bluuebunny/crossref_metadata_2025 huggingface dataset:
N‐butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis
Authors: Kasperzyk Julie L. , El‐Abbadi Mohga M. , Hauser Eric C. , D'Azzo Alessandra , Platt Frances M. , Seyfried Thomas N.
Published: December 2005

GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid β‐galactosidase (β‐gal), the enzyme that catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1) occurs primarily in the brain, leading to progressive neurodegeneration and brain dysfunction. Substrate reduction therapy aims to decrease the rate of GSL biosynthesis to counterbalance the impaired rate of catabolism. The imino sugar N‐butyldeoxygalactonojirimycin (NB‐DGJ) is a competitive inhibitor of the ceramide‐specific glucosyltransferase that catalyzes the first step in GSL biosynthesis. Neonatal C57BL/6J (B6) and β‐gal knockout (–/–) mice were injected daily from post‐natal day 2 (p‐2) to p‐5 with either vehicle or NB‐DGJ at 600 mg or 1200 mg/kg body weight. These drug concentrations significantly reduced total brain ganglioside and GM1 content in the B6 and the β‐gal (–/–) mice. Drug treatment had no significant effect on viability, body weight, brain weight, or brain water content in the B6 and β‐gal (–/–) mice. Significant elevations in neutral lipids (GA1, ceramide, and sphingomyelin) were observed in the NB‐DGJ‐treated β‐gal (–/–) mice, but were not associated with adverse effects. Also, NB‐DGJ treatment of B6 and β‐gal (–/–) mice from p‐2 to p‐5 had no subsequent effect on brain ganglioside content at p‐21. Our results show that NB‐DGJ is effective in reducing total brain ganglioside and GM1 content at early neonatal ages. These findings suggest that substrate reduction therapy using NB‐DGJ may be an effective early intervention for GM1 gangliosidosis and possibly other GSL lysosomal storage diseases.
Vortex formation in an electron plasma with a sheared flow
Authors: Hall J. O. , Shukla P. K.
Published: December 2005

The formation of vortex structures in an electron plasma with a sheared flow is investigated. The electron fluid is drifting in a self-electric field generated by an unshielded electron population. This setting is linearly unstable and an instability of diocotron (slipping-stream) type occurs. The time scale of the dynamics is assumed to be much shorter than the ion plasma and ion gyroperiods. Consequently, the ions do not respond to the wave potential and serve only as a neutralizing background. An equation determining the nonlinear evolution of the electrostatic potential in a plane perpendicular to an external magnetic field is derived within the drift approximation. The governing equation is then analyzed for the case with a localized shear in the electron fluid velocity. Possible final states of the diocotron instability are investigated analytically and solutions in the form of a tripolar vortex, a zonal flow, and a vortex street are found. The nonlinear time evolution of the diocotron instability is investigated by solving the governing equation numerically. In particular, the dynamics of nonlinearly saturated states and the formation of such states are discussed. Numerical solutions show a vortex street structure in a saturated state. The relevance of our investigation for space and laboratory plasmas is discussed.
Bifurcation theory of the transition to collisionless ion-temperature-gradient-driven plasma turbulence
Authors: Kolesnikov R. A. , Krommes J. A.
Published: December 2005

The collisionless limit of the transition to ion-temperature-gradient-driven plasma turbulence is considered with a dynamical-systems approach. The importance of systematic analysis for understanding the differences in the bifurcations and dynamics of linearly damped and undamped systems is emphasized. A model with ten degrees of freedom is studied as a concrete example. A four-dimensional center manifold (CM) is analyzed, and fixed points of its dynamics are identified and used to predict a “Dimits shift” of the threshold for turbulence due to the excitation of zonal flows. The exact value of that shift in terms of physical parameters is established for the model; the effects of higher-order truncations on the dynamics are noted. Multiple-scale analysis of the CM equations is used to discuss possible effects of modulational instability on scenarios for the transition to turbulence in both collisional and collisionless cases.
Grain-boundary recombination in Cu(In,Ga)Se2 solar cells
Authors: Gloeckler Markus , Sites James R. , Metzger Wyatt K.
Published: December 2005

Two-dimensional simulations are performed to investigate the impact of grain boundaries (GBs) on Cu(In,Ga)Se2 (CIGS) solar-cell performance. Charged defect levels and compositional variations at GBs are considered. Neutral grain boundaries in the CIGS layer are predicted to be most detrimental if they are parallel to the main junction and located within the depletion region. For columnar GBs with a grain size near 1μm, the effective grain-boundary recombination velocity must be less than 104cm∕s to allow for record-efficiency devices. The majority-hole repulsion (additional donors at the GB) and the resulting band bending have a small effect on current collection but substantially lower the open-circuit voltage, and the combined effect is generally a lowering of the solar-cell efficiency. Minority-electron repulsion (additional acceptors at the GB) will partially mitigate GB recombination. A downshift of the valence-band energy, as predicted by the observed Cu depletion at CIGS GBs, can effectively block holes from the GB region and allow efficiencies comparable to GB-free material.
Electrophoretic drawing of continuous fibers of single-walled carbon nanotubes
Authors: Annamalai R. , West J. D. , Luscher A. , Subramaniam V. V.
Published: December 2005

Control over the current during electrophoretic drawing of continuous fibers of single-walled carbon nanotubes (SWCNTs) is shown to be critical in producing long fibers with specific diameters. In the process, as-produced SWCNTs are first dispersed in N,N-dimethylformamide (DMF) by sonication. A tungsten probe tip is then immersed in the SWCNT∕DMF solution, and a dc bias is applied between the tip and another electrode at the bottom of the beaker containing the solution. After a dark cloud several millimeters in diameter develops around the tip, the electrode is withdrawn to form continuous macroscopic fibers of SWCNTs. The resulting fiber length and diameter are found to be principally determined by the magnitude of the current. Under constant voltage conditions where the current is allowed to vary, the fibers are short (several millimeters long) and their diameters vary drastically along their lengths. Of significance is the fact that when the current is maintained at constant values, fibers several centimeters in length with uniform diameters ranging from 26to42μm are obtained at a withdrawal rate of 0.85μm∕s. For this withdrawal rate, long fibers (∼3cm and greater) are obtained at an optimum value of the current (400nA) using hybrid conditions where the voltage is maintained constant earlier in the process while the current is maintained constant later in the process. Control of the total current at low values during this process has the potential to produce long fibers with uniform submicron diameters.
Multiferroic composite ferroelectric-ferromagnetic films
Authors: Zurbuchen M. A. , Wu T. , Saha S. , Mitchell J. , Streiffer S. K.
Published: December 2005

Multiferroic behavior was confirmed for epitaxial composite ferroelectric-ferromagnetic heterostructures, using a ferromagnetic crystal as both substrate and straining medium. Heterostructures having 2-2 connectivity (plane-on-plane) were fabricated by chemical solution deposition of Pb(Zr0.3,Ti0.7)O3 (PZT) thin films on La1.2Sr1.8Mn2O7 (LSMO) single crystal substrates. Magnetostriction (0.13%) of the substrate at its transition temperature (∼105K) induces an abrupt 7.3% increase in switchable polarization of the PZT. This confirmation of elastic coupling induced by the onset of ferromagnetism is a first step toward fabricating such structures for study of the interrelationship of their magnetic and electrical field-dependent behaviors.
Synthesis, structural, magnetic, and cytotoxic properties of iron oxide coated iron/iron-carbide nanocomposite particles
Authors: Yu S. , Chow G. M.
Published: December 2005

Iron/iron-carbide nanocomposite particles with surface coating of spinel iron oxide were synthesized by thermal decomposition of iron pentacarbonyl [Fe(CO)5] in various atmospheres of argon, methane, and acetylene at a temperature of 257°C. The microstructure, composition, magnetic properties, thermal stability of as-synthesized particles, and the effects of subsequent heat treatment were investigated. The synthesized nanoparticles exhibited a maximum magnetization of 160emu∕g, which was twice that of commonly used spinel iron oxide nanoparticles. After heating in an acidic solution with a pH value of 5 at 60°C for 20h, the nanocomposite particles retained 90% of their initial magnetization. In addition, x-ray diffraction and Mössbauer investigation indicated that the pyrolysis of Fe(CO)5 under different atmospheres resulted in the formation of crystalline iron carbide. It is noted that only Fe was reported to be formed in the literature using the pyrolysis of Fe(CO)5 under an argon atmosphere. Preliminary cytotoxicity assay suggested that the synthesized nanoparticles had comparable biocompatibility to γ-Fe2O3.
Hot spot formation outside of the fusion-fuel core
Authors: Shen Baifei , Zhang Xiaomei , Yu M. Y.
Published: December 2005

An alternative fast-ignition method is proposed involving the formation of a hot spot outside the precompressed fusion-fuel core by a series of shocks driven directly by the light pressure of laser pulses of increasing intensities. It is shown that a hot spot, which can be of different material from that of the fuel core, with temperature ∼10keV and density ∼200g∕cm2, can be formed. Being an electrically neutral plasma, the hot spot can easily be sent into the fuel core.
Dynamics of intense laser channel formation in an underdense plasma
Authors: Davis J. , Petrov G. M. , Velikovich A. L.
Published: December 2005

Efficient guiding and propagation of multi-keV x-rays in plasmas can be achieved by dynamically modifying the media through plasma channel formation. The dynamics of plasma channel formation is studied in preformed underdense plasma irradiated by a high intensity laser. This is done by a two-dimensional model coupling laser propagation to a relativistic particle-in-cell model. For laser intensity of 1020W∕cm2 and a laser beam width of 5μm the channel formation proceeds on a time scale of 60–70fs in uniform plasma with density 1018cm−3. The channel closes shortly after the rear of the laser pulse has passed due to Coulomb attraction from the ion core. Electron cavitation occurs only if the laser intensity is above a certain threshold intensity and the laser pulse duration exceeds 100fs. X-ray generation and propagation is feasible for ultrarelativistic laser pulses with small beam width, less than ∼20μm, and duration of more than 100fs.
X-ray diffuse scattering holography of a centrosymmetric sample
Authors: Kopecky M. , Fábry J. , Kub J. , Busetto E. , Lausi A.
Published: December 2005

The hologram based on the measurement of anomalous x-ray diffuse scattering is presented for the first time. The experiment was carried out using a rubidium chloride single crystal and anomalous scattering from Rb atoms close to the rubidium K-absorption edge. Holographic oscillations of a few percent of a total detected signal were achieved by choosing a suitable pair of photon energies. The real-space images of nearest neighbors of rubidium atoms were obtained using the standard Helmholz–Kirchhoff reconstruction algorithm.
Printing electrode for top-contact molecular junction
Authors: Ojima Kaoru , Otsuka Yoichi , Matsumoto Takuya , Kawai Tomoji , Nakamatsu Kenichiro , Matsui Shinji
Published: December 2005

We have developed a fabrication method of electrodes for molecular electronics based on nanotransfer printing lithography using a release agent layer and without any surface modification. A gold layer deposited on a release agent layer coating a mold can transfer to the nonmodified surfaces of SiO2, sapphire, or organic layer. The printed electrode has a resistivity of 4×10−6Ωcm which is close to the value of 2.1×10−6Ωcm for bulk gold. The application of this process to top-contact type molecular junctions is demonstrated using carbon nanotubes and the electric potential distribution of the junctions is observed by Kelvin force microscopy.
Approach for fabricating microgated field-emission arrays with individual carbon nanotube emitters
Authors: Ding Ming Q. , Shao Wen S. , Li Xing H. , Bai Guo D. , Zhang Fu Q. , Li Han Y. , Feng Jin J.
Published: December 2005

We propose an approach for fabricating microgated field-emission arrays (FEAs) with individual carbon nanotube (CNT) emitters. Beginning with the fabrication of microgated cell arrays, the process involves depositing a sacrificial layer at a glancing angle to close in the aperture that a small area catalyst can be placed on the bottom of the cells (for type A) or on the predeposited Mo tips (for type B); then, vertically aligned CNTs are grown by a dc plasma-enhanced chemical vapor deposition following a lift-off process. Scanning electron microscopy (SEM) images of both types of CNT FEAs show a large percentage of emitters with single, double or triple CNTs. For a 5×5 type B CNT FEA, at a gate voltage of 100 V, an average anode current reaches 1.4μA per cell while the gate current is less than 5% of the anode current.
Structure and enhancement of negative thermal expansion in the PbTiO3–CdTiO3 system
Authors: Chen J. , Xing X. R. , Yu R. B. , Liu G. R.
Published: December 2005

The structures of Pb1−xCdxTiO3 (x=0.03 and 0.06) were investigated by the x-ray Rietveld method at room temperature. It is surprising to find that the spontaneous polarization displacements of Pb∕Cd and Ti atoms according to the oxygen polyhedron decrease, although the c∕a ratio increases with doping-cadmium content. Cadmium substitution plays a unique role of enhancement of the negative thermal expansion in PbTiO3. The average bulk thermal expansion coefficient decreases from a¯=−1.99×10−5∕°C for pure PbTiO3 to a¯=−2.40×10−5∕°C for Pb0.94Cd0.06TiO3. The negative thermal expansion of PbTiO3 might be a consequence of hybridization between Pb and O atoms.
Allometry for estimating aboveground tree biomass in tropical and subtropical eucalypt woodlands: towards general predictive equations
Authors: Williams Richard J. , Zerihun Ayalsew , Montagu Kelvin D. , Hoffman Madonna , Hutley Lindsay B. , Chen Xiaoyong
Published: December 2005

A fundamental tool in carbon accounting is tree-based allometry, whereby easily measured variables can be used to estimate aboveground biomass (AGB). To explore the potential of general allometry we combined raw datasets from 14 different woodland species, mainly eucalypts, from 11 sites across the Northern Territory, Queensland and New South Wales. Access to the raw data allowed two predictor variables, tree diameter (at 1.3-m height; D) and tree height (H), to be used singly or in various combinations to produce eight candidate models. Following natural log (ln) transformation, the data, consisting of 220 individual trees, were re-analysed in two steps: first as 20 species–site-specific AGB equations and, second, as a single general AGB equation. For each of the eight models, a comparison of the species–site-specific with the general equations was made with the Akaike information criterion (AIC). Further model evaluation was undertaken by a leave-one-out cross-validation technique. For each of the model forms, the species–site-specific equations performed better than the general equation. However, the best performing general equation, ln(AGB) = –2.0596 + 2.1561 ln(D) + 0.1362 (ln(H))2, was only marginally inferior to the species–site-specific equations. For the best general equation, back-transformed predicted v. observed values (on a linear scale) were highly concordant, with a slope of 0.99. The only major deviation from this relationship was due to seven large, hollow trees (more than 35% loss of cross-sectional stem area at 1.3 m) at a single species–site combination. Our best-performing general model exhibited remarkable stability across species and sites, when compared with the species–site equations. We conclude that there is encouraging evidence that general predictive equations can be developed across sites and species for Australia’s woodlands. This simplifies the conversion of long-term inventory measurements into AGB estimates and allows more resources to be focused on the extension of such inventories.
The estimation of carbon budgets of frequently burnt tree stands in savannas of northern Australia, using allometric analysis and isotopic discrimination
Authors: Cook G. D. , Liedloff A. C. , Eager R. W. , Chen X. , Williams R. J. , O'Grady A. P. , Hutley L. B.
Published: December 2005

The stock, rates of sequestration and allocation of carbon were estimated for trees in 14 0.1-ha plots at Kapalga in Kakadu National Park, Northern Territory, using new allometric relationships of carbon stock to stem cross-sectional area and measured growth rates of trees. Carbon stocks of trees ranged from 12 to 58 t ha–1, with sequestration representing ~9% of the total stocks. More than half of the sequestered carbon is allocated to leaves and twigs and ~20% to wood. Only ~25% is retained in the live trees with leaf and twig fall accounting for 80%–84% of the total transfers to the environment. An alternative method of calculating sequestration rates from consideration of water use and carbon-isotope discrimination data had a close to 1 : 1 match with estimates from allometric relationships. We developed and applied algorithms to predict the impacts of fire on carbon stocks of live trees. This showed that the reduction in live carbon stocks caused by single fires increased with increasing intensity, but the impact was highly dependent on the tree stand structure.
A regional interpretation of rules and good practice for greenhouse accounting: northern Australian savanna systems
Authors: Henry Beverley , Mitchell Chris , Cowie Annette , Woldring Oliver , Carter John
Published: December 2005

Land-use change, particularly clearing of forests for agriculture, has contributed significantly to the observed rise in atmospheric carbon dioxide concentration. Concern about the impacts on climate has led to efforts to monitor and curtail the rapid increase in concentrations of carbon dioxide and other greenhouse gases in the atmosphere. Internationally, much of the current focus is on the Kyoto Protocol to the United Nations Framework Convention on Climate Change (UNFCCC). Although electing to not ratify the Protocol, Australia, as a party to the UNFCCC, reports on national greenhouse gas emissions, trends in emissions and abatement measures. In this paper we review the complex accounting rules for human activities affecting greenhouse gas fluxes in the terrestrial biosphere and explore implications and potential opportunities for managing carbon in the savanna ecosystems of northern Australia. Savannas in Australia are managed for grazing as well as for cultural and environmental values against a background of extreme climate variability and disturbance, notably fire. Methane from livestock and non-CO2 emissions from burning are important components of the total greenhouse gas emissions associated with management of savannas. International developments in carbon accounting for the terrestrial biosphere bring a requirement for better attribution of change in carbon stocks and more detailed and spatially explicit data on such characteristics of savanna ecosystems as fire regimes, production and type of fuel for burning, drivers of woody encroachment, rates of woody regrowth, stocking rates and grazing impacts. The benefits of improved biophysical information and of understanding the impacts on ecosystem function of natural factors and management options will extend beyond greenhouse accounting to better land management for multiple objectives.
Are retinal and retinal-binding proteins involved in stomatal response to blue light?
Authors: Paolicchi Fabio , Lombardi Lara , Ceccarelli Nello , Lorenzi Roberto
Published: December 2005

Stomata respond to blue light and it is generally believed that the photoreceptor for this response is located inside the guard cells. Only a small number of blue light photoreceptors have been identified so far, namely cryptochromes and phototropins, and they show overlapping functions in regulating many different responses to light. The possibility that plants may possess other receptors regulating blue light responses under different light conditions cannot be excluded. In this paper we show the presence of two retinal-binding proteins in Commelina communis and we report the identification of retinal, a chromophore usually bound to the photoreceptor rhodopsin and previously identified in algae and other higher plants. We show that, under our experimental conditions, stomata open promptly when exposed to blue light and we demonstrated that this response is dependent on retinal. We hypothesise that rhodopsin-like retinal-binding proteins might be involved in stomatal response to blue light.
Integrated responses of rosette organogenesis, morphogenesis and architecture to reduced incident light in Arabidopsis thaliana results in higher efficiency of light interception
Authors: Chenu Karine , Franck Nicolas , Dauzat Jean , Barczi Jean-François , Rey Hervé , Lecoeur Jérémie
Published: December 2005

Plants have a high phenotypic plasticity in response to light. We investigated changes in plant architecture in response to decreased incident light levels in Arabidopsis thaliana (L.) Heynh, focusing on organogenesis and morphogenesis, and on consequences for the efficiency of light interception of the rosette. A. thaliana ecotype Columbia plants were grown under various levels of incident photosynthetically active radiation (PAR), with blue light (BL) intensity proportional to incident PAR intensity and with a high and stable red to far-red light ratio. We estimated the PAR absorbed by the plant, using data from precise characterisation of the light environment and 3-dimensional simulations of virtual plants generated with AMAPsim software. Decreases in incident PAR modified rosette architecture; leaf area decreased, leaf blades tended to be more circular and petioles were longer and thinner. However, the efficiency of light interception by the rosette was slightly higher in plants subjected to lower PAR intensities, despite the reduction in leaf area. Decreased incident PAR delayed leaf initiation and slowed down relative leaf expansion rate, but increased the duration of leaf expansion. The leaf initiation rate and the relative expansion rate during the first third of leaf development were related to the amount of PAR absorbed. The duration of leaf expansion was related to PAR intensity. The relationships identified could be used to analyse the phenotypic plasticity of various genotypes of Arabidopsis. Overall, decreases in incident PAR result in an increase in the efficiency of light interception.
The effects of resource availability and environmental conditions on genetic rankings for carbon isotope discrimination during growth in tomato and rice
Authors: Comstock Jonathan P. , McCouch Susan R. , Martin Bjorn C. , Tauer Charles G. , Vision Todd J. , Xu Yunbi , Pausch Roman C.
Published: December 2005

Carbon isotope discrimination (Δ) is frequently used as an index of leaf intercellular CO2 concentration (ci) and variation in photosynthetic water use efficiency. In this study, the stability of Δ was evaluated in greenhouse-grown tomato and rice with respect to variable growth conditions including temperature, nutrient availability, soil flooding (in rice), irradiance, and root constriction in small soil volumes. Δ exhibited several characteristics indicative of contrasting set-point behaviour among genotypes of both crops. These included generally small main environmental effects and lower observed levels of genotype-by-environment interaction across the diverse treatments than observed in associated measures of relative growth rate, photosynthetic rate, biomass allocation pattern, or specific leaf area. Growth irradiance stood out among environmental parameters tested as having consistently large main affects on Δ for all genotypes screened in both crops. We suggest that this may be related to contrasting mechanisms of stomatal aperture modulation associated with the different environmental variables. For temperature and nutrient availability, feedback processes directly linked to ci and / or metabolite pools associated with ci may have played the primary role in coordinating stomatal conductance and photosynthetic capacity. In contrast, light has a direct effect on stomatal aperture in addition to feedback mediated through ci.
Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis
Authors: Clancy Lauren , Mruk Karen , Archer Kristina , Woelfel Melissa , Mongkolsapaya Juthathip , Screaton Gavin , Lenardo Michael J. , Chan Francis Ka-Ming
Published: December 2005

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytokine with potential therapeutic value against cancers because of its selective cytotoxicity to many transformed, but not normal, cells. The “decoy receptors” TRAIL-R3 (TR3) and TRAIL-R4 (TR4) were believed to negatively regulate TRAIL-induced cytotoxicity by competing for ligand binding with TRAIL-R1 (TR1) and TRAIL-R2 (TR2). Here, we show that inhibition of TRAIL-induced apoptosis by TR4 critically depends on its association with TR2 via the NH2-terminal preligand assembly domain overlapping the first partial cysteine-rich domain of both receptors. By contrast, ligand binding by TR4 is dispensable for its apoptosis inhibitory function, thereby excluding the possibility that TR4 was a “decoy” to inhibit apoptosis by binding up TRAIL. In primary CD8+T cells, which express only TR2 and TR4 and are resistant to TRAIL-induced apoptosis, stimulation with phorbol myristate acetate abrogated the ligand-independent interaction between TR2 and TR4 and enhanced their sensitivity to TRAIL-induced apoptosis. Hence, whereas most TNF receptors normally form only homotrimeric complexes, the preligand assembly domains in TR2 and TR4 permit mixed complex formation as a means to regulate apoptosis induction. We propose that TR4 is a “regulatory” rather than “decoy” receptor that inhibits apoptosis signaling by TRAIL through this previously uncharacterized ligand-independent mechanism.
Path integrals and symmetry breaking for optimal control theory
Authors: Kappen H J
Published: December 2005

This paper considers linear-quadratic control of a non-linear dynamical system subject to
arbitrary cost. I show that for this class of stochastic control problems the non-linear
Hamilton–Jacobi–Bellman equation can be transformed into a linear equation.
The transformation is similar to the transformation used to relate the classical
Hamilton–Jacobi equation to the Schrödinger equation. As a result of the linearity, the usual
backward computation can be replaced by a forward diffusion process that can
be computed by stochastic integration or by the evaluation of a path integral.
It is shown how in the deterministic limit the Pontryagin minimum principle
formalism is recovered. The significance of the path integral approach is that it
forms the basis for a number of efficient computational methods, such as Monte
Carlo sampling, the Laplace approximation and the variational approximation.
We show the effectiveness of the first two methods in a number of examples.
Examples are given that show the qualitative difference between stochastic and
deterministic control and the occurrence of symmetry breaking as a function of the noise.
A Critical Role for Eukaryotic Elongation Factor 1A-1 in Lipotoxic Cell Death
Authors: Borradaile Nica M. , Buhman Kimberly K. , Listenberger Laura L. , Magee Carolyn J. , Morimoto Emiko T.A. , Ory Daniel S. , Schaffer Jean E.
Published: December 2005

The deleterious consequences of fatty acid (FA) and neutral lipid accumulation in nonadipose tissues, such as the heart, contribute to the pathogenesis of type 2 diabetes. To elucidate mechanisms of FA-induced cell death, or lipotoxicity, we generated Chinese hamster ovary (CHO) cell mutants resistant to palmitate-induced death and isolated a clone with disruption of eukaryotic elongation factor (eEF) 1A-1. eEF1A-1 involvement in lipotoxicity was confirmed in H9c2 cardiomyoblasts, in which small interfering RNA-mediated knockdown also conferred palmitate resistance. In wild-type CHO and H9c2 cells, palmitate increased reactive oxygen species and induced endoplasmic reticulum (ER) stress, changes accompanied by increased eEF1A-1 expression. Disruption of eEF1A-1 expression rendered these cells resistant to hydrogen peroxide- and ER stress-induced death, indicating that eEF1A-1 plays a critical role in the cell death response to these stressors downstream of lipid overload. Disruption of eEF1A-1 also resulted in actin cytoskeleton defects under basal conditions and in response to palmitate, suggesting that eEF1A-1 mediates lipotoxic cell death, secondary to oxidative and ER stress, by regulating cytoskeletal changes critical for this process. Furthermore, our observations of oxidative stress, ER stress, and induction of eEF1A-1 expression in a mouse model of lipotoxic cardiomyopathy implicate this cellular response in the pathophysiology of metabolic disease.
Protease Nexin-1 Promotes Secretory Granule Biogenesis by Preventing Granule Protein Degradation
Authors: Kim Taeyoon , Loh Y. Peng
Published: December 2005

Dense-core secretory granule (DCG) biogenesis is a prerequisite step for the sorting, processing, and secretion of neuropeptides and hormones in (neuro)endocrine cells. Previously, chromogranin A (CgA) has been shown to play a key role in the regulation of DCG biogenesis in vitro and in vivo. However, the underlying mechanism of CgA-mediated DCG biogenesis has not been explored. In this study, we have uncovered a novel mechanism for the regulation of CgA-mediated DCG biogenesis. Transfection of CgA into endocrine 6T3 cells lacking CgA and DCGs not only recovered DCG formation and regulated secretion but also prevented granule protein degradation. Genetic profiling of CgA-expressing 6T3 versus CgA- and DCG-deficient 6T3 cells, followed by real-time reverse transcription-polymerase chain reaction and Western blotting analyses, revealed that a serine protease inhibitor, protease nexin-1 (PN-1), was significantly up-regulated in CgA-expressing 6T3 cells. Overexpression of PN-1 in CgA-deficient 6T3 cells prevented degradation of DCG proteins at the Golgi apparatus, enhanced DCG biogenesis, and recovered regulated secretion. Moreover, depletion of PN-1 by antisense RNAs in CgA-expressing 6T3 cells resulted in the specific degradation of DCG proteins. We conclude that CgA increases DCG biogenesis in endocrine cells by up-regulating PN-1 expression to stabilize granule proteins against degradation.
A role for the CPF 3′-end processing machinery in RNAP II-dependent gene looping
Authors: Ansari Athar , Hampsey Michael
Published: December 2005

The prevailing view of the RNA polymerase II (RNAP II) transcription cycle is that RNAP II is recruited to the promoter, transcribes a linear DNA template, then terminates transcription and dissociates from the template. Subsequent rounds of transcription are thought to require de novo recruitment of RNAP II to the promoter. Several recent findings, including physical interaction of 3′-end processing factors with both promoter and terminator regions, challenge this concept. Here we report a physical association of promoter and terminator regions of the yeast BUD3 and SEN1 genes. These interactions are transcription-dependent, require the Ssu72 and Pta1 components of the CPF 3′-end processing complex, and require the phosphatase activity of Ssu72. We propose a model for RNAP II transcription in which promoter and terminator regions are juxtaposed, and that the resulting gene loops facilitate transcription reinitiation by the same molecule of RNAP II in a manner dependent upon Ssu72-mediated CTD dephosphorylation.
A dynamic balance between gene activation and repression regulates the shade avoidance response inArabidopsis
Authors: Sessa Giovanna , Carabelli Monica , Sassi Massimiliano , Ciolfi Andrea , Possenti Marco , Mittempergher Francesca , Becker Jorg , Morelli Giorgio , Ruberti Ida
Published: December 2005

Plants grown under dense canopies perceive through the phytochrome system a reduction in the ratio of red to far-red light as a warning of competition, and this triggers a series of morphological changes to avoid shade. Several phytochrome signaling intermediates acting as positive regulators of accelerated elongation growth and induction of flowering in shade avoidance have been identified. Here we report that a negative regulatory mechanism ensures that in the presence of far-red-rich light an exaggerated plant response does not occur. Strikingly, this unpredicted negative regulatory mechanism is centrally involved in the attenuation of virtually all plant responses to canopy shade.
Hippocampal inactivation enhances taste learning
Authors: Stone Martha E. , Grimes Brandon S. , Katz Donald B.
Published: December 2005

Learning tasks are typically thought to be either hippocampal-dependent (impaired by hippocampal lesions) or hippocampal-independent (indifferent to hippocampal lesions). Here, we show that conditioned taste aversion (CTA) learning fits into neither of these categories. Rats were trained to avoid two taste stimuli, one novel and one familiar. Muscimol infused through surgically implanted intracranial cannulae temporarily inactivated the dorsal hippocampus during familiarization, subsequent CTA training, or both. As shown previously, hippocampal inactivation during familiarization enhanced the effect of that familiarization on learning (i.e., hippocampal inactivation enhanced latent inhibition of CTA); more novel and surprising, however, was the finding that hippocampal inactivation during training sessions strongly enhanced CTA learning itself. These phenomena were not caused by specific aspects of our infusion technique—muscimol infusions into the hippocampus during familiarization sessions did not cause CTAs, muscimol infusions into gustatory cortex caused the expected attenuation of CTA, and hippocampal inactivation caused the expected attenuation of spatial learning. Thus, we suggest that hippocampal memory processes interfere with the specific learning mechanisms underlying CTA, and more generally that multiple memory systems do not operate independently.
Acetylcholine release in the hippocampus and striatum during place and response training
Authors: Pych Jason C. , Chang Qing , Colon-Rivera Cynthia , Haag Renee , Gold Paul E.
Published: December 2005

These experiments examined the release of acetylcholine in the hippocampus
and striatum when rats were trained, within single sessions, on place or
response versions of food-rewarded mazes. Microdialysis samples of
extra-cellular fluid were collected from the hippocampus and striatum at 5-min
increments before, during, and after training. These samples were later
analyzed for ACh content using HPLC methods. In Experiment 1, ACh release in
both the hippocampus and striatum increased during training on both the place
and response tasks. The magnitude of increase of training-related ACh release
in the striatum was greater in rats trained on the response task than in rats
trained on the place task, while the magnitude of ACh release in the
hippocampus was comparable in the two tasks. Experiment 2 tested the
possibility that the hippocampus was engaged and participated in learning the
response task, as well as the place task, because of the availability of
extra-maze cues. Rats were trained on a response version of a maze under
either cue-rich or cue-poor conditions. The findings indicate that ACh release
in the hippocampus increased similarly under both cue conditions, but declined
during training on the cue-poor condition, when spatial processing by the
hippocampus would not be suitable for solving the maze. In addition, high
baseline levels of ACh release in the hippocampus predicted rapid learning in
the cue-rich condition and slow learning in the cue-poor condition. These
findings suggest that ACh release in the hippocampus augments response
learning when extra-maze cues can be used to solve the maze but impairs
response learning when extra-maze cues are not available for use in solving
the maze.
The role of metabotropic glutamate receptors and cortical adaptation in habituation of odor-guided behavior
Authors: Yadon Carly A. , Wilson Donald A.
Published: December 2005

Decreases in behavioral investigation of novel stimuli over time may be mediated by a variety of factors including changes in attention, internal state, and motivation. Sensory cortical adaptation, a decrease in sensory cortical responsiveness over prolonged stimulation, may also play a role. In olfaction, metabotropic glutamate receptors on cortical afferent pre-synaptic terminals have been shown to underlie both cortical sensory adaptation and habituation of odor-evoked reflexes. The present experiment examined whether blockade of sensory cortical adaptation through bilateral infusion of the group III metabotropic glutamate receptor antagonist cyclopropyl-4-phosphonophenylglycine (CPPG) into the anterior piriform cortex could reduce habituation of a more complex odor-driven behavior such as investigation of a scented object or a conspecific. The results demonstrate that time spent investigating a scented jar, or a conspecific, decreases over the course of a continuous 10 minute trial. Acute infusion of CPPG bilaterally into the anterior piriform cortex significantly enhanced the time spent investigating the scented jar compared to investigation time in control rats, without affecting overall behavioral activity levels. Infusions into the brain outside of the piriform cortex were without effect. CPPG infusion into the piriform cortex also produced an enhancement of time spent investigating a conspecific, although this effect was not significant.
Crystal structures of the tryptophan repressor binding protein WrbA and complexes with flavin mononucleotide
Authors: Gorman Jason , Shapiro Lawrence
Published: December 2005

The tryptophan repressor binding protein WrbA binds to the tryptophan repressor protein TrpR. Although the biological role of WrbA remains unclear, it has been proposed to function in enhancing the stability of TrpR–DNA complexes. Sequence database analysis has identified WrbA as a founding member of a flavodoxin‐like family of proteins. Here we present crystal structures of WrbA from Deinococcus radiodurans and Pseudomonas aeruginosa and their complexes with flavin mononucleotide. The protomer structure is similar to that of previously determined long‐chain flavodoxins; however, each contains a conserved inserted region unique to the WrbA family. Interestingly, each WrbA protein forms a homotetramer with 222 symmetry, unique among flavodoxin‐like proteins, in which each protomer binds one flavin mononucleotide cofactor molecule.
Protein surface analysis for function annotation in high‐throughput structural genomics pipeline
Authors: Binkowski T. Andrew , Joachimiak Andrzej , Liang Jie
Published: December 2005

Structural genomics (SG) initiatives are expanding the universe of protein fold space by rapidly determining structures of proteins that were intentionally selected on the basis of low sequence similarity to proteins of known structure. Often these proteins have no associated biochemical or cellular functions. The SG success has resulted in an accelerated deposition of novel structures. In some cases the structural bioinformatics analysis applied to these novel structures has provided specific functional assignment. However, this approach has also uncovered limitations in the functional analysis of uncharacterized proteins using traditional sequence and backbone structure methodologies. A novel method, named pvSOAR (pocket and void Surface of Amino Acid Residues), of comparing the protein surfaces of geometrically defined pockets and voids was developed. pvSOAR was able to detect previously unrecognized and novel functional relationships between surface features of proteins. In this study, pvSOAR is applied to several structural genomics proteins. We examined the surfaces of YecM, BioH, and RpiB from Escherichia coli as well as the CBS domains from inosine‐5′‐monosphate dehydrogenase from Streptococcus pyogenes, conserved hypothetical protein Ta549 from Thermoplasm acidophilum, and CBS domain protein mt1622 from Methanobacterium thermoautotrophicum with the goal to infer information about their biochemical function.
The crystal structure of a bacterial Class II ketol‐acid reductoisomerase: Domain conservation and evolution
Authors: Tyagi Rajiv , Duquerroy Stephane , Navaza Jorge , Guddat Luke W. , Duggleby Ronald G.
Published: December 2005

Ketol‐acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes two steps in the biosynthesis of branched‐chain amino acids. Amino acid sequence comparisons across species reveal that there are two types of this enzyme: a short form (Class I) found in fungi and most bacteria, and a long form (Class II) typical of plants. Crystal structures of each have been reported previously. However, some bacteria such as Escherichia coli possess a long form, where the amino acid sequence differs appreciably from that found in plants. Here, we report the crystal structure of the E. coli enzyme at 2.6 Å resolution, the first three‐dimensional structure of any bacterial Class II KARI. The enzyme consists of two domains, one with mixed α/β structure, which is similar to that found in other pyridine nucleotide‐dependent dehydrogenases. The second domain is mainly α‐helical and shows strong evidence of internal duplication. Comparison of the active sites between KARI of E. coli, Pseudomonas aeruginosa, and spinach shows that most residues occupy conserved positions in the active site. E. coli KARI was crystallized as a tetramer, the likely biologically active unit. This contrasts with P. aeruginosa KARI, which forms a dodecamer, and spinach KARI, a dimer. In the E. coli KARI tetramer, a novel subunit‐to‐subunit interacting surface is formed by a symmetrical pair of bulbous protrusions.
Variability of fish diets between dry and flood periods in an arid zone floodplain river
Authors: Balcombe S. R. , Bunn S. E. , McKenzie‐Smith F. J. , Davies P. M.
Published: December 2005

The fish assemblages of an arid zone floodplain river, Cooper Creek, Queensland, Australia, were sampled during two dry periods in isolated waterholes and on the inundated floodplain during the early and late phase of a major flood event. Diets were described for nine native species and compared within and between dry and flood periods. In the dry season, when fishes were restricted to waterholes, diets were characteristically simple with narrow diet breadths. Movement onto the floodplain during flooding clearly increased feeding opportunities, with greater diet breadths evident in all species. Despite obvious potential for terrestrial inputs, diets tended to be dominated by aquatic resources in both the waterholes and on the floodplain. Stomach fullness, however, varied little between dry season waterhole and floodplain samples. Fishes appeared to feed on potentially lower value resources such as detritus and calanoid copepods during the dry season, when waterholes were isolated and food resources were limited. They were then able to capitalize on the ‘boom’ of aquatic production and more diverse food resources associated with episodic flood events.
Fish assemblages of Cais do Carvão Bay (Madeira Island) determined by the visual census technique
Authors: Ribeiro C. , Almeida A. J. , Araújo R. , Biscoito M. , Freitas M.
Published: December 2005

Fish assemblages in Cais do Carvão Bay, Madeira Island, a proposed marine protected area (MPA), were determined from a diver visual census. A total of 32 transect counts were performed. Habitats sampled included sandy bottom, rocky boulders, vertical walls and rocky outcrops. Species richness, diversity, density, trophic structure, size and spatial organization were documented for the fish assemblages. Forty‐four species from 23 families were encountered; 32% belonged to Sparidae (10) and Labridae (four). The greatest species richness (25) was observed in rocky boulder habitat at 10–15 m depth, while the lowest (five) occurred over a deeper sand habitat. The greatest density (760·5 individuals per 100 m2) was recorded over rocky outcropping (20–25 m deep), and the lowest of 11·6 individuals per 100 m2 was over a sand bottom at 10–15 m depth. Thalassoma pavo, Abudefduf luridus and Chromis limbata had higher densities on hard bottoms, while Heteroconger longissimus was the most abundant species in sand bottom habitats. No significant differences were detected for all indices calculated among depth intervals for sand and rocky boulder stations. Sand and rock boulder substratum, however, differed significantly for the 10–15 m depth stratum.
Comparison of hospital episodes with ‘drug‐induced’ disorders and spontaneously reported adverse drug reactions
Authors: Barrow Paul , Waller Patrick , Wise Lesley
Published: December 2005

Aims

To compare Hospital Episode Statistics for ‘drug‐related’ admissions with spontaneously reported adverse drug reactions (ADRs) using UK Yellow Card data for the period 1996–2000.

Methods

This was a descriptive study for which we matched the relevant datasets in respect of time, place, evidence of hospitalization and disease terminology. The principal outcome was the ratio of ADRs leading to hospitalization which had been reported spontaneously during the whole study period.

Results

Twenty types of ADR were included and between them there was a wide spread of overall ratios (range 0–130%). The general tendency was for under‐reporting on Yellow Cards but for ADRs with a fatal outcome this appeared to be less (range 7–168%).

Conclusions

This study provides some broad indications of the degree of under‐reporting of ADRs that occurs despite a clinical diagnosis of a serious ADR being made and recorded.