bluuebunny/crossref_metadata_2025 huggingface dataset:
Are the Wall Street Analyst Rankings Popularity Contests?
Authors: Emery Douglas R. , Li Xi
Published: June 2009

We investigate the (sell-side) analyst rankings ofInstitutional Investor(I/I) andThe Wall Street Journal(WSJ), using data from 1993–2005. We find that factors with a primary component of recognition are the most important determinants of the rankings, although performance measures are statistically significant determinants in some cases. The single exception to this finding is with existing WSJ stars, where industry-adjusted investment-recommendation performance is theonlysignificant determinant of repeating as a star. Further, in the year after becoming stars, the recommendations of WSJ stars are significantly worse than those of nonstars; and the recommendations and earnings forecasts of I/I stars, as well as the earnings forecasts of WSJ stars, are not significantly different from those of nonstars. We conclude that these rankings are largely “popularity contests.”
Testing Theories of Capital Structure and Estimating the Speed of Adjustment
Authors: Huang Rongbing , Ritter Jay R.
Published: June 2009

This paper examines time-series patterns of external financing decisions and shows that publicly traded U.S. firms fund a much larger proportion of their financing deficit with external equity when the cost of equity capital is low. The historical values of the cost of equity capital have long-lasting effects on firms’ capital structures through their influence on firms’ historical financing decisions. We also introduce a new econometric technique to deal with biases in estimates of the speed of adjustment toward target leverage. We find that firms adjust toward target leverage at a moderate speed, with a half-life of 3.7 years for book leverage, even after controlling for the traditional determinants of capital structure and firm fixed effects.
Money and the C-CAPM
Authors: Balvers Ronald J. , Huang Dayong
Published: June 2009

We consider asset pricing in a monetary economy where liquid assets are held to lower transaction costs. The ensuing model extends the capital asset pricing model (CAPM) and the consumption CAPM by deriving real money growth as an additional factor determining returns. Empirically, the two model versions compare favorably to other theoretical asset pricing models along several dimensions, supporting the traditional intertemporal asset pricing perspective. A value premium arises because value firms are sensitive to liquidity shocks but growth firms are not. Although no alternative factor drives out the money growth factor, the conditioning CAY factors of Lettau and Ludvigson (2001b) add explanatory power.
Hedge Funds for Retail Investors? An Examination of Hedged Mutual Funds
Authors: Agarwal Vikas , Boyson Nicole M. , Naik Narayan Y.
Published: June 2009

Recently, there has been rapid growth in the assets managed by “hedged mutual funds”—mutual funds mimicking hedge fund strategies. We examine the performance of these funds relative to hedge funds and traditional mutual funds. Despite using similar trading strategies, hedged mutual funds underperform hedge funds. We attribute this finding to hedge funds’ lighter regulation and better incentives. Conversely, hedged mutual funds outperform traditional mutual funds. Notably, this superior performance is driven by managers with experience implementing hedge fund strategies. Our findings have implications for investors seeking hedge-fund-like payoffs at a lower cost and within the comfort of a regulated environment.
Distribution of Diplolaimella and Diplolaimelloides species from Patagonian lagoons and coastal waters (Nematoda: Monhysteridae), Chubut and Santa Cruz provinces (Argentina)
Authors: Pastor de Ward Catalina T. , Lo Russo Virginia
Published: June 2009

This paper focuses on Diplolaimella and Diplolaimelloides two very cosmopolitan genera inhabiting lotic freshwater to salty water inland, groundwater and coastal waters systems, providing a review of their taxonomy with new keys, and their distribution on the east coast of Patagonia and inland Patagonia. Two new species belonging to the genus Diplolaimelloides of the family Monhysteridae are described from Patagonian salty lagoons and coastal areas, and the Chubut and Santa Cruz provinces of Argentina: Diplolaimelloides tehuelchus sp. nov. has four bursal and three postcloacal papillae, short gubernaculum, and spicules longer than 50 μm; it has been found in Patagonian salty lagoons and in high coastal salt marsh areas. Diplolaimelloides warwicki sp. nov. is characterized by the angular shape of the spicules and the long gubernaculum. Diplolaimella ocellata is recorded for the first time in Patagonian salty lagoons and new localities in coastal waters are recorded for Diplolaimella gerlachi Pastor de Ward, 1984.
Molecular mechanisms of endothelial hyperpermeability: implications in inflammation
Authors: Kumar Puneet , Shen Qiang , Pivetti Christopher D. , Lee Eugene S. , Wu Mack H. , Yuan Sarah Y.
Published: June 2009

Endothelial hyperpermeability is a significant problem in vascular inflammation associated with trauma, ischaemia–reperfusion injury, sepsis, adult respiratory distress syndrome, diabetes, thrombosis and cancer. An important mechanism underlying this process is increased paracellular leakage of plasma fluid and protein. Inflammatory stimuli such as histamine, thrombin, vascular endothelial growth factor and activated neutrophils can cause dissociation of cell–cell junctions between endothelial cells as well as cytoskeleton contraction, leading to a widened intercellular space that facilitates transendothelial flux. Such structural changes initiate with agonist–receptor binding, followed by activation of intracellular signalling molecules including calcium, protein kinase C, tyrosine kinases, myosin light chain kinase, and small Rho-GTPases; these kinases and GTPases then phosphorylate or alter the conformation of different subcellular components that control cell–cell adhesion, resulting in paracellular hypermeability. Targeting key signalling molecules that mediate endothelial-junction–cytoskeleton dissociation demonstrates a therapeutic potential to improve vascular barrier function during inflammatory injury.
Iron limitation of the postbloom phytoplankton communities in the Iceland Basin
Authors: Nielsdóttir Maria C. , Moore Christopher Mark , Sanders Richard , Hinz Daria J. , Achterberg Eric P.
Published: June 2009

Measurements performed on a cruise within the central Iceland Basin in the high‐latitude (>55°N) North Atlantic Ocean during late July to early September 2007 indicated that the concentration of dissolved iron (dFe) in surface waters was very low, with an average of 0.093 (<0.010–0.218, n = 43) nM, while nitrate concentrations ranged from 2 to 5 μM and in situ chlorophyll concentrations ranged from 0.2 to 0.4 mg m−3. In vitro iron addition experiments demonstrated increased photosynthetic efficiencies (Fv/Fm) and enhanced chlorophyll accumulation in treatments amended with iron when compared to controls. Enhanced net growth rates for a number of phytoplankton taxa including the coccolithophore Emiliania huxleyi were also observed following iron addition. These results provide strong evidence that iron limitation within the postspring bloom phytoplankton community contributes to the observed residual macronutrient pool during summer. Low atmospheric iron supply and suboptimal Fe:N ratios in winter overturned deep water are suggested to result in the formation of this seasonal high‐nutrient, low‐chlorophyll (HNLC) condition, representing an inefficiency of the biological (soft tissue) carbon pump in the region.
Primitive shoshonites from Fiji: Geochemistry and source components
Authors: Leslie Roman A. J. , Danyushevsky Leonid V. , Crawford Anthony J. , Verbeeten Alicia C.
Published: June 2009

The eruption of shoshonitic magmas in Fiji during the Late Miocene‐Pliocene (5.5–3 Ma) from 11 main volcanic centers along three broad ENE and NNW trending lineaments coincides with well‐developed spreading in the North Fiji and Lau back‐arc basins and maximum rotation of the Fiji Platform. The most mafic shoshonitic lavas (absarokites) range from 8.4 to 15.2 wt % MgO and are variably clinopyroxene + olivine‐phyric. Fijian shoshonitic suites display a range of enrichment in large ion lithophile elements, Th, U, and P relative to rare earth elements and high field strength elements (HFSE), reflecting variable contributions by the subarc mantle source and subduction‐related components. The subarc mantle source component controls HFSE, heavy rare earth elements, to a lesser degree light rare earth elements (LREE), and most importantly the sensitivity of the mantle source with respect to subduction‐related enrichment processes, whereas Pb, K, Sr, Ba, Rb, Th, U, P2O5, and LREE are contributed by hydrous or supercritical fluid(s) and sediment melts that are added to the subarc mantle. Fijian shoshonitic suites situated ∼150 km apart display a wide range of Nb/Yb (0.3–4.3), implying that there is significant spatial heterogeneity in the sub‐Fijian mantle with respect to the ambient fertility of mantle sources independent of subduction‐related enrichment. The range in incompatible element ratios (e.g., Th/Nb, U/Nb, Ba/Th, Ba/La, P/Nd, and Ce/Pb) displayed by Fijian shoshonitic suites cannot reflect addition of the same subduction‐derived component to variably enriched subarc mantle sources. Differences in the relative amount of fluid versus sediment melt and potentially the composition of the subducted sediment are required to explain the data. The greater overall subduction‐related enrichment in Fijian shoshonites relative to calk‐alkaline and tholeiitic arc magmas is attributed to a melt generation process involving low‐degree partial melting of metsomatized subarc lithosphere in contrast to magmas associated with active or steady state arcs, where higher degrees of melting occur in response to volatile fluxing of the mantle wedge. Shoshonitic magma generation occurs in linear zones during extension of the arc lithosphere preceding arc fragmentation and establishment of back‐arc spreading centers.
Dynamic evolution of energetic outer zone electrons due to whistler mode chorus based on a realistic density model
Authors: Su Zhenpeng , Zheng Huinan , Wang Shui
Published: June 2009

In this paper, we construct a three‐dimensional realistic plasma trough electron density model (particularly a field‐aligned density variation model) following the previous works. We examine the evolution of energetic electrons in the outer radiation belt at locations L = 4.5 and L = 6.0 with and without incorporation of electron density variation along magnetic field lines. Numerical calculation shows that neglect of the density variation along magnetic field lines generally results in overestimates of relativistic electrons phase space density (PSD) due to an underestimate of the plasma parameter fpe/fce along the field lines. Particularly, the overestimates of PSDs due to neglecting field‐aligned density variation are found to increase with kinetic energy Ek and L increasing. At L = 4.5, maximum overestimates of PSDs over all the pitch angles are found to be by a factor of ∼1.5, 2.1, and 4.7 for energies of 1.0, 2.0, and 3.0 MeV in 2 days. At L = 6.0, maximum overestimates of PSDs over all the pitch angles are found to be by a factor of ∼1.5, 18, and 47 for energies of 1.0, 2.0, and 3.0 MeV in 2 days. This result suggests that incorporation of a field‐aligned density variation model is very important to evaluate cyclotron wave‐particle interaction in the outer radiation belt.
Pore pressure development beneath the décollement at the Nankai subduction zone: Implications for plate boundary fault strength and sediment dewatering
Authors: Skarbek Robert M. , Saffer Demian M.
Published: June 2009

Despite its importance for plate boundary fault processes, quantitative constraints on pore pressure are rare, especially within fault zones. Here, we combine laboratory permeability measurements from core samples with a model of loading and pore pressure diffusion to investigate pore fluid pressure evolution within underthrust sediment at the Nankai subduction zone. Independent estimates of pore pressure to ∼20 km from the trench, combined with permeability measurements conducted over a wide range of effective stresses and porosities, allow us to reliably simulate pore pressure development to greater depths than in previous studies and to directly quantify pore pressure within the plate boundary fault zone itself, which acts as the upper boundary of the underthrusting section. Our results suggest that the time‐averaged excess pore pressure (P*) along the décollement ranges from 1.7–2.1 MPa at the trench to 30.2–35.9 MPa by 40 km landward, corresponding to pore pressure ratios of λb = 0.68–0.77. For friction coefficients of 0.30–0.40, the resulting shear strength along the décollement remains <12 MPa over this region. When noncohesive critical taper theory is applied using these values, the required pore pressure ratios within the wedge are near hydrostatic (λw = 0.41–0.59), implying either that pore pressure throughout the wedge is low or that the fault slips only during transient pulses of elevated pore pressure. In addition, simulated downward migration of minima in effective stress during drainage provides a quantitative explanation for down stepping of the décollement that is consistent with observations at Nankai.
Regional and local background ozone in Houston during Texas Air Quality Study 2006
Authors: Langford A. O. , Senff C. J. , Banta R. M. , Hardesty R. M. , Alvarez R. J. , Sandberg Scott P. , Darby Lisa S.
Published: June 2009

Principal Component Analysis (PCA) is used to isolate the common modes of behavior in the daily maximum 8‐h average ozone mixing ratios measured at 30 Continuous Ambient Monitoring Stations in the Houston‐Galveston‐Brazoria area during the Second Texas Air Quality Study field intensive (1 August to 15 October 2006). Three principal components suffice to explain 93% of the total variance. Nearly 84% is explained by the first component, which is attributed to changes in the “regional background” determined primarily by the large‐scale winds. The second component (6%) is attributed to changes in the “local background,” that is, ozone photochemically produced in the Houston area and spatially and temporally averaged by local circulations. Finally, the third component (3.5%) is attributed to short‐lived plumes containing high ozone originating from industrial areas along Galveston Bay and the Houston Ship Channel. Regional background ozone concentrations derived using the first component compare well with mean ozone concentrations measured above the Gulf of Mexico by the tunable profiler for aerosols and ozone lidar aboard the NOAA Twin Otter. The PCA regional background values also agree well with background values derived using the lowest daily 8‐h maximum method of Nielsen‐Gammon et al. (2005), provided the Galveston Airport data (C34) are omitted from that analysis. The differences found when Galveston is included are caused by the sea breeze, which depresses ozone at Galveston relative to sites further inland. PCA removes the effects of this and other local circulations to obtain a regional background value representative of the greater Houston area.
Burial of the Mohn‐Knipovich seafloor spreading ridge by the Bear Island Fan: Time constraints on tectonic evolution from seismic stratigraphy
Authors: Bruvoll Vibeke , Breivik Asbjørn Johan , Mjelde Rolf , Pedersen Rolf B.
Published: June 2009

Six seismic multichannel profiles and multibeam bathymetric data were collected during 2000 and 2001 from the Mohn‐Knipovich spreading ridge bend in the Norwegian‐Greenland seas. The full spreading rate is slow to ultraslow (15–17 mm a−1), characterized by both magmatic and amagmatic spreading and lack of transform faults. The area is covered by sediments from the Bear Island Fan, and the proximity of the ridge to a glacial margin with high sedimentation rates provides a unique opportunity to study the timing and tectonic development from seismic data. The sediments in the current study have been dated by correlation to the Bear Island Fan seismic stratigraphic network. The magma‐starved northern part of the study area has an asymmetric axial valley which is deepest to the west, whereas the axial volcanic ridge in the southern part is more symmetric. The western axial mountains are about 600–800 m higher than the eastern, and the sedimentary architecture shows that almost all tectonic activity after 1.3 Ma occurred on the western side. Low‐angle (20°–50°, typically 25°) faults are ubiquitous, even at initiation. Little interaction between sedimentation and block rotation indicates rapid, short‐lived episodes of fault movement at the axial flank. Detachment and starting core complex development on the western side can explain the asymmetric tectonic development of the axial mountains, difference in elevation, recent quiescence of the eastern axial mountains, and the existence of older corrugated surfaces in the west.
A new time‐space accounting scheme to predict stream water residence time and hydrograph source components at the watershed scale
Authors: Sayama Takahiro , McDonnell Jeffrey J.
Published: June 2009

Hydrograph source components and stream water residence time are fundamental behavioral descriptors of watersheds but, as yet, are poorly represented in most rainfall‐runoff models. We present a new time‐space accounting scheme (T‐SAS) to simulate the pre‐event and event water fractions, mean residence time, and spatial source of streamflow at the watershed scale. We use a physically based hydrologic model together with field data from the well‐studied Maimai M8 watershed and HJ Andrews WS10 watershed to explore how catchment properties, particularly soil depth, controls the age and source of streamflow. Our model simulates unsaturated, saturated subsurface, and surface rainfall‐runoff processes. We first demonstrate the ability of the model to capture hydrograph dynamics and compare the model flow component and age simulations against measured values at the two sites. We show that the T‐SAS approach can capture flow and transport dynamics for the right dominant process reasons. We then conduct a series of virtual experiments by switching soil depths between the two watersheds to understand how soil depth and its distribution control water age and source. Results suggest that thicker soils increase mean residence time and damp its temporal dynamics in response to rainfall inputs. Soil depth influenced the geographic source of streamflow, whereas pre‐event water sources became more concentrated to near stream zones as soil depth increased. Our T‐SAS approach provides a learning tool for linking the dynamics of residence time and time‐space sources of flow at the watershed scale and may be a useful framework for other distributed rainfall‐runoff models.
Position of the Polar Front along the western Iberian margin during key cold episodes of the last 45 ka
Authors: Eynaud Frédérique , de Abreu Lúcia , Voelker Antje , Schönfeld Joachim , Salgueiro Emilia , Turon Jean‐Louis , Penaud Aurélie , Toucanne Samuel , Naughton Filipa , Sánchez Goñi María Fernanda , Malaizé Bruno , Cacho Isabel
Published: June 2009

This paper documents the migration of the Polar Front (PF) over the Iberian margin during some of the cold climatic extremes of the last 45 ka. It is based on a compilation of robust and coherent paleohydrological proxies obtained from eleven cores distributed between 36 and 42°N. Planktonic δ18O (Globigerina bulloides), ice‐rafted detritus concentrations, and the relative abundance of the polar foraminifera Neogloboquadrina pachyderma sinistral were used to track the PF position. These three data sets, compared from core to core, show a consistent evolution of the sea surface paleohydrology along the Iberian margin over the last 45 ka. We focused on five time slices representative of cold periods under distinct paleoenvironmental forcings: the 8.2 ka event and the Younger Dryas (two recent cold events occurring within high values of summer insolation), Heinrich events 1 and 4 (reflecting major episodes of massive iceberg discharges into the North Atlantic), and the Last Glacial Maximum (typifying the highest ice volume accumulated in the Northern Hemisphere). For each event, we generated schematic maps mirroring past sea surface hydrological conditions. The maps revealed that the Polar Front presence along the Iberian margin was restricted to Heinrich events. The sea surface conditions during the Last Glacial Maximum were close to those at present day, except for the northern sites which briefly experienced subarctic conditions.
Coeval blueschist exhumation along thousands of kilometers: Implications for subduction channel processes
Authors: Monié P. , Agard P.
Published: June 2009

We herein focus on understanding what controls the detachment and migration of oceanic crustal slices along subduction zones. We provide evidence for the coeval Middle to Late Cretaceous exhumation of oceanic blueschists in the same Neotethyan subduction zone, across more than 3000 km, from depths around 30–40 km, over a short time interval (∼25 Ma) compared to the duration of subduction (>100 Ma). We stress the importance of such a geodynamic process and suggest that this exhumation was promoted by a regional‐scale change in the long‐term interplate mechanical coupling. On the basis of geological and geophysical evidence, we propose that the upward migration of oceanic fragments in subduction zones is normally inhibited and only occurs discontinuously, as the subduction channel opens up in response to a major change in plate geodynamics, slab geometry and dynamics, mantle wedge and slab hydration, or a combination of these.
Change of mean midlatitude westerlies in 21st century climate simulations
Authors: Ihara Chie , Kushnir Yochanan
Published: June 2009

Changes in midlatitude westerlies over the Pacific jet region between the 20th century and 21st century in general circulation models participating in the recent IPCC‐Forth Assessment are delineated. Outputs derived from individual models reveal that in almost all models analyzed the seasonal mean midlatitude jet streams in the northern hemispheric Pacific and west Atlantic during boreal winter and in the southern hemispheric Pacific during boreal summer are significantly intensified in warmer 21st century climate compared to the state in the 20th century at the upper part of the core, at 200‐100 mb.
Influence of multiple sills upon internal wave generation and the implications for mixing
Authors: Xing Jiuxing , Davies Alan M.
Published: June 2009

A cross sectional non‐hydrostatic model of a fjord is used to examine to what extent the internal tide is modified by two closely spaced sills. The model is forced with an M2 barotropic tide and internal tides, unsteady lee waves and a jet are generated at the sills. In contrast to an isolated sill, calculations with two closely spaced sills show that the presence of the second sill leads to standing internal wave generation with associated changes in wave spectrum and Richardson number in the inter sill region. Associated with these there is a cascade of energy towards short waves leading to enhanced mixing between the sills. This increase in mixing is consistent with enhanced mixing between closely spaced sills found in observations. It is also relevant to enhanced oceanic mixing and suggest that future mixing measurements should focus on these regions.
Evaluating the importance of atmospheric and sedimentary iron sources to Southern Ocean biogeochemistry
Authors: Tagliabue Alessandro , Bopp Laurent , Aumont Olivier
Published: June 2009

The predominant iron sources to the Southern Ocean (SO) are atmospheric deposition and sediment supply from the continental margin and their relative importance in governing SO carbon export remains a subject of great debate. Here we report the results of simulations conducted with an ocean general circulation and biogeochemistry model (OGCBM) to quantify the importance of each source at different spatial scales at quasi‐equilibrium. Overall, we find sediment derived iron is more important than dust derived iron in sustaining SO export production (by 1.4 to 9 times). Although dust iron is important in certain geographic sectors of the SO, this largely depends on the dust model employed. Apparent geographical correlations between dust deposition and export production can be misleading, since sediment iron can be transported to similar regions. Future generation OGCBMs must better represent spatial variability in deposition fluxes and iron solubility from dust, as well as the poorly constrained, yet regionally important, sediment source.
Magnetospheric cavity modes driven by solar wind dynamic pressure fluctuations
Authors: Claudepierre S. G. , Wiltberger M. , Elkington S. R. , Lotko W. , Hudson M. K.
Published: June 2009

We present results from Lyon‐Fedder‐Mobarry (LFM) global, three‐dimensional magnetohydrodynamic (MHD) simulations of the solar wind‐magnetosphere interaction. We use these simulations to investigate the role that solar wind dynamic pressure fluctuations play in the generation of magnetospheric ultra‐low frequency (ULF) pulsations. The simulations presented in this study are driven with idealized solar wind input conditions. In four of the simulations, we introduce monochromatic ULF fluctuations in the upstream solar wind dynamic pressure. In the fifth simulation, we introduce a continuum of ULF frequencies in the upstream solar wind dynamic pressure fluctuations. In this numerical experiment, the idealized nature of the solar wind driving conditions allows us to study the magnetospheric response to only a fluctuating upstream dynamic pressure, while holding all other solar wind driving parameters constant. The simulation results suggest that ULF fluctuations in the solar wind dynamic pressure can drive magnetospheric ULF pulsations in the electric and magnetic fields on the dayside. Moreover, the simulation results suggest that when the driving frequency of the solar wind dynamic pressure fluctuations matches one of the natural frequencies of the magnetosphere, magnetospheric cavity modes can be energized.
Rain splash of soil grains as a stochastic advection‐dispersion process, with implications for desert plant‐soil interactions and land‐surface evolution
Authors: Furbish David Jon , Childs Elise M. , Haff Peter K. , Schmeeckle Mark W.
Published: June 2009

We formulate soil grain transport by rain splash as a stochastic advection‐dispersion process. By taking into account the intermittency of grain motions activated by raindrop impacts, the formulation indicates that gradients in raindrop intensity, and thus grain activity (the volume of grains in motion per unit area) can be as important as gradients in grain concentration and surface slope in effecting transport. This idea is confirmed by rain splash experiments and manifest in topographic roughening via mound growth beneath desert shrubs. The formulation provides a framework for describing transport and dispersal of any soil material moveable by rain splash, including soil grains, soil‐borne pathogens and nutrients, seeds, or debitage. As such it shows how classic models of topographic “diffusion” reflect effects of slope‐dependent grain drift, not diffusion, and it highlights the role of rain splash in the ecological behavior of desert shrubs as “resource islands.” Specifically, the growth of mounds beneath shrub canopies, where differential rain splash initially causes more grains to be splashed inward beneath the protective canopy than outward, involves the “harvesting” of nearby soil material, including nutrients. Mounds thus represent temporary storage of soil derived from areas surrounding the shrubs. As the inward grain flux associated with differential rain splash is sustained over the shrub lifetime, mound material is effectively sequestered from erosional processes that might otherwise move this material downslope. With shrub death and loss of the protective canopy, differential rain splash vanishes and the mound material is dispersed to the surrounding area, again subject to downslope movement.
Annotation and Curation of the Protein Data Bank
Authors: Young Jasmine , Protein Data Bank RCSB PDBj PDBe
Published: June 2009

The Protein Data Bank (PDB) is the worldwide repository for experimentally determined 3D structures of biological macromolecules. Established in 1971 with just seven structures, it presently includes more than 56,000 entries. To maintain the highest standards in curation and processing, the members of the worldwide Protein Data Bank (wwPDB) collaborate in data annotation and the development of procedures, tools, and resources. Annotation-related issues, particularly those impacted by new developmentsin structural biology, are critically reviewed at in-person and virtual meetings regularly and frequently. Comprehensive documentation of the procedures, formats, and related data dictionaries used in data annotation are available at the wwPDB website(www.wwpdb.org).Mindful of the impact that changes in annotation procedures or data format may have on users, changes are carefully managed and communicated in a timely fashion. In cases involving complex scientific or policy issues, input is sought from advisory committees, standing task forces, experimental method developers, and community experts. This is exemplified by creation of the recently-released version of the PDB archive which updates and further standardizes database references, small molecule chemistry, biological assemblies, and active sites.
The insert region of the Rac GTPases is dispensable for activation of superoxide-producing NADPH oxidases
Authors: Miyano Kei , Koga Hirofumi , Minakami Reiko , Sumimoto Hideki
Published: June 2009

Rac1 and Rac2, which belong to the Rho subfamily of Ras-related GTPases, play an essential role in activation of gp91phox/Nox2 (cytochrome b-245, β polypeptide; also known as Cybb), the catalytic core of the superoxide-producing NADPH oxidase in phagocytes. Rac1 also contributes to activation of the non-phagocytic oxidases Nox1 (NADPH oxidase 1) and Nox3 (NADPH oxidase 3), each related closely to gp91phox/Nox2. It has remained controversial whether the insert region of Rac (amino acids 123–135), unique to the Rho subfamily proteins, is involved in gp91phox/Nox2 activation. In the present study we show that removal of the insert region from Rac1 neither affects activation of gp91phox/Nox2, which is reconstituted under cell-free and whole-cell conditions, nor blocks its localization to phagosomes during ingestion of IgG-coated beads by macrophage-like RAW264.7 cells. The insert region of Rac2 is also dispensable for gp91phox/Nox2 activation at the cellular level. Although Rac2, as well as Rac1, is capable of enhancing superoxide production by Nox1 and Nox3, the enhancements by the two GTPases are both independent of the insert region. We also demonstrate that Rac3, a third member of the Rac family in mammals, has an ability to activate the three oxidases and that the activation does not require the insert region. Thus the insert region of the Rac GTPases does not participate in regulation of the Nox family NADPH oxidases.
The steady-state mechanism of cytochrome c oxidase: redox interactions between metal centres
Authors: Mason Maria G. , Nicholls Peter , Cooper Chris E.
Published: June 2009

The steady-state behaviour of isolated mammalian cytochrome c oxidase was examined by increasing the rate of reduction of cytochrome c. Under these conditions the enzyme's 605 (haem a), 655 (haem a3/CuB) and 830 (CuA) nm spectral features behaved as if they were at near equilibrium with cytochrome c (550 nm). This has implications for non-invasive tissue measurements using visible (550, 605 and 655 nm) and near-IR (830 nm) light. The oxidized species represented by the 655 nm band is bleached by the presence of oxygen intermediates P and F (where P is characterized by an absorbance spectrum at 607 nm relative to the oxidized enzyme and F is characterized by an absorbance spectrum at 580 nm relative to the oxidized enzyme) or by reduction of haem a3 or CuB. However, at these ambient oxygen levels (far above the enzyme Km), the populations of reduced haem a3 and the oxygen intermediates were very low (<10%). We therefore interpret 655 nm changes as reduction of the otherwise spectrally invisible CuB centre. We present a model where small anti-cooperative redox interactions occur between haem a–CuA–CuB (steady-state potential ranges: CuA, 212–258 mV; haem a, 254–281 mV; CuB, 227–272 mV). Contrary to static equilibrium measurements, in the catalytic steady state there are no high potential redox centres (>300 mV). We find that the overall reaction is correctly described by the classical model in which the Michaelis intermediate is a ferrocytochrome c–enzyme complex. However, the oxidation of ferrocytochrome c in this complex is not the sole rate-determining step. Turnover is instead dependent upon electron transfer from haem a to haem a3, but the haem a potential closely matches cytochrome c at all times.
The transcriptional activity of Pygopus is enhanced by its interaction with cAMP-response-element-binding protein (CREB)-binding protein
Authors: Andrews Phillip G. P. , He Zhijian , Popadiuk Cathy , Kao Kenneth R.
Published: June 2009

Pygopus is a core component of the β-catenin/TCF (T-cell factor) transcriptional activation complex required for the expression of canonical Wnt target genes. Recent evidence suggests that Pygopus could interpret histone methylation associated with target genes and it was shown to be required for histone acetylation. The involvement of a specific acetyltransferase, however, was not determined. In this report, we demonstrate that Pygopus can interact with the HAT (histone acetyltransferase) CBP [CREB (cAMP-responsive-element-binding protein)-binding protein]. The interaction is via the NHD (N-terminal homology domain) of Pygopus, which binds to two regions in the vicinity of the HAT domain of CBP. Transfected and endogenous hPygo2 (human Pygopus2) and CBP proteins co-immunoprecipitate in HEK-293 (human embryonic kidney 293) cells and both proteins co-localize in SW480 colorectal cancer cells. The interaction with CBP also enhances both DNA-tethered and TCF/LEF1 (lymphoid enhancing factor 1)-dependent transcriptional activity of Pygopus. Furthermore, immunoprecipitated Pygopus protein complexes displayed CBP-dependent histone acetyltransferase activity. Our data support a model in which the NHD region of Pygopus is required to augment TCF/β-catenin-mediated transcriptional activation by a mechanism that includes both transcriptional activation and histone acetylation resulting from the recruitment of the CBP histone acetyltransferase.
Inhibitory effects of kynurenic acid, a tryptophan metabolite, and its derivatives on cytosolic sulfotransferases
Authors: Senggunprai Laddawan , Yoshinari Kouichi , Yamazoe Yasushi
Published: June 2009

KYNA (kynurenic acid) is an endogenous metabolite of tryptophan in the kynurenine pathway and has been characterized as an antagonist of ionotropic glutamate receptors. In addition, we have reported this endogenous compound as a potent inhibitor of SULTs (cytosolic sulfotransferases). In the present study we characterized the inhibitory effects of KYNA on several human (h) and mouse (m) recombinant SULTs. No sulfate metabolite of KYNA was detected with mouse and human SULTs examined under the conditions used, suggesting that it is a bona fide inhibitor of SULTs. Among the mouse enzymes examined, KYNA exhibited selective inhibitory effects on Sult1b1-mediated sulfation of various compounds with IC50 values in the low micromolar range (2.9–4.9 μM). KYNA also exerted an inhibitory activity towards hSULT1A1 and hSULT1B1. The inhibitory potency of KYNA for mSult1b1 was stronger than that of 2,6-dichloro-4-nitrophenol, a known non-specific SULT inhibitor, whereas the potencies of these two inhibitors for hSULT1B1 were comparable. The inhibitory characteristics of KYNA were clearly distinct from those of mefenamic acid, a selective inhibitor of SULT1A enzymes. The KYNA derivatives 5,7-dichlorokynurenic acid and L689,560 exhibited preferential inhibitory effects on hSULT1A1 and hSULT1B1 respectively. Interestingly, gavestinel, another KYNA derivative, was found to be an extremely potent inhibitor of hSULT1B1. Finally, we have demonstrated that the mechanism underlying the KYNA inhibition varied depending on the enzyme and substrate involved. Taken together, the present results unveil another distinct aspect of KYNA and its derivatives as an inhibitor of SULTs.
Crystal structure of Glycine max glutathione transferase in complex with glutathione: investigation of the mechanism operating by the Tau class glutathione transferases
Authors: Axarli Irene , Dhavala Prathusha , Papageorgiou Anastassios C. , Labrou Nikolaos E.
Published: June 2009

Cytosolic GSTs (glutathione transferases) are a multifunctional group of enzymes widely distributed in Nature and involved in cellular detoxification processes. The three-dimensional structure of GmGSTU4-4 (Glycine max GST Tau 4-4) complexed with GSH was determined by the molecular replacement method at 2.7 Å (1 Å=0.1 nm) resolution. The bound GSH is located in a region formed by the beginning of α-helices H1, H2 and H3 in the N-terminal domain of the enzyme. Significant differences in the G-site (GSH-binding site) as compared with the structure determined in complex with Nb-GSH [S-(p-nitrobenzyl)-glutathione] were found. These differences were identified in the hydrogen-bonding and electrostatic interaction pattern and, consequently, GSH was found bound in two different conformations. In one subunit, the enzyme forms a complex with the ionized form of GSH, whereas in the other subunit it can form a complex with the non-ionized form. However, only the ionized form of GSH may form a productive and catalytically competent complex. Furthermore, a comparison of the GSH-bound structure with the Nb-GSH-bound structure shows a significant movement of the upper part of α-helix H4 and the C-terminal. This indicates an intrasubunit modulation between the G-site and the H-site (electrophile-binding site), suggesting that the enzyme recognizes the xenobiotic substrates by an induced-fit mechanism. The reorganization of Arg111 and Tyr107 upon xenobiotic substrate binding appears to govern the intrasubunit structural communication between the G- and H-site and the binding of GSH. The structural observations were further verified by steady-state kinetic analysis and site-directed mutagenesis studies.
Chemokine degradation by the Group A streptococcal serine proteinase ScpC can be reconstituted in vitro and requires two separate domains
Authors: Fritzer Andrea , Noiges Birgit , Schweiger Daniela , Rek Angelika , Kungl Andreas J. , von Gabain Alexander , Nagy Eszter , Meinke Andreas L.
Published: June 2009

Streptococcus pyogenes is one of the most common human pathogens and possesses diverse mechanisms to evade the human immune defence. One example of its immune evasion is the degradation of the chemokine IL (interleukin)-8 by ScpC, a serine proteinase that prevents the recruitment of neutrophils to an infection site. By applying the ANTIGENome technology and using human serum antibodies, we identified Spy0416, annotated as ScpC, as a prominent antigen that induces protective immune responses in animals. We demonstrate here for the first time that the recombinant form of Spy0416 is capable of IL-8 degradation in vitro in a concentration- and time-dependent manner. Mutations in the conserved amino acid residues of the catalytic triad of Spy0416 completely abolished in vitro activity. However, the isolated predicted proteinase domain does not exhibit IL-8-degrading activity, but is dependent on the presence of the C-terminal region of Spy0416. Binding to IL-8 is mainly mediated by the catalytic domain. However, the C-terminal region modulates substrate binding, indicating that the proteolytic activity is amenable to regulation via the non-catalytic regions. The specificity for human substrates is not restricted to IL-8, since we also detected in vitro protease activity for another CXC chemokine GRO-α (growth-related oncogene α), but not for NAP-2 (neutrophil-activating protein 2), SDF (stromal-cell-derived factor)-1α, PF-4 (platelet factor 4), I-TAC (interferon-γ-inducible T-cell α-chemoattractant), IP-10 (interferon-γ-inducible protein 10) and MCP-1 (monocyte chemoattractant protein 1). The degradation of two human CXC chemokines in vitro, the high sequence conservation, the immunogenicity of the protein in humans and the shown protection in animal studies suggest that Spy0416 is a promising vaccine candidate for the prevention of infections by S. pyogenes.
Human haem oxygenase-1 induction by nitro-linoleic acid is mediated by cAMP, AP-1 and E-box response element interactions
Authors: WRIGHT Marcienne M. , KIM Junghyun , HOCK Thomas D. , LEITINGER Norbert , FREEMAN Bruce A. , AGARWAL Anupam
Published: June 2009

Nitro-fatty acid products of oxidative inflammatory reactions mediate anti-inflammatory cell signalling responses. LNO2 (nitrolinoleic acid) induces expression of HO-1 (haem oxygenase-1), an enzyme that catabolizes haem into products exhibiting potent anti-inflammatory properties. In the present manuscript, the molecular mechanisms underlying HO-1 induction by LNO2 were examined in HAEC (human aortic endothelial cells), HEK-293 (human embryonic kidney 293) cells, and in transcription factor-deficient MEF (mouse embryonic fibroblasts). LNO2 induced HO-1 expression in Nrf2 [NF-E2 (nuclear factor-erythroid 2)-related factor 2]-deficient MEF and in HEK-293 cells transfected with Nrf2-specific shRNA (small-hairpin RNA), supporting the fact that LNO2-mediated HO-1 induction can be regulated by Nrf2-independent mechanisms. LNO2 activated expression of a −4.5 kb human HO-1 promoter construct, whereas a −4.0 kb construct with deletion of 500 bp from the 5′ region was unresponsive. Site-directed mutagenesis of a CRE (cAMP-response element) or of a downstream NF-E2/AP-1 (activating protein-1) element, individually, within this 500 bp region modestly reduced activation of the HO-1 promoter by LNO2. Mutations of both the CRE and the NF-E2/AP-1 site also attenuated LNO2-mediated HO-1 promoter expression, whereas the addition of a third mutation in the proximal E-box sequence completely abolished LNO2-induced HO-1 expression. Chromatin immunoprecipitation assays confirmed CREB (CRE-binding protein)-1 binding to the CRE (located at −4.0 kb) and E-box regions (located at −44 bp) of the human HO-1 promoter. A 3C (Chromosome Conformation Capture) assay of intact cells showed LNO2-induced interactions between the CRE- and E-box- containing regions. These observations indicate that regulation of human HO-1 expression by LNO2 requires synergy between CRE, AP-1 and E-box sequences and involves the participation of CREB-1.
A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway
Authors: Li Chunsun , Chen Hongyan , Ding Fang , Zhang Yu , Luo Aiping , Wang Mingrong , Liu Zhihua
Published: June 2009

S100A9 (S100 calcium-binding protein A9) is a calcium-binding protein of the S100 family, and its differential expression has been associated with acute and chronic inflammation and several human cancers. Our previous work showed that S100A9 was severely down-regulated in human ESCC (oesophageal squamous cell carcinoma). To further investigate the transcriptional regulation of S100A9, we analysed the S100A9 promoter region and found several putative p53BS (p53-binding sites). Luciferase reporter assays showed that constructs carrying the p53BS exhibited enhanced luciferase activity in response to wild-type p53 activation. Further study demonstrated that S100A9 mRNA and protein expression could be positively regulated in a p53-dependent manner and p53 could bind to p53BS on the S100A9 promoter. Overexpression of S100A9 could induce cellular apoptosis, and this was partly p53-dependent. Knockdown of S100A9 impaired the apoptosis induced by p53. Thus we conclude that a gene down-regulated in ESCC, S100A9, is a novel p53 transcriptional target, induces cellular apoptosis in a partly p53-dependent manner and mediates the p53 apoptosis pathway.
Human Ccr4–Not complexes contain variable deadenylase subunits
Authors: Lau Nga-Chi , Kolkman Annemieke , van Schaik Frederik M. A. , Mulder Klaas W. , Pijnappel W. W. M. Pim , Heck Albert J. R. , Timmers H. Th. Marc
Published: June 2009

The Ccr4–Not complex is evolutionarily conserved and important for regulation of mRNA synthesis and decay. The composition of the yeast complex has been well described. Orthologues of the yeast Ccr4–Not components have been identified in human cells including multiple subunits with mRNA deadenylase activity. In the present study, we examine the composition of the human Ccr4–Not complex in an in-depth proteomic approach using stable cell lines expressing tagged CNOT proteins. We find at least four different variants of the human complex, consisting of seven stable core proteins and mutually exclusive associated mRNA deadenylase subunits. Interestingly, human CNOT4 is in a separate ~200 kDa complex. Furthermore, analyses of associated proteins indicate involvement of Ccr4–Not complexes in splicing, transport and localization of RNA molecules. Taken together, human Ccr4–Not complexes are heterogeneous in composition owing to differences in their deadenylase subunits, which may reflect the multi-functionality of these complexes in cellular processes.
Two novel phosphatidylinositol-4-phosphate 5-kinase type Iγ splice variants expressed in human cells display distinctive cellular targeting
Authors: Schill Nicholas J. , Anderson Richard A.
Published: June 2009

The generation of various phosphoinositide messenger molecules at distinct locations within the cell is mediated via the specific targeting of different isoforms and splice variants of phosphoinositide kinases. The lipid messenger PtdIns(4,5)P2 is generated by several of these enzymes when targeted to distinct cellular compartments. Several splice variants of the type Iγ isoform of PIPK (PtdIns4P 5-kinase), which generate PtdIns(4,5)P2, have been identified, and each splice variant is thought to serve a unique functional role within cells. Here, we have identified two novel C-terminal splice variants of PIPKIγ in human cells consisting of 700 and 707 amino acids. These two splice variants are expressed in multiple tissue types and display PIPK activity in vitro. Interestingly, both of these novel splice variants display distinct subcellular targeting. With the addition of these two new splice isoforms, there are minimally five PIPKIγ splice variants that have been identified in mammals. Therefore, we propose the use of the HUGO (Human Genome Organization) nomenclature in the naming of the splice isoforms. PIPKIγ_i4 (700 amino acids) is present in the nucleus, a targeting pattern that has not been previously observed in any PIPKIγ splice variant. PIPKIγ_i5 (707 amino acids) is targeted to intracellular vesicle-like structures, where it co-localizes with markers of several types of endosomal compartments. As occurs with other PIPKIγ splice variants, the distinctive C-terminal sequences of PIPKIγ_i4 and PIPKIγ_i5 may facilitate association with unique protein targeting factors, thereby localizing the kinases to their appropriate cellular subdomains for the site-specific generation of PtdIns(4,5)P2.