding was specific, saturable and of high affinity (K(d) of approximately 10 nm). Cell fractionation studies showed that at steady state, the bulk of paxillin and poly(A)-binding protein 1 was present in the "dense" polyribosome-associated endoplasmic reticulum. However, inhibition of nuclear export with leptomycin B caused paxillin and poly(A)-binding protein 1 to accumulate in the nucleus, indicating that they shuttle between the nuclear and cytoplasmic compartments. When cells migrate, poly(A)-binding protein 1 colocalized with paxillin-beta at the tips of lamellipodia. Our results suggest a new mechanism whereby a paxillin x poly(A)-binding protein 1 complex facilitates transport of mRNA from the nucleus to sites of protein synthesis at the endoplasmic reticulum and the leading lamella during cell migration.

The brain-specific double-stranded RNA-binding protein Staufen2: nucleolar accumulation and isoform-specific exportin-5-dependent export.

PubMed

Macchi, Paolo; Brownawell, Amy M; Grunewald, Barbara; DesGroseillers, Luc; Macara, Ian G; Kiebler, Michael A

2004-07-23

The mammalian double-stranded RNA-binding proteins Staufen (Stau1 and Stau2) are involved in RNA localization in polarized neurons. In contrast to the more ubiquitously expressed Stau1, Stau2 is mainly expressed in the nervous system. In Drosophila, the third double-stranded RNA-binding domain (RBD3) of Staufen is essential for RNA interaction. When conserved amino acids within the RBD3 of Stau2 were mutated to render Stau2 defective for RNA binding, the mutant Stau2 proteins accumulate predominantly in the nucleolus. This is in contrast to wild type Stau2 that mostly localizes in the cytosol. The nuclear import is dependent on a nuclear localization signal in close proximity to the RBD3. The nuclear export of Stau2 is not dependent on CRM1 but rather on Exportin-5. We show that Exportin-5 interacts with the RBD3 of wild type Stau2 in an RNA-dependent manner in vitro but not with mutant Stau2. When Exportin-5 is down-regulated by RNA interference, only the largest isoform of Stau2 (Stau2(62)) preferentially accumulates in the nucleolus. It is tempting to speculate that Stau2(62) binds RNA in the nucleus and assembles into ribonucleoparticles, which are then exported via the Exportin-5 pathway to their final destination.

Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase.

PubMed

Kulkarni, Shilpa; Das, Sudipto; Funk, Colin D; Murray, Diana; Cho, Wonhwa

2002-04-12

The activation of 5-lipoxygenase (5-LO) involves its calcium-dependent translocation to the nuclear envelope, where it catalyzes the two-step transformation of arachidonic acid into leukotriene A(4), leading to the synthesis of various leukotrienes. To understand the mechanism by which 5-LO is specifically targeted to the nuclear envelope, we studied the membrane binding properties of the amino-terminal domain of 5-LO, which has been proposed to have a C2 domain-like structure. The model building, electrostatic potential calculation, and in vitro membrane binding studies of the isolated C2-like domain of 5-LO and selected mutants show that this Ca(2+)-dependent domain selectively binds zwitterionic phosphatidylcholine, which is conferred by tryptophan residues (Trp(13), Trp(75), and Trp(102)) located in the putative Ca(2+)-binding loops. The spatiotemporal dynamics of the enhanced green fluorescence protein-tagged C2-like domain of 5-LO and mutants in living cells also show that the phosphatidylcholine selectivity of the C2-like domain accounts for the specific targeting of 5-LO to the nuclear envelope. Together, these results show that the C2-like domain of 5-LO is a genuine Ca(2+)-dependent membrane-targeting domain and that the subcellular localization of the domain is governed in large part by its membrane binding properties.

Role of adipocyte lipid-binding protein (ALBP) and acyl-coA binding protein (ACBP) in PPAR-mediated transactivation.

PubMed

Helledie, Torben; Jørgensen, Claus; Antonius, Marianne; Krogsdam, Ann M; Kratchmarova, Irina; Kristiansen, Karsten; Mandrup, Susanne

2002-10-01

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are activated by a number of fatty acids and fatty acid derivatives. By contrast, we have recently shown that acyl-CoA esters display PPAR antagonistic properties in vitro. We have also shown that the adipocyte lipid binding protein (ALBP), the keratinocyte lipid binding protein (KLBP) and the acyl-CoA binding protein (ACBP) exhibit a prominent nuclear localization in differentiating 3T3-L1 adipocytes. Similarly, ectopic expression of these proteins in CV-1 cells resulted in a primarily nuclear localization. We therefore speculated that FABPs and ACBP might regulate the availability of PPAR agonists and antagonists by affecting not only their esterification in the cytoplasm but also their transport to and availability in the nucleus. We show here that coexpression of ALBP or ACBP exerts a negative effect on ligand-dependent PPAR transactivation, when tetradecylthioacetic (TTA) is used as ligand but not when the thiazolidinedione BRL49653 is used as ligand. The results presented here do not support the hypothesis that ALBP facilitates the transport of the fatty acid-type ligands to the nucleus, rather ALBP appears to sequester or increase the turn-over of the agonist. Similarly, our results are in keeping with a model in which ACBP increase the metabolism of these ligands.

Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP)

PubMed Central

Sato, Shogo; Jung, Hunmin; Nakagawa, Tsutomu; Pawlosky, Robert; Takeshima, Tomomi; Lee, Wan-Ru; Sakiyama, Haruhiko; Laxman, Sunil; Wynn, R. Max; Tu, Benjamin P.; MacMillan, John B.; De Brabander, Jef K.; Veech, Richard L.; Uyeda, Kosaku

2016-01-01

The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis. PMID:26984404

Electromagnetic Nature of Nuclear Energy

NASA Astrophysics Data System (ADS)

Schaeffer, Bernard

2014-09-01

As it is known since two millenaries, there is an attraction between an electric charge and a neutral object. Coulomb found the fundamental laws of electricity two centuries ago. After one century of nuclear physics, the fundamental laws of the strong force are still ignored. It has been found that electric and magnetic Coulomb's laws alone, without any hypothetical centrifugal force, are able to predict the binding energy of the simplest bound nucleus, the deuteron 2 H with a precision of 4 % . The nuclear potential is given by the formula: Uem2 H / A =e2/4 πɛ0 (1/rnp + a - 1/rnp - a ) + μ0 |μnμp |/4 π rnp3. This potential shows a horizontal inflection point where the electric and magnetic forces are equilibrated, coinciding with the experimental deuteron binding energy. Similar results have been obtained for the α particle 4 He where the electric attractive potential is four times larger than that of 2 H while the magnetic repulsion is only 1 . 5 times larger and the 4 HE binding energy six times larger than that of the deuteron. These results, prove the electromagnetic nature of the nuclear energy without the usual assumptions.

Environment, Safety, and Health: Status of DOE’s Reorganization of it’s Safety Oversight Function

DTIC Science & Technology

1990-01-01

facilities. After deliberation, the Congress in late 1988 directed that the Defense Nuclear Facilities Safety Board be established to provide...nuclear safety matters will be conducted by either the Advisory Committee on Nuclear Facility Safety or the recently mandated Defense Nuclear Facilities Safety...the facilities under the statutory purview of the Defense Nuclear Facilities Safety Board once the board determines it is ready to assume independent

Hepatic nuclear factor 3 and nuclear factor 1 regulate 5-aminolevulinate synthase gene expression and are involved in insulin repression.

PubMed

Scassa, María E; Guberman, Alejandra S; Ceruti, Julieta M; Cánepa, Eduardo T

2004-07-02

Although the negative regulation of gene expression by insulin has been widely studied, the transcription factors responsible for the insulin effect are still unknown. The purpose of this work was to explore the molecular mechanisms involved in the insulin repression of the 5-aminolevulinate synthase (ALAS) gene. Deletion analysis of the 5'-regulatory region allowed us to identify an insulin-responsive region located at -459 to -354 bp. This fragment contains a highly homologous insulin-responsive (IRE) sequence. By transient transfection assays, we determined that hepatic nuclear factor 3 (HNF3) and nuclear factor 1 (NF1) are necessary for an appropriate expression of the ALAS gene. Insulin overrides the HNF3beta or HNF3beta plus NF1-mediated stimulation of ALAS transcriptional activity. Electrophoretic mobility shift assay and Southwestern blotting indicate that HNF3 binds to the ALAS promoter. Mutational analysis of this region revealed that IRE disruption abrogates insulin action, whereas mutation of the HNF3 element maintains hormone responsiveness. This dissociation between HNF3 binding and insulin action suggests that HNF3beta is not the sole physiologic mediator of insulin-induced transcriptional repression. Furthermore, Southwestern blotting assay shows that at least two polypeptides other than HNF3beta can bind to ALAS promoter and that this binding is dependent on the integrity of the IRE. We propose a model in which insulin exerts its negative effect through the disturbance of HNF3beta binding or transactivation potential, probably due to specific phosphorylation of this transcription factor by Akt. In this regard, results obtained from transfection experiments using kinase inhibitors support this hypothesis. Due to this event, NF1 would lose accessibility to the promoter. The posttranslational modification of HNF3 would allow the binding of a protein complex that recognizes the core IRE. These results provide a potential mechanism for the insulin-mediated repression of IRE-containing promoters.

Calibration, event reconstruction, data analysis and limits calculation for the LUX dark matter experiment

DOE PAGES

Akerib, DS; Alsum, S; Araújo, HM; ...

2018-01-05

The LUX experiment has performed searches for dark matter particles scattering elastically on xenon nuclei, leading to stringent upper limits on the nuclear scattering cross sections for dark matter. Here, for results derived frommore » $${1.4}\\times 10^{4}\\;\\mathrm{kg\\,days}$$ of target exposure in 2013, details of the calibration, event-reconstruction, modeling, and statistical tests that underlie the results are presented. Detector performance is characterized, including measured efficiencies, stability of response, position resolution, and discrimination between electron- and nuclear-recoil populations. Models are developed for the drift field, optical properties, background populations, the electron- and nuclear-recoil responses, and the absolute rate of low-energy background events. Innovations in the analysis include in situ measurement of the photomultipliers' response to xenon scintillation photons, verification of fiducial mass with a low-energy internal calibration source, and new empirical models for low-energy signal yield based on large-sample, in situ calibrations.« less

Calibration, event reconstruction, data analysis, and limit calculation for the LUX dark matter experiment

DOE PAGES

Akerib, D. S.; Alsum, S.; Araújo, H. M.; ...

2018-05-31

Here, the LUX experiment has performed searches for dark matter particles scattering elastically on xenon nuclei, leading to stringent upper limits on the nuclear scattering cross sections for dark matter. Here, for results derived frommore » $${1.4}\\times 10^{4}\\;\\mathrm{kg\\,days}$$ of target exposure in 2013, details of the calibration, event-reconstruction, modeling, and statistical tests that underlie the results are presented. Detector performance is characterized, including measured efficiencies, stability of response, position resolution, and discrimination between electron- and nuclear-recoil populations. Models are developed for the drift field, optical properties, background populations, the electron- and nuclear-recoil responses, and the absolute rate of low-energy background events. Innovations in the analysis include in situ measurement of the photomultipliers' response to xenon scintillation photons, verification of fiducial mass with a low-energy internal calibration source, and new empirical models for low-energy signal yield based on large-sample, in situ calibrations.« less

Thermal properties of nuclear matter in a variational framework with relativistic corrections

NASA Astrophysics Data System (ADS)

Zaryouni, S.; Hassani, M.; Moshfegh, H. R.

2014-01-01

The properties of hot symmetric nuclear matter for a wide range of densities and temperatures are investigated by employing the AV14 potential within the lowest order constrained variational (LOCV) method with the inclusion of a phenomenological three-body force as well as relativistic corrections. The relativistic corrections of many-body kinetic energies as well as the boot interaction corrections are presented for a wide range of densities and temperatures. The free energy, pressure, incompressibility, and other thermodynamic quantities of symmetric nuclear matter are obtained and discussed. The critical temperature is found, and the liquid-gas phase transition is analyzed both with and without the inclusion of three-body forces and relativistic corrections in the LOCV approach. It is shown that the critical temperature is strongly affected by the three-body forces but does not depend on the relativistic corrections. Finally, the results obtained in the present study are compared with other many-body calculations and experimental predictions.

Nuclear-matter radius studies from 58Ni(α ,α ) experiments at the GSI Experimental Storage Ring with the EXL facility

NASA Astrophysics Data System (ADS)

Zamora, J. C.; Aumann, T.; Bagchi, S.; Bönig, S.; Csatlós, M.; Dillmann, I.; Dimopoulou, C.; Egelhof, P.; Eremin, V.; Furuno, T.; Geissel, H.; Gernhäuser, R.; Harakeh, M. N.; Hartig, A.-L.; Ilieva, S.; Kalantar-Nayestanaki, N.; Kiselev, O.; Kollmus, H.; Kozhuharov, C.; Krasznahorkay, A.; Kröll, Th.; Kuilman, M.; Litvinov, S.; Litvinov, Yu. A.; Mahjour-Shafiei, M.; Mutterer, M.; Nagae, D.; Najafi, M. A.; Nociforo, C.; Nolden, F.; Popp, U.; Rigollet, C.; Roy, S.; Scheidenberger, C.; von Schmid, M.; Steck, M.; Streicher, B.; Stuhl, L.; Thürauf, M.; Uesaka, T.; Weick, H.; Winfield, J. S.; Winters, D.; Woods, P. J.; Yamaguchi, T.; Yue, K.; Zenihiro, J.

2017-09-01

A novel method for measuring nuclear reactions in inverse kinematics with stored ion beams was successfully used to extract the nuclear-matter radius of 58Ni. The experiment was performed at the experimental heavy-ion storage ring at the GSI facility using a stored 58Ni beam at energies of 100 and 150 MeV/u and an internal helium gas-jet target. Elastically scattered α -recoils at low momentum transfers were measured with an in-ring detector system compatible with ultrahigh vacuum. Experimental angular distributions were fitted using density-dependent optical model potentials within the eikonal approximation. This permitted the extraction of the point-matter root-mean-square radius of 58Ni with an average value of 3.70(7) fm. Results from this work are in good agreement with several experiments performed in the past in normal kinematics. This pioneering experiment demonstrates a major breakthrough towards future investigations with far-from-stability stored beams using the present technique.

Effects of the nucleon radius on neutron stars in a quark mean field model

NASA Astrophysics Data System (ADS)

Zhu, Zhen-Yu; Li, Ang

2018-03-01

We study the effects of free space nucleon radius on nuclear matter and neutron stars within the framework of the quark mean field model. The nucleon radius is treated self-consistently with this model, where quark confinement is adjusted to fit different values of nucleon radius. Corrections due to center-of-mass motion, quark-pion coupling, and one gluon exchange are included to obtain the nucleon mass in vacuum. The meson coupling constants that describe the behavior of the many-body nucleonic system are constructed by reproducing the empirical saturation properties of nuclear matter, including the recent determinations of symmetry energy parameters. Our results show that the nucleon radius in free space has negligible effects on the nuclear matter equation of state and neutron star mass-radius relations, which is different from the conclusion drawn in previous studies. We further explore that the sensitivity of star radius on the nucleon radius found in earlier publications is actually from the symmetry energy and its slope.

Nuclear symmetry energy in terms of single-nucleon potential and its effect on the proton fraction of β-stable npeμ matter

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

Sahoo, Babita, E-mail: patra-babita@rediffmail.com; Chakraborty, Suparna, E-mail: banerjee.suparna@hotmail.com; Sahoo, Sukadev, E-mail: sukadevsahoo@yahoo.com

2016-01-15

Momentum and density dependence of single-nucleon potential u{sub τ} (k, ρ, β) is analyzed using a density dependent finite range effective interaction of the Yukawa form. Depending on the choice of the strength parameters of exchange interaction, two different trends of the momentum dependence of nuclear symmetry potential are noticed which lead to two opposite types of neutron and proton effective mass splitting. The 2nd-order and 4th-order symmetry energy of isospin asymmetric nuclear matter are expressed analytically in terms of the single-nucleon potential. Two distinct behavior of the density dependence of 2nd-order and 4th-order symmetry energy are observed depending onmore » neutron and proton effective mass splitting. It is also found that the 4th-order symmetry energy has a significant contribution towards the proton fraction of β-stable npeμ matter at high densities.« less

Calibration, event reconstruction, data analysis, and limit calculation for the LUX dark matter experiment

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

Akerib, D. S.; Alsum, S.; Araújo, H. M.

Here, the LUX experiment has performed searches for dark matter particles scattering elastically on xenon nuclei, leading to stringent upper limits on the nuclear scattering cross sections for dark matter. Here, for results derived frommore » $${1.4}\\times 10^{4}\\;\\mathrm{kg\\,days}$$ of target exposure in 2013, details of the calibration, event-reconstruction, modeling, and statistical tests that underlie the results are presented. Detector performance is characterized, including measured efficiencies, stability of response, position resolution, and discrimination between electron- and nuclear-recoil populations. Models are developed for the drift field, optical properties, background populations, the electron- and nuclear-recoil responses, and the absolute rate of low-energy background events. Innovations in the analysis include in situ measurement of the photomultipliers' response to xenon scintillation photons, verification of fiducial mass with a low-energy internal calibration source, and new empirical models for low-energy signal yield based on large-sample, in situ calibrations.« less

Assessing the environmental impact of phenanthrene in different types of land use based on the binding characteristics with dissolved organic matter.

PubMed

Chen, Xiao-Meng; Zhao, Yue; Ma, Ying-Ying; Zhu, Long-Ji; Yang, Tian-Xue; Wei, Zi-Min; Dong, Ying-Li; Wei, Qing-Bin

2018-01-01

The binding characteristics of phenanthrene with dissolved organic matter (DOM) were studied by the excitation emission matrix fluorescence spectroscopy with parallel factor analysis in four types of land use which derived from forest (F), meadow (M), cropland (C), and greenhouse (G). The results showed that the humification degree and binding characteristics of phenanthrene with DOM were distinct differences in the four soils. The binding capacities of humic-like components with phenanthrene were stronger than those of protein-like components. The log K derived from the Stern-Volmer equation significantly correlated with the humification degree of DOM (p < 0.05) in different types of land use. Besides, correlation analysis demonstrated that the potential binding index (Fk) obtained from the modified Stern-Volmer model was a more accurate parameter to describe the combination degree of DOM with phenanthrene than log K, which presented a decrease order of C > F > M > G. Therefore, the environmental impact of phenanthrene in different types of land use could be assessed deeply based on the Fk and DOM concentration. Copyright © 2017 Elsevier Inc. All rights reserved.

A Low Nuclear Recoil Energy Threshold for Dark Matter Search with CRESST-III Detectors

NASA Astrophysics Data System (ADS)

Mancuso, M.; Angloher, G.; Bauer, P.; Bento, A.; Bucci, C.; Canonica, L.; D'Addabbo, A.; Defay, X.; Erb, A.; von Feilitzsch, Franz; Ferreiro Iachellini, N.; Gorla, P.; Gütlein, A.; Hauff, D.; Jochum, J.; Kiefer, M.; Kluck, H.; Kraus, H.; Lanfranchi, J. C.; Langenkämper, A.; Loebell, J.; Mondragon, E.; Münster, A.; Pagliarone, C.; Petricca, F.; Potzel, W.; Pröbst, F.; Puig, R.; Reindl, F.; Rothe, J.; Schäffner, K.; Schieck, J.; Schipperges, V.; Schönert, S.; Seidel, W.; Stahlberg, M.; Stodolsky, L.; Strandhagen, C.; Strauss, R.; Tanzke, A.; Thi, H. H. Trinh; Türkoglu, C.; Uffinger, M.; Ulrich, A.; Usherov, I.; Wawoczny, S.; Willers, M.; Wüstrich, M.

2018-05-01

The CRESST-III experiment (Cryogenic Rare Events Search with Superconducting Thermometers), located at the underground facility Laboratori Nazionali del Gran Sasso in Italy, uses scintillating CaWO_4 crystals as cryogenic calorimeters to search for direct dark matter interactions in detectors. A large part of the parameter space for spin-independent scattering off nuclei remains untested for dark matter particles with masses below a few GeV/c^2 , despite many naturally motivated theoretical models for light dark matter particles. The CRESST-III detectors are designed to achieve the performance required to probe the low-mass region of the parameter space with a sensitivity never reached before. In this paper, new results on the performance and an overview of the CRESST-III detectors will be presented, emphasizing the results about the low-energy threshold for nuclear recoil of CRESST-III Phase 1 which started collecting data in August 2016.

Opposite nuclear level and binding activity of STAT5B and STAT3 proteins with rat haptoglobin gene under normal and turpentine induced acute phase conditions.

PubMed

Grigorov, I; Lazić, T; Cvetković, I; Milosavljević, T; Petrović, M

2001-01-01

Transcription of the rat gene encoding haptoglobin (Hp) is highly induced during acute phase (AP) response which has been previously shown to be mediated by inducible STAT3 member of the Signal Transducer and Activators of Transcription (STATs) family proteins. In this study, we observed that under normal but not in the turpentine induced AP conditions, another member of the STAT family proteins, STAT5b is expressed and binds to the hormone regulatory element (HRE) of the rat Hp gene. We found that the nuclear amounts of constitutively active STAT5b in rat liver decreased significantly with time of turpentine treatment as opposed to that of cytosol STAT5b, suggesting possible export of constitutive STAT5b from the nucleus. Nuclear accumulation and binding of inducible STAT3 proteins to the rat Hp gene HRE following turpentine treatment implicated that STAT5b negatively regulates Hp gene expression during normal conditions.

Identification of two functional nuclear localization signals in the capsid protein of duck circovirus

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

Xiang, Qi-Wang; Zou, Jin-Feng; Wang, Xin

The capsid protein (CP) of duck circovirus (DuCV) is the major immunogenic protein and has a high proportion of arginine residues concentrated at the N terminus of the protein, which inhibits efficient mRNA translation in prokaryotic expression systems. In this study, we investigated the subcellular distribution of DuCV CP expressed via recombinant baculoviruses in Sf9 cells and the DNA binding activities of the truncated recombinant DuCV CPs. The results showed that two independent bipartite nuclear localization signals (NLSs) situated at N-terminal 1-17 and 18-36 amino acid residue of the CP. Moreover, two expression level regulatory signals (ELRSs) and two DNAmore » binding signals (DBSs) were also mapped to the N terminus of the protein and overlapped with the two NLSs. The ability of CP to bind DNA, coupled with the karyophilic nature of this protein, strongly suggests that it may be responsible for nuclear targeting of the viral genome.« less

MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.

PubMed

Posavec Marjanović, Melanija; Hurtado-Bagès, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Hélène; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M; Ahel, Ivan; Ladurner, Andreas G; Yanes, Oscar; Bouvet, Philippe; Suelves, Mònica; Teperino, Raffaele; Pospisilik, J Andrew; Buschbeck, Marcus

2017-11-01

Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD + -derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD + consumption. The resultant accumulation of the NAD + precursor NMN allows for maintenance of mitochondrial NAD + pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD + consumption and establishing a buffer of NAD + precursors in differentiated cells.

A 1H NMR method for the analysis of antigen-antibody interactions: binding of a peptide fragment of lysozyme to anti-lysozyme monoclonal antibody.

PubMed

Ito, W; Nishimura, M; Sakato, N; Fujio, H; Arata, Y

1987-09-01

A proton nuclear magnetic resonance (NMR) study is reported of the molecular structural basis of antigen-antibody interactions. An immunologically reactive proteolytic fragment corresponding to one of the antigenic regions on hen egg-white lysozyme (HEL) was used in combination with a monoclonal antibody that recognizes this site. Using spin diffusion, we prepared an antibody in which the magnetization of the antigen binding site was saturated by non-specific nuclear Overhauser effect. Under these conditions the effect of the saturation of the antibody was observed to spread over the peptide fragment through the antigen binding site. On the basis of the results obtained for the intermolecular nuclear Overhauser effect, we discuss how the peptide fragment interacts with the antibody. The side chains of aromatic residues, Trp, Tyr, and His, and of ionic residues, especially Arg, Lys, and Glu, are suggested to be important in the antigen-antibody interaction.

LaRbp38: A Leishmania amazonensis protein that binds nuclear and kinetoplast DNAs

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

Lira, C.B.B.; Instituto de Biologia, UNICAMP, Campinas, SP; Siqueira Neto, J.L.

Leishmania amazonensis causes a wide spectrum of leishmaniasis. There are no vaccines or adequate treatment for leishmaniasis, therefore there is considerable interest in the identification of new targets for anti-leishmania drugs. The central role of telomere-binding proteins in cell maintenance makes these proteins potential targets for new drugs. In this work, we used a combination of purification chromatographies to screen L. amazonensis proteins for molecules capable of binding double-stranded telomeric DNA. This approach resulted in the purification of a 38 kDa polypeptide that was identified by mass spectrometry as Rbp38, a trypanosomatid protein previously shown to stabilize mitochondrial RNA andmore » to associate with nuclear and kinetoplast DNAs. Western blotting and supershift assays confirmed the identity of the protein as LaRbp38. Competition and chromatin immunoprecipitation assays confirmed that LaRbp38 interacted with kinetoplast and nuclear DNAs in vivo and suggested that LaRbp38 may have dual cellular localization and more than one function.« less

NF-κB Transcriptional Activity Is Modulated by FK506-binding Proteins FKBP51 and FKBP52

PubMed Central

Erlejman, Alejandra G.; De Leo, Sonia A.; Mazaira, Gisela I.; Molinari, Alejandro M.; Camisay, María Fernanda; Fontana, Vanina; Cox, Marc B.; Piwien-Pilipuk, Graciela; Galigniana, Mario D.

2014-01-01

Hsp90 binding immunophilins FKBP51 and FKBP52 modulate steroid receptor trafficking and hormone-dependent biological responses. With the purpose to expand this model to other nuclear factors that are also subject to nuclear-cytoplasmic shuttling, we analyzed whether these immunophilins modulate NF-κB signaling. It is demonstrated that FKBP51 impairs both the nuclear translocation rate of NF-κB and its transcriptional activity. The inhibitory action of FKBP51 requires neither the peptidylprolyl-isomerase activity of the immunophilin nor its association with Hsp90. The TPR domain of FKBP51 is essential. On the other hand, FKBP52 favors the nuclear retention time of RelA, its association to a DNA consensus binding sequence, and NF-κB transcriptional activity, the latter effect being strongly dependent on the peptidylprolyl-isomerase activity and also on the TPR domain of FKBP52, but its interaction with Hsp90 is not required. In unstimulated cells, FKBP51 forms endogenous complexes with cytoplasmic RelA. Upon cell stimulation with phorbol ester, the NF-κB soluble complex exchanges FKBP51 for FKBP52, and the NF-κB biological effect is triggered. Importantly, FKBP52 is functionally recruited to the promoter region of NF-κB target genes, whereas FKBP51 is released. Competition assays demonstrated that both immunophilins antagonize one another, and binding assays with purified proteins suggest that the association of RelA and immunophilins could be direct. These observations suggest that the biological action of NF-κB in different cell types could be positively regulated by a high FKBP52/FKBP51 expression ratio by favoring NF-κB nuclear retention, recruitment to the promoter regions of target genes, and transcriptional activity. PMID:25104352

Structural mechanism of Smad4 recognition by the nuclear oncoprotein Ski: insights on Ski-mediated repression of TGF-beta signaling.

PubMed

Wu, Jia Wei; Krawitz, Ariel R; Chai, Jijie; Li, Wenyu; Zhang, Fangjiu; Luo, Kunxin; Shi, Yigong

2002-11-01

The Ski family of nuclear oncoproteins represses TGF-beta signaling through interactions with the Smad proteins. The crystal structure of the Smad4 binding domain of human c-Ski in complex with the MH2 domain of Smad4 reveals specific recognition of the Smad4 L3 loop region by a highly conserved interaction loop (I loop) from Ski. The Ski binding surface on Smad4 significantly overlaps with that required for binding of the R-Smads. Indeed, Ski disrupts the formation of a functional complex between the Co- and R-Smads, explaining how it could lead to repression of TGF-beta, activin, and BMP responses. Intriguingly, the structure of the Ski fragment, stabilized by a bound zinc atom, resembles the SAND domain, in which the corresponding I loop is responsible for DNA binding.

Serial interactome capture of the human cell nucleus.

PubMed

Conrad, Thomas; Albrecht, Anne-Susann; de Melo Costa, Veronica Rodrigues; Sauer, Sascha; Meierhofer, David; Ørom, Ulf Andersson

2016-04-04

Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present 'serial RNA interactome capture' (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)-RNA-protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA-RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs.

Microsomal receptor for steroid hormones: functional implications for nuclear activity.

PubMed

Muldoon, T G; Watson, G H; Evans, A C; Steinsapir, J

1988-01-01

Target tissues for steroid hormones are responsive by virtue of and to the extent of their content of functional intracellular receptors. Recent years have seen a shift in considerations of the cellular dynamics and distribution of these receptors, with current views favoring predominant intranuclear localization in the intact cell. This paper summarizes our analyses of the microsomal estrogen and androgen binding capability of rat uterine and ventral prostate tissue, respectively; these studies have revealed a set of high affinity sites that may act as a conduit for estrogen traversing the cell en route to the nucleus. These sites have many properties in common with cytosolic receptors, with the salient difference of a failure to activate to a more avid DNA-binding form under conditions which permit such activation of cytosolic receptors. The microsomal estrogen-binding proteins also have appreciable affinity for progesterone, another distinction from other known cellular estrogen receptor species. Various experimental approaches were employed to demonstrate that the microsomal receptors were not simply cytosol contaminants; the most convincing evidence is the recent successful separation of the cytosolic and microsomal forms by differential ammonium sulfate precipitation. Discrete subfractionation of subcellular components on successive sucrose gradients, with simultaneous assessments of binding capability and marker enzyme concentrations, indicates that the major portion of the binding is localized within the vesicles of the endoplasmic reticulum free of significant plasma membrane contamination. The microsomal receptors are readily solubilized by extraction with high- or low-salt-containing buffers or with steroid. The residual microsomes following such extraction have the characteristics of saturable acceptor sites for cytosolic estrogen-receptor complexes. The extent to which these sites will accept the cytosolic complexes is equal to the concentration of microsomal binding sites extracted. These observations suggest three possible roles for the microsomal receptor-like proteins: (a) modulation of estrogen access to nuclear binding sites; (b) formation of functional complexes which diffuse to other extranuclear sites to alter non-genomic cellular processes; (c) regulation of nuclear concentration of estrogen-receptor complexes by virtue of producing microsomal acceptor sites for uptake of free or loosely associated nuclear complexes, previously thought to exist in the cytoplasm.

The Anzus Rift: The Politics of the Matter

DTIC Science & Technology

1999-04-01

nuclear disaster preoccupied the New Zealand public mind in the early 1980s in contrast to the more explicitly environmental concerns of the 1970s.4...Unpublished paper, Columbia University, May 1997, p 9. 4 A nuclear disaster or accident was thought to be more likely than nuclear war, and as such was

GAO’s Views on DOE’s 1991 Budget for Addressing Problems at the Nuclear Weapons Complex

DTIC Science & Technology

1990-03-02

management, and efforts by DOE to make its contractors more accountable. Also, the Defense Nuclear Facilities Safety Board mandated by the Congress became...and safety matters. 6 Finally, the Defense Nuclear Facilities Safety Board was established. Although not a DOE action, its establishment, nevertheless

10 CFR 2.340 - Initial decision in certain contested proceedings; immediate effectiveness of initial decisions...

Code of Federal Regulations, 2010 CFR

2010-01-01

... those matters, the Commission, the Director, Office of Nuclear Reactor Regulation or Director, Office of... Nuclear Reactor Regulation, as appropriate, after making the requisite findings, will issue, deny or... acceptance criteria in nuclear power reactor combined licenses. In any initial decision under § 52.103(g) of...

10 CFR 2.340 - Initial decision in certain contested proceedings; immediate effectiveness of initial decisions...

Code of Federal Regulations, 2011 CFR

2011-01-01

... those matters, the Commission, the Director, Office of Nuclear Reactor Regulation or Director, Office of... Nuclear Reactor Regulation, as appropriate, after making the requisite findings, will issue, deny or... acceptance criteria in nuclear power reactor combined licenses. In any initial decision under § 52.103(g) of...

10 CFR 2.340 - Initial decision in certain contested proceedings; immediate effectiveness of initial decisions...

Code of Federal Regulations, 2012 CFR

2012-01-01

... those matters, the Commission, the Director, Office of Nuclear Reactor Regulation or Director, Office of... Nuclear Reactor Regulation, as appropriate, after making the requisite findings, will issue, deny or... acceptance criteria in nuclear power reactor combined licenses. In any initial decision under § 52.103(g) of...

Proteomic analysis of the nuclear matrix in the early stages of rat liver carcinogenesis: Identification of differentially expressed and MAR-binding proteins

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

Barboro, Paola; D'Arrigo, Cristina; Repaci, Erica

Tumor progression is characterized by definite changes in the protein composition of the nuclear matrix (NM). The interactions of chromatin with the NM occur via specific DNA sequences called MARs (matrix attachment regions). In the present study, we applied a proteomic approach along with a Southwestern assay to detect both differentially expressed and MAR-binding NM proteins, in persistent hepatocyte nodules (PHN) in respect with normal hepatocytes (NH). In PHN, the NM undergoes changes both in morphology and in protein composition. We detected over 500 protein spots in each two dimensional map and 44 spots were identified. Twenty-three proteins were differentiallymore » expressed; among these, 15 spots were under-expressed and 8 spots were over-expressed in PHN compared to NH. These changes were synchronous with several modifications in both NM morphology and the ability of NM proteins to bind nuclear RNA and/or DNA containing MARs sequences. In PHN, we observed a general decrease in the expression of the basic proteins that bound nuclear RNA and the over-expression of two species of Mw 135 kDa and 81 kDa and pI 6.7-7.0 and 6.2-7.4, respectively, which exclusively bind to MARs. These results suggest that the deregulated expression of these species might be related to large-scale chromatin reorganization observed in the process of carcinogenesis by modulating the interaction between MARs and the scaffold structure.« less

Effects of nuclear structure in the spin-dependent scattering of weakly interacting massive particles

NASA Astrophysics Data System (ADS)

Nikolaev, M. A.; Klapdor-Kleingrothaus, H. V.

1993-06-01

We present calculations of the nuclear from factors for spin-dependent elastic scattering of dark matter WIMPs from123Te and131Xe isotopes, proposed to be used for dark matter detection. A method based on the theory of finite Fermi systems was used to describe the reduction of the single-particle spin-dependent matrix elements in the nuclear medium. Nucleon single-particle states were calculated in a realistic shell model potential; pairing effects were treated within the BCS model. The coupling of the lowest single-particle levels in123Te to collective 2+ excitations of the core was taken into account phenomenologically. The calculated nuclear form factors are considerably less then the single-particle ones for low momentum transfer. At high momentum transfer some dynamical amplification takes place due to the pion exchange term in the effective nuclear interaction. But as the momentum transfer increases, the difference disappears, the momentum transfer increases and the quenching effect disappears. The shape of the nuclear form factor for the131Xe isotope differs from the one obtained using an oscillator basis.

Fermi liquid, clustering, and structure factor in dilute warm nuclear matter

NASA Astrophysics Data System (ADS)

Röpke, G.; Voskresensky, D. N.; Kryukov, I. A.; Blaschke, D.

2018-02-01

Properties of nuclear systems at subsaturation densities can be obtained from different approaches. We demonstrate the use of the density autocorrelation function which is related to the isothermal compressibility and, after integration, to the equation of state. This way we connect the Landau Fermi liquid theory well elaborated in nuclear physics with the approaches to dilute nuclear matter describing cluster formation. A quantum statistical approach is presented, based on the cluster decomposition of the polarization function. The fundamental quantity to be calculated is the dynamic structure factor. Comparing with the Landau Fermi liquid theory which is reproduced in lowest approximation, the account of bound state formation and continuum correlations gives the correct low-density result as described by the second virial coefficient and by the mass action law (nuclear statistical equilibrium). Going to higher densities, the inclusion of medium effects is more involved compared with other quantum statistical approaches, but the relation to the Landau Fermi liquid theory gives a promising approach to describe not only thermodynamic but also collective excitations and non-equilibrium properties of nuclear systems in a wide region of the phase diagram.

Steroid receptor coupling becomes nuclear.

PubMed

Galigniana, Mario D

2012-06-22

In this issue of Chemistry & Biology, Grossman et al. report a study on aldosterone-dependent nuclear translocation of the mineralocorticoid receptor (MR). They analyze the dependency of MR retrotransport, DNA-binding, and transcriptional activity on Hsp90 and demonstrate that MR dimerization is a nuclear event. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quark matter or new particles?

NASA Technical Reports Server (NTRS)

Michel, F. Curtis

1988-01-01

It has been argued that compression of nuclear matter to somewhat higher densities may lead to the formation of stable quark matter. A plausible alternative, which leads to radically new astrophysical scenarios, is that the stability of quark matter simply represents the stability of new particles compounded of quarks. A specific example is the SU(3)-symmetric version of the alpha particle, composed of spin-zero pairs of each of the baryon octet (an 'octet' particle).

BXR, an embryonic orphan nuclear receptor activated by a novel class of endogenous benzoate metabolites

PubMed Central

Blumberg, Bruce; Kang, Heonjoong; Bolado, Jack; Chen, Hongwu; Craig, A. Grey; Moreno, Tanya A.; Umesono, Kazuhiko; Perlmann, Thomas; De Robertis, Eddy M.; Evans, Ronald M.

1998-01-01

Nuclear receptors are ligand-modulated transcription factors that respond to steroids, retinoids, and thyroid hormones to control development and body physiology. Orphan nuclear receptors, which lack identified ligands, provide a unique, and largely untapped, resource to discover new principles of physiologic homeostasis. We describe the isolation and characterization of the vertebrate orphan receptor, BXR, which heterodimerizes with RXR and binds high-affinity DNA sites composed of a variant thyroid hormone response element. A bioactivity-guided screen of embryonic extracts revealed that BXR is activatable by low-molecular-weight molecules with spectral patterns distinct from known nuclear receptor ligands. Mass spectrometry and 1H NMR analysis identified alkyl esters of amino and hydroxy benzoic acids as potent, stereoselective activators. In vitro cofactor association studies, along with competable binding of radiolabeled compounds, establish these molecules as bona fide ligands. Benzoates comprise a new molecular class of nuclear receptor ligand and their activity suggests that BXR may control a previously unsuspected vertebrate signaling pathway. PMID:9573044

Nuclear proteins that bind the human gamma-globin gene promoter: alterations in binding produced by point mutations associated with hereditary persistence of fetal hemoglobin.

PubMed Central

Gumucio, D L; Rood, K L; Gray, T A; Riordan, M F; Sartor, C I; Collins, F S

1988-01-01

The molecular mechanisms responsible for the human fetal-to-adult hemoglobin switch have not yet been elucidated. Point mutations identified in the promoter regions of gamma-globin genes from individuals with nondeletion hereditary persistence of fetal hemoglobin (HPFH) may mark cis-acting sequences important for this switch, and the trans-acting factors which interact with these sequences may be integral parts in the puzzle of gamma-globin gene regulation. We have used gel retardation and footprinting strategies to define nuclear proteins which bind to the normal gamma-globin promoter and to determine the effect of HPFH mutations on the binding of a subset of these proteins. We have identified five proteins in human erythroleukemia cells (K562 and HEL) which bind to the proximal promoter region of the normal gamma-globin gene. One factor, gamma CAAT, binds the duplicated CCAAT box sequences; the -117 HPFH mutation increases the affinity of interaction between gamma CAAT and its cognate site. Two proteins, gamma CAC1 and gamma CAC2, bind the CACCC sequence. These proteins require divalent cations for binding. The -175 HPFH mutation interferes with the binding of a fourth protein, gamma OBP, which binds an octamer sequence (ATGCAAAT) in the normal gamma-globin promoter. The HPFH phenotype of the -175 mutation indicates that the octamer-binding protein may play a negative regulatory role in this setting. A fifth protein, EF gamma a, binds to sequences which overlap the octamer-binding site. The erythroid-specific distribution of EF gamma a and its close approximation to an apparent repressor-binding site suggest that it may be important in gamma-globin regulation. Images PMID:2468996

Yrb4p, a yeast ran-GTP-binding protein involved in import of ribosomal protein L25 into the nucleus.

PubMed Central

Schlenstedt, G; Smirnova, E; Deane, R; Solsbacher, J; Kutay, U; Görlich, D; Ponstingl, H; Bischoff, F R

1997-01-01

Gsp1p, the essential yeast Ran homologue, is a key regulator of transport across the nuclear pore complex (NPC). We report the identification of Yrb4p, a novel Gsp1p binding protein. The 123 kDa protein was isolated from Saccharomyces cerevisiae cells and found to be related to importin-beta, the mediator of nuclear localization signal (NLS)-dependent import into the nucleus, and to Pse1p. Like importin-beta, Yrb4p and Pse1p specifically bind to Gsp1p-GTP, protecting it from GTP hydrolysis and nucleotide exchange. The GTPase block of Gsp1p complexed to Yrb4p or Pse1p is released by Yrb1p, which contains a Gsp1p binding domain distinct from that of Yrb4p. This might reflect an in vivo function for Yrb1p. Cells disrupted for YRB4 are defective in nuclear import of ribosomal protein L25, but show no defect in the import of proteins containing classical NLSs. Expression of a Yrb4p mutant deficient in Gsp1p-binding is dominant-lethal and blocks bidirectional traffic across the NPC in wild-type cells. L25 binds to Yrb4p and Pse1p and is released by Gsp1p-GTP. Consistent with its putative role as an import receptor for L25-like proteins, Yrb4p localizes to the cytoplasm, the nucleoplasm and the NPC. PMID:9321403

REVIEWS OF TOPICAL PROBLEMS: Properties of matter in ultrahigh magnetic fields and the structure of the surface of neutron stars

NASA Astrophysics Data System (ADS)

Liberman, Mikhail A.; Johansson, B.

1995-02-01

The physical properties of atoms, molecules, and solids in ultrahigh magnetic fields B gg 109 G that are believed to exist on the surface of neutron stars are discussed. In these fields, atoms are strongly deformed and elongated along the magnetic field lines; the binding energy and ionizing energy of the atoms are substantially increased and the interatomic interaction is dramatically changed. This strongly modifies the properties of matter at the surface of magnetic neutron stars which are crucial for modelling the pulsar magnetosphere. A scenario for magnetosphere evolution is proposed which suggests free emission for a young pulsar and strong binding of the matter to the surface at a later stage. This later stage is due to strongly bound chains of alternate heavy atoms and light atoms accreted on the surface of the star.

Constraining in-medium nucleon-nucleon interactions via nucleus-nucleus reactions

NASA Astrophysics Data System (ADS)

Sammarruca, Francesca; White, Larz

2010-11-01

The nuclear equation of state is a broadly useful tool. Besides being the main input of stellar structure calculations, it allows a direct connection to the physics of nuclei. For instance, an energy functional (such as a mass formula), together with the energy/particle in nuclear matter, can be used to predict nuclear energies and radii [1]. The single-particle properties are also a key point to link infinite nuclear matter and actual nuclei. The parameters of the single-particle potential, in particular the effective mass, enter the calculations of, for instance, in-medium effective cross sections. From the well-known Glauber reaction theory, the total nucleus-nucleus reaction cross section is expressed in terms of the nuclear transparency, which, in turn, depends on the overlap of the nuclear density distributions and the elementary nucleon-nucleon (NN) cross sections. We explore the sensitivity of the reaction calculation to medium modifications of the NN cross sections to estimate the likelihood of constraining the latter through nuclear reactions. Ultimately, we wish to incorporate isospin asymmetry in the reaction model, having in mind connections with rare isotopes. [1] F. Sammarruca, arXiv:1002.00146 [nucl-th]; International Journal of Modern Physics, in press.

Functions of Intracellular Retinoid Binding-Proteins.

PubMed

Napoli, Joseph L

Multiple binding and transport proteins facilitate many aspects of retinoid biology through effects on retinoid transport, cellular uptake, metabolism, and nuclear delivery. These include the serum retinol binding protein sRBP (aka Rbp4), the plasma membrane sRBP receptor Stra6, and the intracellular retinoid binding-proteins such as cellular retinol-binding proteins (CRBP) and cellular retinoic acid binding-proteins (CRABP). sRBP transports the highly lipophilic retinol through an aqueous medium. The major intracellular retinol-binding protein, CRBP1, likely enhances efficient retinoid use by providing a sink to facilitate retinol uptake from sRBP through the plasma membrane or via Stra6, delivering retinol or retinal to select enzymes that generate retinyl esters or retinoic acid, and protecting retinol/retinal from excess catabolism or opportunistic metabolism. Intracellular retinoic acid binding-proteins (CRABP1 and 2, and FABP5) seem to have more diverse functions distinctive to each, such as directing retinoic acid to catabolism, delivering retinoic acid to specific nuclear receptors, and generating non-canonical actions. Gene ablation of intracellular retinoid binding-proteins does not cause embryonic lethality or gross morphological defects. Metabolic and functional defects manifested in knockouts of CRBP1, CRBP2 and CRBP3, however, illustrate their essentiality to health, and in the case of CRBP2, to survival during limited dietary vitamin A. Future studies should continue to address the specific molecular interactions that occur between retinoid binding-proteins and their targets and their precise physiologic contributions to retinoid homeostasis and function.

Constraining the Speed of Sound inside Neutron Stars with Chiral Effective Field Theory Interactions and Observations

NASA Astrophysics Data System (ADS)

Tews, I.; Carlson, J.; Gandolfi, S.; Reddy, S.

2018-06-01

The dense matter equation of state (EOS) determines neutron star (NS) structure but can be calculated reliably only up to one to two times the nuclear saturation density, using accurate many-body methods that employ nuclear interactions from chiral effective field theory constrained by scattering data. In this work, we use physically motivated ansatzes for the speed of sound c S at high density to extend microscopic calculations of neutron-rich matter to the highest densities encountered in stable NS cores. We show how existing and expected astrophysical constraints on NS masses and radii from X-ray observations can constrain the speed of sound in the NS core. We confirm earlier expectations that c S is likely to violate the conformal limit of {c}S2≤slant {c}2/3, possibly reaching values closer to the speed of light c at a few times the nuclear saturation density, independent of the nuclear Hamiltonian. If QCD obeys the conformal limit, we conclude that the rapid increase of c S required to accommodate a 2 M ⊙ NS suggests a form of strongly interacting matter where a description in terms of nucleons will be unwieldy, even between one and two times the nuclear saturation density. For typical NSs with masses in the range of 1.2–1.4 M ⊙, we find radii between 10 and 14 km, and the smallest possible radius of a 1.4 M ⊙ NS consistent with constraints from nuclear physics and observations is 8.4 km. We also discuss how future observations could constrain the EOS and guide theoretical developments in nuclear physics.

Vector Mesons in Cold Nuclear Matter

NASA Astrophysics Data System (ADS)

Rodrigues, Tulio E.; Dias de Toledo Arruda-Neto, Joāo

2013-03-01

The attenuation of vector mesons in cold nuclear matter is studied through the mechanism of incoherent photoproduction off complex nuclei. The latter is described via the time-dependent multi-collisional Monte Carlo (MCMC) intranuclear cascade model. The results for the transparency ratios of ω mesons reproduce previous measurements of CB-ELSA/TAPS with an inelastic ωN cross section around 40 mb for ρω ~ 1.1 GeV/c. The corresponding in-medium width (nuclear rest frame) is extracted dinamically from the algorithm and depends on the average nuclear density pN and target nucleus: ~ 49.2 MeV/c2 for carbon (pN 0.114 far-3) and ~ 77.3 MeV/c2 for lead (pN 0.137 far--3). The calculations fail to reproduce the huge absorption observed at JLab assuming the same inelastic cross section and the discrepancy between the two experiments remains a challenge.

An Updated Nuclear Equation of State for Neutron Stars and Supernova Simulations

NASA Astrophysics Data System (ADS)

Meixner, M. A.; Mathews, G. J.; Dalhed, H. E.; Lan, N. Q.

2011-10-01

We present an updated and improved Equation of State based upon the framework originally developed by Bowers & Wilson. The details of the EoS and improvements are described along with a description of how to access this EOS for numerical simulations. Among the improvements are an updated compressibility based upon recent measurements, the possibility of the formation of proton excess (Ye> 0.5) material and an improved treatment of the nuclear statistical equilibrium and the transition to pasta nuclei as the density approaches nuclear matter density. The possibility of a QCD chiral phase transition is also included at densities above nuclear matter density. We show comparisons of this EOS with the other two publicly available equations of state used in supernova collapse simulations. The advantages of the present EoS is that it is easily amenable to phenomenological parameterization to fit observed explosion properties and to accommodate new physical parameters.

Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness

NASA Astrophysics Data System (ADS)

Furusawa, Takashi; Rochman, Mark; Taher, Leila; Dimitriadis, Emilios K.; Nagashima, Kunio; Anderson, Stasia; Bustin, Michael

2015-01-01

In most metazoan nuclei, heterochromatin is located at the nuclear periphery in contact with the nuclear lamina, which provides mechanical stability to the nucleus. We show that in cultured cells, chromatin decompaction by the nucleosome binding protein HMGN5 decreases the sturdiness, elasticity and rigidity of the nucleus. Mice overexpressing HMGN5, either globally or only in the heart, are normal at birth but develop hypertrophic heart with large cardiomyoctyes, deformed nuclei and disrupted lamina and die of cardiac malfunction. Chromatin decompaction is seen in cardiomyocytes of newborn mice but misshaped nuclei with disrupted lamina are seen only in adult cardiomyocytes, suggesting that loss of heterochromatin diminishes the ability of the nucleus to withstand the mechanical forces of the contracting heart. Thus, heterochromatin enhances the ability of the nuclear lamina to maintain the sturdiness and shape of the eukaryotic nucleus; a structural role for chromatin that is distinct from its genetic functions.

Liquid-gas phase transition in asymmetric nuclear matter at finite temperature

NASA Astrophysics Data System (ADS)

Maruyama, Toshiki; Tatsumi, Toshitaka; Chiba, Satoshi

2010-03-01

Liquid-gas phase transition is discussed in warm asymmetric nuclear matter. Some peculiar features are figured out from the viewpoint of the basic thermodynamics about the phase equilibrium. We treat the mixed phase of the binary system based on the Gibbs conditions. When the Coulomb interaction is included, the mixed phase is no more uniform and the sequence of the pasta structures appears. Comparing the results with those given by the simple bulk calculation without the Coulomb interaction, we extract specific features of the pasta structures at finite temperature.