bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychological, Psychophysiological, and Personality Assessment of DSM-IV Clusters of Personality Disorders
Authors: Besteiro-González J.L. , Lemos-Giráldez S. , Muñiz J.
Published: March 2004

Testing the construct validity of the three DSM-IV cluster groupings of personality disorders, in terms of neuropsychological, psychophysiological, and personality traits measures, was the purpose of this study. The results hardly confirm significant differences between B and C cluster groups in their neuropsychological functioning, but, instead, suggest that Cluster A could have some empirical validity based on executive prefrontal deficits (concept formation and sustained attention tasks) and clinical features. Similarly, no consistent differences among groups emerge when psychophysiological measures are compared. With regard to the Big-Five personality dimensions, the results also indicate that clusters may be more heterogeneous than the DSM-IV suggests. It appears, therefore, that the categorical division of DSM personality disorders into three discrete clusters may not be empirically justified.
A large‐amplitude meander of the shelfbreak front during summer south of New England: Observations from the Shelfbreak PRIMER experiment
Authors: Gawarkiewicz Glen , Brink Kenneth H. , Bahr Frank , Beardsley Robert C. , Caruso Michael , Lynch James F. , Chiu Ching‐Sang
Published: March 2004

In order to examine spatial and temporal variability of the shelfbreak front during peak stratification, repeated surveys using a towed undulating vehicle (SeaSoar) are used to describe the evolution of shelfbreak frontal structure during 26 July to 1 August 1996 south of New England. Spatial correlation (e‐folding) scales for the upper 60 m of the water column were generally between 8 and 15 km for temperature, salinity, and velocity. Temporal correlation scales were about 1 day. The frontal variability was dominated by the passage of a westward propagating meander that had a wavelength of 40 km, a propagation speed of 0.11 m s−1, and an amplitude of 15 km (30 km from crest to trough). Along‐front geostrophic velocities (referenced to a shipboard acoustic Doppler current profilers) were as large as 0.45 m s−1, although subject to significant along‐front variations. The relative vorticity within the jet was large, with a maximum 0.6 of the local value of the Coriolis parameter. Seaward of the front, a small detached eddy consisting of shelf water was present with a diameter of approximately 15 km. Ageostrophic contributions to the velocity field are estimated to be as large as 0.3 m s−1 in regions of sharp curvature within the meander. These observations strongly suggest that during at least some time periods, shelfbreak exchange is nonlinear (large Rossby number) and dominated by features on a horizontal scale of order 10 km.
Distribution and dynamics of nitrogen and microbial plankton in southern Lake Michigan during spring transition 1999–2000
Authors: Gardner Wayne S. , Lavrentyev Peter J. , Cavaletto Joann F. , McCarthy Mark J. , Eadie Brian J. , Johengen Thomas H. , Cotner James B.
Published: March 2004

Ammonium and amino acid fluxes were examined as indicators of N and microbial food web dynamics in southern Lake Michigan during spring. Either 15NH4+ or a mixture of 15N‐labelled amino acids (both at 4 μM N final concentration) was added to Lake Michigan water. Net fluxes were measured over 24 h under natural light and dark conditions using deck‐top incubators and compared to microbial food web characteristics. Isotope dilution experiments showed similar light and dark NH4+ regeneration rates at lake (6 versus 5 nM N h−1) and river‐influenced (20 versus 24 nM N h−1) sites. Ammonium uptake rates were similar to regeneration rates in dark bottles. Dark uptake (attributed mainly to bacteria) accounted for ∼70% of total uptake (bacteria plus phytoplankton) in the light at most lake sites but only ∼30% of total uptake at river‐influenced sites in or near the St. Joseph River mouth (SJRM). Cluster analysis grouped stations having zero, average, or higher than average N‐cycling rates. Discriminant analysis indicated that chlorophyll concentration, oligotrich ciliate biomass, and total P concentration could explain 66% of N‐cycling rate variation on average. Heterotrophic bacterial N demand was about one third of the NH4+ regeneration rate. Results suggest that, with the exception of SJRM stations, bacterial uptake and protist grazing mediated much of the N dynamics during spring transition. Since NH4+ is more available to bacteria than NO3−, regenerated NH4+ may have a strong influence on spring, lake biochemical energetics by enhancing N‐poor organic matter degradation in this NO3− ‐replete ecosystem.
Geometry of eclogite‐facies structural features: Implications for production and exhumation of ultrahigh‐pressure and high‐pressure rocks, Western Gneiss Region, Norway
Authors: Terry Michael P. , Robinson Peter
Published: March 2004

Well‐preserved eclogite‐facies structural features in metamorphosed gabbro and diorite gneiss in Baltica crust, formed at a minimum depth of 60–70 km during the Scandian orogeny, allow direct inferences to be made regarding the geometry of folds, kinematics, and original structural orientations related to production and exhumation of high‐pressure rocks. Folds associated with eclogite‐facies fabrics are isoclinal to tubular with axes parallel to the trend of a stretching lineation. Strain estimates and L > S or L ≫ S fabrics indicate that these structures were formed in a constrictional strain field. Locally, they are well preserved in eclogite‐facies mylonite zones at least 40 m thick that cut Proterozoic gabbro and adjacent gneiss. Where steeply dipping, they show a north‐side‐up shear sense across a younger, northeast trending, shallowly plunging, amphibolite‐facies anticlinorium formed in a constrictional, noncoaxial strain field. Where original structural facing direction can be inferred, small‐circle rotation of the eclogite‐facies lineation about the anticline axis indicates that the relative motion vector of Baltica with respect to overlying imbricated crust and Laurentia was oriented 320° in a present‐day reference frame. This result is identical to the orientation of the relative motion vector estimated from paleomagnetic plate reconstructions and consistent with Late Silurian to Early Devonian oblique sinistral convergence between Baltica and Laurentia. Results of this study indicate that coherent Baltica crust at 60–70 km depth experienced subvertical and horizontal shortening while extending toward the foreland during tops‐southeast thrusting parallel to plate motion. High‐pressure rocks were progressively imbricated and stacked along eclogite‐facies mylonite zones, with the deforming zone separating coherent Baltica crust from imbricated basement above. The constrictional strains under eclogite‐facies conditions are interpreted to have resulted from stretching associated with sinking of the cool dense mantle lithosphere.
Cluster observations of ULF waves with pulsating electron beams above the high latitude dusk‐side auroral region
Authors: Morooka M. , André M. , Wahlund J.‐E. , Buchert S. C. , Fazakerley A. N. , Winningham J. D. , Rème H. , Dandouras I. , Lavraud B. , Balogh A. , Igenbergs K.
Published: March 2004

We report observations by the four Cluster satellites of particle acceleration associated with ULF (Alfvén) waves at an altitude of 6RE above the dusk‐side auroral region. All satellites observed upward accelerated ions and upgoing electron beams, which coincided with the upward field‐aligned current around the plasmasheet boundary region. Here we study in detail one region of Alfvénic ULF waves observed together with upward electron beams, both having a quasi‐periodicity of about 2 minutes. The ULF waves have a downward Poynting flux. Comparing data from different spacecraft, the observed electron beams are likely caused by the ULF waves in localized (0.5° latitude extension) flux tubes in the plasmasheet boundary region. The high‐energy keV plasmasheet dispersive ion signatures showed similar periodicity, which suggests that the generation region of the ULF Alfvén waves is near the magnetospheric flank, and in turn induce time‐varying particle energization.
Estimate of the global distribution of stratiform supercooled liquid water clouds using the LITE lidar
Authors: Hogan Robin J. , Behera Mukunda D. , O'Connor Ewan J. , Illingworth Anthony J.
Published: March 2004

Supercooled liquid water clouds can occur in the form of thin layers that have a much larger radiative impact than ice clouds of the same water content because of their smaller particle size, yet they are poorly represented in climate models. Such clouds may be easily distinguished from ice by their high lidar backscatter coefficient and sharp backscatter gradient at cloud top. In this paper, data from the Lidar In‐space Technology Experiment (LITE), which flew on the space shuttle in 1994, are used to estimate the fraction of clouds that contain supercooled liquid water over the latitude range ±60°. Around 20% of clouds between −10°C and −15°C were found to contain liquid water, falling with temperature to essentially zero below −35°C. Even from this limited dataset some clear latitudinal clear trends were evident, with a distinctly more frequent occurrence of supercooled water in clouds associated with mid‐latitude weather systems in the southern hemisphere, as well as in tropical clouds warmer than around −15°C. The results between 40 and 60°N agree well with the distribution previously found at Chilbolton in Southern England (51°N), implying that the forthcoming long‐term lidar observations from space will be able to infer the global distribution of mixed‐phase clouds with much greater accuracy and vertical resolution than has been possible until now.
Nonlinear dynamic rupture inversion of the 2000 Western Tottori, Japan, earthquake
Authors: Peyrat S. , Olsen K. B.
Published: March 2004

We have developed a systematic nonlinear inversion method for estimating rupture propagation and the underlying dynamic parameters for large historical earthquakes. The rupture modeling is carried out using a three‐dimensional finite‐difference method, and the inversion is implemented by a neighbourhood algorithm, minimizing the misfit between computed and observed near‐fault seismograms. We test the method by estimating the stress drop within 32 regions on the causative fault for the 2000 magnitude 6.6 Western Tottori, Japan, earthquake. While the dynamic models show both similarities and differences with the conventional kinematic models, our method provides an ensemble of physically‐correct models with plausible rupture propagation for the earthquake.
Impact of a hydrogen economy on the stratosphere and troposphere studied in a 2‐D model
Authors: Warwick N. J. , Bekki S. , Nisbet E. G. , Pyle J. A.
Published: March 2004

A switch from a fossil fuel to a hydrogen‐based energy system could cause significant changes in the magnitude and composition of anthropogenic emissions. Model simulations suggest the most significant impact of these emission changes would occur in the troposphere, affecting OH. This impact is dependent upon the magnitude and nature of trade‐offs in changing fossil fuel use. In the stratosphere, changes in water vapour resulting from expected increases in surface molecular hydrogen emissions via leaks occurring during production, transport and storage, are found to be significantly smaller than previous estimates. We conclude that the expected increase in molecular hydrogen emissions is unlikely to have a substantial impact on stratospheric ozone, certainly much smaller than the ozone changes observed in the last two decades.
Localized deformation at Miyakejima volcano based on JERS‐1 radar interferometry: 1992–1998
Authors: Furuya M.
Published: March 2004

Stacked radar interferograms at Miyakejima volcano (Japan) between 1992 and 1998 showed two localized significantly deforming areas with a magnitude of 4∼6 mm/yr in the radar line of sight. One area is close to the 1983 eruption vent, and, using a simple closed analytical formulation, the deformation is interpreted as due to a thermoelastic contraction of a formerly intruded magma. The other one detected in the previous caldera is explained by a depressurization source, whose depth (500 m) coincides with that of a low resistivity zone interpreted as a hydrothermal reservoir. Also, our computed CO2 flux is consistent with in situ measurement data. The reservoir volume is significantly less than the collapsed volume in 2000, and its depth is much shallower than the void detected prior to the collapse. Hence, the depressurization would not directly induce the caldera collapse in 2000.
Influence of coastal upwelling and El Niño–Southern Oscillation on nearshore water along Baja California and Chile: Shore‐based monitoring during 1997–2000
Authors: Takesue Renee K. , van Geen Alexander , Carriquiry José D. , Ortiz Eduardo , Godínez‐Orta Lucio , Granados Ivette , Saldívar Marco , Ortlieb Luc , Escribano Rubén , Guzman Nury , Castilla Juan Carlos , Varas Manuel , Salamanca Marco , Figueroa Claudia
Published: March 2004

In order to determine the sensitivity of coastal upwelling tracers to seasonal wind forcing and El Niño–Southern Oscillation (ENSO) off Baja California and Chile, nearshore salinity, cadmium (Cd), and nutrients phosphate, silicate, nitrate+nitrite were monitored in surf zone waters at six locations along the North and South American coasts during 1997–2000. The clearest responses to upwelling favorable wind forcing were observed at the southern tip of Baja California (23.3°N) and off central‐southern Chile (36.5°S). Upwelling tracers at 23.3°N were also the most sensitive to El Niño: average summer Cd and nutrient enrichments were 60% lower following El Niño than during the previous non–El Niño upwelling season. At two sites on the northern and central Chile coasts, conditions associated with El Niño resulted in salinity anomalies >1. Such large shifts in nearshore water properties suggest it may be possible to reconstruct past ENSO patterns from geochemical paleonutrient/paleosalinity proxy records preserved in nearshore archives such as mollusc or foraminifera shells.
Variability in satellite winds over the Benguela upwelling system during 1999–2000
Authors: Risien C. M. , Reason C. J. C. , Shillington F. A. , Chelton D. B.
Published: March 2004

Wind stress variability over the Benguela upwelling system is considered using 16 months (01 August 1999 to 29 November 2000) of satellite‐derived QuikSCAT wind data. Variability is investigated using a type of artificial neural network, the self‐organizing map (SOM), and a wavelet analysis. The SOM and wavelet analysis are applied to an extracted data set to find that the system may be divided into six discrete wind regimes. The wavelet power spectra for these wind regions span a range of frequencies from 4 to 64 days, with each region appearing to contain distinct periodicities. To the north, 10°–23.5°S, the majority of the power occurs during austral winter, with a 4–16 day periodicity. Further investigation of National Centers for Environmental Prediction reanalysis outgoing longwave radiation data indicates that the winter intensification of wind stress off the Angolan coast is linked with convective activity over equatorial West Africa. The summer activity appears to be linked with the intensification of the Angolan heat low. Convective activity over the Congo basin appears to impact upon wind stress variability, off the Angolan coast, throughout the year. Farther south, 24°–35°S, the majority of the power occurs in the summer. Here a bimodal distribution occurs, with peaks of 4–12 and 25–50 days. The southernmost regions appear to be forced at higher frequencies by both midlatitude cyclones (austral winter) and mesoscale coastal lows (austral summer). At lower frequencies, eastward propagating periodic wind events that originate over eastern South America appear to be important to the forcing of wind stress over the southern Benguela.
Effects of the fungicides mancozeb and chlorothalonil on fluxes of CO2, N2O, and CH4 in a fertilized Colorado grassland soil
Authors: Kinney Chad A. , Mosier Arvin R. , Ferrer Imma , Furlong Edward T. , Mandernack Kevin W.
Published: March 2004

Management of agricultural soil plays an important role in present and future atmospheric concentrations of the greenhouse gases carbon dioxide (CO2), nitrous oxide (N2O), and methane (CH4). Pesticides are used as management tools in crop production, but little is known about their effects on soil‐atmosphere exchange of CO2, N2O, and CH4. Field studies described in this paper determined the effect of two commonly used fungicides, mancozeb and chlorothalonil, on trace gas exchange. Separate experimental plots, 1 m2, were established in nitrogen fertilized no‐tilled native grassland and tilled soils with and without fungicide application. Two studies were conducted. The first study was initiated in June 1999 and lasted for 1 year with monthly flux measurements from tilled and no‐till soils. The second study commenced in August 2001 with twelve weekly measurements from tilled soils only. From both studies mancozeb suppressed emissions of CO2 and N2O in the tilled soil by an average of 28% and 47%, respectively. This suppression corresponded with efficacy periods of 14–29 and 56–77 days, respectively. From the no‐till soils mancozeb decreased CO2 and N2O emissions by 33% and 80% for periods of 29 and 94 days, respectively. Mancozeb inhibited CH4 consumption in the first study by 46% and 71% in the tilled and no‐till soil for periods of 8 and 29 days, respectively, but had no effect in the second study. From both studies chlorothalonil initially suppressed CO2 and N2O emissions and enhanced CH4 uptake in the tilled soil by an average of 37%, 40%, and 115%, respectively. These effects corresponded with efficacy periods of 14–29, 21–56, and 1–14 days, respectively. In the no‐till soil chlorothalonil inhibited CO2 and N2O emissions and enhanced CH4 uptake by 29%, 48%, and 86% for periods of 29, 56, and 56 days, respectively. Following the initial period of suppression, chlorothalonil subsequently enhanced N2O emissions in the tilled soil by an average of 51% and in the no‐till soil by 81% before returning to near background levels. The beginning of increased N2O emissions from the chlorothalonil‐amended plots corresponded with a maximum soil concentration of the chlorothalonil degradate, 4‐hydroxy‐2, 5, 6‐trichloroisophthalonitrile. The site specific global warming potential (GWP) resulting from the fluxes of CO2, N2O, and CH4 from all soils was determined to decrease by an average 26% and 21% as a result of a single application of mancozeb or chlorothalonil, respectively. The decrease in CO2 emissions in the fungicide‐amended plots potentially could result in the conservation of as much as 1200 and 2400 kg C ha−1 yr−1 organic carbon in the tilled and no‐till plots, respectively. Therefore it is feasible that application of certain fungicides to agricultural soil might lead to enhanced soil carbon sequestration and thus have additional positive effects on atmospheric CO2 concentrations.
Effects of the herbicides prosulfuron and metolachlor on fluxes of CO2, N2O, and CH4 in a fertilized Colorado grassland soil
Authors: Kinney Chad A. , Mosier Arvin R. , Ferrer Imma , Furlong Edward T. , Mandernack Kevin W.
Published: March 2004

The effect that pesticides have on trace gas production and consumption in agricultural soils is often overlooked. Independent field and laboratory experiments were used to measure the effects that the commonly used herbicides prosulfuron and metolachlor have on trace gas fluxes (CO2, N2O, and CH4) from fertilized soil of the Colorado shortgrass steppe. Separate sample plots (1 m2) on tilled and no‐till soil at the sites included the following treatments: 1) a control without fertilizer or herbicide, 2) a fertilized (NH4NO3 equivalent to 244 kg ha−1) control without herbicide, 3) and fertilized plots amended with an herbicide (prosulfuron equivalent to 0.46 kg ha−1 57% by weight active ingredient or metolachlor equivalent to 5.7 L ha−1, 82.4% by weight active ingredient). During an initial study of one year duration, measurement of gas exchange revealed that prosulfuron‐amendment stimulated N2O emissions and CH4 consumption by as much as 1600% and 1300% during a single measurement, respectively. During a second set of flux measurements beginning in August 2001, more frequent weekly measurements were made during a twelve week period. From this second study an increased N2O efflux and CH4 uptake occurred after a 7‐week lag period that persisted for about 5 weeks. These changes in gas flux amounted to an overall increase of 41% and 30% for N2O emission and CH4 consumption, respectively. The co‐occurrence of stimulated N2O and CH4 fluxes suggests a similar cause that is related to prosulfuron degradation. Evidence suggested that prosulfuron degradation stimulated microbial activity responsible for trace gas flux. Ultimately, prosulfuron‐amendment led to an ∼50% reduction in the global warming potential from N2O and CH4 fluxes at this field site, which is equivalent to a reduction of the global warming potential of 0.18 mols CO2 m−2 d−1 from these gases. Metolachlor application did not significantly affect the trace gas fluxes measured. These results demonstrate the potential impact that pesticides have on trace gas fluxes from agricultural soils, which could mean that the effects of other agricultural practices have been over or under estimated.
Reconciling different observations of the CO2 ice mass loading of the Martian north polar cap
Authors: Haberle Robert M. , Mattingly Bridget , Titus Timothy N.
Published: March 2004

The GRS measurements of the peak mass loading of the north polar CO2 ice cap on Mars are about 60% lower than those calculated from MGS TES radiation data and those inferred from the MOLA cap thicknesses. However, the GRS data provide the most accurate measurement of the mass loading. We show that the TES and MOLA data can be reconciled with the GRS data if (1) subsurface heat conduction and atmospheric heat transport are included in the TES mass budget calculations, and (2) the density of the polar deposits is ∼600 kg m−3. The latter is much less than that expected for slab ice (∼1600 kg m−3) and suggests that processes unique to the north polar region are responsible for the low cap density.
Expanding Confusion: Common Misconceptions of Cosmological Horizons and the Superluminal Expansion of the Universe
Authors: Davis Tamara M. , Lineweaver Charles H.
Published: March 2004

We use standard general relativity to illustrate and clarify several common misconceptions about the expansion of the universe. To show the abundance of these misconceptions we cite numerous misleading, or easily misinterpreted, statements in the literature. In the context of the new standard ΛCDM cosmology we point out confusions regarding the particle horizon, the event horizon, the ‘observable universe’ and the Hubble sphere (distance at which recession velocity = c). We show that we can observe galaxies that have, and always have had, recession velocities greater than the speed of light. We explain why this does not violate special relativity and we link these concepts to observational tests. Attempts to restrict recession velocities to less than the speed of light require a special relativistic interpretation of cosmological redshifts. We analyze apparent magnitudes of supernovae and observationally rule out the special relativistic Doppler interpretation of cosmological redshifts at a confidence level of 23σ.
Influence of the Neutron Star 1E 161348–5055 in RCW 103 on the Surrounding Medium
Authors: Reynoso E. M. , Green A. J. , Johnston S. , Goss W. M. , Dubner G. M. , Giacani E. B.
Published: March 2004

We have carried out a study of the neutral hydrogen in the direction of the X-ray source 1E 161348–5055, a compact central object (CCO) located in the interior of the supernova remnant (SNR) RCW 103. The Hi 21 cm line observations were carried out using the Australia Telescope Compact Array, complemented with single dish data from the Parkes radio telescope to recover information at all spatial scales. We derive a distance to RCW 103 of 3.1 kpc, in agreement with previous distance measurements. We have also detected a small hole in the Hi emission which is positionally and kinematically coincident with the location of the CCO which confirms the association between the SNR and the CCO. This is the third case of a depression in Hi emission seemingly associated with CCOs in SNRs. The characteristic parameters of the holes such as their size, eccentricity and evacuated mass are similar in all three cases. We estimate the absorbing HI column density towards 1E 161348–5055 to be ∼6 × 1021 cm–2, a value compatible with a blackbody solution for the CCO X-ray emission. However, the implied temperature and luminosity are very high compared to most neutron stars. Moreover, the strong long-term variability in X-rays favours the hypothesis that 1E 161348–5055 is an accreting binary source rather than an isolated, cooling neutron star. An analysis of the continuum image obtained at 1.4 GHz from these observations shows no trace of a pulsar wind nebula around 1E 161348–5055, in spite of it being a young object.
The Large Scale Distribution of Galaxies in the Shapley Supercluster
Authors: Drinkwater Michael J. , Parker Quentin A. , Proust Dominique , Slezak Eric , Quintana Hernán
Published: March 2004

We present new results of our wide-field redshift survey of galaxies in a 182 square degree region of the Shapley Supercluster (SSC) based on observations with the FLAIR-II spectrograph on the UK Schmidt Telescope (UKST). In this paper we present new measurements to give a total sample of redshifts for 710 bright (R ≤ 16.6) galaxies, of which 464 are members of the SSC (8000 < v < 18 000 km s–1). Our data reveal that the main plane of the SSC (v ≈ 14 500 km s–1) extends further than previously realised, filling the whole extent of our survey region of 10 degrees by 20 degrees on the sky (35 Mpc by 70 Mpc, for H0 = 75 km s–1 Mpc–1). There is also a significant structure associated with the slightly nearer Abell 3571 cluster complex (v ≈ 12 000 km s–1) with a caustic structure evident out to a radius of 6 Mpc. These galaxies seem to link two previously identified sheets of galaxies and establish a connection with a third one at V (V) = 15 000 km s–1 near RA = 13h. They also tend to fill the gap of galaxies between the foreground Hydra-Centaurus region and the more distant SSC. We calculate galaxy overdensities of 5.0 ± 0.1 over the 182 square degree region surveyed and 3.3 ± 0.1 in a 159 square degree region excluding rich clusters. Over the large region of our survey the inter-cluster galaxies make up 46 per cent of all galaxies in the SSC region and may contribute a similar amount of mass to the cluster galaxies.
E1A and E1B proteins inhibit inflammation induced by adenovirus
Authors: Schaack Jerome , Bennett Michael L. , Colbert Jeff D. , Torres Andres Vazquez , Clayton Gerald H. , Ornelles David , Moorhead John
Published: March 2004

Replication-defective human adenovirus (Ad) group C transducing vectors, most of which have theE1A, E1B, andE3genes deleted, are highly inflammatory despite the fact that the parental viruses typically cause subclinical or mild infections. To investigate this paradox, the roles that theE1A, E1B, andE3genes play in inflammation were tested by using replication-incompetent viruses carrying a deletion of the preterminal protein gene. The viruses were injected into BALB/c mouse ears, and edema was monitored as a sensitive surrogate marker of inflammation. A virus deleted for the E1A 289R (transcription activating) protein was noninflammatory, and inhibited edema induced by empty virus particles. The E1A 243R and E1B 55-kDa (p53 binding) proteins play the most important roles in inhibition of inflammation by the noninflammatory virus. The E1B 19-kDa antiapoptotic protein inhibited edema when both the E1A 243R and E1B 55-kDa proteins were expressed but strongly induced edema when only one was expressed. E3 proteins had their greatest effect on the inhibition of edema induced by the E1A 289R protein. The results support a model in which inflammation is countered through a mechanism that involves complex genetic interactions between Ad early region proteins and offer promise for the design and construction of noninflammatory Ad gene therapy vectors that are relatively easy to grow and purify.
Comparisons of pollen coat genes across Brassicaceae species reveal rapid evolution by repeat expansion and diversification
Authors: Fiebig Aretha , Kimport Rebecca , Preuss Daphne
Published: March 2004

Reproductive genes and traits evolve rapidly in many organisms, including mollusks, algae, and primates. Previously we demonstrated that a family of glycine-rich pollen surface proteins (GRPs) from
Arabidopsis thaliana
and
Brassica oleracea
had diverged substantially, making identification of homologous genes impossible despite a separation of only 20 million years. Here we address the molecular genetic mechanisms behind these changes, sequencing the eight members of the GRP cluster, along with 11 neighboring genes in four related species,
Arabidopsis arenosa, Olimarabidopsis pumila, Capsella rubella
, and
Sisymbrium irio
. We found that GRP genes change more rapidly than their neighbors; they are more repetitive and have undergone substantially more insertion/deletion events while preserving repeat amino acid composition. Genes flanking the GRP cluster had an average
K
a
/
K
s
≈ 0.2, indicating strong purifying selection. This ratio rose to ≈0.5 in the first GRP exon, indicating relaxed selective constraints. The repetitive nature of the second GRP exon makes alignment difficult; even so,
K
a
/
K
s
within the
Arabidopsis
genus demonstrated an increase that correlated with exon length. We conclude that rapid GRP evolution is primarily due to duplication, deletion, and divergence of repetitive sequences. GRPs may mediate pollen recognition and hydration by female cells, and divergence of these genes could correlate with or even promote speciation. We tested cross-species interactions, showing that the ability of
A. arenosa
stigmas to hydrate pollen correlated with GRP divergence and identifying
A. arenosa
as a model for future studies of pollen recognition.
Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease
Authors: Casalone Cristina , Zanusso Gianluigi , Acutis Pierluigi , Ferrari Sergio , Capucci Lorenzo , Tagliavini Fabrizio , Monaco Salvatore , Caramelli Maria
Published: March 2004

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrP
Sc
) of the host-encoded cellular prion protein (PrP
C
). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrP
Sc
fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called ”species barrier” between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrP
Sc
accumulation. In addition, Western blot analysis showed a PrP
Sc
type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrP
Sc
. Strikingly, the molecular signature of this previously undescribed bovine PrP
Sc
was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.
Clathrin-mediated endocytosis is required for compensatory regulation of GLR-1 glutamate receptors after activity blockade
Authors: Grunwald Maria E. , Mellem Jerry E. , Strutz Nathalie , Maricq Andres V. , Kaplan Joshua M.
Published: March 2004

Chronic changes in neural activity trigger a variety of compensatory homeostatic mechanisms by which neurons maintain a normal level of synaptic input. Here we show that chronic activity blockade triggers a compensatory change in the abundance of GLR-1, a
Caenorhabditis elegans
glutamate receptor. In mutants lacking a voltage-dependent calcium channel (
unc-2
) or a vesicular glutamate transporter (VGLUT;
eat-4
), the abundance of GLR-1 in the ventral nerve cord was increased. Similarly, the amplitude of glutamate-evoked currents in ventral cord interneurons was increased in
eat-4
VGLUT mutants compared with wild-type controls. The effects of
eat-4
VGLUT mutations on GLR-1 abundance in the ventral cord were eliminated in double mutants lacking both the clathrin adaptin protein
unc-11
AP180 and
eat-4
VGLUT. In contrast, mutations that decreased ubiquitination of GLR-1 did not prevent increased ventral cord abundance of GLR-1 in
eat-4
VGLUT mutants. Taken together, our results suggest that GLR-1 is regulated in a homeostatic manner and that this effect depends on clathrin-mediated endocytosis but does not require ubiquitination of GLR-1.
The MafA transcription factor appears to be responsible for tissue-specific expression of insulin
Authors: Matsuoka Taka-aki , Artner Isabella , Henderson Eva , Means Anna , Sander Maike , Stein Roland
Published: March 2004

Insulin gene expression is regulated by several islet-enriched transcription factors. However, MafA is the only β cell-specific activator. Here, we show that MafA selectively induces endogenous insulin transcription in non-β cells. MafA was also first detected in the insulin-producing cells formed during the second and predominant phase of β cell differentiation, and absent in the few insulin-positive cells found in Nkx6.1
-/-
pancreata, which lack the majority of second-phase β cells. These results demonstrate that MafA is a potent insulin activator that is likely to function downstream of Nkx6.1 during islet insulin-producing cell development.
Minocycline inhibits contusion-triggered mitochondrial cytochrome
c
release and mitigates functional deficits after spinal cord injury
Authors: Teng Yang D. , Choi Howard , Onario Renna C. , Zhu Shan , Desilets Federico C. , Lan Shoumin , Woodard Eric J. , Snyder Evan Y. , Eichler Marc E. , Friedlander Robert M.
Published: March 2004

We investigated whether permeability transition-mediated release of mitochondrial cytochrome
c
is a potential therapeutic target for treating acute spinal cord injury (SCI). Based on previous reports, minocycline, a second-generation tetracycline, exerts neuroprotection partially by inhibiting mitochondrial cytochrome
c
release and reactive microgliosis. We first evaluated cytochrome
c
release at the injury epicenter after a T10 contusive SCI in rats. Cytochrome
c
release peaked at ≈4-8 h postinjury. A dose-response study generated a safe pharmacological regimen that enabled i.p. minocycline to significantly lower cytosolic cytochrome
c
at the epicenter 4 h after SCI. In the long-term study, i.p. minocycline (90 mg/kg administered 1 h after SCI followed by 45 mg/kg administered every 12 h for 5 days) markedly enhanced long-term hind limb locomotion relative to that of controls. Coordinated motor function and hind limb reflex recoveries also were improved significantly. Histopathology suggested that minocycline treatment alleviated later-phase tissue loss, with significant sparing of white matter and ventral horn motoneurons at levels adjacent to the epicenter. Furthermore, glial fibrillary acidic protein and 2′,3′ cyclic nucleotide 3′ phosphodiesterase immunocytochemistry showed an evident reduction in astrogliosis and enhanced survival of oligodendrocytes. Therefore, release of mitochondrial cytochrome
c
is an important secondary injury mechanism in SCI. Drugs with multifaceted effects in antagonizing this process and microgliosis may protect a proportion of spinal cord tissue that is clinically significant for functional recovery. Minocycline, with its proven clinical safety, capability to cross the blood-brain barrier, and demonstrated efficacy during a clinically relevant therapeutic window, may become an effective therapy for acute SCI.
Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux
Authors: Chung Jayong , Haile David J. , Wessling-Resnick Marianne
Published: March 2004

Copper is known to play a role in iron recycling from macrophages. To examine whether cellular copper status affects expression of the iron exporter ferroportin-1 (FPN1), J774 macrophage cells were exposed to 10–100 μM CuSO
4
for up to 20 h. Copper treatment significantly increased FPN1 mRNA in a dose- and time-dependent manner. After 20 h, 100 μM CuSO
4
up-regulated FPN1 transcript levels ≈13-fold compared to untreated controls. Induction was detected 8 h after copper treatment was initiated and markedly increased thereafter. A corresponding increase in FPN1 protein levels was observed upon copper treatment. Induction of J774 cell FPN1 expression by copper was also associated with a dose-dependent increase in
59
Fe release after erythrophagocytosis of labeled red blood cells. Thus, a previously uncharacterized role for copper in the regulation of macrophage iron recycling is suggested by the induction of FPN1 gene expression and iron efflux by this metal.
Imprint of evolution on protein structures
Authors: Tiana Guido , Shakhnovich Boris E. , Dokholyan Nikolay V. , Shakhnovich Eugene I.
Published: March 2004

We attempt to understand the evolutionary origin of protein folds by simulating their divergent evolution with a three-dimensional lattice model. Starting from an initial seed lattice structure, evolution of model proteins progresses by sequence duplication and subsequent point mutations. A new gene's ability to fold into a stable and unique structure is tested each time through direct kinetic folding simulations. Where possible, the algorithm accepts the new sequence and structure and thus a “new protein structure” is born. During the course of each run, this model evolutionary algorithm provides several thousand new proteins with diverse structures. Analysis of evolved structures shows that later evolved structures are more designable than seed structures as judged by recently developed structural determinant of protein designability, as well as direct estimate of designability for selected structures by thermodynamic sampling of their sequence space. We test the significance of this trend predicted on lattice models on real proteins and show that protein domains that are found in eukaryotic organisms only feature statistically significant higher designability than their prokaryotic counterparts. These results present a fundamental view on protein evolution highlighting the relative roles of structural selection and evolutionary dynamics on genesis of modern proteins.
Induction and transmission of
Bacillus thuringiensis
tolerance in the flour moth
Ephestia kuehniella
Authors: Rahman M. Mahbubur , Roberts Harry L. S. , Sarjan Muhammad , Asgari Sassan , Schmidt Otto
Published: March 2004

The use of
Bacillus thuringiensis
(Bt) endotoxins to control insect vectors of human diseases and agricultural pests is threatened by the possible evolution of resistance in major pest species. In addition to high levels of resistance produced by receptor insensitivity (
5
,
16
,
17
), several cases of tolerance to low to medium levels of toxin have been reported in laboratory colonies of lepidopteran species (
3
,
18
). Because the molecular basis of some of these cases of tolerance to the toxin are not known, we explored alternative mechanisms. Here, we present evidence that tolerance to a Bt formulation in a laboratory colony of the flour moth
Ephestia kuehniella
can be induced by preexposure to a low concentration of the Bt formulation and that the tolerance correlates with an elevated immune response. The data also indicate that both immune induction and Bt tolerance can be transmitted to offspring by a maternal effect and that their magnitudes are determined by more than one gene.
P2X7receptors control 2-arachidonoylglycerol production by microglial cells
Authors: Witting Anke , Walter Lisa , Wacker Jennifer , Möller Thomas , Stella Nephi
Published: March 2004

Endogenous cannabinoid ligands (endocannabinoids) produced by neurons, astrocytes, and microglial cells activate cannabinoid receptors, the molecular target for marijuana's bioactive ingredient Δ9-tetrahydrocannabinol. The molecular mechanism underlying the production of the most abundant endocannabinoid, 2-arachidonoylglycerol (2-AG), is unclear. A prevalent hypothesis proposes that activation of metabotropic receptors coupled to the phosphatidylinositol-specific phospholipase C and diacylglycerol (DG) lipase pathway will systematically lead to increases in 2-AG production. Here, we show that ATP increases 2-AG production by cultured microglial cells in a phosphatidylinositol-specific phospholipase C and DG lipase-dependent manner. However, efficacious activation of metabotropic P2Y purinergic receptors coupled to phosphatidylinositol-specific phospholipase C does not increase 2-AG production. This suggests that ionotropic, and not metabotropic, purinergic receptors control 2-AG production at an unexpected enzymatic step of its metabolic pathway. We show that activation of P2X7ionotropic receptors, which are highly permeable to calcium, is necessary and sufficient to increase 2-AG production in microglial cells. We also show that the sustained rise in intracellular calcium induced by activation of P2X7receptors directly increases DG lipase activity while inhibiting the activity of monoacylglycerol lipase, the enzyme that degrades 2-AG. This inverse sensitivity of DG lipase and monoacylglycerol lipase to calcium constitutes an original and efficient modality for sustained accumulation of 2-AG. Because prolonged increases in 2-AG amounts in brain parenchyma are thought to orchestrate neuroinflammation, the enzymatic steps involved in 2-AG synthesis and degradation by microglial cells constitute appealing targets for therapy aimed at controlling exacerbated neuroinflammation.
Astrocyte-mediated activation of neuronal kainate receptors
Authors: Liu Qing-song , Xu Qiwu , Arcuino Gregory , Kang Jian , Nedergaard Maiken
Published: March 2004

Exogenous kainate receptor agonists have been shown to modulate inhibitory synaptic transmission in the hippocampus, but the pathways involved in physiological activation of the receptors remain largely unknown. Accumulating evidence indicates that astrocytes can release glutamate in a Ca
2+
-dependent manner and signal to neighboring neurons. We tested the hypothesis that astrocyte-derived glutamate activates kainate receptors on hippocampal interneurons. We report here that elevation of intracellular Ca
2+
in astrocytes, induced by uncaging Ca
2+
,
o
-nitrophenyl-EGTA, increased action potential-driven spontaneous inhibitory postsynaptic currents in nearby interneurons in rat hippocampal slices. This effect was blocked by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptor antagonists, but not by selective AMPA receptor or
N
-methyl-
d
-aspartate receptor antagonists. This pharmacological profile indicates that kainate receptors were activated during Ca
2+
elevation in astrocytes. Kainate receptors containing the GluR5 subunit seemed to mediate the observed effect because a selective GluR5-containing kainate receptor antagonist blocked the changes in sIPSCs induced by Ca
2+
uncaging, and bath application of a selective GluR5-containing receptor agonist robustly potentiated sIPSCs. When tetrodotoxin was included to block action potentials, Ca
2+
uncaging induced a small decrease in the frequency of miniature inhibitory postsynaptic currents, which was not affected by AMPA/kainate receptor antagonists. Our data suggest that an astrocyte-derived, nonsynaptic source of glutamate represents a signaling pathway that can activate neuronal kainate receptors. By modulating the activity of interneurons, astrocytes may play a critical role in circuit function of hippocampus.
Identification of critical residues in GlnB for its activation of NifA activity in the photosynthetic bacterium
Rhodospirillum rubrum
Authors: Zhang Yaoping , Pohlmann Edward L. , Roberts Gary P.
Published: March 2004

The P
II
regulatory protein family is unusually widely distributed, being found in all three domains of life. Three P
II
homologs called GlnB, GlnK, and GlnJ have been identified in the photosynthetic bacterium
Rhodospirillum rubrum
. These have roles in at least four distinct functions, one of which is activation of the nitrogen fixation-specific regulatory protein NifA. The activation of NifA requires only the covalently modified (uridylylated) form of GlnB. GlnK and GlnJ are not involved. However, the basis of specificity for different P
II
homologs in different processes is poorly understood. We examined this specificity by altering GlnJ to support NifA activation. A small number of amino acid substitutions in GlnJ were important for this ability. Two (affecting residues 45 and 54) are in a loop called the T-loop, which contains the site of uridylylation and is believed to be very important for contacts with other proteins, but other critical residues lie in the C terminus (residues 95–97 and 109–112) and near the N terminus (residues 3–5 and 17). Because many of the residues important for P
II
–NifA interaction lie far from the T-loop in the known x-ray crystal structures of P
II
proteins, our results lead to the hypothesis that the T-loop of GlnB is flexible enough to come into proximity with both the C- and N-terminal regions of the protein to bind NifA. Finally, the results show that the level of P
II
accumulation is also an important factor for NifA activation.
Outer-surface protein C of the Lyme disease spirochete: A protein induced in ticks for infection of mammals
Authors: Grimm Dorothee , Tilly Kit , Byram Rebecca , Stewart Philip E. , Krum Jonathan G. , Bueschel Dawn M. , Schwan Tom G. , Policastro Paul F. , Elias Abdallah F. , Rosa Patricia A.
Published: March 2004

Environmentally responsive synthesis of surface proteins represents a hallmark of the infectious cycle of the Lyme disease agent,
Borrelia burgdorferi
. Here we created and analyzed a
B. burgdorferi
mutant lacking outer-surface protein C (OspC), an abundant Osp that spirochetes normally synthesize in the tick vector during the blood meal and down-regulate after transmission to the mammal. We demonstrate that
B. burgdorferi
strictly requires OspC to infect mice but not to localize or migrate appropriately in the tick. The induction of a spirochetal virulence factor preceding the time and host in which it is required demonstrates a developmental sequence for transmission of this arthropod-borne pathogen.
Prodrugs of dynemicin analogs for selective chemotherapy mediated by an aldolase catalytic Ab
Authors: Sinha Subhash C. , Li Lian-Sheng , Miller Gregory P. , Dutta Shantanu , Rader Christoph , Lerner Richard A.
Published: March 2004

Prodrugs of dynemicin analogs were synthesized, and their activation by aldolase antibody (Ab) 38C2 was evaluated by DNA-cleaving activity, as well as tumor cell growth inhibition. Further, we provide evidence that the activated enediynes underwent covalent crosscoupling with the aldolase Ab, which appears to be a limiting factor of their tumor cell growth-inhibiting activity and should be of general interest in the field of enediyne chemotherapy. These findings might open new avenues for defined conjugations of small molecule drugs to mAbs in general and aldolase Abs in particular.