bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric Properties of the Zuckerman-Kuhlman Personality Questionnaire in a Spanish Sample
Authors: Gomà-i-Freixanet Montserrat , Valero Sergi , Puntí Joaquim , Zuckerman Marvin
Published: March 2004

An important question in trait theory is how many major traits are necessary to describe personality and exactly what traits these are. Several investigators have made attempts to answer these questions with solutions of 3, 5, and even 16 primary factors. The Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) is a questionnaire aimed at the evaluation of a five-factor model, which emerged from factor analyses of scales and items. The results were five basic factors, similar in men and women: Neuroticism-Anxiety, Activity, Sociability, Impulsive Sensation-Seeking, and Aggression-Hostility. This study assesses the psychometric properties of the Catalan translation of the ZKPQ. The ZKPQ was administered to a total sample of 933 subjects with an age range from 17 to 25 years. The results obtained show good internal consistency of all the scales and good discriminant validity shown by the lack of correlation among scales. Gender differences are also in the predicted directions. Finally, the replicability of the original five-component structure was also demonstrated. The present findings show this Catalan version to be a reliable tool for research in the field of personality structure and demonstrate the cross-cultural reliability of the factor structure developed from American subjects.
Cenozoic distributed rotational deformation, South Island, New Zealand
Authors: Hall Lisa S. , Lamb Simon H. , Mac Niocaill Conall
Published: March 2004

New structural and paleomagnetic data from the Marlborough region, New Zealand, provide better constraints on the timing of the formation of the South Island orocline. These data indicate that approximately 100° of clockwise bending of the crust has occurred across this part of the plate boundary zone during the Neogene, most of which took place between the early and late Miocene (circa 25–8 Ma), implying that distributed shear has been an important mechanism in the accommodation of Neogene finite strain. A simple kinematic model suggests that this distributed deformation has been accommodated by the rotation of elongate blocks parallel to the main fabric, in response to continuous deformation in the underlying lithospheric mantle beneath. After the introduction of a significant convergent component to the plate motion in the late Miocene, distributed deformation may have ceased to play such a significant role in the central Marlborough fault zone, with motion becoming concentrated on the Marlborough faults themselves. In the northeastern part of Marlborough, however, an extra clockwise rotation of ∼35° has occurred since this time, which might be explained by the reorganization of the crust into more equidimensional blocks where they terminate against the Hikurangi margin.
Increase of atmospheric CO2 during deglaciation: Constraints on the coral reef hypothesis from patterns of deposition
Authors: Vecsei Adam , Berger Wolfgang H.
Published: March 2004

The “coral reef hypothesis” asserts that carbonate production on newly flooded shelves contributes importantly to the rise of atmospheric carbon dioxide during deglaciation. We seek to constrain the timing and strength of such carbon dioxide flux by re‐assessing reef and platform distribution in the world ocean. The pattern of reef growth that emerges suggests that emission of CO2 resulting from carbonate production was important particularly during the late stages of deglaciation. The effect peaked during the early Holocene and presumably contributed to the warming in the climatic optimum.
Carbon isotope cycle and mantle structure
Authors: Coltice N. , Simon L. , Lécuyer C.
Published: March 2004

Despite that no change is observed in the δ13C of sediments and upper mantle rocks over the Earth's history, the carbon isotope cycle is probably not at steady state. The δ13C of −5‰ of the upper mantle is different from that of the subducted carbon, which is close to −1‰. Indeed, most of the subducted carbon is made of carbonates: 85% of subducted sedimentary carbon plus carbonates formed by low temperature hydrothermal alteration of oceanic crust. Since no long term evolution is observed for the mantle and sedimentary rocks, the net subduction flux of heavy carbon requires to be compensated by a deep mantle process. End‐member models for the carbon isotope cycle at the Gyr scale suggest that it could be a flux from a deep primitive reservoir or the segregation of subducted oceanic crust at the core‐mantle boundary.
A sea ice model for the marginal ice zone with an application to the Greenland Sea
Authors: Pedersen Leif Toudal , Coon Max D.
Published: March 2004

A model is presented that describes the formation, transport, and desalinization of frazil and pancake ice as it is formed in marginal seas. This model uses as input the total ice concentration evaluated from Special Sensor Microwave Imager and wind speed and direction. The model calculates the areal concentration, thickness, volume concentration, and salinity of frazil ice as well as the areal concentration, thickness, and salinity of pancakes. A simple parameterization for the Odden region of the Greenland Sea is presented. The model is run for the winter of 1996–1997. There are direct observations of the thickness and salinity of pancakes and the volume concentration of frazil ice to compare with the model. The model results compare very well with the measured data. This new ice model can be tuned to work in marginal seas elsewhere to calculate ice thickness, motion, and brine rejection. Also, the model can be used to determine the location of the ice edge.
On the wind‐forcing of bottom pressure variability at Amsterdam and Kerguelen Islands, southern Indian Ocean
Authors: Meredith Michael P. , Hughes Chris W.
Published: March 2004

Bottom pressure records from Amsterdam and Kerguelen Islands (southern Indian Ocean) were collected between 1986 and 1989, and interpreted previously in terms of volume transport fluctuations between the islands [Vassie et al., 1994]. Since a substantial portion of the mean transport of the Antarctic Circumpolar Current (ACC) flows between the islands, it was assumed that ACC transport variability was the predominant signal being measured, and comparisons with ACC variability at other longitudes were made. Here we examine the relationship between atmospheric forcing and observed bottom pressure variability. We find that Kerguelen bottom pressure is forced predominantly by wind stress curl over the Kerguelen Plateau for periods between around 5 days and 1 year. A weaker correlation with circumpolar eastward winds is observed, but is seen not to be causal. Amsterdam pressure shows a similar local response to curl for high frequencies (5–10 days), but at longer periods is sensitive to curl over the sub‐basin between Kerguelen Plateau, the Southeast Indian Ridge, and Antarctica. This is the region of long‐wavelength sea level variability observed by Chao and Fu [1995], and interpreted in terms of a geostrophic resonance by Webb and de Cuevas [2002a]. Altimetric studies confirm the usefulness of the Amsterdam location in monitoring this mode. We conclude that the Amsterdam‐Kerguelen pressure difference is not a useful measure of ACC transport variability, and that previous agreement found between variability observed here and other locations is largely fortuitous. Instead, the series separately reflect different important dynamical modes in the southern Indian Ocean.
Chemical characterization of ambient aerosol collected during the northeast monsoon season over the Arabian Sea: Anions and cations
Authors: Johansen Anne M. , Hoffmann Michael R.
Published: March 2004

Ambient aerosol samples were collected over the Arabian Sea during the month of March 1997, aboard the German R/V Sonne, as part of the German JGOFS project (Joint Global Ocean Flux Study). This is the third study in a series of analogous measurements taken over the Arabian Sea during different seasons of the monsoon. Dichotomous high volume collector samples were analyzed for anions and cations upon return to the laboratory. Anthropogenic pollutant concentrations were larger during the first part of the cruise, when air masses originated over the Indian subcontinent. Total NSS‐SO42− concentrations amounted to 2.94 ± 1.06 μg m−3 of which 92.1 ± 4.5% was present in the fine fraction. NSS‐SO42− source apportionment analysis with multivariate linear regression models revealed that in the coarse fraction half is biogenically and half anthropogenically derived, while in the fine fraction only 6% seemed of biogenic origin and 84% anthropogenic and 10% crustal in nature. Chloride deficits up to 99.1% in the fine fraction were observed. The average Cl− deficit in the fine fraction was 89.0 ± 9.4%, potentially related to NSS‐SO42− acid displacement and Cl reactive species formation, while in the coarse fraction it was 25.6 ± 21.3%, with NO3− being the preferred species for acid displacement.
Ba/Ca in Neogloboquadrina pachyderma as an indicator of deglacial meltwater discharge into the western Arctic Ocean
Authors: Hall Jenney M. , Chan L.‐H.
Published: March 2004

Down‐core samples of the planktonic foraminifer Neogloboquadrina pachyderma sinistral from the Mendeleyev Ridge in the western Arctic Ocean have been analyzed for Ba/Ca and δ18O. The apparent distribution coefficient for N. pachyderma sin. is estimated at DBa = 0.22 ± 0.02. A meltwater event is identified at around 11.8 14C kyr BP and is coincident with elevated Ba/Ca ratios. The barium enrichment is believed to be the result of enhanced weathering and erosion following glaciation. Additionally, barium may have desorbed from shelf sediments as sea level rose. Changes in Ba/Ca correlate with the retreat of the Laurentide Ice Sheet and the evolution of the Mackenzie River drainage basin. Therefore maximum Ba/Ca in Arctic surface waters at 11.8 ka may be indicative of an increase in the export of freshwater from the Arctic to the North Atlantic, potentially contributing to the onset of the Younger Dryas. This work suggests that Ba/Ca in planktonic foraminifera may be a useful indicator of the timing and processes associated with deglaciation.
Neogene‐Quaternary tectonic evolution of the southern Apennines
Authors: Catalano S. , Monaco C. , Tortorici L. , Paltrinieri W. , Steel N.
Published: March 2004

In this paper we present a study of a segment of the southern Apennine mountain belt which extends from the Pollino mountain range to the south and the Sele valley to the north. Combining regional data and structural information with the results based on the interpretation of several seismic reflection lines and many deep well logs, three regional cross sections have been constructed. The cross sections highlight the overall architecture of the orogenic belt which is constituted by a thin tectonic layer of allochthonous nappes represented by remnants of the Neotethyan accretionary wedge (e.g., Liguride and Sicilide units) resting above a thick imbricated thrust belt. This latter comprises distinct units represented by platform carbonates (western platform, Monte Alpi, Costamolina and Tempa Rossa units) and pelagic basin domains (Lagonegro, Campomaggiore and Faeto units) deriving from the Late Tortonian‐Quaternary deformation of the Adria paleomargin. The restoration of the three cross sections furnished information on the primary geometry of the Adria paleomargin which was characterized by the occurrence of a large platform domain dissected by distinct pelagic basins with complex and irregular margins represented by pelagic embayments and platform promontories developed during the Mesozoic and the Late Cretaceous‐Tertiary times. The reconstructed geometry of the paleomargin provided, moreover, useful insights to evaluate the mode of deformation and the rates of shortening of the thrust belt and to explain the Neogene stratigraphy of the distinct platform domains. The mode of deformation of this portion of the southern Apennines was dominated by the occurrence of crustal thrusts located along previous weakness zones represented by the boundaries between platform and pelagic domains. These crustal thrusts caused the complete closure of the basin areas and the direct overthrusting of the different buoyant platform domains, with contractional rates characterized by values ranging from 3.1 to 4.3 cm/yr. Finally, a geodynamic model in which the southern Apennine mountain belt is considered the result of lateral extrusion produced by the indentation of the Pelagian block and by the consequent opening of the Tyrrhenian Sea is also proposed.
Does the Electrical Power Industry Need Better Storm Warnings?
Authors: Simpson Sarah
Published: March 2004

Some power industry experts argue that NOAA's K index is inadequate for describing the threat of geomagnetically induced currents.
From the Solar Corona to Clusters of Galaxies: The Radio Astronomy of Bruce Slee
Authors: Orchiston Wayne
Published: March 2004

Owen Bruce Slee is one of the pioneers of Australian radio astronomy. During World War II he independently discovered solar radio emission, and, after joining the CSIRO Division of Radiophysics, used a succession of increasingly more sophisticated radio telescopes to examine an amazing variety of celestial objects and phenomena. These ranged from the solar corona and other targets in our solar system, to different types of stars and the ISM in our Galaxy, and beyond to distant galaxies and clusters of galaxies. Although long retired, Slee continues to carry out research, with emphasis on active stars and clusters of galaxies. A quiet and unassuming man, Slee has spent more than half a century making an important, wide-ranging contribution to astronomy, and his work deserves to be more widely known.
Ultra High Energy Cosmic Rays
Authors: Protheroe R. J. , Clay R. W.
Published: March 2004

Cosmic rays with energies above 1018 eV are currently of considerable interest in astrophysics and are to be further studied in a number of projects which are either currently under construction or the subject of well-developed proposals. This paper aims to discuss some of the physics of such particles in terms of current knowledge and information from particle astrophysics at other energies.
Crystal structure of the complex between thrombin and the central “E” region of fibrin
Authors: Pechik Igor , Madrazo Joel , Mosesson Michael W. , Hernandez Irene , Gilliland Gary L. , Medved Leonid
Published: March 2004

Nonsubstrate interactions of thrombin with fibrin play an important role in modulating its procoagulant activity. To establish the structural basis for these interactions, we crystallized
d
-Phe-Pro-Arg-chloromethyl ketone-inhibited human thrombin in complex with a fragment, E
ht
, corresponding to the central region of human fibrin, and solved its structure at 3.65-Å resolution. The structure revealed that the complex consists of two thrombin molecules bound to opposite sides of the central part of E
ht
in a way that seems to provide proper orientation of their catalytic triads for cleavage of fibrinogen fibrinopeptides. As expected, binding occurs through thrombin's anion-binding exosite I. However, only part of it is involved in forming an interface with the complementary negatively charged surface of E
ht
. Among residues constituting the interface, Phe-34, Ser-36A, Leu-65, Tyr-76, Arg-77A, Ile-82, and Lys-110 of thrombin and the Aα chain Trp-33, Phe-35, Asp-38, Glu-39, the Bβ chain Ala-68 and Asp-69, and the γ chain Asp-27 and Ser-30 of E
ht
form a net of polar contacts surrounding a well defined hydrophobic interior. Thus, despite the highly charged nature of the interacting surfaces, hydrophobic contacts make a substantial contribution to the interaction.
Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I
Authors: Tegeder Irmgard , Del Turco Domenico , Schmidtko Achim , Sausbier Matthias , Feil Robert , Hofmann Franz , Deller Thomas , Ruth Peter , Geisslinger Gerd
Published: March 2004

cGMP-dependent protein kinase I (PKG-I) has been suggested to contribute to the facilitation of nociceptive transmission in the spinal cord presumably by acting as a downstream target of nitric oxide. However, PKG-I activators caused conflicting effects on nociceptive behavior. In the present study we used PKG-I-/-mice to further assess the role of PKG-I in nociception. PKG-I deficiency was associated with reduced nociceptive behavior in the formalin assay and zymosan-induced paw inflammation. However, acute thermal nociception in the hot-plate test was unaltered. After spinal delivery of the PKG inhibitor, Rp-8-Br-cGMPS, nociceptive behavior of PKG-I+/+mice was indistinguishable from that of PKG-I-/-mice. On the other hand, the PKG activator, 8-Br-cGMP (250 nmol intrathecally) caused mechanical allodynia only in PKG-I+/+mice, indicating that the presence of PKG-I was essential for this effect. Immunofluorescence studies of the spinal cord revealed additional morphological differences. In the dorsal horn of 3- to 4-week-old PKG-I-/-mice laminae I-III were smaller and contained fewer neurons than controls. Furthermore, the density of substance P-positive neurons and fibers was significantly reduced. The paucity of substance P in laminae I-III may contribute to the reduction of nociception in PKG-I-/-mice and suggests a role of PKG-I in substance P synthesis.
Solvation in protein folding analysis: Combination of theoretical and experimental approaches
Authors: Fernández-Escamilla A. M. , Cheung M. S. , Vega M. C. , Wilmanns M. , Onuchic J. N. , Serrano L.
Published: March 2004

An effort to combine theoretical analyses and protein engineering methods has been made to probe the folding mechanism of SH3 by using Energy Landscape Theory and a φ-value analysis. Particular emphasis was given to core residues and the effect of desolvation during the folding event by replacing the core valines with isosteric threonines. These mutations have the advantage of keeping the core structurally invariant while affecting core stability relative to the unfolded state. Although the valines that form the core appear spatially invariant, the folding kinetics of their threonine mutants varies, indicating their different extent of solvation in the transition-state ensemble. Theoretical studies predicted the distribution of folding kinetics of threonine mutants without previous knowledge of the measured rates. This initial success encourages further investigations of the molecular details behind these macroscopic phenomena and of the role of solvation in the folding mechanism.
Gene transfer in the evolution of parasite nucleotide biosynthesis
Authors: Striepen Boris , Pruijssers Andrea J. P. , Huang Jinling , Li Catherine , Gubbels Marc-Jan , Umejiego Nwakaso N. , Hedstrom Lizbeth , Kissinger Jessica C.
Published: March 2004

Nucleotide metabolic pathways provide numerous successful targets for antiparasitic chemotherapy, but the human pathogen
Cryptosporidium parvum
thus far has proved extraordinarily refractory to classical treatments. Given the importance of this protist as an opportunistic pathogen afflicting immunosuppressed individuals, effective treatments are urgently needed. The genome sequence of
C. parvum
is approaching completion, and we have used this resource to critically assess nucleotide biosynthesis as a target in
C. parvum
. Genomic analysis indicates that this parasite is entirely dependent on salvage from the host for its purines and pyrimidines. Metabolic pathway reconstruction and experimental validation in the laboratory further suggest that the loss of pyrimidine
de novo
synthesis is compensated for by possession of three salvage enzymes. Two of these, uridine kinase-uracil phosphoribosyltransferase and thymidine kinase, are unique to
C. parvum
within the phylum Apicomplexa. Phylogenetic analysis suggests horizontal gene transfer of thymidine kinase from a proteobacterium. We further show that the purine metabolism in
C. parvum
follows a highly streamlined pathway. Salvage of adenosine provides
C. parvum
's sole source of purines. This renders the parasite susceptible to inhibition of inosine monophosphate dehydrogenase, the rate-limiting enzyme in the multistep conversion of AMP to GMP. The inosine 5′ monophosphate dehydrogenase inhibitors ribavirin and mycophenolic acid, which are already in clinical use, show pronounced anticryptosporidial activity. Taken together, these data help to explain why widely used drugs fail in the treatment of cryptosporidiosis and suggest more promising targets.
Disruption of TRPM6/TRPM7 complex formation by a mutation in the
TRPM6
gene causes hypomagnesemia with secondary hypocalcemia
Authors: Chubanov Vladimir , Waldegger Siegfried , Schnitzler Michael Mederos y , Vitzthum Helga , Sassen Martin C. , Seyberth Hannsjörg W. , Konrad Martin , Gudermann Thomas
Published: March 2004

Impaired magnesium reabsorption in patients with
TRPM6
gene mutations stresses an important role of TRPM6 (melastatin-related TRP cation channel) in epithelial magnesium transport. While attempting to isolate full-length TRPM6, we found that the human
TRPM6
gene encodes multiple mRNA isoforms. Full-length TRPM6 variants failed to form functional channel complexes because they were retained intracellularly on heterologous expression in HEK 293 cells and
Xenopus
oocytes. However, TRPM6 specifically interacted with its closest homolog, the Mg
2+
-permeable cation channel TRPM7, resulting in the assembly of functional TRPM6/TRPM7 complexes at the cell surface. The naturally occurring S141L TRPM6 missense mutation abrogated the oligomeric assembly of TRPM6, thus providing a cell biological explanation for the human disease. Together, our data suggest an important contribution of TRPM6/TRPM7 heterooligomerization for the biological role of TRPM6 in epithelial magnesium absorption.
ADP reduces the oxygen-binding affinity of a sensory histidine kinase, FixL: The possibility of an enhanced reciprocating kinase reaction
Authors: Nakamura Hiro , Kumita Hideyuki , Imai Kiyohiro , Iizuka Tetsutaro , Shiro Yoshitsugu
Published: March 2004

The rhizobial FixL/FixJ system, a paradigm of heme-based oxygen sensors, belongs to the ubiquitous two-component signal transduction system. Oxygen-free (deoxy) FixL is autophosphorylated at an invariant histidine residue by using ATP and catalyzes the concomitant phosphoryl transfer to FixJ, but oxygen binding to the FixL heme moiety inactivates the kinase activity. Here we demonstrate that ADP acts as an allosteric effector, reducing the oxygen-binding affinity of the sensor domain in FixL when it is produced from ATP in the kinase reaction. The addition of ADP to a solution of purified wild-type FixL resulted in an ≈4- to 5-fold decrease in oxygen-binding affinity in the presence of FixJ. In contrast, phosphorylation-deficient mutants, in which the well conserved ATP-binding catalytic site of the kinase domain is impaired, showed no such allosteric effect. This discovery casts light on the significance of homodimerization of two-component histidine kinases; ADP, generated in the phosphorylation reaction in one subunit of the homodimer, enhances the histidine kinase activity of the other, analogous to a two-cylinder reciprocating engine by reducing the ligand-binding affinity.
Portability and fidelity of RNA-repair systems
Authors: Schwer Beate , Sawaya Rana , Ho C. Kiong , Shuman Stewart
Published: March 2004

Yeast tRNA ligase (Trl1) is an essential enzyme that converts cleaved tRNA half-molecules into spliced tRNAs containing a 2′-PO
4
, 3′-5′ phosphodiester at the splice junction. Trl1 also catalyzes splicing of
HAC1
mRNA during the unfolded protein response. Trl1 performs three reactions: the 2′,3′-cyclic phosphate of the proximal RNA fragment is hydrolyzed to a 3′-OH, 2′-PO
4
by a cyclic phosphodiesterase; the 5′-OH of the distal RNA fragment is phosphorylated by a GTP-dependent polynucleotide kinase; and the 3′-OH, 2′-PO
4
, and 5′-PO
4
ends are then sealed by an ATP-dependent RNA ligase. The removal of the 2′-PO
4
at the splice junction is catalyzed by the essential enzyme Tpt1, which transfers the RNA 2′-PO
4
to NAD
+
to form ADP-ribose 1′′-2′′-cyclic phosphate. Here, we show that the bacteriophage T4 enzymes RNA ligase 1 and polynucleotide kinase/phosphatase can fulfill the tRNA and
HAC1
mRNA splicing functions of yeast Trl1
in vivo
and bypass the requirement for Tpt1. These results attest to the portability of RNA-repair systems, notwithstanding the significant differences in the specificities, mechanisms, and reaction intermediates of the individual yeast and T4 enzymes responsible for the RNA healing and sealing steps. We surmise that Tpt1 and its unique metabolite ADP-ribose 1′′-2′′-cyclic phosphate do not play essential roles in yeast independent of the tRNA-splicing reaction. Our finding that one-sixth of spliced
HAC1
mRNAs in yeast cells containing the T4 RNA-repair system suffered deletion of a single nucleotide at the 3′ end of the splice-donor site suggests a model whereby the yeast RNA-repair system evolved a requirement for the 2′-PO
4
for RNA ligation to suppress inappropriate RNA recombination.
Fluorescence correlation spectroscopy with high-order and dual-color correlation to probe nonequilibrium steady states
Authors: Qian Hong , Elson Elliot L.
Published: March 2004

In living cells, biochemical reaction networks often function in nonequilibrium steady states. Under these conditions, the networks necessarily have cyclic reaction kinetics that are maintained by sustained constant input and output, i.e., pumping. To differentiate this state from an equilibrium state without flux, we propose a microscopic method based on concentration fluctuation measurements, via fluorescence correlation spectroscopy, and statistical analyses of high-order correlations and cross correlations beyond the standard fluorescence correlation spectroscopy autocorrelation. We show that, for equilibrium systems with time reversibility, the correlation functions possess certain symmetries, the violation of which is a measure of steady-state fluxes in reaction cycles. This result demonstrates the theoretical basis for experimentally measuring reaction fluxes in a biochemical network
in situ
and the importance of single-molecule measurements in providing fundamental information on nonequilibrium steady-states in biochemistry.
Transgenic male mating advantage provides opportunity for Trojan gene effect in a fish
Authors: Howard Richard D. , DeWoody J. Andrew , Muir William M.
Published: March 2004

Genetically modified (GM) strains now exist for many organisms, producing significant promise for agricultural production. However, if these organisms have some fitness advantage, they may also pose an environmental harm when released. High mating success of GM males relative to WT males provides such an important fitness advantage. Here, we provide documentation that GM male medaka fish modified with salmon growth hormone possess an overwhelming mating advantage. GM medaka offspring possess a survival disadvantage relative to WT, however. When both of these fitness components are included in our model, the transgene is predicted to spread if GM individuals enter wild populations (because of the mating advantage) and ultimately lead to population extinction (because of the viability disadvantage). Mating trials indicate that WT males use alternative mating tactics in an effort to counter the mating advantage of GM males, and we use genetic markers to ascertain the success of these alternative strategies. Finally, we model the impact of alternative mating tactics by WT males on transgene spread. Such tactics may reduce the rate of transgene spread, but not the outcome.
Two routes to emotional memory: Distinct neural processes for valence and arousal
Authors: Kensinger Elizabeth A. , Corkin Suzanne
Published: March 2004

Prior investigations have demonstrated that emotional information is often better remembered than neutral information, but they have not directly contrasted effects attributable to valence and those attributable to arousal. By using functional MRI and behavioral studies, we found that distinct cognitive and neural processes contribute to emotional memory enhancement for arousing information versus valenced, nonarousing information. The former depended on an amygdalar-hippocampal network, whereas the latter was supported by a prefrontal cortex-hippocampal network implicated in controlled encoding processes. A behavioral companion study, with a divided-attention paradigm, confirmed that memory enhancement for valenced, nonarousing words relied on controlled encoding processes: concurrent task performance reduced the enhancement effect. Enhancement for arousing words occurred automatically, even when encoding resources were diverted to the secondary task.
Identification of a target RNA motif for RNA-binding protein HuR
Authors: de Silanes Isabel López , Zhan Ming , Lal Ashish , Yang Xiaoling , Gorospe Myriam
Published: March 2004

HuR, a protein that binds to specific mRNA subsets, is increasingly recognized as a pivotal posttranscriptional regulator of gene expression. Here, HuR was immunoprecipitated under conditions that preserved HuR-RNA interactions, and HuR-bound target mRNAs were identified by cDNA array hybridization. Analysis of primary sequences and secondary structures shared among HuR targets led to the identification of a 17- to 20-base-long RNA motif rich in uracils. This HuR motif was found in almost all mRNAs previously reported to be HuR targets, was located preferentially within 3′ untranslated regions of all unigene transcripts examined, and was conserved in >50% of human and mouse homologous genes. Importantly, the HuR motif allowed the successful prediction and subsequent validation of novel HuR targets from gene databases. This study describes an HuR target RNA motif and presents a general strategy for identifying target motifs for RNA-binding proteins.
Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection
Authors: Shen Yuequan , Zhukovskaya Natalia L. , Zimmer Michael I. , Soelaiman Sandriyana , Bergson Pamela , Wang Chyung-Ru , Gibbs Craig S. , Tang Wei-Jen
Published: March 2004

Edema factor (EF), a key virulence factor in anthrax pathogenesis, has calmodulin (CaM)-activated adenylyl cyclase activity. We have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages. Adefovir diphosphate (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of EF
in vitro
with high affinity (
K
i
= 27 nM). A crystal structure of EF-CaM-PMEApp reveals that the catalytic site of EF forms better van der Waals contacts and more hydrogen bonds with PMEApp than with its endogenous substrate, ATP, providing an explanation for the ≈10,000-fold higher affinity EF-CaM has for PMEApp versus ATP. Adefovir dipivoxil is a clinically approved drug that can block the action of an anthrax toxin. It can be used to address the role of EF in anthrax pathogenesis.
Targeted analysis and discovery of posttranslational modifications in proteins from methanogenic archaea by top-down MS
Authors: Forbes Andrew J. , Patrie Steven M. , Taylor Gregory K. , Kim Yong-Bin , Jiang Lihua , Kelleher Neil L.
Published: March 2004

For more complete characterization of DNA-predicted proteins (including their posttranslational modifications) a “top-down” approach using high-resolution tandem MS is forwarded here by its application to methanogens in both hypothesis-driven and discovery modes, with the latter dependent on new automation benchmarks for intact proteins. With proteins isolated from ribosomes and whole-cell lysates of
Methanococcus jannaschii
(≈1,800 genes) using a 2D protein fractionation method, 72 gene products were identified and characterized with 100% sequence coverage via automated fragmentation of intact protein ions in a custom quadrupole/Fourier transform hybrid mass spectrometer. Three incorrect start sites and two modifications were found, with one of each determined for MJ0556, a 20-kDa protein with an unknown methylation at ≈50% occupancy in stationary phase cells. The separation approach combined with the quadrupole/Fourier transform hybrid mass spectrometer allowed targeted and efficient comparison of histones from
M. jannaschii
,
Methanosarcina acetivorans
(largest Archaeal genome, 5.8 Mb), and yeast. This finding revealed a striking difference in the posttranslational regulation of DNA packaging in Eukarya vs. the Archaea. This study illustrates a significant evolutionary step for the MS tools available for characterization of WT proteins from complex proteomes without proteolysis.
FRIGIDA
-related genes are required for the winter-annual habit in
Arabidopsis
Authors: Michaels Scott D. , Bezerra Isabel C. , Amasino Richard M.
Published: March 2004

In temperate climates, the prolonged cold temperature of winter serves as a seasonal landmark for winter-annual and biennial plants. In these plants, flowering is blocked before winter. In
Arabidopsis thaliana
, natural variation in the
FRIGIDA
(
FRI
) gene is a major determinate of the rapid-cycling vs. winter-annual flowering habits. In winter-annual accessions of
Arabidopsis, FRI
activity blocks flowering through the up-regulation of the floral inhibitor
FLOWERING LOCUS C
(
FLC
). Most rapid-flowering accessions, in contrast, contain null alleles of
FRI
. By performing a mutant screen in a winter-annual strain, we have identified a locus,
FRIGIDA LIKE 1
(
FRL1
), that is specifically required for the up-regulation of
FLC
by
FRI
. Cloning of
FRL1
revealed a gene with a predicted protein sequence that is 23% identical to
FRI
. Despite sequence similarity,
FRI
and
FRL1
do not have redundant functions.
FRI
and
FRL1
belong to a seven-member gene family in
Arabidopsis
, and
FRI, FRL1
, and at least one additional family member,
FRIGIDA LIKE 2
(
FRL2
), are in a clade of this family that is required for the winter-annual habit in
Arabidopsis
.
Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers
Authors: Calin George Adrian , Sevignani Cinzia , Dumitru Calin Dan , Hyslop Terry , Noch Evan , Yendamuri Sai , Shimizu Masayoshi , Rattan Sashi , Bullrich Florencia , Negrini Massimo , Croce Carlo M.
Published: March 2004

A large number of tiny noncoding RNAs have been cloned and named microRNAs (miRs). Recently, we have reported that
miR-15a
and
miR-16a
, located at 13q14, are frequently deleted and/or down-regulated in patients with B cell chronic lymphocytic leukemia, a disorder characterized by increased survival. To further investigate the possible involvement of miRs in human cancers on a genome-wide basis, we have mapped 186 miRs and compared their location to the location of previous reported nonrandom genetic alterations. Here, we show that miR genes are frequently located at fragile sites, as well as in minimal regions of loss of heterozygosity, minimal regions of amplification (minimal amplicons), or common breakpoint regions. Overall, 98 of 186 (52.5%) of miR genes are in cancer-associated genomic regions or in fragile sites. Moreover, by Northern blotting, we have shown that several miRs located in deleted regions have low levels of expression in cancer samples. These data provide a catalog of miR genes that may have roles in cancer and argue that the full complement of miRs in a genome may be extensively involved in cancers.
Kinetic analysis of genomewide gene expression reveals molecule circuitries that control T cell activation and Th1/2 differentiation
Authors: Lu Binfeng , Zagouras Panayiotis , Fischer James E. , Lu Junfeng , Li Baiyong , Flavell Richard A.
Published: March 2004

The global gene expression profiling of early T helper (Th) 1 and Th2 differentiation reveals that this process can be divided into two stages, activation and differentiation. The activation stage is manifested in coordinated mobilization of the replication machinery, a process that we hypothesize may be responsible for establishing genomewide opening of transcription loci. The molecular programs underlying the differentiation stage consist of highly regulated expression of functional groups of genes that are important for the biological properties of Th1/2 cells and transcription factors that are likely important in establishing terminal differentiation of these cells. The kinetics of expression pattern of a number of transcription factors shed new light on the molecular events that shape the outcome of Th1/2 differentiation.
Role of interfacial amino acid residues in assembly, stability, and conformation of a spherical virus capsid
Authors: Reguera Juan , Carreira Aura , Riolobos Laura , Almendral José María , Mateu Mauricio G.
Published: March 2004

Twenty-eight amino acid residues involved in most noncovalent interactions between trimeric protein subunits in the capsid of the parvovirus minute virus of mice were truncated individually to alanine, and the effects on capsid assembly, thermostability, and conformation were analyzed. Only seven side chains were essential for protein subunit recognition. These side chains virtually corresponded with those that either buried a large hydrophobic surface on trimer association or formed buried intertrimer hydrogen bonds or salt bridges. The seven residues are evolutionarily conserved, and they define regularly spaced spots on a thin equatorial belt surrounding each trimer. Truncation of the many side chains that were dispensable for assembly, including those participating in solvent-accessible polar interactions, did not substantially affect capsid thermostability either. However, the interfacial residues located at the base of the pores delineating the capsid five-fold axes participated in a heat-induced conformational rearrangement associated with externalization of the capsid protein N terminus, and they were needed for infectivity. Thus, at the subunit interfaces of this model virus capsid, only key residues involved in the strongest interactions are critical for assembly and stability, but additional residues fulfill other important biological roles.
Almost sharp fronts for the surface quasi-geostrophic equation
Authors: Córdoba Diego , Fefferman Charles , Rodrigo José Luis
Published: March 2004

We investigate the evolution of “almost sharp” fronts for the surface quasi-geostrophic equation. This equation was originally introduced in the geophysical context to investigate the formation and evolution of fronts, i.e., discontinuities between masses of hot and cold air. These almost sharp fronts are weak solutions of quasi-geostrophic with large gradient. We relate their evolution to the evolution of sharp fronts.
Cellular protein is the source of cross-priming antigenin vivo
Authors: Shen Lianjun , Rock Kenneth L.
Published: March 2004

Cross-priming is essential for generating cytotoxic T lymphocytes to viral, tumor, and tissue antigens that are expressed exclusively in parenchymal cells. In this process, the antigen-bearing parenchymal cells must somehow transfer their antigens to bone marrow-derived professional antigen-presenting cells. Although intact proteins, small peptides, or peptide-heat shock protein complexes can all be acquired and presented by antigen-presenting cells, the physiologically relevant form of antigen that is actually transferred from parenchymal cells and cross-presentedin vivois unknown and controversial. To address this issue we have investigated the ability of fibroblasts stably expressing chicken ovalbumin constructs targeted to different subcellular compartments to cross-prime cytotoxic T lymphocytes. Although these transfectants generated similar amounts of the immunogenic ovalbumin peptide, their cross-priming activity differed markedly. Instead, the cells cross-priming ability correlated with their steady-state levels of ovalbumin protein and/or the physical form/location of the protein. Moreover, in subcellular fractionation experiments, the cross-priming activity colocalized with antigenic protein. In addition, depletion of intact protein antigen from these cell fractions eliminated their cross-priming activity. In contrast, the major heat shock protein candidates for cross-presentation were separable from the cell's main sources of cross-priming antigen. Therefore, cellular proteins, rather than peptides or heat shock protein/peptide complexes, are the major source of antigen that is transferred from antigen-bearing cells and cross-presentedin vivo.
Blue light-induced transcription of plastid-encoded
psbD
gene is mediated by a nuclear-encoded transcription initiation factor, AtSig5
Authors: Tsunoyama Yuichi , Ishizaki Yoko , Morikawa Kazuya , Kobori Maki , Nakahira Yoichi , Takeba Go , Toyoshima Yoshinori , Shiina Takashi
Published: March 2004

Light is one of the most important environmental factors regulating expression of photosynthesis genes. The plastid
psbD
gene encoding the photosystem II reaction center protein D2 is under the control of a unique blue light responsive promoter (BLRP) that is transcribed by a bacterial-type plastid RNA polymerase (PEP). Promoter recognition of PEP is mediated by one of the six nuclear-encoded σ factors in
Arabidopsis
. The replacement of the plastid σ factor associated with PEP may be the major mechanism for switching of plastid transcription pattern in response to environmental and developmental signals. This study demonstrates that AtSig5 is a unique σ factor that is essential for
psbD
BLRP activity. A T-DNA insertional mutant with reduced
AtSIG5
expression resulted in loss of primary transcripts from the
psbD
BLRP. Furthermore, transient overexpression of AtSig5 in dark-adapted protoplasts specifically elevated
psbD
and
psbA
transcription activities. On the other hand, overproduction of AtSig2 enhanced the transcription of
psbA
gene and
trnE
operon, but not
psbD
transcription. The
AtSIG5
gene is phylogenetically distinct from other plastid σ factors, and its expression is induced exclusively by blue light. We propose that AtSig5 acts as a mediator of blue light signaling that specifically activates the
psbD
BLRP in response to blue light in
Arabidopsis
.
Intact type 1 immunity and immune-associated coagulative responses in mice lacking IFNγ-inducible fibrinogen-like protein 2
Authors: Hancock Wayne W. , Szaba Frank M. , Berggren Kiera N. , Parent Michelle A. , Mullarky Isis K. , Pearl John , Cooper Andrea M. , Ely Kenneth H. , Woodland David L. , Kim In-Jeong , Blackman Marcia A. , Johnson Lawrence L. , Smiley Stephen T.
Published: March 2004

Fibrinogen-like protein 2 (Fgl2, fibroleukin) is a leukocyte product that exhibits significant homology to secreted proteins of diverse function, including growth factors, lectins, and components of extracellular matrix. Prior studies found that Fgl2 is IFNγ-inducible, possesses direct coagulant activity, and inhibits T cell proliferation and dendritic cell maturationin vitro. Here, we demonstrate that Fgl2 expression is up-regulated during type 1 immunityin vivoand establish that such up-regulation is IFNγ-, signal transducer and activation of transcription protein 1-, and IFN response factor 1-dependent. To investigate functional roles for Fgl2 during type 1 immunity, we generated Fgl2-deficient mice. Those animals are born at predicted Mendelian frequencies, appear overtly healthy, and contain normal numbers and frequencies of lymphoid cells. Although Fgl2 is IFNγ-inducible and putatively regulates T cell activation/proliferation, we demonstrate that Fgl2-deficient and control mice exhibit similar degrees of T cell expansion, immunopathology, and/or pathogen burdens during protozoan (Toxoplasma gondii), bacterial (Yersinia enterocolitica, Listeria monocytogenes, andMycobacterium tuberculosis), and viral (murine γ-herpesvirus-68 and Sendai) infections. Fgl2-deficient mice also reject allografts with similar kinetics as control mice. Moreover, despite prior reports that Fgl2 functions as a procoagulant enzyme, we demonstrate that Fgl2-deficient and control mice produce similar levels of fibrin, a product of the coagulation cascade, duringT. gondiiinfection and allograft rejection. Together, our findings suggest that Fgl2, although highly conserved and IFNγ-inducible, is not a critical mediator of either type 1 immunity or immune-associated coagulant activity.
The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity
Authors: Xu Jianchao , Wang Peili , Li Yanyan , Li Guoyong , Kaczmarek Leonard K. , Wu Yanling , Koni Pandelakis A. , Flavell Richard A. , Desir Gary V.
Published: March 2004

Kv1.3 is a voltage-gated potassium (K) channel expressed in a number of tissues, including fat and skeletal muscle. Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes. Gene inactivation causes mice (Kv1.3-/-) exposed to a high-fat diet to gain less weight and be less obese than littermate control. Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels. This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity. Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivityin vivo. Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice. Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane. It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue. We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane. These results pinpoint a pathway through which K channels regulate peripheral glucose homeostasis, and identify Kv1.3 as a pharmacologic target for the treatment of diabetes.
Metallic single-walled silicon nanotubes
Authors: Bai Jaeil , Zeng X. C. , Tanaka Hideki , Zeng J. Y.
Published: March 2004

Atomistic computer-simulation evidences are presented for the possible existence of one-dimensional silicon nanostructures: the square, pentagonal, and hexagonal single-walled silicon nanotubes (SWSNTs). The local geometric structure of the SWSNTs differs from the local tetrahedral structure of cubic diamond silicon, although the coordination number of atoms of the SWSNTs is still fourfold.
Ab initio
calculations show that the SWSNTs are locally stable in vacuum and have zero band gap, suggesting that the SWSNTs are possibly metals rather than wide-gap semiconductors.