bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herpes Simplex Virus Proteins ICP27 and UL47 Associate with Polyadenylate-Binding Protein and Control Its Subcellular Distribution
Authors: Dobrikova Elena , Shveygert Mayya , Walters Robert , Gromeier Matthias 
Published: October 2009

ABSTRACT

Human pathogenic viruses manipulate host cell translation machinery to ensure efficient expression of viral genes and to thwart host cell protein synthesis. Viral strategies include cleaving translation factors, manipulating translation factor abundance and recruitment into translation initiation complexes, or expressing viral translation factor analogs. Analyzing translation factors in herpes simplex virus type 1 (HSV-1)-infected HeLa cells, we found diminished association of the polyadenylate-binding protein (PABP) with the cap-binding complex. Although total PABP levels were unchanged, HSV-1 infection prompted accumulation of cytoplasmic PABPC1, but not its physiologic binding partner PABP-interacting protein 2 (Paip2), in the nucleus. Using glutathione
S
-transferase-PABP pull-down and proteomic analyses, we identified several viral proteins interacting with PABPC1 including tegument protein UL47 and infected-cell protein ICP27. Transient expression of ICP27 and UL47 in HeLa cells suggested that ICP27 and UL47 jointly displace Paip2 from PABP. ICP27 expression alone was sufficient to cause PABPC1 redistribution to the nucleus. ICP27 and UL47 did not alter translation efficiency of transfected reporter RNAs but modulated transcript abundance and expression of reporter cDNAs in transfected cells. This indicates that redistribution of PABPC1 may be involved in co- and posttranscriptional regulation of mRNA processing and/or nuclear export by HSV-1 gene regulatory proteins.
Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice
Authors: Zhang Wenliang , Choi Youngjoo , Haynes Lia M. , Harcourt Jennifer L. , Anderson Larry J. , Jones Les P. , Tripp Ralph A. 
Published: October 2009

ABSTRACT
Respiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possible to reduce the hospitalization rate for high-risk children by anti-RSV antibody prophylaxis. RSV has been shown to modify the immune response to infection, a feature linked in part to RSV G protein CX3C chemokine mimicry. This study determined if vaccination with G protein polypeptides or peptides spanning the central conserved region of the G protein could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and disease pathogenesis mediated by RSV infection. The results show that mice vaccinated with G protein peptides or polypeptides containing the CX3C motif generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis, reduce lung virus titers, and prevent body weight loss and pulmonary inflammation. The results suggest that RSV vaccines that induce antibodies that block G protein CX3C-CX3CR1 interaction may offer a new, safe, and efficacious RSV vaccine strategy.
Insulin-Degrading Enzyme Binds to the Nonglycosylated Precursor of Varicella-Zoster Virus gE Protein Found in the Endoplasmic Reticulum
Authors: Carpenter J. E. , Jackson W. , de Souza G. A. , Haarr L. , Grose C. 
Published: October 2009

ABSTRACT

Insulin degradation enzyme (IDE) is a 110-kDa zinc metalloprotease found in the cytosol of all cells. IDE degrades insulin and a variety of small proteins including amyloid-β. Recently, IDE has been proposed as the receptor for varicella-zoster virus (VZV) attachment. During our reassessment, some of the original studies were repeated and expanded in scope. We first confirmed that IDE antibody reduced VZV spread. For additional controls, we repeated the same experiments with herpes simplex virus (HSV)-infected cells as well as uninfected cells. There was a visible reduction in HSV spread but less than seen in the VZV system. Of greater importance, IDE antibody also inhibited the growth of uninfected cells. Second, we repeated the coprecipitation assays. We confirmed that antibodies to VZV gE (open reading frame 68) coprecipitated IDE and that anti-IDE antibody coprecipitated gE. However, the detected gE protein was not the mature 98-kDa form; rather, it was a precursor 73-kDa gE form found in the endoplasmic reticulum. Additional control experiments included VZV-infected cell cultures treated with tunicamycin to block gE glycosylation in the endoplasmic reticulum; again, the anti-IDE antibody coprecipitated a 73-kDa gE product. Finally, Orbitrap mass spectrometry analysis of a chromatographically purified gE sample revealed four cellular proteins associated with the unfolded protein response: BiP (HSPA5), HSPA8, HSPD1, and PPIA (peptidyl-propyl
cis
-
trans
isomerase). We conclude that IDE protease binds to the 73-kDa gE precursor and that this event occurs in the cytosol but not as a receptor/ligand interaction.
Production and Function of the Cytoplasmic Deproteinized Relaxed Circular DNA of Hepadnaviruses
Authors: Guo Haitao , Mao Richeng , Block Timothy M. , Guo Ju-Tao 
Published: October 2009

ABSTRACT
Removal of genome-bound viral DNA polymerase ought to be an essential step in the formation of hepadnavirus covalently closed circular DNA (cccDNA). We previously demonstrated that deproteinized (DP) relaxed circular DNA (rcDNA) of hepatitis B virus (HBV) existed in both the cytoplasm and nuclei of infected cells and the vast majority of cytoplasmic DP rcDNA was associated with DNase I-permeable nucleocapsids. In our efforts to investigate the role of the cytoplasmic DP rcDNA in cccDNA formation, we demonstrated that rcDNA deproteinization could occur in an endogenous DNA polymerase reaction with either virion-derived or intracellular nucleocapsids. As observed in the cytoplasm of virally infected cells, in vitro deproteinization requires the maturation of plus-strand DNA and results in changes in nucleocapsid structure that render the DP rcDNA susceptible to DNase I digestion. Remarkably, we found that the cytoplasmic DP rcDNA-containing nucleocapsids could be selectively immunoprecipitated with an antibody against the carboxyl-terminal peptide of HBV core protein and are associated with cellular nuclear transport receptors karyopherin-α and -β. Moreover, transfection of small interfering RNA targeting karyopherin-β1 mRNA or expression of a dominant-negative karyopherin-β1 in a stable cell line supporting HBV replication resulted in the accumulation of DP rcDNA in cytoplasm and reduction of nuclear DP rcDNA and cccDNA. Our results thus favor a hypothesis that completion of plus-strand DNA synthesis triggers the genomic DNA deproteinization and structural changes of nucleocapsids, which leads to the exposure of nuclear localization signals in the C terminus of core protein and mediates the nuclear transportation of DP rcDNA via interaction with karyopherin-α and -β.
Generation of Live Attenuated Novel Influenza Virus A/California/7/09 (H1N1) Vaccines with High Yield in Embryonated Chicken Eggs
Authors: Chen Zhongying , Wang Weijia , Zhou Helen , Suguitan Amorsolo L. , Shambaugh Cindy , Kim Lomi , Zhao Jackie , Kemble George , Jin Hong 
Published: October 2009

ABSTRACT
Several live attenuated influenza virus A/California/7/09 (H1N1) (CA09) candidate vaccine variants that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the CA09 virus and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (H2N2) virus were generated by reverse genetics. The reassortant viruses replicated relatively poorly in embryonated chicken eggs. To improve virus growth in eggs, reassortants expressing the HA and NA of CA09 were passaged in MDCK cells and variants exhibiting large-plaque morphology were isolated. These variants replicated at levels approximately 10-fold higher than the rate of replication of the parental strains in embryonated chicken eggs. Sequence analysis indicated that single amino acid changes at positions 119, 153, 154, and 186 were responsible for the improved growth properties in MDCK cells and eggs. In addition, the introduction of a mutation at residue 155 that was previously shown to enhance the replication of a 1976 swine influenza virus also significantly improved the replication of the CA09 virus in eggs. Each variant was further evaluated for receptor binding preference, antigenicity, attenuation phenotype, and immunogenicity. Mutations at residues 153, 154, and 155 drastically reduced viral antigenicity, which made these mutants unsuitable as vaccine candidates. However, changes at residues 119 and 186 did not affect virus antigenicity or immunogenicity, justifying their inclusion in live attenuated vaccine candidates to protect against the currently circulating 2009 swine origin H1N1 viruses.
META-STABLE BRANE CONFIGURATIONS WITH MULTIPLE NS5-BRANES
Authors: AHN CHANGHYUN 
Published: October 2009

Starting from an [Formula: see text] supersymmetric electric gauge theory with the multiple product gauge group and the bifundamentals, we apply Seiberg dual to each gauge group, obtain the [Formula: see text] supersymmetric dual magnetic gauge theories with dual matters including the gauge singlets. Then we describe the intersecting brane configurations, where there are NS-branes and D4-branes (and anti-D4-branes), of type IIA string theory corresponding to the meta-stable nonsupersymmetric vacua of this gauge theory. We also discuss the case where the orientifold 4-planes are added into the above brane configuration. Next, by adding an orientifold 6-plane, we apply to an [Formula: see text] supersymmetric electric gauge theory with the multiple product gauge group (where a single symplectic or orthogonal gauge group is present) and the bifundamentals. Finally, we describe the other cases where the orientifold 6-plane intersects with NS-brane.
Strong Convergence of Monotone Hybrid Method for Maximal Monotone Operators and Hemirelatively Nonexpansive Mappings
Authors: Klin-eam Chakkrid , Suantai Suthep 
Published: October 2009

AbstractWe prove strong convergence theorems for finding a common element of the zero point set of a maximal monotone operator and the fixed point set of a hemirelatively nonexpansive mapping in a Banach space by using monotone hybrid iteration method. By using these results, we obtain new convergence results for resolvents of maximal monotone operators and hemirelatively nonexpansive mappings in a Banach space.
Strong Convergence of Two Iterative Algorithms for Nonexpansive Mappings in Hilbert Spaces
Authors: Yao Yonghong , Liou Yeong Cheng , Marino Giuseppe 
Published: October 2009

AbstractWe introduce two iterative algorithms for nonexpansive mappings in Hilbert spaces. We prove that the proposed algorithms strongly converge to a fixed point of a nonexpansive mapping "Equation missing".
Disordered aldosterone-volume relationship in end-stage kidney disease
Authors: Bomback Andrew S , Kshirsagar Abhijit V , Ferris Maria E , Klemmer Philip J 
Published: October 2009

Introduction. Sodium loading, and subsequent volume expansion, suppresses aldosterone levels in individuals with normal renal function. We hypothesised that loss of renal function impairs this volume-aldosterone relationship. Materials and methods. With multifrequency bioimpedance spectroscopy, we measured total body water (TBW), extracellular volume (ECV), and intracellular volume in five haemodialysis patients at varied states of hydration and in five healthy volunteers during low-, normal-, and high-salt diets. Serum aldosterone, potassium, and C-reactive protein were measured simultaneously. Scatterplots and general estimating equations were used to examine the relationship among these variables. Results. In healthy volunteers with salt loading, and in haemodialysis subjects with increased inter-dialytic weight gain, expansion of ECV led to reciprocal declines in serum aldosterone concentrations. The relationship was more profound in healthy volunteers (p<0.001) than in haemodialysis subjects (p=0.1). Notably, haemodialysis subjects posted consistently higher levels of ECV (median 49.6% TBW, IQR 43.9—51.8% compared to 41.1%, 39.9—42.8% in volunteers) and serum aldosterone (median 26.7 ng/dl, IQR 19.8—29.6 compared to 12.4 ng/dl, 8.8—16.0 in volunteers). Serum potassium did not appear to influence aldosterone concentration (p=0.9). Conclusions. The shift of the volume-aldosterone curve in haemodialysis subjects suggests that end-stage kidney disease is a state of high volume and inappropriately high aldosterone. These data have important clinical implications, as dialysis patients may benefit from both volume reduction and mineralocorticoid receptor blockade.
Mta3-NuRD complex is a master regulator for initiation of primitive hematopoiesis in vertebrate embryos
Authors: Li Xiang , Jia Shunji , Wang Shaohe , Wang Yuemeng , Meng Anming 
Published: October 2009

AbstractMetastasis-associated antigens 1/2/3 (Mta1/2/3) are components of nucleosome remodeling and deacetylase (NuRD) complexes and have been found to play roles in embryonic development and homeostasis. However, their functions in primitive hematopoiesis are unknown. In this study, we demonstrate that knockdown of mta3 by antisense morpholinos abolishes primitive hematopoietic lineages and causes abnormal angiogenesis in zebrafish embryos. However, the expression of the pronephric duct and paraxial mesoderm markers is unaltered and the specification of angioblasts is unaffected in mta3 morphants. The results suggest that mta3 is specifically required for primitive hematopoiesis. Furthermore, inhibition of deacetylase activity with the inhibitors valproic acid (VPA) or trichostatin A (TSA) in zebrafish embryos completely blocks primitive hematopoiesis, resulting in hematopoietic defects almost identical to those seen in mta3 morphants. Importantly, overexpression of scl or scl and lmo2, 2 master genes for primitive hematopoiesis, is able to overturn effects of mta3 knockdown or VPA/TSA treatment; and overexpression of mta3, and human MBD3 or HDAC1, 2 other components of NuRD complex, enhances the expression of scl and lmo2 in the posterior lateral plate mesoderm during early primitive hematopoiesis. We conclude that Mta3-NuRD complex is essential for the initiation of primitive hematopoiesis. Thus, our findings provide new insight into the regulatory hierarchy of primitive hematopoiesis in vertebrates.
High-Voltage Electron Microscopy Reveals Direct Synaptic Inputs from a Spinal Gastrin-Releasing Peptide System to Neurons of the Spinal Nucleus of Bulbocavernosus
Authors: Sakamoto Hirotaka , Arii Tatsuo , Kawata Mitsuhiro 
Published: October 2009

Abstract
The spinal nucleus of bulbocavernosus (SNB) is a sexually dimorphic motor nucleus located in the anterior horn of the fifth and sixth lumbar segments of the spinal cord that plays a significant role in male sexual function. We recently found that a sexually dimorphic expression of gastrin-releasing peptide (GRP) in the lumbar spinal cord regulates male copulatory reflexes. Although it is reported that these systems are both profoundly regulated by circulating androgen levels in male rats, no direct evidence has been reported regarding GRP synaptic inputs onto SNB motoneurons. The aim of the current study was to determine the axodendritic synaptic inputs of spinal GRP neurons to SNB motoneurons. Immunoelectron microscopy, combined with a retrograde tracing technique using high-voltage electron microscopy (HVEM), provided a three-dimensional visualization of synaptic contacts from the GRP system in the lumbar spinal cord onto SNB motoneurons. HVEM analysis clearly demonstrated that GRP-immunoreactive axon terminals directly contact dendrites that extend into the dorsal gray commissure from the SNB. These HVEM findings provide an ultrastructural basis for understanding how the spinal GRP system regulates male sexual behavior.
Uncomfortable prescribing decisions in hospitals: the impact of teamwork
Authors: Lewis Penny J , Tully Mary P 
Published: October 2009

Summary Objectives Prescribing is not always driven by therapeutic motives alone; social and intrinsic factors also play a part in the decision. However, most research into prescribing influences has been conducted in general practice, with very little conducted within hospitals. One potential influence is the hospital multidisciplinary team, yet little attention has been paid to how interactions between teams and team members may influence prescribing. This study investigated the effect that team interaction and structure had upon UK hospital doctors' prescribing decisions, particularly their discomfort felt prescribing. Design and setting The study used the critical incident technique and in-depth interviews. Prior to an in-depth interview, 48 doctors of varying grades from four hospitals were asked to remember any uncomfortable prescribing decisions that they had recently made. These ‘incidents’ were discussed in depth. All interviews were tape-recorded and transcribed verbatim. A grounded theory approach to data analysis was taken. Results There were 193 critical incidents described in the interviews. Over one-third were related to the difficulties of prescribing within a team environment. Discomfort frequently arose because of factors relating to the hierarchical structure; in particular, junior doctors described their discomfort when they were uncertain of seniors' prescribing decisions. Prescribers also adhered to rules of prescribing etiquette, including the maintenance of other doctors'/teams' prescribing decisions and adherence to prescribing norms. Discomfort also arose from a perceived pressure to prescribe from the nursing team. Doctors admitted to prescribing to maintain overall team relationships, sometimes ignoring hospital regulations and best practice to do so. Conclusion Overall, this study demonstrated that hospital doctors' prescribing decisions were strongly influenced by relationships with other team members, particularly nurses and senior doctors. Ways of reducing this discomfort should be explored and further research is advocated in this area.
Chemical speciation of environmentally significant metals with inorganic ligands. Part 3: The Pb2+ + OH–, Cl–, CO32–, SO42–, and PO43– systems (IUPAC Technical Report)
Authors: Powell Kipton J. , Brown Paul L. , Byrne Robert H. , Gajda Tamás , Hefter Glenn , Leuz Ann-Kathrin , Sjöberg Staffan , Wanner Hans 
Published: October 2009

Abstract
Complex formation between PbII and the common environmental inorganic ligands, Cl–, OH–, CO3
2–, SO4
2–, and PO4
3–, can be significant in natural waters with low concentrations of organic matter. Numerical modeling of the speciation of PbII amongst these inorganic ligands requires reliable values for the relevant stability (formation) constants. This paper provides a critical review of such constants and related thermodynamic data. It recommends values of log10 β

p,q,r
° valid at I

m
= 0 mol kg–1 and 25 °C (298.15 K), along with the equations and empirical coefficients required to calculate log10
β

p,q,r
values at higher ionic strengths using the Brønsted–Guggenheim–Scatchard specific ion interaction theory (SIT). Some values for reaction enthalpies, Δr
H, are also reported. In weakly acidic fresh water systems (–log10 {[H+]/c°} &lt; 6), the speciation of PbII is similar to that of CuII. In the absence of organic ligands, PbII speciation is dominated by Pb2+(aq), with PbSO4(aq) as a minor species. In weakly alkaline solutions, 8.0 &lt; –log10 {[H+]/c°} &lt; 9.0, the speciation is dominated by the carbonato species PbCO3(aq) and Pb(CO3)2
2–. In weakly acidic saline systems (–log10 {[H+]/c°} &lt; 6), the speciation is dominated by PbCl
n

(2–

n

)+ complexes, (n = 0–3), with Pb2+(aq) as a minor species. In this medium (and in seawater), the speciation contrasts with that of CuII because of the higher stability of the Pb2+-chlorido- complexes. In seawater at –log10 {[H+]/c°} = 8.2, the calculated speciation is less well defined, although it is clearly dominated by the uncharged species PbCO3(aq) (41 % of [Pb]T) with a significant contribution (16 %) from Pb(CO3)Cl– and minor contributions (5–10 %) from PbCl
n

(2–

n

)+, (n = 0–3) and Pb(CO3)2
2–. The uncertainty in calculations of PbII speciation in seawater arises from (a) the large uncertainty in the stability constant for the apparently dominant species PbCO3(aq), (b) the reliance on statistical predictions for stability constants of the ternary species Pb(CO3)Cl– and Pb(CO3)OH–, and (c) the uncertainty in the stability constant for PbCl4
2–, the available value being considered "indicative" only. There is scope for additional detailed high-quality measurements in the Pb2+ + CO3
2– + Cl– system.
Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts
Authors: Kamiya Nobuhiro , Kobayashi Tatsuya , Mochida Yoshiyuki , Yu Paul B , Yamauchi Mitsuo , Kronenberg Henry M , Mishina Yuji 
Published: October 2009

Abstract
The bone morphogenetic protein (BMP) and Wnt signaling pathways both contribute essential roles in regulating bone mass. However, the molecular interactions between these pathways in osteoblasts are poorly understood. We recently reported that osteoblast-targeted conditional knockout (cKO) of BMP receptor type IA (BMPRIA) resulted in increased bone mass during embryonic development, where diminished expression of Sost as a downstream effector of BMPRIA resulted in increased Wnt/β-catenin signaling. Here, we report that Bmpr1a cKO mice exhibit increased bone mass during weanling stages, again with evidence of enhanced Wnt/β-catenin signaling as assessed by Wnt reporter TOPGAL mice and TOPFLASH luciferase. Consistent with negative regulation of the Wnt pathway by BMPRIA signaling, treatment of osteoblasts with dorsomorphin, an inhibitor of Smad-dependent BMP signaling, enhanced Wnt signaling. In addition to Sost, Wnt inhibitor Dkk1 also was downregulated in cKO bone. Expression levels of Dkk1and Sost were upregulated by BMP2 treatment and downregulated by Noggin. Moreover, expression of a constitutively active Bmpr1a transgene in mice resulted in the upregulation of both Dkk1 and Sost and partially rescued the Bmpr1a cKO bone phenotype. These effectors are differentially regulated by mitogen-activated protein kinase (MAPK) p38 because pretreatment of osteoblasts with SB202190 blocked BMP2-induced Dkk1 expression but not Sost. These results demonstrate that BMPRIA in osteoblasts negatively regulates endogenous bone mass and Wnt/β-catenin signaling and that this regulation may be mediated by the activities of Sost and Dkk1. This study highlights several interactions between BMP and Wnt signaling cascades in osteoblasts that may be amenable to therapeutic intervention for the modification of bone mass density. © 2010 American Society for Bone and Mineral Research