bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of In Vivo-Interacting Domains of the Murine Coronavirus Nucleocapsid Protein
Authors: Hurst Kelley R. , Koetzner Cheri A. , Masters Paul S.
Published: May 2009

The coronavirus nucleocapsid protein (N), together with the large, positive-strand RNA viral genome, forms a helically symmetric nucleocapsid. This ribonucleoprotein structure becomes packaged into virions through association with the carboxy-terminal endodomain of the membrane protein (M), which is the principal constituent of the virion envelope. Previous work with the prototype coronavirus mouse hepatitis virus (MHV) has shown that a major determinant of the N-M interaction maps to the carboxy-terminal domain 3 of the N protein. To explore other domain interactions of the MHV N protein, we expressed a series of segments of the MHV N protein as fusions with green fluorescent protein (GFP) during the course of viral infection. We found that two of these GFP-N-domain fusion proteins were selectively packaged into virions as the result of tight binding to the N protein in the viral nucleocapsid, in a manner that did not involve association with either M protein or RNA. The nature of each type of binding was further explored through genetic analysis. Our results defined two strongly interacting regions of the N protein. One is the same domain 3 that is critical for M protein recognition during assembly. The other is domain N1b, which corresponds to the N-terminal domain that has been structurally characterized in detail for two other coronaviruses, infectious bronchitis virus and the severe acute respiratory syndrome coronavirus.
Respiratory Syncytial Virus-Induced Activation and Migration of Respiratory Dendritic Cells and Subsequent Antigen Presentation in the Lung-Draining Lymph Node
Authors: Lukens Michaël V. , Kruijsen Debby , Coenjaerts Frank E. J. , Kimpen Jan L. L. , van Bleek Grada M.
Published: May 2009

In the respiratory tract, different dendritic cell (DC) populations guard a tight balance between tolerance and immunity to infectious or harmless materials to which the airways are continuously exposed. For infectious and noninfectious antigens administered via different routes, different subsets of DC might contribute during the induction of T-cell tolerance and immunity. We studied the impact of primary respiratory syncytial virus (RSV) infection on respiratory DC composition in C57BL/6 mice. We also tracked the migration of respiratory DC to the lymph nodes and studied antigen presentation by lung-derived and lymph node-resident DC to CD4
+
and CD8
+
T cells. We observed a massive influx of mainly CD103
−
CD11b
high
CD11c
+
conventional DC (cDC) and plasmacytoid DC during the first 7 days of RSV infection, while CD103
+
CD11b
low
CD11c
+
cDC disappeared from the lung. The two major subsets of lung tissue DC, CD103
+
CD11b
low
CD11c
+
and CD103
−
CD11b
high
CD11c
+
cDC, both transported RSV RNA to the lung-draining lymph node. Furthermore, these lung-derived cDC subsets as well as resident LN DC, which did not contain viral RNA, displayed viral antigen by major histocompatibility complex class I and class II to CD8
+
and CD4
+
T cells. Taken together, our data indicate that during RSV infections, at least three DC subsets might be involved during the activation of lymph node-homing naïve and memory CD4
+
and CD8
+
T cells.
Antiapoptotic Activity of the Cardiovirus Leader Protein, a Viral “Security” Protein
Authors: Romanova Lyudmila I. , Lidsky Peter V. , Kolesnikova Marina S. , Fominykh Ksenia V. , Gmyl Anatoly P. , Sheval Eugene V. , Hato Stanleyson V. , van Kuppeveld Frank J. M. , Agol Vadim I.
Published: May 2009

Apoptosis is a common antiviral defensive mechanism that potentially limits viral reproduction and spread. Many viruses possess apoptosis-suppressing tools. Here, we show that the productive infection of HeLa cells with encephalomyocarditis virus (a cardiovirus) was not accompanied by full-fledged apoptosis (although the activation of caspases was detected late in infection) but rather elicited a strong antiapoptotic state, as evidenced by the resistance of infected cells to viral and nonviral apoptosis inducers. The development of the antiapoptotic state appeared to depend on a function(s) of the viral leader (L) protein, since its mutational inactivation resulted in the efflux of cytochrome
c
from mitochondria, the early activation of caspases, and the appearance of morphological and biochemical signs of apoptosis in a significant proportion of infected cells. Infection with both wild-type and L-deficient viruses induced the fragmentation of mitochondria, which in the former case was not accompanied with cytochrome
c
efflux. Although the exact nature of the antiapoptotic function(s) of cardioviruses remains obscure, our results suggested that it includes previously undescribed mechanisms operating upstream and possibly downstream of the mitochondrial level, and that L is involved in the control of these mechanisms. We propose that cardiovirus L belongs to a class of viral proteins, dubbed here security proteins, whose roles consist solely, or largely, in counteracting host antidefenses. Unrelated L proteins of other picornaviruses as well as their highly variable 2A proteins also may be security proteins. These proteins appear to be independent acquisitions in the evolution of picornaviruses, implying multiple cases of functional (though not structural) convergence.
Variation in Antagonism of the Interferon Response to Rotavirus NSP1 Results in Differential Infectivity in Mouse Embryonic Fibroblasts
Authors: Feng N. , Sen A. , Nguyen H. , Vo P. , Hoshino Y. , Deal E. M. , Greenberg H. B.
Published: May 2009

Rotavirus NSP1 has been shown to function as an E3 ubiquitin ligase that mediates proteasome-dependent degradation of interferon (IFN) regulatory factors (IRF), including IRF3, -5, and -7, and suppresses the cellular type I IFN response. However, the effect of rotavirus NSP1 on viral replication is not well defined. Prior studies used genetic analysis of selected reassortants to link NSP1 with host range restriction in the mouse, suggesting that homologous and heterologous rotaviruses might use their different abilities to antagonize the IFN response as the basis of their host tropisms. Using a mouse embryonic fibroblast (MEF) model, we demonstrate that heterologous bovine (UK and NCDV) and porcine (OSU) rotaviruses fail to effectively degrade cellular IRF3, resulting in IRF3 activation and beta IFN (IFN-β) secretion. As a consequence of this failure, replication of these viruses is severely restricted in IFN-competent wild-type, but not in IFN-deficient (IFN-α/β/γ receptor- or STAT1-deficient) MEFs. On the other hand, homologous murine rotaviruses (ETD or EHP) or the heterologous simian rotavirus (rhesus rotavirus [RRV]) efficiently degrade cellular IRF3, diminish IRF3 activation and IFN-β secretion and are not replication restricted in wild-type MEFs. Genetic reassortant analysis between UK and RRV maps the distinctive phenotypes of IFN antagonism and growth restriction in wild-type MEFs to NSP1. Therefore, there is a direct relationship between the replication efficiencies of different rotavirus strains in MEFs and strain-related variations in NSP1-mediated antagonism of the type I IFN response.
Finger Domain Mutation Affects Enzyme Activity, DNA Replication Efficiency, and Fidelity of an Exonuclease-Deficient DNA Polymerase of Herpes Simplex Virus Type 1
Authors: Tian Wang , Hwang Ying T. , Lu Qiangsheng , Hwang Charles B. C.
Published: May 2009

The catalytic subunit of herpes simplex virus DNA polymerase (Pol), a member of the B family polymerases, possesses both polymerase and exonuclease activities. We previously demonstrated that a recombinant virus (YD12) containing a double mutation within conserved exonuclease motif III of the Pol was highly mutagenic and rapidly evolved to contain an additional leucine-to-phenylalanine mutation at residue 774 (L774F), which is located within the finger subdomain of the polymerase domain. We further demonstrated that the recombinant L774F virus replicated DNA with increased fidelity and that the L774F mutant Pol exhibited altered enzyme kinetics and impaired polymerase activity to extension from mismatched primer termini. In this study, we demonstrated that addition of the L774F mutation to the YD12 Pol did not restore the exonuclease deficiency. However, the polymerase activity of the YD12 Pol to extension from mismatched primer termini and on the nucleotide incorporation pattern was altered upon addition of the L774F mutation. The L774F mutation-containing YD12 Pol also supported the growth of viral progeny and replicated DNA more efficiently and more accurately than did the YD12 Pol. Together, these studies demonstrate that a herpes simplex virus Pol mutant with a highly mutagenic ability can rapidly acquire additional mutations, which may be selected for their survival and outgrowth. Furthermore, the studies demonstrate that the polymerase activity of HSV-1 Pol on primer extension is influenced by sequence context and that herpes simplex virus type 1 Pol may dissociate more frequently at G·C sites during the polymerization reaction. The implications of the findings are discussed.
Evolution of the factor of safety following excavation in clay
Authors: L’Heureux J. S. , Leroueil S. , Laflamme J. F.
Published: May 2009

Numerical analyses have been performed to study the evolution of the factor of safety following the excavation of a cut in clay. The analyses consider variable thickness of the clayey soil deposit under the excavation. The results show that, for a given clayey soil, there is a relation between the time for full dissipation of excess pore-water pressure from the soil mass following the excavation and the geometry of the cut (Htot/Hexc). The analytical results agree reasonably well with pore pressure measurements made in excavations in clay deposits from eastern Canada. This suggests that time to reach full pore pressure equilibration following the excavation of a cut in homogenous clayey soil deposits can be predicted when knowledge of the coefficient of swelling–consolidation is available. Lastly, results obtained in the present study show that 50% of the difference between the short- and long-term factors of safety may be lost at values as low as about 8% of the time to reach equilibration of pore pressures. This means that the time during which one can rely on the short-term strength of the clayey soil following the excavation may be relatively short, especially for soft clays.
Modified state-surface approach to the study of unsaturated soil behavior. Part I: Basic concept
Authors: Zhang Xiong , Lytton Robert L.
Published: May 2009

The traditional state-surface approach to the study of unsaturated soil behavior is becoming much less popular these days, as it uses unique constitutive surfaces to represent unsaturated soil behavior. This approach is essentially a nonlinear elastic formation and cannot be used to explain complex stress-path dependency for unsaturated soils. In this paper, a modified state-surface approach (MSSA) is proposed to represent unsaturated soil behavior under isotropic stress conditions in which a conventional void-ratio state surface is considered to be made up of an elastic surface and a plastic hardening surface. The plastic hardening surface remains stationary at all times, whereas the elastic surface remains unchanged when the soil experiences elastic deformation and moves downward when there is plastic hardening occurrence. Using the MSSA, the loading–collapse (LC) and the suction increase (SI) yield curves in the Barcelona basic model (BBM) are derived. The prediction of three typical cases of soils under isotropic conditions and experimental results using the proposed approach confirmed its feasibility, simplicity, and potential for the study of unsaturated soil behavior.
Kinematic response analysis of piled foundations under seismic excitation
Authors: Maiorano Rosa Maria Stefania , de Sanctis Luca , Aversa Stefano , Mandolini Alessandro
Published: May 2009

This paper presents the results of an extensive parametric study on single piles and pile groups embedded in a two-layer subsoil profile, and is aimed to evaluate kinematic bending moments developing during earthquakes. A quasi three-dimensional finite element program has been used to perform dynamic analyses in the time domain. Piles have been considered as elastic beams, while the soil has been modelled using a linear elastic constitutive model. The aims of the paper are: (i) to evaluate kinematic bending moments in single piles and pile groups with dynamic analyses in the time domain, in different subsoil conditions; (ii) to review some existing design methods; (iii) to propose a simplified analysis procedure to evaluate maximum kinematic bending moments between two subsequent soil layers. The results of the dynamic analyses have shown that some of the simplified approaches provided in published literature tend to be conservative and can predict bending moments at the soil-layer interface with adequate accuracy only within certain depths of the soil layer interface. On the basis of the obtained results, a modified criterion to evaluate the transient peak bending moments at interfaces between layers is proposed.
Amplification of seismic accelerations at slope crests
Authors: Brennan A. J. , Madabhushi S. P.G.
Published: May 2009

Earthquake accelerations can cause many problems in sloping ground. One such problem is that accelerations are greatly amplified at the crest of slopes. This topographic amplification can lead to acceleration gradients along the ground surface, which could create tensile forces in long surface structures that extend between areas of different amplifications. This paper uses centrifuge modelling to demonstrate and quantify this as a problem for a particular slope configuration. A special brittle structure has been constructed to undergo damage in the presence of large differential accelerations. The structure is seen to connect the crest to the level ground behind the crest during an earthquake, reducing the amplitude of the crest motion at the expense of structural tension. Topographic amplification is shown to be a clear function of frequency, and is especially serious for loading frequencies above the natural frequency of the soil layer.
CLASSICAL EVOLUTION OF FRACTAL MEASURES GENERATED BY A SCALAR FIELD ON THE LATTICE
Authors: ANTONIOU N. G. , DIAKONOS F. K. , SARIDAKIS E. N. , TSOLIAS G. A.
Published: May 2009

We investigate the classical evolution of a ϕ4 scalar field theory, using in the initial state random field configurations possessing a fractal measure expressed by a noninteger mass dimension. These configurations resemble the equilibrium state of a critical scalar condensate. The measures of the initial fractal behavior vary in time following the mean field motion. We show that the remnants of the original fractal geometry survive and leave an imprint in the system time averaged observables, even for large times compared to the approximate oscillation period of the mean field, determined by the model parameters. This behavior becomes more transparent in the evolution of a deterministic Cantor-like scalar field configuration. We extend our study to the case of two interacting scalar fields, and we find qualitatively similar results. Therefore, our analysis indicates that the geometrical properties of a critical system initially at equilibrium could sustain for several periods of the field oscillations in the phase of nonequilibrium evolution.
WARM INFLATION MODEL BUILDING
Authors: BASTERO-GIL MAR , BERERA ARJUN
Published: May 2009

We review the main aspects of the warm inflation scenario, focusing on the inflationary dynamics and the predictions related to the primordial spectrum of perturbations, to be compared with the recent cosmological observations. We study in detail three different classes of inflationary models, chaotic, hybrid models and hilltop models, and discuss their embedding into supersymmetric models and the consequences for model building of the warm inflationary dynamics based on first principles calculations. Due to the extra friction term introduced in the inflaton background evolution generated by the dissipative dynamics, inflation can take place generically for smaller values of the field, and larger values of couplings and masses. When the dissipative dynamics dominates over the expansion, in the so-called strong dissipative regime, inflation proceeds with sub-Planckian inflaton values. Models can be naturally embedded into a supergravity framework, with SUGRA corrections suppressed by the Planck mass now under control, for a larger class of Kähler potentials. In particular, this provides a simpler solution to the "eta" problem in supersymmetric hybrid inflation, without restricting the Kähler potentials compatible with inflation. For chaotic models dissipation leads to a smaller prediction for the tensor-to-scalar ratio and a less tilted spectrum when compared to the cold inflation scenario. We find in particular that a small component of dissipation renders the quartic model now consistent with the current CMB data.
KALUZA–KLEIN BLACK HOLES WITH SQUASHED HORIZONS AND HAWKING–HOROWITZ MASS
Authors: SAITO MICHIYOSHI , NODA HUJIO , TASHIRO TSUTOMU
Published: May 2009

The mass of the Kaluza–Klein black holes is investigated by means of the thermodynamic potential and the Hawking–Horowitz mass. It is pointed out that the mass estimated from the thermodynamic potential agrees with the Hawking–Horowitz mass. The mass of the limiting cases of the Kaluza–Klein black holes is discussed.
MATTER-DENSITY DISTRIBUTION IN THREE-NUCLEON NUCLEI AND THEIR DIFFRACTIVE INTERACTION WITH HEAVY NUCLEI
Authors: BEREZHNOY YU. A. , KORDA V. YU. , GAKH A. G.
Published: May 2009

The nonrelativistic wave functions of3H and3He nuclei have been obtained on the basis of the experimentally measured charge form factors. The differential cross section of the elastic3He -nucleus scattering has been calculated with the help of the wave function derived. This cross section agrees with the experimental data on the elastic scattering of3He by90Zr ,120Sn , and208Pb nuclei at 130 and 217 MeV. The integrated cross sections of various processes of3H and3He interaction with heavy nuclei have also been calculated.
ROLE OF STATIC DEFORMATION AND COMPACT ORIENTATION OF TARGET NUCLEUS IN MEASURED FUSION, FUSION-FISSION AND CAPTURE CROSS-SECTIONS OF 244Pu+48Ca REACTION
Authors: GUPTA RAJ K. , NIYTI  , MANHAS MONIKA , HOFMANN SIGURD , GREINER WALTER
Published: May 2009

The dynamical cluster-decay model (DCM), with deformations and orientation degrees of freedom of the incoming nuclei and of outging fragments included, is used to study the excitation functions of the "equatorial" compact hot fusion reaction 244 Pu +48 Ca →292114* (compact orientation angle θc=90° for 244 Pu ). Considering the higher multipole deformations up to hexadecapole deformation β4 and configurations with "compact" orientation θc, the model is shown to give a good description of the measured individual light-particle decay channels σxn, here x=3, 4 and 5, and other decay channels, the fusion-fission σff and quasi-fission σqf (equivalently, capture σ cap ) with in one parameter fitting, the neck length ΔR. The quasi-fission is also considered as a cold process with an elongated "polar" configuration. The xn-channel cross-sections for collisions between nuclei with static deformations at their respective compact orientations are shown to be much more than for the case of the nuclei taken to be spherical, signifying the increase in fusion threshold for an intermediate hot fusion reaction to be associated with the static deformation of the target nucleus and its orientation at the point of collision in its path toward the (spherical) compound nucleus. The shell effects in both the potential and kinetic energy (the mass parameters) terms of the Hamiltonian are shown to be important. The free parameter ΔR of the model is shown to depend strongly on limiting angular momentum, which in turn depends on the use of sticking or non-sticking moment of inertia for angular momentum effects. For the sticking moment of inertia, the evaporation residue (neutron emission) is shown to occur almost promptly (largest ΔR), followed by the competing (hot/cold) quasi-fission and ending finally with fusion-fission of hot compound nucleus. Different ΔR's (equivalently, relative separations) for the three processes means to predict that the processes ER, ff and qf happen in different time-scales, in agreement with the indications of experiments.
QUARK MODEL WITH A REGULARIZED BREIT POTENTIAL
Authors: JIRIMUTU  , WANG HAI-JUN , ZHANG WEI-NING , WONG CHEUK-YIN
Published: May 2009

The Breit interaction contains terms that are singular in nature and cannot be used non-perturbatively for quark–antiquark bound state studies. We regularize the Breit interaction by subtraction such that the interaction is not singular at the origin but the intermediate and long-range parts of the interaction remain unchanged. With the regularized quark–antiquark potential and the confining potential, the solution of [Formula: see text] bound states are therefore stable possessing wave functions that can be used for future applications in other study of scattering and reaction problems.
SIMULATION OF SYMMETRIC NUCLEI AND THE ROLE OF PAULI POTENTIAL IN BINDING ENERGIES AND RADII
Authors: PÉREZ-GARCÍA M. ÁNGELES , TSUSHIMA K. , VALCARCE A.
Published: May 2009

It is shown that the use of a density-dependent effective Pauli potential together with a generic nucleon–nucleon interaction potential plays a crucial role to reproduce not only the binding energies but also the matter root mean square radii of medium mass range spin–isospin saturated nuclei. This study is performed with a semiclassical Monte Carlo many-body simulation within the context of a simplified nucleon–nucleon interaction to focus on the effect of the genuine correlations due to the fermionic nature of nucleons. The procedure obtained is rather robust and it does not depend on the detailed features of the nucleon–nucleon interaction. For nuclei below saturation the density dependence may be represented in terms either of the nucleon number, A, or the associated Fermi momenta. When testing the simulation procedure for idealized "infinite" symmetric nuclear matter within the corresponding range of densities, we find that, beyond the low particle number limit, finite size effects do not affect the Pauli potential strength parametrization.
Palaeoenvironmental significance of carbon- and oxygen-isotope stratigraphy of marine Triassic–Jurassic boundary sections in SW Britain
Authors: Korte Christoph , Hesselbo Stephen P. , Jenkyns Hugh C. , Rickaby Rosalind E.M. , Spötl Christoph
Published: May 2009

Carbon-isotope stratigraphy is a useful tool for stratigraphic correlation, especially for strata deposited during major perturbations of the carbon cycle that affected the marine, terrestrial and atmospheric reservoirs. For the Triassic–Jurassic boundary, effectively defined by a first-order mass extinction, major fluctuations in carbon-isotope values have been well documented, but these datasets have generally been derived from bulk-rock samples. Hence, the extent to which features of the isotopic curve reflect diagenetic alteration or changing proportions of constituent materials is unconstrained. Here, carbon- and oxygen-isotope data are presented from well-preserved oyster shells (
Liostrea
) comprising low-magnesium calcite, a mineral species relatively resistant to diagenetic alteration. Samples were obtained from Lavernock Point, Glamorgan, Wales, a coastal section close to a candidate stratotype for the base of the Jurassic at St Audrie's Bay, Somerset, England. The carbon-isotope signature from St Audrie's Bay, previously defined on the basis of analysis of bulk organic matter, is confirmed by our new data. Major features are (1) the upper part of an ’initial' negative isotope excursion in the lowest part of the section, followed by (2) a pronounced positive excursion, and (3) an extended ’main' negative isotope excursion in the highest part of the section. The data confirm that the carbon-isotope stratigraphy previously documented from bulk organic matter in SW England records the chemical composition of the contemporaneous seawater. Bulk carbonates sampled over the same interval near Lyme Regis, England, show similar trends to those from oyster calcite in the lower part of the study section, but there are more
13
C-depleted values up-section. These lower values probably result from an admixture of primary and diagenetic carbonate. Palaeotemperatures calculated from oxygen-isotope values from Lavernock Point oyster shells are relatively cool at the beginning of the positive carbon-isotope excursion, and increased by up to 10 °C during the main negative carbon-isotope excursion. The new results are compatible with the view that positive carbon-isotope excursions correspond to times of low atmospheric carbon dioxide content, whereas negative carbon-isotope excursions correspond to times of high atmospheric carbon dioxide content, as is also found to be the case during the Early Jurassic (Toarcian) Oceanic Anoxic Event. The Mg/Ca and Sr/Ca ratios and δ
18
O of investigated
Liostrea hisingeri
show no correlation, supporting data from modern bivalves that indicate that incorporation of Mg and Sr is controlled mainly by factors other than temperature.
Timing, relations and cause of plutonic and volcanic activity of the Siluro-Devonian post-collision magmatic episode in the Grampian Terrane, Scotland
Authors: Neilson J.C. , Kokelaar B.P. , Crowley Q.G.
Published: May 2009

Calc-alkaline magmatism in the Grampian Terrane started at
c
. 430 Ma, after subduction of the edge of continental Avalonia beneath Laurentia, and it then persisted for at least 22 Ma. Isotope dilution thermal ionization mass spectrometry U–Pb zircon dating yields 425.0 ± 0.7 Ma for the Lorn Lava Pile, 422.5 ± 0.5 Ma for Rannoch Moor Pluton, 419.6 ± 5.4 Ma for a fault-intrusion at Glencoe volcano, 417.9 ± 0.9 Ma for Clach Leathad Pluton in Glencoe, and, in the Etive Pluton, 414.9 ± 0.7 Ma for the Cruachan Intrusion and 408.0 ± 0.5 Ma for the Inner Starav Intrusion. The Etive Dyke Swarm was mostly emplaced during 418–414 Ma, forming part of the plumbing of a large volcano (≥2000 km
3
) that became intruded by the Etive Pluton and was subsequently removed by erosion. During the magmatism large volumes (thousands of km
3
) of high Ba–Sr andesite and dacite were erupted repeatedly, but were mostly removed by contemporaneous uplift and erosion. This volcanic counterpart to the ’Newer Granite' plutons has not previously been fully recognized. The intermediate magmas forming both plutons and volcanoes originated mainly by partial melting of heterogeneous mafic to intermediate lowermost crust that had high Ba–Sr derived from previous melting of large ion lithophile element (LILE)-enriched mantle, possibly at
c
. 1.8 Ga. This crustal recycling was induced by heat and volatiles from underplated small-degree melts of LILE- and light REE-enriched lithospheric mantle (appinite–lamprophyre magmas). The post-collision magmatism and uplift resulted from breakoff of subducted oceanic lithosphere and consequent rise of asthenosphere.

Supplementary material:

Geochronological methods, tabulated data and additional figures are available at
http://www.geolsoc.org.uk/SUP18343
.
Detrital zircon provenance and Ordovician terrane amalgamation, western Ireland
Authors: McConnell Brian , Riggs Nancy , Crowley Quentin G.
Published: May 2009

Detrital zircon analysis of sandstones interbedded with
c
. 464 Ma ignimbrites in the lower Mweelrea Formation of the South Mayo Trough, western Ireland, suggests Ordovician source-rock provenance that corresponds to two distinct volcanic-arc phases on the Laurentian margin. East-derived sandstones contain a suite of zircons with a mean age of
c
. 487 Ma that suggests derivation from the Cambrian to early Ordovician Baie Verte Oceanic Tract arc–ophiolite complex, locally represented by the Lough Nafooey arc rocks and the Clew Bay Complex. Zircons from south-derived sandstones within the Bunnacunneen conglomerate fan have average ages of
c
. 467–474 Ma, and correspond to the Notre Dame arc and locally the Connemara metagabbro and orthogneiss suite. Granite clasts in the Bunnacunneen conglomerate are similar to the Connemara orthogneiss suite, in terms of both their geochemistry and their age (
c
. 471 Ma). The southerly derived sedimentary strata also include Archaean and Proterozoic zircon age spectra consistent with a Dalradian source. A southern provenance from the Notre Dame arc and Dalradian rocks suggests that the Connemara terrane lay to the south of the South Mayo Trough during middle Llanvirn times, from at least 464 Ma.

Supplementary material:

U–Pb laser ablation multicollector inductively coupled plasma mass spectrometry data for detrital zircons and details of analytical methods for U–Pb LA-MC-ICPMS and U–Pb isotope dilution thermal ionization mass spectrometry analyses are available at
http://www.geolsoc.org.uk/SUP18331
.
Triassic continental rifting of Pangaea: direct evidence from the Alpujarride carbonates, Betic Cordillera, SE Spain
Authors: MARTIN-ROJAS I. , SOMMA R. , DELGADO F. , ESTéVEZ A. , IANNACE A. , PERRONE V. , ZAMPARELLI V.
Published: May 2009

Evidence is presented for Triassic rift-related palaeo-structures from the Alpujarride Complex carbonates of the Betic Cordillera, SE Spain. Direct evidence of synsedimentary extensional tectonics is provided by macro- to meso-scale normal faults overstepped by younger strata. Most faults define domino-like horst and graben structures. The faults are associated with an expanded synrift sedimentary prism in which soft-sediment deformation, gravity-flow deposits and unconformities are widely developed. Syntectonic mafic igneous intrusions also occur. The age of this phase of extension is constrained as Ladinian–Carnian (
c
. 237–216 Ma). From a palaeogeographical standpoint, the thick Triassic carbonates of the Betic Internal Zone, together with comparable successions in Northern Calabria (Southern Apennines), occupied a belt with elevated subsidence connecting the Neo-Tethys to the east with the eastern North American intracontinental rift system to the west. Their carbonate facies, intermediate between classical Alpine- and Germanic-type Triassic facies, recorded the main episodes of rifting affecting Central Pangaea.
Arc–continent collision and the formation of continental crust: a new geochemical and isotopic record from the Ordovician Tyrone Igneous Complex, Ireland
Authors: Draut Amy E. , Clift Peter D. , Amato Jeffrey M. , Blusztajn Jerzy , Schouten Hans
Published: May 2009

Collisions between oceanic island-arc terranes and passive continental margins are thought to have been important in the formation of continental crust throughout much of Earth's history. Magmatic evolution during this stage of the plate-tectonic cycle is evident in several areas of the Ordovician Grampian–Taconic orogen, as we demonstrate in the first detailed geochemical study of the Tyrone Igneous Complex, Ireland. New U–Pb zircon dating yields ages of 493 ± 2 Ma from a primitive mafic intrusion, indicating intra-oceanic subduction in Tremadoc time, and 475 ± 10 Ma from a light rare earth element (LREE)-enriched tonalite intrusion that incorporated Laurentian continental material by early Arenig time (Early Ordovician, Stage 2) during arc–continent collision. Notably, LREE enrichment in volcanism and silicic intrusions of the Tyrone Igneous Complex exceeds that of average Dalradian (Laurentian) continental material that would have been thrust under the colliding forearc and potentially recycled into arc magmatism. This implies that crystal fractionation, in addition to magmatic mixing and assimilation, was important to the formation of new crust in the Grampian–Taconic orogeny. Because similar super-enrichment of orogenic melts occurred elsewhere in the Caledonides in the British Isles and Newfoundland, the addition of new, highly enriched melt to this accreted arc terrane was apparently widespread spatially and temporally. Such super-enrichment of magmatism, especially if accompanied by loss of corresponding lower crustal residues, supports the theory that arc–continent collision plays an important role in altering bulk crustal composition toward typical values for ancient continental crust.
New evidence concerning the age and biotic effects of the Chicxulub impact in NE Mexico
Authors: Keller Gerta , Adatte Thierry , Juez Alfonso Pardo , Lopez-Oliva Jose G.
Published: May 2009

In the 1990s the Chicxulub impact was linked to the K–T boundary by impact spherules at the base of a sandstone complex that was interpreted as an impact-generated tsunami deposit. Since that time a preponderance of evidence has failed to support this interpretation, revealing long-term deposition of the sandstone complex, the K–T boundary above it and the primary impact spherule ejecta interbedded in Late Maastrichtian marls below. Based on evidence from Mexico and Texas we suggested that the Chicxulub impact predates the K–T boundary. Impact-tsunami proponents have challenged this evidence largely on the basis that the stratigraphically lower spherule layer in Mexico represents slumps and widespread tectonic disturbance, although no such evidence has been presented. The decades-old controversy over the cause of the K–T mass extinction will never achieve consensus, but careful documentation of results that are reproducible and verifiable will uncover what really happened at the end of the Crectaceous. This study takes an important step in that direction by showing (1) that the stratigraphically older spherule layer from El Peñon, NE Mexico, represents the primary Chicxulub impact spherule ejecta in tectonically undisturbed sediments and (2) that this impact caused no species extinctions.
Downregulation of cilia-localized Il-6Rα by 17β-estradiol in mouse and human fallopian tubes
Authors: Shao Ruijin , Nutu Magdalena , Karlsson-Lindahl Linda , Benrick Anna , Weijdegård Birgitta , Lager Susanne , Egecioglu Emil , Fernandez-Rodriguez Julia , Gemzell-Danielsson Kristina , Ohlsson Claes , Jansson John-Olov , Billig Håkan
Published: May 2009

The action of interleukin-6 (IL-6) impacts female reproduction. Although IL-6 was recently shown to inhibit cilia activity in human fallopian tubes in vitro, the molecular mechanisms underlying IL-6 signaling to tubal function remain elusive. Here, we investigate the cellular localization, regulation, and possible function of two IL-6 receptors (IL-6Rα and gp130) in mouse and human fallopian tubes in vivo. We show that IL-6Rα is restricted to the cilia of epithelial cells in both mouse and human fallopian tubes. Exogenous 17β-estradiol (E2), but not progesterone (P4), causes a time-dependent decrease in IL-6Rα expression, which is blocked by the estrogen receptor (ER) antagonist ICI-182,780. Exposure of different ER-selective agonists propyl-(1H)-pyrazole-1,3,5-triyl-trisphenol or 2,3-bis-(4-hydroxyphenyl)-propionitrile demonstrated an ER subtype-specific regulation of IL-6Rα in mouse fallopian tubes. In contrast to IL-6Rα, gp130 was detected in tubal epithelial cells in mice but not in humans. In humans, gp130 was found in the muscle cells and was decreased in the periovulatory and luteal phases during the reproductive cycles, indicating a species-specific expression and regulation of gp130 in the fallopian tube. Expression of tubal IL-6Rα and gp130 in IL-6 knockout mice was found to be normal; however, E2 treatment increased IL-6Rα, but not gp130, in IL-6 knockout mice when compared with wild-type mice. Furthermore, expression levels of IL-6Rα, but not gp130, decreased in parallel with estrogenic accelerated oocyte-cumulus complex (OCC) transport in mouse fallopian tubes. Our findings open the posibility that cilia-specific IL-6Rα may play a role in the regulation of OCC transport and suggest an estrogen-regulatory pathway of IL-6Rα in the fallopian tube.
The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway
Authors: Levecque Clotilde , Velayos-Baeza Antonio , Holloway Zoe G. , Monaco Anthony P.
Published: May 2009

Recently, genetic studies have implicated KIAA0319 in developmental dyslexia, the most common of the childhood learning disorders. The first functional data indicated that the KIAA0319 protein is expressed on the plasma membrane and may be involved in neuronal migration. Further analysis of the subcellular distribution of the overexpressed protein in mammalian cells indicates that KIAA0319 can colocalize with the early endosomal marker early endosome antigen 1 (EEA1) in large intracellular vesicles, suggesting that it is endocytosed. Antibody internalization assays with full-length KIAA0319 and deletion constructs confirmed that KIAA0319 is internalized and showed the importance of the cytoplasmic juxtamembranal region in this process. The present study has identified the medium subunit (μ2) of adaptor protein 2 (AP-2) as a binding partner of KIAA0319 in a yeast two-hybrid screen. Using Rab5 mutants or depletion of the μ-subunit of AP-2 or clathrin heavy chain by RNA interference, we demonstrate that KIAA0319 follows a clathrin-mediated endocytic pathway. We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. These results suggest the surface expression of KIAA0319 is regulated by endocytosis, supporting the idea that the internalization and recycling of the protein may be involved in fine tuning its role in neuronal migration.
AMP-activated protein kinase phosphorylation of the R domain inhibits PKA stimulation of CFTR
Authors: King J Darwin , Fitch Adam C. , Lee Jeffrey K. , McCane Jill E. , Mak Don-On Daniel , Foskett J. Kevin , Hallows Kenneth R.
Published: May 2009

The metabolic sensor AMP-activated protein kinase (AMPK) has emerged as an important link between cellular metabolic status and ion transport activity. We previously found that AMPK binds to and phosphorylates CFTR in vitro and inhibits PKA-dependent stimulation of CFTR channel gating in Calu-3 bronchial serous gland epithelial cells. To further characterize the mechanism of AMPK-dependent regulation of CFTR, whole cell patch-clamp measurements were performed with PKA activation in Calu-3 cells expressing either constitutively active or dominant-negative AMPK mutants (AMPK-CA or AMPK-DN). Baseline CFTR conductance in cells expressing AMPK-DN was substantially greater than controls, suggesting that tonic AMPK activity in these cells inhibits CFTR under basal conditions. Although baseline CFTR conductance in cells expressing AMPK-CA was comparable to that of controls, PKA stimulation of CFTR was completely blocked in AMPK-CA-expressing cells, suggesting that AMPK activation renders CFTR resistant to PKA activation in vivo. Phosphorylation studies of CFTR in human embryonic kidney-293 cells using tetracycline-inducible expression of AMPK-DN demonstrated AMPK-dependent phosphorylation of CFTR in vivo. However, AMPK activity modulation had no effect on CFTR in vivo phosphorylation in response to graded doses of PKA or PKC agonists. Thus, AMPK-dependent CFTR phosphorylation renders the channel resistant to activation by PKA and PKC without preventing phosphorylation by these kinases. We found that Ser768, a CFTR R domain residue considered to be an inhibitory PKA site, is the dominant site of AMPK phosphorylation in vitro. Ser-to-Ala mutation at this site enhanced baseline CFTR activity and rendered CFTR resistant to inhibition by AMPK, suggesting that AMPK phosphorylation at Ser768 is required for its inhibition of CFTR. In summary, our findings indicate that AMPK-dependent phosphorylation of CFTR inhibits CFTR activation by PKA, thereby tuning the PKA-responsiveness of CFTR to metabolic and other stresses in the cell.
Balance point characterization of interstitial fluid volume regulation
Authors: Dongaonkar R. M. , Laine G. A. , Stewart R. H. , Quick C. M.
Published: May 2009

The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure ( P i) and protein concentrations ( C i) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P i and C i as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P i and C i arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P i and C i result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P i is unaffected by interstitial compliance. These simple algebraic solutions predict P i and C i that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.
Social cues from conspecifics alter electrical activity of gonadotropin-releasing hormone neurons in the terminal nerve via visual signals
Authors: Ramakrishnan Siddharth , Wayne Nancy L.
Published: May 2009

There are multiple populations of gonadotropin-releasing hormone (GnRH) neurons in the brains of vertebrates. The population located in the hypothalamus/preoptic area is the best studied and is known to ultimately control reproduction. Teleost fish have an additional population of GnRH neurons in the terminal nerve (TN) associated with the olfactory bulbs, the physiological function of which is still unclear. Anatomical and physiological studies provide evidence that TN-GnRH neurons have extensive projections in the brain and modulate neuronal activity. Although there is anatomical evidence that the TN receives olfactory and optic sensory inputs, it is not known if sensory information is transmitted to TN-GnRH neurons to modulate their activity. In the present study, we tested the hypothesis that social cues from conspecifics modulate electrical activity of TN-GnRH neurons from the intact brain of female medaka fish ( Oryzias latipes). We further investigated the potential roles of chemosensory and visual signals in mediating the social cue response. We used a transgenic line of medaka with TN-GnRH neurons genetically tagged with green fluorescent protein, allowing visualization of specific neurons for whole-cell current clamp electrophysiology. We demonstrated that 24-h exposure to male visual and chemosensory cues suppressed the electrical activity of female TN-GnRH neurons compared with exposure to other females. Chemosensory cues alone were insufficient to induce this social cue response. However, visual cues alone replicated the “combined” social cue response. These findings support our hypothesis that sensory signals—and specifically, visual social cues—modulate electrical activity of TN-GnRH neurons.
Increased prolyl 4-hydroxylase expression and differential regulation of hypoxia-inducible factors in the aged rat brain
Authors: Ndubuizu Obinna I. , Chavez Juan C. , LaManna Joseph C.
Published: May 2009

Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors that mediate the adaptive response of mammalian cells and tissues to changes in tissue oxygenation. In the present study, we show an age-dependent decline in cortical HIF-1α accumulation and activation of HIF target genes in response to hypoxia. This inducible response is significantly attenuated in the cerebral cortex of 18-mo-old Fischer 344 rat yet virtually absent in the cerebral cortex of 24-mo-old Fischer 344 rat. This attenuated HIF-1α response had no effect on mRNA upregulation of HIF-independent genes in the aged cortex. We have provided evidence that this absent HIF-1α response is directly correlated with an increase in the expression of the HIF regulatory enzyme, prolyl 4-hydroxylase (PHD). In addition, our study shows that cortical HIF-2α expression in senescent normoxic controls is also significantly greater than that of younger normoxic controls, despite no difference in HIF-2α mRNA levels. The posttranslational regulation of HIF-2α under normoxic conditions seems to be attenuated in the aged rat brain, which is an in vivo demonstration of differential regulation of HIF-1α and HIF-2α.
Effect of acute and chronic caloric restriction and metabolic glucoprivation on spontaneous physical activity in obesity-prone and obesity-resistant rats
Authors: Teske J. A. , Kotz C. M.
Published: May 2009

Caloric restriction (CR) and metabolic glucoprivation affect spontaneous physical activity (SPA), but it's unknown whether these treatments similarly affect SPA in selectively bred obesity-prone (OP) and -resistant (OR) rats. OR rats have greater basal SPA and are more responsive to treatments that modulate SPA, such as orexin A administration. We hypothesized that OR rats would be more sensitive to other treatments modulating SPA. To test this, continuous 24-h SPA was measured before and during acute (24 h) and chronic (8 wk) CR in OR, OP, and Sprague-Dawley rats. Pharmacological glucoprivation was produced by injection of 2-deoxyglucose (2-DG), and SPA was measured 5 h postinjection. Acute CR increased SPA in all groups; however, the effect was dependent on the index of SPA and time interval during the 24-h time period. In contrast to OR rats, chronic CR increased distance traveled, ambulatory episodes, and time spent in ambulation and stereotypy during the time interval preceding anticipation of food in OP and Sprague-Dawley rats. Although the effects of 2-DG treatment on SPA were minimal, OR rats had significantly greater SPA than OP and Sprague-Dawley rats independent of treatment. That chronic CR failed to result in significant changes in SPA in OR rats suggests that these rats may be especially unresponsive to treatments modulating feeding. This insensitivity coupled with elevated basal SPA levels may in part mediate phenotypic traits of lean rats.