bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms
Authors: Callera Glaucia E. , Tostes Rita C. , Yogi Alvaro , Montezano Augusto C. I. , Touyz Rhian M.
Published: January 2006

We have demonstrated recently [Callera, Touyz, Teixeira, Muscara, Carvalho, Fortes, Schiffrin and Tostes (2003) Hypertension 42, 811–817] that increased vascular oxidative stress in DOCA (deoxycorticosterone acetate)-salt rats is associated with activation of the ET (endothelin) system via ETA receptors. The exact source of ET-1-mediated oxidative stress remains unclear. The aim of the present study was to investigate whether ET-1 increases generation of ROS (reactive oxygen species) in DOCA-salt hypertension through NADPH-oxidase-dependent mechanisms. Xanthine oxidase, eNOS (endothelial nitric oxide synthase) and COX-2 (cyclo-oxygenase-2) were also examined as potential ET-1 sources of ROS as well as mitochondrial respiration. DOCA-salt and control UniNX (uninephrectomized) rats were treated with the ETA antagonist BMS182874 (40 mg·day−1·kg−1 of body weight) or vehicle. Plasma TBARS (thiobarbituric acid-reacting substances) were increased in DOCA-salt compared with UniNX rats. Activity of NADPH and xanthine oxidases in aorta, mesenteric arteries and heart was increased in DOCA-salt rats. BMS182874 decreased plasma TBARS levels without influencing NADPH and xanthine oxidase activities in DOCA-salt rats. Increased p22phox protein expression and increased p47phox membrane translocation in arteries from DOCA-salt by rats were not affected by BMS182874 treatment. Increased eNOS and COX-2 expression, also observed in aortas from DOCA-salt rats, was unaltered by BMS182874. Increased mitochondrial generation of ROS in DOCA-salt rats was normalized by BMS182874. ETA antagonism also increased the expression of mitochondrial MnSOD (manganese superoxide dismutase) in DOCA-salt rats. In conclusion, activation of NADPH oxidase does not seem to be the major source of oxidative stress induced by ET-1/ETA in DOCA-salt hypertension, which also appears to be independent of increased activation of xanthine oxidase or eNOS/COX-2 overexpression. Mitochondria may play a role in ET-1-driven oxidative stress, as evidenced by increased mitochondrial-derived ROS in this model of hypertension.
Basin hopping simulations for all-atom protein folding
Authors: Verma A. , Schug A. , Lee K. H. , Wenzel W.
Published: January 2006

We investigate different protocols of the basin hopping technique for de novo protein folding. Using the protein free-energy force field PFF01 we report the reproducible all-atom folding of the 20-amino-acid tryptophan-cage protein [Protein Data Bank (PDB) code: 112y] and of the recently discovered 26-amino-acid potassium channel blocker (PDB code: 1wqc), which exhibits an unusual fold. We find that simulations with increasing cycle length and random starting temperatures perform best in comparison with other parametrizations. The basin hopping technique emerges as a simple but very efficient and robust workhorse for all-atom protein folding.
Structures of bimetallic clusters
Authors: Hsu P. J. , Lai S. K.
Published: January 2006

We report an optimization algorithm for studying bimetallic nanoclusters. The algorithm combines two state-of-the-art methods, the genetic algorithm and the basin hopping approach, widely employed in the literature for predicting structures of pure metallic and nonmetallic clusters. To critically test the present algorithm and its use in determining the lowest-energy structures of bimetallic nanoclusters, we apply it to study the bimetallic clusters CunAu38−n (0⩽n⩽38). It is predicted that the Au atoms, being larger in size than the Cu atoms, prefer to occupy surface sites showing thus the segregating behavior. As the atom fraction of Cu increases, the bimetallic cluster CunAu38−n, as a whole, first takes on an amorphous structure and is followed by dramatic changes in structure with the Cu atoms revealing hexagonal, then assuming pentagonal, and finally shifting to octahedral symmetry in the Cu-rich range.
Calculation of the crystal-melt interfacial free energy of succinonitrile from molecular simulation
Authors: Feng Xiaobing , Laird Brian B.
Published: January 2006

The crystal-metal interfacial free energy for a six-site model of succinonitrile [NC–(CH2)2–CN] has been calculated using molecular-dynamics simulation from the power spectrum of capillary fluctuations in interface position. The orientationally averaged magnitude of the interfacial free energy is determined to be (7.0±0.4)×10−3Jm−2. This value is in agreement (within the error bars) with the experimental value [(7.9±0.8)×10−3Jm−2] of Maraşli et al. [J. Cryst. Growth 247, 613 (2003)], but is about 20% lower than the earlier experimental value [(8.9±0.5)×10−3Jm−2] obtained by Schaefer et al. [Philos. Mag. 32, 725 (1975)]. In agreement with the experiment, the calculated anisotropy of the interfacial free energy of this body-centered-cubic material is small. In addition, the Turnbull coefficient from our simulation is also in agreement with the experiment. This work demonstrates that the capillary fluctuation method of Hoyt et al. [Phys. Rev. Lett. 86, 5530 (2001)] can be successfully applied to determine the crystal-melt interfacial free energy of molecular materials.
Generation and characterization of highly vibrationally excited molecular beam
Authors: Hsu Hsu-Chen , Lyu Jia-Jia , Liu Chen-Lin , Huang Cheng-Liang , Ni Chi-Kung
Published: January 2006

A simple method to generate and characterize a pure highly vibrationally excited azulene molecular beam is demonstrated. Azulene molecules initially excited to the S4 state by 266-nm UV photons reach high vibrationally excited levels of the ground electronic state upon rapid internal conversion from the S4 electronically excited state. VUV laser beams at 157 and 118nm, respectively, are used to characterize the relative concentrations of the highly vibrationally excited azulene and the rotationally and vibrationally cooled azulene in the molecular beam. With a laser intensity of 34mJ∕cm2, 75% of azulene molecules absorb a single 266-nm photon and become highly vibrationally excited molecules. The remaining ground-state azulene molecules absorb two or more UV photons, ending up either as molecular cations, which are repelled out of the beam by an electric field, or as dissociation fragments, which veer off the molecular-beam axis. No azulene without absorption of UV photons is left in the molecular beam. The molecular beam that contains only highly vibrationally excited molecules and carrier gas is useful in various experiments related to the studies of highly vibrationally excited molecules.
Energy transfer of highly vibrationally excited azulene: Collisions between azulene and krypton
Authors: Liu Chen-Lin , Hsu Hsu-Chen , Lyu Jia-Jia , Ni Chi-Kung
Published: January 2006

The energy-transfer dynamics between highly vibrationally excited azulene molecules and Kr atoms in a series of collision energies (i.e., relative translational energies 170, 410, and 780cm−1) was studied using a crossed-beam apparatus along with time-sliced velocity map ion imaging techniques. “Hot” azulene (4.66eV internal energy) was formed via the rapid internal conversion of azulene initially excited to the S4 state by 266-nm photons. The shapes of the collisional energy-transfer probability density functions were measured directly from the scattering results of highly vibrationally excited or hot azulene. At low enough collision energies an azulene-Kr complex was observed, resulting from small amounts of translational to vibrational-rotational (T-VR) energy transfer. T-VR energy transfer was found to be quite efficient. In some instances, nearly all of the translational energy is transferred to vibrational-rotational energy. On the other hand, only a small fraction of vibrational energy is converted to translational energy (V-T). The shapes of V-T energy-transfer probability density functions were best fit by multiexponential functions. We find that substantial amounts of energy are transferred in the backward scattering direction due to supercollisions at high collision energies. The probability for supercollisions, defined arbitrarily as the scattered azulene in the region 160°<θ<180° and ΔEd>2000cm−1 is 1% and 0.3% of all other collisions at collision energies 410 and 780cm−1, respectively.
One- and two-body densities of carbon isoelectronic series in their low-lying multiplet states from explicitly correlated wave functions
Authors: Gálvez F. J. , Buendía E. , Sarsa A.
Published: January 2006

The P3 ground state and both the D1 and S1 excited states arising from the low-lying 1s22s22p2 configuration of the carbon isoelectronic series are studied starting from explicitly correlated multiconfigurational wave functions. One- and two-body densities in position space have been calculated and different one- and two-body expectation values have been obtained. The effects of electronic correlations have been systematically studied. All the calculations have been done by means of variational Monte Carlo.
Analysis of the shape of dendrimers under shear
Authors: Bosko Jaroslaw T. , Todd B. D. , Sadus Richard J.
Published: January 2006

Nonequilibrium molecular-dynamics simulations are used to investigate the molecular shape of dendrimers and linear polymers in a melt and under shear. Molecules are modeled at the coarse-grained level using a finitely extensible nonlinear elastic bead-spring model. The shape of dendrimers and linear polymers at equilibrium and undergoing planar Couette flow is analyzed quantitatively and it is related to the shear viscosity. The shape of dendrimers responds differently to the influence of shear compared with linear polymers of equivalent molecular mass. However, in both cases the transition from Newtonian to non-Newtonian viscosity behavior corresponds to significant changes in molecular symmetry. This suggests that a shape analysis could be used to estimate the onset of shear thinning in polymers.
Fractional Lindstedt series
Authors: Gallavotti G. , Gentile G. , Giuliani A.
Published: January 2006

The parametric equations of the surfaces on which highly resonant quasiperiodic motions develop (lower-dimensional tori) cannot be analytically continued, in general, in the perturbation parameter ε, i.e., they are not analytic functions of ε. However rather generally quasiperiodic motions whose frequencies satisfy only one rational relation (“resonances of order 1”) admit formal perturbation expansions in terms of a fractional power of ε depending on the degeneration of the resonance. We find conditions for this to happen, and in such a case we prove that the formal expansion is convergent after suitable resummation.
Attosecond pulse generation in the relativistic regime of the laser-foil interaction: The sliding mirror model
Authors: Pirozhkov Alexander S. , Bulanov Sergei V. , Esirkepov Timur Zh. , Mori Michiaki , Sagisaka Akito , Daido Hiroyuki
Published: January 2006

Theory of the attosecond pulse generation during the interaction of a short relativistic-irradiance laser pulse with a thin overdense plasma slab is developed. The nonlinear electric current caused by the electron motion at relativistic velocity generates the high-order harmonics of the incident radiation. These harmonics are phase locked and can produce pulses with attosecond duration after spectral filtering. Conditions for the most efficient generation of single-attosecond pulses are discussed. A very efficient regime of attosecond pulse train generation without spectral filtering is proposed. The results are verified by the particle-in-cell simulations.
Kinetic stability of complex molecular clusters
Authors: Natarajan Sukina , Harris Sarah A. , Ford Ian J.
Published: January 2006

This investigation is concerned with modeling the evaporation, or decay, of n-nonane molecular clusters. We use a unique cluster decay model that was first developed to estimate the decay time scale of argon clusters using molecular-dynamics simulations. In this study we seek to enhance the model so that it represents a more complex cluster decay dynamic, suitable for n-nonane clusters. Experimental measurements of nucleation rates of n-nonane droplets have been used to deduce the rate at which a molecule escapes from the cluster. Typically for an n-nonane cluster containing 40molecules, at an experimental temperature of 225K, the empirical decay time, which is the inverse of the decay rate, is estimated to be 50ns. For this time scale, the direct observation of n-nonane cluster decay from a molecular-dynamics trajectory is not feasible, since decay events are so rare. However, the cluster decay model uses a combination of molecular dynamics and stochastic dynamics in order to resolve the problem associated with long decay time scales. The model is based on a Langevin treatment that views cluster decay as single-particle escape from a confining potential of mean force. It is used to predict kinetic decay times of n-nonane clusters. We discover this result differs significantly from a classically derived decay time scale determined from a continuum thermodynamic treatment of the population balance equations of clusters. However, the dynamically generated results obtained from the kinetic decay model compare more favorably than the classical results with the empirical decay times that are deduced from experimental measurements of n-nonane clusters.
Conditional equilibrium constants in multicomponent heterogeneous adsorption: The conditional affinity spectrum
Authors: Garcés Josep L. , Mas Francesc , Puy Jaume
Published: January 2006

The concept of conditional stability constant is extended to the competitive binding of small molecules to heterogeneous surfaces or macromolecules via the introduction of the conditional affinity spectrum (CAS). The CAS describes the distribution of effective binding energies experienced by one complexing agent at a fixed concentration of the rest. We show that, when the multicomponent system can be described in terms of an underlying affinity spectrum [integral equation (IE) approach], the system can always be characterized by means of a CAS. The thermodynamic properties of the CAS and its dependence on the concentration of the rest of components are discussed. In the context of metal/proton competition, analytical expressions for the mean (conditional average affinity) and the variance (conditional heterogeneity) of the CAS as functions of pH are reported and their physical interpretation discussed. Furthermore, we show that the dependence of the CAS variance on pH allows for the analytical determination of the correlation coefficient between the binding energies of the metal and the proton. Nonideal competitive adsorption isotherm and Frumkin isotherms are used to illustrate the results of this work. Finally, the possibility of using CAS when the IE approach does not apply (for instance, when multidentate binding is present) is explored.
Grand canonical Markov model: A stochastic theory for open nonequilibrium biochemical networks
Authors: Heuett William J. , Qian Hong
Published: January 2006

In this paper we present the results of a stochastic model of reversible biochemical reaction networks that are being driven through an open boundary, such that the system is interacting with its surrounding environment with explicit material exchange. The stochastic model is based on the master equation approach and is intimately related to the grand canonical ensemble of statistical mechanics. We show that it is possible to analytically calculate the joint probability function of the random variables describing the number of molecules in each state of the system for general linear networks. Definitions of reaction chemical potentials and conductances follow from inherent properties of this model, providing a description of energy dissipation in the system. We are also able to suggest novel methods for experimentally determining reaction fluxes and biochemical affinities at nonequilibrium steady state as well as the overall network connectivity.
A quasiclassical trajectory study for the N(S4)+O2(XΣg−3)→NO(XΠ2)+O(P3) reaction on the new A′2 and A′4 potential-energy surfaces
Authors: He Jianfeng , Chen Feng , Li Jing
Published: January 2006

A quasiclassical trajectory study with the sixth-order explicit symplectic algorithm of the N(S4)+O2(XΣg−3)→NO(XΠ2)+O(P3) atmospheric reaction has been performed by employing the new A′2 and A′4 potential-energy surfaces reported by Sayós et al. [J. Chem. Phys. 117, 670 (2002)]. For the translational temperature considered up to 10000K, the larger relative translational energy and the higher rovibrational levels of O2 molecule with respect to the previous works have been taken into account, and a clearer database about the character of the total reaction cross section has been presented in this work. The dependence of microscopic rate constants on the vibrational level of O2 molecule at T=3000, 5000, and 10000K has been exhibited, and we can see that the values of log10k(T,v,J) vary almost linearly with the vibrational level of O2 molecule. The thermal rate constants at the translational temperature between 300 and 10000K have been evaluated and compared with the experimental and previous theoretical results. It is found that the thermal rate constants determined in this work have a better agreement with the experimental data and can provide a more valid theoretical reference at the translational temperature considered for the title reaction.
Large room-temperature magnetoresistance in Pd-added manganites
Authors: Yuan Xiao-Bo , Liu Yi-Hua , Wang Cheng-Jian , Mei Liang-Mo
Published: January 2006

A series of La0.67(Ca0.65Ba0.35)0.33MnO3∕Pdx composites were synthesized using a sol-gel method followed by a conventional solid-state reaction route. The results show that the resistivity of the composites decreases dramatically with Pd addition, while the room-temperature magnetoresistance (MR) increases remarkably. A large MR of about 170% is obtained at room temperature and 1T applied magnetic field for x=0.27 sample. The large enhancement of the MR can be attributed to the decrease in resistivity caused by the good conductive metal Pd, which improves the disordered atomic structure and magnetic property on the grain surfaces/boundaries. In addition, the polarization of Pd atoms near the Mn ions on the grain surfaces/boundaries also plays a very important role on the enhancement of the MR, which induces a large number of spin clusters.
In situ epitaxial growth of TiO2 on RuO2 nanorods with reactive sputtering
Authors: Cheng Kai-Wen , Lin Yu-Tsun , Chen Chun-Yu , Hsiung Chang-Po , Gan Jon-Yiew , Yeh Jien-Wei , Hsieh Chin-Hua , Chou Li-Jen
Published: January 2006

In this work, TiO2 deposition on RuO2 nanorods with reactive sputtering was studied. The TiO2 deposition was performed in situ after the RuO2 nanorod deposition at the same substrate temperature of 450 °C. The morphology examination and structure analysis have indicated a uniform and pure rutile TiO2 deposition on RuO2 nanorods. High-resolution transmission electron microscopy images also revealed an epitaxial growth of TiO2 on RuO2 nanorods. Such a low-temperature fabrication technique for one-dimensional (1D) heteronanostructure may apply to other functional materials. Since RuO2 is a good electric conductor, 1D heteronanostructures made from RuO2 nanorods are expected to exhibit enhanced functionality particularly in electrical and electrochemical applications.
Demonstration of an electrostatic-shielded cantilever
Authors: Pingue P. , Piazza V. , Baschieri P. , Ascoli C. , Menozzi C. , Alessandrini A. , Facci P.
Published: January 2006

The fabrication and performances of cantilevered probes with reduced parasitic capacitance starting from a commercial Si3N4 cantilever chip is presented. Nanomachining and metal deposition induced by focused ion beam techniques were employed in order to modify the original insulating pyramidal tip and insert a conducting metallic tip. Two parallel metallic electrodes deposited on the original cantilever arms are employed for tip biasing and as ground plane in order to minimize the electrostatic force due to the capacitive interaction between cantilever and sample surface. Excitation spectra and force-to-distance characterization are shown with different electrode configurations. Applications of this scheme in electrostatic force microscopy, Kelvin probe microscopy and local anodic oxidation is discussed.
Single-shot, interferometric, high-resolution, terahertz field diagnostic
Authors: Kim K. Y. , Yellampalle B. , Rodriguez G. , Averitt R. D. , Taylor A. J. , Glownia J. H.
Published: January 2006

We present a single-shot, high-temporal-resolution terahertz diagnostic capable of measuring free-space far-infrared electromagnetic fields in time and space. We show that by using a chirped probe electro-optic sampling technique, in combination with a recently described interferometric retrieval algorithm [Appl. Phys. Lett. 87, 211109 (2005)], the diagnostic can provide transform-limited temporal resolution, mainly limited by the spectral bandwidth of the optical probe pulse, regardless of its chirp.
Determination of MgO∕GaN heterojunction band offsets by x-ray photoelectron spectroscopy
Authors: Chen J.-J. , Gila B. P. , Hlad M. , Gerger A. , Ren F. , Abernathy C. R. , Pearton S. J.
Published: January 2006

MgO is a promising gate dielectric and surface passivation film for GaN transistors but little is known of the band offsets in the MgO∕GaN system. X-ray photoelectron spectroscopy was used to measure the energy discontinuity in the valence band (ΔEv) of MgO∕GaN heterostructures in which the MgO was grown by rf plasma-assisted molecular beam epitaxy on top of thick GaN templates on sapphire substrates. A value of ΔEv=1.06±0.15eV was obtained by using the Ga 3d energy level as a reference. Given the experimental band gap of 7.8eV for the MgO, this would indicate a conduction band offset ΔEC of 3.30eV in this system.
High-frequency modulation and bandwidth limitations of GaInNAs double-quantum-well lasers
Authors: Wei Y. Q. , Gustavsson J. S. , Haglund Å. , Modh P. , Sadeghi M. , Wang S. M. , Larsson A.
Published: January 2006

We have studied the modulation bandwidth of high-speed GaInNAs double-quantum-well lasers emitting at 1.28–1.30μm. A 400μm long ridge waveguide laser exhibits a small signal modulation bandwidth of 14 GHz. The intrinsic damping limited modulation bandwidth is as high as 25 GHz (K=0.35ns), and the actual modulation bandwidth is limited by thermal effects under continuous operation. The saturation of the resonance frequency at 10 GHz was found to be the result of a thermal reduction of the differential gain and a rapid increase of the threshold current when the temperature exceeds 80 °C.
Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus
Authors: Chen Zhaochun , Earl Patricia , Americo Jeffrey , Damon Inger , Smith Scott K. , Zhou Yi-Hua , Yu Fujuan , Sebrell Andrew , Emerson Suzanne , Cohen Gary , Eisenberg Roselyn J. , Svitel Juraj , Schuck Peter , Satterfield William , Moss Bernard , Purcell Robert
Published: January 2006

Chimpanzee Fabs against the B5 envelope glycoprotein of vaccinia virus were isolated and converted into complete mAbs with human γ1 heavy chain constant regions. The two mAbs (8AH8AL and 8AH7AL) displayed high binding affinities to B5 (
K
d
of 0.2 and 0.7 nM). The mAb 8AH8AL inhibited the spread of vaccinia virus as well as variola virus (the causative agent of smallpox)
in vitro
, protected mice from subsequent intranasal challenge with virulent vaccinia virus, protected mice when administered 2 days after challenge, and provided significantly greater protection than that afforded by a previously isolated rat anti-B5 mAb (19C2) or by vaccinia immune globulin. The mAb bound to a conformational epitope between amino acids 20 and 130 of B5. These chimpanzee/human anti-B5 mAbs may be useful in the prevention and treatment of vaccinia virus-induced complications of vaccination against smallpox and may also be effective in the immunoprophylaxis and immunotherapy of smallpox.
TheSaccharomyces cerevisiaeSpindle Pole Body (SPB) Component Nbp1p Is Required for SPB Membrane Insertion and Interacts with the Integral Membrane Proteins Ndc1p and Mps2p
Authors: Araki Yasuhiro , Lau Corine K. , Maekawa Hiromi , Jaspersen Sue L. , Giddings Thomas H. , Schiebel Elmar , Winey Mark
Published: January 2006

The spindle pole body (SPB) in Saccharomyces cerevisiae functions to nucleate and organize spindle microtubules, and it is embedded in the nuclear envelope throughout the yeast life cycle. However, the mechanism of membrane insertion of the SPB has not been elucidated. Ndc1p is an integral membrane protein that localizes to SPBs, and it is required for insertion of the SPB into the nuclear envelope during SPB duplication. To better understand the function of Ndc1p, we performed a dosage suppressor screen using the ndc1-39 temperature-sensitive allele. We identified an essential SPB component, Nbp1p. NBP1 shows genetic interactions with several SPB genes in addition to NDC1, and two-hybrid analysis revealed that Nbp1p binds to Ndc1p. Furthermore, Nbp1p is in the Mps2p-Bbp1p complex in the SPB. Immunoelectron microscopy confirmed that Nbp1p localizes to the SPB, suggesting a function at this location. Consistent with this hypothesis, nbp1-td (a degron allele) cells fail in SPB duplication upon depletion of Nbp1p. Importantly, these cells exhibit a “dead” SPB phenotype, similar to cells mutant in MPS2, NDC1, or BBP1. These results demonstrate that Nbp1p is a SPB component that acts in SPB duplication at the point of SPB insertion into the nuclear envelope.
PARP1 Is a TRF2-associated Poly(ADP-Ribose)Polymerase and Protects Eroded Telomeres
Authors: Gomez Marla , Wu Jun , Schreiber Valérie , Dunlap John , Dantzer Françoise , Wang Yisong , Liu Yie
Published: January 2006

Poly(ADP-ribose)polymerase 1 (PARP1) is well characterized for its role in base excision repair (BER), where it is activated by and binds to DNA breaks and catalyzes the poly(ADP-ribosyl)ation of several substrates involved in DNA damage repair. Here we demonstrate that PARP1 associates with telomere repeat binding factor 2 (TRF2) and is capable of poly(ADP-ribosyl)ation of TRF2, which affects binding of TRF2 to telomeric DNA. Immunostaining of interphase cells or metaphase spreads shows that PARP1 is detected sporadically at normal telomeres, but it appears preferentially at eroded telomeres caused by telomerase deficiency or damaged telomeres induced by DNA-damaging reagents. Although PARP1 is dispensable in the capping of normal telomeres, Parp1 deficiency leads to an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA in primary murine cells after induction of DNA damage. Our results suggest that upon DNA damage, PARP1 is recruited to damaged telomeres, where it can help protect telomeres against chromosome end-to-end fusions and genomic instability.
HIV-1 Tat Regulates Endothelial Cell Cycle Progression via Activation of the Ras/ERK MAPK Signaling Pathway
Authors: Toschi Elena , Bacigalupo Ilaria , Strippoli Raffaele , Chiozzini Chiara , Cereseto Anna , Falchi Mario , Nappi Filomena , Sgadari Cecilia , Barillari Giovanni , Mainiero Fabrizio , Ensoli Barbara
Published: January 2006

Tat, the transactivator of HIV-1 gene expression, is released by acutely HIV-1-infected T-cells and promotes adhesion, migration, and growth of inflammatory cytokine-activated endothelial and Kaposi's sarcoma cells. It has been previously demonstrated that these effects of Tat are due to its ability to bind through its arginine-glycine-aspartic (RGD) region to the α5β1 and αvβ3 integrins. However, the signaling pathways linking Tat to the regulation of cellular functions are incompletely understood. Here, we report that Tat ligation on human endothelial cells results in the activation of the small GTPases Ras and Rac and the mitogen-activated protein kinase ERK, specifically through its RGD region. In addition, we demonstrated that Tat activation of Ras, but not of Rac, induces ERK phosphorylation. We also found that the receptor proximal events accompanying Tat-induced Ras activation are mediated by tyrosine phosphorylation of Shc and recruitment of Grb2. Moreover, Tat enabled endothelial cells to progress through the G1 phase in response to bFGF, and the process is linked to ERK activation. Taken together, these data provide novel evidence about the ability of Tat to activate the Ras-ERK cascade which may be relevant for endothelial cell proliferation and for Kaposi's sarcoma progression.
Kiss-and-Coat and Compartment Mixing: Coupling Exocytosis to Signal Generation and Local Actin Assembly
Authors: Sokac Anna M. , Bement William M.
Published: January 2006

Regulated exocytosis is thought to occur either by “full fusion,” where the secretory vesicle fuses with the plasma membrane (PM) via a fusion pore that then dilates until the secretory vesicle collapses into the PM; or by “kiss-and-run,” where the fusion pore does not dilate and instead rapidly reseals such that the secretory vesicle is retrieved almost fully intact. Here, we describe growing evidence for a third form of exocytosis, dubbed “kiss-and-coat,” which is characteristic of a broad variety of cell types that undergo regulated exocytosis. Kiss-and-coat exocytosis entails prolonged maintenance of a dilated fusion pore and assembly of actin filament (F-actin) coats around the exocytosing secretory vesicles followed by direct retrieval of some fraction of the emptied vesicle membrane. We propose that assembly of the actin coats results from the union of the secretory vesicle membrane and PM and that this compartment mixing represents a general mechanism for generating local signals via directed membrane fusion.
Heteromerization of Innexin Gap Junction Proteins Regulates Epithelial Tissue Organization inDrosophila
Authors: Lehmann Corinna , Lechner Hildegard , Löer Birgit , Knieps Martin , Herrmann Sonja , Famulok Michael , Bauer Reinhard , Hoch Michael
Published: January 2006

Gap junctions consist of clusters of intercellular channels, which enable direct cell-to-cell communication and adhesion in animals. Whereas deuterostomes, including all vertebrates, use members of the connexin and pannexin multiprotein families to assemble gap junction channels, protostomes such as Drosophila and Caenorhabditis elegans use members of the innexin protein family. The molecular composition of innexin-containing gap junctions and the functional significance of innexin oligomerization for development are largely unknown. Here, we report that heteromerization of Drosophila innexins 2 and 3 is crucial for epithelial organization and polarity of the embryonic epidermis. Both innexins colocalize in epithelial cell membranes. Innexin3 is mislocalized to the cytoplasm in innexin2 mutants and is recruited into ectopic expression domains defined by innexin2 misexpression. Conversely, RNA interference (RNAi) knockdown of innexin3 causes mislocalization of innexin2 and of DE-cadherin, causing cell polarity defects in the epidermis. Biochemical interaction studies, surface plasmon resonance analysis, transgenesis, and biochemical fractionation experiments demonstrate that both innexins interact via their C-terminal cytoplasmic domains during the assembly of heteromeric channels. Our data provide the first molecular and functional demonstration that innexin heteromerization occurs in vivo and reveal insight into a molecular mechanism by which innexins may oligomerize into heteromeric gap junction channels.
ADVERTISING RESTRICTIONS AND CIGARETTE SMOKING: EVIDENCE FROM MYOPIC AND RATIONAL ADDICTION MODELS
Authors: IWASAKI NATSUKO , TREMBLAY CAROL HORTON , TREMBLAY VICTOR J.
Published: January 2006

Because of the high social cost of cigarette smoking, many countries impose advertising restrictions to reduce cigarette consumption. Yet previous studies conclude that advertising constraints have been ineffective at reducing cigarette smoking. This conclusion is incorrect because it ignores the fact that advertising restrictions have supply as well as demand effects. The authors extend existing research by showing that advertising regulations, especially those found in the recent National Tobacco Settlement, have decreased the equilibrium level of cigarette consumption in the United States, a result that holds for both myopic and rational addiction models. (JEL L50, L66, M37)
A single‐base change in the tyrosine kinase II domain of ovine FGFR3 causes hereditary chondrodysplasia in sheep
Authors: Beever J. E. , Smit M. A. , Meyers S. N. , Hadfield T. S. , Bottema C. , Albretsen J. , Cockett N. E.
Published: January 2006

Ovine hereditary chondrodysplasia, or spider lamb syndrome (SLS), is a genetic disorder that is characterized by severe skeletal abnormalities and has resulted in substantial economic losses for sheep producers. Here we demonstrate that a non‐synonymous T>A transversion in the highly conserved tyrosine kinase II domain of a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3), is responsible for SLS. We also demonstrate that the mutant FGFR3 allele has an additive effect on long‐bone length, calling into question the long‐standing belief that SLS is inherited as a strict monogenic, Mendelian recessive trait. Instead, we suggest that SLS manifestation is determined primarily by the presence of the mutant FGFR3 allele, but it is also influenced by an animal's genetic background. In contrast to FGFR3 mutations causing dwarfism in humans, this single‐base change is the only known natural mutation of FGFR3 that results in a skeletal overgrowth phenotype in any species.
Psychometric evaluation of the Hendrich Fall Risk Model
Authors: Heinze Cornelia , Halfens Ruud J.G. , Roll Stephanie , Dassen Theo
Published: January 2006

Aims.  The aim of this paper is to report a psychometric evaluation of the Hendrich Fall Risk Model.

Background.  Thoroughly developed and tested instruments for assessment of fall risk are needed to identify patients at risk of falling, to enable the implementation of preventative measures.

Method.  Data from 1977 patients/residents in 45 nursing homes and 7197 patients from 47 hospitals were evaluated in a cross‐sectional survey. The internal consistency of the Hendrich Fall Risk Model was examined using the Kuder–Richardson Test. The dimensions of the model were revealed by exploratory factor analysis and the Care Dependency Scale was used to investigate construct validity. Using Spearman Rho the sum of weighted items was correlated with the sum of unweighted items to obtain information about the practicability of a weighted total score. The study was carried out in 2003.

Results.  The internal consistency of the model was not high (α = 0·54). Additionally, factor analysis showed that the model had more than one dimension. The correlation between the fall risk model and Care Dependency Scale was quite high for hospital patients and the total group (Spearman Rho = −0·71 or −0·76 respectively, P < 0·01) and medium for nursing home residents (Spearman Rho = −0·51, P < 0·01). The total scores of the weighted and unweighted items correlated highly (Spearman Rho = 0·96, P < 0·01).

Conclusions.  The use of this risk model is not recommended for nursing homes. For hospitals, we advise the use of unweighted items.
Microstructure of pharyngeal tooth enameloid in the parrotfish Scarus rivulatus (Pisces: Scaridae)
Authors: CARR A. , KEMP A. , TIBBETTS I. , TRUSS R. , DRENNAN J.
Published: January 2006

The microstructure of parrotfish pharyngeal teeth was examined using scanning electron microscopy to infer possible mechanical properties of the dentition with respect to their function. Parrotfish tooth enameloid is formed from fluorapatite crystals grouped into bundles. In the upper and lower pharyngeal jaw, the majority of the crystal bundles are orientated either perpendicularly or vertically to the enameloid surface. The only exception is in the trailing apical enameloid in which the majority of bundles are orientated perpendicularly or horizontally to the trailing surface. A distinct transition occurs through the middle of the apex between the leading and trailing enameloid in teeth of the lower pharyngeal jaw. This transition appears less distinct in the teeth of the upper pharyngeal jaw. Enameloid microstructure indicates that shear forces predominate at the apex of the teeth. In the remainder of the enameloid, the microstructure indicates that wear is predominant, and the shear forces are of less importance.
An approach to the systematic distortion correction in aberration‐corrected HAADF images
Authors: SANCHEZ A. M. , GALINDO P. L. , KRET S. , FALKE M. , BEANLAND R. , GOODHEW P. J.
Published: January 2006

Systematic distortion has been analysed in high‐angle annular dark‐field (HAADF) images which may be caused by electrical interference. Strain mapping techniques have been applied to a strain‐free GaAs substrate in order to provide a broad analysis of the influence of this distortion on the determination of local strain in the heterostructure. We have developed a methodology for estimating the systematic distortion, and we correct the original images by using an algorithm that removes this systematic distortion.
On the accuracy of lattice‐distortion analysis directly from high‐resolution transmission electron micrographs
Authors: DU K. , PHILLIPP F.
Published: January 2006

Lattice‐distortion analysis from high‐resolution transmission electron micrographs offers a convenient and fast tool for direct measurement of strains in materials over a large area. In the present work, we have evaluated the accuracy of the strain measurement when the effects of the realistic experimental variables are explicitly taken into account by the use of image simulation techniques. These variables are focal setting and variation, local thickness and orientation of the sample, as well as misalignments of the sample and the incident beam. The evaluation reveals that consistency of image features and contrast within the micrographs is desired for the analysis to eliminate effects of the variations of local focus value and specimen thickness. After proper orientation of a crystalline specimen, the misorientation of the object will not notably influence the strain measurement even though a local bending may exist within the sample. However, the incident beam of the microscope needs to be aligned carefully as the beam misalignment may introduce a notable artefact around the interface region.
A simple and stable autofocusing protocol for long multidimensional live cell microscopy
Authors: WOLF F. , GELEY S.
Published: January 2006

Focus maintenance is a challenging problem in multidimensional wide‐field microscopy. Most automated microscopes use software algorithms, which are applied to z‐sections of the object, to select for the plane with the best signal to noise ratio. When applied automatically in multidimensional imaging applications, autofocus routines significantly increase light exposure and can become cytotoxic if applied too frequently. In addition, automated focusing procedures can readily focus on unwanted high contrast objects. By labelling a defined position with a fluorescent marker, we were able to separate the focusing procedure from the actual image acquisition positions and therefore overcome some of the major drawbacks of routine autofocus procedures. To implement this method in a multidimensional acquisition experiment, we created a visual basic‐based program, which is run prior to each image acquisition. This technique allows tight control of focus whilst keeping light toxicity in live cell imaging experiments to a minimum.
Bitumen morphologies by phase‐detection atomic force microscopy
Authors: MASSON J‐F. , LEBLOND V. , MARGESON J.
Published: January 2006

Bitumen is a complex mixture of hydrocarbons for which microstructural knowledge is incomplete. In an effort to detail this microstructure, 13 bitumens were analysed by phase‐detection atomic force microscopy. Based on morphology, the bitumens could be classified into three distinct groups. One group showed fine domains down to 0.1 µm, another showed domains of about 1 µm, and a third group showed up to four different domains or phases of different sizes and shapes. No correlation was found between the atomic force microscopy morphology and the composition based on asphaltenes, polar aromatics, naphthene aromatics and saturates. A high correlation was found between the area of the ‘bee‐like’ structures and the vanadium and nickel content in bitumen, and between the atomic force microscopy groups and the average size of molecular planes made of fused aromatics. The morphology and the molecular arrangements in bitumen thus appear to be partly governed by the molecular planes and the polarity defined by metallic cations.
Aspects regarding measurement of thickness of intergranular glassy films
Authors: BHATTACHARYYA S. , SUBRAMANIAM A. , KOCH C. T. , RÜHLE M.
Published: January 2006

Materials such as Si3N4, SiC and SrTiO3 can have grain boundaries characterized by the presence of a thin intergranular amorphous film of nearly constant thickness, in some cases (e.g. Si3N4) almost independent of the orientation of the bounding grains, but dependent on the composition of the ceramic. Microscopy techniques such as high‐resolution lattice fringe imaging, Fresnel fringe imaging and diffuse dark field imaging have been applied to the study of intergranular glassy films. The theme of the current investigation is the use of Fresnel fringes and Fourier filtering for the measurement of the thickness of intergranular glassy films. Fresnel fringes hidden in high‐resolution micrographs can be used to objectively demarcate the glass–crystal interface and to measure the thickness of intergranular glassy films. Image line profiles obtained from Fourier filtering the high‐resolution micrographs can yield better estimates of the thickness. Using image simulation, various kinds of deviation from an ideal square‐well potential profile and their effects on the Fresnel image contrast are considered. A method is also put forth to objectively retrieve Fresnel fringe spacing data by Fourier filtering Fresnel contrast images. Difficulties arising from the use of the standard Fresnel fringe extrapolation technique are outlined and an alternative method for the measurement of the thickness of intergranular glassy films, based on zero‐defocus (in‐focus) Fresnel contrast images is suggested. The experimental work is from two ceramic systems: Lu‐Mg‐doped Si3N4 and SrTiO3 (stoichiometric and nonstoichiometric). Further, a comparison is made between the standard high‐resolution lattice fringe technique, the standard Fresnel fringe extrapolation technique and the methods of analyses introduced in the current work, to illustrate their utility and merits. Taking experimental difficulties into account, this work is intended to be a practical tool kit for the study of intergranular glassy films.
Analysis of protein phosphorylation: methods and strategies for studying kinases and substrates
Authors: Peck Scott C.
Published: January 2006

Protein phosphorylation is a highly conserved mechanism for regulating protein function, being found in all prokaryotes and eukaryotes examined. Phosphorylation can alter protein activity or subcellular localization, target proteins for degradation and effect dynamic changes in protein complexes. In many cases, different kinases may be involved in each of these processes for a single protein, allowing a large degree of combinatorial regulation at the post‐translational level. Therefore, knowing which kinases are activated during a response and which proteins are substrates is integral to understanding the mechanistic regulation of a wide range of biological processes. In this paper, I will describe methods for monitoring kinase activity, investigating kinase–substrate specificity, examining phosphorylationin plantaand the determination of phosphorylation sites in a protein. In addition, strategic considerations for experimental design and variables will be discussed.
Transactivated and chemically inducible gene expression in plants
Authors: Moore Ian , Samalova Marketa , Kurup Smita
Published: January 2006

Several vector systems are available for tissue‐specific transactivation or chemical induction of transgene expression in plants. The choice facing researchers is which promoter system to commit to as this determines the range and characteristics of the expression resources available. The decision will not be the same for all species or applications. We present some general discussion on the use of these technologies and review in detail the properties in various (mainly angiosperm) species of the most promising: mGal4:VP16/UAS and pOp/LhG4 for transactivation, and the alc‐switch, GVE/VGE, GVG, pOp6/LhGR, and XVE systems for chemical induction.
Study of Fas (CD95) and FasL (CD178) polymorphisms in liver transplant recipients
Authors: Marín L. A. , Muro M. , Moya‐Quiles M. R. , Miras M. , Minguela A. , Bermejo J. , Sanchez‐Bueno F. , Parrilla P. , Alvarez‐López M. R.
Published: January 2006

The Fas receptor is capable of transducing apoptotic cell death upon interaction with their ligand (FasL). Recent studies suggest that the Fas/FasL system is involved both in graft rejection and in transplantation tolerance. In this study, we analyzed the effect of Fas and FasL polymorphisms in liver allograft outcome. Fas and FasL polymorphisms were analyzed in 151 primary liver graft recipients. The Fas (−670 A/G) and the FasL (IVS2nt −124 A/G and IVS3nt 169 T/delT) polymorphisms were analyzed by polymerase chain reaction‐restriction fragment length polymorphism. Fas −1377 G/A polymorphism was determined by allele‐specific amplification. Fas and FasL polymorphisms were not associated with acute and chronic rejection in liver transplant. In contrast, those recipients bearing the AA −670 Fas genotype showed significantly lower graft survival rate (S = 40%) than those bearing the GA genotype (S = 63.1%). These differences were detected from the first year post‐transplant. Multivariate analysis confirmed that the AA genotype increased the risk of liver graft loss. This work suggests for the first time a possible harmful effect of Fas −670 AA genotype on liver graft survival, whereas the Fas and FasL polymorphisms are not associated with acute or chronic rejection in liver graft recipients.
Identification and analysis of MHC class II DRB1 (Patr‐DRB1) alleles in chimpanzees
Authors: Bak E. J. , Ishii Y. , Omatsu T. , Kyuwa S. , Tetsuya T. , Hayasaka I. , Yoshikawa Y.
Published: January 2006

The MHC‐DRB1 gene is known to display the most extensive allelic polymorphisms among MHC class II genes. We attempted the selective identification of chimpanzee (Pan troglodytes) DRB1 (Patr‐DRB1) alleles using the polymerase chain reaction (PCR) technique in three steps: first, we performed Patr‐DRB1*02 lineage‐specific 8‐kb PCR for *02 lineage detection in each chimpanzee; second, we performed 620‐bp PCR for amplification of full‐length exon 2; and finally, we carried out an insert check using the pattern of microsatellite repeat length variability. In the genomic DNA of 23 chimpanzees, nine Patr‐DRB1 alleles containing two new alleles were detected. Our approach provides a relatively effective method of identifying Patr‐DRB1 alleles in individual chimpanzees and should also contribute to our understanding of the features of MHC molecules in non‐human primates.