bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vesicular Stomatitis Virus as a Vector To Deliver Virus-Like Particles of Human Norovirus: a New Vaccine Candidate against an Important Noncultivable Virus
Authors: Ma Yuanmei , Li Jianrong 
Published: January 2011

ABSTRACTHuman norovirus (HuNoV) is a major causative agent of food-borne gastroenteritis worldwide. Currently, there are no vaccines or effective therapeutic interventions for this virus. Development of an attenuated vaccine for HuNoV has been hampered by the inability to grow the virus in cell culture. Thus, a vector-based vaccine may be ideal. In this study, we constructed a recombinant vesicular stomatitis virus (rVSV-VP1) expressing VP1, the major capsid protein of HuNoV. Expression of the capsid protein by VSV resulted in the formation of HuNoV virus-like particles (VLPs) that are morphologically and antigenically similar to native virions. Recombinant rVSV-VP1 was attenuated in cultured mammalian cells as well as in mice. Mice inoculated with a single dose of rVSV-VP1 through intranasal and oral routes stimulated a significantly stronger humoral and cellular immune response than baculovirus-expressed VLP vaccination. Moreover, we demonstrated that mice inoculated with rVSV-VP1 triggered a comparable level of fecal and vaginal IgA antibody. Taken together, the VSV recombinant system not only provides a new approach to generate HuNoV VLPsin vitrobut also a new avenue for the development of vectored vaccines against norovirus and other noncultivable viruses.
Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin
Authors: Capodagli Glenn C. , McKercher Marissa A. , Baker Erica A. , Masters Emily M. , Brunzelle Joseph S. , Pegan Scott D. 
Published: January 2011

ABSTRACTCrimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(−)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 Å, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.
Cooperative Cleavage of the R Peptide in the Env Trimer of Moloney Murine Leukemia Virus Facilitates Its Maturation for Fusion Competence
Authors: Löving Robin , Kronqvist Malin , Sjöberg Mathilda , Garoff Henrik 
Published: January 2011

ABSTRACT

The spike protein of murine leukemia virus, MLV, is made as a trimer of the Env precursor. This is primed for receptor-induced activation of its membrane fusion function first by cellular furin cleavage in the ectodomain and then by viral protease cleavage in the endodomain. The first cleavage separates the peripheral surface (SU) subunit from the transmembrane (TM) subunit, and the latter releases a 16-residue-long peptide (R) from the TM endodomain. Here, we have studied the distribution of R peptide cleavages in the spike TM subunits of Moloney MLV preparations with partially R-peptide-processed spikes. The spikes were solubilized as trimers and separated with an R peptide antibody. This showed that the spikes were either uncleaved or cleaved in all of its TM subunits. Further studies showed that R peptide cleavage-inhibited Env mutants, L
649
V and L
649
I, were rescued by wild-type (wt) Env in heterotrimeric spikes. These findings suggested that the R peptide cleavages in the spike are facilitated through positive allosteric cooperativity; i.e., the cleavage of the TM subunit in one Env promoted the cleavages of the TMs in the other Envs. The mechanism ensures that protease cleavage in newly released virus will generate R-peptide-cleaved homotrimers rather than heterotrimeric intermediates. However, using a cleavage site Env mutant, L
649
R, which was not rescued by wt Env, it was possible to produce virus with heterotrimers. These were shown to be less fusion active than the R-peptide-cleaved homotrimers. Therefore, the cooperative cleavage will speed up the maturation of released virus for fusion competence.
The Herpes Simplex Virus 1 IgG Fc Receptor Blocks Antibody-Mediated Complement Activation and Antibody-Dependent Cellular CytotoxicityIn Vivo
Authors: Lubinski John M. , Lazear Helen M. , Awasthi Sita , Wang Fushan , Friedman Harvey M. 
Published: January 2011

ABSTRACTHerpes simplex virus 1 (HSV-1) glycoprotein E (gE) mediates cell-to-cell spread and functions as an IgG Fc receptor (FcγR) that blocks the Fc domain of antibody targeting the virus or infected cell. Efforts to assess the functions of the HSV-1 FcγRin vivohave been hampered by difficulties in preparing an FcγR-negative strain that is relatively intact for spread. Here we report the FcγR and spread phenotypes of NS-gE264, which is a mutant strain that has four amino acids inserted after gE residue 264. The virus is defective in IgG Fc binding yet causes zosteriform disease in the mouse flank model that is only minimally reduced compared with wild-type and the rescue strains. The presence of zosteriform disease suggests that NS-gE264 spread functions are well maintained. The HSV-1 FcγR binds the Fc domain of human, but not murine IgG; therefore, to assess FcγR functionsin vivo, mice were passively immunized with human IgG antibody to HSV. When antibody was inoculated intraperitoneally 20 h prior to infection or shortly after virus reached the dorsal root ganglia, disease severity was significantly reduced in mice infected with NS-gE264, but not in mice infected with wild-type or rescue virus. Studies of C3 knockout mice and natural killer cell-depleted mice demonstrated that the HSV-1 FcγR blocked both IgG Fc-mediated complement activation and antibody-dependent cellular cytotoxicity. Therefore, the HSV-1 FcγR promotes immune evasion from IgG Fc-mediated activities and likely contributes to virulence at times when antibody is present, such as during recurrent infections.
Multimodal endovascular therapy of traumatic and spontaneous carotid cavernous fistula using coils, n-BCA, Onyx and stent graft
Authors: Zaidat Osama O , Lazzaro Marc A , Niu Tianyi , Hong Sang Hun , Fitzsimmons Brian-Fred , Lynch John R , Sinson Grant P 
Published: January 2011

Background and purposeCarotid cavernous fistula (CCF) can be classified as either direct or indirect according to the arterial feeder source. The current standard treatment for CCF is endovascular embolization. In this case series, 21 CCF (direct and indirect) embolization procedures were treated with multimodal endovascular therapy to explore safety, technique and clinical efficacy.Method and patientsThe neurointerventional database was reviewed for all cases of CCF. Demographic information, indications for the procedure, presenting symptoms, endovascular therapy types, complications and procedure angiographic and clinical efficacy were collected.Results21 CCF embolization procedures were performed using multimodal therapy on 15 patients (eight females and seven males) with a mean age of 56.4±22.4 years (15–90 years), with 60% traumatic CCF and 40% spontaneous CCF presenting mainly with typical visual symptoms. 10 patients were treated in one session, four patients underwent two sessions and one required three sessions of endovascular therapy. Complete fistula occlusion was achieved in 10/15 patients (73.3%) in one session and in 14/15 (93.3%) patients after two or more sessions. One patient's symptoms (case No 15) improved dramatically after the second session despite incomplete obliteration of the CCF. No periprocedural complications were reported. Long term follow-up showed one recurrence of the CCF with a mean follow-up time of 201±17.2 months (range 1–56 months). Patient No 6 was lost to follow-up.ConclusionMultimodal endovascular embolization of CCF appears to be safe with a high success rate of complete obliteration. This case series demonstrates complete occlusion in 73.3% of the patients after one session and in 93.3% after the second session.
Spatial patterns in defoliation and the expression of clonal traits in grazed meadows
Authors: Benot Marie-Lise , Bonis Anne , Rossignol Nicolas , Mony Cendrine 
Published: January 2011

Clonal plant species dominate meadow vegetation where grazing can generate spatial heterogeneity at different scales and can select for species that express particular sets of clonal traits. This in situ study aimed to characterize fine-grained spatial patterns of defoliation (<1 m) induced by contrasting cattle grazing intensities and to link these spatial patterns with the abundance of species-specific clonal traits. Using correlogams and synthetic spatio-temporal indices, the heterogeneity of vegetation height and leaf damage was monitored along a cattle grazing gradient. Species were identified and their clonal traits retrieved from the database CLO-PLA3. Under moderate grazing, fine-grained spatial patterns of defoliation were not stable over time. Defoliation was heterogeneous during the first months of the grazing season and then became homogeneous. Intensive grazing generated homogeneous defoliation, regardless of the date. In the study meadow, grazing gave rise to communities containing a greater abundance of annual species. However, clonal traits assumed to enable clonal fragments to benefit from heterogeneity do not seem advantageous. Increasing grazing intensity promoted species with clonal traits expected to minimize costs associated with clonality (aboveground clonal growth forms, short-distance lateral spread, and (or) short-lived connections). Ungrazed conditions favoured species with clonal traits associated with a high competitive ability.
LARGE EDDY SIMULATION OF HYDROELASTIC VIBRATION USING THE FINITE ELEMENT METHOD
Authors: WANG W. Q. , ZHANG L. X. , HE X. Q. , GUO Y. 
Published: January 2011

This work is concerned with modeling the interaction of fluid flow with flexible solid structures. An improving spring smooth analogy and an improved constant volume transfer (ICVT) are used to provide fluid mesh control and transfer the information on the interfaces between fluid and structure, respectively. The time integrating algorithm is based on the predictor multi-corrector algorithm (PMA). An important aspect of this work is that we present a directly coupled approach, in which a large eddy simulation (LES) fluid solver and a structure solver have been coupled together to solve a hydroelasticity problem using the finite element method. To demonstrate the performance of the proposed approach, two working examples were used. One is the vibration of a beam immersed in incompressible fluid, another is the hydroelastic behavior of an ideal guide vane in a hydro turbine passage. The numerical results show the validity of the proposed approach.
Fractal analysis of the ore-forming process in a skarn deposit: a case study in the Shizishan area, China
Authors: Wang Qingfei , Deng Jun , Liu Huan , Wan Li , Zhang Zhijun 
Published: January 2011

Abstract

This paper presents a tool for analysing the element distribution and mineralization intensity. The Hurst exponents and
a
-
f
(
a
) multifractal spectrum are utilized to analyse the irregular element distribution in Shizishan skarn orefield, China. The Hurst exponents reveal the Cu, Ag, Au and Zn distributions in the skarn-dominated drill cores are persistent and those in marble-dominated drill core are nearly random; the persistence indicates the mineralized segments are repeatedly developed, with accordance to multi-layer structure of the ore-controlling bedding faults and orebodies. The small
a
min
(minimum multifractal singularity) of the Cu, Ag and Au in M
1
reflect bare mineralization. The
a
min
also displays that the mineralization intensities are varied for distinct elements and for different locations, yet the similarity of the distinct ore-forming processes is manifested by constant
a
min
/
f
(
a
min
) ratio. The constant ratio indicates the wider mineralization range denotes a more compact concentration distribution. The compact distributions represent the wide Cu, Ag and Au mineralization in skarns, and the loose distributions reflect the bare Cu, Ag and Au mineralization in marbles. Moreover
a
min
shows a positive correlation with Hurst exponents in the Shizishan skarn orefield. Using fractal analysis the author's show that although the mineralization intensities for different elements and different locations along the Shizishan skarn orefield is not consistent, similar mineralization processes can be correlated to similar fractal exponents.
Geological setting, alteration, and fluid inclusion characteristics of Zaglic and Safikhanloo epithermal gold prospects, NW Iran
Authors: Ebrahimi Susan , Alirezaei Saeed , Pan Yuanming 
Published: January 2011

Abstract
The Zaglic and Safikhanloo epithermal gold prospects are located in the Arasbaran zone, to the west of the Cenozoic Alborz-Azarbaijan magmatic belt in NW Iran. Mineralization is mainly restricted to quartz and quartz -carbonate veins and veinlets. Pyrite is the main sulphide, associated with subordinate chalcopyrite and bornite. Gold occurs as microscopic and submicroscopic grains in quartz and pyrite.
The country rocks are Tertiary intermediate–mafic volcanic and volcaniclastic rocks of andesite to trachy-andesite composition intruded by a composite granitic to syenitic pluton. They are medium- to high-K, calc-alkaline and alkaline rocks and display fractionated REE (rare earth element) patterns, with light rare earth elements (LREE) significantly enriched relative to the heavy rare elements (HREE). On primitive mantle normalized plots, they display depletions in Nb, Ti and P, and enrichments in Pb, which are common characteristics of arc-related magmas worldwide. Hydrothermal alteration minerals developed in the wall rocks include quartz, calcite, pyrite, kaolinite, montmorillonite, illite, chlorite, and epidote. Minor alunite occurs in Safikhanloo. Gold is locally enriched in the altered rocks immediate to the veins.
The ore-stage quartz from both prospects is dominated by liquid-rich fluid inclusions; vapour-rich inclusions are rare. The homogenization temperature varies between 170–230 and 170–330 °C and salinity varies between 1.4 to 9.5 and <1 to 6.7 wt% NaCl equivalent, for Safikhanloo and Zaglic, respectively. The occurrence of hydrothermal breccias, bladed calcite, adularia, and rare coexisting vapour- and liquid-dominant inclusions suggest that boiling occurred in the course of the evolution of the ore fluids. The large variations in Th and the salinity values can be explained by boiling and/or mixing.

Lack of sulphate minerals in the veins suggests that sulphides and gold precipitated from a reduced, H
2
S-dominant fluid. Calculated δ
34
S values for the ore fluid vary between −4.6 and −9.3‰. Sulphur could have been derived directly from magmatic sources, or leached from the volcanic and plutonic country rocks. Ore formation in Zaglic and Safikhanloo occurred in response to mixing, boiling, and interactions with wall rocks. Considering the intermediate-argillic alteration, the low contents of base metal sulphides, and the overall low salinities, the Zaglic and Safikhanloo can be classified as low-sulphidation epithermal systems.
Strong Convergence Theorem for Equilibrium Problems and Fixed Points of a Nonspreading Mapping in Hilbert Spaces
Authors: Plubtieng Somyot , Chornphrom Sukanya 
Published: January 2011

AbstractWe introduce an iterative method for finding a common element of the set of solutions of equilibrium problems and the set of fixed points of a nonspreading mapping in a Hilbert space. Then, we prove a strong convergence theorem which is connected with the work of S. Takahashi and W. Takahashi (2007) and Iemoto and Takahashi (2009).
Finding Common Solutions of a Variational Inequality, a General System of Variational Inequalities, and a Fixed-Point Problem via a Hybrid Extragradient Method
Authors: Ceng Lu-Chuan , Guu Sy-Ming , Yao Jen-Chih 
Published: January 2011

AbstractWe propose a hybrid extragradient method for finding a common element of the solution set of a variational inequality problem, the solution set of a general system of variational inequalities, and the fixed-point set of a strictly pseudocontractive mapping in a real Hilbert space. Our hybrid method is based on the well-known extragradient method, viscosity approximation method, and Mann-type iteration method. By constrasting with other methods, our hybrid approach drops the requirement of boundedness for the domain in which various mappings are defined. Furthermore, under mild conditions imposed on the parameters we show that our algorithm generates iterates which converge strongly to a common element of these three problems.
Amiloride Modulates Alternative Splicing in Leukemic Cells and Resensitizes Bcr-AblT315I Mutant Cells to Imatinib
Authors: Chang Wen-Hsin , Liu Ta-Chih , Yang Wen-Kuang , Lee Chien-Chih , Lin Yi-Hsiung , Chen Tsai-Yun , Chang Jan-Gowth 
Published: January 2011

Abstract
The antihypertensive drug amiloride is being considered as a tactic to improve cancer therapy including that for chronic myelogenous leukemia. In this study, we show that amiloride modulates the alternative splicing of various cancer genes, including Bcl-x, HIPK3, and BCR/ABL, and that this effect is not mainly related to pH alteration, which is a known effect of the drug. Splice modulation involved various splicing factors, with the phosphorylation state of serine-arginine–rich (SR) proteins also altered during the splicing process. Pretreatment with okadaic acid to inhibit protein phosphatase PP1 reversed partially the phosphorylation levels of SR proteins and also the amiloride-modulated yields of Bcl-xs and HIPK3 U(-) isoforms. Genome-wide detection of alternative splicing further revealed that many other apoptotic genes were regulated by amiloride, including APAF-1, CRK, and SURVIVIN. Various proteins of the Bcl-2 family and MAPK kinases were found to be involved in amiloride-induced apoptosis. Moreover, the effect of amiloride on mRNA levels of Bcl-x was demonstrated to translate to the protein levels. Cotreatment of K562 and BaF3/Bcr-AblT315I cells with amiloride and imatinib induced more loss of cell viability than either agent alone. Our findings suggest that amiloride may offer a potential treatment option for chronic myelogenous leukemia either alone or in combination with imatinib. Cancer Res; 71(2); 383–92. ©2011 AACR.
Chromosome Breakage Is Regulated by the Interaction of the BLM Helicase and Topoisomerase IIα
Authors: Russell Beatriz , Bhattacharyya Saumitri , Keirsey Jeremy , Sandy April , Grierson Patrick , Perchiniak Erin , Kavecansky Juraj , Acharya Samir , Groden Joanna 
Published: January 2011

Abstract
Cells deficient in the recQ-like helicase BLM are characterized by chromosome changes that suggest the disruption of normal mechanisms needed to resolve recombination intermediates and to maintain chromosome stability. Human BLM and topoisomerase IIα interact directly via amino acids 489–587 of BLM and colocalize predominantly in late G2 and M phases of the cell cycle. Deletion of this region does not affect the inherent in vitro helicase activity of BLM but inhibits the topoisomerase IIα–dependent enhancement of its activity, based on the analysis of specific DNA substrates that represent some recombination intermediates. Deletion of the interaction domain from BLM fails to correct the elevated chromosome breakage of transfected BLM-deficient cells. Our results demonstrate that the BLM–topoisomerase IIα interaction is important for preventing chromosome breakage and elucidate a DNA repair mechanism that is critical to maintain chromosome stability in cells and to prevent tumor formation. Cancer Res; 71(2); 561–71. ©2011 AACR.
Phosphorylation of H2AX at Ser139 and a New Phosphorylation Site Ser16 by RSK2 Decreases H2AX Ubiquitination and Inhibits Cell Transformation
Authors: Zhu Feng , Zykova Tatyana A. , Peng Cong , Zhang Jishuai , Cho Yong-Yeon , Zheng Duo , Yao Ke , Ma Wei-Ya , Lau Andy T. Y. , Bode Ann M. , Dong Zigang 
Published: January 2011

Abstract
Histone H2AX is a histone H2A variant that is ubiquitously expressed throughout the genome. It plays a key role in the cellular response to DNA damage and has been designated as the histone guardian of the genome. Histone H2AX deficiency decreases genomic stability and increases tumor susceptibility of normal cells and tissues. However, the role of histone H2AX phosphorylation in malignant transformation and cancer development is not totally clear. Herein, we found that ribosomal S6 kinase 2 (RSK2) directly phosphorylates histone H2AX at Ser139 and also at a newly discovered site, Ser16. Epidermal growth factor (EGF)–induced phosphorylation of histone H2AX at both sites was decreased in RSK2 knockout cells. Phosphorylated RSK2 and histone H2AX colocalized in the nucleus following EGF treatment, and the phosphorylation of histone H2AX by RSK2 enhanced the stability of histone H2AX and prevented cell transformation induced by EGF. RSK2 and DNA-PK, but not ATM or ATR, are required for EGF-induced phosphorylation of H2AX at Ser139; however, only RSK2 is required for phosphorylation of H2AX at Ser16. Phosphorylation of histone H3 was suppressed in cells expressing wild-type H2AX compared with H2AX knockout (H2AX−/−) cells. EGF-associated AP-1 transactivation activity was dramatically lower in H2AX−/− cells overexpressing wild-type H2AX than H2AX−/− cells expressing mutant H2AX-AA. Thus, the RSK2/H2AX signaling pathway negatively regulates the RSK2/histone H3 pathway and therefore maintains normal cell proliferation. Cancer Res; 71(2); 393–403. ©2011 AACR.