bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of Tokamak Fusion Test Reactor performance by lithium conditioning
Authors: Mansfield D. K. , Hill K. W. , Strachan J. D. , Bell M. G. , Scott S. D. , Budny R. , Marmar E. S. , Snipes J. A. , Terry J. L. , Batha S. , Bell R. E. , Bitter M. , Bush C. E. , Chang Z. , Darrow D. S. , Ernst D. , Fredrickson E. , Grek B. , Herrmann H. W. , Janos A. , Jassby D. L. , Jobes F. C. , Johnson D. W. , Johnson L. C. , Levinton F. M. , Mikkelsen D. R. , Mueller D. , Owens D. K. , Park H. , Ramsey A. T. , Roquemore A. L. , Skinner C. H. , Stevenson T. , Stratton B. C. , Synakowski E. , Taylor G. , von Halle A. , von Goeler S. , Wong K. L. , Zweben S. J. ,   TFTR Group
Published: July 2002

Wall conditioning in the Tokamak Fusion Test Reactor (TFTR) [K. M. McGuire et al., Phys. Plasmas 2, 2176 (1995)] by injection of lithium pellets into the plasma has resulted in large improvements in deuterium–tritium fusion power production (up to 10.7 MW), the Lawson triple product (up to 1021 m−3 s keV), and energy confinement time (up to 330 ms). The maximum plasma current for access to high-performance supershots has been increased from 1.9 to 2.7 MA, leading to stable operation at plasma stored energy values greater than 5 MJ. The amount of lithium on the limiter and the effectiveness of its action are maximized through (1) distributing the Li over the limiter surface by injection of four Li pellets into Ohmic plasmas of increasing major and minor radius, and (2) injection of four Li pellets into the Ohmic phase of supershot discharges before neutral-beam heating is begun.
High efficiency cavity design of a 170 GHz gyrotron for fusion applications
Authors: Correa R. A. , Levush B. , Antonsen T. M.
Published: July 2002

The design of high power, continuous wave (cw), 170 GHz gyrotron cavities is considered. The anticipated degradation of efficiency with beam velocity spread places a premium on the optimization of efficiency. For parameters of interest achievement of high efficiency requires utilization of a high quality cavity. Two options are considered: a barrel cavity and a long simple tapered cavity operating at low voltage. The cavities are examined for their sensitivity to velocity spread, their mode competition, and their maximum Ohmic power dissipation.
The shear Alfvén wave in a resistive plasma with a shearless magnetic field
Authors: Tataronis John A. , Rauf Shahid
Published: July 2002

In this Brief Communication, the time development of the shear Alfvén wave in a resistive magnetohydrodynamic plasma is treated. The analysis is restricted to a pressureless plasma confined in a planar sheet pinch with a constant equilibrium magnetic field directed parallel to the magnetic surface wave vector. The equilibrium mass density depends on the spatial coordinate orthogonal to the planar magnetic surfaces. Under these conditions, the shear Alfvén mode decouples from the compressional Alfvén mode. The time behavior of the wave fields is governed by a second-order scalar partial differential equation. Laplace transform techniques are used to solve the equation, and to explore the limiting form of the solution as resistivity passes to zero.
Parametric instabilities due to relativistic electron mass variation
Authors: Guérin S. , Mora P. , Laval G.
Published: July 2002

The stability of an electronic plasma in a large-amplitude dipolar field is analyzed. In such a wave the relativistic electron mass variation must be taken into account and in an overdense plasma an instability arises. The corresponding weakly relativistic theory of Tsintsadze [Sov. Phys. JETP 32, 684 (1971)] is extended to the fully relativistic regime. The growth rate of the instability can attain a significant fraction of the dipolar field frequency. The relevance of this instability to the fast ignitor concept is discussed.
On neoclassical transport near the magnetic axis
Authors: Helander P.
Published: July 2002

The theory of neoclassical transport near the magnetic axis in a tokamak is discussed. It is shown that the ordinary treatment of transport in the plateau regime holds in most of the region within a trapped orbit width of the magnetic axis, and is not modified by “potato” orbits. It is also demonstrated that transport at low collisionality is not diffusive in nature and cannot be described independently of the sources of particles and heat in the region near the magnetic axis. A variational principle is formulated for the near-axis transport problem.
Phase variation of focused surface acoustic wave
Authors: Jen C. K. , Cielo P. , Bussiere J. , Nadeau F. , Farnell G. W.
Published: July 2002

Converging and diverging surface acoustic waves (SAW) have been generated and detected using a noncontacting method. A yttrium aluminum garnet laser together with an axicon lens produces a focused optical ring which excites both converging and diverging SAW on the test sample. An optical interferometer is used to measure the vertical displacement of the SAW. Variations of the SAW pulse waveforms in different positions along the radial direction of the ring are given. It is found that about 10 SAW wavelengths away from the focus, a 90° phase difference exists between the Fourier components of the SAW going toward the focus and of that having passed through and moving away.
Surface-energy-driven secondary grain growth in thin Au films
Authors: Wong Chee C. , Smith Henry I. , Thompson C. V.
Published: July 2002

Secondary grain growth in thin Au films on SiO2 substrates is reported. Secondary grains have {111} texture which minimizes the surface energy. This indicates that surface energy anisotropy provides selectivity in the driving force for growth of secondary grains. In thin Au films on SiO2, surface-energy-driven secondary grain growth occurs at room temperature as soon as a film becomes continuous. This mode of grain growth is, most likely, responsible for the development of the frequently observed {111} deposition texture in thin Au films.
Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels
in vivo
Authors: Winkler G. Sebastiaan , Kristjuhan Arnold , Erdjument-Bromage Hediye , Tempst Paul , Svejstrup Jesper Q.
Published: July 2002

The elongating, hyperphosphorylated form of RNA polymerase II is associated with the Elongator complex, which has the histone acetyltransferase (HAT) Elp3 as a subunit. Here we show that, in contrast to the isolated Elp3 subunit, the activity of intact Elongator complex is directed specifically toward the amino-terminal tails of histone H3 and H4, and that Elongator can acetylate both core histones and nucleosomal substrates. The predominant acetylation sites are lysine-14 of histone H3 and lysine-8 of histone H4. The three smallest Elongator subunits—Elp4, Elp5, and Elp6—are required for HAT activity, and Elongator binds to both naked and nucleosomal DNA. By using chromatin immunoprecipitation, we show that the levels of multiply acetylated histone H3 and H4 in chromatin are decreased
in vivo
in yeast cells lacking
ELP3
.
Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP
Authors: Maita Nobuo , Okada Kengo , Hatakeyama Kazuyuki , Hakoshima Toshio
Published: July 2002

In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. The crystal structure of the stimulatory complex reveals that the GTPCHI decamer is sandwiched by two GFRP homopentamers. Each GFRP pentamer forms a symmetrical five-membered ring similar to β-propeller. Five phenylalanine molecules are buried inside each interface between GFRP and GTPCHI, thus enhancing the binding of these proteins. The complex structure suggests that phenylalanine-induced GTPCHI⋅GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state.
Mutated plant lectin library useful to identify different cells
Authors: Yim Mijung , Ono Takashi , Irimura Tatsuro
Published: July 2002

The 24 nucleotides comprising the carbohydrate-recognition domain
of
Maackia amurensis
hemagglutinin (MAH) cDNA were
randomly mutated. The mutant lectins were expressed as
glutathione-
S
-transferase fusion proteins in
Escherichia coli
and 16 clones were randomly chosen.
Although all of 16 recombinant lectins reacted strongly with anti-MAH
polyclonal antibody, the carbohydrate-recognition domain of each was
unique. As shown by agglutination studies, each mutant MAH lectin was
able to bind to erythrocytes from one or more of five animal species in
very distinct patterns. Thus, novel plant lectin libraries can be used
to discriminate in a highly specific manner among a variety of cell
types. This technology may prove to be very useful in a number of
different applications requiring a high level of specificity in cell
identification.
ACVR1B
(
ALK4
, activin receptor type 1B) gene mutations in pancreatic carcinoma
Authors: Su Gloria H. , Bansal Ravi , Murphy Kathleen M. , Montgomery Elizabeth , Yeo Charles J. , Hruban Ralph H. , Kern Scott E.
Published: July 2002

DPC4
is known to mediate signals initiated by type
β transforming growth factor (TGFβ) as well as by other TGFβ
superfamily ligands such as activin and BMP (bone morphogenic
proteins), but mutational surveys of such non-TGFβ receptors have
been negative to date. Here we describe the gene structure and novel
somatic mutations of the activin type I receptor,
ACVR1B
, in pancreatic cancer.
ACVR1B
has
not been described previously as a mutated tumor-suppressor gene.
Synechocystis
HSP17 is an amphitropic protein that stabilizes heat-stressed membranes and binds denatured proteins for subsequent chaperone-mediated refolding
Authors: Török Zsolt , Goloubinoff Pierre , Horváth Ibolya , Tsvetkova Nelly M. , Glatz Attila , Balogh Gábor , Varvasovszki Viktória , Los Dmitry A. , Vierling Elizabeth , Crowe John H. , Vígh László
Published: July 2002

The small heat shock proteins (sHSPs) are ubiquitous stress
proteins proposed to act as molecular chaperones to prevent
irreversible protein denaturation. We characterized the chaperone
activity of
Synechocystis
HSP17 and found that it has
not only protein-protective activity, but also a previously
unrecognized ability to stabilize lipid membranes. Like other sHSPs,
recombinant
Synechocystis
HSP17 formed stable complexes
with denatured malate dehydrogenase and served as a reservoir for the
unfolded substrate, transferring it to the DnaK/DnaJ/GrpE and
GroEL/ES chaperone network for subsequent refolding. Large
unilamellar vesicles made of synthetic and cyanobacterial lipids were
found to modulate this refolding process. Investigation of HSP17-lipid
interactions revealed a preference for the liquid crystalline phase and
resulted in an elevated physical order in model lipid membranes. Direct
evidence for the participation of HSP17 in the control of thylakoid
membrane physical state
in vivo
was gained by examining
an
hsp
17
−
deletion mutant compared with the
isogenic wild-type
hsp
17
+
revertant
Synechocystis
cells. We suggest that, together with
GroEL, HSP17 behaves as an amphitropic protein and plays a dual role.
Depending on its membrane or cytosolic location, it may function as a
“membrane stabilizing factor” as well as a member of a
multichaperone protein-folding network. Membrane association of sHSPs
could antagonize the heat-induced hyperfluidization of specific
membrane domains and thereby serve to preserve structural and
functional integrity of biomembranes.
Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors α- and γ-mediated gene expression via liver fatty acid binding protein: A signaling path to the nucleus
Authors: Wolfrum Christian , Borrmann Carola M. , Börchers Torsten , Spener Friedrich
Published: July 2002

Peroxisome proliferator-activated receptor α (PPARα) is a key
regulator of lipid homeostasis in hepatocytes and target for fatty
acids and hypolipidemic drugs. How these signaling molecules reach the
nuclear receptor is not known; however, similarities in ligand
specificity suggest the liver fatty acid binding protein (L-FABP) as a
possible candidate. In localization studies using laser-scanning
microscopy, we show that L-FABP and PPARα colocalize in the nucleus
of mouse primary hepatocytes. Furthermore, we demonstrate by pull-down
assay and immunocoprecipitation that L-FABP interacts directly with
PPARα. In a cell biological approach with the aid of a mammalian
two-hybrid system, we provide evidence that L-FABP interacts with
PPARα and PPARγ but not with PPARβ and retinoid X receptor-α by
protein–protein contacts. In addition, we demonstrate that the
observed interaction of both proteins is independent of ligand binding.
Final and quantitative proof for L-FABP mediation was obtained in
transactivation assays upon incubation of transiently and stably
transfected HepG2 cells with saturated, monounsaturated, and
polyunsaturated fatty acids as well as with hypolipidemic drugs. With
all ligands applied, we observed strict correlation of PPARα and
PPARγ transactivation with intracellular concentrations of L-FABP.
This correlation constitutes a nucleus-directed signaling by fatty
acids and hypolipidemic drugs where L-FABP acts as a cytosolic gateway
for these PPARα and PPARγ agonists. Thus, L-FABP and the respective
PPARs could serve as targets for nutrients and drugs to affect
expression of PPAR-sensitive genes.
Inactivating one hippocampus impairs avoidance of a stable room-defined place during dissociation of arena cues from room cues by rotation of the arena
Authors: Cimadevilla J. M. , Wesierska M. , Fenton A. A. , Bures J.
Published: July 2002

Unilateral intrahippocampal injections of tetrodotoxin were
used to temporarily inactivate one hippocampus during specific phases
of training in an active allothetic place avoidance task. The rat was
required to use landmarks in the room to avoid a room-defined sector of
a slowly rotating circular arena. The continuous rotation dissociated
room cues from arena cues and moved the arena surface through a part of
the room in which foot-shock was delivered. The rat had to move away
from the shock zone to prevent being transported there by the rotation.
Unilateral hippocampal inactivations profoundly impaired acquisition
and retrieval of the allothetic place avoidance. Posttraining
unilateral hippocampal inactivation also impaired performance in
subsequent sessions. This allothetic place avoidance task seems more
sensitive to hippocampal disruption than the standard water maze task
because the same unilateral hippocampal inactivation does not impair
performance of the variable-start, fixed hidden goal task after
procedural training. The results suggest that the hippocampus not only
encodes allothetic relationships amongst landmarks, it also organizes
perceived allothetic stimuli into systems of mutually stable
coordinates. The latter function apparently requires greater
hippocampal integrity.
Abnormal accumulation of hyaluronan matrix diminishes contact inhibition of cell growth and promotes cell migration
Authors: Itano Naoki , Atsumi Fukiko , Sawai Takahiro , Yamada Yoichi , Miyaishi Osamu , Senga Takeshi , Hamaguchi Michinari , Kimata Koji
Published: July 2002

Elevated hyaluronan biosynthesis and matrix deposition correlates with cell proliferation and migration. We ectopically expressed three isoforms of hyaluronan synthase (HAS1, HAS2, or HAS3) in nontransformed rat 3Y1 cells and observed a
de novo
, massive formation of a hyaluronan matrix that resulted in a partial loss of contact-mediated inhibition of cell growth and migration. All three HAS transfectants showed an enhanced motility in scratch wound assays, and a significant increase in their confluent cell densities. In high-density cultures, the HAS transfectants had a fibroblastic cell shape and markedly formed overlapping cell layers. This phenotype was more pronounced in the HAS2 transfectants than HAS1 or HAS3 transfectants, and occurred with significant alterations in the microfilament organization and N-cadherin distribution at the cell–cell border. Inhibition of a phosphatidylinositol 3-kinase (PI3-kinase) pathway resulted in reacquisition of the normal phenotype of HAS2 transfectants, suggesting that the intracellular PI3-kinase signaling regulates diminution of contact inhibition induced by formation of the massive hyaluronan matrix. Our observations suggest that hyaluronan and its matrix can modulate contact inhibition of cell growth and migration, and provide evidence for functional differences between hyaluronan synthesized by the different HAS proteins.
The
mur2
mutant of
Arabidopsis thaliana
lacks fucosylated xyloglucan because of a lesion in fucosyltransferase AtFUT1
Authors: Vanzin Gary F. , Madson Michael , Carpita Nicholas C. , Raikhel Natasha V. , Keegstra Kenneth , Reiter Wolf-Dieter
Published: July 2002

Cell walls of the
Arabidopsis
mutant
mur2
contain less than 2% of the wild-type amount of fucosylated xyloglucan because of a point mutation in the fucosyltransferase
AtFUT1
. The
mur2
mutation eliminates xyloglucan fucosylation in all major plant organs, indicating that
Arabidopsis thaliana
fucosyltransferase 1 (AtFUT1) accounts for all of the xyloglucan fucosyltransferase activity in
Arabidopsis
. Despite this alteration in structure,
mur2
plants show a normal growth habit and wall strength. In contrast,
Arabidopsis mur1
mutants that are defective in the
de novo
synthesis of
l
-fucose exhibit a dwarfed growth habit and decreased wall strength [Reiter, W. D., Chapple, C. & Somerville, C. R. (1993)
Science
261, 1032–1035]. Because the
mur1
mutation affects several cell wall polysaccharides, whereas the
mur2
mutation is specific to xyloglucan, the phenotypes of
mur1
plants appear to be caused by structural changes in fucosylated pectic components such as rhamnogalacturonan-II. The normal growth habit and wall strength of
mur2
plants casts doubt on hypotheses regarding roles of xyloglucan fucosylation in facilitating xyloglucan–cellulose interactions or in modulating growth regulator activity.
sgk
, a primary glucocorticoid-induced gene, facilitates memory consolidation of spatial learning in rats
Authors: Tsai Kuen J. , Chen Shau K. , Ma Yun L. , Hsu Wei L. , Lee Eminy H. Y.
Published: July 2002

By using differential display PCR, we have identified 98 cDNA fragments from the rat dorsal hippocampus that are expressed differentially between the fast learners and slow learners in the water maze learning task. One of these cDNA fragments encodes the rat serum- and glucocorticoid-inducible kinase (
sgk
) gene. Northern blot analysis revealed that the
sgk
mRNA level was approximately 4-fold higher in the hippocampus of fast learners than slow learners.
In situ
hybridization results indicated that
sgk
mRNA level was increased markedly in CA1, CA3, and dentate gyrus of hippocampus in fast learners. Transient transfection of the
sgk
mutant DNA to the CA1 area impaired, whereas transfection of the
sgk
wild-type DNA facilitated water maze performance in rats. These results provide direct evidence that enhanced
sgk
expression facilitates memory consolidation of spatial learning in rats. These results also elucidate the molecular mechanism of glucocorticoid-induced memory facilitation in mammals.
Mutation of the myosin converter domain alters cross-bridge elasticity
Authors: Köhler Jan , Winkler Gerhard , Schulte Imke , Scholz Tim , McKenna William , Brenner Bernhard , Kraft Theresia
Published: July 2002

Elastic distortion of a structural element of the actomyosin complex is fundamental to the ability of myosin to generate motile forces. An elastic element allows strain to develop within the actomyosin complex (cross-bridge) before movement. Relief of this strain then drives filament sliding, or more generally, movement of a cargo. Even with the known crystal structure of the myosin head, however, the structural element of the actomyosin complex in which elastic distortion occurs remained unclear. To assign functional relevance to various structural elements of the myosin head, e.g., to identify the elastic element within the cross-bridge, we studied mechanical properties of muscle fibers from patients with familial hypertrophic cardiomyopathy with point mutations in the head domain of the β-myosin heavy chain. We found that the Arg-719 → Trp (Arg719Trp) mutation, which is located in the converter domain of the myosin head fragment, causes an increase in force generation and fiber stiffness under isometric conditions by 48–59%. Under rigor and relaxing conditions, fiber stiffness was 45–47% higher than in control fibers. Yet, kinetics of active cross-bridge cycling were unchanged. These findings, especially the increase in fiber stiffness under rigor conditions, indicate that cross-bridges with the Arg719Trp mutation are more resistant to elastic distortion. The data presented here strongly suggest that the converter domain that forms the junction between the catalytic and the light-chain-binding domain of the myosin head is not only essential for elastic distortion of the cross-bridge, but that the main elastic distortion may even occur within the converter domain itself.
Frequency-dependent synchrony in locus ceruleus: Role of electrotonic coupling
Authors: Alvarez Veronica A. , Chow Carson C. , Van Bockstaele Elisabeth J. , Williams John T.
Published: July 2002

Electrotonic coupling synchronizes the spontaneous firing of locus ceruleus (LC) neurons in the neonatal rat brain, whereas in adults, synchronous activity is rare. This report examines the role of action potential frequency on synchronous activity in the adult LC. Decreasing the firing frequency in slices from adult animals facilitated the appearance of subthreshold oscillations and increased the correlation of the membrane potential between pairs of neurons. Conversely, increasing the firing frequency decreased the amplitude and synchrony of the oscillations among pairs. The frequency-dependent synchrony was not observed in slices from neonatal rats, where synchrony was observed at all frequencies, suggesting a developmental change in the properties of the LC network. A mathematical model confirmed that a reduction of the coupling strength among a pair of coupled neurons could generate frequency-dependent synchrony. In slices from adult animals, the combination of electrotonic coupling and firing frequency are the key elements that regulate synchronous firing in this nucleus.
Effects of temporal association on recognition memory
Authors: Wallis Guy , Bülthoff Heinrich H.
Published: July 2002

The influence of temporal association on the representation and
recognition of objects was investigated. Observers were shown sequences
of novel faces in which the identity of the face changed as the head
rotated. As a result, observers showed a tendency to treat the views as
if they were of the same person. Additional experiments revealed that
this was only true if the training sequences depicted head rotations
rather than jumbled views; in other words, the sequence had to be
spatially as well as temporally smooth. Results suggest that we are
continuously associating views of objects to support later recognition,
and that we do so not only on the basis of the physical similarity, but
also the correlated appearance in time of the objects.
A strategy for the identification of proteins targeted by thioredoxin
Authors: Yano Hiroyuki , Wong Joshua H. , Lee Young Moo , Cho Myeong-Je , Buchanan Bob B.
Published: July 2002

Thioredoxins are 12-kDa proteins functional in the regulation
of cellular processes throughout the animal, plant, and microbial
kingdoms. Growing evidence with seeds suggests that an
h
-type of thioredoxin, reduced by NADPH via
NADP-thioredoxin reductase, reduces disulfide bonds of target proteins
and thereby acts as a wakeup call in germination. A better
understanding of the role of thioredoxin in seeds as well as other
systems could be achieved if more were known about the target proteins.
To this end, we have devised a strategy for the comprehensive
identification of proteins targeted by thioredoxin. Tissue extracts
incubated with reduced thioredoxin are treated with a fluorescent probe
(monobromobimane) to label sulfhydryl groups. The newly labeled
proteins are isolated by conventional two-dimensional electrophoresis:
(
i
) nonreducing/reducing or (
ii
)
isoelectric focusing/reducing SDS/PAGE. The isolated proteins are
identified by amino acid sequencing. Each electrophoresis system offers
an advantage: the first method reveals the specificity of thioredoxin
in the reduction of intramolecular vs. intermolecular disulfide bonds,
whereas the second method improves the separation of the labeled
proteins. By application of both methods to peanut seed extracts, we
isolated at least 20 thioredoxin targets and identified 5—three
allergens (Ara h2, Ara h3, and Ara h6) and two proteins not known to
occur in peanut (desiccation-related and seed maturation protein).
These findings open the door to the identification of proteins targeted
by thioredoxin in a wide range of systems, thereby enhancing our
understanding of its function and extending its technological and
medical applications.
Prediction of protein deamidation rates from primary and three-dimensional structure
Authors: Robinson Noah E. , Robinson Arthur B.
Published: July 2002

A method for the quantitative estimation of instability with respect to deamidation of the asparaginyl (Asn) residues in proteins is described. The procedure involves the observation of several simple aspects of the three-dimensional environment of each Asn residue in the protein and a calculation that includes these observations, the primary amino acid residue sequence, and the previously reported complete set of sequence-dependent rates of deamidation for Asn pentapeptides. This method is demonstrated and evaluated for 23 proteins in which 31 unstable and 167 stable Asn residues have been reported and for 7 unstable and 63 stable Asn residues that have been reported in 61 human hemoglobin variants. The relative importance of primary structure and three-dimensional structure in Asn deamidation is estimated.
Bartonella
-associated endothelial proliferation depends on inhibition of apoptosis
Authors: Kirby James E. , Nekorchuk Dawn M.
Published: July 2002

Bartonella
is a Gram-negative pathogen that is unique among bacteria in being able to induce angioproliferative lesions. Cultured human endothelial cells have provided an
in vitro
system in which to study the basis of angioproliferation. Previous studies have attributed the organism's ability to induce angioproliferative lesions to direct mitotic stimulation of endothelial cells by these bacteria. Here we show that
Bartonella
inhibits apoptosis of endothelial cells
in vitro
, and that its ability to stimulate proliferation of endothelial cells depends to a large extent on its antiapoptotic activity.
Bartonella
suppresses both early and late events in apoptosis, namely caspase activation and DNA fragmentation, respectively. Its ability to inhibit death of endothelial cells after serum starvation can be recapitulated by media conditioned by bacteria, indicating that direct cell contact is not necessary. Among tested strains, the activity is produced only by
Bartonella
species that are significant human pathogens and are associated with angioproliferative lesions. We suggest that endothelial cells normally respond to infection by undergoing apoptosis and that
Bartonella
evolved the antiapoptotic activity to enhance survival of the host cells and therefore itself. We propose that
Bartonella
's antiapoptotic mechanism accounts at least in part for its ability to induce vascular proliferation
in vivo
.
Ca
2+
channels at the plasma membrane of stomatal guard cells are activated by hyperpolarization and abscisic acid
Authors: Hamilton David W. A. , Hills Adrian , Köhler Barbara , Blatt Michael R.
Published: July 2002

In stomatal guard cells of higher-plant leaves, abscisic acid (ABA) evokes increases in cytosolic free Ca
2+
concentration ([Ca
2+
]
i
) by means of Ca
2+
entry from outside and release from intracellular stores. The mechanism(s) for Ca
2+
flux across the plasma membrane is poorly understood. Because [Ca
2+
]
i
increases are voltage-sensitive, we suspected a Ca
2+
channel at the guard cell plasma membrane that activates on hyperpolarization and is regulated by ABA. We recorded single-channel currents across the
Vicia
guard cell plasma membrane using Ba
2+
as a charge-carrying ion. Both cell-attached and excised-patch measurements uncovered single-channel events with a maximum conductance of 12.8 ± 0.4 pS and a high selectivity for Ba
2+
(and Ca
2+
) over K
+
and Cl
−
. Unlike other Ca
2+
channels characterized to date, these channels rectified strongly toward negative voltages with an open probability (
P
o
) that increased with [Ba
2+
] outside and decreased roughly 10-fold when [Ca
2+
]
i
was raised from 200 nM to 2 μM. Adding 20 μM ABA increased
P
o
, initially by 63- to 260-fold; in both cell-attached and excised patches, it shifted the voltage sensitivity for channel activation, and evoked damped oscillations in
P
o
with periods near 50 s. A similar, but delayed response was observed in 0.1 μM ABA. These results identify a Ca
2+
-selective channel that can account for Ca
2+
influx and increases in [Ca
2+
]
i
triggered by voltage and ABA, and they imply a close physical coupling at the plasma membrane between ABA perception and Ca
2+
channel control.
Covert attention accelerates the rate of visual information processing
Authors: Carrasco Marisa , McElree Brian
Published: July 2002

Whenever we open our eyes, we are confronted with an overwhelming
amount of visual information. Covert attention allows us to select
visual information at a cued location, without eye movements, and to
grant such information priority in processing. Covert attention can be
voluntarily allocated, to a given location according to goals, or
involuntarily allocated, in a reflexive manner, to a cue that appears
suddenly in the visual field. Covert attention improves
discriminability in a wide variety of visual tasks. An important
unresolved issue is whether covert attention can also speed the rate at
which information is processed. To address this issue, it is necessary
to obtain conjoint measures of the effects of covert attention on
discriminability and rate of information processing. We used the
response-signal speed-accuracy tradeoff (SAT) procedure to derive
measures of how cueing a target location affects speed and accuracy in
a visual search task. Here, we show that covert attention not only
improves discriminability
but also
accelerates the rate
of information processing.
Geometric constraints explain much of the species richness pattern in African birds
Authors: Jetz Walter , Rahbek Carsten
Published: July 2002

The world contains boundaries (e.g., continental edge for terrestrial taxa) that impose geometric constraints on the distribution of species ranges. Thus, contrary to traditional thinking, the expected species richness pattern in absence of ecological or physiographical factors is unlikely to be uniform. Species richness has been shown to peak in the middle of a bounded one-dimensional domain, even in the absence of ecological or physiographical factors. Because species ranges are not linear, an extension of the approach to two dimensions is necessary. Here we present a two-dimensional null model accounting for effects of geometric constraints. We use the model to examine the effects of continental edge on the distribution of terrestrial animals in Africa and compare the predictions with the observed pattern of species richness in birds endemic to the continent. Latitudinal, longitudinal, and two-dimensional patterns of species richness are predicted well from the modeled null effects alone. As expected, null effects are of high significance for wide ranging species only. Our results highlight the conceptual significance of an until recently neglected constraint from continental shape alone and support a more cautious analysis of species richness patterns at this scale.
Unfolding proteins by external forces and temperature: The importance of topology and energetics
Authors: Paci Emanuele , Karplus Martin
Published: July 2002

Unfolding of proteins by forced stretching with atomic force microscopy or laser tweezer experiments complements more classical techniques using chemical denaturants or temperature. Forced unfolding is of particular interest for proteins that are under mechanical stress in their biological function. For β-sandwich proteins (a fibronectin type III and an immunoglobulin domain), both of which appear in the muscle protein titin, the results of stretching simulations show important differences from temperature-induced unfolding, but there are common features that point to the existence of folding cores. Intermediates detected by comparing unfolding with a biasing perturbation and a constant pulling force are not evident in temperature-induced unfolding. For an α-helical domain (α-spectrin), which forms part of the cytoskeleton, there is little commonality in the pathways from unfolding induced by stretching and temperature. Comparison of the forced unfolding of the two β-sandwich proteins and two α-helical proteins (the α-spectrin domain and an acyl-coenzyme A-binding protein) highlights important differences within and between protein classes that are related to the folding topologies and the relative stability of the various structural elements.
Non-Arrhenius kinetics for the loop closure of a DNA hairpin
Authors: Wallace Mark I. , Ying Liming , Balasubramanian Shankar , Klenerman David
Published: July 2002

Intramolecular chain diffusion is an elementary process in the
conformational fluctuations of the DNA hairpin-loop. We have studied
the temperature and viscosity dependence of a model DNA hairpin-loop by
FRET (fluorescence resonance energy transfer) fluctuation spectroscopy
(FRETfs). Apparent thermodynamic parameters were obtained by analyzing
the correlation amplitude through a two-state model and are consistent
with steady-state fluorescence measurements. The kinetics of closing
the loop show non-Arrhenius behavior, in agreement with theoretical
prediction and other experimental measurements on peptide folding. The
fluctuation rates show a fractional power dependence (β = 0.83)
on the solution viscosity. A much slower intrachain diffusion
coefficient in comparison to that of polypeptides was derived based on
the first passage time theory of SSS [Szabo, A., Schulten, K. &
Schulten, Z. (1980)
J. Chem. Phys.
72,
4350–4357], suggesting that intrachain interactions, especially
stacking interaction in the loop, might increase the roughness of the
free energy surface of the DNA hairpin-loop.
Fast-phase space computation of multiple arrivals
Authors: Fomel S. , Sethian J. A.
Published: July 2002

We present a fast, general computational technique for computing the phase-space solution of static Hamilton–Jacobi equations. Starting with the Liouville formulation of the characteristic equations, we derive “Escape Equations” which are static, time-independent Eulerian PDEs. They represent all arrivals to the given boundary from all possible starting configurations. The solution is numerically constructed through a “one-pass” formulation, building on ideas from semi-Lagrangian methods, Dijkstra-like methods for the Eikonal equation, and Ordered Upwind Methods. To compute all possible trajectories corresponding to all possible boundary conditions, the technique is of computational order
O(N
log
N),
where
N
is the total number of points in the computational phase-space domain; any particular set of boundary conditions then is extracted through rapid post-processing. Suggestions are made for speeding up the algorithm in the case when the particular distribution of sources is provided in advance. As an application, we apply the technique to the problem of computing first, multiple, and most energetic arrivals to the Eikonal equation.
Assembly and transport of a premessenger RNP particle
Authors: Daneholt Bertil
Published: July 2002

Salivary gland cells in the larvae of the dipteran
Chironomus tentans
offer unique possibilities to visualize the assembly and nucleocytoplasmic transport of a specific transcription product. Each nucleus harbors four giant polytene chromosomes, whose transcription sites are expanded, or puffed. On chromosome IV, there are two puffs of exceptional size, Balbiani ring (BR) 1 and BR 2. A BR gene is 35–40 kb, contains four short introns, and encodes a 1-MDa salivary polypeptide. The BR transcript is packed with proteins into a ribonucleoprotein (RNP) fibril that is folded into a compact ring-like structure. The completed RNP particle is released into the nucleoplasm and transported to the nuclear pore, where the RNP fibril is gradually unfolded and passes through the pore. On the cytoplasmic side, the exiting extended RNP fibril becomes engaged in protein synthesis and the ensuing polysome is anchored to the endoplasmic reticulum. Several of the BR particle proteins have been characterized, and their fate during the assembly and transport of the BR particle has been elucidated. The proteins studied are all added cotranscriptionally to the pre-mRNA molecule. The various proteins behave differently during RNA transport, and the flow pattern of each protein is related to the particular function of the protein. Because the cotranscriptional assembly of the pre-mRNP particle involves proteins functioning in the nucleus as well as proteins functioning in the cytoplasm, it is concluded that the fate of the mRNA molecule is determined to a considerable extent already at the gene level.
Long-term enzyme correction and lipid reduction in multiple organs of primary and secondary transplanted Fabry mice receiving transduced bone marrow cells
Authors: Takenaka Toshihiro , Murray Gary J. , Qin Gangjian , Quirk Jane M. , Ohshima Toshio , Qasba Pankaj , Clark Kelly , Kulkarni Ashok B. , Brady Roscoe O. , Medin Jeffrey A.
Published: July 2002

Fabry disease is a compelling target for gene therapy as a treatment strategy. A deficiency in the lysosomal hydrolase α-galactosidase A (α-gal A; EC
3.2.1.22
) leads to impaired catabolism of α-galactosyl-terminal lipids such as globotriaosylceramide (Gb3). Patients develop vascular occlusions that cause cardiovascular, cerebrovascular, and renal disease. Unlike for some lysosomal storage disorders, there is limited primary nervous system involvement in Fabry disease. The enzyme defect can be corrected by gene transfer. Overexpression of α-gal A by transduced cells results in secretion of this enzyme. Secreted enzyme is available for uptake by nontransduced cells presumably by receptor-mediated endocytosis. Correction of bystander cells may occur locally or systemically after circulation of the enzyme in the blood. In this paper we report studies on long-term genetic correction in an α-gal A-deficient mouse model of Fabry disease. α-gal A-deficient bone marrow mononuclear cells (BMMCs) were transduced with a retrovirus encoding α-gal A and transplanted into sublethally and lethally irradiated α-gal A-deficient mice. α-gal A activity and Gb3 levels were analyzed in plasma, peripheral blood mononuclear cells, BMMCs, liver, spleen, heart, lung, kidney, and brain. Primary recipient animals were followed for up to 26 weeks. BMMCs were then transplanted into secondary recipients. Increased α-gal A activity and decreased Gb3 storage were observed in all recipient groups in all organs and tissues except the brain. These effects occurred even with a low percentage of transduced cells. The findings indicate that genetic correction of bone marrow cells derived from patients with Fabry disease may have utility for phenotypic correction of patients with this disorder.
Specificity requirements for selection and effector functions of CD25+4+regulatory T cells in anti-myelin basic protein T cell receptor transgenic mice
Authors: Hori Shohei , Haury Matthias , Coutinho António , Demengeot Jocelyne
Published: July 2002

CD25+4+regulatory T cells (Treg) play an indispensable role in preventing autoimmunity. Little is known, however, about the antigen specificities required for their development and effector functions. Mice transgenic for an anti-myelin basic protein (MBP) T cell antigen receptor (TCR) spontaneously develop experimental autoimmune encephalomyelitis (EAE) when deficient for the RAG-1 gene (T/R−), whereas RAG-1-competent transgenic animals (T/R+) remain healthy, protected by CD4+Treg-expressing endogenous TCRs. We have now investigated the role and specificity of CD25+4+Tregin this system. The results show that T/R+animals contain MBP-specific suppressive CD25+4+cells, whereas T/R−do not. Adoptive transfer of CD25+4+cells from nontransgenic or T/R+donors into T/R−mice prevented the development of EAE. Surprisingly, transfer of nontransgenic CD25+4+cells purified from T/R+donors conferred only a limited protection, possibly because of their restricted repertoire diversity that we demonstrate here. Absence of transgenic CD25+4+cells in animals deficient for endogenous TCRα chains and analyses of endogenous TCR gene expression in subsets of CD4+cells from T/R+mice demonstrate that development of transgenic MBP-specific CD25+4+Tregdepends on the coexpression of endogenous TCRα chains. Taken together, these results indicate that specificity to MBP is required for effector functions but is not sufficient for thymic selection/commitment of CD25+4+Tregpreventing EAE.
Expression cloning of two genes that together mediate organic solute and steroid transport in the liver of a marine vertebrate
Authors: Wang Wei , Seward David J. , Li Liqiong , Boyer James L. , Ballatori Nazzareno
Published: July 2002

Uptake of organic solutes and xenobiotics by mammalian cells is mediated by ATP-independent transporters, and four families of transporters have now been identified. To search for novel organic solute transporters, a liver cDNA library from an evolutionarily primitive marine vertebrate, the little skate
Raja erinacea
, was screened for taurocholate transport activity by using
Xenopus
laevis
oocytes. In contrast to the organic anion transporters identified to date, a transport activity was identified in this library that required the coexpression of two distinct gene products, termed organic solute transporter α and β (Ostα, Ostβ). Ostα cDNA encodes for a protein of 352 aa and seven putative transmembrane (TM) domains. Ostβ contains 182 aa and has at least one and perhaps two TM domains. There is no significant sequence identity between Ostα and Ostβ, and only low identity with sequences in the databases; however, Ostα bears a resemblance to some G protein-coupled receptors, and Ostβ exhibits 22% amino acid identity with the C-terminal TM and intracellular domains of protocadherin-γ, a cell surface glycoprotein.
Xenopus
oocytes injected with the cRNA for both Ostα and Ostβ, but not each separately, were able to take up taurocholate, estrone sulfate, digoxin, and prostaglandin E
2
, but not
p
-aminohippurate or
S
-dinitrophenyl glutathione. Transport was sodium-independent, saturable, and inhibited by organic anions and steroids, including the major skate bile salt, scymnol sulfate. These results identify an organic anion transporter composed of a putative seven-helix TM protein and an ancillary membrane polypeptide.
Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: Selective actions via GalR1 and GalR2 receptors
Authors: Liu Hong-Xiang , Brumovsky Pablo , Schmidt Ralf , Brown William , Payza Kemal , Hodzic Lejla , Pou Chantevy , Godbout Claude , Hökfelt Tomas
Published: July 2002

Galanin is a 29-aa neuropeptide with a complex role in pain
processing. Several galanin receptor subtypes are present in dorsal
root ganglia and spinal cord with a differential distribution. Here, we
describe a generation of a specific galanin R2 (GalR2) agonist,
AR-M1896, and its application in studies of a rat neuropathic pain
model (Bennett). The results show that in normal rats mechanical and
cold allodynia of the hindpaw are induced after intrathecal infusion of
low-dose galanin (25 ng per 0.5 μl/h). The same effect is seen with
equimolar doses of AR-M1896 or AR-M961, an agonist both at GalR1 and
GalR2 receptors. In allodynic Bennett model rats, the mechanical
threshold increased dose-dependently after intrathecal injection of a
high dose of AR-M961, whereas no effect was observed in the control or
AR-M1896 group. No effect of either of the two compounds was observed
in nonallodynic Bennett model rats. These data indicate that a low dose
of galanin has a nociceptive role at the spinal cord level mediated by
GalR2 receptors, whereas the antiallodynic effect of high-dose galanin
on neuropathic pain is mediated by the GalR1 receptors. Thus, a
selective GalR1 agonist may be used to treat neuropathic pain.
Global warming in the twenty-first century: An alternative scenario
Authors: Hansen James , Sato Makiko , Ruedy Reto , Lacis Andrew , Oinas Valdar
Published: July 2002

A common view is that the current global warming rate will continue or accelerate. But we argue that rapid warming in recent decades has been driven mainly by non-CO
2
greenhouse gases (GHGs), such as chlorofluorocarbons, CH
4
, and N
2
O, not by the products of fossil fuel burning, CO
2
and aerosols, the positive and negative climate forcings of which are partially offsetting. The growth rate of non-CO
2
GHGs has declined in the past decade. If sources of CH
4
and O
3
precursors were reduced in the future, the change in climate forcing by non-CO
2
GHGs in the next 50 years could be near zero. Combined with a reduction of black carbon emissions and plausible success in slowing CO
2
emissions, this reduction of non-CO
2
GHGs could lead to a decline in the rate of global warming, reducing the danger of dramatic climate change. Such a focus on air pollution has practical benefits that unite the interests of developed and developing countries. However, assessment of ongoing and future climate change requires composition-specific long-term global monitoring of aerosol properties.
Molecular determinants of coordinated proton and zinc inhibition of
N-
methyl-
d
-aspartate NR1/NR2A receptors
Authors: Low Chian-Ming , Zheng Fang , Lyuboslavsky Polina , Traynelis Stephen F.
Published: July 2002

Modulation of the
N-
methyl-
d
-aspartate (NMDA)-selective
glutamate receptors by extracellular protons and Zn
2+
may
play important roles during ischemia in the brain and during seizures.
Recombinant NR1/NR2A receptors exhibit a much higher apparent
affinity for voltage-independent Zn
2+
inhibition than
receptors with other subunit combinations. Here, we show that the
mechanism of this apparent high-affinity, voltage-independent
Zn
2+
inhibition for NR2A-containing receptors results from
the enhancement of proton inhibition. We also show that the N-terminal
leucine/isoleucine/valine binding protein (LIVBP)-like domain of
the NR2A subunit contains critical determinants of the apparent
high-affinity, voltage-independent Zn
2+
inhibition.
Mutations H42A, H44G, or H128A greatly increase the Zn
2+
IC
50
(by up to ≈700-fold) with no effect on the potencies
of glutamate and glycine or on voltage-dependent block by
Mg
2+
. Furthermore, the amino acid residue substitution
H128A, which mediates the largest effect on the apparent high-affinity
Zn
2+
inhibition among all histidine substitutions we
tested, is also critical to the pH-dependency of Zn
2+
inhibition. Our data revealed a unique interaction between two
important extracellular modulators of NMDA receptors.