bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural characterization and low temperature growth of ferromagnetic Bi–Cu codoped ZnO bicrystal nanowires
Authors: Xu C. , Chun J. , Kim D. , Chon B. , Joo T.
Published: October 2007

Ferromagnetic Bi–Cu codoped ZnO nanowires were fabricated at temperatures as low as 300°C via a vapor phase transport using the mixture of Zn, BiI3 and CuI powders. They are grown as a bicrystal, along the [011¯2] direction, have a width of 40–150nm, and a length of a few microns. The investigation of the growth mechanism proposes that the synergy of BiCu and iodine/iodide induces the formation of bicrystallinity. The photoluminescence measurement shows the cooperative effect of Bi and Cu ions. The ferromagnetism observed in this study is the result of the combined effect of structural defects, the substitution of Cu into Zn site along the c axis, and codoping of Bi.
Quantitative analysis of transient surface reactions on planar catalyst with time-resolved time-of-flight mass spectrometry
Authors: Okumura Kohei , Sakamoto Yoshiyuki , Kayama Tomoyuki , Kizaki Yoshimi , Shinjoh Hirofumi , Motohiro Tomoyoshi
Published: October 2007

A procedure for the quantitative analysis of transient surface catalytic reactions in millisecond time resolution has been studied constructing a specially designed apparatus employing (1) pulsed-gas valves for the injection of reactant molecules onto catalysts and (2) a time-of-flight mass spectrometer (TOF-MS) to detect every reaction product simultaneously. For a better understanding of the catalytic activity and selectivity for products quantitatively, a procedure for measuring an amount of reactant molecules injected onto catalyst surface and calibrating the intensity of mass signal were proposed and implemented. We tested the applicability of this procedure for the quantitative analysis of products of NO+H2 reaction on Pt–Al2O3 catalysts (a planar catalyst: Pt–Al2O3∕Si substrates inserted into a micro-tube-reactor with SiC balls). Although the surface area of the planar catalyst was very small, the mass signal intensities of the reaction products were found to be sufficient for the above procedure. We measured the fragmentation patterns and the inherent sensitivity factors in the TOF-MS using the mixture of the internal standard gas Ar and the N-containing gases. The relative sensitivity factors for NH3, N2, NO, and N2O and the relative intensities of fragment peaks to the molecular ion peak of H2O and N2O were estimated. The procedure constructed here has enabled us to analyze the transient consecutive secondary catalytic reactions as well as primary reactions based on the formation rate of product molecules per millisecond instead of the mass signal intensities of the reaction products.
Dislocation reduction in gallium nitride films using scandium nitride interlayers
Authors: Moram M. A. , Zhang Y. , Kappers M. J. , Barber Z. H. , Humphreys C. J.
Published: October 2007

We describe a method of reducing threading dislocation densities in 0001-oriented GaN from (5.0±0.5)×109cm−2to(3.1±0.4)×107cm−2 (for coalesced films) or to below 5×106cm−2 (for partially coalesced films) in a single step, without lithography. Lattice-matched, dislocation-blocking scandium nitride interlayers are deposited on a 500nm GaN-on-sapphire template. Dislocation-free GaN islands grown on the ScN interlayer nucleate both on the interlayer and on tiny areas of the GaN template exposed through openings in the interlayer. However, some dislocations are generated above the interlayer during subsequent island coalescence.
A new parallel plate shear cell for in situ real-space measurements of complex fluids under shear flow
Authors: Wu Yu Ling , Brand Joost H. J. , van Gemert Josephus L. A. , Verkerk Jaap , Wisman Hans , van Blaaderen Alfons , Imhof Arnout
Published: October 2007

We developed and tested a parallel plate shear cell that can be mounted on top of an inverted microscope to perform confocal real-space measurements on complex fluids under shear. To follow structural changes in time, a plane of zero velocity is created by letting the plates move in opposite directions. The location of this plane is varied by changing the relative velocities of the plates. The gap width is variable between 20 and 200μm with parallelism better than 1μm. Such a small gap width enables us to examine the total sample thickness using high numerical aperture objective lenses. The achieved shear rates cover the range of 0.02–103s−1. This shear cell can apply an oscillatory shear with adjustable amplitude and frequency. The maximum travel of each plate equals 1cm, so that strains up to 500 can be applied. For most complex fluids, an oscillatory shear with such a large amplitude can be regarded as a continuous shear. We measured the flow profile of a suspension of silica colloids in this shear cell. It was linear except for a small deviation caused by sedimentation. To demonstrate the excellent performance and capabilities of this new setup we examined shear induced crystallization and melting of concentrated suspensions of 1μm diameter silica colloids.
Structure-function relationships of conjugated polyelectrolyte electron injection layers in polymer light emitting diodes
Authors: Garcia Andres , Yang Renqiang , Jin Youngeup , Walker Bright , Nguyen Thuc-Quyen
Published: October 2007

The characteristics of conjugated polymer light-emitting diodes containing poly(2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylene vinylene) as the emissive layer and cationic or anionic conjugated polyelectrolytes (CPEs) as the electron injection layer are reported. Structure variations involving backbone, type of counterion, and charge were used to establish structure-function relationships. More efficient electron injection from Al and better device performance are attained with CPEs bearing negative charges. For cationic CPEs having the same counterion but different conjugated structures, one observes better device efficiency using the material with higher electron mobility. Thus, both charge and backbone are important for optimizing device performance.
Surface plasmon coupled fluorescence from copper substrates
Authors: Previte Michael J. R. , Zhang Yongxia , Aslan Kadir , Geddes Chris D.
Published: October 2007

Previously, we reported the observation of metal enhanced emission from copper nanoparticles. In this letter, we report the observation of surface plasmon coupled fluorescence (SPCF) or emission from thin copper (Cu) continuous films. Using Fresnel calculations to theoretically calculate the reflectance curves for polymethyl methacrylate films doped with sulforhodamine 101, we correlated the minimum reflectance angles for both s- and p-polarized lights with maximum fluorescence emission. These observations reveal that we can achieve SPCF with copper substrates and possibly design inexpensive copper substrates for fluorescent sensing applications and potentially, fluorescent based electrical signals and circuits.
Real-time detection, control, and sorting of microfluidic droplets
Authors: Niu Xize , Zhang Mengying , Peng Suili , Wen Weijia , Sheng Ping
Published: October 2007

We report the design and implementation of capacitive detection and control of microfluidic droplets in microfluidic devices. Integrated microfluidic chip(s) with detection/control circuit enables us to monitor in situ the individual volume of droplets, ranging from nanoliter to picoliter, velocity and even composition, with an operation frequency of several kilohertz. Through electronic feedback, we are able to easily count, sort, and direct the microfluidic droplets. Potential applications of this approach can be employed in the areas of biomicrofluidic processing, microchemical reactions as well as digital microfluidics.
Reduction of impact-ionization threshold energies for performance enhancement of complementary impact-ionization metal-oxide-semiconductor transistors
Authors: Toh Eng-Huat , Wang Grace Huiqi , Chan Lap , Samudra Ganesh , Yeo Yee-Chia
Published: October 2007

We explore the improvement of electrical performance of impact-ionization metal-oxide-semiconductor (I-MOS) transistors by the reduction of impact-ionization threshold energy through incorporation of materials with smaller bandgaps. Silicon-germanium (SiGe) I-MOS transistors were demonstrated. The lower bandgap of SiGe, as compared to Si, contributes to lower electron and hole impact-ionization threshold energies, leading to avalanche breakdown at a much reduced source voltage and enhanced device performance. Both n- and p-channel I-MOS devices were fabricated on Si0.60Ge0.40-on-insulator substrates using a complementary metal-oxide-semiconductor compatible process flow. Excellent subthreshold swings as low as 5mV/decade were achieved for the SiGe I-MOS devices. Reduction in breakdown voltage VBD was as large as 1.3 and 1.6V, respectively, for the n- and p-channel Si0.60Ge0.40 I-MOS devices.
Nanopore in metal-dielectric sandwich for DNA position control
Authors: Polonsky Stas , Rossnagel Steve , Stolovitzky Gustavo
Published: October 2007

We present the concept of a nanoelectromechanical device capable of controlling the position of DNA inside a nanopore with a single nucleotide accuracy. The device utilizes the interaction of discrete charges along the backbone of a DNA molecule with the electric field inside the nanopore. In analogy to solid state transistors in which a small voltage controls the current between two electrodes, a voltage strategically located inside the nanopore can control the translocation of a single DNA molecule between a cis and a trans reservoirs. We propose an immediate application of the device as a replacement of capillary electrophoresis in DNA sequencing.
Two-dimensional polymer photonic crystal band-edge lasers fabricated by nanoimprint lithography
Authors: Reboud V. , Lovera P. , Kehagias N. , Zelsmann M. , Schuster C. , Reuther F. , Gruetzner G. , Redmond G. , Sotomayor Torres C. M.
Published: October 2007

We report on the fabrication and characterization of two-dimensional polymer photonic crystal band-edge lasers operating in the visible range. The components have been fabricated in a dye chromophore-loaded polymer matrix by nanoimprint lithography. High-symmetry band-edge modes are used to generate laser emission. The experimental lasing frequencies are in good agreement with those calculated using a two-dimensional plane wave algorithm. These results demonstrate the potential of nanoimprint lithography for the fabrication of two-dimensional planar photonic crystal structures in an active medium in a one-step process.
Magnetic properties and microstructure of FePt∕BN nanocomposite films with perpendicular magnetic anisotropy
Authors: Li Bao-He , Feng Chun , Gao Xin , Teng Jiao , Yu Guang-Hua , Xing Xianran , Liu Zhong-Yuan
Published: October 2007

We have prepared L10-FePt∕BN nanocomposite films by depositing the FePt∕BN mutilayers on the MgO(100) substrates using magnetron sputtering followed by a postannealing process. We found the excellent perpendicular magnetic anisotropy of [FePt(2nm)∕BN(0.5nm)]10 film after annealing at 700°C for 1h x-ray diffraction patterns also indicate an excellent (001) texture of the film. This film shows a perpendicular coercivity of 7.48kOe and the ratio of the remnant magnetization Mr to the saturation one MS of as high as 0.93. We also found the good epitaxial growth of FePt grains on the MgO(100) substrate by cross-section high resolution transmitting microscopy.
Motor Preparation of Manual Aiming at a Visual Target Manipulated in Size, Luminance Contrast, and Location
Authors: Ishihara Masami , Imanaka Kuniyasu
Published: October 2007

We conducted two experiments to investigate whether the motor preparation of manual aiming to a visual target is affected by either the physical characteristics (size or luminance contrast) or spatial characteristics (location) of the target. Reaction time (RT) of both finger lifting (ie stimulus-detection time) and manual aiming (ie movement-triggering time) to the onset of the target was measured. The difference of RT (DRT) between two tasks (ie the difference of task complexity) was examined to clarify the temporal characteristics of manual aiming per se during visuomotor integration. Results show classical characteristics: RT decreased as either the target size or luminance contrast increased. Furthermore, the task-complexity and target-location factors significantly interacted with each other, where the aiming RT was longer than the finger-lifting RT and the effects of target location on RT differed for each task. However, the task factor did not interact with either the size or luminance-contrast factor, implying that the motor preparation of manual aiming is associated with the spatial characteristics rather than the physical characteristics of the target. Inspection of DRT revealed that the time needed for motor preparation for an ipsilateral target was significantly shorter than that for a contralateral target. This was the case both for the left and for the right hand. Foveal targets required longer processing time, implying a disadvantageous function of motor preparation for the gazed target. The left-hand superiority for the target appearing in the left visual field was also observed. Such lateralised effect and left-hand advantage to the left visual field in manual aiming suggest that visuospatial information processing is activated during the preparation of aiming action, with faster processing in the right hemisphere.
Real-World Face Recognition: The Importance of Surface Reflectance Properties
Authors: Russell Richard , Sinha Pawan
Published: October 2007

The face recognition task we perform most often in everyday experience is the identification of people with whom we are familiar. However, because of logistical challenges, most studies focus on unfamiliar-face recognition, wherein subjects are asked to match or remember images of unfamiliar people's faces. Here we explore the importance of two facial attributes—shape and surface reflectance—in the context of a familiar-face recognition task. In our experiment, subjects were asked to recognise color images of the faces of their friends. The images were manipulated such that only reflectance or only shape information was useful for recognizing any particular face. Subjects were actually better at recognizing their friends' faces from reflectance information than from shape information. This provides evidence that reflectance information is important for face recognition in ecologically relevant contexts.
Localisation of Auditory Targets during Optokinetic Nystagmus
Authors: Königs Kerstin , Knöll Jonas , Bremmer Frank
Published: October 2007

Previous studies have shown that the perceived location of visual stimuli briefly flashed during smooth pursuit, saccades, or optokinetic nystagmus (OKN) is not veridical. We investigated whether these mislocalisations can also be observed for brief auditory stimuli presented during OKN. Experiments were carried out in a lightproof sound-attenuated chamber. Participants performed eye movements elicited by visual stimuli. An auditory target (white noise) was presented for 5 ms. Our data clearly indicate that auditory targets are mislocalised during reflexive eye movements. OKN induces a shift of perceived location in the direction of the slow eye movement and is modulated in the temporal vicinity of the fast phase. The mislocalisation is stronger for look- as compared to stare-nystagmus. The size and temporal pattern of the observed mislocalisation are different from that found for visual targets. This suggests that different neural mechanisms are at play to integrate oculomotor signals and information on the spatial location of visual as well as auditory stimuli.
Investigation of the Experimental Factors Affecting the Trithiocarbonate-Mediated RAFT Polymerization of Methyl Acrylate
Authors: Wood Murray R. , Duncalf David J. , Findlay Paul , Rannard Steven P. , Perrier Sébastien
Published: October 2007

The reversible addition–fragmentation chain transfer polymerization of acrylates, using methyl acrylate (MA) as a monomer model, mediated by a trithiocarbonate was tested under several conditions where the experimental parameters were systematically altered. The most significant parameter in controlling the rate and control of the polymerization was found to be the ratio of chain transfer agent (CTA) to initiator. Decreasing this ratio increased the rate of polymerization and had little noticeable effect on the control over molecular weight distribution. A ratio of CTA to initiator of unity was shown to give the best compromise between rate and control of the polymerization. Targeted degrees of polymerization (equivalent to ratios of monomer to CTA) had negligible effect on the rate of polymerization and polydispersity index (PDI). Performing the polymerization in the presence of solvent (up to 41.2% (w/w) in toluene) had no negative effect on the rate of polymerization. Indeed, marginally higher conversions and lower PDIs than for bulk polymerization were achieved for similar reaction times. A higher amount of toluene (66.6% (w/w)) induced a lower rate of polymerization, but the evolution of molecular weight and PDI were unaffected. Polymerizations performed in the presence of toluene, N,N′-dimethylformamide, and methyl ethyl ketone showed that solvent polarity and aromaticity had no observable effect on the rate of polymerization and over the control of molecular weight distribution. The optimum conditions for the polymerization of MA, mediated by 2-ethylthiocarbonylsulfanyl-propionic acid ethyl ester at 50°C were found to be [CTA]/[AIBN] = 1/1 and ~40% solvent (w/w).
Comparing active and repressed expression states of genes controlled by the Polycomb/Trithorax group proteins
Authors: Beisel Christian , Buness Andreas , Roustan-Espinosa Ian M. , Koch Britta , Schmitt Sabine , Haas Stefan A. , Hild Marc , Katsuyama Tomonori , Paro Renato
Published: October 2007

Drosophila
Polycomb group (PcG) and Trithorax group (TrxG) proteins are responsible for the maintenance of stable transcription patterns of many developmental regulators, such as the homeotic genes. We have used ChIP-on-chip to compare the distribution of several PcG/TrxG proteins, as well as histone modifications in active and repressed genes across the two homeotic complexes ANT-C and BX-C. Our data indicate the colocalization of the Polycomb repressive complex 1 (PRC1) with Trx and the DNA binding protein Pleiohomeotic (Pho) at discrete sequence elements as well as significant chromatin assembly differences in active and inactive regions. Trx binds to the promoters of active genes and noncoding transcripts. Most strikingly, in the active state, Pho covers extended chromatin domains over many kilobases. This feature of Pho, observed on many polytene chromosome puffs, reflects a previously undescribed function. At the
hsp70
gene, we demonstrate in mutants that Pho is required for transcriptional recovery after heat shock. Besides its presumptive function in recruiting PcG complexes to their site of action, our results now uncover that Pho plays an additional role in the repression of already induced genes.
Variant estrogen receptor–c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation
Authors: Li Lei , Hisamoto Koji , Kim Kyung Hee , Haynes M. Page , Bauer Philip M. , Sanjay Archana , Collinge Mark , Baron Roland , Sessa William C. , Bender Jeffrey R.
Published: October 2007

Little is known about the tyrosine kinase c-Src's function in the systemic circulation, in particular its role in arterial responses to hormonal stimuli. In human aortic and venous endothelial cells, c-Src is indispensable for 17β-estradiol (E2)-stimulated phosphatidylinositol 3-kinase/Akt/endothelial NO synthase (eNOS) pathway activation, a possible mechanism in E2-mediated vascular protection. Here we show that c-Src supports basal and E2-stimulated NO production and is required for E2-induced vasorelaxation in murine aortas. Only membrane c-Src is structurally and functionally involved in E2-induced eNOS activation. Independent of c-Src kinase activity, c-Src is associated with an N-terminally truncated estrogen receptor α variant (ER46) and eNOS in the plasma membrane through its “open” (substrate-accessible) conformation. In the presence of E2, c-Src kinase is activated by membrane ER46 and in turn phosphorylates ER46 for subsequent ER46 and c-Src membrane recruitment, the assembly of an eNOS-centered membrane macrocomplex, and membrane-initiated eNOS activation. Overall, these results provide insights into a critical role for the tyrosine kinase c-Src in estrogen-stimulated arterial responses, and in membrane-initiated rapid signal transduction, for which obligate complex assembly and localization require the c-Src substrate-accessible structure.
Structural basis for antiactivation in bacterial quorum sensing
Authors: Chen Guozhou , Jeffrey Philip D. , Fuqua Clay , Shi Yigong , Chen Lingling
Published: October 2007

Bacteria can communicate via diffusible signal molecules they generate and release to coordinate their behavior in response to the environment. Signal molecule concentration is often proportional to bacterial population density, and when this reaches a critical concentration, reflecting a bacterial quorum, specific behaviors including virulence, symbiosis, and horizontal gene transfer are activated. Quorum-sensing regulation in many Gram-negative bacteria involves acylated homoserine lactone signals that are perceived through binding to LuxR-type, acylated-homoserine-lactone-responsive transcription factors. Bacteria of the rhizobial group employ the LuxR-type transcriptional activator TraR in quorum sensing, and its activity is further regulated through interactions with the TraM antiactivator. In this study, we have crystallographically determined the 3D structure of the TraR–TraM antiactivation complex from
Rhizobium
sp. strain NGR234. Unexpectedly, the antiactivator TraM binds to TraR at a site distinct from its DNA-binding motif and induces an allosteric conformational change in the protein, thereby preventing DNA binding. Structural analysis reveals a highly conserved TraR–TraM interface and suggests a mechanism for antiactivation complex formation. This structure may inform alternative strategies to control quorum-sensing-regulated microbial activity including amelioration of infectious disease and antibiotic resistance. In addition, the structural basis of antiactivation presents a regulatory interaction that provides general insights relevant to the field of transcription regulation and signal transduction.
Quantitative genetic correlation between trait and preference supports a sexually selected sperm process
Authors: Simmons Leigh W. , Kotiaho Janne S.
Published: October 2007

Sperm show patterns of rapid and divergent evolution that are characteristic of sexual selection. Sperm competition has been proposed as an important selective agent in the evolution of sperm morphology. However, several comparative analyses have revealed evolutionary associations between sperm length and female reproductive tract morphology that suggest patterns of male–female coevolution. In the dung beetle
Onthophagus taurus
, males with short sperm have a fertilization advantage that depends on the size of the female's sperm storage organ, the spermatheca; large spermathecae select for short sperm. Sperm length is heritable and is genetically correlated with male condition. Here we report significant additive genetic variation and heritability for spermatheca size and genetic covariance between spermatheca size and sperm length predicted by both the “good-sperm” and “sexy-sperm” models of postcopulatory female preference. Our data thus provide quantitative genetic support for the role of a sexually selected sperm process in the evolutionary divergence of sperm morphology, in much the same manner as precopulatory female preferences drive the evolutionary divergence of male secondary sexual traits.
A multifunctional desaturase involved in the biosynthesis of the processionary moth sex pheromone
Authors: Serra Montserrat , Piña Benjamin , Abad José Luis , Camps Francisco , Fabriàs Gemma
Published: October 2007

The sex pheromone of the female processionary moth,
Thaumetopoea pityocampa
, is a unique C16 enyne acetate that is biosynthesized from palmitic acid. Three consecutive desaturation reactions transform this saturated precursor into the triunsaturated fatty acyl intermediate: formation of (
Z
)-11-hexadecenoic acid, acetylenation to 11-hexadecynoic acid, and final Δ
13
desaturation to (
Z
)-13-hexadecen-11-ynoic acid. By using degenerate primers common to all reported insect desaturases, a single cDNA sequence was isolated from total RNA of
T. pityocampa
female pheromone glands. The full-length transcript of this putative desaturase was expressed in
elo1
Δ/
ole1
Δ yeast mutants (both elongase 1 and Δ
9
desaturase-deficient) for functional assays. The construct fully rescued the Δ
ole1
yeast phenotype, confirming its desaturase activity. Analysis of the unsaturated products from transformed yeast extracts demonstrated that the cloned enzyme showed Δ
11
desaturase, Δ
11
acetylenase, and Δ
13
desaturase activities. Therefore, this single desaturase may account for the three desaturation steps involved in the sex pheromone biosynthetic pathway of the processionary moth.
Impaired glutathione synthesis in schizophrenia: Convergent genetic and functional evidence
Authors: Gysin René , Kraftsik Rudolf , Sandell Julie , Bovet Pierre , Chappuis Céline , Conus Philippe , Deppen Patricia , Preisig Martin , Ruiz Viviane , Steullet Pascal , Tosic Mirjana , Werge Thomas , Cuénod Michel , Do Kim Q.
Published: October 2007

Schizophrenia is a complex multifactorial brain disorder with a genetic component. Convergent evidence has implicated oxidative stress and glutathione (GSH) deficits in the pathogenesis of this disease. The aim of the present study was to test whether schizophrenia is associated with a deficit of GSH synthesis. Cultured skin fibroblasts from schizophrenia patients and control subjects were challenged with oxidative stress, and parameters of the rate-limiting enzyme for the GSH synthesis, the glutamate cysteine ligase (GCL), were measured. Stressed cells of patients had a 26% (
P
= 0.002) decreased GCL activity as compared with controls. This reduction correlated with a 29% (
P
< 0.001) decreased protein expression of the catalytic GCL subunit (GCLC). Genetic analysis of a trinucleotide repeat (TNR) polymorphism in the GCLC gene showed a significant association with schizophrenia in two independent case-control studies. The most common TNR genotype 7/7 was more frequent in controls [odds ratio (OR) = 0.6,
P
= 0.003], whereas the rarest TNR genotype 8/8 was three times more frequent in patients (OR = 3.0,
P
= 0.007). Moreover, subjects with disease-associated genotypes had lower GCLC protein expression (
P
= 0.017), GCL activity (
P
= 0.037), and GSH contents (
P
= 0.004) than subjects with genotypes that were more frequent in controls. Taken together, the study provides genetic and functional evidence that an impaired capacity to synthesize GSH under conditions of oxidative stress is a vulnerability factor for schizophrenia.
Kinetic evidence for a ligand-binding-induced conformational transition in the T cell receptor
Authors: Gakamsky Dmitry M. , Lewitzki Erwin , Grell Ernst , Saulquin Xavier , Malissen Bernard , Montero-Julian Felix , Bonneville Marc , Pecht Israel
Published: October 2007

Thermodynamics and kinetics of the interaction between T cell receptor specific for cytomegalovirus peptide (TCRCMV) and its specific ligand, pp65–HLA-A*0201 complex, were studied by surface plasmon resonance and stopped-flow methods. In the latter measurements, fluorescence resonance energy transfer (FRET) between fluorescently labeled reactants was used. Thermodynamic data derived from surface plasmon resonance measurements suggest that the complex formation is driven by both favorable enthalpy and entropy. Two reaction phases were resolved by the stopped-flow measurements. The rate constant of the first step was calculated to be close to the diffusion-controlled limit rate (3·105to 106M−1·s−1), whereas the second step's reaction rate was found to be concentration independent and relatively slow (2–4 s−1at 25°C). These findings strongly suggest that the interactions between the TCR and its ligand, the peptide–MHC complex, proceed by a two-step mechanism, in which the second step is an induced-fit process, rate determining for antigen recognition by TCR.
CRF–CRF1system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats
Authors: George Olivier , Ghozland Sandy , Azar Marc R. , Cottone Pietro , Zorrilla Eric P. , Parsons Loren H. , O'Dell Laura E. , Richardson Heather N. , Koob George F.
Published: October 2007

Nicotine, the main psychoactive ingredient of tobacco, induces negative emotional symptoms during abstinence that contribute to a profound craving for nicotine. However, the neurobiological mechanisms underlying how nicotine produces dependence remains poorly understood. We demonstrate one mechanism for both the anxiety-like symptoms of withdrawal and excessive nicotine intake observed after abstinence, through recruitment of the extrahypothalamic stress peptide corticotropin-releasing factor (CRF) system and activation of CRF1receptors. Overactivation of the CRF–CRF1system may contribute to nicotine dependence and may represent a prominent target for investigating the vulnerability to tobacco addiction.
A mouse model of conditional lipodystrophy
Authors: Kim Suyeon , Huang Li-Wen , Snow Kathy J. , Ablamunits Vitaly , Hasham Muneer G. , Young Timothy H. , Paulk Angelique C. , Richardson Joel E. , Affourtit Jason P. , Shalom-Barak Tali , Bult Carol J. , Barak Yaacov
Published: October 2007

Lipodystrophies are syndromes of adipose tissue degeneration associated with severe defects in lipid and glucose homeostasis. We report here the generation and analysis of

Pparg
ldi

, a targeted allele that confers conditional dominant lipodystrophy in mice. The

Pparg
ldi

allele was generated by insertion of the Tet activator (tTA) and a tTA-regulated
Flag-Pparg1
transgene into the
Pparg
gene. Unexpectedly, tTA elicits mild lipodystrophy, insulin resistance, and dyslipidemia, and the Flag-PPARγ1 transgene surprisingly exacerbates these traits. Doxycycline can both completely prevent and reverse these phenotypes, providing a mouse model of inducible lipodystrophy. Embryonic fibroblasts from either
Pparg

ldi
/+

or the phenotypically similar
aP2-nSrebp1c
(
Sr
) transgenic mice undergo robust adipogenesis, suggesting that neither strain develops lipodystrophy because of defective adipocyte differentiation. In addition,
Pparg

ldi
/+

adipose tissue shares extensive gene expression aberrations with that of
Sr
mice, authenticating the phenotype at the molecular level and revealing a common expression signature of lipodystrophic fat. Thus, the
Pparg

ldi
/+

mouse provides a conditional animal model for studying lipodystrophy and its associated physiology and gene expression.
A glycosyltransferase with a length-controlling activity as a mechanism to regulate the size of polysaccharides
Authors: Ciocchini Andrés E. , Guidolin L. Soledad , Casabuono Adriana C. , Couto Alicia S. , Iñón de Iannino Nora , Ugalde Rodolfo A.
Published: October 2007

Cyclic β-1,2-glucans (CβG) are osmolyte homopolysaccharides with a cyclic β-1,2-backbone of 17–25 glucose residues present in the periplasmic space of several bacteria. Initiation, elongation, and cyclization, the three distinctive reactions required for building the cyclic structure, are catalyzed by the same protein, the CβG synthase. The initiation activity catalyzes the transference of the first glucose from UDP-glucose to a yet-unidentified amino acid residue in the same protein. Elongation proceeds by the successive addition of glucose residues from UDP-glucose to the nonreducing end of the protein-linked β-1,2-oligosaccharide intermediate. Finally, the protein-linked intermediate is cyclized, and the cyclic glucan is released from the protein. These reactions do not explain, however, the mechanism by which the number of glucose residues in the cyclic structure is controlled. We now report that control of the degree of polymerization (DP) is carried out by a β-1,2-glucan phosphorylase present at the CβG synthase C-terminal domain. This last activity catalyzes the phosphorolysis of the β-1,2-glucosidic bond at the nonreducing end of the linear protein-linked intermediate, releasing glucose 1-phosphate. The DP is thus regulated by this “length-controlling” phosphorylase activity. To our knowledge, this is the first description of a control of the DP of homopolysaccharides.
Declining p53 function in the aging process: A possible mechanism for the increased tumor incidence in older populations
Authors: Feng Zhaohui , Hu Wenwei , Teresky Angelika K. , Hernando Eva , Cordon-Cardo Carlos , Levine Arnold J.
Published: October 2007

Cancer is a disease of aging. The accumulation of mutations in individual cells over a lifetime is thought to be the reason. In this work, we explored an additional hypothesis: could p53 function decline with age, which would contribute to an enhanced mutation frequency and tumorigenesis in the aging process? The efficiency of the p53 response to γ-irradiation was found to decline significantly in various tissues of aging mice from several inbred strains, including lower p53 transcriptional activity and p53-dependent apoptosis. This decline resulted from a decreased stabilization of the p53 protein after stress. The function of the
Ataxia-telangiectasia
mutated (ATM) kinase declined significantly with age, which may then be responsible for the decline of the p53 response to radiation. Declining p53 responses to other stresses were also observed in the cultured splenocytes from aging mice. Interestingly, the time of onset of this decreased p53 response correlated with the life span of mice; mice that live longer delay their onset of decreased p53 activity with time. These results suggest an enhanced fixation of mutations in older individuals because of the declining fidelity of p53-mediated apoptosis or senescence in response to stress, and they suggest a plausible explanation for the correlation between tumorigenesis and the aging process.
Psychological Morbidity in Australian Doctors who have and have not Experienced a Medico-Legal Matter: Cross-Sectional Survey
Authors: Nash Louise , Daly Michele , Johnson Maree , Walter Garry , Walton Merrilyn , Willcock Simon , Coulston Carissa , van Ekert Elizabeth , Tennant Chris
Published: October 2007

Objective: To describe the differences in psychological morbidity between Australian general practitioners (GPs) who have experienced a medico-legal matter and those who have not.

Methods: A total of 1499 GPs were initially invited to participate in the study. Two hundred and sixty requested not to participate, with 1239 subsequently being sent a survey. There were 566 respondents (45.7% response rate to survey). There were two sources of data. First, a cross-sectional survey sought demographic information, personality traits via the Eysenck Personality Questionnaire (EPQ), history of a medico-legal matter with any medical defence organization, and measures of psychological morbidity, including the General Health Questionnaire (GHQ), Sheehan Disability Scale (SDS), and Alcohol Use Disorders Identification Test. Second, information was extracted from the United Medical Protection database on medico-legal matters.

Results: Fifty-nine per cent of respondents to the survey reported ever having a medico-legal matter, with 13% having a current medico-legal matter. Those with a current matter reported increased levels of disability (in work, social or family life) and higher prevalence of psychiatric morbidity (45% vs 27% GHQ ‘case identification’ rates), compared to those with no current matter. Those respondents with a history of past medico-legal matters reported increased levels of disability (SDS) and depression subscores (GHQ). Male respondents drank significantly more alcohol than female respondents, and male respondents with current or past medico-legal matters had significantly higher levels of alcohol use than male respondents with no experience of medico-legal matters.

Conclusions: Doctors who have current and past medico-legal matters have a higher level of psychological morbidity. The study design was unable to distinguish cause or effect. A longitudinal study is planned to investigate this. The findings have significant implications for medical training, doctor support systems and medical insurance groups.
Roger Tsien: Bringing color to cell biology
Authors: Williams Ruth
Published: October 2007

A passion for chemistry, color, and conversations with cells is what drives Roger Tsien.
Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice
Authors: Olsen Olav , Funke Lars , Long Jia-fu , Fukata Masaki , Kazuta Toshinari , Trinidad Jonathan C. , Moore Kimberly A. , Misawa Hidemi , Welling Paul A. , Burlingame Alma L. , Zhang Mingjie , Bredt David S.
Published: October 2007

Kidney development and physiology require polarization of epithelia that line renal tubules. Genetic studies show that polarization of invertebrate epithelia requires the crumbs, partition-defective-3, and discs large complexes. These evolutionarily conserved protein complexes occur in mammalian kidney; however, their role in renal development remains poorly defined. Here, we find that mice lacking the small PDZ protein mammalian LIN-7c (MALS-3) have hypomorphic, cystic, and fibrotic kidneys. Proteomic analysis defines MALS-3 as the only known core component of both the crumbs and discs large cell polarity complexes. MALS-3 mediates stable assembly of the crumbs tight junction complex and the discs large basolateral complex, and these complexes are disrupted in renal epithelia from MALS-3 knockout mice. Interestingly, MALS-3 controls apico-basal polarity preferentially in epithelia derived from metanephric mesenchyme, and defects in kidney architecture owe solely to MALS expression in these epithelia. These studies demonstrate that defects in epithelial cell polarization can cause cystic and fibrotic renal disease.
Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy
Authors: Jablonka Sibylle , Beck Marcus , Lechner Barbara Dorothea , Mayer Christine , Sendtner Michael
Published: October 2007

Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. In animal models of SMA, spinal motoneurons exhibit reduced axon elongation and growth cone size. These defects correlate with reduced β-actin messenger RNA and protein levels in distal axons. We show that survival motoneuron gene (Smn)–deficient motoneurons exhibit severe defects in clustering Cav2.2 channels in axonal growth cones. These defects also correlate with a reduced frequency of local Ca2+ transients. In contrast, global spontaneous excitability measured in cell bodies and proximal axons is not reduced. Stimulation of Smn production from the transgenic SMN2 gene by cyclic adenosine monophosphate restores Cav2.2 accumulation and excitability. This may lead to the development of new therapies for SMA that are not focused on enhancing motoneuron survival but instead investigate restoration of growth cone excitability and function.
Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis
Authors: Halter David , Neumann Sylvia , van Dijk Suzanne M. , Wolthoorn Jasja , de Mazière Ann M. , Vieira Otilia V. , Mattjus Peter , Klumperman Judith , van Meer Gerrit , Sprong Hein
Published: October 2007

Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate across to the Golgi lumen for LacCer synthesis. However, only very little natural GlcCer translocates across the Golgi in vitro. As GlcCer reaches the cell surface when Golgi vesicular trafficking is inhibited, it must translocate across a post-Golgi membrane. Concanamycin, a vacuolar proton pump inhibitor, blocks translocation independently of multidrug transporters that are known to translocate short-chain GlcCer. Concanamycin did not reduce LacCer and GM3 synthesis. Thus, GlcCer destined for glycolipid synthesis follows a different pathway and transports back into the endoplasmic reticulum (ER) via the late Golgi protein FAPP2. FAPP2 knockdown strongly reduces GM3 synthesis. Overall, we show that newly synthesized GlcCer enters two pathways: one toward the noncytosolic surface of a post-Golgi membrane and one via the ER toward the Golgi lumen LacCer synthase.
Annotation of selection strengths in viral genomes
Authors: McCauley Stephen , de Groot Saskia , Mailund Thomas , Hein Jotun
Published: October 2007

Motivation: Viral genomes tend to code in overlapping reading frames to maximize informational content. This may result in atypical codon bias and particular evolutionary constraints. Due to the fast mutation rate of viruses, there is additional strong evidence for varying selection between intra- and intergenomic regions. The presence of multiple coding regions complicates the concept of Ka/Ks ratio, and thus begs for an alternative approach when investigating selection strengths. Building on the paper by McCauley and Hein, we develop a method for annotating a viral genome coding in overlapping reading frames. We introduce an evolutionary model capable of accounting for varying levels of selection along the genome, and incorporate it into our prior single sequence HMM methodology, extending it now to a phylogenetic HMM. Given an alignment of several homologous viruses to a reference sequence, we may thus achieve an annotation both of coding regions as well as selection strengths, allowing us to investigate different selection patterns and hypotheses.

Results: We illustrate our method by applying it to a multiple alignment of four HIV2 sequences, as well as of three Hepatitis B sequences. We obtain an annotation of the coding regions, as well as a posterior probability for each site of the strength of selection acting on it. From this we may deduce the average posterior selection acting on the different genes. Whilst we are encouraged to see in HIV2, that the known to be conserved genes gag and pol are indeed annotated as such, we also discover several sites of less stringent negative selection within the env gene. To the best of our knowledge, we are the first to subsequently provide a full selection annotation of the Hepatitis B genome by explicitly modelling the evolution within overlapping reading frames, and not relying on simple Ka/Ks ratios.

Availability: The Matlab code can be downloaded from http://www.stats.ox.ac.uk/mccauley/

Contact:  degroot@stats.ox.ac.uk
OSCAR: One-class SVM for accurate recognition ofcis-elements
Authors: Jiang Bo , Zhang Michael Q. , Zhang Xuegong
Published: October 2007

Motivation: Traditional methods to identify potential binding sites of known transcription factors still suffer from large number of false predictions. They mostly use sequence information in a position-specific manner and neglect other types of information hidden in the proximal promoter regions. Recent biological and computational researches, however, suggest that there exist not only locational preferences of binding, but also correlations between transcription factors.

Results: In this article, we propose a novel approach, OSCAR, which utilizes one-class SVM algorithms, and incorporates multiple factors to aid the recognition of transcription factor binding sites. Using both synthetic and real data, we find that our method outperforms existing algorithms, especially in the high sensitivity region. The performance of our method can be further improved by taking into account locational preference of binding events. By testing on experimentally-verified binding sites of GATA and HNF transcription factor families, we show that our algorithm can infer the true co-occurring motif pairs accurately, and by considering the co-occurrences of correlated motifs, we not only filter out false predictions, but also increase the sensitivity.

Availability: An online server based on OSCAR is available at http://bioinfo.au.tsinghua.edu.cn/oscar.

Contact:  zhangxg@tsinghua.edu.cn
Identification and visualization of cage-shaped proteins
Authors: Hu Min , Wang Junhui , Peng Qunsheng
Published: October 2007

Summary: Cage-shaped protein, with its special structure, may have potential applications in biomedicine and nanotechnology. We developed a program CSPro (Cage-Shaped Protein) for efficient identification of cage-shaped proteins based on quaternary structure. CSPro is capable of revealing the corresponding cage-shaped feature more clearly and quickly than traditional visualization tools. Using CSPro, we have searched the full set of PDB (protein data bank) and three types of proteins are retrieved with notably large central cavities inside. CSPro can be used to validate if the quaternary structure of a protein is cage shaped in molecular simulation.

Availability:  http://www.cad.zju.edu.cn/home/humin

Contact:  humin@cad.zju.edu.cn

Supplementary information: Supplementary data are available at Bioinformatics online.
XtalPred: a web server for prediction of protein crystallizability
Authors: Slabinski Lukasz , Jaroszewski Lukasz , Rychlewski Leszek , Wilson Ian A. , Lesley Scott A. , Godzik Adam
Published: October 2007

Summary: XtalPred is a web server for prediction of protein crystallizability. The prediction is made by comparing several features of the protein with distributions of these features in TargetDB and combining the results into an overall probability of crystallization. XtalPred provides: (1) a detailed comparison of the protein's features to the corresponding distribution from TargetDB; (2) a summary of protein features and predictions that indicate problems that are likely to be encountered during protein crystallization; (3) prediction of ligands; and (4) (optional) lists of close homologs from complete microbial genomes that are more likely to crystallize.

Availability: The XtalPred web server is freely available for academic users on http://ffas.burnham.org/XtalPred

Contact:  adam@burnham.org
Laughter, Humor and Pain Perception in Children: A Pilot Study
Authors: Stuber Margaret , Hilber Sherry Dunay , Mintzer Lisa Libman , Castaneda Marleen , Glover Dorie , Zeltzer Lonnie
Published: October 2007

Although there are many clinical programs designed to bring humor into pediatric hospitals, there has been very little research with children or adolescents concerning the specific utility of humor for children undergoing stressful or painful procedures. Rx Laughter™, a non‐profit organization interested in the use of humor for healing, collaborated with UCLA to collect preliminary data on a sample of 18 children aged 7–16 years. Participants watched humorous video‐tapes before, during and after a standardized pain task that involved placing a hand in cold water. Pain appraisal (ratings of pain severity) and pain tolerance (submersion time) were recorded and examined in relation to humor indicators (number of laughs/smiles during each video and child ratings of how funny the video was). Whereas humor indicators were not significantly associated with pain appraisal or tolerance, the group demonstrated significantly greater pain tolerance while viewing funny videos than when viewing the videos immediately before or after the cold‐water task. The results suggest that humorous distraction is useful to help children and adolescents tolerate painful procedures. Further study is indicated to explore the specific mechanism of this benefit.