bluuebunny/crossref_metadata_2025 huggingface dataset:
Demonstration of an InGaN-based light-emitting diode on an AlN/sapphire template by metalorganic chemical vapor deposition
Authors: Egawa T. , Ohmura H. , Ishikawa H. , Jimbo T.
Published: July 2002

Structural, electrical, and optical properties of an InGaN-based light-emitting diode (LED) on an AlN/sapphire template have been studied and compared with the conventional LED properties on a sapphire substrate. In comparison to the LED on sapphire, the LED on AlN/sapphire template has shown better electrical and optical characteristics, which are due to a low threading dislocation density, high resistive, and thermal conductive AlN layer. An additional advantage is to grow a high-quality LED structure on an AlN/sapphire template without using low-temperature-grown GaN or an AlN buffer layer.
Phase field microelasticity theory and modeling of elastically and structurally inhomogeneous solid
Authors: Wang Yu U. , Jin Yongmei M. , Khachaturyan Armen G.
Published: July 2002

The phase field microelasticity theory of a three-dimensional elastically anisotropic solid of arbitrarily inhomogeneous modulus also containing arbitrary structural inhomogeneities is proposed. The theory is based on the equation for the strain energy of the elastically and structurally inhomogeneous system presented as a functional of the phase field, which is the effective stress-free strain of the “equivalent” homogeneous modulus system. It is proved that the stress-free strain minimizing this functional fully determines the exact elastic equilibrium in the elastically and structurally inhomogeneous solid. The stress-free strain minimizer is obtained as a steady state solution of the time-dependent Ginzburg–Landau equation. The long-range strain-induced interaction due to the elastic and structural inhomogeneities is explicitly taken into account. Systems with voids and cracks are the special cases covered by this theory since voids and cracks are elastic inhomogeneities that have zero modulus. Other misfitting defects, such as dislocations and coherent precipitates, are also integrated into this theory. Examples of elastic equilibrium of elastically inhomogeneous solid under applied stress are considered.
Nephelauxetic effect in LiNbO3:Cr3+ crystals
Authors: Biernacki S. W. , Kamińska A. , Suchocki A. , Arizmendi L.
Published: July 2002

A model, based on the Harrison theory of bonding is developed for quantitative explanation of the nephelauxetic effect, i.e., a reduction of interelectronic crystal field Racah repulsion parameters B and C due to the covalency of bonds. The results are used for a description of the effect in chromium-doped lithium niobate crystals. The model can be also applied to other systems.
Band gap narrowing of titanium dioxide by sulfur doping
Authors: Umebayashi T. , Yamaki T. , Itoh H. , Asai K.
Published: July 2002

Titanium dioxide (TiO2) doped with sulfur (S) was synthesized by oxidation annealing of titanium disulfide (TiS2). According to the x-ray diffraction patterns, TiS2 turned into anatase TiO2 when annealed at 600 °C. The residual S atoms occupied O-atom sites in TiO2 to form Ti–S bonds. The S doping caused the absorption edge of TiO2 to be shifted into the lower-energy region. Based on the theoretical analyses using ab initio band calculations, mixing of the S 3p states with the valence band was found to contribute to the band gap narrowing.
Intense visible light emission from stress-activated ZrO2:Ti
Authors: Akiyama Morito , Xu Chao-Nan , Nonaka Kazuhiro
Published: July 2002

We have investigated the luminescence phenomena from stress-activated ZrO2:Ti. The luminescence is clearly visible to the naked eye in the atmosphere. The luminescence center has been identified as the Ti4+ ion from spectra of the mechanoluminescence and also from photoluminescence studies of ZrO2:Ti. The mechanoluminescence intensity decreases on repetitive application of stress but recovers completely on irradiation with ultraviolet light. ZrO2 is an n-type semiconductor and has electron traps. It is suggested that the mechanoluminescence mechanism arises from the movement of dislocations and recombination between electrons and holes released from these traps which are associated with the Ti4+ centers.
Growth and characterization of CaF2/Ge/CaF2/Si(111) quantum dots for resonant tunneling diodes operating at room temperature
Authors: Yakimov A. I. , Derjabin A. S. , Sokolov L. V. , Pchelyakov O. P. , Dvurechenskii A. V. , Moiseeva M. M. , Sokolov N. S.
Published: July 2002

Resonant tunneling diodes were implemented on Ge quantum dots fabricated using Stranski–Krastanov growth mode on CaF2 matrix, lattice matched to Si(111) substrates. The negative differential conductance and conductance oscillations due to hole resonant tunneling through the zero-dimensional states of Ge quantum dots are clearly observed at room temperature. From the period of conductance oscillations, the energy separations between the states of the quantum dots with different sizes are estimated to be 40–50 meV (i.e., >kT=26 meV at T=300 K).
The anomalous bandgap bowing in GaAsN
Authors: Tisch U. , Finkman E. , Salzman J.
Published: July 2002

The composition dependence of the fundamental bandgap of thin, pseudomorphic GaAs1−xNx layers (0⩽x⩽5%) on GaAs substrates is studied by optical transmission measurements and high resolution x-ray diffraction. We present a very large set of consistent experimental data. An empirical double exponential composition dependence of the bowing parameter is obtained. This expression accurately describes the measured bandgaps, and allows estimations for higher N incorporations. The bowing parameter reaches 40 eV for very low N incorporations (x≈0.1%), and strongly decreases with increasing N molar fraction. We estimate that the bowing parameter would reach a constant value of 7.5 eV for x≳8%, as in an alloy. This bowing would not be sufficient to close the bandgap for higher N incorporations.
Exploring grain size as a cause for “dead-layer” effects in thin film capacitors
Authors: Sinnamon L. J. , Saad M. M. , Bowman R. M. , Gregg J. M.
Published: July 2002

Pulsed laser deposition was used to make a series of Au/Ba0.5Sr0.5TiO3 (BST)/SrRuO3/MgO thin film capacitors with dielectric thickness ranging from ∼15 nm to ∼1 μm. Surface grain size of the dielectric was monitored as a function of thickness using both atomic force microscopy and transmission electron microscopy. Grain size data were considered in conjunction with low field dielectric constant measurements. It was observed that the grain size decreased with decreasing thickness in a manner similar to the dielectric constant. Simple models were developed in which a functionally inferior layer at the grain boundary was considered as responsible for the observed dielectric behavior. If a purely columnar microstructure was assumed, then constant thickness grain-boundary dead layers could indeed reproduce the series capacitor dielectric response observed, even though such layers would contribute electrically in parallel with unaffected bulk-like BST. Best fits indicated that the dead layers would have a relative dielectric constant ∼40, and thickness of the order of tens of nanometers. For microstructures that were not purely columnar, models did not reproduce the observed dielectric behavior well. However, cross-sectional transmission electron microscopy indicated columnar microstructure, suggesting that grain boundary dead layers should be considered seriously in the overall dead-layer debate.
Fabrication of nanoscale gaps in integrated circuits
Authors: Krahne Roman , Yacoby Amir , Shtrikman Hadas , Bar-Joseph Israel , Dadosh Tali , Sperling Joseph
Published: July 2002

Nanosize objects such as metal clusters present an ideal system for the study of quantum phenomena and for the construction of practical quantum devices. Integrating these small objects in a macroscopic circuit is, however, a difficult task. So far, nanoparticles have been contacted and addressed by highly sophisticated techniques not suitable for large-scale integration in macroscopic circuits. We present an optical lithography method that allows for the fabrication of a network of electrodes separated by gaps of controlled nanometer size. The main idea is to control the gap size with subnanometer precision using a structure grown by molecular-beam epitaxy.
Accurate modeling of direct tunneling hole current in p-metal–oxide–semiconductor devices
Authors: Haque A. , Alam K.
Published: July 2002

We critically examine a number of important issues related to modeling hole direct tunneling in p-metal–oxide–semiconductor devices with p+-polycrystalline silicon gate. By comparing our simulated direct tunneling hole current with experimental data, several observations are made. It is found that inelastic trap scattering of holes in the gate-oxide region increases the hole tunneling current significantly at lower gate voltages in devices with gate-oxide thickness greater than 2 nm. Appropriate spatial and gate bias dependence of the scattering rate needs to be considered for accurately predicting experimental current over the entire gate voltage range. Effective mass of holes in gate-oxide region is not a constant, rather, it increases with increasing gate bias voltage and we propose a relationship between the two. Bulk values for hole effective masses in silicon may be used to accurately model the hole tunneling current even in the presence of hole quantization. The contribution of split-off holes to direct tunneling current is not negligible in strong inversion.
Fluorescence quantum efficiency measurements of excitation and nonradiative deexcitation processes of rare earth 4f-states in chalcogenide glasses
Authors: Lima S. M. , de Camargo A. S. S. , Nunes L. A. O. , Catunda T. , Hewak D. W.
Published: July 2002

Thermal lens spectroscopic measurements were performed to quantitatively determine the fluorescence quantum efficiency (η) of different luminescence mechanisms in Nd3+ chalcogenide glasses. Low energy (<1.7 eV) direct resonant pumping at Nd3+ infrared lines resulted in η∼1. High energy (∼2.4 eV) indirect excitation via energy transfer (ET) from glass conduction band to Nd3+ 4f states, resulted in η=∼0.4 (ET probability∼40%). A minimum η∼0.2 was obtained for intermediate excitation energies (∼2.2 eV) and attributed to back ET from the Nd3+ 4f state to the glass host.
Thermal annealing below the glass transition temperature: A general way to increase performance of light-emitting diodes based on copolyfluorenes
Authors: Niu Yu-Hua , Hou Qiong , Cao Yong
Published: July 2002

Polymer light-emitting diodes based on copolyfluorene with barium/aluminum cathode were thermally annealed at different temperatures through different time periods. It was found that by annealing just below the glass transition temperature (sub-Tg) of these copolymers the device performance was greatly enhanced. Lower turn-on voltage, higher maximum brightness, and more than two times higher external electroluminescent (EL) quantum efficiency could be achieved in this way. We found out that the enhancement in electron injection and the increase in carrier mobility after thermal annealing at a temperature close to Tg of the EL polymers are responsible for the improvement in device performance.
Carbon nanotubes as a tip calibration standard for electrostatic scanning probe microscopies
Authors: Kalinin Sergei V. , Bonnell Dawn A. , Freitag Marcus , Johnson A. T.
Published: July 2002

Scanning surface potential microscopy (SSPM) is one of the most widely used techniques for the characterization of electrical properties at small dimensions. Applicability of SSPM and related electrostatic scanning probe microscopies for imaging of potential distributions in active micro- and nanoelectronic devices requires quantitative knowledge of tip–surface contrast transfer. Here we demonstrate the utility of carbon-nanotube-based circuits to characterize geometric properties of the tip in the electrostatic scanning probe microscopies. Based on experimental observations, an analytical form for the differential tip–surface capacitance is obtained.
High performance germanium-on-silicon detectors for optical communications
Authors: Famà Silvia , Colace Lorenzo , Masini Gianlorenzo , Assanto Gaetano , Luan Hsin-Chiao
Published: July 2002

We demonstrate fast and efficient germanium-on-silicon p-i-n photodetectors for optical communications, with responsivities as high as 0.89 and 0.75 A/W at 1.3 and 1.55 μm, respectively, time response <200 ps and dark currents as low as 1.2 μA. Ge was epitaxially grown on Si by chemical vapor deposition, employing a low temperature buffer and cyclic thermal annealing to reduce the dislocation density. The overall performance is well suited for >2.5 Gb/s integrated receivers for the second and third fiber spectral windows.
Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors
Authors: Brooks Andrew I. , Stein Colleen S. , Hughes Stephanie M. , Heth Jason , McCray Paul M. , Sauter Sybille L. , Johnston Julie C. , Cory-Slechta Deborah A. , Federoff Howard J. , Davidson Beverly L.
Published: July 2002

Gene transfer vectors based on lentiviruses can transduce terminally differentiated cells in the brain; however, their ability to reverse established behavioral deficits in animal models of neurodegeneration has not previously been tested. When recombinant feline immunodeficiency virus (FIV)-based vectors expressing β-glucuronidase were unilaterally injected into the striatum of adult β-glucuronidase deficient [mucopolysaccharidosis type VII (MPS VII)] mice, an animal model of lysosomal storage disease, there was bihemispheric correction of the characteristic cellular pathology. Moreover, after the injection of FIV-based vectors expressing β-glucuronidase into brains of β-glucuronidase-deficient mice with established impairments in spatial learning and memory, there was dramatic recovery of behavioral function. Cognitive improvement resulting from expression of β-glucuronidase was associated with alteration in expression of genes associated with neuronal plasticity. These data suggest that enzyme replacement to the MPS VII central nervous system goes beyond restoration of β-glucuronidase activity in the lysosome, and imparts improvements in plasticity and spatial learning.
The final acylation step in Taxol biosynthesis: Cloning of the taxoid C13-side-chain
N
-benzoyltransferase from
Taxus
Authors: Walker Kevin , Long Robert , Croteau Rodney
Published: July 2002

The formation of several acyl groups and an amide group of Taxol is catalyzed by regioselective CoA thioester-dependent acyltransferases. Several full-length acyltransferase sequences, obtained from a cDNA library constructed from mRNA isolated from
Taxus cuspidata
cells induced for Taxol production with methyl jasmonate, were individually expressed in
Escherichia coli
, from which a cDNA clone encoding a 3′-
N
-debenzoyl- 2′-deoxytaxol
N
-benzoyltransferase was identified. This recombinant enzyme catalyzes the stereoselective coupling of the surrogate substrate
N
-debenzoyl-(3′
RS
)-2′-deoxytaxol with benzoyl-CoA to form predominantly one 3′-epimer of 2′-deoxytaxol. The product 2′-deoxytaxol was confirmed by radio-HPLC,
1
H-NMR, and chemical ionization-MS. This enzymatic reaction constitutes the final acylation in the Taxol biosynthetic pathway. The full-length cDNA coding for the
N
-benzoyltransferase has an ORF of 1,323 nucleotides and encodes a 441-residue protein with a calculated molecular weight of 49,040. The recombinant enzyme expressed in
E. coli
has a pH optimum at 8.0, a
k
cat
≈ 1.5 ± 0.3 s
−1
and
K
m
values of 0.42 mM and 0.40 mM for the
N
-deacylated taxoid and benzoyl-CoA, respectively. In addition to improving the production yields of Taxol in genetically engineered host systems, this enzyme provides a means of attaching modified aroyl groups to taxoid precursors for the purpose of improving drug efficacy.
Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V
1b
receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders
Authors: Griebel Guy , Simiand Jacques , Serradeil-Le Gal Claudine , Wagnon Jean , Pascal Marc , Scatton Bernard , Maffrand Jean-Pierre , Soubrié Philippe
Published: July 2002

The limbic localization of the arginine vasopressin V
1b
receptor has prompted speculation as to a potential role of this receptor in the control of emotional processes. To investigate this possibility, we have studied the behavioral effects of SSR149415, the first selective and orally active non-peptide antagonist of vasopressin V
1b
receptors, in a variety of classical (punished drinking, elevated plus-maze, and light/dark tests) and atypical (fear/anxiety defense test battery and social defeat-induced anxiety) rodent models of anxiety, and in two models of depression [forced swimming and chronic mild stress (CMS)]. When tested in classical tests of anxiety, SSR149415 produced anxiolytic-like activity at doses that ranged from 1 to 30 mg/kg (i.p. or p.o.), but the magnitude of these effects was overall less than that of the benzodiazepine anxiolytic diazepam, which was used as a positive control. In contrast, SSR149415 produced clear-cut anxiolytic-like activity in models involving traumatic stress exposure, such as the social defeat paradigm and the defense test battery (1–30 mg/kg, p.o.). In the forced swimming test, SSR149415 (10–30 mg/kg, p.o.) produced antidepressant-like effects in both normal and hypophysectomized rats. Moreover, in the CMS model in mice, repeated administration of SSR149415 (10 and 30 mg/kg, i.p.) for 39 days improved the degradation of the physical state, anxiety, despair, and the loss of coping behavior produced by stress. These findings point to a role for vasopressin in the modulation of emotional processes via the V
1b
receptor, and suggest that its blockade may represent a novel avenue for the treatment of affective disorders.
Inhibition of mitochondrial respiration by endogenous nitric oxide: A critical step in Fas signaling
Authors: Beltrán Belén , Quintero Marisol , García-Zaragozá Eugenia , O'Connor Enrique , Esplugues Juan V. , Moncada Salvador
Published: July 2002

We have found that activation of human adult T cell leukemia (Jurkat) cells with anti-Fas Ab leads, in a concentration-dependent manner, to an early burst of production of nitric oxide (NO), which inhibits cell respiration. This results in mitochondrial hyperpolarization, dependent on the hydrolysis of glycolytic ATP by the F1Fo-ATPase acting in reverse mode. During this early phase of activation, there is a transient release of superoxide anion. All these processes can be prevented by an inhibitor of NO synthase. Approximately 2 h after stimulation with anti-Fas Ab, a distinct second phase can be detected. This comprises a concentration-dependent collapse in mitochondrial membrane potential, a second wave of free radical production, and activation of caspase-8 leading to apoptosis. This second phase is abolished by an inhibitor of caspase activation. In contrast, inhibition of NO synthesis leads to an enhancement and acceleration of these latter processes, suggesting that the early NO-dependent phase represents a protective mechanism. The significance of the two phases in relation to cell survival and death remains to be studied.
1
H and
13
C MAS NMR evidence for pronounced ligand–protein interactions involving the ionone ring of the retinylidene chromophore in rhodopsin
Authors: Creemers Alain F. L. , Kiihne Suzanne , Bovee-Geurts Petra H. M. , DeGrip Willem J. , Lugtenburg Johan , de Groot Huub J. M.
Published: July 2002

Rhodopsin is a member of the superfamily of G-protein-coupled receptors. This seven α-helix transmembrane protein is the visual pigment of the vertebrate rod photoreceptor cells that mediate dim light vision. In the active binding site of this protein the ligand or chromophore, 11-
cis
-retinal, is covalently bound via a protonated Schiff base to lysine residue 296. Here we present the complete
1
H and
13
C assignments of the 11-
cis
-retinylidene chromophore in its ligand-binding site determined with ultra high field magic angle spinning NMR. Native bovine opsin was regenerated with 99% enriched uniformly
13
C-labeled 11-
cis
-retinal. From the labeled pigment,
13
C carbon chemical shifts could be obtained by using two-dimensional radio frequency-driven dipolar recoupling in a solid-state magic angle spinning homonuclear correlation experiment. The
1
H chemical shifts were assigned by two-dimensional heteronuclear (
1
H-
13
C) dipolar correlation spectroscopy with phase-modulated Lee–Goldburg homonuclear
1
H decoupling applied during the
t
1
period. The data indicate nonbonding interactions between the protons of the methyl groups of the retinylidene ionone ring and the protein. These nonbonding interactions are attributed to nearby aromatic acid residues Phe-208, Phe-212, and Trp-265 that are in close contact with, respectively, H-16/H-17 and H-18. Furthermore, binding of the chromophore involves a chiral selection of the ring conformation, resulting in equatorial and axial positions for CH
3
-16 and CH
3
-17.
Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components
Authors: Timasheff Serge N.
Published: July 2002

Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential exclusion (preferential hydration). The driving force is the perturbation by the protein of the chemical potential of the cosolvent. It is shown that the measured change of the amount of water in contact with protein during the course of the reaction modulated by an osmolyte is a change in preferential hydration that is strictly a measure of the cosolvent chemical potential perturbation by the protein in the ternary water–protein–cosolvent system. It is not equal to the change in water of hydration, because water of hydration is a reflection strictly of protein–water forces in a binary system. There is no direct relation between water of preferential hydration and water of hydration.
Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon
Authors: Anderson Christine B. , Neufeld Kristi L. , White Raymond L.
Published: July 2002

Mutations in the
APC
tumor suppressor gene are present in approximately 85% of colorectal tumors and are thought to contribute early in the process of tumorigenesis. The truncated protein resulting from most
APC
mutations can lead to elevated β-catenin levels in colon tumor cells. APC and associated proteins thus form a β-catenin regulatory complex, with axin playing a key role. Although cell culture studies have revealed intriguing aspects of this complex, little characterization has been done in human colonocytes, the target tissue of colon carcinogenesis. The present study of intact human colon crypts, adenomatous polyps, and adenocarcinomas focuses on subcellular localization of some key elements of the complex: β-catenin, APC, axin, and axin2. We examined endogenous protein localization within the framework of three-dimensional tissue architecture by using laser scanning confocal microscopy, and immunofluorescence staining of whole-mount fixed tissue from more than 50 patients. Expression patterns suggest that APC and axin colocalize in the nucleus and at lateral cell borders, and show that axin2 is limited to the nucleus. Altered nuclear expression of axin seen in colon polyps and carcinomas may be a consequence of the loss of full-length APC and the advent of nuclear β-catenin. The observation of nuclear β-catenin in fewer than half of carcinoma images and only rarely in polyps indicates that nuclear translocation of β-catenin may not be an immediate consequence of the loss of APC.
Time-critical integration of formants for perception of communication calls in mice
Authors: Geissler Diana B. , Ehret Günter
Published: July 2002

Brain mechanisms in humans group together acoustical frequency components both in the spectral and temporal domain, which leads to the perception of auditory objects and of streams of sound events that are of biological and communicative significance. At the perceptual level, behavioral data on mammals that clearly support the presence of common concepts for processing species-specific communication sounds are unavailable. Here, we synthesize 17 models of mouse pup wriggling calls, present them in sequences of four calls to the pups' mothers in a natural communication situation, and record the maternal response behavior. We show that the biological significance of a call sequence depends on grouping together three predominant frequency components (formants) to an acoustic object within a critical time window of about 30-ms lead or lag time of the first formant. Longer lead or lag times significantly reduce the maternal responsiveness. Central inhibition seems to be responsible for setting this time window, which is also found in numerous perceptual studies in humans. Further, a minimum of 100-ms simultaneous presence of the three formants is necessary for occurrence of response behavior. As in humans, onset-time asynchronies of formants and formant durations interact nonlinearly to influence the adequate perception of a stream of sounds. Together, these data point to common rules for time-critical spectral integration, perception of acoustical objects, and auditory streaming (perception of an acoustical Gestalt) in mice and humans.
Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming
Authors: Varoqueaux Frederique , Sigler Albrecht , Rhee Jeong-Seop , Brose Nils , Enk Carsten , Reim Kerstin , Rosenmund Christian
Published: July 2002

Synaptic vesicles must be primed to fusion competence before they can fuse with the plasma membrane in response to increased intracellular Ca
2+
levels. The presynaptic active zone protein Munc13-1 is essential for priming of glutamatergic synaptic vesicles in hippocampal neurons. However, a small subpopulation of synapses in any given glutamatergic nerve cell as well as all γ-aminobutyratergic (GABAergic) synapses are largely independent of Munc13-1. We show here that Munc13-2, the only Munc13 isoform coexpressed with Munc13-1 in hippocampus, is responsible for vesicle priming in Munc13-1 independent hippocampal synapses. Neurons lacking both Munc13-1 and Munc13-2 show neither evoked nor spontaneous release events, yet form normal numbers of synapses with typical ultrastructural features. Thus, the two Munc13 isoforms are completely redundant in GABAergic cells whereas glutamatergic neurons form two types of synapses, one of which is solely Munc13-1 dependent and lacks Munc13-2 whereas the other type employs Munc13-2 as priming factor. We conclude that Munc13-mediated vesicle priming is not a transmitter specific phenomenon but rather a general and essential feature of multiple fast neurotransmitter systems, and that synaptogenesis during development is not dependent on synaptic secretory activity.
Reconstitution in yeast of the
Arabidopsis
SOS signaling pathway for Na
+
homeostasis
Authors: Quintero Francisco J. , Ohta Masaru , Shi Huazhong , Zhu Jian-Kang , Pardo Jose M.
Published: July 2002

The
Arabidopsis thaliana
SOS1 protein is a putative Na
+
/H
+
antiporter that functions in Na
+
extrusion and is essential for the NaCl tolerance of plants.
sos1
mutant plants share phenotypic similarities with mutants lacking the protein kinase SOS2 and the Ca
2+
sensor SOS3. To investigate whether the three SOS proteins function in the same response pathway, we have reconstituted the SOS system in yeast cells. Expression of SOS1 improved the Na
+
tolerance of yeast mutants lacking endogenous Na
+
transporters. Coexpression of SOS2 and SOS3 dramatically increased SOS1-dependent Na
+
tolerance, whereas SOS2 or SOS3 individually had no effect. The SOS2/SOS3 kinase complex promoted the phosphorylation of SOS1. A constitutively active form of SOS2 phosphorylated SOS1
in vitro
independently of SOS3, but could not fully substitute for the SOS2/SOS3 kinase complex for activation of SOS1
in vivo
. Further, we show that SOS3 recruits SOS2 to the plasma membrane. Although
sos1
mutant plants display defective K
+
uptake at low external concentrations, neither the unmodified nor the SOS2/SOS3-activated SOS1 protein showed K
+
transport capacity
in vivo
, suggesting that the role of SOS1 on K
+
uptake is indirect. Our results provide an example of functional reconstitution of a plant response pathway in a heterologous system and demonstrate that the SOS1 ion transporter, the SOS2 protein kinase, and its associated Ca
2+
sensor SOS3 constitute a functional module. We propose a model in which SOS3 activates and directs SOS2 to the plasma membrane for the stimulatory phosphorylation of the Na
+
transporter SOS1.
Hidden Markov models from molecular dynamics simulations on DNA
Authors: Thayer Kelly M. , Beveridge D. L.
Published: July 2002

An enhanced bioinformatics tool incorporating the participation of molecular structure as well as sequence in protein DNA recognition is proposed and tested. Boltzmann probability models of sequence-dependent DNA structure from all-atom molecular dynamics simulations were obtained and incorporated into hidden Markov models (HMMs) that can recognize molecular structural signals as well as sequence in protein–DNA binding sites on a genome. The binding of catabolite activator protein (CAP) to cognate DNA sequences was used as a prototype case for implementation and testing of the method. The results indicate that even HMMs based on probabilistic
roll
/
tilt
dinucleotide models of sequence-dependent DNA structure have some capability to discriminate between known CAP binding and nonbinding sites and to predict putative CAP binding sites in unknowns. Restricting HMMs to sequence only in regions of strong consensus in which the protein makes base specific contacts with the cognate DNA further improved the discriminatory capabilities of the HMMs. Comparison of results with controls based on sequence only indicates that extending the definition of consensus from sequence to structure improves the transferability of the HMMs, and provides further supportive evidence of a role for dynamical molecular structure as well as sequence in genomic regulatory mechanisms.
The complete genome sequence of
Chlorobium tepidum
TLS, a photosynthetic, anaerobic, green-sulfur bacterium
Authors: Eisen Jonathan A. , Nelson Karen E. , Paulsen Ian T. , Heidelberg John F. , Wu Martin , Dodson Robert J. , Deboy Robert , Gwinn Michelle L. , Nelson William C. , Haft Daniel H. , Hickey Erin K. , Peterson Jeremy D. , Durkin A. Scott , Kolonay James L. , Yang Fan , Holt Ingeborg , Umayam Lowell A. , Mason Tanya , Brenner Michael , Shea Terrance P. , Parksey Debbie , Nierman William C. , Feldblyum Tamara V. , Hansen Cheryl L. , Craven M. Brook , Radune Diana , Vamathevan Jessica , Khouri Hoda , White Owen , Gruber Tanja M. , Ketchum Karen A. , Venter J. Craig , Tettelin Hervé , Bryant Donald A. , Fraser Claire M.
Published: July 2002

The complete genome of the green-sulfur eubacterium
Chlorobium tepidum
TLS was determined to be a single circular chromosome of 2,154,946 bp. This represents the first genome sequence from the phylum
Chlorobia
, whose members perform anoxygenic photosynthesis by the reductive tricarboxylic acid cycle. Genome comparisons have identified genes in
C. tepidum
that are highly conserved among photosynthetic species. Many of these have no assigned function and may play novel roles in photosynthesis or photobiology. Phylogenomic analysis reveals likely duplications of genes involved in biosynthetic pathways for photosynthesis and the metabolism of sulfur and nitrogen as well as strong similarities between metabolic processes in
C. tepidum
and many Archaeal species.
Mutually regulated expression of
Pax6
and
Six3
and its implications for the
Pax6
haploinsufficient lens phenotype
Authors: Goudreau Guy , Petrou Petros , Reneker Lixing W. , Graw Jochen , Löster Jana , Gruss Peter
Published: July 2002

Pax6
is a key regulator of eye development in vertebrates and invertebrates, and heterozygous loss-of-function mutations of the mouse
Pax6
gene result in the
Small eye
phenotype, in which a small lens is a constant feature. To provide an understanding of the mechanisms underlying this haploinsufficient phenotype, we evaluated in
Pax6
heterozygous mice the effects of reduced
Pax6
gene dosage on the activity of other transcription factors regulating eye formation. We found that
Six3
expression was specifically reduced in lenses of
Pax6
heterozygous mouse embryos. Interactions between orthologous genes from the
Pax
and
Six
families have been identified in
Drosophila
and vertebrate species, and we examined the control of
Pax6
and
Six3
gene expression in the developing mouse lens. Using
in vitro
and transgenic approaches, we found that either transcription factor binds regulatory sequences from the counterpart gene and that both genes mutually activate their expression. These studies define a functional relationship in the lens in which
Six3
expression is dosage-dependent on
Pax6
and where, conversely,
Six3
activates
Pax6
. Accordingly, we show a rescue of the
Pax6
haploinsufficient lens phenotype after lens-specific expression of
Six3
in transgenic mice. This phenotypic rescue was accompanied by cell proliferation and activation of the platelet-derived growth factor α-R/cyclin D1 signaling pathway. Our findings thus provide a mechanism implicating gene regulatory interactions between
Pax6
and
Six3
in the tissue-specific defects found in
Pax6
heterozygous mice.
A cytosine methyltransferase homologue is essential for repeat-induced point mutation in
Neurospora crassa
Authors: Freitag Michael , Williams Rebecca L. , Kothe Gregory O. , Selker Eric U.
Published: July 2002

During sexual development,
Neurospora crassa
inactivates genes in duplicated DNA segments by a hypermutation process, repeat-induced point mutation (RIP). RIP introduces C:G to T:A transition mutations and creates targets for subsequent DNA methylation in vegetative tissue. The mechanism of RIP and its relationship to DNA methylation are not fully understood. Mutations in DIM-2, a DNA methyltransferase (DMT) responsible for all known cytosine methylation in
Neurospora
, does not prevent RIP. We used RIP to disrupt a second putative DMT gene in the
Neurospora
genome and tested mutants for defects in DNA methylation and RIP. No effect on DNA methylation was detected in the tissues that could be assayed, but the mutants showed recessive defects in RIP. Duplications of the
am
and
mtr
genes were completely stable in crosses homozygous for the mutated potential DMT gene, which we call
rid
(
RI
P
d
efective). The same duplications were inactivated normally in heterozygous crosses. Disruption of the
rid
gene did not noticeably affect fertility, growth, or development. In contrast, crosses homozygous for a mutation in a related gene in
Ascobolus immersus
,
masc1
, reportedly fail to develop and heterozygous crosses reduce methylation induced premeiotically [Malagnac, F., Wendel, B., Goyon, C., Faugeron, G., Zickler, D.,
et al
. (1997)
Cell
91, 281–290]. We isolated homologues of
rid
from
Neurospora tetrasperma
and
Neurospora intermedia
to identify conserved regions. Homologues possess all motifs characteristic of eukaryotic DMTs and have large distinctive C- and N-terminal domains.
Semidwarf (
sd-1
), “green revolution” rice, contains a defective gibberellin 20-oxidase gene
Authors: Spielmeyer Wolfgang , Ellis Marc H. , Chandler Peter M.
Published: July 2002

The introduction of semidwarf rice (
Oryza sativa
L.) led to record yield increases throughout Asia in the 1960s. The major semidwarfing allele,
sd-1
, is still extensively used in modern rice cultivars. The phenotype of
sd-1
is consistent with dwarfism that results from a deficiency in gibberellin (GA) plant growth hormones. We propose that the semidwarf (
sd-1
) phenotype is the result of a deficiency of active GAs in the elongating stem arising from a defective 20-oxidase GA biosynthetic enzyme. Sequence data from the rice genome was combined with previous mapping studies to locate a putative GA 20-oxidase gene
(Os20ox2)
at the predicted map location of
sd-1
on chromosome 1. Two independent
sd-1
alleles contained alterations within
Os20ox2:
a deletion of 280 bp within the coding region of
Os20ox2
was predicted to encode a nonfunctional protein in an
indica
type semidwarf (Doongara), whereas a substitution in an amino acid residue (Leu-266) that is highly conserved among dioxygenases could explain loss of function of Os20ox2 in a
japonica
semidwarf (Calrose76). The quantification of GAs in elongating stems by GC-MS showed that the initial substrate of GA 20-oxidase activity (GA
53
) accumulated, whereas the content of the major product (GA
20
) and of bioactive GA
1
was lower in semidwarf compared with tall lines. We propose that the
Os20ox2
gene corresponds to the
sd-1
locus.
Influence of the
period
-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in
Drosophila
melanogaster
Authors: Lin Yiing , Han Mei , Shimada Brian , Wang Lin , Gibler Therese M. , Amarakone Aloka , Awad Tarif A. , Stormo Gary D. , Van Gelder Russell N. , Taghert Paul H.
Published: July 2002

We measured daily gene expression in heads of control and
period
mutant
Drosophila
by using oligonucleotide microarrays. In control flies, 72 genes showed diurnal rhythms in light-dark cycles; 22 of these also oscillated in free-running conditions. The
period
gene significantly influenced the expression levels of over 600 nonoscillating transcripts. Expression levels of several hundred genes also differed significantly between control flies kept in light-dark versus constant darkness but differed minimally between
per
01
flies kept in the same two conditions. Thus, the
period
-dependent circadian clock regulates only a limited set of rhythmically expressed transcripts. Unexpectedly,
period
regulates basal and light-regulated gene expression to a very broad extent.
Tracking the ecological overshoot of the human economy
Authors: Wackernagel Mathis , Schulz Niels B. , Deumling Diana , Linares Alejandro Callejas , Jenkins Martin , Kapos Valerie , Monfreda Chad , Loh Jonathan , Myers Norman , Norgaard Richard , Randers Jørgen
Published: July 2002

Sustainability requires living within the regenerative capacity of
the biosphere. In an attempt to measure the extent to which humanity
satisfies this requirement, we use existing data to translate human
demand on the environment into the area required for the production of
food and other goods, together with the absorption of wastes. Our
accounts indicate that human demand may well have exceeded the
biosphere's regenerative capacity since the 1980s. According to this
preliminary and exploratory assessment, humanity's load corresponded
to 70% of the capacity of the global biosphere in 1961, and grew to
120% in 1999.
Nuclear K
ATP
channels trigger nuclear Ca
2+
transients that modulate nuclear function
Authors: Quesada Ivan , Rovira Juan M. , Martin Franz , Roche Enrique , Nadal Angel , Soria Bernat
Published: July 2002

Glucose, the principal regulator of endocrine pancreas, has several effects on pancreatic beta cells, including the regulation of insulin release, cell proliferation, apoptosis, differentiation, and gene expression. Although the sequence of events linking glycemia with insulin release is well described, the mechanism whereby glucose regulates nuclear function is still largely unknown. Here, we have shown that an ATP-sensitive K
+
channel (K
ATP
) with similar properties to that found on the plasma membrane is also present on the nuclear envelope of pancreatic beta cells. In isolated nuclei, blockade of the K
ATP
channel with tolbutamide or diadenosine polyphosphates triggers nuclear Ca
2+
transients and induces phosphorylation of the transcription factor cAMP response element binding protein. In whole cells, fluorescence
in situ
hybridization revealed that these Ca
2+
signals may trigger c-
myc
expression. These results demonstrate a functional K
ATP
channel in nuclei linking glucose metabolism, nuclear Ca
2+
signals, and nuclear function.
Overt female mate competition and preference for central males in a lekking antelope
Authors: Bro-Jørgensen Jakob
Published: July 2002

In mammals, there exists only scant evidence of female mate choice in species mating on arenas, so-called leks. This has led to hypotheses of lek evolution that are based on benefits to females from reduced harassment by males, low predation risk, or improved availability of scarce nutrients. Here I report that female topi antelopes (
Damaliscus lunatus
) compete aggressively for matings with preferred males on central lek territories. Females fight at higher rates and more likely disrupt mating attempts of others in the lek center than elsewhere. Contrary to the predictions of the alternative hypotheses, food resources were insignificant, and harassment levels and estimated predation risk were higher on than off lek. These results clearly demonstrate female competition for mates in a lekking mammal in which a female chooses between males for the sole purpose of mating. The finding suggests that the forces leading to lek evolution in mammals and birds may be more similar than previously acknowledged.
Assaying gene content in
Arabidopsis
Authors: Allen Keith D.
Published: July 2002

Arabidopsis
has been popular as a model plant system for decades. Completion of the
Arabidopsis
genome and the availability of large expressed sequence-tag collections from other dicot species provides an opportunity to assess gene content in
Arabidopsis
, specifically by identifying genes from dicot test species that are absent from
Arabidopsis
. I report here results from these sorts of comparisons, carried out in part to assess the extent to which
Arabidopsis
is representative of dicot genomes and also the degree to which gene loss and novel gene acquisition has accompanied angiosperm speciation. More than 10% of the contigs from each of three dicot test species have no detectable homologue in
Arabidopsis
. By means of cross comparison among the test species, 154 specific cases of gene loss in the lineage leading to
Arabidopsis
were identified, including several well characterized enzymes and a group of proteins with strong homologs in the photosynthetic bacterium
Synechocystis
. These results show that although
Arabidopsis
is broadly representative of the other dicot genomes, there seems to be substantial variation even among relatively closely related genera. Further, although we cannot yet draw a causative link, variation in actual gene content seems appears to be a feature of angiosperm speciation.
Early experience is associated with the development of categorical representations for facial expressions of emotion
Authors: Pollak Seth D. , Kistler Doris J.
Published: July 2002

A fundamental issue in human development concerns how the young infant's ability to recognize emotional signals is acquired through both biological programming and learning factors. This issue is extremely difficult to investigate because of the variety of sensory experiences to which humans are exposed immediately after birth. We examined the effects of emotional experience on emotion recognition by studying abused children, whose experiences violated cultural standards of care. We found that the aberrant social experience of abuse was associated with a change in children's perceptual preferences and also altered the discriminative abilities that influence how children categorize angry facial expressions. This study suggests that affective experiences can influence perceptual representations of basic emotions.
The fifth essential DNA polymerase φ inSaccharomyces cerevisiaeis localized to the nucleolus and plays an important role in synthesis of rRNA
Authors: Shimizu Kikuo , Kawasaki Yasuo , Hiraga Shin-Ichiro , Tawaramoto Maki , Nakashima Naomi , Sugino Akio
Published: July 2002

We report thatPOL5encodes the fifth essential DNA polymerase inSaccharomyces cerevisiae. Pol5p was identified and purified from yeast cell extracts and is an aphidicolin-sensitive DNA polymerase that is stimulated by yeast proliferating cell nuclear antigen (PCNA). Thus, we named Pol5p DNA polymerase φ. Temperature-sensitivepol5-1∼–3mutants did not arrest at G2/M at the restrictive temperature. Furthermore, the polymerase active-site mutantPOL5dngene complements the lethality of Δpol5. These results suggest that the polymerase activity of Pol5p is not required for thein vivofunction of Pol5p. rRNA synthesis was severely inhibited at the restrictive temperature in the temperature-sensitivepol5-3mutant cells, suggesting that an essential function of Pol5p is rRNA synthesis. Pol5p is localized exclusively to the nucleolus and binds near or at the enhancer region of rRNA-encoding DNA repeating units.
Trace fear conditioning involves hippocampal α
5
GABA
A
receptors
Authors: Crestani F. , Keist R. , Fritschy J.-M. , Benke D. , Vogt K. , Prut L. , Blüthmann H. , Möhler H. , Rudolph U.
Published: July 2002

The heterogeneity of γ-aminobutyric acid type A (GABA
A
) receptors contributes to the diversity of neuronal inhibition in the regulation of information processing. Although most GABA
A
receptors are located synaptically, the small population of α
5
GABA
A
receptors is largely expressed extrasynaptically. To clarify the role of the α
5
GABA
A
receptors in the control of behavior, a histidine-to-arginine point mutation was introduced in position 105 of the murine α
5
subunit gene, which rendered the α
5
GABA
A
receptors diazepam-insensitive. Apart from an incomplete muscle relaxing effect, neither the sedative, anticonvulsant, nor anxiolytic-like activity of diazepam was impaired in α
5
(H105R) mice. However, in hippocampal pyramidal cells, the point mutation resulted in a selective reduction of α
5
GABA
A
receptors, which altered the drug-independent behavior. In line with the role of the hippocampus in certain forms of associative learning, trace fear conditioning, but not delay conditioning or contextual conditioning, was facilitated in the mutant mice. Trace fear conditioning differs from delay conditioning in that the conditioned and unconditioned stimulus are separated by a time interval. Thus, the largely extrasynaptic α
5
GABA
A
receptors in hippocampal pyramidal cells are implicated as control elements of the temporal association of threat cues in trace fear conditioning.
Erk5 null mice display multiple extraembryonic vascular and embryonic cardiovascular defects
Authors: Regan Christopher P. , Li Wei , Boucher Diane M. , Spatz Stephen , Su Michael S. , Kuida Keisuke
Published: July 2002

Erk5 is a mitogen-activated protein kinase, the biological role of which is largely undefined. Therefore, we deleted the
erk5
gene in mice to assess its function
in vivo
. Inactivation of the
erk5
gene resulted in defective blood-vessel and cardiac development leading to embryonic lethality around embryonic days 9.5–10.5. Cardiac development was retarded largely, and the heart failed to undergo normal looping. Endothelial cells that line the developing myocardium of
erk5
−/− embryos displayed a disorganized, rounded morphology. Vasculogenesis occurred, but extraembryonic and embryonic blood vessels were disorganized and failed to mature. Furthermore, the investment of embryonic blood vessels with smooth muscle cells was attenuated. Together, these data define an essential role for Erk5 in cardiovascular development. Moreover, the inability of Erk5-deficient mice to form a complex vasculature suggests that Erk5 may play an important role in controlling angiogenesis.