bluuebunny/crossref_metadata_2025 huggingface dataset:
A possible role for AMP-activated protein kinase in exercise-induced glucose utilization: insights from humans and transgenic animals
Authors: Nielsen J.N. , Jørgensen S.B. , Frøsig C. , Viollet B. , Andreelli F. , Vaulont S. , Kiens B. , Richter E.A. , Wojtaszewski J.F.P.
Published: December 2008

Exercise-induced glucose uptake in skeletal muscle is mediated by an insulin-independent mechanism, but the actual signals to glucose transport in response to muscle contraction have not been identified. The 5´-AMP-activated protein kinase (AMPK) has emerged as a putative mediator of contraction-induced glucose transport, although no conclusive evidence has been provided so far. Recent experiments in AMPK transgenic mice suggest that glucose transport induced by 5-amino-4-imidazolecarboxamide riboside (AICAR) or hypoxia is mediated by AMPK. In contrast, contraction-induced glucose transport in rodent skeletal muscle induced by electrical stimulation in vitro or in situ is not influenced or is only partially reduced by abolishing both or one of the catalytic AMPK subunits. This is compatible with exercise studies done in humans, where no tight correlation is found between AMPK activity and glucose uptake during exercise. Taken together, these results question an essential role of AMPK in exercise-induced glucose uptake and imply that one or more additional pathways are involved in mediating glucose transport in skeletal muscle during exercise.
Role of AMP-activated protein kinase in leptin-induced fatty acid oxidation in muscle
Authors: Minokoshi Y. , Kahn B.B.
Published: December 2008

Leptin regulates energy homoeostasis through central and peripheral mechanisms. Initial steps in leptin action include signalling through a cytokine-like receptor which activates the JAK/STAT pathway. We investigated whether the metabolic effects of leptin in muscle could be mediated by the AMP-activated protein kinase (AMP kinase). Through studies involving leptin injection intrahypothalamically or intravenously, as well as incubation of soleus muscle or cultured muscle cells with leptin, we determined that leptin stimulates fatty acid oxidation in skeletal muscle by activating AMP kinase. Leptin exerts this effect directly at the level of muscle and also through the hypothalamic sympathetic nervous system, specifically engaging α-adrenergic receptors in muscle. This represents a novel and important pathway mediating leptin's metabolic actions.
New targets of AMP-activated protein kinase
Authors: Hue L. , Beauloye C. , Bertrand L. , Horman S. , Krause U. , Marsin A.-S. , Meisse D. , Vertommen D. , Rider M.H.
Published: December 2008

The discovery of the AMP-activated protein kinase (AMPK) more than a decade ago has shed much light on the cellular response to stresses characterized by a fall in the concentration of ATP and an increase in the AMP/ATP ratio. All conditions known to increase this ratio activate AMPK, whose major role is to act as an emergency signal to conserve ATP. It does so by inhibiting anabolic processes and by activating pathways producing ATP. In recent years, our laboratory has discovered new targets of AMPK. The purpose of this short review is to summarize our contribution to this field.
AMP-activated protein kinase and hepatic genes involved in glucose metabolism
Authors: Ferré P. , Azzout-Marniche D. , Foufelle F.
Published: December 2008

Mammalian AMP-activated protein kinase presents strong structural and functional similarities with the yeast sucrose non-fermenting 1 (Snf1) kinase involved in the derepression of glucose-repressed genes. It is now clearly established that AMP-activated protein kinase in the liver decreases glycolytic/lipogenic gene expression as well as genes involved in hepatic glucose production. This is achieved through a decreased transcriptional efficiency of transcription factors such as sterol-regulatory-element-binding protein-1c, carbohydrate-response-element-binding protein, hepatocyte nuclear factor 4α or forkhead-related protein. Clearly, the long-term consequences of AMP-activated protein kinase activation have to be taken into account if activators of this enzyme are to be designed as anti-diabetic drugs.
Identification and characterization of AMPK γ3 mutations in the pig
Authors: Andersson L.
Published: December 2008

The RN− (rendement Napole, French for Napole yield) phenotype is common in Hampshire pigs and is characterized by a 70% increase in glycogen content in skeletal muscle and large effects on meat characteristics (pH, water content, technological yield and lean meat content). The phenotype is controlled by an autosomal dominant allele designated RN−. The protein kinase AMP-activated γ3 subunit gene, PRKAG3, which encodes the γ3 isoform of AMP-activated protein kinase (AMPK), was identified as the causative gene for this phenotype by a pure positional cloning approach. There are now several lines of evidence supporting our interpretation that the RN− phenotype is caused by a missense mutation (Arg200→Gln) in PRKAG3. Recent data from another group have revealed the presence of a third functional allele at the PRKAG3 locus, probably caused by a Val199→Ile missense mutation. This allele has opposite effects compared with RN, as it is associated with a low glycogen content. We have confirmed the phenotypic effect of this third allele in a meat-quality study of a Hampshire/Landrace intercross. A physiological characterization of RN− carriers and normal pigs showed that the RN− pigs utilized glycogen during exercise to the same extent as normal pigs and they showed a significantly faster resynthesis of glycogen after exercise. The results strongly suggest that the Arg200→Gln substitution is not associated with a defect in glycogen degradation, but rather with an increased glucose uptake in skeletal muscle.
The RAD30 cancer susceptibility gene
Authors: Carty M.P. , Glynn M. , Maher M. , Smith T. , Yao J. , Dixon K. , McCann J. , Rynn L. , Flanagan A.
Published: December 2008

The human skin cancer-prone disease xeroderma pigmentosum variant (XPV) results from a mutation in RAD30, which encodes the novel lesion bypass DNA polymerase η. XPV cells are characterized by delayed completion of DNA replication and increased mutagenesis following UV irradiation. In cell-free extracts of XPV lymphoblasts, functional DNA polymerase η is required for the complete replication of a double-stranded plasmid containing either a single (6–4) photoproduct or a cyclobutane pyrimidine dime(CPD), the major mutagenic UV-induced lesion. In cultured XPV cells, replication arrest activates downstream signalling pathways, leading to hyperphosphorylation of the 34-kDa subunit of the trimeric single-stranded DNA-binding protein, RPA (replication protein A). Many of the RAD30 mutations identified in XPV cells result in truncation and inactivation of DNA polymerase η. To examine whether polymorphisms in the RAD30 gene that result in altered polymerase η function, rather than enzyme inactivation, might contribute to individual susceptibility to skin cancer, methods to screen for sequence changes in the RAD30 gene in human genomic DNA have been developed.
Obesity and diabetes: lipids, ‘nowhere to run to'
Authors: Hill Margaret J. , Metcalfe David , McTernan Philip G.
Published: December 2008

Although specific pathogenic entities contributing to diabetic risk, such as central adiposity, ectopic fat accumulation, hyperlipidaemia and inflammation, are well-characterized, the response of cellular systems to such insults are less well understood. This short review highlights the effect of increasing fat mass on ectopic fat accumulation, the role of triacylglycerols (triglycerides) in Type 2 diabetes mellitus and cardiovascular disease pathogenesis, and selected current therapeutic strategies used to ameliorate these risk factors.
Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes
Authors: Jin Wanzhu , Patti Mary-Elizabeth
Published: December 2008

T2DM (Type 2 diabetes mellitus) has reached epidemic proportions worldwide, exerting major health consequences at an individual and public health level alike. Unfortunately, the molecular pathophysiology of diabetes remains incompletely understood, impairing progress towards more effective prevention and treatment strategies. Although the rapid increase in the prevalence of insulin resistance and T2DM over the past several decades highlights a major environmental contribution related to overnutrition, obesity and inactivity, susceptibility is likely to reflect individual differences in complex gene–environment interactions. In the present review, we focus on mediators of genetic and environmental risk for T2DM at a molecular level.
Enabling ab initio Hessian and frequency calculations of large molecules
Authors: Rahalkar Anuja P. , Ganesh V. , Gadre Shridhar R.
Published: December 2008

A linear scaling method, termed as cardinality guided molecular tailoring approach, is applied for the estimation of the Hessian matrix and frequency calculations of spatially extended molecules. The method is put to test on a number of molecular systems largely employing the Hartree–Fock and density functional theory for a variety of basis sets. To demonstrate its ability for correlated methods, we have also performed a few test calculations at the Møller–Plesset second order perturbation theory. A comparison of central processing unit and memory requirements for medium-sized systems with those for the corresponding full ab initio computation reveals substantial gains with negligible loss of accuracy. The technique is further employed for a set of larger molecules, Hessian and frequency calculations of which are not possible on commonly available personal-computer-type hardware.
An ab initio/Rice–Ramsperger–Kassel–Marcus prediction of rate constant and product branching ratios for unimolecular decomposition of propen-2-ol and related H+CH2COHCH2 reaction
Authors: Zhou Chong-Wen , Li Ze-Rong , Liu Cun-Xi , Li Xiang-Yuan
Published: December 2008

Enols have been found to be important intermediates in the combustion flames of hydrocarbon [C. A. Taatjes et al., Science 308, 1887 (2005)]. The removal mechanism of enols in combustion flame has not been established yet. In this work, the potential energy surface for the unimolecular decomposition of syn-propen-2-ol and H+CH2COHCH2 recombination reactions have been first investigated by CCSD(T) method. The barrier heights, reaction energies, and geometrical parameters of the reactants, products, intermediates, and transition states have been investigated theoretically. The results show that the formation of CH3CO+CH3 via the CH3COCH3 intermediate is dominant for the unimolecular decomposition of syn-propen-2-ol and its branching ratio is over 99% in the whole temperature range from 700 to 3000 K, and its rate constant can be expressed as an analytical form in the range of T=700–3000 K at atmospheric pressure. This can be attributed to the lower energy barrier of this channel compared to the other channels. The association reaction of H with CH2COHCH2 is shown to be a little more complicated than the unimolecular decomposition of syn-propen-2-ol. The channel leading to CH3CO+CH3 takes a key role in the whole temperature range at atmospheric pressure. However at the higher pressure of 100 atm, the recombination by direct formation of syn-propen-2-ol through H addition is important at T<1000 K. In the range of T>1400 K, the recombination channel leading to CH3CO+CH3 turns out to be significant.
Optimal nuclear magnetic resonance excitation schemes for the central transition of a spin 3/2 in the presence of residual quadrupolar coupling
Authors: Lee Jae-Seung , Regatte Ravinder R. , Jerschow Alexej
Published: December 2008

Optimal control theory is applied for enhancing the intensity of the central peak of a spin 3/2 signal in the presence of a residual quadrupolar coupling. While a maximum enhancement is always possible in the regime ωrf⪡ωQ via the use of modulated and shaped pulses, the intermediate rf-power regime ωrf∼ωQ does not admit simple solutions based on intuition. In this work we present optimized shaped pulses that have been derived using an optimization algorithm based on optimal control and test these with N23a NMR in this regime. In addition to enhancing the intensity of the central transition signal, the satellite peaks can be effectively suppressed, which is a useful feature for the implementation in N23a imaging sequences.
Interplay among multidressed four-wave mixing processes
Authors: Zheng Huaibin , Zhang Yanpeng , Nie Zhiqiang , Li Changbiao , Chang Hong , Song Jianping , Xiao Min
Published: December 2008

We report our experimental studies of interplays between four-wave mixing (FWM) processes in multidressed two- and three-level atomic systems. The Autler–Townes splitting of the FWM signal within the electromagnetically induced transparency window has been experimentally observed. Under the same experimental conditions in different energy-level systems, the dressing effects strongly depend on the dipole moments of the transitions, which can provide an easy and qualitative way to determine the orders of magnitude of the effective dipole moments for different transitions by comparing the FWM suppressing effects.
Long-range multipolar potentials of the 18 spin-orbit states arising from the C(P3)+OH(X Π2) interaction
Authors: Bussery-Honvault Béatrice , Dayou Fabrice , Zanchet Alexandre
Published: December 2008

We present multipolar potentials at large intermolecular distances for the 18 doubly degenerate spin-orbit states arising from the interaction between the two open-shell systems, C(P3) and OH(X Π2). With OH fixed at its ground vibrational state-averaged distance r0, the long-range potentials are two-dimensional potential energy surfaces (PESs) that depend on the intermolecular distance R and the angle γ=CĜH, where G represents the mass center of OH. The 18×18 diabatic potential matrix elements are built up from the perturbation theory up to second order and from a two-center expansion of the Coulombic interaction potential, resulting in a multipolar expansion of the potential expressed as a series of terms varying in R−n. The expressions for the long-range coefficients of the expansion are explicitly given in terms of monomer properties such as permanent multipole moments, and static and dynamic polarizabilities. Accurate values for the monomer properties are used to properly determine the long-range interaction coefficients. The diagonalization of the full 18×18 potential matrix generates adiabatic long-range PESs in good agreement with their ab initio counterparts.
A new crossover sine model based on trigonometric model and its application to the crossover lattice equation of state
Authors: Lee Yongjin , Shin Moon Sam , Kim Hwayong
Published: December 2008

In this study, a new crossover sine model (CSM) n was developed from a trigonometric model [M. E. Fisher, S. Zinn, and P. J. Upton, Phys. Rev. B 59, 14533 (1999)]. The trigonometric model is a parametric formulation model that is used to represent the thermodynamic variables near a critical point. Although there are other crossover models based on this trigonometric model, such as the CSM and the analytical sine model, which is an analytic formulation of the CSM, the new sine model (NSM) employs a different approach from these two models in terms of the connections between the parametric variables of the trigonometric model and thermodynamic variables. In order to test the performance of the NSM, the crossover lattice equation of state [M. S. Shin, Y. Lee, and H. Kim, J. Chem. Thermodyn. 40, 174 (2008)] was applied using the NSM for correlations of various pure fluids and fluid mixtures. The results showed that over a wide range of states, the crossover lattice fluid (xLF)/NSM yields the saturated properties of pure fluids and the phase behavior of binary mixtures more accurately than the original lattice equation of state. Moreover, a comparison with the crossover lattice equation of state using the CSM (xLF/CSM) showed that the new model presents good correlation results that are comparable to the xLF/CSM.
Solving the structure of reaction intermediates by time-resolved synchrotron x-ray absorption spectroscopy
Authors: Wang Qi , Hanson Jonathan C. , Frenkel Anatoly I.
Published: December 2008

We present a robust data analysis method of time-resolved x-ray absorption spectroscopy experiments suitable for chemical speciation and structure determination of reaction intermediates. Chemical speciation is done by principal component analysis (PCA) of the time-resolved x-ray absorption near-edge structure data. Structural analysis of intermediate phases is done by theoretical modeling of their extended x-ray absorption fine-structure data isolated by PCA. The method is demonstrated using reduction and reoxidation of Cu-doped ceria catalysts where we detected reaction intermediates and measured fine details of the reaction kinetics. This approach can be directly adapted to many time-resolved x-ray spectroscopy experiments where new rapid throughput data collection and analysis methods are needed.
Simultaneous particle-image velocimetry–planar laser-induced fluorescence measurements of Richtmyer–Meshkov instability growth in a gas curtain with and without reshock
Authors: Balakumar B. J. , Orlicz G. C. , Tomkins C. D. , Prestridge K. P.
Published: December 2008

The structure of the concentration and velocity fields in a light-heavy-light fluid layer subjected to an impulsive acceleration by a shock wave (Richtmyer–Meshkov instability) is studied using simultaneous particle-image velocimetry and planar laser-induced fluorescence (PLIF) measurements (performed in such flows for the first time). The initial condition prior to shock impact is accurately characterized using calibrated PLIF measurements to enable comparisons of the evolving structure to numerical simulations. Experiments performed on a SF6 curtain in air (Atwood number, At=0.67), after single shock by a Mach 1.2 shock wave and reshock by the reflected wave, show that the reshock wave has a dramatic impact on the evolution of the unstable structure. After first shock and in the absence of reshock(s), the structure widths agree well with an analytical extension to the nonlinear point vortex model [J. W. Jacobs et al., “Nonlinear growth of the shock-accelerated instability of a thin fluid layer,” J. Fluid Mech. 295, 23 (1995)] that accounts for the nonuniform spacing of the row of counter-rotating vortices that drive the flow. However, upon reshock, the width deviates significantly from the singly shocked case, and a substantial rise in the growth rate is observed. Enhanced mixing, destruction of the ordered velocity field, and an increase in both the positive and negative circulations ensue. Large velocity fluctuations relative to the mean flow, and the advection of a wide spectrum of vortex scales combine to mix the flow well and create turbulent conditions in the reshocked structure.
All ink-jet-printed carbon nanotube thin-film transistor on a polyimide substrate with an ultrahigh operating frequency of over 5 GHz
Authors: Vaillancourt Jarrod , Zhang Haiyan , Vasinajindakaw Puminun , Xia Haitao , Lu Xuejun , Han Xuliang , Janzen Daniel C. , Shih Wu-Sheng , Jones Carissa S. , Stroder Mike , Chen Maggie Yihong , Subbaraman Harish , Chen Ray T. , Berger Urs , Renn Mike
Published: December 2008

We report a flexible carbon nanotube (CNT) thin-film transistor (TFT) fabricated solely by ink-jet printing technology. The TFT is top gate configured, consisting of source and drain electrodes, a carrier transport layer based on an ultrapure, high-density (>1000 CNTs/μm2) CNT thin film, an ion-gel gate dielectric layer, and a poly(3,4-ethylenedioxythiophene) top gate electrode. All the TFT elements are ink-jet printed at room temperature on a polyimide substrate without involving any photolithography patterning or surface pretreatment steps. This CNT-TFT exhibits a high operating frequency of over 5 GHz and an on-off ratio of over 100. Such an all-ink-jet-printed process eliminates the need for lithography, vacuum processing, and metallization procedures and thus provides a promising technology for low-cost, high-throughput fabrication of large-area high-speed flexible electronic circuits on virtually any desired flexible substrate.
The ground state correlation energy of the random phase approximation from a ring coupled cluster doubles approach
Authors: Scuseria Gustavo E. , Henderson Thomas M. , Sorensen Danny C.
Published: December 2008

We present an analytic proof demonstrating the equivalence between the random phase approximation (RPA) to the ground state correlation energy and a ring-diagram simplification of the coupled cluster doubles (CCD) equations. In the CCD framework, the RPA equations can be solved in O(N4) computational effort, where N is proportional to the number of basis functions.
Measuring far-ultraviolet whispering gallery modes with high energy electrons
Authors: Hyun J. K. , Couillard M. , Rajendran P. , Liddell C. M. , Muller D. A.
Published: December 2008

Dielectric nanospheres are important components for photonic applications, where interactions between whispering gallery modes (WGMs) can be used to construct photonic band structures. Using the electromagnetic fields generated by relativistic electrons in a monochromated 200 keV scanning transmission electron microscope, we record electron energy loss spectral features reflecting the density of states (DOS) of the electric-type WGMs in SiO2 nanospheres over an energy range extending into the far-ultraviolet regime. These results demonstrate possibilities for mapping the local DOS of photonic systems in an electron microscope with a spatial resolution of a few nanometers.
Nanobending of nanowires: A molecular dynamics study
Authors: Yan Y. D. , Zhang J. J. , Sun T. , Fei W. D. , Liang Y. C. , Dong S.
Published: December 2008

Three-dimensional molecular dynamics simulations of the nanobending of copper nanowires are carried out. Simulation results show that the loading and unloading cycles of the nanobending test can reveal the full spectrum of the nanowires’ mechanical properties. Up-tensile and bottom-compressive features have been observed along with the neck zone formation. Amorphous region formation is the mechanism of fracture and final breakage. The measured elastic modulus and yield stress are 49 and 7.6 GPa, respectively. Moreover, the effect of the adhesion on the nanobending process is revealed.
Room temperature ferromagnetism in carbon-implanted ZnO
Authors: Zhou Shengqiang , Xu Qingyu , Potzger Kay , Talut Georg , Grötzschel Rainer , Fassbender Jürgen , Vinnichenko Mykola , Grenzer Jörg , Helm Manfred , Hochmuth Holger , Lorenz Michael , Grundmann Marius , Schmidt Heidemarie
Published: December 2008

Unexpected ferromagnetism has been observed in carbon doped ZnO films grown by pulsed laser deposition [H. Pan et al., Phys. Rev. Lett. 99, 127201 (2007)]. In this letter, we introduce carbon into ZnO films by ion implantation. Room temperature ferromagnetism has been observed. Our analysis demonstrates that (1) C-doped ferromagnetic ZnO can be achieved by an alternative method, i.e., ion implantation, and (2) the chemical involvement of carbon in the ferromagnetism is indirectly proven.
Wavevector filtering through single-layer and bilayer graphene with magnetic barrier structures
Authors: Masir M. Ramezani , Vasilopoulos P. , Peeters F. M.
Published: December 2008

We show that the angular range of the transmission through magnetic barrier structures can be efficiently controlled in single-layer and bilayer graphenes and this renders the structure’s efficient wavevector filters. As the number of magnetic barriers increases, this range shrinks, the gaps in the transmission versus energy become wider, and the conductance oscillates with the Fermi energy.
Infrared spectroscopy of the interface charge in a ZnO field-effect transistor
Authors: Kim Jooyoun , Jung SungHoon , Choi E. J. , Kim Kitae , Lee Kimoon , Im Seongil
Published: December 2008

We used far-infrared transmission spectroscopy to probe the electrostatically induced charge carriers in a ZnO field-effect transistor. The carrier absorption spectrum exhibits a non-Drude, incoherent conduction behavior at low gate-source voltages (VGS<40V), which evolves toward a standard Drude behavior as VGS is increased. This change is explained successfully by a generalized Drude model. We find that the interface carriers undergo strong backscattering collisions during the channel conduction and the microscopic scattering angle changes with VGS.
Demonstration of multilevel cell spin transfer switching in MgO magnetic tunnel junctions
Authors: Lou Xiaohua , Gao Zheng , Dimitrov Dimitar V. , Tang Michael X.
Published: December 2008

Multilevel cell is an important concept to improve the density of spin transfer torque memory. We demonstrated two-bit multilevel cell spin transfer switching using MgO-based magnetic tunnel junctions. Two types of cell structural design are discussed. Multiple resistance levels are depicted in a current-driven spin transfer switching loop, which shows a switching current density of ∼2×106A∕cm2. Reversible transitions between high and low states of the soft bit are achieved using minor-loop spin transfer switching. The influence of external magnetic field to spin transfer switching is also discussed.
Points of View: Where Do We Look When We Watch TV?
Authors: Brasel S Adam , Gips James
Published: December 2008

How is our gaze dispersed across the screen when watching television? An exploratory eyetracker study with a custom-designed show indicated a very strong center-of-screen bias with gaze points following a roughly normal distribution peaked near screen center. Examining the show across time revealed that people were rarely all looking at the same location, and the amount of gaze dispersion within frames was highly variable. Different forms of programming yielded different levels of dispersion: static network ‘bumpers’ created the tightest visual groupings, and gaze dispersion for frames with show content was less than the dispersion for commercials. Advertising frames with brand logos generated higher dispersion than the non-branded advertisement portions, and repeated advertisements generated higher dispersion than their first-run counterparts.
Odours Grab His Hand but Not Hers
Authors: Tubaldi Federico , Ansuini Caterina , Tirindelli Roberto , Castiello Umberto
Published: December 2008

Gender is important for the determination of olfactory abilities. Previous reports on gender differences in human odour perception claimed that the sensitivity and discrimination ability of females for odours is superior to that of males. Evolutionary theories, however, open up the possibility of an interesting dissociation between females and males in terms of odour processing: there is an advantage for women for the perceptual aspects of olfactory stimuli and an advantage for men when translating perceptual olfactory information into action. In line with this hypothesis our observations suggest that encoding odours has the ability to guide the movement of males but not that of females.
The transcript abundance of an expansin gene in ripe sapodilla (Manilkara zapota) fruit is negatively regulated by ethylene
Authors: Kunyamee Sutin , Ketsa Saichol , Imsabai Wachiraya , van Doorn Wouter G.
Published: December 2008

After harvest, mature fruit of sapodilla (Manilkara zapota van Royen) exhibit rapid softening. The decrease in fruit firmness was hastened by ethylene and delayed by 1-methylcyclopropene (1-MCP). Two genes encoding expansins (called MzEXP1 and MzEXP2) were isolated. In both cultivars studied (Makok-Yai and Kra-Suay), MzEXP1 was transiently expressed early during fruit development on the plant. This suggests that it is involved in cell wall loosening during early fruit growth. In cv. Makok-Yai, MzEXP2 was expressed between 1 day before harvest and day 4 after harvest. In cv. Kra-Suay, the expression of MzEXP2 started 8 weeks before the normal harvest stage, and ended on day 3 after harvest. When the fruit of both cultivars was treated with ethylene (50 µL L−1 for 20 h at 25°C) just after harvest, the expression of MzEXP2 became undetectable. After treatment with 1-MCP MzEXP2 mRNA was highly abundant until day 5 after harvest, when in controls the transcript abundance had become undetectable. The onset of MzEXP2 expression seems not regulated by ethylene, as the concomitant ethylene levels are very low. The data strongly indicate that the decrease of MzEXP2 transcript abundance is due to ethylene production by the fruit, which is by then high. The expression of MzEXP2 ceased, both in controls and in ethylene-treated material, when the fruit had reached a rather low threshold firmness. The data suggest that the protein has a supporting and cooperative role in fruit softening.
Identification of grapevine MLO gene candidates involved in susceptibility to powdery mildew
Authors: Feechan Angela , Jermakow Angelica M. , Torregrosa Laurent , Panstruga Ralph , Dry Ian B.
Published: December 2008

The European cultivated grapevine, Vitis vinifera L., is a host for the powdery mildew pathogen Erisyphe necator, which is the most economically important fungal disease of viticulture. MLO proteins mediate powdery mildew susceptibility in the model plant species Arabidopsis and the crop plants barley and tomato. Seven VvMLO cDNA sequences were isolated from grapevine and were subsequently identified as part of a 17 member VvMLO gene family within the V. vinifera genome. Phylogenetic analysis of the 17 VvMLO genes in the grape genome indicated that the proteins they encode fall into six distinct clades. The expression of representative VvMLOs from each clade were analysed in a range of grape tissues, as well as in response to a range of biotic and abiotic factors. The VvMLOs investigated have unique, but overlapping tissue expression patterns. Expression analysis of VvMLO genes following E. necator infection identified four upregulated VvMLOs which are orthologous to the Arabidopsis AtMLO2, AtMLO6 and AtMLO12 and tomato SlMLO1 genes required for powdery mildew susceptibility. This suggests a degree of functional redundancy between the proteins encoded by these genes in terms of susceptibility to powdery mildew, and, as such, represent potential targets for modification to generate powdery mildew resistant grapevines.
Habitat selection by European badgers at multiple spatial scales in Portuguese Mediterranean ecosystems
Authors: Santos Maria J. , Beier Paul
Published: December 2008

Different habitat features can limit animal populations at different spatial scales. We examined habitat selection by Eurasian badger in a montado landscape in southern Portugal at four scales: core area (1 km2), home range (4 km2), social group territory (25 km2), and local population (100 km2). Our goals were to identify important habitats for conservation at each spatial scale (cell size) using candidate variables shown to be important by previous research. As expected, across all scales, badger occurrence was consistently and strongly correlated with dominance of cork oak and deciduous woodlands, and badgers seemed to avoid cultivated fields. Contrary to expectation, monocultures of conifers contributed positively to badger detection. The predictive ability of the models was poor at all scales, probably owing to our inability to include factors such as food, competitors, predators, undercover vegetation, and roads. Nonetheless, the models illustrate the importance to badgers of the montado, an ancient human-modified ecosystem that is threatened by current European Union agricultural conversion policies.
Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3
Authors: Baird Dan , Stefan Chris , Audhya Anjon , Weys Sabine , Emr Scott D.
Published: December 2008

The phosphoinositide phosphatidylinositol 4-phosphate (PtdIns4P) is an essential signaling lipid that regulates secretion and polarization of the actin cytoskeleton. In Saccharomyces cerevisiae, the PtdIns 4-kinase Stt4 catalyzes the synthesis of PtdIns4P at the plasma membrane (PM). In this paper, we identify and characterize two novel regulatory components of the Stt4 kinase complex, Ypp1 and Efr3. The essential gene YPP1 encodes a conserved protein that colocalizes with Stt4 at cortical punctate structures and regulates the stability of this lipid kinase. Accordingly, Ypp1 interacts with distinct regions on Stt4 that are necessary for the assembly and recruitment of multiple copies of the kinase into phosphoinositide kinase (PIK) patches. We identify the membrane protein Efr3 as an additional component of Stt4 PIK patches. Efr3 is essential for assembly of both Ypp1 and Stt4 at PIK patches. We conclude that Ypp1 and Efr3 are required for the formation and architecture of Stt4 PIK patches and ultimately PM-based PtdIns4P signaling.
Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy
Authors: Cowling Belinda S. , McGrath Meagan J. , Nguyen Mai-Anh , Cottle Denny L. , Kee Anthony J. , Brown Susan , Schessl Joachim , Zou Yaqun , Joya Josephine , Bönnemann Carsten G. , Hardeman Edna C. , Mitchell Christina A.
Published: December 2008

Regulators of skeletal muscle mass are of interest, given the morbidity and mortality of muscle atrophy and myopathy. Four-and-a-half LIM protein 1 (FHL1) is mutated in several human myopathies, including reducing-body myopathy (RBM). The normal function of FHL1 in muscle and how it causes myopathy remains unknown. We find that FHL1 transgenic expression in mouse skeletal muscle promotes hypertrophy and an oxidative fiber-type switch, leading to increased whole-body strength and fatigue resistance. Additionally, FHL1 overexpression enhances myoblast fusion, resulting in hypertrophic myotubes in C2C12 cells, (a phenotype rescued by calcineurin inhibition). In FHL1-RBM C2C12 cells, there are no hypertrophic myotubes. FHL1 binds with the calcineurin-regulated transcription factor NFATc1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1), enhancing NFATc1 transcriptional activity. Mutant RBM-FHL1 forms aggregate bodies in C2C12 cells, sequestering NFATc1 and resulting in reduced NFAT nuclear translocation and transcriptional activity. NFATc1 also colocalizes with mutant FHL1 to reducing bodies in RBM-afflicted skeletal muscle. Therefore, via NFATc1 signaling regulation, FHL1 appears to modulate muscle mass and strength enhancement.
PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling
Authors: Nikonenko Irina , Boda Bernadett , Steen Sylvain , Knott Graham , Welker Egbert , Muller Dominique
Published: December 2008

Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ2 domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA–mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS–PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons.
Assembly of normal actomyosin rings in the absence of Mid1p and cortical nodes in fission yeast
Authors: Huang Yinyi , Yan Hongyan , Balasubramanian Mohan K.
Published: December 2008

Cytokinesis in many eukaryotes depends on the function of an actomyosin contractile ring. The mechanisms regulating assembly and positioning of this ring are not fully understood. The fission yeast Schizosaccharomyces pombe divides using an actomyosin ring and is an attractive organism for the study of cytokinesis. Recent studies in S. pombe (Wu, J.Q., V. Sirotkin, D.R. Kovar, M. Lord, C.C. Beltzner, J.R. Kuhn, and T.D. Pollard. 2006. J. Cell Biol. 174:391–402; Vavylonis, D., J.Q. Wu, S. Hao, B. O'Shaughnessy, and T.D. Pollard. 2008. Science. 319:97–100) have suggested that the assembly of the actomyosin ring is initiated from a series of cortical nodes containing several components of this ring. These studies have proposed that actomyosin interactions bring together the cortical nodes to form a compacted ring structure. In this study, we test this model in cells that are unable to assemble cortical nodes. Although the cortical nodes play a role in the timing of ring assembly, we find that they are dispensable for the assembly of orthogonal actomyosin rings. Thus, a mechanism that is independent of cortical nodes is sufficient for the assembly of normal actomyosin rings.
FoxK mediates TGF-β signalling during midgut differentiation in flies
Authors: Casas-Tinto Sergio , Gomez-Velazquez Melisa , Granadino Begoña , Fernandez-Funez Pedro
Published: December 2008

Inductive signals across germ layers are important for the development of the endoderm in vertebrates and invertebrates (Tam, P.P., M. Kanai-Azuma, and Y. Kanai. 2003. Curr. Opin. Genet. Dev. 13:393–400; Nakagoshi, H. 2005. Dev. Growth Differ. 47:383–392). In flies, the visceral mesoderm secretes signaling molecules that diffuse into the underlying midgut endoderm, where conserved signaling cascades activate the Hox gene labial, which is important for the differentiation of copper cells (Bienz, M. 1997. Curr. Opin. Genet. Dev. 7:683–688). We present here a Drosophila melanogaster gene of the Fox family of transcription factors, FoxK, that mediates transforming growth factor β (TGF-β) signaling in the embryonic midgut endoderm. FoxK mutant embryos fail to generate midgut constrictions and lack Labial in the endoderm. Our observations suggest that TGF-β signaling directly regulates FoxK through functional Smad/Mad-binding sites, whereas FoxK, in turn, regulates labial expression. We also describe a new cooperative activity of the transcription factors FoxK and Dfos/AP-1 that regulates labial expression in the midgut endoderm. This regulatory activity does not require direct labial activation by the TGF-β effector Mad. Thus, we propose that the combined activity of the TGF-β target genes FoxK and Dfos is critical for the direct activation of lab in the endoderm.
Traction stress in focal adhesions correlates biphasically with actin retrograde flow speed
Authors: Gardel Margaret L. , Sabass Benedikt , Ji Lin , Danuser Gaudenz , Schwarz Ulrich S. , Waterman Clare M.
Published: December 2008

How focal adhesions (FAs) convert retrograde filamentous actin (F-actin) flow into traction stress on the extracellular matrix to drive cell migration is unknown. Using combined traction force and fluorescent speckle microscopy, we observed a robust biphasic relationship between F-actin speed and traction force. F-actin speed is inversely related to traction stress near the cell edge where FAs are formed and F-actin motion is rapid. In contrast, larger FAs where the F-actin speed is low are marked by a direct relationship between F-actin speed and traction stress. We found that the biphasic switch is determined by a threshold F-actin speed of 8–10 nm/s, independent of changes in FA protein density, age, stress magnitude, assembly/disassembly status, or subcellular position induced by pleiotropic perturbations to Rho family guanosine triphosphatase signaling and myosin II activity. Thus, F-actin speed is a fundamental regulator of traction force at FAs during cell migration.
Quantification of Mesophyll Resistance and Apoplastic Ascorbic Acid as an Antioxidant for Tropospheric Ozone in Durum Wheat (Triticum durumDesf. cv. Camacho)
Authors: de la Torre Daniel
Published: December 2008

The daily variations in cellular and apoplastic ascorbic acid and dehydroascorbic acid levels in a Mediterranean durum wheat cultivar (Triticum durumDesf. cv. Camacho) were analyzed in order to relate them to ambient ozone exposure and to subsequent stomatally absorbed ozone fluxes. The aim of this study is to prove the effectiveness and accuracy of a computer model (SODA) to calculate the mesophyll resistance (rm) to ozone uptake, the percentage of ozone detoxification by apoplastic ascorbic acid, and the ozone flux to the plasmalemma (Fm) in a Mediterranean durum wheat cultivar. These calculated factors were related to apoplastic ascorbic acid levels and to ambient ozone concentrations. These relationships were obtained with a view to explaining the detoxification of ozone by apoplastic ascorbic acid. Ozone detoxifications of up to 52% were found at midday, when maximum ozone concentrations and maximum apoplastic ascorbic acid are seen. Mesophyll resistance was minimum at this time, and ozone flux to the plasmalemma was reduced because of the reaction of ozone with apoplastic ascorbic acid.
Critical role for constitutive type I interferon signaling in the prevention of cellular transformation
Authors: Chen Hui‐min , Tanaka Nobuyuki , Mitani Yukiko , Oda Eri , Nozawa Hiroaki , Chen Jian‐zhong , Yanai Hideyuki , Negishi Hideo , Choi Myoung Kwon , Iwasaki Toshiroh , Yamamoto Hiroyuki , Taniguchi Tadatsugu , Takaoka Akinori
Published: December 2008

Interferons‐α/β, which are produced upon viral infection, are key soluble factors for the establishment of an antiviral state, but are also produced at low levels in the absence of infection. Herein, we demonstrate that a weak signal by these constitutively produced IFN‐α/β show a preventive role in cellular transformation. Ifnar1‐deficient (Ifnar1−/–) MEF, which are devoid of IFN‐α/β signal, undergo a spontaneous transformation during long‐term cell culture. Similar to Irf1−/– MEF, primary Ifnar1−/– MEF become tumorigenic in nude mice by the expression of activated c‐Ha‐Ras oncoprotein. However, Ifnar1−/– MEF do not show any abnormal growth properties. A similar observation is made in Ifnb−/– MEF that fail to produce constitutive IFN‐α/β, whereas such a transforming property is not found in MEF that lack any of the IFN receptor downstream molecules including Stat1, IRF9 and IRF1. Furthermore, Ifnar1−/– mice develop chemically‐induced skin papilloma more severely than wild‐type mice. In addition, the expression levels of IFNAR1 mRNA are significantly decreased in human gastric cancer tissues. These results suggest a cell‐intrinsic role of the weak signal by constitutively produced IFN‐α/β to prevent cells from transformation, which may be mediated by a hitherto‐unknown pathway(s) downstream of the IFN‐α/β receptor. (Cancer Sci 2009; 100: 449–456)
Dysregulation of innate immunity: hereditary periodic fever syndromes
Authors: Bodar Evelien J. , Drenth Joost P. H. , Van Der Meer Jos W. M. , Simon Anna
Published: December 2008

The hereditary periodic fever syndromes encompass a rare group of diseases that have lifelong recurrent episodes of inflammatory symptoms and an acute phase response in common. Clinical presentation can mimic that of lymphoproliferative disorders and patients often go undiagnosed for many years. These syndromes follow an autosomal inheritance pattern, and the major syndromes are linked to specific genes, most of which are involved in regulation of the innate immune response through pathways of apoptosis, nuclear factor κΒ activation and cytokine production. In others, the link between the protein involved and inflammation is less clear. The recurrent inflammation can lead to complications, such as renal impairment due to amyloidosis and vasculitis, visual impairment, hearing loss, and joint destruction, depending on the specific syndrome. In recent years, treatment options for these diseases have improved significantly. Early establishment of an accurate diagnosis and start of appropriate therapy improves prognosis in these patients.
BCL2 protein expression in follicular lymphomas with t(14;18) chromosomal translocations
Authors: Masir Noraidah , Campbell Lisa J. , Goff Lindsey K. , Jones Margaret , Marafioti Teresa , Cordell Jacqueline , Clear Andrew J. , Lister T. Andrew , Mason David Y. , Lee Abigail M.
Published: December 2008

The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)‐positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 ‘pseudo‐negative’ cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these ‘pseudo‐negative’ cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo‐negative immunostaining.