bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Acetyl-Esterase Activity of the Hemagglutinin-Esterase Protein of Human Coronavirus OC43 Strongly Enhances the Production of Infectious Virus
Authors: Desforges Marc , Desjardins Jessica , Zhang Chengsheng , Talbot Pierre J. 
Published: January 2013

ABSTRACT

Most betacoronaviruses possess an hemagglutinin-esterase (HE) protein, which appears to play a role in binding to or release from the target cell. Since this HE protein possesses an acetyl-esterase activity that removes acetyl groups from O-acetylated sialic acid, a role as a receptor-destroying enzyme has been postulated. However, the precise function of HE and of its enzymatic activity remains poorly understood. Making use of neutralizing antibody and of molecular clones of recombinant human coronavirus OC43 (HCoV-OC43), our results suggest that the HE protein of this HCoV could be associated with infection of target cells and, most notably, is important in the production of infectious viral particles. Indeed, after transfecting BHK-21 cells with various cDNA infectious clones of HCoV-OC43, either lacking the HE protein or bearing an HE protein with a nonfunctional acetyl-esterase enzymatic activity, we were reproducibly unable to detect recombinant infectious viruses compared to the reference infectious HCoV-OC43 clone pBAC-OC43
FL
. Complementation experiments, using BHK-21 cells expressing wild-type HE, either transiently or in a stable ectopic expression, demonstrate that this protein plays a very significant role in the production of infectious recombinant coronaviral particles that can subsequently more efficiently infect susceptible epithelial and neuronal cells. Even though the S protein is the main viral factor influencing coronavirus infection of susceptible cells, our results taken together indicate that a functionally active HE protein enhances the infectious properties of HCoV-OC43 and contributes to efficient virus dissemination in cell culture.
5-(Perylen-3-yl)Ethynyl-arabino-Uridine (aUY11), an Arabino-Based Rigid Amphipathic Fusion Inhibitor, Targets Virion Envelope Lipids To Inhibit Fusion of Influenza Virus, Hepatitis C Virus, and Other Enveloped Viruses
Authors: Colpitts Che C. , Ustinov Alexey V. , Epand Raquel F. , Epand Richard M. , Korshun Vladimir A. , Schang Luis M. 
Published: January 2013

ABSTRACT

Entry of enveloped viruses requires fusion of viral and cellular membranes. Fusion requires the formation of an intermediate stalk structure, in which only the outer leaflets are fused. The stalk structure, in turn, requires the lipid bilayer of the envelope to bend into negative curvature. This process is inhibited by enrichment in the outer leaflet of lipids with larger polar headgroups, which favor positive curvature. Accordingly, phospholipids with such shape inhibit viral fusion. We previously identified a compound, 5-(perylen-3-yl)ethynyl-2′-
deoxy
-uridine (dUY11), with overall shape and amphipathicity similar to those of these phospholipids. dUY11 inhibited the formation of the negative curvature necessary for stalk formation and the fusion of a model enveloped virus, vesicular stomatitis virus (VSV). We proposed that dUY11 acted by biophysical mechanisms as a result of its shape and amphipathicity. To test this model, we have now characterized the mechanisms against influenza virus and HCV of 5-(perylen-3-yl)ethynyl-
arabino
-uridine (aUY11), which has shape and amphipathicity similar to those of dUY11 but contains an arabino-nucleoside. aUY11 interacted with envelope lipids to inhibit the infectivity of influenza virus, hepatitis C virus (HCV), herpes simplex virus 1 and 2 (HSV-1/2), and other enveloped viruses. It specifically inhibited the fusion of influenza virus, HCV, VSV, and even protein-free liposomes to cells. Furthermore, aUY11 inhibited the formation of negative curvature in model lipid bilayers. In summary, the arabino-derived aUY11 and the deoxy-derived dUY11 act by the same antiviral mechanisms against several enveloped but otherwise unrelated viruses. Therefore, chemically unrelated compounds of appropriate shape and amphipathicity target virion envelope lipids to inhibit formation of the negative curvature required for fusion, inhibiting infectivity by biophysical, not biochemical, mechanisms.
Structure of a VP1-VP3 Complex Suggests How Birnaviruses Package the VP1 Polymerase
Authors: Bahar Mohammad W. , Sarin L. Peter , Graham Stephen C. , Pang Jances , Bamford Dennis H. , Stuart David I. , Grimes Jonathan M. 
Published: January 2013

ABSTRACT

Infectious pancreatic necrosis virus (IPNV), a member of the family
Birnaviridae
, infects young salmon, with a severe impact on the commercial sea farming industry. Of the five mature proteins encoded by the IPNV genome, the multifunctional VP3 has an essential role in morphogenesis; interacting with the capsid protein VP2, the viral double-stranded RNA (dsRNA) genome and the RNA-dependent RNA polymerase VP1. Here we investigate one of these VP3 functions and present the crystal structure of the C-terminal 12 residues of VP3 bound to the VP1 polymerase. This interaction, visualized for the first time, reveals the precise molecular determinants used by VP3 to bind the polymerase. Competition binding studies confirm that this region of VP3 is necessary and sufficient for VP1 binding, while biochemical experiments show that VP3 attachment has no effect on polymerase activity. These results indicate how VP3 recruits the polymerase into birnavirus capsids during morphogenesis.
Constitutive HER2 Signaling Promotes Breast Cancer Metastasis through Cellular Senescence
Authors: Angelini Pier Davide , Fluck Mariano F. Zacarias , Pedersen Kim , Parra-Palau Josep Lluís , Guiu Marc , Bernadó Morales Cristina , Vicario Rocio , Luque-García Antonio , Navalpotro Nerea Peiró , Giralt Jordi , Canals Francesc , Gomis Roger R. , Tabernero Josep , Baselga José , Villanueva Josep , Arribas Joaquín 
Published: January 2013

Abstract
Senescence, a terminal cell proliferation arrest, can be triggered by oncogenes. Oncogene-induced senescence is classically considered a tumor defense barrier. However, several findings show that, under certain circumstances, senescent cells may favor tumor progression because of their secretory phenotype. Here, we show that the expression in different breast epithelial cell lines of p95HER2, a constitutively active fragment of the tyrosine kinase receptor HER2, results in either increased proliferation or senescence. In senescent cells, p95HER2 elicits a secretome enriched in proteases, cytokines, and growth factors. This secretory phenotype is not a mere consequence of the senescence status and requires continuous HER2 signaling to be maintained. Underscoring the functional relevance of the p95HER2-induced senescence secretome, we show that p95HER2-induced senescent cells promote metastasis in vivo in a non–cell-autonomous manner. Cancer Res; 73(1); 450–8. ©2012 AACR.
Human Papilloma Virus (HPV) E7-Mediated Attenuation of Retinoblastoma (Rb) Induces hPygopus2 Expression via Elf-1 in Cervical Cancer
Authors: Tzenov Youlian R. , Andrews Phillip G. , Voisey Kim , Popadiuk Paul , Xiong Jieying , Popadiuk Catherine , Kao Kenneth R. 
Published: January 2013

Abstract
The human papillomavirus (HPV) is the etiologic agent of cervical cancer. In this study, we provide evidence for the human Pygopus (hPygo)2 gene as a cellular biomarker for HPV-related disease. In a tumor microarray of cervical cancer progression, hPygo2 levels were greater in high-grade lesions and squamous cell carcinomas than in normal epithelia. Similarly, hPygo2 mRNA and protein levels were greater in HPV-positive cervical cancer cells relative to uninfected primary cells. RNA interference (RNAi)-mediated depletion of HPV-E7 increased whereas E74-like factor (Elf)-1 RNAi decreased association of Retinoblastoma (Rb) tumor suppressor with the hPygo2 promoter in cervical cancer cell lines. Transfection of dominant-active Rb inhibited Elf-1-dependent activation of hPygo2, whereas Elf-1 itself increased hPygo2 expression. Chromatin immunoprecipitation assays showed that Rb repressed hPygo2 by inhibiting Elf-1 at the Ets-binding site in the hPygo2 promoter. These results suggested that abrogation of Rb by E7 resulted in derepression of Elf-1, which in turn stimulated expression of hPygo2. Thus, initiation of hPygo2 expression by Elf-1 was required for proliferation of cervical cancer cells and its expression therefore may act as a surrogate marker for dysplasia. Mol Cancer Res; 11(1); 19–30. ©2012 AACR.
A Constraint-Based Hypergraph Partitioning Approach to Coreference Resolution
Authors: Sapena Emili , Padró Lluís , Turmo Jordi 
Published: January 2013

This work is focused on research in machine learning for coreference resolution. Coreference resolution is a natural language processing task that consists of determining the expressions in a discourse that refer to the same entity. The main contributions of this article are (i) a new approach to coreference resolution based on constraint satisfaction, using a hypergraph to represent the problem and solving it by relaxation labeling; and (ii) research towards improving coreference resolution performance using world knowledge extracted from Wikipedia. The developed approach is able to use an entity-mention classification model with more expressiveness than the pair-based ones, and overcome the weaknesses of previous approaches in the state of the art such as linking contradictions, classifications without context, and lack of information evaluating pairs. Furthermore, the approach allows the incorporation of new information by adding constraints, and research has been done in order to use world knowledge to improve performances. RelaxCor, the implementation of the approach, achieved results at the state-of-the-art level, and participated in international competitions: SemEval-2010 and CoNLL-2011. RelaxCor achieved second place in CoNLL-2011.
Plagiarism Meets Paraphrasing: Insights for the Next Generation in Automatic Plagiarism Detection
Authors: Barrón-Cedeño Alberto , Vila Marta , Martí M. , Rosso Paolo 
Published: January 2013

Although paraphrasing is the linguistic mechanism underlying many plagiarism cases, little attention has been paid to its analysis in the framework of automatic plagiarism detection. Therefore, state-of-the-art plagiarism detectors find it difficult to detect cases of paraphrase plagiarism. In this article, we analyze the relationship between paraphrasing and plagiarism, paying special attention to which paraphrase phenomena underlie acts of plagiarism and which of them are detected by plagiarism detection systems. With this aim in mind, we created the P4P corpus, a new resource that uses a paraphrase typology to annotate a subset of the PAN-PC-10 corpus for automatic plagiarism detection. The results of the Second International Competition on Plagiarism Detection were analyzed in the light of this annotation. The presented experiments show that (i) more complex paraphrase phenomena and a high density of paraphrase mechanisms make plagiarism detection more difficult, (ii) lexical substitutions are the paraphrase mechanisms used the most when plagiarizing, and (iii) paraphrase mechanisms tend to shorten the plagiarized text. For the first time, the paraphrase mechanisms behind plagiarism have been analyzed, providing critical insights for the improvement of automatic plagiarism detection systems.
Efficacy of Commercial Earplugs in Preventing Water Intrusion during Swimming
Authors: Mahboubi Hossein , Lee Austin , Kiumehr Saman , Zardouz Shawn , Shahriari Shawhin , Djalilian Hamid R. 
Published: January 2013

ObjectiveTo evaluate and compare the efficacy of commercially available earplugs in preventing water intrusion in healthy individuals.Study DesignExperimental study.SettingTertiary care medical center.Subjects and MethodsTen subjects (20 ears) were assessed. After insertion of the earplugs, subjects underwent 3 standardized head‐wetting protocols, including (1) surface swimming for 10 minutes, which entailed no head submersion and moderate splashing; (2) head submersion at a 90‐cm depth for 20 seconds with their head upright; and (3) head submersion at a 90‐cm depth with head tilted 90 degrees left and then tilted 90 degrees right for 10 seconds on each side to apply vertical pressure. Color change of a wetness indicator was used to determine water intrusion after each protocol. The same protocol was repeated for all 9 earplugs.ResultsWater intrusion was observed in 44%, 67%, and 88% of ears after surface swimming, horizontal submersion, and vertical submersion, respectively. The results revealed a significant difference in the waterproofing qualities of the various types of earplugs. The soft silicone type (Pillow Soft) earplug had the lowest rate of water penetration during all 3 protocols (P <. 001). The difference between the most effective earplugs, Pillow Soft and Aquaseal, were only significant during the horizontal submersion protocol (P =. 008).ConclusionWater intrusion occurred even with the use of earplugs. The intrusion was more significant with horizontal or vertical head submersion. The soft silicone Pillow Soft earplug was the most effective earplug for preventing water intrusion in surface swimming.
The M235T polymorphism in the angiotensinogen gene and myocardial infarction risk: A meta-analysis
Authors: Wang Yu-Jing , Pan Yan 
Published: January 2013

Objective: The angiotensinogen (AGT) gene M235T polymorphism has been reported to be associated with myocardial infarction (MI), but previous studies have been inconsistent. The present study aimed at assessing the association of M235T polymorphism in the AGT gene with MI using a meta-analysis. Methods: We retrieved literature in Google Scholar, PubMed, Cochrane Library and the China National Knowledge Infrastructure database (January 1990–December 2011) for the relevant studies on the AGT polymorphism M235T and risk of MI. Statistical analyses were carried out using Stata 10.0 for combining all the relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Begg’s test was used to measure publication bias. Results: A total of 21 case-control studies containing 5887 patients and 6164 controls were enrolled into this meta-analysis. Overall, significant association was found between the AGT gene M235T polymorphism and risk of MI in the subgroup analysis for TT vs MT in Asians (OR 1.47, 95% CI: 1.01–2.12; p = 0.04). No associations were detected between AGT M235T and the risk of MI in total population and Caucasians. Conclusions: This meta-analysis demonstrated that the AGT M235T polymorphism could be a prediction marker for risk of MI in Asians. Conclusive evidence on the effects of the variants in MI should be addressed in further studies.
Cholecalciferol administration blunts the systemic renin–angiotensin system in essential hypertensives with hypovitaminosis D
Authors: Carrara Davide , Bernini Matteo , Bacca Alessandra , Rugani Ilaria , Duranti Emiliano , Virdis Agostino , Ghiadoni Lorenzo , Taddei Stefano , Bernini Giampaolo 
Published: January 2013

Introduction: Vitamin D plasma levels are negatively associated with blood pressure and cardiovascular mortality, and vitamin D supplementation reduces cardiovascular events. Renin–angiotensin system (RAS) suppression may be one of the mechanisms involved. However, there are no interventional prospective studies demonstrating a reduction in circulating RAS components after vitamin D treatment. Methods: Fifteen consecutive drug-free patients with essential hypertension and hypovitaminosis D underwent therapy with an oral dose of 25000 I.U. of cholecalciferol once a week for two months, while maintaining a constant-salt diet. In basal conditions and at the end of the study, RAS activity (plasma angiotensinogen, renin, PRA, angiotensin II, aldosterone and urinary angiotensinogen) was investigated, in addition to blood pressure and plasma vitamin D levels (25(OH)D). Results: After cholecalciferol administration, all patients exhibited normalized plasma 25(OH)D values. At the end of the study, a reduction ( p < 0.05) in plasma renin and aldosterone, and a decrement, although not significant, of PRA and angiotensin II, was observed. No difference was found in plasma and urinary angiotensinogen or blood pressure values. Conclusions: Our data indicate that in essential hypertensives with hypovitaminosis D, pharmacological correction of vitamin D levels can blunt systemic RAS activity.
Left ventricular remodelling after acute myocardial infarction: Impact of clinical, echocardiographic parameters and polymorphism of angiotensinogen gene
Authors: Zaliaduonyte-Peksiene Diana , Simonyte Sandrita , Lesauskaite Vaiva , Vaskelyte Jolanta , Gustiene Olivija , Mizariene Vaida , Jurkevicius Renaldas , Jariene Giedre , Tamosiunas Abdonas , Zaliunas Remigijus 
Published: January 2013

Introduction: The development of left ventricular remodelling after acute myocardial infarction is a predictor of heart failure and mortality. The purpose of the present study was to assess whether the polymorphism of angiotensinogen ( AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 ( M235T) had effects on cardiac remodelling after acute myocardial infarction. Methods: One hundred and forty-one patients (mean age 56.4±11.1 years) with a first acute myocardial infarction were enrolled. Within 24–72 hours of the onset of the symptoms and at a four month period two-dimensional echocardiography was performed. Remodelling was defined as a 20% increase from the baseline in left ventricular end-diastolic volume. The genotypes of the study group were compared with the reference group ( n=1010) genotypes. AGT M235T polymorphism was determined using polymerase chain reaction amplification. Results: At follow-up, 49 patients (34.7%) were classified as having left ventricular remodelling. Anterior localization of the infarct ( p=0.008), leucocyte count at admission ( p=0.040), global left ventricular longitudinal strain ( p=0.021) and MM genotype of AGT ( p=0.024) were independent predictors of ventricular remodelling after myocardial infarction. Conclusions: Anterior wall infarction, increased leucocyte count, decreased longitudinal strain of left ventricular and polymorphism of AGT M235T may predict remodelling after myocardial infarction.
Central statistical monitoring: Detecting fraud in clinical trials
Authors: Pogue Janice M , Devereaux PJ , Thorlund Kristian , Yusuf Salim 
Published: January 2013

Background Central statistical monitoring in multicenter trials could allow trialists to identify centers with problematic data or conduct and intervene while the trial is still ongoing. Currently, there are few published models that can be used for this purpose. Purpose To develop and validate a series of risk scores to identify fabricated data within a multicenter trial, to be used in central statistical monitoring. Methods We used a database from a multicenter trial in which data from 9 of 109 centers were documented to be fabricated. These data were used to build a series of risk scores to predict fraud at centers. All analyses were performed at the level of the center. Exploratory factor analysis was used to select from 52 possible predictors, chosen from a variety of previously published methods. The final models were selected from a total of 18 independent predictors, based on the factors identified. These models were converted to risk scores for each center. Results Five different risk scores were identified, and each had the ability to discriminate well between centers with and without fabricated data (area under the curve values ranged from 0.90 to 0.95). True- and false-positive rates are presented for each risk score to arrive at a recommended cutoff of seven or above (high risk score). We validated these risk scores, using an independent multicenter trial database that contained no data fabrication and found the occurrence of false-positive high scores to be low and comparable to the model-building data set. Limitations These risk score have been validated only for their false-positive rate and require validation within another trial that contains centers that have fabricated data. Validation in noncardiovascular trials is also required to gage the usefulness of these risk scores in central statistical monitoring. Conclusions With further validation, these risk scores could become part of a series of tools that provide evidence-based central statistical monitoring, which in turn can improve the efficiency of trials, and minimize the need for more expensive on-site monitoring.
Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia
Authors: Ghobrial Irene M. , Campigotto Federico , Murphy Timothy J. , Boswell Erica N. , Banwait Ranjit , Azab Feda , Chuma Stacey , Kunsman Janet , Donovan Amanda , Masood Farzana , Warren Diane , Rodig Scott , Anderson Kenneth C. , Richardson Paul G. , Weller Edie , Matous Jeffrey 
Published: January 2013

Key Points
Presents the data from a phase 2 clinical trial of panobinostat in patients with relapsed WM. Establishes a role for histone deacetylase inhibitors as an active class of therapeutic agents in WM.
Sense and nonsense of high-dose cytarabine for acute myeloid leukemia
Authors: Löwenberg Bob 
Published: January 2013

Abstract
High-dose cytarabine applied during remission induction or as consolidation after attainment of a complete remission has become an established element in the treatment of adults with acute myeloid leukemia. Recent evidence has challenged the need for these exceptionally high-dose levels of cytarabine. In this review, we present a reappraisal of the usefulness of high-dose cytarabine for acute myeloid leukemia treatment.
Cytotoxic function of CD8+ T lymphocytes isolated from patients with acute severe cerebral infarction: an assessment of stroke-induced immunosuppression
Authors: Li Gang , Wang Xin , Huang Li-hong , Wang Yue , Hao Jun-jie , Ge Xia , Xu Xiao-yun 
Published: January 2013

Abstract

Background
There is increasing evidence on complex interaction between the nervous and immune systems in patients with cerebral infarction. This study was conducted to evaluate cytotoxic function of CD8+ T lymphocytes isolated from patients with acute severe cerebral infarction. In order to determine role of immune system in stroke, peripheral blood mononuclear cells (PBMCs) were taken and cytotoxic function of CD8+ T lymphocytes were induced by virus peptides and cells were analyzed on a four-color flow cytometer. Expression of CD107a, intracellular expression of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), and cell proliferation assay were analyzed by using carboxyl fluorescein diacetate succinimidyl ester (CFSE).

Results
A total of 30 patients with cerebral infarction and 30 healthy volunteers with an average age 57 (range, 49 to 71) years, were evaluated. The PBMCs were separated from blood samples of both, patients with cerebral infarction 6 hours after onset of stroke and healthy volunteers. After stimulation with virus peptides, CD107a expression and intracellular production of IFN-γ and TNF-α was decreased in patients with cerebral infarction as compared to healthy volunteers (p < 0.01). Degranulation analysis reported decreased expression of CD107a + in patient group as compared to healthy group, p <0.01. A mild decrease in intracellular expression of IFN-γ and TNF-α was also shown in patients without stimulation of virus peptides (p < 0.05). However, proliferation of CD8+ T lymphocytes in patients with acute severe cerebral infarction was not decreased.

Conclusions
The study results indicated that cytotoxic function of CD8+ T lymphocytes were suppressed in patients with acute severe cerebral infarction. This could possibly be associated with complicated infectious diseases and neuroprotective mechanism.