bluuebunny/crossref_metadata_2025 huggingface dataset:
SHP (small heterodimer partner) suppresses the transcriptional activity and nuclear localization of Hedgehog signalling protein Gli1
Authors: Kim KyeongJin , Kim Kook Hwan , Cho Hyun Kook , Kim Hye Young , Kim Hyeong Hoe , Cheong JaeHun
Published: February 2010

Gli (glioma-associated oncogene homologue) proteins act as terminal effectors of the Hedgehog signalling pathway, which is implicated in the development of many human malignancies. Gli activation is important for cell proliferation and anti-apoptosis in various cancers. Several studies have suggested that nuclear receptors have anti-cancer effects by inhibiting the activation of various oncoproteins. However, the involvement of nuclear receptors on the Hedgehog/Gli signalling pathway is poorly defined. In the present study we identified SHP (small heterodimer partner) as a nuclear receptor that decreased the expression of Gli target genes by repressing the transcriptional activity of Gli1. The inhibitory effect of SHP was associated with the inhibition of Gli1 nuclear localization via protein–protein interaction. Finally, SHP overexpression decreased the expression of Gli target genes and SHP knockdown increased the expression of these genes. Taken together, these results suggest that SHP can play a negative role in Hedgehog/Gli1 signalling.
Recent advances in understanding the roles of transglutaminase 2 in alcoholic steatohepatitis
Authors: Tatsukawa Hideki , Kojima Soichi
Published: February 2010

Tissue TG (transglutaminase) or TG2 is the most ubiquitously expressed member of the large TG family that catalyses deamidation of a glutamine residue, formation of an N ε(γ‐glutamyl)‐lysine cross‐linking between lysine and glutamine residues and/or covalent incorporation of polyamines into a glutamine residue, exerting a number of physiological and/or pathological functions. Extracellular TG2 contributes to wound healing and exacerbation of liver fibrosis through a role in extracellular matrix assembly and cell adhesion. Intracellular TG2 acts as a GTPase in normal cells when the intracellular Ca2+ concentration is as low as 10–20 nM, participating in the transmembrane signalling of phospholipase Cδ as a component of α1‐adrenergic receptor complexes, and thereby supporting the growth of hepatic cells. When cells are injured and the intracellular Ca2+ concentration rises to more than 700–800 nM, TG2 dramatically alters its structure and transforms into a cross‐linking enzyme. TG2 primarily exists in the cytosol in normal cells, but is distributed among multiple intracellular milieus during tissue injury or apoptosis. In particular, TG2 has been shown to be abundant in the nuclei of cells undergoing apoptosis, although its role in the nucleus and the underlying mechanisms remain unresolved. Recently, three findings in the study of alcoholic steatohepatitis have shed light on these issues. Omary's group disclosed that TG2‐mediated cross‐linking of keratin 8 is essential for the formation of Mallory–Denk bodies. We have demonstrated that in both mouse models of alcoholic steatohepatitis and human patients with alcoholic steatohepatitis, TG2 translocates into the nucleus and provokes hepatocyte death via cross‐linking and inactivation of a transcription factor, Sp1, leading to down‐regulation of the hepatocyte growth factor receptor, c‐Met. Furthermore, Giebeler et al. has reported that down‐regulation of c‐Met is associated with liver fibrosis. In the present review article, we introduce these recent advances in knowledge with regard to the the roles of TG2 in alcoholic steatohepatitis.
Effect of VEGF (vascular endothelial growth factor) on expression of IL‐8 (interleukin‐8), IL‐1β and their receptors in bovine theca cells
Authors: Murayama Chiaki , Kaji Ayami , Miyauchi Kazuki , Matsui Motozumi , Miyamoto Akio , Shimizu Takashi
Published: February 2010

Cytokines such as VEGF (vascular endothelial growth factor) and ILs (interleukins) are involved in follicular development in the mammalian ovary. The aim of the present study is to examine the transcripts of IL‐8 and ‐1 that differ during follicular development; the relationships between IL‐8, IL‐1 and VEGF in theca cells is still unknown. We first examined the gene expression of IL‐8, IL‐1β and their respective receptors, CXCR1 and IL‐1R1 in the theca cells of PRF (preselection) and POF (postselection follicles) from the bovine ovary. Expression of IL‐8 and CXCR1 genes were observed in POF, whereas expression of IL‐1β and IL‐1R1 genes was observed in both follicles. Secondly, we examined the effects of VEGF on the expression of IL‐8, IL‐1β and their receptors genes in cultured bovine theca cells. mRNA expression was quantified by using real‐time PCR methods. VEGF stimulates the expression of IL‐8 and CXCR1 mRNA. However, VEGF down‐regulates the expression of CXCR2 mRNA during the culture period. Expression of IL‐1β and ‐1R1 mRNA was induced in the cultured theca cells at 48 h. Our data demonstrate that VEGF stimulated the expression of the IL‐8 and CXCR1 genes and that CXCR2 expression was suppressed by VEGF, suggesting a follicle stage‐dependent expression pattern for the IL‐8 system. Furthermore, our results suggest that the transcription system for CXCR genes may have different pathways of VEGF stimulation in bovine theca cells. Taken together, our data suggested that VEGF is associated with the IL system in theca cells in bovine ovary.
Results with the electron cyclotron resonance charge breeder for the C252f fission source project (Californium Rare Ion Breeder Upgrade) at Argonne Tandem Linac Accelerator System
Authors: Vondrasek R. , Kondrashev S. , Pardo R. , Scott R. , Zinkann G. P.
Published: February 2010

The construction of the Californium Rare Ion Breeder Upgrade, a new radioactive beam facility for the Argonne Tandem Linac Accelerator System (ATLAS), is nearing completion. The facility will use fission fragments from a 1 Ci C252f source; thermalized and collected into a low-energy particle beam by a helium gas catcher. In order to reaccelerate these beams, an existing ATLAS electron cyclotron resonance (ECR) ion source was redesigned to function as an ECR charge breeder. Thus far, the charge breeder has been tested with stable beams of rubidium and cesium achieving charge breeding efficiencies of 9.7% into R85b17+ and 2.9% into C133s20+.
Electronic structure of nanopolycrystalline pulsed laser deposited LaB6 films and single crystals: The boron perspective
Authors: Liu Lijia , Yiu Y. M. , Sham T. K. , Yang Dongfang , Zuin Lucia
Published: February 2010

We report an investigation of the electronic structure of LaB6 nanopolycrystalline pulsed laser deposited (PLD) film and single crystal with x-ray absorption near edge structures (XANES) spectroscopy at the B K-edge. The experimental results are compared with theoretical calculations using density functional theory, and real space multiple scattering. It is found that (i) the LaB6 PLD film is of high quality and metallic albeit it is a polycrystalline phase of nanocrystallites and (ii) the B K-edge XANES for the single crystal specimens exhibit well defined spectral features corresponding to the theoretical partial densities of states of B p character and the threshold energy is relatively low and free electronlike, revealing its metallic character. The implications of these observations to the enhancement in electron emission from the PLD films are discussed.
Fokker–Planck description of the scattering of radio frequency waves at the plasma edge
Authors: Hizanidis Kyriakos , Ram Abhay K. , Kominis Yannis , Tsironis Christos
Published: February 2010

In magnetic fusion devices, radio frequency (rf) waves in the electron cyclotron (EC) and lower hybrid (LH) range of frequencies are being commonly used to modify the plasma current profile. In ITER, EC waves are expected to stabilize the neoclassical tearing mode (NTM) by providing current in the island region [R. Aymar et al., Nucl. Fusion 41, 1301 (2001)]. The appearance of NTMs severely limits the plasma pressure and leads to the degradation of plasma confinement. LH waves could be used in ITER to modify the current profile closer to the edge of the plasma. These rf waves propagate from the excitation structures to the core of the plasma through an edge region, which is characterized by turbulence—in particular, density fluctuations. These fluctuations, in the form of blobs, can modify the propagation properties of the waves by refraction. In this paper, the effect on rf due to randomly distributed blobs in the edge region is studied. The waves are represented as geometric optics rays and the refractive scattering from a distribution of blobs is formulated as a Fokker–Planck equation. The scattering can have two diffusive effects—one in real space and the other in wave vector space. The scattering can modify the trajectory of rays into the plasma and it can affect the wave vector spectrum. The refraction of EC waves, for example, could make them miss the intended target region where the NTMs occur. The broadening of the wave vector spectrum could broaden the wave generated current profile. The Fokker–Planck formalism for diffusion in real space and wave vector space is used to study the effect of density blobs on EC and LH waves in an ITER type of plasma environment. For EC waves the refractive effects become important since the distance of propagation from the edge to the core in ITER is of the order of a meter. The diffusion in wave vector space is small. For LH waves the refractive effects are insignificant but the diffusion in wave vector space is important. The theoretical model is general enough to study the effect of density blobs on all propagating cold plasma waves.
Plasticization and antiplasticization of polymer melts diluted by low molar mass species
Authors: Stukalin Evgeny B. , Douglas Jack F. , Freed Karl F.
Published: February 2010

An analysis of glass formation for polymer melts that are diluted by structured molecular additives is derived by using the generalized entropy theory, which involves a combination of the Adam–Gibbs model and the direct computation of the configurational entropy based on a lattice model of polymer melts that includes monomer structural effects. Our computations indicate that the plasticization and antiplasticization of polymer melts depend on the molecular properties of the additive. Antiplasticization is accompanied by a “toughening” of the glass mixture relative to the pure polymer, and this effect is found to occur when the diluents are small species with strongly attractive interactions with the polymer matrix. Plasticization leads to a decreased glass transition temperature Tg and a “softening” of the fragile host polymer in the glass state. Plasticization is prompted by small additives with weakly attractive interactions with the polymer matrix. However, the latter situation can lead to phase separation if the attractive interactions are sufficiently strong. The shifts in Tg of polystyrene diluted by fully flexible short oligomers (up to 20% mass of diluent) are evaluated from the computations, along with the relative changes in the isothermal compressibility at Tg (a softening or toughening effect) to characterize the extent to which the additives act as antiplasticizers or plasticizers. The theory predicts that a decreased fragility can accompany both antiplasticization and plasticization of the glass by molecular additives. The general reduction in the Tg of polymers by molecular additives is rationalized by analyzing the influence of the diluent’s properties (cohesive energy, chain length, and stiffness) on glass formation in fluid mixtures and the variation of fragility is discussed in relation to changes in the molecular packing in diluted polymer melts. Our description of constant temperature glass formation upon increasing the diluent concentration directly leads to the Angell equation (τα∼A exp{B/(ϕ0,p−ϕp)}) for the structural relaxation time as function of the polymer concentration, where the extrapolated “zero mobility concentration” ϕ0,p calculated from the theory scales linearly with the inverse polymerization index N.
Laser wavelength effects on the charge state resolved ion energy distributions from laser-produced Sn plasma
Authors: Burdt Russell A. , Tao Yezheng , Tillack Mark S. , Yuspeh Sam , Shaikh Nek M. , Flaxer Eli , Najmabadi Farrokh
Published: February 2010

The effects of laser wavelength on the charge state resolved ion energy distributions from laser-produced Sn plasma freely expanding into vacuum are investigated. Planar Sn targets are irradiated at laser wavelengths of 10.6 and 1.064 μm and intensities of 1.8×1010 and 3.4×1011 W/cm2, respectively. These parameters are relevant to the extreme ultraviolet x-ray source application. An electrostatic deflection probe and single channel electron multiplier are used to record the charge state resolved ion energy distributions 100 cm from the laser plasma source. At the longer laser wavelength, higher charge state ions are observed. At both laser wavelengths, the peak ion energies increase approximately linearly as a function of charge state, and all ion energies greatly exceed the initial thermal electron temperature. The differences in the ion energy distributions are attributed to the laser wavelength dependence of the laser energy absorption, the resulting plasma density in the corona, and the subsequent recombination after the laser pulse. Numerical simulations of the plasma expansion from a collisional-radiative steady state model support the experimental results.
Spectroscopic study of a long high-electron-density argon plasma column generated at atmospheric pressure
Authors: Li Shou-Zhe , Huang Wen-Tong , Wang Dezhen
Published: February 2010

A stable plasma column is generated in a quartz tube using a pair of hollow electrodes driven by a sinusoidal power supply of 45 kHz at atmospheric pressure in argon. Two distinct operating modes (low-current and high-current modes) are identified through observing its discharge phenomena, measuring its electrical characteristics, and determining the gas temperatures by spectroscopic diagnosis of Q branch of UV OH spectrum. The electron density in the high-current mode is diagnosed by Stark broadening and is found to be two orders higher than that in low-current mode.
Ensemble-averaged particle orientation and shear viscosity of single-wall-carbon-nanotube suspensions under shear and electric fields
Authors: Lin Chen , Shan Jerry W.
Published: February 2010

The ensemble-averaged particle-orientation angles and apparent shear viscosities of dilute suspensions of single-wall carbon nanotubes (SWNTs) in a liquid solvent, α-terpineol, were experimentally studied under combined shear flow and electric fields. An optical polarization-modulation method was used to measure the orientation angles of individual and small bundles of SWNTs, while a modified concentric-cylinder viscometer was used to make simultaneous electrorheological measurements of the apparent viscosity. The particle-orientation response occurs on time scales one to two orders of magnitude faster than the macroscopic electrorheological response, and does not appear to directly affect the apparent viscosity at these low concentrations. Particle-orientation angles for various shear rates and electric fields are found to collapse when plotted against the parameter, f∼E2/γ̇, as predicted by the theory developed by Mason and co-workers for the equilibrium orientation angle of ellipsoids under electric fields and shear flow. However, comparison between measured and predicted particle-orientation angles shows poor agreement at intermediate values of f. Electrostatic interactions between large-aspect-ratio particles are shown to be significant, and may account for the discrepancy between the measurements and classical theory for even dilute suspensions of nanotubes under both shear and electric fields.
Maximal extension of the Schwarzschild space-time inspired by noncommutative geometry
Authors: Arraut I. , Batic D. , Nowakowski M.
Published: February 2010

We derive a transformation of the noncommutative geometry inspired Schwarzschild solution into new coordinates, such that the apparent unphysical singularities of the metric are removed. Moreover, we give the maximal singularity-free atlas for the manifold with the metric under consideration. This atlas reveals many new features e.g., it turns out to describe an infinite lattice of asymptotically flat universes connected by black hole tunnels.
Experimental verification of the suppression of spatial dispersion in artificial plasma
Authors: Luukkonen Olli , Alitalo Pekka , Costa Filippo , Simovski Constantin , Monorchio Agostino , Tretyakov Sergei
Published: February 2010

In this paper, we verify experimentally the recently proposed theory on suppression of the spatial dispersion in an artificial plasma. We make use of the image principle and assume effectively local material parameters of the artificial plasma, in which the spatial dispersion has been suppressed, and measure the reflection from an impenetrable grounded surface. The plasma resonance can be clearly distinguished from the measurement results at the plasma frequency independently from the incidence angle. The agreement between the measurement results and the theory and simulations is very good.
Marine reserves as linked social–ecological systems
Authors: Pollnac Richard , Christie Patrick , Cinner Joshua E. , Dalton Tracey , Daw Tim M. , Forrester Graham E. , Graham Nicholas A. J. , McClanahan Timothy R.
Published: February 2010

Marine reserves are increasingly recognized as having linked social and ecological dynamics. This study investigates how the ecological performance of 56 marine reserves throughout the Philippines, Caribbean, and Western Indian Ocean (WIO) is related to both reserve design features and the socioeconomic characteristics in associated coastal communities. Ecological performance was measured as fish biomass in the reserve relative to nearby areas. Of the socioeconomic variables considered, human population density and compliance with reserve rules had the strongest effects on fish biomass, but the effects of these variables were region specific. Relationships between population density and the reserve effect on fish biomass were negative in the Caribbean, positive in the WIO, and not detectable in the Philippines. Differing associations between population density and reserve effectiveness defy simple explanation but may depend on human migration to effective reserves, depletion of fish stocks outside reserves, or other social factors that change with population density. Higher levels of compliance reported by resource users was related to higher fish biomass in reserves compared with outside, but this relationship was only statistically significant in the Caribbean. A heuristic model based on correlations between social, cultural, political, economic, and other contextual conditions in 127 marine reserves showed that high levels of compliance with reserve rules were related to complex social interactions rather than simply to enforcement of reserve rules. Comparative research of this type is important for uncovering the complexities surrounding human dimensions of marine reserves and improving reserve management.
Adaptive management of the Great Barrier Reef: A globally significant demonstration of the benefits of networks of marine reserves
Authors: McCook Laurence J. , Ayling Tony , Cappo Mike , Choat J. Howard , Evans Richard D. , De Freitas Debora M. , Heupel Michelle , Hughes Terry P. , Jones Geoffrey P. , Mapstone Bruce , Marsh Helene , Mills Morena , Molloy Fergus J. , Pitcher C. Roland , Pressey Robert L. , Russ Garry R. , Sutton Stephen , Sweatman Hugh , Tobin Renae , Wachenfeld David R. , Williamson David H.
Published: February 2010

The Great Barrier Reef (GBR) provides a globally significant demonstration of the effectiveness of large-scale networks of marine reserves in contributing to integrated, adaptive management. Comprehensive review of available evidence shows major, rapid benefits of no-take areas for targeted fish and sharks, in both reef and nonreef habitats, with potential benefits for fisheries as well as biodiversity conservation. Large, mobile species like sharks benefit less than smaller, site-attached fish. Critically, reserves also appear to benefit overall ecosystem health and resilience: outbreaks of coral-eating, crown-of-thorns starfish appear less frequent on no-take reefs, which consequently have higher abundance of coral, the very foundation of reef ecosystems. Effective marine reserves require regular review of compliance: fish abundances in no-entry zones suggest that even no-take zones may be significantly depleted due to poaching. Spatial analyses comparing zoning with seabed biodiversity or dugong distributions illustrate significant benefits from application of best-practice conservation principles in data-poor situations. Increases in the marine reserve network in 2004 affected fishers, but preliminary economic analysis suggests considerable net benefits, in terms of protecting environmental and tourism values. Relative to the revenue generated by reef tourism, current expenditure on protection is minor. Recent implementation of an Outlook Report provides regular, formal review of environmental condition and management and links to policy responses, key aspects of adaptive management. Given the major threat posed by climate change, the expanded network of marine reserves provides a critical and cost-effective contribution to enhancing the resilience of the Great Barrier Reef.
Toward discovery science of human brain function
Authors: Biswal Bharat B. , Mennes Maarten , Zuo Xi-Nian , Gohel Suril , Kelly Clare , Smith Steve M. , Beckmann Christian F. , Adelstein Jonathan S. , Buckner Randy L. , Colcombe Stan , Dogonowski Anne-Marie , Ernst Monique , Fair Damien , Hampson Michelle , Hoptman Matthew J. , Hyde James S. , Kiviniemi Vesa J. , Kötter Rolf , Li Shi-Jiang , Lin Ching-Po , Lowe Mark J. , Mackay Clare , Madden David J. , Madsen Kristoffer H. , Margulies Daniel S. , Mayberg Helen S. , McMahon Katie , Monk Christopher S. , Mostofsky Stewart H. , Nagel Bonnie J. , Pekar James J. , Peltier Scott J. , Petersen Steven E. , Riedl Valentin , Rombouts Serge A. R. B. , Rypma Bart , Schlaggar Bradley L. , Schmidt Sein , Seidler Rachael D. , Siegle Greg J. , Sorg Christian , Teng Gao-Jun , Veijola Juha , Villringer Arno , Walter Martin , Wang Lihong , Weng Xu-Chu , Whitfield-Gabrieli Susan , Williamson Peter , Windischberger Christian , Zang Yu-Feng , Zhang Hong-Ying , Castellanos F. Xavier , Milham Michael P.
Published: February 2010

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's “functional connectome.” Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain–behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at
www.nitrc.org/projects/fcon_1000/
.
Appropriate maturation and folding of 16S rRNA during 30S subunit biogenesis are critical for translational fidelity
Authors: Roy-Chaudhuri Biswajoy , Kirthi Narayanaswamy , Culver Gloria M.
Published: February 2010

Ribosomal protein S5 is critical for small ribosomal subunit (SSU) assembly and is indispensable for SSU function. Previously, we identified a point mutation in S5, (G28D) that alters both SSU formation and translational fidelity in vivo, which is unprecedented for other characterized S5 mutations. Surprisingly, additional copies of an extraribosomal assembly factor, RimJ, rescued all the phenotypes associated with S5(G28D), including fidelity defects, suggesting that the effect of RimJ on rescuing the miscoding of S5(G28D) is indirect. To understand the underlying mechanism, we focused on the biogenesis cascade and observed defects in processing of precursor 16S (p16S) rRNA in the S5(G28D) strain, which were rescued by RimJ. Analyses of p16S rRNA-containing ribosomes from other strains further supported a correspondence between the extent of 5′end maturation of 16S rRNA and translational miscoding. Chemical probing of mutant ribosomes with additional leader sequences at the 5′end of 16S rRNA compared to WT ribosomes revealed structural differences in the region of helix 1. Thus, the presence of additional nucleotides at the 5′end of 16S rRNA could alter fidelity by changing the architecture of 16S rRNA in translating ribosomes and suggests that fidelity is governed by accuracy and completeness of the SSU biogenesis cascade.
Specificity landscapes of DNA binding molecules elucidate biological function
Authors: Carlson Clayton D. , Warren Christopher L. , Hauschild Karl E. , Ozers Mary S. , Qadir Naveeda , Bhimsaria Devesh , Lee Youngsook , Cerrina Franco , Ansari Aseem Z.
Published: February 2010

Evaluating the specificity spectra of DNA binding molecules is a nontrivial challenge that hinders the ability to decipher gene regulatory networks or engineer molecules that act on genomes. Here we compare the DNA sequence specificities for different classes of proteins and engineered DNA binding molecules across the entire sequence space. These high-content data are visualized and interpreted using an interactive “specificity landscape” which simultaneously displays the affinity and specificity of a million-plus DNA sequences. Contrary to expectation, specificity landscapes reveal that synthetic DNA ligands match, and often surpass, the specificities of eukaryotic DNA binding proteins. The landscapes also identify differential specificity constraints imposed by diverse structural folds of natural and synthetic DNA binders. Importantly, the sequence context of a binding site significantly influences binding energetics, and utilizing the full contextual information permits greater accuracy in annotating regulatory elements within a given genome. Assigning such context-dependent binding values to every DNA sequence across the genome yields predictive genome-wide binding landscapes (genomescapes). A genomescape of a synthetic DNA binding molecule provided insight into its differential regulatory activity in cultured cells. The approach we describe will accelerate the creation of precision-tailored DNA therapeutics and uncover principles that govern sequence-specificity of DNA binding molecules.
Rotational dynamics of DNA on the nucleosome surface markedly impact accessibility to a DNA repair enzyme
Authors: Hinz John M. , Rodriguez Yesenia , Smerdon Michael J.
Published: February 2010

Histones play a crucial role in the organization of DNA in the nucleus, but their presence can prevent interactions with DNA binding proteins responsible for repair of DNA damage. Uracil is an abundant mutagenic lesion recognized by uracil DNA glycosylase (UDG) in the first step of base excision repair (BER). In nucleosome core particles (NCPs), we find substantial differences in UDG-directed cleavage at uracils rotationally positioned toward (U-In) or away from (U-Out) the histone core, or midway between these orientations (U-Mid). Whereas U-Out NCPs show a cleavage rate just below that of naked DNA, U-In and U-Mid NCPs have markedly slower rates of cleavage. Crosslinking of U-In DNA to histones in NCPs yields a greater reduction in cleavage rate but, surprisingly, yields a higher rate of cleavage in U-Out NCPs compared with uncrosslinked NCPs. Moreover, the next enzyme in BER, APE1, stimulates the activity of human UDG in U-Out NCPs, suggesting these enzymes interact on the surface of histones in orientations accessible to UDG. These data indicate that the activity of UDG likely requires “trapping” transiently exposed states arising from the rotational dynamics of DNA on histones.
Female-specific flightless phenotype for mosquito control
Authors: Fu Guoliang , Lees Rosemary S. , Nimmo Derric , Aw Diane , Jin Li , Gray Pam , Berendonk Thomas U. , White-Cooper Helen , Scaife Sarah , Kim Phuc Hoang , Marinotti Osvaldo , Jasinskiene Nijole , James Anthony A. , Alphey Luke
Published: February 2010

Dengue and dengue hemorrhagic fever are increasing public health problems with an estimated 50–100 million new infections each year.Aedes aegyptiis the major vector of dengue viruses in its range and control of this mosquito would reduce significantly human morbidity and mortality. Present mosquito control methods are not sufficiently effective and new approaches are needed urgently. A “sterile-male-release” strategy based on the release of mosquitoes carrying a conditional dominant lethal gene is an attractive new control methodology. Transgenic strains ofAedes aegyptiwere engineered to have a repressible female-specific flightless phenotype using either two separate transgenes or a single transgene, based on the use of a female-specific indirect flight muscle promoter from theAedes aegypti Actin-4gene. These strains eliminate the need for sterilization by irradiation, permit male-only release (“genetic sexing”), and enable the release of eggs instead of adults. Furthermore, these strains are expected to facilitate area-wide control or elimination of dengue if adopted as part of an integrated pest management strategy.
Solving the apparent diversity-accuracy dilemma of recommender systems
Authors: Zhou Tao , Kuscsik Zoltán , Liu Jian-Guo , Medo Matúš , Wakeling Joseph Rushton , Zhang Yi-Cheng
Published: February 2010

Recommender systems use data on past user preferences to predict possible future likes and interests. A key challenge is that while the most useful individual recommendations are to be found among diverse niche objects, the most reliably accurate results are obtained by methods that recommend objects based on user or object similarity. In this paper we introduce a new algorithm specifically to address the challenge of diversity and show how it can be used to resolve this apparent dilemma when combined in an elegant hybrid with an accuracy-focused algorithm. By tuning the hybrid appropriately we are able to obtain, without relying on any semantic or context-specific information, simultaneous gains in both accuracy and diversity of recommendations.
High-throughput identification of protein localization dependency networks
Authors: Christen Beat , Fero Michael J. , Hillson Nathan J. , Bowman Grant , Hong Sun-Hae , Shapiro Lucy , McAdams Harley H.
Published: February 2010

Bacterial cells are highly organized with many protein complexes and DNA loci dynamically positioned to distinct subcellular sites over the course of a cell cycle. Such dynamic protein localization is essential for polar organelle development, establishment of asymmetry, and chromosome replication during the
Caulobacter crescentus
cell cycle. We used a fluorescence microscopy screen optimized for high-throughput to find strains with anomalous temporal or spatial protein localization patterns in transposon-generated mutant libraries. Automated image acquisition and analysis allowed us to identify genes that affect the localization of two polar cell cycle histidine kinases, PleC and DivJ, and the pole-specific pili protein CpaE, each tagged with a different fluorescent marker in a single strain. Four metrics characterizing the observed localization patterns of each of the three labeled proteins were extracted for hundreds of cell images from each of 854 mapped mutant strains. Using cluster analysis of the resulting set of 12-element vectors for each of these strains, we identified 52 strains with mutations that affected the localization pattern of the three tagged proteins. This information, combined with quantitative localization data from epitasis experiments, also identified all previously known proteins affecting such localization. These studies provide insights into factors affecting the PleC/DivJ localization network and into regulatory links between the localization of the pili assembly protein CpaE and the kinase localization pathway. Our high-throughput screening methodology can be adapted readily to any sequenced bacterial species, opening the potential for databases of localization regulatory networks across species, and investigation of localization network phylogenies.
Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis
Authors: Huang Haochu , Benoist Christophe , Mathis Diane
Published: February 2010

There is increasing appreciation of the important role of B cells in many autoimmune diseases and consequently, increasing interest in treating these disorders through B cell-depletion therapy with rituximab, an anti-CD20 monoclonal antibody. Yet, precisely how this and related drugs exert their therapeutic effects remains controversial. In particular, it is unclear how, in a number of contexts, rituximab can greatly reduce the titer of serum autoantibodies without substantially altering the overall antibody titer. We have studied the action of this drug in the K/BxN mouse model of inflammatory arthritis after first crossing in a human CD20 transgene. Rituximab treatment of these mice led to a decrease in the titer of serum antibodies targeting glucose-6-phosphate isomerase, the relevant autoantigen, but not in the total antibody titer. Glucose-6-phosphate isomerase-specific plasma cells did not reside primarily in the bone marrow as expected but rather in the spleen and lymph nodes, where they had short lives, expressed CD20, and were rapidly depleted by rituximab. These data support a model whereby autoreactive plasma cells (at least certain specificities thereof) are intrinsically different from protective antimicrobial plasma cells in their differentiation, migration, and survival properties. Rituximab targets the former and spares the latter.
Use of Social Marketing Concepts to Evaluate Ocean Sustainability Campaigns
Authors: Bates Cynthia H.
Published: February 2010

The importance of preserving the world's oceans cannot be overemphasized. Part of the responsibility for the long-term sustainability of this natural resource lies in the hands of individuals and their communities. For the ocean-related issues of sustainable seafood, coastal pollution, marine protected areas, specific marine species preservation, and sustainable ocean use, campaigns have been used to increase awareness, knowledge, and conservation behaviors. Unfortunately, there is a dearth of rigorous reviews and meta-analyses of environmental campaigns in general, and ocean-oriented campaigns in particular. The goal of this literature review is to learn from the successes and failures of past marine-based campaigns in a methodical way to make recommendations for the design, implementation, and evaluation of ocean conservation programs. The review is organized according to the main components of social marketing: audience analysis and segmentation; consumer orientation; theory, appropriate, and realistic objectives; message and channel design; and evaluation research. Specific implications for campaign evaluation are emphasized.
Social Networking Websites as a Platform for Disseminating Social Marketing Interventions: An Exploratory Pilot Study
Authors: Uhrig Jennifer , Bann Carla , Williams Peyton , Evans W. Douglas
Published: February 2010

Social networking websites (SNSs) focus on building online social networks or communities of people who share interests and activities and provide ways for users to interact with each other online. Our exploratory pilot study gauged users' receptivity to receiving health information via the SNSs they use. We presented several hypothetical scenarios and explored respondents' reactions to each of them. Consistent with other research, we found that most respondents reported using SNSs to interact with people they already know as opposed to using SNSs to meet new people. Overall, respondents were generally receptive to the scenarios we explored. Spending more time on the Internet, spending a higher percentage of one's Internet time on SNSs, and currently participating in online discussion groups were significantly associated with receptivity across several of the scenarios. These reactions suggest an association between heavier Internet use and receptivity to getting health information through this channel. The rapid growth of SNSs presents a significant opportunity to reach individuals with health communication and social marketing messages.
What's the Catch? Reducing Consumption of Contaminated Fish among Anglers
Authors: Jonick Tiffany , Anderson Elizabeth L. , Lin Sharon , Bruni Coral M. , Schultz P. Wesley , Groner Stephen , Orrala Frankie
Published: February 2010

In Southern California, white croaker caught within proximity to the Palos Verdes Shelf Superfund Site have been found to be contaminated with such high levels of dichloro-diphenyl-trichloroethane and polychlorinated biphenyls that fish consumption advisories recommend that this fish should not be consumed. In response to this risk, the U.S. Environmental Protection Agency has initiated an Angler Outreach Program designed to reduce the quantity of contaminated fish (specifically, white croaker) anglers bring back to the community. The current project describes the development of a community-based social marketing campaign targeting anglers, and reports results comparing the number of white croaker anglers took back to the community before and after a strategic intervention. Results indicate that the program was highly successful in positively modifying angler behavior. Postintervention results demonstrate that the strategic intervention reduced the number of white croaker entering the community by 93%, and also produced a large reduction in the percentage of anglers who left the fishing site with white croaker. In addition, anglers reported an increase in positive behavior with regard to their white croaker consumption habits.
Determining the Level of Interest in a Professional Association for Social Marketing in the United States: Results of a National Survey
Authors: Marshall Robert J. , Sundstrom Beth
Published: February 2010

Recent proposals about a professional organization for social marketing in public health led to a web-based survey of 430 anonymous respondents. The analysis explored the various characteristics of respondents (e.g., career status, experience, and work setting) in addition to the kind of organization they prefer, its benefits, and membership fees. The results indicate strong support for a professional organization and encourage further developmental efforts.
Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation
Authors: Rowland Sarah L. , DePersis Corinne L. , Torres Raul M. , Pelanda Roberta
Published: February 2010

B cell receptors (BCRs) generate tonic signals critical for B cell survival and early B cell development. To determine whether these signals also mediate the development of transitional and mature B cells, we examined B cell development using a mouse strain in which nonautoreactive immunoglobulin heavy and light chain–targeted B cells express low surface BCR levels. We found that reduced BCR expression translated into diminished tonic BCR signals that strongly impaired the development of transitional and mature B cells. Constitutive expression of Bcl-2 did not rescue the differentiation of BCR-low B cells, suggesting that this defect was not related to decreased cell survival. In contrast, activation of the Ras pathway rescued the differentiation of BCR-low immature B cells both in vitro and in vivo, whereas extracellular signal-regulated kinase (Erk) inhibition impaired the differentiation of normal immature B cells. These results strongly suggest that tonic BCR signaling mediates the differentiation of immature into transitional and mature B cells via activation of Erk, likely through a pathway requiring Ras.
Docetaxel suppresses invasiveness of head and neck cancer cells in vitro
Authors: Kogashiwa Yasunao , Sakurai Hiroyuki , Kimura Toru , Kohno Naoyuki
Published: February 2010

The combination of docetaxel, cisplatin, and fluorouracil significantly enhances the survival of head and neck cancer patients compared to cisplatin and fluorouracil. We hypothesized that docetaxel may affect invasiveness of the head and neck cancer cells in addition to its tumor‐killing effect. Two different head and neck cancer cell lines (HEp‐2 and Ca9‐22) were treated with docetaxel at IC10 and IC50 concentrations. Cell migration and invasive growth was evaluated by wound healing assay and three‐dimensional (3D) culture of multicellular tumor spheroids, respectively. Expression levels of possible downstream effectors for cell migration/invasiveness were measured by immunoblotting in conditions with or without docetaxel. Docetaxel, but not cisplatin, suppressed filopodia formation compared with no treatment (control) condition. Consistent with this, docetaxel suppressed two‐dimensional (2D) cell migration and 3D cell invasion compared with control or cisplatin. Only docetaxel treated cells exhibited thick tubulin bundle and had lower activity of Cdc42, a member of the Rho family of small GTPases. In conclusion, Docetaxel treatment suppressed migration and invasiveness of head and neck cancer cells in vitro, which is likely to be mediated by regulating Cdc42 activity. (Cancer Sci 2010; 00: 000–000)
ORIGINAL ARTICLE: Dysregulation of plasma ghrelin in alcoholic cirrhosis
Authors: Goodyear Stephen J. , Mottershead Marcus , Sung Edmond Z. H. , Wong Ling S. , McTernan Philip G. , Kumar Sudhesh , Nwokolo Chuka U.
Published: February 2010

Objective  Abnormalities in circulating ghrelin have been reported in chronic liver disease. This study assessed the response of anabolic peptides ghrelin, growth hormone (GH) and insulin‐like growth factor 1 (IGF‐1) in patients with alcoholic cirrhosis and healthy subjects to oral glucose. In a previous study, using oral glucose we identified loss of ghrelin regulation in nonalcoholic steato‐hepatitis.

Patients/Design/Measurements  Fourteen patients with alcoholic cirrhosis were compared with 11 healthy subjects. Patients with cirrhosis were studied when adjudged clinically stable in hospital. After an overnight fast, they ingested 100‐g glucose dissolved in 250 ml of water. Blood was sampled before and every 20 minutes after ingestion for 120 minutes. Plasma acylated and des‐acyl ghrelin, GH, IGF‐1 and insulin were assayed by ELISA.

Results  Expressed as median (95% CI): 120‐minutes integrated acylated ghrelin was 26 (19–66) in controls compared to 170 (129–252) pg/ml per hour in patients with cirrhosis; P < 0·001. Both groups exhibited a normal postglucose plasma total ghrelin profile. Among patients with cirrhosis (compared to controls), growth hormone was increased 15‐fold and IGF‐1 decreased 4‐fold. Acylated ghrelin correlated with GH (Spearman r = 0·69, P = 0·0015) in control subjects but not in patients with cirrhosis.

Conclusions  Acylated ghrelin is markedly increased in alcoholic cirrhosis, with apparent preservation of normal postprandial mechanisms of gastric ghrelin secretion. GH is also increased; however, its correlation with acylated ghrelin (confirmed in healthy subjects) is absent in patients with cirrhosis. Despite increased ghrelin and GH, patients with alcoholic cirrhosis remain anorexic and catabolic suggesting potential tissue resistance to the actions of these anabolic peptides.
ORIGINAL ARTICLE: Leuprolide stimulation testing for the evaluation of early female sexual maturation
Authors: Sathasivam Anpalakan , Garibaldi Luigi , Shapiro Sofia , Godbold James , Rapaport Robert
Published: February 2010

Context  Low concentrations of serum LH and/or oestradiol (E2) in girls with early physical signs of precocious puberty pose a diagnostic challenge.

Objective  To assess the diagnostic value of the leuprolide stimulation test in female precocious puberty.

Design  Retrospective Chart Review.

Setting  Outpatient clinic.

Patients and intervention  Thirty‐nine girls, 6·9 (1·4) years, with premature stage II–III breast development, with or without pubarche, underwent stimulation testing with subcutaneous leuprolide (20 μg/kg) with the following hormonal measurements in serum: FSH, LH, oestradiol at baseline; FSH and LH at 1 and 2 h; oestradiol at 24 h. Twelve girls with isolated pubarche were also tested with leuprolide.

Main outcome measure  A pubertal hormonal pattern was defined as at least one of the following: a baseline serum level of LH ≥ 0·3 U/l, a baseline oestradiol ≥ 37 pmol/l (10 ng/l), a stimulated (peak) LH ≥ 5·0 U/l, a stimulated oestradiol ≥ 184 pmol/l (50 ng/l) to leuprolide. The hormonal response was related to the clinical course during a period of observation of at least 6 months.

Results  Following leuprolide stimulation, the hormonal response was concordant with pubertal progression (n = 23) or lack thereof (n = 16) in all children. At baseline, pubertal serum concentrations of LH and/or oestradiol were associated with pubertal progression in all, while serum prepubertal LH and/or oestradiol concentrations were associated with pubertal progression in approximately 50% of the patients.

Conclusions  In girls with early clinical signs of precocious puberty and low serum concentrations of LH and oestradiol in random samples, the LH and oestradiol responses to leuprolide stimulation accurately predict pubertal progression.
AphidBase: a centralized bioinformatic resource for annotation of the pea aphid genome
Authors: Legeai F. , Shigenobu S. , Gauthier J.‐P. , Colbourne J. , Rispe C. , Collin O. , Richards S. , Wilson A. C. C. , Murphy T. , Tagu D.
Published: February 2010

AphidBase is a centralized bioinformatic resource that was developed to facilitate community annotation of the pea aphid genome by the International Aphid Genomics Consortium (IAGC). The AphidBase Information System designed to organize and distribute genomic data and annotations for a large international community was constructed using open source software tools from the Generic Model Organism Database (GMOD). The system includes Apollo and GBrowse utilities as well as a wiki, blast search capabilities and a full text search engine. AphidBase strongly supported community cooperation and coordination in the curation of gene models during community annotation of the pea aphid genome. AphidBase can be accessed at http://www.aphidbase.com.