bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular dissection of the APC/C inhibitor Rca1 shows a novel F‐box‐dependent function
Authors: Zielke Norman , Querings Silvia , Grosskortenhaus Ruth , Reis Tânia , Sprenger Frank
Published: November 2006

Rca1 (regulator of Cyclin A)/Emi (early mitotic inhibitor) proteins are essential inhibitors of the anaphase‐promoting complex/cyclosome (APC/C). In Drosophila, Rca1 is required during G2 to prevent premature cyclin degradation by the Fizzy‐related (Fzr)‐dependent APC/C activity. Here, we present a structure and function analysis of Rca1 showing that a carboxy‐terminal fragment is sufficient for APC/C inhibition. Rca1/Emi proteins contain a conserved F‐box and interact with components of the Skp–Cullin–F‐box (SCF) complex. So far, no function has been ascribed to this domain. We find that the F‐box of Rca1 is dispensable for APC/C–Fzr inhibition during G2. Nevertheless, we show that Rca1 has an additional function at the G1–S transition, which requires the F‐box. Overexpression of Rca1 accelerates the G1–S transition in an F‐box‐dependent manner. Conversely, S‐phase entry is delayed in cells in which endogenous Rca1 is replaced by a transgene lacking the F‐box. We propose that Rca1 acts as an F‐box protein in an as yet uncharacterized SCF complex, which promotes S‐phase entry.
Schmidt number effects in dissipative particle dynamics simulation of polymers
Authors: Symeonidis Vasileios , Karniadakis George Em , Caswell Bruce
Published: November 2006

Simulation studies for dilute polymeric systems are presented using the dissipative particle dynamics method. By employing two different thermostats, the velocity-Verlet and Lowe’s scheme, we show that the Schmidt number (Sc) of the solvent strongly affects nonequilibrium polymeric quantities. The fractional extension of wormlike chains subjected to steady shear is obtained as a function of Sc. Poiseuille flow in microchannels for fixed polymer concentration and varying number of repeated units within a chain is simulated. The nonuniform concentration profiles and their dependence on Sc are computed. We show the effect of the bounce-forward wall boundary condition on the depletion layer thickness. A power law fit of the velocity profile in stratified Poiseuille flow in a microchannel yields wall viscosities different from bulk values derived from uniform, steady plane Couette flow. The form of the velocity profiles indicates that the slip flow model is not useful for the conditions of these calculations.
Photoluminescence properties and energy transfer processes from excitons to Mn2+ ions in Mn2+-doped CdS quantum dots prepared by a reverse-micelle method
Authors: Kim D. , Miyamoto M. , Nakayama M.
Published: November 2006

We investigated the photoluminescence (PL) properties of Mn2+-doped CdS (CdS:Mn2+) quantum dots (QDs) prepared by a reverse-micelle method. A PL band which originates from the intracation transition, the so-called d-d transition, of tetrahedrally coordinated Mn2+ ions, is clearly observed at ∼2.1eV, indicating that Mn2+ ions are thoroughly doped inside CdS QDs. By surface modification with a Cd(OH)2 layer, the intensity of the Mn2+-related PL band is increased approximately ten times compared with that without modification, and strong enhancement of the band-edge PL band is observed. The decay profile of the band-edge PL in surface-modified CdS:Mn2+ QDs is much faster than that in undoped CdS QDs; this shortened decay time originates from the effective energy transfer process from the excitons of host QDs to Mn2+ ions. The PL decay profiles are quantitatively explained on the basis of a three-level model including both the dark-exciton state and the energy transfer process.
Electrical current-induced structural changes and chemical functionalization of carbon nanotubes
Authors: Agrawal S. , Raghuveer M. S. , Kröger R. , Ramanath G.
Published: November 2006

We demonstrate that high current densities, combined with air exposure can slice, weld, and chemically functionalize multiwalled carbon nanotubes (CNTs) with carboxyl and allyl moieties, and alter the electrical properties. The conductance of thin film assemblies of CNTs increases by 150%, indicating that the increase in the number of low-resistance pathways caused by CNT junction formation offsets the conductance decrease expected from defect creation, surface functionalization, and fissure. Such welded high-conductance CNT networks of functionalized CNTs could be useful for device and sensor applications, and may serve as high mechanical toughness mat fillers that are amenable to integration with nanocomposite matrices.
Formation of Cu2O quantum dots on SrTiO3 (100): Self-assembly and directed self-assembly
Authors: Du Yingge , Groves James F. , Lyubinetsky Igor , Baer Donald R.
Published: November 2006

Cu 2 O quantum dots (QDs) have been synthesized on single crystal SrTiO3 (100) substrates with focused ion beam (FIB) modification using oxygen plasma-assisted molecular beam epitaxy. In a set of experiments, QD growth location has been controlled using FIB implants to modify the growth surface in discrete locations prior to dot synthesis. Atomic force microscopy has been used to characterize this directed self-assembly of oxide QDs. QDs have been observed to form first in the FIB generated surface features, filling those features before additional QDs have nucleated on neighboring, unmodified surface regions. The nature of the QDs on the modified surface is compared to those grown on unmodified substrate regions. While FIB modification provides lateral control over QDs, the QDs formed on the undamaged surfaces were more uniform in shape and size than those that nucleated in the FIB produced pits.
Distant perturbation asymptotics in window-coupled waveguides. I. The nonthreshold case
Authors: Borisov D. , Exner P.
Published: November 2006

We consider a pair of straight adjacent quantum waveguides of constant, and in general different widths. These waveguides are coupled laterally by a pair of windows in the common boundary, not necessarily of the same length, at a distance 2l. The Hamiltonian is the respective Dirichlet Laplacian. We analyze the asymptotic behavior of the discrete spectrum as the window distance tends to infinity for the generic case, i.e., for eigenvalues of the corresponding one-window problems separated from the threshold.
Collisionality and magnetic geometry effects on tokamak edge turbulent transport. I. A two-region model with application to blobs
Authors: Myra J. R. , Russell D. A. , D’Ippolito D. A.
Published: November 2006

A two-region model is proposed to study the effect of collisionality and magnetic geometry on electrostatic turbulence and on the propagation of filamentary coherent structures (blobs) in the edge and scrape-off layer. The model invokes coupled vorticity and continuity equations in two different spatial regions along the magnetic field, taking into account the effect of magnetic field fanning and shear, e.g., near magnetic X-points. A linear dispersion relation for unstable modes illustrates the physics of mode disconnection (ballooning) along the magnetic field and its dependence on collisionality and wave number (scale size). Employing an invariant scaling analysis, dimensionless parameters for the nonlinear model are developed and used to describe the regimes of the system. A blob correspondence rule is postulated to relate the linear mode growth rates and regimes to the convective velocity of blobs. Nonlinear numerical simulations of blob convection show good agreement with a blob dispersion relation derived from the correspondence rule. It is found that collisionality increases the convective velocity. The convective velocity also depends on blob scale size, with either positive or negative exponent, depending on the collisionality regime. Finally, the dimensionless scaling analysis is employed to obtain bounds on the convective velocity suitable for experimental tests.
Characterization of organic photovoltaic devices with indium-tin-oxide anode treated by plasma in various gases
Authors: Hong Z. R. , Liang C. J. , Sun X. Y. , Zeng X. T.
Published: November 2006

Indium-tin-oxide (ITO) anode treated by different gas plasma or UV ozone has been used for photovoltaic (PV) cells with structure of ITO/copper phthalocyanine (CuPc)/C60/bathocuproine/Al. Both surface energy and work function of the ITO substrates were affected by these treatments. However, the main performance parameters of PV cells, including short circuit current, open circuit voltage, power conversion efficiency, and fill factor, were almost unaffected. On the other hand, series and shunt resistances of the PV cells derived from numerical fitting of I-V curves were not significantly changed with different treatments. Therefore, no significant impact of substrate treatment on hole collection was concluded, although hole injection under forward bias showed strong dependence on treatment methods. It indicates that hole transfer from CuPc layer to ITO is not the bottleneck in the CuPc/C60 based organic solar cells.
On existence of matter outside a static black hole
Authors: Shiromizu Tetsuya , Yamada Sumio , Yoshino Hirotaka
Published: November 2006

It is expected that matter composed of a perfect fluid cannot be at rest outside of a black hole if the spacetime is asymptotically flat and static (nonrotating). However, there has not been rigorous proof for this expectation without assuming spherical symmetry. In this paper, we provide a proof of nonexistence of matter composed of a perfect fluid in static black hole spacetimes under certain conditions, which can be interpreted as a relation between the stellar mass and the black hole mass.
Temperature dependence of the gain in p-doped and intrinsic 1.3μm InAs∕GaAs quantum dot lasers
Authors: Massé N. F. , Sweeney S. J. , Marko I. P. , Adams A. R. , Hatori N. , Sugawara M.
Published: November 2006

The gain of p-doped and intrinsic InAs∕GaAs quantum dot lasers is studied at room temperature and at 350K. Our results show that, although one would theoretically expect a higher gain for a fixed carrier density in p-doped devices, due to the wider nonthermal distribution of carriers amongst the dots at T=293K, the peak net gain of the p-doped lasers is actually less at low injection than that of the undoped devices. However, at higher current densities, p doping reduces the effect of gain saturation and therefore allows ground-state lasing in shorter cavities and at higher temperatures.
Epitaxial ScAlMgO4(0001) films grown on sapphire substrates by flux-mediated epitaxy
Authors: Obata T. , Takahashi R. , Ohkubo I. , Oshima M. , Nakajima K. , Chikyow T. , Koinuma H. , Matsumoto Y.
Published: November 2006

Sc Al Mg O 4 ( 0001 ) epitaxial films have been synthesized on sapphire (0001) substrates by flux-mediated epitaxy. The key points were high temperature deposition and the use of additive BiOx, which was simultaneously supplied during the deposition; otherwise the growth of spinel phase such as MgAl2O4 was dominant. The BiOx is thus considered to promote the growth of ScAlMgO4 like a flux. This result indicates that the flux-mediated epitaxy is a promising way to high quality single crystal ScAlMgO4 films as a lattice-matched substrate for p-type ZnO and GaN films.
Diffusion driven reconstruction for positron emission tomography
Authors: Mondal Partha P. , Rajan K.
Published: November 2006

Reconstruction map of the radionucleus distribution in positron emission tomography imaging is an ill-posed inverse problem. Existing reconstruction methodologies based on maximum a posteriori principle reconstruct images that suffer from artifacts. A method is proposed for generating better map of radionucleus distribution primarily based on surface diffusion model. The mean curvature diffusion has resulted in efficient noise suppression when applied to an isolated edge embedded in noise. Experimental results show that the proposed approach has better image resolution and edge-preservation capability. The reconstruction methodology will therefore find applications in biomedical imaging and bioengineering.
A direct measurement of the dissociation energy of water
Authors: Maksyutenko Pavlo , Rizzo Thomas R. , Boyarkin Oleg V.
Published: November 2006

We have performed a direct measurement of one of the most fundamental thermochemical values: the O-H bond energy in water. Using a triple-resonance laser excitation scheme, we excite the molecule through a series of vibrational overtone transitions to access directly the onset of the dissociative continuum. The disociation energy obtained from our experiments, 41145.94±0.15cm−1, is ∼30 times more accurate than the currently accepted value and has important implications for other thermochemical quantities linked to the bond energy of water.
Free-space quantum key distribution with Rb vapor filters
Authors: Shan Xin , Sun Xianping , Luo Jun , Tan Zheng , Zhan Mingsheng
Published: November 2006

By using Rb vapor filters, free-space quantum key distribution with the B92 protocol was realized experimentally; the filters based on the Faraday anomalous dispersion effect were used to suppress strong background light. With these atomic filters as spectral filtering, average transmission rates of sifted keys and corrected keys have reached as high as 3.14 and 1.56kbits∕s, respectively, while the error rate was maintained at a reasonable low level of 5.10%. The experimental results show that our Rb vapor filters with transmission efficiency of around 60% operate well under the condition of the mean photon number n¯⩽0.1.
Determination and evolution of tunneling distances in Ge nanocrystal based memories
Authors: Beyer V. , von Borany J. , Klimenkov M.
Published: November 2006

A Ge nanocrystal layer embedded in a thin gate oxide was prepared by ion beam synthesis in direct-tunneling distance to the Si substrate. The write performance was investigated in metal-oxide-semiconductor capacitors by means of capacitance measurements. With the experimental data and calculations using a floating-gate-like approach, the distribution of the tunneling oxide thickness dtox can be determined in high precision confirmed by high-angle annular dark-field scanning transmission electron microscopy imaging. The evolution of dtox during heat treatment is discussed in terms of Ostwald ripening; i.e., dtox increases with annealing time.
Iron deficiency and adventitious rooting in peach hardwood cuttings (cv. Early Crest)
Authors: Tsipouridis C. , Thomidis T. , Zakinthinos Z.
Published: November 2006

The effect of iron deficiency on adventitious rooting of peach hardwood cuttings (cv. Early Crest) was investigated. The results showed significant differences between rooting, root numbers and dry weights of roots per cutting. Significant differences were also shown between cuttings from healthy trees (control) and cuttings from iron-deficient trees. Leaf samples taken from iron-deficient trees (before the application of an iron compound) exhibited higher levels of K, Ca and Mn than healthy trees, although the iron content was higher in the healthy tree samples. The bark of healthy trees showed a significantly greater content of Fe and Zn than samples taken from the bark of the iron-deficient trees. Magnesium, K and Ca levels were lower in bark samples taken from healthy trees. Application of iron compounds (especially iron sulfate and iron chelate) significantly reduced chlorotic symptoms, and also improved rooting of cuttings from iron-deficient trees, although it produced a somewhat negative effect on the rooting percentages of cuttings from healthy trees. Endogenous indole-3-acetic acid levels were higher in the bark and bud samples taken from healthy trees than in the samples of bark and buds taken from iron-deficient trees. Abscisic acid levels were found to be very high in the buds of iron-deficient trees.
Osmotic adjustment segregates with and is positively related to seed yield in F3 lines of crosses between Brassica napus and B. juncea subjected to water deficit
Authors: Ma Q. , Turner D. W.
Published: November 2006

For osmotic adjustment to be used as a selection criterion for adaptation to drought there is a need to demonstrate its segregation and association with seed yield in a population. This study examined osmotic adjustment and seed yield in F3 lines derived from crosses between Brassica napus (cvv. Karoo, Monty) and B. juncea (line JN25). A clear separation of the level of osmotic adjustment was observed among 20 F3 lines of Karoo × JN25 (7 high and 13 low) and 20 F3 lines of Monty × JN25 (8 high and 12 low) under glasshouse conditions. When the 3 parents and 8 selected F3 lines were grown in a low-rainfall environment in the field, the segregation of osmotic adjustment was largely similar to that observed in the glasshouse. Yield reduction, with irrigated plots as controls, was up to 30% for genotypes with low osmotic adjustment but only 10% for those with high osmotic adjustment. Osmotic adjustment was closely correlated with the accumulation of K+ (r = 0.91), soluble sugars (r = 0.90) and proline (r = 0.96), whereas other solutes (Na+, NH4+, Cl–, NO3–, Mg2+ and Ca2+) made little or no contribution to osmotic adjustment. Proline concentrations were very low in well-watered plants but sharply increased by 5- to 15-fold in plants subjected to water deficit, and net proline accumulation showed a higher association with total seed number (r = 0.86) and yield (r = 0.89) than did the concentrations of K+ (r = 0.75 to 0.82) or soluble sugars (r = 0.68 to 0.72). The study suggests that leaf proline concentration could be a good indicator of osmotic adjustment in Brassica oilseeds.
General Relativity in the English-speaking World: The Contributions of Henry L. Brose
Authors: König Heidi
Published: November 2006

The story of how the theory of general relativity found its way into the English speaking world during the Great War has often been told: it is dominated by the towering figure of the Cambridge astronomer Arthur Stanley Eddington, who (in 1916, and through the good services of the Dutch physicist Willem de Sitter) received copies of the papers Einstein had presented to the Berlin Academy in 1915. Eddington engaged in promoting the new theory, and in order to put one of its predictions — the bending of light in a gravitational field — to the test, he arranged for the famous expeditions to observe the eclipse of 29 May 1919 to be mounted, the results of which, presented in November of the same year, were the major breakthrough of general relativity and provoked a public interest unprecedented in the whole history of science.
But a history of general relativity in the English-speaking world would be thoroughly incomplete if it did not take into account the contributions made by another, nowadays almost forgotten but at that time probably the most prolific and most dedicated of its popularizers, the Australian physicist and translator Henry L. Brose. Largely overlooked in recent accounts of the history of general relativity, Brose's rendering into English of a series of excellent German works on the theory was decisive for its understanding in the Anglo-Saxon world. The texts he chose (including Moritz Schlick's Space and Time in Contemporary Physics and Hermann Weyl's Space, Time, Matter) were among the first and most important that had so far appeared on the subject, and their English translations were published at a time when accounts of what was to be called 'one of the greatest of achievements in the history of human thought' were scarce and badly needed in Britain. Also, it will become clear from a closer look at both Brose's biography and the tense political situation between Britain and Germany shortly after the Great War, that hardly any of those works would have made its way into England so promptly (if at all) if not for Brose's enormous personal efforts and dedication. This paper retraces Brose's role as a translator and promotor of general relativity in its early days, thus shedding light on the mechanisms of knowledge transfer during and after the First World War.
Ferdinand Mueller and the Shape of Nature: Nineteenth-century Systems of Plant Classification
Authors: Maroske Sara
Published: November 2006

In the nineteenth century, systematic botanists were preoccupied with the search for a so-called 'natural' system of classification, in which the names, order and rank of groups conveyed information about the relationships between plants. One such was Ferdinand Mueller who first identified this as a problem in which he was interested as a young man in Schleswig-Holstein. After moving to Australia in 1847, he encountered a flora so rich and diverse that he was emboldened to draw his own conclusions in systematics. These incorporated ideas originating in the previous century such as 'continuity' and the 'constancy' of species, evident in the work of Linnaeus and Jussieu, but also newer ideas, especially in relation to gymnosperms. Mueller met with resistance to his version of the natural system from Joseph Hooker and George Bentham at Kew Gardens in England, but received tacit support from colleagues in continental Europe who were busy making their own changes to classification. In Australia, Mueller was able to bring his influence to bear more successfully, and those who followed his version of the natural system helped him to establish a more independent local tradition in science.
Global mapping of c-Myc binding sites and target gene networks in human B cells
Authors: Zeller Karen I. , Zhao XiaoDong , Lee Charlie W. H. , Chiu Kuo Ping , Yao Fei , Yustein Jason T. , Ooi Hong Sain , Orlov Yuriy L. , Shahab Atif , Yong How Choong , Fu YuTao , Weng Zhiping , Kuznetsov Vladimir A. , Sung Wing-Kin , Ruan Yijun , Dang Chi V. , Wei Chia-Lin
Published: November 2006

The protooncogene
MYC
encodes the c-Myc transcription factor that regulates cell growth, cell proliferation, cell cycle, and apoptosis. Although deregulation of
MYC
contributes to tumorigenesis, it is still unclear what direct Myc-induced transcriptomes promote cell transformation. Here we provide a snapshot of genome-wide, unbiased characterization of direct Myc binding targets in a model of human B lymphoid tumor using ChIP coupled with pair-end ditag sequencing analysis (ChIP-PET). Myc potentially occupies >4,000 genomic loci with the majority near proximal promoter regions associated frequently with CpG islands. Using gene expression profiles with ChIP-PET, we identified 668 direct Myc-regulated gene targets, including 48 transcription factors, indicating that Myc is a central transcriptional hub in growth and proliferation control. This first global genomic view of Myc binding sites yields insights of transcriptional circuitries and cis regulatory modules involving Myc and provides a substantial framework for our understanding of mechanisms of Myc-induced tumorigenesis.
Understanding ensemble protein folding at atomic detail
Authors: Hubner Isaac A. , Deeds Eric J. , Shakhnovich Eugene I.
Published: November 2006

It has long been known that a protein's amino acid sequence dictates its native structure. However, despite significant recent advances, an ensemble description of how a protein achieves its native conformation from random coil under physiologically relevant conditions remains incomplete. Here we present a detailed all-atom model with a transferable potential that is capable of
ab initio
folding of entire protein domains using only sequence information. The computational efficiency of this model allows us to perform thousands of microsecond-time scale-folding simulations of the engrailed homeodomain and to observe thousands of complete independent folding events. We apply a graph-theoretic analysis to this massive data set to elucidate which intermediates and intermediary states are common to many trajectories and thus important for the folding process. This method provides an atomically detailed and complete picture of a folding pathway at the ensemble level. The approach that we describe is quite general and could be used to study the folding of proteins on time scales orders of magnitude longer than currently possible.
Viscoelastic properties of individual glial cells and neurons in the CNS
Authors: Lu Yun-Bi , Franze Kristian , Seifert Gerald , Steinhäuser Christian , Kirchhoff Frank , Wolburg Hartwig , Guck Jochen , Janmey Paul , Wei Er-Qing , Käs Josef , Reichenbach Andreas
Published: November 2006

One hundred fifty years ago glial cells were discovered as a second, non-neuronal, cell type in the central nervous system. To ascribe a function to these new, enigmatic cells, it was suggested that they either glue the neurons together (the Greek word “γλια” means “glue”) or provide a robust scaffold for them (“support cells”). Although both speculations are still widely accepted, they would actually require quite different mechanical cell properties, and neither one has ever been confirmed experimentally. We investigated the biomechanics of CNS tissue and acutely isolated individual neurons and glial cells from mammalian brain (hippocampus) and retina. Scanning force microscopy, bulk rheology, and optically induced deformation were used to determine their viscoelastic characteristics. We found that (
i
) in all CNS cells the elastic behavior dominates over the viscous behavior, (
ii
) in distinct cell compartments, such as soma and cell processes, the mechanical properties differ, most likely because of the unequal local distribution of cell organelles, (
iii
) in comparison to most other eukaryotic cells, both neurons and glial cells are very soft (“rubber elastic”), and (
iv
) intriguingly, glial cells are even softer than their neighboring neurons. Our results indicate that glial cells can neither serve as structural support cells (as they are too soft) nor as glue (because restoring forces are dominant) for neurons. Nevertheless, from a structural perspective they might act as soft, compliant embedding for neurons, protecting them in case of mechanical trauma, and also as a soft substrate required for neurite growth and facilitating neuronal plasticity.
Inhibition of dynamin completely blocks compensatory synaptic vesicle endocytosis
Authors: Newton A. Jamila , Kirchhausen Tom , Murthy Venkatesh N.
Published: November 2006

The ability of synapses to sustain signal propagation relies on rapid recycling of transmitter-containing presynaptic vesicles. Clathrin- and dynamin-mediated retrieval of vesicular membrane has an undisputed role in synaptic vesicle recycling. There is also evidence for other modes of vesicle retrieval, including bulk retrieval and the so-called kiss-and-run recycling. Whether dynamin in required for these other modes of synaptic vesicle endocytosis remains unclear. Here, we have tested the role of dynamin in synaptic vesicle endocytosis by using a small molecule called dynasore, which rapidly inhibits the GTPase activity of dynamin with high specificity. Endocytosis after sustained or brief stimuli was completely and reversibly blocked by dynasore in cultured hippocampal neurons expressing the fluorescent tracer synaptopHluorin. By contrast, dynasore had no effect on exocytosis. In the presence of dynasore, low-frequency stimulation led to sustained accumulation of synaptopHluorin and other vesicular proteins on the surface membrane at a rate predicted from net exocytosis. These vesicular components remained on surface membranes even after the stimulus was terminated, suggesting that all endocytic events rely on dynamin during low-frequency activity as well as in the period after it. Ultrastructural analysis revealed a reduction in the density of synaptic vesicles and the presence of endocytic structures only at synapses that were stimulated in the presence of dynasore. In sum, our data indicate that dynamin is essential for all forms of compensatory synaptic vesicle endocytosis including any kiss-and-run events.
Bcl10 and Malt1 control lysophosphatidic acid-induced NF-κB activation and cytokine production
Authors: Klemm Stefanie , Zimmermann Stephanie , Peschel Christian , Mak Tak W. , Ruland Jürgen
Published: November 2006

Lysophosphatidic acid (LPA) is a potent bioactive phospholipid that stimulates a variety of cellular responses by acting on cognate G protein-coupled receptors (GPCRs). There is increasing evidence that LPA signaling reprograms gene expression, but the GPCR-induced pathways connecting LPA receptor stimulation to downstream transcription factors are not well characterized. Here, we identify the adapter proteins Bcl10 and Malt1 as essential mediators of LPA-induced NF-κB activation. Both proteins were previously known to activate NF-κB in response to antigen receptor ligation on lymphocytes, but their functions in nonimmune cells are still largely undefined. By using murine embryonic fibroblasts from Bcl10- or Malt1-deficient mice as a genetic model, we report that Bcl10 and Malt1 are critically required for the degradation of IκB-α and the subsequent NF-κB induction in response to LPA stimulation. Bcl10 and Malt1 cooperate with PKCs selectively for LPA-induced NF-κB activation but are dispensable for the activation of the Jnk, p38, Erk MAP kinase, and Akt signaling pathways. In a biological readout, we demonstrate that LPA-induced IL-6 production is abolished in the absence of Bcl10. Thus, our results identify a NF-κB-inducing signaling pathway downstream of GPCRs and reveal previously unrecognized functions for Bcl10/Malt1 signaling in nonimmune cells.
Lipocalin-type prostaglandin D synthase produces prostaglandin D
2
involved in regulation of physiological sleep
Authors: Qu Wei-Min , Huang Zhi-Li , Xu Xin-Hong , Aritake Kosuke , Eguchi Naomi , Nambu Fumio , Narumiya Shu , Urade Yoshihiro , Hayaishi Osamu
Published: November 2006

Prostaglandin (PG) D
2
has been proposed to be essential for the initiation and maintenance of the physiological sleep of rats because intracerebroventricular administration of selenium tetrachloride (SeCl
4
), a selective inhibitor of PGD synthase (PGDS), was shown to reduce promptly and effectively the amounts of sleep during the period of infusion. However, gene knockout (KO) mice of PGDS and prostaglandin D receptor (DP
1
R) showed essentially the same circadian profiles and daily amounts of sleep as wild-type (WT) mice, raising questions about the involvement of PGD
2
in regulating physiological sleep. Here we examined the effect of SeCl
4
on the sleep of WT and KO mice for PGDS and DP
1
R and that of a DP
1
R antagonist, ONO-4127Na, on the sleep of rats. The i.p. injection of SeCl
4
into WT mice decreased the PGD
2
content in the brain without affecting the amounts of PGE
2
and PGF
2α
. It inhibited sleep dose-dependently and immediately after the administration during the light period when mice normally sleep, increasing the wake time; and the treatment with this compound resulted in a distinct sleep rebound during the following dark period. The SeCl
4
-induced insomnia was observed in hematopoietic PGDS KO mice but not at all in lipocalin-type PGDS KO, hematopoietic and lipocalin-type PGDS double KO or DP
1
R KO mice. Furthermore, the DP
1
R antagonist ONO-4127Na reduced sleep of rats by 30% during infusion into the subarachnoid space under the rostral basal forebrain at 200 pmol/min. These results clearly show that the lipocalin-type PGDS/PGD
2
/DP
1
R system plays pivotal roles in the regulation of physiological sleep.
l
,
l
-diaminopimelate aminotransferase, a trans-kingdom enzyme shared by
Chlamydia
and plants for synthesis of diaminopimelate/lysine
Authors: McCoy Andrea J. , Adams Nancy E. , Hudson André O. , Gilvarg Charles , Leustek Thomas , Maurelli Anthony T.
Published: November 2006

The synthesis of
meso
-diaminopimelic acid (
m
-DAP) in bacteria is essential for both peptidoglycan and lysine biosynthesis. From genome sequencing data, it was unclear how bacteria of the Chlamydiales order would synthesize
m
-DAP in the absence of
dapD
,
dapC
, and
dapE
, which are missing from the genome. Here, we assessed the biochemical capacity of
Chlamydia trachomatis
serovar L2 to synthesize
m
-DAP. Expression of the chlamydial
asd
,
dapB
, and
dapF
genes in the respective
Escherichia coli
m
-DAP auxotrophic mutants restored the mutants to DAP prototrophy. Screening of a
C. trachomatis
genomic library in an
E. coli
Δ
dapD
DAP auxotroph identified
ct390
as encoding an enzyme that restored growth to the
Escherichia coli
mutant.
ct390
also was able to complement an
E. coli
Δ
dapD
Δ
dapE
, but not a Δ
dapD
Δ
dapF
mutant, providing genetic evidence that it encodes an aminotransferase that may directly convert tetrahydrodipicolinate to
l
,
l
-diaminopimelic acid. This hypothesis was supported by
in vitro
kinetic analysis of the CT390 protein and the fact that similar properties were demonstrated for the
Protochlamydia amoebophila
homologue, PC0685.
In vivo
, the
C. trachomatis
m
-DAP synthesis genes are expressed as early as 8 h after infection. An aminotransferase activity analogous to CT390 recently has been characterized in plants and cyanobacteria. This previously undescribed pathway for
m
-DAP synthesis supports an evolutionary relationship among the chlamydiae, cyanobacteria, and plants and strengthens the argument that chlamydiae synthesize a cell wall despite the inability of efforts to date to detect peptidoglycan in these organisms.
Refolding of a paramyxovirus F protein from prefusion to postfusion conformations observed by liposome binding and electron microscopy
Authors: Connolly Sarah A. , Leser George P. , Yin Hsien-Shen , Jardetzky Theodore S. , Lamb Robert A.
Published: November 2006

For paramyxoviruses, two viral glycoproteins are key to the entry process: an attachment protein (HN, H, or G) and the fusion protein (F). The F protein folds to a metastable state that can be triggered to undergo large conformational rearrangements to a fusogenic intermediate and a more stable postfusion state. The triggering mechanism that controls paramyxovirus fusion has not been elucidated. To correlate the molecular structure of a soluble form of the prefusion F (PIV5 F-GCNt) with the biological function of F, soluble F protein was triggered to refold. In the absence of HN, heat was found to function as a surrogate F trigger, and F associated with liposomes and aggregated on sucrose density gradients. Electron microscopy data showed that triggered F formed rosettes. Taken together these data suggest that release and membrane insertion of the hydrophobic fusion peptide require both cleavage of F and heat. Heating of cleaved F causes conversion to a postfusion form as judged by its “golf tee” morphology in the electron microscope. Heating of uncleaved F also causes conversion of F to a morphologically similar form. The reactivity of the F protein with conformation-specific mAbs and peptide binding suggest that soluble F-GCNt and membrane-bound F proteins refold through a comparable pathway.
How do World-Class Cricket Batsmen Anticipate a Bowler's Intention?
Authors: Müller Sean , Abernethy Bruce , Farrow Damian
Published: November 2006

Four experiments are reported that examine the ability of cricket batsmen of different skill levels to pick up advance information to anticipate the type and length of balls bowled by swing and spin bowlers. The information available upon which to make the predictive judgements was manipulated through a combination of temporal occlusion of the display and selective occlusion or presentation of putative anticipatory cues. In addition to a capability to pick up advance information from the same cues used by intermediate and low-skilled players, highly skilled players demonstrated the additional, unique capability to pick up advance information from some specific early cues (especially bowling hand and arm cues) to which the less skilled players were not attuned. The acquisition of expert perceptual-motor skill appears to involve not only refinement of information extraction but also progression to the use of earlier, kinematically relevant sources of information.
Regulation of Cdc42 GTPase Activity in the Formation of Hyphae inCandida albicans
Authors: Court Helen , Sudbery Peter
Published: November 2006

The human fungal pathogen Candida albicans can switch between yeast, pseudohyphal, and hyphal morphologies. To investigate whether the distinctive characteristics of hyphae are due to increased activity of the Cdc42 GTPase, strains lacking negative regulators of Cdc42 were constructed. Unexpectedly, the deletion of the Cdc42 Rho guanine dissociation inhibitor RDI1 resulted in reduced rather than enhanced polarized growth. However, when cells lacking both Cdc42 GTPase-activating proteins, encoded by RGA2 and BEM3, were grown under pseudohyphal-promoting conditions the bud was highly elongated and lacked a constriction at its base, so that its shape resembled a hyphal germ tube. Moreover, a Spitzenkörper was present at the bud tip, a band of disorganized septin was present at bud base, true septin rings formed within the bud, and nuclei migrated out of the mother cell before the first mitosis. These are all characteristic features of a hyphal germ tube. Intriguingly, we observed hyphal-specific phosphorylation of Rga2, suggesting a possible mechanism for Cdc42 activation during normal hyphal development. In contrast, expression of Cdc42G12V, which is constitutively GTP bound because it lacks GTPase activity, resulted in swollen cells with prominent and stable septin bars. These results suggest the development of hyphal-specific characteristics is promoted by Cdc42-GTP in a process that also requires the intrinsic GTPase activity of Cdc42.
Endocytic Recycling in Yeast Is Regulated by Putative Phospholipid Translocases and the Ypt31p/32p–Rcy1p Pathway
Authors: Furuta Nobumichi , Fujimura-Kamada Konomi , Saito Koji , Yamamoto Takaharu , Tanaka Kazuma
Published: November 2006

Phospholipid translocases (PLTs) have been implicated in the generation of phospholipid asymmetry in membrane bilayers. In budding yeast, putative PLTs are encoded by the DRS2 gene family of type 4 P-type ATPases. The homologous proteins Cdc50p, Lem3p, and Crf1p are potential noncatalytic subunits of Drs2p, Dnf1p and Dnf2p, and Dnf3p, respectively; these putative heteromeric PLTs share an essential function for cell growth. We constructed temperature-sensitive mutants of CDC50 in the lem3Δ crf1Δ background (cdc50-ts mutants). Screening for multicopy suppressors of cdc50-ts identified YPT31/32, two genes that encode Rab family small GTPases that are involved in both the exocytic and endocytic recycling pathways. The cdc50-ts mutants did not exhibit major defects in the exocytic pathways, but they did exhibit those in endocytic recycling; large membranous structures containing the vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor Snc1p intracellularly accumulated in these mutants. Genetic results suggested that the YPT31/32 effector RCY1 and CDC50 function in the same signaling pathway, and simultaneous overexpression of CDC50, DRS2, and GFP-SNC1 restored growth as well as the plasma membrane localization of GFP-Snc1p in the rcy1Δ mutant. In addition, Rcy1p coimmunoprecipitated with Cdc50p-Drs2p. We propose that the Ypt31p/32p–Rcy1p pathway regulates putative phospholipid translocases to promote formation of vesicles destined for the trans-Golgi network from early endosomes.
Depletion of E-Cadherin Disrupts Establishment but Not Maintenance of Cell Junctions in Madin-Darby Canine Kidney Epithelial Cells
Authors: Capaldo Christopher T. , Macara Ian G.
Published: November 2006

E-cadherin forms calcium-dependent homophilic intercellular adhesions between epithelial cells. These contacts regulate multiple aspects of cell behavior, including the organization of intercellular tight junctions (TJs). To distinguish between the roles of E-cadherin in formation versus maintenance of junctions, Madin-Darby canine kidney (MDCK) cells were depleted of E-cadherin by RNA interference. Surprisingly, reducing E-cadherin expression had little effect on the protein levels or localization of adherens junction (AJ) or TJ markers. The cells underwent morphological changes, as the normally flat apical surface swelled into a dome. However, apical–basal polarity was not compromised, transmembrane resistance was normal, and zonula occludin protein 1 dynamics at the TJs were unchanged. Additionally, an E-cadherin/Cadherin-6 double knockdown also failed to disrupt established TJs, although β-catenin was lost from the cell cortex. Nevertheless, cells depleted of E-cadherin failed to properly reestablish cell polarity after junction disassembly. Recovery of cell–cell adhesion, transepithelial resistance, and the localization of TJ and AJ markers were all delayed. In contrast, depletion of α-catenin caused long-term disruption of junctions. These results indicate that E-cadherin and Cadherin-6 function as a scaffold for the construction of polarized structures, and they become largely dispensable in mature junctions, whereas α-catenin is essential for the maintenance of functional junctions.
PGY Repeats and N-Glycans Govern the Trafficking of Paranodin and Its Selective Association with Contactin and Neurofascin-155
Authors: Bonnon Carine , Bel Christophe , Goutebroze Laurence , Maigret Bernard , Girault Jean-Antoine , Faivre-Sarrailh Catherine
Published: November 2006

Formation of nodes of Ranvier requires contact of axons with myelinating glial cells, generating specialized axo-glial subdomains. Caspr/paranodin is required for the formation of septate-like junctions at paranodes, whereas the related caspr2 is essential for the organization of juxtaparanodes. The molecular mechanisms underlying the segregation of these related glycoproteins within distinct complexes are poorly understood. Exit of paranodin from the endoplasmic reticulum (ER) is mediated by its interaction with F3/contactin. Using domain swapping with caspr2, we mapped a motif with Pro-Gly-Tyr repeats (PGY) in the ectodomain of paranodin responsible for its ER retention. Deletion of PGY allows cell surface delivery of paranodin bypassing the calnexin-calreticulin quality control. Conversely, insertion of PGY in caspr2 or NrCAM blocks these proteins in the ER. PGY is a novel type of processing signal that compels chaperoning of paranodin by contactin. Contactin associated with paranodin is expressed at the cell surface with high-mannose N-glycans. Using mutant CHO lines altered in the processing of N-linked carbohydrates, we show that the high-mannose glycoform of contactin strongly binds neurofascin-155, its glial partner at paranodes. Thus, the unconventional processing of paranodin and contactin may determine the selective association of axo-glial complexes at paranodes.
The Interplay of the N- and C-Terminal Domains of MCAK Control Microtubule Depolymerization Activity and Spindle Assembly
Authors: Ems-McClung Stephanie C. , Hertzer Kathleen M. , Zhang Xin , Miller Mill W. , Walczak Claire E.
Published: November 2006

Spindle assembly and accurate chromosome segregation require the proper regulation of microtubule dynamics. MCAK, a Kinesin-13, catalytically depolymerizes microtubules, regulates physiological microtubule dynamics, and is the major catastrophe factor in egg extracts. Purified GFP-tagged MCAK domain mutants were assayed to address how the different MCAK domains contribute to in vitro microtubule depolymerization activity and physiological spindle assembly activity in egg extracts. Our biochemical results demonstrate that both the neck and the C-terminal domain are necessary for robust in vitro microtubule depolymerization activity. In particular, the neck is essential for microtubule end binding, and the C-terminal domain is essential for tight microtubule binding in the presence of excess tubulin heterodimer. Our physiological results illustrate that the N-terminal domain is essential for regulating microtubule dynamics, stimulating spindle bipolarity, and kinetochore targeting; whereas the C-terminal domain is necessary for robust microtubule depolymerization activity, limiting spindle bipolarity, and enhancing kinetochore targeting. Unexpectedly, robust MCAK microtubule (MT) depolymerization activity is not needed for sperm-induced spindle assembly. However, high activity is necessary for proper physiological MT dynamics as assayed by Ran-induced aster assembly. We propose that MCAK activity is spatially controlled by an interplay between the N- and C-terminal domains during spindle assembly.
Inferential, robust non-negative matrix factorization analysis of microarray data
Authors: Fogel Paul , Young S. Stanley , Hawkins Douglas M. , Ledirac Nathalie
Published: November 2006

Motivation: Modern methods such as microarrays, proteomics and metabolomics often produce datasets where there are many more predictor variables than observations. Research in these areas is often exploratory; even so, there is interest in statistical methods that accurately point to effects that are likely to replicate. Correlations among predictors are used to improve the statistical analysis. We exploit two ideas: non-negative matrix factorization methods that create ordered sets of predictors; and statistical testing within ordered sets which is done sequentially, removing the need for correction for multiple testing within the set.

Results: Simulations and theory point to increased statistical power. Computational algorithms are described in detail. The analysis and biological interpretation of a real dataset are given. In addition to the increased power, the benefit of our method is that the organized gene lists are likely to lead better understanding of the biology.

Availability: An SAS JMP executable script is available from

Contact:  young@niss.org

Supplementary information:
Neural network prediction of peptide separation in strong anion exchange chromatography
Authors: Oh Cheolhwan , Żak Stanislaw H. , Mirzaei Hamid , Buck Charles , Regnier Fred E. , Zhang Xiang
Published: November 2006

Motivation: The still emerging combination of technologies that enable description and characterization of all expressed proteins in a biological system is known as proteomics. Although many separation and analysis technologies have been employed in proteomics, it remains a challenge to predict peptide behavior during separation processes. New informatics tools are needed to model the experimental analysis method that will allow scientists to predict peptide separation and assist with required data mining steps, such as protein identification.

Results: We developed a software package to predict the separation of peptides in strong anion exchange (SAX) chromatography using artificial neural network based pattern classification techniques. A multi-layer perceptron is used as a pattern classifier and it is designed with feature vectors extracted from the peptides so that the classification error is minimized. A genetic algorithm is employed to train the neural network. The developed system was tested using 14 protein digests, and the sensitivity analysis was carried out to investigate the significance of each feature.

Availability: The software and testing results can be downloaded from .

Contact:  zhang100@purdue.edu
AGScan: a pluggable microarray image quantification software based on the ImageJ library
Authors: Cathelin R. , Lopez F. , Klopp Ch.
Published: November 2006

Summary: Many different programs are available to analyze microarray images. Most programs are commercial packages, some are free. In the latter group only few propose automatic grid alignment and batch mode. More often than not a program implements only one quantification algorithm. AGScan is an open source program that works on all major platforms. It is based on the ImageJ library [Rasband (1997–2006)] and offers a plug-in extension system to add new functions to manipulate images, align grid and quantify spots. It is appropriate for daily laboratory use and also as a framework for new algorithms.

Availability: The program is freely distributed under X11 Licence. The install instructions can be found in the user manual. The software can be downloaded from . The questions and plug-ins can be sent to the contact listed below.

Contact:  christophe.klopp@toulouse.inra.fr