bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-independent square patterns in surface-tension-driven Bénard convection
Authors: Schatz Michael F. , VanHook Stephen J. , McCormick W. D. , Swift J. B. , Swinney Harry L.
Published: July 2002

The transition between hexagonal and square patterns is investigated in laboratory experiments on surface-tension-driven Bénard (Marangoni) convection in a fluid of Prandtl number 81. As the Marangoni number M is increased, an ideal hexagonal pattern is supplanted by a defect-free square pattern; the transition occurs gradually with patterns of mixed hexagonal, pentagonal, and square symmetry arising at intermediate values of M. An elementary topological process associated with two-dimensional patterns governs local changes in morphology; the dynamics are relaxational with all patterns becoming stationary with M fixed for a sufficiently long time. The transition is hysteretic and depends strongly on the pattern wave number.
Thermodynamically consistent hydrodynamic computational models for high-Knudsen-number gas flows
Authors: Myong R. S.
Published: July 2002

In high-Knudsen-number flows nonequilibrium effects become dominant and the use of Navier–Stokes–Fourier equations becomes questionable since they are based on small deviation from local thermodynamic equilibrium. In this paper new hydrodynamic computational models are proposed for modeling gases in the transition regime. They are based on Eu’s generalized hydrodynamic equations and it turns out that they apply in all Mach numbers and satisfy the second law of thermodynamics to every order of approximation. In order to learn more about the new equations a model equation similar to the Burgers’ equation is studied. From this analysis new insight into constitutive relations of various hydrodynamic equations has been gained. In addition, a convergent iterative method for solving the highly nonlinear constitutive equations is developed. Finally, the shock structure and slip flow problems are computed by using high resolution numerical schemes and issues of extending the one-dimensional solver to multidimensional problems are discussed.
Beam smoothing effects on the stimulated Brillouin scattering (SBS) instability in Nova exploding foil plasmas
Authors: Moody J. D. , Baldis H. A. , Montgomery D. S. , Berger R. L. , Estabrook K. , Kruer W. L. , Lasinski B. F. , Williams E. A. , Dixit S. , Labaune C.
Published: July 2002

The effects of beam smoothing on the stimulated Brillouin and Raman backscattering instabilities (SBBS and SRBS) in a long scale length exploding foil plasma are experimentally investigated using the Nova laser. We observe strongly time-dependent and blueshifted SBS emission and broadband SRS emission in time-resolved spectral measurements of the backscattered light. The results of this paper focus on the SBS scattering, where we find that random phase plate spatial beam smoothing leads to a decrease in the total SBS reflectivity. Adding temporal smoothing to this spatial smoothing leads to an even greater decrease in the total reflectivity, as well as changes in the spectral nature of the backscattered light. Beam smoothing induced changes to the instabilities are limited to plasmas with a peak density below about 0.2ncr; beam smoothing causes little change in the backscattered emission for higher densities. We describe the measurements and discuss models that may explain certain aspects of the results.
Eddy viscosity and hyperviscosity in spectral simulations of 2D drift wave turbulence
Authors: Smith S. A. , Hammett G. W.
Published: July 2002

A wavenumber dependent eddy viscosity is calculated for a simple two-dimensional drift wave model from direct numerical simulations for a wide range of parameters and cutoff wavenumber. The damping rate given by this eddy viscosity is well modeled by a hyperviscosity, where the power and magnitude are parameterized as functions of the shear in the resolved advecting velocity. Tests in simulations with low resolution find that the use of this parameterized hyperviscosity yields somewhat better results than the use of hyperviscosity with fixed power and is significantly better the use of no extra damping term or a Smagorinsky type eddy viscosity. This parameterized hyperviscosity is very useful computationally, since reducing resolution requirements by even a factor of 2 reduces the computational requirements by a factor of 8 in two dimensions, or 16 in three dimensions.
Comment on “Collisionless m=1 reconnection in tokamaks” [Phys. Plasmas 3, 2411 (1996)]
Authors: Wang Xiaogang , Bhattacharjee A.
Published: July 2002

We comment on the numerical simulation of the m = 1 mode based on two-fluid equations in slab geometry for magnetic reconnection in Tokamaks. The Rogers and Zakharov numerical simulation confirm our earlier analytical solution and predictins. (AIP)
The dust charging effect on electrostatic ion waves in a dusty plasma with trapped electrons
Authors: Nejoh Y.-N.
Published: July 2002

The effect of the dust charging and the influence of the ion density and temperature on electrostatic nonlinear ion waves in a dusty plasma having trapped electrons are investigated by numerical calculation. The nonlinear structure of the dust charging is examined, and it is shown that the characteristics of the dust charge number sensitively depend on the electrostatic potential, Mach number, trapped electron temperature, ion density, and temperature. An increase of the ion temperature decreases the dust charging rate and the propagation speed of ion waves. It turns out that a decrease of the trapped electron temperature increases the charging rate of dust grains. It is found that the existence of ion waves sensitively depends on the ion to electron density ratio. New findings of variable-charge dust grain particles, ion density, and temperature in a dusty plasma with trapped electrons are predicted.
Nonlinear saturation of stimulated Raman scattering in laser hot spots
Authors: Russell David A. , DuBois D. F. , Rose Harvey A.
Published: July 2002

Two-dimensional simulation studies are reported of the nonlinear development of stimulated Raman scattering (SRS) from a compact laser hot spot using a reduced model, which includes saturation by pump depletion, Langmuir wave decay cascades, Langmuir wave collapse, and ponderomotive density profile modification. The needle-like intensity distribution in a speckle arising from a random phase plate processed laser beam promotes backscatter SRS. The dependence of the saturated reflectivity and (the comparable in magnitude) absorptivity, on ion acoustic wave and Langmuir wave damping, laser power, electron density, and temperature is studied. There are regimes in which the ponderomotive potential (as well as the Ohmic dissipation) of the induced Langmuir turbulence exceeds that of the localized laser pump. The results support the conclusion that the Langmuir wave Landau damping must be determined by an electron velocity distribution modified by quasilinear and Ohmic heating to account for SRS observed at low densities and high temperatures.
Pulsed high rate plasma etching with variable Si/SiO2 selectivity and variable Si etch profiles
Authors: Boswell R. W. , Henry D.
Published: July 2002

Very high etch rates of Si in SF6 have been obtained in a low-pressure resonant rf discharge. By pulsing the discharge the etch selectivity between Si and SiO2 can be varied from greater than 100 at high repetition rates to around 6 at low repetition rates or continuous operation. A ‘‘lifetime’’ of atomic fluorine has been derived which is in agreement with previous measurements. With a biased substrate the etch profile can be varied from isotropic at high repetition rates to anisotropic with continuous operation.
GaSe detectors for x-ray beams
Authors: Castellano Alfredo
Published: July 2002

The possibility of using GaSe detectors for x-ray beams dosimetry has been evaluated. Direct current produced by high fluxes of 130 and 170 kV x ray at different exposure rates was measured.
(AlAs)0.5(GaAs)0.5 fractional-layer superlattices grown on (001) vicinal surfaces by metalorganic chemical vapor deposition
Authors: Fukui Takashi , Saito Hisao
Published: July 2002

(AlAs)0.5(GaAs)0.5 fractional-layer superlattices with a new periodicity perpendicular to the growth direction was successfully grown by metalorganic chemical vapor deposition on (001) GaAs substrates slightly misoriented toward [110]. The atomic structures were analyzed by x-ray superlattice satellite diffraction. Superlattice periods were exactly the same as the mean distance of each atomic step on the (001) vicinal surface. The results indicate that lateral growth from nucleation at the step edge is the dominant process compared with the two-dimensional nucleation on atomically flat terraces.
‘‘Oxide-free’’ tip for scanning tunneling microscopy
Authors: Colton R. J. , Baker S. M. , Baldeschwieler J. D. , Kaiser W. J.
Published: July 2002

We report a new tip for scanning tunneling microscopy and a tip repair procedure that allows one to reproducibly obtain atomic images of highly oriented pyrolytic graphite with previously inoperable tips. The tips are shown to be relatively oxide-free and highly resistant to oxidation. The tips are fabricated with graphite by two distinct methods.
New hydride vapor phase epitaxy for GaP growth on Si
Authors: Mori H. , Ogasawara M. , Yamamoto M. , Tachikawa M.
Published: July 2002

Gallium phosphide films are successfully grown on (100) Si substrates by a new hydride vapor phase epitaxy. Mixing of reactant vapors just above the substrate makes the growth rate as high as 50 nm/min even in the temperature range of 350–450 °C. This makes the two-step growth procedure applicable for growing a single domain GaP film on Si from H2-HCl-PH3-Ga reactants. An etch pit density of 7.5×106 cm−2 and a full width at half-maximum of 93 arcsec in a double-crystal x-ray rocking curve are achieved. Green light-emitting diodes with 565 nm peak wavelength are successfully fabricated using nitrogen-doped GaP films grown on Si.
Electronic properties of sol-gel-derived oxides on silicon
Authors: Weimer R. A. , Lenahan P. M. , Marchione T. A. , Brinker C. J.
Published: July 2002

Sol-gel-derived SiO2, borosilicate, and aluminosilicate thin films deposited on silicon and heated for 5 min at temperatures of 1000 °C or lower exhibit dielectric strength as great as 5 MV/cm and interface state densities as low as ∼1×1011/cm2 eV. These values represent significant improvements over previous sol-gel-derived oxides on semiconductors and indicate that sol-gel processing can provide device quality oxides in situations where native oxides are unavailable or exhibit poor dielectric behavior, e.g., amorphous, hydrogenated silicon or III-V compound semiconductors.
Stress variations due to microcracks in GaAs grown on Si
Authors: Yacobi B. G. , Zemon S. , Norris P. , Jagannath C. , Sheldon P.
Published: July 2002

Luminescence studies of thick (≥5 μm) GaAs epitaxial layers grown on Si substrates reveal regions of nonuniform stress associated with the presence of microcracks. Using cathodoluminescence spectroscopy as a tool for microcharacterization, the magnitude of the stress, derived from the peak positions of the luminescence spectra, is shown to increase gradually as a function of distance from the intersection of two microcracks. The greatest degree of stress relief was found at this intersection.
Stress variations and relief in patterned GaAs grown on mismatched substrates
Authors: Yacobi B. G. , Jagannath C. , Zemon S. , Sheldon P.
Published: July 2002

Cathodoluminescence scanning electron microscopy studies reveal significant variations in stress across etched patterns of GaAs grown on both InP and Si substrates. The stress in the epilayer is relieved at convex corners and in patterned areas with dimensions on the order of 10 μm. The stress is uniaxial near the edge of a patterned region and changes to biaxial away from the edge, producing nonuniformities in the optical properties of patterned regions.
Superconducting oxide films with high transition temperature prepared from metal trifluoroacetate precursors
Authors: Gupta A. , Jagannathan R. , Cooper E. I. , Giess E. A. , Landman J. I. , Hussey B. W.
Published: July 2002

Superconducting thin films of Y-Ba-Cu oxide have been prepared on yttria-stabilized zirconia substrates using metal trifluoroacetate spin-on precursors. The films exhibit an extremely sharp resistive transition with zero resistance at temperatures as high as 94 K. The superconducting phase is formed by a three-step process: (a) decomposition of the spun-on trifluoroacetate film to the fluorides, (b) conversion of the fluorides to oxides by reacting with water vapor, and (c) annealing followed by slow cooling in oxygen. The properties of the films depend on the amount of conversion of the fluorides by reaction with water. Films which show the presence of some unreacted barium fluoride have strong c-axis normal preferred orientation, with a sharp resistive transition. When all the barium fluoride is converted, the film is more randomly oriented and exhibits a broader transition to zero resistance.
Function of the voltage gate of gap junction channels: Selective exclusion of molecules
Authors: Qu Yang , Dahl Gerhard
Published: July 2002

Gap junction channels span the membranes of two adjacent cells and allow the gated transit of molecules as large as second messengers from cell to cell. In vertebrates, gap junctions are composed of proteins from the connexin (cx) gene family. Gap junction channels formed by most connexins are affected by transjunctional voltage. The function of the voltage gate is unclear, because substantial electrical coupling typically remains with activated gates because of the channels dwelling in subconductance rather than closed states. Here, we find inXenopusoocytes expressing cx43 or cx46 that the activated voltage gate preferentially restricts the passage of larger ions, such as fluorescent tracer molecules and cAMP, while having little effect on the electrical coupling arising from the passage of small electrolytes. Thus, a conceivable physiological role of the voltage gate is to selectively restrict the passage of large molecules between cells while allowing electrical coupling.
Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice
Authors: You Mingjian James , Castrillon Diego H. , Bastian Boris C. , O'Hagan Rónán C. , Bosenberg Marcus W. , Parsons Ramon , Chin Lynda , DePinho Ronald A.
Published: July 2002

Dual inactivation of PTEN and INK4a/ARF tumor suppressor genes is a common feature observed in a broad spectrum of human cancer types. To validate functional collaboration between these genes in tumor suppression, we examined the biological consequences of Pten and/or Ink4a/Arf deficiency in cells and mice. Relative to single mutant controls,
Ink4a
/
Arf
−/−
Pten
+/− mouse embryonic fibroblast cultures exhibited faster rates of growth in reduced serum, grew to higher saturation densities, produced more colonies upon low density seeding, and showed increased susceptibility to transformation by oncogenic H-
Ras
. Ink4a/Arf deficiency reduced tumor-free survival and shortened the latency of neoplasias associated with
Pten
heterozygosity, specifically pheochromocytoma, prostatic intraepithelial neoplasia, and endometrial hyperplasia. Compound mutant mice also exhibited an expanded spectrum of tumor types including melanoma and squamous cell carcinoma. Functional synergy between Ink4a/Arf and Pten manifested most prominently in the development of pheochromocytoma, prompting an analysis of genes and loci implicated in this rare human neoplasm. The classical pheochromocytoma genes
Ret
,
Vhl
, and
Nf-1
remained intact, a finding consistent with the intersection of these genes with pathways engaged by Pten and Ink4a/Arf. Notably, conventional and array-comparative genomic hybridization revealed frequent loss of distal mouse chromosome 4 in a region syntenic to human chromosome 1p that is implicated in human pheochromocytoma. This study provides genetic evidence of collaboration between Pten and Ink4a/Arf in constraining the growth and oncogenic transformation of cultured cells and in suppressing a wide spectrum of tumors
in vivo
.
Defensive extrusive ectosymbionts of
Euplotidium
(Ciliophora) that contain microtubule-like structures are bacteria related to
Verrucomicrobia
Authors: Petroni Giulio , Spring Stefan , Schleifer Karl-Heinz , Verni Franco , Rosati Giovanna
Published: July 2002

Epixenosomes, ectosymbionts on hypotrich ciliates (genus
Euplotidium
) defend their host against the ciliate predator
Litonotus lamella.
Although here only
Euplotidium itoi
and
Euplotidium arenarium
from tide pools along a rocky shore near Leghorn (Ligurian sea) were studied in detail, these epibionts are certainly present on specimens of
E. itoi
and on other
Euplotidium
species in similar north coastal habitats. The complex life history of epixenosomes has two main stages. In stage I, cells with typical prokaryotic structure divide by binary fission. Stage II cells show complex organization with different cytoplasmic compartments where an extrusive apparatus within a proteinaceous matrix, although not membrane-bounded, differs from the remaining cytoplasm. The ejection process is involved in defense; extrusive apparatus is surrounded by a basket consisting of bundles of tubules. These tubules, 22 ± 3 nm in diameter, delimited by a wall made up of globular structures, are sensitive to inhibitor of tubulin polymerization (nocodazole/4°C temperature) and react positively with different antitubulin antibodies, two of which are monoclonal. The prokaryotic vs. eukaryotic nature of epixenosomes was resolved by comparative sequence analysis of amplified small subunit rRNA genes and
in situ
hybridization with fluorescently labeled rRNA-targeted polynucleotide probes. These unique ectosymbionts are phylogenetically related to
Verrucomicrobia
. Epixenosomes represent marine symbionts in this recently discovered division of the Bacteria.
Glacial meltwater dynamics in coastal waters west of the Antarctic peninsula
Authors: Dierssen Heidi M. , Smith Raymond C. , Vernet Maria
Published: July 2002

The annual advance and retreat of sea ice has been considered a major physical determinant of spatial and temporal changes in the structure of the Antarctic coastal marine ecosystem. However, the role of glacial meltwater on the hydrography of the Antarctic Peninsula ecosystem has been largely ignored, and the resulting biological effects have only been considered within a few kilometers from shore. Through several lines of evidence collected in conjunction with the Palmer Station Long-Term Ecological Research Project, we show that the freshening and warming of the coastal surface water over the summer months is influenced not solely by sea ice melt, as suggested by the literature, but largely by the influx of glacial meltwater. Moreover, the seasonal variability in the amount and extent of the glacial meltwater plume plays a critical role in the functioning of the biota by influencing the physical dynamics of the water (e.g., water column stratification, nearshore turbidity). From nearly a decade of observations (1991–1999), the presence of surface meltwater is correlated not only to phytoplankton blooms nearshore, but spatially over 100 km offshore. The amount of meltwater will also have important secondary effects on the ecosystem by influencing the timing of sea ice formation. Because air temperatures are statistically increasing along the Antarctic Peninsula region, the presence of glacial meltwater is likely to become more prevalent in these surface waters and continue to play an ever-increasing role in driving this fragile ecosystem.
Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A
Authors: Brazin Kristine N. , Mallis Robert J. , Fulton D. Bruce , Andreotti Amy H.
Published: July 2002

Interleukin-2 tyrosine kinase (Itk) is a nonreceptor protein tyrosine kinase of the Tec family that participates in the intracellular signaling events leading to T cell activation. Tec family members contain the conserved SH3, SH2, and catalytic domains common to many kinase families, but they are distinguished by unique sequences outside of this region. The mechanism by which Itk and related Tec kinases are regulated is not well understood. Our studies indicate that Itk catalytic activity is inhibited by the peptidyl prolyl isomerase activity of cyclophilin A (CypA). NMR structural studies combined with mutational analysis show that a proline-dependent conformational switch within the Itk SH2 domain regulates substrate recognition and mediates regulatory interactions with the active site of CypA. CypA and Itk form a stable complex in Jurkat T cells that is disrupted by treatment with cyclosporin A. Moreover, the phosphorylation levels of Itk and a downstream substrate of Itk, PLCγ1, are increased in Jurkat T cells that have been treated with cyclosporin A. These findings support a novel mode of tyrosine kinase regulation for a Tec family member and provide a molecular basis for understanding a cellular function of the ubiquitous peptidyl prolyl isomerase, CypA.
Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1
Authors: Murer Valérie , Spetz Jean François , Hengst Ulrich , Altrogge Ludger Maria , de Agostini Ariane , Monard Denis
Published: July 2002

Understanding infertility and sterility requires knowledge of the molecular mechanisms underlying sexual reproduction. We have found that male mice deficient for the gene encoding the protease inhibitor protease nexin-1 (PN-1) show a marked impairment in fertility from the onset of sexual maturity. Absence of PN-1 results in altered semen protein composition, which leads to inadequate semen coagulation and deficient vaginal plug formation upon copulation. Progressive morphological changes of the seminal vesicles also are observed. Consistent with these findings, abnormal PN-1 expression was found in the semen of men displaying seminal dysfunction. The data demonstrate that the level of extracellular proteolytic activity is a critical element in controlling male fertility.
Activity-dependent CREB phosphorylation: Convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway
Authors: Wu Gang-Yi , Deisseroth Karl , Tsien Richard W.
Published: July 2002

The cAMP-responsive element binding protein (CREB), a key regulator
of gene expression, is activated by phosphorylation on Ser-133. Several
different protein kinases possess the capability of driving this
phosphorylation, making it a point of potential convergence for
multiple intracellular signaling cascades. Previous work in neurons has
indicated that physiologic synaptic stimulation recruits a fast
calmodulin kinase IV (CaMKIV)-dependent pathway that
dominates early signaling to CREB. Here we show in hippocampal neurons
that the fast, CaMK-dependent pathway can be followed by a slower
pathway that depends on Ras/mitogen-activated protein kinase (MAPK),
along with CaMK. This pathway was blocked by dominant-negative Ras and
was specifically recruited by depolarizations that produced strong
intracellular Ca
2+
transients. When both pathways were
recruited, phosphorylated CREB (pCREB) formation was overwhelmingly
dominated by the CaMK pathway between 0 and 10 min, and by the MAPK
pathway at 60 min, whereas the two pathways acted in concert at 30 min.
The Ca
2+
signals that produced only rapid CaMK signaling to
pCREB or both rapid CaMK and slow MAPK signaling deviated significantly
for only ≈1 min, yet their differential impact on pCREB extended over
a much longer period, between 20 and 60 min and beyond, which is of
likely significance for gene expression. The CaMK-dependent MAPK
pathway may inform the nucleus about stimulus amplitude. In contrast,
the CaMKIV pathway may be well suited to conveying information on the
precise timing of localized synaptic stimuli, befitting its greater
speed and sensitivity, whereas the previously described calcineurin
pathway may carry information about stimulus duration.
Feeding specialization and host-derived chemical defense in Chrysomeline leaf beetles did not lead to an evolutionary dead end
Authors: Termonia Arnaud , Hsiao Ting H. , Pasteels Jacques M. , Milinkovitch Michel C.
Published: July 2002

Combination of molecular phylogenetic analyses of Chrysomelina beetles and chemical data of their defensive secretions indicate that two lineages independently developed, from an ancestral autogenous metabolism, an energetically efficient strategy that made the insect tightly dependent on the chemistry of the host plant. However, a lineage (theinterruptagroup) escaped this subordination through the development of a yet more derived mixed metabolism potentially compatible with a large number of new host-plant associations. Hence, these analyses on leaf beetles document a mechanism that can explain why high levels of specialization do not necessarily lead to “evolutionary dead ends.”
Increased CNS levels of apolipoprotein D in schizophrenic and bipolar subjects: Implications for the pathophysiology of psychiatric disorders
Authors: Thomas Elizabeth A. , Dean Brian , Pavey Geoffrey , Sutcliffe J. Gregor
Published: July 2002

Chronic administration of the atypical antipsychotic drug, clozapine, to rodents has been shown to increase the concentration of apolipoprotein D (apoD) in several area of the brain, suggesting that apoD could be involved in the therapeutic effects of antipsychotic drugs and/or the pathology of psychotic illnesses. Here, we measured a significant decrease in the concentration of apoD in serum samples from schizophrenic patients. In contrast, apoD levels were significantly increased (92–287%) in dorsolateral prefrontal cortex (Brodmann's area 9) of schizophrenic and bipolar subjects. Elevated levels of apoD expression were also observed in the caudate of schizophrenic and bipolar subjects (68–89%). No differences in apoD immunoreactivity were detected in occipital cortex (Brodmann's area 18) in either group, or in the hippocampus, substantia nigra, or cerebellum of the schizophrenic group. The low serum concentrations of apoD observed in these patients supports recent hypotheses involving systemic insufficiencies in lipid metabolism/signaling in schizophrenia. Elevation of apoD expression selectively within central nervous system regions implicated in the pathology of these neuropsychiatric disorders suggests a focal compensatory response that neuroleptic drug regimens may augment.
Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension
Authors: Holla Vijaykumar R. , Adas Fadi , Imig John D. , Zhao Xueying , Price Edward , Olsen Nancy , Kovacs William J. , Magnuson Mark A. , Keeney Diane S. , Breyer Matthew D. , Falck John R. , Waterman Michael R. , Capdevila Jorge H.
Published: July 2002

Hypertension is a leading cause of cardiovascular, cerebral, and
renal disease morbidity and mortality. Here we show that disruption of
the Cyp 4a14 gene causes hypertension, which is, like most human
hypertension, more severe in males. Male Cyp 4a14 (−/−) mice show
increases in plasma androgens, kidney Cyp 4a12 expression, and the
formation of prohypertensive 20-hydroxyarachidonate. Castration
normalizes the blood pressure of Cyp 4a14 (−/−) mice and minimizes
Cyp 4a12 expression and arachidonate ω-hydroxylation. Androgen
replacement restores hypertensive phenotype, Cyp 4a12 expression, and
20-hydroxy-arachidonate formation. We conclude that the
androgen-mediated regulation of Cyp 4a arachidonate monooxygenases is
an important component of the renal mechanisms that control systemic
blood pressures. These results provide direct evidence for a role of
Cyp 4a isoforms in cardiovascular physiology, establish Cyp 4a14
(−/−) mice as a monogenic model for the study of cause/effect
relationships between blood pressure, sex hormones, and P450
ω-hydroxylases, and suggest the human CYP 4A homologues as candidate
genes for the analysis of the genetic and molecular basis of human
hypertension.
Heterologous reconstitution in yeast of the polyunsaturated fatty acid biosynthetic pathway
Authors: Beaudoin Frédéric , Michaelson Louise V. , Hey Sandra J. , Lewis Mervyn J. , Shewry Peter R. , Sayanova Olga , Napier Johnathan A.
Published: July 2002

A
Caenorhabditis elegans
ORF encoding the presumptive condensing enzyme activity of a fatty acid elongase has been characterized functionally by heterologous expression in yeast. This ORF (F56H11.4) shows low similarity to
Saccharomyces cerevisiae
genes involved in fatty acid elongation. The substrate specificity of the
C. elegans
enzyme indicated a preference for Δ
6
-desaturated C18 polyunsaturated fatty acids. Coexpression of this activity with fatty acid desaturases required for the synthesis of C20 polyunsaturated fatty acids resulted in the accumulation of arachidonic acid from linoleic acid and eicosapentaenoic acid from α-linolenic acid. These results demonstrate the reconstitution of the
n-3
and
n-6
polyunsaturated fatty acid biosynthetic pathways. The
C. elegans
ORF is likely to interact with endogenous components of a yeast elongation system, with the heterologous nematode condensing enzyme F56H11.4 causing a redirection of enzymatic activity toward polyunsaturated C18 fatty acid substrates.
Evidence for clonal propagation in natural isolates of
Plasmodium falciparum
from Venezuela
Authors: Urdaneta Ludmel , Lal Altaf , Barnabé Christian , Oury Bruno , Goldman Ira , Ayala Francisco J. , Tibayrenc Michel
Published: July 2002

We have analyzed 75 isolates of
Plasmodium
falciparum
, collected in Venezuela during both the dry
(November) and rainy (May–July) seasons, with a range of genetic
markers including antigen genes and 14 random amplified polymorphic DNA
(RAPD) primers. Thirteen
P. falciparum
stocks from Kenya
and four other
Plasmodium
species are included in the
analysis for comparison. Cross-hybridization shows that the 14 RAPD
primers reveal 14 separate regions of the parasite's genome. The
P. falciparum
isolates are a monophyletic clade,
significantly different from the other
Plasmodium
species. We identify three RAPD characters that could be useful as
“tags” for rapid species identification. The Venezuelan genotypes
fall into two discrete genetic subdivisions associated with either the
dry or the rainy season; the isolates collected in the rainy season
exhibit greater genetic diversity. There is significant linkage
disequilibrium in each seasonal subsample and in the full sample. In
contrast, no linkage disequilibrium is detected in the African sample.
These results support the hypothesis that the population structure of
P. falciparum
in Venezuela, but not in Africa, is
predominantly clonal. However, the impact of genetic recombination on
Venezuelan
P. falciparum
seems higher than in parasitic
species with long-term clonal evolution like
Trypanosoma
cruzi
, the agent of Chagas' disease. The genetic structure of
the Venezuelan samples is similar to that of
Escherichia
coli
, a bacterium that propagates clonally, with occasional
genetic recombination.
Enhanced synthesis of choline and glycine betaine in transgenic tobacco plants that overexpress phosphoethanolamine
N
-methyltransferase
Authors: McNeil Scott D. , Nuccio Michael L. , Ziemak Michael J. , Hanson Andrew D.
Published: July 2002

Choline (Cho) is the precursor of the osmoprotectant glycine
betaine and is itself an essential nutrient for humans. Metabolic
engineering of Cho biosynthesis in plants could therefore enhance both
their resistance to osmotic stresses (drought and salinity) and their
nutritional value. The key enzyme of the plant Cho-synthesis pathway is
phosphoethanolamine
N
-methyltransferase, which catalyzes
all three of the methylations required to convert phosphoethanolamine
to phosphocholine. We show here that overexpressing this enzyme in
transgenic tobacco increased the levels of phosphocholine by 5-fold and
free Cho by 50-fold without affecting phosphatidylcholine content or
growth. Moreover, the expanded Cho pool led to a 30-fold increase in
synthesis of glycine betaine via an engineered glycine betaine pathway.
Supplying the transgenics with the Cho precursor ethanolamine (EA)
further enhanced Cho levels even though the supplied EA was extensively
catabolized. These latter results establish that there is further scope
for improving Cho synthesis by engineering an increased
endogenous supply of EA and suggest that this could be
achieved by enhancing EA synthesis and/or by suppressing its
degradation.
Multiple independent origins of Shigella clones ofEscherichia coliand convergent evolution of many of their characteristics
Authors: Pupo Gulietta M. , Lan Ruiting , Reeves Peter R.
Published: July 2002

The evolutionary relationships of 46 Shigella strains representing each of the serotypes belonging to the four traditional Shigella species (subgroups), Dysenteriae, Flexneri, Boydii, and Sonnei, were determined by sequencing of eight housekeeping genes in four regions of the chromosome. Analysis revealed a very similar evolutionary pattern for each region. Three clusters of strains were identified, each including strains from different subgroups. Cluster 1 contains the majority of Boydii and Dysenteriae strains (B1–4, B6, B8, B10, B14, and B18; and D3–7, D9, and D11–13) plus Flexneri 6 and 6A. Cluster 2 contains seven Boydii strains (B5, B7, B9, B11, B15, B16, and B17) and Dysenteriae 2. Cluster 3 contains one Boydii strain (B12) and the Flexneri serotypes 1–5 strains. Sonnei and three Dysenteriae strains (D1, D8, and D10) are outside of the three main clusters but, nonetheless, are clearly withinEscherichia coli. Boydii 13 was found to be distantly related toE. coli. Shigella strains, like the other pathogenic forms ofE. coli, do not have a single evolutionary origin, indicating convergent evolution of Shigella phenotypic properties. We estimate the three main Shigella clusters to have evolved within the last 35,000 to 270,000 years, suggesting that shigellosis was one of the early infectious diseases of humans.
Femtosecond dynamics of a drug–protein complex: Daunomycin with Apo riboflavin-binding protein
Authors: Zhong Dongping , Pal Samir Kumar , Wan Chaozhi , Zewail Ahmed H.
Published: July 2002

In this contribution, we report studies of the primary dynamics of the drug–protein complexes of daunomycin with apo riboflavin-binding protein. With femtosecond resolution, we observed the ultrafast charge separation between daunomycin and aromatic amino acid residues of the protein, tryptophan(s). Electron transfer occurs from tryptophan(s) to daunomycin with two reaction times, 1 ps and 6 ps, depending on the local complex structure. The formation of anionic daunomycin radical is crucial for triggering a series of chemical reactions in redox cycling. One of the subsequent reactions is the reduction of dioxygen to form active superoxide by the reduced daunomycin. This catalytic process was found to occur within 10 ps. In the absence of dioxygen, charge recombination takes a much longer time, more than 100 ps. These results, along with similar findings in DNA and nucleotides, elucidate that the ultrafast generation of reduced daunomycin radicals by photoactivation is a primary step for the observed photoenhancement of drug cytotoxicity by several orders of magnitude. We also studied the dependence of the dynamics on protein conformations at different ionic strengths and denaturant concentrations. We observe a sharp transition from the tertiary structure to the unfolding state at 2 M of denaturant concentration.
Segmentation gene product Fushi tarazu is an LXXLL motif-dependent coactivator for orphan receptor FTZ-F1
Authors: Suzuki Taiga , Kawasaki Haruhisa , Yu Ruth T. , Ueda Hitoshi , Umesono Kazuhiko
Published: July 2002

Orphan receptors for whom cognate ligands have not yet been identified form a large subclass within the nuclear receptor superfamily. To address one aspect of how they might regulate transcription, we analyzed the mode of interaction between the
Drosophila
orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product Fushi tarazu (FTZ). Strong interaction between these two factors was detected by use of the mammalian one- and two-hybrid interaction assays without addition of ligand. This interaction required the AF-2 core and putative ligand-binding domain of FTZ-F1 and the LXXLL motif of FTZ. The requirement of these elements was further confirmed by examination of their target gene expression in
Drosophila
embryos and observation of a cuticle phenotype in transgenic fly lines that express mutated factors. In
Drosophila
cultured cells, FTZ is required for FTZ-F1 activation of a FTZ-F1 reporter gene. These results reveal a resemblance in the mode of interaction between FTZ-F1 and FTZ and that of nuclear receptor-coactivator and indicate that direct interaction is required for regulation of gene expression by FTZ-F1. Thus, we propose that FTZ may represent a category of LXXLL motif-dependent coactivators for nuclear receptors.
The transcriptional responses of respiratory epithelial cells toBordetella pertussisreveal host defensive and pathogen counter-defensive strategies
Authors: Belcher Christopher E. , Drenkow Jörg , Kehoe Bettina , Gingeras Thomas R. , McNamara Nancy , Lemjabbar Hassan , Basbaum Carol , Relman David A.
Published: July 2002

Bordetella pertussis, the causative agent of whooping cough, has many well-studied virulence factors and a characteristic clinical presentation. Despite this information, it is not clear howB. pertussisinteraction with host cells leads to disease. In this study, we examined the interaction ofB. pertussiswith a human bronchial epithelial cell line (BEAS-2B) and measured host transcriptional profiles by using high-density DNA microarrays. The early transcriptional response to this pathogen is dominated by altered expression of cytokines, DNA-binding proteins, and NFκB-regulated genes. This previously unrecognized response toB. pertussiswas modified in similar but nonidentical fashions by the antiinflammatory agents dexamethasone and sodium salicylate. Cytokine protein expression was confirmed, as was neutrophil chemoattraction. We show thatB. pertussisinduces mucin gene transcription by BEAS-2B cells then counters this defense by using mucin as a binding substrate. A set of genes is described for which the catalytic activity of pertussis toxin is both necessary and sufficient to regulate transcription. Host genomic transcriptional profiling, in combination with functional assays to evaluate subsequent biological events, provides insight into the complex interaction of host and pathogen.
Identification of the residues in the Myb domain of maize C1 that specify the interaction with the bHLH cofactor R
Authors: Grotewold Erich , Sainz Manuel B. , Tagliani Laura , Hernandez J. Marcela , Bowen Ben , Chandler Vicki L.
Published: July 2002

The maize Myb transcription factor C1 depends on the basic
helix–loop–helix (bHLH) proteins R or B for regulatory function, but
the closely related Myb protein P does not. We have used the similarity
between the Myb domains of C1 and P to identify residues that specify
the interaction between the Myb domain of C1 and the N-terminal region
of R. Substitution of four predicted solvent-exposed residues in the
first helix of the second Myb repeat of P with corresponding residues
from C1 is sufficient to confer on P the ability to physically interact
with R. However, two additional Myb domain amino acid changes are
needed to make the P regulatory activity partially dependent on R in
maize cells. Interestingly, when P is altered so that it interacts with
R, it can activate the
Bz1
promoter, normally regulated
by C1 + R but not by P. Together, these findings demonstrate that the
change of a few amino acids within highly similar Myb domains can
mediate differential interactions with a transcriptional coregulator
that plays a central role in the regulatory specificity of C1, and that
Myb domains play important roles in combinatorial
transcriptional regulation.
IFNα/β promotes cell survival by activating NF-κB
Authors: Yang Chuan He , Murti Aruna , Pfeffer Susan R. , Basu Leela , Kim Jong G. , Pfeffer Lawrence M.
Published: July 2002

IFNs play critical roles in host defense by modulating the
expression of various genes via signal transducer and activator of
transcription factors. We show that IFNα/β activates
another important transcription factor, NF-κB. DNA-binding activity
of NF-κB was induced by multiple type 1 IFNs and was promoted by IFN
in a diverse group of human, monkey, rat, and murine cells. Human IFN
promoted NF-κB activation in murine cells that express the human
IFNα/β receptor-1 signal-transducing chain of the type 1 IFN
receptor. IFN promotes inhibitor of kappa B α (IκBα) serine
phosphorylation and degradation, and stimulates NF-κB DNA-binding and
transcriptional activity. Importantly, IFN promotes cell survival by
protecting cells against a variety of proapoptotic stimuli,
such as virus infection and antibody-mediated crosslinking. Expression
of superrepressor forms of IκBα, besides inhibiting IFN-mediated
NF-κB activation and IκBα degradation, also enhanced
apoptotic cell death in IFN-treated cells. We conclude that
NF-κB activation by IFNα/β is integrated into a
signaling pathway through the IFNα/β receptor-1 chain of the type
1 IFN receptor that promotes cell survival in apposition to various
apoptotic stimuli.
The KCl cotransporter isoform KCC3 can play an important role in cell growth regulation
Authors: Shen Meng-Ru , Chou Cheng-Yang , Hsu Keng-Fu , Liu Hsiao-Sheng , Dunham Philip B. , Holtzman Eli J. , Ellory J. Clive
Published: July 2002

The KCl cotransporter (KCC) plays a significant role in the
ionic and osmotic homeostasis of many cell types. Four KCC isoforms
have been cloned. KCC1 and KCC4 activity is osmolality-sensitive and
involved in volume regulation. KCC2, a neuronal-specific isoform, can
lower intracellular Cl
−
and is critical for inhibitory
GABA responses in the mature central nervous system. KCC3, initially
cloned from vascular endothelial cells, is widely but not universally
distributed and has an unknown physiological significance. Here we show
a tight link between the expression and activity of KCC3 and cell
growth by a NIH/3T3 fibroblast expression system. KCC3 activity is
sensitive to [(dihydroindenyl)oxy] alkanoic acid (DIOA) and
N
-ethylmaleimide and is regulated by tyrosine
phosphorylation. Osmotic swelling does not activate KCC3, and the
process of regulatory volume decrease is refractory to DIOA, indicating
that KCC3 is not involved in volume regulation. KCC3 expression
enhances cell proliferation, and this growth advantage can be abolished
by the inhibition of KCC3 by DIOA. Fluorescence-activated cell sorting
measurements and Western blot analysis show DIOA caused a significant
reduction of the cell fraction in proliferative phase and a change in
phosphorylation of retinoblastoma protein (Rb) and cdc2, suggesting
that KCC3 activity is important for cell cycle progression.
Insulin-like growth factor-1 up-regulates KCC3 expression and
stimulates cell growth. Tumor necrotic factor-α down-regulates KCC3
expression and causes growth arrest. These data indicate that KCC3 is
an important KCC isoform that may be involved in cell proliferation.
Calsarcins, a novel family of sarcomeric calcineurin-binding proteins
Authors: Frey Norbert , Richardson James A. , Olson Eric N.
Published: July 2002

The calcium- and calmodulin-dependent protein
phosphatase calcineurin has been implicated in the transduction of
signals that control the hypertrophy of cardiac muscle and slow fiber
gene expression in skeletal muscle. To identify proteins that mediate
the effects of calcineurin on striated muscles, we used the calcineurin
catalytic subunit in a two-hybrid screen for cardiac
calcineurin-interacting proteins. From this screen, we discovered a
member of a novel family of calcineurin-interacting proteins, termed
calsarcins, which tether calcineurin to α-actinin at the z-line of
the sarcomere of cardiac and skeletal muscle cells. Calsarcin-1 and
calsarcin-2 are expressed in developing cardiac and skeletal muscle
during embryogenesis, but calsarcin-1 is expressed specifically in
adult cardiac and slow-twitch skeletal muscle, whereas calsarcin-2 is
restricted to fast skeletal muscle. Calsarcins represent a novel family
of sarcomeric proteins that link calcineurin with the contractile
apparatus, thereby potentially coupling muscle activity to calcineurin
activation.
The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression.
Authors: Rehemtulla A , Warwar R , Kumar R , Ji X , Zack D J , Swaroop A
Published: July 2002

The retinal protein Nrl belongs to a distinct subfamily of basic motif-leucine zipper DNA-binding proteins and has been shown to bind extended AP-1-like sequence elements as a homo- or heterodimer. Here, we demonstrate that Nrl can positively regulate the expression of the photoreceptor cell-specific gene rhodopsin. Electrophoretic mobility-shift analysis reveals that a protein(s) in nuclear extracts from bovine retina and the Y79 human retinoblastoma cell line binds to a conserved Nrl response element (NRE) in the upstream promoter region of the rhodopsin gene. Nrl or an antigenically similar protein is shown to be part of the bound protein complex by supershift experiments using Nrl-specific antiserum. Cotransfection studies using an Nrl-expression plasmid and a luciferase reporter gene demonstrate that interaction of the Nrl protein with the -61 to -84 region of the rhodopsin promoter (which includes the NRE) stimulates expression of the reporter gene in CV-1 monkey kidney cells. This Nrl-mediated transactivation is specifically inhibited by coexpression of a naturally occurring truncated form of Nrl (dominant negative effect). Involvement of Nrl in photoreceptor gene regulation and its continued high levels of expression in the adult retina suggest that Nrl plays a significant role in controlling retinal function.
Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle.
Authors: Telford S R , Dawson J E , Katavolos P , Warner C K , Kolbert C P , Persing D H
Published: July 2002

A human-derived strain of the agent of human granulocytic ehrlichiosis, a recently described emerging rickettsial disease, has been established by serial blood passage in mouse hosts. Larval deer ticks acquired infection by feeding upon such mice and efficiently transmitted the ehrlichiae after molting to nymphs, thereby demonstrating vector competence. The agent was detected by demonstrating Feulgen-positive inclusions in the salivary glands of the experimentally infected ticks and from field-derived adult deer ticks. White-footed mice from a field site infected laboratory-reared ticks with the agent of human granulocytic ehrlichiosis, suggesting that these rodents serve as reservoirs for ehrlichiae as well as for Lyme disease spirochetes and the piroplasm that causes human babesiosis. About 10% of host-seeking deer ticks were infected with ehrlichiae, and of these, 20% also contained spirochetes. Cotransmission of diverse pathogens by the aggressively human-biting deer tick may have a unique impact on public health in certain endemic sites.
Positive genetic feedback governs cAMP spiral wave formation in Dictyostelium.
Authors: Levine H , Aranson I , Tsimring L , Truong T V
Published: July 2002

The aggregation stage of the life cycle of Dictyostelium discoideum is governed by the chemotactic response of individual amoebae to excitable waves of cAMP. We modeled this process through a recently introduced hybrid automata-continuum scheme and used computer simulation to unravel the role of specific components of this complex developmental process. Our results indicated an essential role for positive feedback between the cAMP signaling and the expression of the genes encoding the signal transduction and response machinery.