bluuebunny/crossref_metadata_2025 huggingface dataset:
Cluster size effects on CO oxidation activity, adsorbate affinity, and temporal behavior of model Aun∕TiO2 catalysts
Authors: Lee Sungsik , Fan Chaoyang , Wu Tianpin , Anderson Scott L.
Published: September 2005

Model catalysts were prepared by deposition of size-selected Aun(n=1–7) on rutile TiO2(110), and characterized by a combination of electron spectroscopy, ion scattering, temperature-programmed desorption, and pulse-dosing mass spectrometry. CO oxidation activity was found to vary strongly with deposited cluster size, with significant activity appearing at Au3. Activity is not obviously correlated with affinity for CO, or with cluster morphology, but is strongly correlated with the clusters’ ability to bind oxygen (during O2 exposure) on top of the gold. The temporal dependence of CO2 evolution in reaction of O2 pre-exposed samples with CO pulses shows an interesting cluster size dependence. For Au5 and Au6, the peak CO2 production is coincident with the peak CO flux, but for Au3,Au4, and Au7, there are significant induction periods for CO2 evolution. In addition, it is observed that some of the most active cluster sizes have the slowest CO2 evolution rates. Several mechanistic scenarios capable of accounting for the observations are laid out.
Complex polarization propagator method for calculation of dispersion coefficients of extended π-conjugated systems: The C6 coefficients of polyacenes and C60
Authors: Jiemchooroj Auayporn , Norman Patrick , Sernelius Bo E.
Published: September 2005

The frequency-dependent polarizabilities and the C6 dipole-dipole dispersion coefficients for the first members of the polyacenes namely benzene, naphthalene, anthracene, and naphthacene as well as the fullerene C60 have been calculated at the time-dependent Hartree-Fock level and the time-dependent density-functional theory level with the hybrid B3LYP exchange-correlation functional. The dynamic polarizabilities at imaginary frequencies are obtained with use of the complex linear polarization propagator method and the C6 coefficients are subsequently determined from the Casimir-Polder relation. We report the first ab initio calculations of the C6 coefficients for the molecules under consideration, and our recommended value for the dispersion coefficient of the fullerene is 101.0a.u.
All-exchanges parallel tempering
Authors: Calvo F.
Published: September 2005

An alternative exchange strategy for parallel tempering simulations is introduced. Instead of attempting to swap configurations between two randomly chosen but adjacent replicas, the acceptance probabilities of all possible swap moves are calculated a priori. One specific swap move is then selected according to its probability and enforced. The efficiency of the method is illustrated first on the case of two Lennard-Jones (LJ) clusters containing 13 and 31 atoms, respectively. The convergence of the caloric curve is seen to be at least twice as fast as in conventional parallel tempering simulations, especially for the difficult case of LJ31. Further evidence for an improved efficiency is reported on the ergodic measure introduced by Mountain and Thirumalai [J. Phys. Chem. 93, 6975 (1989)], calculated here for LJ13 close to the melting point. Finally, tests on two simple spin systems indicate that the method should be particularly useful when a limited number of replicas are available.
Effect of thermal transport on spatiotemporal emergence of lamellar branching morphology during polymer spherulitic growth
Authors: Xu Haijun , Keawwattana Wirunya , Kyu Thein
Published: September 2005

Spatiotemporal emergence of lamellar branching morphology of polymer spherulite has been investigated theoretically in the framework of a phase field model by coupling a crystal solidification potential pertaining to a nonconserved crystal order parameter with a temperature field generated by latent heat of crystallization. A local free-energy density having an asymmetric double well has been utilized to account for a first-order phase transition such as crystallization. To account for the polymorphous nature of polymer crystallization, the phase field order parameter of crystal at the solidification potential of the double-well local free-energy density is modified to be supercooling dependent. The heat conduction equation, incorporating liberation of latent heat along the nonuniform solid-liquid interface, has led to directional growth of various hierarchical structures including lamella, sheaflike structure, and spherulite. Two-dimensional calculations have been carried out based on experimentally accessible material parameters and experimental conditions for the growth of syndiotactic polypropylene spherulite. The simulations illustrate that, under self-generated thermal field, the initial nucleus is anisotropic having lamellar stacks that transforms to a sheaflike structure and eventually to a lamellar branching morphology with a dual-eye-pocket texture at the core. It appears that the released latent heat is responsible for the lamellar side branching and splaying from the main lamellae. On the same token, the heat build-up seemingly prevents the interface boundaries of neighboring spherulites from over running on each other during impingement, thereby forming the grain boundary.
An empirical potential-energy surface for the He–I2(BΠu3) van der Waals complex including three-body effects
Authors: García-Vela A.
Published: September 2005

An empirical intermolecular potential surface is proposed for the He–I2(BΠu3) complex, modeled as a sum of pairwise He–I Morse interactions plus a three-body interaction term. The potential reproduces with very good agreement the spectral blueshifts and vibrational predissociation lifetimes measured for He–I2(B,υ′) in the range υ′=10–67 of I2 vibrational excitations. In particular, the accuracy achieved in the description of the experimental data for high υ′ levels is attributed to the three-body interaction term included in the potential. The behavior of the potential surface with the I–I separation is analyzed and correlated with the experimental findings.
Inelastic electronic excitation and electron transfer processes in collisions between Mg(3S1) atoms and K+(S1) ions studied by crossed beams in the 0.10-3.80-keV energy range
Authors: Sabidó M. , de Andrés J. , Sogas J. , Lucas J. M. , Albertí M. , Bofill J. M. , Aguilar A.
Published: September 2005

Inelastic and charge-transfer excitation processes in collisions between ground-state neutral Mg atoms and K+ ions have been studied by means of a crossed molecular-beam technique. Decay fluorescent emissions from Mg(3P11),Mg(4S13), and Mg(3s13d1,3D3,2,13) as well as the phosphorescent emission due to Mg(3P13) have been observed from excited Mg atoms and the charge-transfer emission decays from K(4P3∕2,1∕22),K(5P3∕2,1∕22),K(6S1∕22), and K(4D5∕2,3∕22) for excited K atoms. The corresponding absolute cross-sections values versus collision energy functions were determined in the 0.10–3.80 keV laboratory energy range. In order to interpret the experimental results, accurate ab initio full configuration-interaction calculations using pseudopotentials have been performed for the (Mg–K)+ system, giving a manifold of adiabatic singlet and triplet potential-energy curves correlating with the different collision channels, which allow a qualitative interpretation of the emission excitation functions measured for the different processes studied. A comparative study with other Mg-alkali ion systems previously studied is also included.
Ultrafast direct writing scheme with unipolar field pulses for synthetic antiferromagnetic magnetic random access memory cells
Authors: Nembach H. T. , Bayer C. , Schultheiss H. , Weber M. C. , Pimentel P. Martin , Beck P. A. , Leven B. , Hillebrands B.
Published: September 2005

A writing scheme is presented for Savtchenko-type magnetic random access memory (MRAM) cells, which allows for ultrafast direct writing with high stability against half select switching, using two orthogonally oriented unipolar magnetic field pulses with time delay, which allows for backswitching by reversing the temporal sequence of the two pulses. The numerical simulations are based on the Stoner–Wohlfarth model and a Runge Kutta integration of the Landau–Lifshitz and Gilbert equation.
Production of methyl-oxonium ion and its complexes in the core-excited (HC(O)OCH3)n clusters: H∕H+ transfer from the α carbonyl
Authors: Tada S. , Harada C. , Yoshida H. , Wada S. , Hiraya A. , Tanaka K. , Tabayashi K.
Published: September 2005

Dissociation of free methyl-formate (MF), HC(O)OCH3, and its clusters (MF)n, (HC(O)OCH3)n, induced by core-level excitation was studied near the oxygen K edge by time-of-flight fragment-mass spectroscopy. Besides the protonated clusters, (MF)nH+ with n≦15, we identified the production for another series of (MF)mCH3OH2+ with m≦14 as well as methyl-oxonium ion, CH3OH2+, characteristic of hydrogen transfer reactions in the cationic clusters. Here, specifically labeled methyl-formate-d (MFD), DC(O)OCH3 was also used to examine the core-excited dissociation mechanisms. Deuterium-labeled experiments indicated that MFD+ with low internal energies, partially generated after the core excitation, produces CH3OD+ via a site-specific deuterium transfer from the α carbonyl in the molecular cation and that CH3OD2+ can be formed via the successive transfer of another deuterium from the neighbor molecule in the clusters. The deuteron (proton) transfer was also found to take place preferentially from the α carbonyl of the neighbor molecule for the production of deuteronated (MFD)nD+, (protonated (MF)nH+), clusters. The minimal energy requirement paths were examined for dimer (MF)2+ cation to support the present dissociation mechanisms of core-excited (MF)n clusters using ab initio molecular-orbital calculations.
Gold-particle-mediated detection of ferroelectric domains on the nanometer scale
Authors: Härtling Thomas , Eng Lukas M.
Published: September 2005

We report on an unique optical method which facilitates detection of ferroelectric (FE) domain orientation on the subwavelength scale. The FE material of interest is decorated with Au nanoparticles of 100nm diameter and then completely covered with a thin film of birefringent liquid-crystal (LC) molecules. The latter align to the FE surface in accordance to the domain-specific electric stray field, which causes a characteristic spatial orientation of the dielectric tensor ε̂m of the LC layer. As their spectral response strongly depends on the dielectric constant of the surrounding medium, the embedded Au particles are used as nanoscale optical antennas revealing either an intensity, a polarization, or a spectral contrast. This technique provides an ultrafast optical read-out mechanism for detecting antiparallel oriented FE domains with subwavelength resolution.
Relaxation dynamics in AgI-doped silver vanadate superionic glasses
Authors: Bhattacharya S. , Ghosh A.
Published: September 2005

Relaxation dynamics of Ag+ ions in several series of AgI-Ag2O-V2O5 superionic glasses has been studied in the frequency range from 10Hzto2MHz and in the temperature range from 93to323K. The composition dependence of the dc conductivity and the activation energy of these glasses has been compared with those of AgI-doped silver phosphate and borate glasses. The frequency-dependent electrical data have been analyzed in the framework of conductivity formalism. We have obtained the mobile ion concentration and the power-law exponent from the analysis of the conductivity spectra. We have observed that the concentration of Ag+ ions is independent of temperature and the conductivity is primarily determined by the mobility. A fraction of the Ag+ ions in the glass compositions are involved in the dynamic process. We have also shown that the power-law exponent is independent of temperature. The results are also supported by the temperature and composition independence of the scaling of the conductivity spectra.
Effect of structural variation on the photonic band gap in woodpile photonic crystal with body-centered-cubic symmetry
Authors: Lin Yuankun , Herman P. R.
Published: September 2005

A woodpile photonic crystal template with body-centered-cubic symmetry can be fabricated by exposing the photoresist to a four-beam interference pattern or a pattern generated through a diffractive optical element. We present detailed photonic band-gap calculations for photonic structures obtained under various possible fabrication conditions. The woodpile photonic crystal has a full photonic band gap up to 19% of the gap center frequency when the photoresist template is converted into silicon. The tolerance of the band gap to deviations of the structural parameters from their optimum values indicates great flexibility of the holographic fabrication process.
Nonlinear AlGaAs waveguide for the generation of counterpropagating twin photons in the telecom range
Authors: Ravaro M. , Seurin Y. , Ducci S. , Leo G. , Berger V. , De Rossi A. , Assanto G.
Published: September 2005

We have designed and fabricated a set of AlGaAs multilayer waveguides, which can serve as a source of entangled photons at 1.55μm through parametric fluorescence. In our scheme two counterpropagating, orthogonally polarized signal/idler modes are nonlinearly generated by a pump wave impinging on the upper surface of the waveguide. To check the compliance with design specifications on phase-matching wavelength and parametric gain, we have systematically measured effective indices and surface-emitting second-harmonic generation, respectively. This characterization allowed us to single out a nominal sample with optimum performances, which we numerically modeled for counterpropagating parametric fluorescence. We predict a pair generation efficiency ηPF=4×10−13 (signal photons per pump photon). For a 1W (peak), 100ns pump pulse at normal incidence, this corresponds to about 14 photons per dark count with state-of-the-art avalanche photodiodes.
Structural and magnetic properties of CrPt3(111) films grown on WSe2(0001)
Authors: Guhr I. L. , Riedlinger B. , Maret M. , Mazur U. , Barth A. , Treubel F. , Albrecht M. , Schatz G.
Published: September 2005

We report on the growth-induced properties of 30 Å thick CrPt3(111) deposits on surfaces of WSe2(0001) with a van der Waals interaction. Assemblies of (111)-oriented fcc grains are obtained with average lateral sizes ranging from 5 to 15 nm for growth temperatures increasing from 50 °C to 550 °C. The grains develop a partial L12-type chemical long-range order starting at a deposition temperature as low as 50 °C, much lower than reported for films grown on other suitable substrate surfaces. An ordering parameter of about 0.3 was found over a wide temperature range between 200 °C and 550 °C, for a deposition rate of 0.1 Å/s. Lowering the deposition rate by a factor of 5 results in a higher ordering parameter of about 0.4. Above 400 °C, ordering is accompanied by a pronounced segregation of Se atoms toward the free surface, forming a (4×4) superstructure. All samples exhibit superparamagnetic behavior with blocking temperatures that scale with the activation volume of the ferrimagnetic grains. This work shows the importance of substrate choice in reducing the ordering temperature of thin CrPt3 films, an effect that might also occur in other alloy systems.
Resonant-cavity-enhanced photodetectors for the mid-infrared
Authors: Arnold Martin , Zimin Dmitry , Zogg Hans
Published: September 2005

High-efficiency resonant-cavity-enhanced photodetectors for the mid-wavelength infrared range have been realized. Spectral linewidths as narrow as 0.07μm at 4.13μm and 0.24μm at 8.41μm center wavelength, respectively, have been achieved. Peak quantum efficiencies are up to above 50%. The photovoltaic devices are based on IV-VI semiconductor layers grown epitaxially on Si substrates and employing a distributed Bragg mirror to form the cavity.
Superconducting NbSe2 nanowires and nanoribbons converted from NbSe3 nanostructures
Authors: Hor Y. S. , Welp U. , Ito Y. , Xiao Z. L. , Patel U. , Mitchell J. F. , Kwok W. K. , Crabtree G. W.
Published: September 2005

We describe the synthesis of superconducting NbSe2 nanowires and nanoribbons by the nondestructive removal of Se from one-dimensional NbSe3 nanostructure precursors. We report scanning electron microscopy imaging, x-ray diffraction, and transmission electron microscopy analyses of the morphology, composition, and crystallinity of the converted NbSe2 nanostructures. Transport measurements on individual nanowires/ribbons confirm their superconductivity with Tc∼7.2K, and the appearance of current-induced resistance steps is attributed to localized phase slip centers, akin to those reported in other superconducting nanostructures.
Preamorphization implantation-assisted boron activation in bulk germanium and germanium-on-insulator
Authors: Chao Y.-L. , Prussin S. , Woo J. C. S. , Scholz R.
Published: September 2005

The effect of preamorphization implantation (PAI) on boron activation in germanium was studied. It was found that following PAI, significant dynamic annealing occurred during boron implantation in germanium. For small PAI energy which leads to a thin amorphous layer, recrystallization is completed via dynamic annealing during the boron implantation. As a result, a high-temperature postimplant anneal is required to activate the remaining interstitial boron and to annihilate implantation defects. For high PAI energy, while the thick amorphous layer did not recrystallize during the dynamic annealing, it requires a high-temperature anneal in order to completely recrystallize by solid phase epitaxial regrowth (SPER). The optimized PAI energy needs to be tailored such that the surface amorphous layer not only survives dynamic annealing during boron implantation, but also completes the SPER within the designed thermal budget. Full activation of boron can then be achieved without being limited by its solid solubility in germanium. An electrically active boron concentration as high as 4.7×1020∕cm3 was obtained after 400°C rapid thermal annealing. PAI causes a similar effect in GeOI substrates.
Evidence of an enhanced interband absorption in Au nanoparticles: Size-dependent electronic structure and optical properties
Authors: Balamurugan B. , Maruyama Toshiro
Published: September 2005

The present study reports clear evidence and physical significance of an interband transition due to the transition from the d band to an empty state in the conduction band in the optical absorption spectra of Au nanoparticles. The optical absorption due to interband transitions has been observed to dominate the plasmon absorption on decreasing the particle size. X-ray photoelectron spectroscopy and optical absorption studies reveal the metallic nature even for smaller sizes of 2.5nm.
Nanodevice design through the functional abstraction of biological macromolecules
Authors: Bhalerao Kaustubh D. , Eteshola Edward , Keener Matthew , Lee Stephen C.
Published: September 2005

Biologic macromolecules are prefabricated, functional nanocomponents readily incorporated into nanodevices. Semibiologic nanodevice design typically depends on knowledge of specific biomolecules by individual biologist designers, so individual devices seldom take full advantage of available biodiversity and are poorly optimized. Available informational resources (proteomic and genomic databases) were built to reflect evolutionary relationships between organisms, molecules, and biologic systems, and are lacking in their explicit functional properties. This limits their direct utility in nanodevice design. We discuss the need, and possible structure for an information framework that captures the function of biological macromolecules to enable rational nanodevice design and optimization.
Polymer bulk homojunction photonic devices
Authors: Tracy Corey , Gao Jun
Published: September 2005

We demonstrate polymer photonic devices based on the formation of multiple p-n junctions within the bulk of the active polymer film. By simple mixing of metallic particles into an electrolyte/electroluminescent composite polymer film, thousands of tiny light-emitting p-n junctions are formed in situ by electrochemical p- and n-doping. This bulk homojunction device exhibits a large active light-emitting area, as well as a giant open-circuit voltage of 25.5V, when operated as a photovoltaic cell. All devices are constructed in an extremely large planar configuration that can be directly imaged with a digital camera.
Optical detection of deoxyribonucleic acid hybridization using an anchoring transition of liquid crystal alignment
Authors: Kim Hak-Rin , Kim Jae-Hoon , Kim Tae-Sun , Oh Sang-Wook , Choi Eui-Yul
Published: September 2005

We demonstrate an optical method for detecting specific binding events in an oligo deoxyribonucleic acid (DNA) chip using an anchoring transition of a nematic liquid crystal (NLC) as a result of DNA hybridization. A homeotropic orientation of the NLC supported by oligoDNA changes to a random planar orientation after hybridization. Such DNA hybridization and subsequent NLC reorientation are easily observable with a simple detection system via long-range orientational order and large optical anisotropy of the NLC.
Influence of microdefects on the polarization properties of polymeric optical waveguides studied by polarized near-field scanning optical microscopy
Authors: Mitsui Tadashi
Published: September 2005

In the present study, the polarization properties of propagation light within a polymeric optical waveguide were characterized by means of a polarized guide-collection-mode near-field scanning optical microscopy (NSOM) technique, and changes in the polarization properties around an indentation were evaluated. When transverse magnetic polarized light enters a waveguide, the light intensity becomes greater on the near side of the indentation than on the far side, as measured by a linearly polarized component perpendicular to the direction of light propagation. The most probable cause of this phenomenon is microdefects generated by the printing of the indentation. The polarized NSOM technique is useful in searching for small defects or stresses within integrated photonic devices.
Diversification of stem cell molecular repertoire by alternative splicing
Authors: Pritsker Moshe , Doniger Tirza T. , Kramer Laurie C. , Westcot Stephanie E. , Lemischka Ihor R.
Published: September 2005

Complete information regarding transcriptional and posttranscriptional gene regulation in stem cells is necessary to understand the regulation of self-renewal and differentiation. Alternative splicing is a prevalent mode of posttranscriptional regulation, and occurs in approximately one half of all mammalian genes. The frequency and functional impact of alternative splicing in stem cells are yet to be determined. In this study we combine computational and experimental methods to identify splice variants in embryonic and hematopoietic stem cells on a genome-wide scale. Using EST collections derived from stem cells, we detect alternative splicing in >1,000 genes. Systematic RT-PCR and sequencing studies show confirmation of computational predictions at a level of 80%. We find that alternative splicing can modify multiple components of signaling pathways important for stem cell function. We also analyze the distribution of splice variants across different classes of genes. We find that tissue-specific genes have a higher tendency to undergo alternative splicing than ubiquitously expressed genes. Furthermore, the patterns of alternative splicing are only weakly conserved between orthologous genes in human and mouse. Our studies reveal extensive modification of the stem cell molecular repertoire by alternative splicing and provide insights into its overall role as a mechanism of generating genomic diversity.
Anterior tooth growth periods in Neandertals were comparable to those of modern humans
Authors: Guatelli-Steinberg Debbie , Reid Donald J. , Bishop Thomas A. , Larsen Clark Spencer
Published: September 2005

A longstanding controversy in paleoanthropology surrounds the question of whether Neandertals shared the prolonged growth periods of modern humans. To address this question, this investigation compares the duration of enamel formation in Neandertals with that of three comparative modern human groups. Because dental and somatic growth are correlated with each other, dental growth periods are indicative of overall periods of growth. Growth increments on the anterior teeth of Neandertals, modern Inuit, and modern people from Newcastle and southern Africa were counted and their means compared. In addition, potential variation in the time spans represented by growth increments was considered and incorporated into the analysis of enamel formation times. These analyses show that Neandertal imbricational enamel formation times, although likely to have been faster than those of the Inuit, are not likely to have been faster than those of the Newcastle sample and for some teeth are clearly slower than those of the southern African sample. Thus, Neandertal tooth growth and, by extension, somatic growth, appears to be encompassed within the modern human range of interpopulation variation.
DNA replication during sporulation in
Myxococcus xanthus
fruiting bodies
Authors: Tzeng Linfong , Singer Mitchell
Published: September 2005

During the developmental process of the Gram-negative soil bacterium
Myxococcus xanthus
, vegetatively growing rod cells differentiate to ultimately become metabolically quiescent and environmentally resistant myxospores encased within fruiting bodies. This program, initiated by nutrient deprivation, is propagated by both cell-autonomous and cell-nonautonomous signals. Our goal was to determine whether
M. xanthus
, like many other developmental systems, uses cell-cycle cues to regulate and control its developmental program. To address this question, the DNA replication cycle was used as a marker to monitor progression through the cell cycle in vegetative, stationary, and developing
M. xanthus
populations. Using flow cytometry, quantitative fluorescence microscopy, and FISH to establish the chromosome copy number of myxospores, it was determined that vegetatively growing cells contain one to two copies of the genome, but upon entry into stationary phase, the chromosome copy number drops to a single copy. Of particular interest, fruiting body-derived myxospores contain a specific two-chromosome DNA complement with both origin and terminus regions localized to the periphery of the myxospore. We speculate that this duplication of genetic information in the myxospore would help assure viability during germination by providing a second copy of each gene. The results of this study imply that not only is DNA replication tightly regulated during the developmental process of
M. xanthus
, but that there are also regulatory mechanisms to ensure that all myxospores acquire two copies of the chromosome.
Incorporation of the acrosome into the oocyte during intracytoplasmic sperm injection could be potentially hazardous to embryo development
Authors: Morozumi Kazuto , Yanagimachi Ryuzo
Published: September 2005

In mice and humans, a normal offspring can be obtained by injecting a single spermatozoon into an oocyte, the process called intracytoplasmic sperm injection (ICSI). When three or more mouse spermatozoa with intact acrosomes were injected into individual mouse oocytes, an increasing proportion of oocytes became deformed and lysed. Oocytes did not deform and lyse when acrosome-less spermatozoa were injected, regardless of the number of spermatozoa injected. Injection of more than four human spermatozoa into a mouse oocyte produced vacuole-like structures in each oocyte. This vacuolation did not happen when spermatozoa were freed from acrosomes before injection. Hamsters, cattle, and pigs have much larger acrosomes than the mouse or human. Injection of a single acrosome-intact hamster, bovine, and porcine spermatozoon deformed and lysed many or all mouse oocytes. This deformation did not happen when these spermatozoa were freed from acrosomes before ICSI, regardless of the number of spermatozoa injected. Because trypsin and hyaluronidase mimicked the action of acrosome-intact spermatozoa, it is likely that the acrosomal enzymes deform and lyse the oocytes. Injection of small amounts of trypsin and hyaluronidase into normally fertilized mouse eggs disturbed their pre- and postimplantation development. In view of potentially harmful effects of acrosomal enzymes on embryo development, the removal of acrosomes before ICSI is recommended for animals with large sperm acrosomes. The removal of acrosomes may increase the efficiency of ICSI in these animals. Although human and mouse spermatozoa do not need to be freed from acrosomes, the removal of acrosomes before ICSI is theoretically preferable.
The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex
Authors: Mertens Alexander E.E. , Rygiel Tomasz P. , Olivo Cristina , van der Kammen Rob , Collard John G.
Published: September 2005

The GTPases Rac and Cdc42 play a pivotal role in the establishment of cell polarity by stimulating biogenesis of tight junctions (TJs). In this study, we show that the Rac-specific guanine nucleotide exchange factor Tiam1 (T-lymphoma invasion and metastasis) controls the cell polarity of epidermal keratinocytes. Similar to wild-type (WT) keratinocytes, Tiam1-deficient cells establish primordial E-cadherin–based adhesions, but subsequent junction maturation and membrane sealing are severely impaired. Tiam1 and V12Rac1 can rescue the TJ maturation defect in Tiam1-deficient cells, indicating that this defect is the result of impaired Tiam1–Rac signaling. Tiam1 interacts with Par3 and aPKCζ, which are two components of the conserved Par3–Par6–aPKC polarity complex, and triggers biogenesis of the TJ through the activation of Rac and aPKCζ, which is independent of Cdc42. Rac is activated upon the formation of primordial adhesions (PAs) in WT but not in Tiam1-deficient cells. Our data indicate that Tiam1-mediated activation of Rac in PAs controls TJ biogenesis and polarity in epithelial cells by association with and activation of the Par3–Par6–aPKC polarity complex.
Spines and neurite branches function as geometric attractors that enhance protein kinase C action
Authors: Craske Madeleine L. , Fivaz Marc , Batada Nizar N. , Meyer Tobias
Published: September 2005

Ca2+ and diacylglycerol-regulated protein kinase Cs (PKCs; conventional PKC isoforms, such as PKCγ) are multifunctional signaling molecules that undergo reversible plasma membrane translocation as part of their mechanism of activation. In this article, we investigate PKCγ translocation in hippocampal neurons and show that electrical or glutamate stimulation leads to a striking enrichment of PKCγ in synaptic spines and dendritic branches. Translocation into spines and branches was delayed when compared with the soma plasma membrane, and PKCγ remained in these structures for a prolonged period after the response in the soma ceased. We have developed a quantitative model for the translocation process by measuring the rate at which PKCγ crossed the neck of spines, as well as cytosolic and membrane diffusion coefficients of PKCγ. Our study suggests that neurons make use of a high surface-to-volume ratio of spines and branches to create a geometric attraction process for PKC that imposes a delayed enhancement of PKC action at synapses and in peripheral processes.
Lithium induces autophagy by inhibiting inositol monophosphatase
Authors: Sarkar Sovan , Floto R. Andres , Berger Zdenek , Imarisio Sara , Cordenier Axelle , Pasco Matthieu , Cook Lynnette J. , Rubinsztein David C.
Published: September 2005

Macroautophagy is a key pathway for the clearance of aggregate-prone cytosolic proteins. Currently, the only suitable pharmacologic strategy for up-regulating autophagy in mammalian cells is to use rapamycin, which inhibits the mammalian target of rapamycin (mTOR), a negative regulator of autophagy. Here we describe a novel mTOR-independent pathway that regulates autophagy. We show that lithium induces autophagy, and thereby, enhances the clearance of autophagy substrates, like mutant huntingtin and α-synucleins. This effect is not mediated by glycogen synthase kinase 3β inhibition. The autophagy-enhancing properties of lithium were mediated by inhibition of inositol monophosphatase and led to free inositol depletion. This, in turn, decreased myo-inositol-1,4,5-triphosphate (IP3) levels. Our data suggest that the autophagy effect is mediated at the level of (or downstream of) lowered IP3, because it was abrogated by pharmacologic treatments that increased IP3. This novel pharmacologic strategy for autophagy induction is independent of mTOR, and may help treatment of neurodegenerative diseases, like Huntington's disease, where the toxic protein is an autophagy substrate.
PKA-catalyzed phosphorylation of tomosyn and its implication in Ca2+-dependent exocytosis of neurotransmitter
Authors: Baba Takeshi , Sakisaka Toshiaki , Mochida Sumiko , Takai Yoshimi
Published: September 2005

Neurotransmitter is released from nerve terminals by Ca2+-dependent exocytosis through many steps. SNARE proteins are key components at the priming and fusion steps, and the priming step is modulated by cAMP-dependent protein kinase (PKA), which causes synaptic plasticity. We show that the SNARE regulatory protein tomosyn is directly phosphorylated by PKA, which reduces its interaction with syntaxin-1 (a component of SNAREs) and enhances the formation of the SNARE complex. Electrophysiological studies using cultured superior cervical ganglion (SCG) neurons revealed that this enhanced formation of the SNARE complex by the PKA-catalyzed phosphorylation of tomosyn increased the fusion-competent readily releasable pool of synaptic vesicles and, thereby, enhanced neurotransmitter release. This mechanism was indeed involved in the facilitation of neurotransmitter release that was induced by a potent biological mediator, the pituitary adenylate cyclase-activating polypeptide, in SCG neurons. We describe the roles and modes of action of PKA and tomosyn in Ca2+-dependent neurotransmitter release.
Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart
Authors: Tomita Yuichi , Matsumura Keisuke , Wakamatsu Yoshio , Matsuzaki Yumi , Shibuya Isao , Kawaguchi Haruko , Ieda Masaki , Kanakubo Sachiko , Shimazaki Takuya , Ogawa Satoshi , Osumi Noriko , Okano Hideyuki , Fukuda Keiichi
Published: September 2005

Arodent cardiac side population cell fraction formed clonal spheroids in serum-free medium, which expressed nestin, Musashi-1, and multi-drug resistance transporter gene 1, markers of undifferentiated neural precursor cells. These markers were lost following differentiation, and were replaced by the expression of neuron-, glial-, smooth muscle cell–, or cardiomyocyte-specific proteins. Cardiosphere-derived cells transplanted into chick embryos migrated to the truncus arteriosus and cardiac outflow tract and contributed to dorsal root ganglia, spinal nerves, and aortic smooth muscle cells. Lineage studies using double transgenic mice encoding protein 0–Cre/Floxed-EGFP revealed undifferentiated and differentiated neural crest-derived cells in the fetal myocardium. Undifferentiated cells expressed GATA-binding protein 4 and nestin, but not actinin, whereas the differentiated cells were identified as cardiomyocytes. These results suggest that cardiac neural crest-derived cells migrate into the heart, remain there as dormant multipotent stem cells—and under the right conditions—differentiate into cardiomyocytes and typical neural crest-derived cells, including neurons, glia, and smooth muscle.
Selective role for superoxide in InsP3 receptor–mediated mitochondrial dysfunction and endothelial apoptosis
Authors: Madesh Muniswamy , Hawkins Brian J. , Milovanova Tatyana , Bhanumathy Cunnigaiper D. , Joseph Suresh K. , RamachandraRao Satish P. , Sharma Kumar , Kurosaki Tomohiro , Fisher Aron B.
Published: September 2005

Reactive oxygen species (ROS) play a divergent role in both cell survival and cell death during ischemia/reperfusion (I/R) injury and associated inflammation. In this study, ROS generation by activated macrophages evoked an intracellular Ca2+ ([Ca2+]i) transient in endothelial cells that was ablated by a combination of superoxide dismutase and an anion channel blocker. [Ca2+]i store depletion, but not extracellular Ca2+ chelation, prevented [Ca2+]i elevation in response to O2.− that was inositol 1,4,5-trisphosphate (InsP3) dependent, and cells lacking the three InsP3 receptor (InsP3R) isoforms failed to display the [Ca2+]i transient. Importantly, the O2.−-triggered Ca2+ mobilization preceded a loss in mitochondrial membrane potential that was independent of other oxidants and mitochondrially derived ROS. Activation of apoptosis occurred selectively in response to O2.− and could be prevented by [Ca2+]i buffering. This study provides evidence that O2.− facilitates an InsP3R-linked apoptotic cascade and may serve a critical function in I/R injury and inflammation.
Dnm1 forms spirals that are structurally tailored to fit mitochondria
Authors: Ingerman Elena , Perkins Edward M. , Marino Michael , Mears Jason A. , McCaffery J. Michael , Hinshaw Jenny E. , Nunnari Jodi
Published: September 2005

Dynamin-related proteins (DRPs) are large self-assembling GTPases whose common function is to regulate membrane dynamics in a variety of cellular processes. Dnm1, which is a yeast DRP (Drp1/Dlp1 in humans), is required for mitochondrial division, but its mechanism is unknown. We provide evidence that Dnm1 likely functions through self-assembly to drive the membrane constriction event that is associated with mitochondrial division. Two regulatory features of Dnm1 self-assembly were also identified. Dnm1 self-assembly proceeded through a rate-limiting nucleation step, and nucleotide hydrolysis by assembled Dnm1 structures was highly cooperative with respect to GTP. Dnm1 formed extended spirals, which possessed diameters greater than those of dynamin-1 spirals but whose sizes, remarkably, were equal to those of mitochondrial constriction sites in vivo. These data suggest that Dnm1 has evolved to form structures that fit the dimensions of mitochondria.
The vacuolar DHHC-CRD protein Pfa3p is a protein acyltransferase for Vac8p
Authors: Smotrys Jessica E. , Schoenfish Marissa J. , Stutz Monica A. , Linder Maurine E.
Published: September 2005

Palmitoylation of the vacuolar membrane protein Vac8p is essential for vacuole fusion in yeast (Veit, M., R. Laage, L. Dietrich, L. Wang, and C. Ungermann. 2001. EMBO J. 20:3145–3155; Wang, Y.X., E.J. Kauffman, J.E. Duex, and L.S. Weisman. 2001. J. Biol. Chem. 276:35133–35140). Proteins that contain an Asp-His-His-Cys (DHHC)–cysteine rich domain (CRD) are emerging as a family of protein acyltransferases, and are therefore candidates for mediators of Vac8p palmitoylation. Here we demonstrate that the DHHC-CRD proteins Pfa3p (protein fatty acyltransferase 3, encoded by YNL326c) and Swf1p are important for vacuole fusion. Cells lacking Pfa3p had fragmented vacuoles when stressed, and cells lacking both Pfa3p and Swf1p had fragmented vacuoles under normal growth conditions. Pfa3p promoted Vac8p membrane association and palmitoylation in vivo and partially purified Pfa3p palmitoylated Vac8p in vitro, establishing Vac8p as a substrate for palmitoylation by Pfa3p. Vac8p is the first N-myristoylated, palmitoylated protein identified as a substrate for a DHHC-CRD protein.
Endogenous Protease Activation of ENaC
Authors: Adebamiro Adedotun , Cheng Yi , Johnson John P. , Bridges Robert J.
Published: September 2005

Endogenous serine proteases have been reported to control the reabsorption of Na+ by kidney- and lung-derived epithelial cells via stimulation of electrogenic Na+ transport mediated by the epithelial Na+ channel (ENaC). In this study we investigated the effects of aprotinin on ENaC single channel properties using transepithelial fluctuation analysis in the amphibian kidney epithelium, A6. Aprotinin caused a time- and concentration-dependent inhibition (84 ± 10.5%) in the amiloride-sensitive sodium transport (INa) with a time constant of 18 min and half maximal inhibition constant of 1 μM. Analysis of amiloride analogue blocker–induced fluctuations in INa showed linear rate–concentration plots with identical blocker on and off rates in control and aprotinin-inhibited conditions. Verification of open-block kinetics allowed for the use of a pulse protocol method (Helman, S.I., X. Liu, K. Baldwin, B.L. Blazer-Yost, and W.J. Els. 1998. Am. J. Physiol. 274:C947–C957) to study the same cells under different conditions as well as the reversibility of the aprotinin effect on single channel properties. Aprotinin caused reversible changes in all three single channel properties but only the change in the number of open channels was consistent with the inhibition of INa. A 50% decrease in INa was accompanied by 50% increases in the single channel current and open probability but an 80% decrease in the number of open channels. Washout of aprotinin led to a time-dependent restoration of INa as well as the single channel properties to the control, pre-aprotinin, values. We conclude that protease regulation of INa is mediated by changes in the number of open channels in the apical membrane. The increase in the single channel current caused by protease inhibition can be explained by a hyperpolarization of the apical membrane potential as active Na+ channels are retrieved. The paradoxical increase in channel open probability caused by protease inhibition will require further investigation but does suggest a potential compensatory regulatory mechanism to maintain INa at some minimal threshold value.
Pharmacological Properties and Functional Role of Kslow Current in Mouse Pancreatic β-Cells
Authors: Zhang Min , Houamed Khaled , Kupershmidt Sabina , Roden Dan , Satin Leslie S.
Published: September 2005

The pharmacological properties of slow Ca2+-activated K+ current (Kslow) were investigated in mouse pancreatic β-cells and islets to understand how Kslow contributes to the control of islet bursting, [Ca2+]i oscillations, and insulin secretion. Kslow was insensitive to apamin or the KATP channel inhibitor tolbutamide, but UCL 1684, a potent and selective nonpeptide SK channel blocker reduced the amplitude of Kslow tail current in voltage-clamped mouse β-cells. Kslow was also selectively and reversibly inhibited by the class III antiarrythmic agent azimilide (AZ). In isolated β-cells or islets, pharmacologic inhibition of Kslow by UCL 1684 or AZ depolarized β-cell silent phase potential, increased action potential firing, raised [Ca2+]i, and enhanced glucose-dependent insulin secretion. AZ inhibition of Kslow also supported mediation by SK, rather than cardiac-like slow delayed rectifier channels since bath application of AZ to HEK 293 cells expressing SK3 cDNA reduced SK current. Further, AZ-sensitive Kslow current was extant in β-cells from KCNQ1 or KCNE1 null mice lacking cardiac slow delayed rectifier currents. These results strongly support a functional role for SK channel-mediated Kslow current in β-cells, and suggest that drugs that target SK channels may represent a new approach for increasing glucose-dependent insulin secretion. The apamin insensitivity of β-cell SK current suggests that β-cells express a unique SK splice variant or a novel heteromultimer consisting of different SK subunits.
Gating and Ionic Currents Reveal How the BKCa Channel's Ca2+ Sensitivity Is Enhanced by its β1 Subunit
Authors: Bao Lin , Cox Daniel H.
Published: September 2005

Large-conductance Ca2+-activated K+ channels (BKCa channels) are regulated by the tissue-specific expression of auxiliary β subunits. β1 is predominately expressed in smooth muscle, where it greatly enhances the BKCa channel's Ca2+ sensitivity, an effect that is required for proper regulation of smooth muscle tone. Here, using gating current recordings, macroscopic ionic current recordings, and unitary ionic current recordings at very low open probabilities, we have investigated the mechanism that underlies this effect. Our results may be summarized as follows. The β1 subunit has little or no effect on the equilibrium constant of the conformational change by which the BKCa channel opens, and it does not affect the gating charge on the channel's voltage sensors, but it does stabilize voltage sensor activation, both when the channel is open and when it is closed, such that voltage sensor activation occurs at more negative voltages with β1 present. Furthermore, β1 stabilizes the active voltage sensor more when the channel is closed than when it is open, and this reduces the factor D by which voltage sensor activation promotes opening by ∼24% (16.8→12.8). The effects of β1 on voltage sensing enhance the BKCa channel's Ca2+ sensitivity by decreasing at most voltages the work that Ca2+ binding must do to open the channel. In addition, however, in order to fully account for the increase in efficacy and apparent Ca2+ affinity brought about by β1 at negative voltages, our studies suggest that β1 also decreases the true Ca2+ affinity of the closed channel, increasing its Ca2+ dissociation constant from ∼3.7 μM to between 4.7 and 7.1 μM, depending on how many binding sites are affected.
A CaVβ SH3/Guanylate Kinase Domain Interaction Regulates Multiple Properties of Voltage-gated Ca2+ Channels
Authors: Takahashi Shoji X. , Miriyala Jayalakshmi , Tay Lai Hock , Yue David T. , Colecraft Henry M.
Published: September 2005

Auxiliary Ca2+ channel β subunits (CaVβ) regulate cellular Ca2+ signaling by trafficking pore-forming α1 subunits to the membrane and normalizing channel gating. These effects are mediated through a characteristic src homology 3/guanylate kinase (SH3–GK) structural module, a design feature shared in common with the membrane-associated guanylate kinase (MAGUK) family of scaffold proteins. However, the mechanisms by which the CaVβ SH3–GK module regulates multiple Ca2+ channel functions are not well understood. Here, using a split-domain approach, we investigated the role of the interrelationship between CaVβ SH3 and GK domains in defining channel properties. The studies build upon a previously identified split-domain pair that displays a trans SH3–GK interaction, and fully reconstitutes CaVβ effects on channel trafficking, activation gating, and increased open probability (Po). Here, by varying the precise locations used to separate SH3 and GK domains and monitoring subsequent SH3–GK interactions by fluorescence resonance energy transfer (FRET), we identified a particular split-domain pair that displayed a subtly altered configuration of the trans SH3–GK interaction. Remarkably, this pair discriminated between CaVβ trafficking and gating properties: α1C targeting to the membrane was fully reconstituted, whereas shifts in activation gating and increased Po functions were selectively lost. A more extreme case, in which the trans SH3–GK interaction was selectively ablated, yielded a split-domain pair that could reconstitute neither the trafficking nor gating-modulation functions, even though both moieties could independently engage their respective binding sites on the α1C (CaV1.2) subunit. The results reveal that CaVβ SH3 and GK domains function codependently to tune Ca2+ channel trafficking and gating properties, and suggest new paradigms for physiological and therapeutic regulation of Ca2+ channel activity.