bluuebunny/crossref_metadata_2025 huggingface dataset:
α-Tocopherol attenuates NF-κB activation and pro-inflammatory cytokine IL-6 secretion in cancer-bearing mice
Authors: Sharma Renu , Vinayak Manjula
Published: February 2011

Cancer development and progression are closely associated with inflammation. NF-κB (nuclear factor κB) provides a mechanistic link between inflammation and cancer, and is a major factor controlling the ability of malignant cells to resist tumour surveillance mechanisms. NF-κB might also regulate tumour angiogenesis and invasiveness and the signalling pathways that mediate its activation provide attractive targets for new chemopreventive and chemotherapeutic approaches. ROS (reactive oxygen species) initiate inflammation by up-regulation of pro-inflammatory cytokines and therefore antioxidants provide a major defence against inflammation. α-Tocopherol is a lipid-soluble antioxidant. In addition to decreasing lipid peroxidation, α-tocopherol may exert intracellular effects. Hence, the aim of this study was to test the effect of α-tocopherol supplementation in cancer prevention via suppression of NF-κB-mediated pro-inflammatory cytokines. α-Tocopherol treatment significantly down-regulates expression, synthesis as well as secretion of pro-inflammatory cytokine IL-6 (interleukin-6) in cancerous mice. It also suppresses NF-κB binding to IL-6 promoter in liver leading to decreased secretion of IL-6 in serum. The regulation of the signalling pathway by α-tocopherol is found apart from its antioxidant capacity to reduce lipid peroxidation. Thus, the present study provides evidence for the hypothesis that besides the powerful free radical scavenging effects, α-tocopherol has genomic effects in down-regulation of pro-inflammatory cytokine and cancer prevention via the NF-κB-dependent pathway.
Impaired resistance artery function in patients with end-stage renal disease
Authors: Luksha Natallia , Luksha Leanid , Carrero Juan Jesús , Hammarqvist Folke , Stenvinkel Peter , Kublickiene Karolina
Published: February 2011

We investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (≈ 200 μm) isolated from subcutaneous fat biopsies obtained from 35 ESRD (end-stage renal disease) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients compared with controls. NO (nitric oxide) contribution to flow was lacking in ESRD patients, but present in the controls. ADMA (asymmetrical dimethyl L-arginine) levels were higher in the ESRD group compared with the control group. Dilatation in response to acetylcholine was reduced in ESRD patients compared with controls, but response to NO donor was similar. Expression of nitrotyrosine and heat shock proteins 70 and 27, but not 90, was increased in arteries from ESRD patients compared with controls. Arterial remodelling was absent in ESRD patients. There was no difference between the groups in myogenic tone, vascular reactivity or sensitivity to several vasoconstrictors. Arterial distensibility, reflecting passive properties of the vascular wall, was reduced in ESRD patients compared with controls. Exclusion of ESRD patients with diabetes and/or cardiovascular disease from analyses had no influence on the main findings. Thus we propose that uraemia has a strong impact on endothelial function and passive properties of the arterial wall of human peripheral resistance vasculature. The reduced contribution of NO to flow stimulus via enhanced nitrosative stress and higher plasma concentrations of ADMA may suggest potential mechanisms behind endothelial dysfunction in the resistance peripheral circulation in ESRD.
Regulation of IL-17 in chronic inflammation in the human lung
Authors: Pridgeon Carol , Bugeon Laurence , Donnelly Louise , Straschil Ursula , Tudhope Susan J. , Fenwick Peter , Lamb Jonathan R. , Barnes Peter J. , Dallman Margaret J.
Published: February 2011

The regulation of human Th17 cell effector function by Treg cells (regulatory T-cells) is poorly understood. In the present study, we report that human Treg (CD4+CD25+) cells inhibit the proliferative response of Th17 cells but not their capacity to secrete IL (interleukin)-17. However, they could inhibit proliferation and cytokine production by Th1 and Th2 cells as determined by IFN-γ (interferon-γ) and IL-5 biosynthesis. Currently, as there is interest in the role of IL-17-producing cells and Treg cells in chronic inflammatory diseases in humans, we investigated the presence of CD4+CD25+ T-cells and IL-17 in inflammation in the human lung. Transcripts for IL-17 were expressed in mononuclear cells and purified T-cells from lung tissue of patients with chronic pulmonary inflammation and, when activated, these cells secrete soluble protein. The T-cell-specific transcription factors RORCv2 (retinoic acid-related orphan receptor Cv2; for Th17) and FOXP3 (forkhead box P3; for Treg cells) were enriched in the T-cell fraction of lung mononuclear cells. Retrospective stratification of the patient cohort into those with COPD (chronic obstructive pulmonary disease) and non-COPD lung disease revealed no difference in the expression of IL-17 and IL-23 receptor between the groups. We observed that CD4+CD25+ T-cells were present in comparable numbers in COPD and non-COPD lung tissue and with no correlation between the presence of CD4+CD25+ T-cells and IL-17-producing cells. These results suggest that IL-17-expressing cells are present in chronically inflamed lung tissue, but there is no evidence to support this is due to the recruitment or expansion of Treg cells.
Electron ionization of SiCl4
Authors: King Simon J. , Price Stephen D.
Published: February 2011

Relative partial ionization cross sections (PICS) for the formation of fragment ions following electron ionization of SiCl4, in the electron energy range 30–200 eV, have been determined using time-of-flight mass spectrometry coupled with an ion coincidence technique. By this method, the contributions to the yield of each fragment ion from dissociative single, double, and triple ionization, are distinguished. These yields are quantified in the form of relative precursor-specific PICS, which are reported here for the first time for SiCl4. For the formation of singly charged ionic fragments, the low-energy maxima appearing in the PICS curves are due to contributions from single ionization involving predominantly indirect ionization processes, while contributions to the yields of these ions at higher electron energies are often dominated by dissociative double ionization. Our data, in the reduced form of relative PICS, are shown to be in good agreement with a previous determination of the PICS of SiCl4. Only for the formation of doubly charged fragment ions are the current relative PICS values lower than those measured in a previous study, although both datasets agree within combined error limits. The relative PICS data presented here include the first quantitative measurements of the formation of Cl2+ fragment ions and of the formation of ion pairs via dissociative double ionization. The peaks appearing in the 2D ion coincidence data are analyzed to provide further information concerning the mechanism and energetics of the charge-separating dissociations of SiCl42+. The lowest energy dicationic precursor state, leading to SiCl3+ + Cl+ formation, lies 27.4 ± 0.3 eV above the ground state of SiCl4 and is in close agreement with a calculated value of the adiabatic double ionization energy (27.3 eV).
A noncontact thermal microprobe for local thermal conductivity measurement
Authors: Zhang Yanliang , Castillo Eduardo E. , Mehta Rutvik J. , Ramanath Ganpati , Borca-Tasciuc Theodorian
Published: February 2011

We demonstrate a noncontact thermal microprobe technique for measuring the thermal conductivity κ with ∼3 μm lateral spatial resolution by exploiting quasiballistic air conduction across a 10–100 nm air gap between a joule-heated microprobe and the sample. The thermal conductivity is extracted from the measured effective thermal resistance of the microprobe and the tip–sample thermal contact conductance and radius in the quasiballistic regime determined by calibration on reference samples using a heat transfer model. Our κ values are within 5%–10% of that measured by standard steady-state methods and theoretical predictions for nanostructured bulk and thin film assemblies of pnictogen chalcogenides. Noncontact thermal microprobing demonstrated here mitigates the strong dependence of tip–sample heat transfer on sample surface chemistry and topography inherent in contact methods, and allows the thermal characterization of a wide range of nanomaterials.
Competitions between Rayleigh–Taylor instability and Kelvin–Helmholtz instability with continuous density and velocity profiles
Authors: Ye W. H. , Wang L. F. , Xue C. , Fan Z. F. , He X. T.
Published: February 2011

In this research, competitions between Rayleigh–Taylor instability (RTI) and Kelvin–Helmholtz instability (KHI) in two-dimensional incompressible fluids within a linear growth regime are investigated analytically. Normalized linear growth rate formulas for both the RTI, suitable for arbitrary density ratio with continuous density profile, and the KHI, suitable for arbitrary density ratio with continuous density and velocity profiles, are obtained. The linear growth rates of pure RTI (γRT), pure KHI (γKH), and combined RTI and KHI (γtotal) are investigated, respectively. In the pure RTI, it is found that the effect of the finite thickness of the density transition layer (Lρ) reduces the linear growth of the RTI (stabilizes the RTI). In the pure KHI, it is found that conversely, the effect of the finite thickness of the density transition layer increases the linear growth of the KHI (destabilizes the KHI). It is found that the effect of the finite thickness of the density transition layer decreases the “effective” or “local” Atwood number (A) for both the RTI and the KHI. However, based on the properties of γRT∝A and γKH∝1−A2, the effect of the finite thickness of the density transition layer therefore has a completely opposite role on the RTI and the KHI noted above. In addition, it is found that the effect of the finite thickness of the velocity shear layer (Lu) stabilizes the KHI, and for the most cases, the combined effects of the finite thickness of the density transition layer and the velocity shear layer (Lρ=Lu) also stabilize the KHI. Regarding the combined RTI and KHI, it is found that there is a competition between the RTI and the KHI because of the completely opposite effect of the finite thickness of the density transition layer on these two kinds of instability. It is found that the competitions between the RTI and the KHI depend, respectively, on the Froude number, the density ratio of the light fluid to the heavy one, and the finite thicknesses of the density transition layer and the velocity shear layer. Furthermore, for the fixed Froude number, the linear growth rate ratio of the RTI to the KHI decreases with both the density ratio and the finite thickness of the density transition layer, but increases with the finite thickness of the velocity shear layer and the combined finite thicknesses of the density transition layer and the velocity shear layer (Lρ=Lu). In summary, our analytical results show that the effect of the finite thickness of the density transition layer stabilizes the RTI and the overall combined effects of the finite thickness of the density transition layer and the velocity shear layer (Lρ=Lu) also stabilize the KHI. Thus, it should be included in applications where the transition layer effect plays an important role, such as the formation of large-scale structures (jets) in high energy density physics and astrophysics and turbulent mixing.
Debye–Hückel theory for mixtures of rigid rodlike ions and salt
Authors: Bohinc Klemen , Reščič Jurij , Maset Stefano , May Sylvio
Published: February 2011

Like-charged surfaces are able to attract each other if they are embedded in an electrolyte solution of multivalent rodlike ions, even if the rods are long. To reproduce this ability the Poisson–Boltzmann model has recently been extended so as to account for the rodlike structure of the mobile ions. Our model properly accounts for intraionic correlations but still neglects correlations between different rodlike ions. For sufficiently long rods, the model shows excellent agreement with Monte Carlo simulations and exhibits two minima – a depletion and a bridging minimum – in the interaction free energy. In the present work, we generalize the Poisson–Boltzmann model to systems with polydisperse rod lengths and arbitrary charge distributions along the rods, including the presence of salt. On the level of the linearized Debye–Hückel model we derive a general criterion for whether an electrolyte with given distribution of rodlike ions is able to mediate attraction between like-charged surfaces. We numerically analyze two special cases, namely the influence of salt on symmetric and asymmetric mixtures of monodisperse rodlike ions. The symmetric mixture is characterized by the presence of both negatively and positively charged (but otherwise identical) rodlike ions. For the asymmetric mixture, the system contains rodlike ions of only one type. We demonstrate that the addition of salt retains the depletion minimum but tends to eliminate the bridging minimum.
Quantum-mechanical method for estimating ion distributions in spinel ferrites
Authors: Tang G. D. , Ji D. H. , Yao Y. X. , Liu S. P. , Li Z. Z. , Qi W. H. , Han Q. J. , Hou X. , Hou D. L.
Published: February 2011

A quantum-mechanical method for estimating the cation distribution in spinel ferrites is proposed, by which the ionization energy of the cations and the Pauli repulsion energy is considered, together with the magnetic ordered energy and the tendency toward charge density balance. Using this method, not only can the difference between the observed and the traditional theoretical magnetic moments of the spinel structure ferrites MFe2O4 (M=Mn,Fe,Co,Ni,Cu) be explained, but also the dependence of the magnetic moments of the ferrites M1−xZnxFe2O4 (M=Mn,Fe,Co,Ni,Cu) on the doping level x can be fitted.
Enhanced magnetization drift velocity and current polarization in (CoFe)1−xGex alloys
Authors: Zhu M. , Soe B. D. , McMichael R. D. , Carey M. J. , Maat S. , Childress J. R.
Published: February 2011

A spin-wave Doppler technique is used to measure the drift velocity of the magnetization in current-carrying (CoFe)1−xGex alloys. For a current density of 1011 A/m2, we obtain a large enhancement of drift velocity with increased Ge concentration from 3.1±0.2 m/s for CoFe to 8.2±0.6 m/s for (CoFe)0.7Ge0.3. Interpretation of these values yields current polarization increasing from 0.84±0.04 to 0.95±0.05 as the Ge doping increases. While both spin-dependent conductivities decrease with increasing Ge concentration, the maximum in polarization is associated with a stronger relative change in the minority spin conductivity.
High-Q whispering-gallery mode lasing from nanosphere-patterned GaN nanoring arrays
Authors: Li K. H. , Ma Zetao , Choi H. W.
Published: February 2011

A hexagonal-close-packed ordered array of nanorings was fabricated on GaN with a modified nanosphere lithography process. The spheres initially served as etch masks for the formation of closed-packed nanopillars. The spheres were then shrunk and, with a layer of oxide deposited, the roles of the spheres became masks for liftoff. The final etch produced nanorings with wall widths of 140 nm. Photopumped lasing with splitting modes was observed at room temperature, with a low lase threshold of ∼10 mJ/cm2 and high quality factor of ∼5000, via whispering-gallery modes. The resonant frequencies were verified through finite-difference time-domain simulations.
Vertical n-type organic transistors with tri(8-hydroxyquinoline) aluminum as collector and fullerene as emitter
Authors: Yi Mingdong , Xia Xianhai , Yang Tao , Liu Yuyu , Xie Linghai , Zhou Xinhui , Huang Wei
Published: February 2011

A vertical n-type permeable organic metal-base transistor was demonstrated. In this transistor, two kinds of n-type organic semiconductors of fullerene (C60) and tri(8-hydroxyquinoline) aluminum (Alq3) were used as emitter and collector, respectively, and the metal base was comprised of Al/Al2O3/LiF. The formation of a thin oxide film (Al2O3) on the metal aluminum (Al) surface by thermally annealing makes the base self-selected charge carrier characteristic. As a result, the device exhibits low leakage current, and the common-base and common-emitter current gains reach near 1 and 30 at less than 1 V bias, respectively.
Roles of silver oxide in the bipolar resistance switching devices with silver electrode
Authors: Dong C. Y. , Shang D. S. , Shi L. , Sun J. R. , Shen B. G. , Zhuge F. , Li R. W. , Chen W.
Published: February 2011

Three devices, Ag/WO3−x/Pt, Ag/AgOx/Pt, and Ag/AgOx/WO3−x/Pt, were investigated to elucidate the influence of the silver oxide on the bipolar resistive switching behavior. The silver oxide films were obtained by depositing silver at oxygen atmosphere. We find that the resistive switching behavior was determined by the silver oxide layer. Bulk and interface resistive switching were observed in the Ag/AgOx/Pt and Ag/AgOx/WO3−x/Pt devices, respectively. By the micro-x-ray photoemission spectroscopy analysis, it was demonstrated that the electrochemical redox reaction occurred in the AgOx layer is responsible for the resistive switching behavior at silver/oxide interface.
The catalytic potential of high-κ dielectrics for graphene formation
Authors: Scott Andrew , Dianat Arezoo , Börrnert Felix , Bachmatiuk Alicja , Zhang Shasha , Warner Jamie H. , Borowiak-Paleń Ewa , Knupfer Martin , Büchner Bernd , Cuniberti Gianaurelio , Rümmeli Mark H.
Published: February 2011

The growth of single and multilayer graphene nanoflakes on MgO and ZrO2 at low temperatures is shown through transmission electron microscopy. The graphene nanoflakes are ubiquitously anchored at step edges on MgO (100) surfaces. Density functional theory investigations on MgO (100) indicate C2H2 decomposition and carbon adsorption at step-edges. Hence, both the experimental and theoretical data highlight the importance of step sites for graphene growth on MgO.
Carbon Monoxide Thermophysical Properties from 68 to 1000 K at Pressures to 100 MPa
Authors: Goodwin Robert D.
Published: February 2011

An improved form of the nonanalytic equation of state is used to compute thermodynamic properties of carbon monoxide along isobars up to 100 MPa, at integral temperatures from coexistence to 1000 K.
Viscosity and Thermal Conductivity of Dry Air in the Gaseous Phase
Authors: Kadoya K. , Matsunaga N. , Nagashima A.
Published: February 2011

In view of the importance of air in science and technology and the abundance of experimental data, we present in this report a consistent set of critically evaluated data and an up-to-date correlation of the viscosity and the thermal conductivity of air in the gaseous phase over a wide range of temperature and pressure. This is especially important for the viscosity, since the recent data show systematic differences compared with the old standard value used for many years. The present paper was written in order to document the critical evaluation of the latest data sets and to present a new set of correlations of the viscosity and the thermal conductivity of air. The range covered is from 85 to 2000 K for temperature and up to 100 MPa for pressure.
Charge Transfer of Hydrogen Ions and Atoms in Metal Vapors
Authors: Morgan T. J. , Olson R. E. , Schlachter A. S. , Gallagher J. W.
Published: February 2011

Cross sections and equilibrium fractions for energetic H+, H−, and H0 in collisions with metal-vapor targets have been compiled and evaluated. Both experimental and theoretical results are reported. Sources of errors are discussed, and recommended values for the data are presented.
Assessing specific agronomic responses of wheat cultivars in a winter rainfall environment
Authors: Anderson W. K. , van Burgel A. J. , Sharma D. L. , Shackley B. J. , Zaicou-Kunesch C. M. , Miyan M. S. , Amjad M.
Published: February 2011

When new wheat cultivars are released for commercial production it is desirable to assist farmers to maximise the yield advantage by providing information about their responses to agronomic practices such as seeding rate and nitrogen (N) fertiliser. Over 3 years in 22 field experiments in the Mediterranean-type environment of Western Australia the response to seed rate and applied N fertiliser of current and recently released wheat cultivars was measured in factorial experiments under rain-fed conditions. A cross-site analysis showed that the environment × cultivar (location and year) or management (seed rate and N rate) interactions were relatively minor, explaining only 5% or less of the yield variation, in contrast to 89% accounted for by the environment. The analyses of individual experiments revealed that cultivars interacted more often with seeding rate (12 sites) than with applied N fertiliser rates (4 sites). Further, despite a frequent occurrence, the cultivar × seed rate interaction had only a marginal practical significance because the cultivar rankings at a site varied with season and the differences in optimum plant population were greater between sites and seasons than between cultivars at a site. The number of sites with positive and significant cultivar × N rate interaction was insufficient to generalise about the validity of the responses. The lack of any large differences between cultivars for their response to either seed rate or N rate implies the presence of a high inherent ability for compensation among yield components, thereby enabling the cultivars to exhibit an apparently high similarity for response to input levels. As such, it was not possible to generalise across environments in making clear suggestions for farmers to follow in respect of managing new cultivars differently from each other. It was concluded that despite the apparent desirability of providing information about differences between new and existing cultivars in their responses to seed and N rates at the time of release, they are more likely to be found where the differences between the cultivars are large, the testing sites are chosen so as to reduce the yield variance, and the yield level achieved in the experiments is above 2 t/ha.
Wheat physiology: a review of recent developments
Authors: Fischer R. A.
Published: February 2011

This review focuses on recent advances in some key areas of wheat physiology, namely phasic development, determination of potential yield and water-limited potential yield, tolerance to some other abiotic stresses (aluminium, salt, heat shock), and simulation modelling. Applications of the new knowledge to breeding and crop agronomy are emphasized. The linking of relatively simple traits like time to flowering, and aluminium and salt tolerance, in each case to a small number of genes, is being greatly facilitated by the development of molecular gene markers, and there is some progress on the functional basis of these links, and likely application in breeding. However with more complex crop features like potential yield, progress at the gene level is negligible, and even that at the level of the physiology of seemingly important component traits (e.g., grain number, grain weight, soil water extraction, sensitivity to water shortage at meiosis) is patchy and generally slow although a few more heritable traits (e.g. carbon isotope discrimination, coleoptile length) are seeing application. This is despite the advent of smart tools for molecular analysis and for phenotyping, and the move to study genetic variation in soundly-constituted populations. Exploring the functional genomics of traits has a poor record of application; while trait validation in breeding appears underinvested. Simulation modeling is helping to unravel G × E interaction for yield, and is beginning to explore genetic variation in traits in this context, but adequate validation is often lacking. Simulation modelling to project agronomic options over time is, however, more successful, and has become an essential tool, probably because less uncertainty surrounds the influence of variable water and climate on the performance of a given cultivar. It is the ever-increasing complexity we are seeing with genetic variation which remains the greatest challenge for modelling, molecular biology, and indeed physiology, as they all seek to progress yield at a rate greater than empirical breeding is achieving.
Natural language generation of biomedical argumentation for lay audiences
Authors: Green Nancy , Dwight Rachael , Navoraphan Kanyamas , Stadler Brian
Published: February 2011

This article presents an architecture for natural language generation of biomedical argumentation. The goal is to reconstruct the normative arguments that a domain expert would provide, in a manner that is transparent to a lay audience. Transparency means that an argument's structure and functional components are accessible to its audience. Transparency is necessary before an audience can fully comprehend, evaluate or challenge an argument, or re-evaluate it in light of new findings about the case or changes in scientific knowledge. The architecture has been implemented and evaluated in the Genetics Information Expression Assistant, a prototype system for drafting genetic counselling patient letters. Argument generation makes use of abstract argumentation schemes. Derived from the analysis of arguments used in genetic counselling, these mainly causal argument patterns refer to abstract properties of qualitative causal domain models.
Hairless is a cofactor for Runt-dependent transcriptional regulation
Authors: Walrad Pegine B. , Hang Saiyu , Gergen J. Peter
Published: February 2011

Runt is a vital transcriptional regulator in the developmental pathway responsible for segmentation in the Drosophila embryo. Runt activates or represses transcription in a manner that is dependent on both cellular context and the specific downstream target. Here we identify Hairless (H) as a Runt-interacting molecule that functions during segmentation. We find that H is important for maintenance of engrailed (en) repression as was previously demonstrated for Groucho (Gro), Rpd3, and CtBP. H also contributes to the Runt-dependent repression of sloppy-paired-1 (slp1), a role that is not shared with these other corepressors. We further find distinct roles for these different corepressors in the regulation of other Runt targets in the early Drosophila embryo. These findings, coupled with observations on the distinct functional requirements for Runt in regulating these several different targets, indicate that Runt-dependent regulation in the Drosophila blastoderm embryo relies on unique, target-gene-specific molecular interactions.
Mitotic progression becomes irreversible in prometaphase and collapses when Wee1 and Cdc25 are inhibited
Authors: Potapova Tamara A. , Sivakumar Sushama , Flynn Jennifer N. , Li Rong , Gorbsky Gary J.
Published: February 2011

Mitosis requires precise coordination of multiple global reorganizations of the nucleus and cytoplasm. Cyclin-dependent kinase 1 (Cdk1) is the primary upstream kinase that directs mitotic progression by phosphorylation of a large number of substrate proteins. Cdk1 activation reaches the peak level due to positive feedback mechanisms. By inhibiting Cdk chemically, we showed that, in prometaphase, when Cdk1 substrates approach the peak of their phosphorylation, cells become capable of proper M-to-G1 transition. We interfered with the molecular components of the Cdk1-activating feedback system through use of chemical inhibitors of Wee1 and Myt1 kinases and Cdc25 phosphatases. Inhibition of Wee1 and Myt1 at the end of the S phase led to rapid Cdk1 activation and morphologically normal mitotic entry, even in the absence of G2. Dampening Cdc25 phosphatases simultaneously with Wee1 and Myt1 inhibition prevented Cdk1/cyclin B kinase activation and full substrate phosphorylation and induced a mitotic “collapse,” a terminal state characterized by the dephosphorylation of mitotic substrates without cyclin B proteolysis. This was blocked by the PP1/PP2A phosphatase inhibitor, okadaic acid. These findings suggest that the positive feedback in Cdk activation serves to overcome the activity of Cdk-opposing phosphatases and thus sustains forward progression in mitosis.
Identifying dispersed epigenomic domains from ChIP-Seq data
Authors: Song Qiang , Smith Andrew D.
Published: February 2011

Motivation: Post-translational modifications to histones have several well known associations with regulation of gene expression. While some modifications appear concentrated narrowly, covering promoters or enhancers, others are dispersed as epigenomic domains. These domains mark contiguous regions sharing an epigenomic property, such as actively transcribed or poised genes, or heterochromatically silenced regions. While high-throughput methods like ChIP-Seq have led to a flood of high-quality data about these epigenomic domains, there remain important analysis problems that are not adequately solved by current analysis tools.

Results: We present the RSEG method for identifying epigenomic domains from ChIP-Seq data for histone modifications. In contrast with other methods emphasizing the locations of ‘peaks’ in read density profiles, our method identifies the boundaries of domains. RSEG is also able to incorporate a control sample and find genomic regions with differential histone modifications between two samples.

Availability: RSEG, including source code and documentation, is freely available at http://smithlab.cmb.usc.edu/histone/rseg/.

Contact:  andrewds@usc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Intrahepatic Biliary Anomalies in a Patient With Mowat‐Wilson Syndrome Uncover a Role for the Zinc Finger Homeobox Gene zfhx1b in Vertebrate Biliary Development
Authors: Cui Shuang , Erlichman Jessi , Russo Pierre , Haber Barbara A , Matthews Randolph P
Published: February 2011

Background:

zfhz1b is the causative gene for Mowat‐Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.

Materials and Methods:

We identified a patient with Mowat‐Wilson syndrome who also developed cholestasis and histopathologic features consistent with biliary atresia, suggesting that mutations involving zfhz1b may lead to biliary developmental anomalies or injury to the biliary tract. We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development.

Results:

Using zebrafish we determined that zfhx1b was expressed in the developing liver during biliary growth and remodeling, and that morpholino antisense oligonucleotide–mediated knockdown of zfhx1b led to defects in biliary development. These findings were associated with decreased expression of vhnf1, a transcription factor known to be important in biliary development in zebrafish and in mammals.

Conclusions:

Our studies underscore the importance of genetic contributions in the etiology of infantile hepatobiliary disorders, including biliary atresia.
Iron Load and Liver Enzymes in 10‐ and 13‐year‐olds
Authors: Okuda Masayuki , Sasaki Satoshi , Kunitsugu Ichiro , Sakurai Ryuta , Yoshitake Norikazu , Hobara Tatsuya
Published: February 2011

Objectives:

Iron plays a pivotal role in adult steatosis, but its role in child and adolescent steatosis is unclear. We investigated the effect of dietary iron, serum iron, and ferritin on serum transaminases and γ‐glutamyltransferase in 10‐ and 13‐year‐olds.

Patients and Methods:

The study included 4894 fifth and eighth graders enrolled between 2006 and 2009 in all schools in Shunan City, Japan. Multiple regression analyses were performed with adjustments for grade, sex, z score of the body mass index, serum lipids, plasma glucose, frequency of sports activities, having a single parent, number of siblings, tobacco smoking behavior, passive smoking at home, resident areas, and schools, using linear mixed models. In addition, we analyzed ferritin and insulin resistance in randomly selected subset of participants.

Results:

Dietary iron intake was positively associated with serum alanine aminotransferase levels (standardized coefficient β = 2.35, P = 0.019). Serum iron concentrations were associated with transaminase and γ‐glutamyltransferase levels (β = 3.22, and 4.05, respectively, P < 0.01). In the subset of 421 subjects with further serum analysis, serum ferritin levels were significantly associated with serum enzyme levels (β = 2.43–3.35; P < 0.05) and showed significant odds ratio for the elevated alanine aminotransferase levels (1.05 for 1 SD with 95% confidence intervals 1.02–1.08). However, iron load did not show a positive association with insulin resistance.

Conclusions:

Although an effect size for iron is small in regression analyses, iron is implicated in increased transaminase levels in prepubertal and pubertal children.
Dietary Intake of Polyunsaturated Fatty Acids Among Breast‐feeding and Non–breast‐feeding 24‐ to 48‐month‐old Children in Bangladesh
Authors: Yakes Elizabeth A , Arsenault Joanne E , Islam M Munirul , Ahmed Tahmeed , German J Bruce , Drake Christiana , Hossain Mohammad B , Lewis Bess L , Rahman Ahmed Shafiqur , Jamil Kazi M , Brown Kenneth H
Published: February 2011

Objective:

The aim of the study was to assess the adequacy of polyunsaturated fatty acid intake by rural Bangladeshi children 24 to 48 months old in relation to their breast‐feeding status.

Materials and Methods:

Multistage sampling was used to select a representative sample of children 24 to 48 months of age from 2 rural districts in Bangladesh (n = 479). Two nonconsecutive 24‐hour periods of dietary data were collected via 12‐hour daytime in‐home observations and recall. Breast milk intake was estimated using test weighing. The National Cancer Institute (NCI) method for episodically consumed foods was used to estimate distributions of usual food and nutrient intakes.

Results:

Based on the estimated intake distributions, >95% of the children had usual fat intakes <30% of total energy. Among 24‐ to 35‐month‐old (younger) and 36‐ to 48‐month‐old (older) children, respectively, 4% and 16% of breast‐feeding children and 31% and 41% of non–breast‐feeding children were estimated to consume <10% of total energy from fat. An estimated 80% of all of the children consumed <4% of total energy as linoleic acid, and 99% consumed <1% of energy as α‐linolenic acid. Younger breast‐feeding children had higher estimated average docosahexaenoic acid (DHA) intakes (0.04 g DHA/day) than their non–breast‐feeding counterparts (0.01 g DHA/day; P = 0.0005). Both breast‐feeding and non–breast‐feeding older children had estimated mean DHA intakes of 0.02 g/day (P = 0.74).

Conclusions:

Rural Bangladeshi children 24 to 48 months old, and especially those who have discontinued breast‐feeding, may benefit from increased fat consumption.
Double‐blind Randomized Trial of Quadruple Sequential Helicobacter pylori Eradication Therapy in Asymptomatic Infected Children in El Paso, Texas
Authors: Prieto‐Jimenez Carmen A , Cardenas Victor M , Fischbach Lori A , Mulla Zuber D , Rivera Jose O , Dominguez Delfina C , Graham David Y , Ortiz Melchor
Published: February 2011

Objectives:

We assessed the efficacy of a novel quadruple sequential 10‐day eradication therapy, its compliance, and reported adverse events in a sample of asymptomatically Helicobacter pylori–infected children in El Paso, Texas, as part of a study aiming to assess the influence of this infection on the levels of markers of iron stores.

Patients and Methods:

Using a double‐blind randomized trial design, 110 asymptomatic children ages 3 to 11 with H pylori infection were randomly assigned to receive either a 10‐day course of sequential eradication therapy plus 6 weeks of iron supplementation, eradication therapy plus placebo, iron supplementation plus placebo, or placebo only. H pylori infection status was assessed ≥45 days after treatment using the urea breath test. Analyses compared the proportion of subjects cured according to assignment to and completion of the sequential eradication therapy.

Results:

Intent‐to‐treat and per‐protocol analyses indicated that 44.3% and 52.9%, respectively, of the children receiving the novel quadruple sequential therapy had their infection eradicated compared with 12.2% and 15.4% in the arms receiving iron or placebo only, respectively (P < 0.001 in both analyses). Study medications were taken with no or only mild adverse events in most children.

Conclusions:

A quadruple sequential regimen eradicated H pylori in only half the asymptomatic children receiving this treatment. There was no difference in the cure rates of those receiving iron supplementation and those receiving placebo.
ICP27 protein of Marek’s disease virus interacts with SR proteins and inhibits the splicing of cellular telomerase chTERT and viral vIL8 transcripts
Authors: Amor S. , Strassheim S. , Dambrine G. , Remy S. , Rasschaert D. , Laurent S.
Published: February 2011

All herpesviruses have a post-transcriptional regulatory protein that prevents precursor mRNA splicing and leads to the shutting off of host protein synthesis. The ICP27 protein of herpes simplex virus 1 (HSV-1) is the prototype of these proteins. Marek’s disease virus (MDV-1), an alphaherpesvirus that induces lymphoma in birds, also has an ICP27 protein that is produced in lytic MDV-1-infected cells. We characterized this protein. We demonstrated ICP27 production in latently infected MSB-1 cells, but only on MDV-1 reactivation. ICP27 was found predominantly in specific structures within the nucleus. The ICP27 of MDV-1 colocalized and interacted with SR proteins. We demonstrated inhibitory effects of MDV-1 ICP27 on the splicing of both the viral vIL8 and cellular chTERT (telomerase reverse transcriptase) genes. Thus, the ICP27 of MDV-1 plays a similar role to the ICP27 of HSV-1 and may be involved in MDV-1 replication and the development of Marek’s disease.
Helicoverpa armigera nucleopolyhedrovirus occlusion-derived virus-associated protein, HA100, affects oral infectivity in vivo but not virus replication in vitro
Authors: Luo Sijiani , Zhang Yanfang , Xu Xushi , Westenberg Marcel , Vlak Just M. , Wang Hualin , Hu Zhihong , Deng Fei
Published: February 2011

ORF100 (ha100) of Helicoverpa armigera nucleopolyhedrovirus (HearNPV) has been reported as one of the unique genes of group II alphabaculoviruses encoding a protein located in the occlusion-derived virus (ODV) envelope and nucleocapsid. The protein consists of 510 aa with a predicted mass of 58.1 kDa and is a homologue of poly(ADP–ribose) glycohydrolase in eukaryotes. Western blot analysis detected a 60 kDa band in HearNPV-infected HzAM1 cells starting at 18 h post-infection. Transient expression of GFP-fused HA100 in HzAM1 cells resulted in cytoplasmic localization of the protein, but after superinfection with HearNPV, GFP-fused HA100 was localized in the nucleus. To study the function of HA100 further, an ha100-null virus was constructed using bacmid technology. Viral one-step growth curve analyses showed that the ha100-null virus had similar budded virus production kinetics to that of the parental virus. Electron microscopy revealed that deletion of HA100 did not alter the morphology of ODVs or occlusion bodies (OBs). However, bioassays in larvae showed that the 50 % lethal concentration (LC50) value of HA100-null OBs was significantly higher than that of parental OBs; the median lethal time (LT50) of ha100-null OBs was about 24 h later than control virus. These results indicate that HA100 is not essential for virus replication in vitro. However, it significantly affects the oral infectivity of OBs in host insects, suggesting that the association HA100 with the ODV contributes to the infectivity of OBs in vivo.
Deletion of the GluA1 AMPA receptor subunit alters the expression of short-term memory
Authors: Sanderson David J. , Sprengel Rolf , Seeburg Peter H. , Bannerman David M.
Published: February 2011

Deletion of the GluA1 AMPA receptor subunit selectively impairs short-term memory for spatial locations. We further investigated this deficit by examining memory for discrete nonspatial visual stimuli in an operant chamber. Unconditioned suppression of magazine responding to visual stimuli was measured in wild-type and GluA1 knockout mice. Wild-type mice showed less suppression to a stimulus that had been presented recently than to a stimulus that had not. GluA1 knockout mice, however, showed greater suppression to a recent stimulus than to a nonrecent stimulus. Thus, GluA1 is not necessary for encoding, but affects the way that short-term memory is expressed.
iTRAQ Analysis Reveals Mechanisms of Growth Defects Due to Excess Zinc in Arabidopsis
Authors: Fukao Yoichiro , Ferjani Ali , Tomioka Rie , Nagasaki Nahoko , Kurata Rie , Nishimori Yuka , Fujiwara Masayuki , Maeshima Masayoshi
Published: February 2011

The micronutrient zinc is essential for all living organisms, but it is toxic at high concentrations. Here, to understand the effects of excess zinc on plant cells, we performed an iTRAQ (for isobaric tags for relative and absolute quantification)-based quantitative proteomics approach to analyze microsomal proteins from Arabidopsis (Arabidopsis thaliana) roots. Our approach was sensitive enough to identify 521 proteins, including several membrane proteins. Among them, IRT1, an iron and zinc transporter, and FRO2, a ferric-chelate reductase, increased greatly in response to excess zinc. The expression of these two genes has been previously reported to increase under iron-deficient conditions. Indeed, the concentration of iron was significantly decreased in roots and shoots under excess zinc. Also, seven subunits of the vacuolar H+-ATPase (V-ATPase), a proton pump on the tonoplast and endosome, were identified, and three of them decreased significantly in response to excess zinc. In addition, excess zinc in the wild type decreased V-ATPase activity and length of roots and cells to levels comparable to those of the untreated de-etiolated3-1 mutant, which bears a mutation in V-ATPase subunit C. Interestingly, excess zinc led to the formation of branched and abnormally shaped root hairs, a phenotype that correlates with decreased levels of proteins of several root hair-defective mutants. Our results point out mechanisms of growth defects caused by excess zinc in which cross talk between iron and zinc homeostasis and V-ATPase activity might play a central role.
Allogeneic haematopoietic cell transplantation for myelofibrosis in 30 patients 60–78 years of age
Authors: Samuelson Scott , Sandmaier Brenda M. , Heslop Helen E. , Popat Uday , Carrum George , Champlin Richard E. , Storb Rainer , Prchal Josef T. , Gooley Theodore A. , Joachim Deeg H.
Published: February 2011

We analysed the results of haematopoietic cell transplantation (HCT) in 30 patients aged 60–78 (median 65) years, with primary myelofibrosis or myelofibrosis evolving from antecedent polycythaemia vera or essential thrombocythaemia. Donors were human leucocyte antigen (HLA)‐identical siblings (N = 15) or unrelated individuals (N = 15). Various conditioning regimens were used, ranging from very low intensity (fludarabine plus 2 Gy total body irradiation) to high dose (busulfan plus cyclophosphamide). Stem cell sources were granulocyte colony‐stimulating factor mobilized peripheral blood progenitor cells in 29 patients and marrow in one patient. Sustained engraftment was documented in 27 of 30 patients. Day ‐100 mortality was 13%. With a median follow‐up of 22 (range 0·5–69) months, 3‐year overall survival and progression‐free survival were 45% and 40%, respectively. Currently, 13 patients are surviving. Seven patients died with disease progression at 0·5–22 months, and 10 patients died from other causes at 1·5–37.5 months after HCT. While the selection of older patients for transplantation was probably biased, the present results are encouraging. Motivated older patients with myelofibrosis without substantial comorbid conditions should be offered the option of allogeneic HCT.
Recombinant human CD19‐ligand protein as a potent anti‐leukaemic agent
Authors: Uckun Fatih M. , Sun Lei , Qazi Sanjive , Ma Hong , Ozer Zahide
Published: February 2011

We report the cloning and characterization of a novel 54‐kDa high‐mobility group (HMG)‐box protein as the ligand for the human pan‐B cell co‐receptor CD19 (CD19‐L), which interacts with the extracellular domain of CD19 in trans. CD19‐L is the first CD19‐specific recombinant human protein with potent anti‐leukaemic activity against B‐lineage acute lymphoblastic leukaemia (ALL), the most common form of childhood cancer and the second most common form of acute leukaemia in adults. Soluble recombinant CD19‐L protein exhibited exquisite specificity for the extracellular domain of CD19 and strong binding to the surface of B‐lineage leukaemia/lymphoma cells. Engagement of CD19 co‐receptor on B‐lineage ALL cells with CD19‐L perturbed the CD19‐associated signalling network, altering the expression levels of multiple genes directly involved in regulation of apoptosis, and triggered rapid apoptotic cell death in a CD19‐specific manner. The identification of human CD19‐L may lead to therapeutic innovation for B‐lineage ALL and other B‐lineage lymphoid malignancies as well as B‐cell lymphoproliferative states and systemic autoimmunity.
Emerging diseases in freshwater systems
Authors: OKAMURA BETH , FEIST STEPHEN W.
Published: February 2011

1. Emerging diseases in marine and terrestrial systems have been the subject of several high‐profile syntheses but there are no such overviews of emerging diseases in fresh waters. The distinct differences associated with fresh waters merit the separate consideration given to freshwater emerging diseases in this Special Issue.

2. Unique aspects of freshwater environments that can be expected to influence disease emergence include the following: the extreme levels of environmental degradation, overfishing and biodiversity loss arising from preferential human settlement near freshwater bodies for millenia; their relatively small volume and the attraction of animal aggregations that promote disease transmission; and their role as arteries linking terrestrial and marine environments.

3. Understanding emerging diseases entails addressing the multiple drivers that influence the dynamics of host–parasite interactions in a changing world. Structural and functional transformations of ecosystems caused by overfishing may act as an important underlying driver.

4. Climate change may promote disease emergence, but environmental change may cause some diseases to diminish as a result of changes in distributions and abundances of hosts and disease agents. Furthermore, rapid evolution may constrain disease emergence despite environmental change.

5. Appreciating that parasites and pathogens are functional components of healthy ecosystems and that their dynamics may even portend ecosystem change would foster a more complete and balanced view of the value of biodiversity and the ecological role of disease.

6. A multidisciplinary approach will enable a better understanding of disease ecology in general and of freshwater emerging diseases as manifestations of host–parasite interactions to a specific range of conditions.