bluuebunny/crossref_metadata_2025 huggingface dataset:
Propagation of kinetic Alfvén waves in the ionospheric Alfvén resonator in the presence of density cavities
Authors: Lysak R. L. , Song Y.
Published: October 2008

Recent observations of particle distributions that are narrow in pitch angle and broad in energy have suggested that kinetic Alfvén waves are a significant contributor to auroral particle acceleration. Oscillations at frequencies near 1 Hz are a natural consequence of the propagation of Alfvén waves in the strongly varying Alfvén speed profile above the auroral ionosphere, the so‐called ionospheric Alfvén resonator. These waves often propagate in the presence of perpendicular density gradients at various spatial scales. Simulations have been performed to study the evolution of these fields including both parallel and perpendicular inhomogeneity. Phase mixing at the boundaries of the density cavity leads to small‐scale Alfvén waves, which can develop the parallel electric fields needed to accelerate the Alfvénic aurora. These simulations verify the kinetic Alfvén wave dispersion relation in the electron inertial limit, which predicts that the perpendicular phase and group velocity of these waves are in the opposite direction. In addition, the results show that narrow spatial scales are favored by high ionospheric conductance.
An empirical model of Saturn's bow shock: Cassini observations of shock location and shape
Authors: Masters A. , Achilleos N. , Dougherty M. K. , Slavin J. A. , Hospodarsky G. B. , Arridge C. S. , Coates A. J.
Published: October 2008

We present a new empirical model of Saturn's bow shock that utilizes observations from the Cassini spacecraft. Shock crossings are identified in magnetic field and plasma observations made by Cassini between June 2004 and August 2005. The Cassini crossings are then combined with the crossings made during the Saturn flybys of Pioneer 11, Voyager 1, and Voyager 2. Solar wind dynamic pressures for the Cassini crossings are estimated using upstream electron densities determined from Langmuir wave observations made by the Radio and Plasma Wave System. The crossing positions are rotated into aberrated coordinates to correct for the effect of the planet's orbital motion. In the case of Saturn this rotation is by ∼1°. To correct for solar wind dynamic pressure variations, the crossing positions are normalized to the average pressure 〈PSW〉 = 0.048 nPa. The model is then obtained by fitting a conic section to the crossings using a nonlinear least squares technique. To validate the assumptions made in constructing the model, we treat the parameters previously assumed to be constants as variables and fit their values using an optimization routine; this leads to a conic section that is within the positional uncertainty of the model. The spacecraft trajectories are considered, and we conclude that they do not significantly bias the model. The new model is compared to the existing models, and the similarities and differences are discussed. We suggest that the new model gives the most accurate empirical representation of the shape and location of Saturn's bow shock.
Mesoarchean assembly and stabilization of the eastern Kaapvaal craton: A structural‐thermochronological perspective
Authors: Schoene Blair , de Wit Maarten J. , Bowring Samuel A.
Published: October 2008

Understanding the construction and stabilization of Archean continental lithosphere has important implications for models of tectonic and thermal regimes in the early Earth, as well as for the subsequent evolution of continents. We provide new constraints for the amalgamation and stabilization of the eastern Kaapvaal craton in the vicinity of the Barberton greenstone belt circa 3.3–3.1 Ga. Isotope dilution thermal ionization mass spectrometry U‐Pb geochronology and thermochronology are combined with mapping and structural analysis around the margins of this belt in order to constrain movement on major shear zones that separate high‐grade orthogneiss terranes from low‐grade supracrustal rocks and to relate this movement to the timing of differential exhumation. New and existing data are consistent with accretion at ∼3.23 Ga within an oblique subduction plate boundary manifested in the BGB as an asymmetric flower‐like structural geometry. For >100 Ma following terrane assembly, transform boundary tectonics, manifested partially as transtension on reactivated faults, led to large‐scale juxtaposition of middle to lower crustal basement orthogneiss complexes against upper crustal greenstone sequences and episodic emplacement of granitic batholiths. Stabilization of this portion of Archean lithosphere involved at least a three‐stage process: (1) creation of a thick and rigid mantle lithosphere during crustal growth, subduction, and terrane assembly from circa 3.30 to 3.23 Ga, (2) generation of a rigid crust during strike‐slip and transtensional tectonics coupled with migration of granites and heat‐producing elements into the upper crust between circa 3.2 and 3.1 Ga, and (3) erosion and removal of the uppermost crust during regional peneplanation that lasted until circa 2.9 Ga.
An amino acid at position 142 in nitrilase fromRhodococcus rhodochrousATCC 33278 determines the substrate specificity for aliphatic and aromatic nitriles
Authors: Yeom Soo-Jin , Kim Hye-Jung , Lee Jung-Kul , Kim Dong-Eun , Oh Deok-Kun
Published: October 2008

Nitrilase from Rhodococcus rhodochrous ATCC 33278 hydrolyses both aliphatic and aromatic nitriles. Replacing Tyr-142 in the wild-type enzyme with the aromatic amino acid phenylalanine did not alter specificity for either substrate. However, the mutants containing non-polar aliphatic amino acids (alanine, valine and leucine) at position 142 were specific only for aromatic substrates such as benzonitrile, m-tolunitrile and 2-cyanopyridine, and not for aliphatic substrates. These results suggest that the hydrolysis of substrates probably involves the conjugated π-electron system of the aromatic ring of substrate or Tyr-142 as an electron acceptor. Moreover, the mutants containing charged amino acids such as aspartate, glutamate, arginine and asparagine at position 142 displayed no activity towards any nitrile, possibly owing to the disruption of hydrophobic interactions with substrates. Thus aromaticity of substrate or amino acid at position 142 in R. rhodochrous nitrilase is required for enzyme activity.
The life of a cell: apoptosis regulation by the PI3K/PKB pathway
Authors: Duronio Vincent
Published: October 2008

The activation of PI3K (phosphoinositide 3-kinase) family members is a universal event in response to virtually all cytokines, growth factors and hormones. As a result of formation of PtdIns with an added phosphate at the 3 position of the inositol ring, activation of the protein kinases PDK1 (phosphoinositide-dependent kinase 1) and PKB (protein kinase B)/Akt occurs. The PI3K/PKB pathway impinges upon a remarkable array of intracellular events that influence either directly or indirectly whether or not a cell will undergo apoptosis. In this review, the many ways in which PI3K/PKB can control these processes are summarized. Not all of the events described will necessarily play a role in any one cell type, but a subset of these events is probably essential for the survival of every cell.
Deterioration in cardiac systolic and diastolic function late in normal human pregnancy
Authors: Zentner Dominica , du Plessis Moira , Brennecke Shaun , Wong James , Grigg Leeanne , Harrap Stephen B.
Published: October 2008

The aim of the present study was to undertake a longitudinal study of systolic and diastolic cardiac function during normal pregnancy. At a median of 16 weeks of gestation, 100 primiparous women underwent echocardiography, including tissue Doppler imaging, determining left ventricular mass, cardiac output, systolic and diastolic velocities, and wall stress. A total of 32 were assessed again at a median of 37 weeks of gestation. Non-pregnant control estimates (n=9) were obtained by averaging four separate measures over two menstrual cycles. Initially, the pregnant women had significantly higher pulse rates than controls, associated with greater ventricular wall stress (two-tailed P value=0.015), and systolic (two-tailed P value=0.005) and diastolic (two-tailed P value=0.018) lateral wall myocardial velocities, but no differences in systolic blood pressure, left ventricular mass or cardiac output. By 37 weeks of gestation, increased blood pressure (two-tailed P value <0.001) and left ventricular mass (two-tailed P value=0.002) were associated with a significant increase in ventricular wall stress (two-tailed P value <0.001), and reductions in septal systolic (two-tailed P value=0.004) and septal and lateral early diastolic (two-tailed P value <0.001) myocardial velocities. The diastolic velocities at 37 weeks correlated inversely with maternal weight and age. In conclusion, by term pregnancy, an increase in ventricular wall stress is accompanied by a deterioration in cardiac function.
A comprehensive assessment of endothelial function in overweight women with and without polycystic ovary syndrome
Authors: Moran Lisa J. , Hutchison Samantha K. , Meyer Caroline , Zoungas Sophia , Teede Helena J.
Published: October 2008

PCOS (polycystic ovary syndrome) is associated with reproductive abnormalities, IR (insulin resistance) and elevated risk factors for CVD (cardiovascular disease) and Type 2 diabetes, including endothelial dysfunction. The present study aimed to assess a range of circulating markers of endothelial function in overweight women with and without PCOS. Overweight and obese age- and BMI (body mass index)-matched women with (n=80) and without (n=27) PCOS were assessed in a cross-sectional study. End-point measures were HOMA (homoeostasis model assessment)-IR, androgens, lipids, inflammatory markers [hsCRP (high-sensitivity C-reactive protein)] and endothelial function [FMD (flow-mediated dilation), ADMA (asymmetric dimethylarginine), PAI-1 (plasminogen activator inhibitor-1) and vWF (von Willebrand factor)]. Women with PCOS had elevated HOMA-IR (4.1±3.4 compared with 1.9±1.4), free androgen index (9.3±5.6 compared with 4.6±3.8), total cholesterol (5.2±1.0 compared with 4.7±0.9 mmol/l) and triacylglycerols (triglycerides; 1.4±0.7 compared with 0.9±0.3 mmol/l) (P<0.05 for all), but similar hsCRP compared with women without PCOS. With regard to endothelial function, women with PCOS had elevated ADMA (1.0±0.4 compared 0.3±0.1 μmol/l, P<0.001) and PAI-1 (5.6±1.8 compared with 4.6±1.1 units/ml, P=0.006), a trend towards worsened FMD (11.8±5.0 compared with 13.5±4.0%, P=0.075) and no difference in vWF compared with controls. For all subjects, ADMA (P=0.002) and PAI-1 (P<0.001) were increased with higher tertiles of HOMA-IR. Women with PCOS are hyperandrogenic, dyslipidaemic and have IR, and have risk factors for CVD and diabetes including increased circulating markers of endothelial function (ADMA and PAI-1) and a trend towards worse FMD as a global marker of endothelial function. In PCOS, deterioration in endothelial function is related to IR, hyperandrogenism and other factors.
Structure, stability, and infrared spectroscopy of (H2O)nNH4+ clusters: A theoretical study at zero and finite temperature
Authors: Douady J. , Calvo F. , Spiegelman F.
Published: October 2008

The combined effects of size and temperature on the stable structures of water clusters doped with one ammonium molecule have been investigated theoretically using an empirical potential and density-functional theory (DFT) calculations. Global optimization with Monte Carlo methods has been performed using an explicit intermolecular potential based on the Kozack–Jordan polarizable model. Putative lowest-energy structures based on this empirical potential are reported. Our results indicate a high propensity for the NH4+ impurity to be fully solvated by water molecules. Clathratelike patterns are formed for clusters containing more than 11 molecules. Local reoptimizations of candidate structures carried out at the DFT level with the B3LYP hybrid functional and the 6-311++G(d,p) basis set confirm the general trends obtained with the intermolecular potential. However, some reorderings between isomers often due to zero-point energy corrections are found in small clusters, leading to stable geometries in agreement with other first-principles studies. Temperature effects have been assessed using a simple harmonic superposition approximation for selected cluster sizes and using dedicated Monte Carlo simulations for (H2O)20NH4+. The clusters are found to melt near 200 K, and possibly isomerize already below 50 K. The free energy barrier for core/surface isomerization of the impurity in the 21-molecule cluster is estimated to be only a few kcal/mol at 150 K. The vibrational spectroscopic signatures of the clusters obtained from the electronic structure calculations show the usual four O–H stretching bands. As the cluster size increases, the double acceptor-single donor band near 3700 cm−1 increasingly dominates over the three other bands. While we do not find conclusive evidence for a O–H stretching spectroscopic signature of the ammonium impurity to be in the core or at the surface in the 20-molecule cluster, a possible signature via the N–H stretching bands is suggested near 2800–2900 cm−1. In the larger (H2O)49NH4+ cluster, the impurity is slightly more stable at the surface.
Characterization of molecular motions in biomolecular systems by elastic incoherent neutron scattering
Authors: Magazù Salvatore , Maisano Giacomo , Migliardo Federica , Galli Giovanni , Benedetto Antonio , Morineau Denis , Affouard F. , Descamps M.
Published: October 2008

In the present work the role played by the instrumental resolution function in elastic incoherent neutron scattering (EINS) experiment is discussed. An important result consists in the definition of an equivalent time t*, which depends both on the characteristic system time and on the resolution time, for which the spatial Fourier transform of EINS intensity profile and the self-distribution function (SDF) evaluated at t=t* are proportional. Then the equivalent time t* is introduced in the SDF procedure, an operational recipe for the mean square displacement determination. The new revised procedure is applied on data of myoglobin in trehalose dry environment and of hydrated homologous disaccharides (sucrose and trehalose).
Effect of grain size on thermoelectric properties of n-type nanocrystalline bismuth-telluride based thin films
Authors: Takashiri M. , Miyazaki K. , Tanaka S. , Kurosaki J. , Nagai D. , Tsukamoto H.
Published: October 2008

The effect of grain size on the thermoelectric properties of n-type nanocrystalline bismuth-telluride based thin films is investigated. We prepare the nanocrystalline thin films with average grain sizes of 10, 27, and 60 nm by a flash-evaporation method followed by a hydrogen annealing process. The thermoelectric properties, in terms of the thermal conductivity by a differential 3ω method, the electrical conductivity, and the Seebeck coefficient are measured at room temperature and used to evaluate the figure of merit. The minimum thermal conductivity is 0.61 W m−1 K−1 at the average grain size of 10 nm. We also estimate the lattice thermal conductivity of the nanocrystalline thin films and compare it with a simplified theory of phonon scattering on grain boundaries. For nanosized grains, the lattice thermal conductivity of nanocrystalline thin films decreases rapidly for smaller grains, corresponding to the theoretical calculation. The figure of merit is also decreased as the grain size decreases, which is attributed to the increased number of defects at the grain boundaries.
A formula for the minimal coordination number of a parallel bundle
Authors: Starostin E. L.
Published: October 2008

An exact formula for the minimal coordination numbers of the parallel packed bundle of rods is presented based on an optimal thickening scenario. Hexagonal and square lattices are considered.
Beyond ray tracing for internal waves. II. Finite-amplitude effects
Authors: Brown Geoffrey L. , Bush Andrew B. G. , Sutherland Bruce R.
Published: October 2008

We examine the transmission of small and moderately large internal gravity wavepackets through uniformly and nonuniformly stratified fluids using fully nonlinear numerical simulations. The simulations of finite-amplitude waves in a uniformly stratified fluid show that the weakly nonlinear theory developed for horizontally periodic wavepackets extends well to the dynamics of wavepackets with horizontal extent comparable to the horizontal wavelength. In simulations of small-amplitude wavepackets in a nonuniformly stratified fluid the transmission coefficient is found to be comparable to that computed analytically for horizontally periodic waves that radiate continuously (nontransiently) on a reflection level. Simulations of finite-amplitude waves in a nonuniformly stratified fluid show little dependence of transmission coefficient on the wavepacket extent. However, for a wide range of incident wave frequencies the simulations exhibit a monotonic increase in the transmission coefficient as a function of the incident wave amplitude.
Brillouin scattering studies of liquid argon at high temperatures and high pressures
Authors: Jia Ru , Li Fangfei , Li Min , Cui Qiliang , He Zhi , Wang Liancheng , Zhou Qiang , Cui Tian , Zou Guangtian , Bi Yan , Hong Shiming , Jing Fuqian
Published: October 2008

Brillouin scattering measurements were performed on liquid argon in a diamond anvil cell at various solidification points up to 503K. With the measured results from the 60° platelet-and 180° back-scattering geometries, the sound velocity, refractive index, experimental equation of state, and adiabatic bulk modulus of liquid argon as a function of pressure were determined. The discrepancy between experimental and previous calculated equation of state indicates that the many-body contribution to the density of liquid argon increases with increasing pressure and decreases with increasing temperature. By analyzing the Brillouin spectra in the coexistence of liquid and solid phase regions, the volume change and latent heat of solid-liquid transformation along the equilibrium curve have been also obtained for the first time.
A challenge in Navier–Stokes-based continuum modeling: Maxwell–Burnett slip law
Authors: Weng Huei Chu , Chen Cha'o-Kuang
Published: October 2008

In this paper, we provide an analytical solution of the Navier–Stokes equations subject to second-order slip boundary conditions for gas flow in a long open-ended parallel-plate microchannel with variable working temperature. Comparisons with available experimental data show the limits of various slip laws in the experimental setups. It is found that the Maxwell (first-order) slip law can be valid for average Knudsen numbers up to 0.255 and that the Maxwell–Burnett slip law should be preferred and can be valid for values up to 1.60. The influences of working temperature on the appearance of the Knudsen paradox and the change in the centerline pressure curvature for different values of the pressure-drop parameter are further predicted. Results reveal that the value of the Knudsen number where the Knudsen paradox appears is always greater than the value where the pressure curvature changes. When the working temperature rises, both the critical values increase. However, both the corresponding values of the mass flow rate decrease. For low values of the pressure-drop parameter, this effect seems to be negligible on the critical Knudsen number and constant on the corresponding mass flow rate.
Field emission from vertically aligned few-layer graphene
Authors: Malesevic Alexander , Kemps Raymond , Vanhulsel Annick , Chowdhury Manish Pal , Volodin Alexander , Van Haesendonck Chris
Published: October 2008

The electric field emission behavior of vertically aligned few-layer graphene was studied in a parallel plate–type setup. Few-layer graphene was synthesized in the absence of any metallic catalyst by microwave plasma enhanced chemical vapor deposition with gas mixtures of methane and hydrogen. The deposit consists of nanostructures that are several micrometers wide, highly crystalline stacks of four to six atomic layers of graphene, aligned vertically to the substrate surface in a high density network. The few-layer graphene is found to be a good field emitter, characterized by turn-on fields as low as 1 V/μm and field amplification factors up to several thousands. We observe a clear dependence of the few-layer graphene field emission behavior on the synthesis parameters: Hydrogen is identified as an efficient etchant to improve field emission, and samples grown on titanium show lower turn-on field values and higher amplification factors when compared to samples grown on silicon.
Electrical bistability and charge transport behavior in Au nanoparticle/poly(N-vinylcarbazole) hybrid memory devices
Authors: Lai Pei Ying , Chen J. S.
Published: October 2008

Polymer memory devices using poly(N-vinylcarbazole) (PVK) as the active layer, incorporated with various weight ratios (0, 0.083, and 0.2) of dodecanethiol capped gold nanoparticles (Au NPs), are investigated. Electrical bistability is demonstrated for all three PVK-based devices, regardless of Au-NP ratios. However, current fluctuation is observed during stress test for both zero (PVK-only) and Au NPs:PVK=0.2:1 devices, while good current stability is obtained for the Au NPs:PVK=0.083:1 device. Capacitance-frequency (C-f) curves present the comparable negative capacitance feature for all three devices in both high-conductivity (“on”) state and low-conductivity (“off”) state, indicating that the carrier transport is dominated by the PVK matrix. However, minor differences in the C-f curves are dependent on the weight ratios of Au NPs, and the connection is discussed.
Beef quality grades as determined by Korean and Australian consumers
Authors: Thompson J. M. , Polkinghorne R. , Hwang I. H. , Gee A. M. , Cho S. H. , Park B. Y. , Lee J. M.
Published: October 2008

Consumer responses were examined in an incomplete factorial design where Australian consumers evaluated 216 beef samples derived from 18 cattle killed in Australia and Korean consumers evaluated 216 samples from the same 18 cattle, plus 216 similar samples from 18 Korean cattle. Samples of the Mm. triceps brachii, longissimus dorsi and semimembranosus were cooked using grill and Korean barbeque methods. Each sample was sensory tested by 10 consumers, who scored it for tenderness, juiciness, like flavour, and overall liking. Consumers then graded each sample as either unsatisfactory (2 star), good every day (3 star), better than every day (4 star), or premium (5 star) quality.
For those samples assessed by both Australian and Korean consumers, the Korean consumers graded a higher proportion of samples ‘unsatisfactory’ and a lower proportion of samples ‘premium’ grade product than Australian consumers. Using a composite meat quality score (MQ4) to predict grade, a discriminant analysis showed that the Korean consumers had boundary cut-offs for the lower grades, which were ~4–10 palatability units higher than the Australian consumers.
Analysis of the residuals between actual and predicted palatability scores showed that the Meat Standards Australia (MSA) grading model produced relatively unbiased estimates within ±2 MQ4 units for the different consumer groups, muscle and carcass suspension treatments, with the exception of the M. semimembranosus samples. Implications of the results for both Korean and Australian beef markets through the use of an empirical grading model to predict palatability are discussed.
Current usage and future development of the Meat Standards Australia (MSA) grading system
Authors: Polkinghorne R. , Watson R. , Thompson J. M. , Pethick D. W.
Published: October 2008

Progress in the development and adoption of the Meat Standards Australia system has encouraged substantial change and an improved consumer awareness at all points of the Australian beef production chain. The system is moving from niche to mainstream market application with the exciting potential to transform many industry practices and build a more direct consumer focus. The system aims to accurately predict consumer satisfaction levels for individual cooked beef portions. This is a major advance on grading systems that classify carcasses into groups of like appearance. A prediction model was developed based on consumer testing and has proved to be useful in categorising a wide range of beef into consumer grades within cooking methods. These provide a basis to ensure a predictable eating quality result for the consumer and a mechanism to align product description and pricing throughout the production chain. When used in value-based marketing systems financial reward can be directly linked to consumer satisfaction encouraging a consumer-focussed industry. Research is proceeding to extend and improve the accuracy of the prediction model encompassing additional cattle types and cooking methods. Several projects in other countries are adding insights into the relative response of consumers from varied cultural backgrounds. It is hoped that further international collaboration will facilitate use of the developed technology to improve consumer value and industry returns through improved product consistency in global markets.
A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex
Authors: Wang Huaixing , Stradtman George G. , Wang Xiao-Jing , Gao Wen-Jun
Published: October 2008

In the prefrontal cortex, NMDA receptors are important for normal prefrontal functions such as working memory, and their dysfunction plays a key role in the pathological processes of psychiatric disorders such as schizophrenia. Little is known, however, about the synaptic properties of NMDA receptors in the local circuits of recurrent excitation, a leading candidate mechanism underlying working memory. We investigated the NMDA receptor-mediated currents at monosynaptic connections between pairs of layer 5 pyramidal neurons. We found that NMDA receptor-mediated currents at prefrontal synapses in the adult, but not young, rats exhibit a twofold longer decay time-constant and temporally summate a train of stimuli more effectively, compared to those in the primary visual cortex. Experiments with pharmacological, immunocytochemical, and biochemical approaches further suggest that, in the adult animals, neurons express significantly more NR2B subunits in the prefrontal cortex than the visual cortex. The NR2B-rich synapses in the prefrontal circuitry may be critically implicated in online cognitive computations and plasticity in learning, as well as psychiatric disorders.
A loss of function allele for murine Staufen1 leads to impairment of dendritic Staufen1-RNP delivery and dendritic spine morphogenesis
Authors: Vessey John P. , Macchi Paolo , Stein Joel M. , Mikl Martin , Hawker Kelvin N. , Vogelsang Petra , Wieczorek Krzysztof , Vendra Georgia , Riefler Julia , Tübing Fabian , Aparicio Samuel A. J. , Abel Ted , Kiebler Michael A.
Published: October 2008

The dsRNA-binding protein Staufen was the first RNA-binding protein proven to play a role in RNA localization in
Drosophila
. A mammalian homolog, Staufen1 (Stau1), has been implicated in dendritic RNA localization in neurons, translational control, and mRNA decay. However, the precise mechanisms by which it fulfills these specific roles are only partially understood. To determine its physiological functions, the murine Stau1 gene was disrupted by homologous recombination. Homozygous

stau1
tm1Apa

mutant mice express a truncated Stau1 protein lacking the functional RNA-binding domain 3. The level of the truncated protein is significantly reduced. Cultured hippocampal neurons derived from

stau1
tm1Apa

homozygous mice display deficits in dendritic delivery of Stau1-EYFP and β-
actin
mRNA-containing ribonucleoprotein particles (RNPs). Furthermore, these neurons have a significantly reduced dendritic tree and develop fewer synapses. Homozygous

stau1
tm1Apa

mutant mice are viable and show no obvious deficits in development, fertility, health, overall brain morphology, and a variety of behavioral assays, e.g., hippocampus-dependent learning. However, we did detect deficits in locomotor activity. Our data suggest that Stau1 is crucial for synapse development
in vitro
but not critical for normal behavioral function.
Chromosome replication dynamics in the archaeon
Sulfolobus acidocaldarius
Authors: Duggin Iain G. , McCallum Simon A. , Bell Stephen D.
Published: October 2008

The “baby machine” provides a means of generating synchronized cultures of minimally perturbed cells. We describe the use of this technique to establish the key cell-cycle parameters of hyperthermophilic archaea of the genus
Sulfolobus
. The 3 DNA replication origins of
Sulfolobus acidocaldarius
were mapped by 2D gel analysis to near 0 (
oriC2
), 579 (
oriC1
), and 1,197 kb (
oriC3
) on the 2,226-kb circular genome, and we present a direct demonstration of their activity within the first few minutes of a synchronous cell cycle. We also detected X-shaped DNA molecules at the origins in log-phase cells, but these were not directly associated with replication initiation or ongoing chromosome replication in synchronized cells. Whole-genome marker frequency analyses of both synchronous and log-phase cultures showed that origin utilization was close to 100% for all 3 origins per round of replication. However,
oriC2
was activated slightly later on average compared with
oriC1
and
oriC3
. The DNA replication forks moved bidirectionally away from each origin at ≈88 bp per second in synchronous culture. Analysis of the 3 Orc1/Cdc6 initiator proteins showed a uniformity of cellular abundance and origin binding throughout the cell cycle. In contrast, although levels of the MCM helicase were constant across the cell cycle, its origin localization was regulated, because it was strongly enriched at all 3 origins in early S phase.
A host dicer is required for defective viral RNA production and recombinant virus vector RNA instability for a positive sense RNA virus
Authors: Zhang Xuemin , Nuss Donald L.
Published: October 2008

Defective interfering (DI) RNAs, helper virus-dependent deletion mutant RNAs derived from the parental viral genomic RNA during replication, have been described for most RNA virus taxonomic groups. We now report that DI RNA production in the chestnut blight fungus,
Cryphonectria parasitica
, persistently infected by virulence-attenuating positive sense RNA hypoviruses, depends on one of two host dicer genes,
dcl-2
. We further report that nonviral sequences that are rapidly deleted from recombinant hypovirus RNA virus vectors in wild-type and dicer gene
dcl-1
deletion mutant strains are stably maintained and expressed in the Δ
dcl-2
mutant strain. These results establish a requirement for
dcl-2
, the
C. parasitica
dicer gene responsible for antiviral defense and generation of virus-derived small interfering RNAs, in DI RNA production and recombinant virus vector RNA instability.
RhoE Is Required for Keratinocyte Differentiation and Stratification
Authors: Liebig Timo , Erasmus Jennifer , Kalaji Ruba , Davies Derek , Loirand Gervaise , Ridley Anne , Braga Vania M.M.
Published: October 2008

The molecular mechanism via which keratinocyte differentiation assembles multiple layers of cells (stratification) is poorly understood. We describe here a novel function of the Rho family member RhoE as a regulator of epidermal morphogenesis. RhoE protein levels are specifically and transiently up-regulated upon keratinocyte differentiation. RhoE up-regulation requires the activity of Rho kinase (ROCK) I, suggesting that both RhoE and ROCKI are important during keratinocyte differentiation. RhoE overexpression results in a striking enlargement of cell size and the number of stratified cells. In contrast, RhoE depletion induces hyperproliferation and delays initiation of keratinocyte differentiation. Interestingly, up-regulation of RhoE protein is seen primarily in basal, undifferentiated cells, in which commitment to differentiation and stratification takes place. RhoE activation in basal cells negatively modulates integrin adhesion, thereby facilitating detachment from the substratum and migration to form suprabasal layers. Thus, RhoE integrates two processes essential for keratinocyte differentiation and stratification: regulation of proliferative status and integrin adhesion.
Gemin3Is an Essential Gene Required for Larval Motor Function and Pupation inDrosophila
Authors: Shpargel Karl B. , Praveen Kavita , Rajendra T. K. , Matera A. Gregory
Published: October 2008

The assembly of metazoan Sm-class small nuclear ribonucleoproteins (snRNPs) is an elaborate, step-wise process that takes place in multiple subcellular compartments. The initial steps, including formation of the core RNP, are mediated by the survival motor neuron (SMN) protein complex. Loss-of-function mutations in human SMN1 result in a neuromuscular disease called spinal muscular atrophy. The SMN complex is comprised of SMN and a number of tightly associated proteins, collectively called Gemins. In this report, we identify and characterize the fruitfly ortholog of the DEAD box protein, Gemin3. Drosophila Gemin3 (dGem3) colocalizes and interacts with dSMN in vitro and in vivo. RNA interference for dGem3 codepletes dSMN and inhibits efficient Sm core assembly in vitro. Transposon insertion mutations in Gemin3 are larval lethals and also codeplete dSMN. Transgenic overexpression of dGem3 rescues lethality, but overexpression of dSMN does not, indicating that loss of dSMN is not the primary cause of death. Gemin3 mutant larvae exhibit motor defects similar to previously characterized Smn alleles. Remarkably, appreciable numbers of Gemin3 mutants (along with one previously undescribed Smn allele) survive as larvae for several weeks without pupating. Our results demonstrate the conservation of Gemin3 protein function in metazoan snRNP assembly and reveal that loss of either Smn or Gemin3 can contribute to neuromuscular dysfunction.
The OGF–OGFr Axis Utilizes the p16INK4aand p21WAF1/CIP1Pathways to Restrict Normal Cell Proliferation
Authors: Cheng Fan , McLaughlin Patricia J. , Verderame Michael F. , Zagon Ian S.
Published: October 2008

Opioid growth factor (OGF) is an endogenous opioid peptide ([Met5]enkephalin) that interacts with the OGF receptor (OGFr) and serves as a tonically active negative growth factor in cell proliferation of normal cells. To clarify the mechanism by which OGF inhibits cell replication in normal cells, we investigated the effect of the OGF–OGFr axis on cell cycle activity in human umbilical vein endothelial cells (HUVECs) and human epidermal keratinocytes (NHEKs). OGF markedly depressed cell proliferation of both cell lines by up to 40% of sterile water controls. Peptide treatment induced cyclin-dependent kinase inhibitor (CKI) p16INK4aprotein expression and p21WAF1/CIP1protein expression in HUVECs and NHEKs, but had no effect on p15, p18, p19, or p27 protein expression in either cell type. Inhibition of either p16INK4aor p21WAF1/CIP1activation by specific siRNAs blocked OGF inhibitory action. Human dermal fibroblasts and mesenchymal stem cells also showed a similar dependence of OGF action on p16INK4aand p21WAF1/CIP1. Collectively, these results indicate that both p16INK4aand p21WAF1/CIP1are required for the OGF–OGFr axis to inhibit cell proliferation in normal cells.
Virulence factors and biofilm production among Escherichia coli strains causing bacteraemia of urinary tract origin
Authors: Rijavec Matija , Müller-Premru Manca , Zakotnik Breda , Žgur-Bertok Darja
Published: October 2008

The aim of the present study was to gain an insight into the role of virulence determinants and biofilm production in bacteraemia of urinary tract origin. For this purpose 105 Escherichia coli isolates from patients with bacteraemia of urinary tract origin, isolated at the Institute of Microbiology and Immunology, University of Ljubljana, Slovenia, were investigated. A total of 88 strains (84 %) were isolated from immunocompromised patients and 17 (16 %) from non-immunocompromised patients. The prevalence of virulence factor (VF)-encoding genes and associations with phylogenetic background, antibiotic resistance, biofilm production and patient status were analysed by PCR and bioassay. Biofilm was produced by 55 (53 %) of the strains. No combination of VFs was highly associated with biofilm production. Of the tested VF-encoding genes, usp, papC and the adhesin-encoding sfa/foc were significantly more prevalent among strains from non-immunocompromised patients. Our results indicate that the uropathogenic specific protein (USP) may be, as judged by predominance and associations of the usp gene, an important VF contributing significantly to bacteraemia of urinary tract origin.
Molecular analysis of the Penicillium marneffei glyceraldehyde-3-phosphate dehydrogenase-encoding gene (gpdA) and differential expression of gpdA and the isocitrate lyase-encoding gene (acuD) upon internalization by murine macrophages
Authors: Thirach Sophit , Cooper Chester R. , Vanittanakom Nongnuch
Published: October 2008

Penicillium marneffei is an intracellular dimorphic fungus that can cause a fatal disseminated disease in human immunodeficiency virus-infected patients. The factors that affect the pathogenicity of this fungus remain unclear. Here, we report the isolation and characterization of the gpdA cDNA and genomic clones encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in P. marneffei. Phylogenetic analysis of GAPDH amino acid sequences demonstrated the evolutionary relationship of P. marneffei to other fungi, including the intracellular pathogen Ajellomyces capsulatus. To assess the central importance of phagocytic cells in defence against P. marneffei infection, we used Northern blotting to investigate the response of the isocitrate lyase-encoding gene (acuD) and gpdA to nutrient deprivation inside macrophages. The results revealed that after macrophage internalization, the gene involved in the glyoxylate cycle, acuD, showed higher expression levels as early as 2 h from the start of co-incubation, and the differential expression could be observed again at 8 h after infection. In contrast, the expression of gpdA was downregulated in the yeast phase, as well as during macrophage infection after 2, 4 and 8 h of infection. The induction of P. marneffei acuD was shown to be coordinated with the downregulation of the glycolytic gpdA gene, implying that the cytoplasmic environment of macrophages is deficient in glucose and the glyoxylate pathway could be used by this pathogen to allow subsistence on two-carbon compounds within the host cell following its intracellular persistence.
Attentional bias training and cue reactivity in cigarette smokers
Authors: Attwood Angela S. , O'Sullivan Hayley , Leonards Ute , Mackintosh Bundy , Munafò Marcus R.
Published: October 2008

Aims  Attentional bias for drug‐related cues has been associated with drug maintenance and relapse. We investigated whether attentional bias for smoking‐related stimuli could be altered using a modified visual probe task in cigarette smokers. We also sought to determine whether changes in attentional bias were associated with changes in subsequent craving and cue reactivity.

Participants  Male and female (n = 54) current smokers (≥5 cigarettes per day), aged between 18 and 40 years, were recruited from staff and students of the University of Bristol, and from the general population.

Design  Participants attended a single test session and completed an attentional training procedure in which they were either trained to attend to smoking‐related pictorial stimuli (attend group) or to neutral pictorial stimuli (avoid group). Group allocation was randomized.

Measurements  Following attentional training, participants underwent a smoking cue exposure procedure in which they were exposed to smoking‐related stimuli. Subjective measures of mood and craving were taken at baseline and before and after cue exposure. Participants then smoked a cigarette and smoking topography was measured.

Findings  Attentional training increased attentional bias among participants in the attend group, and decreased attentional bias among those in the avoid group. There were also differences between the attend and avoid groups in post‐training changes in craving during exposure to in vivo smoking cues, reflecting greater increases in craving in the attend group, although these effects were observed in males only.

Conclusions  These data are the first to show alterations in attentional bias for smoking‐related stimuli following a modified visual probe training procedure. Furthermore, post‐training group differences in subjective craving suggest potential clinical utility of training procedures, although these effects may operate only in males. Future research should investigate whether multiple training sessions enhance post‐training reductions in craving and cue reactivity, and the longer‐term persistence of training effects.
Counsellor behaviours and patient language during brief motivational interventions: a sequential analysis of speech
Authors: Gaume Jacques , Gmel Gerhard , Faouzi Mohamed , Daeppen Jean‐Bernard
Published: October 2008

Aims  To investigate empirically the hypothesized relationship between counsellor motivational interviewing (MI) skills and patient change talk (CT) by analysing the articulation between counsellor behaviours and patient language during brief motivational interventions (BMI) addressing at‐risk alcohol consumption.

Design  Sequential analysis of psycholinguistic codes obtained by two independent raters using the Motivational Interviewing Skill Code (MISC), version 2.0.

Setting  Secondary analysis of data from a randomized controlled trial evaluating the effectiveness of BMI in an emergency department.

Participants  A total of 97 patients tape‐recorded when receiving BMI.

Measurements  MISC variables were categorized into three counsellor behaviours (MI‐consistent, MI‐inconsistent and ‘other’) and three kinds of patient language (CT, counter‐CT (CCT) and utterances not linked with the alcohol topic). Observed transition frequencies, conditional probabilities and significance levels based on odds ratios were computed using sequential analysis software.

Findings  MI‐consistent behaviours were the only counsellor behaviours that were significantly more likely to be followed by patient CT. Those behaviours were significantly more likely to be followed by patient change exploration (CT and CCT) while MI‐inconsistent behaviours and ‘other’ counsellor behaviours were significantly more likely to be followed by utterances not linked with the alcohol topic and significantly less likely to be followed by CT. MI‐consistent behaviours were more likely after change exploration, whereas ‘other’ counsellor behaviours were more likely only after utterances not linked with the alcohol topic.

Conclusions  Findings lend support to the hypothesized relationship between MI‐consistent behaviours and CT, highlight the importance of patient influence on counsellor behaviour and emphasize the usefulness of MI techniques and spirit during brief interventions targeting change enhancement.
Early cannabis use and DSM‐IV nicotine dependence: a twin study
Authors: Agrawal Arpana , Lynskey Michael T. , Pergadia Michele L. , Bucholz Kathleen K. , Heath Andrew C. , Martin Nicholas G. , Madden Pamela A. F.
Published: October 2008

Background  Evidence suggests that cannabis users are at increased risk for cigarette smoking—if so, this may potentially be the single most alarming public health challenge posed by cannabis use. We examine whether cannabis use prior to age 17 years is associated with an increased likelihood of DSM‐IV nicotine dependence and the extent to which genetic and environmental factors contribute to this association.

Methods  A population‐based cohort of 24–36‐year‐old Australian male and female twins (n = 6257, 286 and 229 discordant pairs) was used. The co‐twin–control method, with twin pairs discordant for early cannabis use, was used to examine whether, after controlling for genetic and familial environmental background, there was evidence for an additional influence of early cannabis use on DSM‐IV nicotine dependence. Bivariate genetic models were fitted to the full data set to quantify the genetic correlation between early cannabis use and nicotine dependence.

Results  The early cannabis‐using twin was about twice as likely to report nicotine dependence, when compared to their co‐twin who had experimented with cigarettes but had never used cannabis. Even when analyses were restricted to cannabis users, earlier age cannabis use onset conferred greater risk (1.7) for nicotine dependence than did later onset. This association was governed largely by common genetic liability to early cannabis use and nicotine dependence, as demonstrated by genetic correlations of 0.41–0.52.

Conclusions  Early‐onset cannabis users are at increased risk for nicotine dependence, but this risk is attributable largely to common genetic vulnerability. There is no evidence for a causal relationship between cannabis use and nicotine dependence.
Association of serum interleukin‐33 level and the interleukin‐33 genetic variant with Japanese cedar pollinosis
Authors: Sakashita M. , Yoshimoto T. , Hirota T. , Harada M. , Okubo K. , Osawa Y. , Fujieda S. , Nakamura Y. , Yasuda K. , Nakanishi K. , Tamari M.
Published: October 2008

Background
IL‐33, an IL‐1‐like cytokine, is a ligand for IL1RL1, which is an important effector molecule of type 2 T helper responses. Although IL‐33/IL1RL1 interaction has been suggested to be important in induction of allergic airway inflammation, serum levels of IL‐33 and the genetic influences of the polymorphisms of IL‐33 in human allergic diseases are unclear.

Objective
The aim of this study was to examine whether the serum IL‐33 level and polymorphisms in IL‐33 are associated with Japanese cedar (JC) pollinosis, the most common form of allergic rhinitis, and a major public health problem, in Japan.

Methods
We performed linkage disequilibrium (LD) mapping of the gene using the HapMap database, and two selected tag single nucleotide polymorphisms were genotyped. We conducted an association study of IL‐33 (JC pollinosis, n=170; normal controls, n=100) and measured the IL‐33 levels in sera of the 270 subjects by ELISA.

Results
Serum levels of IL‐33 were significantly higher in patients with JC pollinosis (P=0.0018) than in controls. In genetic association analysis, we found a positive association between the polymorphism and JC pollinosis (P=0.048).

Conclusion
Our results support a role for IL‐33 in the pathogenesis of JC pollinosis.
Effect of muramyl peptides on mitochondrial respiration
Authors: El-Jamal N , Bahr G M , Echtay K S
Published: October 2008

Muramyl peptides have been shown to exert several biological activities including potentiation of humoral and cell-mediated immunity and stimulation of natural resistance. The mode of action of muramyl peptides has not been elucidated fully and the immunological activities of some derivatives have been associated with toxic effects, including pyrogenicity and inflammatory reactions. Nevertheless, the impact of muramyl peptides on mitochondrial respiration has never been addressed. In this study, the in vitro effects of muramyl peptides on rat liver mitochondria were examined. Toxic muramyl peptides induced a significant decrease in respiratory control ratio versus non-toxic analogues. These results were confirmed by in vivo studies in mice and were extended to mitochondria isolated from spleens. Our data address, for the first time, the effect of muramyl peptides on mitochondrial bioenergetics. Further studies are required to reveal the mechanism of mitochondrial toxicity in relation to the damaging effects of toxic muramyl peptides.