bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of negative capacitance in a nanocolloid
Authors: Shulman J. , Xue Y. Y. , Tsui S. , Chen F. , Chu C. W.
Published: February 2011

Negative capacitance (NC) is a rather ubiquitous phenomenon that is found in many complex materials ranging from semiconductor devices to biological membranes. The underlying physical processes in this diverse collection differ considerably. However, we previously demonstrated that a relationship exists between NC and the conductivity of the material. Here, we examine and exploit this relationship in an effort to pinpoint the source of NC in a nanocolloid, composed of urea coated nanoparticles in silicone oil, which has previously been shown to exhibit the NC effect. This is accomplished by investigating the influence of several external parameters, such as temperature and moisture content, on the NC and conductance of the colloid as well as solid materials created from the nanoparticles used in the colloid. In addition to NC, the colloid demonstrates the electrorheological (ER) effect. It is shown that large scale particle motions, such as those that generate the ER effect, are not responsible for the NC. The results demonstrate that the nanoparticle surface conductivity is the relevant parameter to the NC in this system, effectively isolating the origin of the NC to nanoparticle surface. Further, this appears to be a rather general feature of NC in dielectric nanosystems.
Locating a weak change using diffuse waves: Theoretical approach and inversion procedure
Authors: Rossetto Vincent , Margerin Ludovic , Planès Thomas , Larose Éric
Published: February 2011

We describe a time-resolved monitoring technique for heterogeneous media. Our approach is based on the spatial variations of the cross-coherence of diffuse waves acquired at fixed positions but at different dates. The technique applies to all kind of waves, provided that waveforms can be acquired with a sampling frequency much larger than the wave frequency. To locate and characterize a weak change that occurred between successive acquisitions, we use a maximum likelihood approach combined with a diffusive propagation model. We characterize this technique, locating a weak change using diffuse waves, called LOCADIFF, with the aid of numerical simulations. In several illustrative examples, we show that the change can be located with a precision of a few wavelengths and that its effective scattering cross-section can be retrieved. We investigate how the accuracy and precision of the method depends on the number of source-receiver pairs, on the time window used to compute the cross-correlation and on the errors in the propagation model. Applications can be found in nondestructive testing, seismology, radar, and sonar location.
Phase-space path integral and Brownian motion
Authors: Yamashita Hideyasu
Published: February 2011

We formulate and examine a phase-space path integral representation of a quantum time evolution in terms of Fock–Bargmann spaces and stochastic line integrals. The Fock–Bargmann space \documentclass[12pt]{minimal}\begin{document}${{\cal H}_{\rm FB}}$\end{document}H FB is a closed subspace of \documentclass[12pt]{minimal}\begin{document}$L^2({\cal M})$\end{document}L2(M), where \documentclass[12pt]{minimal}\begin{document}${\cal M}$\end{document}M is the phase space. Let EFB be the orthogonal projection onto \documentclass[12pt]{minimal}\begin{document}${{\cal H}_{\rm FB}}$\end{document}H FB , and h the classical Hamiltonian, then H = EFBhEFB is understood as a quantization of h. The quantum time evolution e−itH is asymptotically represented by the solution of a variant of diffusion equation with the imaginary potential ih. Thus the quantum time evolution can be represented stochastically, in terms of Brownian motions and stochastic integrals.
Fast numerical treatment of nonlinear wave equations by spectral methods
Authors: Skjaeraasen Olaf , Robinson P. A. , Newman D. L.
Published: February 2011

A method is presented that accelerates spectral methods for numerical solution of a broad class of nonlinear partial differential wave equations that are first order in time and that arise in plasma wave theory. The approach involves exact analytical treatment of the linear part of the wave evolution including growth and damping as well as dispersion. After introducing the method for general scalar and vector equations, we discuss and illustrate it in more detail in the context of the coupling of high- and low-frequency plasma wave modes, as modeled by the electrostatic and electromagnetic Zakharov equations in multiple dimensions. For computational efficiency, the method uses eigenvector decomposition, which is particularly advantageous when the wave damping is mode-dependent and anisotropic in wavenumber space. In this context, it is shown that the method can significantly speed up numerical integration relative to standard spectral or finite difference methods by allowing much longer time steps, especially in the limit in which the nonlinear Schrödinger equation applies.
Laser prepulse induced plasma channel formation in air and relativistic self focusing of an intense short pulse
Authors: Kumar Ashok , Dahiya Deepak , Sharma A. K.
Published: February 2011

An analytical formalism is developed and particle-in-cell simulations are carried out to study plasma channel formation in air by a two pulse technique and subsequent relativistic self focusing of the third intense laser through it. The first prepulse causes tunnel ionization of air. The second pulse heats the plasma electrons and establishes a prolonged channel. The third pulse focuses under the combined effect of density nonuniformity of the channel and relativistic mass nonlinearity. A channel with 20% density variation over the spot size of the third pulse is seen to strongly influence relativistic self focusing at normalized laser amplitude ∼0.4–1. In deeper plasma channels, self focusing is less sensitive to laser amplitude variation. These results are reproduced in particle-in-cell simulations. The present treatment is valid for millimeter range plasma channels.
Time sequence of energetic particle spectra in quasiparallel shocks in large simulation systems
Authors: Sugiyama Tooru
Published: February 2011

We have performed collisionless shock simulations using a one-dimensional hybrid particle-in-cell method to investigate the energy spectra of the differential intensity around the quasiparallel shocks. The system size is sufficiently large (200 000 ion inertia length) in order to eliminate the unphysical effect caused by the upstream boundary. The obtained spectrum of the differential intensity have the shape of the power-law with exponentially falling off in higher energy as predicted in previous simulations, however, the power-law indices and e-folding energy do not depend on the shock parameters, the shock Mach number MA (7.1–11.7) and the shock angle θBN (10°–40°). The power-law index is ∼1.0. This number is close to the prediction by the standard diffusive shock acceleration theory. However, the reason for the agreements between the values is not clear because an additional acceleration process is also observed in the present runs; this process was reported in [Sugiyama and Terasawa, Adv. Space Res. 24, 73 (1999)] and [Sugiyama et al., J. Geophys. Res. 106, 21657 (2001)]. The e-folding energy linearly increases in time for all runs. One of the reasons for these independent profiles on shock parameters is that the pitch angle distribution in the upstream region shows similar profiles in each run.
Structural and magnetic properties of Ru/Ni multilayers
Authors: Mergia K , Tomou A , Panagiotopoulos I , Ott F
Published: February 2011

Ru/Ni multilayers of different Ni thicknesses have been fabricated using magnetron sputtering. The structure of the multilayers has been determined by grazing incidence x-ray diffraction and x-ray reflectivity and their magnetic properties by magnetization and polarized neutron reflectivity measurements. The presence of Ru leads to the formation of a hexagonal Ni structure within an interfacial layer ∼1 nm above each Ru layer, while the rest of the Ni layer relaxes to the equilibrium fcc structure. The hcp Ni interfacial layer has a substantially increased cell volume, and is ferromagnetic with an atomic magnetic moment that increases with Ni layer thickness but remains lower than the value predicted from ab initio calculations.
The surface defect-related electroluminescence from the ZnO microwire
Authors: Ding Meng , Zhao Dongxu , Yao Bin , Li Binghui , Zhang Zhenzhong , Shan Chongxin , Shen Dezhen
Published: February 2011

Surface defect-related electroluminescence (EL) was realized from a single ZnO microwire-based metal–semiconductor–metal structure on a glass substrate. ZnO microwires were successfully fabricated using a simple chemical vapour deposition approach. Schottky contacts were detected between Au electrodes and the ZnO microwire. The EL spectrum showed a broad emission band covering the visible range from 400 to 700 nm. The possible EL emission mechanism is discussed in detail in this paper.
Silicon–germanium interdiffusion in strained Ge/SiGe multiple quantum well structures
Authors: Xue-Chao Liu  , D R Leadley
Published: February 2011

The corresponding author, Xue-Chao Liu, would like to apologize for the omission of some of the contributing authors from this published paper. The full list of contributing authors should read:

Xue-Chao Liu, R J H Morris, M Myronov, A Dobbie and D R Leadley

Dr R J H Morris contributed the secondary ion mass spectrometry measurement and analysis, shown in figure 2. Drs M Myronov and A Dobbie contributed by growing the samples.
Geometry of the Siegel modular threefold with paramodular level structure
Authors: Yu Chia-Fu
Published: February 2011

In this paper we extend some results of Norman and Oort and of de Jong, and give an explicit description of the geometry of the Siegel modular threefold with paramodular level structure. We also discuss advantages and restrictions of three standard methods for studying moduli spaces of abelian varieties.
A dichotomy for Fatou components of polynomial skew products
Authors: Roeder Roland
Published: February 2011

We consider polynomial maps of the form

f
(
z
,
w
)
=
(
p
(
z
)
,
q
(
z
,
w
)
)

f(z,w) = (p(z),q(z,w))

that extend as holomorphic maps of

C
P

2

\mathbb {CP}^2

. Mattias Jonsson introduces in “Dynamics of polynomial skew products on

C

2

\mathbf {C}^2

” [Math. Ann., 314(3): 403–447, 1999] a notion of connectedness for such polynomial skew products that is analogous to connectivity for the Julia set of a polynomial map in one-variable. We prove the following dichotomy: if

f
f

is an Axiom-A polynomial skew product, and

f
f

is connected, then every Fatou component of

f
f

is homeomorphic to an open ball; otherwise, some Fatou component of

F
F

has infinitely generated first homology.
Regulation of flagellar motility by the conserved flagellar protein CG34110/Ccdc135/FAP50
Authors: Yang Yong , Cochran Deborah A. , Gargano Mary D. , King Iryna , Samhat Nayef K. , Burger Benjain P. , Sabourin Katherine R. , Hou Yuqing , Awata Junya , Parry David A.D. , Marshall Wallace F. , Witman George B. , Lu Xiangyi
Published: February 2011

Eukaryotic cilia and flagella are vital sensory and motile organelles. The calcium channel PKD2 mediates sensory perception on cilia and flagella, and defects in this can contribute to ciliopathic diseases. Signaling from Pkd2-dependent Ca2+rise in the cilium to downstream effectors may require intermediary proteins that are largely unknown. To identify these proteins, we carried out genetic screens for mutations affecting Drosophila melanogaster sperm storage, a process mediated by Drosophila Pkd2. Here we show that a new mutation lost boys (lobo) encodes a conserved flagellar protein CG34110, which corresponds to vertebrate Ccdc135 (E = 6e-78) highly expressed in ciliated respiratory epithelia and sperm, and to FAP50 (E = 1e-28) in the Chlamydomonas reinhardtii flagellar proteome. CG34110 localizes along the fly sperm flagellum. FAP50 is tightly associated with the outer doublet microtubules of the axoneme and appears not to be a component of the central pair, radial spokes, dynein arms, or structures defined by the mbo waveform mutants. Phenotypic analyses indicate that both Pkd2 and lobo specifically affect sperm movement into the female storage receptacle. We hypothesize that the CG34110/Ccdc135/FAP50 family of conserved flagellar proteins functions within the axoneme to mediate Pkd2-dependent processes in the sperm flagellum and other motile cilia.
The proteomics of quiescent and nonquiescent cell differentiation in yeast stationary-phase cultures
Authors: Davidson George S. , Joe Ray M. , Roy Sushmita , Meirelles Osorio , Allen Chris P. , Wilson Melissa R. , Tapia Phillip H. , Manzanilla Elaine E. , Dodson Anne E. , Chakraborty Swagata , Carter Mark , Young Susan , Edwards Bruce , Sklar Larry , Werner-Washburne Margaret
Published: February 2011

As yeast cultures enter stationary phase in rich, glucose-based medium, differentiation of two major subpopulations of cells, termed quiescent and nonquiescent, is observed. Differences in mRNA abundance between exponentially growing and stationary-phase cultures and quiescent and nonquiescent cells are known, but little was known about protein abundance in these cells. To measure protein abundance in exponential and stationary-phase cultures, the yeast GFP-fusion library (4159 strains) was examined during exponential and stationary phases, using high-throughput flow cytometry (HyperCyt). Approximately 5% of proteins in the library showed twofold or greater changes in median fluorescence intensity (abundance) between the two conditions. We examined 38 strains exhibiting two distinct fluorescence-intensity peaks in stationary phase and determined that the two fluorescence peaks distinguished quiescent and nonquiescent cells, the two major subpopulations of cells in stationary-phase cultures. GFP-fusion proteins in this group were more abundant in quiescent cells, and half were involved in mitochondrial function, consistent with the sixfold increase in respiration observed in quiescent cells and the relative absence of Cit1p:GFP in nonquiescent cells. Finally, examination of quiescent cell–specific GFP-fusion proteins revealed symmetry in protein accumulation in dividing quiescent and nonquiescent cells after glucose exhaustion, leading to a new model for the differentiation of these cells.
Mitochondrial proteomic approach reveals galectin-7 as a novel BCL-2 binding protein in human cells
Authors: Villeneuve Christelle , Baricault Laurent , Canelle Ludovic , Barboule Nadia , Racca Carine , Monsarrat Bernard , Magnaldo Thierry , Larminat Florence
Published: February 2011

Although the anti-apoptotic activity of Bcl-2 has been extensively studied, its mode of action remains incompletely understood. Deciphering the network of Bcl-2 interacting factors is necessary to better understand the key function of Bcl-2 in apoptosis initiation. To identify novel Bcl-2 mitochondrial partners, we have combined a Bcl-2 immunocapture with a mass spectrometry analysis using highly pure mitochondrial fractions isolated from human cancer cells. We identified at high confidence 127 potential Bcl-2–interacting proteins. Gene ontology mining reveals enrichment for mitochondrial proteins, endoplasmic reticulum–associated proteins, and cytoskeleton-associated proteins. Importantly, we report the identification of galectin-7 (Gal7), a member of a family of β-galactoside–binding lectins that was already known to exhibit a pro-apoptotic function, as a new mitochondrial Bcl-2 interacting partner. Our data further show that endogenous Bcl-2 coimmunoprecipitates with Gal7 and that recombinant Gal7 directly interacts with recombinant Bcl-2. A fraction of Gal7 is constitutively localized at mitochondria in a Bcl-2–dependent manner and sensitizes the mitochondria to the apoptotic signal. In addition, we show that the Bcl-2/Gal7 interaction is abolished following genotoxic stress. Taken together, our findings suggest that the binding of Gal7 to Bcl-2 may constitute a new target for enhancing the intrinsic apoptosis pathway.
CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell trafficking and CD43 phosphorylation
Authors: Cannon J. L. , Mody P. D. , Blaine K. M. , Chen E. J. , Nelson A. D. , Sayles L. J. , Moore T. V. , Clay B. S. , Dulin N. O. , Shilling R. A. , Burkhardt J. K. , Sperling A. I.
Published: February 2011

Cell polarization is a key feature of cell motility, driving cell migration to tissues. CD43 is an abundantly expressed molecule on the T-cell surface that shows distinct localization to the migrating T-cell uropod and the distal pole complex (DPC) opposite the immunological synapse via association with the ezrin-radixin-moesin (ERM) family of actin regulatory proteins. CD43 regulates multiple T-cell functions, including T-cell activation, proliferation, apoptosis, and migration. We recently demonstrated that CD43 regulates T-cell trafficking through a phosphorylation site at Ser-76 (S76) within its cytoplasmic tail. Using a phosphorylation-specific antibody, we now find that CD43 phosphorylation at S76 is enhanced by migration signals. We further show that CD43 phosphorylation and normal T-cell trafficking depend on CD43 association with ERM proteins. Interestingly, mutation of S76 to mimic phosphorylation enhances T-cell migration and CD43 movement to the DPC while blocking ERM association, showing that CD43 movement can occur in the absence of ERM binding. We also find that protein kinase Cθ can phosphorylate CD43. These results show that while CD43 binding to ERM proteins is crucial for S76 phosphorylation, CD43 movement and regulation of T-cell migration can occur through an ERM-independent, phosphorylation–dependent mechanism.
Nuclear import of an intact preassembled proteasome particle
Authors: Savulescu Anca F. , Shorer Hagai , Kleifeld Oded , Cohen Ilana , Gruber Rita , Glickman Michael H. , Harel Amnon
Published: February 2011

The 26S proteasome is a conserved 2.5 MDa protein degradation machine that localizes to different cellular compartments, including the nucleus. Little is known about the specific targeting mechanisms of proteasomes in eukaryotic cells. We used a cell-free nuclear reconstitution system to test for nuclear targeting and import of distinct proteasome species. Three types of stable, proteolytically active proteasomes particles were purified from Xenopus egg cytosol. Two of these, the 26S holoenzyme and the 20S core particle, were targeted to the nuclear periphery but did not reach the nucleoplasm. This targeting depends on the presence of mature nuclear pore complexes (NPCs) in the nuclear envelope. A third, novel form, designated here as 20S+, was actively imported through NPCs. The 20S+ proteasome particle resembles recently described structural intermediates from other systems. Nuclear import of this particle requires functional NPCs, but it is not directly regulated by the Ran GTPase cycle. The mere presence of the associated “+” factors is sufficient to reconstitute nuclear targeting and confer onto isolated 20S core particles the ability to be imported. Stable 20S+ particles found in unfertilized eggs may provide a means for quick mobilization of existing proteasome particles into newly formed nuclear compartments during early development.
Functional characterization of putative cilia genes by high-content analysis
Authors: Lai Cary K. , Gupta Nidhi , Wen Xiaohui , Rangell Linda , Chih Ben , Peterson Andrew S. , Bazan J. Fernando , Li Li , Scales Suzie J.
Published: February 2011

Cilia are microtubule-based protrusions from the cell surface that are involved in a number of essential signaling pathways, yet little is known about many of the proteins that regulate their structure and function. A number of putative cilia genes have been identified by proteomics and comparative sequence analyses, but functional data are lacking for the vast majority. We therefore monitored the effects in three cell lines of small interfering RNA (siRNA) knockdown of 40 of these genes by high-content analysis. We assayed cilia number, length, and transport of two different cargoes (membranous serotonin receptor 6-green fluorescent protein [HTR6-GFP] and the endogenous Hedgehog [Hh] pathway transcription factor Gli3) by immunofluorescence microscopy; and cilia function using a Gli-luciferase Hh signaling assay. Hh signaling was most sensitive to perturbations, with or without visible structural cilia defects. Validated hits include Ssa2 and mC21orf2 with ciliation defects; Ift46 with short cilia; Ptpdc1 and Iqub with elongated cilia; and Arl3, Nme7, and Ssna1 with distinct ciliary transport but not length defects. Our data confirm various ciliary roles for several ciliome proteins and show it is possible to uncouple ciliary cargo transport from cilia formation in vertebrates.
Localization of Pom121 to the inner nuclear membrane is required for an early step of interphase nuclear pore complex assembly
Authors: Funakoshi Tomoko , Clever Michaela , Watanabe Ai , Imamoto Naoko
Published: February 2011

The nuclear pore complex (NPC) is a large protein assembly that mediates molecular trafficking between the cytoplasm and the nucleus. NPCs assemble twice during the cell cycle in metazoans: postmitosis and during interphase. In this study, using small interfering RNA (siRNA) in conjunction with a cell fusion–based NPC assembly assay, we demonstrated that pore membrane protein (Pom)121, a vertebrate-specific integral membrane nucleoporin, is indispensable for an early step in interphase NPC assembly. Functional domain analysis of Pom121 showed that its nuclear localization signals, which bind to importin β via importin α and likely function with RanGTP, play an essential role in targeting Pom121 to the interphase NPC. Furthermore, a region of Pom121 that interacts with the inner nuclear membrane (INM) and lamin B receptor was found to be crucial for its NPC targeting. Based on these findings and on evidence that Pom121 localizes at the INM in the absence of a complete NPC structure, we propose that the nuclear migration of Pom121 and its subsequent interaction with INM proteins are required to initiate interphase NPC assembly. Our data also suggest, for the first time, the importance of the INM as a seeding site for “prepores” during interphase NPC assembly.
Dual function of Rpn5 in two PCI complexes, the 26S proteasome and COP9 signalosome
Authors: Yu Zanlin , Kleifeld Oded , Lande-Atir Avigail , Bsoul Maisa , Kleiman Maya , Krutauz Daria , Book Adam , Vierstra Richard D. , Hofmann Kay , Reis Noa , Glickman Michael H. , Pick Elah
Published: February 2011

Subunit composition and architectural structure of the 26S proteasome lid is strictly conserved between all eukaryotes. This eight-subunit complex bears high similarity to the eukaryotic translation initiation factor 3 and to the COP9 signalosome (CSN), which together define the proteasome CSN/COP9/initiation factor (PCI) troika. In some unicellular eukaryotes, the latter two complexes lack key subunits, encouraging questions about the conservation of their structural design. Here we demonstrate that, in Saccharomyces cerevisiae, Rpn5 plays dual roles by stabilizing proteasome and CSN structures independently. Proteasome and CSN complexes are easily dissected, with Rpn5 the only subunit in common. Together with Rpn5, we identified a total of six bona fide subunits at roughly stoichiometric ratios in isolated, affinity-purified CSN. Moreover, the copy of Rpn5 associated with the CSN is required for enzymatic hydrolysis of Rub1/Nedd8 conjugated to cullins. We propose that multitasking by a single subunit, Rpn5 in this case, allows it to function in different complexes simultaneously. These observations demonstrate that functional substitution of subunits by paralogues is feasible, implying that the canonical composition of the three PCI complexes in S. cerevisiae is more robust than hitherto appreciated.
DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin
Authors: Yeh Yi-Chun , Wu Chia-Ching , Wang Yang-Kao , Tang Ming-Jer
Published: February 2011

Discoidin domain receptor 1 (DDR1) promotes E-cadherin–mediated adhesion. The underlying mechanism and its significance, however, have not been elucidated. Here we show that DDR1 overexpression augmented, whereas dominant negative mutant (DN-DDR1) or knockdown of DDR1 inhibited E-cadherin localized in cell-cell junctions in epithelial cells. DDR1 changed the localization and abundance of E-cadherin, as well as epithelial plasticity, as manifested by enhancement of microvilli formation and alteration of cytoskeletal organization. DDR1 also reduced protein abundance of mesenchymal markers, whereas DN-DDR1 and sh-DDR1 showed opposite effects. These results suggest that expression of DDR1 increases epithelial plasticity. Expression of DDR1 augmented E-cadherin protein levels by decreasing its degradation rate. Photobleaching and photoconversion of E-cadherin conjugated with Eos fluorescence protein demonstrated that DDR1 increased the stability of E-cadherin on the cell membrane, whereas sh-DDR1 decreased it. Pull-down assay and expression of constitutively active or dominant-negative Cdc42 showed that DDR1 stabilized E-cadherin through inactivation of Cdc42. Altogether, our results show that DDR1 promotes cell-cell adhesion and differentiation through stabilization of E-cadherin, which is mediated by Cdc42 inactivation.
Class V β-tubulin alters dynamic instability and stimulates microtubule detachment from centrosomes
Authors: Bhattacharya Rajat , Yang Hailing , Cabral Fernando
Published: February 2011

A multigene family produces tubulin isotypes that are expressed in a tissue-specific manner, but the role of these isotypes in microtubule assembly and function is unclear. Recently we showed that overexpression or depletion of β5-tubulin, a minor isotype with wide tissue distribution, inhibits cell division. We now report that elevated β5-tubulin causes uninterrupted episodes of microtubule shortening and increased shortening rates. Conversely, depletion of β5-tubulin reduces shortening rates and causes very short excursions of growth and shortening. A tubulin conformation-sensitive antibody indicated that the uninterrupted shortening can be explained by a relative absence of stabilized patches along the microtubules that contain tubulin in an assembly-competent conformation and normally act to restore microtubule growth. In addition to these changes in dynamic instability, overexpression of β5-tubulin causes fragmentation that results from microtubule detachment from centrosomes, and it is this activity that best explains the effects of β5 on cell division. Paclitaxel inhibits microtubule detachment, increases the number of assembly-competent tubulin patches, and inhibits microtubule shortening, thus providing an explanation for why the drug can counteract the phenotypic effects of β5 overexpression. On the basis of these observations, we propose that cells can use β5-tubulin expression to adjust the behavior of the microtubule cytoskeleton.
A decisive function of transforming growth factor-β/Smad signaling in tissue morphogenesis and differentiation of human HaCaT keratinocytes
Authors: Buschke Susanne , Stark Hans-Jürgen , Cerezo Ana , Prätzel-Wunder Silke , Boehnke Karsten , Kollar Jasmin , Langbein Lutz , Heldin Carl-Henrik , Boukamp Petra
Published: February 2011

The mechanism by which transforming growth factor-β (TGFβ) regulates differentiation in human epidermal keratinocytes is still poorly understood. To assess the role of Smad signaling, we engineered human HaCaT keratinocytes either expressing small interfering RNA against Smads2, 3, and 4 or overexpressing Smad7 and verified impaired Smad signaling as decreased Smad phosphorylation, aberrant nuclear translocation, and altered target gene expression. Besides abrogation of TGFβ-dependent growth inhibition in conventional cultures, epidermal morphogenesis and differentiation in organotypic cultures were disturbed, resulting in altered tissue homeostasis with suprabasal proliferation and hyperplasia upon TGFβ treatment. Neutralizing antibodies against TGFβ, similar to blocking the actions of EGF-receptor or keratinocyte growth factor, caused significant growth reduction of Smad7-overexpressing cells, thereby demonstrating that epithelial hyperplasia was attributed to TGFβ-induced “dermis”-derived growth promoting factors. Furthermore impaired Smad signaling not only blocked the epidermal differentiation process or caused epidermal-to-mesenchymal transition but induced a switch to a complex alternative differentiation program, best characterized as mucous/intestinal-type epithelial differentiation. As the same alternative phenotype evolved from both modes of Smad-pathway interference, and reduction of Smad7-overexpression caused reversion to epidermal differentiation, our data suggest that functional TGFβ/Smad signaling, besides regulating epidermal tissue homeostasis, is not only essential for terminal epidermal differentiation but crucial in programming different epithelial differentiation routes.
Index Funds, Financialization, and Commodity Futures Markets
Authors: Irwin Scott H. , Sanders Dwight R.
Published: February 2011

Some market participants and policy‐makers believe that index fund investment was a major driver of the 2007‐2008 spike in commodity futures prices. One group of empirical studies does find evidence that commodity index investment had an impact on the level of futures prices. However, the data and methods used in these studies are subject to criticisms that limit the confidence one can place in their results. Moreover, another group of studies provides no systematic evidence of a relationship between positions of index funds and the level of commodity futures prices. The lack of a direct empirical link between index fund trading and commodity futures prices casts considerable doubt on the belief that index funds fueled a price bubble.
Executive Summary: International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases
Authors: Gupta Kalpana , Hooton Thomas M. , Naber Kurt G. , Wullt Björn , Colgan Richard , Miller Loren G. , Moran Gregory J. , Nicolle Lindsay E. , Raz Raul , Schaeffer Anthony J. , Soper David E.
Published: February 2011

A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases–Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.
Augmentation of left ventricular mechanics by recirculation‐mediated AAV2/1–SERCA2a gene delivery in experimental heart failure
Authors: Mariani Justin A. , Smolic Anka , Preovolos Arthur , Byrne Melissa J. , Power John M. , Kaye David M.
Published: February 2011

Aims

Down‐regulation of sarcoplasmic reticulum calcium ATPase (SERCA2a) is a key molecular abnormality in heart failure (HF), which is not currently addressed by specific pharmacotherapy. We sought to evaluate, in detail, the impact of augmented SERCA2a expression on left ventricular (LV) mechanics in a large animal model of HF.

Methods and results

Heart failure was induced in adult sheep by rapid pacing (180 b.p.m.) for 1 month, followed by delivery of adeno‐associated virus (AAV) 2/1–SERCA, using a percutaneous, recirculating system for gene delivery over a 10 min period. Left ventricular mechanics was investigated by echocardiography and conductance catheter measurements in sheep receiving AAV2/1–SERCA2a after a further 4 weeks of pacing in comparison with untreated HF controls. Left ventricular function was significantly improved in the AAV2/1–SERCA2a‐treated group, despite continued pacing, as measured by fractional shortening (delta absolute FS, control −4.2 ± 1.5% vs. treatment 4.4 ± 1.5%; P < 0.01) and conductance catheterization (delta Ees, control −1.22 ± 0.60 vs. treatment 0.65 ± 0.51; P < 0.05). Western blots showed an increase in SERCA protein in AAV2/1–SERCA2a‐treated animals, and an analysis of gene delivery showed no evidence of regional myocardial heterogeneity in the distribution of AAV2/1–SERCA.

Conclusion

In a large animal model, AAV2/1‐mediated SERCA2a gene delivery using percutaneous, recirculating cardiac delivery leads to improved LV function.
Bio-electrospraying and aerodynamically assisted bio-jetting the model eukaryotic
Dictyostelium discoideum
: assessing stress and developmental competency post treatment
Authors: Pakes Nicholl K. , Jayasinghe Suwan N. , Williams Robin S. B.
Published: February 2011

Bio-electrospraying (BES) and aerodynamically assisted bio-jetting (AABJ) have recently been established as important novel biospray technologies for directly manipulating living cells. To elucidate their potential in medical and clinical sciences, these bio-aerosol techniques have been subjected to increasingly rigorous investigations. In parallel to these studies, we wish to introduce these unique biotechnologies for use in the basic biological sciences, for handling a wide range of cell types and systems, thus increasing the range and the scope of these techniques for modern research. Here, the authors present the analysis of the new use of these biospray techniques for the direct handling of the simple eukaryotic biomedical model organism
Dictyostelium discoideum
. These cells are widely used as a model for immune cell chemotaxis and as a simple model for development. We demonstrate that AABJ of these cells did not cause cell stress, as defined by the stress-gene induction, nor affect cell development. Furthermore, although BES induced the increased expression of one stress-related gene (
gapA
), this was not a generalized stress response nor did it affect cell development. These data suggest that these biospray techniques can be used to directly manipulate single cells of this biomedical model without inducing a generalized stress response or perturbing later development.
HEPES inhibits the conversion of prion protein in cell culture
Authors: Delmouly Karine , Belondrade Maxime , Casanova Danielle , Milhavet Ollivier , Lehmann Sylvain
Published: February 2011

HEPES is a well-known buffering reagent used in cell-culture medium. Interestingly, this compound is also responsible for significant modifications of biological parameters such as uptake of organic molecules, alteration of oxidative stress mechanisms or inhibition of ion channels. While using cell-culture medium supplemented with HEPES on prion-infected cells, it was noticed that there was a significant concentration-dependent inhibition of accumulation of the abnormal isoform of the prion protein (PrPSc). This effect was present only in live cells and was thought to be related to modification of the PrP environment or biology. These results could modify the interpretation of cell-culture assays of prion therapeutic agents, as well as of previous cell biology results obtained in the field using HEPES buffers. This inhibitory effect of HEPES could also be exploited to prevent contamination or propagation of prions in cell culture.
Inactivation of hantaviruses by N-ethylmaleimide preserves virion integrity
Authors: Strandin Tomas , Hepojoki Jussi , Wang Hao , Vaheri Antti , Lankinen Hilkka
Published: February 2011

Thiol groups of cysteine residues are crucial for the infectivity of various enveloped viruses, but their role in the infectivity of viruses of the family Bunyaviridae has thus far not been studied. This report shows that thiol groups are essential to the infectivity of hantaviruses. Alkylation of the thiol functional groups using the membrane-permeable compound N-ethylmaleimide (NEM) and membrane-impermeable compound 5,5′-dithio-bis-(2-nitrobenzoic acid) (DTNB) showed NEM to be a highly effective inactivator of Puumala and Tula hantaviruses. The NEM-inactivated hantavirus maintained the buoyant density of the wild-type virus. Furthermore, the antigenicity of glycoproteins and the cell attachment capacity of virions were retained at NEM concentrations that totally abolished virus infectivity. These results signified preservation of virion integrity following inactivation with NEM, making chemically inactivated virions valuable research antigens. It was demonstrated with biotin-conjugated maleimide, a mechanistic analogue of NEM, that all the structural proteins of hantavirus were sensitive towards thiol alkylation. In contrast to hantaviruses, NEM did not abolish Uukuniemi phlebovirus infectivity to the same extent. This indicates differences in the use of free thiols in virus entry among members of the family Bunyaviridae.
Preclinical efficacy studies of influenza A haemagglutinin precursor cleavage loop peptides as a potential vaccine
Authors: Miller Darren S. , Finnie John , Bowden Timothy R. , Scholz Anita C. , Oh Sawyin , Kok Tuckweng , Burrell Christopher J. , Trinidad Lee , Boyle David B. , Li Peng
Published: February 2011

A universal influenza vaccine that does not require annual reformulation would have clear advantages over the currently approved seasonal vaccine. In this study, we combined the mucosal adjuvant alpha-galactosylceramide (αGalCer) and peptides designed across the highly conserved influenza precursor haemagglutinin (HA0) cleavage loop as a vaccine. Peptides designed across the HA0of influenza A/H3N2 viruses, delivered to mice via the intranasal route with αGalCer as an adjuvant, provided 100 % protection following H3N2 virus challenge. Similarly, intranasal inoculation of peptides across the HA0of influenza A/H5N1 with αGalCer completely protected mice against heterotypic challenge with H3N2 virus. Our data suggest that these peptide vaccines effectively inhibited subsequent influenza A/H3N2 virus replication. In contrast, only 20 % of mice vaccinated with αGalCer-adjuvanted peptides spanning the HA0of H5N1 survived homologous viral challenge, possibly because the HA0of this virus subtype is cleaved by intracellular furin-like enzymes. Results of these studies demonstrated that HA0peptides adjuvanted with αGalCer have the potential to form the basis of a synthetic, intranasal influenza vaccine.
Old World hantaviruses do not produce detectable amounts of dsRNA in infected cells and the 5′ termini of their genomic RNAs are monophosphorylated
Authors: Wang Hao , Vaheri Antti , Weber Friedemann , Plyusnin Alexander
Published: February 2011

dsRNA and 5′-triphosphate RNA are considered critical activators of the innate immune response because of their interaction with pattern recognition receptors. It has been reported that no dsRNA is detected in negative-sense RNA virus-infected cells and that Hantaan virus (HTNV) genomic RNA bears a 5′ monophosphate group. In this paper we examine the 5′ termini of genomic RNAs of and dsRNA production by two major groups of Old World hantaviruses. No detectable amounts of dsRNA were found in infected cells. Also, the genomic RNAs of these hantaviruses bear a 5′ monophosphate group and therefore are unable to trigger interferon induction. Taken together with the earlier data on HTNV, these results suggest that in addition to the dsRNA and genomic RNA, which may be only minimally involved in the induction of innate immunity, other cellular signalling pathways may also be involved and that these await further investigation.
Yeast cells can access distinct quiescent states
Authors: Klosinska Maja M. , Crutchfield Christopher A. , Bradley Patrick H. , Rabinowitz Joshua D. , Broach James R.
Published: February 2011

We conducted a phenotypic, transcriptional, metabolic, and genetic analysis of quiescence in yeast induced by starvation of prototrophic cells for one of three essential nutrients (glucose, nitrogen, or phosphate) and compared those results with those obtained with cells growing slowly due to nutrient limitation. These studies address two related questions: (1) Is quiescence a state distinct from any attained during mitotic growth, and (2) does the nature of quiescence differ depending on the means by which it is induced? We found that either limitation or starvation for any of the three nutrients elicits all of the physiological properties associated with quiescence, such as enhanced cell wall integrity and resistance to heat shock and oxidative stress. Moreover, the starvations result in a common transcriptional program, which is in large part a direct extrapolation of the changes that occur during slow growth. In contrast, the metabolic changes that occur upon starvation and the genetic requirements for surviving starvation differ significantly depending on the nutrient for which the cell is starved. The genes needed by cells to survive starvation do not overlap the genes that are induced upon starvation. We conclude that cells do not access a unique and discrete G0 state, but rather are programmed, when nutrients are scarce, to prepare for a range of possible future stressors. Moreover, these survival strategies are not unique to quiescence, but are engaged by the cell in proportion to nutrient scarcity.
CDK prevents Mcm2–7 helicase loading by inhibiting Cdt1 interaction with Orc6
Authors: Chen Shuyan , Bell Stephen P.
Published: February 2011

In Saccharomyces cerevisiae cells, B-type cyclin-dependent kinases (CDKs) target two origin recognition complex (ORC) subunits, Orc2 and Orc6, to inhibit helicase loading. We show that helicase loading by ORC is inhibited by two distinct CDK-dependent mechanisms. Independent of phosphorylation, binding of CDK to an “RXL” cyclin-binding motif in Orc6 sterically reduces the initial recruitment of the Cdt1/Mcm2–7 complex to ORC. CDK phosphorylation of Orc2 and Orc6 inhibits the same step in helicase loading. This phosphorylation of Orc6 is stimulated by the RXL motif and mediates the bulk of the phosphorylation-dependent inhibition of helicase loading. Direct binding experiments show that CDK phosphorylation specifically blocks one of the two Cdt1-binding sites on Orc6. Consistent with the inactivation of one Cdt1-binding site preventing helicase loading, CDK phosphorylation of ORC causes a twofold reduction of initial Cdt1/Mcm2–7 recruitment but results in nearly complete inhibition of Mcm2–7 loading. Intriguingly, in addition to being a target of both CDK inhibitory mechanisms, the Orc6 RXL/cyclin-binding motif plays a positive role in the initial recruitment of Cdt1/Mcm2–7 to the origin, suggesting that this motif is critical for the switch between active and inhibited ORC function at the G1-to-S-phase transition.
Major histocompatibility complex heterozygosity enhances reproductive success
Authors: THOß M. , ILMONEN P. , MUSOLF K. , PENN D. J.
Published: February 2011

We investigated how heterozygosity at the major histocompatibility complex (MHC) affects fitness in wild‐derived (F2) house mice (Mus musculus musculus). To compare and control for potential confounding effects from close inbreeding and genome‐wide heterozygosity, we used mice that were systematically outbred. We assessed how heterozygosity at MHC and background loci (using 15 microsatellite markers on 11 different chromosomes) affects individual survival and reproductive success (RS) in large, semi‐natural population enclosures. We found that overall heterozygosity significantly increased RS, and this correlation was entirely explained by heterozygosity at two MHC loci. Moreover, we found that the effects of MHC heterozygosity depend on the level of background heterozygosity, and the benefits of maximal MHC heterozygosity show a curvilinear effect with increasing background heterozygosity. The enhanced RS from MHC heterozygosity was not because of increased survival, and although MHC heterozygosity was correlated with body mass, body mass did not correlate with RS when heterozygosity is controlled. Breeders were more MHC heterozygous than nonbreeders for both sexes, indicating that MHC heterozygosity enhanced fecundity, mating success or both. Our results show that (i) MHC heterozygosity enhances fitness among wild, outbred as well as congenic laboratory mice; (ii) heterozygosity–fitness correlations can potentially be explained by a few loci, such as MHC; (iii) MHC heterozygosity can increase fitness, even without affecting survival, by increasing mating and RS; and (iv) MHC effects depend on background genes, and maximal MHC heterozygosity is most beneficial at intermediate or optimal levels of background heterozygosity.
THE ORIGIN AND SIGNIFICANCE OF SAND VOLCANOES IN THE BUDE FORMATION (CORNWALL)
Authors: BURNE R. V.
Published: February 2011

Sand volcanoes have been found in three sedimentary associations in the Upper Carboniferous Bude Formation. In two of these associations they formed when the dewatering of fluidized sand beds, deposited from traction carpets, was temporarily inhibited by the deposition of overlying units. In the third association the volcanoes formed during the normal post‐depositional compaction of fluidized, muddy, poorly sorted units deposited from subaqueous mudflows. While is seems that the tops of fluidized sand beds were characteristically sheared by a fairly powerful current immediately after being deposited, the waters above the recently deposited mudflow units were commonly stagnant, allowing sand volcano growth.
THE FABRIC OF SHALE—AN ELECTRON‐MICROSCOPE STUDY
Authors: O'BRIEN NEAL R.
Published: February 2011

Scanning and transmission electron micrographs of various shales establish the close correlation between clay‐flake orientation and fissility. The shales with the best fissility have the highest degree of preferred orientation. Randomness of clay flakes prevails in non‐fissile claystones. The results suggest that the fabric of shales may result either from the deposition of dispersed clay or by the collapse of clay floccules after deposition.